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Nuciferine alleviates collagen-induced arthritic in rats by inhibiting the proliferation and invasion of human arthritis-derived fibroblast-like synoviocytes and rectifying Th17/Treg imbalance

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chinese Journal of Natural medicines 2024年第4期22卷 341-355页

作者： WANG Hao GENG Xiaolong AI Fangbin YU Zhilun ZHANG Yan ZHANG Beibei LV Cheng GAO Ruiyang YUE Bei DOU Wei The MOE Key Laboratory of Standardization of chinese medicines Shanghai Key Laboratory of Compound Chinese Medicinesand the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese MedicineInstitute of Chinese Materia MedicaSchool of Traditional Chinese Materia MedicaShanghai University of Traditional Chinese Medicine(SHUTCM)Shanghai 201203China

Rheumatoid arthritis(RA)is a chronic autoimmune disorder marked by persistent synovial inflammation and joint degradation,posing challenges in the development of effective ***,an alkaloid found in lotus leaf,has shown promising anti-inflammatory and anti-tumor effects,yet its efficacy in RA treatment remains *** study investigated the antiproliferative effects of nuciferine on the MH7A cell line,a human RA-derived fibroblast-like synoviocyte,revealing its ability to inhibit cell proliferation,promote apoptosis,induce apoptosis,and cause G1/S phase ***,nuciferine significantly reduced the migration and invasion capabilities of MH7A *** therapeutic potential of nuciferine was further evaluated in a collagen-induced arthritis(CIA)rat model,where it markedly alleviated joint swelling,synovial hyperplasia,cartilage injury,and inflammatory *** also improved collagen-induced bone erosion,decreased pro-inflammatory cytokines and serum immunoglobulins(IgG,IgG1,IgG2a),and restored the balance between T helper(Th)17 and regulatory T cells in the spleen of CIA *** results indicate that nuciferine may offer therapeutic advantages for RA by decreasing the proliferation and invasiveness of FLS cells and correcting the Th17/Treg cell imbalance in CIA rats.

关键词： Rheumatoid arthritis Collagen-induced arthritis Fibroblast-like synoviocyte Immune imbalance Nuciferine

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LH-Nts Neurons Regulate VTA Calcium Dynamics Via Releasing GABA and Nts

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Neuroscience Bulletin 2024年第4期40卷 550-552页

作者： Danni Chen Yinfeng Yuan Zhihui Huang Yongjie Wang school of Pharmacy Hangzhou Normal UniversityHangzhou311121ZhejiangChina Key Laboratory of Element Class Anti-Cancer chinese medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhou311121ZhejiangChina

The peripheral and central nervous systems have numerous examples of two or more neuroactive products co-existing in the same neuron[1],which can simultaneously be released as both fast-acting neurotransmitters and slow-acting regulatory neuropeptides[2].For example,neurons in the lateral hypothalamus(LH)release both irritant neurotensin(Nts)and inhibitory-aminobutyric acid(GABA),two counterproductive substances[3].LH-Nts neurons project to the ventral tegmental area(VTA)and form synaptic connections with dopamine(DA)neurons to regulate reward[4-6].More critically,VTA-DA neurons express the Nts receptor Ntsrl and play a crucial role in cognition,anesthesia,reward,and disgust[4,7,8].Nevertheless,a mechanistic understanding of how stimulation and inhibition work together to control the output of neural circuits remains *** is very difficult to selectively isolate these signaling pathways in cell and circuit-specific manners.

关键词： anesthesia stimulation dopamine

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Notoginsenoside Ft1 inhibits colorectal cancer growth by increasing CD8^(+)T cell proportion in tumor-bearing mice through the USP9X signaling pathway

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chinese Journal of Natural medicines 2024年第4期22卷 329-340页

作者： FENG Yutao LI Yuan MA Fen WU Enjiang CHENG Zewei ZHOU Shiling WANG Zhengtao YANG Li SUN Xun ZHANG Jiwei Shanghai Key Laboratory of Compound chinese medicines The MOE Key Laboratory for Standardization of Chinese MedicinesInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China Gastrointestinal surgery Longhua HospitalShanghai University of Traditional Chinese MedicineShanghai 200032China

The management of colorectal cancer(CRC)poses a significant challenge,necessitating the development of innovative and effective *** research has shown that notoginsenoside Ft1(Ng-Ft1),a small molecule,markedly inhibits subcutaneous tumor formation in CRC and enhances the proportion of CD8^(+)T cells in tumor-bearing mice,thus restraining tumor *** into the mechanism revealed that Ng-Ft1 selectively targets the deubiquitination enzyme USP9X,undermining its role in shieldingβ-*** leads to a reduction in the expression of downstream effectors in the Wnt signaling *** findings indicate that Ng-Ft1 could be a promising small-molecule treatment for CRC,working by blocking tumor progression via the Wnt signaling pathway and augmenting CD8^(+)T cell prevalence within the tumor environment.

关键词： Notoginsenoside Ft1 Colorectal cancer CD8^(+)T cell Ubiquitin-specific peptidase 9 X-linked β-Catenin Wnt

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Elemene Antitumor Drugs Development Based on "Molecular Compatibility Theory" and Clinical Application: A Retrospective and Prospective Outlook

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chinese Journal of Integrative Medicine 2024年第1期30卷 62-74页

作者： JIANG Xiao-ying SHI Li-ping ZHU Jun-long BAI Ren-ren XIE Tian school of Pharmacy Hangzhou Normal UniversityHangzhou(311121)China Key Laboratory of Elemene Class Anti-cancer chinese medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhou(311121)China Good Clinical Practice Center Affliliated Hospital of Nanjing University of Chinese MedicineNanjing(210000)China

Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian introduced the innovative concept of "molecular compatibility theory" by combining chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".

关键词： molecular compatibility theory chinese integrative medicine elemene antitumor activity drug delivery structural modification

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Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathway

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Food Science and Human Wellness 2024年第1期13卷 414-420页

作者： Zitian Gao Gaorui Wang Yujie Chen Wuke Yuan Jun Cai Aiping Feng Jie Fang Qi Xu Xiaojun Wu school of Public Health Shanghai University of Traditional Chinese MedicineShanghai 201203China Shanghai Key Laboratory of Compound chinese medicines The Ministry of Education(MOE)Key Laboratory for Standardization of Chinese MedicineInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai 201203China Longhua Hospital affiliated to Shanghai University of traditional chinese Medicine Shanghai University of Traditional Chinese MedicineShanghai 201203China

Parkinson’s disease(PD)is a common neurodegenerative disorder with no *** membranaceus is used in chinese culture as a food supplement to boost *** present study aimed to explore the neuroprotective effects of total flavonoids extracted from ***(TFA)and their protective *** offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of *** also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen *** addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.

关键词： Parkinson’s disease Total fl avonoids of Astragalus membranaceus Ferroptosis SLC7A11

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Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets

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chinese Journal of Integrative Medicine 2024年第7期30卷 664-672页

作者： LIU Su-su YU Tong QIAO Yan-fang GU Shu-xiao CHAI Xin-lou school of traditional chinese Medicine Beijing University of Traditional Chinese MedicineBeijing102401China

The prevalence of hyperlipidemia has increased significantly due to genetic, dietary, nutritional and pharmacological factors, and has become one of the most common pathological conditions in humans. Hyperlipidemia can lead to a range of diseases such as atherosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, and kidney failure, etc. High circulating low-density lipoprotein cholesterol (LDL-C) is one of the causes of hyperlipidemia. LDL-C in the blood binds to LDL receptor (LDLR) and regulates cholesterol homeostasis through endocytosis. In contrast, proprotein convertase subtilisin/kexin type 9 (PCSK9) mediates LDLR degradation via the intracellular and extracellular pathways, leading to hyperlipidemia. Targeting PCSK9-synthesizing transcription factors and downstream molecules are important for development of new lipid-lowering drugs. Clinical trials regarding PCSK9 inhibitors have demonstrated a reduction in atherosclerotic cardiovascular disease events. The purpose of this review was to explore the target and mechanism of intracellular and extracellular pathways in degradation of LDLR and related drugs by PCSK9 in order to open up a new pathway for the development of new lipid-lowering drugs.

关键词： hyperlipidemia proprotein convertase subtilisin/kexin type 9 low-density lipoprotein receptor intracellular pathway extracellular pathway

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The roles and mechanisms of SREBP1 in cancer development and drug response

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Genes & Diseases 2024年第4期11卷 258-269页

作者： Ying He Shasha Qi Lu Chen Jinyu Zhu Linda Liang Xudong Chen Hao Zhang Lvjia Zhuo Shujuan Zhao Shuiping Liu Tian Xie school of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang 311121China Key Laboratory of Elemene Class Anti-Cancer chinese medicines Engineering Laboratory of Development and Application of Traditional Chinese MedicinesCollaborative Innovation Center of Traditional Chinese Medicines of Zhejiang ProvinceHangzhou Normal UniversityHangzhouZhejiang 311121China Laboratory of Cancer Genomics Division of Cellular and Molecular ResearchNational Cancer Centre SingaporeSingapore 169610Singapore

Cancer occurrence and development are closely related to increased lipid produc-tion and glucose *** are the basic component of the cell membrane and play a significant role in cancer cell processes such as cell-to-cell recognition,signal transduction,and energy supply,which are vital for cancer cell rapid proliferation,invasion,and *** regulatory element-binding transcription factor 1(SREBP1)is a key transcription factor regulating the expression of genes related to cholesterol biosynthesis,lipid homeostasis,and fatty acid *** addition,SREBP1 and its upstream or downstream target genes are implicated in various metabolic diseases,particularly ***,no review of sREBP1 in cancer biology has yet been ***,we summarized the roles and mechanisms of SREBP1 biological processes in cancer cells,including SREBP1 modification,lipid metabolism and reprogramming,glucose and mitochondrial metabolism,immunity,and tumor microenvi-ronment,epithelial-mesenchymal transition,cell cycle,apoptosis,and ***-ally,we discussed the potential role of SREBP1 in cancer prognosis,drug response such as drug sensitivity to chemotherapy and radiotherapy,and the potential drugs targeting SREBP1 and its corresponding pathway,elucidating the potential clinical application based on SREBP1 and its corresponding signal pathway.

关键词： Cancer Drug Lipid metabolism reprogramming Resistance SREBP1

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Pathophysiological changes of muscle after ischemic stroke:a secondary consequence of stroke injury

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Neural Regeneration Research 2024年第4期19卷 737-746页

作者： Hu Qi Dan Tian Fei Luan Ruocong Yang Nan Zeng State Key Laboratory of Southwestern chinese Medicine Resources Chengdu University of Traditional Chinese Medicine school of Pharmacy Chengdu University of Traditional Chinese Medicine Acupuncture and Tuina school Chengdu University of Traditional Chinese Medicine

Sufficient clinical evidence suggests that the damage caused by ischemic stroke to the body occurs not only in the acute phase but also during the recovery period,and that the latter has a greater impact on the long-term prognosis of the ***,current stroke studies have typically focused only on lesions in the central nervous system,ignoring secondary damage caused by this *** a phenomenon arises from the slow progress of pathophysiological studies examining the central nervous ***,the appropriate therapeutic time window and benefits of thrombolytic therapy are still controversial,leading scholars to explore more pragmatic intervention *** treatment measures targeting limb symptoms can greatly improve a patient’s quality of life,they have become a critical intervention *** the most vital component of the limbs,skeletal muscles have become potential points of *** this,to the best of our knowledge,there are no comprehensive reviews of pathophysiological changes and potential treatments for post-stroke skeletal *** current review seeks to fill a gap in the current understanding of the pathological processes and mechanisms of muscle wasting atrophy,inflammation,neuroregeneration,mitochondrial changes,and nutritional dysregulation in stroke *** addition,the challenges,as well as the optional solutions for individualized rehabilitation programs for stroke patients based on motor function are discussed.

关键词： inflammation ischemic stroke mitochondria muscle atrophy muscle fiber muscle nutrition quality of life rehabilitation ubiquitin

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Adenosine triphosphate mediates the pain tolerance effect of manual acupuncture at Zusanli(ST36) in mice

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Journal of traditional chinese Medicine 2024年第4期44卷 660-669页

作者： LI Zhongzheng ZHAO Yadan Ma Weigang Zhang Yonglong XU Zhifang XI Qiang LI Yanqi QIN Siru ZHANG Zichen WANG Songtao ZHAO Xue LIU Yangyang GUO Yi GUO Yongming Research Center of Experimental Acupuncture Science Tianjin University of Traditional Chinese Medicine National Clinical Research Center for chinese Medicine Acupuncture and Moxibustion Department of Acupuncture and Moxibustion Qingdao Hiser Hospital Affiliated of Qingdao University(Qingdao Traditional Chinese Medicine Hospital) school of traditional chinese Medicine Tianjin University of Traditional Chinese Medicine school of Acupuncture and Moxibustion and Tuina Tianjin University of Traditional Chinese Medicine

OBJECTIVE: To investigate the mechanisms behind the effects of acupuncture in traditional chinese Medicine,we delved into the adenosine triphosphate/peripheral purinergic P2X receptor 3(ATP/P2X3) receptor signaling system as an indicator of the body's energy state,commonly referred to as "Qi".METHODS: The tail-flick test was utilized to explore the impact of acupuncture on pain tolerance threshold(PTT)in mice, while also assessing adenosine(ADO) levels and adenylate energy charge(EC) at Zusanli(ST36). The study further investigated the dose-dependent effects of acupuncture on PTT and ADO levels at Zusanli(ST36).To shed light on the underlying mechanisms of acupuncture's effects, the study examined the impact of ATP, a P2X3 receptor antagonist, and adenosine disodium on PTT following acupuncture administration. RESULTS: Acupuncture at Zusanli(ST36) led to significant improvements in PTT in mice, with the most effective interventions being twirling for 2 min and needle retention for 28 min. These interventions also resulted in significant increases in ATP levels. The effects of acupuncture were further augmented by administration of different doses of ATP at Zusanli(ST36), and pretreatment with a P2X3 receptor antagonist decreased PTT. Adenylate EC peaked at 30 min after intraperitoneal injection of ATP, and pretreatment with various doses of i.p. ATP 30 min prior to acupuncture increased PTT in a dose-dependent manner. Additionally, pretreatment with an i.p. or intramuscular injection of adenosine disodium enhanced the effects of acupuncture. CONCLUSION: This research provides compelling evidence that ATP is involved in the regulation of PTT through acupuncture, revealing new avenues for achieving enhanced clinical outcomes.

关键词： acupuncture adenosine triphosphate energy state point ST36 (Zusanli) receptors, purinergic P2X3

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Early Growth Response Gene-1 Deficiency Interrupts TGFβ1 Signaling Activation and Aggravates Neurodegeneration in Experimental Autoimmune Encephalomyelitis Mice

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Neuroscience Bulletin 2024年第3期40卷 283-292页

作者： Yunyi Lan Xinyan Han Fei Huang Hailian Shi Hui Wu Liu Yang Zhibi Hu Xiaojun Wu Shanghai Key Laboratory of Compound chinese medicines The Ministry of Education Key Laboratory for Standardization of Chinese MedicinesThe State Administration of TCM Key Laboratory for New Resources and Quality Evaluation of Chinese MedicineInstitute of Chinese Materia MedicaShanghai University of Traditional Chinese MedicineShanghai201203China Central Laboratory Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai200021China

Early growth response protein 1(Egr-1)triggers the transcription of many genes involved in cell growth,differentiation,synaptic plasticity,and ***,its mechanism in neuronal survival and degeneration is still poorly *** study demonstrated that Egr-1 was down-regulated at mRNA and protein levels in the central nervous system(CNS)of experimental autoimmune encephalomyelitis(EAE)***-1 knockout exacerbated EAE progression in mice,as shown by increased disease severity and incidence;it also aggravated neuronal apoptosis,which was associated with weakened activation of the BDNF/TGFβ1/MAPK/Akt signaling pathways in the CNS of EAE ***,Egr-1 siRNA promoted apoptosis but mitigated the activation of BDNF/TGFβ1/MAPK/Akt signaling in SH-SY5Y *** results revealed that Egr-1 is a crucial regulator of neuronal survival in EAE by regulating TGFβ1-mediated signaling activation,implicating the important role of Egr-1 in the pathogenesis of multiple sclerosis as a potential novel therapy target.

关键词： Early growth response protein 1 Transforming growth factor-beta 1 Multiple sclerosis Experimental autoimmune encephalomyelitis Neurodegeneration

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