Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

Objective To investigate the heterogeneity and key molecular features of epithelial cells in triple-negative breast cancer (TNBC), identify prognostic biomarkers, and develop a robust survival prediction model. Methods Using TNBC single-cell transcriptomic data, epithelial cells were extracted, normalized, and subclustered to characterize their molecular signatures and functional differences. High-dimensional weighted gene co-expression network analysis (hdWGCNA) was applied to establish co-expression modules in epithelial cells. Multiple machine learning algorithms were integrated to select key prognostic genes and develop a risk-score model, whose performance was evaluated using receiver operating characteristic (ROC) curves and Kaplan-Meier (K-M) survival analysis. In addition, the immune microenvironment features and potential drug-response differences between the high- and low-risk groups were systematically assessed. Finally, PCR was performed to validate the expression differences of the key genes between tumor and normal tissues. Results We characterized the composition and molecular features of TNBC epithelial subpopulations and identified a TNBC-associated epithelial subset. By integrating hdWGCNA with machine learning approaches, 10 key genes were selected to construct a prognostic model, which effectively stratified patients into distinct survival-risk groups and demonstrated favorable predictive performance in ROC and K-M analyses. Immune profiling revealed the differences in the infiltration levels of seven immune cell types and immune function-related features between the high- and low-risk groups. Drug-sensitivity analysis suggested potential differential responses to eight agents across the risk groups. PCR validation further confirmed the differential expression of the ten signature genes between tumor and normal tissues. Conclusion This study reveals epithelial heterogeneity in TNBC at single-cell resolution and establishes a 10-gene prognostic model, which may facilitate the stratification of TNBC risk and the evaluation of immune characteristics and potential therapeutic strategies.

Lung cancer remains one of the leading causes of cancer-related morbidity and mortality worldwide, and its treatment continues to face major challenges such as therapeutic resistance and tumor recurrence. Pyroptosis, a newly characterized form of programmed cell death, induces tumor cell death through gasdermin-mediated membrane pore formation and is accompanied by the release of inflammatory mediators, thereby playing complex roles in lung cancer initiation, progression, and modulation of the tumor microenvironment. Active components and herbal formulas derived from traditional Chinese medicine can modulate pyroptosis-related signaling pathways through multi-target mechanisms, showing potential advantages in inducing lung cancer cell death, inhibiting proliferation and migration, and reversing chemoresistance. This review systematically summarizes relevant studies from domestic and international sources, focusing on the molecular mechanisms of pyroptosis, its roles in lung cancer development and tumor microenvironment remodeling, and the current research progress on traditional Chinese medicine-based interventions targeting pyroptosis, with the aim of providing references for the prevention and treatment of lung cancer using traditional Chinese medicine.

Objective This study reports on the obligatory parasitism of water mites Arrenurus sp. on Anopheles messeae at the Manzhouli Port, Inner Mongolia, China. Methods Duing July 2024, a survey on the mosquito diversity was conducted at the Manzhouli Port. Captured mosquitoes and their ectoparasites were identified to species level. Results A total of 1840 adult mosquitoes were collected, representing species from three genera: Culex(Cx. modestus, Cx. pipiens pallens), Aedes(Ae. dorsalis, Ae. flavidorsalis, Ae. flavescens), and Anopheles (An. messeae). Among all the mosqutioes specimens,3 out of 150 captured An. messeae were found to carry ectoparasitic mites, with number of 2,4,27 mites separately. Morphological and molecular identification reached the same result as water mites(Hydrachnidiae, Hydracrina). COI gene sequence showed 94% similarity with the closest species Arrenurus truncatellus. Conlusions Literature review suggests water mites are host-specific parasitism of mosquito species and herein with the first record of Arrenurus sp. parasiting on An. Messeae in the most high-latitude region globally.

In order to investigate whether the effect of Yuxuebi Tablets on the peripheral and central inflammation resolution of mice with inflammatory pain is related to their regulation of G protein-coupled receptor 37(GPR37), an inflammatory pain model was established by injecting complete Freund's adjuvant(CFA) into the paws of mice, with a sham-operated group receiving a similar volume of normal saline. The mice were assigned randomly to the sham-operated group, model group, ibuprofen group(91 mg·kg~(-1)), and low-, medium-, and high-dose groups of Yuxuebi Tablets(60, 120, and 240 mg·kg~(-1)). The drug was administered orally from days 1 to 19 after modeling. Von Frey method and the hot plate test were used to detect mechanical pain thresholds and heat hyperalgesia. The levels of interleukin-10(IL-10) and transforming growth factor-beta(TGF-β) in the spinal cord were quantified using enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein expression of GPR37 in the spinal cord was measured by real-time quantitative reverse transcription PCR(qRT-PCR) and Western blot. Additionally, immunofluorescence was used to detect the expression of macrosialin antigen(CD68), mannose receptor(MRC1 or CD206), and GPR37 in dorsal root ganglia, as well as the expression of calcium-binding adapter molecule 1(IBA1), CD206, and GPR37 in the dorsal horn of the spinal cord. The results showed that compared with those of the sham-operated group, the mechanical pain thresholds and hot withdrawal latency of the model group significantly declined, and the expression of CD68 in the dorsal root ganglia and the expression of IBA1 in the dorsal horn of the spinal cord significantly increased. The expression of CD206 and GPR37 significantly decreased in the dorsal root ganglion and dorsal horn of the spinal cord, and IL-10 and TGF-β levels in the spinal cord were significantly decreased. Compared with those of the model group, the mechanical pain thresholds and hot withdrawal latency of the high-dose group of Yuxuebi Tablets significantly increased, and the expression of CD68 in the dorsal root ganglion and IBA1 in the dorsal horn of the spinal cord significantly decreased. The expression of CD206 and GPR37 in the dorsal root ganglion and dorsal horn of the spinal cord significantly increased, as well as IL-10 and TGF-β levels in the spinal cord. These findings indicated that Yuxuebi Tablets may reduce macrophage(microglial) infiltration and foster M2 macrophage polarization by enhancing GPR37 expression in the dorsal root ganglia and dorsal horn of the spinal cord of CFA-induced mice, so as to improve IL-10 and TGF-β levels, promote resolution of both peripheral and central inflammation, and play analgesic effects.
Inflammation/genetics* ; Pain/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Mice ; Freund's Adjuvant/pharmacology* ; Ibuprofen ; Pain Threshold/drug effects* ; Hyperalgesia/genetics* ; Ganglia, Spinal ; Interleukin-10/genetics* ; Transforming Growth Factor beta/genetics* ; Reverse Transcriptase Polymerase Chain Reaction ; Tablets ; Receptors, G-Protein-Coupled

This study aimed to compare the ameliorative effects of Lycii Fructus and Chrysanthemi Flos at different ratios on retinal damage in mice and to elucidate the underlying mechanisms. A retinal injury model was established by intraperitoneal injection of sodium iodate(NaIO_3) solution. The mice were divided into the following groups: blank group, model group, positive drug(AREDS 2) group, low-and high-dose groups of Lycii Fructus and Chrysanthemi Flos at 1∶1, low-and high-dose groups at 3∶1, and low-and high-dose groups at 1∶3. Administration was carried out 15 days after modeling. The visual acuity of the mice was assessed using the black-and-white box test. The fundus was observed using an optical coherence tomography device, and retinal thickness was measured. HE staining was used to observe the morphology and pathological changes of the retina. The levels of oxidative factors in serum and ocular tissues were measured using assay kits. The levels of inflammatory factors in serum and ocular tissues were detected by enzyme-linked immunosorbent assay(ELISA), and the expression of Nrf2, HO-1, and NF-κB proteins in ocular tissues was analyzed by Western blot. The results showed that after administration of Lycii Fructus and Chrysanthemi Flos at different ratios, the model group showed improved retinal thinning and disordered arrangement of retinal layers, elevated content of SOD and GSH in the serum and ocular tissues, and reduced levels of MDA, TNF-α, IL-1β, and IL-6. Lycii Fructus and Chrysanthemi Flos at 1∶1 and 1∶3 showed better improvement effects. The combination significantly upregulated the expression levels of Nrf2 and HO-1 and downregulated the expression of NF-κB p65. These results indicate that Lycii Fructus and Chrysanthemi Flos at different ratios can improve retinal damage, reduce oxidative stress, and alleviate inflammation in both the body and ocular tissues of mice. The mechanism may be related to the regulation of the Nrf2/HO-1 and NF-κB signaling pathways in ocular tissues. These findings provide a theoretical basis for the clinical application of Lycii Fructus and Chrysanthemi Flos in the treatment of dry age-related macular degeneration.
Animals ; Mice ; Retina/injuries* ; Male ; Lycium/chemistry* ; Drugs, Chinese Herbal/administration & dosage* ; Chrysanthemum/chemistry* ; NF-kappa B/genetics* ; Humans ; Retinal Diseases/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress/drug effects* ; Flowers/chemistry* ; Heme Oxygenase-1/genetics*

This study aims to explore the role and mechanism of berberine in promoting the expression of aquaporin 4(AQP4) in astrocytes by regulating the expression of miR-383-5p in HepG2 cell-derived exosomes under insulin resistance(IR). The IR-HepG2 cell model was established with 1×10~(-6) mol·L~(-1) insulin. With metformin as the positive control, the safe concentrations of berberine and metformin were screened by cell counting kit-8(CCK-8) and lactate dehydrogenase(LDH) leakage assays, and the effect of berberine on the IR of HepG2 cells was evaluated by glucose consumption. NanoSight was used to measure the particle size and concentration of exosomes secreted by HepG2 cells in each group. HepG2 cell-derived exosomes in each group were incubated with astrocytes for 24 h, and the protein and mRNA levels of AQP4 in HA1800 cells were determined by Western blot and qRT-PCR, respectively. qRT-PCR was performed to determine the expression of miR-383-5p in HepG2 cell-derived exosomes and HA1800 cells after co-incubation. Western blotting was employed to determine the expression levels of miRNAs and proteins associated with exosome production and release in HepG2 cells. The results showed that 10 μmol·L~(-1) berberine and 1 mmol·L~(-1) metformin significantly alleviated the IR of HepG2 cells and reduced the concentration of exosomes in HepG2 cells. The exosomes of HepG2 cells treated with berberine and metformin significantly up-regulated the protein and mRNA levels of AQP4 in HA1800 cells. The mRNA level of miR-383-5p in HepG2 cell exosomes and HA1800 cells co-incubated with berberine and metformin decreased significantly. The intervention with berberine and metformin significantly down-regulated the expression of proteins associated with the production of miRNAs(Dicer, Drosha) as well as the production(Alix, Vps4A) and release(Rab35, VAMP3) of exosomes in IR-HepG2 cells. In conclusion, berberine can promote the expression of AQP4 in astrocytes by inhibiting the production and release of miR-383-5p in HepG2-derived exosomes under IR.
Humans ; MicroRNAs/metabolism* ; Berberine/pharmacology* ; Hep G2 Cells ; Exosomes/genetics* ; Aquaporin 4/metabolism* ; Insulin Resistance ; Astrocytes/drug effects*

In recent years, the reform of the registration, evaluation, and approval system for traditional Chinese medicine(TCM) has been promoted at the national level, with establishment of an evaluation evidence system for TCM registration that combines TCM theory, human use experience, and clinical trials(known as the "three-combined" evaluation evidence system). This system, which aligns with the characteristics of TCM clinical practice and the laws of TCM research and development, recognizes the unique value of human use experience in medicine and returns to the essence of medicine as an applied science, thus receiving widespread recognition from both academia and industry. However, it meanwhile poses new and higher challenges. This article delves into the value and challenges faced by the "three-combined" evaluation evidence system from three perspectives: registration management, medical institutions, and the TCM industry. Furthermore, it discusses how the China Association of Chinese Medicine, leveraging its academic platform advantages and leading roles, has made exploratory and practical efforts to facilitate the research and development of new TCM drugs and the implementation of the "three-combined" evaluation evidence system.
Drugs, Chinese Herbal/standards* ; Humans ; Medicine, Chinese Traditional/standards* ; China ; Drug Development

In the present study, a mouse model of coronary artery ligation was employed to evaluate the effects of Jiming Powder on mitophagy in the mouse model of myocardial infarction and elucidate its underlying mechanisms. A mouse model of myocardial infarction post heart failure was constructed by ligating the left anterior descending branch of the coronary artery. The therapeutic efficacy of Jiming Powder was assessed from multiple perspectives, including ultrasonographic imaging, hematoxylin-eosin(HE) staining, Masson staining, and serum cardiac enzyme profiling. Dihydroethidium(DHE) staining was employed to evaluate the oxidative stress levels in the hearts of mice from each group. Mitophagy levels were assessed by scanning electron microscopy and immunofluorescence co-localization. Western blot was employed to determine the levels of key proteins involved in mitophagy, including Bcl-2-interacting protein beclin 1(BECN1), sequestosome 1(SQSTM1), microtubule-associated protein 1 light chain 3 beta(LC3B), PTEN-induced putative kinase 1(PINK1), phospho-Parkinson disease protein(p-Parkin), and Parkinson disease protein(Parkin). The results demonstrated that compared with the model group, high and low doses of Jiming Powder significantly reduced the left ventricular internal diameter in systole(LVIDs) and left ventricular internal diameter in diastole(LVIDd) and markedly improved the left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS), effectively improving the cardiac function in post-myocardial infarction mice. Jiming Powder effectively reduced the levels of myocardial injury markers such as creatine kinase(CK), creatine kinase isoenzyme(CK-MB), and lactate dehydrogenase(LDH), thereby protecting ischemic myocardium. HE staining revealed that Jiming Powder attenuated inflammatory cell infiltration after myocardial infarction. Masson staining indicated that Jiming Powder effectively inhibited ventricular remodeling. Western blot results showed that Jiming Powder activated the PINK1-Parkin pathway, up-regulated the protein level of BECN1, down-regulated the protein level of SQSTM1, and increased the LC3Ⅱ/LC3Ⅰ ratio to promote mitophagy. In conclusion, Jiming Powder exerts therapeutic effects on myocardial infarction by inhibiting ventricular remodeling. The findings pave the way for subsequent pharmacological studies on the active components of Jiming Powder.
Animals ; Myocardial Infarction/physiopathology* ; Mitophagy/drug effects* ; Mice ; Drugs, Chinese Herbal/administration & dosage* ; Protein Kinases/genetics* ; Male ; Ubiquitin-Protein Ligases/genetics* ; Humans ; Disease Models, Animal ; Mice, Inbred C57BL ; Signal Transduction/drug effects*