This document summarizes research on the physiological functions of LMP2/β1i in the female reproductive system. It discusses how LMP2/β1i is involved in embryo implantation by regulating trophoblast cell invasion and extracellular matrix degradation through modulation of MMP expression. It also reports that LMP2/β1i deficient mice exhibit uterine neoplasms, and overexpression of LMP2/β1i in trophoblast cells of hydatidiform moles contributes to their highly invasive phenotype. The document further examines the role of LMP2/β1i in preventing spontaneous transformation of uterine mesenchymal cells into tumors.
1) The study investigates the role of b-catenin in myogenesis using P19 cells with reduced b-catenin activity (P19[shb-cat] cells) compared to control cells.
2) The loss of b-catenin resulted in reduced expression of genes involved in premyogenic mesoderm formation and skeletal myogenesis.
3) While retinoic acid could partially compensate by upregulating some precursor genes in P19[shb-cat] cells, it could not compensate for the expression of genes required for terminal myogenesis or overall skeletal muscle formation.
overexpression of mrps18 2 in cancer cell lines resultsAnimatedWorld
Human mitochondrial ribosomal protein MRPS18-2 (S18-2) is encoded by a cellular gene that is located on the human chromosome 6p21.3.
They observed the overexpression of the S18-2 protein led to immortalization and de-differentiation of primary rat embryonic fibroblasts and then Cells showed anchorage-independent growth pattern.
There observation is not limited to overexpression but they also see the evidence of s18-2 somehow involves in cell cycle regulation and cause disturbances.
S18-2 protein when over expressed it also cause appearance of multinucleated cells in the selected clones.
Characterizing Mouse Mammary Epithelial Cell Response to Activin and TGFbNatalia Trikoz
• Research Poster presented at the state-wide Undergraduate Research Conference in Spring 2014
• Studied effects of cytokines TGFb and Activin on mammosphere forming potential and on epithelial to mesenchymal transition (EMT) phenotypic and genotypic markers
Animal Lectin Galectin-8 by Hadas Shatz-Azoulay, Yaron Vinik, Roi Isaac, Ulri...Sima Lev
This study found that the animal lectin galectin-8 (gal-8) promotes cytokine expression and metastatic tumor growth in mice. Specifically:
- Gal-8 induces the expression and secretion of cytokines like SDF-1 and MCP-1 in various cell types through binding to a uPAR/LRP1/integrin complex that activates the JNK and NFkB pathways.
- Cytokines induced by gal-8 promote cancer cell migration toward cells treated with gal-8. Knockout mice lacking gal-8 have lower cytokine levels and reduced tumor growth and metastasis compared to normal mice.
- Gal-8 treatment of osteoblasts increases expression of cytokines that attract prostate cancer
Basic Mutagenic signal Transduction or the cancer signal transduction that control cell cycle are important pathways to understand cancer in molecular level and to invent targeted treatment.
This document discusses protein kinase B (Akt), which plays roles in processes like glucose metabolism and cell proliferation. It describes the three main types of Akt (Akt1, Akt2, Akt3) and their physiological functions. Akt1 promotes cell survival and growth, while Akt2 functions in insulin signaling pathways. Akt3's role is less clear. The document outlines Akt's involvement in signaling pathways and its implications for pharmacology. Akt signaling is implicated in cancer development and progression through processes like angiogenesis and glucose metabolism. Several Akt inhibitors are discussed that are in clinical trials for conditions like cancer and Proteus syndrome.
Sima Lev The AXL PYK2 PKC axis as a nexus of stemness circuits in TNBCSima Lev
1) The study identifies a signaling circuit involving AXL receptor, PYK2 kinase, and PKCα kinase (the AXL-PYK2-PKCα axis) that regulates stemness in triple-negative breast cancer (TNBC).
2) Depletion of PYK2 or PKCα reduces expression of proteins in the axis like AXL and transcription factor FRA1, and decreases formation of mammospheres and expression of cancer stem cell markers.
3) PYK2 depletion decreases AXL transcription through feedback involving FRA1 and TAZ transcription factors, while PKCα inhibition enhances AXL degradation. PYK2 and PKCα cooperate to regulate stemness pathways through the axis
This document discusses fibroblast growth factors (FGFs) and their receptors (FGFRs) in cancer. It notes that FGFRs are cell surface receptors involved in normal cellular processes but also cancer development and progression. FGFRs may promote cancer cell growth, invasion, and angiogenesis. The document provides details on FGF signaling pathways, mutations in FGFR genes linked to various cancers, and differential expression of FGFs/FGFRs across cancer types like breast, bladder, prostate, lung and multiple myeloma. It concludes that deregulation of FGFs/FGFRs supports cancer progression and discusses challenges in targeting them for cancer therapy.
1) The study investigates the role of b-catenin in myogenesis using P19 cells with reduced b-catenin activity (P19[shb-cat] cells) compared to control cells.
2) The loss of b-catenin resulted in reduced expression of genes involved in premyogenic mesoderm formation and skeletal myogenesis.
3) While retinoic acid could partially compensate by upregulating some precursor genes in P19[shb-cat] cells, it could not compensate for the expression of genes required for terminal myogenesis or overall skeletal muscle formation.
overexpression of mrps18 2 in cancer cell lines resultsAnimatedWorld
Human mitochondrial ribosomal protein MRPS18-2 (S18-2) is encoded by a cellular gene that is located on the human chromosome 6p21.3.
They observed the overexpression of the S18-2 protein led to immortalization and de-differentiation of primary rat embryonic fibroblasts and then Cells showed anchorage-independent growth pattern.
There observation is not limited to overexpression but they also see the evidence of s18-2 somehow involves in cell cycle regulation and cause disturbances.
S18-2 protein when over expressed it also cause appearance of multinucleated cells in the selected clones.
Characterizing Mouse Mammary Epithelial Cell Response to Activin and TGFbNatalia Trikoz
• Research Poster presented at the state-wide Undergraduate Research Conference in Spring 2014
• Studied effects of cytokines TGFb and Activin on mammosphere forming potential and on epithelial to mesenchymal transition (EMT) phenotypic and genotypic markers
Animal Lectin Galectin-8 by Hadas Shatz-Azoulay, Yaron Vinik, Roi Isaac, Ulri...Sima Lev
This study found that the animal lectin galectin-8 (gal-8) promotes cytokine expression and metastatic tumor growth in mice. Specifically:
- Gal-8 induces the expression and secretion of cytokines like SDF-1 and MCP-1 in various cell types through binding to a uPAR/LRP1/integrin complex that activates the JNK and NFkB pathways.
- Cytokines induced by gal-8 promote cancer cell migration toward cells treated with gal-8. Knockout mice lacking gal-8 have lower cytokine levels and reduced tumor growth and metastasis compared to normal mice.
- Gal-8 treatment of osteoblasts increases expression of cytokines that attract prostate cancer
Basic Mutagenic signal Transduction or the cancer signal transduction that control cell cycle are important pathways to understand cancer in molecular level and to invent targeted treatment.
This document discusses protein kinase B (Akt), which plays roles in processes like glucose metabolism and cell proliferation. It describes the three main types of Akt (Akt1, Akt2, Akt3) and their physiological functions. Akt1 promotes cell survival and growth, while Akt2 functions in insulin signaling pathways. Akt3's role is less clear. The document outlines Akt's involvement in signaling pathways and its implications for pharmacology. Akt signaling is implicated in cancer development and progression through processes like angiogenesis and glucose metabolism. Several Akt inhibitors are discussed that are in clinical trials for conditions like cancer and Proteus syndrome.
Sima Lev The AXL PYK2 PKC axis as a nexus of stemness circuits in TNBCSima Lev
1) The study identifies a signaling circuit involving AXL receptor, PYK2 kinase, and PKCα kinase (the AXL-PYK2-PKCα axis) that regulates stemness in triple-negative breast cancer (TNBC).
2) Depletion of PYK2 or PKCα reduces expression of proteins in the axis like AXL and transcription factor FRA1, and decreases formation of mammospheres and expression of cancer stem cell markers.
3) PYK2 depletion decreases AXL transcription through feedback involving FRA1 and TAZ transcription factors, while PKCα inhibition enhances AXL degradation. PYK2 and PKCα cooperate to regulate stemness pathways through the axis
This document discusses fibroblast growth factors (FGFs) and their receptors (FGFRs) in cancer. It notes that FGFRs are cell surface receptors involved in normal cellular processes but also cancer development and progression. FGFRs may promote cancer cell growth, invasion, and angiogenesis. The document provides details on FGF signaling pathways, mutations in FGFR genes linked to various cancers, and differential expression of FGFs/FGFRs across cancer types like breast, bladder, prostate, lung and multiple myeloma. It concludes that deregulation of FGFs/FGFRs supports cancer progression and discusses challenges in targeting them for cancer therapy.
Growth factors are proteins that bind to cell surface receptors and regulate cellular proliferation, differentiation, and other functions. They include transforming growth factor beta (TGF-β), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and fibroblast growth factors (FGFs). TGF-β in particular is important for bone homeostasis and is produced in its inactive form, requiring activation before exerting its effects on cells. Growth factors signal through membrane receptors and regulate gene expression.
Activation of AMPK inhibits cervical cancer cell growth through AKT/FOXO3a/FO...Enrique Moreno Gonzalez
Although advanced-stage cervical cancer can benefit from current treatments, approximately 30% patients may fail after definitive treatment eventually. Therefore, exploring alternative molecular therapeutic approaches is imperatively needed for this disease. We have recently shown that activation of AMP-activated protein kinase (AMPK), a metabolic sensor, hampers cervical cancer cell growth through blocking the Wnt/β-catenin signaling activity. Here, we report that activated AMPK (p-AMPK) also inhibits cervical cancer cell growth by counteracting FOXM1 function.
This document provides an overview of several polypeptide growth factors that may have therapeutic applications, including insulin-like growth factor 1 (IGF-1), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast growth factors (FGFs), and transforming growth factors (TGFs). It describes the discovery and roles of each growth factor in wound healing and other cellular processes. IGF-1 regulates growth and differentiation of many cell types. EGF was first isolated from urine and stimulates skin and wound healing. PDGF stimulates growth of fibroblasts, smooth muscle and glial cells. FGFs induce mitogenic, chemotactic and angiogenic responses. TGFs represent another family
Fibroblast growth factors (FGFs) are a family of paracrine factors that play important roles in development, wound healing, and maintenance of tissues. There are nearly two dozen FGFs that can generate hundreds of isoforms and have separate functions. FGFs act as mitogens, promoting cell proliferation, and are critical for development of vertebrates and invertebrates. FGFs function by activating fibroblast growth factor receptors, causing phosphorylation of proteins that perform new functions. The receptor tyrosine kinase pathway is an important signal transduction pathway where FGF binding activates a cascade of phosphorylation leading to transcription factors that determine the developmental course of the cell.
The TGF-beta superfamily is a large family of secreted signaling molecules that mediate many key events in growth and development. It includes over 30 members such as Activins, Nodals, BMPs, and GDFs. These proteins signal through cell-surface receptors and Smad proteins to regulate gene expression and control processes like proliferation, differentiation, and matrix production. Aberrant TGF-beta superfamily signaling is associated with several human diseases including cancer and fibrosis.
This document discusses EGF and SDF signaling and Akt-mediated resistance to apoptosis in human breast cancer cells. It summarizes that EGF and SDF can both activate the Akt pathway through different mechanisms, either directly or indirectly, leading to increased cell survival, proliferation, and resistance to apoptosis. Western blotting of breast cancer cells treated with EGF or SDF showed both ligands activated Akt, though EGF activated Akt more sharply while SDF activated it more quickly. The document reviews the pathways of EGF and SDF signaling that result in Akt activation and discusses potential targets in these pathways for inhibiting Akt's anti-apoptotic effects in cancer treatment.
The document discusses cell cycle checkpoints which monitor cell growth, DNA replication, and chromosome segregation. It describes the different phases of the cell cycle including interphase and mitosis. Checkpoints at the G1, G2, and M phases are controlled by regulators like cyclins, CDKs, and inhibitors. Dysregulation of cell cycle progression can lead to diseases like cancer. Targeting cell cycle checkpoints and regulators is a potential approach for cancer treatment.
Cell growth can refer to the increase in cell size and organelles during interphase (G1 and G2 phases) or the growth of a cell population through cell division (M phase). The cell cycle consists of G1, S, G2, and M phases, separated by gap phases G1 and G2. Growth factors such as EGF, TGF-α, HGF, and PDGF act as ligands that bind to cell surface receptors and transmit signals to regulate the cell cycle. These signals activate intracellular pathways using second messengers to induce transcription factors that drive expression of genes controlling cell cycle progression and cell growth.
Down regulationof forkheadboxm1transcriptionfactorleadstotheinhibitionofinvas...Chau Chan Lao
Down-regulation of Forkhead Box M1 Transcription Factor Leads to the Inhibition of Invasion and Angiogenesis of Pancreatic Cancer Cells.
Zhiwei Wang, Sanjeev Banerjee, Dejuan Kong, Yiwei Li, and Fazlul H. Sarkar
Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
Cancer Res 2007; 67: (17). September 1, 2007
The PI3K-Akt-mTOR pathway is an intracellular signal transduction pathway that promotes metabolism, proliferation, cell survival, growth and angiogenesis. Key components include receptor tyrosine kinases, PI3K, PIP2, PIP3, and Akt. Akt is activated by phosphorylation and regulates various proteins involved in functions like cell growth. Dysregulation of this pathway can lead to cancer due to abnormal cell proliferation and is associated with neurodevelopmental disorders.
This presentation gives the basic idea, about the information on the role of tyrosine kinases in cancer. I have also included a phylogenetic tree for finding the relatedness between different organisms.
The PI3K-Akt pathway promotes metabolism, proliferation, cell survival, growth and angiogenesis through phosphorylation of downstream substrates. Key proteins in this pathway are phosphatidylinositol 3-kinase (PI3K) and Akt/Protein Kinase B. Research into this pathway began with the discovery of the oncogene ATK8 in 1977 and the cloning of PKB/Akt in 1991. It was later found that PI3K activates Akt and that phospholipids generated by PI3K are required for Akt activation.
Includes notes about Akt/Protein kinase B.Protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation).
Protein kinase B (PKB), also known as Akt, is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration
This file also includes the types, \signalling pathways and inhibitors of protein kinase B.
This document discusses signal transduction and how it relates to cancer. It describes how growth factors and receptors contribute to normal signal transduction and how this process is deregulated in cancer. It explains that growth factors regulate growth, proliferation and survival, which are all altered in cancer. Several growth factors and receptors that can contribute to oncogenesis are identified. It also summarizes several key intracellular signaling pathways, like MAPK pathways, that are activated by growth factors and can result in the cancer phenotype if altered.
1362575848 growth factos presentation a baldfsimedia
Growth factors play an essential role in diabetic foot ulcer management. Platelet-derived growth factor (PDGF) is a significant growth factor that is released during wound healing and promotes angiogenesis, fibroblast proliferation, and re-epithelialization. Recombinant human PDGF-BB (rhPDGF-BB) has been shown to accelerate wound healing in diabetic foot ulcers by stimulating cellular processes involved in repair when applied topically according to dosage guidelines.
The PTEN and PI3-Kinase Pathway in Cancer pptBernard Bahaah
The document presents information on PTEN and the PI3-kinase pathway in cancer. It discusses how PTEN acts as a tumor suppressor by negatively regulating the PI3-kinase pathway, which promotes cell growth and survival. Mutations or deletions of the PTEN gene are common in many cancer types as they lead to overactivation of the PI3-kinase pathway. The document outlines the signaling events in the PI3-kinase pathway, how PTEN regulates it, additional functions of PTEN, and potential cancer therapeutics that target this pathway.
TGF-β is a polypeptide cytokine that performs many cellular functions and controls processes like cell proliferation, immune regulation, apoptosis, and tissue repair. It signals through Smad-dependent and Smad-independent pathways. The Smad-dependent pathway involves TGF-β binding to receptors that phosphorylate R-Smads, which then complex with Co-Smads and regulate transcription of target genes. The Smad-independent pathway activates proteins like MAPKs, PI3K/Akt, and TRAF6. TGF-β signaling regulates diverse biological processes through these pathways.
The document summarizes the AKT/PKB signaling pathway. It discusses that AKT/PKB promotes metabolism, proliferation, and cell survival as an intracellular signal transduction pathway. Key proteins in the pathway are AKT/PKB and PI3K. The pathway regulates processes like protein synthesis, cell survival, cell proliferation, and glucose metabolism. Dysregulation of the pathway through mutations can contribute to cancer due to AKT/PKB's role in regulating critical cellular functions, making it a potential therapeutic target.
The document discusses checkpoints in the cell cycle that control progression from one phase to the next. It describes the G1, G2, and M phase checkpoints, noting that the G1 checkpoint determines whether a cell will continue through the cell cycle or become quiescent. It also explains that the G2 checkpoint is driven by maturation promoting factor, a protein complex of cyclins and cyclin-dependent kinases, and that the M phase checkpoint ensures proper chromosome attachment before anaphase.
A cell cycle is a series of events that takes place in a cell as it grows and divides. The process has to be correct and regulated. This slide illustrated Cell cycle and its regulation. Check the slides to know more.
1) The document discusses candidate molecules that may act as tumor suppressors for human uterine mesenchymal tumors. It focuses on LMP2/β1i, which is expressed in normal myometrium but defective or absent in human uterine leiomyosarcoma (Ut-LMS).
2) Mice deficient in LMP2/β1i spontaneously develop Ut-LMS, with similarities to the human disease. This suggests LMP2/β1i may function as a tumor suppressor for Ut-LMS.
3) While tumor suppressor pathways like p53 and Rb are often disrupted in cancers, their roles in Ut-LMS tumorigenesis are unclear
Potential Diagnostic Biomarkers for Human Uterine Mesenchymal Tumours Especia...ijtsrd
Aims Although the majority of smooth muscle neoplasms found in the uterus are benign, uterine leiomyosarcoma is extremely malignant, with high rates of recurrence and metastasis. The development of gynecologic tumors is often correlated with secretion of female hormone however, the development of human uterine leiomyosarcoma is not substantially correlated with hormonal conditions, and the risk factors are unclearly understood. Importantly, a diagnostic biomarker, which distinguishes malignant human uterine leiomyosarcoma from benign tumor leiomyoma is yet to be established. It is necessary to analyze risk factors associated with human uterine leiomyosarcoma, in order to establish a diagnostic biomarker and a clinical treatment method. Methodology Histology and Immunofluorescence Staining tissue sections 5 µm were prepared and stained with HandE for routine histological examination or were processed further for immunofluorescence staining with appropriate antibodies. Furthermore, a total of 57 patients between 32 and 83 years of age and diagnosed as having smooth muscle tumors of the uterus were selected from pathological files. Immunohistochemistry staining for LMP2 1i and cyclin E1 was performed on serial human uterine leiomyosarcoma, leiomyoma and myometrium sections. Results Homozygous deficient mice for a proteasome subunit LMP2 1i spontaneously develop uterine leiomyosarcoma, with a disease prevalence of ~40 by 14 months of age. Defective LMP2 1i and cyclin E1 positive expressions in human uterine leiomyosarcoma were demonstrated, but the reverse result was obtained in human leiomyoma and myometrium. Conclusions LMP2 1i and cyclin E1 differential expressions may be one of the risk factors for human uterine leiomyosarcoma. LMP2 1i and cyclin E1 may be potential diagnostic biomarker and targeted molecule for a new therapeutic approach. Takuma Hayashi | Hiroyuki Aburatani | Ikuo Konishi "Potential Diagnostic Biomarkers for Human Uterine Mesenchymal Tumours: Especially LMP2/1i and Cyclin E1-Differential Expressions" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd62380.pdf Paper Url: https://www.ijtsrd.com/medicine/other/62380/potential-diagnostic-biomarkers-for-human-uterine-mesenchymal-tumours-especially-lmp21i-and-cyclin-e1differential-expressions/takuma-hayashi
Growth factors are proteins that bind to cell surface receptors and regulate cellular proliferation, differentiation, and other functions. They include transforming growth factor beta (TGF-β), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and fibroblast growth factors (FGFs). TGF-β in particular is important for bone homeostasis and is produced in its inactive form, requiring activation before exerting its effects on cells. Growth factors signal through membrane receptors and regulate gene expression.
Activation of AMPK inhibits cervical cancer cell growth through AKT/FOXO3a/FO...Enrique Moreno Gonzalez
Although advanced-stage cervical cancer can benefit from current treatments, approximately 30% patients may fail after definitive treatment eventually. Therefore, exploring alternative molecular therapeutic approaches is imperatively needed for this disease. We have recently shown that activation of AMP-activated protein kinase (AMPK), a metabolic sensor, hampers cervical cancer cell growth through blocking the Wnt/β-catenin signaling activity. Here, we report that activated AMPK (p-AMPK) also inhibits cervical cancer cell growth by counteracting FOXM1 function.
This document provides an overview of several polypeptide growth factors that may have therapeutic applications, including insulin-like growth factor 1 (IGF-1), epidermal growth factor (EGF), platelet-derived growth factor (PDGF), fibroblast growth factors (FGFs), and transforming growth factors (TGFs). It describes the discovery and roles of each growth factor in wound healing and other cellular processes. IGF-1 regulates growth and differentiation of many cell types. EGF was first isolated from urine and stimulates skin and wound healing. PDGF stimulates growth of fibroblasts, smooth muscle and glial cells. FGFs induce mitogenic, chemotactic and angiogenic responses. TGFs represent another family
Fibroblast growth factors (FGFs) are a family of paracrine factors that play important roles in development, wound healing, and maintenance of tissues. There are nearly two dozen FGFs that can generate hundreds of isoforms and have separate functions. FGFs act as mitogens, promoting cell proliferation, and are critical for development of vertebrates and invertebrates. FGFs function by activating fibroblast growth factor receptors, causing phosphorylation of proteins that perform new functions. The receptor tyrosine kinase pathway is an important signal transduction pathway where FGF binding activates a cascade of phosphorylation leading to transcription factors that determine the developmental course of the cell.
The TGF-beta superfamily is a large family of secreted signaling molecules that mediate many key events in growth and development. It includes over 30 members such as Activins, Nodals, BMPs, and GDFs. These proteins signal through cell-surface receptors and Smad proteins to regulate gene expression and control processes like proliferation, differentiation, and matrix production. Aberrant TGF-beta superfamily signaling is associated with several human diseases including cancer and fibrosis.
This document discusses EGF and SDF signaling and Akt-mediated resistance to apoptosis in human breast cancer cells. It summarizes that EGF and SDF can both activate the Akt pathway through different mechanisms, either directly or indirectly, leading to increased cell survival, proliferation, and resistance to apoptosis. Western blotting of breast cancer cells treated with EGF or SDF showed both ligands activated Akt, though EGF activated Akt more sharply while SDF activated it more quickly. The document reviews the pathways of EGF and SDF signaling that result in Akt activation and discusses potential targets in these pathways for inhibiting Akt's anti-apoptotic effects in cancer treatment.
The document discusses cell cycle checkpoints which monitor cell growth, DNA replication, and chromosome segregation. It describes the different phases of the cell cycle including interphase and mitosis. Checkpoints at the G1, G2, and M phases are controlled by regulators like cyclins, CDKs, and inhibitors. Dysregulation of cell cycle progression can lead to diseases like cancer. Targeting cell cycle checkpoints and regulators is a potential approach for cancer treatment.
Cell growth can refer to the increase in cell size and organelles during interphase (G1 and G2 phases) or the growth of a cell population through cell division (M phase). The cell cycle consists of G1, S, G2, and M phases, separated by gap phases G1 and G2. Growth factors such as EGF, TGF-α, HGF, and PDGF act as ligands that bind to cell surface receptors and transmit signals to regulate the cell cycle. These signals activate intracellular pathways using second messengers to induce transcription factors that drive expression of genes controlling cell cycle progression and cell growth.
Down regulationof forkheadboxm1transcriptionfactorleadstotheinhibitionofinvas...Chau Chan Lao
Down-regulation of Forkhead Box M1 Transcription Factor Leads to the Inhibition of Invasion and Angiogenesis of Pancreatic Cancer Cells.
Zhiwei Wang, Sanjeev Banerjee, Dejuan Kong, Yiwei Li, and Fazlul H. Sarkar
Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
Cancer Res 2007; 67: (17). September 1, 2007
The PI3K-Akt-mTOR pathway is an intracellular signal transduction pathway that promotes metabolism, proliferation, cell survival, growth and angiogenesis. Key components include receptor tyrosine kinases, PI3K, PIP2, PIP3, and Akt. Akt is activated by phosphorylation and regulates various proteins involved in functions like cell growth. Dysregulation of this pathway can lead to cancer due to abnormal cell proliferation and is associated with neurodevelopmental disorders.
This presentation gives the basic idea, about the information on the role of tyrosine kinases in cancer. I have also included a phylogenetic tree for finding the relatedness between different organisms.
The PI3K-Akt pathway promotes metabolism, proliferation, cell survival, growth and angiogenesis through phosphorylation of downstream substrates. Key proteins in this pathway are phosphatidylinositol 3-kinase (PI3K) and Akt/Protein Kinase B. Research into this pathway began with the discovery of the oncogene ATK8 in 1977 and the cloning of PKB/Akt in 1991. It was later found that PI3K activates Akt and that phospholipids generated by PI3K are required for Akt activation.
Includes notes about Akt/Protein kinase B.Protein kinase is a kinase enzyme that modifies other proteins by chemically adding phosphate groups to them (phosphorylation).
Protein kinase B (PKB), also known as Akt, is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration
This file also includes the types, \signalling pathways and inhibitors of protein kinase B.
This document discusses signal transduction and how it relates to cancer. It describes how growth factors and receptors contribute to normal signal transduction and how this process is deregulated in cancer. It explains that growth factors regulate growth, proliferation and survival, which are all altered in cancer. Several growth factors and receptors that can contribute to oncogenesis are identified. It also summarizes several key intracellular signaling pathways, like MAPK pathways, that are activated by growth factors and can result in the cancer phenotype if altered.
1362575848 growth factos presentation a baldfsimedia
Growth factors play an essential role in diabetic foot ulcer management. Platelet-derived growth factor (PDGF) is a significant growth factor that is released during wound healing and promotes angiogenesis, fibroblast proliferation, and re-epithelialization. Recombinant human PDGF-BB (rhPDGF-BB) has been shown to accelerate wound healing in diabetic foot ulcers by stimulating cellular processes involved in repair when applied topically according to dosage guidelines.
The PTEN and PI3-Kinase Pathway in Cancer pptBernard Bahaah
The document presents information on PTEN and the PI3-kinase pathway in cancer. It discusses how PTEN acts as a tumor suppressor by negatively regulating the PI3-kinase pathway, which promotes cell growth and survival. Mutations or deletions of the PTEN gene are common in many cancer types as they lead to overactivation of the PI3-kinase pathway. The document outlines the signaling events in the PI3-kinase pathway, how PTEN regulates it, additional functions of PTEN, and potential cancer therapeutics that target this pathway.
TGF-β is a polypeptide cytokine that performs many cellular functions and controls processes like cell proliferation, immune regulation, apoptosis, and tissue repair. It signals through Smad-dependent and Smad-independent pathways. The Smad-dependent pathway involves TGF-β binding to receptors that phosphorylate R-Smads, which then complex with Co-Smads and regulate transcription of target genes. The Smad-independent pathway activates proteins like MAPKs, PI3K/Akt, and TRAF6. TGF-β signaling regulates diverse biological processes through these pathways.
The document summarizes the AKT/PKB signaling pathway. It discusses that AKT/PKB promotes metabolism, proliferation, and cell survival as an intracellular signal transduction pathway. Key proteins in the pathway are AKT/PKB and PI3K. The pathway regulates processes like protein synthesis, cell survival, cell proliferation, and glucose metabolism. Dysregulation of the pathway through mutations can contribute to cancer due to AKT/PKB's role in regulating critical cellular functions, making it a potential therapeutic target.
The document discusses checkpoints in the cell cycle that control progression from one phase to the next. It describes the G1, G2, and M phase checkpoints, noting that the G1 checkpoint determines whether a cell will continue through the cell cycle or become quiescent. It also explains that the G2 checkpoint is driven by maturation promoting factor, a protein complex of cyclins and cyclin-dependent kinases, and that the M phase checkpoint ensures proper chromosome attachment before anaphase.
A cell cycle is a series of events that takes place in a cell as it grows and divides. The process has to be correct and regulated. This slide illustrated Cell cycle and its regulation. Check the slides to know more.
1) The document discusses candidate molecules that may act as tumor suppressors for human uterine mesenchymal tumors. It focuses on LMP2/β1i, which is expressed in normal myometrium but defective or absent in human uterine leiomyosarcoma (Ut-LMS).
2) Mice deficient in LMP2/β1i spontaneously develop Ut-LMS, with similarities to the human disease. This suggests LMP2/β1i may function as a tumor suppressor for Ut-LMS.
3) While tumor suppressor pathways like p53 and Rb are often disrupted in cancers, their roles in Ut-LMS tumorigenesis are unclear
Potential Diagnostic Biomarkers for Human Uterine Mesenchymal Tumours Especia...ijtsrd
Aims Although the majority of smooth muscle neoplasms found in the uterus are benign, uterine leiomyosarcoma is extremely malignant, with high rates of recurrence and metastasis. The development of gynecologic tumors is often correlated with secretion of female hormone however, the development of human uterine leiomyosarcoma is not substantially correlated with hormonal conditions, and the risk factors are unclearly understood. Importantly, a diagnostic biomarker, which distinguishes malignant human uterine leiomyosarcoma from benign tumor leiomyoma is yet to be established. It is necessary to analyze risk factors associated with human uterine leiomyosarcoma, in order to establish a diagnostic biomarker and a clinical treatment method. Methodology Histology and Immunofluorescence Staining tissue sections 5 µm were prepared and stained with HandE for routine histological examination or were processed further for immunofluorescence staining with appropriate antibodies. Furthermore, a total of 57 patients between 32 and 83 years of age and diagnosed as having smooth muscle tumors of the uterus were selected from pathological files. Immunohistochemistry staining for LMP2 1i and cyclin E1 was performed on serial human uterine leiomyosarcoma, leiomyoma and myometrium sections. Results Homozygous deficient mice for a proteasome subunit LMP2 1i spontaneously develop uterine leiomyosarcoma, with a disease prevalence of ~40 by 14 months of age. Defective LMP2 1i and cyclin E1 positive expressions in human uterine leiomyosarcoma were demonstrated, but the reverse result was obtained in human leiomyoma and myometrium. Conclusions LMP2 1i and cyclin E1 differential expressions may be one of the risk factors for human uterine leiomyosarcoma. LMP2 1i and cyclin E1 may be potential diagnostic biomarker and targeted molecule for a new therapeutic approach. Takuma Hayashi | Hiroyuki Aburatani | Ikuo Konishi "Potential Diagnostic Biomarkers for Human Uterine Mesenchymal Tumours: Especially LMP2/1i and Cyclin E1-Differential Expressions" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd62380.pdf Paper Url: https://www.ijtsrd.com/medicine/other/62380/potential-diagnostic-biomarkers-for-human-uterine-mesenchymal-tumours-especially-lmp21i-and-cyclin-e1differential-expressions/takuma-hayashi
This document discusses using stem cells for diabetes treatment. It mentions:
1. Human embryonic stem cells, induced pluripotent stem cells, umbilical cord blood, and mesenchymal stromal cells can potentially be used for diabetes treatment.
2. Human embryonic stem cells can be differentiated into insulin-expressing cells through a stepwise process involving definitive endoderm and embryoid body formation under specific factors.
3. The goal is to generate enough functional insulin-producing beta cells to restore normal blood glucose levels in diabetics through cell-based therapies.
Preeclampsia and Eclampsia: A consequence of Immunological maladaptationiosrjce
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
Modulation of pluripotency in the porcine embryo and i ps cells (Dec.27,2012) Ahmad Usama
1) The study investigated signaling pathways involved in formation of the porcine inner cell mass (ICM) and methods to increase pluripotency in porcine embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs).
2) They found that inhibiting MEK and GSK3β signaling pathways in porcine embryos and iPSCs, combined with LIF treatment, promoted a naive pluripotent state similar to mouse ESCs.
3) Naive piPSCs expressed genes associated with naive pluripotency and showed higher germline differentiation potential than non-naive piPSCs. The study provides insights into regulating pluripotency in
This document provides an overview of myeloid leucopoiesis, or the formation of white blood cells from myeloid progenitor cells. It discusses the sites where white blood cell formation occurs, the growth factors involved in differentiation and proliferation, and the maturation process for granulocytes and monocytes. The key functions of neutrophils, eosinophils, basophils and monocytes/macrophages are also summarized, including their roles in phagocytosis and the innate immune response.
The document provides an overview of bacterial cell structure and its relationship to pathogenicity. It describes the key components of bacterial cells, including the capsule, cell wall, cytoplasmic membrane, flagella, pili, and differences between Gram-positive and Gram-negative bacteria. Specifically, it compares the thicker peptidoglycan cell wall of Gram-positive bacteria to the thinner cell wall and additional outer membrane of Gram-negative bacteria. It also discusses how various bacterial cell structures like the capsule, cell wall components, and lipopolysaccharides can induce pathogenic effects or immune responses in the host.
In principle, anti-growth signals can prevent cell proliferation by several complementary mechanisms.
The signal may cause dividing cells to enter G0, where they remain until external cues prod their re-entry into the proliferative pool.
Alternatively, the cells may enter a postmitotic, differentiated pool and lose replicative potential.
Non-replicative senescence, is another mechanism of escape from sustained cell growth.
And, as a last-ditch effort, the cells may be programmed for death by apoptosis.
Therefore, tumor suppressor genes have all these “tricks” in their toolbox designed to halt wayward cells from becoming malignant.
This research article investigates the effects of the natural flavonoid luteolin on colon cancer cells. The researchers found that physiological concentrations of luteolin induce apoptosis in colon cancer cells by increasing levels of the sphingolipid ceramide. Luteolin inhibits the conversion of ceramide to more complex sphingolipids and disrupts the transport of ceramide between organelles. These effects are mediated by luteolin's ability to inhibit the enzymes sphingosine kinase 2 and Akt, thereby reducing levels of the molecule sphingosine-1-phosphate which normally promotes cell survival. Overall, the study reveals that luteolin exerts anticancer effects by targeting the balance between ceramide and sphingosine-1-
Escrt proteins in physiology and diseasesSandeep Kumar
The document summarizes the roles of ESCRT proteins in various physiological processes and diseases. It discusses how ESCRT proteins mediate multivesicular body formation and are involved in cytokinesis, HIV budding, development, signal attenuation, cancer, autophagy, and neurodegeneration. It also provides unanswered questions about ESCRT protein functions in MVBs fusing with lysosomes vs plasma membrane, their specific roles in neurodegenerative diseases, and how ESCRT mutations can be lethal in multicellular organisms but not yeast.
This document provides an overview of bacteriology and bacterial structure-function relationships. It discusses the key differences between gram-positive and gram-negative bacteria, including their cell walls, membranes, and presence or absence of an outer membrane/periplasmic space. The growth curve of bacteria is also summarized, outlining the lag, exponential, stationary, and decline phases. Several bacterial structures are described in detail, including capsules, cell walls, flagella, pili, and their roles in pathogenicity.
The document is a lecture on bacteriology that covers:
1. The structure of bacterial cells and how it relates to pathogenicity, comparing Gram-positive and Gram-negative bacteria.
2. Key structures of bacterial cells like capsules, cell walls, membranes, pili and flagella and how they contribute to virulence.
3. The bacterial growth curve and the different phases bacteria go through - lag, exponential, stationary and decline.
4. How exposure to bacterial components over the growth cycle can induce both pathology and immune responses in the host.
The cell cycle and molecular basis of cancer can be summarized as follows:
The cell cycle is tightly regulated by cyclins, cyclin-dependent kinases (CDKs), and their inhibitors to ensure proper cell division and growth. Defects in cell cycle regulation can lead to uncontrolled cell growth and cancer. Cancer develops through the accumulation of genetic mutations in oncogenes and tumor suppressor genes, which disrupt the normal cell cycle checkpoints and allow cells to proliferate uncontrollably. Key cellular capabilities acquired during cancer progression include self-sufficiency in growth signals, insensitivity to anti-growth signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis.
The document discusses how immunologists have recently rediscovered the importance of metabolism in immune cell function. Technological advances like metabolomics have allowed researchers to better understand how metabolic pathways are directly linked to immune cell effector functions. The review will provide an overview of six major metabolic pathways (glycolysis, TCA cycle, pentose phosphate pathway, fatty acid oxidation, fatty acid synthesis, amino acid metabolism) and their roles in immune cells like T cells, macrophages, and dendritic cells. It aims to encourage immunologists to incorporate the perspective of immunometabolism into their research.
This thesis examines how probiotics modulate immune responses by stimulating bone marrow-derived dendritic cells (BMDCs) and basophils (BMBs) in co-culture experiments. Flow cytometry was used to analyze cell surface markers, transcription factors, and cytokines produced. Results showed that BMBs stimulated with probiotics increased IL-4 production, which is involved in Th2 polarization. BMDCs stimulated with probiotics increasingly produced cytokines that promote Th1, Th17, and Treg polarization. Co-cultures of BMDCs and BMBs likely enhanced Th2 immune responses. The probiotic strains Lactobacillus plantarum WCFS1 and Lactobacillus casei BL
Protein Structure, Post Translational Modifications and Protein FoldingSuresh Antre
Post-translational modifications (PTMs) are covalent processing events that change the properties of a protein by proteolytic cleavage or by addition of a modifying group to one or more amino acids.
Protein post-translational modification (PTM) plays an essential role in various cellular processes that modulates the physical and chemical properties, folding, conformation, stability and activity of proteins, thereby modifying the functions of proteins
This presentation provides an overview of the endoplasmic reticulum (ER), including its structure, functions, and regulation. Key points include: the ER is a network of tubules and sacs that synthesizes proteins and lipids, stores calcium, and aids protein folding; its shape is maintained by membrane-shaping proteins and interactions with other organelles; and the ER adapts in response to stresses through signaling pathways like the unfolded protein response. The presentation was given to undergraduate students to provide foundational knowledge about this important intracellular organelle.
Mast cells arise from bone marrow precursors and mature in tissues where they store preformed mediators in secretory granules. These granules contain histamine, proteases, cytokines and other compounds that are rapidly released during degranulation to influence immune responses. Mast cells are found near host-environment barriers and can promote both protective and harmful inflammatory reactions through granule mediator release. Their granules are heterogeneous and composed of electron-dense cores surrounded by translucent areas, though granule composition varies between tissue-derived versus cultured mast cells.
UPS in diabetic microvascular complicationsSaeed Aghdam
The document discusses the ubiquitin-proteasome system (UPS) and its role in the development of microvascular complications of diabetes, specifically diabetic retinopathy and diabetic nephropathy. The UPS regulates protein quality control and degradation in cells and is involved in processes like cell cycle regulation and signal transduction. Dysregulation of the UPS due to hyperglycemia and oxidative stress may contribute to retinal and kidney damage caused by diabetes. Studies have shown UPS activity is altered in the retina and kidney under diabetic conditions. Better understanding how diabetes affects UPS function in the eye could lead to new treatment strategies for diabetic retinopathy.
‘Six Sigma Technique’ A Journey Through its Implementationijtsrd
The manufacturing industries all over the world are facing tough challenges for growth, development and sustainability in today’s competitive environment. They have to achieve apex position by adapting with the global competitive environment by delivering goods and services at low cost, prime quality and better price to increase wealth and consumer satisfaction. Cost Management ensures profit, growth and sustainability of the business with implementation of Continuous Improvement Technique like Six Sigma. This leads to optimize Business performance. The method drives for customer satisfaction, low variation, reduction in waste and cycle time resulting into a competitive advantage over other industries which did not implement it. The main objective of this paper ‘Six Sigma Technique A Journey Through Its Implementation’ is to conceptualize the effectiveness of Six Sigma Technique through the journey of its implementation. Aditi Sunilkumar Ghosalkar "‘Six Sigma Technique’: A Journey Through its Implementation" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64546.pdf Paper Url: https://www.ijtsrd.com/other-scientific-research-area/other/64546/‘six-sigma-technique’-a-journey-through-its-implementation/aditi-sunilkumar-ghosalkar
Edge Computing in Space Enhancing Data Processing and Communication for Space...ijtsrd
Edge computing, a paradigm that involves processing data closer to its source, has gained significant attention for its potential to revolutionize data processing and communication in space missions. With the increasing complexity and data volume generated by modern space missions, traditional centralized computing approaches face challenges related to latency, bandwidth, and security. Edge computing in space, involving on board processing and analysis of data, offers promising solutions to these challenges. This paper explores the concept of edge computing in space, its benefits, applications, and future prospects in enhancing space missions. Manish Verma "Edge Computing in Space: Enhancing Data Processing and Communication for Space Missions" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64541.pdf Paper Url: https://www.ijtsrd.com/computer-science/artificial-intelligence/64541/edge-computing-in-space-enhancing-data-processing-and-communication-for-space-missions/manish-verma
Dynamics of Communal Politics in 21st Century India Challenges and Prospectsijtsrd
Communal politics in India has evolved through centuries, weaving a complex tapestry shaped by historical legacies, colonial influences, and contemporary socio political transformations. This research comprehensively examines the dynamics of communal politics in 21st century India, emphasizing its historical roots, socio political dynamics, economic implications, challenges, and prospects for mitigation. The historical perspective unravels the intricate interplay of religious identities and power dynamics from ancient civilizations to the impact of colonial rule, providing insights into the evolution of communalism. The socio political dynamics section delves into the contemporary manifestations, exploring the roles of identity politics, socio economic disparities, and globalization. The economic implications section highlights how communal politics intersects with economic issues, perpetuating disparities and influencing resource allocation. Challenges posed by communal politics are scrutinized, revealing multifaceted issues ranging from social fragmentation to threats against democratic values. The prospects for mitigation present a multifaceted approach, incorporating policy interventions, community engagement, and educational initiatives. The paper conducts a comparative analysis with international examples, identifying common patterns such as identity politics and economic disparities. It also examines unique challenges, emphasizing Indias diverse religious landscape, historical legacy, and secular framework. Lessons for effective strategies are drawn from international experiences, offering insights into inclusive policies, interfaith dialogue, media regulation, and global cooperation. By scrutinizing historical epochs, contemporary dynamics, economic implications, and international comparisons, this research provides a comprehensive understanding of communal politics in India. The proposed strategies for mitigation underscore the importance of a holistic approach to foster social harmony, inclusivity, and democratic values. Rose Hossain "Dynamics of Communal Politics in 21st Century India: Challenges and Prospects" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64528.pdf Paper Url: https://www.ijtsrd.com/humanities-and-the-arts/history/64528/dynamics-of-communal-politics-in-21st-century-india-challenges-and-prospects/rose-hossain
Assess Perspective and Knowledge of Healthcare Providers Towards Elehealth in...ijtsrd
Background and Objective Telehealth has become a well known tool for the delivery of health care in Saudi Arabia, and the perspective and knowledge of healthcare providers are influential in the implementation, adoption and advancement of the method. This systematic review was conducted to examine the current literature base regarding telehealth and the related healthcare professional perspective and knowledge in the Kingdom of Saudi Arabia. Materials and Methods This systematic review was conducted by searching 7 databases including, MEDLINE, CINHAL, Web of Science, Scopus, PubMed, PsycINFO, and ProQuest Central. Studies on healthcare practitioners telehealth knowledge and perspectives published in English in Saudi Arabia from 2000 to 2023 were included. Boland directed this comprehensive review. The researchers examined each connected study using the AXIS tool, which evaluates cross sectional systematic reviews. Narrative synthesis was used to summarise and convey the data. Results Out of 1840 search results, 10 studies were included. Positive outlook and limited knowledge among providers were seen across trials. Healthcare professionals like telehealth for its ability to improve quality, access, and delivery, save time and money, and be successful. Age, gender, occupation, and work experience also affect health workers knowledge. In Saudi Arabia, healthcare professionals face inadequate expert assistance, patient privacy, internet connection concerns, lack of training courses, lack of telehealth understanding, and high costs while performing telemedicine. Conclusions Healthcare practitioners telehealth perceptions and knowledge were examined in this systematic study. Its collection of concerned experts different personal attitudes and expertise would help enhance telehealths implementation in Saudi Arabia, develop its healthcare delivery alternative, and eliminate frequent problems. Badriah Mousa I Mulayhi | Dr. Jomin George | Judy Jenkins "Assess Perspective and Knowledge of Healthcare Providers Towards Elehealth in Saudi Arabia: A Systematic Review" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64535.pdf Paper Url: https://www.ijtsrd.com/medicine/other/64535/assess-perspective-and-knowledge-of-healthcare-providers-towards-elehealth-in-saudi-arabia-a-systematic-review/badriah-mousa-i-mulayhi
The Impact of Digital Media on the Decentralization of Power and the Erosion ...ijtsrd
The impact of digital media on the distribution of power and the weakening of traditional gatekeepers has gained considerable attention in recent years. The adoption of digital technologies and the internet has resulted in declining influence and power for traditional gatekeepers such as publishing houses and news organizations. Simultaneously, digital media has facilitated the emergence of new voices and players in the media industry. Digital medias impact on power decentralization and gatekeeper erosion is visible in several ways. One significant aspect is the democratization of information, which enables anyone with an internet connection to publish and share content globally, leading to citizen journalism and bypassing traditional gatekeepers. Another aspect is the disruption of conventional media industry business models, as traditional organizations struggle to adjust to the decrease in advertising revenue and the rise of digital platforms. Alternative business models, such as subscription models and crowdfunding, have become more prevalent, leading to the emergence of new players. Overall, the impact of digital media on the distribution of power and the weakening of traditional gatekeepers has brought about significant changes in the media landscape and the way information is shared. Further research is required to fully comprehend the implications of these changes and their impact on society. Dr. Kusum Lata "The Impact of Digital Media on the Decentralization of Power and the Erosion of Traditional Gatekeepers" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64544.pdf Paper Url: https://www.ijtsrd.com/humanities-and-the-arts/political-science/64544/the-impact-of-digital-media-on-the-decentralization-of-power-and-the-erosion-of-traditional-gatekeepers/dr-kusum-lata
Online Voices, Offline Impact Ambedkars Ideals and Socio Political Inclusion ...ijtsrd
This research investigates the nexus between online discussions on Dr. B.R. Ambedkars ideals and their impact on social inclusion among college students in Gurugram, Haryana. Surveying 240 students from 12 government colleges, findings indicate that 65 actively engage in online discussions, with 80 demonstrating moderate to high awareness of Ambedkars ideals. Statistically significant correlations reveal that higher online engagement correlates with increased awareness p 0.05 and perceived social inclusion. Variations across colleges and a notable effect of college type on perceived social inclusion highlight the influence of contextual factors. Furthermore, the intersectional analysis underscores nuanced differences based on gender, caste, and socio economic status. Dr. Kusum Lata "Online Voices, Offline Impact: Ambedkar's Ideals and Socio-Political Inclusion - A Study of Gurugram District" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64543.pdf Paper Url: https://www.ijtsrd.com/humanities-and-the-arts/political-science/64543/online-voices-offline-impact-ambedkars-ideals-and-sociopolitical-inclusion--a-study-of-gurugram-district/dr-kusum-lata
Problems and Challenges of Agro Entreprenurship A Studyijtsrd
Noting calls for contextualizing Agro entrepreneurs problems and challenges of the agro entrepreneurs and for greater attention to the Role of entrepreneurs in agro entrepreneurship research, we conduct a systematic literature review of extent research in agriculture entrepreneurship to overcome the study objectives of complications of agro entrepreneurs through various factors, Development of agriculture products is a key factor for the overall economic growth of agro entrepreneurs Agro Entrepreneurs produces firsthand large scale employment, utilizes the labor and natural resources, This research outlines the problems of Weather and Soil Erosions, Market price fluctuation, stimulates labor cost problems, reduces concentration of Price volatility, Dependency on Intermediaries, induces Limited Bargaining Power, and Storage and Transportation Costs. This paper mainly devoted to highlight Problems and challenges faced for the sustainable of Agro Entrepreneurs in India. Vinay Prasad B "Problems and Challenges of Agro Entreprenurship - A Study" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64540.pdf Paper Url: https://www.ijtsrd.com/other-scientific-research-area/other/64540/problems-and-challenges-of-agro-entreprenurship--a-study/vinay-prasad-b
Comparative Analysis of Total Corporate Disclosure of Selected IT Companies o...ijtsrd
Disclosure is a process through which a business enterprise communicates with external parties. A corporate disclosure is communication of financial and non financial information of the activities of a business enterprise to the interested entities. Corporate disclosure is done through publishing annual reports. So corporate disclosure through annual reports plays a vital role in the life of all the companies and provides valuable information to investors. The basic objectives of corporate disclosure is to give a true and fair view of companies to the parties related either directly or indirectly like owner, government, creditors, shareholders etc. in the companies act, provisions have been made about mandatory and voluntary disclosure. The IT sector in India is rapidly growing, the trend to invest in the IT sector is rising and employment opportunities in IT sectors are also increasing. Therefore the IT sector is expected to have fair, full and adequate disclosure of all information. Unfair and incomplete disclosure may adversely affect the entire economy. A research study on disclosure practices of IT companies could play an important role in this regard. Hence, the present research study has been done to study and review comparative analysis of total corporate disclosure of selected IT companies of India and to put forward overall findings and suggestions with a view to increase disclosure score of these companies. The researcher hopes that the present research study will be helpful to all selected Companies for improving level of corporate disclosure through annual reports as well as the government, creditors, investors, all business organizations and upcoming researcher for comparative analyses of level of corporate disclosure with special reference to selected IT companies. Dr. Vaibhavi D. Thaker "Comparative Analysis of Total Corporate Disclosure of Selected IT Companies of India" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64539.pdf Paper Url: https://www.ijtsrd.com/other-scientific-research-area/other/64539/comparative-analysis-of-total-corporate-disclosure-of-selected-it-companies-of-india/dr-vaibhavi-d-thaker
The Impact of Educational Background and Professional Training on Human Right...ijtsrd
This study investigated the impact of educational background and professional training on human rights awareness among secondary school teachers in the Marathwada region of Maharashtra, India. The key findings reveal that higher levels of education, particularly a master’s degree, and fields of study related to education, humanities, or social sciences are associated with greater human rights awareness among teachers. Additionally, both pre service teacher training and in service professional development programs focused on human rights education significantly enhance teacher’s knowledge, skills, and competencies in promoting human rights principles in their classrooms. Baig Ameer Bee Mirza Abdul Aziz | Dr. Syed Azaz Ali Amjad Ali "The Impact of Educational Background and Professional Training on Human Rights Awareness among Secondary School Teachers" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64529.pdf Paper Url: https://www.ijtsrd.com/humanities-and-the-arts/education/64529/the-impact-of-educational-background-and-professional-training-on-human-rights-awareness-among-secondary-school-teachers/baig-ameer-bee-mirza-abdul-aziz
A Study on the Effective Teaching Learning Process in English Curriculum at t...ijtsrd
“One Language sets you in a corridor for life. Two languages open every door along the way” Frank Smith English as a foreign language or as a second language has been ruling in India since the period of Lord Macaulay. But the question is how much we teach or learn English properly in our culture. Is there any scope to use English as a language rather than a subject How much we learn or teach English without any interference of mother language specially in the classroom teaching learning scenario in West Bengal By considering all these issues the researcher has attempted in this article to focus on the effective teaching learning process comparing to other traditional strategies in the field of English curriculum at the secondary level to investigate whether they fulfill the present teaching learning requirements or not by examining the validity of the present curriculum of English. The purpose of this study is to focus on the effectiveness of the systematic, scientific, sequential and logical transaction of the course between the teachers and the learners in the perspective of the 5Es programme that is engage, explore, explain, extend and evaluate. Sanchali Mondal | Santinath Sarkar "A Study on the Effective Teaching Learning Process in English Curriculum at the Secondary Level of West Bengal" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd62412.pdf Paper Url: https://www.ijtsrd.com/humanities-and-the-arts/education/62412/a-study-on-the-effective-teaching-learning-process-in-english-curriculum-at-the-secondary-level-of-west-bengal/sanchali-mondal
The Role of Mentoring and Its Influence on the Effectiveness of the Teaching ...ijtsrd
This paper reports on a study which was conducted to investigate the role of mentoring and its influence on the effectiveness of the teaching of Physics in secondary schools in the South West Region of Cameroon. The study adopted the convergent parallel mixed methods design, focusing on respondents in secondary schools in the South West Region of Cameroon. Both quantitative and qualitative data were collected, analysed separately, and the results were compared to see if the findings confirm or disconfirm each other. The quantitative analysis found that majority of the respondents 72 of Physics teachers affirmed that they had more experienced colleagues as mentors to help build their confidence, improve their teaching, and help them improve their effectiveness and efficiency in guiding learners’ achievements. Only 28 of the respondents disagreed with these statements. With majority respondents 72 agreeing with the statements, it implies that in most secondary schools, experienced Physics teachers act as mentors to build teachers’ confidence in teaching and improving students’ learning. The interview qualitative data analysis summarized how secondary school Principals use meetings with mentors and mentees to promote mentorship in the school milieu. This has helped strengthen teachers’ classroom practices in secondary schools in the South West Region of Cameroon. With the results confirming each other, the study recommends that mentoring should focus on helping teachers employ social interactions and instructional practices feedback and clarity in teaching that have direct measurable impact on students’ learning achievements. Andrew Ngeim Sumba | Frederick Ebot Ashu | Peter Agborbechem Tambi "The Role of Mentoring and Its Influence on the Effectiveness of the Teaching of Physics in Secondary Schools in the South West Region of Cameroon" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64524.pdf Paper Url: https://www.ijtsrd.com/management/management-development/64524/the-role-of-mentoring-and-its-influence-on-the-effectiveness-of-the-teaching-of-physics-in-secondary-schools-in-the-south-west-region-of-cameroon/andrew-ngeim-sumba
Design Simulation and Hardware Construction of an Arduino Microcontroller Bas...ijtsrd
This study primarily focuses on the design of a high side buck converter using an Arduino microcontroller. The converter is specifically intended for use in DC DC applications, particularly in standalone solar PV systems where the PV output voltage exceeds the load or battery voltage. To evaluate the performance of the converter, simulation experiments are conducted using Proteus Software. These simulations provide insights into the input and output voltages, currents, powers, and efficiency under different state of charge SoC conditions of a 12V,70Ah rechargeable lead acid battery. Additionally, the hardware design of the converter is implemented, and practical data is collected through operation, monitoring, and recording. By comparing the simulation results with the practical results, the efficiency and performance of the designed converter are assessed. The findings indicate that while the buck converter is suitable for practical use in standalone PV systems, its efficiency is compromised due to a lower output current. Chan Myae Aung | Dr. Ei Mon "Design Simulation and Hardware Construction of an Arduino-Microcontroller Based DC-DC High-Side Buck Converter for Standalone PV System" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64518.pdf Paper Url: https://www.ijtsrd.com/engineering/mechanical-engineering/64518/design-simulation-and-hardware-construction-of-an-arduinomicrocontroller-based-dcdc-highside-buck-converter-for-standalone-pv-system/chan-myae-aung
Sustainable Energy by Paul A. Adekunte | Matthew N. O. Sadiku | Janet O. Sadikuijtsrd
Energy becomes sustainable if it meets the needs of the present without compromising the ability of future generations to meet their own needs. Some of the definitions of sustainable energy include the considerations of environmental aspects such as greenhouse gas emissions, social, and economic aspects such as energy poverty. Generally far more sustainable than fossil fuel are renewable energy sources such as wind, hydroelectric power, solar, and geothermal energy sources. Worthy of note is that some renewable energy projects, like the clearing of forests to produce biofuels, can cause severe environmental damage. The sustainability of nuclear power which is a low carbon source is highly debated because of concerns about radioactive waste, nuclear proliferation, and accidents. The switching from coal to natural gas has environmental benefits, including a lower climate impact, but could lead to delay in switching to more sustainable options. “Carbon capture and storage” can be built into power plants to remove the carbon dioxide CO2 emissions, but this technology is expensive and has rarely been implemented. Leading non renewable energy sources around the world is fossil fuels, coal, petroleum, and natural gas. Nuclear energy is usually considered another non renewable energy source, although nuclear energy itself is a renewable energy source, but the material used in nuclear power plants is not. The paper addresses the issue of sustainable energy, its attendant benefits to the future generation, and humanity in general. Paul A. Adekunte | Matthew N. O. Sadiku | Janet O. Sadiku "Sustainable Energy" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64534.pdf Paper Url: https://www.ijtsrd.com/engineering/electrical-engineering/64534/sustainable-energy/paul-a-adekunte
Concepts for Sudan Survey Act Implementations Executive Regulations and Stand...ijtsrd
This paper aims to outline the executive regulations, survey standards, and specifications required for the implementation of the Sudan Survey Act, and for regulating and organizing all surveying work activities in Sudan. The act has been discussed for more than 5 years. The Land Survey Act was initiated by the Sudan Survey Authority and all official legislations were headed by the Sudan Ministry of Justice till it was issued in 2022. The paper presents conceptual guidelines to be used for the Survey Act implementation and to regulate the survey work practice, standardizing the field surveys, processing, quality control, procedures, and the processes related to survey work carried out by the stakeholders and relevant authorities in Sudan. The conceptual guidelines are meant to improve the quality and harmonization of geospatial data and to aid decision making processes as well as geospatial information systems. The established comprehensive executive regulations will govern and regulate the implementation of the Sudan Survey Geomatics Act in all surveying and mapping practices undertaken by the Sudan Survey Authority SSA and state local survey departments for public or private sector organizations. The targeted standards and specifications include the reference frame, projection, coordinate systems, and the guidelines and specifications that must be followed in the field of survey work, processes, and mapping products. In the last few decades, there has been a growing awareness of the importance of geomatics activities and measurements on the Earths surface in space and time, together with observing and mapping the changes. In such cases, data must be captured promptly, standardized, and obtained with more accuracy and specified in much detail. The paper will also highlight the current situation in Sudan, the degree to which survey standards are used, the problems encountered, and the errors that arise from not using the standards and survey specifications. Kamal A. A. Sami "Concepts for Sudan Survey Act Implementations - Executive Regulations and Standards" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd63484.pdf Paper Url: https://www.ijtsrd.com/engineering/civil-engineering/63484/concepts-for-sudan-survey-act-implementations--executive-regulations-and-standards/kamal-a-a-sami
Towards the Implementation of the Sudan Interpolated Geoid Model Khartoum Sta...ijtsrd
The discussions between ellipsoid and geoid have invoked many researchers during the recent decades, especially during the GNSS technology era, which had witnessed a great deal of development but still geoid undulation requires more investigations. To figure out a solution for Sudans local geoid, this research has tried to intake the possibility of determining the geoid model by following two approaches, gravimetric and geometrical geoid model determination, by making use of GNSS leveling benchmarks at Khartoum state. The Benchmarks are well distributed in the study area, in which, the horizontal coordinates and the height above the ellipsoid have been observed by GNSS while orthometric heights were carried out using precise leveling. The Global Geopotential Model GGM represented in EGM2008 has been exploited to figure out the geoid undulation at the benchmarks in the study area. This is followed by a fitting process, that has been done to suit the geoid undulation data which has been computed using GNSS leveling data and geoid undulation inspired by the EGM2008. Two geoid surfaces were created after the fitting process to ensure that they are identical and both of them could be counted for getting the same geoid undulation with an acceptable accuracy. In this respect, statistical operation played an important role in ensuring the consistency and integrity of the model by applying cross validation techniques splitting the data into training and testing datasets for building the geoid model and testing its eligibility. The geometrical solution for geoid undulation computation has been utilized by applying straightforward equations that facilitate the calculation of the geoid undulation directly through applying statistical techniques for the GNSS leveling data of the study area to get the common equation parameters values that could be utilized to calculate geoid undulation of any position in the study area within the claimed accuracy. Both systems were checked and proved eligible to be used within the study area with acceptable accuracy which may contribute to solving the geoid undulation problem in the Khartoum area, and be further generalized to determine the geoid model over the entire country, and this could be considered in the future, for regional and continental geoid model. Ahmed M. A. Mohammed. | Kamal A. A. Sami "Towards the Implementation of the Sudan Interpolated Geoid Model (Khartoum State Case Study)" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd63483.pdf Paper Url: https://www.ijtsrd.com/engineering/civil-engineering/63483/towards-the-implementation-of-the-sudan-interpolated-geoid-model-khartoum-state-case-study/ahmed-m-a-mohammed
Activating Geospatial Information for Sudans Sustainable Investment Mapijtsrd
Sudan is witnessing an acceleration in the processes of development and transformation in the performance of government institutions to raise the productivity and investment efficiency of the government sector. The development plans and investment opportunities have focused on achieving national goals in various sectors. This paper aims to illuminate the path to the future and provide geospatial data and information to develop the investment climate and environment for all sized businesses, and to bridge the development gap between the Sudan states. The Sudan Survey Authority SSA is the main advisor to the Sudan Government in conducting surveying, mappings, designing, and developing systems related to geospatial data and information. In recent years, SSA made a strategic partnership with the Ministry of Investment to activate Geospatial Information for Sudans Sustainable Investment and in particular, for the preparation and implementation of the Sudan investment map, based on the directives and objectives of the Ministry of Investment MI in Sudan. This paper comes within the framework of activating the efforts of the Ministry of Investment to develop technical investment services by applying techniques adopted by the Ministry and its strategic partners for advancing investment processes in the country. Kamal A. A. Sami "Activating Geospatial Information for Sudan's Sustainable Investment Map" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd63482.pdf Paper Url: https://www.ijtsrd.com/engineering/information-technology/63482/activating-geospatial-information-for-sudans-sustainable-investment-map/kamal-a-a-sami
Educational Unity Embracing Diversity for a Stronger Societyijtsrd
In a rapidly changing global landscape, the importance of education as a unifying force cannot be overstated. This paper explores the crucial role of educational unity in fostering a stronger and more inclusive society through the embrace of diversity. By examining the benefits of diverse learning environments, the paper aims to highlight the positive impact on societal strength. The discussion encompasses various dimensions, from curriculum design to classroom dynamics, and emphasizes the need for educational institutions to become catalysts for unity in diversity. It highlights the need for a paradigm shift in educational policies, curricula, and pedagogical approaches to ensure that they are reflective of the diverse fabric of society. This paper also addresses the challenges associated with implementing inclusive educational practices and offers practical strategies for overcoming barriers. It advocates for collaborative efforts between educational institutions, policymakers, and communities to create a supportive ecosystem that promotes diversity and unity. Mr. Amit Adhikari | Madhumita Teli | Gopal Adhikari "Educational Unity: Embracing Diversity for a Stronger Society" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64525.pdf Paper Url: https://www.ijtsrd.com/humanities-and-the-arts/education/64525/educational-unity-embracing-diversity-for-a-stronger-society/mr-amit-adhikari
Integration of Indian Indigenous Knowledge System in Management Prospects and...ijtsrd
The diversity of indigenous knowledge systems in India is vast and can vary significantly between different communities and regions. Preserving and respecting these knowledge systems is crucial for maintaining cultural heritage, promoting sustainable practices, and fostering cross cultural understanding. In this paper, an overview of the prospects and challenges associated with incorporating Indian indigenous knowledge into management is explored. It is found that IIKS helps in management in many areas like sustainable development, tourism, food security, natural resource management, cultural preservation and innovation, etc. However, IIKS integration with management faces some challenges in the form of a lack of documentation, cultural sensitivity, language barriers legal framework, etc. Savita Lathwal "Integration of Indian Indigenous Knowledge System in Management: Prospects and Challenges" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd63500.pdf Paper Url: https://www.ijtsrd.com/management/accounting-and-finance/63500/integration-of-indian-indigenous-knowledge-system-in-management-prospects-and-challenges/savita-lathwal
DeepMask Transforming Face Mask Identification for Better Pandemic Control in...ijtsrd
The COVID 19 pandemic has highlighted the crucial need of preventive measures, with widespread use of face masks being a key method for slowing the viruss spread. This research investigates face mask identification using deep learning as a technological solution to be reducing the risk of coronavirus transmission. The proposed method uses state of the art convolutional neural networks CNNs and transfer learning to automatically recognize persons who are not wearing masks in a variety of circumstances. We discuss how this strategy improves public health and safety by providing an efficient manner of enforcing mask wearing standards. The report also discusses the obstacles, ethical concerns, and prospective applications of face mask detection systems in the ongoing fight against the pandemic. Dilip Kumar Sharma | Aaditya Yadav "DeepMask: Transforming Face Mask Identification for Better Pandemic Control in the COVID-19 Era" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd64522.pdf Paper Url: https://www.ijtsrd.com/engineering/electronics-and-communication-engineering/64522/deepmask-transforming-face-mask-identification-for-better-pandemic-control-in-the-covid19-era/dilip-kumar-sharma
Streamlining Data Collection eCRF Design and Machine Learningijtsrd
Efficient and accurate data collection is paramount in clinical trials, and the design of Electronic Case Report Forms eCRFs plays a pivotal role in streamlining this process. This paper explores the integration of machine learning techniques in the design and implementation of eCRFs to enhance data collection efficiency. We delve into the synergies between eCRF design principles and machine learning algorithms, aiming to optimize data quality, reduce errors, and expedite the overall data collection process. The application of machine learning in eCRF design brings forth innovative approaches to data validation, anomaly detection, and real time adaptability. This paper discusses the benefits, challenges, and future prospects of leveraging machine learning in eCRF design for streamlined and advanced data collection in clinical trials. Dhanalakshmi D | Vijaya Lakshmi Kannareddy "Streamlining Data Collection: eCRF Design and Machine Learning" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-8 | Issue-1 , February 2024, URL: https://www.ijtsrd.com/papers/ijtsrd63515.pdf Paper Url: https://www.ijtsrd.com/biological-science/biotechnology/63515/streamlining-data-collection-ecrf-design-and-machine-learning/dhanalakshmi-d
How to Make a Field Mandatory in Odoo 17Celine George
In Odoo, making a field required can be done through both Python code and XML views. When you set the required attribute to True in Python code, it makes the field required across all views where it's used. Conversely, when you set the required attribute in XML views, it makes the field required only in the context of that particular view.
Exploiting Artificial Intelligence for Empowering Researchers and Faculty, In...Dr. Vinod Kumar Kanvaria
Exploiting Artificial Intelligence for Empowering Researchers and Faculty,
International FDP on Fundamentals of Research in Social Sciences
at Integral University, Lucknow, 06.06.2024
By Dr. Vinod Kumar Kanvaria
বাংলাদেশের অর্থনৈতিক সমীক্ষা ২০২৪ [Bangladesh Economic Review 2024 Bangla.pdf] কম্পিউটার , ট্যাব ও স্মার্ট ফোন ভার্সন সহ সম্পূর্ণ বাংলা ই-বুক বা pdf বই " সুচিপত্র ...বুকমার্ক মেনু 🔖 ও হাইপার লিংক মেনু 📝👆 যুক্ত ..
আমাদের সবার জন্য খুব খুব গুরুত্বপূর্ণ একটি বই ..বিসিএস, ব্যাংক, ইউনিভার্সিটি ভর্তি ও যে কোন প্রতিযোগিতা মূলক পরীক্ষার জন্য এর খুব ইম্পরট্যান্ট একটি বিষয় ...তাছাড়া বাংলাদেশের সাম্প্রতিক যে কোন ডাটা বা তথ্য এই বইতে পাবেন ...
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বিসিএস ও ব্যাংক এর লিখিত পরীক্ষা ...+এছাড়া মাধ্যমিক ও উচ্চমাধ্যমিকের স্টুডেন্টদের জন্য অনেক কাজে আসবে ...
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2. International Journal of Trend in Scientific Research and Development (IJTSRD) @ www.ijtsrd.com eISSN: 2456-6470
@ IJTSRD | Unique Paper ID - IJTSRD23892 | Volume – 3 | Issue – 4 | May-Jun 2019 Page: 598
presentation (TAP) 1 and TAP2 genes [11]. Several
experiments have shown that IFN-γ-induced-incorporation
of LMP2/β1i and LMP7/β5i into the 20S proteasome is
responsible for antigen presentation [12,13]. Furthermore,
the proteasome reconstructed by LMP2/β1i and LMP7/β5i,
referred to as immuno-proteasome, produced increased
chymotryptic and tryptic protease activities and modulated
cleavage-site preferences of the proteasome [14-17]. Thus,
immuno-proteasomes in different cells normally differ in
subunit composition and functional activities in a way that
correlates with the cell’s capacity for antigen presentation
[1]. This review shows that physiological functions of
LMP2/β1i are important for maintaining embryo
implantation and transforming mesenchymal cell in the
female genital system.
Physiological significance of LMP2/ββββ1i in embryo
implantation
Implantation of the embryo into the uterine endometriumis
a highly regulated event critical for the establishment of
pregnancy. Successful embryo implantation depends upon
the synchronized development of both the invasiveness of
the embryo and receptivity of the endometrium [18]. This
process is accompanied by extensive degradation and
remodeling of the extracellular matrix (ECM). Numerous
studies in mice, primates, and humans have shown that
matrix metalloproteinases (MMPs), which are responsible
for degrading the ECM, are key regulators for blastocyst
implantation [19-21]. Ubiquitin-related proteins were
shown to be present in human, baboon,rhesusmonkey, cow,
sheep, and mouse pregnant uteri [22-26], and may be
essential for endometrial modification and placental
development during early pregnancy. However, no direct
evidence has show whether the UPS is involved in embryo
implantation or has a regulatory effect on the activities of
MMP-2 and MMP-9.
The expression levels of LMP2/β1i and LMP7/β5i
significantly increased with the elongation of pregnancy.
LMP2/β1i and LMP7/β5i mRNAs were mainly expressed in
the luminal and glandular epithelia on Day 12 of pregnancy.
On Days 18 and 26 of pregnant Macaca mulatta, strong
signals of LMP2/β1i and LMP7/β5i mRNAs were detected in
the placental villi, trophoblastic column, and arterial
endothelial cells close to the implantation site, and moderate
expressions were found in the trophoblastic shell and
glandular epithelium (Fig. 1). LMP2/β1i and LMP7/β5i
mRNAs were extensivelydistributed inthestromaon Day 26
of pregnancy. The expression patterns of LMP2/β1i and
LMP7/β5i were like those of theirtranscripts,whereas weak
immunostaining LMP2/β1i and LMP7/β5i were detected in
stroma at all stages of pregnancy. LMP2/β1i and LMP7/β5i
may be involved in placental villi invasion, degradation of
ECM, immune tolerance, glandular secretion, and
angiogenesis. The regulatory mechanismofLMP2/β1ionthe
expression and activities of MMP-2 and MMP-9 was
examined using the human invasiveextravilloustrophoblast
cell line, HTR8/Svneo. Although in LMP2/β1i-inhibited cells,
the expression of mRNA encodingthenuclearfactorkappa-B
(NF-κB)1 subunits, p105 and RelAp65 remainednormal,the
20S proteasome processes NF-κB1 p105 into p50 is not
observed [27]. In defective condition of LMP2/β1i, inactive
NF-κB1 results in defects in MMP-2 and MMP-9 activation.
Embryo implantation involvestheinvasion of placentalextra
villous trophoblast cells (EVTs) into the uterus. Hyperactive
EVT invasion occurs in hydatidiform moles and
choriocarcinomas. Normal human placentas or placentas
from hydatidiform mole patients were collected and the
expression of LMP2/β1i in different cell types including
trophoblastic column (TC), cytotrophoblast cells (CTB) and
syncytiotro phoblasts (STB) was examined under different
pathological states by immunohistochemical analysis. The
expression of LMP2/β1i in TC of partial hydatidiform mole
and complete hydatidiform mole placentas, was higher than
that in TC of normal human placentas.Theoverexpression of
LMP2/β1i in trophoblast cells of hydatidiform moles may
contribute to its highly invasive phenotype (Fig. 1).
Figure1. This picture shows implantation of the blastocyst,
an early stage in embryo development,into the uterine
epithelium. Cooperative interactions between trophoblast
cells and maternal cells then form the placenta.In mammals,
trophoblast cells lie adjacent to the surface epitheliumof the
uterus, but they do not invade it. Natural killer (NK) cellsare
also not present. Nutrients are transferred to the fetus from
maternal blood vessels close totheuterine epithelium and in
glandular secretions. This arrangement is known as an
epitheliochorial placenta. The endometrium does not
transform into the decidua, which is the name given to an
endometrium that has differentiated under the influence of
progesterone. In human placentation, trophoblast cells
invade blood vessels as in rhesus macaques,buttheyreplace
the vascular endothelium in the myometrium to a greater
degree. Invasion extends beyond the endometrium into the
myometrium, whereas it is restricted to the endometrium in
rhesus macaques. In addition, trophoblast cells invade the
decidua, replacing the medial smooth muscle with fibrinoid
material. Accompanying these changes is the presence of
numerous NK cells. The expression of LMP2/β1i was
observed in the placental villi, trophoblastic column, and
arterial endothelial cells close to the implantation site, and
the moderate expression of LMP2/β1i was found in the
trophoblastic shell and glandular epithelium. LMP2/β1i
expression in trophoblast cells of hydatidiform moles may
contribute to its highly invasive phenotype.
Physiological role of LMP2/ββββ1i in uterine mesenchymal
tumorigenesis
UPS is essential physiological function for many cellular
processes, including the cell cycle, regulation of gene
expression, cell survival and immunological functions. The
individual expression of LMP2/β1i, LMP7/β5i, and
LMP10(MECL-1)/β2i subunits is believed to contribute to
the initiation and development of disorders including
tumorigenesis [27-29]. A recentstudy revealed auniquerole
3. International Journal of Trend in Scientific Research and Development (IJTSRD) @ www.ijtsrd.com eISSN: 2456-6470
@ IJTSRD | Unique Paper ID - IJTSRD23892 | Volume – 3 | Issue – 4 | May-Jun 2019 Page: 599
for LMP7/β5i in controlling pathogenic immune responses
and provided a therapeutic rationalefor targetingLMP7/β5i
in autoimmune disorders, especially rheumatoid arthritis
(RA) [30]. In mouse models of RA, a LMP7/β5i-inhibitory
treatment reversed the signs of disease and resulted in
reductions in cellular infiltration, cytokine production, and
autoantibody levels. Homozygous mice deficient in
LMP2/β1i exhibit tissue- and substrate-dependent
abnormalities in the physiological functions of UPS [31,32].
Uterine leiomyosarcoma (uLMS) reportedly occurred in
female LMP2/β1i-deficient mice at the age of 6 months or
older, and the incidence at 14 months of age was about 37%
[32-34]. Disease prevalence in mice is similar to that of
human uLMS, which occurs after menopause. Histological
studies of LMP2/β1i-deficient uterine tumors revealed the
characteristic abnormalities of human uLMS [32]. Recent
reports have demonstrated that LMP2/β1i is obligatory for
tumor surveillance and the tissue-specific role of LMP2/β1i
in protection from spontaneous uterus neoplasms [31,32].
The nuclei of tumor cells varied in size and shape;
furthermore, mitosis is frequently observed. The tumors
lacked lymphoid infiltrates, a sign of immune-recognition,
and consisted of uniformly elongated myometrium cells
arranged into bundles. The nuclei of tumor cells varied in
size and shape. In contrast, the myometrium cells of
C57BL/6 mice were normal in appearance [32]. Whereas
relatively few ki-67-positive cells, which are proliferating
cells, were observed in the basal cell layer of the normal
myometrium, most of the basal cells in LMP2/β1i-deficient
mice strongly expressed ki-67 [32]. This immunological
staining indicates the abnormal proliferation of LMP2/β1i-
lacking cells in the basal layer. Although the immuno-
proteasome from LMP7/β5i knock out mice showed altered
proteolytic activitiesandcleavagesitepreferences,noreport
has shown that LMP7/β5i knock out mice exhibit uterine
neoplasms [35]. Therefor complex of molecule of LMP2/β1i
with cellular cofactor(s), neither than physiologicalfunction
of immunoproteasome, likely prevents initiation of uterine
mesenchymal tumor [36,37].
Furthermore, immune-staining experiments revealed a
serious loss in the ability to induce LMP2/β1i expression in
human uLMS tissue relative to that in leiomyoma (LMA)ora
normal myometrium located in the same section [36,37]. Of
the 54 cases we examined with human uLMS, 46 were
negative for LMP2/β1i expression, 4 were focally positive,
and 2 were partially positive [37]. In two uLMS cases,
expression levels of LMP2/β1i were also evaluated in
skeletal muscle and rectum metastases from individual
patients with uLMS [37,38]. All lymph nodes were negative
for human uLMS metastases, and IHC studies showed
positivity for ki-67 and negativityfor LMP2/β1i[37-39].UPS
regulates the turnover and functions of hundreds of cellular
proteins in uterine tumorigenesis [40].
Final Consideration
In conclusion, LMP2/β1i was highly overexpressed in
trophoblast cells of hydatidiform moles, and expression of
LMP2/β1i in aggressive EVT cells directly regulated cell
invasion. Human uLMS is refractory to chemotherapy and
has a poor prognosis. Defective expressionof LMP2/β1imay
be one of the risk factors for the development of human
uLMS-like neoplasm. The physiological functions of
LMP2/β1i with cellular cofactor(s) are important to
maintain embryo implantation and the transformation of
mesenchymal cells in the female reproductive system.
Conflict of interest
All authors report no conflict of interest.
Acknowledgements: We sincerely thankProfessor LucVan
Kaer (Vanderbilt University Medical Center). Thisstudy was
supported in part by grants from the Ministry of Education,
Culture, Science and Technology, The Foundation of Osaka
Cancer Research, The Ichiro Kanehara Foundation for the
Promotion of Medical Science and Medical Care, The
Foundation for the Promotion of Cancer Research, The
Kanzawa MedicalResearch Foundation,TheShinshu Medical
Foundation, and TheTakeda Foundation forMedicalScience.
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