Biology subjects

Hossain, E.

Publications and source records attributed to Hossain, E..

9 recordsLinked to original sources

bioRxiv2023

Persistent biofluid small molecule alterations induced by Trypanosoma cruzi infection are not restored by antiparasitic treatment

Table of contents graphic O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/543565v1_figu1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@10c3a0aorg.highwire.dtl.DTLVardef@1b69d6dorg.highwire.dtl.DTLVardef@199867org.highwire.dtl.DTLVardef@64b20b_HPS_FORMAT_FIGEXP M_FIG C_FIG Chagas Disease (CD), caused by Trypanosoma cruzi (T. cruzi) protozoa, is a complicated parasitic illness with inadequate medical measures for diagnosing infection and monitoring treatment success. To address this gap, we analyzed changes in the metabolome of T. cruzi-infected mice via liquid chromatography tandem mass spectrometry analysis of clinically-accessible biofluids: saliva, urine, and plasma. Urine was the most indicative of infection status, across mouse and parasite genotypes. Metabolites perturbed by infection in the urine include kynurenate, acylcarnitines, and threonylcarbamoyladenosine. Based on these results, we sought to implement urine as a tool for assessment of CD treatment success. Strikingly, it was found that mice with parasite clearance following benznidazole antiparasitic treatment had comparable overall urine metabolome to mice that failed to clear parasites. These results match with clinical trial data in which benznidazole treatment did not improve patient outcomes in late-stage disease. Overall, this study provides insights into new small molecule-based CD diagnostic methods and a new approach to assess functional treatment response.

microbiology↗

bioRxiv2023

A high-throughput multiplex array for antigen-specific serology with automated analysis.

High-throughput customizable CBA automated script-based analysisThe utility of high-throughput systems to evaluate antigen-specific antibody (Ab) has been highlighted by the SARS-CoV-2 pandemic. Pathogen-specific Ab levels are often used to assess protection following vaccination and, in the case of novel pathogens, an indication of prior exposure. Several platforms exist to visualize antigen-specific Ab, however most are not quantitative and are difficult to scale for population level studies. Additionally, the sensitivity across platforms differs making direct comparisons between studies difficult. Cytometric bead arrays (CBA) are an attractive platform for antigen-specific Ab measurements as they can be used to assess Ab reactivity against several antigens and of several isotypes to be performed simultaneously. Additionally, CBAs exhibit high sensitivity and can be designed to provide quantitative measurements. Using commercially available particles, a biotin-Streptavidin bead loading strategy, and the inclusion of indirect standards, we describe a flexible system that can be modified to include a variety of antigens. Here we describe two arrays, focused on antigens derived from either {beta}-coronaviruses or influenza virus. To support the high-throughput capacity of this system, we developed a suit of automated software tools, the CBA Toolbox, to process raw data into antigen-reactive IgM, IgA, and IgG concentrations. We describe quality control requirements, assay performance, and normalizations to accurately quantitate antigen-specific Ig.

immunology↗

bioRxiv2021

Spatial metabolomics reveals localized impact of influenza virus infection on the lung tissue metabolome

The influenza virus (IAV) is a major cause of respiratory disease, with significant infection increases in pandemic years. Vaccines are a mainstay of IAV prevention, but are complicated by consideration of IAVs vast strain diversity, manufacturing and vaccine uptake limitations. While antivirals may be used for treatment of IAV, they are most effective in early stages of the infection and several virus strains have become drug resistant. Therefore, there is a need for advances in IAV treatment, especially host-directed, personalized therapeutics.Given the spatial dynamics of IAV infection and the relationship between viral spatial distribution and disease severity, a spatial approach is necessary to expand our understanding of IAV pathogenesis. We used spatial metabolomics to address this issue. Spatial metabolomics combines liquid chromatography-tandem mass spectrometry of metabolites extracted from systematic organ sections, 3D models and computational techniques, to develop spatial models of metabolite location and their role in organ function and disease pathogenesis. In this project, we analyzed plasma and systematically sectioned lung tissue samples from uninfected or infected mice. Spatial mapping of sites of metabolic perturbations revealed significantly lower metabolic perturbation in the trachea compared to other lung tissue sites. Using random forest machine learning, we identified metabolites that responded differently in each lung position based on infection, including specific amino acids, lipids and lipid-like molecules, and nucleosides. These results support the implementation of spatial metabolomics to understand metabolic changes upon IAV infection and to identify candidate pathways to be targeted for IAV therapeutics. ImportanceThe influenza virus is a major health concern. Over 1 billion people become infected annually despite the wide distribution of vaccines, and antiviral agents are insufficient to address current clinical needs. In this study, we used spatial metabolomics to understand changes in the lung and plasma metabolome of mice infected with influenza A virus, compared to uninfected controls. We determined metabolites altered by infection in specific lung tissue sites and distinguished metabolites perturbed by infection between lung tissue and plasma samples. Our findings highlight the importance of a spatial approach to understanding the intersection between lung metabolome, viral infection and disease severity. Ultimately, this approach will expand our understanding of respiratory disease pathogenesis and guide the development of novel host-directed therapeutics.

microbiology↗

bioRxiv2021

Optimized extraction method enables quantitative analysis of surface metabolite recovery for exposomics and behavioral studies

Workplace chemical exposures are a major source of occupational injury. Although over half of these are skin exposures, exposomics research often focuses on chemical levels in the air or in worker biofluids such as blood and urine. Until now, one limitation has been the lack of methods to quantitatively measure surface chemical transfer. Outside the realm of harmful chemicals, the small molecules we leave behind on surfaces can also reveal important aspects of human behavior. In this study, we developed a swab-based quantitative approach to determine small molecule concentrations across common surfaces. We demonstrate its utility using one drug, cyclobenzaprine, and two human-derived metabolites, carnitine and phenylacetylglutamine, on four common surfaces: linoleum flooring, plastified laboratory workbench, metal and Plexiglass. This approach enabled linear small molecule recovery and quantification of molecule abundance on workplace built environment surfaces. Overall, this method paves the way for future quantitative exposomics studies.

biochemistry↗

bioRxiv2021

The Core Human Fecal Metabolome

Summary ParagraphAmong the biomolecules at the center of human health and molecular biology is a system of molecules that defines the human phenotype known as the metabolome. Through an untargeted metabolomic analysis of fecal samples from human individuals from Africa and the Americas--the birthplace and the last continental expansion of our species, respectively--we present the characterization of the core human fecal metabolome. The majority of detected metabolite features were ubiquitous across populations, despite any geographic, dietary, or behavioral differences. Such shared metabolite features included hyocholic acid and cholesterol. However, any characterization of the core human fecal metabolome is insufficient without exploring the influence of industrialization. Here, we show chemical differences along an industrialization gradient, where the degree of industrialization correlates with metabolomic changes. We identified differential metabolite features like leucyl-leucine dipeptides and urobilin as major metabolic correlates of these behavioral shifts. Our results indicate that industrialization significantly influences the human fecal metabolome, but diverse human lifestyles and behavior still maintain a core human fecal metabolome. This study represents the first characterization of the core human fecal metabolome through untargeted analyses of populations along an industrialization gradient.

biochemistry↗

bioRxiv2020

Alterations to the cardiac metabolome induced by chronic T. cruzi infection relate to the degree of cardiac pathology

Chronic Chagasic cardiomyopathy (CCC) is a Neglected Tropical Disease caused by the parasite Trypanosoma cruzi. The pathognomonic findings in symptomatic CCC patients and animal models includes diffuse cardiac fibrosis and inflammation with persistent parasite presence in the heart. This study investigated chemical alterations in different regions of the heart in relation to cardiac pathology indicators to better understand the long-term pathogenesis of this neglected disease. We used data from echocardiography, fibrosis biomarkers, and histopathological analysis to fully evaluate cardiac pathology. Metabolites isolated from the pericardial and endocardial sides of the right ventricular myocardium were analyzed by liquid chromatography tandem mass spectrometry. The endocardial sections contained significantly less cardiac inflammation and fibrosis than the pericardial sections. Cardiac levels of acylcarnitines, phosphocholines, and other metabolites were significantly disrupted in accordance with cardiac fibrosis, inflammation, and serum fibrosis biomarker levels. These findings have potential implications in treatment and monitoring for CCC patients.

microbiology↗

bioRxiv2019

3D mapping of host-parasite-microbiome interactions reveals metabolic determinants of tissue tropism and disease tolerance in Chagas disease

Chagas disease (CD) is a parasitic infection caused by Trypanosoma cruzi protozoa. Over 8 million people worldwide are T. cruzi-positive, 20-30% of which will develop cardiomyopathy, megaoesophagus and/or megacolon. The mechanisms leading to gastrointestinal (GI) symptom development are however poorly understood. To address this issue, we systematically characterized the spatial impact of experimental T. cruzi infection on the microbiome and metabolome across the GI tract. The largest microbiota perturbations were observed in the proximal large intestine in both acute and chronic disease, with chronic-stage effects also observed in the cecum. Strikingly, metabolomic impact of acute-to-chronic stage transition differed depending on the organ, with persistent large-scale effects of infection primarily in the oesophagus and large intestine, providing a potential mechanism for GI pathology tropism in CD. Infection particularly affected acylcarnitine and lipid metabolism. Building on these observations, treatment of infected mice with carnitine-supplemented drinking water prevented acute-stage mortality with no changes in parasite burden. Overall, these results identified a new mechanism of disease tolerance in CD, with potential for the development of new therapeutic regimens. More broadly, these results highlight the potential of spatially-resolved metabolomic approaches to provide insight into disease pathogenesis, with translational applications for infectious disease drug development.

microbiology↗

bioRxiv2019

Characterization of the workplace chemical exposome using untargeted LC-MS/MS: a case study

Western people now spend close to 90% of their time indoors, one-quarter of which occurs at their place of employment. As such, interactions between employees and the workplace built environment have significant potential impact on employee health and safety. However, the range of workers daily chemical exposures is still poorly understood. Likewise, the influence of workers themselves and of worker behavior on the chemical composition of the workplace is still unknown. In this case study, we used untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) to compare the chemical signatures of three different types of workplaces: scientific research buildings, office buildings, and one mixed-purpose building. Our results identified differential signatures of public building surfaces based on building purpose, sampling location and surface materials. Overall, these results are helping define the influence of human behavior on the workplace chemical environment and identify the chemical hazards to which people are exposed throughout their workday. HighlightsO_LIImplementation of untargeted liquid chromatography-tandem mass spectrometry to study workplace chemical exposures. C_LIO_LIShared chemical signatures were identified based on building purpose. C_LIO_LIDifferential chemical signatures were identified based on surface material and sampling location. C_LIO_LIAnnotated molecules include pharmaceuticals, illicit drugs, food chemicals, constituents of paints and stains, and cleaning products. C_LI

biochemistry↗

bioRxiv2018

Elevation of intracellular levels of nitric oxide in SHR attenuates hyperproliferation of vascular smooth muscle cells through the inhibition of AT1 receptor expression and c-Src/growth factor receptor signaling pathways

We previously showed that decreased levels of intracellular nitric oxide (NO) contribute to the hyperproliferation of vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR). The present study investigates if elevation of intracellular levels of NO by in vivo treatment of SHR with NO donor, sodium nitroprusside (SNP) that was shown to attenuate hypertension could attenuate the hyperproliferation of VSMC and identify the molecular mechanisms. Intraperitoneal injection of SNP (0.5 mg/kg BW) into 8-week-old SHR and WKY rats twice a week for two weeks increased significantly the intracellular levels of NO in aortic VSMC and resulted in the attenuation of hyperproliferation of VSMC from SHR to control levels. The antiproliferative effect of SNP was associated with the restoration of the overexpression of cell cycle proteins, cyclins D1, E, Cdk2, Cdk4, phosphorylated pRB and decreased expression of Cdk inhibitors p21Cip1 and p27Kip1 towards control levels. In addition, SNP treatment also attenuated the overexpression of angiotensin II receptor type 1 (AT1) receptor, phosphorylation of c-Src, EGF-R, PDGF-R, IGF-IR and ERK1/2 in VSMC from SHR to control levels. These results suggest that the augmentation of intracellular levels of NO elicits antiproliferative effect that may be mediated through its ability to inhibit the enhanced expression of AT1 receptor, activation of c- Src, growth factor receptors and MAP kinase signaling and overexpression of cell cycle proteins.

cell biology↗