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Human umbilical cord mesenchymal stem cell-derived exosomes loaded into a composite conduit promote functional recovery after peripheral nerve injury in rats

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Neural Regeneration Research 2024年第4期19卷 900-907页

作者： Haoshuai Tang Junjin Li Hongda Wang Jie Ren Han Ding Jun Shang Min Wang Zhijian Wei Shiqing Feng Department of Othopaedics Tianjin Medical University General Hospital International Science and Technology Cooperation Base of Spinal Cord Injury Tianjin Key Laboratory of Spine and Spinal Cord InjuryDepartment of OrthopedicsTianjin Medical University General Hospital Tianjin Key Laboratory of Lung cancer Metastasis and Tumor Microenvironment Tianjin Lung Cancer InstituteTianjin Medical University General Hospital Department of Othopaedics Qilu Hospital of Shandong UniversityShandong University Centre for OthopedicsAdvanced Medical Research InstituteShandong University Orthopedic Research Center of Shandong University&Advanced Medical Research Institute Cheeloo College of MedicineShandong University

Complete transverse injury of peripheral nerves is challenging to *** secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue *** previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal *** three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)***,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains *** this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived *** effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in *** results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft *** CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve ***,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.

关键词： axon growth collagen exosome human umbilical cord mesenchymal stem cells hyaluronic acid muscular atrophy nerve guidance conduits peripheral nerve regeneration

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Lipid-derived radical-trapping antioxidants suppress ferroptosis

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Life Metabolism 2024年第2期3卷 6-8页

作者： Ruoxi Zhang Guido Kroemer Daolin Tang Department of Surgery UT Southwestern Medical CenterDallasTX 75390United States centre de Recherche des Cordeliers INSERM U1138Equipe labellisée-Ligue contre le cancerUniversitéParis CitéSorbonne UniversitéInstitut Universitaire de FranceParis 75006France Metabolomics and Cell Biology Platforms Gustave Roussy Cancer CampusVillejuif 94800France Institut du cancer Paris CARPEM Department of BiologyHôpital Européen Georges PompidouAssistance Publique-Hôpitaux de ParisParis 75015France

Ferroptosis,characterized by lipid peroxidation-mediated cell demise,is governed by a nuanced interplay of lipid species influencing its *** recent publications in Nature discovered 7-dehydrocholesterol,a cholesterol precursor,as a radical-trapping antioxidant that can suppress ferroptosis,thereby presenting a novel metabolic target to improve ferroptosis-related cancer therapy.

关键词： Lipid peroxidation cholesterol

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Design consideration of phthalocyanines as sensitizers for enhanced sono-photodynamic combinatorial therapy of cancer

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1077-1097页

作者： Lindokuhle Cindy Nene Heidi Abrahamse Laser Research centre Faculty of Health SciencesUniversity of JohannesburgDoornfontein 2028South Africa

cancer remains one of the diseases with the highest incidence and mortality *** treatment modalities have demonstrated threatening drawbacks including invasiveness,noncontrollability,and development of resistance for some,including chemotherapy,radiation,and ***-photodynamic combinatorial therapy(SPDT)has been developed as an alternative treatment modality which offers a non-invasive and controllable therapeutic *** combines the mechanism of action of sonodynamic therapy(SDT),which uses ultrasound,and photodynamic therapy(PDT),which uses light,to activate a sensitizer and initiate cancer *** use of phthalocyanines(Pcs)as sensitizers for SPDT is gaining interest owing to their ability to induce intracellular oxidative stress and initiate toxicity under SDT and *** review discusses some of the structural prerequisites of Pcs which may influence their overall SPDT activities in cancer therapy.

关键词： Sonodynamic therapy Photodynamic therapy Combinatorial therapy Phthalocyanines Sensitizer cancer

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Efficacy and safety of utidelone for the treatment of patients with locally advanced or metastatic non-small-cell lung cancer who have failed standard second-line treatment:A phase 2 clinical trial(BG01-1801)

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cancer Pathogenesis and Therapy 2024年第2期2卷 103-111页

作者： Yuankai Shi Gongyan Chen Yanqiu Zhao Jing Zhao Lin Lin Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing Key Laboratory of Clinical Study On Anticancer Molecular Targeted DrugsBeijing 100021China Department of Respiration Harbin Medical University Cancer HospitalHarbinHeilongjiang 150040China Respiratory Department of Internal Medicine Henan Provincial Cancer HospitalZhengzhouHenan 450003China Department of Pulmonary and Critcal Care Medicine Peking Union Medical College HospitaChinese Academy of Medical Sciences&Peking Union Medical College Beijing100021China

Background:Chemotherapy remains the standard-of-care for many patients with locally advanced or metastatic non-small-cell lung cancer(NSCLC),but acquired resistance presents *** aim of this open-label,multicenter phase 2 clinical trial was to determine the efficacy and safety of utidelone,a novel genetically engineered epothilone analog and microtubule-stabilizing agent,as a third-or later-line treatment for locally advanced ormetastatic ***:Patients who had failed standard second-line treatment(including platinum-containing chemotherapy or targeted therapy)received utidelone(40 mg/m?via intravenous injection daily,day 1-5)every 21 *** primary endpoint was the objective response rate(ORR).Secondary endpoints were the duration of response(DoR),progression-free survival(PFS),overall survival(OS),and ***:From March 12,2019 to January 18,2021,26 pretreated patients with locally advanced or metastatic NSCLC(100%of patients had received prior platinum and 65.4%patients had received prior taxane treatment)were enrolled(80.8%of patients had adenocarcinoma).At baseline,nine(34.6%)patients had received secondline treatment,10(38.5%)patients had received third-line treatment,and seven(26.9%)patients had received fourth-or later-line *** the data cut-off date of August 10,2021,the median follow-up was 7.49 months(range,1.4-26.7 months).The ORR was 15.4%(95%confidence interval[CI],4.4%-34.9%)in the intention-totreat(ITT)cohort(N=26)and 19.0%(95%CI,5.4%-41.9%)in the per-protocol(PP)cohort(N=21).The disease control rate was 69.2%(95%CI,48.2%-85.7%)and 81.0%(95%CI,58.1%-94.6%)in the ITT and PP cohorts,*** median DoR was 4.1 months(95%CI,3.1-5.1 months)in the ITT *** median PFS was 4.37 months(95%CI,2.50-5.29 months)in the ITT cohort and 4.37 months(95%CI,2.50-9.76 months)in the PP *** median OS was not reached,and the 12-month OS rate was 69%(95%CI,45.1%-84.1%).Grade 3/4 treatment-emergent adverse events occur

关键词： Utidelone Locally advanced or metastatic non-small-cell lung cancer Efficacy Platinum-and taxane-refractory

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Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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Neural Regeneration Research 2024年第11期19卷 2532-2542页

作者： Aina Bellver-Sanchis Pedro AAvila-López Iva Tic David Valle-García Marta Ribalta-Vilella Luis Labrador Deb Ranjan Banerjee Ana Guerrero Gemma Casadesus Coralie Poulard Mercè Pallàs Christian Grinán-Ferré Department of Pharmacology and Therapeutic Chemistry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Molecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Institute of Biotechnology National Autonomous University of MexicoCuernavacaMexico Department of Pharmacology and Therapeutics Health Science Center-University of FloridaGainesvilleFLUSA Department of Chemistry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia cancer Research cancer Lyon Universitéde LyonLyonFrance Inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRS UMR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Investigación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neuroimmunology Department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative ***,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s ***,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and *** better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor *** found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)***,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control *** also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a *** confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative *** this setting,treatment with G9a inhibitor increases both cell survival and antioxidant ***,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and *** addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers ***,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a ***,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRNAs miR-128 peroxisome-proliferator activator receptorγ(PPARγ) PPARG SAMP8

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Remote-controlled dexamethasone-duration on eye-surface with a micelle-magnetic nanoparticulate co-delivery system for dry eye disease

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3730-3745页

作者： Qinxiang Zheng Chaoxiang Ge Kexin Li Longxin Wang Xiaoyu Xia Xiao Liu Rashid Mehmood Jianliang Shen Kaihui Nan Wei Chen Sen Lin National Engineering Research Center of Ophthalmology and Optometry Eye HospitalWenzhou Medical UniversityWenzhou 325027China National Clinical Research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhou 325027China Zhejiang Engineering Research Center for Tissue Repair Materials Wenzhou InstituteUniversity of Chinese Academy of SciencesWenzhou 325000China School of Chemical Engineering UNSW SydneyHigh StreetBuilding E10KensingtonNSW 2052Australia Adult cancer Program Lowy Cancer Research CentreUNSW SydneyCorner Botany&High StreetsKensingtonNSW 2052Australia

Dexamethasone(DEX)is used to treat ocular surface ***,regulating DEX duration in tears while preventing its absorption into the anterior chamber is critical for balancing its therapy effects and the side *** this study,a novel magnetic nanoparticle(MNP)-micelle(MC)codelivery system(MMDS)was *** MC moiety in the MMDS served as the carrier for DEX and the MNP part endowed the MMDS with magnetic-responsive *** extend its residency,the MMDS was magnetically attracted by an external magnet after instilling,which acted as a precorneal drug-depot enabling a sustainable release of DEX in *** combination of magnet treatment,the topical instillation of MMDS@DEX significantly prolonged the DEX-retention in tears and increased the DEX-concentration in the cornea and conjunctiva,as well as concurrently reduced the DEX-level in the aqueous humor,when compared with the commercial DEX eye drop *** combination of MMDS@DEX and magnet treatment exerted significantly better therapeutic effects against DED with smaller side effects than conventional treatments including DEX suspension,commercial DEX eye drops,as well as the MMDS@DEX treatment *** present work provided a new method for the effective delivery of DEX to ocular surface tissues while reducing its side effects,which will be beneficial to the treatments of a wide range of ocular surface diseases.

关键词： Magnetic nanoparticle Micelle Dexamethasone Eye drop Bioavailability Dry eye disease Cornea Conjunctiva

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A comprehensive review on the potential therapeutic benefits of prospective probiotic Christensenella minuta

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Food Science and Human Wellness 2024年

作者： Yueyao Fan Yuhang Xiao Yingying Zhang Shiqing Zhang Weibin Bai Jiali Chen Department of Food Science and Engineering Institute of Food Safety and Nutrition Guangdong Engineering Technology Center of Food Safety Molecular Rapid Detection Jinan University State Key Laboratory of Bioactive Molecules and Druggability Assessment Jinan University centre for cancer and Inflammation Research School of Chinese Medicine Hong Kong Baptist University

Bacterial family Christensenellaceae performed high heritability and associated with human health status. Numerous studies observed that the abundance of Christensenellaceae could be significantly reduced in patients with intestinal diseases or metabolic disorders， inferred that it may be treated as an effective biomarker. Christensenella minuta (C. minuta) was the first member of Christensenellaceae family isolated from human fecal samples. Accumulating evidences suggested that C. minuta may demonstrate a positive bio-therapeutic effects toward unhealthy status. Hence， this review aimed to systematically summarize the characterization of Christensenellaceae under specific health or diseases， and discover its promising application. Besides， the latest studies on the pharmacological research of C. minuta also summarized. Current important literatures grasped the potential health benefits of C. minuta in managing metabolic disorders， gut ecosystem， and inflammation. Whereas， several critical knowledge gaps about the safe and clinical application remain should be addressed in future verification. C. minuta is worthy to be elevated as the next prospective probiotic star in nutraceutical or medical field and should not be overlooked.

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A prospective cohort of men with localized prostate cancer on active surveillance protocol in Hong Kong,China:what did we learn?

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Asian Journal of Andrology 2024年第3期26卷 245-249页

作者： Xiaobo Wu Ivan Ching-Ho Ko Cindy Yeuk-Lam Hong Samuel Chi-Hang Yee Jeremy Yuen-Chun Teoh Samson Yun-Sang Chan Ho-Man Tam Chi-Kwok Chan Chi-Fai Ng Peter Ka-Fung Chiu SH Ho Urology centre Department of SurgeryFaculty of MedicineThe Chinese University of Hong KongHong KongChina

This study aimed to report the outcomes of active surveillance(AS)in the management of low-risk prostate cancer(PCa).It recruited87 men who were prospectively followed up according to the Prostate cancer Research International Active Surveillance(PRIAS)protocol with local adaptation at SH Ho Urology centre,Prince of Wales Hospital,Hong Kong,*** investigated the predictorsof disease progression and found that baseline prostate-specific antigen density(PSAD)and the presence of the highest ProstateImaging-Reporting and Data System(PI-RADS)score 5 lesion on magnetic resonance imaging(MRI)are significantly correlatedwith disease ***,men with PSAD>0.2 ng ml^(−2)or PI-RADS 4 or 5 lesions had significantly worse upgradingfree survival compared to those with PSAD≤0.2 ng ml−2 and PI-RADS 2 or 3 *** study concludes that AS is a safe andeffective management strategy for selected patients to defer radical treatment and that most disease progression can be detectedafter the first repeated *** combination of PSAD>0.2 ng ml^(−2)and PI-RADS 4 or 5 lesions may serve as a useful predictorof early disease progression and provide a guide to optimize follow-up protocols for men in different risk groups.

关键词： active surveillance cohort localized prostate cancer

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Downregulation of the circadian clock gene period 2 aggravates prognosis in breast cancer patients with obesity

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Oncology and Translational Medicine 2024年第2期10卷 73-78页

作者： Ru-Xing Wu Dan Hu Han-Wang Zhang Xiao-Yuan Huang Liang Zhuang Reproductive Medicine Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina cancer Biology Research centre Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina cancer Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Background:Obese individuals diagnosed with breast cancer often experience a less favorable prognosis;however,the underlying mechanisms linking obesity to breast cancer outcomes remain *** study aimed to identify and validate novel prognostic markers associated with breast cancer in patients with ***:We conducted a reanalysis of gene expression profiles from normal-weight,overweight,and obese breast cancer patients to identify candidate ***,we validated the protein levels of these candidates using ***,we investigated the association between candidate genes and breast cancer prognosis at Tongji Hospital,utilizing data from an 8-year follow-up through the Kaplan-Meier method and univariate and multivariate Cox regression ***:The fold change of the circadian clock gene period 2(PER2),which exhibited a declining trend with increasing body mass index,was 0.76 in obese patients compared with normal-weight *** expression rates of PER2 protein were 44.7%,51.5%,and 61.3%in normal-weight,overweight,and obese patients,*** 8-year recurrence-free survival rates were 75.9%,69.6%,and 64.1%,whereas the 8-year overall survival rates were 86.8%,83.0%,and 76.1%in normal-weight,overweight,and obese patients,respectively(Pcancer prognosis and may contribute to the unfavorable outcomes observed in obese patients.

关键词： Breast cancer Obesity PER2 Prognosis

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MiR-450b-5p enhances the radiosensitivity of HR^(+) and HER2^(−) breast cancer by targeting CDK6

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Oncology and Translational Medicine 2024年第4期10卷 198-203页

作者： Ruxing Wu Hanwang Zhang Xiaoyuan Huang Liang Zhuang Reproductive Medicine Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina cancer Biology Research centre Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina cancer Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

Background:The sensitivity of breast cancer cells to radiation is a key cause of locoregional recurrence after postoperative *** studies have reported that microRNAs(miRNAs)are involved in the radiosensitivity of human breast cancer *** miRNA microarray study showed that miR-450b-5p was overexpressed 13.3-fold in patients with estrogen receptor–positive(ER^(+))and human epidermal growth factor receptor 2–negative(HER2−)breast cancer and no local relapse compared with local relapse ***,its underlying mechanism of action remains ***:The predicted target mRNAs of miR-450b-5p were screened using the TargetScan,miRDB,and miRWalk *** blotting,quantitative polymerase chain reaction,and dual-luciferase reporter assays explored the association between cyclindependent kinase 6(CDK6)and *** cell counting kit-8 assay and flow cytometry detected the proliferation of transfected MCF7 *** formation and xenograft tumors detected the radiosensitivity of the transfected MCF7 ***:Bioinformatics analysis,Western blotting,quantitative polymerase chain reaction,and dual-luciferase reporter assays demonstrated that CDK6 was the target gene of ***,in vitro and in vivo experiments showed that miR-450b-5p inhibited MCF7 cell proliferation and cell cycle progression,increased the sensitizer enhancement ratio,and decreased the volume of xenograft tumors after irradiation by regulating ***:This study demonstrates that miR-450b-5p enhances the radiosensitivity of hormone receptor–positive(HR^(+))and HER2−breast cancer cells and elucidates its ***-450b-5p may be considered a therapeutic target in HR^(+)and HER2−breast cancer treated with radiotherapy.

关键词： Breast cancer Cyclin-dependent kinase 6 miR-450b-5p Radiosensitivity

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