Project description:Metagenomics analysis reveals co-infection of fungi and bacteria isolated from different regions of brain tissue from elderly persons and patients with Alzheimer's disease.
Project description:To investigate the early immune profiles of patients, particularly those with HIV and tuberculosis co-infection, we collected blood samples from three individuals in the HIV/MTB co-infection group, three HIV/AIDS patients, and three healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated, and the MobiNova®-100 Single Cell System (MobiDrop (Zhejiang) Co., Ltd.) was employed to prepare single-cell sequencing libraries. Subsequently, a single-cell RNA expression matrix was generated using the Illumina NovaSeq 6000 System, yielding a total of 113,816 cells for further analysis.
Project description:Background and aims: The intrahepatic processes associated with chronic hepatitis B (CHB), especially in the context of HDV and HIV co-infection, require a better understanding. Spatial transcriptomics can provide new insights into the complex intrahepatic biological processes, guiding new personalized treatments. Our aim is to evaluate this method to characterize the hepatic transcriptional landscape, cellular composition and biological pathways in liver biopsy samples from patients infected with HBV and HDV or HIV co-infection. Method: The GeoMx nanostring Digital Spatial Profiling (DSP) platform was employed to assess expression of HBsAg and CD45 in formalin fixed paraffin embedded (FFPE) biopsies from three treatment-naïve patients with chronic HBV and HDV or HIV co-infection. The GeoMx whole transcriptome human atlas assay quantified the expression of genes enriched in specific regions of interest (ROIs). Cell type proportions within ROIs were deconvoluted using a training matrix from the human liver cell atlas. A weighted gene correlation network analysis (WGCNA) evaluated transcriptomic signatures across sampled regions. Results: We identified spatially discrete transcriptomic signatures and distinct biological pathways that associate with HBV infection/disease status and immune responses. Shared features including cytotoxicity and B cell receptor signaling were consistent across patients, suggesting common elements alongside individual traits. HDV/HBV co-infection exhibited upregulated genes linked to apoptosis and immune cell recruitment, whereas HIV/HBV co-infection featured genes related to interferon response regulation. Varied cellular characteristics and immune cell populations, with an abundance of T cells in the HDV/HBV sample, were observed within analyzed regions. Transcriptional differences in hepatocyte function suggest disrupted metabolic processes in HDV/HBV co-infection potentially impacting disease progression. Conclusion: This proof-of-principle study shows the value of this platform in investigating the complex immune landscape highlighting relevant host pathways to disease pathogenesis.
Project description:The aim of this study was to identify differential gene and protein expression associated with GBV-C that may be of importance in reduction of HCV-related liver disease. GB virus C (GBV-C) infection leads to improved outcomes in human immunodeficiency virus (HIV) infection. Furthermore, GBV-C has been shown to reduce hepatitis C virus (HCV)-related liver disease in HCV/HIV co-infection. We aimed to identify differential gene expression associated with GBV-C in HCV/HIV co-infection by comparing RNA expression from liver biopsies of HCV/HIV co-infected patients with and without GBV-C infection. Liver biopsies were obtained from 10 Patients with HCV/HIV co-infection; 4 of these patients were positive for GBV-C infection and 6 were negative for GBV-C infection. The tissue was stored in RNAlater and RNA was extracted for hybridisation to Affymetrix Human Genome U133 plus 2.0 microarrays at the University of Texas Medical Branch Molecular Genomics Core Laboratory. The data was analysed for genes differentially expressed between GBV-C positive and negative patients using Partek Genomics suite and applying a custom CDF file (Hs133P_Hs_UG_8), available from Molecular and Behavioural Neuroscience Institute, University of Michigan.
Project description:Co-infection with soil transmitted helminths (STH) and Plasmodium spp. parasites is a common occurrence in tropical developing countries, but the consequences of this interaction remain poorly understood. Here, we performed a multi-omic analysis on the peripheral blood and fecal samples of 130 individuals in Tierralta, Córdoba, Colombia who were infected with P. vivax alone (n = 33), co-infected with P. vivax and STH (n = 27), infected with STH alone (n = 39) or were infected with neither P. vivax nor STH (n = 31). In addition to Complete Blood Count (CBC) with differential, transcriptional profiling of peripheral blood samples was performed by RNA-Seq, fecal microbial communities were determined by 16S ribosomal RNA gene sequencing and circulating cytokine levels were measured by bead-based immunoassays. Differences in blood cell counts were driven primarily by P. vivax infection, including an increased percentage of neutrophils that was associated with a transcriptional signature of neutrophil activation in the blood. P. vivax infection was also associated with increased levels of IL-6, IL-8 and IL-10 and these cytokine levels were not affected by STH co-infection. Surprisingly, P. vivax infection was more strongly associated with changes in the microbiome than STH infection. Children infected with P. vivax exhibited elevated Bacteroides and reduced Prevotella and Clostridiaceae, but these differences were not observed in individuals co-infected with STH. We also observed that P. vivax parasitemia is higher in STH-infected population. When we used machine learning to identify the most important predictors of P. vivax parasite burden from all measured variables, bacterial taxa were the strongest predictors of parasitemia levels in P. vivax infected individuals. In contrast, circulating TGF- β was identified as the strongest predictor of T. trichiura egg burden. This study provides unexpected evidence that the gut microbiota may have a stronger link with P. vivax than with STH infection.