Overactivation of the Transforming Growth Factor Beta (TGF-β) pathway is implicated in the pathogenesis of cytopenias in Myelodysplastic syndromes (MDS) and Acute Myeloid Leukemia (AML). IOA-359 and IOA-360 are potent small molecule inhibitors of the TGF-beta Receptor type I kinase (TGF-βRI, also referred to as ALK5, activin receptor-like kinase 5) that abrogate SMAD phosphorylation in hematopoietic cell lines. Both inhibitors were able to inhibit TGF-β mediated gene transcription at specific doses.
View Article and Find Full Text PDFIn the present day electricity demand, demand response programs support mitigating the power demand and help to improve stability. Within this framework, the Home Energy Management System (HEMS) plays a critical role in optimizing energy consumption patterns by redistributing loads from peak to off-peak hours, thereby subsequently contributing to grid stability. The existing HEMS model often fails to simultaneously address the three important issues.
View Article and Find Full Text PDFCentrioles are subcellular organelles found at the cilia base with an evolutionarily conserved structure and a shock absorber-like function. In sperm, centrioles are found at the flagellum base and are essential for embryo development in basal animals. Yet, sperm centrioles have evolved diverse forms, sometimes acting like a transmission system, as in cattle, and sometimes becoming dispensable, as in house mice.
View Article and Find Full Text PDFAberrant overexpression of Interleukin-8 (IL8) has been reported in Myelodysplastic Syndromes (MDS), Acute Myeloid Leukemia (AML), Myeloproliferative Neoplasms (MPNs) and other myeloid malignancies. IL8 (CXCL8) is a CXC chemokine that is secreted by aberrant hematopoietic stem and progenitors as well as other cells in the tumor microenvironment. IL8 can bind to CXCR1/CXCR2 receptors and activate oncogenic signaling pathways, and also increase the recruitment of myeloid derived suppressor cells to the tumor microenvironment.
View Article and Find Full Text PDFhas been linked to airway structural changes in patients with asthma, leading to airway hyperresponsiveness, narrowing, and ultimately poor treatment responsiveness. This study aimed to evaluate the genetic association of SNPs with asthma, disease severity, and treatment responsiveness to ICS+LABA in the South Indian population. In this case-control study (486 controls and 503 cases), we performed genotyping using MassArray for six SNPs of , namely rs2280091, rs2787094, rs3918396, rs67044, rs2853209, and rs3918392.
View Article and Find Full Text PDFAvicenna J Med Biotechnol
January 2022
Background: Type 2 Diabetes Mellitus (T2DM) has emerged as a major threat to global health that fosters life-threatening clinical complications, taking a huge toll on our society. More than 65 million Indians suffer from T2DM, making it one of the leading causes of death. T2DM and associated complications have to be constantly monitored and managed which reduces the overall quality of life and increases socioeconomic burden.
View Article and Find Full Text PDFThe septation defect is one of the main categories of congenital heart disease (CHD). They can affect the septation of the atria leading to atrial septal defect (ASD), septation of ventricles leading to ventricular septal defect (VSD), and formation of the central part of the heart leading to atrioventricular septal defect (AVSD). Disruption of critical genetic factors involved in the proper development of the heart structure leads to CHD manifestation.
View Article and Find Full Text PDFUnlabelled: Heat shock proteins are essential in maintaining cellular protein function, especially during stress. Their influence in managing drug-induced stress in Tuberculosis is not clearly understood.
Aims: Study the expression of select genes of the DnaK/ClpB chaperone network to evaluate their role in stress response in Mycobacterium tuberculosis clinical isolates during exposure to Isoniazid (INH) and Rifampicin (RIF).
Gut-Brain Axis provides a bidirectional communicational route, an imbalance of which can have pathophysiological consequences. Differential gut microbiome studies have become a frontier in autism research, affecting 85% of autistic children. The present study aims to understand how gut microbiota of autism subjects differ from their neurotypical counterparts.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2021
Reduced succinate dehydrogenase (SDH) activity resulting in adverse succinate accumulation was previously considered relevant only in 0.05 to 0.5% of kidney cancers associated with germline SDH mutations.
View Article and Find Full Text PDFThe BCL2-inhibitor, Venetoclax (VEN), has shown significant anti-leukemic efficacy in combination with the DNMT-inhibitor, Azacytidine (AZA). To explore the mechanisms underlying the selective sensitivity of mutant leukemia cells to VEN and AZA, we used cell-based isogenic models containing a common leukemia-associated mutation in the epigenetic regulator ASXL1. KBM5 cells with CRISPR/Cas9-mediated correction of the ASXL1 mutation showed reduced leukemic growth, increased myeloid differentiation, and decreased HOXA and BCL2 gene expression in vitro compared to uncorrected KBM5 cells.
View Article and Find Full Text PDFCytorace-3 is a laboratory evolved hybrid lineage of Drosophila nasuta nasuta males and Drosophila nasuta albomicans females currently passing ~850 generations. To assess interracial hybridization effects on gene expression in Cytorace-3 we profiled the transcriptomes of mature ovaries and testes by employing Illumina sequencing technology and de novo transcriptome assembling strategies. We found 26% of the ovarian, and 14% of testis genes to be differentially expressed in Cytorace-3 relative to the expressed genes in the parental gonadal transcriptomes.
View Article and Find Full Text PDFAvicenna J Med Biotechnol
January 2021
Background: The prevalence of Coronary Artery Disease (CAD) in developing countries is on the rise, owing to rapidly changing lifestyle. Therefore, it is imperative that the underlying genetic and molecular mechanisms be understood to develop specific treatment strategies. Comprehensive disease network and Gene Ontology (GO) studies aid in prioritizing potential candidate genes for CAD and also give insights into gene function by establishing gene and disease pathway relationships.
View Article and Find Full Text PDFThe () is a member of subgroup of species group of widely distributed across South-East Asia and central to Southern Africa. It displays morphological similarities with other members of the subgroup with which it has a recent divergence history. The genomic DNA of Coorg strain was paired-end sequenced using Illumina HiSeq 2500 technology to obtain a draft genome assembly of 145.
View Article and Find Full Text PDFDrosophila nasuta nasuta and Drosophila nasuta albomicans represent cross fertile members of the immigrans species group of Drosophila with an allopatric mode of distribution exhibiting characteristic novelties. Illumina sequencing technology and de novo transcriptome assembling strategies were used for the current study. The analysis revealed 8% of the transcriptome to be differentially expressed between the ovaries of these two species, of which 9% was related to female reproduction.
View Article and Find Full Text PDFThrombocytopenia remains a challenge in myeloid malignancies, needing safer and more effective therapies. JNJ-26366821, a pegylated synthetic peptide thrombopoietin (TPO) mimetic not homologous to endogenous TPO, has an in-vitro EC50 of 0.2 ng/mL for the TPO receptor and dose dependently elevates platelets in volunteers.
View Article and Find Full Text PDFAutism Spectrum Disorders (ASD) are caused by disrupted neurodevelopment leading to socio-communication and behavioural abnormalities. Although genetic anomalies like Copy Number Variations (CNV) have been implicated in ASD, their overall genomic landscape and pathogenicity remain elusive. Therefore, we created a CNV map for ASD using 9337 cases and 5650 controls from SFARI database, statistically marked genomic regions with high and low frequencies of CNVs (i.
View Article and Find Full Text PDFInfect Disord Drug Targets
September 2021
Unlabelled: A molecular method for diagnosis of drug-resistant Tuberculosis is Multiplex allele-specific PCR (MAS-PCR), which is more time-efficient, and its accuracy is studied using DNA sequencing. Also, understanding the role of mutations, when translated to protein, in causing resistance helps in better drug designing.
Aim: To study MAS-PCR in the detection of drug resistance in comparison to DNA sequencing in Mycobacterium tuberculosis, and understand the mechanism of interaction of drugs with mutant proteins.
Background & Objectives: ADAM33 is implicated as a potentially strong candidate gene for asthma and bronchial hyper-responsiveness. Many polymorphisms of ADAM33 have been studied along with ADAM33 expression in various cells of the lungs. Haplotype analysis also showed association with asthma in different populations across the world.
View Article and Find Full Text PDFAcute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with disease-initiating stem cells that are not eliminated by conventional therapies. Transcriptomic analysis of stem and progenitor populations in MDS and AML demonstrated overexpression of STAT3 that was validated in an independent cohort. STAT3 overexpression was predictive of a shorter survival and worse clinical features in a large MDS cohort.
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