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Effect on serum metabolomics of rats with premature ovarian insufficiency by Zhibian(BL54) through Shuidao(ST28) acupuncture

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Journal of Traditional Chinese medicine 2024年第4期44卷 722-733页

作者： YAN Jing FENG Huimin QIU Fang WANG Haijun YIN Luyun JIN Xiaofei ZHAO Jiyu WANG Hongyang YAN Xiaoqin Second Clinical college of Shanxi university of Traditional Chinese medicine Research Center of Experimental Acupuncture Science Tianjin University of Traditional Chinese Medicine Department of Cervical and Lumbar Vertebral Diseases Jinzhong Hospital Affiliated to Shanxi University of Traditional Chinese Medicine

OBJECTIVE: To analyze the serum metabolic targets of the "Zhibian(BL54) through Shuidao(ST28)" acupuncture technique in cyclophosphamide(CTX)-induced premature ovarian insufficiency(POI) model rats and to elucidate the potential molecular mechanism of acupuncture in improving POI. METHODS: We used an intraperitoneal injection of CTX to establish the POI rat model(POI group) and compared serum hormone levels and ovarian histopathological changes to evaluate the effect of the Zhibian(BL54) through Shuidao(ST28) technique(ZS + POI group) on ovarian function. Then, nontargeted metabolomics was performed using rat serum by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF/MS). RESULTS: After acupuncture intervention, the serum hormone levels and ovarian pathological morphology of POI rats were effectively improved. Moreover, UPLC-Q-TOF/MS results showed that the ZS+POI group showed a significant reversal of the levels of 6 differential metabolites. Among them, the levels of four serum metabolic markers, divanillyltetrahydrofuran ferulate, trans-ferulic acid, tryptamine, and neuraminic acid, increased significantly. Further analysis of biological effects showed that all metabolites were involved in the regulation of reproductive hormone levels and antioxidant and antiapoptotic effects. CONCLUSIONS: The "Zhibian(BL54) through Shuidao(ST28)" acupuncture method may improve the ovarian function of POI rats by regulating serum metabolite markers to exert antioxidant and antiapoptotic effects, which provides a theoretical basis for the clinical application of acupuncture in the treatment of POI.

关键词： Zhibian (BL54) through Shuidao (ST28) acupuncture metabolomics premature ovarian insufficiency ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry

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Isorhamnetin Downregulates MMP2 and MMP9 to Inhibit Development of Rheumatoid Arthritis through SRC/ERK/CREB Pathway

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Chinese Journal of Integrative medicine 2024年第4期30卷 299-310页

作者： LIU Xiao-rong LI Shuo-fu MEI Wen-ya LIU Xiang-dan ZHOU Ri-bao college of Pharmacy Hunan University of Chinese MedicineChangsha(410208)China Department of Orthopaedics The First Hospital of Hunan University of Chinese MedicineChangsha(410007)China

Objective To investigate the effect of isorhamnetin on the pathology of rheumatoid arthritis(RA).Methods Tumor necrosis factor(TNF)-α-induced fibroblast-like synoviocytes(FLS)was exposed to additional isorhamnetin(10,20 and 40µmol/L).Overexpression vectors for matrix metalloproteinase-2(MMP2)or MMP9 or SRC were transfected to explore their roles in isorhamnetin-mediated RA-FLS ***-FLS viability,migration,and invasion were ***,a collagen-induced arthritis(CIA)rat model was *** were randomly divided to sham,CIA,low-,medium-,and high-dosage groups using a random number table(n=5 in each group)and administed with normal saline or additional isorhamnetin[2,10,and 20 mg/(kg·day)]for 4 weeks,*** index was calculated and synovial tissue inflammation was determined in CIA *** levels of MMP2,MMP9,TNF-α,interleukin-6(IL-6),and IL-1β,as well as the phosphorylation levels of SRC,extracellular regulated kinase(ERK),and cyclic adenosine monophosphate response element-binding(CREB),were detected in RA-FLS and synovial *** docking was also used to analyze the binding of isorhamnetin to *** In in vitro studies,isorhamnetin inhibited RA-FLS viability,migration and invasion(P<0.05).Isorhamnetin downregulated the levels of MMP2,MMP9,TNF-α,IL-6,and IL-1βin RA-FLS(P<0.05).The overexpression of either MMP2 or MMP9 reversed isorhamnetin-inhibited RA-FLS migration and invasion,as well as the levels of TNF-α,IL-6,and IL-1β(P<0.05).Furthermore,isorhamnetin bound to SRC and reduced the phosphorylation of SRC,ERK,and CREB(P<0.05).SRC overexpression reversed the inhibitory effect of isorhamnetin on RA-FLS viability,migration and invasion,as well as the negative regulation of MMP2 and MMP9(P<0.05).In in vivo studies,isorhamnetin decreased arthritis index scores(P<0.05)and alleviated synovial *** reduced the levels of MMP2,MMP9,TNF-α,IL-6,and IL-1β,as well as the phosphorylation of SRC,ERK,and CRE

关键词： rheumatoid arthritis isorhamnetin SRC/ERK/CREB matrix metalloproteinase

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Extracellular vesicles for neural regeneration after spinal cord injury

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Neural Regeneration Research 2024年第3期19卷 491-492页

作者： Young-Ju Lim Wook-Tae Park Gun Woo Lee Department of Orthopedic Surgery Yeungnam University Medical CenterYeungnam University College of MedicineDaeguKorea

What is spinal cord injury:Spinal cord injury(SCI)is the damage to the structure of the bundles of cells and nerves that communicate signals from the brain to the body and *** pathology of SCI includes both primary and secondary injuries(Morales et al.,2016).Physical forces such as compression,shearing,contusion,and tearing are major causes of primary injury in *** are two main processes in primary injury:acute and *** acute phase includes traumatic disruption of axons and hemorrhage of the blood vessels around the spinal *** injury to the vessels can lead to increased edema within the neural and cord tissues,susceptibility to infiltration by microglia and astrocytes,excitotoxicity,and ***,disruption of the blood-spinal cord barrier results in the release of inflammatory cytokines from specific cells and vessels.

关键词： acute injuries nerves

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Mechanism of acupuncture in attenuating cerebral ischaemia-reperfusion injury based on nuclear receptor coactivator 4 mediated ferritinophagy

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Journal of Traditional Chinese medicine 2024年第2期44卷 345-352页

作者： ZHANG Xinchang HUANG Zheng HUANG Peiyan YANG Mengning ZHANG Zhihui NI Guangxia college of Acupuncture-Moxibustion and Tuina Nanjing University of Chinese MedicineNanjing 210023China Key Laboratory of Acupuncture and medicine Research of Ministry of Education Nanjing University of Chinese MedicineNanjing 210023China

OBJECTIVE:To explore the effect of acupuncture treatment on cerebral ischaemia-reperfusion injury(CIRI)and reveal the underlying mechanism of the effect based on nuclear receptor coactivator 4(NCOA4)mediated ***:Sprague-Dawley male rats were divided into four groups:the sham group,model group,acupuncture group,and sham acupuncture *** 2 h of middle cerebral artery occlusion(MCAO),reperfusion was performed for 24 h to induce *** rats were treated with acupuncture at the Neiguan(PC6)and Shuigou(GV26)*** neurological function was evaluated by taking their Bederson scores at 2 h after ischaemia and 24 h after *** chloride staining was applied to assess the cerebral infarct volume at 24 h after *** malondialdehyde(MDA)and ferrous iron(Fe^(2+))levels were observed after 24 h of reperfusion using an assay *** blotting was performed to detect the expression of NCOA4 and ferritin heavy chain 1(FTH1)at 24 h after ***,the colocalization of ferritin with neurons,NCOA4 with microtubule-associated protein 1 light chain 3(LC3),and NCOA4 with ferritin was visualized using immunofluorescence ***:Acupuncture significantly improved neurological function and decreased cerebral infarct volume in the acupuncture *** CIRI,the expression of NCOA4,LC3 and FTH1 was increased,which enhanced ferritinophagy and induced an inappropriate accumulation of Fe^(2+)and MDA in the ischaemic ***,acupuncture dramatically downregulated the expression of NCOA4,LC3 and FTH1,inhibited the overactivation of ferritinophagy,and decreased the levels of MDA and Fe^(2+).CONCLUSIONS:Acupuncture can inhibit NCOA4-mediated ferritinophagy and protect neurons against CIRI in a rat model.

关键词： acupuncture ferritinophagy ferroptosis ferritin nuclear receptor coactivator 4 cerebral ischaemia-reperfusion injury

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Yanggan Jiangmei Formula alleviates hepatic inflammation and lipid accumulation in non-alcoholic steatohepatitis by inhibiting the NF-κB/NLRP3 signaling pathway

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Chinese Journal of Natural medicines 2024年第3期22卷 224-234页

作者： WU Yuanyuan ZHOU Jingwen ZUO Xinchen KUANG Yufeng SUN Lixia ZHANG Xiaolong The First Clinical Medical college Nanjing University of Chinese MedicineNanjing 210023China The Affiliated Hospital of Nanjing university of Chinese medicine Jiangsu Province Hospital of Chinese MedicineNanjing 210029China

The role of NF-κB and the NLRP3 inflammasome in the chronic inflammatory microenvironment of non-alcoholic steatohepatitis(NASH)has been posited as *** Yanggan Jiangmei Formula(YGJMF)has shown promise in ameliorating hepatic steatosis in NASH patients,yet its pharmacological mechanisms remain largely *** study was conducted to investigate the efficacy of YGJMF in NASH and to elucidate its pharmacological *** simulate NASH both in vivo and in vitro,high-fat-diet(HFD)rats and HepG2 cells stimulated with free fatty acids(FFAs)were *** severity of liver injury and lipid deposition was assessed using serum indicators,histopathological staining,micro-magnetic resonance imaging(MRI),and the liver-tomuscle signal intensity ratio(SIRL/M).Furthermore,a combination of enzyme-linked immunosorbent assay(ELISA),immunohistochemistry(IHC),immunofluorescence,real-time quantitative polymerase chain reaction(RT-qPCR),and Western blotting analyses was employed to investigate the NF-κB/NLRP3 signaling pathway and associated cytokine *** results from liver pathology,MRI assessments,and biochemical tests in rat models demonstrated YGJMF’s significant effectiveness in reducing liver damage and lipid ***,YGJMF markedly reduced hepatocyte inflammation by downregulating inflammatory cytokines in both liver tissue and ***,YGJMF was found to disrupt NF-κB activation,consequently inhibiting the assembly of the NLRP3 inflammasome in both the in vitro and in vivo *** preliminary findings of this study suggest that YGJMF may alleviate hepatic steatosis and inhibit the NF-κB/NLRP3 signaling pathway,thereby exerting anti-inflammatory effects in NASH.

关键词： Non-alcoholic steatohepatitis Nuclear factor kappa B NLRP3 inflammasome Yanggan Jiangmei Formula

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Alginate oligosaccharide-mediated butyrate-HIF-1a axis improves skin aging in mice

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Journal of Pharmaceutical Analysis 2024年第5期14卷 678-692页

作者： Ting Gao Yixuan Li Xiaoyu Wang Fazheng Ren Department of Nutrition and Health College of Veterinary MedicineChina Agricultural UniversityBeijing100083China

The“gut-skin”axis has been proved and is considered as a novel therapy for the prevention of skin *** antioxidant efficacy of oligomannonic acid(MAOS)makes it an intriguing target for use to improve skin *** present study further explored whereby MAOS-mediated gut-skin axis balance prevented skin aging in *** data indicated the skin aging phenotypes,oxidative stress,skin mitochondrial dysfunction,and intestinal dysbiosis(especially the butyrate and HIF-1a levels decreased)in aging ***,fecal microbiota transplantation(FMT)from aging mice rebuild the aging-like ***,we demonstrated MAOS-mediated colonic butyrate-HIF-1a axis homeostasis promoted the entry of butyrate into the skin,upregulated mitophagy level and ultimately improving skin aging via HDAC3/PHD/HIF-1a/mitophagy loop in skin of ***,our study offered a better insights of the effectiveness of alginate oligosaccharides(AOS),promised to become a personalized targeted therapeutic agents,on gut-skin axis disorder inducing skin aging.

关键词： Alginate oligosaccharide Skin aging Butyrate HIF-1a Mitophagy

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Self-assembly of tau fragments as a key pathologic event in tauopathies

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Neural Regeneration Research 2024年第12期19卷 2565-2566页

作者： Ly Thi Huong Luu Le Jung Hoon Lee Min Jae Lee Department of Biochemistry and Molecular Biology Seoul National University College of MedicineSeoulKorea

Tau protein is encoded by the microtubuleassociated protein tau(MAPT)gene and stabilizes microtubules in the *** has unique biophysical properties that make it both highly water-soluble and positively *** tau is an intrinsically disordered protein lacking defined secondary structures,it can acquire highly organized-sheet structures and stack into a filamentous inclusion such as a paired helical filament(PHF).

关键词： tau pathologic assembly

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Acupotomy alleviates knee osteoarthritis in rabbit by regulating chondrocyte mitophagy via Pink1-Parkin pathway

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Journal of Traditional Chinese medicine 2024年第3期44卷 468-477页

作者： ZHU Wenting GUO Changqing DU Mei MA Yunxuan CUI Yongqi CHEN Xilin GUO Changqing the Third Affiliated Hospital of Beijing university of Chinese medicine School of Acupuncture-Moxibustion and Tuina Beijing University of Chinese Medicine Department of Medical Technology Shijiazhuang Medical College

OBJECTIVE: To investigate the effect of acupotomy, on mitophagy and the Pink1-Parkin pathway in chondrocytes from rabbits with knee osteoarthritis(KOA).METHODS: A KOA model was established via the modified Videman method. Rabbits were randomly divided into a control group(CON), KOA group and KOA + acupotomy group(Acu). Rabbits in the acupotomy group were subjected to acupotomy for 4 weeks after model establishment. The behavior of the rabbits before and after intervention was recorded. Cartilage degeneration was evaluated by optical microscopy and fluorescence microscopy. The level of mitophagy was evaluated by transmission electron microscopy,immunofluorescence and enzyme-linked immunosorbent assay(ELISA). The expression of phosphatase and tensin homolog(PTEN)-induced kinase 1(Pink1)-Parkin mitophagy pathway components was evaluated by immunofluorescence, Western blotting and real-time polymerase chain ***: In rabbits with KOA, joint pain, mobility disorders and cartilage degeneration were observed, the Mankin score was increased, collagen type Ⅱ(Col-Ⅱ)expression was significantly decreased, mitophagy was inhibited, mitochondrial function was impaired, and factors associated with the Pink1-Parkin pathway were inhibited. Acupotomy regulated the expression of Pink1-Parkin pathway-related proteins, the mitophagy-related protein microtubule-associated protein-1 light chain-3,the translocase of the outer membrane, and the inner mitochondrial membrane 23; increased the colocalization of mitochondria and autophagosomes; promoted the removal of damaged mitochondria;restored mitochondrial adenosine-triphosphate(ATP) production;and alleviated cartilage degeneration in rabbits with ***: Acupotomy played a role in alleviating KOA in rabbits by activating mitophagy in chondrocytes via the regulation of proteins that are related to the Pink1-Parkin pathway.

关键词： PTEN phosphohydrolase acupuncture therapy cartilage mitophagy osteoarthritis, knee

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Effect of mitomycin C on the corneal endothelial cells of Saudi patients with myopia after transepithelial photorefractive keratectomy:a two-armed cohort study

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 909-915页

作者： Sultan H Alrashidi Department of Ophthalmology College of MedicineQassim UniversityBuraidah 51452Saudi Arabia

AIM:To study the effect of mitomycin C(MMC)applied during transepithelial photorefractive keratectomy(TPRK)on the corneal endothelium one week(W1)and three months(M3)after surgery and its ***:In this two-armed cohort study conducted in 2022,eyes treated with MMC during TPRK(group 1)were compared with eyes not treated with MMC(group 2).The corneal endothelial cell(EC)count,EC density(ECD;cells/mm2),average(μm2),standard deviation(μm2),coefficient of variation(CV%),ECmax,ECmin,and EC percentage of hexagonality were estimated at W1 and *** postoperative changes in the EC count in the two groups were compared and correlated with the other independent ***:Group 1 had 26 eyes,and group 2 had 78 *** TPRK indices were significantly higher for the eyes in group 1 than for those in group *** MMC usage was not a significant predictor of the change in ECD(P=0.644),change in CV(P=0.374),and change in the percentage of hexagonality of EC(P=0.164)at ***,the use of MMC was a significant predictor of changes in CV(P=0.014)and the change in the percentage of hexagonality of EC(P=0.039)at *** duration of laser exposure and the size of the optical zone influenced the correlation of MMC use with the changes in EC indices,***:The use of MMC doesn’t affect ECD,CV,and percentage of hexagonality at W1 if other surgical indices are *** M3 after operating myopic eyes by TPRK,MMC significantly influence the CV and percentage of *** duration of the laser application and the size of the optical zone should be considered when determining the effect of MMC on the EC indices.

关键词： transepithelial photorefractive keratectomy mitomycin-C corneal endothelium

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First total synthesis,antitumor evaluation and target identification of mornaphthoate E:A new tubulin inhibitor template acting on PI3K/Akt signaling pathway

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2177-2193页

作者： Peipei Shan Tao Ye Ying-De Tang Hui Song Chao Wang Kongkai Zhu Feifei Yang Shi-Lei Zhang Pei-Wen Su Shuanhu Gao Hua Zhang Institute of Translational medicine the Affiliated Hospital of Qingdao UniversityCollege of MedicineQingdao UniversityQingdao 266021China School of Biological Science and Technology University of JinanJinan 250022China Advanced Medical Research Institute Cheeloo College of MedicineShandong UniversityJinan 250012China college of Pharmaceutical Sciences Soochow UniversitySuzhou 215127China School of Chemistry and Molecular Engineering East China Normal UniversityShanghai 200062China

Mornaphthoate E(MPE)is a prenylated naphthoic acid methyl ester isolated from the roots of a famous Chinese medicinal plant Morinda officinalis and shows remarkable cytotoxicity against several human tumor cell *** the current project,the first total synthesis of(±)-MPE was achieved in seven steps and 5.6%overall *** the in vitro anti-tumor activity of MPE was first assessed for both enantiomers in two breast cancer cells,with the levoisomer exerting slightly better *** in vivo anti-tumor effect was further verified by applying the racemate in an orthotopic autograft mouse ***,MPE exerted promising anti-metastasis activity both in vitro and in vivo and showed no obvious toxicity on mice at the therapeutic *** investigations demonstrated that MPE acted as a tubulin polymerization stabilizer and disturbed the dynamic equilibrium of microtubules via regulating PI3K/Akt *** conclusion,our work has provided a new chemical template for the future design and development of next-generation tubulin-targeting chemotherapies.

关键词： Mornaphthoate E Tubulin inhibitor Antitumor Anti-metastasis Breast cancer PI3K/Akt

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