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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

Sequential bowel necrosis and large gastric ulcer in a patient with a ruptured femoral artery:A case report

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2337-2342页

作者： Peng Wang Ting-Gang Wang An-Yong Yu Department of Emergency The Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina

BACKGROUND Severe bleeding as a result of a major vascular injury is a potentially fatal event commonly observed in the emergency *** necrosis and gastric ulcers secondary to ischemia are rare due to their rich blood *** this case,we present the case of a patient who was treated successfully following rupture of his femoral artery resulting in bowel necrosis and an unusually large gastric *** SUMMARY A 28-year-old male patient sustained a knife stab wound to the right thigh,causing rupture of his femoral artery and leading to massive *** underwent cardiopulmonary resuscitation and received a large blood *** surgeries confirmed bowel necrosis,and jejunostomy was *** necrotic intestine was removed,the remaining intestine was anastomosed,and the right thigh was *** three surgeries,the patient's overall condition gradually improved,and the patient was discharged from the ***,one day after discharge,the patient was admitted again due to dizziness and melena,and a gastroduodenoscopy revealed a giant banded *** 2 weeks of treatment,the ulcer had decreased in size without *** months after the last surgery,enterostomy and reintroduction surgery were *** patient was fitted with a right lower limb prosthesis one year after *** 3 years of follow-up,the patient did not complain of *** Trauma department physicians need to be aware of the possible serious complications involving the abdomen of trauma patients with massive bleeding.

关键词： Bowel necrosis Gastric ulcer Trauma Femoral artery rupture Ischemia Case report

Glutamatergic neurons of piriform cortex delay induction of inhalational general anesthesia

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Fundamental Research 2024年第4期4卷 829-840页

作者： Liang Zhou Qipeng Ran Rulan Yi Huanyao Tang Yu Zhang Tian Yu Key Laboratory of Brain Science Zunyi Medical UniversityZunyi 563003China Department of Anesthesiology Affiliated Hospital of Zunyi Medical UniversityZunyi 563003China Guizhou Key Laboratory of Anesthesia and Organ Protection Zunyi Medical UniversityZunyi 563003China

Since their clinical application in the 1840s,the greatest mystery surrounding general anesthesia(GA)is how different kinds of general anesthetics cause reversible unconsciousness,and the precise neural mechanisms underlying the *** past years,although many studies revealed the roles of cortex,thalamus,brainstem,especially the sleep-wake circuits in GA-induced loss of consciousness(LOC),the full picture of the neural circuit mechanism of GA is still largely *** studies have focused on the importance of other brain ***,we report that the activity of glutamatergic(Glu)neurons in the piriform cortex(PC),a critical brain region for odor encoding,began to increase during the LOC of GA and gradually recovered after recovery of *** lesions of the anterior PC(APC)neurons accelerated the induction time of isoflurane *** and optogenetic activation of APcGlu neurons prolonged isoflurane and sevoflurane anesthesia induction,whereas APcclu neuron inhibition displayed the opposite ***,the modification of APcclu neurons did not affect the induction or emergence time of propofol *** addition,odor processing may be partially involved in the induction of isoflurane and sevofurane GA regulated by APCclu *** conclusion,our findings reveal a critical role of APCGlu neurons in inhalational GA induction.

关键词： Piriform cortex Inhalationalgeneral anesthesia Glutamatergic Induction time odor

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

Elimination of methicillin‑resistant Staphylococcus aureus biofilms on titanium implants via photothermally‑triggered nitric oxide and immunotherapy for enhanced osseointegration

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Military medical Research 2024年第2期11卷 157-179页

作者： Yong‑Lin Yu Jun‑Jie Wu Chuan‑Chuan Lin Xian Qin Franklin R.Tay Li Miao Bai‑Long Tao Yang Jiao Department of Pathology Affiliated Hospital of Zunyi Medical UniversityZunyi 563003GuizhouChina Laboratory Research Center the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Blood Transfusion Laboratory of Radiation Biologythe Second Affiliated HospitalArmy Military Medical UniversityChongqing 400037China Department of Reproductive Endocrinology Chongqing Health Center for Women and ChildrenChongqing 401147China The Graduate School Augusta UniversityAugustaGA 30912USA Department of Stomatology the Seventh Medical Center of PLA General HospitalBeijing 100700China

Background:Treatment of methicillin-resistant Staphylococcus aureus(MRSA)biofilm infections in implant placement surgery is limited by the lack of antimicrobial activity of titanium(Ti)*** is a need to explore more effective approaches for the treatment of MRSA biofilm ***:Herein,an interfacial functionalization strategy is proposed by the integration of mesoporous polydopamine nanoparticles(PDA),nitric oxide(NO)release donor sodium nitroprusside(SNP)and osteogenic growth peptide(OGP)onto Ti implants,denoted as Ti-PDA@*** physical and chemical properties of Ti-PDA@SNP-OGP were assessed by scanning electron microscopy,X-ray photoelectron spectroscope,water contact angle,photothermal property and NO release *** synergistic antibacterial effect and elimination of the MRSA biofilms were evaluated by 2′,7′-dichlorofluorescein diacetate probe,1-N-phenylnaphthylamine assay,adenosine triphosphate intensity,O-nitrophenyl-β-D-galactopyranoside hydrolysis activity,bicinchoninic acid *** staining,assays for alkaline phosphatase activity,collagen secretion and extracellular matrix mineralization,quantitative real‑time reverse transcription‑polymerase chain reaction,and enzyme-linked immunosorbent assay(ELISA)were used to evaluate the inflammatory response and osteogenic ability in bone marrow stromal cells(MSCs),RAW264.7 cells and their co-culture *** staining,ELISA,micro-CT,hematoxylin and eosin,Masson's trichrome and immunohistochemistry staining were used to evaluate the eradication of MRSA biofilms,inhibition of inflammatory response,and promotion of osseointegration of Ti-PDA@SNP-OGP in ***:Ti-PDA@SNP-OGP displayed a synergistic photothermal and NO-dependent antibacterial effect against MRSA following near-infrared light(NIR)irradiation,and effectively eliminated the formed MRSA biofilms by inducing reactive oxygen species(ROS)-mediated oxidative stress,destroying bacterial membrane integrity and

关键词： Polydopamine nanoparticles Methicillin-resistant Staphylococcus aureus Nitric oxide Osseointegration Osteo-immunomodulation Photothermal effect Titanium implants

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

Bioinformatics comprehensive analysis confirmed the potential involvement of SLC22A1 in lower-grade glioma progression and prognosis

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BIOCELL 2024年第5期48卷 803-815页

作者： JING HUI NANA SUN YONG LIU CHUNBO YU YONG KE YONG CAO ANXIAO YU QINGHONG KONG YUN LIU Guizhou Provincial College-Based Key Lab for Tumor Prevention and Treatment with DistinctiveMedicines Zunyi Medical UniversityZunyi563000China College of Basic Medicine Zunyi Medical UniversityZunyi563000China Department of Dermatology Guizhou Province Cosmetic Plastic Surgery HospitalAffiliated Hospital of Zunyi Medical UniversityZunyi563000China School of Forensic Medicine Zunyi Medical UniversityZunyi563000China

Background:Although it has been established that the human Solute Carrier Family 22(SLC22)functions as a cationic transporter,influencing cellular biological metabolism by modulating the uptake of various cations,its impact on cancer prognosis remains ***:We conducted a comprehensive analysis utilizing data from The Cancer Genome Atlas(TCGA)and other databases to assess the prognostic value and functional implications across various *** of SLC22A1 RNA in glioma U251 cells was performed to access the impact of SLC22A1 on lowergrade glioma(LGG)***:Our findings demonstrated a significant correlation between SLC22A1 expression and the survival time of patients with various cancers(p0.8).Cell proliferation and clone formation experiment proved that decreased expression of SLC22A1 in glioma U251 cells inhibited glioma cell ***:Our findings suggest SLC22A1 has huge prospects as a promising biomarker and therapeutic target for LGG ***22A1 has only been proved to support cellular function *** findings demonstrated a robust connection between the tumor microenvironment and functional proteins that maintain basal cell metabolism,which gifts unique tumor immune characteristics of ***,we provide a highly practical prediction model for estimating the survival rate of LGG patients.

关键词： SLC22A1 LGG prognosis immune nomogram

Gastric metastasis of small cell lung carcinoma:Three case reports and review of literature

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World Journal of Gastroenterology 2024年第31期30卷 3717-3725页

作者： Shan Yang Qing-Yun He Qing-Jing Zhao Han-Tao Yang Zheng-Yi Yang Wen-Yi Che Hua-Mei Li Hui-Chao Wu Department of Gastroenterology The Affiliated Hospital of Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina Department of Gastroenterology Guizhou Hospital of The First Affiliated HospitalSun Yat-sen UniversityGuiyang 550000Guizhou ProvinceChina Department of Gastroenterology Zhejiang Provincial People's Hospital Bijie HospitalBijie 551700Guizhou ProvinceChina Department of Gastroenterology Zunyi Medical UniversityZunyi 563000Guizhou ProvinceChina

BACKGROUND Small cell lung carcinoma(SCLC)is highly susceptible to metastasis in the early stages of the ***,the stomach is an uncommon site of metastasis in SCLC,and only a few cases of this type of metastasis have been ***,SCLC gastric metastases have not been systematically characterized and are easily missed and *** SUMMARY We report three cases of gastric metastasis from SCLC in this *** first patient presented primarily with cough,hemoptysis,and epigastric *** other two patients presented primarily with abdominal discomfort,epigastric distension,and *** patients underwent gastroscopy and imaging ***,the immunohistochemical results of the lesions in three patients were suggestive of small cell ***,the three patients were diagnosed with gastric metastasis of SCLC through a comprehensive *** three patients did not receive appropriate treatment and died within a short *** Here,we focused on summarizing the characteristics of gastric metastasis of SCLC to enhance clinicians'understanding of this disease.

关键词： Small cell lung cancer Gastric neoplasms Neoplasm metastasis Diagnosis Case report

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