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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 *** 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 *** 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 factor κB ***,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 *** 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 *** 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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The compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one alleviates neuroinflammation and cognitive impairment in a mouse model of Alzheimer's disease

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Neural Regeneration Research 2025年第11期20卷 3330-3344页

作者： Xueyan Liu Wei Wu Xuejuan Li Chengyan Wang Ke Chai Fanru Yuan Huijuan Zheng Yuxing Yao Chenlu Li Zu-Cheng Ye Daijun Zha department of Medicinal Chemistry School of PharmacyFujian Medical UniversityFuzhouFujian ProvinceChina fujian provincial Key Laboratory of Brain Aging and Neurodegenerative Diseases School of Basic Medical SciencesFujian Medical UniversityFuzhouFujian ProvinceChina Institute of Laboratory Animal Center Fujian Medical UniversityFuzhouFujian ProvinceChina department of Neurosurgery Neurosurgery Research InstituteThe First Affiliated HospitalFujian Medical UniversityFuzhouFujian ProvinceChina department of Hyperbaric Oxygen National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouFujian ProvinceChina

Previous studies have shown that the compound(E)-2-(3,4-dihydroxystyryl)-3-hydroxy-4H-pyran-4-one(D30),a pyromeconic acid derivative,possesses antioxidant and anti-inflammatory properties,inhibits amyloid-β aggregation,and alleviates scopolamine-induced cognitive impairment,similar to the phase Ⅲ clinical drug *** this study,we established a mouse model of Alzheimer's disease via intracerebroventricular injection of fibrillar amyloid-β to investigate the effect of D30 on fibrillar amyloid-β-induced *** results showed that D30 alleviated fibrillar amyloid-β-induced cognitive impairment,promoted fibrillar amyloid-β clearance from the hippocampus and cortex,suppressed oxidative stress,and inhibited activation of microglia and astrocytes.D30 also reversed the fibrillar amyloid-β-induced loss of dendritic spines and synaptic protein ***,we demonstrated that exogenous fibrillar amyloid-βintroduced by intracerebroventricular injection greatly increased galectin-3 expression levels in the brain,and this increase was blocked by *** the role of D30 in clearing amyloid-β,inhibiting neuroinflammation,protecting synapses,and improving cognition,this study highlights the potential of galectin-3 as a promising treatment target for patients with Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β astrocyte cognitive impairment D30 dendritic spines galectin-3 microglia neuroinflammation neuron

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Unlocking the future:Mitochondrial genes and neural networks in predicting ovarian cancer prognosis and immunotherapy response

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World Journal of Clinical Oncology 2025年第1期16卷 43-52页

作者： Zhi-Jian Tang Yuan-Ming Pan Wei Li Rui-Qiong Ma Jian-Liu Wang department of Obstetrics and Gynecology Peking University People’s HospitalBeijing 100044China Cancer Research Center Beijing Chest HospitalBeijing 101149China department of thoracic surgery Sichuan Provincial People's HospitalChengdu 610072Sichuan ProvinceChina

BACKGROUND Mitochondrial genes are involved in tumor metabolism in ovarian cancer(OC)and affect immune cell infiltration and treatment *** To predict prognosis and immunotherapy response in patients diagnosed with OC using mitochondrial genes and neural *** Prognosis,immunotherapy efficacy,and next-generation sequencing data of patients with OC were downloaded from The Cancer Genome Atlas and Gene Expression *** genes were sourced from the MitoCarta3.0 *** discovery cohort for model construction was created from 70% of the patients,whereas the remaining 30% constituted the validation *** the expression of mitochondrial genes as the predictor variable and based on neural network algorithm,the overall survival time and immunotherapy efficacy(complete or partial response)of patients were *** In total,375 patients with OC were included to construct the prognostic model,and 26 patients were included to construct the immune efficacy *** average area under the receiver operating characteristic curve of the prognostic model was 0.7268[95% confidence interval(CI):0.7258-0.7278]in the discovery cohort and 0.6475(95%CI:0.6466-0.6484)in the validation *** average area under the receiver operating characteristic curve of the immunotherapy efficacy model was 0.9444(95%CI:0.8333-1.0000)in the discovery cohort and 0.9167(95%CI:0.6667-1.0000)in the validation *** The application of mitochondrial genes and neural networks has the potential to predict prognosis and immunotherapy response in patients with OC,providing valuable insights into personalized treatment strategies.

关键词： Ovarian cancer Mitochondria Prognosis Immunotherapy Neural network

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Potassium and calcium channels in different nerve cells act as therapeutic targets in neurological disorders

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Neural Regeneration Research 2025年第5期20卷 1258-1276页

作者： Qing Qiu Mengting Yang Danfeng Gong Haiying Liang Tingting Chen department of Pharmacology School of PharmacyNantong UniversityNantongJiangsu ProvinceChina Jiangsu Province Key Laboratory of Inflammation and Molecular Drug Target NantongJiangsu ProvinceChina department of Pharmacy Longyan First Affiliated Hospital of Fujian Medical UniversityLongyanFujian ProvinceChina

The central nervous system, information integration center of the body, is mainly composed of neurons and glial cells. The neuron is one of the most basic and important structural and functional units of the central nervous system, with sensory stimulation and excitation conduction functions. Astrocytes and microglia belong to the glial cell family, which is the main source of cytokines and represents the main defense system of the central nervous system. Nerve cells undergo neurotransmission or gliotransmission, which regulates neuronal activity via the ion channels, receptors, or transporters expressed on nerve cell membranes. Ion channels, composed of large transmembrane proteins, play crucial roles in maintaining nerve cell homeostasis. These channels are also important for control of the membrane potential and in the secretion of neurotransmitters. A variety of cellular functions and life activities, including functional regulation of the central nervous system, the generation and conduction of nerve excitation, the occurrence of receptor potential, heart pulsation, smooth muscle peristalsis, skeletal muscle contraction, and hormone secretion, are closely related to ion channels associated with passive transmembrane transport. Two types of ion channels in the central nervous system, potassium channels and calcium channels, are closely related to various neurological disorders, including Alzheimer's disease, Parkinson's disease, and epilepsy. Accordingly, various drugs that can affect these ion channels have been explored deeply to provide new directions for the treatment of these neurological disorders. In this review, we focus on the functions of potassium and calcium ion channels in different nerve cells and their involvement in neurological disorders such as Parkinson's disease, Alzheimer's disease, depression, epilepsy, autism, and rare disorders. We also describe several clinical drugs that target potassium or calcium channels in nerve cells and could be u

关键词： astrocytes calcium channels central nervous system extracellular ion concentration microglia neurological disorders neurons potassium channels

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Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

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Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： Xihang Chen Zhifeng Chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi Shi Wei Chen Shiming Yang Senior department of Otolaryngology Head and Neck surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of Hearing and Balance Science BeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Laboratory of Hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of Hearing Impairment Prevention and Treatment BeijingChina department of Otorhinolaryngology Head and Neck surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina department of Otolaryngology Head and Neck surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

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Cytotoxic Activities of Total Saponins from Plena Clematis on Human Tumor Cell Lines In Vitro

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Chinese Journal of Integrative Medicine 2018年第10期24卷 763-767页

作者： ZHU Fu-rong LI Yong-ning HE Shu-lan CHEN Qian-shun XU Xun-yu department of Pharmacy Fujian Health College provincial Clinical College of fujian Medical University Department of Thoracic Surgery Fujian Provincial Hospital

Objective： To investigate the anti-proliferative effects of saponins prepared from Plena Clematis （PC） cultured in fujian Province, China on 4 human tumor cell lines and its possible anti-tumor mechanism. Methods： The growth inhibition assays of saponins on human esophageal squamous carcinoma cell line （EC9706）, human hepatoma cell line （HepG-2）, human oral cancer cell line （KB） and human gastric cancer cell line （BGC-823） were evaluated in vitro by thiazolyl blue （MTT） method. The inhibitory effects on EC9706 treated with different concentrations of saponins （15.62, 31.25, 62.50, 125, 250 and 500 μg/mL） were performed in vitro by MTT method. The morphology and nuclear staining with acridine orange/ethidium bromide of EC9706 calls treated with saponins were illustrated under an inverted phase fluorescence microscope. The apoptotic effects of saponins were further evaluated by annexin-V/propidium iodide dual staining experiment to examine the occurrence of phosphatidylserine externalization onto the call surface by a flow cytometer. Results： MTT assay showed that the saponins could inhibit the proliferation of 4 tumor cell lines. Among them, the maximum inhibition rate of 73.1% was detected in EC9706 cells at the saponins concentration of 250 μg/mL for 24 h. Further investigation indicated that the saponins induced EC9706 cells apoposis. The EC9706 cells presented apoptotic characteristics when treated with saponins, including that the morphologies of EC9706 cells were appeared round-shaped with higher refraction, and the cell nuclear stained orange with EB after 250 μ g/mL saponins exposure. The flow cytometry analysis results showed that the induction of cell cycle arrest in apoptotic system may participate in the anti-proliferative activity of saponins on EC9706 cells. Conclusion： The saponins from PC exhibited significant cytotoxicity against human EC9706, KB, BGC-823, and HepG-2 cells and might be beneficial to development of ethnic pharmaceutical plant for pote

关键词： Plena Clematis Clematis florida var. plena D cytotoxic activity saponins human esophageal cancer cell

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Eukaryotic elongation factor-1α 2 knockdown inhibits hepatocarcinogenesis by suppressing PI3K/Akt/NF-κB signaling

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World Journal of Gastroenterology 2016年第16期22卷 4226-4237页

作者： Fu-Nan Qiu Yi Huang Dun-Yan Chen Feng Li Yan-An Wu Wen-Bing Wu Xiao-Li Huang provincial Clinical College Fujian Medical University department of Hepatobiliary surgery Fujian Provincial Hospital department of Clinical Laboratory Fujian Provincial Hospital department of Pathology Fujian Provincial Hospital

AIM: To assess the impact of eukaryotic elongation factor 1 alpha 2 (eEF1A2) on hepatocellular carcinoma (HCC) cell proliferation, apoptosis, migration and invasion, and determine the underlying ***: eEF1A2 levels were detected in 62 HCC tissue samples and paired pericarcinomatous specimens, and the human HCC cell lines SK-HEP-1, HepG2 and BEF-7402, by real-time PCR and immunohistochemistry. Experimental groups included eEF1A2 silencing in BEL-7402 cells with lentivirus eEF1A2-shRNA (KD group) and eEF1A2 overexpression in SK-HEP-1 cells with eEF1A2 plasmid (OE group). Non-transfected cells (control group) and lentivirus-based empty vector transfected cells (NC group) were considered control groups. Cell proliferation (MTT and colony formation assays), apoptosis (Annexin V-APC assay), cell cycle (DNA ploidy assay), and migration and invasion (Transwell assays) were assessed. Protein levels of PI3K/Akt/NF-κB signaling effectors were evaluated by Western ***: eEF1A2 mRNA and protein levels were significantly higher in HCC cancer tissue samples than in paired pericarcinomatous and normal specimens. SK-HEP-1 cells showed lower eEF1A2 mRNA levels; HepG2 and BEL-7402 cells showed higher eEF1A2 mRNA levels, with BEL-7402 cells displaying the highest amount. Efficient eEF1A2 silencing resulted in reduced cell proliferation, migration and invasion, increased apoptosis, and induced cell cycle arrest. The PI3K/Akt/NF-κB signaling pathway was notably inhibited. Inversely, eEF1A2 overexpression resulted in promoted cell proliferation, migration and ***: eEF1A2, highly expressed in HCC, is a potential oncogene. Its silencing significantly decreases HCC tumorigenesis, likely by inhibiting PI3K/Akt/NF-κB signaling.

关键词： Hepatocellular carcinoma Carcinogenesis Eukaryotic elongation factor 1 alpha 2 Proliferation PI3K/Akt/NF-κ B signaling pathway

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Analysis of factors influencing skip lymphatic metastasis in pN_2 non-small cell lung cancer

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Chinese Journal of Cancer Research 2012年第4期24卷 340-345页

作者： Gui-Long Li Yong Zhu Wei Zheng Chao-Hui Guo Chun Chen department of thoracic surgery Fujian Medical University Union Hospital

Objective： Although many clinical studies on skip lymphatic metastasis in non-small cell lung cancer have been reported, the risk factors for skip lymphatic metastasis are still controversy and debatable. This study investigated, by multivariate logistic regression analysis, the clinical features of skip metastasis to mediastinal lymph nodes （N2） in non-small cell lung cancer 0NISCLC） patients. Methods： We collected the clinicopathological data of 256 pN2-NSCLC patients who underwent lobectomy plus systemic lymph node dissection in fujian Medical University Union hospital. The cases in the present study were divided into two groups： skip metastasis （N2 skip＋） and non- skip metastasis （N2 skip-）. A retrospective analysis of clinical pathological features of two groups was performed, rib determine an independent factor, multivariate logistic regression analysis was used to identify possible risk factors. Results： A total of 256 pN2-NSCLC patients were recruited. The analysis results showed that gender, pathologic types, surgery, pleural involvement, smoking history, age, tumor stages, and differentiation were not statistical significant factors impacting on skip metastasis in pN2-NSCLC （P〉0.05）, whereas tumor size was an independent factor for skip metastasis （P=0.02）. Conclusions： The rate of skip lymphatic metastasis increases in pN2-NSCLC patients, in accompany with an increased tumor size.

关键词： Lung cancer lymph node skip metastasis

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Novel technique for lymphadenectomy along left recurrent laryngeal nerve during thoracoscopic esophagectomy

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World Journal of Gastroenterology 2020年第12期26卷 1340-1351页

作者： Wen-Shu Chen Li-Huan Zhu Wu-Jin Li Peng-Jie Tu Jian-Yuan Huang Pei-Lin You Xiao-Jie Pan department of thoracic surgery Shengli Clinical Medical College of Fujian Medical UniversityFujian Provincial HospitalFuzhou 350001Fujian ProvinceChina

BACKGROUND In esophageal squamous carcinoma,lymphadenectomy along the left recurrent laryngeal nerve(RLN)is recommended owing to its highly metastatic ***,this procedure is difficult due to limited working space in the left upper mediastinum,and increases postoperative *** To present a novel method for lymphadenectomy along the left RLN during thoracoscopic esophagectomy in the semi-prone *** The fundamental concept of this novel method is to exfoliate a bilateral pedicled nerve flap,which is a two-dimensional membrane,which includes the left RLN,lymph nodes(LNs)along the left RLN,and tracheoesophageal vessels,by suspending the esophagus to the dorsal side and pushing the trachea to the ventral side(named“bilateral exposure method”).Then,the hollow-out method is performed to transform the two-dimensional membrane to a three-dimensional structure,in which the left RLN and tracheoesophageal vessels are easily distinguished and preserved during lymphadenectomy along the left *** novel method was retrospectively evaluated in 116 consecutive patients with esophageal squamous carcinoma from August 2016 to February *** There were 58 patients in each *** significant difference was found between the two groups in terms of age,gender,postoperative pneumonia,anastomotic fistula,and postoperative ***,the number of dissected LNs along the left RLN in this novel method was significantly higher than that in the conventional method(4.17±0.359 vs 2.93±0.463,P=0.0447).Moreover,the operative time and the rate of postoperative hoarseness in the novel method were significantly lower than those in the conventional method(306.0±6.774 vs 335.2±7.750,P=0.0054;4/58 vs 12/58,P=0.0312).CONCLUSION This novel method for lymphadenectomy along the left RLN during thoracoscopic esophagectomy in the semi-prone position is much safer and more effective.

关键词： Bilateral pedicled nerve flap Bilateral exposure method Hollow-out method Left recurrent laryngeal nerve Lymphadenectomy Thoracoscopic esophagectomy

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Prediction and stratification for the surgical adverse events after minimally invasive esophagectomy:A two-center retrospective study

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World Journal of Gastroenterology 2025年第3期31卷 50-61页

作者： Qi-Hong Zhong Jiang-Shan Huang Fei-Long Guo Jing-Yu Wu Mao-Xiu Yuan Jia-Fu Zhu Wen-Wei Lin Sui Chen Zhen-Yang Zhang Jiang-Bo Lin department of thoracic surgery Fujian Medical University Union HospitalFuzhou 350001Fujian ProvinceChina The Graduate School Fujian Medical UniversityFuzhou 350001Fujian ProvinceChina department of thoracic surgery Affiliated Hospital of Jinggangshan UniversityJi’an 343000Jiangxi ProvinceChina

BACKGROUND Minimally invasive esophagectomy(MIE)is a widely accepted treatment for esophageal cancer,yet it is associated with a significant risk of surgical adverse events(SAEs),which can compromise patient recovery and long-term *** preoperative identification of high-risk patients is critical for improving *** To establish and validate a risk prediction and stratification model for the risk of SAEs in patients with *** This retrospective study included 747 patients who underwent MIE at two centers from January 2019 to February *** were separated into a train set(n=549)and a validation set(n=198).After screening by least absolute shrinkage and selection operator regression,multivariate logistic regression analyzed clinical and intraoperative variables to identify independent risk factors for SAEs.A risk stratification model was constructed and validated to predict the probability of *** SAEs occurred in 10.2%of patients in train set and 13.6%in the validation *** with SAE had significantly higher complication rate and a longer hospital stay after *** key independent risk factors identified included chronic obstructive pulmonary disease,a history of alcohol consumption,low forced expiratory volume in the first second,and low albumin *** stratification model has excellent prediction accuracy,with an area under the curve of 0.889 for the training set and an area under the curve of 0.793 for the validation *** The developed risk stratification model effectively predicts the risk of SAEs in patients undergoing MIE,facilitating targeted preoperative interventions and improving perioperative management.

关键词： Surgical adverse events Minimally invasive esophagectomy Esophageal cancer Stratification model Perioperative management

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