Simvastatin Treatment Prevents Cell Damage and Regulates Angiogenesis in a Rat Ovarian Torsion and Detorsion Model: An Immunohistochemical Study of Caspase-3 and sFlt-1 Expression
This study investigated the effects of simvastatin treatment on a rat model of ovarian torsion and detorsion. Rats were divided into four groups: control, ischemia, ischemia-reperfusion, and ischemia-reperfusion treated with simvastatin. Ovarian tissue samples were analyzed for markers of oxidative damage (MDA and GSH-Px) and apoptosis (caspase-3 and sFlt-1 expression). Results showed that simvastatin decreased MDA levels and increased GSH levels, suggesting it reduced oxidative damage. Simvastatin also decreased caspase-3 and sFlt-1 expression, indicating it prevented cell apoptosis and regulated angiogenesis. The study concludes that simvastatin administration protects against cell
Objective: To investigate the effect of sildenafil on reducing the impact of hepatic ischemia/reperfusion (HIR) injury established by Pringle maneuver on the heart of rats.
Study Design: Forty Wistar albino rats were divided into 4 groups: Sham (laparotomy only), Control (laparotomy following sildenafil application), IR (ischemia/reperfusion injured by HIR), and IR+SIL (injured by HIR following sildenafil application). Ischemia was developed by clamping the hepatoduodenal ligament for 30 minutes; then reperfusion was applied for 30 minutes. Sildenafil (single dose of 50 mg/kg) was administered by oral gavage for 15 minutes before ischemia. Blood samples of rats were collected from Sham and Control groups at 60 minutes and from IR and IR+SIL groups at 30 minutes after initiation of reperfusion for biochemical analysis. Meanwhile, heart tissues were sampled for biochemical analysis. Malondialdehyde (MDA) and total antioxidant capacity (TAC) in serum samples and TAC, total oxidative capacity (TOC), and oxidative stress index in heart tissues were examined biochemically.
Results: Serum MDA levels were elevated significantly in the IR and IR+SIL groups as compared to the sham group. Sildenafil treatment inhibited MDA increase considerably in the IR+SIL group as compared to the IR group. Serum TAC levels were elevated significantly in the sildenafil and control groups (compared with sham groups) and in the IR+SIL group (compared with the IR group). TAC levels detected in heart tissue increased significantly in the IR group as compared to the sham group; however, sildenafil treatment had no effect on this increase.
Conclusion: Heart tissue was affected by HIR. It was revealed that sildenafil treatment may prevent the oxidative stress via increasing serum TAC levels in both control and IR+SIL groups.
This study investigated the effects of spinal cord injury on the bladder tissue of rats. Twenty rats were divided into a control group and spinal cord injury (SCI) group. The SCI group exhibited statistically higher levels of oxidative stress markers (MDA, MPO), epithelial degeneration, vascular dilation, inflammation, and expression of VEGF and APAF-1 compared to the control group. The SCI group also had lower levels of the antioxidant GSH. Histological examination of the SCI group showed degeneration of epithelial cells, thickened fibrosis, dilated blood vessels, and increased VEGF and APAF-1 expression compared to the control group. The results suggest that spinal cord injury leads to increased oxidative stress, inflammation and apoptosis in
Objective: To study the effects of resveratrol in neuronal structures in traumatic brain injury (TBI).
Study Design: Thirty rats were categorized as (1) control group (n=10), saline solution administered i.p. for 14 days, (2) TBI group (n=10), trauma induced by weight-drop model on brain, and (3) TBI+Resveratrol group (n=10), 15 minutes after injury the rats were given resveratrol (10 μmoL/kg/i.p.) for 14 days. At the end of the experiment the cerebellum was excised for routine paraffin tissue protocol. Blood samples were tested for serum biochemical markers (MDA, SOD, CAT, and GSH-x).
Results: SOD, GPx, and CAT values were lowest in the TBI group. MDA and histological scores of dilations in vessels, inflammation, degeneration in neurons, apoptosis in microglia, ADAMTS8, and GFAP expressions were highest in the TBI group. Sections of the control group showed normal cerebellar histology. The trauma group showed degenerated ganglion layer, pyknotic and apoptotic Purkinje cell nuclei. Vascular thrombus was seen in the substantia alba and substantia grisea. In the Trauma+Resveratrol group, most pa- thologies observed in the TBI group were improved. In the control group, GFAP protein was expressed in granular cells, axons, dendrites, Purkinje cells, and microglia cells. In the trauma group, increased GFAP expression was observed in glial processes, neurons, and Purkinje cells. In the Trauma+Resveratrol group, GFAP was expressed in molecular layer and glial processes. In the control group, ADAMTS-4 activity was observed in granulosa layer, glial cells, and Purkinje cells. In the trauma group, ADAMTS-4 expression was positive in Purkinje cells and glial cells. In the Trauma+ Resveratrol group, ADAMTS-4 was expressed in Purkinje cells, granular cells, and glial cells.
Conclusion: GFAP and ADAMTS-4 proteins may be involved in regeneration of damaged astroglial cells and other glial cells, Purkinje cells, and synaptic extensions. We suggest that antioxidative drugs such as resveratrol may be alternative target agents in neurological disease.
Keywords: ADAMTS-4, brain, cerebellum, GFAP, rat, resveratrol, traumatic brain injury
This study investigated the effects of gallic acid on testicular injury caused by ischemia-reperfusion in a rat testicular torsion model. Forty rats were divided into four groups: a control group, a torsion group, a torsion/detorsion group, and a torsion/detorsion plus gallic acid group. Biochemical markers and immunohistochemical staining for caspase-3 and TNF-α were analyzed. The results showed that gallic acid treatment decreased oxidative stress markers, reduced apoptosis and inflammation, and helped protect testicular tissue compared to the torsion/detorsion group without treatment. The study suggests that gallic acid may be a potential therapeutic agent for testicular ischemia-reperfusion injury.
Effect of Gonadotrophin (Pergonal®) on Haematological and Serum Biochemical P...Agriculture Journal IJOEAR
Abstract— Twelve Ouda rams aged 2 – 2.6 years and weighed between 40.21 – 40.32kg were randomly distributed into 3 groups of 4 animals with one ram per replicate in a completely randomized design and used to determine the effect of Pergonal® on haematology and serum biochemistry. These groups were assigned to 3 levels of Pergonal® injection as treatments. The injections were 0.00i.u, 49.50i.u, and 99.00i.u Pergonal® represented as T1 (control), T2, and T3, respectively. All the treatments were administered by intramuscular injections. The injections were divided into three doses each and administered intramuscularly in the thigh for three consecutive days. The results of the study showed that apart from Alanine transaminase and eosinophils, the haematological and serum biochemical parameters and immune status of ouda rams may be affected when 49.50i.u or more of Pergonal are used for induction of spermatogenesis. These parameters should be constantly monitored during pergonal administration in ouda rams.
This study developed a new method for transplanting islet cells for diabetes treatment. The researchers engineered monolayer sheets of islet cells on temperature-responsive culture dishes coated with laminin-5. They then transplanted these sheets subcutaneously in rats and found the sheets maintained islet cell characteristics, secreted insulin in vivo, and engrafted successfully without triggering an immune response. This method could provide a new minimally invasive approach for islet cell transplantation therapy for diabetes.
Runx1 contributes to parathyroid hormone (PTH)-induced chondrogenesis of mesenchymal progenitor cells. The study found that PTH treatment of mouse limb bud cells in micromass culture enhanced chondrogenesis, increasing expression of chondrogenic markers. Runx1 expression was also increased with PTH treatment. Knockdown of Runx1 prevented PTH-mediated chondrogenesis, indicating Runx1 is critical. PTH-induced chondrogenesis and Runx1 expression were reduced by inhibiting protein kinase A signaling, suggesting this pathway is involved. Therefore, PTH promotes chondrogenesis by upregulating Runx1 through activation of protein kinase A signaling.
This document summarizes a study examining insulin signaling in the livers of a murine model of Alström Syndrome. The study found that at 6 weeks of age, mice with a mutation in the ALMS1 gene showed normal insulin-stimulated phosphorylation of AKT in the liver, indicating their livers were not insulin resistant at this early age. However, the livers of older mutant mice exhibited fatty deposits and fibrosis, suggesting hepatic insulin resistance develops later. The study concludes that hepatic insulin resistance is not a primary defect caused by ALMS1 mutations.
Objective: To investigate the effect of sildenafil on reducing the impact of hepatic ischemia/reperfusion (HIR) injury established by Pringle maneuver on the heart of rats.
Study Design: Forty Wistar albino rats were divided into 4 groups: Sham (laparotomy only), Control (laparotomy following sildenafil application), IR (ischemia/reperfusion injured by HIR), and IR+SIL (injured by HIR following sildenafil application). Ischemia was developed by clamping the hepatoduodenal ligament for 30 minutes; then reperfusion was applied for 30 minutes. Sildenafil (single dose of 50 mg/kg) was administered by oral gavage for 15 minutes before ischemia. Blood samples of rats were collected from Sham and Control groups at 60 minutes and from IR and IR+SIL groups at 30 minutes after initiation of reperfusion for biochemical analysis. Meanwhile, heart tissues were sampled for biochemical analysis. Malondialdehyde (MDA) and total antioxidant capacity (TAC) in serum samples and TAC, total oxidative capacity (TOC), and oxidative stress index in heart tissues were examined biochemically.
Results: Serum MDA levels were elevated significantly in the IR and IR+SIL groups as compared to the sham group. Sildenafil treatment inhibited MDA increase considerably in the IR+SIL group as compared to the IR group. Serum TAC levels were elevated significantly in the sildenafil and control groups (compared with sham groups) and in the IR+SIL group (compared with the IR group). TAC levels detected in heart tissue increased significantly in the IR group as compared to the sham group; however, sildenafil treatment had no effect on this increase.
Conclusion: Heart tissue was affected by HIR. It was revealed that sildenafil treatment may prevent the oxidative stress via increasing serum TAC levels in both control and IR+SIL groups.
This study investigated the effects of spinal cord injury on the bladder tissue of rats. Twenty rats were divided into a control group and spinal cord injury (SCI) group. The SCI group exhibited statistically higher levels of oxidative stress markers (MDA, MPO), epithelial degeneration, vascular dilation, inflammation, and expression of VEGF and APAF-1 compared to the control group. The SCI group also had lower levels of the antioxidant GSH. Histological examination of the SCI group showed degeneration of epithelial cells, thickened fibrosis, dilated blood vessels, and increased VEGF and APAF-1 expression compared to the control group. The results suggest that spinal cord injury leads to increased oxidative stress, inflammation and apoptosis in
Objective: To study the effects of resveratrol in neuronal structures in traumatic brain injury (TBI).
Study Design: Thirty rats were categorized as (1) control group (n=10), saline solution administered i.p. for 14 days, (2) TBI group (n=10), trauma induced by weight-drop model on brain, and (3) TBI+Resveratrol group (n=10), 15 minutes after injury the rats were given resveratrol (10 μmoL/kg/i.p.) for 14 days. At the end of the experiment the cerebellum was excised for routine paraffin tissue protocol. Blood samples were tested for serum biochemical markers (MDA, SOD, CAT, and GSH-x).
Results: SOD, GPx, and CAT values were lowest in the TBI group. MDA and histological scores of dilations in vessels, inflammation, degeneration in neurons, apoptosis in microglia, ADAMTS8, and GFAP expressions were highest in the TBI group. Sections of the control group showed normal cerebellar histology. The trauma group showed degenerated ganglion layer, pyknotic and apoptotic Purkinje cell nuclei. Vascular thrombus was seen in the substantia alba and substantia grisea. In the Trauma+Resveratrol group, most pa- thologies observed in the TBI group were improved. In the control group, GFAP protein was expressed in granular cells, axons, dendrites, Purkinje cells, and microglia cells. In the trauma group, increased GFAP expression was observed in glial processes, neurons, and Purkinje cells. In the Trauma+Resveratrol group, GFAP was expressed in molecular layer and glial processes. In the control group, ADAMTS-4 activity was observed in granulosa layer, glial cells, and Purkinje cells. In the trauma group, ADAMTS-4 expression was positive in Purkinje cells and glial cells. In the Trauma+ Resveratrol group, ADAMTS-4 was expressed in Purkinje cells, granular cells, and glial cells.
Conclusion: GFAP and ADAMTS-4 proteins may be involved in regeneration of damaged astroglial cells and other glial cells, Purkinje cells, and synaptic extensions. We suggest that antioxidative drugs such as resveratrol may be alternative target agents in neurological disease.
Keywords: ADAMTS-4, brain, cerebellum, GFAP, rat, resveratrol, traumatic brain injury
This study investigated the effects of gallic acid on testicular injury caused by ischemia-reperfusion in a rat testicular torsion model. Forty rats were divided into four groups: a control group, a torsion group, a torsion/detorsion group, and a torsion/detorsion plus gallic acid group. Biochemical markers and immunohistochemical staining for caspase-3 and TNF-α were analyzed. The results showed that gallic acid treatment decreased oxidative stress markers, reduced apoptosis and inflammation, and helped protect testicular tissue compared to the torsion/detorsion group without treatment. The study suggests that gallic acid may be a potential therapeutic agent for testicular ischemia-reperfusion injury.
Effect of Gonadotrophin (Pergonal®) on Haematological and Serum Biochemical P...Agriculture Journal IJOEAR
Abstract— Twelve Ouda rams aged 2 – 2.6 years and weighed between 40.21 – 40.32kg were randomly distributed into 3 groups of 4 animals with one ram per replicate in a completely randomized design and used to determine the effect of Pergonal® on haematology and serum biochemistry. These groups were assigned to 3 levels of Pergonal® injection as treatments. The injections were 0.00i.u, 49.50i.u, and 99.00i.u Pergonal® represented as T1 (control), T2, and T3, respectively. All the treatments were administered by intramuscular injections. The injections were divided into three doses each and administered intramuscularly in the thigh for three consecutive days. The results of the study showed that apart from Alanine transaminase and eosinophils, the haematological and serum biochemical parameters and immune status of ouda rams may be affected when 49.50i.u or more of Pergonal are used for induction of spermatogenesis. These parameters should be constantly monitored during pergonal administration in ouda rams.
This study developed a new method for transplanting islet cells for diabetes treatment. The researchers engineered monolayer sheets of islet cells on temperature-responsive culture dishes coated with laminin-5. They then transplanted these sheets subcutaneously in rats and found the sheets maintained islet cell characteristics, secreted insulin in vivo, and engrafted successfully without triggering an immune response. This method could provide a new minimally invasive approach for islet cell transplantation therapy for diabetes.
Runx1 contributes to parathyroid hormone (PTH)-induced chondrogenesis of mesenchymal progenitor cells. The study found that PTH treatment of mouse limb bud cells in micromass culture enhanced chondrogenesis, increasing expression of chondrogenic markers. Runx1 expression was also increased with PTH treatment. Knockdown of Runx1 prevented PTH-mediated chondrogenesis, indicating Runx1 is critical. PTH-induced chondrogenesis and Runx1 expression were reduced by inhibiting protein kinase A signaling, suggesting this pathway is involved. Therefore, PTH promotes chondrogenesis by upregulating Runx1 through activation of protein kinase A signaling.
This document summarizes a study examining insulin signaling in the livers of a murine model of Alström Syndrome. The study found that at 6 weeks of age, mice with a mutation in the ALMS1 gene showed normal insulin-stimulated phosphorylation of AKT in the liver, indicating their livers were not insulin resistant at this early age. However, the livers of older mutant mice exhibited fatty deposits and fibrosis, suggesting hepatic insulin resistance develops later. The study concludes that hepatic insulin resistance is not a primary defect caused by ALMS1 mutations.
This study investigates the role of O-GlcNAc signaling in porcine muscle satellite cells. Satellite cells are adult stem cells that reside in muscle and contribute to muscle growth, repair, and regeneration. The addition or removal of O-linked β-D-N-acetylglucosamine (O-GlcNAc) by specific enzymes forms a signaling pathway that senses nutrients. Using inhibitors of these enzymes in cell culture and an in vivo muscle injury model, the study found that excessive O-GlcNAcylation from inhibiting the removing enzyme impaired late-stage muscle differentiation and regeneration by decreasing expression of the myogenin gene. Therefore, satellite cells appear to use O-GlcNAc signaling as a
Involvement of nitric oxide and the ovarian blood follicle barrier in murine ...Rashmi Nemade
Chronic treatment with hCG induced enlarged ovaries containing multiple follicular cysts in immature mice. These cysts had few granulosa cells, secreted high levels of testosterone, and had impaired blood follicle barrier function. Inhibiting nitric oxide synthesis using L-NAME during cyst formation reduced cyst size, maintained normal testosterone levels, and preserved blood follicle barrier reactivity in cystic follicles. This suggests nitric oxide is involved in the formation of hCG-induced murine follicular cysts and their associated complications.
This study investigated the effects of soft diet and omega-3 fortified soft diet on neurogenesis in the dentate gyrus and subventricular zone of rats. Thirty rats were divided into three groups: a control group fed a hard diet, a group fed a soft diet, and a group fed a soft diet fortified with omega-3 fatty acids. Immunohistochemistry was used to detect bromodeoxyuridine-labeled proliferating cells at various time points. Results showed that the hard diet and omega-3 fortified soft diet increased neurogenesis in the dentate gyrus compared to the soft diet. In the subventricular zone, the omega-3 fortified soft diet increased proliferation and survival
CD34+ cells were isolated from the PLC/PRF/5 hepatoma cell line. These CD34+ cells appeared to function as liver cancer stem cells (LCSCs) based on their ability to form human liver carcinomas (HLCs) in immunodeficient mice with as few as 100 cells injected. When various subpopulations of these CD34+ PLC cells were injected into mice, they generated three types of HLCs - hepatocellular carcinomas (HCCs), cholangiocarcinomas (CCs), and combined hepatocellular cholangiocarcinomas (CHCs). The expression of different cell surface antigens like OV6 and CD31 on CD
1) Treatment with 50 nM of the histone deacetylase inhibitor trichostatin A (TSA) improved the developmental competence of interspecies somatic cell nuclear transfer (iSCNT) embryos reconstructed from cat somatic cells and bovine oocytes.
2) TSA treatment at 50 nM resulted in significantly higher rates of cleavage and blastocyst formation compared to untreated iSCNT embryos.
3) TSA treatment at 50 nM increased histone H3 lysine 9 (H3K9) acetylation levels in iSCNT embryos to levels similar to in vitro fertilized embryos, whereas untreated iSCNT embryos had lower acetylation levels.
Repair and regeneration of tissues using stem cellsBhanu Jaseja
Stem cells are undifferentiated cells that can differentiate into specialized cell types and potentially be used to treat diseases. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem cell therapies show promise for treating conditions like Parkinson's disease, spinal cord injuries, blood disorders, and more. Key factors that must be considered for stem cell therapies include their availability, ability to differentiate, safety, and adherence to manufacturing standards.
This chapter discusses perspectives on employing mesenchymal stem cells from Wharton's jelly of the umbilical cord for peripheral nerve repair. It provides background on regenerative medicine and peripheral nerve injuries. Various biomaterials that have been tested as scaffolds for delivering mesenchymal stem cells in models of rat sciatic nerve injury are described, including chitosan-silicate hybrid, collagen, PLGA90:10, poly(DL-lactide-e-caprolactone), and poly(vinyl alcohol) with conductive materials. The importance of a multidisciplinary approach to tissue engineering the peripheral nerve through development of biomaterials, cell therapies, and preclinical studies is emphasized.
This document outlines a two-phase methodology to compare various induced pluripotent stem cell (iPSC) generation protocols and their ability to differentiate into hematopoietic stem cells (HSCs). Phase 1 will use three methods to generate iPSCs from different cell sources: peripheral blood mononuclear cells, a PiggyBac transposon system using mouse embryonic fibroblasts, and lentiviral gene transduction of fibroblasts and keratinocytes. Phase 2 will differentiate the iPSCs using OP9 coculture and assess differentiation using in vitro and in vivo assays. The document provides detailed protocols for each phase and predicts the peripheral blood mononuclear cell method will be most effective based on prior research.
This study evaluated whether the phenotype and therapeutic potency of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) were affected by cryopreservation and thawing. Specifically, the study compared cultured UC-MSCs to those freshly thawed after cryopreservation. Results showed that the immunophenotype and immunomodulatory and angiogenic properties of UC-MSCs were not impaired by cryopreservation and thawing, as demonstrated by in vitro and in vivo assays. This suggests that potency impairment related to cryopreservation can be avoided through the specific production process used for these UC-MSCs.
Dinâmica da secreção de insulina, dm2,obesidadeRuy Pantoja
This document reviews the dynamics of insulin secretion and its clinical implications for obesity and diabetes. It discusses insulin secretion at multiple levels from single beta cells to intact organisms. Insulin secretion is regulated by glucose, hormones, and neural inputs in a highly dynamic process. Studies have begun to analyze the cellular and molecular mechanisms underlying the dynamics of insulin secretion. The review focuses on current understanding of insulin secretion dynamics in vitro and in vivo, and discusses the clinical relevance, including implications for obesity and diabetes.
Asymmetric stem cell division leads to self-renewal of one stem cell and differentiation of the other cell. Experimental studies in model organisms like C. elegans, Drosophila, and mice have identified conserved molecules like Aurora-A, aPKC, Mud/NuMa, and Numb that regulate this process. Understanding asymmetric stem cell division enhances our knowledge of stem cell biology and is important for regenerative medicine, as it provides a source for targeted cell replacement and tissue regeneration.
International Journal of Stem Cell Research and Transplantation (IJST) is an international, Open Access, peer-reviewed journal, which mainly focuses, on the advancements made in the field of cell biology, specifically in the field of Stem Cells.
International Journal of Stem Cell Research and Transplantation (IJST) is a peer-reviewed journal, and is dedicated to providing information with respect to the latest advancements that are being upgraded in our everyday life with respect to the application of Stem cells.
International Journal of Stem Cell Research and Transplantation (IJST) ISSN:2328-3548, is a free, Open Access, Peer-reviewed, exclusive online journal covering areas of Stem cell research, translational work and Clinical studies in the specialty of Stem Cells and Transplantation including allied specialties relevant to the core subject, which is dedicated in publishing high quality manuscripts.
This document defines and describes several types of adaptive cellular responses: atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia. It provides the definitions and examples of each type of response. Atrophy is a decrease in cell size, hypertrophy is an increase in cell size, hyperplasia is an increase in cell number, metaplasia is a change from one adult cell type to another, and dysplasia is disordered cellular development. The document also discusses the causes and mechanisms of these adaptive responses and includes images to illustrate examples.
This document describes a study examining the role of the zinc transporter Zip14 in adipose tissue regulation and metabolism. The key findings are:
1) Mice lacking the Zip14 zinc transporter had increased adiposity, hypertrophied adipocytes, impaired insulin signaling, and chronic inflammation in adipose tissue.
2) Adipose tissue from Zip14 knockout mice showed increased cytokine production, activation of inflammatory pathways, and impaired adipocyte differentiation.
3) The metabolic changes in adipose tissue were linked to increased circulating endotoxin levels caused by the Zip14 deletion.
4) Knocking down Zip14 in cultured adipocytes impaired their ability to mobilize zinc and dysregulated inflammatory pathways
Stem cell therapy shows promise for treating bladder dysfunction. Mesenchymal stem cells from sources like bone marrow, adipose tissue, and skeletal muscle have been used in experimental studies. The main mechanisms of action are migration of stem cells to the bladder, differentiation into bladder cells, and paracrine effects from growth factors secreted by stem cells. Studies have used various bladder dysfunction models including bladder outlet obstruction, ischemia, diabetes, spinal cord injury, and cryoinjury. Stem cell transplantation has led to improvements in bladder activity and function in these models based on urodynamic studies, though differentiation of stem cells into bladder cells is limited. Further research is still needed to advance stem cell therapy for bladder dysfunction.
This study investigated the protective effects of allopurinol on experimentally induced ovarian ischemia-reperfusion injury in rats. Rats were divided into four groups: a sham group, an ischemia group, an ischemia-reperfusion group, and an ischemia-reperfusion + allopurinol treated group. The study found that allopurinol decreased MDA levels and increased GSH levels compared to the ischemia and ischemia-reperfusion groups, indicating it reduced oxidative load. Allopurinol also decreased caspase-3 and sFlt-1 expression, suggesting it inhibited apoptosis and protected the ovaries from damage caused by ischemia-reperfusion.
This study investigated the effects of carvacrol, a natural compound found in oregano and thyme, on an experimental model of ovarian ischemia/reperfusion injury in rats. Rats were divided into four groups: a control group, an ischemia group, an ischemia/reperfusion group, and an ischemia/reperfusion plus carvacrol group. The left ovaries of rats in the ischemia and ischemia/reperfusion groups were subjected to 3 hours of ischemia followed by 3 hours of reperfusion to induce injury. The carvacrol group received carvacrol orally after reperfusion. Histological analysis found that carvacrol reduced degenerative changes, vascular pathology, and the expression of endothelin-1 and ADAMTS-5, markers
1) Short-term expression of constitutively active Akt1 in the endothelium of mice leads to non-anemic stress erythropoiesis (increased red blood cell production) in the spleen, independent of erythropoietin and BMP4.
2) This stress erythropoiesis was observed even when endothelial myrAkt1 mice were reconstituted with wild-type bone marrow, suggesting endothelial cell hyperactivation can induce red cell production under stress through a novel pathway.
3) The study examines the role of the endothelium in regulating erythropoiesis and identifies endothelial Akt1 activation as a potential novel mechanism for inducing stress erythropoiesis independent of known
This study investigates the role of O-GlcNAc signaling in porcine muscle satellite cells. Satellite cells are adult stem cells that reside in muscle and contribute to muscle growth, repair, and regeneration. The addition or removal of O-linked β-D-N-acetylglucosamine (O-GlcNAc) by specific enzymes forms a signaling pathway that senses nutrients. Using inhibitors of these enzymes in cell culture and an in vivo muscle injury model, the study found that excessive O-GlcNAcylation from inhibiting the removing enzyme impaired late-stage muscle differentiation and regeneration by decreasing expression of the myogenin gene. Therefore, satellite cells appear to use O-GlcNAc signaling as a
Involvement of nitric oxide and the ovarian blood follicle barrier in murine ...Rashmi Nemade
Chronic treatment with hCG induced enlarged ovaries containing multiple follicular cysts in immature mice. These cysts had few granulosa cells, secreted high levels of testosterone, and had impaired blood follicle barrier function. Inhibiting nitric oxide synthesis using L-NAME during cyst formation reduced cyst size, maintained normal testosterone levels, and preserved blood follicle barrier reactivity in cystic follicles. This suggests nitric oxide is involved in the formation of hCG-induced murine follicular cysts and their associated complications.
This study investigated the effects of soft diet and omega-3 fortified soft diet on neurogenesis in the dentate gyrus and subventricular zone of rats. Thirty rats were divided into three groups: a control group fed a hard diet, a group fed a soft diet, and a group fed a soft diet fortified with omega-3 fatty acids. Immunohistochemistry was used to detect bromodeoxyuridine-labeled proliferating cells at various time points. Results showed that the hard diet and omega-3 fortified soft diet increased neurogenesis in the dentate gyrus compared to the soft diet. In the subventricular zone, the omega-3 fortified soft diet increased proliferation and survival
CD34+ cells were isolated from the PLC/PRF/5 hepatoma cell line. These CD34+ cells appeared to function as liver cancer stem cells (LCSCs) based on their ability to form human liver carcinomas (HLCs) in immunodeficient mice with as few as 100 cells injected. When various subpopulations of these CD34+ PLC cells were injected into mice, they generated three types of HLCs - hepatocellular carcinomas (HCCs), cholangiocarcinomas (CCs), and combined hepatocellular cholangiocarcinomas (CHCs). The expression of different cell surface antigens like OV6 and CD31 on CD
1) Treatment with 50 nM of the histone deacetylase inhibitor trichostatin A (TSA) improved the developmental competence of interspecies somatic cell nuclear transfer (iSCNT) embryos reconstructed from cat somatic cells and bovine oocytes.
2) TSA treatment at 50 nM resulted in significantly higher rates of cleavage and blastocyst formation compared to untreated iSCNT embryos.
3) TSA treatment at 50 nM increased histone H3 lysine 9 (H3K9) acetylation levels in iSCNT embryos to levels similar to in vitro fertilized embryos, whereas untreated iSCNT embryos had lower acetylation levels.
Repair and regeneration of tissues using stem cellsBhanu Jaseja
Stem cells are undifferentiated cells that can differentiate into specialized cell types and potentially be used to treat diseases. There are two main types of stem cells: embryonic stem cells and adult stem cells. Stem cell therapies show promise for treating conditions like Parkinson's disease, spinal cord injuries, blood disorders, and more. Key factors that must be considered for stem cell therapies include their availability, ability to differentiate, safety, and adherence to manufacturing standards.
This chapter discusses perspectives on employing mesenchymal stem cells from Wharton's jelly of the umbilical cord for peripheral nerve repair. It provides background on regenerative medicine and peripheral nerve injuries. Various biomaterials that have been tested as scaffolds for delivering mesenchymal stem cells in models of rat sciatic nerve injury are described, including chitosan-silicate hybrid, collagen, PLGA90:10, poly(DL-lactide-e-caprolactone), and poly(vinyl alcohol) with conductive materials. The importance of a multidisciplinary approach to tissue engineering the peripheral nerve through development of biomaterials, cell therapies, and preclinical studies is emphasized.
This document outlines a two-phase methodology to compare various induced pluripotent stem cell (iPSC) generation protocols and their ability to differentiate into hematopoietic stem cells (HSCs). Phase 1 will use three methods to generate iPSCs from different cell sources: peripheral blood mononuclear cells, a PiggyBac transposon system using mouse embryonic fibroblasts, and lentiviral gene transduction of fibroblasts and keratinocytes. Phase 2 will differentiate the iPSCs using OP9 coculture and assess differentiation using in vitro and in vivo assays. The document provides detailed protocols for each phase and predicts the peripheral blood mononuclear cell method will be most effective based on prior research.
This study evaluated whether the phenotype and therapeutic potency of umbilical cord tissue-derived mesenchymal stromal cells (UC-MSCs) were affected by cryopreservation and thawing. Specifically, the study compared cultured UC-MSCs to those freshly thawed after cryopreservation. Results showed that the immunophenotype and immunomodulatory and angiogenic properties of UC-MSCs were not impaired by cryopreservation and thawing, as demonstrated by in vitro and in vivo assays. This suggests that potency impairment related to cryopreservation can be avoided through the specific production process used for these UC-MSCs.
Dinâmica da secreção de insulina, dm2,obesidadeRuy Pantoja
This document reviews the dynamics of insulin secretion and its clinical implications for obesity and diabetes. It discusses insulin secretion at multiple levels from single beta cells to intact organisms. Insulin secretion is regulated by glucose, hormones, and neural inputs in a highly dynamic process. Studies have begun to analyze the cellular and molecular mechanisms underlying the dynamics of insulin secretion. The review focuses on current understanding of insulin secretion dynamics in vitro and in vivo, and discusses the clinical relevance, including implications for obesity and diabetes.
Asymmetric stem cell division leads to self-renewal of one stem cell and differentiation of the other cell. Experimental studies in model organisms like C. elegans, Drosophila, and mice have identified conserved molecules like Aurora-A, aPKC, Mud/NuMa, and Numb that regulate this process. Understanding asymmetric stem cell division enhances our knowledge of stem cell biology and is important for regenerative medicine, as it provides a source for targeted cell replacement and tissue regeneration.
International Journal of Stem Cell Research and Transplantation (IJST) is an international, Open Access, peer-reviewed journal, which mainly focuses, on the advancements made in the field of cell biology, specifically in the field of Stem Cells.
International Journal of Stem Cell Research and Transplantation (IJST) is a peer-reviewed journal, and is dedicated to providing information with respect to the latest advancements that are being upgraded in our everyday life with respect to the application of Stem cells.
International Journal of Stem Cell Research and Transplantation (IJST) ISSN:2328-3548, is a free, Open Access, Peer-reviewed, exclusive online journal covering areas of Stem cell research, translational work and Clinical studies in the specialty of Stem Cells and Transplantation including allied specialties relevant to the core subject, which is dedicated in publishing high quality manuscripts.
This document defines and describes several types of adaptive cellular responses: atrophy, hypertrophy, hyperplasia, metaplasia, and dysplasia. It provides the definitions and examples of each type of response. Atrophy is a decrease in cell size, hypertrophy is an increase in cell size, hyperplasia is an increase in cell number, metaplasia is a change from one adult cell type to another, and dysplasia is disordered cellular development. The document also discusses the causes and mechanisms of these adaptive responses and includes images to illustrate examples.
This document describes a study examining the role of the zinc transporter Zip14 in adipose tissue regulation and metabolism. The key findings are:
1) Mice lacking the Zip14 zinc transporter had increased adiposity, hypertrophied adipocytes, impaired insulin signaling, and chronic inflammation in adipose tissue.
2) Adipose tissue from Zip14 knockout mice showed increased cytokine production, activation of inflammatory pathways, and impaired adipocyte differentiation.
3) The metabolic changes in adipose tissue were linked to increased circulating endotoxin levels caused by the Zip14 deletion.
4) Knocking down Zip14 in cultured adipocytes impaired their ability to mobilize zinc and dysregulated inflammatory pathways
Stem cell therapy shows promise for treating bladder dysfunction. Mesenchymal stem cells from sources like bone marrow, adipose tissue, and skeletal muscle have been used in experimental studies. The main mechanisms of action are migration of stem cells to the bladder, differentiation into bladder cells, and paracrine effects from growth factors secreted by stem cells. Studies have used various bladder dysfunction models including bladder outlet obstruction, ischemia, diabetes, spinal cord injury, and cryoinjury. Stem cell transplantation has led to improvements in bladder activity and function in these models based on urodynamic studies, though differentiation of stem cells into bladder cells is limited. Further research is still needed to advance stem cell therapy for bladder dysfunction.
Similar to Simvastatin Treatment Prevents Cell Damage and Regulates Angiogenesis in a Rat Ovarian Torsion and Detorsion Model: An Immunohistochemical Study of Caspase-3 and sFlt-1 Expression
This study investigated the protective effects of allopurinol on experimentally induced ovarian ischemia-reperfusion injury in rats. Rats were divided into four groups: a sham group, an ischemia group, an ischemia-reperfusion group, and an ischemia-reperfusion + allopurinol treated group. The study found that allopurinol decreased MDA levels and increased GSH levels compared to the ischemia and ischemia-reperfusion groups, indicating it reduced oxidative load. Allopurinol also decreased caspase-3 and sFlt-1 expression, suggesting it inhibited apoptosis and protected the ovaries from damage caused by ischemia-reperfusion.
This study investigated the effects of carvacrol, a natural compound found in oregano and thyme, on an experimental model of ovarian ischemia/reperfusion injury in rats. Rats were divided into four groups: a control group, an ischemia group, an ischemia/reperfusion group, and an ischemia/reperfusion plus carvacrol group. The left ovaries of rats in the ischemia and ischemia/reperfusion groups were subjected to 3 hours of ischemia followed by 3 hours of reperfusion to induce injury. The carvacrol group received carvacrol orally after reperfusion. Histological analysis found that carvacrol reduced degenerative changes, vascular pathology, and the expression of endothelin-1 and ADAMTS-5, markers
1) Short-term expression of constitutively active Akt1 in the endothelium of mice leads to non-anemic stress erythropoiesis (increased red blood cell production) in the spleen, independent of erythropoietin and BMP4.
2) This stress erythropoiesis was observed even when endothelial myrAkt1 mice were reconstituted with wild-type bone marrow, suggesting endothelial cell hyperactivation can induce red cell production under stress through a novel pathway.
3) The study examines the role of the endothelium in regulating erythropoiesis and identifies endothelial Akt1 activation as a potential novel mechanism for inducing stress erythropoiesis independent of known
This study examined the effects of desloratadine on ovarian ischemia-reperfusion injury in rats. Rats were divided into three groups: an ischemia-reperfusion injury group, an ischemia-reperfusion injury group treated with desloratadine, and a sham group. Ovarian tissue was analyzed for markers of oxidative stress and inflammation after ischemia and reperfusion. Results showed that desloratadine significantly reduced oxidative stress markers like MDA and increased antioxidant markers like GSH compared to the ischemia-reperfusion injury group. Desloratadine also decreased levels of proinflammatory cytokines like NF-κB, IL-1β, and TNF-α. Histological analysis revealed that desl
The study investigated the protective effects of losartan, an angiotensin II type 1 receptor blocker, on intestinal ischemia-reperfusion injury in rats. Forty rats were divided into four groups: sham operation, ischemia, ischemia/reperfusion (I/R), and I/R + losartan treatment. Biochemical markers and histopathological analysis of the jejunum tissue were performed. Losartan treatment reduced oxidative stress markers, inflammation, and apoptosis compared to the I/R group. This suggests losartan may protect against intestinal damage caused by ischemia-reperfusion injury.
Background: Body of literature are becoming pronounced that pathological condition in one organ of the body might have an effect on other distal organs owing to the fact, that the entire body metabolism is orchestrated centrally.
Pathological events occurring in an organ are likely to be extended to other organs. Pretreatment that minimize these events are presumed to be beneficial to the extended organs.
Methods: Following 30 min of ischemia and 48 h of reperfusion in the kidney, rats under anesthesia were sacrificed and blood sample collected through cardiac puncture. Serum level of troponin I, and activities of total creatine kinase (CK), mass creatine kinase (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma –glutamyl transferase (GGT) were estimated spectrophotometrically.
Results: Serum troponin I increased to 0.031 ± 0.001 ng/ml in the ischemic group, and following pretreatment with Lmm (600mg/kg), serum level of troponin I decreased significantly to 0.021 ± 0.001 ng/ml (P<.05).><.05),><.05)><.05).
Morphofunctional Changes in the Thymus Gland under the Influence of Psychogen...YogeshIJTSRD
In the thymus of animals subjected to acute stress, a decrease in lymphoid tissue was found, accompanied by the death of lymphocytes in the cortex and medulla. Acute stress leads to the appearance in the thymus of a large number of degranulating mast cells and actively functioning epithelial tubules.Psychological stress has great impacts on the immune system, particularly the leukocytes distribution. Although the impacts of acute stress on blood leukocytes distribution are well studied, however, it remains unclear how chronic stress affects leukocytes distribution in peripheral circulation. Furthermore, there is no report about the role of spleen in the blood leukocytes distribution induced by stress. Here we show that spleen contributes to the alteration of restraint stress induced blood leukocytes distribution. Our data confirmed that restraint stress induced anxiety like behavior in mice. Furthermore, we found that restraint stress decreased the CD4 CD8 ratio and elevated the percentages of natural killer cells, monocytes and polymorphonuclear myeloid derived suppressor cell. We demonstrated that activation of hypothalamic pituitary adrenal axis HPA and sympathetic nervous system SNS contributes to restraint stress induced alteration of blood leukocyte distribution. Interestingly, we found that splenectomy could reverse the change of CD4 CD8 ratio induced by restraint stress. Together, our findings suggest that activation of HPA axis and SNS was responsible for the blood leukocyte subsets changes induced by restraint stress. Spleen, at least in part, contributed to the alteration in peripheral circulation induced by restraint stress. Asadova Nigora Khamroevna "Morphofunctional Changes in the Thymus Gland under the Influence of Psychogenic Factors" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Special Issue | International Research Development and Scientific Excellence in Academic Life , March 2021, URL: https://www.ijtsrd.com/papers/ijtsrd38735.pdf Paper Url: https://www.ijtsrd.com/medicine/other/38735/morphofunctional-changes-in-the-thymus-gland-under-the-influence-of-psychogenic-factors/asadova-nigora-khamroevna
This study investigated the protective effects of losartan, an AT1 receptor blocker, on testicular injury caused by ischemia/reperfusion in a rat testicular torsion model. Forty rats were divided into four groups: a control group, a torsion group, a torsion/detorsion group, and a torsion/detorsion plus losartan group. Biochemical assays and histopathological analysis showed that losartan prevented oxidative damage and reduced apoptosis in germ cells compared to the torsion/detorsion group, suggesting losartan has a protective role against ischemia/reperfusion injury in rat testes.
This study explored whether the compound Rhein can inhibit stress in the endoplasmic reticulum and mitochondria caused by acute myocardial infarction through activating the PI3K/Akt/ERK signaling pathway. A rat model of myocardial infarction was used. Rats treated with Rhein showed improved cardiac function and reduced cardiomyocyte apoptosis compared to untreated rats. Rhein was found to inhibit expression of endoplasmic reticulum and mitochondrial proteins associated with stress and apoptosis, while elevating expression of proteins in the PI3K/Akt/ERK pathway. The results suggest Rhein can protect against myocardial damage from infarction by reducing endoplasmic reticulum and mitochondrial dysfunction through this signaling pathway.
This study aimed to evaluate the protective effects of zofenopril on intestinal ischemia-reperfusion injury using a rat model. Rats were divided into five groups: sham surgery, ischemia only, ischemia-reperfusion, ischemia-reperfusion with zofenopril pretreatment, and zofenopril only. Biochemical markers of oxidative stress and apoptosis were measured in intestinal tissue samples. Histopathological examination and immunohistochemical staining for caspase-3 was also performed. Results showed that ischemia-reperfusion caused intestinal damage including mucosal destruction and cell apoptosis. Zofenopril pretreatment reduced oxidative stress markers and inhibited apoptosis, protecting against ischemia-reperfusion injury on histological and biochemical evaluation. The
This study investigated the antioxidant effects of nebivolol in protecting against testicular damage caused by torsion-detorsion injury in rats. Forty rats were divided into four groups: a control group, a torsion group, a torsion/detorsion group, and a torsion/detorsion+nebivolol group. Biochemical assays and histopathological examination found that torsion-detorsion injury increased oxidative stress markers and apoptosis in testicular tissue, while administration of nebivolol before detorsion decreased oxidative stress and apoptosis. The study suggests that nebivolol has a protective effect against ischemia-reperfusion injury in the testes caused by torsion-
1) A study investigated the vasodilatory and toxic effects of a crude extract of Ruta graveolens (Ruta) on rat aortas and CRL1730 endothelial cells.
2) The Ruta extract generated vasodilation in rat aortas at subtoxic concentrations, partially dependent on the endothelium. It caused a loss of cell viability in CRL1730 cells at high concentrations but did not induce oxidative stress or DNA fragmentation.
3) The results suggest Ruta extract regulates vascular tone through a complex, partially endothelium-dependent mechanism and has vasodilatory activity at subtoxic levels without damaging cell membranes or viability.
This study investigated the protective effects of carvacrol on testicular damage caused by experimental testicular torsion-detorsion in rats. The study consisted of 4 groups of rats: a control group, a torsion group, a torsion-detorsion group, and a torsion-detorsion group treated with carvacrol. Histopathological analysis found increased damage in spermatogenic cells and decreased antioxidant levels in the torsion and torsion-detorsion groups compared to the control and carvacrol groups. Immunohistochemical staining showed increased endothelin-1 expression in the torsion and detorsion groups but not in the carvacrol group. The results suggest that carvacrol may prevent
Cellular adaptations are reversible changes that allow cells to survive in abnormal environments. There are several types of cellular adaptations, including atrophy, hypertrophy, hyperplasia, and metaplasia. Atrophy is a shrinkage in cell size due to decreased workload, loss of innervation, or inadequate nutrition. Hypertrophy is an increase in cell size due to increased functional demands or hormonal stimulation. Hyperplasia is an increase in cell number, usually due to hormonal stimulation or tissue loss. Metaplasia is when one adult cell type replaces another, such as squamous cells replacing bronchial epithelium in smokers. Cellular adaptations allow cells to modulate their structure and function to avoid injury in stressful environments.
This study examined placental samples from 60 women with preeclampsia and 60 healthy women at 29-35 weeks of gestation. It investigated the expression levels of ADAMTS-1 and ADAMTS-4, which are involved in extracellular matrix remodeling, between the two groups. The study found significantly lower expression levels of ADAMTS-1 and ADAMTS-4 in placental samples from women with preeclampsia compared to healthy women. It also observed morphological changes in the placentas of women with preeclampsia. The study concluded that decreased expression of ADAMTS-1 and ADAMTS-4 may affect placental morphology, trophoblast invasion, and angiogenesis in preeclampsia
This document summarizes research examining the effects of taurine supplementation on cardiac abnormalities in NZB/W F1 mice fed a high-cholesterol diet. The study found that mice fed a cholesterol/taurine diet had less abnormal cardiac histology, fewer apoptotic cardiac cells, and decreased levels of proteins involved in apoptosis compared to mice fed a cholesterol-only diet or control diet. This suggests taurine has protective effects against cardiac abnormalities induced by a high-cholesterol diet in this mouse model of systemic lupus erythematosus.
The Importance Of Animal Uses In AnimalsJessica Lopez
This document discusses using bromophenols as potential therapeutics for treating type 2 diabetes mellitus (T2DM). Bromophenols have been identified as inhibitors of the enzyme tyrosine phosphatase 1B (PTP1B), which is involved in insulin signaling. A series of new bromophenol analogs will be synthesized and tested for PTP1B inhibitory activity using in vitro enzyme assays to elucidate their mechanism of action. Bromophenols occur naturally in marine organisms and have attracted interest as anti-diabetic agents due to their suspected PTP1B inhibitory activity. However, quinone species formed from bromophenols could be toxic, so further study is needed to
Sodium Thiosulfate (Hydrogen Sulfide Donor): Ameliorates the Pituitary-testic...BRNSSPublicationHubI
This study investigated the protective effects of sodium thiosulfate (STS) on the pituitary-testicular axis dysfunction caused by cyclophosphamide (CYP) and/or ionizing gamma radiation (IR) in rats. Rats received STS before and during treatment with CYP and/or IR, while control groups received CYP and/or IR only. STS significantly reduced oxidative stress in the pituitary gland and testes by lowering malondialdehyde and increasing antioxidant enzyme activities. It also elevated reduced luteinizing hormone, follicle-stimulating hormone, and testosterone levels. Furthermore, STS reduced pathological changes and apoptosis in the pituitary and testes induced by CYP and/or IR. This study demonstrates
The aim of the study was to investigate the damage created in tissue by using an in vivo isolated portal ischemia and reperfusion model in the rat liver and the effects of heparin administration on the complement system. A total of 25 male rats weighing 150-290 gr were used in the study. Following anesthesia with ketamine hydrochloride and xylazine hydrochloride, the incision area was shaved in all rats except the control group. The portal vein was isolated and clamped, and ischemia and reperfusion created. Two groups were sacrificed at the 24th hour and two at the 48th hour. Heparin was administered to one of the groups sacrificed at the 24th hour and not to the other group, and similarly one of the groups sacrificed at the 48th hour received heparin while the other did not. Biochemical and pathologic parameters were used to evaluate the damage using serum and liver tissue samples from the sacrificed rats. We used the liver GSH, MPO and C3 levels and the serum IL-6 level to evaluate the ischemia and reperfusion damage in the liver tissue. Heparin was shown to decrease the damage occurring after ischemia and reperfusion by decreasing complement activation and the MPO and IL-6 levels while increasing GSH levels as a result of the statistical analysis performed. Heparin was shown to prevent tissue damage after ischemia and reperfusion by decreasing complement activation and inflammation.
This study examined the effects of bacterial endotoxin (LPS) on myocardial function during ischemia-reperfusion injury. Rabbits were injected with increasing doses of LPS or saline prior to inducing myocardial ischemia through coronary artery occlusion. Higher LPS doses suppressed cardiac contractility and worsened injury compared to lower doses or saline. Blocking TNF-alpha prevented the additional harmful effects of LPS on cardiac function after ischemia. The findings suggest that bacterial endotoxins can exacerbate ischemia-reperfusion injury in a dose-dependent manner mediated through TNF-alpha.
Similar to Simvastatin Treatment Prevents Cell Damage and Regulates Angiogenesis in a Rat Ovarian Torsion and Detorsion Model: An Immunohistochemical Study of Caspase-3 and sFlt-1 Expression (20)
BACKGROUND: Sequential Epstein-Barr virus (EBV)–positive B cell lymphoma to the initial diagnosis of angioimmunoblastic T cell lymphoma (AITL) is very rare, the exact mechanism and standard therapy of which is still being explored. CASE: A 50-year-old man was admitted to our hospital in January 2014 with a three-week history of enlargement of multiple lymph nodes. His initial pathological evaluation indicated AILT. The reactivation of EBV was observed during the immunosuppression therapy for AITL, accompanied by onset of subcutaneous nodules proven to be EBV-positive diffuse large B cell lymphoma (DLBCL) based on the pathological findings of rebiopsy. The patient was successfully treated with chidamide, a histone deacetylase (HDAC) inhibitor, and rituximab.
Conclusion: The sufficient surveillance for serum EBV and repeat biopsy is necessary for patients with AITL, and this treatment modality may become an active option.
Keywords: angioimmunoblastic T cell lymphoma, Epstein-Barr virus, HDAC inhibitor, non-Hodgkin lymphoma, peripheral T cell lymphoma
Objective: The association between telomerase reverse transcriptase (TERT) promoter mutation and outcome of melanoma is unclear and controversial. We aim to conduct a meta-analysis and investigate whether the TERT promoter mutation is a prognostic factor of melanoma.
Study Design: Appropriate studies were searched in 3 databases: PubMed, Web of Science, and Embase. Pooled hazard ratios (HRs) were counted through random effects model.
Results: Heterogeneity was moderate in overall survival (OS) (I2=43.7%, p=0.059) and low in disease-free survival (DFS) (I2=0.0%, p=0.587). Sensitivity analysis indicated that the removal of any of the study did not affect the final results. Evidence for publication bias was not found (Begg’s test, p=0.281; Egger’s test, p=0.078). The pooled OS HRs from combined effects analysis was determined (HR 1.07; 95% CI 0.83–1.39, p=0.585), together with the pooled HRs of DFS (HR 1.65; 95% CI 1.02–2.66, p=0.042). TERT promoter mutation predicted a good outcome in meta-static melanoma patients (HR 0.66; 95% CI 0.46–0.96, p=0.042). The pooled HRs of combined mutation in TERT promoter and BRAF (HR 6.27; 95% CI 2.7–14.58, p=0.000) predicted a bad outcome in melanoma patients.
Conclusion: TERT promoter mutation significantly predicted poor DFS outcome but, on the contrary, predicted a good outcome in metastatic melanoma patients. The combined TERT promoter and BRAF mutation was a significant independent factor of OS in melanoma patients.
Keywords: melanoma; meta-analysis; mutation; prognosis; promoter regions, genetic; skin neoplasms; telomerase; TERT promoter mutation; TERT protein, human
Objective: In order to reduce complications accompanied with dental implant restoration, this study strives to prepare a novel sealant and lubricant that can be used in dental implant systems as well as to evaluate its characteristics.
Study Design: Chitosan (CS), β-glycerophosphate pentahydrate (β-GP), and nano silver (nAg) were used to prepare thermosensitive hydrogel. According to the different volume ratios of CS to β-GP, 3 experimental groups were established, namely 16/4, 13/7, and 10/10 groups. Their morphology, composition, and chemical properties were analyzed via SEM, EDS, and FTIR. In addition, the effect of the hydrogel on the stability of dental implant-abutment connection was investigated by removal torque test combined with dynamic cyclic loading experiment. The maximum fracture load was measured under different lubricating conditions by electronic universal testing machine. The cytotoxicity and in vitro antibacterial effect of the hydrogel were examined respectively by CCK-8 test and the spread plate method.
Results: The CS/β-GP/nAg thermosensitive hydro-gel was successfully prepared in this study, which was found to be a porous structure through SEM. The removal torque test and the dynamic cyclic loading experiment showed that the removal torque of the experimental group was greater than that of the control group. Furthermore, the single load-to-fracture test indicated that the 16/4 group had the greatest maximum bearing load. The in vitro cytotoxicity test using rat bone marrow stromal cells (rBMSCs) and human gingival fibroblast cells (hGFCs) showed no cytotoxicity in all 3 groups. The 3 experimental groups had obvious antibacterial effects against E. coli, S. aureus, and P. gingivalis.
Conclusion: A nontoxic antibacterial CS/β-GP/nAg thermosensitive hydrogel for lubricating purpose was successfully fabricated. When the volume ratio of CS to β-GP was 16/4, this thermosensitive hydrogel demonstrated better sealing and lubricating abilities and had a positive influence on the reliability of dental implant-abutment connection.
Keywords: abutment, dental implant, dental implant restoration, dental sealant, lubrication, thermosensitive hydrogel
Objective: To investigate the bond strength of resin-modified glass ionomer enhanced with bioactive glass (Activa BioActive-Base/Liner) to composite resin using different dental adhesive systems.
Study Design: In this study, Activa BioActive-Base/Liner (ABA/BL) was placed in cylindrical cavities formed in acrylic blocks. In blocks divided into 6 groups according to the adhesive system to be applied, two-step etch-and-rinse Gluma 2 Bond (Heraeus Kulzer, Germany), one-step self-etch Gluma Self Etch (Heraeus Kulzer), universal system Gluma Universal (Heraeus Kulzer), two-step self-etch Clearfil SE Protect (Kuraray, Japan), one-step self-etch Clearfil S3 Bond Plus (Kuraray), and universal system Clearfil S3 Bond Universal (Kuraray) adhesive systems were applied on ABA/BL. After composite resin (3M ESPE Filtek Ultimate) was applied to the prepared surfaces, the specimens were placed in a universal test device and shear bond strength test was determined. Fracture types were evaluated using a stereomicroscope and scanning electron microscope. Data were analyzed by Shapiro-Wilk, two-way ANOVA, Kruskal-Wallis, and Post-Hoc Multiple Comparisons tests.
Results: In terms of bond strength values, the highest bond value was seen in the two-step self-etch (Clearfil SE Protect) group, and the lowest bond strength value was seen in the universal system (Clearfil S3 Bond Universal) group. There was no statistically significant difference between the adhesive agent groups in terms of bond strength values (p>0.05).
Conclusion: It is thought that choosing the two-step self-etch technique as an adhesive system when resin-modified glass ionomer enhanced with bioactive glass (ABA/BL) is used as the pulp capping/base material will be more appropriate in terms of bond strength.
Keywords: adhesive systems, bioactive materials, bond strength, cariostatic agents, composite resins, dental materials, fluorides, glass ionomer, glass ionomer cements, materials testing, vital pulp therapy
Objective: To analyze the sonographic features of different histopathological subtypes of borderline ovarian tumors (BOTs) confirmed by pathology, and to study the ultrasound performances of various types in borderline ovarian tumors.
Study Design: Retrospective analysis was performed on the pathological results and ultrasound projection findings of 129 patients diagnosed as BOTs by ultrasound department of our hospital from January 2012 to November 2019. All patients were confirmed by surgical pathology and scanned consecutively by the investigators using transabdominal or transvaginal ultrasound examination.
Results: Serous borderline tumors (SBOTs) were observed, and the prevalence rate (53%) was significantly higher than that of other subtypes, and the probability of bilateral lesions was higher (40%). The sonogram often showed ultrasound features of papillary neoplasm in the lesion and good internal echo (p<0.05). Mucinous borderline ovarian tumors (MBOTs) were mostly unilateral lesions (86%). The prevalence was second only to SBOTs. Histomorphological examinations were divided into gastrointestinal-type and endocervical-type. Among them, the gastrointestinal type of MBOTs were mostly unilateral, and their incidence was higher than that of endocervical-type of MBOTs. Compared with other pathological subtypes, the gastrointestinal type is more likely to show the sonographic characteristics of huge space occupying in the pelvic and abdominal cavity (mean diameter >10 cm), polycystic, multiple septums, and poor internal echo (p<0.05). The ultrasonographic features of the endocervical-type of MBOTs were similar to those of SBOTs. Compared with gastrointestinal type, the sonographic images showed smaller lesion diameter, less septal or cyst, and more papillary excrescences in the tumor (p<0.05). The borderline clear cell tumor is the intermediate transition between the clear cell adenofibroma and the clear cell carcinoma. The clinical manifestations are diverse and lack specificity. The histology of sonography was mainly solid, and the multiple microcapsules were honeycomb-like. It can also be shown as cystic. Among the 169 patients with BOTs, 20 cases of SBOTs, 17 cases of MBOTs, and 10 cases of other rare subtypes were complicated with other diseases or multiple subtypes. This study did not find significant ultrasonic characteristics were used for distinguish them from other subtypes.
Conclusion: BOTs is a common disease in women during the reproductive period. It is characterized by the development of malignant tumors. Its clinical and pathological subtypes are complex and diverse. It leads many doctors to use the terms “large pelvic mass” and “solid ovarian mass” for diagnosis because of their lack of experience and understanding.
Keywords: adenocarcinoma, mucinous; adenocarcinoma, serous; borderline ovarian tumors; diagnostic imaging; ovarian neoplasms; papillary neoplasms; prognosis; transvaginal ultrasound, ultrasonography
Objective: To evaluate the results of the effect of nebivolol on tibial bone defect and graft application in new bone development in the rat.
Study Design: Thirty Wistar albino rats were divided into 3 groups. In the Control group, tibia bone defect was created without any treatment. In the Defect+ Graft group, allograft treatment was performed by forming a 6 mm tibial bone defect. In the Defect+Graft+ Nebivolol group, alloplastic bone graft was placed in the calvarial bone defect and then nebivolol (0.34 mg/mL solution/day) treatment was intraperitoneally applied for 28 days.
Results: Histopathological examination revealed inflammation in the defect area, congestion in the vessels, degeneration in collagen fibers, and an increase in osteoclast cells. There was an increase in inflammation and blood vessel structure in graft application, and osteoblastic activity matrix formation after reorganization nebivolol application in collagen fibers. Osteonectin expression was positive in the collagen fiber and matrix, starting in the Graft group, in osteoblasts, whereas in the Nebivolol group, osteoblasts increased in osteocytes and new bone formation.
Conclusion: Nebivolol is thought to have a positive effect on osteoinductive bone growth factors and contribute to the cell-matrix interaction, in addition to the supporting effect of the graft with its antioxidative effect.
Keywords: allograft; bone; bone regeneration; disease models, animal; nebivolol; orthopedic procedures; osteonectin; rats; tibia; tibial defect
Objective: The prognostic indictors of age-related poor outcomes in patients with acute myeloid leukemia (AML) are still controversial. The aim of this work was to provide comprehensive insights into the effect of different hemocytes and to investigate the association between age and clinical features in adult patients with AML.
Study Design: A retrospective study was performed to determine the role of age in the therapeutic outcomes of AML. A total of 166 newly diagnosed adult patients’ data from January 2015 to November 2019 in Zhongshan Hospital of Xiamen University were collected and analyzed.
Results: Older patients presented a poorer prognosis (p=0.001) with shorter overall survival, which is served as age-related outcomes. Binary logistic regression demonstrated that cytogenetic risk (OR=4.508, 95% CI 2.733–7.435), leukocyte (OR=7.410, 95% CI 1.139–5.910), and bone marrow blast cells (OR=3.261, 95% CI 1.075–5.615) were independent indictors for age-related prognosis. In addition, Kaplan-Meier curve also revealed that the above factors were associated with overall survival (all p values <0.001).
Conclusion: Cytogenetic risk, leukocyte, and bone marrow blast cells are dominant factors which account for the age-related poor outcomes and shorter overall survival in AML.
Keywords: acute myeloid leukemia, adult, cytogenetic risk, hemocyte, leukemia, overall survival
This study investigated the effects of intracoronary nicorandil and tirofiban on no-reflow phenomenon and clinical outcomes in 438 patients with acute coronary syndrome undergoing percutaneous coronary intervention. Both nicorandil and tirofiban improved TIMI blood flow grades after PCI, with TIMI grade 3 flow in 85.2% and 81.4% of patients respectively. There was no significant difference in major adverse cardiac events between the two groups. The study concluded that intracoronary nicorandil can improve coronary perfusion in ACS patients, but its effect on long-term prognosis requires further research.
Objective: To identify interstitial cells of Cajal (ICC) in the common bile duct of Kunming mice.
Study Design: Common bile ducts obtained from the Kunming mice were prepared for immunohistochemical investigations using the c-kit antibody. Immunoelectron microscopy was used to detect the expression of c-kit in the ICC of the common bile duct. Transmission electron microscopy showed ultrastructure of ICC in the murine bile duct. Reverse transcription–polymerase chain reaction (RT-PCR) and western blot were used to confirm the expression of mRNA specific for the c-kit gene and production of c-kit protein in the Kunming mice common bile duct.
Results: Immunohistochemistry revealed that ICC in the murine common bile duct are c-kit positive and the ICC are located in the tela submucosa and the tunica muscularis of the murine common bile duct and do not connect with each other. Immunoelectron microscopy confirmed the expression of Kit by ICC in the murine common bile duct. Transmission electron microscopy showed that ICC in the murine common bile duct have long processes, abundant mitochondria, plenty of smooth endoplasmic reticulum (sER), a lot of lysosomes, and dense bodies. The caveolae of ICC are distinctive. At the same time, RT-PCR indicated that the Kunming mice common bile duct expressed mRNA specific for the c-kit gene, and western blot analysis showed the evidence of production of c-kit protein in the Kunming mice common bile duct.
Conclusion: ICC are found in the Kunming mice common bile duct, which is likely to lead to the development of motility study of the common bile duct.
Keywords: common bile duct; electron microscopy; immuno-electron microscopy; interstitial cells of Cajal; intestines; smooth muscle; tyrosine kinase receptor (c-kit)
Objective: To evaluate the antibacterial effects of 4 different cavity disinfectants on Streptococcus mutans, Lactobacillus acidophilus, and Enterococcus faecalis bacteria in different time periods.
Study Design: The antibacterial effects of Cavity Cleanser, Tubulicid Red Label, Chloraxid 2%, and Oxygenated Water cavity disinfectant solutions on E. faecalis (ATCC 29212), S. mutans (ATCC 25175), and L. acidophilus (RSKK 03037) bacterial strains were evaluated by disk diffusion method. In the study where vancomycin antibiogram disc constituted the positive control group, physiological saline solution was used as the negative control group. Standard, sterile, blank antibiogram discs of 5 mm in diameter, in which 15 μL of each material were added, were placed on agar plates at 2.5–3 cm intervals. The inhibition zone diameters formed around the discs that were left to incubate for 24–48 hours at 37°C were measured in millimeters. Statistical analysis of the data was performed using one-way analysis of variance, Kolmogorov-Smirnov, Levene, and Bonferroni tests.
Results: At the end of the study the solutions tested showed a statistically significant antibacterial effect on all bacterial strains used (p<0.05). Cavity Cleanser disinfectant containing 2% chlorhexidine showed the highest antibacterial effect on S. mutans and L. acidophilus, and benzalkonium-containing Tubulicid Red disinfectant on E. faecalis.
Conclusion: The antibacterial effect of all cavity disinfectants used in the study was found to be higher at the end of the 48th hour than at the end of the 24th hour, but there was no statistically significant difference (p>0.05).
Keywords: antibacterial agents; antibacterial effect; cavity disinfectants; chlorhexidine; contamination; dental caries; disinfection; disc diffusion; gram-negative bacteria; gram-positive bacteria
Objective: To probe into the influence of miR-21 on the proliferation as well as apoptosis of oral squamous cell carcinoma (OSCC) and its causative role.
Study Design: We adopted microarray for detecting the differentially expressed genes in OSCC tumor tis-sues and paracancerous tissues. We assessed the link of miR-21 expression with tumor size, lymph node metastasis, and tumor differentiation. We employed CCK-8 and EdU assay for detecting the impact of miR-21 inhibitor and miR-21 mimic on Cal-27 cell proliferation, as well as TUNEL and AnnexinV-FITC/PI double staining for detecting miR-21 expression on cell apoptosis. We forecasted the possible target of miR-21 via TargetScan, as well as detected the interaction of miR-21 with PTEN via luciferase reporter experiment. The function of miR-21 expression in PTEN signaling pathway was monitored via western blot. We constructed PTEN overexpression plasmid and conducted rescue experiment to evaluate overexpressed PTEN on miR-21–induced proliferation.
Results: Microarray and RT-qPCR indicated that miR-21 expression increased demonstrably in OSCC. Subsequently, statistical analysis showed that miR-21 expression was plainly correlated with tumor size, lymph node metastasis, tumor differentiation, and smoking history. CCK-8 and EdU method exhibited that miR-21 mimics manifestly promoted Cal-27 cell proliferation, while miR-21 inhibitor blatantly inhibited Cal-27 cell proliferation. TUNEL and V-FITC/PI double staining assay showed that miR-21 inhibitor conspicuously promoted Cal-27 cell apoptosis. CCK-8 and EdU assay exhibited that overexpressed PTEN abolished the pro-proliferation influence of miR-21 mimic. TUNEL and V-FITC/PI experiments pointed out that knocking down PTEN abrogated the pro-apoptosis impact of miR-21 inhibitor.
Conclusion: miR-21 contributes to OSCC cell proliferation via targeting PTEN and inhibits its apoptosis.
Keywords: Akt/PKB signaling pathway; apoptosis; biomarkers, tumor; carcinoma, squamous cell; cell line, tumor; cell proliferation; microRNAs; miR-21; miRNA-21; mouth neoplasms; oral cancer; oral squamous cell carcinoma; proliferation; real time PCR
This study examined the effects of prolonged simvastatin (SIM) treatment on ischemia-reperfusion (I/R) induced acute kidney injury in rats. Rats were divided into four groups: sham, ischemia, I/R, and I/R+SIM treated. The I/R group showed intense inflammation, necrosis, and apoptosis in kidney tissue. The I/R+SIM group showed reduced inflammation and tissue damage. Biochemical analysis found increased oxidative stress and inflammation markers in the ischemia and I/R groups compared to control, but levels in the I/R+SIM group were similar to control. Histological analysis also showed more damage in ischemia and I/R groups versus control, while the I/R+
Objective: To investigate the changes in the retina due to deltamethrin toxicity and the process in cell inflammation and apoptosis.
Study Design: Sixteen Wistar albino rats were randomly divided into two groups as control (n=8) and deltamethrin (n=8) groups. Saline was given to the control group, and 0.5 mL of 5 mg/kg deltamethrin was given to the deltamethrin group for 14 days each. Blood was collected for biochemical analysis. Retinal tissue was processed for histological examination.
Results: Compared to the control group, MDA levels were high while GSH and CAT levels were low in the deltamethrin group. Histopathological analysis showed spaces between the pigment epithelium, irregularity in the delimiting membrane, degenerated ganglion, cone and bacillus cell, pyknotic nuclei, thinned inner limitation membrane, and thickened vascular wall. The control group showed FAS expression in the pigment layer limiting membranes, in the nuclei of many cone and bacillus cells, and ganglion cells in the control group sections. In the deltamethrin group, FAS expression was observed in the inner and outer limiting membranes of the pigment epithelium, cone and bacillus cells, and ganglion cell nuclei. In the control group, negative NOS expression in the pigment epithelium and outer limiting membranes, internal limitation membrane, and ganglion cells in the cone and bacillus cell nuclei were observed. In the deltamethrin group, NOS expression was positive in the pigment epithelium, cone and bacillus, and ganglion cell nuclei.
Conclusion: We suggest that deltamethrin toxicity induced apoptotic process due to increased inflammation in the retina and may cause visual impairment as a result of neural damage.
Keywords: deltamethrin, FAS, insecticides, NOS, nitric oxide synthase, retina
Objective: Tongue squamous cell carcinoma (TSCC) is a prominent type of oral cancer. Despite the numerous research studies on SCC and microRNAs (miRs), the relation between TSCC and miR-135b-5p is poorly discussed. This experiment aims to find out the possible effect of miR-135b-5p on TSCC with the network of its downstream genes.
Study Design: TSCC tissues and adjacent normal tissues were harvested. Then, expression of miR-135b-5p and AT-rich interactive domain‑containing protein 1A gene (ARID1A) and the phosphatidyl inositol 3-kinase/protein kinase B (PI3K/AKT) pathway was analyzed. After the transfection of miR-135b-5p inhibitor and its negative control into TSCC cells, functional assays were employed to measure cell proliferation, apoptosis, and cycle. Next, the target relation between miR-135b-5p and ARID1A was confirmed. In addition, the fact that miR-135b-5p promoted TSCC development via mediating ARID1A was demonstrated by functional rescue experiment.
Results: miR-135b-5p was upregulated in TSCC tissues and cells, while ARID1A was suppressed (p< 0.05). Silenced miR-135b-5p discouraged TSCC cell proliferation, improved apoptosis, induced cell cycle arrest, and increased ARID1A expression while inactivating the PI3K/AKT axis (p<0.05). Furthermore, knockdown of ARID1A reversed the impacts on TSCC cell proliferation and apoptosis exerted by silencing miR-135b-5p.
Conclusion: This research supported that silenced miR-135b-5p impeded TSCC proliferation and apoptosis by promoting ARID1A and inactivating the PI3K/AKT axis, which may provide some indications for TSCC alleviation.
Keywords: apoptosis; ARID1A; ARID1A protein, human; carcinoma, squamous cell; cell line, tumor; cell proliferation; drug resistance, neoplasm; microRNA-135b-5p; microRNAs; PI3K/AKT pathway; neoplasm metastasis; neoplastic stem cells; proliferation; protein binding; tongue; tongue squamous cell carcinoma
Objective: To investigate the immunohistochemical staining of hypoxia-inducible factor 1-alpha (HIF-1α) and Ki-67 expression in the placenta of pregnant women with placenta previa and placenta accreta.
Study Design: Thirty placentas (10 normotensive, 10 placenta previa, and 10 placenta accreta) were processed for routine histological tissue processing. The biochemical parameters of patients were recorded. Placentas were stained with hematoxylin-eosin and HIF-1α and Ki-67 immunostaining.
Results: Normal histology was observed in placentas of normotensive pregnant women. Placenta previa sections showed increased syncytial knots, intervillous hemorrhage, fibrin accumulation, and hyalinization. In placenta accreta sections, increased syncytial nodes, vascular dilation/congestion, fibrin accumulation, and hyalinization were observed. Normotensive placentas showed no HIF-1α expression. In placenta previa tissues, high HIF-1α expression was observed in vascular endothelial cells, villous stromal cells, and syncytial knots. High HIF-1α expression was recorded in villous stromal cells and cytotrophoblast cells in placenta accreta. In normotensive placental tissues, no Ki-67 expression was observed. In placenta previa sections, high Ki-67 expression was observed mostly in root villi stromal cells and some endothelial cells. High Ki-67 expression was observed mostly in villi stromal cells of placenta accreta.
Conclusion: It is thought that HIF-1α is an important regulatory gene in the development of villus in trophoblast invasion such as placenta accreta and previa, while Ki-67 will play a key role in the development of abnormal placenta with its stimulating effect on inflammatory cell development and angiogenesis in accreta and preeclampsia.
Objective: To examine the oropharynx of patients with ectodermal dysplasia showing maxillary retrusion and mandibular protrusion with a short and concave facial structure using cone-beam computed tomography method. Ectodermal dysplasia refers to the congenital disorder defined by the abnormal development of the structure originating from the ectoderm.
Study Design: In order to examine the oropharynx airway, measurements and statistical evaluations were made in 3 levels in sagittal and transversal directions on three-dimensional cone beam computed tomography images obtained from 14 individuals divided into 2 groups as Ectodermal Dysplasia group (n=7) and Control group (n=7).
Results: As a result of statistical analysis, no statistically significant difference was found between the groups at any level or direction in metric measurements performed on all 3 planes taken at the sagittal and transversal levels (p>0.05).
Conclusion: Our findings on ectodermal dysplasia are similar to Class III malpositions that show similarity with ectodermal dysplasia.
Objective: Diabetic nephropathy is one of the most serious complications of diabetes mellitus. It develops in approximately one-third of diabetic patients, years after the onset of metabolic abnormalities.
Study Design: The biopsy specimens were evaluated with the focus on light microscopy. The aim of our study was to reveal differences in the details and the frequency of occurrence of individual histomorphological changes in diabetic nephropathy and other glomerulonephritides.
Results: Diabetic nephropathy accounted for 14 out of 82 analyzed biopsies. Isolated thickening of the glomerular basement membrane was not present in any case, but along with some degree of mesangial expansion, hypercellularity or glomerulosclerosis was seen in 12 out of 14 findings of diabetic nephropathy. In other glomerular diseases, mesangial changes, but without glomerular basement membrane thickening, were the most frequent findings. In addition to glomerular lesions, some of the tubular, interstitial, and vascular changes were seen in 13 out of 14 patients with diabetic nephropathy. In other glomerulonephritides the combination of all these changes was a rare finding.
Conclusion: There are cases where immunofluorescence and electron microscopy cannot be performed or their results are not helpful. In such cases we must rely on light microscopic histomorphological changes.
The document describes an experiment that aimed to establish a model of cardiomyocyte hypertrophy using cultured neonatal rat cardiomyocytes treated with angiotensin II (Ang II). The effects of rutin treatment on various markers of hypertrophy were then observed. Rutin treatment inhibited Ang II-induced increases in cardiomyocyte surface area, intracellular calcium levels, and expression of hypertrophy marker proteins. Rutin also inhibited decreases in calcium ATPase activity and nitric oxide levels caused by Ang II. The results suggest rutin has protective effects against Ang II-induced cardiomyocyte hypertrophy, potentially by regulating intracellular calcium handling and nitric oxide signaling.
This study investigated the expression of Caspase-12 and ADAMTS-5 in placental samples from 15 pregnant women with placenta previa and 15 healthy pregnant women. Histopathological examination found significant degeneration and apoptotic changes in the placenta previa group. Immunohistochemical analysis showed increased expression of ADAMTS-5 and Caspase-12 in the placenta previa group. The researchers concluded that increased expression of these proteins, which are involved in extracellular matrix development, inflammation, and angiogenesis, may negatively impact maternal function and fetal development in placenta previa.
This document describes a case study of a rare case of cardiac metastases from solid papillary carcinoma (SPC) of the breast. A 67-year-old woman with a history of breast cancer underwent surgery to remove a tumor in her right atrium. Pathological examination of the tumor found that it was an invasive SPC of the breast that had metastasized to the heart. Immunohistochemical staining confirmed the diagnosis. Analysis of this case improves understanding of the diagnosis and treatment of metastatic SPC of the breast to rare sites like the heart.
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Simvastatin Treatment Prevents Cell Damage and Regulates Angiogenesis in a Rat Ovarian Torsion and Detorsion Model: An Immunohistochemical Study of Caspase-3 and sFlt-1 Expression
2. cells in the corpus luteum showed decreased sFlt-1
expression, whereas sFlt-1 expression was positive in
vascular endothelial cells.
CONCLUSION: We suggest that simvastatin admin
istration could prevent cell damage by affecting pro
apoptosis activation. Simvastatin administration may
induce the regulation of angiogenesis. (Anal Quant
Cytopathol Histpathol 2020;42:85–94)
Keywords: apoptosis; immunohistochemistry; ne-
crosis; ovarian diseases; ovarian torsion; ovary;
rats, Wistar; reperfusion injury; simvastatin; tor-
sion abnormality; torsion-detorsion.
Ovarian torsion is a vascular occlusion condition
that adversely affects the development of ovaries
and restricts blood flow. Ovarian torsion accounts
for approximately 3% of gynecological emergen
cies and occurs most frequently in women of
reproductive age. Delay in torsion resolution may
result in necrosis and ovarian loss.1 Ischemia-
reperfusion injury is defined as a major cause of
ovarian tissue damage caused by torsion and de-
torsion.
Although reperfusion largely restores ischemic
tissue to normal functional tissue, it does harm
to the tissue. Inflammatory response by reperfu
sion is associated with complementary and poly
morphonuclear leukocyte (PMNL)–endothelial ac-
tivation. If inflammatory response occurs at the
site of the reperfusion, many cytokines, chemo-
kines, and proinflammatory metabolites are re-
leased through the site.2
MDA formed by lipid peroxidation causes
cross-linking and polymerization of membrane
structures. This event changes the intrinsic mem
brane properties such as deformation, ion tran
sport, enzyme activity, and aggregation of cell
surface components. MDA levels were measured
in ovarian tissue to determine and confirm the de-
gree of ischemia-reperfusion injury. Ovarian tissue
MDA levels in the ischemia-reperfusion groups
were higher than those in the control groups. This
result suggests that ischemia reperfusion causes
oxidative damage in the ovarian tissue and causes
lipid peroxidation.3
Caspases are a family of genes maintaining
homeostasis through regulating cell death and in-
flammation. They participate in ordered processes
such as apoptosis and inflammation. Caspases
are classified according to their roles in apopto
sis; caspase-3 acts as an executioner caspase.4 A
study showed caspase-3 expression in granulosa
cells from human ovarian tissue, suggesting that
caspase-3 activation plays a role in the formation
of apoptotic cell death. They observed apoptotic
morphological features such as DNA fragmenta-
tion in granulosa cells of ovarian follicles.5
Vascular endothelial growth factor–A (VEGF-A),
a member of vascular endothelial growth factor,
induces endothelial cell proliferation and increases
endothelial cell permeability.6 VEGF regulates three
tyrosine kinase family receptors (Flt-1, KDR/Flk-1,
and Flt-4) and binds only two receptors, KDR and
Flt-1, with a high affinity.7 Soluble fms-like tyro
sine kinase–1 (sFlt-1) is secretory and functions as
a decoy receptor for VEGF ligands to compete with
VEGF receptors in target cells.8
Effector caspases are responsible for cleavage
of basic apoptotic substrates such as cell signaling
molecules, DNA repair enzymes, mRNA process
ing components, cell skeleton and nuclear scaffold
proteins, and nuclease activator factors.9 It is rec
ognized that caspase-3 is a key effector, and it is
common to both the mitochondria and the death
receptor pathway.10 Peluffo et al have shown that
apoptosis plays a key role in tissue remodeling
associated with regression of the rodent corpus
luteum and that caspase protein expression and/
or enzyme activity will increase during luteolysis
in the natural estrous cycle of the rat.11
Simvastatin is a modification of lovastatin,
serving as a rate-limiting enzyme in cholesterol
synthesis.12 Simvastatin is not well absorbed, and
less than 5% of an oral dose reaches the systemic
circulation. Simvastatin exerts anti-inflammatory
effects, induces angiogenesis, and promotes endo
thelial cell growth.13
The aim of this study is to investigate the pro
tective effect of simvastatin in the ovarian damage
caused by torsion and detorsion.
Materials and Methods
Experimental Design
All procedures performed in this experiment were
approved by the Ethics Committee for the Treat-
ment of Experimental Animals (Dicle University
Faculty of Medicine, Turkey). Healthy female Wis
tar rats (250–280 g) were maintained under a con
trolled temperature of 22±1°C and 12-hour light/
dark cycles, with free access to standard pellet
food (ad libitum). Estrus cycles were evaluated by
daily vaginal smear. Anesthesia was applied before
the surgical procedure because of high anxiety in
86 Analytical and Quantitative Cytopathology and Histopathology®
Toğrul and Deveci
3. the rats. Intramuscular ketamine hydrochloride (50
mg/kg Ketalar; Eczacibasi, Istanbul, Turkey) and
xylazine hydrochlo
ride (10 mg/kg Rompun; Bayer
Türk I
·
laç Ltd, Istanbul, Turkey) were administered
to each rat for this purpose. In all of the groups, a
midline abdominal incision of 2.5 cm (laparotomy)
was performed under sterile conditions.
The groups were randomly divided as follows:
1. Control group (n=8). After anesthetizing all the
experimental animals, the ovaries were surgi
cally opened and then closed. Blood and ova-
rian tissue samples of the animals were taken.
2. Ischemia group (n=8). The ovaries of the anes
thetized animals were surgically opened, and the
left ovaries were sealed for ischemia.
3. Ischemia-reperfusion group (n=8). After 2 hours
of ischemia, blood flow was re-allowed for 2.5
hours of reperfusion. Then, the animals were
sacrificed with overdose anesthetic and ovarian
tissue samples were taken.
4. Ischemia-reperfusion+simvastatin group (n=8):
10 mg/kg simvastatin was given orally after the
reperfusion, and tissue specimens were taken
after 3 hours.
Malondialdehyde (MDA) and Glutathione Peroxidase
(GSH-Px) Assays
MDA levels and GSH-Px activities were deter-
mined in the ovary of each rat, and the average
values of each group were calculated. Each ovary
sample was prepared as a 10% homogenate (ac-
cording to weight) in 0.9% saline using a homog
enizer on ice. Then, the homogenate was centri-
fuged at 2,000 rpm for 10 minutes, and the
supernatant was collected. MDA levels were de-
termined using the double heating method of
Draper and Hadley.14 The GSH-Px activity was
measured by the method of Paglia and Valentine.15
An enzymatic reaction was initiated by the addi-
tion of hydrogen peroxide (H2O2) to a tube that
contained reduced nicotinamide adenine dinu
cleotide phosphate, reduced glutathione, sodium
azide, and glutathione reductase. The change in
absorbance at 340 nm was monitored by spec-
trophotometry. Data were expressed as U/g pro
tein.
Histopathologic Analysis
The ovarium samples were fixed with neutral
buffered 10% formalin solution. After preserva
tion, ovarian samples were directly dehydrated
in a graded series of ethanol and embedded into
paraffin wax. Five mm sections were cut with a
microtome (Rotatory Microtome, Leica, RM 2265,
Germany) and stained with hematoxylin and eosin
in order to be observed under light microscope.
Immunohistochemical Staining
Formaldehyde-fixed tissues were embedded in
paraffin wax for further immunohistochemical
examination. Sections were deparaffinized in xy-
lene and passed through descending alcohols.
Antigen retrieval process was performed in citrate
buffer solution (pH 6.0) for 5 minutes at 90°C in a
conventional microwave oven. They were allowed
to cool at room temperature for 30 minutes and
washed twice in distilled water for 5 minutes. En-
dogenous peroxidase activity was blocked in 0.1%
hydrogen peroxide for 20 minutes. Ultra V block
(Cat. No. 85-9043; Invitrogen, Carlsbad, California,
USA) was applied for 10 minutes prior to the
application of primary antibodies sFlt-1 antibody
(dilution rate, 1/100), cluster of differentiation
caspase-3 antibody (dilution rate, 1/100) over
night. Secondary antibody (Cat. No. 85-9043; Invi
trogen) was applied for 20 minutes. Slides were
then exposed to streptavidin-peroxidase for 20
minutes. Chromogen diaminobenzidine (DAB; In-
vitrogen) was used. Control slides were prepared
as mentioned above but omitting the primary
antibodies. After counterstaining with hematoxy
lin and holding in distilled water for 10 minutes,
the slides were mounted with Entellan (Merck,
Germany).
Ovary sections were blindly analyzed by the
same histopathologist. Random areas from each
tissue were scored for each feature using a scale
of 0 to 3 (0=none, 1=mild, 2=moderate, 3=se-
vere, and 4=most severe).16 Histopathological fea-
tures for ovarian injury were follicular cell de-
generation (granulosa cells), vascular occlusion,
hemorrhage, and inflammation (neutrophil infil
tration). Histopathological tissue injury scores
were determined as explained above. Tissue in-
jury scores of the groups are shown in Table I.
We compared follicle degeneration, vascular con
gestion, edema, and inflammation between groups
(Figure 1).
Statistical Analysis
Statistical analysis of histopathological and bio
chemical parameters was performed with SPSS
Volume 42, Number 3/June 2020 87
Simvastatin for Ovarian Torsion and Detorsion
4. (Version 22.0, SPSS Inc., Chicago, Illinois, USA).
Descriptive statistics were presented as median
(min-max) and mean±standard deviation values.
The significance of the difference among more
than two groups was evaluated by using the
Kruskal-Wallis test since data did not meet the
assumptions of the parametric test ANOVA. Post-
hoc tests with Bonferroni correction were used to
determine which groups differed with pairwise
comparison. A value of p<0.05 was considered as
statistically significant.
Results
We evaluated biochemical, histopathological, and
immunohistochemical parameters to determine
the efficacy of simvastatin on ischemia and reper
fusion injury of rat ovaries. Parameter results are
statistically shown in Table I. When we compared
the groups in terms of MDA levels, a statistically
significant difference was found (p<0.05), espe
cially in the ischemia and ischemia-reperfusion
groups: MDA values increased as compared to
the control group. In simvastatin administration,
88 Analytical and Quantitative Cytopathology and Histopathology®
Toğrul and Deveci
Table I Histopathological Parameters, Immunohistochemical Parameters, and Biochemical Parameters in All Studied Groups
Kruskal- Multiple
Wallis comparisons
Mean test for groups
Parameter Group N Mean±SD rank value (p<0.05)
Granular cell degeneration (1) Control 8 0.62±0.51 6.8 25,185 (2)(3)
p=0
(2) Ischemia 8 3.62±0.51 25.6 (1)(4)
(3) I/R 8 3.25±0.70 23.1 (1)(4)
(4) I/R+simvastatin 8 1.12±0.64 10.2 (2)(3)
Vascular dilation and congestion (1) Control 8 0.25±0.46 6.5 26,309 (2)(3)
p=0
(2) Ischemia 8 3.75±0.46 26.7 (1)(3)(4)
(3) I/R 8 3.00±0.75 22.2 (1)(2)(4)
(4) I/R+simvastatin 8 0.75±0.46 10.5 (2)(3)
Inflammation (1) Control 8 0.62±0.51 8.0 25,295 (2)(3)
p=0
(2) Ischemia 8 3.50±0.75 24.3 (1)(4)
(3) I/R 8 3.62±0.51 24.6 (1)(4)
(4) I/R+simvastatin 8 0.75±0.46 9.0 (2)(3)
Caspase-3 expression (1) Control 8 0.87±0.64 8.5 25,315 (2)(3)
p=0
(2) Ischemia 8 3.75±0.46 26.0 (1)(4)
(3) I/R 8 3.37±0.51 23.0 (1)(4)
(4) I/R+simvastatin 8 0.87±0.64 8.5 (2)(3)
sFlt-1 expression (1) Control 8 3.00±0.75 12.3 3,720
p=0.293
(2) Ischemia 8 3.37±0.51 16.6
(3) I/R 8 3.37±0.51 16.6
(4) I/R+simvastatin 8 3.62±0.51 20.3
GSH (1) Control 8 10.22±1.28 26.25 26,569 (2)(3)
p=0
(2) Ischemia 8 3.56±0.92 4.63 (1)(4)
(3) I/R 8 5.94±0.59 12.38 (1)(4)
(4) I/R+simvastatin 8 9.34±0.91 22.75 (2)(3)
MDA (1) Control 8 2.76±0.29 6.50 25,452 (2)(3)
p=0
(2) Ischemia 8 6.02±0.76 27.31 (1)(4)
(3) I/R 8 5.05±0.63 21.69 (1)(4)
(4) I/R+simvastatin 8 3.16±0.51 10.50 (2)(3)
GSH = glutathione, I/R = ischemia-reperfusion, MDA = malondialdehyde.
5. MDA decreased. GSH values decreased in the
ischemia and ischemia-reperfusion groups as com
pared to the control group. In the simvastatin-
treated group, GSH value increased.
Discussion
Ovarian ischemia causes cell death due to in-
sufficient oxygen in the tissue. Ischemic tissues
need to recover blood supply for regeneration of
cells and disposal of toxic metabolites. However,
reperfusion of the ischemic tissue paradoxically
leads to much more serious damage to the tissue
than the damage caused by the ischemia.17 In
patients with adnexal torsion, an important fac-
tor for the prevention or reduction in ovarian
tissue damage is to keep the duration of ische-
mia brief. Currently, early conserving surgery
(detorsion/unwinding of the ovary) is considered
to be the most effective clinical approach to
treating ovarian torsion in girls and adolescents.16
Malondialdehyde (MDA) is the basic product of
polyunsaturated fatty acid peroxidation and is
quite a toxic molecule. Therefore, it is used to
determine in vivo and in vitro oxidative stress
levels.18
In a study by Cadirci et al that investigated the
efficacy of atorvastatin in the treatment of ovarian
ischemia-reperfusion injury,19 it was found that
MDA increased in ovarian tissue of the ischemia-
reperfusion group. In our study, while the MDA
level was high in both the ischemia and ischemia-
reperfusion groups, it decreased in the simvastat-
in group. Ischemia-reperfusion injury leads to the
production of excess amounts of highly reactive
molecules that cause damage to lipids, proteins,
and DNA as a result of a series of toxic events.20
GSH is one of the most important indicators of
antioxidant capacity which protects the tissues
against damage caused by oxidative stress. In the
study by Aksak Karamese et al21 it was reported
that GSH levels were significantly suppressed
when 3 hours of ischemia was followed by the
same period of reperfusion. In a study by Soylu
Karapinar et al,22 vascular congestion, edema,
Volume 42, Number 3/June 2020 89
Simvastatin for Ovarian Torsion and Detorsion
Figure 1 Comparison of histopathological, immunohistochemical, and biochemical parameters in all groups. MDA values were
increased in the ischemia and ischemia-reperfusion groups, close to the control group in the simvastatin-treated group as compared to
the control group. GSH values were decreased in the ischemia and ischemia-reperfusion groups and increased in the simvastatin-treated
group as compared to the control group. For the histopathological parameters, granular cell degeneration, vascular dilation, hemorrhage,
and inflammation levels were increased in the ischemia and ischemia-reperfusion groups as compared to the control group, but they
were similar to the control group in the simvastatin-treated group. Caspase-3 expression was increased by degeneration and apoptosis
in the ischemia and ischemia-reperfusion groups as compared to the control group. However, it was similar to the control group in the
simvastatin-treated group.
6. hemorrhage, and inflammatory cell infiltration
were observed in the ovarian tissue due to 3
hours of ischemia or 3 hours ischemia/3 hours
reperfusion.
Ozler et al16 showed that the number of follicles
decreased after torsion, reflecting the size of the
primitive follicle pool. They stated that a decrease
in the number of growing follicles was higher in
the detorsion group with dense cellular ischemia-
reperfusion injury. Our histochemical results are
shown in Figure 2. The control group showed a
normal appearance of the ovary with its follicles
and oocyte (Figure 2A). In the ischemia group,
oocyte cells and their associated structures were
mostly degenerated. Blood vessels were dilated and
congested with inflammation around them (Fig
ure 2B). The ischemia-reperfusion group showed
histopathology similar to that of the ischemia
group (Figure 2C). The ischemia-reperfusion+
simvastatin–treated group seemed to be histolo
90 Analytical and Quantitative Cytopathology and Histopathology®
Toğrul and Deveci
Figure 2 Hematoxylin and eosin staining of all groups. In the control group, oocytes of mature follicles were normal in shape with
oval nuclei surrounded by corona cells and granular cells. Theca externa was outside of follicles with dense connective fibers (A).
In the ischemia group, a degenerated oocyte with its degenerated corona and surrounding granular cells were observed. Atrophied
collagen fibrils, dilated blood vessels and intense congestion, and interfollicular inflammation and necrotic cells were also seen (B). In
the ischemia-reperfusion group, oocyte nuclei of the antral follicle were pyknotic. Surrounding cells were degenerated with apoptotic
changes. Stromal inflammation, dilated blood vessels, and congestion were also recorded (C). In the ischemia-reperfusion+simvastatin–
treated group, granular cells in the antral follicle were rich in chromatin. In fibrils around the follicle, stromal cells were regular. Slightly
dilated blood vessels and some apoptotic cells in the corpus luteum were observable (D).
7. gically normal, but some apoptotic figures were
still observable (Figure 2D).
In the reperfusion process that develops after
reactive oxygen derivatives after ischemia, acti
vation of proapoptotic genes and proteases and
apoptosis in the caspase family occur. However,
it causes lipid peroxidation and cell damage by
disrupting the permeability of the cell membrane
structure.24 Many studies have shown that oxi
dative stress and excessive inflammatory prod
ucts, depending on their densities in ischemia-
reperfusion injuries, cause either reversible cell
damage or irreversible, lethal cell damage such as
apoptosis and necrosis.23
Sapmaz-Metin et al found that the number of
apoptotic cells increased significantly in the ova
ries after ischemia-reperfusion.25 They detected
TUNEL-positive granulosa cells only in medium
or large ovarian follicles. They reported that
ischemia-reperfusion injury does not reduce the
ovarian germ cell pool but instead leads to oocyte
maturation problems due to loss of some internal
factors mediated by granulosa cell death. Our
caspase-3 immune staining results showed that
caspase-3 expression was predominantly negative
in follicular structures (Figure 3A). Degenerated
granular, luteal, and inflammatory cells expressed
caspase-3 (Figure 3B). The ischemia-reperfusion
group showed positive caspase-3 expression in oo-
cyte, granular, stromal cells, and theca cells in the
Volume 42, Number 3/June 2020 91
Simvastatin for Ovarian Torsion and Detorsion
Figure 3 Caspase-3 immunostaining of all groups. In the control group, caspase-3 expression in the oocyte and granular cells in the
preantral and antral follicles was negative, but it was positive in stromal cells adjacent to follicles (A). In the ischemia group, degenerated
granular cells in the antral follicle, luteal cells in the corpus luteum, and intense inflammatory cells in the stromal region showed positive
expression of caspase-3 (B). In the ischemia-reperfusion group, caspase-3 expression was positive in oocyte, granular, stromal cells, and
theca cells in the mature antral follicle (C). Caspase-3 expression was negative in preantral follicular cells and granular cells around the
antral follicle in the ischemia-reperfusion+simvastatin group, whereas it was positive in some stromal cells and corpus luteum cells (D).
8. mature antral follicle (Figure 3C). In the ischemia-
reperfusion+simvastatin group, caspase-3 expres
sion was negative in follicular structures but pos
itive in some stromal cells and corpus luteum cells
(Figure 3D).
Angiogenesis is one of the major features of the
early corpus luteum. VEGF is the most important
factor in the regulation of both normal and ab-
normal angiogenesis.7 VEGF-A, a potent stimula
tor of endothelial cell proliferation and migration
and also a promoter of vascular permeability, is
the major angiogenic factor that controls follicu-
lar angiogenesis.26 An increase in VEGF-A expres
sion and neovascularization by atorvastatin was
previously reported by Matsumura et al.27 By in-
creasing neovascularization, statins maintain mi-
crovascular circulation and improve tissue per
fusion.28 sFlt-1 is secreted from endothelial cells
into their immediate extracellular space as well as
into the general circulation and reduces the bio-
availability of VEGF by binding and sequester-
ing this growth factor.29 Our sFlt-1 immunostain
ing results are shown in Figure 4. In the control
group, sFlt-1 expression was positive in vascular-
associated structures (Figure 4A). sFlt-1 was posi-
tively expressed in degenerated follicular cells,
92 Analytical and Quantitative Cytopathology and Histopathology®
Toğrul and Deveci
Figure 4 sFlt-1 immunostaining of all groups. In the control group, sFlt-1 expression was positive in the vascular endothelial cells
between the preantral and antral follicles and in some stromal macrophage cells (A). In the ischemia group, the expression of sFlt-1
was positive in degenerated preantral and antral follicle cells, vascular endothelial cells, and inflammatory cells (B). In the ischemia-
reperfusion group, increased sFlt-1 expression was observed in luteal cells of the corpus luteum, vascular endothelial, and inflammatory
cells (C). In the ischemia-reperfusion+simvastatin group, follicular and corpus luteum cells showed decreased sFlt-1 expression, whereas
sFlt-1 expression was positive in vascular endothelial cells (D).
9. vascular cells, and inflammatory cells in the ische
mia group (Figure 4B). The ischemia-reperfusion
group showed increased sFlt-1 expression in cor-
pus luteum, vascular endothelial inflammatory
cells (Figure 4C). In the ischemia-reperfusion+sim
vastatin group, sFlt-1 expression was decreased in
follicular structures (Figure 4D).
Depending on the duration of torsion and de-
torsion, apoptosis may be increased due to pro
apoptotic activation, and simvastatin adminis-
tration could prevent cell damage by affecting
proapoptosis activation. Simvastatin administra
tion was thought to induce the regulation of
angiogenesis.
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