IOSR Journal of Pharmacy and Biological Sciences(IOSR-JPBS) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of Pharmacy and Biological Science. The journal welcomes publications of high quality papers on theoretical developments and practical applications in Pharmacy and Biological Science. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
This document discusses genetic markers related to non-alcoholic fatty liver disease (NAFLD). The study aimed to identify genetic markers that could help develop non-invasive diagnostic methods for NAFLD. The study identified 6 potentially associated genes, including the first association between SLC2A1 and NAFLD. Investigation of these genes in liver biopsies found they are regulated in NAFLD, and regulation increases with disease advancement, suggesting they could serve as markers for diagnosing NAFLD development phases.
This study examined the effects of valproic acid (VPA), a histone deacetylase inhibitor, on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Rats were divided into control, fibrotic, and VPA-treated groups. The fibrotic group received CCl4 injections to induce liver fibrosis, while the VPA-treated group also received VPA. After 6 weeks, liver tissue was analyzed. The fibrotic group showed disrupted liver architecture and hepatocyte damage. VPA treatment attenuated CCl4-induced fibrosis by preserving liver structure and reducing hepatocyte vacuolization. VPA also decreased expression of fibrosis markers α-SMA and Smad4, and lowered serum TGF
Cancer cells have altered metabolism compared to normal cells. They rely more on glycolysis even in the presence of oxygen (Warburg effect). This produces less ATP but helps cancer cells proliferate rapidly. Glutamine can also be used as an energy source. Targeting cancer cell metabolism through drugs like dichloroacetate is a potential treatment strategy. Cancers are heterogeneous so their metabolic profiles vary between cancer types and individual cells.
This study investigated the relationship between methylation of the MTHFR gene promoter and biomarkers in type 2 diabetes patients with and without complications. The researchers found that hypermethylation of the MTHFR promoter was associated with diabetic retinopathy and higher cholesterol/LDL levels. Patients with diabetic nephropathy and hypermethylation had higher levels of inflammation markers and antioxidant capacity compared to patients without complications. The results suggest DNA methylation of the MTHFR gene is linked to diabetic complications and altered metabolic and inflammatory states.
The document summarizes a study that examined the prevalence of metabolic syndrome across 7 Latin American cities according to NCEP ATP III criteria. Key findings include:
1) Metabolic syndrome prevalence ranged from 14% to 27% across cities, highest in Mexico City and Barquisimeto, and lowest in Quito.
2) Prevalence increased with age and more number of metabolic syndrome components.
3) Participants with metabolic syndrome had higher carotid intima-media thickness and more prevalent carotid plaque than those without.
4) Over half of individuals with certain metabolic abnormalities like high triglycerides or glucose issues met criteria for full metabolic syndrome.
Therapeutic targeting of cancer cell metabolism --role of metabolic enzymes, ...Younis I Munshi
The document summarizes recent developments in understanding the role of metabolic enzymes, oncogenes, and tumor suppressor genes in cancer progression and their potential as therapeutic targets. It discusses how cancer cells reprogram their metabolism to support uncontrolled proliferation. Key enzymes and pathways discussed include hexokinase, which phosphorylates glucose and fuels glycolysis; phosphofructokinase-2 and its role in regulating glycolytic flux; and pyruvate kinase isoforms PKM1 and PKM2 and their different functions in cancer metabolism. The document also examines how oncogenes like MYC and hypoxia-inducible factors influence these metabolic pathways to promote the Warburg effect and support tumor growth.
Serum zinc, copper and iron in children with chronic liver diseasesNoha Lotfy Ibrahim
Trace elements play a major role as both oxidants and antioxidants, promoting and protecting from tissue damage. The liver plays a pivotal role in the metabolism of trace elements and consequently their bioavailability. Therefore, we aimed to measure serum levels of essential trace elements in children with chronic liver diseases (CLDs) and to study their correlation with liver function tests.
Brian Covello: Diabetes Research ProposalBrian Covello
Brian Covello's diabetes research proposal. Type 2 diabetes mellitus consists of an array of dysfunctions characterized by hyperglycemia and resulting from the combination of resistance to insulin action, inadequate insulin secretion, and excessive or inappropriate glucagon secretion.
Essential update: FDA approves subcutaneous albiglutide for management of DM2
The FDA has approved once-weekly injectable albiglutide (Tanzeum), a glucagonlike peptide 1 (GLP-1) receptor agonist, along with diet and exercise for the treatment of type 2 diabetes.[1, 2] This agent may be used either as monotherapy or in combination with metformin, glimepiride, pioglitazone, or insulin.
Albiglutide should not be used for the following[1, 2] :
Patients with type 1 diabetes
Patients with diabetic ketoacidosis
First-line therapy in patients who can’t be managed with diet and exercise
Patients who have a personal or family history of medullary thyroid carcinoma (MTC)
Patients who have multiple endocrine neoplasia syndrome type 2
The most common adverse reactions associated with albiglutide were nausea/diarrhea and injection-site reactions.
There will be a boxed warning on albiglutide’s labeling about thyroid C-cell tumors being observed in rodent studies with this class of drugs; it is currently unknown whether albiglutide causes these tumors in humans, including MTC.[1, 2] Moreover, the FDA is also requiring a number of postmarketing studies, including a pediatric trial; an MTC case registry (≥15 y); and a cardiovascular (CV)-outcomes trial in patients with a baseline high risk of CV disease.
Signs and symptoms
Many patients with type 2 diabetes are asymptomatic. Clinical manifestations include the following:
Classic symptoms: Polyuria, polydipsia, polyphagia, and weight loss
Blurred vision
Lower-extremity paresthesias
Yeast infections (eg, balanitis in men)
See Presentation for more detail.
Diagnosis
Diagnostic criteria by the American Diabetes Association (ADA) include the following[3] :
A fasting plasma glucose (FPG) level of 126 mg/dL (7.0 mmol/L) or higher, or
A 2-hour plasma glucose level of 200 mg/dL (11.1 mmol/L) or higher during a 75-g oral glucose tolerance test (OGTT), or
A random plasma glucose of 200 mg/dL (11.1 mmol/L) or higher in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis
Whether a hemoglobin A1c (HbA1c) level of 6.5% or higher should be a primary diagnostic criterion or an optional criterion remains a point of controversy.
Indications for diabetes screening in asymptomatic adults includes the following[4, 5] :
Sustained blood pressure >135/80 mm Hg
Overweight and 1 or more other risk factors for diabetes (eg, first-degree relative with diabetes, BP >140/90 mm Hg, and HDL < 35 mg/dL and/or triglyceride level >250 mg/dL)
ADA recommends screening at age 45 years in the absence of the above criteria
See Workup for more detail.
This document discusses genetic markers related to non-alcoholic fatty liver disease (NAFLD). The study aimed to identify genetic markers that could help develop non-invasive diagnostic methods for NAFLD. The study identified 6 potentially associated genes, including the first association between SLC2A1 and NAFLD. Investigation of these genes in liver biopsies found they are regulated in NAFLD, and regulation increases with disease advancement, suggesting they could serve as markers for diagnosing NAFLD development phases.
This study examined the effects of valproic acid (VPA), a histone deacetylase inhibitor, on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Rats were divided into control, fibrotic, and VPA-treated groups. The fibrotic group received CCl4 injections to induce liver fibrosis, while the VPA-treated group also received VPA. After 6 weeks, liver tissue was analyzed. The fibrotic group showed disrupted liver architecture and hepatocyte damage. VPA treatment attenuated CCl4-induced fibrosis by preserving liver structure and reducing hepatocyte vacuolization. VPA also decreased expression of fibrosis markers α-SMA and Smad4, and lowered serum TGF
Cancer cells have altered metabolism compared to normal cells. They rely more on glycolysis even in the presence of oxygen (Warburg effect). This produces less ATP but helps cancer cells proliferate rapidly. Glutamine can also be used as an energy source. Targeting cancer cell metabolism through drugs like dichloroacetate is a potential treatment strategy. Cancers are heterogeneous so their metabolic profiles vary between cancer types and individual cells.
This study investigated the relationship between methylation of the MTHFR gene promoter and biomarkers in type 2 diabetes patients with and without complications. The researchers found that hypermethylation of the MTHFR promoter was associated with diabetic retinopathy and higher cholesterol/LDL levels. Patients with diabetic nephropathy and hypermethylation had higher levels of inflammation markers and antioxidant capacity compared to patients without complications. The results suggest DNA methylation of the MTHFR gene is linked to diabetic complications and altered metabolic and inflammatory states.
The document summarizes a study that examined the prevalence of metabolic syndrome across 7 Latin American cities according to NCEP ATP III criteria. Key findings include:
1) Metabolic syndrome prevalence ranged from 14% to 27% across cities, highest in Mexico City and Barquisimeto, and lowest in Quito.
2) Prevalence increased with age and more number of metabolic syndrome components.
3) Participants with metabolic syndrome had higher carotid intima-media thickness and more prevalent carotid plaque than those without.
4) Over half of individuals with certain metabolic abnormalities like high triglycerides or glucose issues met criteria for full metabolic syndrome.
Therapeutic targeting of cancer cell metabolism --role of metabolic enzymes, ...Younis I Munshi
The document summarizes recent developments in understanding the role of metabolic enzymes, oncogenes, and tumor suppressor genes in cancer progression and their potential as therapeutic targets. It discusses how cancer cells reprogram their metabolism to support uncontrolled proliferation. Key enzymes and pathways discussed include hexokinase, which phosphorylates glucose and fuels glycolysis; phosphofructokinase-2 and its role in regulating glycolytic flux; and pyruvate kinase isoforms PKM1 and PKM2 and their different functions in cancer metabolism. The document also examines how oncogenes like MYC and hypoxia-inducible factors influence these metabolic pathways to promote the Warburg effect and support tumor growth.
Serum zinc, copper and iron in children with chronic liver diseasesNoha Lotfy Ibrahim
Trace elements play a major role as both oxidants and antioxidants, promoting and protecting from tissue damage. The liver plays a pivotal role in the metabolism of trace elements and consequently their bioavailability. Therefore, we aimed to measure serum levels of essential trace elements in children with chronic liver diseases (CLDs) and to study their correlation with liver function tests.
Brian Covello: Diabetes Research ProposalBrian Covello
Brian Covello's diabetes research proposal. Type 2 diabetes mellitus consists of an array of dysfunctions characterized by hyperglycemia and resulting from the combination of resistance to insulin action, inadequate insulin secretion, and excessive or inappropriate glucagon secretion.
Essential update: FDA approves subcutaneous albiglutide for management of DM2
The FDA has approved once-weekly injectable albiglutide (Tanzeum), a glucagonlike peptide 1 (GLP-1) receptor agonist, along with diet and exercise for the treatment of type 2 diabetes.[1, 2] This agent may be used either as monotherapy or in combination with metformin, glimepiride, pioglitazone, or insulin.
Albiglutide should not be used for the following[1, 2] :
Patients with type 1 diabetes
Patients with diabetic ketoacidosis
First-line therapy in patients who can’t be managed with diet and exercise
Patients who have a personal or family history of medullary thyroid carcinoma (MTC)
Patients who have multiple endocrine neoplasia syndrome type 2
The most common adverse reactions associated with albiglutide were nausea/diarrhea and injection-site reactions.
There will be a boxed warning on albiglutide’s labeling about thyroid C-cell tumors being observed in rodent studies with this class of drugs; it is currently unknown whether albiglutide causes these tumors in humans, including MTC.[1, 2] Moreover, the FDA is also requiring a number of postmarketing studies, including a pediatric trial; an MTC case registry (≥15 y); and a cardiovascular (CV)-outcomes trial in patients with a baseline high risk of CV disease.
Signs and symptoms
Many patients with type 2 diabetes are asymptomatic. Clinical manifestations include the following:
Classic symptoms: Polyuria, polydipsia, polyphagia, and weight loss
Blurred vision
Lower-extremity paresthesias
Yeast infections (eg, balanitis in men)
See Presentation for more detail.
Diagnosis
Diagnostic criteria by the American Diabetes Association (ADA) include the following[3] :
A fasting plasma glucose (FPG) level of 126 mg/dL (7.0 mmol/L) or higher, or
A 2-hour plasma glucose level of 200 mg/dL (11.1 mmol/L) or higher during a 75-g oral glucose tolerance test (OGTT), or
A random plasma glucose of 200 mg/dL (11.1 mmol/L) or higher in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis
Whether a hemoglobin A1c (HbA1c) level of 6.5% or higher should be a primary diagnostic criterion or an optional criterion remains a point of controversy.
Indications for diabetes screening in asymptomatic adults includes the following[4, 5] :
Sustained blood pressure >135/80 mm Hg
Overweight and 1 or more other risk factors for diabetes (eg, first-degree relative with diabetes, BP >140/90 mm Hg, and HDL < 35 mg/dL and/or triglyceride level >250 mg/dL)
ADA recommends screening at age 45 years in the absence of the above criteria
See Workup for more detail.
This study investigated the effects of reducing Fsp27 (fat-specific protein 27) levels through antisense oligonucleotides (ASOs) in mouse models of obesity and insulin resistance. Mice fed a high-fat diet or leptin-deficient ob/ob mice were treated with Fsp27 ASOs. Partial reduction of Fsp27 resulted in decreased visceral fat, improved insulin sensitivity and blood glucose control, and changes in genes related to lipid metabolism. The results suggest that reducing FSP27 activity through ASOs could be a potential therapeutic approach for insulin resistance and obesity in patients.
A reading report for <Tumor microenvironment derived exosomes pleiotropically...星云 王
A reading report for <Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism
>, only for private study use, please do not use it for profit or public.
This document discusses various disorders of lipid metabolism. It begins by describing Fredrickson's classification of hyperlipidemias. It then discusses specific disorders in more detail, including chylomicron syndrome, familial hypercholesterolemia, familial defective apoB3500, familial combined hyperlipidemia, familial hypertriglyceridemia, type III hyperlipoproteinemia, and polygenic hypercholesterolemia. For each disorder, it provides information on prevalence, genetic factors, clinical presentation, diagnostic criteria, and treatment approaches.
This document provides information about the January 2014 issue of the Biomed newsletter from the Department of Biochemistry at Adichunchanagiri Institute of Medical Sciences. It includes an editorial welcoming the fourth issue and focusing on cardiovascular disease. It also features several articles on biomarkers for cardiovascular disease such as D-dimer, lipoprotein(a), heart-type fatty acid binding protein, and serum paraoxonase. The editorial board members and department staff are pictured.
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-
This document summarizes Alexion's activities and key messages from three European congresses in 2016 focused on hepatology and lipidology. The congresses aimed to raise awareness of lysosomal acid lipase deficiency (LAL-D) and novel treatment options. Alexion attended the congresses with commercial booths, symposia, and market research. LAL-D is a rare genetic disorder caused by LAL enzyme deficiency that causes multi-organ damage. It can be misdiagnosed due to similarities with other conditions but diagnosis is important to identify patients who may benefit from new enzyme replacement therapy.
This study analyzed plasma levels of antithrombin-III (AT-III) and serum aminotransferase activity in 60 participants, including 20 with chronic hepatitis, 20 with cirrhosis, and 20 healthy controls. The study found that AT-III levels and aminotransferase activity were significantly different between the patient groups and controls. Specifically, patients with cirrhosis had significantly lower AT-III levels than those with chronic hepatitis. The study concludes that plasma AT-III levels may be a useful non-invasive marker for diagnosing cirrhosis in patients with chronic liver disease.
Hiperuricemia diabetes y sindrome metabolico2Residentes1hun
Insulin resistance plays a potentially key role in the causal relationship between metabolic syndrome, type 2 diabetes and hyperuricemia. Evidence suggests that insulin resistance may be a mediator linking obesity, inflammation, and hyperuricemia. Furthermore, hyperuricemia and insulin resistance likely share a bidirectional causal effect, as insulin resistance can lead to hyperuricemia through impaired kidney function, while hyperinsulinemia can also decrease uric acid excretion and lead to hyperuricemia.
Protein glycation occurs spontaneously when sugars attach to proteins or lipids, forming advanced glycation end products (AGEs) that accumulate over time and contribute to aging and disease pathology. AGEs form through reactions like the Maillard reaction and can crosslink or modify proteins, DNA and lipids. They are implicated in diseases associated with aging like diabetes, where hyperglycemia overwhelms the body's ability to break down AGEs. AGEs bind receptors on macrophages, stimulating inflammation and complications in diabetes such as nephropathy, neuropathy and retinopathy. The accumulation of AGEs over a lifetime may accelerate aging through molecular damage and chronic inflammation.
Cancer cells exhibit altered metabolism compared to normal cells. They metabolize glucose to lactate through aerobic glycolysis even when oxygen is present, known as the Warburg effect. Normal cells only undergo glycolysis and produce lactate under low oxygen conditions. Cancer cells also rely on glutaminolysis and have hyperpolarized mitochondria. Inhibiting key steps in glycolysis and mitochondrial metabolism may be potential anti-tumor strategies. Targeting glucose transport, pyruvate oxidation, and mitochondrial metabolism are emerging areas of research.
Exercise and nutrition in Mitochondrial Diseasemitoaction
Mark Tarnopolsky, MD, PhD, FRCP,
Depts. of Pediatrics (Neuromuscular + Neurometabolic Disease) and Medicine (Cell Biology/Metabolism, Neurology and Rehabilitation), McMaster University, Hamilton, CANADA
This document summarizes a study that assessed the potential for plasma fatty acid analysis to diagnose cystic fibrosis (CF). The study found that CF patients have distinct plasma fatty acid profiles compared to healthy controls, particularly lower levels of linoleic acid and docosahexaenoic acid. In a non-blinded trial, the researchers identified that the product of linoleic acid and docosahexaenoic acid levels best distinguished CF patients from controls. A subsequent blinded trial confirmed this calculation accurately identified CF patients. The researchers conclude plasma fatty acid analysis, particularly this calculation, shows promise as a diagnostic tool for CF.
This summary provides the key details from the document in 3 sentences:
This document describes a study that used random forest models to integrate data from metabolomics, lipidomics, and clinical studies on rats treated with a PPAR agonist. The random forest models were able to select a small set of discriminatory metabolites that predicted dose levels with high accuracy and link clinical phenotypes to specific metabolite changes. The results provide insights into PPAR metabolism and side effects by linking classical toxicology data to modern omics datasets.
This study investigated the effects of isomaltulose compared to sucrose on insulin resistance and metabolite levels in 5 male patients with non-alcoholic fatty liver disease (NAFLD). The patients consumed either 20g of isomaltulose or sucrose and blood samples were taken before and 15 minutes after to measure changes. While blood glucose levels did not differ significantly between groups, the isomaltulose group had a significantly greater decrease in the insulin resistance marker C-peptide. Metabolomic analysis also found significant alterations in 52 metabolites after isomaltulose, including a large increase in taurodeoxycholic acid and decrease in arachidonic acid. The study suggests isomaltulose may improve insulin resistance in NA
Comparative Study of Serum Electrolytes among Treated Diabetic SubjectsMatiaAhmed
This study was designed to investigate the measurements of serum levels of Na+
, K+
, Mg2+
and Ca2+ and their changes with serum glucose levels. Thirty treated diabetic patients (diet
/ OHA), aged between 23 to 27 years and having BMI of 17.9 to 22.54 kg/m2
were selected
randomly from the outpatient department of BIRDEM.
This document summarizes recent research on the mechanisms of catabolite repression and inducer control in low-GC Gram-positive bacteria. It finds that while the mechanisms are similar to E. coli in involving the phosphotransferase system (PTS) and HPr protein, the regulatory proteins and mechanisms involved are different. Phosphorylation of a serine residue in HPr by a metabolite-activated ATP-dependent protein kinase regulates enzyme synthesis, inducer exclusion, and inducer expulsion in Gram-positive bacteria. This phosphorylation controls the initiation of carbohydrate metabolism at both the protein and gene expression levels through different target proteins.
This case report describes a novel mitochondrial metabolic myopathy (mtMM) caused by a variant in mitochondrial DNA. A 26-year-old male presented with episodic rhabdomyolysis and elevated creatine kinase. Genetic testing found a homoplasmic variant in the cytochrome c oxidase subunit III gene, encoding a defective protein. This pathogenic variant likely causes a defect in oxidative phosphorylation. Management focuses on diet, hydration and avoiding strenuous exercise to prevent rhabdomyolysis and damage to muscles, liver and kidneys. This condition represents a new mtMM identified through mitochondrial genome sequencing.
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
O documento lista 10 livros de ficção populares na semana de 26 de novembro a 02 de dezembro, incluindo os livros da série "Cinquenta Sombras" de E.L. James e obras de autores portugueses como José Rodrigues dos Santos, Ricardo Araújo Pereira e Mário Zambujal.
O documento discute o princípio inteligente como um atributo essencial do Espírito. A inteligência é compartilhada entre Espíritos e seres humanos, embora no homem tenha passado por uma elaboração maior. O princípio inteligente se desenvolve gradualmente no Espírito e individualiza-se em cada ser, desde animais até o homem, recebendo quantidades diferentes de acordo com sua função na Natureza.
Расширение возможностей профильного и предпрофильного обучения, проектной и и...Maria1808
Цель: качественная образовательная и социальная подготовка,
направленная на формирование способности гимназистов к осознанному
выбору профессии в соответствии с их склонностями, возможностями и
способностями на основе социального партнерства.
This study investigated the effects of reducing Fsp27 (fat-specific protein 27) levels through antisense oligonucleotides (ASOs) in mouse models of obesity and insulin resistance. Mice fed a high-fat diet or leptin-deficient ob/ob mice were treated with Fsp27 ASOs. Partial reduction of Fsp27 resulted in decreased visceral fat, improved insulin sensitivity and blood glucose control, and changes in genes related to lipid metabolism. The results suggest that reducing FSP27 activity through ASOs could be a potential therapeutic approach for insulin resistance and obesity in patients.
A reading report for <Tumor microenvironment derived exosomes pleiotropically...星云 王
A reading report for <Tumor microenvironment derived exosomes pleiotropically modulate cancer cell metabolism
>, only for private study use, please do not use it for profit or public.
This document discusses various disorders of lipid metabolism. It begins by describing Fredrickson's classification of hyperlipidemias. It then discusses specific disorders in more detail, including chylomicron syndrome, familial hypercholesterolemia, familial defective apoB3500, familial combined hyperlipidemia, familial hypertriglyceridemia, type III hyperlipoproteinemia, and polygenic hypercholesterolemia. For each disorder, it provides information on prevalence, genetic factors, clinical presentation, diagnostic criteria, and treatment approaches.
This document provides information about the January 2014 issue of the Biomed newsletter from the Department of Biochemistry at Adichunchanagiri Institute of Medical Sciences. It includes an editorial welcoming the fourth issue and focusing on cardiovascular disease. It also features several articles on biomarkers for cardiovascular disease such as D-dimer, lipoprotein(a), heart-type fatty acid binding protein, and serum paraoxonase. The editorial board members and department staff are pictured.
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-
This document summarizes Alexion's activities and key messages from three European congresses in 2016 focused on hepatology and lipidology. The congresses aimed to raise awareness of lysosomal acid lipase deficiency (LAL-D) and novel treatment options. Alexion attended the congresses with commercial booths, symposia, and market research. LAL-D is a rare genetic disorder caused by LAL enzyme deficiency that causes multi-organ damage. It can be misdiagnosed due to similarities with other conditions but diagnosis is important to identify patients who may benefit from new enzyme replacement therapy.
This study analyzed plasma levels of antithrombin-III (AT-III) and serum aminotransferase activity in 60 participants, including 20 with chronic hepatitis, 20 with cirrhosis, and 20 healthy controls. The study found that AT-III levels and aminotransferase activity were significantly different between the patient groups and controls. Specifically, patients with cirrhosis had significantly lower AT-III levels than those with chronic hepatitis. The study concludes that plasma AT-III levels may be a useful non-invasive marker for diagnosing cirrhosis in patients with chronic liver disease.
Hiperuricemia diabetes y sindrome metabolico2Residentes1hun
Insulin resistance plays a potentially key role in the causal relationship between metabolic syndrome, type 2 diabetes and hyperuricemia. Evidence suggests that insulin resistance may be a mediator linking obesity, inflammation, and hyperuricemia. Furthermore, hyperuricemia and insulin resistance likely share a bidirectional causal effect, as insulin resistance can lead to hyperuricemia through impaired kidney function, while hyperinsulinemia can also decrease uric acid excretion and lead to hyperuricemia.
Protein glycation occurs spontaneously when sugars attach to proteins or lipids, forming advanced glycation end products (AGEs) that accumulate over time and contribute to aging and disease pathology. AGEs form through reactions like the Maillard reaction and can crosslink or modify proteins, DNA and lipids. They are implicated in diseases associated with aging like diabetes, where hyperglycemia overwhelms the body's ability to break down AGEs. AGEs bind receptors on macrophages, stimulating inflammation and complications in diabetes such as nephropathy, neuropathy and retinopathy. The accumulation of AGEs over a lifetime may accelerate aging through molecular damage and chronic inflammation.
Cancer cells exhibit altered metabolism compared to normal cells. They metabolize glucose to lactate through aerobic glycolysis even when oxygen is present, known as the Warburg effect. Normal cells only undergo glycolysis and produce lactate under low oxygen conditions. Cancer cells also rely on glutaminolysis and have hyperpolarized mitochondria. Inhibiting key steps in glycolysis and mitochondrial metabolism may be potential anti-tumor strategies. Targeting glucose transport, pyruvate oxidation, and mitochondrial metabolism are emerging areas of research.
Exercise and nutrition in Mitochondrial Diseasemitoaction
Mark Tarnopolsky, MD, PhD, FRCP,
Depts. of Pediatrics (Neuromuscular + Neurometabolic Disease) and Medicine (Cell Biology/Metabolism, Neurology and Rehabilitation), McMaster University, Hamilton, CANADA
This document summarizes a study that assessed the potential for plasma fatty acid analysis to diagnose cystic fibrosis (CF). The study found that CF patients have distinct plasma fatty acid profiles compared to healthy controls, particularly lower levels of linoleic acid and docosahexaenoic acid. In a non-blinded trial, the researchers identified that the product of linoleic acid and docosahexaenoic acid levels best distinguished CF patients from controls. A subsequent blinded trial confirmed this calculation accurately identified CF patients. The researchers conclude plasma fatty acid analysis, particularly this calculation, shows promise as a diagnostic tool for CF.
This summary provides the key details from the document in 3 sentences:
This document describes a study that used random forest models to integrate data from metabolomics, lipidomics, and clinical studies on rats treated with a PPAR agonist. The random forest models were able to select a small set of discriminatory metabolites that predicted dose levels with high accuracy and link clinical phenotypes to specific metabolite changes. The results provide insights into PPAR metabolism and side effects by linking classical toxicology data to modern omics datasets.
This study investigated the effects of isomaltulose compared to sucrose on insulin resistance and metabolite levels in 5 male patients with non-alcoholic fatty liver disease (NAFLD). The patients consumed either 20g of isomaltulose or sucrose and blood samples were taken before and 15 minutes after to measure changes. While blood glucose levels did not differ significantly between groups, the isomaltulose group had a significantly greater decrease in the insulin resistance marker C-peptide. Metabolomic analysis also found significant alterations in 52 metabolites after isomaltulose, including a large increase in taurodeoxycholic acid and decrease in arachidonic acid. The study suggests isomaltulose may improve insulin resistance in NA
Comparative Study of Serum Electrolytes among Treated Diabetic SubjectsMatiaAhmed
This study was designed to investigate the measurements of serum levels of Na+
, K+
, Mg2+
and Ca2+ and their changes with serum glucose levels. Thirty treated diabetic patients (diet
/ OHA), aged between 23 to 27 years and having BMI of 17.9 to 22.54 kg/m2
were selected
randomly from the outpatient department of BIRDEM.
This document summarizes recent research on the mechanisms of catabolite repression and inducer control in low-GC Gram-positive bacteria. It finds that while the mechanisms are similar to E. coli in involving the phosphotransferase system (PTS) and HPr protein, the regulatory proteins and mechanisms involved are different. Phosphorylation of a serine residue in HPr by a metabolite-activated ATP-dependent protein kinase regulates enzyme synthesis, inducer exclusion, and inducer expulsion in Gram-positive bacteria. This phosphorylation controls the initiation of carbohydrate metabolism at both the protein and gene expression levels through different target proteins.
This case report describes a novel mitochondrial metabolic myopathy (mtMM) caused by a variant in mitochondrial DNA. A 26-year-old male presented with episodic rhabdomyolysis and elevated creatine kinase. Genetic testing found a homoplasmic variant in the cytochrome c oxidase subunit III gene, encoding a defective protein. This pathogenic variant likely causes a defect in oxidative phosphorylation. Management focuses on diet, hydration and avoiding strenuous exercise to prevent rhabdomyolysis and damage to muscles, liver and kidneys. This condition represents a new mtMM identified through mitochondrial genome sequencing.
International Journal of Pharmaceutical Science Invention (IJPSI) is an international journal intended for professionals and researchers in all fields of Pahrmaceutical Science. IJPSI publishes research articles and reviews within the whole field Pharmacy and Pharmaceutical Science, new teaching methods, assessment, validation and the impact of new technologies and it will continue to provide information on the latest trends and developments in this ever-expanding subject. The publications of papers are selected through double peer reviewed to ensure originality, relevance, and readability. The articles published in our journal can be accessed online.
O documento lista 10 livros de ficção populares na semana de 26 de novembro a 02 de dezembro, incluindo os livros da série "Cinquenta Sombras" de E.L. James e obras de autores portugueses como José Rodrigues dos Santos, Ricardo Araújo Pereira e Mário Zambujal.
O documento discute o princípio inteligente como um atributo essencial do Espírito. A inteligência é compartilhada entre Espíritos e seres humanos, embora no homem tenha passado por uma elaboração maior. O princípio inteligente se desenvolve gradualmente no Espírito e individualiza-se em cada ser, desde animais até o homem, recebendo quantidades diferentes de acordo com sua função na Natureza.
Расширение возможностей профильного и предпрофильного обучения, проектной и и...Maria1808
Цель: качественная образовательная и социальная подготовка,
направленная на формирование способности гимназистов к осознанному
выбору профессии в соответствии с их склонностями, возможностями и
способностями на основе социального партнерства.
Francisco es un niño de 8 años diagnosticado con déficit atencional sin hiperactividad y trastorno de lectoescritura. Presenta dificultades en el control motor, mental y emocional. Recibe tratamiento psicológico, farmacológico e intervención psicopedagógica. Muestra rendimiento bajo en lectura y escritura. Se recomienda continuar con su tratamiento y apoyo diferencial en el aula.
Lunch and Learn Becoming a Prime Contractor Final Rev 1 (5-20-16)Gary Fitch
This document provides information on becoming a government prime contractor and growing a small business into a big business. It discusses the progression from subcontractor to prime contractor, the attributes of each, and how to identify "finders, minders, and grinders" within a business. The document outlines a roadmap for growing a small business, including strategizing, structuring the business, developing skills, systematizing processes, and transitioning to the new structure. Overall, the document offers advice on developing the capabilities required to become a prime contractor and scaling a small business in a strategic, structured manner.
El documento contiene información sobre un estudiante llamado Elias Ribeiro que está en la clase 33 de FA, con el número CGM 25697-8 y su profesor orientador de pasantía es Ricardo Ichiura. No se proporciona ninguna nota.
ANSHAL Advocates is an international law firm based in Dubai offering a wide range of legal services including civil, family, criminal, labor, property, commercial, and corporate law. They have experienced lawyers specializing in various areas of law and offer services like drafting contracts, providing legal opinions, representing clients in litigation and arbitration, and handling matters related to incorporation of companies and investment in free zones. Their goal is to provide clients with the highest level of legal services and satisfaction.
Novo(a) documento do microsoft office word (3)catagerio
O vereador Catanese pediu ao presidente da Câmara Municipal a implantação de uma Sala de Vídeo Conferência para oferecer cursos à distância aos servidores, trabalhadores e estudantes do município. A sala de vídeo conferência permitiria aulas online para professores de cursinhos e seria útil para a população. A vídeo conferência é amplamente utilizada no mundo atual.
Este documento discute três tópicos principais: 1) os riscos ergonômicos do esforço estático e da compressão mecânica e como pausas curtas podem ajudar; 2) a definição e operação básica de caldeiras; 3) os critérios legais para desligar representantes dos empregados na CIPA e as precauções necessárias.
Connie Major is seeking a career in the legal field where she can utilize her skills and knowledge. She has over 15 years of experience in various legal roles such as paralegal, legal secretary, and notary. Her experience includes drafting and revising legal documents, communicating with clients and attorneys, scheduling, and other administrative tasks.
This document provides information on maintenance workshops offered by Henkel to teach skills for improving plant reliability. It highlights common equipment failures that can be addressed by machinery adhesives taught in the workshops. The workshops include a plant survey, hands-on training modules, and aim to shift maintenance from reactive to proactive. Attendees learn about fastener loosening, leaks, wear issues, and other topics. The goal is reducing costs from improved repair methods and preventative maintenance.
Aryabhatta was a mathematician and astronomer from India who lived in the late 400s-early 500s. He made important contributions to mathematics including introducing the concept of zero and approximations of pi. He also had significant astronomical theories like that the Earth rotates on its axis and revolves around the sun. Aryabhatta's work was commemorated through naming India's first satellite and an astronomy research institute after him.
Core Components of the Metabolic Syndrome in Nonalcohlic Fatty Liver DiseaseIOSR Journals
This study examined the association between nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) in Bangladeshi patients. The study included 67 patients diagnosed with NAFLD and 50 healthy controls matched for age and BMI. Results found that NAFLD patients had higher levels of insulin resistance, triglycerides, and central obesity compared to controls. However, no significant association was found between MetS and NAFLD when defined by common diagnostic criteria. Individual components of MetS like dyslipidemia, central obesity, and high postprandial glucose were significantly associated with NAFLD on logistic regression analysis. The study concludes that while various MetS components are linked to NAFLD in
The document discusses non-alcoholic fatty liver disease (NAFLD), which includes a spectrum of conditions from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is strongly associated with obesity and metabolic syndrome. The prevalence of NAFLD is increasing globally and varies from 5-30% in different regions. Diagnosis requires imaging and liver biopsy. Treatment focuses on lifestyle modifications and medications to improve insulin resistance.
This study investigated the role of gut microbiota and bile acid metabolism in the development of non-alcoholic steatohepatitis (NASH)-associated hepatocellular carcinoma (HCC) in mice fed a high-fat diet. The mice developed NASH and HCC within 9 weeks of being fed the steatohepatitis-inducing diet without carcinogens. The gut microbiota was found to promote secondary bile acid production, which activated mTOR signaling in hepatocytes and contributed to oncogenesis. The findings suggest that metabolites produced by gut microbiota like secondary bile acids may mediate HCC development in NASH through mTOR pathway activation in liver cells.
Non-alcoholic fatty liver disease (NAFLD) is the buildup of fat in the liver not caused by alcohol. It is the most common form of chronic liver disease, affecting 10-20% of children globally. Risk factors include obesity, diabetes, and metabolic syndrome. NAFLD can progress from a harmless fat buildup (steatosis) to a serious inflammation (NASH), and eventually fibrosis and cirrhosis if not addressed. The pathogenesis involves genetic predisposition combined with environmental factors like diet, gut bacteria, and insulin resistance that together cause liver damage over time.
Non Alcoholic Fatty Liver Disease: A New Urban Epidemic.KETAN VAGHOLKAR
This document discusses non-alcoholic fatty liver disease (NAFLD), which has become very common in urban populations. NAFLD ranges from simple fatty liver to non-alcoholic steatohepatitis (NASH), which is characterized by fatty changes, inflammation, and fibrosis that can progress to cirrhosis. The main causes are obesity, insulin resistance, and dyslipidemia. Weight loss and improving insulin sensitivity through diet and exercise are the primary treatment approaches. Medications like vitamin E, pioglitazone, and metformin may also provide benefits, but more research is still needed on medical therapies for NAFLD.
EVALUATION OF SERUM LEVELS OF FASTING LIPID PROFILE IN PRE-ECLAMPTIC WOMEN
Wuraola Serah Nnaemeka, Olisekodiaka, MJ, Onuegbu, AJ, Ezeugwunne, IP, Maduka, IG, Suru, SM , Johnkennedy Nnodim
IRO INTERNATIONAL JOURNAL OF MEDICAL AND APPLIED SCIENCES 2018, 1(1):20-23.
The document discusses focal nodular hyperplasia (FNH), a benign hepatic tumor. It describes the histopathology of classic and nonclassic FNH and notes that nonclassic FNH lacks one or more key elements of classic FNH, which includes abnormal nodular architecture, cholangiolar proliferation, and malformed vessels. Imaging features of FNH are also provided, noting FNH typically appears as a well-circumscribed lesion with isointense or slightly hyperintense signal on T1-weighted MRI and markedly hyperintense signal on T2-weighted MRI.
1) Fatty liver, measured using CT scans, was present in 17% of participants.
2) Fatty liver was associated with higher risk of diabetes, metabolic syndrome, hypertension, and insulin resistance even after accounting for other measures of obesity like BMI and visceral fat.
3) Fatty liver was also linked to dyslipidemia (higher triglycerides and lower HDL) and dysglycemia (impaired fasting glucose) independent of other fat depots.
Linking uric acid metabolism to diabetic complicationsMohamedKhamis77
This document discusses the relationship between uric acid metabolism and diabetic complications. It begins by providing background on uric acid metabolism and the factors that determine serum uric acid levels. It then discusses how uric acid levels are associated with type 2 diabetes and metabolic syndrome. Higher uric acid levels have been linked to an increased risk of developing type 2 diabetes. The document also reviews evidence that elevated uric acid levels are associated with a higher risk and worsening of diabetic complications, including neuropathy, retinopathy, nephropathy, foot ulcers, and macrovascular complications. Oxidative stress from xanthine oxidoreductase activity may play a role in these relationships through vascular endothelial damage and insulin resistance.
This document discusses nonalcoholic fatty liver disease (NAFLD), its causes and risk factors. NAFLD is caused by fat accumulation in the liver from factors other than alcohol consumption, including genetic predisposition, environmental stresses, and metabolic stresses. The main causes discussed are insulin resistance, lipid metabolism disorders, mitochondrial dysfunction, and oxidative stress. Prevention and treatment involves lifestyle changes like a healthy diet and exercise, as well as medication to treat underlying conditions and reduce liver damage.
NAFLD non alcoholic fatty liver disease.pptxSyedFurqan30
This document provides an overview of non-alcoholic fatty liver disease (NAFLD). It discusses that NAFLD is increasingly a cause of liver disease globally, with a prevalence of 25% worldwide and 9-53% in India. NAFLD refers to hepatic fat accumulation in the absence of excessive alcohol use or other known liver diseases. The spectrum of NAFLD ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) which is characterized by inflammation and cellular injury, and can progress to cirrhosis. Genetic and environmental factors contribute to NAFLD pathogenesis. Insulin resistance is a major driver, and comorbidities like obesity, diabetes, and obstructive
This document summarizes statistics on adverse drug events (ADEs) and how drug metabolism and transport may be altered in patients with nonalcoholic steatohepatitis (NASH). Over 3 million ADEs were reported from 2011-2012, with over 100,000 deaths. The top drugs associated with ADEs are metabolized by CYP3A4 and transported by MRP proteins. Patients with NASH have changes in expression of various cytochrome P450 enzymes and transporters that could impact drug metabolism and disposition. Altered pharmacokinetics may contribute to the frequency and severity of ADEs in NASH patients.
A mild reduction of food intake slows disease progression in an orthologous m...Mina Rezaei
A mild 23% reduction in food intake (RFI) significantly slowed disease progression in a mouse model of polycystic kidney disease (PKD). RFI suppressed renal cyst growth, with kidney weight increasing 41% compared to 151% in controls. Proliferation of cyst-lining cells was also reduced from 15.9% in controls to 7.7% with RFI. RFI maintained kidney function and prevented progression to end-stage renal disease. RFI activated AMPK and inhibited both branches of mTOR signaling in cyst cells, more broadly than rapamycin which primarily inhibits one branch. These results suggest a mild decrease in caloric intake may slow disease progression in human ADPKD patients.
Alterations of Mitochondrial Functions and DNA in Diabetic Cardiomyopathy of ...CrimsonPublishersIOD
Alterations of Mitochondrial Functions and DNA in Diabetic Cardiomyopathy of CCK1 Receptors-Deficient Rats by Abdelbary Prince, Magdy A Ghoneim, Abdallah M El-Ebidi, Hala A Mousa and Jin Han in Interventions in Obesity & Diabetes
This document provides an overview of current treatment and updates on non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). It begins with definitions of NAFLD and NASH. It then discusses the prevalence of NAFLD globally and in Asian countries. Risk factors and the pathogenesis involving the gut microbiota and a potential role in lean NASH are reviewed. Current methods for diagnosis including laboratory tests, imaging, serum biomarkers, and liver biopsy are summarized. Current treatment options including lifestyle modifications, metformin, pioglitazone, and vitamin E are mentioned. Several newer potential treatment approaches are also listed. The role of transient elastography in management is
This document discusses the relationship between non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease. Some key points:
- NAFLD is one of the most common forms of liver disease, affecting 10-24% of the general population. It is strongly associated with obesity and metabolic syndrome.
- Patients with NAFLD have a higher risk of cardiovascular diseases like atherosclerosis, the leading cause of mortality. NAFLD is linked to traditional risk factors as well as surrogate markers for cardiovascular disease.
- Epicardial fat thickness, as measured by echocardiography, is increased in patients with NAFLD and metabolic syndrome. Increased epicardial fat is associated with atherosclerosis
This document summarizes the effects of diet and exercise on liver lipid metabolism. It discusses the normal pathways of hepatic lipid metabolism, including lipid influx from adipose tissue and diet, de novo lipogenesis from carbohydrates, and lipid oxidation and secretion. Dietary fat and carbohydrates can accumulate in the liver as triglycerides if uptake and synthesis exceed oxidation and secretion. The roles of different transcription factors and enzymes involved in lipogenesis are also described.
Similar to Biochemical Study on Endothelial Nitric Oxide Gene Polymorphism in Fatty Liver Patients (20)
An Examination of Effectuation Dimension as Financing Practice of Small and M...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Does Goods and Services Tax (GST) Leads to Indian Economic Development?iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Childhood Factors that influence success in later lifeiosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Emotional Intelligence and Work Performance Relationship: A Study on Sales Pe...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Customer’s Acceptance of Internet Banking in Dubaiiosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
A Study of Employee Satisfaction relating to Job Security & Working Hours amo...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Consumer Perspectives on Brand Preference: A Choice Based Model Approachiosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Student`S Approach towards Social Network Sitesiosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Broadcast Management in Nigeria: The systems approach as an imperativeiosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
A Study on Retailer’s Perception on Soya Products with Special Reference to T...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
A Study Factors Influence on Organisation Citizenship Behaviour in Corporate ...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Consumers’ Behaviour on Sony Xperia: A Case Study on Bangladeshiosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Design of a Balanced Scorecard on Nonprofit Organizations (Study on Yayasan P...iosrjce
1. The document describes a study that designed a balanced scorecard for a nonprofit organization called Yayasan Pembinaan dan Kesembuhan Batin (YPKB) in Malang, Indonesia.
2. The balanced scorecard translated YPKB's vision and mission into strategic objectives across four perspectives: financial, customer, internal processes, and learning and growth.
3. Key strategic objectives included donation growth, budget effectiveness, customer satisfaction, reputation, service quality, innovation, and employee development. Customers perspective had the highest weighting, suggesting a focus on public service over financial growth.
Public Sector Reforms and Outsourcing Services in Nigeria: An Empirical Evalu...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Media Innovations and its Impact on Brand awareness & Considerationiosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Customer experience in supermarkets and hypermarkets – A comparative studyiosrjce
- The document examines customer experience in supermarkets and hypermarkets in India through a survey of 418 customers.
- It finds that in supermarkets, previous experience, atmosphere, price, social environment and experience in other channels most influence customer experience, while in hypermarkets, previous experience, product assortment, social environment and experience in other channels are most influential.
- The study provides insights for retailers on key determinants of customer experience in each format to help them improve strategies and competitive positioning.
Social Media and Small Businesses: A Combinational Strategic Approach under t...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Secretarial Performance and the Gender Question (A Study of Selected Tertiary...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
Implementation of Quality Management principles at Zimbabwe Open University (...iosrjce
This document discusses the implementation of quality management principles at Zimbabwe Open University's Matabeleland North Regional Centre. It begins with background information on ZOU and the importance of quality management in open and distance learning institutions. The study aimed to determine if quality management and its principles were being implemented at the regional centre. Key findings included that the centre prioritized customer focus and staff involvement. Decisions were made based on data analysis. The regional centre implemented a quality system informed by its policy documents. The document recommends ensuring staffing levels match needs and providing sufficient resources to the regional centre.
Organizational Conflicts Management In Selected Organizaions In Lagos State, ...iosrjce
IOSR Journal of Business and Management (IOSR-JBM) is a double blind peer reviewed International Journal that provides rapid publication (within a month) of articles in all areas of business and managemant and its applications. The journal welcomes publications of high quality papers on theoretical developments and practical applications inbusiness and management. Original research papers, state-of-the-art reviews, and high quality technical notes are invited for publications.
The use of Nauplii and metanauplii artemia in aquaculture (brine shrimp).pptxMAGOTI ERNEST
Although Artemia has been known to man for centuries, its use as a food for the culture of larval organisms apparently began only in the 1930s, when several investigators found that it made an excellent food for newly hatched fish larvae (Litvinenko et al., 2023). As aquaculture developed in the 1960s and ‘70s, the use of Artemia also became more widespread, due both to its convenience and to its nutritional value for larval organisms (Arenas-Pardo et al., 2024). The fact that Artemia dormant cysts can be stored for long periods in cans, and then used as an off-the-shelf food requiring only 24 h of incubation makes them the most convenient, least labor-intensive, live food available for aquaculture (Sorgeloos & Roubach, 2021). The nutritional value of Artemia, especially for marine organisms, is not constant, but varies both geographically and temporally. During the last decade, however, both the causes of Artemia nutritional variability and methods to improve poorquality Artemia have been identified (Loufi et al., 2024).
Brine shrimp (Artemia spp.) are used in marine aquaculture worldwide. Annually, more than 2,000 metric tons of dry cysts are used for cultivation of fish, crustacean, and shellfish larva. Brine shrimp are important to aquaculture because newly hatched brine shrimp nauplii (larvae) provide a food source for many fish fry (Mozanzadeh et al., 2021). Culture and harvesting of brine shrimp eggs represents another aspect of the aquaculture industry. Nauplii and metanauplii of Artemia, commonly known as brine shrimp, play a crucial role in aquaculture due to their nutritional value and suitability as live feed for many aquatic species, particularly in larval stages (Sorgeloos & Roubach, 2021).
Remote Sensing and Computational, Evolutionary, Supercomputing, and Intellige...University of Maribor
Slides from talk:
Aleš Zamuda: Remote Sensing and Computational, Evolutionary, Supercomputing, and Intelligent Systems.
11th International Conference on Electrical, Electronics and Computer Engineering (IcETRAN), Niš, 3-6 June 2024
Inter-Society Networking Panel GRSS/MTT-S/CIS Panel Session: Promoting Connection and Cooperation
https://www.etran.rs/2024/en/home-english/
The technology uses reclaimed CO₂ as the dyeing medium in a closed loop process. When pressurized, CO₂ becomes supercritical (SC-CO₂). In this state CO₂ has a very high solvent power, allowing the dye to dissolve easily.
Immersive Learning That Works: Research Grounding and Paths ForwardLeonel Morgado
We will metaverse into the essence of immersive learning, into its three dimensions and conceptual models. This approach encompasses elements from teaching methodologies to social involvement, through organizational concerns and technologies. Challenging the perception of learning as knowledge transfer, we introduce a 'Uses, Practices & Strategies' model operationalized by the 'Immersive Learning Brain' and ‘Immersion Cube’ frameworks. This approach offers a comprehensive guide through the intricacies of immersive educational experiences and spotlighting research frontiers, along the immersion dimensions of system, narrative, and agency. Our discourse extends to stakeholders beyond the academic sphere, addressing the interests of technologists, instructional designers, and policymakers. We span various contexts, from formal education to organizational transformation to the new horizon of an AI-pervasive society. This keynote aims to unite the iLRN community in a collaborative journey towards a future where immersive learning research and practice coalesce, paving the way for innovative educational research and practice landscapes.
ESR spectroscopy in liquid food and beverages.pptxPRIYANKA PATEL
With increasing population, people need to rely on packaged food stuffs. Packaging of food materials requires the preservation of food. There are various methods for the treatment of food to preserve them and irradiation treatment of food is one of them. It is the most common and the most harmless method for the food preservation as it does not alter the necessary micronutrients of food materials. Although irradiated food doesn’t cause any harm to the human health but still the quality assessment of food is required to provide consumers with necessary information about the food. ESR spectroscopy is the most sophisticated way to investigate the quality of the food and the free radicals induced during the processing of the food. ESR spin trapping technique is useful for the detection of highly unstable radicals in the food. The antioxidant capability of liquid food and beverages in mainly performed by spin trapping technique.
EWOCS-I: The catalog of X-ray sources in Westerlund 1 from the Extended Weste...Sérgio Sacani
Context. With a mass exceeding several 104 M⊙ and a rich and dense population of massive stars, supermassive young star clusters
represent the most massive star-forming environment that is dominated by the feedback from massive stars and gravitational interactions
among stars.
Aims. In this paper we present the Extended Westerlund 1 and 2 Open Clusters Survey (EWOCS) project, which aims to investigate
the influence of the starburst environment on the formation of stars and planets, and on the evolution of both low and high mass stars.
The primary targets of this project are Westerlund 1 and 2, the closest supermassive star clusters to the Sun.
Methods. The project is based primarily on recent observations conducted with the Chandra and JWST observatories. Specifically,
the Chandra survey of Westerlund 1 consists of 36 new ACIS-I observations, nearly co-pointed, for a total exposure time of 1 Msec.
Additionally, we included 8 archival Chandra/ACIS-S observations. This paper presents the resulting catalog of X-ray sources within
and around Westerlund 1. Sources were detected by combining various existing methods, and photon extraction and source validation
were carried out using the ACIS-Extract software.
Results. The EWOCS X-ray catalog comprises 5963 validated sources out of the 9420 initially provided to ACIS-Extract, reaching a
photon flux threshold of approximately 2 × 10−8 photons cm−2
s
−1
. The X-ray sources exhibit a highly concentrated spatial distribution,
with 1075 sources located within the central 1 arcmin. We have successfully detected X-ray emissions from 126 out of the 166 known
massive stars of the cluster, and we have collected over 71 000 photons from the magnetar CXO J164710.20-455217.
Phenomics assisted breeding in crop improvementIshaGoswami9
As the population is increasing and will reach about 9 billion upto 2050. Also due to climate change, it is difficult to meet the food requirement of such a large population. Facing the challenges presented by resource shortages, climate
change, and increasing global population, crop yield and quality need to be improved in a sustainable way over the coming decades. Genetic improvement by breeding is the best way to increase crop productivity. With the rapid progression of functional
genomics, an increasing number of crop genomes have been sequenced and dozens of genes influencing key agronomic traits have been identified. However, current genome sequence information has not been adequately exploited for understanding
the complex characteristics of multiple gene, owing to a lack of crop phenotypic data. Efficient, automatic, and accurate technologies and platforms that can capture phenotypic data that can
be linked to genomics information for crop improvement at all growth stages have become as important as genotyping. Thus,
high-throughput phenotyping has become the major bottleneck restricting crop breeding. Plant phenomics has been defined as the high-throughput, accurate acquisition and analysis of multi-dimensional phenotypes
during crop growing stages at the organism level, including the cell, tissue, organ, individual plant, plot, and field levels. With the rapid development of novel sensors, imaging technology,
and analysis methods, numerous infrastructure platforms have been developed for phenotyping.
The binding of cosmological structures by massless topological defectsSérgio Sacani
Assuming spherical symmetry and weak field, it is shown that if one solves the Poisson equation or the Einstein field
equations sourced by a topological defect, i.e. a singularity of a very specific form, the result is a localized gravitational
field capable of driving flat rotation (i.e. Keplerian circular orbits at a constant speed for all radii) of test masses on a thin
spherical shell without any underlying mass. Moreover, a large-scale structure which exploits this solution by assembling
concentrically a number of such topological defects can establish a flat stellar or galactic rotation curve, and can also deflect
light in the same manner as an equipotential (isothermal) sphere. Thus, the need for dark matter or modified gravity theory is
mitigated, at least in part.
Describing and Interpreting an Immersive Learning Case with the Immersion Cub...Leonel Morgado
Current descriptions of immersive learning cases are often difficult or impossible to compare. This is due to a myriad of different options on what details to include, which aspects are relevant, and on the descriptive approaches employed. Also, these aspects often combine very specific details with more general guidelines or indicate intents and rationales without clarifying their implementation. In this paper we provide a method to describe immersive learning cases that is structured to enable comparisons, yet flexible enough to allow researchers and practitioners to decide which aspects to include. This method leverages a taxonomy that classifies educational aspects at three levels (uses, practices, and strategies) and then utilizes two frameworks, the Immersive Learning Brain and the Immersion Cube, to enable a structured description and interpretation of immersive learning cases. The method is then demonstrated on a published immersive learning case on training for wind turbine maintenance using virtual reality. Applying the method results in a structured artifact, the Immersive Learning Case Sheet, that tags the case with its proximal uses, practices, and strategies, and refines the free text case description to ensure that matching details are included. This contribution is thus a case description method in support of future comparative research of immersive learning cases. We then discuss how the resulting description and interpretation can be leveraged to change immersion learning cases, by enriching them (considering low-effort changes or additions) or innovating (exploring more challenging avenues of transformation). The method holds significant promise to support better-grounded research in immersive learning.
The debris of the ‘last major merger’ is dynamically youngSérgio Sacani
The Milky Way’s (MW) inner stellar halo contains an [Fe/H]-rich component with highly eccentric orbits, often referred to as the
‘last major merger.’ Hypotheses for the origin of this component include Gaia-Sausage/Enceladus (GSE), where the progenitor
collided with the MW proto-disc 8–11 Gyr ago, and the Virgo Radial Merger (VRM), where the progenitor collided with the
MW disc within the last 3 Gyr. These two scenarios make different predictions about observable structure in local phase space,
because the morphology of debris depends on how long it has had to phase mix. The recently identified phase-space folds in Gaia
DR3 have positive caustic velocities, making them fundamentally different than the phase-mixed chevrons found in simulations
at late times. Roughly 20 per cent of the stars in the prograde local stellar halo are associated with the observed caustics. Based
on a simple phase-mixing model, the observed number of caustics are consistent with a merger that occurred 1–2 Gyr ago.
We also compare the observed phase-space distribution to FIRE-2 Latte simulations of GSE-like mergers, using a quantitative
measurement of phase mixing (2D causticality). The observed local phase-space distribution best matches the simulated data
1–2 Gyr after collision, and certainly not later than 3 Gyr. This is further evidence that the progenitor of the ‘last major merger’
did not collide with the MW proto-disc at early times, as is thought for the GSE, but instead collided with the MW disc within
the last few Gyr, consistent with the body of work surrounding the VRM.
The debris of the ‘last major merger’ is dynamically young
Biochemical Study on Endothelial Nitric Oxide Gene Polymorphism in Fatty Liver Patients
1. IOSR Journal of Pharmacy and Biological Sciences (IOSR-JPBS)
e-ISSN: 2278-3008, p-ISSN:2319-7676. Volume 10, Issue 6 Ver. I (Nov - Dec. 2015), PP 26-33
www.iosrjournals.org
DOI: 10.9790/3008-10612633 www.iosrjournals.org 26 | Page
Biochemical Study on Endothelial Nitric Oxide Gene
Polymorphism in Fatty Liver Patients
Rizk Ahmed El-Baz1
, Alaa Wafa2
, Nasser Mohammed Hosny3
,
Sameh Refaat El-Saka4
1
Children Hospital – Genetic Unit, Faculty of Medicine, Mansoura University
2
Internal Medicine Department, Faculty of Medicine, Mansoura University
3
Inorganic Chemistry Department, Faculty of Science, Port-Said University
4
B.Sc. Zology& Chemistry, Faculty of Science, Mansoura University
Abstract: Endothelial nitric oxide synthase (eNOS) gene polymorphism association with non-alcoholic fatty
liver disease (NAFLD).
Objective: to check for association of polymorphism of eNOS gene with susceptibility and severity of NAFLD in
cases from Egypt.
Subjects: This work included 100 cases with NAFLD from Internal,liver unit and 100 healthy individuals. The
mean age of cases was 45.45 ± 15.29 (range: 18 – 80 years).
Results: Total cases showed significant frequency of G894T GG (P < 0.001, OR = 0.24), 894 TT (P < 0.001,
OR = 4.68), T786C CC (P < 0.001, OR = 8.0), 786 CT (P < 0.05, OR = 0.52). 27bp bb (P < 0.001, OR = 4.2),
ab (P < 0.001, OR = 0.30). These were considered risk genotypes for disease of NAFLD in Egypt.
Conclusion: This study suggest that eNOS homozygous 894TT, 786C genotype may be increase risk of NAFLD
in Egypt.
Abbreviations: eNOS: Endothelial nitric oxide synthase, NAFLD: non-alcoholic fatty liver disease, PCR-SSP:
polymerase chain reaction with sequence specific primers.
I. Introduction:
Non alcoholic fatty liver disease (NAFLD) is progressively diagnosed worldwide and is considered to
be the most common liver disorder in Western countries, estimated to affect at least one-quarter of the general
population (Rector, et al., 2008; Lazo; Clark, et al., 2008). NAFLD used to be almost exclusively a disease of
adults but is now becoming a significant health issue also in obese children. The prevalence of childhood
obesity has significantly increased over the past three decades (Janssen, et al., 2005; park, et al., 2005). and
boosted the prevalence of NAFLD in adolescents (Barshop, et al., 2008).
Lipid accumulation in the liver is the major hallmark of NAFLD. A comprehensive understanding of
the mechanisms leading to liver steatosis and further transition to nonalcoholic steatohepatitis (NASH) still
remains elusive. There is no simple solution to understand the multi-factorial nature of NAFLD appearance and
progression, presumably due to the nonlinear interactions of those factors. Abnormalities in lipid and lipoprotein
metabolism accompanied by chronic inflammation are considered to be the central pathway for the development
of several obesity-related co-morbidities such as NAFLD and cardio-vascular disease (CVD) (Schindhelm, et
al., 2007; Loria, et al., 2007).
NAFLD is also very common in type 1 diabetes and is strongly associated with increased
prevalence of CVD independent of other confounding factors (Targher , et al., 2010). In addition to the liver-
related causes, CVD represents the major survival risk of patients with NASH (Ekstedt, et al., 2006). However,
the nature of the relationship NAFLD/CVD is still under debate. McKimmie and coauthors (Mckimmie et al.,
2008).did not find independent association between hepatic steatosis and CVD in a subset of participants in
Diabetes Heart Study. They suggested that hepatic steatosis is more a secondary phenomenon than a direct
mediator of CVD. Even so, sufficient evidence exists that CVD risk assessment seems mandatory in NAFLD
patients.
Non-alcoholic fatty liver disease (NAFLD) occurs across all age groups and ethnicities and is
recognised to occur in 14%–30% of the general population ( Nomura, et al., 1988 ; Browning, et al., 2004).
Primary NAFLD is related to insulin resistance and thus frequently occurs as part of the metabolic changes that
accompany obesity, diabetes, and hyperlipidaemia. However, it is important to exclude secondary causes of
hepatic steatosis by clinical assessment. Treatment of these conditions differs and revolves around correcting the
underlying cause (Angulo , 2002).
Lipid transport in plasma utilizes highly specialized lipoprotein complexes. After a meal, dietary fat
and cholesterol are absorbed into intestinal cells and incorporated in nascent chylomicrons. The liver is another
important source of lipoproteins. A central metabolic role of the liver is to maintain plasma glucose within
2. Biochemical Study on Endothelial Nitric Oxide Gene Polymorphism in Fatty Liver Patients
DOI: 10.9790/3008-10612633 www.iosrjournals.org 27 | Page
narrow physiological limits regardless of the nutritional state of the animal. In energy excess, glucose is
converted to fatty acids, which are further used to synthesize triglycerides. Triglycerides can be stored as lipid
droplets within hepatocytes or incorporated into very-low-density lipoproteins (VLDL) and secreted into the
blood. Once in the blood, triglyceride content of these particles is progressively reduced by the action of
lipoprotein lipase (LPL), eventually resulting in intermediate-density lipoproteins (IDLs) and low-density
lipoproteins (LDL) with relatively high cholesterol content (Tulenko and Sumner, 2002). LDL circulates and
is absorbed by the liver by binding of LDL to LDL receptor (Brown and Goldstein, ,1997).
The blockade of hepatic VLDL secretion results in accumulation of triglycerides in the liver.
Microsomal triglyceride transfer protein (MTTP) is essential for the formation of VLDL in the liver
(Olofsson, et al., 2000). Mice that cannot secrete VLDL due to the conditional knockout of MTTP in the
liver exhibit markedly reduced levels of triglycerides in the plasma and develop hepatic steatosis (Raabe, et al.,
1999; Bjorkegren, et al., 2002).However, without insulin resistance and inflammation (Minehira, et al., 2008).
In line with the rodent data, human MTTP polymorphisms lead to decreased MTTP activity and VLDL export
and are associated with greater intracellular triglyceride accumulation. Altogether, this impacts NASH
pathogenesis (Namikawa, et al., 2004).possibly through.
Abnormal lipoprotein concentration in plasma reflects disturbances in homeostasis of major lipid
components of lipoproteins, triglycerides, cholesterol, and cholesterol esters. Excessive accumulation of
triglycerides in the liver is the hall- mark of NAFLD. The potential sources of fat contributing to hepatic
steatosis are dietary fatty acids through uptake of intestine-borne chylomicron remnants, increased lipolysis of
peripheral fat store, and de novo synthesis. Tracer studies in obese humans with NASH demonstrated that 60%
of triglycerides in the liver arose from free fatty acids, 25% from de novo lipogenesis, and 15% from the diet
(Donnelly, et al., 2005).
Recent evidence suggests that NAFLD might be a mitochondrial disease. Mitochondrial dysfunction
contribute to the pathogenesis of NAFLD since it affects hepatic lipid homeostasis, promotes ROS production
and lipid peroxidation, cytokine release and cell death (Begriche, K.; Igoudjil, A.; Pessayre, D.; Fromenty, B.
2006). Selected recent published studies linking mitochondrial dysfunction to NAFLD. NAFLD has been shown
to be associated with mitochondrial paracrystalline inclusions (Caldwell, S.H.;. 2004 - Sanyal, A.J.;. 2001).
These paracrystalline inclusions have been observed in many mitochondrial myopathies (Lammens, M.; Laak,
H. 2005) Uncoupling of the oxidation and the phosphorylation and increased free radical production and lipid
peroxidation causes cell injury .(Lammens, M.; Laak, H. 2005).ROS production causes lipid peroxidation of
mitochondrial membranes which can contribute to impaired mitochondrial function and perpetuate the ROS
generation. Oxidative stress also triggers production of inflammatory cytokines, causing inflammation and
fibrogenic response. This ultimately results in the development of NASH (Rolo, A.P.; Teodoro, J.S.;
Palmeira, C.M. 2012).
II. Subject and Methods
This study included 100 cases with (NAFLD) recruited from hepatology Department of Internal
Medicine, Mansoura university hospital with an age ranging between 19-67 years
Case genotypes were compared to 100 healthy unrelated volunteers from the same locality DNA extraction and
purification
Fasting blood samples (3mL) were collected into two sets of tubes: the first set was ethylene diamine
tetra acetic acid (EDTA)–coated vacuum tubes stored at 4°C for DNA extractionand purification was performed
using QIAamp DNA Blood Mini Kits (Qiagen, Hilden, Germany).
Screening for the eNOS gene by PCR-restriction fragment length polymorphism
A- Detection of G894T Mutation using PCR Amplification/RFLP (Restriction Fragment Length
Polymorphism)
Estimation of G894T gen mutation was described by (Papazoglou et al. 2004). PCR is based on the enzymatic
of fragment of DNA that is flanked by two primers (short olignucleotide)
G894T genotype was performed using PCR amplification. Briefly, primer sequences were: Forward:
5`-CAT GAG GCT CAG CCC CAG-3` and reverse 5`-AGT CAA TCC CTT TGG TGC TCA C-3`.
These primers amplified 206 bpfragment . Cycling conditions were as follow: initial denaturation step
94ºC for 5 min, 35 cycling of 94ºC for 5 min, 95ºC for 25 min, 64ºC for 35 min, and 72ºC for 40min, and final
extension of 72؛C for 5min. The amplified product was digested with Mbo1 fragments separated on 2% Agarose
gel (Laboratories Canda, Madrid, and Spain). The G894 allele remained uncut (20 6bp), while the 894T was cut
into two fragments of 119 and 87 bp (Papazoglou et al. 2004).
B. Detection of T786C Gene Mutation
By applies the same mentioned before except for using the following primers and restriction enzyme.
Primers for T786C:
Forward primer: 5`-ATGCTCCCACCAGGGCATCA-3`
3. Biochemical Study on Endothelial Nitric Oxide Gene Polymorphism in Fatty Liver Patients
DOI: 10.9790/3008-10612633 www.iosrjournals.org 28 | Page
Reverseprimer:5`-GTCCTTGAGTCTGACATTAGGG-3` Cycling conditions were as
follow: initial denaturation step 94ºC for 5 min, 30 cycling of 94ºC for 20 sec, 57ºC for 30 sec, and 72ºC for
30sec, and final extension of 72ºC for 5min. The amplified product was digested with NgoMIV enzyme and
fragments separated on 2% Agarose gel (Laboratories Canda, Madrid, and Spain)The T786C substitution at bp
786 creatsNgOMIV recognition sequence. By abolishing aNgOMIV restriction site, the T786C mutation results
in the digestion of the 236 bpamplicon into 203- and 33 bp fragments. Wild types (786TT) produced a single
band at 236bp, heterozygote (786CT) produced 236, 203-, and 33-bp fragments, and homozygous mutants
(786CC) produced 203 and 33bp fragments (Banyasz et al., 2006).
C. Detection of interon 4b/a Gene Mutation using PCR Amplification
By applies the same mentioned before except for using the following primers and no restriction
enzyme.
Primer for interon 4b/a:
Forward primer: 5`-AGGCCCTATGGTAGTGGCCTTT-3`
Reverse primer: 5`-TGCTCCTGCTACTGACAGCA-3`
Cycling conditions were as follow: initial denaturation step 94ºC for 5 min, 35 cycling of 94ºC for
1min, 56ºC for 1 min, and 72ºC for 2min, and final extension of 72ºC for 5min. The amplified product was
separated on 2% Agarose gel (Laboratories Canda, Madrid, and Spain)Theinteron 4b/a genotype was
determined using PCR analysis. The interon 4b/a variant was identified using PCR ,No restriction enzyme
digestion of the amplified product.
The interon 4b/a substitution at bp 193,220. (interon 4b/a) produced a double band at 193bp,
220bpCarier heterozygote (ba), produced Single band at 193-bp (aa) Carier homozygous and 220-bp (bb) Carier
homozygous (Banyasz et al., 2006).
III. Result
Comparison between all cases with NAFLD and healthy control regarding to their genotype (T786C)
distribution of (eNOS) gene polymorphisms.
T786C
Cases
(n = 100)
Control
(n = 100) P OR (95% CI)
N (%) N (%)
Genotypes TT 33 (33%) 38 (38%) > 0.05 0.80(0.45 – 1.44)
CC 25 (25%) 4 (4%) <0.001* 8.0(2.67 – 23.98)
CT 42 (42%) 58 (58%) <0.05* 0.52(0.30 – 0.92)
Alleles T 108 (54%) 134 (67%) <0.01* 0.58(0.39 – 0.87)
C 92 (46%) 66 (33%) <0.01* 1.33(1.07 – 1.65)
* Significant P < 0.05
There were significant difference between two groups where CC homozygous mutated is 25% vs 4% (P <
0.001).
Comparison between all cases with NAFLD and healthy control regarding to their genotype (27pb) intron
4b/a allele of (eNOS) gene polymorphisms.
27pb
Cases
(n = 100)
Control
(n = 100) P OR (95% CI)
N (%) N (%)
Genotypes aa 9 (9%) 14 (14%) > 0.05 0.61(0.25 – 1.48)
bb 62 (62%) 28 (28%) <0.001* 4.20(2.32 – 7.60)
ab 29 (29%) 58 (58%) <0.001* 0.30(0.16 – 0.53)
Alleles a 47 (23.5%) 86 (43%) <0.001* 0.41(0.27 – 0.63)
b 153 (76.5%) 114 (57%) <0.001* 1.51(1.26 – 1.83)
* Significant P < 0.05
There were significant difference between two groups where bb mutated homozygous is high
significant (62% vs 28%, P < 0.001).
4. Biochemical Study on Endothelial Nitric Oxide Gene Polymorphism in Fatty Liver Patients
DOI: 10.9790/3008-10612633 www.iosrjournals.org 29 | Page
Comparison between two sex group of NAFLD subjects regarding to their genotypes distribution of
(eNOS) gene polymorphisms.
Male
(n = 76)
Female
(n = 24) P
N (%)
27pb
(aa) 7 (77.8%) 2 (22.2%)
0.866(ab) 21 (7.24%) 8 (27.6%)
(bb) 48 (77.4%) 14 (22.6%)
T786C
(TT) 26 (78.8%) 7 (21.2%)
0.882(CT) 31 (73.8%) 11 (26.2%)
(CC) 19 (76%) 6 (24%)
G894T
(GG) 13 (86.7%) 2 (13.3%)
0.275(GT) 48 (78.1%) 14 (21.%)
(TT) 15 (65.2%) 8 (34.8%)
This table show there are no any significant difference between two sex groups (P > 0.05).
Fig (2): PCR amplification of intron 4b/a polymorphism of eNOS gene PCR product of intron 4b/a
polymorphism have ban size (220) bp in bb carrier homozygous and ba carrier heterozygous which has (220,
193 pb fragments bane 2 and 4) (by using DNA size marker 50 bp).
Fig (3): Enzymatic digestion of T786C polymorphism of eNOS gene. Wild type TT is found which appears at
236 bp in lanes 1,2,3& 5, digestion of PCR product of T786C polymorphism of eNOS gene using N90MIV
enzyme. Which digests the 236-bp fragment into 203 and 33-bp fragments (heterozygous mutated genotype CT
which has 236, 203, 33 bp fragments langes 6 only) (homozygous mutated genotype CC is found which has
203, 33 bp fragments lanes 4,7) (By using DNA size marker 50 bp).
Fig. (4): Enzymatic digestion of G894T polymorphism of eNOS gene. Wild type GG is found which appears at
206 bp only lanes 4 and 6. digetion of PCR product of G894T polymorphism of eNOS gene using MboI
enzyme. Which digests the 206-bp fragment into 119- and 87-bp fragments (heterozygous mutated genotype GT
which has 206, 119,87bp fragments lanes 2 and 7) (homozygous mutated genotype TT is found which has 119,
87 bp fragments lanes 1,3,5) (By using DNA size marker 50 bp).
5. Biochemical Study on Endothelial Nitric Oxide Gene Polymorphism in Fatty Liver Patients
DOI: 10.9790/3008-10612633 www.iosrjournals.org 30 | Page
IV. Discussion
NAFLD is defined as an excess of fat in the liver in which at least 5% of hepatocytes display lipid
droplets (Neuschwander-Tetri, 2005) that exceed 5%-10% of liver weight (Adams et al., 2005 and Browning
& Horton, 2004) in patients who do not A currently favored hypothesis is that “two hits” are required for a
subject to develop NASH (Day and James, 1998). The first hit leads to hepatic steatosis, and the second to
hepatocyte injury and inflammation. However, the primary metabolic abnormalities leading to lipid
accumulation within hepatocytes has remained poorly understood. Accumulating evidence indicates that
mitochondrial dysfunction plays a central role in the pathogenesis of NAFLD, and that NAFLD is a
mitochondrial disease (Pessayre and Fromenty, 2005).
The liver, as a super metabolic achiever in the body, plays a critical role in metabolism of
carbohydrate, protein and fat to maintain blood glucose and energy homeostasis.
Mitochondria serve as the cellular powerhouse that generates ATP or heat by using substrates derived
from fat and glucose. Hepatocytes are normally rich in mitochondria and each hepatocyte contains about 800
mitochondria occupying about 18% of the entire liver cell volume. Mitochondria play an important role in
hepatocyte metabolism, being the primary site for the oxidation of fatty acids and oxidative phosphorylation. A
mitochondrion contains inner and outer membranes composed of phospholipid bilayers and proteins. The outer
mitochondrial membrane contains numerous integral proteins called porins, which contain a relatively large
internal channel that is permeable to all molecules of 5000 daltons or less (Yongzhong et al., 2008).Hepatic free
fatty acids sources: (a) dietary triglycerides (TG) as chylomicron particles from the intestine; (b) de novo
synthesis in the liver; (c) Free fatty acids (FFA). influx into the liver from lipolysis of adipose tissue; (d)
diminished export of lipids from the liver; and (e) reduced oxidation of fatty acids. Imbalance of these metabolic
steps will increased TG accumulation within the cytoplasm of hepatocytes.
Fatty acid oxidation (FAO) is the major source of energy for skeletal muscle and the heart, while the
liver oxidizes fatty acids primarily under the conditions of prolonged fasting, during illness, and during periods
of increased physical activity (Pessayre et al., 2005).While long-chain FFAs entry into the mitochondria is
regulated by the activity of the enzyme carnitinepalmitoyltransferase I (CPT-I). Glycolysis generates pyruvate,
which is transformed by mitochondria into acetyl-CoA, an intermediate that goes through the citric acid cycle
for the production of reducing agents and ATP. However, when glucose and energy levels are elevated, acetyl-
CoA is converted to citrate which can leak out of the mitochondrial matrix into the cytosol through the
tricarboxylate carrier. In the cytosol, citrate regenerates acetyl-CoA which is converted to malonyl-CoA by
acetyl-CoA carboxylase. Malonyl-CoA plays important roles in both hepatic fatty acid oxidation and lipid
synthesis. Malonyl-CoA is the initial component for fatty acid synthesis. High malonyl-CoA levels also actively
inhibit CPT-I enzyme activity thus robustly decreasing fatty acid oxidation by reducing the rate of fatty acid
entry into the mitochondria. Thus, periods of caloric overconsumption, and excessive energy supply, increase
malonyl-CoA levels which promotes hepatic fatty acid synthesis (storage) and suppresses fatty acid oxidation
(catabolism). Conversely, in the fasting state, hepatic malonyl-CoA levels are low, allowing extensive
mitochondrial import of long-chain FFAs and high rates of β-oxidation. During β-oxidation in mitochondria,
FFAs undergo a dehydrogenation, then hydration, followed by a second dehydrogenation, and finally thiolysis,
releasing one 2-carbon acetyl-CoA molecule and a shortened fatty acid. The cycle is repeated to split the fatty
acid into acetyl-CoA subunits. The acetyl-CoA units enter the citric acid cycle to produce reducing agents which
can be converted to ATP in the electron transport chain. Under fasting conditions, acetyl-CoA moieties can be
converted into ketone bodies (acetoacetate and β-hydroxybutyrate), which are released by the liver to be
oxidized in peripheral tissues by the tricarboxylic acid cycle (Caldwell et al.,1999). Although the mechanisms
responsible for fatty liver are still not fully elucidated, decreased capacity to oxidize fatty acids, increased
delivery and transport of FFAs into the liver, and augmented hepatic fatty acid synthesis are likely to play a
significant role in the pathogenesis of NAFLD. We and others have shown that mitochondrial abnormalities are
closely related to the pathogenesis of NAFLD which raised the possibility that NAFLD (Ibdah et al., 2005).
In this study we search about relation between CNOS polymorphism of NAFLD. So that we start with
definition of NAFLD and causes and when we know that one hepatocyte have 800 mitochondria and the most of
metabolism process occur in liver. So we sure that impairment of mitochondria and metabolism is the main
cause of fatty acid deposition in hepatocyte the increase of synthesis of fatty acid or (FFA) up take and the
decrease in oxidation which occur by mitochondria on the other hand we study the role of (eNO) in metabolism
and mitochondria we obtain that eNO regulate metabolism and mitochondrial oxidation.
Our study sugest that (eNO) polymorphism dysfunction is the main cause of (NAFLD). In this study,
when we extracted the (DNA) from whole blood and using (PCR) and primer specific for alleles of (eNOS)
gene.
our study on three region of (eNOS) gene by three primer and using distinct enzyme then using gel
electrophrosis, we obtained result show relation between this three area of genotypes.
6. Biochemical Study on Endothelial Nitric Oxide Gene Polymorphism in Fatty Liver Patients
DOI: 10.9790/3008-10612633 www.iosrjournals.org 31 | Page
G894T: We obtain thee form (a) TT homozygous mutant 23%, (b) GT heterozygous carrier 62%, and
(c) GG homozygous normal 15%; T786C: (a) CC homozygous mutant 25%, (b) CT heterozygous carrier 42%,
and (c) TT homozygous normal 33%; and Intron 4b/a: (a) bb homozygous carrier 62%, (b) aa homozygous
carrier 9%, (c) and ba heterozygous normal 29%.
Our study verified that (eNOS) gene polymorphism is responsible for development of (NAFLD) and
hope to use that in treatment of NAFLD by:
a- Regulation of (eNOS) gene or control on metabolism of (FA) by lipoic acid or propionyl-L-
carnitine(Nicole Cutler, 2011).
b- Supplement (NO) by direct method or indirect by supplement of L arginine or C-activate (ePCs) endo-
progenator cells by Phytosterol(Da-long chen et al., 2015).
This study showed an excess of homozygosity for the (TT),(CC) mutant excess among NAFLD cases
by comparison of healthy.
Hence the results of this study suggest that eNOS homozygous (894TT), (786CC) genotype may be at
increased risk of NAFLD in Egypt.
NAFLD is defined as an excess of fat in the liver in which at least 5% of hepatocytes display lipid droplets
that excess 5%-10% of liver weight in patients who do not consume alcohol.
From this study we can conclude that G894T/T786C, intron 4b/a polymorphism of eNOS gene was
found to be associated with development of NAFLD and mutant TT genotypes of G894T ,CC of T786C and bb,
genotype of intron 4b/a may considered as genetic risk factors for development of NAFLD in Egypt.
Our result are in agreement with result of (Petrtyl, 2013) the study of Petrtyl that includes one hundred
and thirty-two patients with liver cirrhosis (age 36-72 years) and 101 controls were examined for functional
variants of eNOS (E298D, 27bpintr4, 786T/CThe frequency of E298D (GG 12%, GT 41%, TT 47%), 28bpintr4
(AA 6%, AB 28%, BB 66%), 786T/C genotypes (CC 17%, CT 45%, TT 38%)Examined eNOS variants have no
relationship to pathogenesis of liver cirrhosis. Severity of portal hypertension was associated with the changes in
endothelial activation in Scandinavian population .
Our result are in agreement with result of (Vanessa Helena desouzazago, 2013), LDL, nitrite and
lipid-protein ratios (HDL2 and HDL3) (p < 0.001) in both genotypes. Interestingly, we observed genotype/drug
interactions on CETP (p < 0.07) and lipoprotein (a) (Lp(a)) (p < 0.056), leading to a borderline This study aimed
at evaluating if the T-786C polymorphism is associated with changes of atorvastatin effects on the lipid profile,
on the concentrations of metabolites of nitric oxide (NO) and of high sensitivity C-reactive protein (hsCRP).
After each treatment lipids, lipoproteins, HDL2 and HDL3 composition, cholesteryl ester transfer
protein (CETP) activity, metabolites of NO and hsCRP were evaluated.
The comparisons between genotypes after placebo showed an increase in CETP activity in a
polymorphism-dependent way (TT, 12±7; CC, 22±12; p < 0.05). The interaction analyses between treatments
indicated that (eNOS) gene polymorphism associated with lipid profile in brazil population.
The our result are in agreement with result of (Farookthameem, 2008) study participants (N = 670; 39
families) were genotyped for the three polymorphisms using polymerase chain reaction followed by restriction
fragment length polymorphism assay. Association analyses between these polymorphisms and T2DM and its
related phenotypes were carried out using a measured genotype approach as implemented in the computer
program SOLAR. Of the variants examined, only the 27bp-VNTR variant exhibited significant association with
high density lipoprotein cholesterol (HDL-C) (P = 0.04) and diastolic blood pressure (DBP) levels (P = 0.02)
after accounting for trait- examined at the eNOS locus, only 27bp-VNTR appears to be a minor contributor to
the variation in T2DM-related traits in Mexican Americans.specific covariates. The carriers of the rare allele
(27bp-VNTR-4a) are associated with decreased HDL-C and increased DBP levels in Mexican American
population.
Our result are in agreement with result of (Liucs 2013) this study investigated the role of three NOS3
polymorphisms (T-786C, intron 4b/a, and G894T) in the risk of MetS using a hospital-based case-control study.
We recruited 339 MetS cases and 783 non-MetS controls at a central Taiwanese hospital.
The T-786C TC+CC genotype was significantly associated with a decreased risk of MetS (odds ratio
(OR), 0.63; 95% confidence interval (CI), 0.43-0.91), compared to the T-786C TT genotype, according to a
logistic regression analysis. This beneficial effect was much greater for those who had ever smoked cigarettes
(OR, 0.47; 95% CI, 0.26-0.87) or those who had not consumed alcohol (OR, 0.45; 95% CI, 0.26-0.77). In
addition, the intron 4b/a variant genotype was marginally associated with a reduced risk of MetS (OR, 0.68;
95% CI, 0.47-1.00), compared to the intron 4b/a bb genotype, particularly for never alcohol consumers (OR,
0.56; 95% CI, 0.33-0.95). thisresults suggest that the NOS3 T-786C and intron 4b/a polymorphisms may
contribute to the risk of MetS in taiwan population ..our result are in agreement with result of (Imamura,
2008). The allele frequencies of both polymorphisms showed no considerable differences in 233 non-diabetic
subjects and 301 patients with Type II (non-insulin-dependent) diabetes mellitus. Non-diabetic subjects with the
(-)786C allele had (p<0.05) higher fasting plasma insulin and homeostasis model assessment of insulin
7. Biochemical Study on Endothelial Nitric Oxide Gene Polymorphism in Fatty Liver Patients
DOI: 10.9790/3008-10612633 www.iosrjournals.org 32 | Page
resistance than those with the (-) 786T/ (-)786T genotype. Diabetic subjects with (-)786C allele showed higher
HbA(1c) than those with the (-)786T/(-)786T genotype. A euglycaemichyperinsulinemic clamp study done on
71 of the 301 patients showed a lower glucose infusion rate in diabetic patients with the (-)786C allele than
those without it. In diabetic patients with the (-)786C allele, plasma nitrate and nitrite concentrations were lower
than in subjects without it (p=0.026). No differences were observed between mutant carriers of Glu298Asp and
non-carriers among both non-diabetic subjects and Type II diabetic patients.
The (-)786T-C mutation of the eNOS gene is associated with insulin resistance in both Japanese non-
diabetic subjects and Type II diabetic patients.
Our study in agreement with result of (Miranda, 2013).Haplotypes in the three groups of subjects. The
CC genotype for the T(786)C polymorphism was more common in the MetS group than in the control group
(OR = 3.27; CI 1.81-9.07; P < 0.05). However, we found no significant differences in the distribution of eNOS
haplotypes (P > 0.00625; P for significance after correction for multiple comparisons). Our findings suggest that
while eNOS haplotypes are not relevant, the CC genotype for the T(786)C polymorphism is associated with
MetS in obese children and adolescents. in brazil
Our study in agreement with result of (Alkharfy,2012) in Saudi Arabia. (eNOS) gene polymorphisms
and MetS in a Saudi Arabian Arabians (477 MetS and 409 Non-MetS). The genotype distribution (TT, p=0.001;
TC, p=0.001; TC+CC, p=0.001) and allele (T, p=0.007; C, p=0.007) frequency of the -786T>C SNP were
significantly different between Non-MetS and MetS subjects which remained significant after Bonferroni
correction. Moreover: 1) the GT and GT+TT genotypes of the 894G>T SNP were associated with elevated
blood pressure (p=0.017, and p=0.022, respectively); 2) the ab variant of 4a/b polymorphism was associated
with decreased HDL levels (p= 0.044); and 3) the TC+CC genotype and C allele of the -786T>C SNP were
associated with increased fasting glucose levels (p=0.039, and p=0.028, respectively). Also, G-a-C was
identified as the risk haplotype for MetS susceptibility (p=0.034). The results suggest a significant association of
894G>T, 4a/b and -786T>C polymorphisms with MetS and its components is present in an Arab population.
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