Association between the gut microbiota and nonalcoholic fatty liver disease: A two-sample Mendelian randomization study.

BACKGROUND: Increasing studies have shown that there is a significant association between gut microbiota and non-alcoholic fatty liver disease. AIMS: To show the potential association between gut microbiota and non-alcoholic fatty liver disease, we performed a two-sample Mendelian randomization analysis. METHODS: We analyzed summary statistics from genome-wide association studies of gut microbiota and non-alcoholic fatty liver disease and conducted Mendelian randomization studies to evaluate relationships between these factors. RESULTS: Of the 211 gut microbiota taxa examined, the inverse variance weighted method identified Lactobacillaceae (OR = 0.83, 95% CI = 0.72 - 0.95, P = 0.007), Christensenellaceae (OR = 0.74, 95% CI = 0.59 - 0.92, P = 0.007), and Intestinibacter (OR = 0.85, 95% CI = 0.73 - 0.99, P = 0.035) were negatively correlated with non-alcoholic fatty liver disease. And Coriobacteriia (OR = 1.22, 95% CI = 1.01 - 1.42, P = 0.038), Actinomycetales (OR = 1.25, 95% CI = 1.02 - 1.53, P = 0.031), Oxalobacteraceae (OR = 1.10, 95% CI = 1.01 - 1.21, P = 0.036), Ruminococcaceae_UCG005 (OR = 1.18, 95% CI = 1.01 - 1.38, P = 0.033) are positively associated with non-alcoholic fatty liver disease. CONCLUSIONS: Our study found that the abundance of certain strains was associated with the progression of nonalcoholic fatty liver disease.

Plasmodium infection suppresses colon cancer growth by inhibiting proliferation and promoting apoptosis associated with disrupting mitochondrial biogenesis and mitophagy in mice.

BACKGROUND: Colon cancer is a common gastrointestinal tumor with a poor prognosis, and thus new therapeutic strategies are urgently needed. The antitumor effect of Plasmodium infection has been reported in some murine models, but it is not clear whether it has an anti-colon cancer effect. In this study, we investigated the anti-colon cancer effect of Plasmodium infection and its related mechanisms using a mouse model of colon cancer. METHODS: An experimental model was established by intraperitoneal injection of Plasmodium yoelii 17XNL-infected erythrocytes into mice with colon cancer. The size of tumors was observed dynamically in mice, and the expression of Ki67 detected by immunohistochemistry was used to analyze tumor cell proliferation. Apoptosis was assessed by terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) staining, and the expression of apoptosis-related proteins including Bax, Bcl-2, caspase-9, and cleaved caspase-3 was detected by western blot and immunohistochemistry, respectively. Transmission electron microscopy (TEM) was used to observe the ultrastructural change in colon cancer cells, and the expression of mitochondrial biogenesis correlative central protein, PGC-1α, and mitophagy relevant crucial proteins, PINK1/Parkin, were detected by western blot. RESULTS: We found that Plasmodium infection reduced the weight and size of tumors and decreased the expression of Ki67 in colon cancer-bearing mice. Furthermore, Plasmodium infection promoted mitochondria-mediated apoptosis in colon cancer cells, as evidenced by the increased proportion of TUNEL-positive cells, the upregulated expression of Bax, caspase-9, and cleaved caspase-3 proteins, and the downregulated expression of Bcl-2 protein. In colon cancer cells, we found destroyed cell nuclei, swollen mitochondria, missing cristae, and a decreased number of autolysosomes. In addition, Plasmodium infection disturbed mitochondrial biogenesis and mitophagy through the reduced expression of PGC-1α, PINK1, and Parkin proteins in colon cancer cells. CONCLUSIONS: Plasmodium infection can play an anti-colon cancer role in mice by inhibiting proliferation and promoting mitochondria-mediated apoptosis in colon cancer cells, which may relate to mitochondrial biogenesis and mitophagy.

Layered Double Hydroxides-Loaded Sorafenib Inhibit Hepatic Stellate Cells Proliferation and Activation In Vitro and Reduce Fibrosis In Vivo.

A core feature of liver fibrosis is the activation of hepatic stellate cells (HSCs), which are transformed into myofibroblasts and lead to the accumulation of extracellular matrix (ECM) proteins. In this study, we combined in vitro cellular efficacy with in vivo antifibrosis performance to evaluate the outcome of sorafenib (SRF) loaded layered double hydroxide (LDH) nanocomposite (LDH-SRF) on HSCs. The cellular uptake test has revealed that sorafenib encapsulated LDH nanoparticles were efficiently internalized by the HSC-T6 cells, synergistically inducing apoptosis of hepatic stellate cells. Moreover, the apoptosis rate and the migration inhibition rate induced by LDHs-SRF were 2.5 and 1.7 times that of SRF. Western Blot showed that the TGF-ß1/Smad/EMT and AKT signaling pathway was significantly inhibited in HSC-T6 cells treated with LDHs-SRF. For the in vivo experiment, LDHs-SRF were administered to rat models of CCl4-induced liver fibrosis. H&E, masson and sirius red staining showed that LDHs-SRF could significantly reduce inflammatory infiltrate and collagen fiber deposition and immunohistochemical results found that LDHs-SRF treatment significantly inhibited the protein expressions of α-SMA in the liver, these results suggesting that LDHs-SRF exhibited better anti-fibrotic effect than SRF alone and significantly inhibited the proliferation and activation of rat hepatic stellate cells and collagen fiber synthesis.

[Effect of trypsin and Triton-X 100 for decellularization of porcine aortic heart valves].

OBJECTIVE: To test two decellularization procedures for their potential of cell removal and mormal matrix preservation. METHODS: Porcine aortic valve leaflets were treated with either 0.05% trypsin or 0.25% Triton-X 100 respertively for 48 h for decellularization and with fresh untreated valve leaflets as control. Two tissue samples from each group were stained with hematoxylin and eosin and observed light-microscopically followed by scanning electron microscopy. Ten valve leaflets in each group were measured for shrinkage temperature, tensile strength/fracture toughnes and percentage elongation. RESULTS: Trypsin and Triton-X 100 all achieved complete decellularization but Triton-X 100 caused stronger structural alterations. No significant difference was identified between untreated and trypsin groups in shrinkage temperature, tensile strength/fracture toughnes and percentage elongation, but Triton-X 100 group showed significant difference from the other two groups. CONCLUSION: Decellularization using trypsin is superior to Triton-X100 in efficiency and matrix preservation.