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Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway:a potential therapeutic approach for neurodegenerative diseases

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Neural Regeneration Research 2025年第11期20卷 3095-3112页

作者： Fengcheng Deng Dan Yang Lingxi Qing Yifei Chen Jilian Zou Meiling Jia Qian Wang Runda Jiang Lihua Huang college of Pharmacy Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina State Key Laboratory of Southwestern chinese medicine Resources Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina

The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain *** gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine ***,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host *** reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological *** coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological *** study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological *** pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional *** can be achieved through various methods such as dietary modifications,probiotic supplements,chinese herbal extracts,combinations of chinese herbs,and innovative dosage *** findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

关键词： cyclic adenosine monophosphate emotional disorders gut microbiota neurodegenerative diseases neurological diseases protein kinase A reciprocal regulation signaling pathway strategy therapies

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Deep learning identification of novel autophagic protein-protein interactions and experimental validation of Beclin 2-Ubiquilin 1 axis in triple-negative breast cancer

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Oncology Research 2025年第1期33卷 67-81页

作者： XIANG LI WENKE JIN LIFENG WU HUAN WANG XIN XIE WEI HUANG BO LIU State Key Laboratory of Southwestern chinese medicine Resources School of Pharmacy and College of Medical TechnologyChengdu University of Traditional Chinese MedicineChengdu611137China Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu610041China

Background:Triple-negative breast cancer(TNBC),characterized by its lack of traditional hormone receptors and HER2,presents a significant challenge in oncology due to its poor response to conventional *** is an important process for maintaining cellular homeostasis,and there are currently autophagy biomarkers that play an effective role in the clinical treatment of *** contrast to targeting protein activity,intervention with proteinprotein interaction(PPI)can avoid unrelated crosstalk and regulate the autophagy process with minimal interference ***:Here,we employed Naive Bayes,Decision Tree,and k-Nearest Neighbors to elucidate the complex PPI network associated with autophagy in TNBC,aiming to uncover novel therapeutic ***,the candidate proteins interacting with Beclin 2 were initially screened in MDA-MB-231 cells using Beclin 2 as bait protein by immunoprecipitation-mass spectrometry assay,and the interaction relationship was verified by molecular docking and CO-IP experiments after *** formation,cellular immunofluorescence,cell scratch and 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)tests were used to predict the clinical therapeutic effects of manipulating candidate ***:By developing three PPI classification models and analyzing over 13,000 datasets,we identified 3733 previously unknown autophagy-related *** network analysis revealed the central role of Beclin 2 in autophagy regulation,uncovering its interactions with 39 newly identified ***,the CO-IP studies identified the substantial interaction between Beclin 2 and Ubiquilin 1,which was anticipated by our model and discovered in immunoprecipitation-mass spectrometry assay ***,in vitro investigations showed that overexpressing Beclin 2 increased Ubiquilin 1,promoted autophagy-dependent cell death,and inhibited proliferation and metastasis in MDA-MB-231 ***:This study not

关键词： Triple-negative breast cancer(TNBC) Autophagy Protein-protein interactions(PPI) Artificial intelligence(AI) Beclin 2 Ubiquilin 1

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Decline and fall of aging astrocytes:the human perspective

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Neural Regeneration Research 2025年第6期20卷 1713-1714页

作者： Alexei Verkhratsky Alexey Semyanov Faculty of Biology Medicine and HealthThe University of ManchesterManchesterUK Department of Neurosciences University of the Basque Country UPV/EHU and CIBERNEDLeioaSpain Department of Forensic Analytical Toxicology School of Forensic MedicineChina Medical UniversityShenyangLiaoning ProvinceChina Department of Stem Cell Biology State Research Institute Centre for Innovative MedicineVilniusLithuania International Collaborative Center on Big Science Plan for Purinergic Signalling Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina Department of Physiology Jiaxing University College of MedicineJiaxingZhejiang ProvinceChina

“Last scene of all that ends this strange,eventful history,is second childishness and mere oblivion.I am sans teeth,sans eyes,sans taste,sans everything.”William Shakespeare‘As You Like It'Act 2,Sc.7,l.139Aging of the human brain is characterized by a progressive decline of its functional capacity;this decline however varies widely,and cognitive longevity differs substantially between individuals.

关键词： aging teeth progressive

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Potassium dehydroandrographolide succinate regulates the MyD88/CDH13 signaling pathway to enhance vascular injuryinduced pathological vascular remodeling

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chinese Journal of Natural medicines 2024年第1期22卷 62-74页

作者： GUO Qiru LI Jiali WANG Zheng WU Xiao JIN Zhong ZHU Song LI Hongfei ZHANG Delai HU Wangming XU Huan YANG Lan SHI Liangqin WANG Yong college of Basic medicine Chengdu University of Traditional Chinese MedicineChengdu 610000China chengdu university of traditional chinese medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610000China

Pathological vascular remodeling is a hallmark of various vascular *** research has established the significance of andrographolide in maintaining gastric vascular homeostasis and its pivotal role in modulating endothelial barrier dysfunction,which leads to pathological vascular *** dehydroandrographolide succinate(PDA),a derivative of andrographolide,has been clinically utilized in the treatment of inflammatory diseases precipitated by viral *** study investigates the potential of PDA in regulating pathological vascular *** effect of PDA on vascular remodeling was assessed through the complete ligation of the carotid artery in C57BL/6 *** approaches,including rat aortic primary smooth muscle cell culture,flow cytometry,bromodeoxyuridine(BrdU)incorporation assay,Boyden chamber cell migration assay,spheroid sprouting assay,and Matrigel-based tube formation assay,were employed to evaluate the influence of PDA on the proliferation and motility of smooth muscle cells(SMCs).Molecular docking simulations and co-immunoprecipitation assays were conducted to examine protein *** results revealed that PDA exacerbates vascular injury-induced pathological remodeling,as evidenced by enhanced neointima *** treatment significantly increased the proliferation and migration of *** mechanistic studies disclosed that PDA upregulated myeloid differentiation factor 88(MyD88)expression in SMCs and interacted with T-cadherin(CDH13).This interaction augmented proliferation,migration,and extracellular matrix deposition,culminating in pathological vascular *** findings underscore the critical role of PDA in the regulation of pathological vascular remodeling,mediated through the MyD88/CDH13 signaling pathway.

关键词： Potassium dehydroandrographolide succinate Smooth muscle cell Myeloid differentiation factor 88 T-cadherin Pathological vascular remodeling

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Mechanistic evaluation of gastro-protective effects of KangFuXinYe on indomethacin-induced gastric damage in rats

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chinese Journal of Natural medicines 2020年第1期18卷 47-56页

作者： LI Qi-Juan WANG Zhan-Guo XIE Yu LIU Qiao HU Hui-Ling GAO Yong-Xiang college of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China Metabonomics Synergy Innovation Laboratory School of Medicine and NursingChengdu UniversityChengdu 610106China college of Basic medicine Chengdu University of Traditional Chinese MedicineChengdu 611137China

KangFuXinYe(KFX),the ethanol extract of the dried whole body of Periplaneta americana,is a well-known important chinese medicine preparation that has been used to treat digestive diseases such as gastric ulcers for many years in ***,its therapeutic effect and mechanism are not yet well ***,the aim of this study was to investigate the gastroprotective effects of KangFuXinYe(KFX)in indomethacin-induced gastric *** were randomly divided into six groups as follows:control,treated with indomethacin(35 mg·kg^-1),different dosages of KFX(2.57,5.14 and 10.28 mL·kg^-1,respectively)plus indomethacin,and sucralfate(1.71 mL·kg^-1)plus *** treatment,rat serum,stomach and gastric homogenates were collected for biochemical tests and examination of histopathology *** serum was further used for metabolomics analysis to research possible *** results showed that KFX treatment alleviated indomethacin-induced histopathologic damage in rat gastric ***,its treatment significantly increased cyclooxygenase-1(COX-1),prostaglandin E2(PGE2)and epidermal growth factor(EGF)levels in rat serum and gastric ***,KFX decreased cyclooxygenase-2(COX-2)and interleukin-6(IL-6)*** metabolites were identified which intensities significantly changed in gastric damage rats,including 5-hydroxyindoleacetic acid,indoxylsulfuric acid,indolelactic acid,4-hydroxyindole,pantothenic acid,isobutyryl carnitine,3-methyl-2-oxovaleric acid,sphingosine 1-phosphate,and *** metabolic deviations came to closer to normal levels after KFX *** results indicate that KFX(10.28 mL·kg^-1)exerts protective effects on indomethacin-induced gastric damage by possible mechanisms of action(regulating tryptophan metabolism,protecting the mitochondria,and adjusting lipid metabolism,and reducing excessive indomethacin).

关键词： KangFuXinYe Indomethacin-induced gastric damage Inflammation Metabonomic analysis

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Targeting STAT3 with SH-4-54 suppresses stemness and chemoresistance in cancer stem-like cells derived from colorectal cancer

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World Journal of Clinical Oncology 2025年第2期16卷 63-75页

作者： Xu-Fan Zhang Qian Chen Qin Jiang Qiong-Ying Hu Department of Nuclear medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina college of Medical Technology Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina Department of Laboratory medicine Hospital of Mianyang Traditional Chinese MedicineChengdu 641000Sichuan ProvinceChina Department of Laboratory medicine Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072Sichuan ProvinceChina

BACKGROUND Over the years,the numbers of treatment options for colorectal cancer(CRC)have increased,leading to notable improvements in the overall survival of CRC *** therapy may initially yield positive results,the development of drug resistance can result in treatment failure and cancer *** resistance is often attributed to the presence of cancer stem cells(CSCs).These CSCs not only contribute to therapeutic resistance but also play crucial roles in the initiation and development of tumor *** To investigate the antitumor effects of SH-4-54,which are mediated by targeting CSCs relative to treatment *** CSCs were enriched by culturing CRC cells in serum-free *** of stemness and IL-6/JAK2/STAT3 signaling were detected by Western *** of CSC malignancy,including proliferation,invasion,and tumor formation,were *** In this study,we employed SH-4-54,which exhibits anticancer activity in solid tumors through targeting the SH2 domain of both the signal transducer and activator of transcription(STAT)3 and the STAT5,and evaluated its effects on stemness and chemoresistance in colorectal *** expected,SH-4-54 treatment inhibited the phosphorylation of STAT3(p-STAT3)and decreased the percentage of ALDH1A1-positive CRC *** addition of SH-4-54 dissociated colorectal spheroids and decreased the expression of stemness markers,including ALDH1A1,CD44 and ***-4-54 treatment decreased IL-6/JAK2/STAT3 signaling by inhibiting p-STAT3 and thus inhibited spheroid formation by SW480 and LoVo ***,SH-4-54 treatment inhibited indicators of malignancy,including cell proliferation,invasion,and tumor formation,in CSCs in vitro and in ***,SH-4-54 treatment significantly increased chemosensitivity to *** Taken together,these results indicate that SH-4-54 is a promising molecule that exerts antitumor effects on colorectal CSCs by inhibiting STAT3 signaling.

关键词： SH-4-54 Colorectal cancer Cancer stem-like cells Stemness Chemosensitivity

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Current Situation and Evaluation of Clinical Studies on Acupuncture and Moxibustion Treatment of Peripheral Facial Paralysis at Selected Stages

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Journal of traditional chinese medicine 2010年第2期30卷 153-159页

作者：李瑛吴曦胡卡明陈晓琴王友京 college of Acupuncture & Tuina Chengdu University of Traditional Chinese Medicine Department of Acupuncture & Moxibustion Affiliated Hospital of Chengdu University of Traditional Chinese Medicine Graduate Student of 2006 College of Acupuncture & TuinaChengdu University of Traditional Chinese Medicine

Peripheral facial paralysis is a frequently encountered disease with a high incidence, and it is one of the most common diseases in acupuncture and moxibustion treatment. Because there are rich

关键词：针灸治疗临床评价治疗效果发病率疾病艾灸

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traditional Uses,Phytochemistry,Pharmacology and Toxicology of Rhizoma phragmitis:A Narrative Review

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chinese Journal of Integrative medicine 2022年第12期28卷 1127-1136页

作者： REN Yuan CUI Ge-dan HE Li-sha YAO Huan ZI Chang-yan GAO Yong-xiang Department of Rheumatology Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610072China School of Basic medicine Chengdu University of Traditional Chinese MedicineChengdu 611130China International Education college Chengdu University of Traditional Chinese MedicineChengdu 610075China

Rhizomaphragmitis isa common chinese herbal medicine whose effects are defined as'clearing heat and fire,promoting fluid production to quench thirst,eliminating irritability,stopping vomiting,and disinhibiting *** the Novel Coronavirus epidemic in 2020,the Weijing Decoction and Wuye Lugen Decoction,with Rhizoma phragmitis as the main herbal component,were included in The Pneumonia Treatment Protocol for Novel Coronavirus Infection(Trial Version 5)due to remarkable antiviral *** pharmacological studies have shown that Rhizoma phragmitis has antiviral,antioxidative,anti-inflammatory,analgesic,and hypoglycemic functions,lowers blood lipids and protects the liver and *** review aims to provide a systematic summary of the botany,traditional applications,phytochemistry,pharmacology and toxicology of Rhizoma phragmitis.

关键词： Rhizoma phragmitis pharmacology phytochemistry chinese medicine

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Synchronous Dynamic Research on Respiratory and Intestinal Microflora of Chronic Bronchitis Rat Model

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chinese Journal of Integrative medicine 2017年第3期23卷 196-200页

作者： ZHENG Xiu-li YANG Yu WANG Bao-jia WANG Ju TANG Hong-qu college of Basic medicine Chengdu University of Traditional Chinese Medicine

Objective： To investigate the mechanism of the chinese medicine theory that Fei（Lung） and Dachang（Large Intestine） are exteriorly and interiorly related via synchronous observation on the dynamic changes of the respiratory and intestinal microflora. Methods： Forty specific pathogen free Sprague-Dawley rats were selected and randomly divided into blank（10 rats） and chronic bronchitis model groups（30 rats）. The blank group rats were put into the smoke-free environment and the model group rats were put into the smoke environment in order to establish pulmonary disease（chronic bronchitis） model. Then the corresponding changes of the respiratory and intestinal microflora of the model on 20th, 50th and 70th days were synchronously observed. Results： The respiratory tract microflora showed an increase in the total aerobic and Staphylococcus aureus and reduced anaerobic amount significantly on 20th day in the respiratory tract microflora（P〈0.05 or 0.01）. On 50th day, total aerobic, total anaerobic amount and bifidobacterium significantly increased（P〈0.05）. On 70th day, Staphylococcus aureus reduced and lactobacillus increased significantly（P〈0.01）. The intestinal microflora showed an increase in the total aerobic, Clostridium perfringens, enterobacter and enterococcus significantly increased on 20th day（P〈0.05 or 0.01）. Staphylococcus aureus on 50th day increased significantly（P〈0.05）. Total aerobic and enterococcus increased, total anaerobic and Clostridium perfringens reduced significantly on 70th day（P〈0.05 or 0.01）. Conclusions： The microecosystem of respiratory tract and intestine of rat model during the pathological process showed a dynamic disorder, indicating an interaction between the lung and large intestine which may be one of the connotations as they exteriorly and interiorly related.

关键词： respiratory intestinal pulmonary disease microflora micro-ecology chronic bronchitis chinese medicine theory

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Stationary Treatment Compared with Individualized chinese medicine for Type 2 Diabetes Patients with Microvascular Complications:Study Protocol for a Randomized Controlled Trial

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chinese Journal of Integrative medicine 2018年第10期24卷 728-733页

作者： HUO Jian LIU Li-sha JIAN Wen-yuan ZENG Jie-ping DUAN Jun-guo LU Xue-jing YIN Shuo college of Ophthalmology Chengdu University of Traditional Chinese Medicine Good Clinical Practice Center the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine

Background： Microvascular complications in type 2 diabetes （T2DM）, including diabatic retinopathy （DR）, diabetic kidney disease （DKD）, diabetic peripheral neuropathy （DPN） are the leading causes of visual loss, end-stage renal disease or amputation, while the current therapies are still unsatisfactory. chinese medicine （CM） has been widely used for treating diabetic mettitus. However, most of the previous studies focused on the single complication. The role of CM treatment in T2DM patients with 2 or multiple microvascular complications is not clear. Objective： To appraise the curative effect of CM in T2DM patients with 2 or multiple microvascular complications, and to compare the effects of stationary treatment and individualized treatment in T2DM patients with microvascular complications. Methods： This trial will be an 8-center, randomized, controlled study with 8 parallel groups. A total of 432 patients will be randomized to 8 groups： DR study group （32 cases） and a corresponding control group （32 cases）, DR＋DKD study group （64 cases） and a corresponding control group （64 cases）, DR＋DPN study group （64 cases） and a corresponding control group （64 cases）, DR＋DKD＋DPN study group （56 cases） and a corresponding control group （56 cases）. The control group will receive stationary treatment, and the study group will receive individualized treatment based on CM syndrome differentiation in addition to stationary treatment. The study duration will be 50 weeks, comprising a 2-week run-in period, 24 weeks of intervention, and 24 weeks of follow-up. The outcomes will assess efficacy of treatment, improvement in CM symptoms, safety assessments, adherence to the treatment, and adverse events. Conclusion： This study will provide evidence of evidence-based medicine for CM treatment in two or multiple microvascular complications caused by T2DM. （Registration No. ChiCTR-IPR-15007072）

关键词： chinese medicine diabetic microvascular complications randomized controlled trial Qiming Granule

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