Bone marrow-fibroblast progenitor cell-derived small extracellular vesicles promote cardiac fibrosis via miR-21-5p and integrin subunit αV signalling.

Cardiac fibrosis is the hallmark of cardiovascular disease (CVD), which is leading cause of death worldwide. Previously, we have shown that interleukin-10 (IL10) reduces pressure overload (PO)-induced cardiac fibrosis by inhibiting the recruitment of bone marrow fibroblast progenitor cells (FPCs) to the heart. However, the precise mechanism of FPC involvement in cardiac fibrosis remains unclear. Recently, exosomes and small extracellular vesicles (sEVs) have been linked to CVD progression. Thus, we hypothesized that pro-fibrotic miRNAs enriched in sEV-derived from IL10 KO FPCs promote cardiac fibrosis in pressure-overloaded myocardium. Small EVs were isolated from FPCs cultured media and characterized as per MISEV-2018 guidelines. Small EV's miRNA profiling was performed using Qiagen fibrosis-associated miRNA profiler kit. For functional analysis, sEVs were injected in the heart following TAC surgery. Interestingly, TGFß-treated IL10-KO-FPCs sEV increased profibrotic genes expression in cardiac fibroblasts. The exosomal miRNA profiling identified miR-21a-5p as the key player, and its inhibition with antagomir prevented profibrotic signalling and fibrosis. At mechanistic level, miR-21a-5p binds and stabilizes ITGAV (integrin av) mRNA. Finally, miR-21a-5p-silenced in sEV reduced PO-induced cardiac fibrosis and improved cardiac function. Our study elucidates the mechanism by which inflammatory FPC-derived sEV exacerbate cardiac fibrosis through the miR-21a-5p/ITGAV/Col1α signalling pathway, suggesting miR-21a-5p as a potential therapeutic target for treating hypertrophic cardiac remodelling and heart failure.

Early detection of breast cancer through the diagnosis of Nipple Aspirate Fluid (NAF).

The development of breast cancer has been mainly reported in women who have reached the post-menopausal stage; therefore, it is the primary factor responsible for death amongst postmenopausal women. However, if treated on time it has shown a survival rate of 20 years in about two-thirds of women. Cases of breast cancer have also been reported in younger women and the leading cause in them is their lifestyle pattern or they may be carriers of high penetrance mutated genes. Premenopausal women who have breast cancer have been diagnosed with aggressive build-up of tumors and are therefore at more risk of loss of life. Mammography is an effective way to test for breast cancer in women after menopause but is not so effective for premenopausal women or younger females. Imaging techniques like contrast-enhanced MRI can up to some extent indicate the presence of a tumor but it cannot adequately differentiate between benign and malignant tumors. Although the 'omics' strategies continuing for the last 20 years have been helpful at the molecular level in enabling the characteristics and proper understanding of such tumors over long-term longitudinal monitoring. Classification, diagnosis, and prediction of the outcomes have been made through tissue and serum biomarkers but these also fail to diagnose the disease at an early stage. Considerably there is no adequate detection technique present globally that can help early detection and provide adequate specificity, safety, sensitivity, and convenience for the younger and premenopausal women, thereby it becomes necessary to take early measures and build efficient tools and techniques for the same. Through biopsies of nipple aspirate fluid (NAF) biomarker profiling can be performed. It is a naturally secreted fluid from the cells of epithelium found in the breast. Nowadays, home-based liquid biopsy collection kits are also available through which a routine check on breast health can be performed with the help of NAF. Herein, we will review the biomarker screening liquid biopsy, and the new emerging technologies for the examination of cancer at an early stage, especially in premenopausal women.

Major transcription factor families at the nexus of regulating abiotic stress response in millets: a comprehensive review.

Millets stand out as a sustainable crop with the potential to address the issues of food insecurity and malnutrition. These small-seeded, drought-resistant cereals have adapted to survive a broad spectrum of abiotic stresses. Researchers are keen on unravelling the regulatory mechanisms that empower millets to withstand environmental adversities. The aim is to leverage these identified genetic determinants from millets for enhancing the stress tolerance of major cereal crops through genetic engineering or breeding. This review sheds light on transcription factors (TFs) that govern diverse abiotic stress responses and play role in conferring tolerance to various abiotic stresses in millets. Specifically, the molecular functions and expression patterns of investigated TFs from various families, including bHLH, bZIP, DREB, HSF, MYB, NAC, NF-Y and WRKY, are comprehensively discussed. It also explores the potential of TFs in developing stress-tolerant crops, presenting a comprehensive discussion on diverse strategies for their integration.

Symptoms 6 months following SARS-CoV-2 infection in Nepali women.

In Nepal, over 1 million individuals have tested positive for SARS-CoV-2. We sought to describe the frequency of nonrecovery from this infection at 6 months and associated symptoms. We conducted a retrospective cohort study of 6142 women who had positive and negative PCR tests for this infection 6 months previously at 3 institutions in Kathmandu. In telephone interviews women provided information on 22 symptoms and their intensities, health status and history, and functional status. Of 3732 women who had tested PCR positive, 630 (16.9%) reported that they were unrecovered. These 630 unrecovered women were distinguished statistically from the 3102 recovered women by more frequent histories of allergies, rheumatoid disease, BCG immunization, Covid vaccination, strep throat and recent URIs, and both weight gain and weight losses of more than 5 kg in the 6 months following testing, and stressful events in the preceding year. Fatigue, pain, difficulty remembering, shortness of breath, heat and cold intolerance and unrefreshing sleep were reported in 41.9% to 10.5% of these 630 unrecovered women. Six months after confirmed SARS-CoV-2 infection 16.9% of Nepali women have long-COVID manifested as an immune, metabolic, and hormonal systems disruptive and dysfunction syndrome.

A FACS-based novel isolation technique identifies heterogeneous CTCs in oral squamous cell carcinoma.

Purpose: Isolating circulating tumour cells (CTCs) from the blood is challenging due to their low abundance and heterogeneity. Limitations of conventional CTC detection methods highlight the need for improved strategies to detect and isolate CTCs. Currently, the Food and Drug Administration (FDA)-approved CellSearch™ and other RUO techniques are not available in India. Therefore, we wanted to develop a flexible CTC detection/isolation technique that addresses the limitation(s) of currently available techniques and is suitable for various downstream applications. Methods: We developed a novel, efficient, user-friendly CTC isolation strategy combining density gradient centrifugation and immuno-magnetic hematogenous cell depletion with fluorescence-activated cell sorting (FACS)-based positive selection using multiple CTC-specific cell-surface markers. For FACS, a stringent gating strategy was optimised to exclude debris and doublets by side scatter/forward scatter (SSC/FSC) discriminator, remove dead cells by 4',6-diamidino-2-phenylindole (DAPI) staining, and eliminate non-specific fluorescence using a "dump" channel. APC-labelled anti-CD45mAB was used to gate remaining hematogenous cells, while multiple epithelial markers (EpCAM, EGFR, and Pan-Cytokeratin) and an epithelial-mesenchymal transition (EMT) marker (Vimentin) labelled with fluorescein isothiocyanate (FITC) were used to sort cancer cells. The technique was initially developed by spiking Cal 27 cancer cells into the blood of healthy donors and then validated in 95 biopsy-proven oral squamous cell carcinoma (OSCC) patients. CTCs isolated from patients were reconfirmed by Giemsa staining, immuno-staining, and whole transcriptome amplification (WTA), followed by qRT-PCR. In vitro culture and RNA sequencing (RNA-Seq) were also performed to confirm their suitability for various downstream applications. Results: The mean detection efficiency for the Cal 27 tongue cancer cells spiked in the whole blood of healthy donors was 32.82% ± 12.71%. While ~75% of our patients (71/95) had detectable CTCs, the CTC positivity was independent of the TNM staging. The isolated potential cancer cells from OSCC patients were heterogeneous in size. They expressed different CTC-specific markers in various combinations as identified by qRT-PCR after WTA in different patients. Isolated CTCs were also found to be suitable for downstream applications like short-term CTC culture and RNA-Seq. Conclusion: We developed a sensitive, specific, flexible, and affordable CTC detection/isolation technique, which is scalable to larger patient cohorts, provides a snapshot of CTC heterogeneity, isolates live CTCs ready for downstream molecular analysis, and, most importantly, is suitable for developing countries.

Is there a relationship between somatic sensations, impaired vision, and cognitive performance using the factor structure of the convergence insufficiency symptoms survey questionnaire?

AIMS: This study aims to evaluate the relationship between somatic sensations, impaired vision, and cognitive performance using the factor structure convergence insufficiency symptoms survey questionnaire in university undergraduate and post-graduate students. SETTINGS AND DESIGN: Centre-based and questionnaire-based. SUBJECTS AND METHODS: Subjects were recruited from a university. First, an e-Survey was conducted with the help of Google form and distributed through WhatsApp and Gmail to carry out the survey. The age group of participants was ranged from 18 to 30 years. A total number of 561 responses was received during the data collection period. As per the exclusion criteria, 230 responses were excluded from the study. Out of 331 students, 154 were male while 177 were female. Out of 331 participants, 213 were undergraduates and 118 were postgraduate's students. RESULTS: A total of 331 participants took part in the study. The minimum age was 18 years and the maximum age was 30 years. The mean age of the participants was 23.40 ± 2.42. Among all students, 23.81% had somatic sensations followed by 10.49% had impaired vision, and 16.31% had a poor cognitive function. The correlation between somatic sensations-impaired visions was a moderate positive correlation and a strong positive correlation between somatic sensations-cognitive performance and impaired vision-cognitive performance. CONCLUSIONS: A significant relationship between somatic sensations, impaired vision, and cognitive performance was found in the study. The students had more somatic sensations than impaired vision and cognitive performance.

Molecular detection of Listeria monocytogenes from different dairy and street food sources in North Karnataka, India.

BACKGROUND: Food-borne pathogen Listeria monocytogenes is abundantly present in nature and accountable for sporadic and epidemic cases of listeriosis in humans. The objective of this study was to screen common food sources for L. monocytogenes using biochemical and molecular methods to detect and characterise its toxin genes as well as for biofilm formation. METHODS: A total of 92 samples, comprising dairy and street food products, were randomly collected from various sources for this investigation. The collected samples were processed for biochemical and molecular methods to detect L. monocytogenes. Additionally, virulence factors associated genes, antibiogram profiles and biofilm formation related assays were determined. RESULTS: L. monocytogenes presence was confirmed using molecular detection methods targeting prs and lmo1030 genes, along with MALDI-TOF MS. Following 16 S rRNA sequencing, the identified Listeria species were further categorised into two groups. L. monocytogenes was detected in two (2.17%) food samples tested (L-23 and L-74). Multiplex PCR indicated the presence of seven virulence-related genes in L. monocytogenes isolates, i.e., inlA, inlB, prfA, iap, actA, plcB, and hlyA. In addition, 17 antibiotics were tested, whereby two isolates showed resistance to clindamycin and azithromycin, while one isolate (L-74) was also resistant to nalidixic acid, co-trimoxazole, ampicillin, norfloxacin, and cefotaxime. L-23 and L-74 isolates showed biofilm formation, especially at pH 8.6 and 37°C. CONCLUSIONS: Besides the demonstration of the presence of L. monocytogenes in some dairy and street food products, this study underscores the need to increase the standards of hygiene on the one hand and the importance of the surveillance of food-borne pathogens on the other.

Newly identified Pijx gene: a weapon against both seedling and panicle blast in rice.

KEY MESSAGE: A recently reported Pijx gene interacts and promotes the ATPb degradation through 26 proteasomal pathways activate OsRbohC mediated ROS burst, leading to broad-spectrum rice blast resistance in seedling and panicle.

Exploring knowledge, perceptions, and practices of antimicrobials, and their resistance among medicine dispensers and community members in Kavrepalanchok District of Nepal.

BACKGROUND: Inappropriate use of antimicrobials is a global public health issue, particularly in developing countries, including Nepal, where over-the-counter sales and self-medication of antimicrobials are common. OBJECTIVES: To explore knowledge, perceptions, and practices of antimicrobials and their resistance among medicine dispensers and community members in Nepal. METHODS: The study was conducted in three rural and five urban municipalities of the Kavrepalanchok district from May 2021 to August 2021. Data were collected using two qualitative approaches: In-Depth Interviews (IDIs) and Focus Group Discussions (FGDs). Data were analyzed using thematic analysis that combined deductive and inductive approaches to identify codes under pre-specified themes. RESULTS: A total of 16 In-depth interviews with medicine dispensers and 3 focus group discussions with community members were conducted. Knowledge regarding antimicrobial resistance varied among dispensers. Those with a prior educational background in pharmacy often had good knowledge about the causes and consequences of antimicrobial resistance. Meanwhile, consumers were less aware of antimicrobial resistance. Community members perceived antimicrobials as effective medicines but not long-term solution for treating diseases. They reported that dispensing without a prescription was common and that both consumers and dispensers were responsible for the inappropriate use of antimicrobials. On the contrary, several dispensers said that self-medication was common among the consumers, especially among more educated groups. The medicine dispensers and consumers expressed concerns about the weak enforcement of policies regarding pharmacy drug use and dispensing practices. CONCLUSION: Promoting and strengthening the appropriate use of antimicrobials among medicine dispensers and community members is crucial. Bold policies and collective implementation of regulations could help combat antimicrobial resistance.

Multi-environment GWAS identifies genomic regions underlying grain nutrient traits in foxtail millet (Setaria italica).

KEY MESSAGE: A total of 104 foxtail millet accessions were evaluated for 11 nutrients in three environments and 67 high-confidence marker-trait associations (MTAs) were identified. Six SNPs showed pleiotropic effect and associated with two or more nutrients, whereas 24 candidate genes were identified for 28 MTAs involving seven traits. Millets are known for their better nutritional profiles compared to major cereals. Foxtail millet (Setaria italica) is rich in nutrients essential to circumvent malnutrition and hidden hunger. However, the genetic determinants underlying this trait remain elusive. In this context, we evaluated 104 diverse foxtail millet accessions in three different environments (E1, E2, and E3) for 11 nutrients and genotyped with 30K SNPs. The genome-wide association study showed 67 high-confidence (Bonferroni-corrected) marker-trait associations (MTAs) for the nutrients except for phosphorus. Six pleiotropic SNPs were also identified, which were associated with two or more nutrients. Around 24 candidate genes (CGs) were identified for 28 MTAs involving seven nutrients. A total of 17 associated SNPs were present within the gene region, and five (5) were mapped in the exon of the CGs. Significant SNPs, desirable alleles and CGs identified in the present study will be useful in breeding programmes for trait improvement.

Safely managed sanitation practice and childhood stunting among under five years old children in Myanmar.

In 2020, 149 million children under the age of five were estimated to be stunted globally. Around half of deaths among children under 5 years of age are related to under-nutrition. Objective of this study is to determine the association between safely managed sanitation and childhood stunting among under-five years old children in Myanmar. This cross-sectional analytical study was conducted in 16 townships across three regions and five states in Myanmar. Multiple logistic regressions analysis was performed to determine the associations. This study found that 327 (27.09%) under-five children were stunted among a total of 1207 children in Myanmar. Children with unsafely managed sanitation were 2.88 times more likely to be stunting compared with children who access to safely managed sanitation services (AOR = 2.88, 95% CI: 2.16 to 3.85; p-value <0.01). Other associated factors for childhood stunting were needs 1-15 minutes for water collection (AOR = 2.07, 95% CI: 1.46 to 2.94; p-value <0.01), 15-60 minutes for water collection times (AOR = 1.55, 95% CI: 1.08 to 2.23; p-value 0.02), improper waste water disposal (AOR = 1.99, 95% CI: 1.47 to 2.70; p-value <0.01), boys children (AOR = 4.49, 95% CI: 3.30 to 6.12; p-value <0.01), did not take vitamin A supplements(AOR = 1.64, 95% CI: 1.22 to 2.20; p-value <0.01), mothers height shorter than 153.4cm (AOR = 1.94, 95% CI: 1.45 to 2.58; p-value <0.01), and the lower minimal diet diversity (AOR = 1.47, 95% CI: 1.08 to 2.01; p-value 0.02). More access to safely managed sanitation facilities, technical sharing for proper waste water disposal, promoting household water supply system, health promotion for children's diet eating pattern, and regular support for Vitamin A supplementation are critical to reduce childhood stunting among children under the age of five in Myanmar.

Spatial association and modelling of under-5 mortality in Thailand, 2020.

Under-5 mortality rate (U5MR) is a key indicator of child health and overall development. In Thailand, despite significant steps made in child health, disparities in U5MR persist across different provinces. We examined various socio-economic variables, health service availability and environmental factors impacting U5MR in Thailand to model their influences through spatial analysis. Global and Local Moran's I statistics for spatial autocorrelation of U5MR and its related factors were used on secondary data from the Ministry of Public Health, National Centers for Environmental Information, National Statistical Office, and the Office of the National Economic and Social Development Council in Thailand. The relationships between U5MR and these factors were modelled using ordinary least squares (OLS) estimation, spatial lag model (SLM) and spatial error model (SEM). There were significant spatial disparities in U5MR across Thailand. Factors such as low birth weight, unemployment rate, and proportion of land use for agricultural purposes exhibited significant positive spatial autocorrelation, directly influencing U5MR, while average years of education, community organizations, number of beds for inpatients per 1,000 population, and exclusive breastfeeding practices acted as protective factors against U5MR (R2 of SEM = 0.588).The findings underscore the need for comprehensive, multi-sectoral strategies to address the U5MR disparities in Thailand. Policy interventions should consider improving socioeconomic conditions, healthcare quality, health accessibility, and environmental health in high U5M areas. Overall, this study provides valuable insights into the spatial distribution of U5MR and its associated factors, which highlights the need for tailored and localized health policies and interventions.

Fluoroquinolone resistance mutations among Mycobacterium tuberculosis and their interconnection with treatment outcome.

Background: Fluoroquinolone (FQ) antibiotics are among the most potent second-line antitubercular drugs these days. The aim of the study was to analyze the frequency and pattern of genetic mutation in preextensive (pre-XDR) and extensively drug-resistant Mycobacterium tuberculosis using second-line line probe assay (LPA) and to compare drug-resistant mutations with different treatment outcomes. Methods: Sputum, lymph node aspirate, and cold accesses from patients with rifampicin-resistant Tuberculosis (TB) were subjected to first-line and second-line LPA (Genotype MTBDRsl by Hain Life Science, Germany) to assess additional drug resistance to fluoroquinolones (levofloxacin and moxifloxacin). Final treatment outcomes as per the National TB Elimination Program were assessed and compared with the mutation profile. Results: One hundred and fifty subjects were observed to have mutations associated with resistance to FQs and constituted the final study population. The most frequent mutation observed among GyrA drug resistance mutation was D94G (Gyr A MUT3C, 44/150, 66%) corresponding to high-level resistance to levofloxacin and moxifloxacin. The same mutation was associated with poor treatment outcome as died or treatment failure (odds ratio 2.50, relative risk 1.67, P = 0.043). The most common hetero-resistance mutation pattern observed in GyrA gene was wild type plus Asp94Gly mutation in 24.6% of isolates. Conclusions: GyrA MUT3C hybridization corresponding to single-point mutation of aspartic acid to glycine at codon 94 constitutes the most common mutation in GyrA gene locus in M. tuberculosis with significant association with treatment outcome as died compared to those with treatment outcome as cured.

Comment on Xiang et al. Association between the Triglyceride-Glucose Index and Vitamin D Status in Type 2 Diabetes Mellitus. Nutrients 2023, 15, 639.

We read with great interest the article entitled "Association between the Triglyceride-Glucose Index and Vitamin D Status in Type 2 Diabetes Mellitus" by Xiang Q et al. [...].

Dynamics of epigenetic control in plants via SET domain containing proteins: Structural and functional insights.

Plants control expression of their genes in a way that involves manipulating the chromatin structural dynamics in order to adapt to environmental changes and carry out developmental processes. Histone modifications like histone methylation are significant epigenetic marks which profoundly and globally modify chromatin, potentially affecting the expression of several genes. Methylation of histones is catalyzed by histone lysine methyltransferases (HKMTs), that features an evolutionary conserved domain known as SET [Su(var)3-9, E(Z), Trithorax]. This methylation is directed at particular lysine (K) residues on H3 or H4 histone. Plant SET domain group (SDG) proteins are categorized into different classes that have been conserved through evolution, and each class have specificity that influences how the chromatin structure operates. The domains discovered in plant SET domain proteins have typically been linked to protein-protein interactions, suggesting that majority of the SDGs function in complexes. Additionally, SDG-mediated histone mark deposition also affects alternative splicing events. In present review, we discussed the diversity of SDGs in plants including their structural properties. Additionally, we have provided comprehensive summary of the functions of the SDG-domain containing proteins in plant developmental processes and response to environmental stimuli have also been highlighted.

An insight into the roles of regulatory ncRNAs in plants: An abiotic stress and developmental perspective.

Different environmental cues lead to changes in physiology, biochemistry and molecular status of plant's growth. Till date, various genes have been accounted for their role in regulating plant development and response to abiotic stress. Excluding genes that code for a functional protein in a cell, a large chunk of the eukaryotic transcriptome consists of non-coding RNAs (ncRNAs) which lack protein coding capacity but are still functional. Recent advancements in Next Generation Sequencing (NGS) technology have led to the unearthing of different types of small and large non-coding RNAs in plants. Non-coding RNAs are broadly categorised into housekeeping ncRNAs and regulatory ncRNAs which work at transcriptional, post-transcriptional and epigenetic levels. Diverse ncRNAs play different regulatory roles in nearly all biological processes including growth, development and response to changing environments. This response can be perceived and counteracted by plants using diverse evolutionarily conserved ncRNAs like miRNAs, siRNAs and lncRNAs to participate in complex molecular regimes by activating gene-ncRNA-mRNA regulatory modules to perform the downstream function. Here, we review the current understanding with a focus on recent advancements in the functional studies of the regulatory ncRNAs at the nexus of abiotic stresses and development. Also, the potential roles of ncRNAs in imparting abiotic stress tolerance and yield improvement in crop plants are also discussed with their future prospects.

Feasibility of implementing public-private mix approach for tuberculosis case management in Pokhara Metropolitan City of western Nepal: a qualitative study.

Background: The Public-Private Mix (PPM) approach is a strategic initiative that involves engaging all private and public health care providers in the fight against tuberculosis using international health care standards. For tuberculosis control in Nepal, the PPM approach could be a milestone. This study aimed to explore the barriers to a public-private mix approach in the management of tuberculosis cases in Nepal. Methods: We conducted key informant interviews with 20 participants, 14 of whom were from private clinics, polyclinics, and hospitals where the PPM approach was used, two from government hospitals, and four from policymakers. All data were audio-recorded, transcribed, and translated into English. The transcripts of the interviews were manually organized, and themes were generated and categorized into 1. TB case detection, 2. patient-related barriers, and 3. health-system-related barriers. Results: A total of 20 respondents participated in the study. Barriers to PPM were identified into following three themes: (1) Obstacles related to TB case detection, (2) Obstacles related to patients, and (3) Obstacles related to health-care system. PPM implementation was challenged by following sub-themes that included staff turnover, low private sector participation in workshops, a lack of trainings, poor recording and reporting, insufficient joint monitoring and supervision, poor financial benefit, lack of coordination and collaboration, and non-supportive TB-related policies and strategies. Conclusion: Government stakeholders can significantly benefit by applying a proactive role working with the private in monitoring and supervision. The joint efforts with private sector can then enable all stakeholders to follow the government policy, practice and protocols in case finding, holding and other preventive approaches. Future research are essential in exploring how PPM could be optimized.

Diverse strategies that animals use to deter intraspecific predation.

Intraspecific predation is a special case of prey-predator system that is taxonomically widespread. While a heterospecific predator's main goal is to achieve nutrition, intraspecific predation provides conspecifics with other benefits including elimination of competitors for resources and mates. Traditionally intraspecific predation is termed based on the context they occur within, for example egg cannibalism, infanticide and sexual cannibalism. These diverse forms of intraspecific predation and the strategies by which animals are known to deter them are summarized categorically in this review. The diversity of defence strategies animals deploy against conspecific predators is appreciable and raises interesting questions on their evolution for future research.