Extensive role of the general regulatory factors, Abf1 and Rap1, in determining genome-wide chromatin structure in budding yeast

The packaging of eukaryotic DNA into chromatin has profound consequences for gene regulation, as well as for other DNA transactions such as recombination, replication and repair. Understanding how this packaging is determined is consequently a pressing problem in molecular genetics. DNA sequence, chromatin remodelers and transcription factors affect chromatin structure, but the scope of these influences on genome-wide nucleosome occupancy patterns remains uncertain. Here, we use high resolution tiling arrays to examine the contributions of two general regulatory factors, Abf1 and Rap1, to nucleosome occupancy in Saccharomyces cerevisiae. These factors have each been shown to bind to a few hundred promoters, but we find here that thousands of loci show localized regions of altered nucleosome occupancy within 1 h of loss of Abf1 or Rap1 binding, and that altered chromatin structure can occur via binding sites having a wide range of affinities. These results indicate that DNA-binding transcription factors affect chromatin structure, and probably dynamics, throughout the genome to a much greater extent than previously appreciated

Plant-Based Diets and Phytochemicals in the Management of Diabetes Mellitus and Prevention of Its Complications: A Review

Diabetes mellitus (DM) is currently regarded as a global public health crisis for which lifelong treatment with conventional drugs presents limitations in terms of side effects, accessibility, and cost. Type 2 diabetes (T2DM), usually associated with obesity, is characterized by elevated blood glucose levels, hyperlipidemia, chronic inflammation, impaired β-cell function, and insulin resistance. If left untreated or when poorly controlled, DM increases the risk of vascular complications such as hypertension, nephropathy, neuropathy, and retinopathy, which can be severely debilitating or life-threatening. Plant-based foods represent a promising natural approach for the management of T2DM due to the vast array of phytochemicals they contain. Numerous epidemiological studies have highlighted the importance of a diet rich in plant-based foods (vegetables, fruits, spices, and condiments) in the prevention and management of DM. Unlike conventional medications, such natural products are widely accessible, affordable, and generally free from adverse effects. Integrating plant-derived foods into the daily diet not only helps control the hyperglycemia observed in DM but also supports weight management in obese individuals and has broad health benefits. In this review, we provide an overview of the pathogenesis and current therapeutic management of DM, with a particular focus on the promising potential of plant-based foods

Effects of Aminoglycoside Antibiotics on Human Embryonic Stem Cell Viability during Differentiation In Vitro

Human embryonic stem cells (hESCs) are being used extensively in array of studies to understand different mechanisms such as early human embryogenesis, drug toxicity testing, disease modeling, and cell replacement therapy. The protocols for the directed differentiation of hESCs towards specific cell types often require long-term cell cultures. To avoid bacterial contamination, these protocols include addition of antibiotics such as pen-strep and gentamicin. Although aminoglycosides, streptomycin, and gentamicin have been shown to cause cytotoxicity in various animal models, the effect of these antibiotics on hESCs is not clear. In this study, we found that antibiotics, pen-strep, and gentamicin did not affect hESC cell viability or expression of pluripotency markers. However, during directed differentiation towards neural and hepatic fate, significant cell death was noted through the activation of caspase cascade. Also, the expression of neural progenitor markers Pax6, Emx2, Otx2, and Pou3f2 was significantly reduced suggesting that gentamicin may adversely affect early embryonic neurogenesis whereas no effect was seen on the expression of endoderm or hepatic markers during differentiation. Our results suggest that the use of antibiotics in cell culture media for the maintenance and differentiation of hESCs needs thorough investigation before use to avoid erroneous results

Therapeutic Potential of Medicinal Plants and Their Phytoconstituents in Diabetes, Cancer, Infections, Cardiovascular Diseases, Inflammation and Gastrointestinal Disorders

Conditions like diabetes mellitus (DM), cancer, infections, inflammation, cardiovascular diseases (CVDs), and gastrointestinal (GI) disorders continue to have a major global impact on mortality and morbidity. Medicinal plants have been used since ancient times in ethnomedicine (e.g., Ayurveda, Unani, Traditional Chinese Medicine, and European Traditional Medicine) for the treatment of a wide range of disorders. Plants are a rich source of diverse phytoconstituents with antidiabetic, anticancer, antimicrobial, antihypertensive, antioxidant, antihyperlipidemic, cardioprotective, immunomodulatory, and/or anti-inflammatory activities. This review focuses on the 35 plants most commonly reported for the treatment of these major disorders, with a particular emphasis on their traditional uses, phytoconstituent contents, pharmacological properties, and modes of action. Active phytomolecules with therapeutic potential include cucurbitane triterpenoids, diosgenin, and limonoids (azadiradione and gedunin), which exhibit antidiabetic properties, with cucurbitane triterpenoids specifically activating Glucose Transporter Type 4 (GLUT4) translocation. Capsaicin and curcumin demonstrate anticancer activity by deactivating NF-κB and arresting the cell cycle in the G2 phase. Antimicrobial activities have been observed for piperine, reserpine, berberine, dictamnine, chelerythrine, and allitridin, with the latter two triggering bacterial cell lysis. Quercetin, catechin, and genistein exhibit anti-inflammatory properties, with genistein specifically suppressing CD8+ cytotoxic T cell function. Ginsenoside Rg1 and ginsenoside Rg3 demonstrate potential for treating cardiovascular diseases, with ginsenoside Rg1 activating PPARα promoter, and the PI3K/Akt pathway. In contrast, ternatin, tannins, and quercitrin exhibit potential in gastrointestinal disorders, with quercitrin regulating arachidonic acid metabolism by suppressing cyclooxygenase (COX) and lipoxygenase activity. Further studies are warranted to fully investigate the clinical therapeutic benefits of these plants and their phytoconstituents, as well as to elucidate their underlying molecular mechanisms of action

Insulin secretory actions of polyphenols of <i>Momordica charantia</i> regulate glucose homeostasis in alloxan-induced type 2 diabetic rats

Objective Momordica charantia, commonly known as bitter gourd, is traditionally used as remedies for various diseases including diabetes. The main objective of this study is to investigate the in vitro and in vivo insulinotropic and anti-diabetic effects of an 80% ethanolic extract of Momordica charantia (EEMC) fruit, as well as the underlying molecular mechanism involved and preliminary phytochemical screening. Methods The insulin secretion was measured using clonal pancreatic BRIN-BD11 β-cells and isolated mouse islets. The ability of EEMC to inhibit carbohydrate digestive enzymes and glucose absorption and, scavenge free radicals were assessed via starch digestion, glucose diffusion and DPPH assay methods. The effects of EEMC on a variety of metabolic parameters were evaluated in alloxan-induced type 2 diabetic rats, including lipid profile. Finally, a preliminary phytochemical screening was conducted to identify the active phytoconstituents. Key findings EEMC increased insulin release through the KATP-dependent/cAMP pathway, which depolarizes the β-cell membrane and elevates intracellular calcium. It also inhibited glucose absorption and free radicals, suggesting its potential to delay gastric emptying, attenuate oxidative stress, and reduce inflammatory cytokines. In vivo studies showed that EEMC improves oral glucose tolerance, food intake, fasting blood glucose, plasma insulin, lipids, and promotes intestinal motility. The active phytoconstituents in EEMC, such as flavonoids, alkaloids, tannins, saponins, steroids, and glycosides, are likely responsible for these effects. Conclusion The antihyperglycemic properties of EEMC indicate that it might be a promising candidate for diabetes management. However, additional study into the application of Momordica charantia in type 2 diabetes is essential

Plant-based diets and phytochemicals in the management of diabetes mellitus and prevention of its complications : a review

Diabetes mellitus (DM) is currently regarded as a global public health crisis for which lifelong treatment with conventional drugs presents limitations in terms of side effects, accessibility, and cost. Type 2 diabetes (T2DM), usually associated with obesity, is characterized by elevated blood glucose levels, hyperlipidemia, chronic inflammation, impaired β-cell function, and insulin resistance. If left untreated or when poorly controlled, DM increases the risk of vascular complications such as hypertension, nephropathy, neuropathy, and retinopathy, which can be severely debilitating or life-threatening. Plant-based foods represent a promising natural approach for the management of T2DM due to the vast array of phytochemicals they contain. Numerous epidemiological studies have highlighted the importance of a diet rich in plant-based foods (vegetables, fruits, spices, and condiments) in the prevention and management of DM. Unlike conventional medications, such natural products are widely accessible, affordable, and generally free from adverse effects. Integrating plant-derived foods into the daily diet not only helps control the hyperglycemia observed in DM but also supports weight management in obese individuals and has broad health benefits. In this review, we provide an overview of the pathogenesis and current therapeutic management of DM, with a particular focus on the promising potential of plant-based foods

Therapeutic potential of medicinal plants and their phytoconstituents in diabetes, cancer, infections, cardiovascular diseases, inflammation and gastrointestinal disorders

Conditions like diabetes mellitus (DM), cancer, infections, inflammation, cardiovascular diseases (CVDs), and gastrointestinal (GI) disorders continue to have a major global impact on mortality and morbidity. Medicinal plants have been used since ancient times in ethnomedicine (e.g., Ayurveda, Unani, Traditional Chinese Medicine, and European Traditional Medicine) for the treatment of a wide range of disorders. Plants are a rich source of diverse phytoconstituents with antidiabetic, anticancer, antimicrobial, antihypertensive, antioxidant, antihyperlipidemic, cardioprotective, immunomodulatory, and/or anti-inflammatory activities. This review focuses on the 35 plants most commonly reported for the treatment of these major disorders, with a particular emphasis on their traditional uses, phytoconstituent contents, pharmacological properties, and modes of action. Active phytomolecules with therapeutic potential include cucurbitane triterpenoids, diosgenin, and limonoids (azadiradione and gedunin), which exhibit antidiabetic properties, with cucurbitane triterpenoids specifically activating Glucose Transporter Type 4 (GLUT4) translocation. Capsaicin and curcumin demonstrate anticancer activity by deactivating NF-κB and arresting the cell cycle in the G2 phase. Antimicrobial activities have been observed for piperine, reserpine, berberine, dictamnine, chelerythrine, and allitridin, with the latter two triggering bacterial cell lysis. Quercetin, catechin, and genistein exhibit anti-inflammatory properties, with genistein specifically suppressing CD8+ cytotoxic T cell function. Ginsenoside Rg1 and ginsenoside Rg3 demonstrate potential for treating cardiovascular diseases, with ginsenoside Rg1 activating PPARα promoter, and the PI3K/Akt pathway. In contrast, ternatin, tannins, and quercitrin exhibit potential in gastrointestinal disorders, with quercitrin regulating arachidonic acid metabolism by suppressing cyclooxygenase (COX) and lipoxygenase activity. Further studies are warranted to fully investigate the clinical therapeutic benefits of these plants and their phytoconstituents, as well as to elucidate their underlying molecular mechanisms of action

Fine Tuning of Hepatocyte Differentiation from Human Embryonic Stem Cells: Growth Factor vs. Small Molecule-Based Approaches

Human embryonic stem cells (hESCs) are being utilized in diverse areas of studies such as development and disease modeling, cell replacement therapy, or drug toxicity testing because of their potential to be differentiated into any cell type in the body. The directed differentiation of hESCs into hepatocytes could provide an invaluable source of liver cells for various liver-based applications. Therefore, several protocols have been established in the past for hESC-hepatocyte differentiation based on the knowledge of signaling pathways and growth factors involved in different stages of embryonic hepatogenesis. Although successful derivation of hepatocytes has been achieved through these protocols, the efficiency is not always ideal. Herein, we have tested several combinations of published protocols, for example, growth factor vs. small molecule and different time durations of treatment for definitive endoderm (DE) induction and further hepatocyte differentiation to develop an efficient DE induction and hepatocyte differentiation in a highly reproducible manner based on the stage-specific marker expression and functional analysis