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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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Polydatin ameliorates hepatic ischemia-reperfusion injury by modulating macrophage polarization

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 25-34页

作者： Hai-Li Bao Chuan-Zhi Chen Chang-Zhen Ren Ke-Yan Sun Hao Liu Shao-Hua Song Zhi-Ren Fu Department of Organ Transplantation Shanghai Changzheng HospitalNavy Military Medical UniversityShanghai 200003China Department of Surgical Oncology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Cardiology Shanghai Changzheng HospitalNaval Military Medical UniversityShanghai 200003China Department of General Surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Background:Polydatin,a glucoside of resveratrol,has shown protective effects against various ***,little is known about its effect on hepatic ischemia-reperfusion(I/R)*** study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying ***:After gavage feeding polydatin once daily for a week,mice underwent a partial hepatic I/R *** alanine aminotransferase(ALT)/aspartate aminotransferase(AST),hematoxylin-eosin(H&E)and TdT-mediated dUTP nick-end labeling(TUNEL)staining were used to evaluate liver *** severity related to the inflammatory response and reactive oxygen species(ROS)production was also ***,immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in ***:Compared with the I/R group,polydatin pretreatment significantly attenuated I/R-induced liver damage and *** oxidative stress marker(dihydroethidium fluorescence,malondialdehyde,superoxide dismutase and glutathione peroxidase)and I/R related inflammatory cytokines(interleukin1β,interleukin-10 and tumor necrosis factor-α)were significantly suppressed after polydatin *** addition,the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in *** blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling ***:Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NFκB signaling.

关键词： Hepatic ischemia-reperfusion injury Polydatin Macrophage Polarization Inflammation

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Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第8期30卷 901-918页

作者： Yi-Ying Wang Mei-Mei Shen Jian Gao Department of Gastroenterology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China Department of Gastroenterology and Hepatology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of *** To explore the role of MTDH on stemness and immune infiltration in *** MTDH expression in HCC tissues was detected using TCGA and GEO *** was used to analyze the tissue *** was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell *** invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing ***,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free *** expression was determined by western blotting and quantitative reverse transcri-ption *** cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like *** effects of MTDH inhibition on tumor growth were evaluated in *** correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB *** HCC tissues expressed higher levels of MTDH than normal liver *** MTDH expression was associated with a poor *** cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these *** inhibition suppressed HCC progression and CD133 expression in *** was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T *** was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 a

关键词： Metadherin Hepatocellular carcinoma Cancer stem cells Immune infiltration

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Design,synthesis,and biological evaluation of novel chrysin derivatives as poly(ADP-ribose)polymerase 1(PARP1)inhibitors for the treatment of breast cancer

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Chinese Journal of Natural Medicines 2024年第5期22卷 455-465页

作者： YANG Yao TONG Jing XIE Xianshun CAO Hong FU Yong LUO Yong LIU Shan CHEN Wen YANG Ning Hengyang medical School University of South ChinaHengyang 421200China Emergency Department Hengyang Medical SchoolThe Second Affiliated HospitalUniversity of South ChinaHengyang 421200China Hengyang medical School The Second Affiliated HospitalUniversity of South ChinaHengyang 421200China Hemato-oncology Department Hengyang Medical SchoolThe Second Affiliated HospitalUniversity of South ChinaHengyang 421200China Department of Breast and Thyroid Surgery Hengyang Medical SchoolThe Second Affiliated HospitalUniversity of South ChinaHengyang 421200China

In this study,we reported the discovery and structure-activity relationship analysis of chrysin derivatives as a new class of inhibitors targeting poly(ADP-ribose)polymerase 1(PARP1).Among these derivatives,compound 5d emerged as the most effective chrysin-based inhibitor of PARP1,with an IC50 value of 108 nmol·L^(-1).This compound significantly inhibited the proliferation and migration of breast cancer cell lines HCC-1937 and MDA-MB-436 by inducing DNA ***,5d induced apoptosis and caused an extended G1/S-phase in these cell *** docking studies revealed that 5d possesses a strong binding affinity toward *** vivo,in a xenograft model,5d effectively reduced tumor growth by downregulating PARP1 ***,compound 5d shows promise as a potential therapeutic agent for the treatment of BRCA wild-type breast cancer.

关键词： Chrysin derivatives PARP1 Antitumor DNA damage Small molecules

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Can NogoA Be a Suitable Target to Treat Ischemic Stroke?

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Neuroscience Bulletin 2024年第4期40卷 557-560页

作者： Suliman Khan Abdul Nasir medical Research Center The Second Affiliated Hospital of Zhengzhou UniversityZhengzhou540014China

Treating stroke or restoring brain function after stroke remains challenging for clinicians[1,2].Researchers have largely focused on developing neuroprotective strategies and translating these discoveries from rodent experiments to the clinical setting;however,these have been typified by several failures[2].It is known that astrocytes play a crucial role in the pathogenesis of ischemic stroke[3,4].They are activated in response to stimuli arising from injury,characterized by drastic changes to their morphology and function-associated gene *** astrocytes exacerbate secondary neurodegeneration(repair of nervous tissue by the generation of new neurons,glial cells,axons,myelin,or synapses)[5]as well as provide neuroprotection during CNS pathologies[6].It is worth noting that myelin-related neurite growth inhibitors induce the suppression of axon regeneration after stroke[7].

关键词： protective NogoA clinical

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A Bird’s Eye View of Quantitative Proteome of Tumor Tissues from Lung Cancer Patients by a High Precision Mass Spectrometry Method

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Chemical Research in Chinese Universities 2024年第1期40卷 136-144页

作者： DU Xiaohui LI Encheng WANG Qi YOU Xin Lung Cancer Transitional Medicine Center The Second Affiliated Hospital of Dalian Medical UniversityDalian116023P.R.China Department of Scientific Research Center The Second Affiliated Hospital of Dalian Medical UniversityDalian116023P.R.China Department of Respiratory Medicine The Second Affiliated Hospital of Dalian Medical UniversityDalian116023P.R.China

Lung cancer produces a high incidence of malignant *** have been many studies on lung cancer using mass spectrometry(MS)***,most studies have focused on humoral *** this work,26 pairs of tissue samples(tumor ***-tumor)from patients with lung cancer were analyzed using liquid chromatography-tandem MS(LC-MS/MS)with data-independent acquisition *** total,3152 proteins were quantified from tissue samples with high confidence,including 189 up-regulated and 522 down-regulated proteins(tumor ***-tumor).In addition,79 and 690 proteins were identified only in para-cancerous samples and cancerous samples,*** results from bio-informatics tools indicated that altered proteins like PEBP1,HRG and LYZ could be ideal reservoirs for screening the potential biomarkers for lung *** is believed these tissue-specific proteomics results will assist in the studies of lung cancer.

关键词： Lung cancer Proteome Data-independent aquisition

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Intermittent sliding-lock-knot suture for limbal conjunctival autograft fixation in pterygium surgery:a technique note

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 838-844页

作者： Ling Zhang Run-Hua Lyu Jing-Ru Wang Wen-Jian Shi Feng Zheng Ying-Ying Gao Department of Ophthalmology the Second Affiliated HospitalFujian Medical UniversityQuanzhou 362000Fujian ProvinceChina Department of Neurosurgery the Second Affiliated HospitalFujian Medical UniversityQuanzhou 362000Fujian ProvinceChina

AIM:To report a technique used with intermittent slidinglock-knot(ISLK)fixation for limbal conjunctival autografts in pterygium surgery and compared with those of routine intermittent(RI)***:Consecutive patients with primary pterygium who had undergone pterygium excision combined with limbal conjunctival autograft transplantation between March 2021 and March 2022 at our institute were retrospectively *** outcome measures were mean duration of surgery and suture removal,degree of conjunctival hyperemia on postoperative day 1,pain score at suture removal,postoperative symptoms at 6mo,including conjunctival hyperemia,foreign body sensation,and graft ***:Ninety-eight patients underwent monocular surgery and were divided into ISLK(51 eyes)and RI(47 eyes)groups according to the type of conjunctiva autograft fixation method *** was no significant difference in mean duration of surgery between the two groups(18.59±2.39min vs 18.15±2.20min,P=0.417);however,compared to the RI group,shorter suture removal times were observed in the ISLK group[0.58min(0.42-0.87)vs 3.00min(2.21-4.15),P<0.001].The degree of conjunctival hyperemia on postoperative day 1 was milder in the ISLK group(P<0.001).Pain scores at suture removal were lower in the ISLK group than in RI group[1(0-3)vs 2(1-4),P<0.001].Postoperative symptoms at 6mo were comparable between the groups(P=0.487),with no ***:ISLK is an innovative method for limbal conjunctival autograft fixation after pterygium *** to RI fixation,ISLK facilitates suture removal and reduces discomfort,with comparable surgery duration and less conjunctival hyperemia.

关键词： intermittent sliding-lock-knot fixation pterygium suture removal

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Association between the cumulative triglyceride-glucose index and the recurrence of atrial fibrillation after radiofrequency catheter ablation

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Journal of Geriatric Cardiology 2024年第2期21卷 200-210页

作者： Qing YAN Jia-Qi LIANG Yi-De YUAN Yuan LI Jia-Li FAN Wen-Huan WU Pan XU Jia-Hong XUE Department of Cardiovascular Medicine the Second Affiliated Hospital of Xi’an Jiaotong UniversityShaanxiChina Department of Cardiovascular Medicine Zichang People’s HospitalShaanxiChina Department of Ultrasound Xijing HospitalAir Force Military Medical UniversityShaanxiChina

BACKGROUND Triglyceride-glucose(TyG)index values are a new surrogate marker for insulin *** study aimed to explore the relationship between cumulative TyG index values and atrial fibrillation(AF)recurrence after radiofrequency catheter ablation(RFCA).METHODS A total of 576 patients with AF who underwent RFCA at the second affiliated hospital of Xi'an Jiaotong university were included in this *** participants were grouped based on cumulative TyG index values tertiles within 3 months after *** regression and restricted cubic spline analyses were used to determine the relationship between cumulative TyG index values and AF *** predictive value of all risk factors was assessed by receiver operating curve *** There were 375 patients completed the study(age:63.23±10.73 years,64.27%male).The risk of AF recurrence increased with increasing cumulative TyG index values *** adjusting for potential confounders,patients in the medium cumulative TyG index group[hazard ratio(HR)=4.949,95%CI:1.778–13.778,P=0.002]and the high cumulative TyG index group(HR=8.716,95%CI:3.371–22.536,P<0.001)had a higher risk of AF recurrence than those in the low cumulative TyG index *** restricted cubic spline regression model also showed an increased risk of AF recurrence with increasing cumulative TyG index *** considering cumulative TyG index values,left atrial diameter,and lactate dehydrogenase levels as a comprehensive factor,the model could effectively predict AF recurrence after RFCA[area under the curve(AUC)=0.847,95%CI:0.797–0.897,P<0.001].CONCLUSIONS Cumulative TyG index values were a risk factor for AF recurrence after *** longitudinal TyG index values may assist with optimized for risk stratification and outcome prediction for AF recurrence.

关键词： atrial fibrillation index

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SENP3 Promotes Mantle Cell Lymphoma Development through Regulating Wnt10a Expression

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Current medical Science 2024年第1期44卷 134-143页

作者： Yan-ni MA Yun-ding ZOU Zhi-long LIU Gui-xian WU Yuan-ze ZHOU Cheng-xin LUO Xiang-tao HUANG Ming-ling XIE Shuang-nian XU Xi LI Department of Hematology Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China Department of Hematology the Third Affiliated Hospital(Daping Hospital)Third Military Medical University(Army Medical University)Chongqing 400042China

Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 *** of SENP3 has been proven to be involved in the development of various ***,its role in mantle cell lymphoma(MCL),a highly aggressive lymphoma,remains *** study was aimed to elucidate the effect of SENP3 in *** The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR,Western blotting or *** cells with stable SENP3 knockdown were constructed using short hairpin *** proliferation was assessed by CCK-8 assay,and cell apoptosis was determined by flow *** sequencing(mRNA-seq)was used to investigate the underlying mechanism of SENP3 knockdown on MCL development.A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in *** SENP3 was upregulated in MCL patient samples and *** of SENP3 in MCL cells inhibited cell proliferation and promoted cell ***,the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 ***,the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse *** SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.

关键词： mantle cell lymphoma SENP3 cell proliferation apoptosis

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Ischemic colitis induced by a platelet-raising capsule: A case report

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World Journal of Clinical Cases 2024年第3期12卷 607-615页

作者： Chen-Lu Wang Ze-Kun Si Guo-Hong Liu Chen Chen Hui Zhao Lei Li The affiliated hospital of Shandong second medical university School of Clinical MedicineShandong Second Medical UniversityWeifang 261000Shandong ProvinceChina Department of Gastroenterology The Affiliated Hospital of Shandong Second Medical UniversityWeifang 261000Shandong ProvinceChina

BACKGROUND Ischemic colitis(IC)is also known as colon ischemia and is caused by colon vascular occlusion or nonocclusion,which results in a reduced blood supply to the colon and is not significant enough to maintain the metabolic function of cells,leading to intestinal wall *** main symptoms include abdominal pain,diarrhea,and bloody *** severe cases,intestinal gangrene,peritonitis,intestinal stenosis and even intestinal obstruction may *** induced by long-term use of certain special drugs is relatively rare in clinical *** article describes the clinical diagnosis and treatment of a typical case and provides a new treatment idea for the treatment of *** SUMMARY The patient was admitted to the hospital with"abdominal pain for half a month and bloody stool with mucous and pus for 3 d"and was diagnosed with"IC".Symptomatic and supportive treatment,such as antibiotics(levofloxacin),acid inhibition and stomach protection,fluid replenishment,and intravenous nutrition,was *** patient's colonic ulcers were considered to be related to the oral administration of platelet(PLT)-raising capsules;the patient was asked to stop PLT-raising drugs for selective review via colonoscopy,and antibiotics and mesalazine enteric-coated tablets were *** the guidance of hematology consultation,60 mg of methylprednisolone was given in combination with PLT infusion to increase the *** treatment,the patient's condition stabilized,the patient’s stool turned yellow,the patient’s symptoms improved,and the patient was allowed to leave the *** PLT-raising capsules can lead to IC,so clinicians should have a full understanding of the application of these drugs in the treatment of various causes of thrombocyt-INTRODUCTION Ischemic colitis(IC)is also known as colon ischemia(CI)and is caused by colon vascular occlusion or nonocclusion,which results in a reduced blood supply to the colon;this process is not significant enough to maintai

关键词： Platelet-raising capsule Ischemic colitis Drug-related Colonic ulcer Case report

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