DataSheet_1_Injecting drug use and hepatitis C virus infection independently increase biomarkers of inflammatory disease risk which are incompletely restored by curative direct-acting antiviral therapy.docx

BackgroundHepatitis C virus (HCV) infections are more prevalent in people who inject drugs (PWID) who often experience additional health risks. HCV induces inflammation and immune alterations that contribute to hepatic and non-hepatic morbidities. It remains unclear whether curative direct acting antiviral (DAA) therapy completely reverses immune alterations in PWID.MethodsPlasma biomarkers of immune activation associated with chronic disease risk were measured in HCV-seronegative (n=24) and HCV RNA+ (n=32) PWID at baseline and longitudinally after DAA therapy. Adjusted generalised estimating equations were used to assess longitudinal changes in biomarker levels. Comparisons between community controls (n=29) and HCV-seronegative PWID were made using adjusted multiple regression modelling.ResultsHCV-seronegative PWID exhibited significantly increased levels of inflammatory biomarkers including soluble (s) TNF-RII, IL-6, sCD14 and sCD163 and the diabetes index HbA1c as compared to community controls. CXCL10, sTNF-RII, vascular cell adhesion molecule-1 and lipopolysaccharide binding protein (LBP) were additionally elevated in PWID with viremic HCV infection as compared to HCV- PWID. Whilst curative DAA therapy reversed some biomarkers, others including LBP and sTNF-RII remained elevated 48 weeks after HCV cure.ConclusionElevated levels of inflammatory and chronic disease biomarkers in PWID suggest an increased risk of chronic morbidities such as diabetes and cardiovascular disease. HCV infection in PWID poses an additional disease burden, amplified by the incomplete reversal of immune dysfunction following DAA therapy. These findings highlight the need for heightened clinical surveillance of PWID for chronic inflammatory diseases, particularly those with a history of HCV infection.</p

Additional file 2 of Lactic acid from vaginal microbiota enhances cervicovaginal epithelial barrier integrity by promoting tight junction protein expression

Additional file 2: Supplementary Table 1. Proteins with significantly different abundance in women with high as compared to low L-LDH and D-LDH abundance*. Supplementary Table 2. Barrier-related proteins with significantly different abundance in women with high as compared to low L-LDH abundance*. Supplementary Table 3. Genes differentially expressed by L-LA, D-LA and HCL treatment of Ect cells*. Supplementary Table 4. Gene ontology pathways significantly enriched by L-LA and D-LA treatment of Ect cells. Supplementary Table 5. Tight junction genes differentially expressed by L-LA, D-LA and HCL treatment of Ect cells*. Supplementary Table 6. Tight junction genes differentially expressed by treatment of VK2 cells with bacterial culture supernatants*