Even though advancement in medicine has contributed to the control of many diseases to date, cancer therapy continues to pose several challenges. Hepatocellular carcinoma (HCC) etiology is multifactorial. Recently, non-alcoholic fatty liver disease (NAFLD) has been considered as an important risk factor of HCC. NAFLD can be divided into non-alcoholic simple fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) based on histopathological features. Recently, studies have indicated that the gut microbiota is associated with NAFLD and HCC. Therefore, in this review, we have discussed the effects of gut microbiota-related mechanisms, including dysbiosis and gut barrier function, and gut microbiota-derived metabolites on NAFLD and HCC pathogenesis and the potential therapeutic strategies for NAFLD and HCC. With a better understanding of the gut microbiota composition and function, new and improved diagnostic, prognostic, and therapeutic strategies for common liver diseases can be developed.

Beef extract (BE) is a nutritional supplement obtained by cooking beef meat. Compared with traditional chicken essence or clam extract, BE is cheaper to produce and may be used for wound healing, as a chemotherapy supplement, or to prevent fatigue. In this study, we evaluated the potential beneficial effects of BE on exercise performance and the related role of the gut microbiota. Pathogen-free male BALB/c mice were divided into three groups to receive vehicle or BE (0, 12.3, or 24.6 mL/kg) by oral gavage for 28 days. Exercise performance was evaluated using forelimb grip strength, swimming time to exhaustion, and physiological levels of fatigue-related biomarkers (serum lactate, blood urea nitrogen, and glucose levels) after physical challenges. BE supplementation elevated endurance and grip strength in a dose-dependent manner; significantly decreased lactate and blood urea nitrogen levels after physical challenge; and significantly increased muscle glycogen content. The germ-free mice supplemented with BE or an equal-calorie portion of albumin did not show significant differences from the other groups in exercise performance and levels of related biomarkers. Therefore, BE supplementation improved endurance and reduced fatigue, which might be related to BE composition, but had no correlation with the gut microbiota.

Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a critical enzyme involved in ethanol clearance in acetaldehyde metabolism and plays a key role in protecting the liver. The ALDH2*2 mutation causes a significant decrease in acetaldehyde scavenging capacity, leading to the accumulation of acetaldehyde after consuming alcohol. The prevalence of the ALDH2*2 variant is in 45% of Taiwanese individuals. ALDH2 reportedly has protective properties on myocardial damage, stroke, and diabetic retina damage. However, the effects of ALDH2 in the modulation of metabolic syndromes remain unclear. This study evaluates the roles of ALDH2 in a high-fat-diet-induced metabolic syndrome in mice. Male (M) and female (F) wild-type (WT) and ALDH2 knock-in C57BL/6J mice (4–5 weeks old) were fed a high-fat diet for 16 weeks. Results showed that the body and white-adipose-tissue weights were significantly increased in ALDH2-M compared to those in the other groups. We observed markedly elevated serum levels of alanine transaminase and glucose. Oral glucose-tolerance test and homeostasis-model assessment of insulin resistance (HOMA-IR) values were significantly higher in ALDH2-M mice than those in WT-M mice, with no observable differences in female mice. Abundant steatosis and inflammatory cells were observed in ALDH2-M, with significantly decreased expression of hepatic genes IRS2, GLUT4, and PGC-1α compared to that in WT-M. ALDH2 gene mutation also affected the β-diversity of gut microbiota in ALDH2-M resulting in the decreased abundance of Actinobacteria and an increase in Deferribacteres. Our results suggest that potential changes in gut microbiota may be associated with the defective ALDH2 exacerbation of high-fat-diet-induced liver diseases in male mice. However, female mice were not affected, and sex hormones may be an important factor that requires further investigation.

Spinal cord injury (SCI) can cause loss of mobility in the limbs, and no drugs, surgical procedures, or rehabilitation strategies provide a complete cure. Exercise capacity is thought to be associated with the causes of many diseases. However, no studies to date have assessed whether congenital exercise ability is related to the recovery of spinal cord injury. High congenital exercise ability (HE) and low congenital exercise ability (LE) mice were artificially bred from the same founder ICR mice. The HE and LE groups still exhibited differences in exercise ability after 13 generations of breeding. Histological staining and immunohistochemistry staining indicated no significant differences between the HE and LE groups on recovery of the spinal cord. In contrast, after SCI, the HE group exhibited better mobility in gait analysis and longer endurance times in the exhaustive swimming test than the LE group. In addition, after SCI, the HE group also exhibited less atrophy than the LE group, and no inflammatory cells appeared. In conclusion, we found that high congenital exercise ability may reduce the rate of muscle atrophy. This result can be applied to sports science and rehabilitation science as a reference for preventive medicine research.

Pseudomonas aeruginosa exotoxin A (PEA) causes severe hepatotoxicity in experimental animals and is useful in investigations of immune-mediated liver injury. However, strain differences in the sensitivity to PEA-induced hepatotoxicity in rats remains be elucidated. In this study, we determined the severity of PEA-induced hepatotoxicity in six genetically different rat strains. Male LE (Long Evans), Wistar, F344, WKY, BN/SsN and LEW rats were administered a single intravenous injection of PEA (20 μg/kg). Significantly elevated serum ALT and AST levels, massive necrosis and hemorrhage, and numerous TUNEL-positive hepatocytes were observed in BN/SsN rats. In contrast, low levels of ALT and AST as well as mild changes in liver histopathology were observed in Wistar and F344 rats. Moderate levels of hepatic injuries were observed in LE, WKY, and LEW rats. Pro-inflammatory cytokines including TNF-α, IL-2 and IL-6 serum levels were markedly increased in BN/SsN rats compared to Wistar and F344 rats. However, the hepatic levels of low density lipoprotein receptor-related protein (LRP), which functions as the PEA receptor, were not significantly different in each strain. Taken together, we suggest that BN/SsN is the most sensitive rat strain, whereas Wistar and F344 were the most resistant rat strains to PEA-induced liver damage. The different genetic background of rat strains plays an important role in the susceptibility to PEA-induced epatotoxicity that may depend on immune-regulation but not LRP receptor levels.