The Role of Hematocrit Levels in Diagnosing the Severity of Acute Pancreatitis: A Cross-Sectional Study at a Tertiary Care Center in Nepal.

Background and objective Acute pancreatitis (AP) is a frequent cause of hospitalization for gastrointestinal issues, with a significant proportion of cases requiring intensive care. Although various scoring systems are available to predict AP severity, they often involve inconvenience and can be time-consuming and expensive. Hematocrit, a simple, cost-effective, readily available hematological test, has been used to predict AP severity. However, its effectiveness has been inconsistent across different studies. In light of this, we aimed to analyze the role of hematocrit levels in determining AP severity. Methods We conducted a prospective study at Patan Hospital in Lalitpur, Nepal, from June 8, 2022, to June 27, 2023. Sixty-five AP patients were evaluated to determine the prognostic value of hematocrit at admission. The severity of AP was classified per the Revised Atlanta Classification. Results Among the patients, 52 (80%) had mild AP (MAP), five (7.69%) had moderately severe AP (MSAP), and eight (12.31%) had severe AP (SAP). The receiver operating characteristic (ROC) curve for admission hematocrit levels yielded an area under the curve (AUC) of 0.551 (95% CI: 0.423-0.675). A hematocrit cutoff value of 42% resulted in a sensitivity of 69.23% and a specificity of 46.15% for predicting severe AP (MSAP + SAP). Conclusions Based on our findings, hematocrit at admission is not a strong predictor of the severity of AP.

Beta-caryophyllene attenuates experimental hepatocellular carcinoma through downregulation of oxidative stress and inflammation.

Hepatocellular carcinoma (HCC) is caused by various factors including toxic substances and xenobiotics. Numerous treatment strategies are used to address toxicity to the liver and HCC, yet their adverse effects are drawbacks. This study aimed to assess the effect of DEN/CCl4 on morphological changes in the liver, body weight, tumor incidence, and hematological tumor incidence, hematological parameters, hepatic markers, and histopathological analysis in mice following a preventive measure by using ß-caryophyllene (BCP). Adult Balb/c mice were administered a single dose of DEN 1-mg/kg body weight and 0.2-mL CCl4/kg body weight intraperitoneal twice a week (i.p.) for 22 weeks. BCP was treated in one group of mice at 30-mg/kg body weight, intraperitoneal, for 7 weeks. BCP alone was treated in one group of mice at 300-mg/kg body weight intraperitoneal for 22 weeks. DEN/CCl4 caused a reduction in mice's body weight, which was significantly attenuated by BCP administration. BCP supplementation attenuated the tumor incidence DEN/CCl4 (100%) to about 25%. DEN/CCl4 caused alterations in the hematological parameters, serum total protein albumin globulin, A/G ratio, liver function markers (AST, ALT, ALP, GGT, ACP, and bilirubin), and lipid profile markers that were significantly reinstated by BCP administration. Oxidative stress markers (MDA, SOD, CAT, NO, LDH, and GST) were reduced by DEN/CCl4, which were significantly increased in BCP-treated groups. The liver histopathology alterations caused by DEN/CCl4 were amended considerably by BCP treatment. Immunohistochemical studies suggest that AFP, caspase-3, and COX-2 were chronically overexpressed in DEN/CCl4-exposed mice, notably attenuated by BCP administration. BCP suppressed tumor incidence by downregulating inflammation and inducing caspase-3-mediated apoptosis. Conclusively, BCP appears to be a potent natural supplement capable of repressing liver inflammation and carcinoma through the mitigation of oxidative stress and inflammation pathways.

Dietary concoction of formic acid and thymol and its effects on zoo-technical performance, immunity, jejunal architecture and gut health in Turkey.

With increasing demand for improved protein-rich food, diverse poultry birds like turkey are gaining popularity in India. However, with the rising concerns of antibiotic residues and drug resistance, safe alternatives like formic acid (FA) and thymol (TH) have attracted the attention of researchers as effective replacer of antibiotic growth promoters (AGP). This experiment investigated the effects of combinations of FA and TH on growth performance, immunity, gut microflora and jejunal microstructures in turkey. A total of 240 turkey poults were reared in 6 treatment groups for a period of 16 weeks with standard management and feeding: T1 (basal diet only); T2 (AGP); T3 (FA@2.5 ml + TH@240 mg/kg); T4 (FA@2.5 ml + TH@360 mg/kg); T5 (FA@7.5 ml + TH@240 mg/kg) and T6 (FA@7.5 ml + TH@360 mg/kg). The results revealed that T5 group had the highest final body weight and best FCR while the feed consumption across the groups was comparable. The immune status of the turkey improved (p ≤ 0.05) in treatment groups compared to control with T4 and T5 group showcasing the best CBH response, antibody titres and relative immune organ weight index. A significant improvement (p ≤ 0.05) in jejunal microstructures was observed at 16th week in T5 group over control and AGP fed group. There was significant (p ≤ 0.001) reduction in total plate and coliform counts, but a positive shift was seen in Lactobacillus population in T5 group as compared to control and AGP fed group. In conclusion, the concoction of formic acid (7.5 ml/kg) + thymol (240 mg/kg) in-feed supplement improved the performance, immune status and gut health in turkey as an efficient alternative to AGPs.

An ISG15-Based High-Throughput Screening Assay for Identification and Characterization of SARS-CoV-2 Inhibitors Targeting Papain-like Protease.

Emergence of newer variants of SARS-CoV-2 underscores the need for effective antivirals to complement the vaccination program in managing COVID-19. The multi-functional papain-like protease (PLpro) of SARS-CoV-2 is an essential viral protein that not only regulates the viral replication but also modulates the host immune system, making it a promising therapeutic target. To this end, we developed an in vitro interferon stimulating gene 15 (ISG15)-based Förster resonance energy transfer (FRET) assay and screened the National Cancer Institute (NCI) Diversity Set VI compound library, which comprises 1584 small molecules. Subsequently, we assessed the PLpro enzymatic activity in the presence of screened molecules. We identified three potential PLpro inhibitors, namely, NSC338106, 651084, and 679525, with IC50 values in the range from 3.3 to 6.0 µM. These molecules demonstrated in vitro inhibition of the enzyme activity and exhibited antiviral activity against SARS-CoV-2, with EC50 values ranging from 0.4 to 4.6 µM. The molecular docking of all three small molecules to PLpro suggested their specificity towards the enzyme's active site. Overall, our study contributes promising prospects for further developing potential antivirals to combat SARS-CoV-2 infection.

Delineation of loci governing an extra-earliness trait in lentil (Lens culinaris Medik.) using the QTL-Seq approach.

Developing early maturing lentil has the potential to minimize yield losses, mainly during terminal drought. Whole-genome resequencing (WGRS) based QTL-seq identified the loci governing earliness in lentil. The genetic analysis for maturity duration provided a good fit to 3:1 segregation (F2), indicating earliness as a recessive trait. WGRS of Globe Mutant (late parent), late-flowering, and early-flowering bulks (from RILs) has generated 1124.57, 1052.24 million raw and clean reads, respectively. The QTL-Seq identified three QTLs (LcqDTF3.1, LcqDTF3.2, and LcqDTF3.3) on chromosome 3 having 246244 SNPs and 15577 insertions/deletions (InDels) and 13 flowering pathway genes. Of these, 11 exhibited sequence variations between bulks and validation (qPCR) revealed a significant difference in the expression of nine candidate genes (LcGA20oxG, LcFRI, LcLFY, LcSPL13a, Lcu.2RBY.3g060720, Lcu.2RBY.3g062540, Lcu.2RBY.3g062760, LcELF3a, and LcEMF1). Interestingly, the LcELF3a gene showed significantly higher expression in late-flowering genotype and exhibited substantial involvement in promoting lateness. Subsequently, an InDel marker (I-SP-383.9; LcELF3a gene) developed from LcqDTF3.2 QTL region showed 82.35% PVE (phenotypic variation explained) for earliness. The cloning, sequencing, and comparative analysis of the LcELF3a gene from both parents revealed 23 SNPs and InDels. Interestingly, a 52 bp deletion was recorded in the LcELF3a gene of L4775, predicted to cause premature termination of protein synthesis after 4 missense amino acids beyond the 351st amino acid due to the frameshift during translation. The identified InDel marker holds significant potential for breeding early maturing lentil varieties.

Spatio-temporal expression of polyphenol oxidase unveils the dynamics of L-DOPA accumulation in faba bean (Vicia faba L.).

Faba bean (Vicia faba L.) is a winter season grain legume and a rich source of the anti-parkinson drug, L-3,4-dihydroxyphenylalanine (L-DOPA). The biosynthesis of L-DOPA in plants is not uniform and remains largely unexplored. While the hydroxylase activities of Tyrosine Hydroxylase (TH), the Cytochrome P450 (CYP450) class of enzymes, and Polyphenol Oxidases (PPOs) on tyrosine substrate have been reported in plants, only the roles of PPOs in L-DOPA biosynthesis have been recently established in velvet bean (Mucuna pruriens). To understand the differential accumulation of L-DOPA in different tissues of faba bean, profiling of L-Tyrosine, L-DOPA, Tyramine, and Dopamine in different tissues was performed. Differential accumulation of L-DOPA depended on tissue type and maturity. Furthermore, dopamine biosynthesis through L-DOPA from L-Tyr was confirmed in faba bean. The expression analysis of PPOs in leaf and flower tissues revealed the selective induction of only four (HePPO-2, HePPO-7, HePPO-8b, and HePPO-10) out of ten genes encoding different PPOs mined from the faba bean genome. Higher accumulation of L-DOPA in young leaves and flower buds than in mature leaves and flowers was accompanied by significantly higher expression of HePPO-10 and HePPO-7, respectively. The role of various transcription factors contributing to such metabolite dynamics was also predicted. Further exploration of this mechanism using a multi-omics approach can provide meaningful insight and pave the way for enhancing L-DOPA content in crops. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01449-2.

Community-based, cost-effective multispecies mangrove restoration innovation to maximize soil blue carbon pool and humic acid and fulvic acid concentrations at Indian Sundarbans.

Sundarbans is the world's largest and most diverse contiguous mangrove ecosystem. In this pilot study, three plots (around 1 ha each) were selected, where one site (S1) had 1 year of community involvement, another site (S2) had a community network to support the restoration initiatives for 2 years, while a control site (C) was devoid of any post plantation community protection. Rhizophora mucronata (Rhizophoraceae), Sonneretia caseolaris (Lythraceae) and Avicennia marina (Acanthaceae) were planted at the sites in 2012. After 6 years (in 2017), at S1, the monitoring showed low survival rate for salinity-sensitive species, 2% for R. mucronata and 4% for S. caseolaris. At S2, R. mucronata has high survival rates, i.e. 71%, followed by S. caseolaris with 40%, whereas at C, the survival rate of both species was 0%. At S1 and C, the salinity-tolerant A. marina replaced the planted mangroves partially (S1) or entirely (C). At S2, available soil P increased by 17.5%, in 6 years, and the overall blue carbon pool showed a linear increase from 64.4 to 88.6 Mg C ha-1 (34.3% rise). S1 showed a minimum increment in P and the blue carbon pool (6.9% rise), while site C showed fluctuations in the blue carbon pool with only a 3.1% increase. Humic acid and fulvic acid concentrations in the S2 site indicate positive functional carbon sequestration in the edaphic environment. The community involvement increased the plantation cost (567.70 USD) of S2, in comparison to S1 (342.52 USD) and C (117.34 USD), but it has resulted in better restoration and survival of the mangroves. The study concludes that community participation for at least 2 years can play a significant role in the conservation of mangrove ecosystems and the success of restoration initiatives in tidal, saline wetlands and would aid in compliance with the United Nations Sustainable Development Goal 14 (Life Below Water) targets.

Genome-wide discovery of InDels and validation of PCR-Based InDel markers for earliness in a RIL population and genotypes of lentil (Lens culinaris Medik.).

The systematic identification of insertion/deletion (InDel) length polymorphisms from the entire lentil genome can be used to map the quantitative trait loci (QTL) and also for the marker-assisted selection (MAS) for various linked traits. The InDels were identified by comparing the whole-genome resequencing (WGRS) data of two extreme bulks (early- and late-flowering bulk) and a parental genotype (Globe Mutant) of lentil. The bulks were made by pooling 20 extreme recombinant inbred lines (RILs) each, derived by crossing Globe Mutant (late flowering parent) with L4775 (early flowering parent). Finally, 734,716 novel InDels were identified, which is nearly one InDel per 5,096 bp of lentil genome. Furthermore, 74.94% of InDels were within the intergenic region and 99.45% displayed modifier effects. Of these, 15,732 had insertions or deletions of 20 bp or more, making them amenable to the development of PCR-based markers. An InDel marker I-SP-356.6 (chr. 3; position 356,687,623; positioned 174.5 Kb from the LcFRI gene) was identified as having a phenotypic variance explained (PVE) value of 47.7% for earliness when validated in a RIL population. Thus, I-SP-356.6 marker can be deployed in MAS to facilitate the transfer of the earliness trait to other elite late-maturing cultivars. Two InDel markers viz., I-SP-356.6 and I-SP-383.9 (chr. 3; linked to LcELF3a gene) when tested in 9 lentil genotypes differing for maturity duration, clearly distinguished three early (L4775, ILL7663, Precoz) and four late genotypes (Globe Mutant, MFX, L4602, L830). However, these InDels could not be validated in two genotypes (L4717, L4727), suggesting either absence of polymorphism and/or presence of other loci causing earliness. The identified InDel markers can act as valuable tools for MAS for the development of early maturing lentil varieties.

A randomised controlled trial to evaluate the effectiveness of a culture and disease-specific, patient-centric multi-component tobacco cessation intervention package for the patients attending non-communicable disease clinics in Punjab, India.

BACKGROUND: Developing an infrastructure to support tobacco cessation through existing systems and resources is crucial for ensuring the greatest possible access to cessation services. The present study aims to evaluate the effectiveness of a newly developed multi-component cessation among tobacco users in Non- Communicable Disease (NCD) clinics, functioning under the National Programme for Prevention & Control of Cancer, Diabetes, Cardiovascular Diseases, & Stroke (NPCDCS) of the Government of India. METHODS: The intervention package consisting of culture- and disease-specific four face-to-face counselling sessions, pamphlets, and short text messages (bilingual) with follow-ups at 3rd, 6th, and 9th months with an endline assessment at 12th months was delivered to the intervention arm of the two-arm- parallel group randomised controlled trial at two selected NCD clinics. Self-reported seven-day abstinence, frequency of use, expenditure in seven days at each follow-up, FTND score, stage of change and plasma cotinine values were assessed at baseline, follow-ups, and endline (using Liquid Chromatography -Mass Spectrometry), as applicable. RESULTS: The intervention arm reported a significantly more reduction in self-reported frequency of tobacco use at 6 months (mean: 13.6, 95% CI (7.8-19.4)), 9 months (mean: 20.3, 95% CI (12.2-28.4)) and 12 months (mean: 18.7, 95% CI (8.7-28.7)). The plasma cotinine concentration at endline in the intervention arm was statistically significantly lower than the baseline concentration. CONCLUSION: Strengthening existing health systems is crucial for offering cessation support in the resource-restraint setting of LMICs to assist in quitting sustainably.

Exitrons: offering new roles to retained introns-the novel regulators of protein diversity and utility.

Exitrons are exonic introns. This subclass of intron retention alternative splicing does not contain a Pre-Terminating stop Codon. Therefore, when retained, they are always a part of a protein. Intron retention is a frequent phenomenon predominantly found in plants, which results in either the degradation of the transcripts or can serve as a stable intermediate to be processed upon induction by specific signals or the cell status. Interestingly, exitrons have coding ability and may confer additional attributes to the proteins that retain them. Therefore, exitron-containing and exitron-spliced isoforms will be a driving force for creating protein diversity in the proteome of an organism. This review establishes a basic understanding of exitron, discussing its genesis, key features, identification methods and functions. We also try to depict its other potential roles. The present review also aims to provide a fundamental background to those who found such exitronic sequences in their gene(s) and to speculate the future course of studies.

Evaluation of in-feed supplementation of formic acid and thymol as non-antibiotic growth promoters and assessing their effect on antimicrobial resistant E.coli isolated in Turkey.

With the rampant usage of antibiotics as growth promoters (AGPs) in poultry sector, there has been alarming concerns of antimicrobial resistant microbes such as Escherichia coli. Diversification of poultry farming due to consumer demand for safer products with higher protein content, turkey production is gaining popularity. Feed additives such as formic acid (FA) and thymol (TH) are effectively replacing AGPs due to their antimicrobial action. This directed the researchers to find alternatives to antibiotics such as thymol and formic acid because of their strong antimicrobial, anti-oxidative, digestive-stimulating properties. To assess the efficacy of FA and TH as growth promoters and their effect on the antimicrobial resistance (AMR) load, the current study (0-12 weeks) was conducted in CARI VIRAT turkey poults (n = 256; unsexed) those were randomly distributed into eight treatment groups: control(T1), AGP (T2), graded levels of FA (T3 to T5) @ 2.5, 5 and 7.5 ml/kg and TH (T6 to T8) @ 120, 240 and 350 mg/kg. Cloacal swab samples were collected at 0, 4th, 8th and 12th week interval and processed further for isolation, identification and assessment of resistance profile of E. coli. The final body weight, cumulative gain and FCR were significantly (p < 0.05) better for birds under supplementation. The Total plate count (TPC) and coliforms showcased a significant (p < 0.001) reduction in the FA and TH supplement groups as compared to control and AGP group. The resistance profile indicated E. coli isolates from AGP group with significantly (p < 0.001) highest resistivity against antibiotics (viz. chloramphenicol, tetracycline, nalidixic acid, chlortetracycline) while isolates from FA (T5) and TH (T8) groups were the least resistant. blaAmpC gene was significantly (p < 0.001) harbored in T2 isolates whereas least detected in T5 and T8. It was inferred that formic acid (7.5 ml/kg) and thymol (360 mg/kg) can effectively replace AGPs and lower AMR burden in poultry.

Identification of quantitative trait loci (QTLs) regulating leaf SPAD value and trichome density in mungbean (Vigna radiata L.) using genotyping-by-sequencing (GBS) approach.

Quantitative trait loci (QTL) mapping is used for the precise localization of genomic regions regulating various traits in plants. Two major QTLs regulating Soil Plant Analysis Development (SPAD) value (qSPAD-7-1) and trichome density (qTric-7-2) in mungbean were identified using recombinant inbred line (RIL) populations (PMR-1×Pusa Baisakhi) on chromosome 7. Functional analysis of QTL region identified 35 candidate genes for SPAD value (16 No) and trichome (19 No) traits. The candidate genes regulating trichome density on the dorsal leaf surface of the mungbean include VRADI07G24840, VRADI07G17780, and VRADI07G15650, which encodes for ZFP6, TFs bHLH DNA-binding superfamily protein, and MYB102, respectively. Also, candidate genes having vital roles in chlorophyll biosynthesis are VRADIO7G29860, VRADIO7G29450, and VRADIO7G28520, which encodes for s-adenosyl-L-methionine, FTSHI1 protein, and CRS2-associated factor, respectively. The findings unfolded the opportunity for the development of customized genotypes having high SPAD value and high trichome density having a possible role in yield and mungbean yellow vein mosaic India virus (MYMIV) resistance in mungbean.

Naringenin suppresses aluminum-induced experimental hepato-nephrotoxicity in mice through modulation of oxidative stress and inflammation.

Aluminum is a widely used metal substance in daily life activities that has been shown to cause severe hepato-nephrotoxicity with long-term exposure. Natural dietary flavonoids are being utilized as a newer pharmaceutical approach against various acute and chronic diseases. Naringenin (NAR) has shown efficient therapeutic properties, including effects against metal toxicities. However, the protective efficacy of NAR on aluminum chloride (AlCl3)-induced hepato-renal toxicity needs investigation as aluminum has shown serious environmental toxicity and bioaccumulation behavior. In this study, mice were treated with AlCl3 (10 mg/kg b.w./day) to assess toxicities, and a group of mice were co-treated with NAR (10 mg/kg b.w./day) to assess the protective effects of NAR against hepato-nephrotoxicity. The levels of blood serum enzymes, oxidative stress biomarkers, inflammatory cytokines, and the apoptosis marker caspase-3 were measured using histological examinations. NAR treatment in AlCl3-treated mice resulted in maintained levels of liver and kidney function enzymes and lipid profiles. NAR treatment attenuated oxidative stress by regulating the levels of nitric oxide, advance oxidation of protein products, protein carbonylation, and lipid peroxidation. NAR also replenished reduced antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and reduced the levels of glutathione and oxidized glutathione. NAR regulated the levels of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and elevated the levels of anti-inflammatory cytokines (IL-4, IL-10, and IFN-γ). The histological study further confirmed the protective effects of NAR against AlCl3-induced hepato-renal alterations. NAR decreased the expression of caspase-3 as a mechanism of protective effects against apoptotic damage in the liver and kidney of AlCl3-treated mice. In summary, this study demonstrated the antioxidant and anti-inflammatory properties of NAR, leading to the suppression of AlCl3-triggered hepato-renal apoptosis and histological alterations. The results suggest that aluminum toxicity needs to be monitored in daily life usage, and supplementation of the natural dietary flavonoid naringenin may help maintain liver and kidney health.

Genome-wide association studies for earliness, MYMIV resistance, and other associated traits in mungbean (Vigna radiata L. Wilczek) using genotyping by sequencing approach.

Yellow mosaic disease (YMD) remains a major constraint in mungbean (Vigna radiata (L.)) production; while short-duration genotypes offer multiple crop cycles per year and help in escaping terminal heat stress, especially during summer cultivation. A comprehensive genotyping by sequencing (GBS)-based genome-wide association studies (GWAS) analysis was conducted using 132 diverse mungbean genotypes for traits like flowering time, YMD resistance, soil plant analysis development (SPAD) value, trichome density, and leaf area. The frequency distribution revealed a wide range of values for all the traits. GBS studies identified 31,953 high-quality single nucleotide polymorphism (SNPs) across all 11 mungbean chromosomes and were used for GWAS. Structure analysis revealed the presence of two genetically distinct populations based on ΔK. The linkage disequilibrium (LD) varied throughout the chromosomes and at r2 = 0.2, the mean LD decay was estimated as 39.59 kb. Two statistical models, mixed linear model (MLM) and Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) identified 44 shared SNPs linked with various candidate genes. Notable candidate genes identified include FPA for flowering time (VRADI10G01470; chr. 10), TIR-NBS-LRR for mungbean yellow mosaic India virus (MYMIV) resistance (VRADI09G06940; chr. 9), E3 ubiquitin-protein ligase RIE1 for SPAD value (VRADI07G28100; chr. 11), WRKY family transcription factor for leaf area (VRADI03G06560; chr. 3), and LOB domain-containing protein 21 for trichomes (VRADI06G04290; chr. 6). In-silico validation of candidate genes was done through digital gene expression analysis using Arabidopsis orthologous (compared with Vigna radiata genome). The findings provided valuable insight for marker-assisted breeding aiming for the development of YMD-resistant and early-maturing mungbean varieties.

Study of Association of Serum Prolactin Levels with Insulin Resistance in Type 2 Diabetes Mellitus Patients.

Objective: Prolactin (PRL) regulates glucose metabolism and insulin sensitivity. The study aimed to evaluate the role of PRL in glucose homeostasis and its association with insulin resistance in patients with diabetes mellitus (DM). Methods and Materials: This cross-sectional, observational study included 100 patients (25-60 years) with T2DM. Primary information including demographics, anthropometric measurements, and biochemical measures (complete blood count, glucose parameters, liver and kidney function test, lipid profile, thyroid function test, serum fasting insulin levels, serum PRL levels) was collected. Results: A total of 100 patients, 50 men and 50 women (25 premenopausal and 25 postmenopausal), were enrolled in this study. The correlation between serum cholesterol and PRL was found to be statistically non-significant (P = 0.129) in men and significant (P = 0.041) in women. There was an inverse relationship between fasting plasma glucose and serum PRL levels in both men (r = -0.88; P < 0.0001) and women patients (r = -0.768; P < 0.0001). Negative correlation between postprandial plasma glucose and PRL was found to be statistically significant (r = -0.398; P = 0.048) in postmenopausal women. The comparison in both men and women indicated an inverse correlation between serum PRL and glycated haemoglobin levels. There was a significant negative correlation between homeostasis model assessment-estimated insulin resistance (HOMA-IR) and PRL levels in both men (r = -0.362; P = 0.039) and women patients (r = -0.362; P = 0.003). Homeostasis model assessment of ß cell function (HOMA-ß), which directly correlates with residual pancreatic beta cell function, was positively correlated with prolactin levels, irrespective of gender and menopausal status of female subjects. Conclusion: Serum PRL levels correlate with improved glycaemic control.

Association of Sex Hormones and Androgens with Disease Activity in Premenopausal Females with Rheumatoid Arthritis.

Background: Gonadal sex hormone dysfunction is frequently reported in patients with Rheumatoid arthritis (RA). The relationship of these hormones with disease activity is still not clear and whether the hormone imbalance leads to increased severity of RA is not well studied in this part of the world. The present study aimed to elucidate this fact. Methods: It was a cross-sectional observational study performed in 80 premenopausal females with definite RA at a tertiary care hospital in New Delhi, India over one year. Patients were subjected to investigations as per the protocol and a fasting venous blood sample for hormone levels was collected in the follicular phase of their menstrual cycle. Results: A statistically significant correlation by linear logistic regression analysis was found between disease activity (as measured by DAS28) and serum progesterone, FSH, and prolactin, while serum testosterone and DHEAS showed an inverse relationship with disease activity. Low s. prolactin, and s. FSH as well as high s. testosterone and s. DHEAS were found to be associated with target clinical goals in RA (ie, remission and low disease activity). On multivariate logistic regression analysis, serum prolactin showed a direct association. (p=0.016, OR= 1.009. C.I.= 1.0021.017) and serum testosterone were found to have an inverse relationship (p=0.002, OR= 0.017, C.I.=0.001-0.237) with disease activity in this group of individuals. Conclusion: Serum levels of sex hormones may be helpful in predicting disease activity among patients with RA, and in future, may be used to guide treatment of severe refractory disease, unresponsive to conventional treatment with DMARDs, especially in resource-poor settings.

Assessment of Lactobacillus rhamnosus mediated protection against arsenic-induced toxicity in zebrafish: a qPCR-based analysis of Firmicutes and Bacteroidetes groups and embryonic development.

Arsenic poses a significant health risk worldwide, impacting the gut microbiota, reproductive health, and development. To address this issue, a cost-effective method like probiotic supplementation could be beneficial. However, the interplay between arsenic toxicity, probiotics, gut microbiota, and maternal transcript modulation remains unexplored. This study investigates the impact of Lactobacillus rhamnosus (L. rhamnosus) DSM 20021 on the proportions of Firmicutes and Bacteroidetes, as well as its effects on embryonic development in zebrafish induced by arsenic trioxide (As2O3). Adult zebrafish were exposed to both high and environmentally relevant concentrations of As2O3 (10, 50, and 500 ppb) for 1, 6, and 12 weeks. qPCR analysis revealed increased proportions of Firmicutes and Bacteroidetes in all As2O3-exposed and As2O3 + L. rhamnosus-exposed groups, while no significant changes were observed in groups exposed only to L. rhamnosus DSM 20021. The larvae, exposed to 500 ppb of As2O3 for 12 weeks, exhibited low growth, decreased survival rates, and morphological deformities. However, these adverse effects were reversed upon exposure to only L. rhamnosus DSM 20021. Furthermore, the expression of DVR1 and ABCC5, which are involved in defense against xenobiotics and embryo development, decreased significantly in As2O3 (500 ppb) and As2O3 (500 ppb) + L. rhamnosus-exposed groups, whereas ameliorative effects were observed in only L. rhamnosus DSM 20021-exposed groups.

Mechanism of action of certain medicinal plants for the treatment of asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Asthma is often treated and prevented using the pharmacological properties of traditional medicinal plants. These healthcare systems are among the most well-known, conveniently accessible, and economically priced in India and several other Asian countries. Traditional Indian Ayurvedic plants have the potential to be used as phyto-therapeutics, to create novel anti-asthmatic drugs, and as a cost-effective source of pharmaceuticals. Current conventional therapies have drawbacks, including serious side effects and expensive costs that interfere with treatment compliance and affect the patient's quality of life. The primary objective of the article is to comprehensively evaluate the advancement of research on the protective phytochemicals of traditional plants that target immune responses and signaling cascades in inflammatory experimental asthma models. The study would assist in paving the way for the creation of natural phytomedicines that are protective, anti-inflammatory, and immunomodulatory against asthma, which may then be used in individualized asthma therapy. AIM OF THE STUDY: The study demonstrates the mechanisms of action of phytochemicals present in traditional medicinal plants, diminish pulmonary disorder in both in vivo and in vitro models of asthma. MATERIALS AND METHODS: A comprehensive review of the literature on conventional plant-based asthma therapies was performed from 2006 to 2022. The study uses authoritative scientific sources such as PubMed, PubChem Compound, Wiley Online Library, Science Direct, Springer Link, and Google Scholar to collect information on potential phytochemicals and their mechanisms of action. World Flora Online (http://www.worldfloraonline.org) and Plants of the World Online (https://wcsp.science.kew.org) databases were used for the scientific names of medicinal plants. RESULTS: The study outlines the phytochemical mechanisms of some traditional Ayurveda botanicals used to treat asthma. Active phytochemicals including curcumin, withaferin-A, piperine, glabridin, glycyrrhizin, 18ß-glycyrrhetinic acid, trans-cinnamaldehyde, α-hederin, thymoquinone, eugenol, [6]-shogoal, and gingerol may treat asthma by controlling inflammation and airway remodeling. The study concluded that certain Ayurvedic plants' phytochemicals have the ability to reduce inflammation and modulate the immune system, that can effectively cure asthma. CONCLUSION: Plants used in traditional Ayurvedic medicine have been utilized for millennia, advocating phyto-therapy as a treatment for a variety of illnesses. A theoretical foundation for the use of cutting-edge asthma treatments has been built with the growth of experimental research on traditional phytochemicals. In-depth phytochemical research for the treatment of asthma using Indian Traditional Ayurvedic herbs is compiled in the study. The approach for preventative therapeutics and cutting-edge alternatives to battle the molecular pathways in the pathophysiology of asthma are the key themes of the study. The phytochemical mechanism of action of traditional Ayurvedic herbs is explained to get the attention of the pharmaceutical industry so they can make future anti-asthma drugs for personalized asthma care in the community. The study develops strategies for customized phyto-therapeutics, concentrating on low-cost, side-effect-free approaches that employ bioactive phytochemicals from plants as the major source of effective anti-asthmatic therapy.

Broad-Spectrum Small-Molecule Inhibitors Targeting the SAM-Binding Site of Flavivirus NS5 Methyltransferase.

Flavivirus infections, such as those caused by dengue virus (DENV), West Nile virus (WNV), yellow fever virus (YFV), and Zika virus (ZIKV), pose a rising threat to global health. There are no FDA-approved drugs for flaviviruses, although a small number of flaviviruses have vaccines. For flaviviruses or unknown viruses that may appear in the future, it is particularly desirable to identify broad-spectrum inhibitors. The NS5 protein is regarded as one of the most promising flavivirus drug targets because it is conserved across flaviviruses. In this study, we used FL-NAH, a fluorescent analog of the methyl donor S-adenosyl methionine (SAM), to develop a fluorescence polarization (FP)-based high throughput screening (HTS) assay to specifically target methyltransferase (MTase), a vital enzyme for flaviviruses that methylates the N7 and 2'-O positions of the viral 5'-RNA cap. Pilot screening identified two candidate MTase inhibitors, NSC 111552 and 288387. The two compounds inhibited the FL-NAH binding to the DENV3 MTase with low micromolar IC50. Functional assays verified the inhibitory potency of these molecules for the flavivirus MTase activity. Binding studies indicated that these molecules are bound directly to the DENV3 MTase with similar low micromolar affinity. Furthermore, we showed that these compounds greatly reduced ZIKV replication in cell-based experiments at dosages that did not cause cytotoxicity. Finally, docking studies revealed that these molecules bind to the SAM-binding region on the DENV3 MTase, and further mutagenesis studies verified residues important for the binding of these compounds. Overall, these compounds are innovative and attractive candidates for the development of broad-spectrum inhibitors for the treatment of flavivirus infections.

Distribution, speciation, and bioaccumulation of potentially toxic elements in the grey mangroves at Indian Sundarbans, in relation to vessel movements.

Sundarban is the world's largest mangrove wetland and home of 4.6 million people (Indian part), whose principal mode of communication is motorized boats (ferries). This study shed light on the role played by ferry movement in the speciation (following the BCR three-step sequential extraction method), ecological impact and bioaccumulation of potentially toxic elements (PTEs) in plant tissues (root and lamina) of grey mangrove (Avicennia marina) found near the five ferry ghats (ports). One-way ANOVA showed variation in major soil parameters (silt, clay, organic carbon, pH, Electrical conductivity) and PTEs (As, Cd, Cr, Cu, Hg, and Pb) between sites. Sequential extraction revealed that Cd was present in the 'exchangeable' form across the sites, Pb was in the 'reducible' form, and the rest of the PTEs were majorly found in 'residual' phase. Pollution indices revealed moderate to heavy contamination and considerable potential ecological risk due to Cd. Pearson correlation statistics and concentration variations indicate a relation between Pb and ferry movement frequency in the sites. Higher bioconcentration of Pb in the roots of A. marina, indicates phytostabilization action. Translocation factor for Cd in the leaves, indicates phytoextraction by A. marina. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) showed a close association between vehicle movement and Hg, Pb, Silt fraction, electrical conductivity, Cr, and As. This study recommends regular pollution monitoring across Sundarbans, as the PTEs in sediment-plant matrix can impact the higher trophic levels, human health through possible biomagnification in the detritus food chain, and can adversely impact the existing conservation initiatives.