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Metformin is one of the first-line and most widely prescribed drugs to treat type 2 diabetes (T2D). Its clearance from circulation is mostly facilitated by SLC22A2 (OCT2) in the renal cells. SLC22A2 is a polyspecific organic cation transporter and mediate transport of structurally unrelated endogenous and exogenous compounds including many drugs. rs316019 (p.270A > S) is the most common variant of SLC22A2 with a frequency as high as 15% or more in many populations. The 270S form of SLC22A2 clears metformin from circulation at much reduced level compared to the 270A form. If accumulated, metformin increases plasma lactate level in a concentration-dependent manner which can lead to a condition known as metformin-associated lactic acidosis (MALA). MALA is a potentially life-threatening complication with a mortality rate of 30–50%. Pre-existing clinical conditions, such as renal impairment, sepsis, anoxia, etc may make individuals more prone to MALA. In this study, we used computational approaches to investigate the effect of 270A > S change in SLC22A2 on interaction with metformin and other drugs. Based on the structural models, all substrates bind to the same pocket of SLC22A2. The substrates fit better to the binding site of 270A form of SLC22A2. The binding site has a few core interacting residues, among which SER358 appears to be the most important. It is an in silico prediction that the T2D patients, who are under metformin regimen, should be cautious in taking ranitidine (an over-the-counter sold drug) on a regular basis as it may lead to metformin associated lactate accumulation in blood.

Lignocellulosic biomass is the most abundant biomaterial on Earth and holds enormous potential as a source of fermentable sugars for cost-effective biofuel production. The main obstacle is the intractable and convoluted structure and composition of lignocellulosics which are mainly made of lignin, cellulose and hemicellulose. However, nature has equipped microbes with enzymes that can deconstruct lignocellulose and release fermentable sugars. In this study, we selected bacteria (belonging to 6 different genera) from nature that had been grown in minimal culture media with cellulose or lignin as the sole carbon source, and assessed their lignocellulolytic activities in qualitative and quantitative assays. Through sequence analysis of the 16S rRNA gene, we discovered a novel lignocellulolytic bacterial species, Chryseobacterium gleum, capable of degrading both cellulose and lignin. In addition, a few other bacterial species previously known to degrade either cellulose or lignin were found to have lignocellulolytic activities. The majority of these bacterial species were found to produce extracellular lignocellulolytic enzymes. Lignocellulolytic bacteria identified in this study may serve as sources of genes/enzymes which might find applications in biofuel production and other industrial applications.

ABSTRACT:The aim of the study was to investigate the effect of an ethanol extract of leaf (EEL) of Syzygium cumini against Vibrio cholerae serogroups Ogawa and Inaba. The antimicrobial activity of EEL was evaluated by the disc diffusion method against multi-drug resistant Ogawa and Inaba. The EEL effectively inhibited the growth of both serogroups. This growth inhibition was accompanied by fragmentation of genomic DNA as revealed by agarose gel electrophoresis. This result suggested that the EEL might inhibit bacterial growth involving DNA damage either through activation of signal transduction pathways or through direct interaction of the metabolites present in the EEL with DNA. Therefore, EEL of S. cumini has potential growth inhibitory activity against multi drug resistant Vibrios. This inhibitory effect of EEL might be explored to develop effective candidate(s) to combat cholera.

Background: Metformin is prescribed as a first-line drug to treat type 2 diabetes. It is excreted directly and primarily through the SLC22A2 gene-encoded OCT2 transporter in the kidney. rs316019 (c.808G>T, p.270A>S) is the most common variant of SLC22A2, which affects its capacity to clear metformin from the body. Metformin increases the plasma lactate level in a concentration-dependent manner by inhibiting mitochondrial respiration and may lead to a condition known as metformin-associated lactic acidosis (MALA). MALA is a potentially life-threatening complication that can occur within the clinical doses of metformin. Therefore, dose adjustments based on the SLC22A2 rs316019 variants may be beneficial to maximize the efficacy and minimize the toxicity of metformin. Objective: This study was carried out to develop a simple and fast method to define genotype at the rs316019 locus. This method was applied to estimate the rs316019 allele frequencies in the Bangladeshi population. Methods: We designed allele-specific primers to determine genotype at the rs316019 locus using allele-specific polymerase chain reaction (AS-PCR). AS-PCR data were confirmed by targeted sequencing of randomly selected samples. Results: The DNA sequence chromatograms showed the exact genotypes predicted through the AS-PCR method. A proportion of 79.62, 18.01, and 2.37% of Bangladeshi individuals have GG, GT, and TT genotypes, respectively. Conclusion: We report here a simple and fast method to define ge­notypes at the rs316019 locus in diabetic patients who are under metformin regimen. Allele frequencies at the rs316019 locus in the Bangladeshi population are close to those reported in other populations.