Hepatoprotective efficacy of quinoa seed extract against CCl4- induced acute liver toxicity in rat model.

The current research explored the possible protective effect of chenopodium quinoa extract against CCl4 acute liver toxicity in Sprague Dawley rats. Thirty rats were divided into five groups with six rats in each group. CCl4 (Carbon tetrachloride) was administered at a dose rate of 2 mL/kg b.w. intra-peritoneally once a week for 3 weeks. The plant extract was given through oral gavage for a period of 21 days. Group I served as a normal group which was given with basal diet. Group II was referred to as a positive control group and received CCl4 2 mL/kg body weight (i.p.). Group III was the standard treatment group and received 2 mL/kg CCl4 (i.p.) and 16 mg/kg body weight (p.o.) silymarin. Group IV was the plant treatment group, which received 2 mL/kg CCl4 (i.p.) and 600 mg/kg body weight of quinoa seed extract (p.o.). Group V was the combined treatment group, which received 2 mL/kg CCl4 (i.p.) accompanied with a combination of silymarin (p.o.) 16 mg/kg body weight and quinoa seed extract (p.o.) 600 mg/kg body weight. The liver biomarkers were assessed along with histopathological analysis to observe the changes in the liver. The outcome suggested that the treatment, which was given with the combination of silymarin and quinoa seed extract, significantly enhanced the antioxidant levels, reduced the oxidative stress, and restored the liver function as evidenced by biochemical parameters histopathological studies. The hepatoprotective potential may be due to the antioxidant and anti-inflammatory properties of quinoa seed extract.

Impact of Probiotic Lactiplantibacillus plantarum ATCC 14917 on atherosclerotic plaque and its mechanism.

Atherosclerosis is viewed as not just as a problem of lipid build-up in blood vessels, but also as a chronic inflammatory disease involving both innate and acquired immunity. In atherosclerosis, the inflammation of the arterial walls is the key characteristic that significantly contributes to both the instability of plaque and the occlusion of arteries by blood clots. These events ultimately lead to stroke and acute coronary syndrome. Probiotics are living microorganisms that, when consumed in the right quantities, offer advantages for one's health. The primary objective of this study was to investigate the influence of Lactiplantibacillus plantarum ATCC 14917 (ATCC 14917) on the development of atherosclerotic plaques and its underlying mechanism in Apo lipoprotein E-knockout (Apoe-/- mice). In this study, Apoe-/- mice at approximately 8 weeks of age were randomly assigned to three groups: a Normal group that received a normal chow diet, a high fat diet group that received a gavage of PBS, and a Lactiplantibacillus plantarum ATCC 14917 group that received a high fat diet and a gavage of 0.2 ml ATCC 14917 (2 × 109 CFU/mL) per day for a duration of 12 weeks. Our strain effectively reduced the size of plaques in Apoe-/- mice by regulating the expression of inflammatory markers, immune cell markers, chemokines/chemokine receptors, and tight junction proteins (TJPs). Specifically, it decreased the levels of inflammatory markers (ICAM-1, CD-60 MCP-1, F4/80, ICAM-1, and VCAM-1) in the thoracic aorta, (Ccr7, cd11c, cd4, cd80, IL-1ß, TNF-α) in the colon, and increased the activity of ROS-scavenging enzymes (SOD-1 and SOD-2). It also influenced the expression of TJPs (occludin, ZO-1, claudin-3, and MUC-3). In addition, the treatment of ATCC 14917 significantly reduced the level of lipopolysaccharide in the mesenteric adipose tissue. The findings of our study demonstrated that our strain effectively decreased the size of atherosclerotic plaques by modulating inflammation, oxidative stress, intestinal integrity, and intestinal immunity.

Novel Synergistic Probiotic Intervention: Transcriptomic and Metabolomic Analysis Reveals Ameliorative Effects on Immunity, Gut Barrier, and Metabolism of Mice during Salmonella typhimurium Infection.

Salmonella typhimurium (S. typhimurium), a prevalent cause of foodborne infection, induces significant changes in the host transcriptome and metabolome. The lack of therapeutics with minimal or no side effects prompts the scientific community to explore alternative therapies. This study investigates the therapeutic potential of a probiotic mixture comprising Lactobacillus acidophilus (L. acidophilus 1.3251) and Lactobacillus plantarum (L. plantarum 9513) against S. typhimurium, utilizing transcriptome and metabolomic analyses, a novel approach that has not been previously documented. Twenty-four SPF-BALB/c mice were divided into four groups: control negative group (CNG); positive control group (CPG); probiotic-supplemented non-challenged group (LAPG); and probiotic-supplemented Salmonella-challenged group (LAPST). An RNA-sequencing analysis of small intestinal (ileum) tissue revealed 2907 upregulated and 394 downregulated DEGs in the LAPST vs. CPG group. A functional analysis of DEGs highlighted their significantly altered gene ontology (GO) terms related to metabolism, gut integrity, cellular development, and immunity (p ≤ 0.05). The KEGG analysis showed that differentially expressed genes (DEGs) in the LAPST group were primarily involved in pathways related to gut integrity, immunity, and metabolism, such as MAPK, PI3K-Akt, AMPK, the tryptophan metabolism, the glycine, serine, and threonine metabolism, ECM-receptor interaction, and others. Additionally, the fecal metabolic analysis identified 1215 upregulated and 305 downregulated metabolites in the LAPST vs. CPG group, implying their involvement in KEGG pathways including bile secretion, propanoate metabolism, arginine and proline metabolism, amino acid biosynthesis, and protein digestion and absorption, which are vital for maintaining barrier integrity, immunity, and metabolism. In conclusion, these findings suggest that the administration of a probiotic mixture improves immunity, maintains gut homeostasis and barrier integrity, and enhances metabolism in Salmonella infection.

Deciphering Microbiome, Transcriptome, and Metabolic Interactions in the Presence of Probiotic Lactobacillus acidophilus against Salmonella Typhimurium in a Murine Model.

Salmonella enterica serovar Typhimurium (S. Typhimurium), a foodborne pathogen that poses significant public health risks to humans and animals, presents a formidable challenge due to its antibiotic resistance. This study explores the potential of Lactobacillus acidophilus (L. acidophilus 1.3251) probiotics as an alternative strategy to combat antibiotic resistance associated with S. Typhimurium infection. In this investigation, twenty-four BALB/c mice were assigned to four groups: a non-infected, non-treated group (CNG); an infected, non-treated group (CPG); a group fed with L. acidophilus but not infected (LAG); and a group fed with L. acidophilus and challenged with Salmonella (LAST). The results revealed a reduction in Salmonella levels in the feces of mice, along with restored weight and improved overall health in the LAST compared to the CPG. The feeding of L. acidophilus was found to downregulate pro-inflammatory cytokine mRNA induced by Salmonella while upregulating anti-inflammatory cytokines. Additionally, it influenced the expression of mRNA transcript, encoding tight junction protein, oxidative stress-induced enzymes, and apoptosis-related mRNA expression. Furthermore, the LEfSe analysis demonstrated a significant shift in the abundance of critical commensal genera in the LAST, essential for maintaining gut homeostasis, metabolic reactions, anti-inflammatory responses, and butyrate production. Transcriptomic analysis revealed 2173 upregulated and 506 downregulated differentially expressed genes (DEGs) in the LAST vs. the CPG. Functional analysis of these DEGs highlighted their involvement in immunity, metabolism, and cellular development. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway analysis indicated their role in tumor necrosis factor (TNF), mitogen-activated protein kinase (MAPK), chemokine, Forkhead box O (FOXO), and transforming growth factor (TGF-ß) signaling pathway. Moreover, the fecal metabolomic analysis identified 929 differential metabolites, with enrichment observed in valine, leucine, isoleucine, taurine, glycine, and other metabolites. These findings suggest that supplementation with L. acidophilus promotes the growth of beneficial commensal genera while mitigating Salmonella-induced intestinal disruption by modulating immunity, gut homeostasis, gut barrier integrity, and metabolism.

Lacticaseibacillusparacasei BNCC345679 revolutionizes DSS-induced colitis and modulates gut microbiota.

The gut microbiota plays an important role in the disease progression of inflammatory bowel disease. Although probiotics are effective against IBD, not many studies have investigated their effects on gut microbiota composition and immunomodulation in mouse colitis models. Our study aimed at the therapeutic effects of Lacticaseibacillus paracasei BNCC345679 for the first time and explored its impact on gut microbiome dysbiosis, inflammatory cytokines, related miRNAs, VCAM-1, oxidative stress, intestinal integrity, and mucus barrier. We found that oral intervention of L. paracasei BNCC345679 affects recovering beneficial microbial taxa, including lactobacillus spp. and akkermansia spp., followed by improved body weight, DAI score, and inflammatory cytokines. L. paracasei BNCC345679 mitigated oxidative stress and increased the expression of intestinal integrity proteins MUC2 and ZO-1. These results suggested that L. paracasei BNCC345679 has the capacity to reduce DSS-induced colitis and has the potential as a supplement for the mitigation of IBD.

Mood and microbes: a comprehensive review of intestinal microbiota's impact on depression.

Depression is considered a multifaceted and intricate mental disorder of growing concern due to its significant impact on global health issues. The human gut microbiota, also known as the "second brain," has an important role in the CNS by regulating it through chemical, immunological, hormonal, and neurological processes. Various studies have found a significant bidirectional link between the brain and the gut, emphasizing the onset of depression therapies. The biological and molecular processes underlying depression and microbiota are required, as the bidirectional association may represent a novel study. However, profound insights into the stratification and diversity of the gut microbiota are still uncommon. This article investigates the emerging evidence of a bacterial relationship between the gut and the brain's neurological system and its potential pathogenicity and relevance. The interplay of microbiota, immune system, nervous system neurotransmitter synthesis, and neuroplasticity transitions is also widely studied. The consequences of stress, dietary fibers, probiotics, prebiotics, and antibiotics on the GB axis are being studied. Multiple studies revealed the processes underlying this axis and led to the development of effective microbiota-based drugs for both prevention and treatment. Therefore, the results support the hypothesis that gut microbiota influences depression and provide a promising area of research for an improved knowledge of the etiology of the disease and future therapies.

Role of the intestinal microbiome and its therapeutic intervention in cardiovascular disorder.

The gut microbiome is a heterogeneous population of microbes comprising viruses, bacteria, fungi, and protozoa. Such a microbiome is essential for sustaining host equilibrium, and its impact on human health can be altered by a variety of factors such as external variables, social behavior, age, nutrition, and genetics. Gut microbes' imbalances are related to a variety of chronic diseases including cancer, obesity, and digestive disorders. Globally, recent findings show that intestinal microbes have a significant role in the formation of cardiovascular disease (CVD), which is still the primary cause of fatalities. Atherosclerosis, hypertension, diabetes, inflammation, and some inherited variables are all cardiovascular risk variables. However, studies found correlations between metabolism, intestinal flora, and dietary intake. Variations in the diversity of gut microbes and changes in their activity are thought to influence CVD etiology. Furthermore, the gut microbiota acts as an endocrine organ, producing bioactive metabolites such as TMA (trimethylamine)/TMAO (trimethylamine N-oxide), SCFA (short-chain fatty acids), and bile acids, which have a substantial impact on host wellness and disease by multiple mechanisms. The purpose of this overview is to compile current evidence highlighting the intricate links between gut microbiota, metabolites, and the development of CVD. It focuses on how intestinal dysbiosis promotes CVD risk factors such as heart failure, hypertension, and atherosclerosis. This review explores the normal physiology of intestinal microbes and potential techniques for targeting gut bacteria for CVD treatment using various microbial metabolites. It also examines the significance of gut bacteria in disease treatment, including supplements, prebiotics, probiotics, antibiotic therapies, and fecal transplantation, which is an innovative approach to the management of CVD. As a result, gut bacteria and metabolic pathways become increasingly attractive as potential targets for CVD intervention.

Can dynamic elastic therapy be established as the standard protocol of closed reduction for moderately displaced extracapsular condylar fractures?

OBJECTIVE: This study was conducted with the aim to establish standard technique of closed reduction (CR) and compare functional outcomes in patients of moderately displaced unilateral extracapsular condylar fractures. MATERIAL AND METHODS: This study is a retrospective randomized controlled trial, conducted at a tertiary care hospital setting from August, 2013 to November, 2018. Patients of unilateral extracapsular condylar fractures with ramus shortening < 7mm and deviation < 35° were divided in two groups by drawing lots and were treated by dynamic elastic therapy and maxillomandibular fixation (MMF). Mean and standard deviation were calculated for quantitative variables, and one way analysis of variance (ANOVA) and Pearson's Chi-square test were used to determine significance of outcomes between two modalities of CR. P value < 0.05 was taken as significant. RESULTS: The numbers of patients treated by dynamic elastic therapy and MMF were 76 (38 in each group). Out of which 48 (63.15%) were male and 28 (36.84%) were female. The ratio of male to female was 1.7:1. The mean ± standard deviation (SD) of age was 32 ± 9.57 years. In patients treated by dynamic elastic therapy, the mean ± SD (at 6-month follow-up) of loss of ramus height (LRH), maximum incisal opening (MIO) and opening deviation were 4.6mm ± 1.08mm, 40.4mm ± 1.57mm and 1.1mm ± 0.87mm respectively. Whereas, LRH, MIO and opening deviation were 4.6mm ± 0.85mm, 40.4mm ± 2.37mm and 0.8mm ± 0.63mm respectively by MMF therapy. One-way ANOVA was statistically insignificant (P value > 0.05) for above mentioned outcomes. Pre-traumatic occlusion was achieved in 89.47% of patients by MMF and in 86.84% patients by dynamic elastic therapy. Pearson's Chi-square test was statistically insignificant (p value < 0.05) for occlusion. CONCLUSION: Parallel results were obtained for both modalities; thus, the technique as dynamic elastic therapy, which promotes early mobilization and functional rehabilitation, can be favored as standard technique of closed reduction for moderately displaced extracapsular condylar fractures. This technique eases patients' stress associated with MMF and prevents ankylosis.

Biological activities, therapeutic potential, and pharmacological aspects of blackcurrants (Ribes nigrum L): A comprehensive review.

Blackcurrant possesses various health-endorsing attributes owing to its polyphenol profile. Recent studies have demonstrated its therapeutic potential against various health disorders. Various bioactives present in blackcurrants have different functional and pharmacological aspects including anti-inflammatory, antioxidant, and antimicrobial properties. The most dominant and important bioactive include anthocyanins, flavonols, phenolic acids, and polyunsaturated fatty acids. Food formats derived from blackcurrants comprise pomace, juice, powder, and extracts. All these food formats have industrial, prebiotic, and pharmacological benefits. In the current article, the nutritional composition, industrial applications, and therapeutic potential are discussed in the recent literature. Moreover, novel extraction techniques for the extraction of bioactive compounds present in blackcurrants and their safety concerns have been elaborated.

Efficacy of Aristolochia rotunda Linn in hyperuricemia: A randomised standard controlled study.

INTRODUCTION: Hyperuricemia (HU) is a health risk that may go undiagnosed and is on the rise in both developed and developing countries. Gout, the most common inflammatory arthritis characterized by painful, disabling acute attack, is widely known to be caused by hyperuricemia. Its prevalence ranges from 2.6% to 36% in different populations. The commonly used drugs for alleviating uric acid and gout have obvious side effects, so herbal therapeutic drugs are in high demand. The aim of the present study was to evaluate the efficacy and safety of Aristolochia rotunda Linn in Hyperuricemia. METHODS: Present study was designed as a single-blind randomized standard controlled trial with 20 patients in each group. Participants in the test group were administered A. rotunda Linn 4 gms in two divided doses in capsule form and the control group was given Febuxostat 40 mg once daily after meals for 28 days. Participants were asked to follow up weekly for the assessment of subjective parameters. The objective parameter was assessed pre- and post-trial. The results were analysed statistically. RESULTS: After the intervention, the test and control groups showed a statistically significant reduction in serum uric acid p = 0.021 and p < 0.01 respectively, while the reduction in the control group was found to be more statistically significant than the test group (p = 0.009). Subjective parameters also showed statistical significance at the end of the trial. CONCLUSION: This study shows that the A. rotunda Linn in a dose of 4 gm for 28 days effectively lowers serum uric acid. The trial was registered in the clinical trial registry of India under CTRI No. CTRI//2020/02/031587.

Role of doppler ultrasound in detecting vascular complications in recipients of living donor liver transplant (LDLT).

OBJECTIVE: To determine the role of Doppler ultrasound in the detection of vascular complications in recipients of living donor liver transplant, keeping contrast-enhanced computerised tomography of abdomen as the gold standard. METHODS: The retrospective study was conducted from February 16 to April 1, 2022, at the Pakistan Kidney and Liver Institute and Research Centre, Lahore, Pakistan, and comprised data of living donor liver transplant recipients who had undergone contrast-enhanced computerised tomography of abdomen within 24 hours of Doppler ultrasound between January 2021 and January 2022. For the diagnosis of hepatic vascular complications, the diagnostic values of Doppler ultrasound parameters were derived by correlating Doppler ultrasound findings with contrast-enhanced computerised tomography results. Data was analysed using SPSS 20. RESULTS: Of the 35 patients, 24(68.6%) were men and 11(31.4%) were women. The overall mean age was 45.86±13.8 years. For hepatic artery thrombosis, the use of Doppler ultrasound criteria yielded a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 96.6%, 83.3%, 100%, and 97.1% respectively. For hepatic artery stenosis, overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy of Doppler ultrasound was 100%, 96.8%, 75%, 100% and 97.1% respectively. Doppler ultrasound parameters resulted in a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 100% each in detecting portal vein and hepatic venous outflow tract thrombosis. Overall, Doppler ultrasound sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy was found to be 100%, 88.8%, 89.4%, 100% and 94.2% respectively. CONCLUSIONS: Doppler ultrasound was adequate to document vascular complications after living donor liver transplant in majority of the cases with high accuracy and sensitivity.

Translational informatics for human microbiota: data resources, models and applications.

With the rapid development of human intestinal microbiology and diverse microbiome-related studies and investigations, a large amount of data have been generated and accumulated. Meanwhile, different computational and bioinformatics models have been developed for pattern recognition and knowledge discovery using these data. Given the heterogeneity of these resources and models, we aimed to provide a landscape of the data resources, a comparison of the computational models and a summary of the translational informatics applied to microbiota data. We first review the existing databases, knowledge bases, knowledge graphs and standardizations of microbiome data. Then, the high-throughput sequencing techniques for the microbiome and the informatics tools for their analyses are compared. Finally, translational informatics for the microbiome, including biomarker discovery, personalized treatment and smart healthcare for complex diseases, are discussed.

Desulfovibrio desulfuricans aggravates atherosclerosis by enhancing intestinal permeability and endothelial TLR4/NF-κB pathway in Apoe -/- mice.

It is increasingly aware that gut microbiota is closely associated with atherosclerosis. However, which and how specific gut bacteria regulate the progression of atherosclerosis is still poorly understood. In this study, modified linear discriminant analysis was performed in comparing the gut microbiota structures of atherosclerotic and non-atherosclerotic mice, and Desulfovibrio desulfuricans (D. desulfuricans) was found to be associated with atherosclerosis. D. desulfuricans-treated Apoe -/- mice showed significantly aggravated atherosclerosis. The proatherogenic effect of D. desulfuricans was attributed to its ability to increase intestinal permeability and subsequent raise in the transit of lipopolysaccharide (LPS) from the intestine to the bloodstream. Excessive LPS in the blood can elicit local and systemic inflammation and activate Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling of endothelial cells. TAK-242, a specific inhibitor of TLR4, can ameliorate the development of D. desulfuricans-induced atherosclerosis by blocking the LPS-induced activation of TLR4/NF-κB signaling.

Oligosaccharides of Polygonatum Cyrtonema Hua ameliorates dextran sulfate sodium-induced colitis and regulates the gut microbiota.

Ulcerative colitis (UC) is one common chronic inflammatory bowel disease that causes severe side effects, and expensive treatment limits effective and sustained treatment of UC. Fructooligosaccharide was isolated from Polygonatum Cyrtonema Hua (PFOS) and exhibits anti-inflammatory effects. Therefore, we are curious whether PFOS could be used for the treatment of UC. PFOS was introduced via intragastric gavage to C57BL/6 J mice exposed to acute colitis induced by DSS. The results showed that doses of PFOS at 2 and 5 mg/kg/day alleviated the DSS-induced histopathological damage and improved intestinal barrier function. qPCR analysis revealed that PFOS exerted a significant downregulation of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) and upregulation of antioxidant genes, including superoxide dismutase1 (SOD1), glutathion peroxidase2 (GPX2), and nuclear factor erythroid 2 related factor2 (Nrf2). Furthermore, PFOS suppressed the DSS-induced disruption of the mucosal barrier by downregulating MMP13. Moreover, using 16 S rRNA gene-based microbiota analysis, PFOS could selectively enhance the growth of probiotics, including Bifidobacterium, Alloprevofella, and Alistipes. Our findings indicated that PFOS attenuated DSS-induced colitis in mice, suggesting that PFOS might be used as an efficacious supplement for reducing inflammatory bowel disease.

A narrative review: CXC chemokines influence immune surveillance in obesity and obesity-related diseases: Type 2 diabetes and nonalcoholic fatty liver disease.

Adipose tissue develops lipids, aberrant adipokines, chemokines, and pro-inflammatory cytokines as a consequence of the low-grade systemic inflammation that characterizes obesity. This low-grade systemic inflammation can lead to insulin resistance (IR) and metabolic complications, such as type 2 diabetes (T2D) and nonalcoholic fatty liver disease (NAFLD). Although the CXC chemokines consists of numerous regulators of inflammation, cellular function, and cellular migration, it is still unknown that how CXC chemokines and chemokine receptors contribute to the development of metabolic diseases (such as T2D and NAFLD) during obesity. In light of recent research, the objective of this review is to provide an update on the linkage between the CXC chemokine, obesity, and obesity-related metabolic diseases (T2D and NAFLD). We explore the differential migratory and immunomodulatory potential of CXC chemokines and their mechanisms of action to better understand their role in clinical and laboratory contexts. Besides that, because CXC chemokine profiling is strongly linked to leukocyte recruitment, macrophage recruitment, and immunomodulatory potential, we hypothesize that it could be used to predict the therapeutic potential for obesity and obesity-related diseases (T2D and NAFLD).

Study protocol of DIVERGE, the first genetic epidemiological study of major depressive disorder in Pakistan.

INTRODUCTION: Globally, 80% of the burdenof major depressive disorder (MDD) pertains to low- and middle-income countries. Research into genetic and environmental risk factors has the potential to uncover disease mechanisms that may contribute to better diagnosis and treatment of mental illness, yet has so far been largely limited to participants with European ancestry from high-income countries. The DIVERGE study was established to help overcome this gap and investigate genetic and environmental risk factors for MDD in Pakistan. METHODS: DIVERGE aims to enrol 9000 cases and 4000 controls in hospitals across the country. Here, we provide the rationale for DIVERGE, describe the study protocol and characterise the sample using data from the first 500 cases. Exploratory data analysis is performed to describe demographics, socioeconomic status, environmental risk factors, family history of mental illness and psychopathology. RESULTS AND DISCUSSION: Many participants had severe depression with 74% of patients who experienced multiple depressive episodes. It was a common practice to seek help for mental health struggles from faith healers and religious leaders. Socioeconomic variables reflected the local context with a large proportion of women not having access to any education and the majority of participants reporting no savings. CONCLUSION: DIVERGE is a carefully designed case-control study of MDD in Pakistan that captures diverse risk factors. As the largest genetic study in Pakistan, DIVERGE helps address the severe underrepresentation of people from South Asian countries in genetic as well as psychiatric research.

Seroprevalence of Anti-tTg-IgA among Symptomized Celiac Disease Patients and Their Correlation with Rotavirus Infection.

Celiac disease (CD) is a chronic inflammatory disorder in the intestinal tract as a response to the use of gluten in genetically predisposed individuals. It is a worldwide problem, with a high prevalence rate in North America. This is a descriptive cross-sectional study involving 1090 samples collected from different hospitals of Rawalpindi and Islamabad, Pakistan, from January 2019 to December 2019. In this study, 1090 blood samples screened for seroprevalence of anti-tTG antibodies in CD symptomatic patients via ELISA (enzyme-linked immunosorbent assay). 1090 fecal samples from the same CD patients were collected and tested for the presence of rotavirus (RV) via ELISA and RT-PCR. Of the 1090 patients tested for seroprevalence of anti-tTG antibodies, 112/1090 (10.3%) were found to be positive. Of the 112 anti-tTG-positive patients, 78/112 (70%) were positive for RV via ELISA and 74/112 (66.1%) were RV positive via RT-PCR. A statistically significant association was reported between rotavirus infection and celiac disease (p˂0.05). Anti-tTG antibodies were higher in age group 6 (12-18 years) patients (18.4%) and at minimum in age group 3 (1-3 years) patients (4.8%). However, there was a statistically insignificant relationship between group age and CD prevalence (p > 0.05). The highest CD prevalence was noted during winter season (19.6%) and the lowest (3.0%) during fall/autumn. Our study findings demonstrate that Pakistan has a high prevalence of CD compared to other studies. Further studies in the fields of environmental risk factors and treatment with more advanced serological and histopathological studies are needed in the future.

Isolation, characterization, bacteriocin production and biological potential of Bifidobacteria of ruminants.

Bacteriocins exhibited a wide spectrum of antibacterial activity against different pathogens. The aim of current study was to characterize the bacteriocins produced by Bifidobacterium spp. isolated from ruminants. The Bifidobacterium isolates were identified as B. longum, B. pseudolongum, B. bifidum, B. thermophilum, B. boum, B. merycicum and B. ruminantium. Bacteriocins were found to be pH stable, heat resistant, highly diffusible, NaCl tolerant and resistant to UV radiations. SDS, EDTA and urea induced 14%, 21% and 24% bacteriocins activity loss. Modified MRS broth (1% tryptone, 1% yeast extract and 2% glucose) was found to be the best nutrient medium for optimal production of bacteriocins. Minimum inhibitory concentration (MIC) values varied from 300 µl/ml to 500 µl/ml and minimum bactericidal concentration (MBC) values ranged from 500 µl/ml to >500 µl/ml for E. coli and S. aureus respectively. The highest protein concentration (29.0248 mg/ml) was recorded for Bifidobacteria bacteriocin produced by B. longum. Tricine-Sodium Dodecyl Sulfate-Poly Acrylamide Gel Electrophoresis (SDS-PAGE) revealed that molecular weight of isolated bifidobacterial bacteriocins was in the range of 3.6 kDa-30 kDa. Current study indicated that bifidobacterial bacteriocins have considerable potential to be used as biopreservative.

Evaluation of Cardiac Biomarkers and Expression Analysis of IL-1, IL-6, IL-10, IL-17, and IL-25 among COVID-19 Patients from Pakistan.

Coronavirus disease 19 (COVID-19) is caused by viral infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Where upregulation of several important biomarkers and multiple organ dysfunction occurs, this study aimed to evaluate the association of cardiac biomarkers and CS induced acute lung damage with disease severity and mortality in survival of COVID-19 patients. A total of 500 COVID-19 patients with elevated cardiac biomarkers were studied for the analysis of myocardial abnormality through cardiac enzymes, inflammatory biomarkers, and the expression analysis of various cytokines, including IL-1, IL-6, IL-10, IL-17, and IL-25 genes. The elevation of various cardiac enzymes including LDH (87%), CK (78.4%), TNI (80.4%), CK-MB (83%), and D-dimer (80.8%) were found correlated (p < 0.001) with COVID-19 infection. Cardiac enzyme elevation was highly associated with an increased level of inflammatory biomarkers such as CRP (14.2%), SAA (11.4%) and erythrocyte sedimentation rate (ESR) (7.8%) (p = 0.001 for all). The quantitative expression analysis of IL-10, 1L-17, and 1L-25 were found to be high, while those of IL-1 and IL-6 were moderately elevated. The death-to-live ratio of COVID-19 patients was 457:43 indicating that the patients having elevated levels of both CKMB, D-dimer, CK and IL-1, IL-6, IL-10 and D-dimer, Troponin, CK and IL-1, IL-10 had high fatality rate (73% and 12% respectively). The current finding concludes that the evaluation of cardiac biomarkers with cytokine storm plays a significant role in COVID-19-associated anatomical organ damage, myocardial injury, and mortality. Physicians should pay special attention to cardiac biomarkers in patients with old age, inflammation, and comorbidities among COVID-19 infections.

Conformational transitions of the Spindly adaptor underlie its interaction with Dynein and Dynactin.

Cytoplasmic Dynein 1, or Dynein, is a microtubule minus end-directed motor. Dynein motility requires Dynactin and a family of activating adaptors that stabilize the Dynein-Dynactin complex and promote regulated interactions with cargo in space and time. How activating adaptors limit Dynein activation to specialized subcellular locales is unclear. Here, we reveal that Spindly, a mitotic Dynein adaptor at the kinetochore corona, exists natively in a closed conformation that occludes binding of Dynein-Dynactin to its CC1 box and Spindly motif. A structure-based analysis identified various mutations promoting an open conformation of Spindly that binds Dynein-Dynactin. A region of Spindly downstream from the Spindly motif and not required for cargo binding faces the CC1 box and stabilizes the intramolecular closed conformation. This region is also required for robust kinetochore localization of Spindly, suggesting that kinetochores promote Spindly activation to recruit Dynein. Thus, our work illustrates how specific Dynein activation at a defined cellular locale may require multiple factors.