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.
Liver cirrhosis arises from liver fibrosis and necroinflammation caused by various mechanisms of hepatic injury. It is a prevalent condition in clinical practice characterized by hepatocellular dysfunction, portal hypertension, and associated complications. Despite its common occurrence, the etiology and pathogenesis of liver cirrhosis remain incompletely understood, posing a significant health threat. Effective prevention of its onset and progression is paramount in medical research. Symptoms often include discomfort in the liver area, while complications such as sarcopenia, hepatic encephalopathy, ascites, upper gastrointestinal bleeding, and infection can arise. While the efficacy of Western medicine in treating liver cirrhosis is uncertain, Chinese medicine offers distinct advantages. This review explores advancements in liver cirrhosis treatment encompassing non-pharmacological and pharmacological modalities. Chinese medicine interventions, including Chinese medicine decoctions, Chinese patent medicines, and acupuncture, exhibit notable efficacy in cirrhosis reversal and offer improved prognoses. Nowadays, the combination of Chinese and Western medicine in the treatment of liver cirrhosis also has considerable advantages, which is worthy of further research and clinical promotion. Standardized treatment protocols based on these findings hold significant clinical implications.
Liver fibrosis is a common complication of chronic liver disease, significantly affecting patients’ quality of life and potentially leading to cirrhosis and hepatocellular carcinoma. Despite advancements in modern medicine, the treatment of liver fibrosis remains limited and challenging. Thus, identifying new therapeutic strategies is of great clinical importance. Signaling pathways related to liver fibrosis play a crucial regulatory role in immune response and inflammation. Aberrant activation of specific pathways, such as the NF-κB signaling pathway, results in the overexpression of genes associated with liver inflammation and fibrosis, thereby promoting the progression of liver fibrosis. Chinese medicine offers unique potential advantages as a therapeutic approach. Recent studies have increasingly demonstrated that certain Chinese medicines can effectively treat liver fibrosis by regulating relevant signaling pathways. The active ingredients in these medicines can inhibit hepatic inflammatory responses and fibrotic processes by interfering with these pathways, thus reducing the severity of liver fibrosis. This paper aims to investigate the mechanisms of Chinese medicine in treating liver fibrosis and its modulation of related signaling pathways. Additionally, it discusses the prospects of the clinical application of these treatments and provides valuable references for further research and clinical practice.
In recent years, rising living standards and an accelerated lifestyle have led to an increase in the incidence of chronic liver disease. Modern medicine has yet to fully develop effective methods for preventing and treating these conditions due to their complex pathogenesis. Autophagy, a cellular process that maintains homeostasis by removing abnormal proteins, has emerged as a promising therapeutic target for chronic liver diseases. These diseases include liver fibrosis, liver cirrhosis, non-alcoholic steatohepatitis, chronic hepatitis B, and hepatocellular carcinoma. Chinese medicine, with its multi-component, multi-target, and multi-pathway approach, offers unique advantages in treating these conditions, especially given the unclear etiology of chronic liver diseases. Recent research demonstrates that Chinese medicine - comprising single herbs, herbal combinations, and proprietary formulas - can effectively regulate autophagy, thereby providing therapeutic and preventive benefits for chronic liver diseases. This paper reviews recent studies, categorizes various chronic liver diseases, and examines the impact of active ingredients and compound formulas from Chinese medicine on autophagy. These insights are crucial for slowing the progression of chronic liver diseases and pave the way for the future application of Chinese medicine in preventing and managing these conditions through autophagy modulation.
With the general improvement in living standards in recent years, people’s living habits, including their dietary habits, have changed. More people around the world do not follow a healthy diet, leading to an increase in morbidity and even mortality due to digestive system diseases, which shows an increasing trend every year. The advantage of traditional Chinese medicine (TCM) in treating digestive system diseases is evident. Consequently, the mechanisms of action of single Chinese herbs and compound Chinese medicines have become the focus of research. The research method of the network pharmacology system was highly consistent with the holistic concept of TCM, and provided a new perspective and theoretical basis for basic research on digestive system diseases. This article summarizes the common databases currently used in research on TCM. It also briefly introduces the basic methods and technologies of network pharmacology studies. It also summarizes the advancements of network pharmacology technology through a comprehensive literature search on PubMed. Based on this analysis, we further explored the role of TCM in treating digestive system diseases, including chronic gastritis, gastric cancer, ulcerative colitis, and liver cirrhosis. This study provides new ideas and references for treating digestive system diseases with TCM in the future and serves as a reference for relevant researchers.
Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by abnormalities in hepatic fat deposition, the incidence of which has been increasing year by year in recent years. It has become the largest chronic liver disease globally and one of the important causes of cirrhosis and even primary liver cancer formation. The pathogenesis of NAFLD has not yet been fully clarified. Modern medicine lacks targeted clinical treatment protocols for NAFLD, and most drugs lack efficacy and have high side effects. In contrast, Traditional Chinese Medicine (TCM) has significant advantages in the treatment and prevention of NAFLD, which have been widely recognized by scholars around the world. In recent years, through the establishment of a "medicine-disease-target-pathway" network relationship, network pharmacology can explore the molecular basis of the role of medicines in disease prevention and treatment from various perspectives, predicting the pharmacological mechanism of the corresponding medicines. This approach is compatible with the holistic view and treatment based on pattern differentiation of TCM and has been widely used in TCM research. In this paper, by searching relevant databases such as PubMed, Web of Science, and Embase, we reviewed and analyzed the relevant signaling pathways and specific mechanisms of action of single Chinese medicine, Chinese medicine combinations, and Chinese patent medicine for the treatment of NAFLD in recent years. These related studies fully demonstrated the therapeutic characteristics of TCM with multi-components, multi-targets, and multi-pathways, which provided strong support for the exact efficacy of TCM exerted in the clinic. In conclusion, we believe that network pharmacology is more in line with the TCM mindset of treating diseases, but with some limitations. In the future, we should eliminate the potential risks of false positives and false negatives, clarify the interconnectivity between components, targets, and diseases, and conduct deeper clinical or experimental studies.
Chronic hepatitis B (CHB) is a chronic inflammatory disease of the liver caused by infection with the hepatitis B virus (HBV), which in later stages can lead to the development of end-stage liver diseases such as cirrhosis and hepatocellular carcinoma in severe cases, jeopardizing long-term quality of life, with a poor prognosis, and placing a serious financial burden on many families around the world. The pathogenesis of the disease is complex and closely related to the immune function of the body, which has not yet been fully elucidated. The development of chronic hepatitis B is closely related to the involvement of various signaling pathways, such as JAK/STAT, PI3K/Akt, Toll-like receptor, NF-κB and MAPK signaling pathways. A large number of studies have shown that Chinese medicine has obvious advantages in anti-hepatitis B virus, and it can effectively treat the disease by modulating relevant signaling pathways, strengthening immune resistance and defense, and inhibiting inflammatory responses, and certain research progress has been made, but there is still a lack of a comprehensive review on the modulation of relevant signaling pathways in Chinese medicine for the treatment of CHB. Therefore, this article systematically combed and elaborated the relevant literature on the modulation of relevant signaling pathways by traditional Chinese medicine in recent years, with a view to providing new ideas for the treatment of CHB and further drug development.
Backgrounds: Abnormalities in glycometabolism lead to carcinogenesis. UDP-glucose 6-dehydrogenase (UGDH) is the key enzyme of glucuronic acid metabolism and acts as a key mediator in several cancer developmental signaling pathways. In this study, our objective is to offer a more systematic and comprehensive elucidation of the involvement of UGDH in the onset and advancement of various malignancies via an in-depth analysis of UGDH in cancer contexts. Method: We investigated the role of UGDH in cancers using the Human Protein Atlas (HPA), The Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) databases. And analyzed data using various R packages and websites, including TISIDB, cBioPortal, STRING, Cytoscape, GSCALite, and CancerSEA. A rat hepatocellular carcinoma (HCC) model was established using intraperitoneal injection of diethylnitrosamine. Hematoxylin-Eosin (HE) staining, MASSON staining, and KI67 immunohistochemistry of liver tissues were performed. Real-time quantitative PCR (qRT-PCR) and western blotting (WB) were used to detect the expression of UGDH. UGDH gene was knocked down in Huh7 cells, and CCK8 and nude mice tumor xenograft assays were further performed. Results: UGDH high expression is associated with poor clinical outcomes in hepatocellular carcinoma, lung adenocarcinoma, lung squamous cell carcinoma, and sarcoma. And differentially expressed across molecular and immune subtypes. UGDH was primarily involved in the pentose and glucuronate interconversion pathway. Its expression positively correlated with T helper, Tcm, and Th2 cells in most cancers. Moreover, experimental results demonstrated that UGDH expression is elevated in liver cancer and promotes the proliferation of HCC. Conclusions: Our study elucidates that UGDH could be used as a valuable prognostic biomarker and potential therapeutic target in many cancers, especially liver and lung cancer. UGDH could promote the proliferation of HCC cells, possibly by modulating the pentose and glucuronate interconversion pathway.
胃食管反流病(gastroesophageal reflux disease,GERD)是消化系统中的常见病与难治性疾病,症状繁杂,迁延难愈.笔者从"诸气膹郁,皆属于肺"(《素问·至真要大论篇》)的角度出发,探讨全国名中医刘启泉教授从肺辨治GERD的证治思路与用药特色.刘启泉教授认为GERD总以气机失调为基本病机,临证将此病病机特点总结为气(肺胃气逆)、湿(湿滞肺脾)、热(肺胃郁热)、虚(肺胃阴虚),提出了降、宣、清、养四大治法,即:降肺以调胃腑通降,佐斡旋气机;宣肺以辅脾气升清,助运化水湿;清肺以散肺胃郁热,平升降之路;养肺以滋肺胃阴液,厘津亏虚热.刘启泉教授主张以顺气为先、调中为要、兼顾滋阴,旨在燮理气机、开通郁结、调肺安胃、升降有常;在辨证施治的基础上,其用药特色包括慎用开破、妙用轻灵、酌加苦寒、巧佐理气之品等;总以化裁复衡、以调求平为调摄目标,并嘱患者调畅情志、药食并重.刘启泉教授临证中圆机活法,常得佳效,其辨治经验可为临床相关诊疗拓宽思路.
本文从肝脏与胃腑的生理及病理关系出发,并结合临床实际,简要描述了从肝论治慢性萎缩性胃炎的理论基础,认为其病位虽在胃,却与肝密切相关.肝与胃一脏一腑五行相克、经脉相通,其生理特性均与气机有关,肝气对脾胃之气的运动有着重要的调节作用,正所谓"土得木而达",在调理胃病的同时,不忘治肝,在临床中常收奇效.慢性萎缩性胃炎的病机不离肝胃气滞、肝胃郁热、肝胃阴虚、胃络瘀阻四端,从"谨守病机"入手,在临床上运用疏肝降胃、清肝和胃、柔肝养胃、补肝通胃四法,以达到行气不破气、清热不败胃、滋阴不腻胃、养血不伤血的效果,在临证潜方用药时根据患者实际情况之不同而具体化裁,谨守从肝论治四法,且肝为刚脏,遵叶氏"忌刚用柔"之旨,灵活应用疏肝、清肝、柔肝、补肝之药,肝胃同治,气血并调,达到调肝以安胃的目的,同时应注意情绪、饮食等的调控,以期有效逆转萎缩的镜下病理表现,防止进一步恶化.
Network pharmacology is a research method based on a multidisciplinary holistic analysis of biological systems, which coincides with the idea of the holistic view of traditional Chinese medicine. In this review, we summarized the use of network pharmacology technology through studying Chinese medicine single medicine or Chinese medicine compound research ideas and methods for the treatment of ulcerative colitis, based on the application of the current network pharmacology in Chinese medicine research, including the important role in the mechanism of the prediction and verification, to search for new ideas for disease diagnosis and treatment, this study summarizes the application of network pharmacology in the treatment of ulcerative colitis in traditional Chinese medicine, including monotherapy and compound therapy, and considers that relevant research studies have fully demonstrated the function characteristics of the multi-component, multi-target, and multi-pathway of traditional Chinese medicine, and can also explain the connotation of “selecting appropriate treatment methods according to the differences and similarities of pathogenesis” of traditional Chinese medicine. Finally, we raised important questions about the prospects and limitations of network pharmacology, such as differences caused by different data collection methods, a considerable lag, and so on.
Network pharmacology was rapidly developed based on multidisciplinary holistic analysis of biological systems, which has become a popular tool in traditional Chinese medicine (TCM) research in recent years. Its characteristics of integrity and systematization provide a new approach for the study on complex TCM systems, which has many similarities with the holistic concept of TCM. It has been widely used to explain the mechanism of TCM treatment of diseases, drug repositioning, and interpretation of compatibility of TCM prescriptions, to promote the modernization of TCM. The use of TCM have provided crucial support on prevention and treatment of diseases such as the famous "three medicines and three prescriptions ". Furthermore, TCM has become an important part of the treatment of COVID-19 and is one of the main contents of the "Chinese plan " to fight the epidemic. The current review demonstrated the role of TCM in treating diseases with multiple components, multiple targets, and multiple pathways, interprets the connotation of TCM treatment method selection based on pathogenesis and also discusses the application of network pharmacology in the study of COVID-19 treatment in TCM including single drug and prescription. However, there are still some shortcomings such as the lack of experimental verification and regular upgrading of the TCM pharmacology network. Therefore, we must pay attention to the characteristics of TCM and develop a network pharmacology method suitable for TCM system research when applying network pharmacology to TCM research.
Ulcerative colitis (UC) is a common clinical inflammatory bowel disease characterized by repeated attacks, difficult treatment, and great harm to the physical and mental health of the patients. The occurrence and development of UC were closely related to the physiological and pathological processes, such as intestinal inflammatory reaction, oxidizing reaction, and immune response. Treatment of ulcerative colitis using Western medicine is often associated with a number of limitations and adverse events. There is a long history of using traditional Chinese medicine in dealing with this medical condition. Commonly used traditional Chinese medicines for the treatment of UC include Caulis Sargentodoxae, Flos Lonicerae, Fructus Cnidii, etc. Additionally, classic prescriptions such as Gegen Qinlian Formulae and Zuojin Pills can also be used to treat UC. To enrich the traditional Chinese medicine theory, the cognitive theory and perspective of network pharmacology and bioinformatics research of cell signal transduction mechanism of UC are emerging rapidly. Modern pharmacological studies focus on underlying mechanisms for the management of UC with Chinese medicine monomers, single Chinese medicines, and traditional Chinese medicine formulations, alleviating the symptoms of UC, controlling the development of intestinal inflammation, and restoring intestinal function through the regulation of key molecular signaling pathways, including PI3K/Akt, NF-[Formula: see text]B, JAK/STAT, MAPK and Notch. By summarizing current research progressions, this review provides key references for the in-depth exploration of the mechanisms focused on signaling pathways for the clinical management of UC using traditional Chinese medicine.