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Background: Mycobacterium tuberculosis induces cellular necrosis that could promote spread of infection. The aim of this study is to analyze the effects of Vitamin D3 supplementation to improve the effectiveness of 2nd-line anti-tuberculosis (TB) drug therapy, especially in relation with cell death pathways. Methods: Mus musculus C3HeB/FeJ was randomly divided into four groups containing eight animals each. The 1st group (G1), consisting of mice that were intratracheally infected with multidrug-resistant strain of M. tuberculosis and sacrificed on 2-week postinfection to confirm successful infection. (G2) was a group of TB mice without therapy. Then, (G3) was a group of mice with the 2nd-line anti-TB therapy. The last group (G4) was a group of mice receiving not only the 2nd-line anti-TB therapy but also daily oral Vitamin D3 supplementation. Immunohistochemistry was used to measure expression of nuclear Vitamin D receptor, apoptosis marker cleaved caspase-3, cathelin-related antimicrobial peptide (CRAMP) and LC3B autophagy markers, necrosis marker RIPK3, and collagenase matrix metalloproteinase-1 (MMP1). The number of bacteria in the lung was calculated by colony forming units. The partial least square structural equation modeling with SmartPLS 3.2.6 software was used to analyze structural models among the variables. Results: Supplementation of Vitamin D3 on the 2nd-line anti-TB therapy increases Vitamin D3 receptor, CRAMP, LC3B, caspase-3 (P = 0.026, P = 0.000, P = 0.001), presses MMP1, and the number of bacteria (P = 0.010 and P = 0.000, respectively). The structural equation modeling analysis shows that increasing autophagy pathways reduces necrosis by lowering MMP1, whereas apoptosis reduces necrosis by decreasing the number of bacteria (each with indirect effects - 0.543 and - 0.544). Conclusion: A comprehensive analysis with the partial least square structural equation modeling shows decreasing necrosis requires increasing autophagy and apoptosis. [ABSTRACT FROM AUTHOR]

We conducted a systematic review research and meta-analysis to reveal the relationship between the risk of chronic diarrhea and Cryptosporidium infection in people living with HIV in Southeast Asia. We performed online peer-reviewed literature research from January 2005 to December 2017, which included PubMed, Science Direct, ProQuest, EBSCO, Cochrane, and Web of Science databases. Calculation of size effects in the meta-analysis was performed by STATA 13.0 software to estimate relative risks (RRs) with 95% confidence intervals (CIs) for any associations. Seven cross-sectional research articles were recruited in this study based on the inclusion and exclusion criteria. Our analysis revealed a significant relationship between cryptosporidiosis and the risk of chronic diarrhea in people living with HIV, with RR = 1.325; 95% CI = 1.157 to 1.517; and P < .000. Our results suggested that cryptosporidiosis increases the risk of chronic diarrhea, and low CD4 + lymphocyte cell counts aggravate the degree of diarrhea. Therefore, clinicians should be more aware in treating HIV-positive people, especially those with low CD4 + cell counts, and we suggest that Cryptosporidium laboratory examinations be conducted immediately.