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Background and aim: N-acetyl-p-benzoquinoneimine (NAPQI), a toxic byproduct of paracetamol (Acetaminophen, APAP), can accumulate and cause liver damage by depleting glutathione and forming protein adducts in the mitochondria. These adducts disrupt the respiratory chain, increasing superoxide production and reducing ATP. The goal of this study was to provide computational proof that succinate dehydrogenase (SDH), a subunit of complex II in the mitochondrial respiratory chain, is a favorable binding partner for NAPQI in this regard. Method: Molecular docking, molecular dynamics simulation, protein-protein interaction networks (PPI), and KEGG metabolic pathway analysis were employed to identify binding characteristics, interaction partners, and their associations with metabolic pathways. A lipid membrane was added to the experimental apparatus to mimic the natural cellular environment of SDH. This modification made it possible to develop a context for investigating the role and interactions of SDH within a cellular ecosystem that was more realistic and biologically relevant. Result: The molecular binding affinity score for APAP and NAPQI with SDH was predicted -6.5 and -6.7 kcal/mol, respectively. Furthermore, RMSD, RMSF, and Rog from the molecular dynamics simulations study revealed that NAPQI has slightly higher stability and compactness compared to APAP at 100 ns timeframe with mitochondrial SDH. Conclusion: This study serves to predict the mechanistic process of paracetamol toxicity by using different computational approaches. In addition, this study will provide information about the drug target against APAP hepatotoxicity.

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In recent years, the obesity epidemic has escalated into a serious public health catastrophe that is only getting worse. However, research into the pathophysiological pathways behind the obesity development and the illnesses that it is associated with is ongoing. In the last decades, it is now clear that the gut microbiota plays a significant role in the genesis and progression of obesity and obesity-related illnesses, particularly changes in its metabolites and composition as obesity progresses. Here, we provide a summary of the processes by which variations in gut metabolite levels and the composition of gut microbiota affect obesity and associated disorders. The bacteria residing in the gut release several chemicals that influence the appetite control, metabolism, and other systems. Since it can either encourage or restrict the deposition of fat in several different ways, the gut microbiota's role in obesity is debatable. Additionally, we go over potential therapeutic approaches that could be utilized to alter gut microbiota composition and focus on the important metabolic pathways associated with obesity and metabolic disorders linked to obesity.

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Metabolic syndrome refers to a group of several disease conditions together with high glucose triglyceride levels, high blood pressure, lower high-density lipoprotein level, and large waist circumference. About 400 million people worldwide, one-third of the Euro-American population and 27% Chinese population over age 50 have it. microRNAs, an abundant novel class of endogenous small, non-coding RNAs in eukaryotic cells, act as negative controllers of gene expression by promoting either degradation/translational repression of target messenger RNA. More than 2000 microRNAs in the human genome have been identified and they are implicated in various biological & pathophysiological processes, including glucose homeostasis, inflammatory response, and angiogenesis. Destruction of microRNAs has a crucial role in the pathogenesis of obesity, cardiovascular disease, and diabetes. Recently the discovery of circulating microRNAs in human serum may help to promote metabolic crosstalk between organs and serves as a novel approach for the identification of various diseases, like Type 2 diabetes & atherosclerosis. In this review, we will discuss the most recent and up-to-date research on the pathophysiology and histopathology of metabolic syndrome besides their historical background and epidemiological highlight. As well as search the methodologies employed in this field of research and the potential role of microRNAs as novel biomarkers and therapeutic targets for metabolic syndrome in the human body. Furthermore, the significance of microRNAs in promising strategies, like stem cell therapy, which holds enormous promise for regenerative medicine in the treatment of metabolic disorders will also be discussed.

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Momordica dioica (M. dioica) is a gourd like blooming plant that is readily available in Bangladesh, requiring biological research to discover its therapeutic values. The goal of our research was to see if the ethanolic extract of this plant had any anti-hyperglycemic properties. Water, glibenclamide and M. dioica extracts were fed to Streptozocin induced type-2 diabetic rat models at a dose of 1.25 g/kg body weight (bw) for 28 days to see what kind of effects they had on serum glucose, insulin, liver glycogen and lipid contents. Except for the control group, all the groups followed a pattern of maintaining the body weight. The oral glucose tolerance test was observed to be improved in extract after 14 days of the experiment. When assessed with the control group, the M. dioica extract showed a significant (p = 0.0015) decrease in postprandial serum glucose level (M±SD, mmol/l, 13.23 ± 1.03 control Vs 11.47 ± 2.21 extract) at 120 min. The treatment of diabetic model rats with extract resulted in a 7% (p < 0.0001) reduction in serum cholesterol levels. While subsequent 28 days of treatment, insulin levels were found to be lowered in all groups (from 246.76 to 200.44 pg/dL; p < 0.0001 for standard and from 309.01 to 204.61 pg/dL; p < 0.0001 for sample). The results revealed that prolonged administration of M. dioica improved the glycemic and lipidemic state of type-2 diabetic rats, implying that more research is needed to identify the active ingredient (s).

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OBJECTIVE: To study the phytochemical and biological properties (antioxidant, anthelmintic and thrombolytic) of methanolic extracts of Enhydra fluctuans Lour., a plant belonging to the Asteraceae family. METHODS: The phytochemical evaluation was carried out by qualitative analysis. In vitro antioxidant activity of extract was studied using free radical scavenging assay, ability of reduction, total phenol and total flavonoid contents determination assays. The anthelmintic activity was determined using paralysis and death time of Pheretima posthuma (earthworm) and thrombolytic activity by clot disruption assay. RESULTS: The phytochemical evaluation showed significant presence of flavonoids, triterpenes, carbohydrate, reducing sugars, saponins, phenols, diterpenes, protein and tannin. The antioxidant activity was found significant [IC50=(135.20±0.56) µg/mL] as compared to ascorbic acid [(130.00±0.76) µg/mL]. The reducing power was increased with concentration. Total phenol and total flavonoid contents were (153.08±0.38) mg/mL and (172.04±0.56) mg/mL respectively. The paralysis and death time of earthworms for different concentrations of extract were determined and compared with albendazole. The results showed that 10 mg/mL of the crude extract had similar effect with albendazole. Additionally, the crude extract showed a concentration depended relationship with its anthelmintic property. The clot lysis activity of crude extract was compared to the standard streptokinase's clot lysis (40.13%) activity and found significant (31%). CONCLUSIONS: The study proves that the crude methanolic extract of Enhydra fluctuans Lour. has significant antioxidant, anthelmintic and thrombolytic activity containing wide range of phytochemicals.