Rifaximin Prevents Intestinal Barrier Dysfunction and Alleviates Liver Injury in MCT-induced HSOS Mice.

OBJECTIVE: Rifaximin is an effective component of treatment strategies for liver and intestinal diseases. However, the efficacy of rifaximin in hepatic sinusoidal obstruction syndrome (HSOS) has not been explored. The present study aimed to investigate the efficacy and mechanism of rifaximin in HSOS. METHODS: An HSOS model was established in mice through the administration of monocrotaline (MCT, 800 mg/kg), and part of the HSOS mice were intragastrically administered with rifaximin. Then, the efficacy of rifaximin in HSOS was evaluated based on the liver pathological findings, liver proinflammatory cytokines, and alanine aminotransferase and aspartate aminotransferase levels. The Ussing chamber was used to evaluate the intestinal permeability, and tight junction (TJ) proteins were measured by Western blotting and real-time polymerase chain reaction to evaluate the intestinal barrier integrity. Then, the serum proinflammatory cytokine levels were evaluated by enzyme-linked immunosorbent assay. Afterwards, an in vitro experiment was performed to determine the relationship between rifaximin and TJ proteins. RESULTS: Rifaximin effectively alleviated the MCT-induced HSOS liver injury, suppressed the expression of liver proinflammatory cytokines, and reduced the serum levels of tumor necrosis factor-alpha and interleukin-6. Furthermore, rifaximin reduced the intestinal permeability, improved the intestinal barrier integrity, and promoted the expression of TJ proteins. CONCLUSION: The results revealed that the intestinal barrier integrity was destroyed in MCT-induced HSOS. The significant alleviation of MCT-induced HSOS induced by rifaximin might be correlated to the repairment of intestinal barrier integrity via the regulation of the TJ protein expression.

Liver damage at admission is an independent prognostic factor for COVID-19.

OBJECTIVE: Abnormal liver function is a common form of extra-pulmonary organ damage in patients with coronavirus disease 2019 (COVID-19). Patients with severe COVID-19 have a higher probability and progression of liver injury than those without severe disease. We aimed to evaluate the prognosis of liver injury in patients with COVID-19. METHODS: We retrospectively included 502 patients with laboratory-confirmed SARS-CoV-2 infection. Clinical features and survival of patients with and without liver injury were compared. Cox proportional hazards models were used to determine the variables that might have an effect on survival. RESULTS: Among the 502 patients enrolled, 301 patients had abnormal liver function with increased neutrophil count, C-reactive protein, creatinine, troponin I (TnI), D-dimer, lactose dehydrogenase and creatine kinase. Patients with abnormal liver functions had a higher mortality rate (28.9% vs 9.0%, P < 0.001), a higher ratio of male sex (65.1% vs 40.8%, P < 0.001) and a higher chance of developing systemic inflammatory response syndrome (53.5% vs 41.3%, P = 0.007). Among patients with abnormal liver functions, patients with grade 2 liver damage (with both abnormal alanine aminotransferase or aspartate aminotransferase levels and abnormal alkaline phosphatase or gamma-glutamyl transpeptidase levels) had a higher ratio of male patients, elevated neutrophil count, procalcitonin, D-dimer levels and mortality rate. Multivariate Cox regression analyses suggested that the grade of liver damage (hazard ratio: 1.377, 95% confidence interval: 1.000-1.896, P = 0.049) was an independent predictor of death. CONCLUSIONS: Patients with COVID-19 and abnormal liver functions have a higher mortality than those with normal liver functions. Liver damage is an independent prognostic factor of COVID-19.

The microRNA miR-10b as a potentially promising biomarker to predict the prognosis of cancer patients: a meta-analysis.

BACKGROUND: Reported studies on carcinoma have evaluated the significance of the microRNA miR-10b in the development and progression of many cancers. Increased expression of miR-10b is associated with the susceptibility to lymph node metastasis and distant metastasis in various tumors. RESULTS: The results of the meta-analysis revealed that lymph node metastasis occurred more frequently in the patients group with high expression level of miR-10b than in the patients group with low expression level of miR-10b (OR=4.65, 95% CI: 3.40-6.37, P <0.00001, fixed-effects model). Additionally, a similar result was observed in the association between miR-10b expression and distant metastasis (OR=2.70, 95% CI: 1.79-4.08, P <0.00001, fixed-effects model). MATERIALS AND METHODS: In this study, a meta-analysis, including the majority of the relevant articles, was conducted to investigate the association of the miR-10b expression level with metastasis in cancer patients. Systematic literature retrieval was performed by searching in a number of electronic databases. The meta-analysis was conducted using the RevMan 5.2 software and Stata SE12.0 software. A total of 962 patients with carcinoma from 9 studies were included in analysis. CONCLUSIONS: This meta-analysis demonstrated that the overexpression of miR-10b was significantly correlated with metastasis status, and indicated the potential clinical use of miR-10b as a molecular biomarker, particularly in assessing prognosis for patients with cancers.

Quantification of skeletal muscle fibrosis at different healing stages using sonography: a morphologic and histologic study in an animal model.

OBJECTIVES: This study attempted to quantify the degree of muscle fibrosis on sonograms of injured gastrocnemius muscles at different healing stages in a rat model. Correlations between the quantifications and histologic assessments of the injured muscles were also determined. METHODS: Sonograms and histologic findings of gastrocnemius muscle fibrosis were obtained during the second, third, and fourth weeks after surgically induced lesions in the right gastrocnemius muscles of 15 Wistar rats. The echo intensity, reflecting the degree of brightness on a sonogram, was divided into 256 gray levels instead of decibels. The mean echo intensity of each pixel in the region of interest was calculated as a summation of the echo intensities in all pixels divided by the pixel numbers in the region. To control individual variations among the rats, we calculated a K value, defined as the difference in the mean echo intensity between normal and affected muscles. RESULTS: Significant correlations (r > 0.7; P < .05) between mean echo intensity and K values and the fibrous tissue percentage were identified. The mean echo intensity in the injured gastrocnemius muscles was significantly (P = .029) greater than that in the normal muscles 3 weeks after injury. In histologic assessments, muscle fibrosis was most prominent 3 weeks after injury. However, the differences in fibrosis at different healing stages were not significant. CONCLUSIONS: Mean echo intensity and K values can reflect the extent of fibrosis in affected muscles and may be valuable for quantifying muscle fibrosis in clinical practice.