Interleukin inhibitors and the associated risk of candidiasis

Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of Candida infection. Thus, applying IL inhibitors might impact an individual’s susceptibility to Candida infections. Variations in the severity of Candida infections have been observed between individuals with different IL inhibitors, necessitating careful consideration of their specific risk profiles. IL-1 inhibitors (anakinra, canakinumab, and rilonacept), IL-2 inhibitors (daclizumab, and basiliximab), and IL-4 inhibitors (dupilumab) have rarely been associated with Candida infection. In contrast, tocilizumab, an inhibitor of IL-6, has demonstrated an elevated risk in the context of coronavirus disease 2019 (COVID-19) treatment, as evidenced by a 6.9% prevalence of candidemia among patients using the drug. Furthermore, the incidence of Candida infections appeared to be higher in patients exposed to IL-17 inhibitors than in those exposed to IL-23 inhibitors. Therefore, healthcare practitioners must maintain awareness of the risk of candidiasis associated with using of IL inhibitors before prescribing them. Future prospective studies need to exhaustively investigate candidiasis and its associated risk factors in patients receiving IL inhibitors. Implementing enduring surveillance methods is crucial to ensure IL inhibitors safe and efficient utilization of in clinical settings

Alterations in nutrient digestion and utilization associated with different residual feed intake in Hu sheep

Improving feed efficiency is crucial to the animal industry. Residual feed intake (RFI) is now regarded as an index of feed efficiency evaluation and is independent of growth characteristics. Our study aims to explore the alterations in growth performance and nutrient digestion in Hu sheep with different RFI phenotypes. Sixty-four male Hu sheep (body weight = 24.39 ± 1.12 kg; postnatal days = 90 ± 7.9) were selected for the study. After an evaluation period of 56 days and power analysis, samples were collected from 14 low RFI (L-RFI group, power = 0.95) and 14 high RFI sheep (H-RFI group, power = 0.95). The L-RFI sheep yielded a lower (P  0.05). The acid detergent fiber, neutral detergent fiber, organic matter, and crude protein apparent digestibility were higher (P  0.05) was found in urine N output (% of N intake) between the 2 groups. Furthermore, L-RFI sheep gave lower (P < 0.05) serum glucose concentrations and higher (P < 0.05) non-esterified fatty acid concentrations. Meanwhile, a lower ruminal acetate molar proportion (P < 0.05) and higher propionate molar proportion (P < 0.05) were observed in L-RFI sheep. In summary, these results revealed that despite having lower dry matter intake, L-RFI sheep possess higher nutrient digestibility, N retention, ruminal propionate production and serum glucose utilization, in order to meet energy demands. Selection for low RFI sheep could reduce feed costs, which in turn provides economic benefits to the sheep industry

Desulfovibrio fairfieldensis-Derived Outer Membrane Vesicles Damage Epithelial Barrier and Induce Inflammation and Pyroptosis in Macrophages

Sulfate-reducing bacteria Desulfovibrio fairfieldensis is an opportunistic pathogen that widely exists in the human intestine and can cause severe infectious diseases. However, the mechanisms contributing to its pathogenesis remain of great interest. In this study, we aim to investigate the outer membrane vesicles (OMVs) secreted by D. fairfieldensis and their pathogenic effect. The OMVs separated by ultracentrifugation were spherical and displayed a characteristic bilayer lipid structure observed by transmission electron microscopy, with an average hydrodynamic diameter of 75 nm measurement using the particle size analyzer. We identified 1496 and 916 proteins from D. fairfieldensis and its OMVs using label-free non-target quantitative proteomics, respectively. The 560 co-expressed proteins could participate in bacterial life activities by function prediction. The translocation protein TolB, which participates in OMVs biogenesis and transporting toxins was highly expressed in OMVs. The OMVs inhibited the expression of tight junction proteins OCCLUDIN and ZO-1 in human colonic epithelial cells (Caco-2). The OMVs decreased the cell viability of monocyte macrophages (THP-1-M&phi;) and activated various inflammatory factors secretion, including interferon-&gamma; (IFN-&gamma;), tumor necrosis factor (TNF-&alpha;), and many interleukins. Further, we found the OMVs induced the expression of cleaved-gasdermin D, caspase-1, and c-IL-1&beta; and caused pyroptosis in THP-1-M&phi; cells. Taken together, these data reveal that the D. fairfieldensis OMVs can damage the intestinal epithelial barrier and activate intrinsic inflammation

<i>Desulfovibrio fairfieldensis</i>-Derived Outer Membrane Vesicles Damage Epithelial Barrier and Induce Inflammation and Pyroptosis in Macrophages

Sulfate-reducing bacteria Desulfovibrio fairfieldensis is an opportunistic pathogen that widely exists in the human intestine and can cause severe infectious diseases. However, the mechanisms contributing to its pathogenesis remain of great interest. In this study, we aim to investigate the outer membrane vesicles (OMVs) secreted by D. fairfieldensis and their pathogenic effect. The OMVs separated by ultracentrifugation were spherical and displayed a characteristic bilayer lipid structure observed by transmission electron microscopy, with an average hydrodynamic diameter of 75 nm measurement using the particle size analyzer. We identified 1496 and 916 proteins from D. fairfieldensis and its OMVs using label-free non-target quantitative proteomics, respectively. The 560 co-expressed proteins could participate in bacterial life activities by function prediction. The translocation protein TolB, which participates in OMVs biogenesis and transporting toxins was highly expressed in OMVs. The OMVs inhibited the expression of tight junction proteins OCCLUDIN and ZO-1 in human colonic epithelial cells (Caco-2). The OMVs decreased the cell viability of monocyte macrophages (THP-1-Mφ) and activated various inflammatory factors secretion, including interferon-γ (IFN-γ), tumor necrosis factor (TNF-α), and many interleukins. Further, we found the OMVs induced the expression of cleaved-gasdermin D, caspase-1, and c-IL-1β and caused pyroptosis in THP-1-Mφ cells. Taken together, these data reveal that the D. fairfieldensis OMVs can damage the intestinal epithelial barrier and activate intrinsic inflammation

Prevalence of depressive disorders and associated demographic characteristics in Shandong: An epidemiological investigation

BackgroundDepression is characterized by debilitating symptoms and high recurrence rates, and there are relatively few large-scale epidemiological surveys of depressive disorders conducted in Shandong since 2005. Data from the largest Epidemiological Survey of Mental Disorders conducted in 2015 in Shandong were collected to investigate the prevalence of depressive disorders and associated demographic characteristics in general adult population.MethodsA multi-stage stratified cluster sampling method was adopted to select residents and a two-stage screening and assessment process was used to define the prevalence and characteristics of depressive disorders. Respondents were initially screened using the General Health Questionnaire followed by a structured clinical interview using the DSM-IV criteria.ResultsAmong 27,489 respondents who completed the survey, 1277 respondents met the diagnostic criteria for depressive disorders. The adjusted prevalence in the last month was 4.86%, among which the prevalence of major depressive disorder, dysthymia, and unspecified depressive disorder were 2.32%, 1.78%, and 0.75%, respectively. 40.35% of depression patients had moderate or severe functional impairment and only 10.65% of patients had visited a psychiatric service. Univariate and multivariate analyses revealed that age, gender, occupation, education, marital status, and urban/rural living were associated with the prevalence.LimitationsThe key limitation is that this is a cross-sectional survey therefore cannot draw any causal relationship between risk factors and disease progression.ConclusionsFindings from this largest epidemiological study reveal current prevalence of depressive disorders and associated demographic factors and offers opportunities for policy makers and health-care professionals to improve mental health provision in Shandong.</p

Risk of candidiasis associated with interleukin-17 inhibitors: Implications and management

The application of interleukin-17 (IL-17) inhibitors, including secukinumab, ixekizumab, brodalumab, and bimekizumab, are associated with elevated risk of candidiasis. These medications interfere with the IL-17 pathway, which is essential for maintaining mucosal barriers and coordinating the immune response against Candida species. The observational data and clinical trials demonstrate the increased incidence of candidiasis in individuals treated with IL-17 inhibitors. Brodalumab and bimekizumab pose a greater risk than secukinumab in eliciting candidiasis, whereas the data regarding ixekizumab are equivocal. Higher doses and prolonged treatment duration of IL-17 inhibitors increase the risk of candidiasis by compromising the immune response against Candida species. Prior to prescribing IL-17 inhibitors, healthcare professionals should comprehensively evaluate patients’ medical histories and assess their risk factors. Patients should be educated on the signs and symptoms of candidiasis to facilitate early detection and intervention. Future research should focus on identifying the risk factors associated with candidiasis in patients receiving IL-17 inhibitors. Prospective studies and long-term surveillance are required to explore the impact of specific inhibitors on the incidence and severity of candidiasis and to evaluate the effectiveness of combination therapies, such as concurrent use of IL-17 inhibitors and prophylactic antifungal agents