1.Chinese Medicine Regulates JAK2/STAT3 Signaling Pathway to Treat Ovarian Cancer: A Review
Yue ZHANG ; Danni DING ; Jia LI ; Wenwen MA ; Fengjuan HAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):323-330
Ovarian cancer (OC) is one of the most common malignant tumors in women, with the mortality rate being the highest among gynaecological malignant tumors. As the atypical symptoms of OC are difficult to be detected in the early stage, most patients are already in the advanced stage when being diagnosed. As a result, the clinical treatment has limited effects. Currently, the main therapies for OC are surgery and chemotherapy, while their drug resistance and adverse reactions seriously reduce the quality of life of patients. In recent years, traditional Chinese medicine (TCM) has attracted the attention of clinicians and researchers because of its high efficacy, low toxicity, and mild side effects. According to the TCM philosophy of treatment based on syndrome differentiation, the Chinese medicines with multiple targets, wide range, and mild side effects can be screened based on the molecular targets involved in the occurrence and development of OC, which can bring out the unique advantages of TCM in the treatment of OC. Modern studies have shown that the occurrence and development of OC are closely related to the abnormal expression of multiple signaling pathways. The continued abnormal activation of the signal transducer and activator of transcription 3 (STAT3) signaling pathway can lead to abnormal proliferation and malignancy of OC. cause abnormal proliferation and malignant transformation of OC, which is closely related to the development of OC. In addition, studies have shown that Chinese medicine can inhibit the proliferation, angiogenesis, invasion, and metastasis and promote the autophagy and apoptosis of OC cells by regulating the Janus kinase 2 (JAK2)/STAT3 signaling pathway, providing new therapeutic strategies and ideas for the prevention and treatment of OC. This paper summarizes the role of JAK2/STAT3 signaling pathway in OC development by reviewing the relevant articles and reviews the mechanism and research progress of active components and compound prescriptions of Chinese medicine intervening in OC development by regulating the JAK2/STAT3 signaling pathway. This review is expected to provide a systematic reference for clinical research and drug development of OC.
2.Mechanism of imperatorin in ameliorating doxorubicin resistance of breast cancer based on transcriptomics
Yiting LI ; Wei DONG ; Xinli LIANG ; Hu WANG ; Yumei QIU ; Xiaoyun DING ; Hao ZHANG ; Huiyun BAO ; Xianxi LI ; Xilan TANG
China Pharmacy 2025;36(5):529-534
OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin (IMP) on doxorubicin (DOX) resistance in breast cancer. METHODS The effects of maximum non-toxic concentration (100 μg/mL) of IMP combined with different concentrations of DOX (12.5, 25, 50, 75, 100 μg/mL) on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group (1‰ dimethyl sulfoxide), DOX group (50 μg/mL), IMP+DOX group (100 μg/mL IMP+50 μg/mL DOX) and IMP group (100 μg/mL). mRNA and protein expressions of multidrug resistance protein 1 (MDR1) and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology, along with gene ontology (GO) enrichment analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. RESULTS Compared with DOX alone, the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL, the reverse fold was 1.90, and the mRNA expression of MDR1 was significantly down-regulated (P<0.05). The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification, multiple biological processes, and cell killing. The main pathway involved was the p53 signaling pathway, and the key targets mainly included constitutively photomorphogenic protein 1 (COP1), cyclin E1 (CCNE1), growth arrest and DNA damage-inducible protein 45A E-mail:tangxilan1983@163.com (GADD45A) and GADD45B. The results of the verification experiments showed that compared with DOX group, there was a trend of up-regulation of COP1 mRNA, and significant down- regulation of CCNE1, GADD45A, and GADD45B mRNA expression in IMP+DOX group (P<0.05). CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1, CCNE1, GADD45A and GADD45B targets in the p53 signaling pathway.
3.Prognostic Factors of Liposarcoma in Head and Neck
Shuo DING ; Zhigang HUANG ; Jugao FANG ; Yang ZHANG ; Lizhen HOU ; Wei GUO ; Gaofei YIN ; Qi ZHONG
Cancer Research on Prevention and Treatment 2025;52(1):31-35
Objective To explore the pathogenesis and prognostic factors of liposarcoma in the head and neck region, and simultaneously analyze the efficacy of different treatment regimens. Methods A retrospective analysis was performed on all patients with primary untreated head and neck liposarcoma who were diagnosed and underwent surgical treatment at our hospital from January 2008 to January 2024. All patients were monitored during follow-up, and their prognoses were analyzed using SPSS software. Results A total of 30 patients were included in the study. Liposarcoma accounted for up to 60% of the cases in the orbit, while the remaining liposarcomas were primarily located in various interspaces of the neck. Dedifferentiated liposarcoma was the most common type, comprising 33%, while myxoid pleomorphic liposarcoma was the rarest at 4%. The tumor pathological type (P<0.001) and Ki67 (P=0.014) significantly affected the tumor control rate. However, an analysis of disease-specific survival rates revealed no significant differences across various factors (all P>0.05). Conclusion The prognosis of head and neck liposarcoma is better compared to that of liposarcomas in other parts of the body. However, myxoid pleomorphic liposarcoma, pleomorphic fat sarcoma, and high Ki67 levels are indicators of poor prognosis. Additionally, postoperative adjuvant radiotherapy does not significantly enhance disease-specific survival rates.
4.Mechanism of Icariin in Regulating TGF-β1/Smad Pathway to Induce Autophagy in Human Bone Microvascular Endothelial Cells
Yaqi ZHANG ; Yankun JIANG ; Guoyuan SUN ; Bo LI ; Ran DING ; Cheng HUANG ; Weiguo WANG ; Qidong ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):123-130
ObjectiveTo investigate the regulatory effect of icariin (ICA) on transforming growth factor-β1 (TGF-β1)/Smad pathway in bone microvascular endothelial cells (BMECs) and the effect on autophagy in BMECs. MethodsBMECs were isolated and cultured, and the cell types were identified by immunofluorescence. Cells were divided into the control group, model group (0.1 g·L-1 methyl prednisolone), ICA group (0.1 g·L-1 methyl prednisolone +1×10-5 mol·L-1 ICA), and TGF-β inhibitor group (0.1 g·L-1 methyl prednisolone +1×10-5 mol·L-1 ICA +1×10-5 mol·L-1 LY2157299). Transmission electron microscopy was used to observe the ultrastructure and autophagosome number of BMECs. Autophagy double-standard adenovirus was used to monitor the confocal autophagy flow generation of each cell. Real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the gene and protein expression of autophagy in the TGF-β1/ Smad pathway. ResultsAfter cell separation culture, platelet endothelial cell adhesion molecule (CD31) and von willebrand factor (vWF) immunofluorescence identified BMECs. Transmission electron microscopy showed that the cell membrane was damaged, and the nucleus was pyknotic and broken in the model group. Compared with the model group, the ICA group had complete cell membranes, clear structures, with autophagy-lysosome sparsely distributed. The confocal photo showed that BMECs had autophagosomes and autophagy-lysosomes, and the autophagy expression of the ICA group was similar to that of the blank group. Compared with the blank group, in the model group and the LY2157299 group, autophagosomes and autophagy-lysosomes were barely seen in the autophagy flow. Compared with the blank group, the mRNA and protein expressions of autophagy effector protein 1 (Beclin1) and microtubule-associated protein 1 light chain 3B (LC3B) in the model group were significantly decreased (P<0.01), and those of ubiquitin-binding protein (p62) were significantly increased (P<0.01). The mRNA expression of TGF-β1, Smad homolog 2 (Smad2), and Smad homolog 3 (Smad3) decreased (P<0.05, P<0.01). The protein expressions of TGF-β1, p-Smad2, and p-Smad3 were significantly decreased (P<0.01). Compared with those of the model group, the mRNA and protein expression of Beclin1 and LC3B in BMECs of the ICA group increased (P<0.01), and those of p62 significantly reduced (P<0.01). The mRNA expression of TGF-β1, Smad2, and Smad3 increased significantly (P<0.01). The protein expression of TGF-β1, p-Smad2, and p-Smad3 increased significantly (P<0.01). Compared with those in the model group, the mRNA and protein expressions of Beclin1, LC3B, and p62 in the inhibitor group were not statistically significant. The expression of key genes and proteins of the TGF-β1 pathway in the inhibitor group was not statistically significant. ConclusionICA can promote glucocorticoid-induced autophagy expression of BMECs, and its mechanism may be related to activating the TGF-β1/Smad signaling pathway.
5.Mechanism of Traditional Chinese Medicine in Treating Steroid-Induced Osteonecrosis of Femoral Head via Regulating PI3K/Akt Pathway: A Review
Yaqi ZHANG ; Bo LI ; Jiancheng TANG ; Ran DING ; Cheng HUANG ; Yaping XU ; Qidong ZHANG ; Weiguo WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):141-149
Steroid-induced osteonecrosis of the femoral head (SONFH) is a severe musculoskeletal disorder often induced by the prolonged or excessive use of glucocorticoids. Characterized by ischemia of bone cells, necrosis, and trabecular fractures, SONFH is accompanied by pain, femoral head collapse, and joint dysfunction, which can lead to disability in severe cases. The pathogenesis of SONFH involves hormone-induced osteoblast apoptosis, bone microvascular endothelial cell (BMEC) apoptosis, oxidative stress, and inflammatory responses. The phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway plays a pivotal role in the development of the disease. Modulating the PI3K/Akt signaling pathway can promote Akt phosphorylation, thereby stimulating the osteogenic differentiation of bone marrow mesenchymal stem cells and osteoblasts, promoting angiogenesis in BMECs, and inhibiting osteoclastogenesis. The research on the treatment of SONFH with traditional Chinese medicine (TCM) has gained increasing attention. Recent studies have shown that TCM monomers and compounds have potential therapeutic effect on SONFH by intervening in the PI3K/Akt signaling pathway. These studies not only provide a scientific basis for the application of TCM in the treatment of SONFH but also offer new ideas for the development of new therapeutic strategies. This review summarized the progress in Chinese and international research on the PI3K/Akt signaling pathway in SONFH over the past five years. It involved the composition and transmission mechanisms of the signaling pathway, as well as its regulatory effects on osteoblasts, mesenchymal stem cells, osteoclasts, BMECs, and other cells. Additionally, the review explored the TCM understanding of SONFH and the application of TCM monomers and compounds in the intervention of the PI3K/Akt pathway. By systematically analyzing and organizing these research findings, this article aimed to provide references and point out directions for the clinical prevention and treatment of SONFH and promote further development of TCM in this field. With in-depth research on the PI3K/Akt pathway and the modern application of TCM, it is expected to bring safer and more effective treatment options for patients with SONFH.
6.The Effect of Fuzheng Huaji Formula (扶正化积方) for Chronic Hepatitis B on Reduction of the Incidence of Liver Cirrhosis and Hepatocellular Carcinoma:A Retrospective Cohort Study
Simiao YU ; Jiahui LI ; Jing JING ; Tingting HE ; Yongqiang SUN ; Liping WANG ; Aozhe ZHANG ; Xiaohe XIAO ; Xia DING ; Ruilin WANG
Journal of Traditional Chinese Medicine 2025;66(3):268-274
ObjectiveTo evaluate the clinical efficacy of Fuzheng Huaji Formula (扶正化积方) for chronic hepatitis B to reduce the incidence of liver cirrhosis and hepatocellular carcinoma. MethodsA retrospective cohort study was conducted, collecting medical records of 118 patients with chronic hepatitis B and 234 patients with hepatitis B-related cirrhosis who visited the hospital between January 1, 2014, and December 31, 2018. The use of Fuzheng Huaji Formula was designated as the exposure factor. Patients receiving antiviral treatment for hepatitis B without concurrent Fuzheng Huaji Formula therapy were included in the western medicine group, while those receiving antiviral treatment combined with Fuzheng Huaji Formula for a cumulative treatment lasting longer than 3 months were included in the combined treatment group. The follow-up observation period was five years. Kaplan-Meier survival analysis was used to assess the cumulative incidence of cirrhosis in patients with chronic hepatitis B and the cumulative incidence of hepatocellular carcinoma in patients with hepatitis B-related cirrhosis. Univariate and multivariate Cox regression analyses were employed to examine the factors influencing the occurrence of cirrhosis and hepatocellular carcinoma. ResultsAmong patients with chronic hepatitis B, there were 55 cases in the combined treatment group and 63 cases in the western medicine group; among patients with hepatitis B-related cirrhosis, there were 110 cases in the combined treatment group and 124 cases in the western medicine group. Five-year follow-up outcomes for chronic hepatitis B patients showed that the cumulative incidence of cirrhosis was 5.45% (3/55) in the combined treatment group and 17.46% (11/63) in the western medicine group, with a statistically significant difference between groups (Z = 2.003, P = 0.045). Five-year follow-up outcomes for hepatitis B-related cirrhosis patients showed that the cumulative incidence of hepatocellular carcinoma was 8.18% (9/110) in the combined treatment group and 22.58% (28/124) in the western medicine group, also showing a statistically significant difference (Z = 3.007, P = 0.003). Univariate and multivariate Cox regression analyses indicated that treatment with Fuzheng Huaji Formula is an independent protective factor in preventing the progression of chronic hepatitis B to cirrhosis and the progression of hepatitis B-related cirrhosis to hepatocellular carcinoma (P<0.05). ConclusionCombining Fuzheng Huaji Formula with antiviral therapy for hepatitis B can effectively intervene in the disease progression of chronic hepatitis B, reducing the incidence of cirrhosis and hepatocellular carcinoma.
7.Genetic analysis of weak expression of ABO blood group antigens in neonates
Jiali YANG ; Ding ZHAO ; Wei LI ; Xiaopan ZHANG ; Zhihao LI ; Dongdong TIAN
Chinese Journal of Blood Transfusion 2025;38(1):85-90
[Objective] To perform genetic analysis on samples with weak agglutination and mixed agglutination of ABO blood group antigens in neonates, and to investigate the molecular biological characteristics of ABO subtypes in neonates. [Methods] Serological identification of ABO blood group was performed by tube method and microcolumn gel method. The ABO exons 2-7 were amplified by PCR, and the amplified products were sequenced by Sanger sequencing method to determine the genotype. [Results] Among the ABO blood group serological results of 14 neonates, 8 cases showed weakened A antigen, and 6 cases showed weakened B antigen. Seven samples were identified with ABO subtype alleles, with genotypes as A102/B101+c.538C>T, Aw26/B102, A205/O02, A205/B101(2 cases), Aw26/O02, B(A)06/O01, B101/O01(3 cases), A102/O01(2 cases), A102/B101 and B101/O02. Additionally, three other family members were also found to carry B(A)06 allele in a pedigree investigation. [Conclusion] For samples showing weakened antigens in ABO blood type identification of neonates, it is necessary to consider the possibility of ABO subtype in addition to age factors, and genetic testing can be used to prevent missed detection of ABO subtypes in neonates.
8.Optimization of drug management model for investigator-initiated trial with benchmarking analysis
Yufei XI ; Tianxiao WANG ; Xue ZHANG ; Yingzhuo DING ; Li YAN ; Feng JIANG ; Xiangui HE ; Jiannan HUANG ; Qin LI
China Pharmacy 2025;36(3):280-284
OBJECTIVE To optimize the management model of drugs used in investigator-initiated trial (IIT). METHODS With benchmarking analysis, based on the practical work experience of a tertiary specialized hospital in the field of IIT drug management in Shanghai, a thorough review was conducted, involving relevant laws, regulations, and academic literature to establish benchmark criteria and the evaluation standards. Starting from the initiation of IIT projects, a detailed comparative analysis of key processes was carried out, such as the receipt, storage, distribution, use and recycling of drugs for trial. The deficiencies in the current management of IIT drugs were reviewed in detail and a series of optimization suggestions were put forward. RESULTS It was found that the authorized records of drug management were missing, the training before project implementation was insufficient, and the records of receipt and acceptance of IIT drugs were incomplete. In light of these existing problems, improvement measures were put forward, including strengthening the training of drug administrators and stipulating that only drug administrators with pharmacist qualifications be eligible to inspect and accept drugs, etc. The related systems were improved, and 17 key points of quality control for the management of IIT drugs were developed. CONCLUSIONS A preliminary IIT drug management system for medical institutions has been established, which helps to improve the institutional X2023076) framework of medical institutions in this field.
9.Mechanism of depression-related dry eye based on 5-HT/TRPV4/AQP5
Ying YANG ; Jiazhi ZHANG ; Huijie JI ; Yuanchen DING ; Weiping GAO
International Eye Science 2025;25(3):372-377
AIM:To investigate the mechanism of reduced tear secretion in depression-related dry eye rats based on 5-HT/TRPV4/AQP5.METHODS:Healthy SD male rats were established with chronic unpredictable mild stress(CUMS)method to establish a depression-induced dry eye model(n=8), and the control group was blank rats(n=8). The ELISA method was used to compare the 5-hydroxytryptamine(5-HT)in serum and hippocampal tissue of the two groups, and the HE sections of lacrimal gland and AQP5 immunohistochemistry were observed. Western blot and RT-PCR were used to detect the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland tissue of the two groups of rats.RESULTS:The tear secretion in the depression-induced group was significantly reduced(P=0.001), the serum and hippocampal 5-HT levels were significantly reduced(all P<0.05), the expression of AQP5 antibody in the lacrimal gland immunohistochemistry was significantly lower than that in the control group(P<0.001), the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland was significantly reduced(all P<0.05), and no obvious inflammatory cells were found in the lacrimal gland tissue sections.CONCLUSION:Depression-related dry eye may occur through a non-inflammatory 5-HT/TRPV4/AQP5 mechanism.
10.Mechanism of depression-related dry eye based on 5-HT/TRPV4/AQP5
Ying YANG ; Jiazhi ZHANG ; Huijie JI ; Yuanchen DING ; Weiping GAO
International Eye Science 2025;25(3):372-377
AIM:To investigate the mechanism of reduced tear secretion in depression-related dry eye rats based on 5-HT/TRPV4/AQP5.METHODS:Healthy SD male rats were established with chronic unpredictable mild stress(CUMS)method to establish a depression-induced dry eye model(n=8), and the control group was blank rats(n=8). The ELISA method was used to compare the 5-hydroxytryptamine(5-HT)in serum and hippocampal tissue of the two groups, and the HE sections of lacrimal gland and AQP5 immunohistochemistry were observed. Western blot and RT-PCR were used to detect the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland tissue of the two groups of rats.RESULTS:The tear secretion in the depression-induced group was significantly reduced(P=0.001), the serum and hippocampal 5-HT levels were significantly reduced(all P<0.05), the expression of AQP5 antibody in the lacrimal gland immunohistochemistry was significantly lower than that in the control group(P<0.001), the expression of 5-HT3R, TRPV4 and AQP5 in the lacrimal gland was significantly reduced(all P<0.05), and no obvious inflammatory cells were found in the lacrimal gland tissue sections.CONCLUSION:Depression-related dry eye may occur through a non-inflammatory 5-HT/TRPV4/AQP5 mechanism.

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