Ogilvie syndrome, also known as acute colonic pseudo-obstruction, is a form of colonic dilation occurring without underlying mechanical or anatomic etiology. It is a disorder of imbalance in motor innervation of the large intestine, which causes acute colon obstruction in the absence of any physical obstruction. It is associated with high morbidity and mortality due to diagnostic dilemmas and the need for surgical intervention.
View Article and Find Full Text PDFModulation of the Wnt/β-catenin signaling pathway may aid in discovering new medications for the effective management of pulmonary artery hypertension (PAH). Given the therapeutic potential of Mucuna pruriens in several diseases, the present study aimed to analyze interactions of different bioactive compounds of Mucuna pruriens plant seeds with Wnt/β-catenin pathway targeting its various components like Wnt 3a, Frizzled 1, LRP 5/6, β-catenin, Disheveled, cyclin D1 by in silico analysis. The proposed work is based on computational analysis including ADME/T properties, by a Swiss ADME server.
View Article and Find Full Text PDFDrug resistance is a principal limitation to the long-term efficacy of cancer therapies. Cancer genome sequencing can retrospectively delineate the genetic basis of drug resistance, but this requires large numbers of post-treatment samples to nominate causal variants. Here we prospectively identify genetic mechanisms of resistance to ten oncology drugs from CRISPR base editing mutagenesis screens in four cancer cell lines using a guide RNA library predicted to install 32,476 variants in 11 cancer genes.
View Article and Find Full Text PDFThe receptor tyrosine kinase FGFR3 is frequently mutated in bladder cancer and is a validated therapeutic target. Although pan-FGFR tyrosine kinase inhibitors (TKI) have shown clinical efficacy, toxicity and acquired resistance limit the benefit of these agents. While antibody-based therapeutics can offer superior selectivity than TKIs, conventional ligand-blocking antibodies are usually ineffective inhibitors of constitutively active receptor tyrosine kinases.
View Article and Find Full Text PDFThe anticancer therapeutic effects of usnic acid (UA), a lichen secondary metabolite, have been demonstrated and . However, the mechanism underlying the anticancer effect of UA remains to be clarified. In this study, the target protein of UA was identified using a UA-linker-Affi-Gel molecule, which showed that UA binds to the 14-3-3 protein.
View Article and Find Full Text PDFMicrosatellite-unstable (MSI) cancers require WRN helicase to resolve replication stress due to expanded DNA (TA)n dinucleotide repeats. WRN is a promising synthetic lethal target for MSI tumors, and WRN inhibitors are in development. In this study, we used CRISPR-Cas9 base editing to map WRN residues critical for MSI cells, validating the helicase domain as the primary drug target.
View Article and Find Full Text PDFGenetic screens in cancer cell lines inform gene function and drug discovery. More comprehensive screen datasets with multi-omics data are needed to enhance opportunities to functionally map genetic vulnerabilities. Here, we construct a second-generation map of cancer dependencies by annotating 930 cancer cell lines with multi-omic data and analyze relationships between molecular markers and cancer dependencies derived from CRISPR-Cas9 screens.
View Article and Find Full Text PDFInterferon-γ (IFN-γ) signaling mediates host responses to infection, inflammation and anti-tumor immunity. Mutations in the IFN-γ signaling pathway cause immunological disorders, hematological malignancies, and resistance to immune checkpoint blockade (ICB) in cancer; however, the function of most clinically observed variants remains unknown. Here, we systematically investigate the genetic determinants of IFN-γ response in colorectal cancer cells using CRISPR-Cas9 screens and base editing mutagenesis.
View Article and Find Full Text PDFExopolymeric substances (EPS) produced by bacterial cells play a crucial role in the interaction of the cells with the surrounding environment. Halobacillus trueperi manxer mangrove-16, an adhered bacterial isolate from the mangrove ecosystem was found to produce EPS that was observed by Alcian blue staining and congo red-coomassie blue agar. The EPS of the bacterial isolate exhibited emulsifying properties.
View Article and Find Full Text PDFHerein, we report a synthetic protocol for the synthesis of carbamates by employing zinc chloride as a catalyst from carbamoyl chlorides and aromatic/aliphatic alcohols. The developed protocol successfully utilizes the gram-scale synthesis of the FDA-approved rivastigmine drug and its derivative. The utility of zinc chloride over other catalysts such as zinc dust and zinc acetate exhibits a 49-87% yield of carbamates.
View Article and Find Full Text PDFThe rates and patterns of somatic mutation in normal tissues are largely unknown outside of humans. Comparative analyses can shed light on the diversity of mutagenesis across species, and on long-standing hypotheses about the evolution of somatic mutation rates and their role in cancer and ageing. Here we performed whole-genome sequencing of 208 intestinal crypts from 56 individuals to study the landscape of somatic mutation across 16 mammalian species.
View Article and Find Full Text PDFOrganoid cell culture methodologies are enabling the generation of cell models from healthy and diseased tissue. Patient-derived cancer organoids that recapitulate the genetic and histopathological diversity of patient tumours are being systematically generated, providing an opportunity to investigate new cancer biology and therapeutic approaches. The use of organoid cultures for many applications, including genetic and chemical perturbation screens, is limited due to the technical demands and cost associated with their handling and propagation.
View Article and Find Full Text PDFBackground: Divergence in the evolutionary interests of males and females leads to sexual conflict. Traditionally, sexual conflict has been classified into two types: inter-locus sexual conflict (IeSC) and intra-locus sexual conflict (IaSC). IeSC is modeled as a conflict over outcomes of intersexual reproductive interactions mediated by loci that are sex-limited in their effects.
View Article and Find Full Text PDFStudy Design: Retrospective study.
Aim: To retrospectively evaluate and compare the long-term outcome of anterior vertebral body reconstruction in tuberculosis (TB) of the dorsal spine by direct anterior-versus-posterior approach.
Materials And Methods: A total of 127 patients operated by posterior approach, 118 by anterior for TB-thoracic spine with at least 1-year follow-up were included and retrospectively analyzed.
Aim And Objective: The aim of the present study was to evaluate the candidal species among masses with oral potentially malignant disorders and oral squamous cell carcinoma.
Materials And Methods: This prospective and observational study was conducted by the Department of Oral Pathology and Microbiology, S. B.
Twenty-two alkaliphilic bacteria were isolated from spent waters of an agrochemical factory, Goa, India, and screened for exopolymer (EP) production on Horikoshi I/II media. Strain SB-D produced highly viscous cell-bound and extracellular EP quantified by alcian blue adsorption assay. The 16S rRNA gene sequence of strain SB-D showed 97.
View Article and Find Full Text PDFComparative proteome analysis of Erysiphe pisi-infected pea genotypes; JI-2480 carrying er2 resistant gene and Arkel, the susceptible genotype by liquid chromatography- mass spectrometry (LCMS/MS QTOF) at 72 h post inoculation (hpi) revealed several differentially abundant proteins (DAPs) of both the host and the pathogen. The functional annotation of proteins through gene enrichment and KEGG pathway analyses revealed strong up-regulation of pathogenesis related protein NPR1, proteins related to defense, transportation and signal transduction, hypersensitive response, cell wall modifications, phenylpropanoid and metabolic pathways in J-72. Significant abundance of membrane-related polypeptides, kinase domains and small GTPase signal transduction-related proteins suggested their major role in plant defense.
View Article and Find Full Text PDFComparative transcriptome analysis of Erysiphe pisi-infected pea (Pisum sativum) genotypes JI-2480 (resistant) and Arkel (susceptible) at 72 hours post-inoculation (hpi) was carried to detect molecular components involved in compatible and incompatible interactions. Differential gene expression was observed in Arkel and JI-2480 genotype at 72 hpi with E. pisi isolate (Ep01) using EdgeR software.
View Article and Find Full Text PDFAbnormal post-transcriptional regulation induced by alterations of mRNA-protein interactions is critical during tumorigenesis and cancer progression and is a hallmark of cancer cells. A more thorough understanding is needed to develop treatments and foresee outcomes. Cellular and mouse tumor models are insufficient for vigorous investigation as they lack consistency and translatability to humans.
View Article and Find Full Text PDFThe biotrophic fungus, Erysiphe pisi is the chief causal agent of powdery mildew disease of garden pea. A genome-wide search using in-silico approach was carried to detect putative pathogenicity and virulence genes of E. pisi, since information about these genes and their interaction with pea is limited.
View Article and Find Full Text PDFVisualization of the spatio-temporal trafficking of vaccines after their delivery would help evaluate the efficacy of candidate formulations and aid their rational design for preclinical and translational studies. Here, we show that a dual radionuclide-near-infrared probe allows for quantitative, longitudinal and non-invasive monitoring, via positron emission tomography-computed tomography and near-infrared imaging of cynomolgus macaques, of the trafficking dynamics to draining lymph nodes of a model messenger RNA vaccine labelled with the probe. After intramuscular administration of the vaccine to the monkeys, we observed the dynamics of the mRNA vaccine at the injection site and in the draining lymph nodes, performed cellular analyses of the involved tissues using flow cytometry and identified through immunofluorescence that professional antigen-presenting cells are the primary cells containing the injected mRNA and encoding the antigen.
View Article and Find Full Text PDFMultiple signatures of somatic mutations have been identified in cancer genomes. Exome sequences of 1,001 human cancer cell lines and 577 xenografts revealed most common mutational signatures, indicating past activity of the underlying processes, usually in appropriate cancer types. To investigate ongoing patterns of mutational-signature generation, cell lines were cultured for extended periods and subsequently DNA sequenced.
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