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Weichang'an and 5-fluorouracil suppresses colorectal cancer in a mouse model

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World Journal of Gastroenterology 2015年第4期21卷 1125-1139页

作者： Li Tao Jin-Kun Yang Ying Gu Xin Zhou Ai-Guang Zhao Jian Zheng Ying-Jie Zhu Department of Oncology Longhua Hospital Shanghai University of Traditional Chinese Medicine Department of Pharmacy Longhua HospitalShanghai University of Traditional Chinese Medicine

AIM: To examine the effect of Weichang'an(WCA) and 5-fluorouracil(5-Fu) on colorectal tumor and hepatic metastasis in a mouse model. METHODS: Quantitative determination of hesperidin, the effective component in WCA decoction, was performed using Hp LC. In vitro cytotoxicity of WCA was determined by treating HCT-116 cells with WCA diluents or serum extracted from rats that received WCA by oral gavage for 1 wk and MTT assays. Forty-eight nude mice received cecum implantation with tumor blocks subcutaneously amplified from human colon cancer cell line HCT-116. Mice were randomly divided into four treatment groups: control(CON), WCA, 5-Fu and combination(WCA + 5-Fu). pathological examination of tumors consisted of tissue sectioning and hematoxylin and eosin staining. Tumor weight and size were measured, and the number of metastatic l e s i o n s wa s c o u n t e d. S e r u m c a r c i n o e m b r yo n i c antigen(CEA) level was determined by ELISA. The expression levels of tumor genesis and metastasisrelated proteins β-catenin and matrix metalloproteinase(MMp)-7 were measured by real-time quantitative reverse transcriptase polymerase chain reaction(RTp CR), immunohistochemistry and immunoblotting. Cell fractionation was used to investigate intracellular distribution of β-***: parenchymal tumors were palpable in the abdomens of nude mice 2 wk post-implantation and orthotopic tumor formation rate was 100% in all groups. 5-Fu treatment alone significantly decreased tumor weight compared to the CON group(1.203 ± 0.284 g vs 1.804 ± 0.649 g, p < 0.01). WCA treatment alone reduced the rate of metastasis(50% vs 100%,p < 0.05). Combination treatment of WCA + 5-Fu was the most effective, reducing the tumor weight(1.140 ± 0.464 g vs 1.804 ± 0.649 g, p < 0.01) and size(1493.438 ± 740.906 mm3 vs 2180.259 ± 816.556 mm3, p < 0.05), the rate of metastases(40% vs 100%, p < 0.01), and serum CEA levels(31.263 ± 7.421 μg/L vs 43.040 ± 11.273 μg/L, p < 0.05). Expression of β-cat

关键词： Colorectal cancer Hepatic metastasis Weichang’an f

Astragaloside IV Regulates Expression of ATP-sensitive Potassium Channel Subunits after Ischemia-reperfusion in Rat Ventricular Cardiomyocytes

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Journal of Traditional Chinese Medicine 2011年第4期31卷 321-326页

作者：韩向晖刘萍章怡祎张娜陈富荣蔡珏峰 Scientific Research Center Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine Department of Science and Technology Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

Objective: Astragaloside IV (AsIV) is the major effective component extracted from the Chinese herb Astragalus membranaceus, which has been widely used to treat cardiovascular disease. Recent studies have shown that AsIV can potentially protect the heart from myocardial ischemic injury, but the mechanisms of action are unknown. ATP-sensitive potassium (KATP) channels are activated during ischemia and exert a compensatory protective effect on cardiomyocytes. We therefore examined the effects of AsIV on KATP channel currents and channel expression in isolated rat ventricular cardiomyocytes after ischemia-reperfusion injury. Methods: Forty Wistar rats were divided into five groups: control group, ischemia-reperfusion (IP) group, IP + glibenclamide group, IP + pinacidil group and IP + AsIV group. The ischemia-reperfusion injury model was established in enzymatically isolated ventricular cardiomyocytes by perfusion with calcium-free Tyrode solution for 10 min, arrest for 30 min, and reperfusion for 45 min. The different drugs were applied for 10-15 min, and the KATP channel current (IKATP) was recorded with voltage-clamp mode by whole-cell patch-clamp technique. Protein and mRNA expression of the KATP channel subunits Kir6.1, Kir6.2, SUR2A and SUR2B was quantified using western blotting and real-time PCR. Results: The KATP current in IP group was significantly greater than that in control group (211.45±33.67 vs 83.51±23.67 pA; P<0.01). Glibenclamide (10 μmol/L) blocked KATP currents, whereas both AsIV (1 mg/L) and the known channel opener pinacidil (50 μmol/L) significantly increased IKATP (P<0.05). Consistent with this, AsIV significantly up-regulated protein and mRNA expression of Kir6.1, Kir6.2, SUR2A, SUR2B (P<0.01 vs IP group). Conclusion: The protective effects of AsIV in ischemia-reperfusion injury may be related to the up-regulation of several KATP channel subunits and facilitation of KATP currents.

关键词： Astragaloside IV pinacidil myocardial ischemia-reperfusion KATP channels

Systems pharmacology approach reveals the antiinflammatory effects of Ampelopsis grossedentata on dextran sodium sulfate-induced colitis

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World Journal of Gastroenterology 2018年第13期24卷 1398-1409页

作者： You-Lan Chen Ya-Li Zhang Yan-Cheng Dai Zhi-Peng Tang Institute of Digestive Disease Longhua Hospital Shanghai University of Traditional Chinese Medicine Department of Gastroenterology Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine

AIM To investigate the protective effects of Ampelopsis grossedentata(AMP) on dextran sulfate sodium(DSS)-induced colitis in mice based on systems pharmacology *** Systems pharmacology approach was used to predict the active ingredients, candidate targets and the efficacy of AMP on ulcerative colitis(UC) using a holistic process of active compound screening, target fishing, network construction and analysis. A DSSinduced colitis model in C57 BL/6 mice(n = 10/group) was constructed and treated with 5-aminosalicylic acid(100 mg/kg/d) and AMP(400 mg/kg/d) to confirm the underlying mechanisms and effects of AMP on UC with western blot analyses, polymerase chain reaction, histological staining and *** The therapeutic effects of AMP against DSS-induced colitis were determined in the beginning, and the results showed that AMP significantly improved the disease in general observations and histopathology analysis. Subsequent systems pharmacology predicted 89 corresponding targets for the four candidate compounds of AMP, as well as 123 candidate targets of UC, and protein-protein interaction networks were constructed for the interaction of putative targets of AMP against UC. Enrichment analyses on TNF-α and RANKL/RANK, a receptor activator of NF-κB signaling pathways, were then carried out. Experimental validation revealed that inflammation-related signaling pathways were activated in the DSS group, and AMP significantly suppressed DSS-induced high expression of IRAK1, TRAF6, IκB and NF-κB, and inhibited the elevated expression levels of TNF-α, IL-1β, IL-6 and *** AMP could exert protective effects on UC via suppressing the IRAK1/TRAF6/NF-κB-mediated inflammatory signaling pathways.

关键词： Ulcerative colitis Ampelopsis grossedentata Traditional Chinese medicine Systems pharmacology Inflammation

Goodpasture syndrome and hemorrhage after renal biopsy: A case report

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World Journal of Clinical Cases 2020年第2期8卷 404-409页

作者： Wei-Long Li Xi Wang Shu-Yuan Zhang Zi-Gan Xu Ying-Wei Zhang Xing Wei Chun-Di Li Ping Zeng Shao-Dong Luan Department of Nephrology Shenzhen Longhua District Central Hospital

BACKGROUND Goodpasture syndrome(GS) is a rare disease, the morbidity of which is estimated to be 0.5-0.8 per million per year. Hemorrhage is the most serious complication in renal biopsy. Despite the fact that both GS and hemorrhage after renal biopsy are rare, it has not been reported that they are likely to occur in the same *** SUMMARY A 30-year-old man with diffuse pulmonary hemorrhage and rapid progressive renal function caused by anti-glomerular basement membrane disease presented atypical symptoms without hemoptysis, accompanied by life-threatening hypoxemia. Plasmapheresis was performed, and glucocorticoids and cyclophosphamide were administered. The patient started to show signs of improvement. Percutaneous renal biopsy is an appropriate diagnostic measure that is commonly safe, but this patient experienced hemorrhage after operation,thus necessitating embolization of the renal artery to stop the bleeding. The patient’s condition was improved, and the serum anti-glomerular basement membrane antibody level was 106 AU/m L(normal range: < 24 AU/m L) and slowly decreased. His discharge medications were oral daily prednisone(30 mg)and continued maintenance *** GS is a rare organ-specific autoimmune disease that is invariably ubiquitous in the lung and kidney areas. Renal biopsy is the appropriate procedure for the treatment of GS disease, although it is an invasive measure.

关键词： Goodpasture disease Anti-glomerular basement membrane disease Renal biopsy Hemorrhage Glomerular basement membrane Case report

Oleanolic acid inhibits colon cancer cell stemness and reverses chemoresistance by suppressing JAK2/STAT3 signaling pathway

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BIOCELL 2024年第7期48卷 1037-1046页

作者： RUOYU CHEN YIMAN WU FENG WANG JUNTAO ZHOU HUAZHANG ZHUANG WEI LI Department of Anus and Intestine Surgery Shenzhen Longhua District Central HospitalShenzhenChina Department of Urology Shenzhen Longhua District Central HospitalShenzhenChina

Background:Oleanolic acid(OA),a pentacyclic triterpenoid exhibiting speciﬁc anti-cancer properties and highly effective antioxidant activity,was isolated from traditional Chinese medicinal ***,the OA that impacts colon cancer(CC)cells and its underlying mechanisms remain poorly ***:The cytotoxic effect of OA alone or OA-5-Fluorouracil(5-FU)combination on normal and CC cells was analyzed by methyl thiazolyl diphenyl-tetrazolium bromide(MTT).Then,the impact of OA on CC cell lines(LoVo and HT-29)proliferation and stemness were measured using colon formation and tumorsphere formation ***-binding transcription factor 4(Oct4),Prominin-1(CD133),Nanog,and transcription factor SOX-2(SOX2)are cell stemness-related indicators whose expression was assessed usingﬂuorescence qPCR assay,Western blotting,and *** effect of OA on the proliferative potency of CC cells was evaluated using an in vivo ***:The stem-like characteristics and clone production of colon cancer cells were markedly reduced by OA alone or in combination with ***,OA increases the susceptibility of CC cells to 5-FU by blocking the cell stemness-related markers(CD133,Nanog,SOX2,and Oct4)expression levels both in vitro and in vivo,as well as by inactivating the activator of transcription 3(STAT3 signaling)and Janus kinase 2/signal transducer(JAK2).Conclusion:Theseﬁndings imply that oleanolic acid,both in vitro and in vivo,suppresses the JAK2/STAT3 pathway,which in turn reverses chemoresistance and decreases colon cancer cell ***,by reducing the recommended amount of 5-FU,this strategy may improve chemotherapeutic effectiveness and minimize undesired side effects.

关键词： Colon cancer,Oleanolic acid,Stemness,5-FU JAK2/STAT3 signaling pathway

Gitelman syndrome:A case report

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World Journal of Clinical Cases 2022年第17期10卷 5893-5898页

作者： Shi-Yuan Chen Ning Jie Department of Endocrinology Longhua Central HospitalShenzhen 518110Guangdong ProvinceChina

BACKGROUND Gitelman syndrome(GS)is an autosomal recessive salt-losing renal tubulopathy arising from mutations in the thiazide-sensitive Na-Cl cotransporter *** to its low incidence and lack of awareness,GS can be easily misdiagnosed or missed in *** SUMMARY A 24-year-old male presented with>4 years of repeated limb weakness without any *** previous day,the patient was bitten by ants and showed weakness of the lower *** patient had hypokalemia(1.66-2.83 mmol/L),hypomagnesemia(0.4 mmol/L),hypocalciuria(1.51-2.46 mmol/d),metabolic alkalosis(7.47-7.54),normal blood pressure,and increased activity of aldosterone and plasma renin activity(PRA)(PRA 6.4 and 16.45 ng/mL/h and aldosterone 330.64 and 756.82 pg/mL in the supine and upright position,respectively).In addition,SLCI2A3 gene mutation with GS was *** and intravenous supplementation with potassium and magnesium was *** magnesium returned to 0.48 mmol/L and serum potassium returned to 3.08 mmol/L,alleviating the patient’s fatigue *** GS should be considered in patients with hypokalemia complicated with *** testing is essential to confirm the diagnosis.

关键词： Gitelman syndrome Limb weakness Hypokalemia Hypomagnesemia Hypocalciuria Genetic testing Case report

Efficacy of the herbal pair, Radix Achyranthis Bidentatae and Eucommiae Cortex, in preventing glucocorticoid-induced osteoporosis in the zebrafish model

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Journal of Integrative Medicine 2022年第1期20卷 83-90页

作者： Joon-ho Lee Yuan-ji Wei Zhong-yan Zhou Yu-ming Hou Cheng-long Wang Li-bo Wang Hong-jin Wu Yu Zhang Wei-wei Dai Central Laboratory of Science and Technology Department Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Cardiovascular Department Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China

Objective: In traditional Chinese medicine, the herbal pair, Radix Achyranthis Bidentatae(RAB) and Eucommiae Cortex(EC), is widely used to treat osteoporosis. Herein, we determined whether this herbal pair can be used to ameliorate glucocorticoid(GC)-induced osteoporosis(GIOP) and find its optimal dosage in ***: The characteristics of the aqueous extract of RAB and EC were separately characterized using high-performance liquid chromatography. Osteoporosis was induced in 5-day post-fertilization zebrafish larvae by exposing them to 10 lmol/L dexamethasone(Dex) for 96 h. Seven combinations of different ratios of RAB and EC were co-administered. Treatment efficacy was determined by calculating zebrafish vertebral area and sum brightness, via alizarin red staining, and by detecting alkaline phosphatase(ALP)activity. Multiple regression analysis was conducted to test the optimal dosage ***: According to the Chinese Pharmacopoeia(2015), b-ecdysone(b-Ecd) is a major bioactive marker in RAB extract, while pinoresinol diglucoside(PDG) is the major marker in EC extract. Both of b-Ecd and PDG content values aligned with the Chinese Pharmacopoeia standards. Treatment with 10 lmol/L Dex reduced zebrafish vertebral area, sum brightness, and ALP activity, but RAB and EC attenuated these effects. Combining 50 mg/m L RAB and 50 mg/m L EC was optimal for preventing GIOP in *** transcription-quantitative polymerase chain reaction was used to evaluate the m RNA expression of osteogenesis-related genes. A treatment of 10 lmol/L Dex decreased runt-related transcription factor 2(Runx2), osteogenic protein-1(OP-1), bone c-carboxyglutamic acid-containing protein(BGLAP), and bcatenin levels. This effect was counteracted by RAB and EC co-treatment(P < 0.05). Additionally, the effect of using the two herbal extracts together was better than single-herb treatments separately. These results demonstrated that RAB and EC preserve osteoblast function in the pre

关键词： Glucocorticoid Osteoporosis Radix Achyranthis Bidentatae Eucommiae Cortex Zebrafish

Function,mechanism and drug discovery of ubiquitin and ubiquitin-like modification with multiomics profiling for cancer therapy

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Acta Pharmaceutica Sinica B 2023年第11期13卷 4341-4372页

作者： Yanyu Jiang Shuaishuai Ni Biying Xiao Lijun Jia Cancer Institute Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China

Ubiquitin(Ub)and ubiquitin-like(Ubl)pathways are critical post-translational modifications that determine whether functional proteins are degraded or activated/*** date,>600 associated enzymes have been reported that comprise a hierarchical task network(e.g.,E1–E2–E3 cascade enzymatic reaction and deubiquitination)to modulate substrates,including enormous oncoproteins and tumor-suppressive *** strategies,such as classical biochemical approaches,multiomics,and clinical sample analysis,were combined to elucidate the functional relations between these enzymes and *** this regard,the fundamental advances and follow-on drug discoveries have been crucial in providing vital information concerning contemporary translational efforts to tailor individualized treatment by targeting Ub and Ubl ***,emphasizing the current progress of Ub-related pathways as therapeutic targets in cancer is deemed *** the present review,we summarize and discuss the functions,clinical significance,and regulatory mechanisms of Ub and Ubl pathways in tumorigenesis as well as the current progress of small-molecular drug *** particular,multiomics analyses were integrated to delineate the complexity of Ub and Ubl modifications for cancer *** present review will provide a focused and up-to-date overview for the researchers to pursue further studies regarding the Ub and Ubl pathways targeted anticancer strategies.

关键词： Ub and Ubl modifications Ub-activating enzyme Ub-conjugating enzyme Ub ligase Multiomics analyses Drug discovery Small molecule inhibitor Molecular glue

Topic Modeling Analysis of Chinese Medicine Literature on Potential Treatment

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Chinese Journal of Integrative Medicine 2024年第12期30卷 1128-1136页

作者： QIAN Jia-nan KANG Yan-lan HE You-cheng HU Hong-yi Department of Gastroenterology Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Institute of Digestive Diseases Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China Institute of Al and Robotics Academy for Engineering&TechnologyFudan UniversityShanghai 200433China Clinical Research Center Longhua HospitalShanghai 200032China

Objective:To analyze Chinese medicine(CM)prescriptions for gastroesophageal reflux disease(GERD),we model topics on GERD-related classical CM literature,providing insights into the potential ***:Clinical guidelines were used to identify symptom terms for GERD,and CM literature from the database"Imedbooks"was retrieved for related prescriptions and their corresponding sources,indications,and other *** was applied to identify the main topics and visualize the ***:A total of 36,207entries are queried and 1,938 valid entries were acquired after manually *** topics were identified by BERTopic,including digestion function abate,stomach flu,respiratory-related symptoms,gastric dysfunction,regurgitation and gastrointestinal dysfunction in pediatric patients,vomiting,stroke and alcohol accumulation are associated with the risk of GERD,vomiting and its causes,regurgitation,epigastric pain,and symptoms of ***:Topic modeling provides an unbiased analysis of classical CM literature on GERD in a time-efficient and scale-efficient *** on this analysis,we present a range of treatment options for relieving symptoms,including herbal remedies and non-pharmacological interventions such as acupuncture and dietary therapy.

关键词： gastroesophageal reflux disease BERTopic prescription topic modeling Chinese medicine