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Bone marrow-derived mesenchymal stem cell transplantation attenuates overexpression of inflammatory mediators in rat brain after cardiopulmonary resuscitation

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Neural Regeneration Research 2020年第2期15卷 324-331页

作者： Qing-Ming Lin Xia-Hong Tang Shi-Rong Lin Ben-Dun Chen Feng Chen Institute of Fujian Emergency Medicine Clinical College of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of emergency Fujian Provincial HospitalFujian Provincial Emergency CenterFuzhouFujian ProvinceChina

Emerging evidence suggests that bone marrow-derived mesenchymal stem cell transplantation improves neurological function after cardiac arrest and cardiopulmonary resuscitation;however, the precise mechanisms remain unclear. This study aimed to investigate the effect of bone marrow-derived mesenchymal stem cell treatment on expression profiles of multiple cytokines in the brain after cardiac arrest and cardiopulmonary resuscitation. Cardiac arrest was induced in rats by asphyxia and cardiopulmonary resuscitation was initiated 6 minutes after cardiac arrest. One hour after successful cardiopulmonary resuscitation, rats were injected with either phosphate-buffered saline(control) or 1 × 10~6 bone marrow-derived mesenchymal stem cells via the tail vein. Serum S100 B levels were measured by enzyme-linked immunosorbent assay and neurological deficit scores were evaluated to assess brain damage at 3 days after cardiopulmonary resuscitation. Serum S100 B levels were remarkably decreased and neurological deficit scores were obviously improved in the mesenchymal stem cell group compared with the phosphate-buffered saline group. Brains were isolated from the rats and expression levels of 90 proteins were determined using a RayBio Rat Antibody Array, to investigate the cytokine profiles. Brain levels of the inflammatory mediators tumor necrosis factor-α, interferon-γ, macrophage inflammatory protein-1α, macrophage inflammatory protein-2, macrophage inflammatory protein-3α, macrophage-derived chemokine, and matrix metalloproteinase-2 were decreased ≥ 1.5-fold, while levels of the anti-inflammatory factor interleukin-10 were increased ≥ 1.5-fold in the mesenchymal stem cell group compared with the control group. Donor mesenchymal stem cells were detected by immunofluorescence to determine their distribution in the damaged brain, and were primarily observed in the cerebral cortex. These results indicate that bone marrow-derived mesenchymal stem cell transplantation attenuates brain damage induced by cardiac arrest and cardiopul

关键词： antibody array asphyxia brain damage cardiac arrest cardiopulmonary resuscitation global cerebral ischemia inflammatory mediator mesenchymal stem cell neurological deficit score S100B

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Non-cerebral vasospasm factors and cerebral vasospasm predict delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

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Chinese Medical Journal 2022年第2期135卷 222-224页

作者： Yue Chen Guanmin Li Xiaoyong Chen Dengliang Wang Wenhua Fang Dezhi Kang Chenyu Ding Department of Neurosurgery Neurosurgery Research InstituteThe First Affiliated Hospital of Fujian Medical UniversityFujian Provincial Key Laboratory of Precision Medicine for CancerFuzhouFujian 350001China Department of Plastic Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350001China The Graduate School of fujian Medical University FuzhouFujian 350001China

Aneurysmal subarachnoid hemorrhage(aSAH)is a typical neurosurgical emergency.The patient's prognosis is related to the severity of the initial illness and post-operative complications,especially delayed cerebral ischemia(DCI).DCI,which occurs in up to 30%of patients with subarachnoid hemorrhage(SAH),usually 2 weeks after hemorrhage,is one of the leading causes of death and disability in aSAH.

关键词： cerebral hemorrhage ischemia operative death after

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Bradykinin postconditioning protects rat hippocampal neurons after restoration of spontaneous circulation following cardiac arrest via activation of the AMPK/mTOR signaling pathway

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Neural Regeneration Research 2022年第10期17卷 2232-2237页

作者： Shi-Rong Lin Qing-Ming Lin Yu-Jia Lin Xin Qian Xiao-Ping Wang Zheng Gong Feng Chen Bin Song Provincial College of Clinical medicine Fujian Medical UniversityFuzhouFujian ProvinceChina Department of emergency Fujian Provincial Hospital South BranchFuzhouFujian ProvinceChina Department of emergency Fujian Provincial HospitalFuzhouFujian ProvinceChina fujian emergency Medical Center FuzhouFujian ProvinceChina fujian Provincial Key Laboratory of emergency medicine FuzhouFujian ProvinceChina Department of Human Anatomy School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina Key Laboratory of Brain Aging and Neurodegenerative Diseases of fujian Province FuzhouFujian ProvinceChina Laboratory of Clinical Applied Anatomy Fujian Medical UniversityFuzhouFujian ProvinceChina

Bradykinin(BK)is an active component of the kallikrein-kinin system that has been shown to have cardioprotective and neuroprotective effects.We previously showed that BK postconditioning strongly protects rat hippocampal neurons upon restoration of spontaneous circulation(ROSC)after cardiac arrest.However,the precise mechanism underlying this process remains poorly understood.In this study,we treated a rat model of ROSC after cardiac arrest(induced by asphyxiation)with 150μg/kg BK via intraperitoneal injection 48 hours after ROSC following cardiac arrest.We found that BK postconditioning effectively promoted the recovery of rat neurological function after ROSC following cardiac arrest,increased the amount of autophagosomes in the hippocampal tissue,inhibited neuronal cell apoptosis,up-regulated the expression of autophagy-related proteins LC3 and NBR1 and down-regulated p62,inhibited the expression of the brain injury marker S100βand apoptosis-related protein caspase-3,and affected the expression of adenosine monophosphate-activated protein kinase/mechanistic target of rapamycin pathway-related proteins.Adenosine monophosphate-activated protein kinase inhibitor compound C clearly inhibited BK-mediated activation of autophagy in rats after ROSC following cardiac arrest,which aggravated the injury caused by ROSC.The mechanistic target of rapamycin inhibitor rapamycin enhanced the protective effects of BK by stimulating autophagy.Our findings suggest that BK postconditioning protects against injury caused by ROSC through activating the adenosine monophosphate-activated protein kinase/mechanistic target of the rapamycin pathway.

关键词： autophagy bradykinin cardiac arrest cardiopulmonary resuscitation compound C hippocampus neuron rapamycin restoration of spontaneous circulation

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Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

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Neural Regeneration Research 2025年第4期20卷 1103-1123页

作者： Xiahong Tang Nan Zheng Qingming Lin Yan You Zheng Gong Yangping Zhuang Jiali Wu Yu Wang Hanlin Huang Jun Ke Feng Chen Shengli Clinical Medical College of fujian Medical University Fujian Medical UniversityFuzhouFujian ProvinceChina Department of emergency Fujian Provincial HospitalFuzhouFujian ProvinceChina fujian Provincial Key Laboratory of emergency medicine FuzhouFujian ProvinceChina The Second Department of Intensive Care Unit Fujian Provincial Hospital South BranchFuzhouFujian ProvinceChina

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological damage.Hypoxic preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are unknown.To this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factorκB pathways.Subsequently,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by asphyxia.The results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these effects.To conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

关键词： bone marrow–derived mesenchymal stem cells cardiac arrest cardiac resuscitation hypoxic preconditioning liver isoform of phosphofructokinase mitochondria neuroinflammation oxidative stress pyroptosis reactive oxygen species

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Cardiogenic shock and asphyxial cardiac arrest due to glutaric aciduria typeⅡ

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World Journal of emergency medicine 2023年第1期14卷 72-74页

作者： Hai-ping Xie Wei-jia Zeng Li-xun Chen Zhang-xin Xie Xiao-ping Wang Shen Zhao Shengli Clinical Medical College of fujian Medical University Fuzhou 350001China Department of emergency Fujian Provincial HospitalFuzhou 350001China fujian Provincial Key Laboratory of emergency medicine Fuzhou 350001China Department of Critical Care medicine Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China

Lipid storage myopathy(LSM)is a manifestation of lipid dysmetabolism,presenting with lipid accumulation in muscles.The mechanism includes defects in intracellular triglyceride catabolism,transport of long-chain fatty acids and carnitine,or fatty acidβ-oxidation.[1]Among LSMs,the most common type is multiple acyl-coenzyme A dehydrogenase deficiency(MADD).

关键词： oxidation shock

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Intravenous injection of Xuebijing attenuates acute kidney injury in rats with paraquat intoxication

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World Journal of emergency medicine 2017年第1期8卷 61-64页

作者： Jia-jun Xu Jian-tao Zhen Li Tang Qing-ming Lin Department of emergency medicine Quanzhou First Hospital Affiiated Fujian Medical University Department of emergency medicine Fujian Provincial Hospital Shengli Clinical Medical College of Fujian Medical University

BACKGROUND: The study aimed to investigate the therapeutic benefits of intravenous Xuebijing on acute kidney injury(AKI) in rats with paraquat intoxication.METHODS: Male Sprague-Dawley rats were randomly divided equally into three groups: sham group(n=8), paraquat group(n=8) and Xuebijing-treated group(n=8) using a random number table. The rats were intraperitoneally injected with 50 mg/kg of paraquat. One hour after paraquat administration, the rats were treated intravenously with Xuebijing(8 mL /kg). At 12 hours after paraquat administration, serum was collected to evaluate kidney function, then the rats were sacrificed and kidney samples were immediately harvested. AKI scores were evaluated by renal histopathology and pro-in? ammatory cytokines mR NA levels in kidney were assayed using real-time RT-PCR.RESULTS: Serum urea nitrogen, creatinine and AKI scores were significantly higher in the paraquat group, compared with the sham group(P<0.05, respectively). Moreover, interleukin(IL)-1β, IL-6 and TNF-α m RNA levels were signi? cantly higher in the paraquat group(P<0.01, respectively). However, intravenous Xuebijing signi? cantly decreased serum urea nitrogen, creatinine, AKI scores and IL-1β, IL-6 and TNF-α m RNA levels, compared with the paraquat group(P<0.05, respectively).CONCLUSION: Intravenous Xuebijing attenuates AKI following paraquat poisoning by suppressing in? ammatory response.

关键词： Paraquat Xuebijing Kidney injury Inflammation

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Liver Stiffness Measurement can Predict Liver Inflammation in Chronic Hepatitis B Patients with Normal Alanine Transaminase

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Journal of Clinical and Translational Hepatology 2023年第4期11卷 817-826页

作者： Ling-Ling Huang Xue-Ping Yu Qing-Fa Ruan Yan-Xue Lin Huan Li Wen Jin Rui-Feng Liu Yan-Lan Liang Yu-Rui Liu Yue-Yong Zhu Jia-Ji Jiang Ri-Cheng Mao Da-Wu Zeng Department of Hepatology Hepatology Research InstituteThe First Affiliated hospitalFujian Medical UniversityFuzhouFujianChina Department of Infectious Diseases The First Hospital of Quanzhou Affiliated to Fujian Medical UniversityQuanzhouFujianChina Hepatology Center Xiamen Hospital of Traditional Chinese MedicineXiamenFujianChina Department of Infectious Diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency ResponseNational Medical Center for Infectious DiseasesHuashan HospitalFudan UniversityShanghaiChina Hepatology Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouFujianChina Hepatology Fujian Medical University Xiamen Humanity HospitalXiamenFujianChina

Background and Aims:To determine whether liver stiffness measurement(LSM)indicates liver inflammation in chronic hepatitis B(CHB)with different upper limits of normal(ULNs)for alanine aminotransferase(ALT).Methods:We grouped 439 CHB patients using different ULNs for ALT:cohort I,≤40 U/L(439 subjects);cohort II,≤35/25 U/L(males/females;330 subjects);and cohort III,≤30/19 U/L(males/females;231 subjects).Furthermore,84 and 96 CHB patients with normal ALT(≤40 U/L)formed the external and prospective validation groups,respectively We evaluated the correlation between LSM and biopsy-confirmed liver inflammation,and determined diagnostic accuracy using area under the curve(AUC).A noninvasive LSM-based model was developed using multivariate logistic regression.Results:Fibrosis-adjusted LSM values significantly increased with increasing inflammation.The AUCs of LSM in cohorts I,II,and III were 0.799,0.796,and 0.814,respectively,for significant inflammation(A≥2)and 0.779,0.767,and 0.770,respectively,for severe inflammation(A=3).Cutoff LSM values in all cohorts for A≥2and A=3 were 6.3 and 7.5 kPa,respectively.Internal,external,and prospective validations showed high diagnostic accuracy of LSM for A≥2 and A=3,and no significant differences in AUCs among the four groups.LSM and globulin independently predicted A≥2.The AUC of an LSM-globulin model for A≥2 exceeded those of globulin,ALT,and AST,but was similar to that of LSM.Conclusions:LSM predicted liver inflammation and guided the indication of antiviral therapy for CHB in patients with normal ALT.

关键词： Hepatitis B virus Liver inflammation Fibrosis Liver stiffness measurement Alanine aminotransferase

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Application of Paclitaxel-loaded EGFR Peptide-conjugated Magnetic Polymeric Liposomes for Liver Cancer Therapy

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Current Medical Science 2020年第1期40卷 145-154页

作者： Zhen-lv LIN Jian DING Guo-ping SUN Dan LI Shan-shan HE Xiao-fei LIANG Xun-ru HUANG Jie XIE Department of emergency The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005China Department of Gastroenterology The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005China Department of Pharmacy Qingdao Seventh People's HospitalQingdao 266034China Department of Gastroenterology Union Hospital of Fujian Medical UniversityFuzhou 350001China State Key Laboratory of Oncogenes and Related Genes Shanghai Cancer InstituteShanghai Jiaotong University School of MedicineShanghai 200032China Department of Gastroenterology Hospital of Fujian Normal UniversityFujian Normal UniversityFuzhou 350007China

Developing the methodologies that allow for safe and effective delivery of therapeutic drugs to target sites is a very important research area in cancer therapy.In this study,polyethylene glycol(PEG)-coated magnetic polymeric liposome(MPL)nanoparticles(NPs)assembled from octadecyl quatemized carboxymethyl chitosan(OQC),PEGylated OQC,cholesterol,and magnetic NPs,and functionalized with epithelial growth factor receptor(EGFR)peptide,were successfully prepared for in-vivo liver targeting.The two-step liver targeting strategy,based on both magnetic force and EGFR peptide conjugation,was evaluated in a subcutaneous hepatocellular carcinoma model of nude mouse.The results showed that EGFR-conjugated MPLs not only accumulated in the liver by magnetic force,but could also diffuse into tumor cells as a result of EGFR targeting.In addition,paclitaxel(PTX)was incorporated into small EGFR-conjugated MPLs(102.0土0.7 nm),resulting in spherical particles with high drug encapsulation efficiency(>90%).The use of the magnetic targeting for enhancing the transport of PTX-loaded EGFR-conjugated MPLs to the tumor site was further confirmed by detecting PTX levels.In conclusion,PTX-loaded EGFR-conjugated MPLs could potentially be used as an effective drug delivery system for targeted liver cancer therapy.

关键词： drug delivery liver cancer magnetic nanoparticles quatemized chitosan targeted therapy

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Traditional Chinese medicine Treatment, Gua Sha, can Induce Subtle Molecular Changes in Gene Expression

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Biomedical and Environmental Sciences 2023年第5期36卷 441-451页

作者： QI Fei CAI Ye CHEN Jun Jie CHEN Chun Li HAN Xue Er XIA Qiu KAPRANOV Philipp institute of Genomics School of MedicineHuaqiao UniversityXiamen 361021FujianChina Traditional Chinese medicine Hospital of Huian Quanzhou 36200FujianChina

Objective Here, we explored molecular changes that could potentially mediate healing effects of Gua Sha — a method employed by the Chinese traditional medicine with proven track records of safe and efficient applications dating back to ancient times as well as support from randomized controlled trials performed by modern medical studies — yet remaining almost entirely unexplored by the modern-day high-throughput methods of the-omics sciences.Methods We investigated transcriptome changes occurring shortly after Gua Sha treatment in the whole blood of healthy volunteers using bulk RNA-seq analysis. We applied various analytical tools to identify genes with consistent expression changes in multiple individuals in response to Gua Sha and their networks.Results We found that while the changes were very subtle and individual-specific, we could identify consistent upregulation of three histone genes. Further analysis of the potential regulatory networks of these histone genes revealed the enrichment of functions involved in the immune response and inflammation.Conclusion The significance of these results in the context of potential effects of Gua Sha and the next steps in exploring the molecular mechanisms of action of this technique are discussed.

关键词： Gua Sha Transcriptomics Histone Long non-coding RNAs Chinese traditional medicine Immune system Inflammation

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Advantages of a Novel Model for Predicting Hepatic Fibrosis in Chronic Hepatitis B Virus Carriers Compared with APRI and FIB-4 Scores

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Journal of Clinical and Translational Hepatology 2022年第3期10卷 412-419页

作者： Na-Ling Kang Qing-Fa Ruan De-Sheng Zhang Xue-Ping Yu Zhen-Ting Hu Zhi-Min Lin Lu-Ying Wu Meng-Xin Lin Zu-Xiong Huang Jia-Ji Jiang Yu-Rui Liu Ri-Cheng Mao Da-Wu Zeng Department of Hepatology Hepatology Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhouFujianChina Hepatology Center Xiamen Hospital of Traditional Chinese MedicineXiamenFujianChina Department of Pharmacy the First Affiliated HospitalFujian Medical UniversityFuzhouFujianChina Department of Infectious Diseases Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency ResponseNational Medical Center for Infectious DiseasesHuashan HospitalFudan UniversityShanghaiChina Department of Infectious Diseases The First Hospital of Quanzhou Affiliated to Fujian Medical UniversityQuanzhouFujianChina Department of Infectious Disease The Affiliated Hospital of Putian CollegePutianFujianChina Department of Gastroenterology The Second Affiliated Hospital of Xiamen Medical CollegeXiamenFujianChina Hepatology Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouFujianChina

Background and Aims:Aspartate aminotransferase-toplatelet ratio index(APRI)and fibrosis-4 index(FIB-4)are widely used to assess liver fibrosis in chronic hepatitis B virus(HBV)infection.Currently,the definition of normal alanine aminotransferase(ALT)is controversial.We aimed to examine the diagnostic value of APRI and FIB-4 in chronic HBV carriers with different upper limits of normal(ULNs)for ALT.Methods:581 chronic HBV carriers were divided into the following four groups based on different ULNs for ALT:chronic HBV carriers I,II,III,and IV.Furthermore,106 chronic HBV carriers formed an external validation group.Predictive values of APRI and FIB-4 were elucidated using the area under the curve(AUC).A liver fibrosis-predictive model-GPSA(named for its measure of gamma glutamyl transpeptidase,platelet count,HBsAg and albumin)was developed using multivariate logistic regression analysis.Results:In chronic HBV carriers I,the AUCs of APRI and FIB-4 were 0.680 and 0.609 for significant fibrosis and 0.678 and 0.661 for cirrhosis,respectively.The AUCs of GPSA for significant fibrosis in the training group,internal group,and external validation group were 0.877,0.837,and 0.871,respectively.The diagnostic value of GPSA differed among chronic HBV carriers I,II,III,and IV,with AUCs for significant fibrosis being 0.857,0.853,0.868,and 0.905 and AUCs for cirrhosis being 0.901,0.905,0.886,and 0.913,respectively.GPSA showed a higher diagnostic value than APRI and FIB-4 for predicting significant fibrosis in the four groups.Conclusions:The GPSA model allows for accurate diagnosis of liver fibrosis in chronic HBV carriers with different ULN for ALT.

关键词： APRI FIB-4 Liver fibrosis Chronic HBV carriers HBV

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