Ferroptosis is a unique regulated form of cell death that is distinct from apoptosis, necrosis, and other well-characterized regulated cell death types, and plays an important role in the occurrence and development of chronic metabolic diseases, including diabetes, hypertension, hyperlipidemia, and non-alcoholic steatohepatitis. Recently, increasing evidence has supported traditional Chinese medicine (TCM) as a new hot spot for the treatment of chronic metabolic diseases by mediating ferroptosis. Unfortunately, few systematic reviews have described the importance of TCM in treating chronic metabolic diseases through the ferroptosis pathway. In the current review, the mechanism of ferroptosis and the roles of ferroptosis in chronic metabolic diseases are summarized. Additionally, this review illustrates that the regulation of ferroptosis by TCM could be an effective approach for treating chronic metabolic diseases based on experimental evidence and clinical application. In summary, this work will improve the understanding of ferroptosis and the ability of TCM to regulate ferroptosis in chronic metabolic diseases, thereby promoting the development and application of natural TCM.

Image 1.

The study aims to investigate the impacts of prolyl oligopeptidase (POP) on the replication of foot-and-mouth disease virus (FMDV) in BHK-21 cells. Firstly, the effects of FMDV replication on POP expression in BHK-21 cells were analyzed by Western blotting and Real-time reverse transcription polymerase chain reaction (RT-qPCR). Secondly, a eukaryotic expression plasmid for POP was constructed, and the effects of POP overexpression on the replication of two different serotypes of FMDV were assessed by Western blotting, RT-qPCR, and virus titer assays. Thirdly, specific small interfering RNAs (siRNAs) targeting POP were synthesized, and their efficiency in interfering with endogenous POP expression was identified by RT-qPCR. The impacts of downregulating endogenous POP expression on FMDV replication were further evaluated by Western blotting, RT-qPCR, and virus titer assays. The results indicated that FMDV infection did not significantly affect POP expression in BHK-21 cells. Overexpression of POP dose-dependently enhanced the replication of both FMDV/O and FMDV/A serotypes. Conversely, siRNA-mediated downregulation of endogenous POP expression markedly suppressed FMDV/O replication. This study is the first to demonstrated that the role of the host POP protein in promoting FMDV replication in BHK-21 cells, thereby providing a critical theoretical foundation and potential molecular targets for developing efficient candidate cell strains for foot-and-mouth disease inactivated vaccines.
Foot-and-Mouth Disease Virus/genetics* ; Virus Replication/genetics* ; Prolyl Oligopeptidases ; Serine Endopeptidases/physiology* ; Animals ; Cell Line ; RNA, Small Interfering/genetics* ; Foot-and-Mouth Disease/virology* ; Cricetinae

OBJECTIVE To study the protective effect and mechanism of Bupleurum chinense polysaccharides （BCP） on acute liver injury （ALI） in mice. METHODS Overall 40 mice were randomly divided into normal group， model group， positive control group （Baogan tablet， 550 mg/kg）， BCP high-dose and low-dose groups （400， 100 mg/kg）， with 8 mice in each group. The drug was administered intragastrical once a day for 7 days. One hour after the last administration， except for the normal group， mice in other groups were injected with 20 mg/kg concanavalin A solution through the tail vein to establish ALI model. After injection of concanavalin A solution for 12 h， the liver and spleen indexes of mice were measured， and the pathological changes of liver and spleen tissue were observed； the serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT） and lactate dehydrogenase （LDH） were detected， and the levels of superoxide dismutase （SOD） and malondialdehyde （MDA） in liver tissue were detected. The levels of tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in serum and liver tissue of mice were determined， as well as the protein expression levels of nuclear factor-κB （NF-κB）， Toll-like receptor 4 （TLR4）， nuclear factor erythroid 2-related factor 2 （Nrf2） and heme oxygenase-1 （HO-1） in liver tissue were also detected. RESULTS Compared with the normal group， the liver tissue of mice in the model group was necrotic and infiltrated with inflammatory cells； spleen enlargement， increased bleeding and decreased lymphocytes were observed， liver and spleen indexes were increased significantly （P＜0.01）； the serum levels of AST， ALT and LDH， the levels of TNF-α， IL-6 and IL-1β in serum and liver tissue， as well as the MDA level， protein expressions of TLR4， NF- κB and HO-1 in liver tissue were all increased significantly （P＜0.05 or P＜0.01）. The levels of SOD and protein expression of Nrf2 in liver tissue were all decreased significantly （P＜0.05）. Compared with the model group， the pathological damages of the liver and the spleen tissues in mice alleviated in BCP high-dose and low-dose groups， and most of liver and spleen indexes， the above indexes of serum and liver tissue were reversed significantly （P＜0.05 or P＜0.01）. CONCLUSIONS BCP has a protective effect on ALI， the mechanism of which may be related to the inhibition of TLR4/NF-κB signaling pathway and the activation of the Nrf2/HO-1 signaling pathway.

Cancer， one of the deadliest diseases caused by cells escaping homeostasis， abnormal proliferation， and abnormal differentiation， is fast becoming one of the most burdensome diseases of this century. With decades of human research and cognitive changes in cancer， cancer treatment is also developing rapidly， but there is still a lack of effective treatment and countermeasures. Especially， the search for safe， efficient， and non-toxic drugs has become a long-term goal in the field of cancer. Saponins extracted and separated from traditional Chinese medicine can improve cancer through various pathways and have almost no toxic side effects. Therefore， the research on the anti-cancer effect of saponins is heating up. It is found that saponins play anti-tumor roles by inhibiting proliferation， metastasis， and angiogenesis of cancer cells， promoting apoptosis of cancer cells， inducing autophagy of tumor cells， and regulating miRNA expression and immune functions. Chinese herbal medicine saponins can regulate secretory glycoprotein /β-catenin （Wnt/β-catenin）， adenylate activated protein kinase （AMPK）， nuclear transcription factor-κB （NF-κB）， mitogen-activated protein kinase （MAPK）， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）/mammalian target of rapamycin （mTOR）， Janus kinase/activator of signal transduction and transcription 3 （JAK/ STAT3）， hypoxia-inducible factor-1α （HIF-1α）， Toll-like receptor （TLR）， and other related signaling pathways to get involved in the proliferation， metastasis， angiogenesis， apoptosis， autophagy， and other processes of cancer cells， thus interfering with the progression of cancer. Therefore， the focus of this review is to update the discovery and evaluation of Chinese herbal medicine saponins with anti-cancer properties， clarify their mechanism of action， including the progress of related signaling pathways， and deepen the understanding of the anti-cancer function of Chinese herbal medicine saponins， so as to provide a new perspective and direction for the prevention and treatment of tumors by traditional Chinese medicine and better promote the development and utilization of resources.

Clinical trials of drugs for rare diseases face special challenges such as a limited number of patients,difficult recruitment,long trial period,and frequent video interviews during the trial.Therefore,in the clinical operation of rare diseases,a decentralized clinical trials(DCT)model based on the"patient-cen-tred"research and development concept is implemented.With the help of decentralized elements and digital health technology,the barriers of geographical restrictions can be overcome and subjects do not have to be limit-ed to traditional clinical trial sites(hospitals/research centers),which can significantly reduce the burden on subjects,increase their representation,and obtain a wider range of scientific research data.To guide the indus-try's scientific and standardized application of DCT in the research and development of drugs for rare diseases,the Center for Drug Evaluation of the National Medical Products Administration(NMPA)organized the stake holders to draft the Technical Guideline for the Application of Decentralized Clinical Trials in the Research and Development of Drugs for Rare Diseases.This guideline provides scientific recommendations for the development and implementation of DCT for rare disease drugs.It aims to solve the difficult and key problems during rare disease drug research and development,improve the efficiency and optimize patient experience.This article,combining the research and development concepts in the guideline,explains the current research and develop-ment thinking on the application of DCT in the research and development of rare disease drugs,with a view of providing reference for the industry.

Traditional Chinese medicine has the characteristics of multiple components， pathways， and targets in the treatment of fracture healing， and has good therapeutic advantages and potential for fractures with complex pathological mechanisms. Based on this， the author summarized the mechanism of promoting fracture healing by the monomer components and compound formulas of traditional Chinese medicine and found that visfatin A， puerarin， and others can activate the mitogen-activated protein kinase （MAPK） signaling pathway； Xugudan， Guben zenggu formula and others can activate bone morphogenetic protein （BMP） signaling pathway； baicalin， Achyranthes bidentata polysaccharides and others can activate Wnt/β -catenin signaling pathway； apigenin， notoginsenoside and others can activate receptor activator of nuclear factor-κB （NF-κB）/receptor activator of NF-κB ligand/osteoprotegerin （RANK/RANKL/OPG） signaling pathway； Compound huoxue jiegu capsule， Jiangu granule and others can inhibit phosphoinositide 3-kinase/protein kinase B （PI3K/AKT） signaling pathway； icariin can activate Notch signaling pathway； Taohong siwu decoction， crocin and others can activate Hippo signaling pathway； jujuboside A and osthole can inhibit NF-κB signaling pathway， and thus promote fracture healing.

The aim of this study was to produce recombinant porcine interferon gamma (rPoIFN-γ) by Chinese hamster ovarian (CHO) cells expression system and to analyze its antiviral activity. Firstly, we constructed the recombinant eukaryotic expression plasmid pcDNA3.1-PoIFN-γ and transfected into suspension cultured CHO cells for secretory expression of rPoIFN-γ. The rPoIFN-γ was purified by affinity chromatography and identified with SDS-PAGE and Western blotting. Subsequently, the cytotoxicity of rPoIFN-γ was analyzed by CCK-8 test, and the antiviral activity of rPoIFN-γ was evaluated using standard procedures in VSV/PK-15 (virus/cell) test system. Finally the anti-Seneca virus A (SVA) of rPoIFN-γ activity and the induction of interferon-stimulated genes (ISGs) and cytokines were also analyzed. The results showed that rPoIFN-γ could successfully expressed in the supernatant of CHO cells. CCK-8 assays indicated that rPoIFN-γ did not show cytotoxicity on IBRS-2 cells. The biological activity of rPoIFN-γ was 5.59×10⁷ U/mg in VSV/PK-15 system. Moreover, rPoIFN-γ could induced the expression of ISGs and cytokines, and significantly inhibited the replication of SVA. In conclusion, the high activity of rPoIFN-γ was successfully prepared by CHO cells expression system, which showed strong antiviral activity on SVA. This study may facilitate the investigation of rPoIFN-γ function and the development of novel genetically engineered antiviral drugs.
Swine ; Animals ; Cricetinae ; Interferon-gamma/pharmacology* ; Cricetulus ; CHO Cells ; Sincalide ; Recombinant Proteins/pharmacology* ; Antiviral Agents/pharmacology*

Epilepsy is a chronic brain disease characterized by seizures， and is one of the most common nervous system diseases in clinic practice with the recurrent， transient， and refractory characteristics. Clinically， western medicine therapy is mainly adopted in the treatment of epilepsy， but it is not conducive to long-term use for patients on account of severe side effects， which can result in abnormalities in the digestive system， central nervous system， hematopoietic system， urinary system， and liver function to varying degrees. Syndrome differentiation is usually used for the treatment of epilepsy by traditional Chinese medicine （TCM）， which can avoid the side effects of western medicine treatment on the basis of improving patients' syndromes. The literature on TCM in the treatment of epilepsy in China and abroad indicates that the syndrome differentiation in TCM is often based on phlegm， blood stasis， wind， and deficiency， and the treatment methods include acupuncture， acupoint catgut embedding， moxibustion， Chinese medicine monomer， drug pair， and compound decoction. The various treatments of TCM play an important role in the comprehensive treatment of epilepsy through multiple channels and links， such as reducing the degree and number of seizures. This paper comprehensively summarized the clinical experience of TCM in the treatment of epilepsy， systematically expounded various treatment methods and ideas of TCM in the treatment of epilepsy， and deeply discussed the mechanism of TCM in the treatment of epilepsy， aiming to provide a theoretical basis for the clinical formulation of a reasonable individualized treatment plan for epilepsy and diversified ideas for the more effective treatment of epilepsy by TCM.

ObjectiveTo explore the meridian tropism of components in Bupleuri Radix （Chaihu， CH） based on the model of nonalcoholic steatohepatitis （NASH） and clarify the substance basis of the meridian tropism of CH in Xiaoyaosan （XYS） by means of principal component analysis. MethodEighty SPF male C57BL/6 mice were randomly assigned into 8 groups， with 10 mice in each group. Except that the blank group was fed with the methionine choline-sufficient （MCS） diet， the other mice were fed with methionine choline-deficient （MCD） diet for 4 weeks to establish the nonalcoholic steatohepatitis （NASH） model. After the established model was confirmed by hematoxylin-eosin （HE） staining， the mice were administrated with corresponding drugs by gavage once a day for 4 weeks. Specifically， the 8 groups were XYS group （2.874 g·kg^-1）， XYS-CH group （2.445 g·kg^-1）， XYS-CH+volatile oils （Vol， 0.163 mg·kg^-1） group， XYS-CH+polysaccharides （Pol， 24.067 mg·kg^-1） group， XYS-CH+flavones （Fla， 2.241 mg·kg^-1） group， and XYS-CH+saponins （Sap， 2.746 mg·kg^-1） group. The model group and the blank group were administrated with the same volume of normal saline. After the last administration， the mice were sacrificed for the collection of blood and liver tissue. The pathological changes of liver were observed by HE staining and oil red O staining. Enzyme linked immunosorbent assay （ELISA） kits were used to determine the levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， triglyceride （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， and low-density lipoprotein （LDL） in serum as well as malondialdehyde （MDA）， superoxide dismutase （SOD）， catalase （CAT）， and glutathione peroxidase （GSH-Px） in liver. SPSS Statistics 23 was used for principal component analysis and comprehensive evaluation to determine the substance basis of the meridian tropism of CH in NASH mice. ResultCompared with the blank control group， the modeling led to hepatocyte swelling， increased fat vacuoles， and appearance of inflammatory cells. Further， the modeling elevated the levels of ALT， AST， TG， TC， and LDL and lowered the HDL level in serum， and it increased the MDA level and decreased the SOD， CAT， and GSH-Px levels in liver. Compared with the model group， the administration of XYS and XYS-CH in combination with the components of CH alleviated the oxidative damage in liver （P<0.05）. The comprehensive score of the pharmacological efficacy was in a descending order as follows： XYS > XYS-CH+Sap > XYS-CH+Fla > XYS-CH+Pol > XYS-CH+Vol > XYS-CH. Among the chemical components of CH， Sap had the best effect. ConclusionSap lowers the blood lipid level， regulates the abnormal lipid metabolism， and alleviates the oxidative damage of liver， which is the substance basis for CH to exert the meridian tropism in liver.