Yongan Ye

Background: Current treatments for cirrhosis-a progressive disease marked by fibrosis and inflammation-are limited and non-specific. Jinqiancao granules (JQC), a traditional Chinese medicine used for hepatobiliary diseases, could provide a promising new therapeutic approach. Purpose: The objective of this study is to explore the therapeutic effects and potential molecular mechanisms of JQC on CCl ₄ -induced liver cirrhosis in mice, and to analyze its effects on the liver-gut axis, including liver pathology, the intestinal barrier, and gut microbiota. Methods: To investigate the therapeutic effects of JQC and its impact on the liver-gut axis, a mouse model of liver cirrhosis was established by intraperitoneal injection of carbon tetrachloride (CCl ₄ ). The mice were allocated into four groups: the control group (without CCl ₄ induction and receiving normal saline), the model group (CCl ₄ -induced and receiving normal saline), and the two treatment groups which received JQC via gavage at either 500 mg/kg (JQC-H) or 250 mg/kg (JQC-L) after CCl ₄ induction. Upon completion of the treatment, all mice were euthanized to collect serum, fecal samples, liver, and intestinal tissues for subsequent analysis. The assessments encompassed histopathology (H&E, Masson, Picro Sirius Red), immunohistochemistry, immunofluorescence, molecular biology (ELISA, Western blot, qRT-PCR), transcriptomics, and 16S rRNA sequencing. Results: JQC ameliorated CCl ₄ -induced liver cirrhosis in mice by improving liver function and suppressing fibrosis, inflammation, and oxidative stress. Mechanistically, it modulated the PI3K-AKT pathway and restored gut-liver axis homeostasis. This was evidenced by intestinal barrier repair (including upregulation of ZO-1 and occludin, and reduction of LPS) and correction of microbial dysbiosis, specifically enriching beneficial bacteria, such as Bacteroidota and Akkermansia, that correlated negatively with liver injury. Conclusion: This study demonstrates that JQC mitigates liver cirrhosis in mice by modulating the gut-liver axis, enhancing the intestinal barrier, and inhibiting the PI3K-AKT signaling pathway. These results propose JQC as a promising therapeutic candidate, warranting further clinical translation.

Since December 2019, the World Health Organization declared COVID-19 outbreak in the World as a highly contagious respiratory disease poses a significant challenge to the world. The main symptoms of patients are cough, fever, diarrhea, etc. In addition, the COVID-19 genome has strong plasticity, and there is a risk of cross-species transmission. The use of western medicine antibiotics brings good therapeutic effects, but also accompanied by many adverse reactions of physical and mental damage. At present, TCM has achieved remarkable results in the treatment of COVID-19. In addition to enriching the cognitive theories of traditional Chinese medicine in the treatment of COVID-19, studies on the cell signal transduction mechanism of TCM in the treatment of COVID-19 have developed rapidly from the perspective of molecular biology. Through literature search, it is found that the occurrence of COVID-19 is closely related to cellular inflammatory response, immune response, apoptosis, proliferation and other physiological and pathological processes. This study systematically elucidates the molecular mechanisms by which traditional Chinese medicine treats COVID-19 by regulating key signaling pathways such as PI3K/Akt, NF-κB, JAK/STAT, and mTOR. It not only effectively alleviates COVID-19 symptoms and suppresses pulmonary inflammation but also reduces complications and drug-related adverse reactions. The integrated traditional Chinese and Western medicine model demonstrates significant synergistic effects in antiviral treatment and overall regulation. Future research should further explore the cross-mechanisms of signaling pathways, strengthen evidence-based medical validation, promote the modernization of traditional Chinese medicine, and provide safer and more effective treatment strategies for global pandemic control.

Background: As one of the common malignant tumors nowadays, liver cancer has more risk factors for its development and is characterized by a high recurrence rate, high mortality rate, and poor prognosis, which poses a great threat to people's health. The specific efficacy of traditional Chinese medicine is based on clinical practice, which is a high degree of generalization of the characteristics and scope of the clinical effects of prescription medicines and a special form of expression of the medical effects of the human body within the scope of traditional Chinese medicine. Because of its multi-ingredient, multi-target, and multi-pathway characteristics, it has a great advantage in the treatment of liver cancer. Still, at present, its specific molecular mechanism of action has not yet been clarified. Aim: This study reviews the current status and characteristics of network pharmacology research in the treatment of liver cancer, aiming to provide new ideas and methods for traditional Chinese medicine treatment of the disease. Methods: This study was searched on the Web of Science and PubMed using keywords, such as "traditional Chinese medicine", "liver cancer," and "network pharmacology." The citation dates of the literature cited in this review are from 2000 to 2024. Results: The discovery of the key molecular mechanisms of traditional Chinese medicine in the treatment of liver cancer through the network pharmacology approach and the in-depth study of the related signaling pathways are conducive to a more in-depth exploration of traditional Chinese medicine. Conclusion: Network pharmacology research plays a key role in the treatment and prevention of liver cancer and deserves deeper exploration in the future.

Liver cirrhosis is a major manifestation of end-stage liver disease, and its pathogenesis and therapeutic strategies are key areas of research in hepatology. The limitations of traditional treatments have prompted researchers to turn their attention to immune regulatory mechanisms, among which macrophage polarization regulation has become the most promising therapeutic target. In this paper, the central role of macrophages in the development of cirrhosis and their regulatory network are described, with a focus on the critical role of M1/M2 polarization balance in the process of liver fibrosis. The dynamic polarization process of macrophages in the hepatic microenvironment is finely regulated: the M1 type activates hepatic stellate cells through proinflammatory factors, such as TNF-α and IL-1β, and promotes ECM deposition, whereas the M2 type participates in tissue repair and fibrosis reversal through the secretion of anti-inflammatory factors, such as IL-10 and TGF-β, and MMPs. On the basis of this mechanism, three main classes of intervention strategies have been developed: first, immunomodulatory therapies, including CCR2/CCR5 antagonists and cytokine modulation; second, small molecule-targeted drugs, such as JNK inhibitors and natural active ingredients; and third, cutting-edge biotherapeutic technologies, including genetically engineered macrophage and stem cell combination therapies. Importantly, the modulation of macrophage polarization through the targeted delivery of siRNA via nanocarriers or the induction of M2-type polarization using mesenchymal stem cells can significantly reduce the degree of fibrosis. However, these strategies still face challenges in translational applications, such as dynamic changes in the polarization state and insufficient target specificity. In the future, we need to analyse the heterogeneity of macrophages with the help of new technologies such as single-cell sequencing, develop spatiotemporal specific regulation schemes, and explore multitarget synergistic therapeutic strategies. The breakthroughs in this field will not only revolutionize the treatment mode of liver cirrhosis but also provide important reference information for the treatment of fibrotic diseases in other organs, marking the shift in liver disease treatment from traditional symptomatic treatment to a new era of precise immunomodulation. In conclusion, the targeted regulation of macrophage polarization has demonstrated significant therapeutic potential for liver cirrhosis, with its clinical application poised to revolutionize the treatment paradigm for liver diseases. Future studies should focus on leveraging single-cell technologies to elucidate macrophage heterogeneity and develop precision delivery strategies targeting macrophages, thereby advancing the clinical translation of personalized combination therapies based on macrophage modulation.

Background and Aims: In this research, we sought to enhance our comprehension of liver cancer’s genetic architecture by employing Mendelian randomization (MR) techniques to establish causative relationships between particular genetic variations and liver cancer susceptibility. Methods: We integrated data from the public databases with MR analysis to identify differentially expressed genes (DEGs) associated with Hepatocellular Carcinoma (HCC). We conducted functional enrichment analyses to determine the biological processes and signaling cascades associated with the identified DEGs. We also used the CIBERSORT deconvolution method to evaluate immune cell composition in HCC tissues, followed by correlation studies examining relationships between our key genes of interest and various immune cell populations. Additionally, we validated our findings using a rat model of HCC and clinical HCC samples. Results: We obtained two key genes, EHD4 and PPARGC1A, which co-regulated M0 macrophages, suggesting their role in macrophage polarization and tumor progression. In addition, PPARGC1A is associated with resting and activated mast cells, suggesting its involvement in regulating the tumor microenvironment. Detection of rat and clinical samples further confirmed the upregulation of these genes in HCC, supporting their potential as therapeutic targets. Conclusions: Our findings emphasize the significant involvement of EHD4 and PPARGC1A in HCC, specifically regarding their influence on tumor-associated macrophage polarization and broader immune microenvironment modulation. These findings offer new insights into the molecular mechanisms driving HCC and suggest that targeting these genes may provide novel strategies for personalized treatment.

Aims: The TiaoGanXiaoZhi formula (TGXZ), a traditional Chinese medicine, has been shown to alleviate the progression of metabolic‐associated fatty liver disease (MAFLD) clinically. However, its underlying mechanism remains unclear. This study aimed to investigate the effects and mechanisms of TGXZ in treating MAFLD in mouse models. Methods: The MAFLD mouse model was established using a high‐fat diet and 5% fructose water over 16 weeks. At Week 8, mice exhibited significant steatosis, inflammation, and insulin resistance. A total of 42 mice were divided into the normal feed diet (NFD) group ( n = 18) and the high‐fat feed diet (HFD) group ( n = 24). Six mice from each group were killed at Week 8 for serological and histopathological assessments. The remaining mice were allocated into NFD ( n = 6), HFD ( n = 6), HFD + TGXZ ( n = 6), NFD + TGXZ ( n = 6), and HFD + Placebo ( n = 6) groups. TGXZ (or placebo) was administered at a clinical equivalent dose of 7.699 g/(kg·d) to the respective groups, while NFD and HFD groups received distilled water. Daily gavage started in Week 9. At Week 16, after fasting, body weight and liver condition were recorded, and mice were euthanized with pentobarbital sodium. Liver tissue was collected for further analysis, and the remaining tissue and feces were stored at −80°C. Data were graphed using GraphPad Prism 8.0.0 and analyzed with SPSS Statistics 25.0. Results are expressed as mean ± standard deviation. Statistical comparisons were made using Student's t ‐test for two groups and one‐way ANOVA for more than two groups, with significance set at p < 0.05. Results: Compared to the MAFLD mouse model group, TGXZ treatment significantly downregulated the weight of white adipose tissue (1.61 ± 0.66 vs. 3.06 ± 0.34 g, p < 0.0010), liver weight (1.22 ± 0.16 vs. 1.98 ± 0.39 g, p = 0.0031), and the levels of alanine aminotransferase (20.6 ± 3.4 vs. 46.1 ± 12.3 U/L, p < 0.0010), aspartate aminotransferase (99.9 ± 19.1 vs. 168.4 ± 34.3 U/L, p = 0.0014), cholesterol (2.95 ± 0.56 vs. 4.38 ± 0.34 mmol/L, p = 0.0053), triglycerides (2.25 ± 0.41 vs. 4.18 ± 0.67 mmol/L, p < 0.0010), low‐density lipoprotein (0.66 ± 0.11 vs. 1.41 ± 0.52 mmol/L, p = 0.0073), and total bile acid (0.71 ± 0.41 vs. 2.18 ± 0.61 mmol/L, p = 0.0017), except for high‐density lipoprotein (2.41 ± 0.81 vs. 2.55 ± 0.31 mmol/L, p = 0.5655). The liver transcriptome, fecal microbiota sequencing, and fecal lipidomics analysis demonstrated that TGXZ treatment improved the expression of genes related to lipid metabolism, alleviated intestinal microbiota disorders, and mitigated lipid disturbances caused by MAFLD. Conclusions: Our study demonstrated that TGXZ treatment effectively alleviated the progression of MAFLD. The inhibitory effects of TGXZ on MAFLD may be attributed to its regulation of gut microbiota, lipid metabolism, and hepatic inflammation.