Cardiac aging: from hallmarks to therapeutic opportunities.

Cardiac aging is an intricate and multifaceted process with considerable impact on public health, especially given the global demographic shift towards aged populations. This review discusses structural, cellular and functional changes associated with cardiac aging and heart failure with preserved ejection fraction (HFpEF). Key molecular mediators are considered within the framework of the established hallmarks of aging, with particular attention to promising therapeutic candidates.

3Bs of CRISPR-Cas mediated genome editing in plants: exploring the basics, bioinformatics and biosafety landscape.

Unlabelled: The recent thrust in research has projected the type II clustered regularly interspaced short palindromic repeats and associated protein 9 (CRISPR-Cas9) system as an avant-garde plant genome editing tool. It facilitates the induction of site-specific double-stranded DNA cleavage by the RNA-guided DNA endonuclease (RGEN), Cas9. Elimination, addition, or alteration of sections in DNA sequence besides the creation of a knockout genotype (CRISPRko) is aided by the CRISPR-Cas9 system in its wild form (wtCas9).

The machine learning and geostatistical approach for assessment of arsenic contamination levels using physicochemical properties of water.

Arsenic contamination in groundwater due to natural or anthropogenic sources is responsible for carcinogenic and non-carcinogenic risks to humans and the ecosystem. The physicochemical properties of groundwater in the study area were determined in the laboratory using the samples collected across the Varanasi region of Uttar Pradesh, India. This paper analyses the physicochemical properties of water using machine learning, descriptive statistics, geostatistical and spatial analysis.

Effectiveness of Neurofeedback Therapy Adjunct to Cognitive Behavioral Therapy in Agoraphobia: A Case Study.

Agoraphobia has been defined as marked fear or anxiety being in enclosed or open places, using public transportation, and being in a crowd or outside of home alone. Such individuals make active attempts to avoid those places which cause intense distress. The neuronal areas that play a significant role in agoraphobia are uncinate fasciculus, which connects the prefrontal lobe and amygdala and various alterations in anterior cingulate cortex, insula, amygdala, and lateral prefrontal cortex.

Ponatinib Drives Cardiotoxicity by S100A8/A9-NLRP3-IL-1β Mediated Inflammation.

Background: The tyrosine kinase inhibitor ponatinib is the only treatment option for chronic myelogenous leukemia patients with T315I (gatekeeper) mutation. Pharmacovigilance analysis of Food and Drug Administration and World Health Organization datasets has revealed that ponatinib is the most cardiotoxic agent among all Food and Drug Administration-approved tyrosine kinase inhibitors in a real-world scenario. However, the mechanism of ponatinib-induced cardiotoxicity is unknown.

Psychodynamic Perspective of Sexual Obsessions in Obsessive-Compulsive Disorder.

Obsessive-compulsive disorder (OCD) is a disorder that is characterized by the presence of obsessions and compulsions. OCD can occur in a wide range of subtypes, which may include sexual OCD, i.e.

Fibroblast GSK-3α Promotes Fibrosis via RAF-MEK-ERK Pathway in the Injured Heart.

Background: Heart failure is the leading cause of mortality, morbidity, and health care expenditures worldwide. Numerous studies have implicated GSK-3 (glycogen synthase kinase-3) as a promising therapeutic target for cardiovascular diseases. GSK-3 isoforms seem to play overlapping, unique and even opposing functions in the heart.

Optogenetic control of the Bicoid morphogen reveals fast and slow modes of gap gene regulation.

Developmental patterning networks are regulated by multiple inputs and feedback connections that rapidly reshape gene expression, limiting the information that can be gained solely from slow genetic perturbations. Here we show that fast optogenetic stimuli, real-time transcriptional reporters, and a simplified genetic background can be combined to reveal the kinetics of gene expression downstream of a developmental transcription factor in vivo. We engineer light-controlled versions of the Bicoid transcription factor and study their effects on downstream gap genes in embryos.

Safety profile of D-penicillamine: a comprehensive pharmacovigilance analysis by FDA adverse event reporting system.

Background: D-penicillamine (D-pen) is a copper-chelating drug and has immune-modulatory properties. D-pen is used to treat rheumatoid arthritis, Wilson's disease, and kidney stones (cystinuria). However, associated adverse events (AEs) of D-pen treatment are frequent and often serious.

Repurposing Nintedanib for pathological cardiac remodeling and dysfunction.

Heart Failure (HF) is the leading cause of death worldwide. Myocardial fibrosis, one of the clinical manifestations implicated in almost every form of heart disease, contributes significantly to HF development. However, there is no approved drug specifically designed to target cardiac fibrosis.

Effect of Phosphorus Application on Arsenic Species Accumulation and Co-Deposition of Polyphenols in Rice Grain: Phyto and Food Safety Evaluation.

The present study was aimed at exploring the effect of soil application of different concentrations of orthophosphate (P) (0, 10, 20, 30, and 40 mg kg) on rice agronomic and yield parameters, arsenic (As) species accumulation, and polyphenol levels in the grain of rice grown under As spiked soil (10 mg kg). The contents of As species (As(V), As (III), MMA and DMA) and polyphenols in rice grain samples were estimated using LC-ICP-MS and LC-MS/MS, respectively. P treatments significantly reduced the toxic effects of As on agronomic parameters such as root weight and length, shoot and spike length, straw, and grain yield.

Proteotoxicity: A Fatal Consequence of Environmental Pollutants-Induced Impairments in Protein Clearance Machinery.

A tightly regulated protein quality control (PQC) system maintains a healthy balance between correctly folded and misfolded protein species. This PQC system work with the help of a complex network comprised of molecular chaperones and proteostasis. Any intruder, especially environmental pollutants, disrupt the PQC network and lead to PQCs disruption, thus generating damaged and infectious protein.

The BDNF rs6265 Polymorphism is a Modifier of Cardiomyocyte Contractility and Dilated Cardiomyopathy.

Brain-derived neurotrophic factor (BDNF) is a neuronal growth and survival factor that harbors cardioprotective qualities that may attenuate dilated cardiomyopathy. In ~30% of the population, BDNF has a common, nonsynonymous single nucleotide polymorphism rs6265 (Val66Met), which might be correlated with increased risk of cardiovascular events. We previously showed that BDNF correlates with better cardiac function in Duchenne muscular dystrophy (DMD) patients.

A Pharmacovigilance Study of Hydroxychloroquine Cardiac Safety Profile: Potential Implication in COVID-19 Mitigation.

In light of the favorable outcomes of few small, non-randomized clinical studies, the Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) to Hydroxychloroquine (HCQ) for hospitalized coronavirus disease 2019 (COVID-19) patients. In fact, subsequent clinical studies with COVID-19 and HCQ have reported limited efficacy and poor clinical benefits. Unfortunately, a robust clinical trial for its effectiveness is not feasible at this emergency.

Cardiotoxicity of the BCR-ABL1 tyrosine kinase inhibitors: Emphasis on ponatinib.

The advent of tyrosine kinase inhibitors (TKIs) targeted therapy revolutionized the treatment of chronic myeloid leukemia (CML) patients. However, cardiotoxicity associated with these targeted therapies puts the cancer survivors at higher risk. Ponatinib is a third-generation TKI for the treatment of CML patients having gatekeeper mutation T315I, which is resistant to the first and second generation of TKIs, namely, imatinib, nilotinib, dasatinib, and bosutinib.

Deletion of Cardiomyocyte Glycogen Synthase Kinase-3 Beta (GSK-3β) Improves Systemic Glucose Tolerance with Maintained Heart Function in Established Obesity.

Obesity is an independent risk factor for cardiovascular diseases (CVD), including heart failure. Thus, there is an urgent need to understand the molecular mechanism of obesity-associated cardiac dysfunction. We recently reported the critical role of cardiomyocyte (CM) Glycogen Synthase Kinase-3 beta (GSK-3β) in cardiac dysfunction associated with a developing obesity model (deletion of CM-GSK-3β prior to obesity).

Acid-functionalized single-walled carbon nanotubes alter epithelial tight junctions and enhance paracellular permeability.

Due to their unique properties, carbon nanotubes (CNTs) are being widely explored for industrial and medical applications. This has necessitated a thorough assessment of the effect of CNTs on human and animal physiology and health. Impact of CNTs on epithelial tight junctions has not been evaluated in the context of their toxic effects in many biological systems.

Spatial variability of arsenic in Indo-Gangetic basin of Varanasi and its cancer risk assessment.

The Indo-Gangetic alluvium is prime region for intensive agricultural. In some areas of this region, groundwater is now becoming progressively polluted by contamination with poisonous substances like arsenic. Intensive irrigation with arsenic contaminated ground water in dry spell results in the formation of As(III) which is more toxic.

Cardiomyocyte-GSK-3α promotes mPTP opening and heart failure in mice with chronic pressure overload.

Chronic pressure-overload (PO)- induced cardiomyopathy is one of the leading causes of left ventricular (LV) remodeling and heart failure. The role of the α isoform of glycogen synthase kinase-3 (GSK-3α) in PO-induced cardiac remodeling is unclear and its downstream molecular targets are largely unknown. To investigate the potential roles of GSK-3α, cardiomyocyte-specific GSK-3α conditional knockout (cKO) and control mice underwent trans-aortic constriction (TAC) or sham surgeries.

Cardiomyocyte SMAD4-Dependent TGF-β Signaling is Essential to Maintain Adult Heart Homeostasis.

The role of the transforming growth factor (TGF)-β pathway in myocardial fibrosis is well recognized. However, the precise role of this signaling axis in cardiomyocyte (CM) biology is not defined. In TGF-β signaling, SMAD4 acts as the central intracellular mediator.

Ponatinib-induced cardiotoxicity: delineating the signalling mechanisms and potential rescue strategies.

Aims: Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myelogenous leukaemia (CML). However, cardiotoxicity of these agents remains a serious concern. The underlying mechanism of these adverse cardiac effects is largely unknown.

Sequence based prediction of enhancer regions from DNA random walk.

Regulatory elements play a critical role in development process of eukaryotic organisms by controlling the spatio-temporal pattern of gene expression. Enhancer is one of these elements which contributes to the regulation of gene expression through chromatin loop or eRNA expression. Experimental identification of a novel enhancer is a costly exercise, due to which there is an interest in computational approaches to predict enhancer regions in a genome.

Inhibition of GSK-3 to induce cardiomyocyte proliferation: a recipe for in situ cardiac regeneration.

With an estimated 38 million current patients, heart failure (HF) is a leading cause of morbidity and mortality worldwide. Although the aetiology differs, HF is largely a disease of cardiomyocyte (CM) death or dysfunction. Due to the famously limited amount of regenerative capacity of the myocardium, the only viable option for advanced HF patients is cardiac transplantation; however, donor's hearts are in very short supply.