Gallic acid analogues with antibreast cancer and antioxidant action: synthesis and pharmacological assessment

Breast cancer is one of the important public health problems today and recent treatments have not been found to be very effective for advanced-stage metastatic disease of the breast. In the present study ten 3,4,5- trihydroxybenzohy- drazone derivatives (AR 01- AR 10) were synthesized by two different methods viz. reflux and stirring. It was observed that compounds synthesized by stirring method acquire good yield and require less time in comparison to reflux method. Further cytotoxicity activity performed on two breast cancer cell lines viz. MDA-MB-468 and MCF-7 revealed moderate activity in all compounds at 40 μg/mL and 80 μg/mL which has the highest in samples AR 01 and AR 10 for both cell lines. Considerably all compounds have shown potent antioxidant activity at 50 μg/mL and above concentrations. Tumor in mice treated with compound AR 01 was found to be smaller in comparison to control and AR 10. Findings revealed that compound having electron donating group showed more potent activity against breast cancer cell lines both in vitro and in vivo. Cytotoxicity activity also corelates with QSAR study and showed that compounds having donating group showed positive contribution towards the toxicity. These findings suggest that gallic acid derivatives were potent cytotoxic against breast cancer cell lines and may provide potent therapeutic effects against breast cancer

Identification of brain regions associated with working memory deficit in schizophrenia [version 1; peer review: 2 approved]

Background: Schizophrenia, a severe psychological disorder, shows symptoms such as hallucinations and delusions. In addition, patients with schizophrenia often exhibit a deficit in working memory which adversely impacts the attentiveness and the behavioral characteristics of a person. Although several clinical efforts have already been made to study working memory deficit in schizophrenia, in this paper, we investigate the applicability of a machine learning approach for identification of the brain regions that get affected by schizophrenia leading to the dysfunction of the working memory. Methods: We propose a novel scheme for identification of the affected brain regions from functional magnetic resonance imaging data by deploying group independent component analysis in conjunction with feature extraction based on statistical measures, followed by sequential forward feature selection. The features that show highest accuracy during the classification between healthy and schizophrenia subjects are selected. Results: This study reveals several brain regions like cerebellum, inferior temporal gyrus, superior temporal gyrus, superior frontal gyrus, insula, and amygdala that have been reported in the existing literature, thus validating the proposed approach. We are also able to identify some functional changes in the brain regions, such as Heschl gyrus and the vermian area, which have not been reported in the literature involving working memory studies amongst schizophrenia patients. Conclusions: As our study confirms the results obtained in earlier studies, in addition to pointing out some brain regions not reported in earlier studies, the findings are likely to serve as a cue for clinical investigation, leading to better medical intervention

A comprehensive appraisal of mechanism of anti-CRISPR proteins: an advanced genome editor to amend the CRISPR gene editing

The development of precise and controlled CRISPR-Cas tools has been made possible by the discovery of protein inhibitors of CRISPR-Cas systems, called anti-CRISPRs (Acrs). The Acr protein has the ability to control off-targeted mutations and impede Cas protein–editing operations. Acr can help with selective breeding, which could help plants and animals improve their valuable features. In this review, the Acr protein–based inhibitory mechanisms that have been adopted by several Acrs, such as (a) the interruption of CRISPR-Cas complex assembly, (b) interference with target DNA binding, (c) blocking of target DNA/RNA cleavage, and (d) enzymatic modification or degradation of signalling molecules, were discussed. In addition, this review emphasizes the applications of Acr proteins in the plant research

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Antioxidative and antiproliferative activities of isolated compounds from Prunus domestica: an in vitro study

In this investigation the antioxidant as well as antiproliferative activities of different isolated compounds from ethyl acetate fraction of Prunus domestica (peel + flesh) were studied in two human breast cancer cell lines, MCF-7 and MDA-MB-468. Free radical scavengering as done with 2, 2-diphenyl-1-picrylhydrazyl (DPPH) study indicated different degrees of antioxidative activity of the isolated compounds such as chlorogenic acid, protocatechuic acid, vanillic acid, ferulic acid, p-coumaric acid and rutin. However maximum antioxidative activity was observed in chlorogenic acid with IC50 of 0.115 mg/ml. With respect to antiproliferative potential, chlorogenic acid also exhibited the maximum antiproliferative activity on MCF-7 and protocatechuic acid on MDA-MB-468 human breast cancer cell lines. This appears to be the first report that provides a comparative account on the antioxidant and antiproliferative property of some isolated active compounds of the Indian variety of fruit, Prunus domestica

Antioxidative and antiproliferative activities of isolated compounds from Prunus domestica: an in vitro study

In this investigation the antioxidant as well as antiproliferative activities of different isolated compounds from ethyl acetate fraction of Prunus domestica (peel + flesh) were studied in two human breast cancer cell lines, MCF-7 and MDA-MB-468. Free radical scavengering as done with 2, 2-diphenyl-1-picrylhydrazyl (DPPH) study indicated different degrees of antioxidative activity of the isolated compounds such as chlorogenic acid, protocatechuic acid, vanillic acid, ferulic acid, p-coumaric acid and rutin. However maximum antioxidative activity was observed in chlorogenic acid with IC50 of 0.115 mg/ml. With respect to antiproliferative potential, chlorogenic acid also exhibited the maximum antiproliferative activity on MCF-7 and protocatechuic acid on MDA-MB-468 human breast cancer cell lines. This appears to be the first report that provides a comparative account on the antioxidant and antiproliferative property of some isolated active compounds of the Indian variety of fruit, Prunus domestica

Efficacy of different types of phototherapy units on neonatal hyperbilirubinemia

Context: Phototherapy is the mainstay of treatment for about 3% of neonates in India who develop significant jaundice in phototherapy range. New devices have been introduced in the market over the past few years. Aims: To compare the efficacy of three types of phototherapy machines, namely Blue and White, Compact Fluorescent Lamp, and Light Emitting Diode type. Settings and Design: A non-randomized prospective interventional study conducted in a tertiary care hospital of Western India. Material and Methods: Ninety neonates with phototherapy range hyperbilirubinemia were assigned into three groups of 30 neonates each to receive phototherapy using one of the three types of phototherapy machines. Need for exchange transfusion, total serum bilirubin (TSB) at 24 hours post-phototherapy and side effect profile were recorded. Decision to stop phototherapy was based on acceptable reduction of serum bilirubin to below phototherapy range. Statistical analysis used: Medcalc® Version 11.4.2.0 Software was utilised. Comparison of mean TSB was done using one way ANOVA. P-value of <0.05 was considered significant. Results: Baseline parameters, TSB at 24 hour post-phototherapy and at the point of stopping phototherapy in the three groups was not significantly different. None of the babies required exchange transfusion or stopping of therapy. Transient rash was the most commonly observed side effect. Conclusions: The three types of phototherapy equipment studied were comparable in efficacy as measured by need for exchange transfusion and mean TSB values at 24 hrs post-phototherapy. The side effect profile was similar and was not significant enough to stop phototherapy

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research

Sex differences in oncogenic mutational processes

Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.Peer reviewe