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

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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Resident immune responses to spinal cord injury:role of astrocytes and microglia

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Neural Regeneration Research 2024年第8期19卷 1678-1685页

作者： Sydney Brockie Cindy Zhou Michael G.Fehlings Division of Genetics and Development Krembil Research InstituteUniversity Health NetworkTorontoONCanada Institute of Medical Science University of TorontoTorontoONCanada Division of Neurosurgery and Spine program Department of SurgeryUniversity of TorontoTorontoONCanada

Spinal cord injury can be traumatic or non-traumatic in origin,with the latter rising in incidence and prevalence with the aging demographics of our *** r,as the global population ages,individuals with co-existent degenerative spinal pathology comprise a growing number of traumatic spinal cord injury cases,especially involving the cervical spinal *** makes recovery and treatment approaches particula rly challenging as age and comorbidities may limit regenerative *** these reasons,it is critical to better understand the complex milieu of spinal cord injury lesion pathobiology and the ensuing inflammatory *** review discusses microglia-specific purinergic and cytokine signaling pathways,as well as microglial modulation of synaptic stability and plasticity after ***,we evaluate the role of astrocytes in neurotransmission and calcium signaling,as well as their border-forming response to neural *** the inflammatory and reparative roles of these cells have eluded our complete understanding and remain key therapeutic targets due to their extensive structural and functional roles in the nervous *** advances have shed light on the roles of glia in neurotransmission and reparative injury responses that will change how interventions are *** key processes and existing knowledge gaps will allow future research to effectively target these cells and harness their regenerative potential.

关键词： astrocytes glial signaling microglia spinal cord injury synaptic transmission

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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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Timing of hepatectomy following the Omicron variant infection for vaccinated-patients:A retrospective cohort study

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 515-520页

作者： Wu-Gui Yang Yu-Fu Peng Yu-Bo Yang Bo Li Yong-Gang Wei Fei Liu Division of Liver surgery Department of General SurgeryWest China HospitalSichuan UniversityChengdu 610041China

Many previous studies suggested that severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) infection elevated the risk of morbidity and 90-day mortality after operation, especially pulmonary complications [1–7]. Uncertainty about perioperative safety puts off the progress of elective surgery [8]. The Omicron variant has recently become the dominant variant causing prevalence in several countries [9]. Although a high rate of patients with Omicron presented asymptomatic status [10], it is still unclear whether Omicron infection would raise the risk of postoperative complications.

关键词： infection patients elevated

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PCAF-mediated acetylation of METTL3 impairs mRNA translation efficiency in response to oxidative stress

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Science China(Life Sciences) 2024年第10期67卷 2157-2168页

作者： Cheng Liu Miao Yu Mengyuan Wang Siyuan Yang Yenan Fu Lei Zhang Chaoyang Zhu Hongquan Zhang program for Cancer and Cell Biology Department of Human AnatomyHistology and EmbryologySchool of Basic Medical SciencesPeking University International Cancer Instituteand State Key Laboratory of Molecular OncologyPeking University Health Science CenterBeijing 100191China Department of General surgery and Urological surgery Huaihe HospitalHenan UniversityKaifeng 100084China Department of Human Anatomy Histologyand EmbryologyShenzhen University School of MedicineShenzhen 518055China

METTL3 methylates RNA and regulates the fate of mRNA through its methyltransferase ***3 enhances RNA translation independently of its catalytic ***,the underlying mechanism is still ***,we report that METTL3 is both interacted with and acetylated at lysine 177 by the acetyltransferase PCAF and deacetylated by *** the methyltransferase activity nor the stability of METTL3 is affected by its acetylation at ***,acetylation of METTL3 blocks its interaction with EIF3H,a subunit of the translation initiation factor,thereby reducing mRNA translation ***,acetylation of METTL3 responds to oxidative ***,oxidative stress enhances the interaction of PCAF with METTL3,increases METTL3 acetylation,and suppresses the interaction of METTL3 with EIF3H,thereby decreasing the translation efficiency of ribosomes and inhibiting cell ***,we suggest a mechanism by which oxidative stress regulates RNA translation efficiency by the modulation of METTL3 acetylation mediated by PCAF.

关键词： METTL3 acetylation PCAF m^(6)A oxidative stress translation SIRT3

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Effect of high-protein peptide-based formula compared with isocaloric isonitrogenous polymeric formula in critically ill surgical patient

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World Journal of Gastrointestinal surgery 2024年第6期16卷 1765-1774页

作者： Preeda Sumritpradit Prapimporn Chattranukulchai Shantavasinkul Winai Ungpinitpong Pinit Noorit Chotip Gajaseni Division of Trauma surgery and Surgical Critical Care Department of SurgeryFaculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok 10400Thailand Division of Nutrition and Biochemical Medicine Department of MedicineFaculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok 10400Thailand Graduate program in Nutrition Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok 10400Thailand Department of surgery Surin HospitalSurin 32000Thailand Department of surgery Chonburi HospitalChonburi 20000Thailand Department of Nursing Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkok 10400Thailand

BACKGROUND Malnutrition is common in critically ill patients,and it is associated with an increased risk of *** enteral nutrition with adequate caloric and protein intake is critical nevertheless it is difficult to ***-based formulas have been shown to be beneficial in patients with feeding ***,there are limited studies showing the efficacy and safety of high-protein peptide-based formula in critically ill surgical *** To determine the effects of a high-protein peptide formulation on gastrointestinal tolerance,nutritional status,biochemical changes,and adverse events in patients in the surgery intensive care unit(SICU)compared to an isocaloric isonitrogenous standard polymeric *** This study was a multi-center double-blind,randomized controlled *** enrolled adult patients in the surgical intensive care unit,age≥15 years and expected to receive enteral feeding for at least 5-14 d *** were randomly assigned to receive either the high-protein peptide-based formula or the isocaloric isonitrogenous standard formula for 14 *** residual volume(GRV),nutritional status,body composition and biochemical parameters were assessed at baseline and on days 3,5,7,9,11,and *** A total of 19 patients were enrolled,9 patients in the peptide-based formula group and 10 patients in the standard formula *** the study period,there were no differences of the average GRV,body weight,body composition,nutritional status and biochemical parameters in the patients receiving peptide-based formula,compared to the standard ***,participants in the standard formula lost their body weight,body mass index(BMI)and skeletal muscle mass *** body weight,BMI and muscle mass were maintained in the peptide-based formula,from baseline to day ***,the participants in the peptide-based formula tended to reach their caloric target faster than the standard ***

关键词： Peptide-based formula Surgical intensive care Hydrolyzed protein surgery Nutritional support

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HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 344-352页

作者： Qing-Zhi Hu Zhen-Rui Cao Wei-Xiong Zheng Min-Jie Zhao Jun-Hua Gong Cong Chen Zhong-Jun Wu Rui Tao Department of Hepatobiliary surgery Bishan Hospital of Chongqing Medical UniversityChongqing 402760China Department of Cardiothoracic surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China c Department of Hepatobiliary surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Hepatobiliary surgery the Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune *** shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein ***:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using ***-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following *** blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular ***:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer *** HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

关键词： Ischemia-reperfusion injury Liver transplantation Inflammation HSP110 Heat shock proteins NF-κB

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Piezoelectric film promotes skin wound healing with enhanced collagen deposition and vessels regeneration via upregulation of PI3K/AKT

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Nano Research 2024年第8期17卷 7461-7478页

作者： Qi Xu Wufei Dai Peizhe Li Qinglin Li Zhen Gao Xiaoli Wu Wei Liu Wenbo Wang Department of Plastic and Reconstructive surgery Shanghai Key Laboratory of Tissue EngineeringShanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China Research Institute of Plastic surgery Shandong Second Medical UniversityWeifang 261000China Department of surgery Air Force Medical CenterPLABeijing 100142China

Skin wounds are common in accidental injuries,and the intricacies of wound repair are closely linked to endogenous electric *** stimulation plays a pivotal role in the restorative processes of skin injuries,encompassing collagen deposition,angiogenesis,inflammation,and *** electrical stimulation therapy replicates and enhances the effects of endogenous wound electric fields by applying an external electric field to the wound site,thereby promoting skin wound *** this study,we developed a self-powered repetitive mechanical impacts-electrical stimulation(RMI-ES)system utilizing a BaTiO_(3)/polydimethylsiloxane(PDMS)piezoelectric composite *** to conventional electrical stimulation devices,the fabricated piezoelectric composite film efficiently harvests energy from the pressure applied by the stimulation device and the tensile force occurring during natural rat *** results demonstrated that piezoelectric stimulation generated by the composite membrane expedited the cell cycle,promoting fibroblast ***,piezoelectric stimulation induced favorable changes in fibroblast gene expression,including increased expression of transforming growth factor-β1(TGF-β1),connective tissue growth factor(CTGF),collagen 1,collagen 3,vascular endothelial growth factor(VEGF),and alpha-smooth muscle actin(α-SMA),while reducing interleukin-6(IL-6)*** analysis revealed that piezoelectric stimulation may induce fibroblast migration,proliferation,and collagen expression by influencing PI3K/AKT serine/threonine kinase(AKT)*** confirmation through the addition of the PI3K inhibitor LY294002 validated that piezoelectric stimulation can regulate the repair process after skin injury through the ***,in vivo results demonstrated that the electric field at the wound site effectively promoted wound healing,reduced inflammation,and stimulated collagen deposition and ne

关键词： BaTiO3/polydimethylsiloxane(PDMS)nano-composite membrane piezoelectrical stimulation skin wound healing collagen deposition PI3K/AKT serine/threonine kinase(AKT)signaling pathway

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Cholangiocarcinoma combined with biliary obstruction:an exosomal circRNA signature for diagnosis and early recurrence monitoring

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2642-2654页

作者： Ningyuan Wen Dingzhong Peng Xianze Xiong Geng Liu Guilin Nie Yaoqun Wang Jianrong Xu Shaofeng Wang Sishu Yang Yuan Tian Bei Li Jiong Lu Nansheng Cheng Division of Biliary surgery Department of General SurgeryWest China HospitalSichuan UniversityChengduSichuanChina Research Center for Biliary Diseases West China HospitalSichuan UniversityChengduSichuanChina

Cholangiocarcinoma(CCA)is a highly malignant biliary tract cancer with currently suboptimal diagnostic and prognostic *** present a novel system to monitor CCA using exosomal circular RNA(circRNA)via serum and biliary liquid biopsies.A pilot cohort consisting of patients with CCA-induced biliary obstruction(CCA-BO,n=5)and benign biliary obstruction(BBO,n=5)was used to identify CCA-derived exosomal circRNAs through microarray *** was followed by a discovery cohort(n=20)to further reveal a CCA-specific circRNA complex(hsa-circ-0000367,hsa-circ-0021647,and hsa-circ-0000288)in both bile and serum *** vitro and in vivo studies revealed the three circRNAs as promoters of CCA *** and prognostic models were established and verified by two independent cohorts(training cohort,n=184;validation cohort,n=105).An interpreter-free diagnostic model disclosed the diagnostic power of biliary exosomal circRNA signature(Bile-DS,AUROC=0.947,RR=6.05)and serum exosomal circRNA signature(Serum-DS,AUROC=0.861,RR=4.04)compared with conventional CA19-9(AUROC=0.759,RR=2.08).A prognostic model of CCA undergoing curative-intent surgery was established by calculating early recurrence score,verified with bile samples(Bile-ERS,C-index=0.783)and serum samples(Serum-ERS,C-index=0.782).These models,combined with other prognostic factors revealed by COX-PH model,enabled the establishment of nomograms for recurrence monitoring of *** study demonstrates that the exosomal triple-circRNA panel identified in both bile and serum samples serves as a novel diagnostic and prognostic tool for the clinical management of CCA.

关键词： biliary diagnosis Serum

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Colonoscopy plays an important role in detecting colorectal neoplasms in patients with gastric neoplasms

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 133-143页

作者： Xu-Rui Liu Ze-Lin Wen Fei Liu Zi-Wei Li Xiao-Yu Liu Wei Zhang Dong Peng Department of Gastrointestinal surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Gastrointestinal surgery Yongchuan Hospital of Chongqing Medical UniversityChongqing 402160China

BACKGROUND Gastric cancer(GC)and colorectal cancer(CRC)are the fifth and third most common cancer worldwide,***,GC is reported to have a potential predictive value for CRC,especially for advanced *** To evaluate the necessity of colonoscopy for gastric neoplasm(GN)*** Four databases,including PubMed,EMBASE,the Cochrane Library,and Ovid,were used to perform the search strategy on May 2,*** prevalence of colorectal neoplasms(CRN)and baseline characteristics were compared between the neoplasm group and the control *** variables are expressed as the mean difference and standard *** of categorical variables in the two groups are expressed as odds ratios(OR)and 95%confidence intervals(95%CIs).Subgroup analysis according to different kinds of GNs was conducted for more in-depth *** results of this study are represented by forest *** bias was evaluated by a funnel *** data analyses were performed by STATA SE 16.0 *** A total of 3018 patients with GNs and 3905 healthy controls(age and sex matched)were enrolled for *** comparing the prevalence of CRNs between the two groups,CRNs were detected significantly more frequently in GN patients than in controls(OR=1.69,95%CI=1.28 to 2.23,I^(2)=85.12%,P=0.00),especially in patients with GC(OR=1.80,95%CI=1.49 to 2.18,I^(2)=25.55%,P<0.1).Moreover,other risk factors including age(OR=1.08,95%CI=1.00 to 1.17,I^(2)=90.13%,P=0.00)and male sex(OR=2.31,95%CI=1.26 to 4.22,I^(2)=87.35%,P=0.00),were related to the prevalence of *** patients in the GN group,body mass index(BMI,OR=0.88,95%CI=0.80 to 0.98,I^(2)=0.00%,P=0.92)and smoking(OR=1.03,95%CI=1.01 to 1.05,I^(2)=0.00%,P=0.57)were protective and risk factors for CRNs,*** Patients are recommended to undergo colonoscopy when diagnosed with GNs,especially GC patients with a low BMI and a history of smoking.

关键词： Gastric neoplasm Gastric cancer Colorectal neoplasm Colonoscopy

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