Jianfeng Bao

Background: Chaihuang weikuining (CHWKN) is a traditional Chinese medicinal formula with reported anti-ulcer activity. However, the underlying mechanisms remain unclear. This study aimed to investigate the protective effects of CHWKN against ethanol-induced gastric ulcer (GU) and to explore the role of gut microbiota in mediating these effects. Methods: An ethanol-induced GU model was established in rats. Histological staining (H&E and PAS) and biochemical analyses were used to evaluate gastric injury. Antibiotic (ABX) treatment and fecal microbiota transplantation (FMT) were performed to determine the involvement of gut microbiota. 16S rDNA sequencing was conducted to analyse microbial composition. Results: CHWKN markedly alleviated ethanol-induced gastric mucosal injury, as evidenced by improved histopathological features and restored of gastric function. CHWKN significantly reduced myeloperoxidase (MPO) and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and LPS) while increasing IL-10 levels, accompanied by suppression of JAK1/STAT3 signaling. Notably, depletion of gut microbiota abolished the protective and anti-inflammatory effects of CHWKN. Conversely, FMT from CHWKN-treated donors (the donor rats treated with ethanol and CHWKN) restored gastric mucosal integrity and reduced inflammation in recipient rats. Furthermore, CHWKN remodeled the composition of gut microbiota by increasing potentially beneficial bacteria and reversing ethanol-induced dysbiosis. Conclusion: These findings demonstrate that CHWKN exerts protective effects against ethanol-induced GU by modulating of gut microbiota and subsequently inhibiting of JAK1/STAT3 -mediated inflammation. This highlights a microbiota-dependent mechanism underlying its therapeutic action.

Background: Hepatocellular carcinoma (HCC) is a highly lethal malignancy with rising global incidence. Aberrantly activated aerobic glycolysis is a hallmark of HCC, driving excessive lactate production and the formation of an acidic tumor microenvironment (TME) that promotes malignant progression. Elucidating the underlying mechanisms of this metabolic axis is essential for developing targeted therapeutic strategies. Objective: This review systematically examines the role of the aerobic glycolysis-lactate-acidic TME axis in HCC progression, focusing on its molecular basis, multifaceted functions of lactate, and therapeutic implications. Key Findings: HCC progression is driven by a coordinated “production-efflux” mechanism involving glycolytic rate-limiting enzymes (such as HK2, PKM2, LDH) and the lactate transporter such as MCT4, which together facilitate lactate accumulation and TME acidification. Lactate exerts pleiotropic effects within the TME, including metabolic signaling via GPR81 and ASICs, epigenetic regulation through histone lactylation, and inter-organ crosstalk via the gut–liver axis. Current therapeutic strategies targeting GLUTs, glycolytic enzymes, LDH, and MCT4 are reviewed, along with approaches for direct TME alkalinization and combination regimens with targeted agents. Building upon this landscape, the present review is the first to systematically integrate emerging mechanisms such as histone lactylation and the gut-liver axis, and to explore the synergistic potential of combining metabolic inhibitors with immunotherapy, thereby offering a distinct framework that moves beyond traditional glycolysis-centric narratives in HCC. Challenges and Perspectives: Despite the substantial potential of targeting this metabolic axis, a considerable gap remains between preclinical findings and clinical translation. The pronounced heterogeneity of HCC, along with metabolic plasticity and insufficient drug selectivity, poses major challenges. Future efforts should prioritize the development of highly selective inhibitors and the optimization of combination therapies based on metabolic stratification.

Background: Obesity has become a widespread metabolic disorder, marked by its escalating global prevalence. Puerarin, extracted from Pueraria lobata, one of the traditional homologies of medicine and food, demonstrates anti-obesity properties. Nonetheless, the mechanisms through which puerarin exerts its anti-obesity effects remain to be elucidated. This study seeks to highlight the potential application of puerarin in obesity management and to investigate the underlying mechanisms involving gut microbiota and lipid metabolism.Method: Different doses of puerarin were administered to the high-fat diet mice model, and the structure and composition of gut microbiota were analyzed using 16S rRNA sequencing. Q-PCR evaluated the expression of genes related to lipid metabolism.Result: Our findings demonstrate that puerarin treatment significantly reduces body weight and epithelial and beige fat mass. Furthermore, puerarin alters the structure and composition of gut microbiota, which is associated with metabolism. Additionally, puerarin treatment significantly upregulates gene expression, fatty acid transport protein 5 (FATP5) hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL) in epithelial and beige adipose.Conclusion: Puerarin demonstrates potential in ameliorating obesity by changing the structure and composition of gut microbiota, which enhances the transport of fatty acid and triglycerides hydrolysis within adipose tissue. This study provides a novel perspective on puerarin as a dietary supplement for obesity.

Background: Liver fibrosis is a prevalent, chronic inflammatory condition characterized by the excessive accumulation of extracellular matrix components and, primarily, collagen in the liver. Huo-xue-shen (HXS) has proven effective for the treatment of liver fibrosis. However, the mechanism is yet to be deciphered. Methods: Network pharmacology, machine learning algorithms and RNA-seq were used to predict the immune-treated targets and mechanisms associated with HXS in liver fibrosis. Molecular docking was employed to screen for effective agents based on the drug–compound–hub gene network in HXS, aiming to identify the most critical bioactive compound in HXS for the treatment of liver fibrosis. Results: A total of 100 immune-treated targets (ITTs) of HXS were found to significantly regulate the PI3K-Akt signaling pathway and the MAPK signaling pathway. Among these, CDKN1A, NR1I3, and TUBB1, which can concurrently interact with quercetin, were associated with the prognosis of liver fibrosis, indicating that HXS may inhibit or reverse HSC activation primarily by suppressing neutrophil extracellular trap formation, stimulating oxidative phosphorylation and promoting thyroid hormone synthesis in the regulation of the liver microenvironment. Conclusions: Our study suggests that HXS may delay the progression of liver fibrosis by targeting multiple pathways, as shown by the network pharmacology and transcriptome profiling used to examine the liver immune environment. Quercetin, its key ingredient, likely plays an important role by mediating the CDKN1A, NR1I3, and TUBB1 signaling pathways. Overall, our findings provide a new perspective on the potential biological mechanisms of this traditional Chinese medicine formula.

Rationale: Primary sclerosing cholangitis (PSC) is characterized by idiopathic intra- and extrahepatic bile duct inflammation and biliary fibrotic changes. Recurrent bile duct stones due to PLKR and UGT1A1 mutation is an extremely rare complications of PSC. Patient concerns: A 26-year-old male patient complains a history of recurrent yellow skin and urine for over a year. Diagnoses: Following dynamic magnetic resonance cholangiopancreatography imaging, colonoscopic manifestation, liver biopsy and whole exome sequencing, the patient was finally diagnosed with PSC - ulcerative colitis with PLKR and UGT1A1 mutation. Interventions: Following resolution of the obstruction, a long-term regimen of 1000 mg/d ursodeoxycholic acid in combination with 10 mg/d obeticholic acid to improve cholestasis, 8 g/d colestyramine to facilitate adsorption of excess bile acids and 1.2 g/d rifaximin to prevent biliary tract infection were prescribed. Outcomes: The patient’s liver biochemical parameters have improved significantly. His condition is stable and has not undergone liver transplantation at this time. Lessons: Close and dynamic detection of the patient’s biliary ductal lesions play an important role in the diagnosis of PSC. In the event of relatively rare biliary complications, attention should be paid to the presence of gene mutation.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can trigger autoimmune inflammation in the liver, leading to acute autoimmune hepatitis (AIH). We herein report a case involving a 39-year-old woman with a 23-day history of yellow skin and urine. Using the revised original scoring system of the International AIH Group, we definitively diagnosed the patient with acute severe AIH (AS-AIH). She began treatment with 80 mg/day intravenous methylprednisolone, which was gradually reduced and followed by eventual transition to oral methylprednisolone. The patient finally achieved a biochemical response after 30 days of therapy, and liver transplantation was avoided. Clinicians should be aware that the onset of AS-AIH after SARS-CoV-2 infection differs from the onset of conventional AIH with respect to its clinical and pathological features. Early diagnosis and timely glucocorticoid treatment are crucial in improving outcomes.

The cargo content in small extracellular vesicles (sEVs) changes under pathological conditions. Our data shows that in obesity, extracellular matrix protein 1 (ECM1) protein levels are significantly increased in circulating sEVs, which is dependent on integrin-β2. Knockdown of integrin-β2 does not affect cellular ECM1 protein levels but significantly reduces ECM1 protein levels in the sEVs released by these cells. In breast cancer (BC), overexpressing ECM1 increases matrix metalloproteinase 3 (MMP3) and S100A/B protein levels. Interestingly, sEVs purified from high-fat diet-induced obesity mice (D-sEVs) deliver more ECM1 protein to BC cells compared to sEVs from control diet-fed mice. Consequently, BC cells secrete more ECM1 protein, which promotes cancer cell invasion and migration. D-sEVs treatment also significantly enhances ECM1-mediated BC metastasis and growth in mouse models, as evidenced by the elevated tumor levels of MMP3 and S100A/B. Our study reveals a mechanism and suggests sEV-based strategies for treating obesity-associated BC.

Transjugular intrahepatic portosystemic shunt (TIPS) is a life-saving procedure for patients with severe portal hypertension and persistent variceal bleeding. Stent fracture is a rare and severe complication; however, its cause and mechanisms remain poorly defined. This case helps understand the factors contributing to its occurrence, complications, and subsequent poor outcomes. A 63-year-old male was presented with ruptured bare stent after a TIPS procedure. The upper edge of the bare stent was ruptured, and its fraction subsequently migrated to the entrance of the right atrium. Meanwhile, a mural thrombus was formed in the inferior vena cava. A surgery for the removal of free fracture was planned for preventing the form of pulmonary embolism. Before the surgery, the fracture was shifted to the right inferior pulmonary artery. Therefore, the surgery was canceled for further evaluation. Then, hematemesis suddenly occurred with a high possibility of variceal bleeding and/or gastric ulcer bleeding. Despite comprehensive treatments, the patient symptoms were still worsened with the development of chest tightness, shortness of breath, severe hypoxia, and heart failure. Finally, the patient succumbed to systemic multiorgan failure and death. Taken together, a ruptured unstable stent should be removed as early as the patient is hemodynamically stable, as it is difficult to balance between hemostasis therapy and anticoagulation treatment in patients with liver-cirrhosis-related severe portal hypertension. Physicians should be on high alert of the potential complications of bare stent rapture after TIPS.