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The deterministic condition for the ground reaction force acting point on the combined knee valgus and tibial internal rotation moments in early phase of cutting maneuvers in female athletes

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Journal of Sport and Health Science 2024年第3期13卷 376-386页

作者： Issei Ogasawara Ken Ohta Gajanan S.Revankar Shoji Konda Yohei Shimokochi Hideyuki Koga Ken Nakata Department of Health and Sport sciences Graduate School of MedicineOsaka UniversityToyonaka 560-0043Japan Sports Sensing Co. LTD.Fukuoka 815-0035Japan Department of Neurology Graduate School of MedicineOsaka UniversitySuita 565-0871Japan Department of Health and Sport Management Osaka University of Health and Sport SciencesSennan-gun 590-0496Japan Department of Joint Surgery and Sports Medicine Graduate School of Medical and Dental SciencesTokyo Medical and Dental UniversityBunkyo-ku 113-8519Japan

Background:Combined knee valgus and tibial internal rotation(VL+IR)moments have been shown to stress the anterior cruciate ligament(ACL)in several in vitro cadaveric studies.To utilize this knowledge for non-contact ACL injury prevention in sports,it is necessary to elucidate how the ground reaction force(GRF)acting point(center of pressure(CoP))in the stance foot produces combined knee VL+IR moments in risky maneuvers,such as cuttings.However,the effects of the GRF acting point on the development of the combined knee VL+IR moment in cutting are still unknown.Methods:We first established the deterministic mechanical condition that the CoP position relative to the tibial rotational axis differentiates the GRF vector’s directional probability for developing the combined knee VL+IR moment,and theoretically predicted that when the CoP is posterior to the tibial rotational axis,the GRF vector is more likely to produce the combined knee VL+IR moment than when the CoP is anterior to the tibial rotational axis.Then,we tested a stochastic aspect of our theory in a lab-controlled in vivo experiment.Fourteen females performed 60˚cutting under forefoot/rearfoot strike conditions(10 trials each).The positions of lower limb markers and GRF data were measured,and the knee moment due to GRF vector was calculated.The trials were divided into anterior-and posterior-CoP groups depending on the CoP position relative to the tibial rotational axis at each 10 ms interval from 0 to 100 ms after foot strike,and the occurrence rate of the combined knee VL+IR moment was compared between trial groups.Results:The posterior-CoP group showed significantly higher occurrence rates of the combined knee VL+IR moment(maximum of 82.8%)at every time point than those of the anterior-CoP trials,as theoretically predicted by the deterministic mechanical condition.Conclusion:The rearfoot strikes inducing the posterior CoP should be avoided to reduce the risk of non-contact ACL injury associated with the combined knee VL+IR stress.

关键词： Center of pressure Deterministic condition Foot strike pattern Injury mechanism Moment of ground reaction force

Two distinct subpopulations of marginal zone B cells exhibit differential antibody-producing capacities and radioresistance

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Cellular & Molecular Immunology 2024年第4期21卷 393-408页

作者： Sujin Lee Yeunjung Ko Hyun Woo Lee Won Joon Oh Hun Gi Hong Dinuka Ariyaratne Se Jin Im Tae Jin Kim Department of Immunology Graduate School of Basic Medical ScienceSungkyunkwan University School of MedicineSuwon16419Republic of Korea Department of Immunology and Molecular Medicine Faculty of Medical SciencesUniversity of Sri JayewardenepuraNugegodaSri Lanka Present address:Immunology and Microbiology graduate Program Baylor College of MedicineHoustonTX77030USA

Marginal zone(MZ)B cells,which are splenic innate-like B cells that rapidly secrete antibodies(Abs)against blood-borne pathogens,are composed of heterogeneous subpopulations.Here,we showed that MZ B cells can be divided into two distinct subpopulations according to their CD80 expression levels.CD80^(high)MZ B cells exhibited greater Ab-producing,proliferative,and IL-10-secreting capacities than did CD80^(low)MZ B cells.Notably,CD80^(high)MZ B cells survived 2-Gy whole-body irradiation,whereas CD80^(low)MZ B cells were depleted by irradiation and then repleted with one month after irradiation.Depletion of CD80^(low)MZ B cells led to accelerated development of type II collagen(CII)-induced arthritis upon immunization with bovine CII.CD80^(high)MZ B cells exhibited higher expression of genes involved in proliferation,plasma cell differentiation,and the antioxidant response.CD80^(high)MZ B cells expressed more autoreactive B cell receptors(BCRs)that recognized double-stranded DNA or CII,expressed more immunoglobulin heavy chain sequences with shorter complementarity-determining region 3 sequences,and included more clonotypes with no N-nucleotides or with B-1a BCR sequences than CD80^(low)MZ B cells.Adoptive transfer experiments showed that CD21^(+)CD23^(+)transitional 2 MZ precursors preferentially generated CD80^(low)MZ B cells and that a proportion of CD80^(low)MZ B cells were converted into CD80^(high)MZ B cells;in contrast,CD80^(high)MZ B cells stably remained CD80^(high)MZ B cells.In summary,MZ B cells can be divided into two subpopulations according to their CD80 expression levels,Ab-producing capacity,radioresistance,and autoreactivity,and these findings may suggest a hierarchical composition of MZ B cells with differential stability and BCR specificity.

关键词： Marginal Zone B Cell CD80 Autoreactivity Radioresistance

Oncogenic β-catenin-driven liver cancer is susceptible to methotrexate-mediated disruption of nucleotide synthesis

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Chinese medical Journal 2024年第2期137卷 181-189页

作者： Fangming Liu Yuting Wu Baohui Zhang Shuhui Yang Kezhuo Shang Jie Li Pengju Zhang Weiwei Deng Linlin Chen Liang Zheng Xiaochen Gai Hongbing Zhang Department of Physiology State Key Laboratory of Common Mechanism Research for Major DiseasesHaihe Laboratory of Cell EcosystemInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China Department of Physiology Institute of Basic Medical Sciences and School of Basic MedicineGraduate School of Peking Union Medical CollegeChinese Academy of Medical SciencesBeijing100005China Department of Physiology School of Life ScienceChina Medical UniversityShenyangLiaoning 110122China school of Life sciences Westlake UniversityHangzhouZhejiang 310024China Key Laboratory of Pediatric Hematology and Oncology Ministry of HealthInstitute of Pediatric Translational MedicineShanghai Children’s Medical CenterShanghai Jiao Tong School of MedicineShanghai 200127China

Background:Liver cancer is largely resistant to chemotherapy.This study aimed to identify the effective chemotherapeutics forβ-catenin-activated liver cancer which is caused by gain-of-function mutation of catenin beta 1(CTNNB1),the most frequently altered proto-oncogene in hepatic neoplasms.Methods:Constitutiveβ-catenin-activated mouse embryonic fibroblasts(MEFs)were established by deleting exon 3(β-catenin^(Δ(ex3)/+)),the most common mutation site in CTNNB1 gene.A screening of 12 widely used chemotherapy drugs was conducted for the ones that selectively inhibitedβ-catenin^(Δ(ex3)/+)but not for wild-type MEFs.Untargeted metabolomics was carried out to examine the alterations of metabolites in nucleotide synthesis.The efficacy and selectivity of methotrexate(MTX)onβ-catenin-activated human liver cancer cells were determined in vitro.Immuno-deficient nude mice subcutaneously inoculated withβ-catenin wild-type or mutant liver cancer cells and hepatitis B virus(HBV);β-catenin^(lox(ex3)/+)mice were used,respectively,to evaluate the efficacy of MTX in the treatment ofβ-catenin mutant liver cancer.Results:MTX was identified and validated as a preferential agent against the proliferation and tumor formation ofβ-catenin-activated cells.Boosted nucleotide synthesis was the major metabolic aberration inβ-catenin-active cells,and this alteration was also the target of MTX.Moreover,MTX abrogated hepatocarcinogenesis of HBV;β-catenin^(lox(ex3)/+)mice,which stimulated concurrent Ctnnb1-activated mutation and HBV infection in liver cancer.Conclusion:MTX is a promising chemotherapeutic agent forβ-catenin hyperactive liver cancer.Since repurposing MTX has the advantages of lower risk,shorter timelines,and less investment in drug discovery and development,a clinical trial is warranted to test its efficacy in the treatment ofβ-catenin mutant liver cancer.

关键词： Liver cancer β-catenin Methotrexate Nucleotide synthesis Chemotherapy

Hernandezine promotes cancer cell apoptosis and disrupts the lysosomal acidic environment and cathepsin D maturation

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Chinese Journal of Natural Medicines 2024年第5期22卷 387-401页

作者： FENG Qianwen SUN Lu Muhammad Jibran Sualeh ZHAO Qingli ZHAO Songji CUI Zhengguo INADERA Hidekuni Department of Public Health Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyama 930-8501Japan Department of Pediatric Cardiology Heart CenterGuangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510000China Department of Basic medical sciences College of MedicineUniversity of SharjahSharjah 57545United Arab Emirates Department of Radiology Graduate School of Medicine and Pharmaceutical SciencesUniversity of ToyamaToyama 930-8501Japan Advanced Clinical Research Center Fukushima Global Medical Science CenterFukushima Medical UniversityFukushima CityFukushima 960-8074Japan Department of Environmental Health School of Medical SciencesUniversity of FukuiFukui 910-8580Japan

Hernandezine(Her),a bisbenzylisoquinoline alkaloid extracted from Thalictrum flavum,is recognized for its range of biological activities inherent to this herbal medicine.Despite its notable properties,the anti-cancer effects of Her have remained largely unexplored.In this study,we elucidated that Her significantly induced cytotoxicity in cancer cells through the activation of apoptosis and necroptosis mechanisms.Furthermore,Her triggered autophagosome formation by activating the AMPK and ATG5 conjugation systems,leading to LC3 lipidation.Our findings revealed that Her caused damage to the mitochondrial membrane,with the damaged mitochondria undergoing mitophagy,as evidenced by the elevated expression of mitophagy markers.Conversely,Her disrupted autophagic flux,demonstrated by the upregulation of p62 and accumulation of autolysosomes,as observed in the RFP-GFP-LC3 reporter assay.Initially,we determined that Her did not prevent the fusion of autophagosomes and lysosomes.However,it inhibited the maturation of cathepsin D and increased lysosomal pH,indicating an impairment of lysosomal function.The use of the early-stage autophagy inhibitor,3-methyladenine(3-MA),did not suppress LC3II,suggesting that Her also induces noncanonical autophagy in autophagosome formation.The application of Bafilomycin A1,an inhibitor of noncanonical autophagy,diminished the recruitment of ATG16L1 and the accumulation of LC3II by Her,thereby augmenting Her-induced cell death.These observations imply that while autophagy initially plays a protective role,the disruption of the autophagic process by Her promotes programmed cell death.This study provides the first evidence of Her’s dual role in inducing apoptosis and necroptosis while also initiating and subsequently impairing autophagy to promote apoptotic cell death.These insights contribute to a deeper understanding of the mechanisms underlying programmed cell death,offering potential avenues for enhancing cancer prevention and therapeutic strategies.

关键词： Hernandezine Apoptosis Mitophagy Autophagic flux Lysosome Noncanonical autophagy

TRAIL and Celastrol Combinational Treatment Suppresses Proliferation, Migration, and Invasion of Human Glioblastoma Cells via Targeting Wnt/β-catenin Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 322-329页

作者： QIN Jing-jing NIU Meng-da CHA Zhe GENG Qing-hua LI Yu-lin REN Chun-guang David P.Molloy YU Hua-rong Research Center of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China Department of Biochemistry and Molecular Biology School of Basic Medical SciencesChongqing Medical UniversityChongqing(400016)China

Objective To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand(TRAIL)and celastrol combination treatment(TCCT)in glioblastoma cells.Methods Cell counting kit-8 was used to detect the effects of different concentrations of celastrol(0-16µmol/L)and TRAIL(0-500 ng/mL)on the cell viability of glioblastoma cells.U87 cells were randomly divided into 4 groups,namely control,TRAIL(TRAIL 100 ng/mL),Cel(celastrol 0.5µmol/L)and TCCT(TRAIL 100 ng/mL+celastrol 0.5µmol/L).Cell proliferation,migration,and invasion were detected by colony formation,wound healing,and Transwell assays,respectively.Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition(EMT)markers(zona occludens,N-cadherin,vimentin,zinc finger E-box-binding homeobox,Slug,and β-catenin).Wnt pathway was activated by lithium chloride(LiCl,20 mol/L)and the mechanism for action of TCCT was explored.Results Celastrol and TRAIL synergistically inhibited the proliferation,migration,invasion,and EMT of U87 cells(P<0.01).TCCT up-regulated the expression of GSK-3β and down-regulated the expression of β-catenin and its associated proteins(P<0.05 or P<0.01),including c-Myc,Cyclin-D1,and matrix metalloproteinase(MMP)-2.In addition,LiCl,an activator of the Wnt signaling pathway,restored the inhibitory effects of TCCT on the expression of β-catenin and its downstream genes,as well as the migration and invasion of glioblastoma cells(P<0.05 or P<0.01).Conclusions Celastrol and TRAIL can synergistically suppress glioblastoma cell migration,invasion,and EMT,potentially through inhibition of Wnt/β-catenin pathway.This underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.

关键词： celastrol Chinese medicine tumor necrosis factor-related apoptosis-induced ligand glioblastoma β-catenin Tripterygium wilfordii

Single-cell RNA sequencing to understand host-virus interactions

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Virologica Sinica 2024年第1期39卷 1-8页

作者： Jia-Tong Chang Li-Bo Liu Pei-Gang Wang Jing An Department of Microbiology School of Basic Medical SciencesCapital Medical UniversityBeijing 100069China

Single-cell RNA sequencing(scRNA-seq)has allowed for the profiling of host and virus transcripts and host-virus interactions at single-cell resolution.This review summarizes the existing scRNA-seq technologies together with their strengths and weaknesses.The applications of scRNA-seq in various virological studies are discussed in depth,which broaden the understanding of the immune atlas,host-virus interactions,and immune repertoire.scRNA-seq can be widely used for virology in the near future to better understand the pathogenic mechanisms and discover more effective therapeutic strategies.

关键词： Single-cell RNA sequencing(scRNA-seq) Host-virus interaction COVID-19 Flavivirus

Chinese Medicine Combined with Adjuvant Chemotherapy for Improving Myelosuppression in Colorectal Cancer Patients: A Systematic Review and Network Meta-Analysis

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Chinese Journal of Integrative Medicine 2024年第7期30卷 643-652页

作者： LI Rui ZHANG Tong YAN Shao-hua YAN Yun-zi DING Ya-cong WANG Yan-song YANG Yu-fei Department of Oncology China Academy of Chinese Medical Sciences Xiyuan Hospital Department of Oncology Dongfang Hospital Beijing University of Chinese Medicine graduate school Beijing University of Chinese Medicine

Objective: To assess the effectiveness of Chinese herbal medicine(CHM) combined with adjuvant chemotherapy on myelosuppression for colorectal cancer(CRC) patients using network meta-analysis(NMA). Methods: Literature searches in both international(PubMed, Embase, Web of Science, and Cochrane Library) and Chinese(China Science and Technology Journal Database, Wanfang Data, China National Knowledge Infrastructure) databases for relevant randomized controlled trials(RCTs) were conducted from inception until October 10, 2022. We included RCTs of patients who received CHM combined with chemotherapy, including FOLFOX, XELOX, FOLFIRI, and other relevant regimens in the CHM treatment group. The outcomes included the incidence of myelosuppression, leukopenia, hemoglobin reduction, and thrombocytopenia. Two reviewers independently screened the databases, extracted the data, and assessed the risk of bias and credibility of evidence. RevMan 5.4.1 software and STATA 14.0 were used to perform the NMA. Results: A total of 31 RCTs were included, published from 2008 to 2021 in Chinese. Among these, 2,314 participants comparing the following 9 CHMs were identified: Shengbai Recipe(SBR), Bazhen Decoction(BZD), Jianpi Jiedu Recipe(JJR), Jianpi Recipe(JR), Compound Cantharis Capsule(CCC), Zaofan Pill(ZFP), Guilu Erxian Gel(GL), Buzhong Tiaogan Decoction(BZ), and Qiamagu Capsule(QM). The results of NMA found an indirect comparison. Based on the surface under the cumulative ranking curve(SUCRA), the ZFP+ chemotherapy group had the lowest incidence of myelosuppression, with an odds ratio(OR) of 0.08 [95% confidence interval(CI): 0.01, 0.76], whereas the GL+ chemotherapy group had the lowest incidence of leukopenia, hemoglobin reduction, and thrombocytopenia, with an OR of 5.25(95% CI: 2.41, 11.43), 4.66(95% CI: 2.23, 9.72), and 0.27(95% CI: 0.13, 0.54), respectively. Moreover, BZD + chemotherapy could alleviate leukopenia, hemoglobin reduction, and thrombocytopenia(P<0.01). Pairwise comparison showed that there was no difference in the

关键词： Chinese herbal medicine colorectal cancer network meta-analysis systematic review myelosuppression chemotherapy

Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

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Oncology Research 2024年第2期32卷 309-323页

作者： BEHROOZ JOHARI MILAD PARVINZAD LEILAN MAHMOUD GHARBAVI YOUSEF MORTAZAVI ALI SHARAFI HAMED REZAEEJAM Department of medical Biotechnology School of MedicineZanjan University of Medical SciencesZanjanIran Zanjan Pharmaceutical Biotechnology Research Center Zanjan University of Medical SciencesZanjanIran Nanotechnology Research Center Ahvaz Jundishapur University of Medical SciencesAhvazIran Department of Radiology Technology School of Allied Medical SciencesZanjan University of Medical SciencesZanjanIran

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

关键词： Combinational therapy Antisense therapy Myc signaling pathway Niosomes Radiation therapy SeNPs

Prevalence of Anemia in Patients with Diabetes Mellitus:A Systematic Review and Meta-Analysis

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Biomedical and Environmental sciences 2024年第1期37卷 96-107页

作者： Monireh Faghir-Ganji Narjes Abdolmohammadi Maryam Nikbina Alireza Amanollahi Alireza Ansari-Moghaddam Rozhan Khezri Hamidreza Baradaran Student Research Committee Iran University of Medical SciencesTehranIran Department of Epidemiology School of Public HealthIran University of Medical SciencesTehranIran Department of Epidemiology School of Public HealthTehran University of Medical SciencesTehranIran Department of Midwifery Shoushtar Faculty of Medical SciencesShoushtarIran Department of Epidemiology School of Public Health and SafetyShahid Beheshti University of Medical SciencesTehranIran Trauma and Injury Research Center Iran University of Medical SciencesTehranIran Health Promotion Research Center Zahedan University of Medical SciencesZahedanIran Endocrine Research Center Institute of Endocrinology and MetabolismIran University of Medical SciencesTehranIran

Objective Anemia is a common public health concern in patients with type 2 diabetes worldwide.This study aimed to identify the prevalence of anemia among patients with diabetes.Methods Electronic databases,including PubMed,Scopus,Web of sciences,and Google Scholar,were searched systematically for studies published between 2010 and 2021.After removing duplicates and inappropriate reports,the remaining manuscripts were reviewed and appraised using theNewcastleOttawa Scale(NOS)tool.A random-effects model was used to calculate the pooled estimates of the extracted data using Stata version 17.Heterogeneity of the studies was assessed using the Q statistic.Results A total of 51 articles containing information on 26,485 patients with diabetes were included in this study.The articles were mainly from Asia(58.82%)and Africa(35.29%).The overall prevalence of anemia was 35.45%(95%CI:30.30–40.76),with no evidence of heterogeneity by sex.Among the two continents with the highest number of studies,the prevalence of anemia in patients with diabetes was significantly higher in Asia[40.02;95%CI:32.72–47.54]compared to Africa[28.46;95%CI:21.90–35.50](P for heterogeneity=0.029).Moreover,there has been an increasing trend in the prevalence of anemia in patients with diabetes over time,from[15.28;95%CI:9.83–22.21]in 2012 to[40.70;95%CI:10.21–75.93]in 2022.Conclusion Globally,approximately 4 in 10 patients with diabetes suffer from anemia.Therefore,routine anemia screening and control programs every 3 months might be useful in improving the quality of life of these patients.

关键词： Prevalence Diabetic foot Anemia Diabetes mellitus