Gastric ulcer (GU) is the most common health concern that occurs due to alcohol consumption, smoking and physiological stress. Ethanol-induced GU in animal model resembles the pathophysiology of human ulcer. The present study was designed to investigate the cytoprotective and anti-inflammatory properties of tert-butylhydroquinone (tBHQ), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, against gastric mucosal damage induced by acute exposure of ethanol (5 ml/kg). The intervention of tBHQ (25 and 50 mg/kg, per os (po)) and omeprazole (20 mg/kg, po) was done for 10 consecutive days. Omeprazole was chosen as a standard drug because it is prescribed for the treatment of GU. Pretreatment of tBHQ decreased gastric mucosal lesion, ulcer index, apoptotic cells and lipid peroxidation level induced by ethanol. Furthermore, the intervention of tBHQ increased gastric mucosa integrity, pH, reduced glutathione, collagen and mucus-producing goblet cells. Intervention of tBHQ increased the expression of antioxidant markers such as Nrf2, haeme oxygenase-1 and catalase and decreased the expressions of inflammatory markers such as nuclear factor kappa-light-chain-enhancer of activated B cells and cyclooxygenase-2. The cytoprotective potential of tBHQ against gastric mucosal damage might be due to its ability to enhance cellular antioxidants and anti-inflammatory responses.
H3K9 methyltransferase (G9a) and its relevant molecule GLP are the SET domain proteins that specifically add mono, di and trimethyl groups on to the histone H3K9, which lead to the transcriptional inactivation of chromatin and reduce the expression of cancer suppressor genes, which trigger growth and progress of several cancer types. Various studies have demonstrated that overexpression of H3K9 methyltransferase G9a and GLP in different kinds of tumors, like lung, breast, bladder, colon, cervical, gastric, skin cancers, hepatocellular carcinoma and hematological malignancies. Several G9a and GLP inhibitors such as BIX‐01294, UNC0642, A‐366 and DCG066 were developed to combat various cancers; however, there is a need for more effective and less toxic compounds. The current molecular docking study suggested that the selected new compounds such as ninhydrin, naphthoquinone, cysteamine and disulfide cysteamine could be suitable molecules as a G9a and GLP inhibitors. Furthermore, detailed cell based and preclinical animal studies are required to confirm their properties. In the current review, we discussed the role of G9a and GLP mediated epigenetic regulation in the cancers. A thorough literature review was done related to G9a and GLP. The databases used extensively for retrieval of information were PubMed, Medline, Scopus and Science‐direct. Further, molecular docking was performed using Maestro Schrodinger version 9.2 software to investigate the binding profile of compounds with Human G9a HMT (PDB ID: 3FPD, 3RJW) and Human GLP MT (PDB ID: 6MBO, 6MBP).
Background Depression is globally a crucial communal psychiatric disorder, which is more common in older adults. The situation is considerably worse among millions of older (forcibly displaced Myanmar nationals or FDMNs) Rohingya adults, and the coronavirus disease-2019 (COVID-19) pandemic may exacerbate the already existing precarious situation. The present study investigated depressive symptoms and their associated factors in older adult Rohingya FDMNs in Cox Bazar, Bangladesh, during the COVID-19 pandemic. Method A total of 416 older adults aged 60 years and above residing in Rohingya camps situated in the South Eastern part of Bangladesh were interviewed using a 15-item Geriatric Depression Scale (GDS-15) in Bengali language. Chi-square test was performed to compare the prevalence of depressive symptoms within different categories of a variable and a binary logistic regression model was performed to determine the factors associated with depressive symptoms. Results More than 41% of Rohingya older adults had depressive symptoms (DS). Socio-demographic and economic factors such as living alone, dependency on family for living, poor memory, feelings of being left out, difficulty in getting medicine and routine medical care during COVID-19, perception that older adults are at highest risk of COVID-19 and pre-existing non-communicable chronic conditions were found to be significantly associated with developing DS. Higher DS was also evident among older female Rohingya FDMNs. Conclusion DS are highly prevalent in older Rohingya FDMNs during COVID-19. The findings of the present study call for immediate arrangement of mental health care services and highlight policy implications to ensure the well-being of older FDMNs.
The aim of this investigation was to establish potential oxidative effects of glucose, advanced glycation end products (AGE) and nicotine (N) in a fibroblast cell culture model using the anti-oxidants glutathione (G) and insulin like growth factor (IGF). Assays of androgen metabolites were used as biomarkers of healing in this context. Confluent monolayer cultures of human gingival fibroblasts were established in 24 well multiwell plates and incubated in Eagle's MEM for 24h using two radiolabelled androgen substrates 14C-testosterone/14C-4-androstenedione. The established effective concentrations of G1000, glutathione and AGE were used alone and in combination with nicotine and insulin-like growth factor. The medium was then solvent extracted for steroid metabolites, evaporated to dryness and subjected to thin layer chromatography in a benzene acetone solvent system 4:1 v/v for separation of formed metabolites. The metabolites were quantified, using a radioisotope scanner. Significant reduction in the yields of DHT in response to G1000, AGE and nicotine (n=6; p <0.003) were overcome by glutathione (n=6; p <0.002). The stimulatory effect of IGF when combined with AGE was further enhanced by the antioxidant effect of glutathione (n=6; p <0.003). Glucose, AGE and nicotine had a significant inhibitory effect on the yields of the androgen biomarker DHT, overcome by the antioxidant glutathione and IGF, suggestive of an oxidant role for the former agents and an anti-oxidant one for the latter. These agents affected yields of androgen metabolites, biomarkers of oxidative stress and repair, with potential implications on healing in uncontrolled diabetic smokers.
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