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Objectives: Studies have investigated miR‐125a for its predictable role in recurrent pregnancy loss (RPL) cases to regulate many biological events required for the maintenance of pregnancy by regulating its confirmed target genes LIFR, ERBB2 and STAT3. Methods: The present study included 40 cases of women with at least two RPLs in ≤20 weeks of gestation against 40 healthy multiparous women without a previous history of abortion. Expression analysis of ERBB2, LIFR, STAT3 and miR‐125a was conducted by quantitative real‐time PCR (qPCR). Results: The expression of miR‐125a was significantly lower in the plasma of RPL cases (P = 0.0001) and showed a significantly increased mean expression level in product of conception (2.56‐fold, P < 0.0001). Among the target gene of miR‐125a, ERBB2 and STAT3 gene expression level was significantly increased (2.58‐fold, P = 0.04; 1.87‐fold, P = 0.025), respectively in RPL cases while the LIFR gene revealed comparable expression (P = 0.64). Furthermore, expression analysis of ERBB2 gene with respect to its regulatory miR‐125a cases depicted a significant association (P = 0.0005). Kaplan–Meier survival analysis revealed cases with low miR‐125a expression had significantly shorter time to miscarriages, (log‐rank P = 0.02). Also, decreased expression of miR‐125a significantly conferred >2‐fold increased risk for RPL (HR = 2.34: P < 0.05). Conclusion: The overall conclusion of the study was that altered miR‐125a expression may cause deregulation in target genes LIFR, ERBB2 and STAT3 resulting in adverse consequence in the outcome of pregnancy. Synopsis: The impact of altered miR‐125a expression causes deregulation in target genes LIFR, ERBB2 and STAT3 that result in deleterious effect in the outcome of the pregnancy. [ABSTRACT FROM AUTHOR]

Glucokinase (GK), an enzyme critical to glucose metabolism, exhibits thermal instability, which can affect its enzymatic activity under physiological and pathological conditions. This study aims to mathematically model the thermal denaturation kinetics of GK and empirically validate the model using experimental data. To establish a mathematical model on thermal denaturation of glucokinase (E.C.2.7.1.2) and its experimental validation, the enzyme glucokinase was investigated in a 0.075M Tris HCl buffer with pH 9.0 at 30∘C and 0.6M MgCl2. A first-order kinetic model was developed to describe the enzyme’s denaturation, incorporating temperature-dependent reaction rates based on the Arrehenius equation. Empirical data were collected through Spectrophotometer across a temperature range of 20∘–60∘C. Experimental validation revealed that GK undergoes irreversible denaturation above 60∘ with a significant reduction as temperature increases. Moreover, the thermal denaturation of GK in the presence of osmolyte Urea is a critical process affecting enzyme stability and function. This study also aims to mathematically model and empirically validate the impact of Urea on GK’s thermal denaturation behavior. Results demonstrated that Urea significantly reduces the thermal stability of GK, lowering its denaturation temperature. The results are simulated graphically using the Wolfram MATHEMATICA software. The mathematical predictions closely matched experimental data, confirming the model’s accuracy. [ABSTRACT FROM AUTHOR]

Aim: The implications of molecular biomarkers IDH 1/2 mutations and MGMT gene promoter methylation were evaluated for prognostic outcome of glioma patients., Materials & Methods: Glioma cases were analyzed for IDH 1/2 mutations and MGMT promoter methylation by DNA sequencing and methylation-specific PCR, respectively., Results: Mutations found in IDH 1/2 genes totaled 63.4% (N = 40) wherein IDH 1 mutations were significantly associated with oligidendrioglioma (p = 0.005) and astrocytoma (p = 0.0002). IDH 1 mutants presented more, 60.5% in MGMT promoter-methylated cases (p = 0.03). IDH 1 mutant cases had better survival for glioblastoma and oligodendrioglioma (log-rank p = 0.01). Multivariate analysis confirmed better survival in MGMT methylation carriers (hazard ratio [HR]: 0.59; p = 0.031). Combination of both biomarkers showed better prognosis on temozolomide (p < 0.05)., Conclusion: IDH 1/2 mutations proved independent prognostic factors in glioma and associated with MGMT methylation for better survival., Competing Interests: Financial & competing interests disclosure The current study was funded by Department of Science and technology, SERB Division, New Delhi (no. SB/SO/HS-036//2013). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript., (© 2020 Arshad A. Pandith.)

Accumulation of osmolytes, during cell volume perturbations, as cell volume regulators is ensured through their de novo synthesis, decreased degradation and transport from their site of synthesis to the site of utility through various transport systems. Among these, transport system mediated accumulation has been observed to be quite significant during long term cell volume perturbation. Under stress conditions, these osmolyte transporters are regulated at transcriptional as well as translational level. At translational level, protein kinases carry out phosphorylation of osmolyte transporters and have been shown to play a crucial role in cell volume homeostasis. In fact phosphorylation of osmolyte transporters on their conserved residues regulates the uptake and efflux of osmolytes by cells. Additionally, accumulated osmolytes in turn have been shown to modulate the structure and functioning of protein kinases. The present review has tried to provide an overview about the role of protein kinases in regulation of osmolyte accumulation under stress conditions. Due to their ability of regulating osmolyte accumulation, potential of protein kinases as therapeutic targets for diseases like cancer has also been highlighted.