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Pyroptosis,ferroptosis,and autophagy in spinal cord injury:regulatory mechanisms and therapeutic targets

Neural Regeneration Research 2025年第10期20卷 2787-2806页

作者： Qingcong Zheng Du Wang Rongjie Lin Weihong Xu Department of Spinal Surgery the First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Arthritis clinical and Research Center Peking University People’s HospitalBeijingChina Department of Orthopedic Surgery Fujian Medical University Union HospitalFuzhouFujian ProvinceChina

Regulated cell death is a form of cell death that is actively controlled by *** studies have shown that regulated cell death plays a key role after spinal cord *** and ferroptosis are newly discovered types of regulated cell deaths that have been shown to exacerbate inflammation and lead to cell death in damaged spinal ***,a complex form of cell death that is interconnected with various regulated cell death mechanisms,has garnered significant attention in the study of spinal cord *** injury triggers not only cell death but also cellular survival *** signaling pathways play pivotal roles in influencing the processes of both deterioration and repair in spinal cord injury by regulating pyroptosis,ferroptosis,and ***,this review aims to comprehensively examine the mechanisms underlying regulated cell deaths,the signaling pathways that modulate these mechanisms,and the potential therapeutic targets for spinal cord *** analysis suggests that targeting the common regulatory signaling pathways of different regulated cell deaths could be a promising strategy to promote cell survival and enhance the repair of spinal cord ***,a holistic approach that incorporates multiple regulated cell deaths and their regulatory pathways presents a promising multi-target therapeutic strategy for the management of spinal cord injury.

关键词： autophagy cell death ferroptosis inflammation pathological mechanisms pyroptosis regulated cell death regulatory pathways spinal cord injury therapeutic targets

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Mechanism of inflammatory response and therapeutic effects of stem cells in ischemic stroke:current evidence and future perspectives

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Neural Regeneration Research 2025年第1期20卷 67-81页

作者： Yubo Wang Tingli Yuan Tianjie Lyu Ling Zhang Meng Wang Zhiying He Yongjun Wang Zixiao Li Vascular Neurology Department of NeurologyBeijing Tiantan HospitalCapital Medical UniversityBeijingChina China National clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Shanghai Engineering Research Center of Stem Cells Translational Medicine ShanghaiChina National Center for Healthcare Quality management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Institute for Regenerative Medicine Shanghai East HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghaiChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for Neurological Diseases BeijingChina

Ischemic stroke is a leading cause of death and disability worldwide,with an increasing trend and tendency for onset at a younger ***,in particular,bears a high burden of stroke *** recent years,the inflammatory response after stroke has become a research hotspot:understanding the role of inflammatory response in tissue damage and repair following ischemic stroke is an important direction for its *** review summarizes several major cells involved in the inflammatory response following ischemic stroke,including microglia,neutrophils,monocytes,lymphocytes,and ***,we have also highlighted the recent progress in various treatments for ischemic stroke,particularly in the field of stem cell ***,understanding the complex interactions between inflammation and ischemic stroke can provide valuable insights for developing treatment strategies and improving patient *** cell therapy may potentially become an important component of ischemic stroke treatment.

关键词： cell therapy immune cell inflammatory ischemic stroke stem cell

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Steatosis and insulin resistance in hepatitis C: A way out for the virus?

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World Journal of Gastroenterology 2009年第40期15卷 5014-5019页

作者： José A Del Campo Manuel Romero-Gómez Unit for The clinical management of Digestive Diseases and CIBERehd Hospital Universitario de Valme

The hepatitis C virus (HCV) induces lipid accumulation in vitro and in vivo. The pathogenesis of steatosis is due to both viral and host factors. Viral steatosis is mostly reported in patients with genotype 3a, whereas meta-bolic steatosis is often associated with genotype 1 and metabolic syndrome. Several molecular mechanisms responsible for steatosis have been associated with the HCV core protein, which is able to induce gene expres-sion and activity of sterol regulatory element binding protein 1 (SREBP1) and peroxisome proliferator-activat-ed receptor γ (PPARγ), increasing the transcription of genes involved in hepatic fatty acid synthesis. Steatosis has been also implicated in viral replication. In infected cells, HCV core protein is targeted to lipid droplets which serve as intracellular storage organelles. These studies have shown that lipid droplets are essential for virus assembly. Thus, HCV promotes steatosis as an eff icient mechanism for stable viral replication. Chronic HCV in-fection can also induce insulin resistance. In patients with HCV, insulin resistance is more strongly associated with viral load than visceral obesity. HCV seems to lead to insulin resistance through interference of intracellular insulin signalling by HCV proteins, mainly, the serine phosphorylation of insulin receptor-1 (IRS-1) and im-pairment of the downstream Akt signalling pathway. The HCV core protein interferes with in vitro insulin signal-ling by genotype-specif ic mechanisms, where the role of suppressor of cytokine signal 7 (SOCS-7) in genotype 3aand mammalian target of rapamycin (mTOR) in geno-type 1 in IRS-1 downregulation play key roles. Steatosis and insulin resistance have been associated with f ibrosis progression and a reduced rate of sustained response to peginterferon plus ribavirin.

关键词： Steatosis Insulin resistance Hepatitis Cvirus

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Evaluation of the antiulcer activity of Olax suhscorpioidea *** in rats

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Asian Pacific Journal of Tropical Medicine 2010年第1期3卷 13-16页

作者： Ukwe Chinwe Victoria Ubaka Chukwuemeka Michael Madusque Uche Johnny Department of clinical Pharmacy and Pharmacy management Faculty of Pharmaceutical SciencesUniversity of Nigeria

Objective:To evaluated the antiulcer activity of the methanolic root extract of the plant Olax subscorpioidea in experimental ***:Phytochemical tests and acute toxicity tests were carried out on its methanolic root ***-treatments with three doses of the extract（200,400 and 600 mg/kg body weight orally） and Sucralfate at 100 mg/kg orally were used for the various groups of *** indomethacin and ethanol models for experimental induction of ulcers in rats were *** ulcer indices were measured and percentage inhibition was ***: Phytochemistry revealed presence of alkaloids,steroids,glycosides and terpenoids and the extract showed an LD50 of 2 154 mg/kg in *** was produced in all the rats in both models with the extract showing potent antiulcer activity of ethanol *** was no significant ulcer inhibition by any of the treatments compared to control group in the indomethacin model but the extract’s antiulcer effect was dose-dependent（11.8%,19.2%,32.7%,P>0.05）.The ulcer reduction in the ethanol model was significant ulcer reduction in the highest dose group and Sucralfate group compared to control group（79.3%and 82.9%,P <0.05）.However,the extract at all dosage showed a dose-dependent ulcer inhibition in this ***:The above results suggest that the roots of Olax subscorpioidea possess antiulcer activity in experimental rats as claimed by traditional users.

关键词： Ethanol Indomethacin Olax subscorpioidea Ulcer inhibition

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Epigenetic regulation of the inflammatory response in stroke

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Neural Regeneration Research 2025年第11期20卷 3045-3062页

作者： Jingyi Liang Fei Yang Zixiao Li Qian Li School of Basic Medical Sciences Capital Medical UniversityBeijingChina Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Laboratory for clinical Medicine Beijing Key Laboratory of Neural Regeneration and RepairCapital Medical UniversityBeijingChina Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina National Center for Healthcare Quality management in Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Chinese Institute for Brain Research BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Beijing Engineering Research Center of Digital Healthcare for Neurological Diseases BeijingChina Department of Biochemistry and Molecular Biology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Beijing Key Laboratory of Cancer Invasion and Metastasis Research Capital Medical UniversityBeijingChina

Stroke is classified as ischemic or hemorrhagic,and there are few effective treatments for either *** mechanisms play a critical role in secondary brain injury following a stroke,which manifests as cytokine release,blood–brain barrier disruption,neuronal cell death,and ultimately behavioral *** the inflammatory response has been shown to mitigate this cascade of events in experimental stroke ***,in clinical trials of anti-inflammatory agents,longterm immunosuppression has not demonstrated significant clinical benefits for *** may be attributable to the dichotomous roles of inflammation in both tissue injury and repair,as well as the complex pathophysiologic inflammatory processes in *** acute harmful inflammatory responses or inducing a phenotypic shift from a pro-inflammatory to an anti-inflammatory state at specific time points after a stroke are alternative and promising therapeutic *** agents that can modulate inflammation requires a detailed understanding of the inflammatory processes of ***,epigenetic reprogramming plays a crucial role in modulating post-stroke inflammation and can potentially be exploited for stroke *** this review,we summarize current findings on the epigenetic regulation of the inflammatory response in stroke,focusing on key signaling pathways including nuclear factor-kappa B,Janus kinase/signal transducer and activator of transcription,and mitogen-activated protein kinase as well as inflammasome *** also discuss promising molecular targets for stroke *** evidence to date indicates that therapeutic targeting of the epigenetic regulation of inflammation can shift the balance from inflammation-induced tissue injury to repair following stroke,leading to improved post-stroke outcomes.

关键词： DNA methylation histone modification intracerebral hemorrhage ischemic stroke neuroinflammation neuroprotection non-coding RNA RNA methylation subarachnoid hemorrhage treatment

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Antiulcer activity of methanolic extract and fractions of Picralima nitida seeds(Apocynacaea) in rats

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Asian Pacific Journal of Tropical Medicine 2011年第1期4卷 13-15页

作者： Okonta Jegbefume Mathew Adibe Maxwell Ogochukwu Ubaka Chukwuemeka Michael Department of clinical Pharmacy and Pharmacy management Faculty of Pharmaceutical SciencesUniversity of NigeriaNsukka

Objective:To investigated the antisecrectory activities of the methanol extract,chloroform fraction and methanol fraction of Picralima nitida ***:The methanol extract of Picralima nitida seeds was fractionated into chloroform fraction and methanol *** were evaluated for antiulcer activity and gastric emptying time in rats using aspirin-pylorus-ligation ***:Oral administration of the methanol extract,chloroform fraction and methanol fraction at 1 000 mg/kg reduced gastric ulcer by 56.4%,40.0%and 56.3%,respectively;and the fractions of the extract significantly(P<0.05) reduced gastric emptying time when compared to the *** acidity was significandy decreased when compared with saline group,40.25 mEq/ L in methanol extract,50.0 mEq/L in chloroform fraction 51.25 mEq/L in methanol fration but had no significant effect on the gastric secretion ***:These findings showed that methanol extract,chloroform fraction and methanol fraction of the seeds of Picralima possessed potent antiulcer properties and some antisecretory properties.

关键词： Picralima nitida Aspirin-pylorus-ligation Antiulcer Rats

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妊娠期服用利扎曲普坦:截至2004年6月30日上市后的经验

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世界核心医学期刊文摘（神经病学分册） 2005年第12期1卷 27-28页

作者： Fiore M. Shields K.E. Santanello N. Goldberg M.R. 李一明 clinical risk management and safety surveillance Merck Research Laboratories BLX-30 PO Box 4 West Point PA 19486 United States

Merck &Co., Inc. evaluates outcomes of the use of rizatriptan during pregnancy through a Pregnancy Registry in the United States (US) and spontaneous reports for pregnancies reported from sources outside the US. Review of the outcomes of 25 prospective pregnancy reports in the Pregnancy Registry and reports from other sources does not suggest that treatment with rizatriptan predisposes patients to spontaneous abortions or congenital anomalies. However, the number of reports is small. Healthcare providers in the United States are encouraged to report any prenatal exposure to rizatriptan by calling the Pregnancy Registry at +1 (800) 986 8999 or visiting the Registry’s website at http://*** .

关键词：自发流产默克制药公司先天畸形 http

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In vitro and in vivo cytochrome P450 3A enzyme inhibition by Aframomum melengueta and Dennettia tripetala extracts

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Asian Pacific Journal of Tropical Medicine 2017年第6期10卷 645-650页

作者： Sunday O.Nduka Mathew J.Okonta Daniel L.Ajaghaku Chinwe V.Ukwe Department of clinical Pharmacy and Pharmacy management Nnamdi Azikiwe UniversityAwkaAnambra StateNigeria Department of clinical Pharmacy and Pharmacy management University of NigeriaNsukkaEnugu StateNigeria Department of Pharmacology and Toxicology Nnamdi Azikiwe UniversityAwkaAnambra StateNigeria

Objective: To evaluate the in vitro and in vivo inhibitory effects of two commonly used herbs, Aframomum melengueta(A. melengueta) and Dennettia tripetala(D. tripetala) on CYP 3A enzymes. Methods: In vitro inhibition of the enzymes were assessed with microsomes extracted from female albino rats using erythromycin-N-demethylation assay(EMND) method while their in vivo effects were measured by estimating simvastatin plasma concentrations in rats. Pharmacokinetic parameters were determined using non-compartmental anaysis as implemented in Win Nonlin pharmacokinetic program. Results: EMND assay with intestinal microsomes indicated that aqueous extracts of D. tripetala and A. melengueta significantly(P < 0.05) inhibited intestinal CYP 3A activity at both 50 μg and 100 μg concentrations. Petroleum ether extract of D. tripetala and ethanol extracts of A. melengueta inhibited intestinal CYP3 A activity at 100 μg but not at 50 μg concentrations. All the extracts showed an in vitrodose dependent CYP 3A inhibition with liver microsomes. In vivo analysis showed that pretreatment with the extracts enhanced systemic absorption of simvastatin with reductions in metabolizing enzymes activity as indicated in significant increases in maximal concentration, area under curve, area under moment curve and mean resident time of simvastatin(P < 0.05). Conclusions: Herbal preparations containing these plants' extracts should be used with caution especially in patients on CYP450 3A substrate medications.

关键词： Cytochrome P450 enzymes CYP 3A Enzyme inhibition Herbal extracts

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Aircraft conflict resolution method based on hybrid ant colony optimization and artificial potential field

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Science China(Information Sciences) 2018年第12期61卷 190-192页

作者： Huaxian LIU Feng LIU Xuejun ZHANG Xiangmin GUAN Jun CHEN Pascal SAVINAUD School of Electronic and Information Engineering Beihang University National Key laboratory of Communication Navigation Surveillance and Air Traffic Management (CNS/ATM )Beihang University Department of General Aviation Civil Aviation Management Institute of China School of Engineering and Materials Science Queen Mary University of London

Dear editor,With the significant growth of the civil aviation industry and especially its rapid development in booming economies such as that of China, air traffic flow is drastically increasing, leading to greater congestion around airport terminal areas and in busy airspace [1]. The substantial increase in air traffic flow has intensified the risk of violating safe separation regulations, endangering the airspace operational safety. Furthermore, as the result of

关键词： Figure Aircraft conflict resolution method based on hybrid ant colony optimization and artificial potential field

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Neonatal overfeeding in mice aggravates the development of methionine and choline-deficient diet-induced steatohepatitis in adulthood

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Genes & Diseases 2019年第1期6卷 68-77页

作者： Juan Du Xuemei Cao Junlin Diao Qijuan Zhang Chuan Peng Jibin Li Xiaoqiu Xiao Laboratory of Lipid&Glucose Metabolism PR China Department of clinical Nutrition The First Affiliated Hospital of Chongqing Medical UniversityPR China School of Public Health and management Chongqing Medical UniversityResearch Center for Medicine and Social DevelopmentInnovation Center for Social Risk Governance in HealthChongqing400016PR China

Overfeeding in early life is associated with obesity and insulin resistance in *** the present study,a well-characterized mouse model was used to investigate whether neonatal overfeeding increases susceptibility to the development of non-alcoholic steatohepatitis(NASH)following feeding with a methionine and choline-deficient(MCD)*** overfeeding was induced by adjusting litters to 3 pups per dam(small litter size,SL)in contrast to 10 pups per dam as control(normal litter size,NL).At 11 weeks of age,mice were fed with standard(S)or a methionine and choline-deficient(MCD)diet for 4 *** tolerance tests,tissue staining with haematoxylin and eosin,oil-red O and immunohistochemistry for F4/80,reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and western blotting were *** with NL mice,SL mice exhibited higher body weight gain from 2 weeks of age throughout adulthood,and more profound glucose intolerance as *** regulatory element-binding protein 1c and fatty acid synthase mRNA expression levels in liver were upregulated in SL mice at 3 weeks of *** diet induced typical NASH,especially in SL-MCD mice,evidenced by marked fat accumulation,macrovescular steatosis,ballooned hepatocytes,inflammatory cells infiltration and tumour necrosis factor-a mRNA upregulation in the liver,as well as increased alanine aminotransferase and aspartate aminotransferase levels in the *** were no significant differences in liver fibrosis in all *** during early life exhibited effect with administration of MCD diet in inducing adverse effects on the metabolic function and in promoting the progression of NASH in mice,possibly mediated through dysregulated lipid metabolism in hepatocytes and aggravated hepatic inflammation.

关键词： Inflammation Insulin resistance Neonatal overfeeding Non-alcoholic steatohepatitis Obesity

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