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Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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Neural Regeneration research 2024年第6期19卷 1325-1335页

作者： Li Sun Zhaoyan Zhao Jing Guo Yuan Qin Qian Yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang department of experimental surgery The Second Affiliated Hospital of Air Force Medical University department of Anesthesiology The Second Affiliated Hospital of Air Force Medical University

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride(TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9(S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that:(1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis;(2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and(4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-prolifera

关键词： ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis

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Transient receptor potential channels as predictive marker and potential indicator of chemoresistance in colon cancer

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Oncology research 2024年第1期32卷 227-239页

作者： WEI HU THOMAS WARTMANN MARCO STRECKER ARISTOTELIS PERRAKIS ROLAND CRONER ARPAD SZALLASI WENJIE SHI ULF D.KAHLERT The Fourth Clinical Medical College of Yangzhou University Nantong Rich HospitalNantongChina Molecular and experimental surgery Clinic for General-Visceral-Vascular and Transplant SurgeryFaculty of Medicine and University Hospital MagdeburgOtto-von-Guericke UniversityMagdeburgGermany department of Pathology and experimental Cancer research Semmelweis UniversityBudapestHungary

Transient receptor potential(TRP)channels are strongly associated with colon cancer development and *** study leveraged a multivariate Cox regression model on publicly available datasets to construct a TRP channels-associated gene signature,with further validation of signature in real world samples from our hospital treated patient ***-Meier(K-M)survival analysis and receiver operating characteristic(ROC)curves were employed to evaluate this gene signature’s predictive accuracy and robustness in both training and testing cohorts,***,the study utilized the CIBERSORT algorithm and single-sample gene set enrichment analysis to explore the signature’s immune infiltration landscape and underlying functional *** support vector machine algorithm was applied to evaluate the signature’s potential in predicting chemotherapy *** findings unveiled a novel three TRP channels-related gene signature(MCOLN1,TRPM5,and TRPV4)in colon adenocarcinoma(COAD).The ROC and K-M survival curves in the training dataset(AUC=0.761;p=1.58e-05)and testing dataset(AUC=0.699;p=0.004)showed the signature’s robust predictive capability for the overall survival of COAD *** of the immune infiltration landscape associated with the signature revealed higher immune infiltration,especially an increased presence of M2 macrophages,in high-risk group patients compared to their low-risk ***-risk score patients also exhibited potential responsiveness to immune checkpoint inhibitor therapy,evident through increased CD86 and PD-1 expression ***,the TRPM5 gene within the signature was highly expressed in the chemoresistance group(p=0.00095)and associated with poor prognosis(p=0.036)in COAD patients,highlighting its role as a hub gene of ***,this signature emerged as an independent prognosis factor for COAD patients(p=6.48e-06)and expression of model gene are validated by public data a

关键词： Colon cancer Transient receptor potential channels Prognostic signature Chemotherapy efficiency TRPM5

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Feeding the vasculature with cruciferous vegetables:a secret for organ protection

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Signal Transduction and Targeted Therapy 2024年第3期9卷 828-830页

作者： Priya Veluswamy Jens Wippermann Max Wacker Heart surgery research Department of Cardiothoracic SurgeryOtto-von-Guericke University HospitalMagdeburgGermany

Two very recent back-to-back papers published in Nature1,2 decipher the holistic role of the aryl hydrocarbon receptor(AHR)/dietary-ligand axis,in enteric and pulmonary vasculature to emphasize tolerance induction and vessel integrity during homeostasis,sterile inflammation and *** studies spectacularly highlight the significance of endothelium in orchestrating tissue tolerance by demonstrating the multifaceted activities of endothelial-expressed AHR that protects the vasculature to maintain organ homeostasis.

关键词： maintain sterile homeostasis

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Mapping the metabolic responses to oxaliplatin-based chemotherapy with in vivo spatiotemporal metabolomics

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Journal of Pharmaceutical Analysis 2024年第2期14卷 196-210页

作者： Mariola Olkowicz Khaled Ramadan Hernando Rosales-Solano Miao Yu Aizhou Wang Marcelo Cypel Janusz Pawliszyn department of Chemistry University of WaterlooWaterlooONCanada Jagiellonian Centre for experimental Therapeutics(JCET) Jagiellonian UniversityKrakowPoland Latner Thoracic surgery research Laboratories Toronto General Hospital Research InstituteUniversity Health NetworkTorontoONCanada The Jackson Laboratory JAX Genomic MedicineFarmingtonCTUSA Division of Thoracic surgery Department of SurgeryUniversity Health NetworkUniversity of TorontoToronto Lung Transplant ProgramTorontoONCanada

Adjuvant chemotherapy improves the survival outlook for patients undergoing operations for lung metastases caused by colorectal cancer (CRC). However, a multidisciplinary approach that evaluates several factors related to patient and tumor characteristics is necessary for managing chemotherapy treatment in metastatic CRC patients with lung disease, as such factors dictate the timing and drug regimen, which may affect treatment response and prognosis. In this study, we explore the potential of spatial metabolomics for evaluating metabolic phenotypes and therapy outcomes during the local delivery of the anticancer drug, oxaliplatin, to the lung. 12 male Yorkshire pigs underwent a 3 h left lung in vivo lung perfusion (IVLP) with various doses of oxaliplatin (7.5, 10, 20, 40, and 80 mg/L), which were administered to the perfusion circuit reservoir as a bolus. Biocompatible solid-phase microextraction (SPME) microprobes were combined with global metabolite profiling to obtain spatiotemporal information about the activity of the drug, determine toxic doses that exceed therapeutic efficacy, and conduct a mechanistic exploration of associated lung injury. Mild and subclinical lung injury was observed at 40 mg/L of oxaliplatin, and significant compromise of the hemodynamic lung function was found at 80 mg/L. This result was associated with massive alterations in metabolic patterns of lung tissue and perfusate, resulting in a total of 139 discriminant compounds. Uncontrolled inflammatory response, abnormalities in energy metabolism, and mitochondrial dysfunction next to accelerated kynurenine and aldosterone production were recognized as distinct features of dysregulated metabolipidome. Spatial pharmacometabolomics may be a promising tool for identifying pathological responses to chemotherapy.

关键词： Pulmonary metastases Colorectal cancer Adjuvant chemotherapy In vivo lung chemo-perfusion Solid-phase microextraction(SPME)microprobes Spatial metabolomics

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Skeletal interoception in osteoarthritis

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Bone research 2024年第2期12卷 241-254页

作者： Dinglong Yang Jiawen Xu Ke Xu Peng Xu department of Joint surgery Honghui HospitalXi’an Jiaotong UniversityXi’an 710054China department of Orthopedic surgery and Orthopedic research Institute West China HospitalSichuan UniversityChengdu 610041China

The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of the *** its various forms,skeletal interoception specifically regulates the metabolic homeostasis of ***(OA)is a complex joint disorder involving cartilage,subchondral bone,and *** subchondral bone undergoes continuous remodeling to adapt to dynamic joint *** findings highlight that skeletal interoception mediated by aberrant mechanical loads contributes to pathological remodeling of the subchondral bone,resulting in subchondral bone sclerosis in *** skeletal interoception is also a potential mechanism for chronic synovial inflammation in *** this review,we offer a general overview of interoception,specifically skeletal interoception,subchondral bone microenviroment and the aberrant subchondral *** also discuss the role of skeletal interoception in abnormal subchondral bone remodeling and synovial inflammation in OA,as well as the potential prospects and challenges in exploring novel OA therapies that target skeletal interoception.

关键词： homeostasis inflammation releasing

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Engineered stem cells by emerging biomedical stratagems

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Science Bulletin 2024年第2期69卷 248-279页

作者： Jinglin Wang Xiaoxuan Zhang Hanxu Chen Haozhen Ren Min Zhou Yuanjin Zhao department of Vascular surgery.Nanjing Drum Tower Hospital Affliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Division of Hepatobiliary surgery and Transplantation surgery Department of General SurgeryNanjing Drum Tower HospitalSchool of Biological Science and Medical EngineeringSoutheast UniversityNanjing 210096China Shenzhen research Institute Southeast UniversityShenzhen 518038China

Stem cell therapy holds immense potential as a viable treatment for a widespread range of intractable *** the safety of stem cell transplantation having been demonstrated in numerous clinical trials,various kinds of stem cells are currently utilized in medical *** the achievements,the therapeutic benefits of stem cells for diseases are limited,and the data of clinical researches are *** optimize tthe effectiveness of stem cells,engineering approaches have been developed to enhance their inherent abilities and impart them with new functionalities,paving the way for the next generation of stem cell *** review offers a detailed analysis of engineered stem cells,including their clinical applications and potential for future *** begin by briefly introducing the recent advances in the production of stem cells(induced pluripotent stem cells(ipsCs),embryonic stem cells(ESCs),mesenchymal stem cells(MSCs)and hematopoietic stem cells(HSCs).Furthermore,we present the latest developments of engineered strategies in stem cells,including engineered methods in molecular biology and biomaterial fields,and their application in biomedical ***,we summarize the current obstacles and suggest future prospects for engineered stem cells in clinical translations and biomedical applications.

关键词： Stem cells Genetic modification Biomaterials Microfluidics Organ-on-a-chip Bioprinting

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Mission of the National Cancer Center Hospital in Japan to promote clinical trials for precision medicine

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Cancer Biology & Medicine 2024年第1期21卷 1-3页

作者： Kazuaki Shimada Kenichi Nakamura Noboru Yamamoto department of Hepatobiliary and Pancreatic surgery National Cancer Center HospitalTokyo 104-0045Japan Clinical research Support Offce National Cancer Center HospitalTokyo 104-0045Japan department of experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan

Precision medicine is a growing field *** its potential benefit to many patients,several major obstacles must be overcome before precision medicine can be more widely used in clinical *** main obstacles are associated... 详细信息

关键词： clinical Cancer overcome

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Garg incontinence scores: New scoring system on the horizon to evaluate fecal incontinence. Will it make a difference?

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World Journal of Gastroenterology 2024年第3期30卷 204-210页

作者： Petr Tsarkov Inna Tulina Parvez Sheikh Darya D Shlyk Pankaj Garg department of Colorectal surgery Sechenov First Moscow State Medical UniversityMoscow 119991Russia department of Oncologic Colorectal surgery Sechenov First Moscow State Medical UniversityMoscow 119991Russia department of Colorectal surgery Saifee HospitalMumbai 400004MaharashtraIndia department of Colorectal surgery Garg Fistula Research InstitutePanchkula 134113HaryanaIndia

The main aim of this opinion review is to comment on the recent article published by Garg et al in the World Journal of Gastroenterology 2023;29:4593–*** authors in the published article developed a new scoring system,Garg incon-tinence scores(GIS),for fecal incontinence(FI).FI is a chronic debilitating disease that has a severe negative impact on the quality of life of the *** IV criteria define FI as multiple episodes of solid or liquid stool passed into the clothes at least twice a *** associated social stigmatization often leads to significant under-reporting of the condition,which further impairs *** important point is that the complexity and vagueness of the disease make it difficult for the patients to properly define and report the magnitude of the problem to their *** to this,the management becomes even more *** issue is resolved up to a considerable extent by a scoring *** were several scoring systems in use for the last three *** prominent of them were the Cleveland Clinic scoring system or the Wexner scoring system,*** Hospital or Vaizey’s scores,and the FI severity ***,there were several shortcomings in these scoring *** the opinion review,we tried to analyze the strength of GIS and compare it to the existing scoring *** main pitfalls in the existing scoring systems were that most of them gave equal weightage to different types of FI(solid,liquid,flatus,etc.),were not comprehensive,and took only the surgeon’s perception of FI into *** GIS,almost all shortcomings of previous scoring systems had been addressed:different weights were assigned to different types of FI by a robust statistical methodology;the scoring system was made comprehensive by including all types of FI that were previously omitted(urge,stress and mucus FI)and gave priority to patients’rather than the physicians’perceptions while developing the scoring *** to this,GIS in

关键词： Fecal incontinence Scoring system Urge Stress Flatus

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Early-onset and later-onset cancer: trends, risk factors, and prevention in Northern China

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Science China Life Sciences 2024年第9期67卷 1928-1940页

作者： Tong Liu Chen-An Liu Qing-Song Zhang Qi Zhang Yi-Ming Wang Meng-Meng Song Shi-Qi Lin Li Deng Shou-Ling Wu Han-Ping Shi department of Gastrointestinal surgery Department of Clinical Nutrition Beijing Shijitan Hospital Capital Medical University National Clinical research Center for Geriatric Diseases Xuanwu Hospital Capital Medical University Key Laboratory of Cancer FSMP for State Market Regulation Laboratory for Clinical Medicine Capital Medical University department of General surgery Kailuan General Hospital department of Genetics Yale School of Medicine department of Hepatobiliary surgery Kailuan General Hospital Cardiovascular research Institute University of California department of Cardiology Kailuan General Hospital

The characteristics of early-onset(onset age <50 years) and later-onset(onset age ≥50 years) cancers differ significantly. Identifying novel risk factors for both types of cancer is crucial for increasing awareness of cancer prevention and for reducing its burden. This study aimed to analyze the trends in incidence and risk factors for early-onset and late-onset cancers. We conducted a prospective study by drawing data from the Kailuan Study. This study included 6,741 participants with cancer(624 with early-onset cancer and 6,117 with later-onset cancer)and 6,780 matched controls among the 186,249 participants who underwent Kailuan health examinations from 2006 to 2019. The primary outcomes were cancer incidence rates, and associated risk factors for early-and later-onset cancer. Weighted Cox regression was used to calculate hazard ratios and 95% confidence intervals of each exposure factor for early-and later-onset cancer by cancer type. Populationattributable risk proportions were used to estimate the number of cases that could be prevented by eliminating a risk factor from the population. Except for liver cancer, incidence rates for nearly all types of cancer increased during the study period. Smoking, alcohol consumption, lipid metabolism disorders, hypertension, diabetes mellitus, fatty liver, and inflammation were associated with a significantly increased risk of cancer at multiple sites, but risk factors for cancer incidence differed by site. Smoking, alcohol consumption, inflammation,and hypertension were the major contributors to preventable cancer. The incidence of several different types of cancer, including earlyonset cancer, is increasing in northeastern China. Differences in risk factors between early-onset and later-onset malignancies may contribute to the divergence in the observed changes in incidence trends between these two specific types of cancer.

关键词： cancer early-onset later-onset trend risk factor prevention

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Recent progress in diagnostic imaging and therapeutics of osteosarcoma based on multifunctional nanoparticles

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Science China Chemistry 2024年第9期67卷 2864-2889页

作者： Xueke Yan Danmin Lin Dingyuan Yan Dong Wang Huifang Su department of Orthopaedic surgery The First Affiliated Hospital of Zhengzhou University Center for AIE research College of Materials Science and Engineering Shenzhen University

Osteosarcoma is one of the most common primary bone malignancies, mainly occurring in children and adolescents. Traditional diagnosis imaging methods for osteosarcoma contain X-ray, computed tomography and magnetic resonance imaging, and traditional therapy protocols are surgical resection and chemotherapy. However, these strategies are complicated and *** imaging methods, despite their maturity, have drawbacks that prevent them from showing more details. What is more, the prognosis for patients with osteosarcoma remains unsatisfactory due to side effects of chemotherapy, as well as incomplete surgical removal of the tumor. To compensate for the shortcomings of traditional imaging and treatment strategies for osteosarcoma, various types of nanoparticles have been designed and synthesized to selectively target osteosarcoma cells without toxic side effects on healthy organs. At the same time, these nanoparticle-based technologies can integrate the imaging and treatment of osteosarcoma. This review summarizes the application of nanotechnology in the imaging and treatment of osteosarcoma in recent years, and finally discusses the challenges and development prospects, aiming to provide ideas for future research.

关键词： osteosarcoma nanotechnology imaging diagnosis therapy

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