Xue-Feng Yang

BACKGROUND Diabetes mellitus (DM) and metabolic-associated fatty liver disease (MAFLD) are common metabolic disorders, and their coexistence can exacerbate the progression of either disease. Human umbilical cord mesenchymal stem cell (hUC-MSC) therapy has shown promising potential in the treatment of several metabolic diseases. AIM To investigate how hUC-MSCs affect liver metabolism in diabetic rats with MAFLD and assess their therapeutic potential and underlying mechanisms. METHODS A streptozotocin-induced rat model of DM with MAFLD was established, and hUC-MSCs were administered via tail vein injection. Changes in body weight, fasting blood glucose (FBG), and serum triglyceride (TG), alanine aminotransferase, aspartate aminotransferase levels, and pathological changes of liver were evaluated. Receiver operating characteristic analysis was used to assess the diagnostic value of differential metabolites and their ability to predict the therapeutic effects of hUC-MSCs. Spearman correlation was employed to analyze the relationships between liver metabolites and key biochemical markers. RESULTS hUC-MSC treatment significantly reduced FBG and TG levels in diabetic rats with MAFLD and improved histological steatosis and injury in the liver. Metabolomic analysis indicated that hUC-MSCs significantly ameliorated liver metabolic disturbances via their regulatory effect on several key metabolic pathways related to carbohydrate, amino acid, and lipid metabolism. Receiver operating characteristic curve analysis revealed that 70 differential metabolites had good diagnostic value for DM with MAFLD and could effectively predict the therapeutic effect of hUC-MSCs. Moreover, Spearman correlation analysis confirmed that significant correlations existed between differential liver metabolites and the concentrations of biochemical markers (FBG, TG, alanine aminotransferase, aspartate aminotransferase). CONCLUSION hUC-MSCs alleviate liver metabolic disturbances in diabetic rats with MAFLD, thereby mitigating the pathological state of DM and slowing the progression of MAFLD.

Context: COVID-19 is a novel coronavirus pneumonia, which is related to abnormal liver function. Thus, it is important to explore the occurrences and causes of abnormal liver function with COVID-19. Methods: We chose 109 patients with COVID-19 in 2020 and studied the relationship between gender, age, basic diseases, antiviral drug treatment, disease classification, and abnormal liver function, and analyzed the causes of abnormal liver function in patients with COVID-19 Results: Among patients, 46 (42.20%) had abnormal liver function at admission; 37 (80.43%) had mild abnormal liver function; and 9 (19.57%) had severe liver function. Compared with other age groups, the abnormal rate of serum ALP in the group younger than 21 years old were the highest (P < 0.05). The abnormal rates and concentrations of serum ALT, AST and γ-GT in the male groups were higher than in female groups (P < 0.05), basic disease group were higher than those in the non-basic disease group (P < 0.05). Serum γ-GT concentration after 1 week of antiviral treatment was higher than that before treatment (P < 0.05). The abnormal rate of ALT and AST at discharge was lower than that after antiviral treatment for 1 week (P < 0.05). Serum TB and AST concentrations at discharge were lower than those before treatment (P < 0.05). Serum AST and γ-GT concentrations in severe/critical type group were higher than those in mild or ordinary type group (P < 0.05) Conclusions: In this study, we found male sex, basic diseases, antiviral drugs, and severe/critical types are related to the occurrence of abnormal liver function in COVID-19 patients.

Introduction: Non-alcoholic fatty liver disease (NAFLD) has gradually become the primary cause of fatty liver disease. Betel nuts have been used to treat gastrointestinal diseases.Methods: In the present study, we analyzed the pathology, serology, gut flora, and metabolites in a rat model of NAFLD, with and without betel nut alkaloid treatment, using an integrated approach involving pathology, serological testing, 16S rRNA gene sequencing, and ultra-performance liquid chromatography-mass spectrometry metabolomics.Results: Two rats were used for model validation. Thirty SD rats were included and divided into the normal group (C group), NAFLD model group (M group), low-dose group, medium-dose group (T group), and high-dose group with intraperitoneal injection of arecoline. The expression of blood lipids was significantly downregulated at all three arecoline concentrations (p < 0.05). Alpha-diversity analysis of the intestinal flora showed significant differences among the three groups, with a significant reduction in population diversity in the M group and a recovery of population diversity after arecoline treatment. At the phylum level, the relative abundance of Firmicutes was significantly higher in the T group and Proteobacteria in the M group. The KEGG metabolic pathways included polyketide sugar unit biosynthesis and hypertrophic cardiomyopathy. Thirty-three significantly different metabolites were identified among the groups. Significantly different metabolites between groups T and M included indolepyruvate, 2-deoxystreptamine, sakuranetin, glycyl-leucine, and riboflavin. The KEGG metabolic pathway suggested a potential role for arachidonic acid metabolism, serotonergic synapses, neuroactive ligand-receptor interactions, tyrosine metabolism, and regiomelanin. Vitamin digestion and absorption, as well as regulation of lipolysis in adipocytes, were the main metabolic pathways that distinguished the T vs. M groups. PGE2 is involved in several metabolic pathways. Correlation analysis showed that 29 bacterial species were significantly associated with PGE2 levels in the M and T groups. Vagococcus, Lawsonia, Christensenella, unidentified Erysipelotrichaceae, unidentified Coriobacteriaceae, and five other bacterial groups are unique in the PGE2 metabolic pathway regulated by arecoline.Discussion: Arecoline has lipid-lowering effects and may exert therapeutic effects in NAFLD through intestinal metabolites and intestinal flora, as well as through the Butyricicoccus/Christensenella/Coriobacteriaceae-COX2/PGE2 pathway. Thus, arecoline may represent a potential drug or target for NAFLD treatment.

Metabolic-associated fatty liver disease (MAFLD) is a major cause of liver disease worldwide and comprises non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Due to the high...

Coronavirus disease 2019 (COVID-19) combined with liver injury has become a very prominent clinical problem. Due to the lack of a clear definition of liver injury in patients with COVID-19, the different selection of evaluation parameters and statistical time points, there are the conflicting conclusions about the incidence rate in different studies. The mechanism of COVID-19 combined with liver injury is complicated, including the direct injury of liver cells caused by severe acute respiratory syndrome coronavirus 2 replication and liver injury caused by cytokines, ischemia and hypoxia, and drugs. In addition, underlying diseases, especially chronic liver disease, can aggravate COVID-19 liver injury. In the treatment of COVID-19 combined with liver injury, the primary and basic treatment is to treat the etiology and pathogenesis, followed by support, liver protection, and symptomatic treatment according to the clinical classification and severity of liver injury. This article evaluates the incidence, pathogenesis and prevention and treatment of COVID-19 combined with liver injury, and aims to provide countermeasures for the prevention and treatment of COVID-19 combined with liver injury.

Cyclooxygenase-2 (COX-2) is an important rate-limiting enzyme in the synthesis of prostaglandins (PGs), which can be upregulated by various stimuli. COX-2 has been shown to be involved in the occurrence and development of hepatic fibrosis by regulating the proliferation and apoptosis of hepatic stellate cells (HSCs) in previous studies. The aims of the study are to study the mechanism of how COX-2 regulates the proliferation and apoptosis of HSCs and to provide new targets for the prevention and treatment of hepatic fibrosis. A short hairpin RNA targeting COX-2 was constructed, and the changes in proliferation and apoptosis of liver tissue cells and HSCs were observed, respectively. COX-2-shRNA-1 significantly suppressed the proliferation of HSCs in vivo. Moreover, knockdown of COX-2 significantly suppressed cell proliferation and accelerated cell cycle arrest and apoptosis in vitro. Among those differential genes related to cell proliferation and apoptosis, CDC27 and Sh3kbp1 were upregulated, but Plcd4 was suppressed. Mechanistically, the influence of COX-2 on HSCs partly depends on upregulating CDC27. Our results demonstrated that COX-2 regulates the proliferation and apoptosis of activated hepatic stellate cells through the CDC27 pathway. This study contributes to our understanding of the effect of COX-2 for the treatment of hepatic fibrosis.

The novel coronavirus 2019 (2019 nCoV), appeared in Wuhan in December 2019, can cause a novel coronavirus pneumonia (Corona Virus Disease 2019, COVID-19). COVID-19 is highly infectious and easy to infect people. The epidemic has gradually spread to all parts of the country. In order to provide a basis for clinical diagnosis, this study retrospectively analyzed the imaging characteristics, evolution and related imaging manifestations of COVID-19 patients in different stages of the disease. The results suggest that the imaging findings of 48 COVID-19 patients from Hengyang, Hunan Province are comparable in different stages of the disease. Chest CT showed no pneumonia in one mild patient. Chest CT findings of moderate type (n=38) and severe type (n=9) had comparable characteristics. The main manifestations were ground-glass opacity (GGO) (18/38, 47.37%; 1/9, 11.11%), and GGO with consolidation (16/38, 42.11%; 5/9, 55.56%), which respectively presented in bilateral lungs (34/38, 89.47%; 9/9, 100.00%), and multi-lobe distribution (involving 5 lobes) (17/38, 44.74%; 8/9, 88.89%). After treatment, 28 patients were isolated for 14 days and returned to the hospital for re-examination; among them, the pulmonary lesion was completely absorbed in 15 moderate patients, while 13 patients mainly manifested as GGO. The CT imaging findings of patients with COVID-19 can detect the lesions early, observe the scope of the lesions, evaluate the severity of the lesions, and assist the clinician in completing rapid isolation, diagnosis and treatment. At the same time, it can help to understand the performance of COVID-19 in different stages and dynamically detect changes in the patient's condition.