Rice straw mediated green synthesis and characterization of iron oxide nanoparticles and its application to improve thermal stability of endoglucanase enzyme.

Applications of thermostable enzymes in various industries are highly demanding, and considered as one of the most feasible solutions to gain the high productivity of the related bio-processing. Nevertheless, cost-intensive production of enzymes with low reactivity and stability make them non-suitable for different sustainable industrial applications. Focusing on this aspect, the present study deals with the sustainable and low-cost green synthesis of Iron oxide nanoparticles (IONPs) using rice straw extract as the food waste which function as the natural reducing reagent and investigates the utility of IONPs to improve the thermo-stability of enzyme. Herein, physiochemical properties of newly synthesized IONPs have been analyzed through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and field emission scanning electron microscope (FE-SEM). Moreover, impact of green route synthesized IONPs is studied to improve the thermal stability of commercially available endo-glucanase (EG) enzyme as a model system. It is noticed that IONPs significantly supported to enhance the thermal stability of EG enzyme, wherein enzyme exhibited thermal stability at 70 °C up to 15 h, and suggesting high potential of thermally stable enzyme for numerous industrial applications.

Meta-analysis reveals no correlation of caveolin-1 G14713A (G>A) gene polymorphism with increased cancer risk in Taiwanese population.

OBJECTIVES: The role of caveolin-1 (CAV1)(G>A, rs3807987) polymorphism is still dubious in cancer causation in Taiwanese population. The present study is an effort to assess the above relation for precise conclusion. METHODS: EMBASE and PubMed (MEDLINE) databases were explored for the pertinent case-control studies reporting the connection of CAV1 G14713A polymorphism to the vulnerability to cancer. A cumulative analysis using meta-analytic approach was accomplished and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for all the polymorphs. RESULTS: Overall, 2549 subjects and 3161 controls were analyzed from six selected studies. Our study showed no confirmation of noteworthy risk between CAV1 G14713A polymorphism and susceptibility to cancer in any of the polymorph, for instance, allele (A vs. G: P = 0.165; OR = 1.252, 95% CI = 0.911-1.721), homozygous (AA vs. GG: P = 0.252; OR = 1.328, 95% CI = 0.817-2.157), heterozygous (AG vs. GG: P = 0.091; OR = 1.356, 95% CI = 0.952-1.930), dominant (AA vs. GG + AG: P = 0.345; OR = 1.191, 95% CI = 0.829-1.709), and recessive (AA + AG vs. GG: P = 0.125; OR = 1.344, 95% CI = 0.921-1.961). CONCLUSIONS: We conclude that CAV1 G14713A polymorphism does not contribute as an independent predisposing risk factor for developing cancer in Taiwanese population.

Recent developments and obstacles in the treatment of melanoma with BRAF and MEK inhibitors.

Metastatic melanoma is a least common form of cancer as it accounts only for 1% of all cancer cases. But, it is most deadly in nature and is haunting mankind for long emotionally as well as economically. The sites for the onset of the disease are pigment-producing cells of the skin, mucosa, eye etc. It has the potential to spread other sites like subcutaneous tissue, lymph nodes, lungs, liver, bone and brain. The United States Food & Drug Administration has approved various drug molecules from time to time. The molecules (Dabrafenib-BRAF inhibitor and Trametinib-MEK inhibitor) have proved their credentials alone and in combination as well. These molecules have demonstrated good results for various end points like median progression free survival, overall survival, objective response etc. The median progression free survival for patients using dabrafenib and trametinib were 5.1 and 4.8 months, respectively (administered singly). It has increased to 11.4 months in the combination treatment "dabrafenib + trametinib", which is approximately 104% and 138% greater than dabrafenib and trametinib treated groups alone. Similarly, the overall survival rate and objective response rate for the patients administered with "dabrafenib + trametinib" have been increased by 72% 64%, respectively. All these increments in these parameters were for a short period of time as the molecules were unable to withstand the pressure of resistance developed in the patients. So, the current review suggests the use of BRAF and MEK inhibitors as intermittent therapy along with heat shock protein 90 (HSP90) molecules.

Impact of LMP7 (rs2071543) gene polymorphism in increasing cancer risk: evidence from a meta-analysis and trial sequential analysis.

Genetic variant LMP7 (low molecular weight polypeptide 7) -145 C > A may influence the function of immune surveillance of an individual and lead to cancer development. Various studies have investigated the relevance of LMP7 -145 C > A gene polymorphism with cancer risk; but, their results are conflicting and inconsistent. To obtain a comprehensive conclusion, a meta-analysis was performed by including eight eligible published studies retrieved from PubMed (Medline), EMBASE and Google Scholar web search until December 2016. Individuals with AA genotype (AA vs CC: p = 0.001; OR = 2.602, 95% CI = 1.780 to 3.803) of LMP7 -145 C > A were found to have 2 folds higher risk of cancer than those with CC genotype. The recessive genetic model (AA vs AC + CC) also indicated that individuals with AA genotype have 2 folds higher cancer risk than AC and CC genotypes (p = 0.001; OR = 2.216, 95% CI = 1.525 to 3.221). Also, significant increased cancer risk was observed in Asians but not in Caucasians. No publication bias was observed during the analysis. Trial sequential analysis also strengthened our current findings. These results suggest that genetic variant LMP7-145 C > A has significant role in increasing cancer risk in overall and Asian population, and could be useful as a prognostic marker for early cancer predisposition.

Impact of TNF -308 G>A (rs1800629) gene polymorphism in modulation of leprosy risk: a reappraise meta-analysis of 14 case-control studies.

PURPOSE: Earlier studies have shown that tumor necrosis factor (TNF) -308 G>A (rs1800629) gene polymorphism is implicated in the susceptibility to leprosy, but results were inconsistent. METHODS: A meta-analysis of 14 studies involving 3327 leprosy cases and 3203 controls was performed to appraise the association of TNF -308 G>A polymorphism with leprosy using MEDLINE (PUBMED), EMBASE, and Google Scholar web databases. RESULTS: Overall, no significant association was observed in allelic (A vs. G: P=0.068; OR = 0.836, 95% CI = 0.689-1.013), homozygous (AA vs. GG: P=0.394; OR = 0.810, 95% CI = 0.499-1.315), heterozygous (GA vs. GG: P=0.059; OR = 0.780, 95% CI = 0.603-1.010), dominant (AA + GA vs. GG: P=0.067; OR = 0.797, 95% CI = 0.625-1.016), and recessive (AA vs. GG + GA: P=0.594; OR = 0.877, 95% CI = 0.542- 1.420) genetic models. Subgroup analysis showed no association in Asians. Whereas, reduced risk was found in allelic contrast (A vs. G: P=0.014; OR = 0.832, 95% CI = 0.718-0.963) and dominant models (AA + GA vs. GG: P=0.004; OR = 0.790, 95% CI = 0.673-0.928) of the mixed population. CONCLUSIONS: TNF -308 G>A polymorphism is not associated with leprosy risk in the overall population. However, subgroup analysis demonstrated protective effect of the said polymorphism in leprosy risk in the Latin American population, but showed no association in the Asians.

Pembrolizumab's non-cross resistance mechanism of action successfully overthrown ipilimumab.

The incidences of melanomas are increasing by leaps and bounds across the globe despite early detection and intervention. The numbers of patients dying from metastatic melanoma have been continually increased over the past thirty years. It has been considered as one of the most therapy-resistant malignancies due to the cross-resistant mechanism developed by the metastatic cells. With time, many new therapies came and they failed miserably. Ipilimumab, a monoclonal antibody that works to activate the immune system by targeting CTLA-4 proved to be a boon for advance melanoma very recently. But it could not stand firmly against the resistant metastatic skin cancer cells. Now, the new skin cancer drug named pembrolizumab proved as a new miraculous molecule. It's a humanized monoclonal antibody that blocks a biological pathway called programmed cell death-1 (PD-1), which melanoma cells activate to suppress the immune system. This antibody has surpassed ipilimumab at all the stages of clinical trials because of its non-cross resistant mechanism to malignant cells. The present review critically analyses the reasons of efficacy success of pembrolizumab over ipilizumab shown at various stages of clinical trials.

TNF-α -308 G > A (rs1800629) Polymorphism is Associated with Celiac Disease: A Meta-analysis of 11 Case-Control Studies.

Celiac disease (CD) remains one of the most significant autoimmune diseases worldwide. The pathogenesis of CD is not clearly understood and is probably attributed to genomic variations and host genetic make-up. Case-control and cohort studies of the association between the TNF-α -308 G > A (rs1800629) polymorphism and CD susceptibility have yielded inconsistent results. In this study, PubMed, EMBASE, and Google Scholar web-databases were searched for pertinent reports showing association of TNF-α -308 G > A gene with CD risk. A total of eleven reports involving 1774 controls and 1147 CD cases were included. Significant associations in four genetic models, viz. variant allele (A vs. G: p = 0.001; OR = 2.051, 95% CI = 1.452-2.895), variant homozygous (AA vs. GG: p = 0.001; OR = 6.626, 95% CI = 3.569-12.300), recessive (AA vs. GG + AG: p = 0.001; OR = 4.766, 95% CI = 3.177-7.152) and dominant (AA + AG vs. GG: p = 0.008; OR = 1.910, 95% CI = 1.181-3.088) were found in comparison with wild type homozygous GG genotype. However, heterozygous genetic model did not show any association. Sensitivity analysis revealed stable and statistically robust results. Our results suggest that TNF-α -308 G > A gene polymorphism significantly contributes to CD susceptibility.