Tag: nevin manimala

J Gerontol A Biol Sci Med Sci. 2023 Nov 29:glad266. doi: 10.1093/gerona/glad266. Online ahead of print.

ABSTRACT

Previous researchers have tried to explore the association between folate/folic acid intake and dementia incidence, but the results remain controversial. We evaluated the associations of folate/folic acid supplementation alone and in combination with other B vitamins on dementia risk and brain structure. A total of 466,224 UK Biobank participants were investigated. Cox proportional hazards models were used to assess the associations between folate/folic acid supplementation status and the risk of Alzheimer’s disease (AD) and vascular dementia (VD). Multivariable linear regression models were employed to evaluate the association between folate/folic acid supplementation status and brain structure. In the final model, folate/folic acid supplementation alone was significantly associated with a higher risk of AD (hazard ratio [HR] =1.34, 95% confidence interval [CI] =1.06 to 1.69, p=0.015) and VD (HR=1.61, 95% CI=1.21 to 2.13, p=0.001). Folate/folic acid supplementation alone was associated with a reduction in the hippocampus (β= -95.25 mm3, 95% CI= -165.31 to -25.19 mm3, p=0.014) and amygdala (β= -51.85 mm3, 95% CI= -88.02 to -15.68 mm3, p=0.012). The risk of AD and VD, as well as brain structure, in the group with combined folate/folic acid supplementation and other B vitamins did not show a statistically significant difference compared to the reference group (all p>0.05). Folate/folic acid supplementation alone is significantly associated with a higher risk of AD and VD, as well as adverse alterations in brain structure. However, when combined with other B vitamins, these detrimental effects can be counteracted.

PMID:38029284 | DOI:10.1093/gerona/glad266

Front Cell Infect Microbiol. 2023 Oct 31;13:1266446. doi: 10.3389/fcimb.2023.1266446. eCollection 2023.

ABSTRACT

OBJECTIVES: To investigate the urinary microbiota composition in urolithiasis patients compared to healthy controls and to identify potential microbial markers and their association with clinical parameters.

METHODS: A total of 66 samples, comprising 45 from urolithiasis patients and 21 from healthy controls, were analyzed. 16S rRNA gene sequencing was employed to determine the microbiota composition. Various statistical and bioinformatics tools, including ANOVA, PCoA, and LEfSe, were utilized to analyze the sequencing data and identify significant differences in microbial abundance.

RESULTS: No significant demographic differences were observed between the two groups. Post-quality control, clean tags ranged from 60,979 to 68,736. Significant differences in α-diversity were observed between the two groups. β-diversity analysis revealed distinct clustering of the urinary microbiota in urolithiasis patients and controls. Notably, Ruminococcaceae was predominant in urolithiasis samples, while Proteobacteria was more prevalent in healthy samples. Lactobacillus was significantly overrepresented in samples from healthy females.

CONCLUSION: The urinary microbiota composition in urolithiasis patients is distinct from that of healthy controls. Specific microbial taxa, such as Ruminococcaceae and Proteobacteria, could serve as potential biomarkers for urolithiasis. The findings pave the way for further exploration of the role of microbiota in urolithiasis and the development of microbiome-based therapeutic strategies.

PMID:38029257 | PMC:PMC10644862 | DOI:10.3389/fcimb.2023.1266446

Front Cell Infect Microbiol. 2023 Nov 9;13:1235269. doi: 10.3389/fcimb.2023.1235269. eCollection 2023.

ABSTRACT

BACKGROUND: Herein, we applied bioinformatics methods to analyze the crosstalk between septic shock (SS) and venous thromboembolism (VTE), focusing on the correlation with immune infiltrating cells.

METHODS: Expression data were obtained from the Gene Expression Omnibus (GEO) database, including blood samples from SS patients (datasets GSE64457, GSE95233, and GSE57065) and VTE patients (GSE19151). We used the R package “limma” for differential expression analysis (p value<0.05,∣logFC∣≥1). Venn plots were generated to identify intersected differential genes between SS and VTE and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) Enrichment analysis. The protein-protein interaction (PPI) network of intersected genes was constructed by Cytoscape software. The xCell analysis identified immune cells with significant changes in VTE and SS and correlated them with significant molecular pathways of crosstalk. Finally, we validated the mRNA expression of crosstalk genes by qPCR, while Matrix Metalloprotein-9 (MMP-9) protein levels were assessed through Western blotting (WB) and Immunohistochemistry (IHC) in human umbilical vein endothelial cells (HUVECs) and mice.

RESULTS: In the present study, we conducted a comparison between 88 patients with septic shock and 55 control subjects. Additionally, we compared 70 patients with venous thromboembolism to 63 control subjects. Twelve intersected genes and their corresponding three important molecular pathways were obtained: Metabolic, Estrogen, and FOXO signaling pathways. The resulting PPI network has 194 nodes and 388 edges. The immune microenvironment analysis of the two diseases showed that the infiltration levels of M2 macrophages and Class-switched memory B cells were correlated with the enrichment scores of metabolic, estrogen, and FOXO signaling pathways. Finally, qPCR confirmed that the expression of MMP9, S100A12, ARG1, SLPI, and ANXA3 mRNA in the SS with VTE group was significantly elevated. WB and IHC experiments revealed that MMP9 protein was significantly elevated in the experimental group.

CONCLUSION: Metabolic, estrogen, and FOXO pathways play important roles in both SS and VTE and are related to the immune cell microenvironment of M2 macrophages and Class-switched memory B cells. MMP9 shows promise as a biomarker for diagnosing sepsis with venous thrombosis and a potential molecular target for treating this patient population.

PMID:38029239 | PMC:PMC10666789 | DOI:10.3389/fcimb.2023.1235269

Front Cell Infect Microbiol. 2023 Nov 10;13:1107990. doi: 10.3389/fcimb.2023.1107990. eCollection 2023.

ABSTRACT

OBJECTIVE: To evaluate the efficacy of targeted nanopore sequencing technology for the detection of Mycobacterium tuberculosis(M.tb.) in bronchoalveolar lavage fluid(BALF) specimens.

METHODS: A prospective study was used to select 58 patients with suspected pulmonary tuberculosis(PTB) at Henan Chest Hospital from January to October 2022 for bronchoscopy, and BALF specimens were subjected to acid-fast bacilli(AFB) smear, Mycobacterium tuberculosis MGIT960 liquid culture, Gene Xpert MTB/RIF (Xpert MTB/RIF) and targeted nanopore sequencing (TNS) for the detection of M.tb., comparing the differences in the positive rates of the four methods for the detection of patients with different classifications.

RESULTS: Among 58 patients with suspected pulmonary tuberculosis, there were 48 patients with a final diagnosis of pulmonary tuberculosis. Using the clinical composite diagnosis as the reference gold standard, the sensitivity of AFB smear were 27.1% (95% CI: 15.3-41.8); for M.tb culture were 39.6% (95% CI: 25.8-54.7); for Xpert MTB/RIF were 56.2% (95% CI: 41.2-70.5); for TNS were 89.6% (95% CI: 77.3-96.5). Using BALF specimens Xpert MTB/RIF and/or M.tb. culture as the reference standard, TNS showed 100% (30/30) sensitivity. The sensitivity of NGS for pulmonary tuberculosis diagnosis was significantly higher than Xpert MTB/RIF, M.tb. culture, and AFB smear. Besides, P values of <0.05 were considered statistically significant.

CONCLUSION: Using a clinical composite reference standard as a reference gold standard, TNS has the highest sensitivity and consistency with clinical diagnosis, and can rapidly and efficiently detect PTB in BALF specimens, which can aid to improve the early diagnosis of suspected tuberculosis patients.

PMID:38029234 | PMC:PMC10668825 | DOI:10.3389/fcimb.2023.1107990

Adv Pharmacol Pharm Sci. 2023 Nov 18;2023:8902963. doi: 10.1155/2023/8902963. eCollection 2023.

ABSTRACT

The intention of the current work was to develop and optimize the formulation of biodegradable polymeric nanocapsules for lamivudine (LMV) in order to obtain desired physical characteristics so as to have improved liver targetability. Nanocapsules were prepared in this study as aqueous-core nanocapsules (ACNs) with poly(lactide-co-glycolide) using a modified multiple emulsion technique. LMV was taken as a model drug to investigate the potential of ACNs developed in this work in achieving the liver targetability. Three formulations factors were chosen and 3³ factorial design was adopted. The selected formulation factors were optimized statistically so as to have the anticipated characteristics of the ACNs viz. maximum entrapment efficiency, minimum particle size, and less drug release rate constant. The optimized LMV-ACNs were found to have 71.54 ± 1.93% of entrapment efficiency and 288.36 ± 2.53 nm of particle size with zeta potential of -24.7 ± 1.2 mV and 0.095 ± 0.006 h^-1 of release rate constant. This optimized formulation was subjected to surface modification by treating with sodium lauryl sulphate (SLS), which increased the zeta potential to a maximum of -41.6 ± 1.3 mV at a 6 mM concentration of SLS. The results of in vivo pharmacokinetics from blood and liver tissues indicated that hepatic bioavailability of LMV was increased from 13.78 ± 3.48 μg/mL ∗ h for LMV solution to 32.94 ± 5.12 μg/mL ∗ h for the optimized LMV-ACNs and to 54.91 ± 6.68 μg/mL ∗ h for the surface-modified LMV-ACNs.

PMID:38029229 | PMC:PMC10676277 | DOI:10.1155/2023/8902963

Front Microbiol. 2023 Nov 3;14:1269164. doi: 10.3389/fmicb.2023.1269164. eCollection 2023.

ABSTRACT

INTRODUCTION: Grass carp reovirus (GCRV), a member of the Aquareovirus genus in the Reoviridae family, is considered to be the most pathogenic aquareovirus. Productive viral infection requires extensive interactions between viruses and host cells. However, the molecular mechanisms underlying GCRV early infection remains elusive.

METHODS: In this study we performed transcriptome and DNA methylome analyses with Ctenopharyngodon idellus kidney (CIK) cells infected with GCRV at 0, 4, and 8 h post infection (hpi), respectively.

RESULTS: We found that at early infection stage the differentially expressed genes related to defense response and immune response in CIK cells are activated. Although DNA methylation pattern of CIK cells 8 hpi is similar to mock-infected cells, we identified a considerable number of genes that selectively utilize alternative polyadenylation sites. Particularly, we found that biological processes of cytoskeleton organization and regulation of microtubule polymerization are statistically enriched in the genes with altered 3’UTRs.

DISCUSSION: Our results suggest that alternative polyadenylation potentially contributes to GCRV early infection.

PMID:38029205 | PMC:PMC10656684 | DOI:10.3389/fmicb.2023.1269164

Front Microbiol. 2023 Oct 31;14:1270824. doi: 10.3389/fmicb.2023.1270824. eCollection 2023.

ABSTRACT

BACKGROUND: Epstein-Barr virus (EBV) is a human lymphotropic herpesvirus with a causative agent in cancer. There are two genotypes of EBV (EBV genotype 1 and EBV genotype 2) that have been shown to infect humans. This study aimed to characterize the EBV genotype among people with human immunodeficiency virus (PWH) and HIV-negative individuals in Ethiopia.

METHODS: DNA was extracted from peripheral blood mononuclear cells (PBMCs). Conventional polymerase chain reaction (cPCR) targeting EBNA3C genes was performed for genotyping. A quantitative real-time PCR (q-PCR) assay for EBV DNA (EBNA1 ORF) detection and viral load quantification was performed. Statistical significance was determined at a value of p < 0.05.

RESULT: In this study, 155 EBV-seropositive individuals were enrolled, including 128 PWH and 27 HIV-negative individuals. Among PWH, EBV genotype 1 was the most prevalent (105/128, 82.0%) genotype, followed by EBV genotype 2 (17/128, 13.3%), and mixed infection (6/128, 4.7%). In PWH, the median log10 of EBV viral load was 4.23 copies/ml [interquartile range (IQR): 3.76-4.46], whereas it was 3.84 copies/ml (IQR: 3.74-4.02) in the HIV-negative group. The EBV viral load in PWH was significantly higher than that in HIV-negative individuals (value of p = 0.004). In PWH, the median log10 of EBV viral load was 4.25 copies/ml (IQR: 3.83-4.47) in EBV genotype 1 and higher than EBV genotype 2 and mixed infection (p = 0.032).

CONCLUSION: In Ethiopia, EBV genotype 1 was found to be the most predominant genotype, followed by EBV genotype 2. Understanding the genotype characterization of EBV in PWH is essential for developing new and innovative strategies for preventing and treating EBV-related complications in this population.

PMID:38029140 | PMC:PMC10644458 | DOI:10.3389/fmicb.2023.1270824

Front Microbiol. 2023 Oct 31;14:1265786. doi: 10.3389/fmicb.2023.1265786. eCollection 2023.

ABSTRACT

BACKGROUND: Several observational studies have suggested a potential relationship between gut microbiome and psoriatic arthritis (PsA). However, the causality of this relationship still remains unclear. We aim to explore if the specific gut microbiome is causally associated with PsA at the genetic level and offer valuable insights into the etiology of PsA.

METHODS: In this study, we employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate the causal effects of the gut microbiome on PsA. Publicly accessible genome-wide association study summary data of gut microbiome were obtained from the MiBioGen consortium (n = 14,306), while the summary statistics of psoriatic arthropathies were sourced from the FinnGen consortium R8 release data (2,776 cases and 221,323 controls). The primary analytical method employed was inverse variance weighted (IVW), complemented by supplementary methods including MR-Egger, weighted median, weighted mode, maximum likelihood, MR-PRESSO, and cML-MA. Reverse MR analysis was performed on the bacteria that were found to be causally associated with PsA in forward MR analysis. Cochran’s IVW Q statistic was utilized to assess the heterogeneity of instrumental variables among the selected single nucleotide polymorphisms.

RESULTS: IVW estimates revealed that Ruminococcaceae_UCG-002 (odds ratio (OR) = 0.792, 95% confidence interval (CI), 0.643-0.977, p = 0.029) exhibited a protective effect on PsA. Conversely, Blautia (OR = 1.362, 95% CI, 1.008-1.842, p = 0.044), Eubacterium_fissicatena_group (OR = 1.28, 95% CI, 1.075-1.524, p = 0.006), and Methanobrevibacter (OR = 1.31, 95% CI, 1.059-1.621, p = 0.013) showed a positive correlation with the risk of PsA. No significant heterogeneity, horizontal pleiotropy, or outliers were observed, and the results of the MR analysis remained unaffected by any single nucleotide polymorphisms. According to the results of reverse MR analysis, no significant causal effect of PsA was found on gut microbiome.

CONCLUSION: This study establishes for the first time a causal relationship between the gut microbiome and PsA, providing potential valuable strategies for the prevention and treatment of PsA. Further randomized controlled trials are urgently warranted to support the targeted protective mechanisms of probiotics on PsA.

PMID:38029137 | PMC:PMC10644104 | DOI:10.3389/fmicb.2023.1265786

Front Microbiol. 2023 Nov 9;14:1270762. doi: 10.3389/fmicb.2023.1270762. eCollection 2023.

ABSTRACT

Marek’s disease (MD) caused by Marek’s disease virus (MDV), poses a serious threat to the poultry industry by inducing neurological disease and malignant lymphoma in infected chickens. However, the underlying mechanisms how MDV disrupts host cells and causes damage still remain elusive. Recently, the application of metabolomics has shown great potential for uncovering the complex mechanisms during virus-host interactions. In this study, chicken embryo fibroblasts (CEFs) infected with MDV were subjected to ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-QTOF-MS) and multivariate statistical analysis. The results showed that 261 metabolites were significantly altered upon MDV infection, with most changes occurring in amino acid metabolism, energy metabolism, nucleotide metabolism, and lipid metabolism. Notably, MDV infection induces an up-regulation of amino acids in host cells during the early stages of infection to provide the energy and intermediary metabolites necessary for efficient multiplication of its own replication. Taken together, these data not only hold promise in identifying the biochemical molecules utilized by MDV replication in host cells, but also provides a new insight into understanding MDV-host interactions.

PMID:38029131 | PMC:PMC10666056 | DOI:10.3389/fmicb.2023.1270762

Front Microbiol. 2023 Nov 9;14:1257587. doi: 10.3389/fmicb.2023.1257587. eCollection 2023.

ABSTRACT

INTRODUCTION: A healthy vaginal microbiota is represented mainly by Lactobacillus spp. and plays a vital role in maintaining the functional balance in the vaginal environment. Scientists have drawn attention to possible correlations between the vaginal microbiome and gynecological neoplasms. Several recent studies have shown a potential link between the vaginal microbiome and the risk of developing cervical cancer from human papillomavirus (HPV) infection. This study aimed to compare the prevalence and abundance of various lactic acid bacteria species (LABs) in vaginal swabs from healthy controls and patients with abnormal Pap smear results.

METHODS: The study included 100 women (79 patients with abnormal cervical Pap smear results and 21 controls) from whom vaginal swabs were collected. Real-time quantitative PCR was used to determine seven lactic acid bacteria (LAB) species and their quantities.

RESULTS: Most patients were colonized by two Lactobacillus species, primarily Lactobacillus gasseri (93%) and L. crispatus (83%). Patient age and place of residence were associated with the diversity of LAB in the vaginal microbiota. The abundance of L. delbrueckii in the vaginal microbiota increased, whereas the abundance of L. gasseri abundance decreased, with patient age. Lactobacillus acidophilus and Limosilactobacillus fermentum were significantly more often detected in patients living in rural versus urban areas. Statistical analysis did not show any significant differences in LAB between groups of patients with various changes on smear tests.

DISCUSSION: The degree of dysplastic changes in the endothelium or the presence of a group of atypical cervical stratified epithelial cells was not associated with significant changes in the studied vaginal bacteria.

PMID:38029074 | PMC:PMC10666048 | DOI:10.3389/fmicb.2023.1257587