Genetic Disruption of Guanylyl Cyclase/Natriuretic Peptide Receptor-A Triggers Differential Cardiac Fibrosis and Disorders in Male and Female Mutant Mice: Role of TGF-β1/SMAD Signaling Pathway.

The global targeted disruption of the natriuretic peptide receptor-A (NPRA) gene () in mice provokes hypertension and cardiovascular dysfunction. The objective of this study was to determine the mechanisms regulating the development of cardiac fibrosis and dysfunction in mutant mice. knockout (, 0-copy), heterozygous (, 1-copy), and wild-type (, 2-copy) mice were treated with the transforming growth factor (TGF)-β1 receptor (TGF-β1R) antagonist GW788388 (2 µg/g body weight/day; ip) for 28 days.

S-Allylcysteine (SAC) Exerts Renoprotective Effects via Regulation of TGF- β1/Smad3 Pathway Mediated Matrix Remodeling in Chronic Renal Failure.

Background: S-Allylcysteine (SAC), an organosulfur phytochemical sourced from aged garlic extract, is well known for its varied biomedical applications, such as anti-oxidant, anti-inflammatory, and detoxification mechanisms. Despite this, the scientific findings on the defensive impact of SAC against kidney failure (KF) are still unclear. Therefore, in the current investigation, the animal model of KF was induced by adenine in Wistar rats, and the animals were divided into four groups as control, KF induction using adenine, SAC treated KF rats for an experimental duration of 8 weeks.

Lipopolysaccharide Enhances Genotoxicity by Activating GADD45G and NF-B in Human Corneal Epithelial Cells.

As the prevalence of microbial keratitis increases, it creates an environment conducive to genotoxicity response. A potential connection between growth arrest and DNA-damage-inducible 45 gamma (GADD45G) gene expression has not been proven in the corneal epithelial cells. The aim of this study was to determine whether lipopolysaccharide (LPS) enhances genotoxicity, DNA damage, and inflammatory responses in human corneal epithelial cells (HCECs) .

Bioactive Compounds in Oxidative Stress-Mediated Diseases: Targeting the NRF2/ARE Signaling Pathway and Epigenetic Regulation.

Oxidative stress is a pathological condition occurring due to an imbalance between the oxidants and antioxidant defense systems in the body. Nuclear factor E2-related factor 2 (NRF2), encoded by the gene , is the master regulator of phase II antioxidant enzymes that protect against oxidative stress and inflammation. NRF2/ARE signaling has been considered as a promising target against oxidative stress-mediated diseases like diabetes, fibrosis, neurotoxicity, and cancer.

Emerging role of nutritional short-chain fatty acids (SCFAs) against cancer via modulation of hematopoiesis.

The understanding of gut microbiota has emerged as a significant frontier in development of strategies to maintain normal human body's homeostasis and preventing the disease development over the last decade. The composition of the gut microbiota influences the clinical benefit of immune checkpoints in patients with advanced cancer, but the mechanisms underlying this relationship are unclear. Cancer is among the leading causes of mortality worldwide.

Organopesticides and fertility: where does the link lead to?

Organopesticides (OPs) are a group of various synthetic chemicals prevalently used in agriculture and homestead plantations. OPs were originally developed to remove insects, weeds, and other pests from agricultural fields for improving crop yields. Modern pesticides including organochlorine pesticides, organophosphorus pesticides, and amido-formyl ester are closely related to our lives.

Radiation-induced H3K9 methylation on E-cadherin promoter mediated by ROS/Snail axis : Role of G9a signaling during lung epithelial-mesenchymal transition.

Lung cancer patients who have undergone radiotherapy developed severe complications such as pneumonitis and fibrosis. Upon irradiation, epithelial cells acquire mesenchymal phenotype via a process called epithelial to mesenchymal transition (EMT), which plays a vital role in organ fibrosis. Several mechanisms have been studied on EMT, however, the correlation between radiation-induced EMT and epigenetic changes are not well known.

β-Casomorphin: A complete health perspective.

β-Casomorphin-7 (BCM-7) is a heptapeptide dietary molecule derived from the digestion of the β-casein of dairy and dairy products. In this review, we have covered the extensive details about BCM and its derived peptides out of the gastrointestinal and enzymatic digestion of milk and milk products, its structure and properties, and its immunological aspects related to human health among infants and adults of both genders. We have left judgment about BCM's pros and cons to the reader by describing the details in a cyclopedic perspective.

Inhibition of histone deacetylases is the major pathway mediated by astaxanthin to antagonize LPS-induced inflammatory responses in mammary epithelial cells.

Mastitis is a major inflammatory response of the mammary gland due to various pathogenic invasions and is a serious disease that affects the production yield and health status of cows. Astaxanthin (AST), a xanthophyll carotenoid, is a secondary metabolite synthesized by microalgae and yeasts that has been reported to suppress various inflammatory responses. However, the protective effect of AST on lipopolysaccharide (LPS)-induced mammary epithelial cells has not yet been reported.

MicroRNA Profiling of Highly Enriched Human Corneal Epithelial Stem Cells by Small RNA Sequencing.

The objective of the study was to elucidate the microRNA (miRNA) profile of an enriched human corneal epithelial stem cell (CESC) population in comparison to differentiated central corneal epithelial cells (CCECs) by small RNA sequencing. The CESCs were enriched by differential enzymatic treatment to isolate the basal limbal epithelial cells followed by laser capture microdissection of cells with nucleus to cytoplasm ratio ≥0.7, from donor tissues.

Sensitive screen-printed electrodes with the colorimetric zone for simultaneous determination of mastitis and ketosis in bovine milk samples.

Bovine metabolic diseases are silent clinical conditions caused by a disturbance in normal cellular metabolic processes majorly due to the demand for nutrients, physiological stress and inflammation in lactating animals. Even though these are non-devastating diseases, conditions like mastitis and ketosis highly influence cow's lactation and fertility performance that leads to economic losses. Hence, in the present study, a combined detection including a sensitive paper-based colorimetric device for the rapid determination of somatic cells (SCC) and electrochemical detection of β-hydroxybutyrate (BHB) in the milk samples has been developed.

Up-converting phosphor technology-based lateral flow assay for quantitative detection of β-hydroxybutyrate in biological samples.

In the present study, a novel up-converting phosphor technology-based lateral flow (UPT-LF) assay was developed as a point of care testing method for the rapid and quantitative detection of β-Hydroxybutyrate (BHB) in milk and serum samples. BHB is one of the most important serum molecular markers not only in ketosis but also for other metabolic disorders in bovines. The developed UPT-LF assay has high sensitivity compared with existing kits in the market for BHB quantification.

Insights on the current status and advancement of diabetes mellitus type 2 and to avert complications: An overview.

Type 2 diabetes mellitus (T2DM) is an endocrine metabolic disorder, occurring worldwide due to aging, advancement in lifestyle by modernization. T2DM is characterized by higher levels of glucose in the blood due to unresponsive secretion of pancreatic insulin and insulin activity or altogether. T2DM is regarded as a powerful genetic susceptible disease that leads to high risk with insulin resistance and β-cell dysfunction.

Exosomes: Current use and future applications.

Exosomes are endosomal-derived vesicles that play a critical role in cell-to-cell communication and are secreted in several biological fluids including serum, saliva, urine, ascites, and cerebro-spinal fluid amongst others. Exosomes are small (30-150 nm diameter) with a distinctive bilipid protein structure. They can carry and exchange various cargos between cells and are used as a non-invasive biomarker for several diseases.

'Biofilm Clippers'- enzyme formulation for bovine mastitic biofilm therapy.

Mastitis is one of the most important diseases that are threatening modern dairy farms. Biofilms of mastitic teat canal have serious clinical implications because of colonized pathogens having the ability to construct an extracellular polymeric substance (EPS) with increased tolerance to antimicrobials leads to difficulty in eradicating the infection. In this study, we investigated the synergistic biofilm disruptive effect of a combination of carbohydrate hydrolases targeting extracellular polysaccharides of biofilm matrix and we termed it as 'Biofilm Clippers (BC)'.

Performance assessment of variant calling pipelines using human whole exome sequencing and simulated data.

Background: Whole exome sequencing (WES) is a cost-effective method that identifies clinical variants but it demands accurate variant caller tools. Currently available tools have variable accuracy in predicting specific clinical variants. But it may be possible to find the best combination of aligner-variant caller tools for detecting accurate single nucleotide variants (SNVs) and small insertion and deletion (InDels) separately.

Genetic disruption of depletes regulatory T cells and provokes high levels of proinflammatory cytokines and fibrosis in the kidneys of female mutant mice.

The present study was designed to determine the effects of gene knockout of guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) on immunogenic responses affecting kidney function and blood pressure (BP) in (coding for GC-A/NPRA)-null mutant mice. We used female gene-disrupted (, 0 copy), heterozygous (, 1 copy), wild-type (, 2 copy), and gene-duplicated (, 4 copy) mice. Expression levels of Toll-like receptor (TLR)2/TLR4 mRNA were increased 4- to 5-fold in 1-copy mice and 6- to 10-fold in 0-copy mice; protein levels were increased 2.

Inhibition of HDAC enhances STAT acetylation, blocks NF-κB, and suppresses the renal inflammation and fibrosis in haplotype male mice.

Guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) plays a critical role in the regulation of blood pressure and fluid volume homeostasis. Mice lacking functional (coding for GC-A/NPRA) exhibit hypertension and congestive heart failure. However, the underlying mechanisms remain largely less clear.

All-Trans Retinoic Acid supplementation prevents cardiac fibrosis and cytokines induced by Methylglyoxal.

Methylglyoxal (MG), a metabolic intermediate of glycolysis is a precursor for endogeneous production of advanced glycation end-products. The increased production of MG have negative influence over the structure and function of different biomolecules and thus plays an important role in the pathogenesis of diabetic cardiac complications. Retinoic acid (RA), an active metabolite of vitamin A, has a major role in preventing cardiac remodeling and ventricular fibrosis.

Retinoic acid and sodium butyrate suppress the cardiac expression of hypertrophic markers and proinflammatory mediators in Npr1 gene-disrupted haplotype mice.

The objective of the present study was to examine the genetically determined differences in the natriuretic peptide receptor-A (NPRA) gene (Npr1) copies affecting the expression of cardiac hypertrophic markers, proinflammatory mediators, and matrix metalloproteinases (MMPs) in a gene-dose-dependent manner. We determined whether stimulation of Npr1 by all-trans retinoic acid (RA) and histone deacetylase (HDAC) inhibitor sodium butyric acid (SB) suppress the expression of cardiac disease markers. In the present study, we utilized Npr1 gene-disrupted heterozygous (Npr1(+/-), 1-copy), wild-type (Npr1(+/+), 2-copy), gene-duplicated (Npr1(++/+), 3-copy) mice, which were treated intraperitoneally with RA, SB, and a combination of RA/SB, a hybrid drug (HB) for 2 wk.

An In Silico Approach towards the Prediction of Druglikeness Properties of Inhibitors of Plasminogen Activator Inhibitor1.

Diabetic retinopathy is the leading cause of blindness worldwide. It is caused by the abnormal growth of the retinal blood vessels. Plasminogen activator inhibitor1 (PAI1) is the key growth factor and the inhibition of PAI1 can reduce the angiogenesis.