Genetic diversity analysis of Katchaikatty Black – An endangered sheep breed from Tamil Nadu

The study presents the genetic diversity of Katchaikatty Black, an endangered and culturally significant sheep breed of Tamil Nadu. A panel of 25 microsatellite markers recommended for Indian sheep was used for genotyping. Considerable genetic variation in terms of allele diversity and heterozygosity was observed within the investigated breed. A total of 174 distinct alleles were detected across the analyzed microsatellite loci with an average of 6.96 alleles per locus. The average observed and expected heterozygosity values were 0.600 and 0.706, respectively. The positive heterozygote deficiency (FIS) value of 0.171, estimated for this breed may be due to the possibility of Wahlund effect resulting from sampling from different breeding flocks, i.e. different villages and flocks in the same area. A normal L-shaped curve suggested absence of genetic bottleneck in this breed. The information generated will be useful in guiding conservation and management programmes for Katchaikatty Black sheep

Mining of diverse short non-coding RNAs from transcriptome of milk somatic cells of Murrah buffalo

The non-coding RNAs (ncRNA) are known to regulate expression of genes at the transcription, translation and processing levels. The present study was conducted to identify diverse short ncRNAs from milk somatic cells of lactating Murrah buffaloes. Elucidating the molecular drivers of lactation in dairy animals will help understand the process of lactation, eventually leading to improvement in milk production and quality. In order to discover the ncRNA, the transcriptome data of 12 samples of somatic cells from buffalo milk were analyzed. A web based pipeline, exceRpt was used to perform the analysis. The most abundant short ncRNA molecules discovered in buffalo milk were the miRNAs, followed by snRNAs. Least number of rRNAs was discovered in the investigated samples. The total number of rRNAs, tRNAs, snRNAs, snoRNAs and miRNAs were 12, 23, 72, 51 and 229 respectively, in the entire dataset. On matching with miRBase v22.1, a total of 1724, 897, 211 and 4 miRNAs were observed to be common to human, bovine, caprine and ovine genomes. The results provide information on the bioavailability of short ncRNAs in buffalo milk somatic cells, most of which are largely uncharacterized. The generated information is a step towards developing a database for ncRNAs in buffalo species

The Impact of Diabetes Mellitus in Patients with Chronic Obstructive Pulmonary Disease (COPD) Hospitalization

Background: Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. Diabetes mellitus (DM) has been shown to have adverse inflammatory effects on lung anatomy and physiology. We investigated the impact of DM on COPD patient outcomes during inpatient hospitalization. Methods: We conducted a retrospective analysis using the Nationwide Inpatient Sample (NIS) over the years 2002-2014. Three groups, COPD without diabetes, COPD with diabetes but no complication, and COPD with DM and complication, were analyzed. Results: A total of 7,498,577 were COPD hospitalization; of those, 1,799,637 had DM without complications, and 483,467 had DM with complications. After adjusting for clinical, demographic, and comorbidities, the odds of increased LOS in the COPD/DM with complication were 1.37 (confidence interval (CI): 1.326-1.368), and those of DM without complication were 1.061 (1.052-1.070) when compared with COPD alone. The odds of pneumonia, respiratory failure, stroke, and acute kidney injury were also higher in COPD hospitalizations with DM. Both DM with complication (odds ratio (OR): 0.751 (CI 0.727-0.777)) and DM without complication (OR: 0.635 (CI: 0.596-0.675)) have lesser odds of mortality during hospitalization than with COPD alone. Conclusions: There is a considerable inpatient burden among COPD patients with DM in the United States

Hypoxia induced lactate acidosis modulates tumor microenvironment and lipid reprogramming to sustain the cancer cell survival

It is well known that solid hypoxic tumour cells oxidise glucose through glycolysis, and the end product of this pathway is fermented into lactate which accumulates in the tumour microenvironment (TME). Initially, it was proclaimed that cancer cells cannot use lactate; therefore, they dump it into the TME and subsequently augment the acidity of the tumour milieu. Furthermore, the TME acts as a lactate sink with stope variable amount of lactate in different pathophysiological condition. Regardless of the amount of lactate pumped out within TME, it disappears immediately which still remains an unresolved puzzle. Recent findings have paved pathway in exploring the main role of lactate acidosis in TME. Cancer cells utilise lactate in the de novo fatty acid synthesis pathway to initiate angiogenesis and invasiveness, and lactate also plays a crucial role in the suppression of immunity. Furthermore, lactate re-programme the lipid biosynthetic pathway to develop a metabolic symbiosis in normoxic, moderately hypoxic and severely hypoxic cancer cells. For instance: severely hypoxic cancer cells enable to synthesizing poly unsaturated fatty acids (PUFA) in oxygen scarcity secretes excess of lactate in TME. Lactate from TME is taken up by the normoxic cancer cells whereas it is converted back to PUFAs after a sequence of reactions and then liberated in the TME to be utilized in the severely hypoxic cancer cells. Although much is known about the role of lactate in these biological processes, the exact molecular pathways that are involved remain unclear. This review attempts to understand the molecular pathways exploited by lactate to initiate angiogenesis, invasiveness, suppression of immunity and cause re-programming of lipid synthesis. This review will help the researchers to develop proper understanding of lactate associated bimodal regulations of TME

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Amla (Emblica officinalis) alleviates doxorubicin-induced cardiotoxicity and nephrotoxicity in rats

Introduction: Doxorubicin (DOX) is a widely used anticancer drug known for its significant cardiotoxic and nephrotoxic effects. Seeking remedies to mitigate these adverse effects is crucial. This study investigates the potential of Emblica officinalis (Amla) extract, a prominent component in Chinese and Indian traditional medicine systems, in alleviating DOX-induced cardiotoxicity and nephrotoxicity. Methods: DOX (20 mg/kg i.p., once) was given to rats to cause acute cardiotoxicity and nephrotoxicity. Rats received 16 similar and cumulative doses of DOX (1.25 mg/kg, i.p.) on alternate days for chronic cardiotoxicity and nephrotoxicity. Biochemical and histological evaluations were done to confirm the onset of cardiotoxicity and nephrotoxicity. Results: The cardioprotective and nephroprotective effects of Amla extract (AE) (150 mg/kg p.o. and 300 mg/kg p.o) were evaluated in comparison to Vitamin E (25 mg/kg p.o.). The treatment with AE (300 mg/kg/day, p.o.) considerably prevented DOX-induced cardiotoxicity, nephrotoxicity, and oxidative stress by positively altering the integrity of glomeruli, restoring the tissue GSH and decreasing serum TBARS. AE (300 mg/kg) was found to be more cardioprotective and nephroprotective than Vitamin E (25 mg/kg p.o.). Discussion: It may be concluded that the induction of cardiotoxicity and nephrotoxicity in rats may be due to DOX-induced oxidative stress, and chronic treatment with AE (300 mg/kg) is an effective way to alleviate the cardiotoxic and nephrotoxic adverse effects of DOX in rats. Moreover, given Amla's historical and contemporary significance in Chinese and Indian traditional medicine systems, its potential therapeutic role merits further exploration in clinical settings

Expression profiling of cytokine genes in peripheral blood mononuclear cells from <i>Anaplasma marginale</i> infected and healthy cattle

In this study, changes in expression profiles of genes encoding 14 cytokines (IL1A, IL1B, IL2, IL4, IL6, IL8, IL10, IL12A, IL12B, IL16, IFNA, IFNB, TGFB1, and TNFA) were investigated amongst six Anaplasma marginale infected and six healthy crossbred cattle. Health status of the animals was determined based on clinical signs, blood smear examination and molecular detection using A. marginale-specific primers. Total RNA was isolated from the peripheral blood mononuclear cells of the infected animals as well as the healthy controls, which was further reverse transcribed to cDNA. Primers for real time PCR were designed using Primer3 software and the results were analyzed by the 2–ΔΔCt method with RPS15 and GAPDH as the reference genes. The expression levels of IL1A, IL1B, IL6, IL10, IL12A, IL12B, and TNFA varied significantly between the two groups, with higher expression in the infected cattle. The transcript abundance of IL4, IL16, and TGFB1 did not vary between the diseased and healthy animals. The expression of IL2 and IL8 was higher in the healthy animals, but the results were non-significant. Taken together, this study provides evidence for difference in expression of cytokine genes in response to anaplasmosis in crossbred cattle.</p

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Not AvailableThis study describes the muscle transcriptome profile of Bandur breed, a consumer favoured, meat type sheep of India. The transcriptome was compared to the less desirable, unregistered local sheep population, in order to understand the molecular factors related to muscle traits in Indian sheep breeds. Bandur sheep have tender muscles and higher backfat thickness than local sheep. The longissimus thoracis transcriptome profiles of Bandur and local sheep were obtained using RNA sequencing (RNA Seq). The animals were male, non-castrated, with uniform age and reared under similar environment, as well as management conditions. We could identify 568 significantly up-regulated and 538 significantly down-regulated genes in Bandur sheep (p≤0.05). Among these, 181 up-regulated and 142 down-regulated genes in Bandur sheep, with a fold change ≥1.5, were considered for further analysis. Significant Gene Ontology terms for the up-regulated dataset in Bandur sheep included transporter activity, substrate specific transmembrane, lipid and fatty acid binding. The down-regulated activities in Bandur sheep were mainly related to RNA degradation, regulation of ERK1 and ERK2 cascades and innate immune response. The MAPK signaling pathway, Adipocytokine signaling pathway and PPAR signaling pathway were enriched for Bandur sheep. The highly connected genes identified by network analysis were CNOT2, CNOT6, HSPB1, HSPA6, MAP3K14 and PPARD, which may be important regulators of energy metabolism, cellular stress and fatty acid metabolism in the skeletal muscles. These key genes affect the CCR4-NOT complex, PPAR and MAPK signaling pathways. The highly connected genes identified in this study, form interesting candidates for further research on muscle traits in Bandur sheep.Not Availabl