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Objective: The present study aimed to investigate the inhibitory role of second mitochondria determined activator of caspases mimetic on inhibitor of apoptosis proteins (IAPs) and regulation of caspases in nonsmall cell lung cancer cell line.Materials and Methods: Dimethyl sulfoxide and 3-(4, 5-dimethyl thizol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay was done to determine the IC50 of BV6 using NCI-H23 cell line. The levels of mRNA of X-linked IAP (XIAP), cellular IAP (cIAP-1), cIAP-2, caspase-6, and caspase-7 in H23 cell line were evaluated by a quantitative real-time polymerase chain reaction, while their protein expressions were tested using western blotting.Results: Two doses of BV6 dependently downregulated the expression of mRNA of XIAP (P = 0.002, P= 0.0003 vs. untreated), cIAP-1 (P = 0.05, P = 0.005 vs. untreated), and cIAP-2 (P = 0.001, P = 0.0002 vs. untreated), respectively, while the compound upregulated the mRNA expression of caspase-6 (P = 0.001, P < 0.0001 vs. untreated) and caspase-7 (P = 0.001, P = 0.0004 vs. untreated), respectively. Dose dependent of BV6 treatment significantly decreased the protein level of XIAP (P = 0.003, P = 0.007 vs. untreated), cIAP-1 (P = 0.02, P = 0.01 vs. untreated), and cIAP-2 (P = 0.008,P = 0.008 vs. untreated), respectively. However, the compound increased the protein level of caspase-6 and caspase-7 when compared to untreated control (P = 0.006,P = 0.001) and (P = 0.01, P = 0.001), respectively.Conclusions: The result showed that BV6 treatment reduced the level of mRNA of XIAP, cIAP-1, and cIAP-2 and increased the gene expression of caspase-6 and caspase-7 in NCI-H23 cell line. Therefore, the study revealed that BV6 could be used in future as additional therapeutics in lung cancer. [ABSTRACT FROM AUTHOR]

Breast cancer is a heterogeneous disease in which genetic factors are involved in disease worsening and higher mortality. Epidemiological and clinical research revealed that breast cancer incidence continues to rise. 100 histopathologically confirmed untreated newly diagnosed cases of invasive ductal carcinoma (IDC) of breast and 100 healthy subjects were involved and blood samples were collected in non-EDTA plain vials. Serum was separated by centrifugation, total RNA was extracted from serum, and cDNA synthesis was done to study the miRNA-495 and neurexin-1 (NRXN-1) and contactin 1 (CNTN-1) mRNA expression by QRT-PCR. The expression levels of miRNA-495, NRXN-1, and CNTN-1 were expressed in fold change. The present study observed decreased relative miRNA-495 expression (0.07-fold) while an increase in NRXN-1 (11.61-fold) and CNTN-1 (4.92-fold) was observed among breast cancer patients compared to healthy controls. A significant difference was observed in miRNA-495 expression with menopausal status (p = 0.0001) and TNM stages (p = 0.02). It was observed that NRXN-1 expression was significantly associated with menopausal status (p = 0.03), lymph node involvement (p < 0.0001), estrogen receptor (ER) status (p = 0.03), progesterone receptor (PR) status (p = 0.005), TNM stages (p < 0.0001), and distant metastases (p < 0.0001). CNTN-1 expression was also found to be associated with lymph node involvement (p = 0.01), PR status (p = 0.03), HER2 status (p = 0.04), TNM stages (p < 0.0001), and distant metastases (p < 0.0001). ROC suggested that NRXN-1 and CNTN-1 could be the important predictive marker for disease advancement and distant organ metastases. The study concluded that the decreased expression of miR-495 observed in breast cancer patients showed a negative correlation with NRXN-1 while the increased expression of NRXN-1 and CNTN-1 was linked with disease advancement and distant metastases and could be the important predictive marker for breast cancer patients. [ABSTRACT FROM AUTHOR]

Introduction: Glucokinase (GCK) gene alteration or inactivation leads to Maturity-Onset Diabetes of the Young (MODY) and Neonatal Diabetes. Alterations in GCK gene has been shown to be associated with increased risk of type 2 diabetes, hyperglycaemia and impaired beta cell function. Aim: To evaluate the GCK (-30G/A, rs1799884) alterations in Type 2 Diabetes Mellitus (T2DM) patients. Materials and Methods: After patients' selection, blood samples were taken and all biochemical parameters were analysed by auto-analyser using serum. Whole blood samples were used to extract DNA and RNA for genotyping of -30G/A polymorphism using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) as well as GCK mRNA expression using quantitative real time PCR. Results: Several parameters such as fasting sugar, serum uric acid, Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), Triglyceride (TG), Cholesterol, high-sensitivity C-Reactive Protein (hs-CRP) were analysed among T2DM cases and healthy controls and differences among them were found to be significantly associated (p<0.0001). It was observed that patients who were smoking among T2DM cases, were found to be associated with increased fasting sugar (p=0.001), postprandial sugar (p<0.0001), HbA1c (p=0.003), blood urea (p=0.01), cholesterol (p=0.02) compared to those who were not smokers. T2DM patients who were alcoholic, showed increased LDL (p=0.006) and cholesterol (p=0.01) compared to non-alcoholic T2DM patients. T2DM cases which were reported hypertensive, showed increased hs-CRP (p=0.02) and cholesterol (p=0.02), compared to non-hypertensive T2DM cases and differences among them were found to be significantly associated. Significant differences were observed in distribution of GCK -30G/A genotypes among T2DM cases and healthy controls (p<0.0001). Odds ratio was calculated and it was observed that the heterozygous GA genotype had 4.66 odds ratio while odds ratio for mutant AA genotype was 35.98 in reference to wild type. Patients with homozygous GG showed 0.25 mean fold decreased GCK mRNA expression while heterozygous GA and mutant AA genotype showed more than 0.17 and 0.16 fold decreased. GCK mRNA was observed and differences among them was found to be significant (p<0.0001). Conclusion: Study revealed that GCK heterozygous GA and mutant AA genotypes were associated with T2DM risk and decreased expression may be responsible for disease progression and worsening of the disease. [ABSTRACT FROM AUTHOR]

The protozoan parasite, Leishmania donovani, undergoes several molecular adaptations and secretes many effector molecules for host cell manipulation and successful parasitism. The current study identifies an albumin-like secretory protein, expressed in its extracellular promastigote forms. A leishmanial complementary DNA sequence of a partial gene has been cloned, and the encoded peptide (14 kD) is used for the production of polyclonal antibody. This targeted antibody identifies a large native protein (66.421 kD), expressed stage-specifically in promastigotes. Through electron microscopic studies, the native protein is found to be localized in the flagellar pocket and flagella and at the surface of the promastigotes. This native protein is purified with the same customized antibody for future characterization and sequencing. The sequence analysis reveals its homology with the mammalian serum albumin. It is evidenced from in silico studies that this albumin-like protein remains associated with long-chain fatty acids while in vitro studies indicate its close association with membrane cholesterol. Since antibody-mediated blocking compromises the parasite infectivity, these leishmanial albumin-like molecules are hereby proposed to play an instrumental role in the infectivity of L. donovani to peripheral blood monocyte cells. Thus, identification and characterization of an albumin-like protein in L. donovani promastigotes may be interpreted as a molecular adaptation candidate. It may be hypothesized that the parasite mimics the mammalian system for importing fatty acids into the intracellular amastigotes, facilitating its host cell infectivity. [ABSTRACT FROM AUTHOR]

Telomeres are often considered as the 'ageing clock' that determines the lifespan at the cellular level, forming the ends of a chromosome, which shorten each time the cell divides itself to the point where they become so short the cell is unable to divide itself further. Telomere length alteration is often linked with lifestyle factors such as age, obesity, exposure to pesticides and pollution, depression, unhealthy diet, lack of exercise, and stress. The current review discusses the mechanism of telomere shortening in relation to ageing and lifestyle factors in general and its association with chronic diseases like diabetes which may influence the health and lifespan of an individual by increasing telomere shortening. Accelerated or excessive telomere shortening is also associated with the early onset of age-related disorders globally and, hence, reduced lifespan of individuals. Upregulated Telomerase activity and reactivation of telomeres is observed in > 70 % of cancer patients by TERT point mutations, rearrangements, DNA amplifications, and transcript fusions, making it a useful marker in diagnosis and prognosis of various cancers. The study presents a systematic review of the unregulated Telomere activity with progression of various cancer and extrapolation of suitable pathways and prognostic information correlated with mRNA levels of TERT, which are critical among thymic epithelial tumors (TETs). In most cancers, unlimited proliferation is due to the reactivation of reverse transcriptase gene TERT. All these observations are comprehensively presented in the paper and might be useful for researchers working in the field of telomere dynamics and finding the correlation of age shortening with mRNA expression profiling. • Telomere shortening in β cells among T2D patients may lead to enhanced apoptosis and cell senescence. • Various lifestyle factors such as obesity, lack of physical activity, smoking, unhealthy meals, pesticides, and pollution could accelerate telomere shortening. • Telomere dysfunction is closely associated with cancer progression and aging. • Restoring of telomere length may act as a potential therapeutic strategy for age-associated disorders in future. [ABSTRACT FROM AUTHOR]