Metabolite signatures associated with microRNA miR-143-3p serve as drivers of poor lung function trajectories in childhood asthma.

BACKGROUND: Lung function trajectories (LFTs) have been shown to be an important measure of long-term health in asthma. While there is a growing body of metabolomic studies on asthma status and other phenotypes, there are no prospective studies of the relationship between metabolomics and LFTs or their genomic determinants. METHODS: We utilized ordinal logistic regression to identify plasma metabolite principal components associated with four previously-published LFTs in children from the Childhood Asthma Management Program (CAMP) (n = 660). The top significant metabolite principal component (PCLF) was evaluated in an independent cross-sectional child cohort, the Genetic Epidemiology of Asthma in Costa Rica Study (GACRS) (n = 1151) and evaluated for association with spirometric measures. Using meta-analysis of CAMP and GACRS, we identified associations between PCLF and microRNA, and SNPs in their target genes. Statistical significance was determined using an false discovery rate-adjusted Q-value. FINDINGS: The top metabolite principal component, PCLF, was significantly associated with better LFTs after multiple-testing correction (Q-value = 0.03). PCLF is composed of the urea cycle, caffeine, corticosteroid, carnitine, and potential microbial (secondary bile acid, tryptophan, linoleate, histidine metabolism) metabolites. Higher levels of PCLF were also associated with increases in lung function measures and decreased circulating neutrophil percentage in both CAMP and GACRS. PCLF was also significantly associated with microRNA miR-143-3p, and SNPs in three miR-143-3p target genes; CCZ1 (P-value = 2.6 × 10-5), SLC8A1 (P-value = 3.9 × 10-5); and TENM4 (P-value = 4.9 × 10-5). INTERPRETATION: This study reveals associations between metabolites, miR-143-3p and LFTs in children with asthma, offering insights into asthma physiology and possible interventions to enhance lung function and long-term health. FUNDING: Molecular data for CAMP and GACRS via the Trans-Omics in Precision Medicine (TOPMed) program was supported by the National Heart, Lung, and Blood Institute (NHLBI).

Tularemia - a re-emerging disease with growing concern.

Tularemia caused by Gram-negative, coccobacillus bacterium, Francisella tularensis, is a highly infectious zoonotic disease. Human cases have been reported mainly from the United States, Nordic countries like Sweden and Finland, and some European and Asian countries. Naturally, the disease occurs in several vertebrates, particularly lagomorphs. Type A (subspecies tularensis) is more virulent and causes disease mainly in North America; type B (subspecies holarctica) is widespread, while subspecies mediasiatica is present in central Asia. F. tularensis is a possible bioweapon due to its lethality, low infectious dosage, and aerosol transmission. Small mammals like rabbits, hares, and muskrats are primary sources of human infections, but true reservoir of F. tularensis is unknown. Vector-borne tularemia primarily involves ticks and mosquitoes. The bacterial subspecies involved and mode of transmission determine the clinical picture. Early signs are flu-like illnesses that may evolve into different clinical forms of tularemia that may or may not include lymphadenopathy. Ulcero-glandular and glandular forms are acquired by arthropod bite or handling of infected animals, oculo-glandular form as a result of conjunctival infection, and oro-pharyngeal form by intake of contaminated food or water. Pulmonary form appears after inhalation of bacteria. Typhoidal form may occur after infection via different routes. Human-to-human transmission has not been known. Diagnosis can be achieved by serology, bacterial culture, and molecular methods. Treatment for tularemia typically entails use of quinolones, tetracyclines, or aminoglycosides. Preventive measures are necessary to avoid infection although difficult to implement. Research is underway for the development of effective live attenuated and subunit vaccines.

Circulating MicroRNAs associated with Bronchodilator Response in Childhood Asthma.

Rationale: Bronchodilator response (BDR) is a measure of improvement in airway smooth muscle tone, inhibition of liquid accumulation and mucus section into the lumen in response to short-acting beta-2 agonists that varies among asthmatic patients. MicroRNAs (miRNAs) are well-known post-translational regulators. Identifying miRNAs associated with BDR could lead to a better understanding of the underlying complex pathophysiology. Objective: The purpose of this study is to identify circulating miRNAs associated with bronchodilator response in asthma and decipher possible mechanism of bronchodilator response variation. Methods: We used available small RNA sequencing on blood serum from 1,134 asthmatic children aged 6 to 14 years who participated in the Genetics of Asthma in Costa Rica Study (GACRS). We filtered the participants into high and low bronchodilator response (BDR) quartiles and used DeSeq2 to identify miRNAs with differential expression (DE) in high (N= 277) vs low (N= 278) BDR group. Replication was carried out in the Leukotriene modifier Or Corticosteroids or Corticosteroid-Salmeterol trial (LOCCS), an adult asthma cohort. The putative target genes of DE miRNAs were identified, and pathway enrichment analysis was performed. Results: We identified 10 down-regulated miRNAs having odds ratios (OR) between 0.37 and 0.76 for a doubling of miRNA counts and one up-regulated miRNA (OR=2.26) between high and low BDR group. These were assessed for replication in the LOCCS cohort, where two miRNAs (miR-200b-3p and miR-1246) were associated. Further, functional annotation of 11 DE miRNAs were performed as well as of two replicated miRs. Target genes of these miRs were enriched in regulation of cholesterol biosynthesis by SREBPs, ESR-mediated signaling, G1/S transition, RHO GTPase cycle, and signaling by TGFB family pathways. Conclusion: MiRNAs miR-1246 and miR-200b-3p are associated with both childhood and adult asthma BDR. Our findings add to the growing body of evidence that miRNAs play a significant role in the difference of asthma treatment response among patients as it points to genomic regulatory machinery underlying difference in bronchodilator response among patients. Trial registration: LOCCS cohort [ClinicalTrials.gov number: NCT00156819], GACRS cohort [ClinicalTrials.gov number: NCT00021840].

Systems Genomics Reveals microRNA Regulation of ICS Response in Childhood Asthma.

BACKGROUND: Asthmatic patients' responses to inhaled corticosteroids (ICS) are variable and difficult to quantify. We have previously defined a Cross-sectional Asthma STEroid Response (CASTER) measure of ICS response. MicroRNAs (miRNAs) have shown strong effects on asthma and inflammatory processes. OBJECTIVE: The purpose of this study was to identify key associations between circulating miRNAs and ICS response in childhood asthma. METHODS: Small RNA sequencing in peripheral blood serum from 580 children with asthma on ICS treatment from The Genetics of Asthma in Costa Rica Study (GACRS) was used to identify miRNAs associated with ICS response using generalized linear models. Replication was conducted in children on ICS from the Childhood Asthma Management Program (CAMP) cohort. The association between replicated miRNAs and the transcriptome of lymphoblastoid cell lines in response to a glucocorticoid was assessed. RESULTS: The association study on the GACRS cohort identified 36 miRNAs associated with ICS response at 10% false discovery rate (FDR), three of which (miR-28-5p, miR-339-3p, and miR-432-5p) were in the same direction of effect and significant in the CAMP replication cohort. In addition, in vitro steroid response lymphoblastoid gene expression analysis revealed 22 dexamethasone responsive genes were significantly associated with three replicated miRNAs. Furthermore, Weighted Gene Co-expression Network Analysis (WGCNA) revealed a significant association between miR-339-3p and two modules (black and magenta) of genes associated with immune response and inflammation pathways. CONCLUSION: This study highlighted significant association between circulating miRNAs miR-28-5p, miR-339-3p, and miR-432-5p and ICS response. miR-339-3p may be involved in immune dysregulation, which leads to a poor response to ICS treatment.

Shatavarin-IV saponin adjuvant elicits IgG and IgG2b responses against Staphylococcus aureus bacterin in a murine model.

Asparagus adscendens Roxb. also known as "safed musli" or "shatavari" is a medicinal plant commonly found in South Asian countries. Shatavari is effective for the treatment of gastric ulcers, renal stones, bronchitis, diabetes, diabetic neuropathy, irritable bowel syndrome, alcohol withdrawal and has reported immunostimulatory effects. In this study, the adjuvant potential of Shatavarin-IV saponin against Staphylococcus aureus bacterin in mice was investigated. Shatavarin-IV was evaluated for its toxicity and immunomodulatory potential against S. aureus bacterin in mice. Cellular and humoral immune responses were assessed. Shatavarin-IV was isolated from the fruit extract of Asparagus adscendens. The confirmation of the isolated molecule as Shatavarin-IV was done via TLC-based comparison with the standard molecule. Further, the structure was confirmed by using extensive spectroscopic analyses and comparing the observed data with literature reports. It was found safe up to the dose of 0.1 mg in the mice model. Shatavarin-IV adjuvant elicited IgG and IgG2b responses at the dose of 40 µg against S. aureus bacterin. However, the cell-mediated immune response was lesser as compared with the commercial Quil-A saponin . We demonstrated that Shatavarin-IV saponin adjuvant produced an optimum humoral immune response against S. aureus bacterin. These results highlight the potential of Shatavarin-IV as an adjuvant in a combination adjuvant in vaccine formulations for induction of potent immune response.

Intrauterine Smoke Exposure, microRNA Expression during Human Lung Development, and Childhood Asthma.

Intrauterine smoke (IUS) exposure during early childhood has been associated with a number of negative health consequences, including reduced lung function and asthma susceptibility. The biological mechanisms underlying these associations have not been established. MicroRNAs regulate the expression of numerous genes involved in lung development. Thus, investigation of the impact of IUS on miRNA expression during human lung development may elucidate the impact of IUS on post-natal respiratory outcomes. We sought to investigate the effect of IUS exposure on miRNA expression during early lung development. We hypothesized that miRNA-mRNA networks are dysregulated by IUS during human lung development and that these miRNAs may be associated with future risk of asthma and allergy. Human fetal lung samples from a prenatal tissue retrieval program were tested for differential miRNA expression with IUS exposure (measured using placental cotinine concentration). RNA was extracted and miRNA-sequencing was performed. We performed differential expression using IUS exposure, with covariate adjustment. We also considered the above model with an additional sex-by-IUS interaction term, allowing IUS effects to differ by male and female samples. Using paired gene expression profiles, we created sex-stratified miRNA-mRNA correlation networks predictive of IUS using DIABLO. We additionally evaluated whether miRNAs were associated with asthma and allergy outcomes in a cohort of childhood asthma. We profiled pseudoglandular lung miRNA in n = 298 samples, 139 (47%) of which had evidence of IUS exposure. Of 515 miRNAs, 25 were significantly associated with intrauterine smoke exposure (q-value < 0.10). The IUS associated miRNAs were correlated with well-known asthma genes (e.g., ORM1-Like Protein 3, ORDML3) and enriched in disease-relevant pathways (oxidative stress). Eleven IUS-miRNAs were also correlated with clinical measures (e.g., Immunoglobulin E andlungfunction) in children with asthma, further supporting their likely disease relevance. Lastly, we found substantial differences in IUS effects by sex, finding 95 significant IUS-miRNAs in male samples, but only four miRNAs in female samples. The miRNA-mRNA correlation networks were predictive of IUS (AUC = 0.78 in males and 0.86 in females) and suggested that IUS-miRNAs are involved in regulation of disease-relevant genes (e.g., A disintegrin and metalloproteinase domain 19 (ADAM19), LBH regulator of WNT signaling (LBH)) and sex hormone signaling (Coactivator associated methyltransferase 1(CARM1)). Our study demonstrated differential expression of miRNAs by IUS during early prenatal human lung development, which may be modified by sex. Based on their gene targets and correlation to clinical asthma and atopy outcomes, these IUS-miRNAs may be relevant for subsequent allergy and asthma risk. Our study provides insight into the impact of IUS in human fetal lung transcriptional networks and on the developmental origins of asthma and allergic disorders.

Evaluation of immunological adjuvant activities of saponin rich fraction from the fruits of Asparagus adscendens Roxb. with less adverse reactions.

The hemolytic activity, in vitro as well as in vivo toxicity, and immunomodulatory potential of saponins-rich fraction of Asparagus adscendens Roxb. fruit (AA-SRF) have been assessed in this study in order to explore AA-SRF as an alternative safer adjuvant to standard Quil-A saponin. The AA-SRF showed lower hemolytic activity (HD50 = 301.01 ± 1.63 µg/ml) than Quil-A (HD50 = 17.15 ± 2.12 µg/ml). The sulforhodamine B assay also revealed that AA-SRF was less toxic to VERO cells (IC50≥200 ± 4.32 µg/ml) than Quil-A (IC50 = 60 ± 2.78 µg/ml). The AA-SRF did not lead to mortality in mice up to 1.6 mg and was much safer than Quil-A for in vivo use. Conversely, mice were subcutaneously immunized with OVA 100 µg alone or along with Alum (200 µg) or Quil-A (10 µg) or AA-SRF (50 µg/100 µg/200 µg) on days 0 and 14. The AA-SRF at 100 µg dose best supported the LPS/Con A primed splenocyte proliferation activity, elevated the serum OVA-specific total IgG antibody, IL-12, CD4 titer and upsurged CD3/CD19 expression in spleen as well as lymph node sections which in turn advocated its adjuvant potential. Thus, AA-SRF can be further studied for use as a safe alternative adjuvant in vaccines.

Recent miRNA Research in Asthma.

PURPOSE OF REVIEW: The study of microRNA in asthma has revealed a vibrant new level of gene regulation underlying asthma pathology. Several miRNAs have been shown to be important in asthma, influencing various biological mechanisms which lead to asthma pathology and symptoms. In addition, miRNAs have been proposed as biomarkers of asthma affection status, asthma severity, and asthma treatment response. We review all recent asthma-miRNA work, while also presenting comprehensive tables of all miRNA results related to asthma. RECENT FINDINGS: We here reviewed 63 recent studies published reporting asthma and miRNA research, and an additional 14 reviews of the same. We summarized the information for both adult and childhood asthma, as well as research on miRNAs in asthma-COPD overlap syndrome (ACOs), and virus-induced asthma exacerbations. We attempted to present a comprehensive collection of recently published asthma-associated miRNAs as well as tables of all published asthma-related miRNA results.

Hemodynamic functional connectivity optimization of frequency EEG microstates enables attention LSTM framework to classify distinct temporal cortical communications of different cognitive tasks.

Temporal analysis of global cortical communication of cognitive tasks in coarse EEG information is still challenging due to the underlying complex neural mechanisms. This study proposes an attention-based time-series deep learning framework that processes fMRI functional connectivity optimized quasi-stable frequency microstates for classifying distinct temporal cortical communications of the cognitive task. Seventy volunteers were subjected to visual target detection tasks, and their electroencephalogram (EEG) and functional MRI (fMRI) were acquired simultaneously. At first, the acquired EEG information was preprocessed and bandpass to delta, theta, alpha, beta, and gamma bands and then subjected to quasi-stable frequency-microstate estimation. Subsequently, time-series elicitation of each frequency microstates is optimized with graph theory measures of simultaneously eliciting fMRI functional connectivity between frontal, parietal, and temporal cortices. The distinct neural mechanisms associated with each optimized frequency-microstate were analyzed using microstate-informed fMRI. Finally, these optimized, quasi-stable frequency microstates were employed to train and validate the attention-based Long Short-Term Memory (LSTM) time-series architecture for classifying distinct temporal cortical communications of the target from other cognitive tasks. The temporal, sliding input sampling windows were chosen between 180 to 750 ms/segment based on the stability of transition probabilities of the optimized microstates. The results revealed 12 distinct frequency microstates capable of deciphering target detections' temporal cortical communications from other task engagements. Particularly, fMRI functional connectivity measures of target engagement were observed significantly correlated with the right-diagonal delta (r = 0.31), anterior-posterior theta (r = 0.35), left-right theta (r = - 0.32), alpha (r = - 0.31) microstates. Further, neuro-vascular information of microstate-informed fMRI analysis revealed the association of delta/theta and alpha/beta microstates with cortical communications and local neural processing, respectively. The classification accuracies of the attention-based LSTM were higher than the traditional LSTM architectures, particularly the frameworks that sampled the EEG data with a temporal width of 300 ms/segment. In conclusion, the study demonstrates reliable temporal classifications of global cortical communication of distinct tasks using an attention-based LSTM utilizing fMRI functional connectivity optimized quasi-stable frequency microstates.

Evolutionary and functional characterisation of glutathione peroxidases showed splicing mediated stress responses in Maize.

Maize (Zea mays L) is an important cereal with extensive adaptability and multifaceted usages. However, various abiotic and biotic stresses limit the productivity of maize across the globe. Exposure of plant to stresses disturb the balance between reactive oxygen species (ROS) production and scavenging, which subsequently increases cellular damage and death of plants. Tolerant genotypes have evolved higher output of scavenging antioxidative defence compounds (ADCs) during stresses as one of the protective mechanisms. The glutathione peroxidases (GPXs) are the broad class of ADCs family. The plant GPXs catalyse the reduction of hydrogen peroxide (H2O2), lipid hydroperoxides and organic hydroperoxides to the corresponding alcohol, and facilitate the regulation of stress tolerance mechanisms. The present investigation was framed to study the maize GPXs using evolutionary and functional analyses. Seven GPX genes with thirteen splice-variants and sixty-three types of cis-acting elements were identified through whole-genome scanning in maize. Evolutionary analysis of GPXs in monocots and dicots revealed mixed and lineage-specific grouping patterns in phylogeny. The expression of ZmGPX splice variants was studied in drought and waterlogging tolerant (L1621701) and sensitive (PML10) genotypes in root and shoot tissues. Further, the differential expression of splice variants of ZmGPX1, ZmGPX3, ZmGPX6 and ZmGPX7 and regulatory network analysis suggested the splicing and regulatory elements mediated stress responses. The present investigation suggests targeting the splicing machinery of GPXs as an approach to enhance the stress tolerance in maize.

A comparative analysis of saponin-enriched fraction from Silene vulgaris (Moench) Garcke, Sapindus mukorossi (Gaertn) and Chlorophytum borivilianum (Santapau and Fernandes): an in vitro hemolytic and cytotoxicity evaluation.

To explore the newer saponin resources, in vitro toxicity of saponin-enriched fraction (SEF) extracted from Silene vulgaris(SV) was evaluated for first time and compared with in vitro toxicity of SEF extracted from Sapindus mukorossi (SM) and Chlorophytum borivilianum (CV). All extracted SEF from diverse resources were characterized by immersing TLC plates in 0.5% RBC suspension method, by ethanol: sulfuric acid method and by estimating hRst values. Each extracted SEF clearly portrayed specific pattern with varied hRst range. White spots against a pinkish-red background and greenish-black spots in case of immersion method and spraying method respectively were observed. After initial characterization, in vitro 0.5% sheep RBC lytic activities and VERO cell cytotoxic activities (via SRB assay) of each extracted SEF were also evaluated. Furthermore, SEF of SV showed very less hemolytic activity compared to SM and CB. The HD50 values for SV, SM, and CB were 736.7 ± 2.824, 18.0 ± 1.894, and 170.70 ± 2.783 µg/mL, respectively. SEF of SV (IC50 ≥ 200 µg/mL) was less toxic for VERO cell line than SEF of SM (IC50 = 150.8 µg/mL) and CB (IC50 = 137.1 µg/mL). Hence, the SEF of SV was found to be less toxic and can be used as a new and safer source of saponins.

Meta-analysis of transcriptomics data identifies potential biomarkers and their associated regulatory networks in gallbladder cancer.

Aim: This study aimed to identify key genes, non-coding RNAs, and their possible regulatory interactions during gallbladder cancer (GBC). Background: The early detection of GBC, i.e. before metastasis, is restricted by our limited knowledge of molecular markers and mechanism(s) involved during carcinogenesis. Therefore, identifying important disease-associated transcriptome-level alterations can be of clinical importance. Methods: In this study, six NCBI-GEO microarray dataseries of GBC and control tissue samples were analyzed to identify differentially expressed genes (DEGs) and non-coding RNAs {microRNAs (DEmiRNAs) and long non-coding RNAs (DElncRNAs)} with a computational meta-analysis approach. A series of bioinformatic methods were applied to enrich functional pathways, create protein-protein interaction networks, identify hub genes, and screen potential targets of DEmiRNAs and DElncRNAs. Expression and interaction data were consolidated to reveal putative DElncRNAs:DEmiRNAs:DEGs interactions. Results: In total, 351 DEGs (185 downregulated, 166 upregulated), 787 DEmiRNAs (299 downregulated, 488 upregulated), and 7436 DElncRNAs (3127 downregulated, 4309 upregulated) were identified. Eight genes (FGF, CDK1, RPN2, SEC61A1, SOX2, CALR, NGFR, and NCAM) were identified as hub genes. Genes associated with ubiquitin ligase activity, N-linked glycosylation, and blood coagulation were upregulated, while those for cell-cell adhesion, cell differentiation, and surface receptor-linked signaling were downregulated. DEGs-DEmiRNAs-DElncRNAs interaction network identified 46 DElncRNAs to be associated with 28 DEmiRNAs, consecutively regulating 27 DEGs. DEmiRNAs-hsa-miR-26b-5p and hsa-miR-335-5p; and DElnRNAs-LINC00657 and CTB-89H12.4 regulated the highest number of DEGs and DEmiRNAs, respectively. Conclusion: The current study has identified meaningful transcriptome-level changes and gene-miRNA-lncRNA interactions during GBC and laid a platform for future studies on novel prognostic and diagnostic markers in GBC.

Functional connectivity between frontal/parietal regions and MTL-basal ganglia during feedback learning and declarative memory retrieval.

Feedback assists the memory system in preserving the learnings from ongoing activities and updating it for future retrievals. Thus, the feedback coming from an individual's performance affects the behavior and, thereby, the performance. However, little is known regarding the interactions of learning and memory associated regions. Thus, we employ a combination of functional connectivity and neurovascular approach to explore the significance of these interactions. Our study comprises thirty-five volunteers who undergo a feedback declarative memory task using simultaneous EEG-fMRI data acquisition. Functional connectivity analysis showed that medial temporal lobe (MTL) and basal ganglia possess significant connectivity but differential relationships during feedback learning and memory retrieval. Specifically, Putamen and pallidum (sub-regions of basal ganglia) are the central hubs in these mechanisms. The neurovascular analysis reveals the increased correlation of frontal-alpha and theta powers with the bold activity of MTL during memory retrievals. The results also report the role of the frontal (and parietal) alpha-beta powers in de-synchronization (and synchronization) of the bold activity of caudate; and parietal-theta (frontal-higher-alpha) power in de-synchronization (and synchronization) of bold activity of right accumbens. Hence, the study demonstrates the significant role of the frontal-parietal EEG powers in MTL-basal ganglia relationships and neuronal adaptations during declarative memory retrieval.

Preparedness of primary and secondary health facilities in India to address major noncommunicable diseases: results of a National Noncommunicable Disease Monitoring Survey (NNMS).

BACKGROUND: The monitoring framework for evaluating health system response to noncommunicable diseases (NCDs) include indicators to assess availability of affordable basic technologies and essential medicines to treat them in both public and private primary care facilities. The Government of India launched the National Program for Prevention and Control of Cancer, Diabetes, Cardiovascular diseases and Stroke (NPCDCS) in 2010 to strengthen health systems. We assessed availability of trained human resources, essential medicines and technologies for diabetes, cardiovascular and chronic respiratory diseases as one of the components of the National Noncommunicable Disease Monitoring Survey (NNMS - 2017-18). METHODS: NNMS was a cross-sectional survey. Health facility survey component covered three public [Primary health centre (PHC), Community health centre (CHC) and District hospital (DH)] and one private primary in each of the 600 primary sampling units (PSUs) selected by stratified multistage random sampling to be nationally representative. Survey teams interviewed medical officers, laboratory technicians, and pharmacists using an adapted World Health Organization (WHO) - Service Availability and Readiness Assessment (SARA) tool on handhelds with Open Data Kit (ODK) technology. List of essential medicines and technology was according to WHO - Package of Essential Medicines and Technologies for NCDs (PEN) and NPCDCS guidelines for primary and secondary facilities, respectively. Availability was defined as reported to be generally available within facility premises. RESULTS: Total of 537 public and 512 private primary facilities, 386 CHCs and 334 DHs across India were covered. NPCDCS was being implemented in 72.8% of CHCs and 86.8% of DHs. All essential technologies and medicines available to manage three NCDs in primary care varied between 1.1% (95% CI; 0.3-3.3) in rural public to 9.0% (95% CI; 6.2-13.0) in urban private facilities. In NPCDCS implementing districts, 0.4% of CHCs and 14.5% of the DHs were fully equipped. DHs were well staffed, CHCs had deficits in physiotherapist and specialist positions, whereas PHCs reported shortage of nurse-midwives and health assistants. Training under NPCDCS was uniformly poor across all facilities. CONCLUSION: Both private and public primary care facilities and public secondary facilities are currently not adequately prepared to comprehensively address the burden of NCDs in India.

Baseline risk factor prevalence among adolescents aged 15-17 years old: findings from National Non-communicable Disease Monitoring Survey (NNMS) of India.

OBJECTIVE: To generate national estimates of key non-communicable disease (NCD) risk factors for adolescents (15-17 years) identified in the National NCD Monitoring Framework and, study the knowledge, attitudes and practices towards NCD risk behaviours among school-going adolescents. DESIGN AND SETTING: A community-based, national, cross-sectional survey conducted during 2017-2018. The survey was coordinated by the Indian Council of Medical Research-National Centre for Disease Informatics and Research with 10 reputed implementing research institutes/organisations across India in urban and rural areas. PARTICIPANTS: A multistage sampling design was adopted covering ages between 15 and 69 years-adolescents (15-17 years) and adults (18-69 years). The sample included 12 000 households drawn from 600 primary sampling units. All available adolescents (15-17 years) from the selected households were included in the survey. MAIN OUTCOME MEASURES: Key NCD risk factors for adolescents (15-17 years)-current tobacco and alcohol use, dietary behaviours, insufficient physical activity, overweight and obesity. RESULTS: Overall, 1402 households and 1531 adolescents completed the survey. Prevalence of current daily use of tobacco was 3.1% (95% CI: 2.0% to 4.7%), 25.2% (95% CI: 22.2% to 28.5%) adolescents showed insufficient levels of physical activity, 6.2% (95% CI: 4.9% to 7.9%) were overweight and 1.8% (95% CI: 1.0% to 2.9%) were obese. Two-thirds reported being imparted health education on NCD risk factors in their schools/colleges. CONCLUSION: The survey provides baseline data on NCD-related key risk factors among 15-17 years in India. These national-level data fill information gaps for this age group and help assess India's progress towards NCD targets set for 2025 comprehensively. Though the prevalence of select risk factors is much lower than in many developed countries, this study offers national evidence for revisiting and framing appropriate policies, strategies for prevention and control of NCDs in younger age groups.

National noncommunicable disease monitoring survey (NNMS) in India: Estimating risk factor prevalence in adult population.

BACKGROUND: The primary objective of National NCD monitoring survey (NNMS) was to generate national-level estimates of key NCD indicators identified in the national NCD monitoring framework. This paper describes survey study protocol and prevalence of risk factors among adults (18-69 years). MATERIALS AND METHODS: NNMS was a national level cross-sectional survey conducted during 2017-18. The estimated sample size was 12,000 households from 600 primary sampling units. One adult (18-69 years) per household was selected using the World Health Organization-KISH grid. The study tools were adapted from WHO-STEPwise approach to NCD risk factor surveillance, IDSP-NCD risk factor survey and WHO-Global adult tobacco survey. Total of 8/10 indicators of adult NCD risk factors according to national NCD disease monitoring framework was studied. This survey for the first time estimated dietary intake of salt intake of population at a national level from spot urine samples. RESULTS: Total of 11139 households and 10659 adults completed the survey. Prevalence of tobacco and alcohol use was 32.8% (95% CI: 30.8-35.0) and 15.9% (95% CI: 14.2-17.7) respectively. More than one-third adults were physically inactive [41.3% (95% CI: 39.4-43.3)], majority [98.4% (95% CI: 97.8-98.8)] consumed less than 5 servings of fruits and / or vegetables per day and mean salt intake was 8 g/day (95% CI: 7.8-8.2). Proportion with raised blood pressure and raised blood glucose were 28.5% (95% CI: 27.0-30.1) and 9.3% (95% CI: 8.3-10.5) respectively. 12.8% (95% CI: 11.2-14.5) of adults (40-69 years) had ten-year CVD risk of ≥30% or with existing CVD. CONCLUSION: NNMS was the first comprehensive national survey providing relevant data to assess India's progress towards targets in National NCD monitoring framework and NCD Action Plan. Established methodology and findings from survey would contribute to plan future state-based surveys and also frame policies for prevention and control of NCDs.

Abiotic Stress-Responsive miRNA and Transcription Factor-Mediated Gene Regulatory Network in Oryza sativa: Construction and Structural Measure Study.

Climate changes and environmental stresses have a consequential association with crop plant growth and yield, meaning it is necessary to cultivate crops that have tolerance toward the changing climate and environmental disturbances such as water stress, temperature fluctuation, and salt toxicity. Recent studies have shown that trans-acting regulatory elements, including microRNAs (miRNAs) and transcription factors (TFs), are emerging as promising tools for engineering naive improved crop varieties with tolerance for multiple environmental stresses and enhanced quality as well as yield. However, the interwoven complex regulatory function of TFs and miRNAs at transcriptional and post-transcriptional levels is unexplored in Oryza sativa. To this end, we have constructed a multiple abiotic stress responsive TF-miRNA-gene regulatory network for O. sativa using a transcriptome and degradome sequencing data meta-analysis approach. The theoretical network approach has shown the networks to be dense, scale-free, and small-world, which makes the network stable. They are also invariant to scale change where an efficient, quick transmission of biological signals occurs within the network on extrinsic hindrance. The analysis also deciphered the existence of communities (cluster of TF, miRNA, and genes) working together to help plants in acclimatizing to multiple stresses. It highlighted that genes, TFs, and miRNAs shared by multiple stress conditions that work as hubs or bottlenecks for signal propagation, for example, during the interaction between stress-responsive genes (TFs/miRNAs/other genes) and genes involved in floral development pathways under multiple environmental stresses. This study further highlights how the fine-tuning feedback mechanism works for balancing stress tolerance and how timely flowering enable crops to survive in adverse conditions. This study developed the abiotic stress-responsive regulatory network, APRegNet database (http://lms.snu.edu.in/APRegNet), which may help researchers studying the roles of miRNAs and TFs. Furthermore, it advances current understanding of multiple abiotic stress tolerance mechanisms.

Comparative Transcriptome Analysis of Iron and Zinc Deficiency in Maize (Zea mays L.).

Globally, one-third of the population is affected by iron (Fe) and zinc (Zn) deficiency, which is severe in developing and underdeveloped countries where cereal-based diets predominate. The genetic biofortification approach is the most sustainable and one of the cost-effective ways to address Fe and Zn malnutrition. Maize is a major source of nutrition in sub-Saharan Africa, South Asia and Latin America. Understanding systems' biology and the identification of genes involved in Fe and Zn homeostasis facilitate the development of Fe- and Zn-enriched maize. We conducted a genome-wide transcriptome assay in maize inbred SKV616, under -Zn, -Fe and -Fe-Zn stresses. The results revealed the differential expression of several genes related to the mugineic acid pathway, metal transporters, photosynthesis, phytohormone and carbohydrate metabolism. We report here Fe and Zn deficiency-mediated changes in the transcriptome, root length, stomatal conductance, transpiration rate and reduced rate of photosynthesis. Furthermore, the presence of multiple regulatory elements and/or the co-factor nature of Fe and Zn in enzymes indicate their association with the differential expression and opposite regulation of several key gene(s). The differentially expressed candidate genes in the present investigation would help in breeding for Fe and Zn efficient and kernel Fe- and Zn-rich maize cultivars through gene editing, transgenics and molecular breeding.

Exploring the possible use of saponin adjuvants in COVID-19 vaccine.

There is an urgent need for a safe, efficacious, and cost-effective vaccine for the coronavirus disease 2019 (COVID-19) pandemic caused by novel coronavirus strain, severe acute respiratory syndrome-2 (SARS-CoV-2). The protective immunity of certain types of vaccines can be enhanced by the addition of adjuvants. Many diverse classes of compounds have been identified as adjuvants, including mineral salts, microbial products, emulsions, saponins, cytokines, polymers, microparticles, and liposomes. Several saponins have been shown to stimulate both the Th1-type immune response and the production of cytotoxic T lymphocytes against endogenous antigens, making them very useful for subunit vaccines, especially those for intracellular pathogens. In this review, we discuss the structural characteristics, mechanisms of action, structure-activity relationship of saponins, biological activities, and use of saponins in various viral vaccines and their applicability to a SARS-CoV-2 vaccine.