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

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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Substrate topography as a powerful tool to modify glial cell biology and interactions

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Neural Regeneration Research 2025年第5期20卷 1390-1391页

作者： Pascal Achenbach Haktan Altinova Gary A.Brook Institute of Neuropathology RWTH Aachen University Hospital department of Neurosurgery RWTH Aachen University Hospital Aachen Germany Berlin state Office for Health and Social Affairs(LAGeSo) BerlinGermany

Traumatic injuries to the central nervous system(CNS) result in disruption of the intricate network of axons which connect functionally related neurons that are widely distributed throughout the brain and spinal *** normal conditions,maintenance of this complex system is structurally and functionally supported by astrocytes (ACs)and other glial cells,the processes of which form a framework surrounding neuronal cell bodies,dendrites,axons,and synapses.

关键词： injuries topography system

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Nigella sativa relieves the deleterious effects of ischemia reperfusion injury on liver

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World Journal of Gastroenterology 2008年第33期14卷 5204-5209页

作者： Fahrettin Yildiz Sacit Coban Alpaslan Terzi Mustafa Ates Nurten Aksoy Hale Cakir Ali Riza Ocak Muharrem Bitiren Harran University Medical Faculty Department of General SurgerySanli Urfa 63300 Turkey Gaziantep University Medical Faculty Department of General SurgeryGaziantep 27310 Turkey malatya state hospital department of general surgery Malatya 44100 Turkey Harran University Medical Faculty Department of BiochemistrySanli Urfa 63300 Turkey Harran University Medical Faculty department of Pathology Sanli Urfa 63300 Turkey

AIM: To determine whether Nigella sativa prevents hepatic ischemia-reperfusion injury to the liver. METHODS: Thirty rats were divided into three groups as sham (Group 1), control (Group 2), and Nigella sati-va (NS) treatment group (Group 3). All rats underwent hepatic ischemia for 45 min followed by 60 min period of reperfusion. Rats were intraperitoneally infused with only 0.9% saline solution in group 2. Rats in group 3 received NS (0.2 mL/kg) intraperitoneally, before isch-emia and before reperfusion. Blood samples and liver tissues were harvested from the rats, and then the rats were sacrifi ced. Serum aspartate aminotransfera-se (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) levels were determined. Total antioxidant capacity (TAC), catalase (CAT), total oxida-tive status (TOS), oxidative stress index (OSI) and my-eloperoxidase (MPO) in hepatic tissue were measured. Also liver tissue histopathology was evaluated by light microscopy. RESULTS: The levels of liver enzymes in group 3 weresignifi cantly lower than those in the group 2. TAC in liver tissue was significantly higher in group 3 than in group 2. TOS, OSI and MPO in hepatic tissue were signifi cantly lower in group 3 than the group 2. Histo-logical tissue damage was milder in the NS treatment group than that in the control group. CONCLUSION: Our results suggest that Nigella sa-tiva treatment protects the rat liver against to hepatic ischemia-reperfusion injury.

关键词： Nigella sativa Ischemia reperfusion injury Liver

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New parameter in diagnosis of acute appendicitis:Platelet distribution width

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World Journal of Gastroenterology 2015年第6期21卷 1821-1826页

作者： Bulent Dinc Alten Oskay Selcan Enver Dinc Bilge Bas Sabri Tekin department of general surgery Ataturk State Hospital department of Emergency Denizli State Hospital department of Emergency Isparta State Hospital department of Gastroenterology Ataturk State Hospital department of surgery Medical Park Hospitals

AIM:To investigate the diagnostic accuracy of the mean platelet volume and platelet distribution width in acute ***:This retrospective,case-controlled study compared 295 patients with acute appendicitis(Group?Ⅰ),100 patients with other intra-abdominal infections(GroupⅡ),and 100 healthy individuals(GroupⅢ)between January 2012 and January *** age,gender,and white blood cell count,neutrophil percentage,mean platelet volume,and platelet distribution width values from blood samples were compared among the *** analyses were performed using SPSS for Windows 21.0 *** addition,the sensitivity,specificity,positive and negative predictive values and likelihood ratios,and diagnostic accuracy were ***:The mean ages of patients were 29.9±12.0years for Group?Ⅰ,31.5±14.0 years for GroupⅡ,and30.4±13.0 years for GroupⅢ.Demographic features such as age and gender were not significantly different among the *** blood cell count,neutrophil percentage and platelet distribution width were significantly higher in Group?Ⅰ?compared to groupsⅡandⅢ(P<0.05).Diagnostically,the sensitivity,specificity and diagnostic accuracy were 73.1%,94.0%,and 78%for white blood cell count,70.0%,96.0%,and 76.0%for neutrophil percentage,29.5%,49.0%,and 34.0%for mean platelet volume,and 97.1%,93.0%,and 96.0%for platelet distribution width,*** highest diagnostic accuracy detected was for platelet distribution width between Group?Ⅰ?and GroupⅢ(P<0.01).CONCLUSION:Platelet distribution width analysis can be used for diagnosis of acute appendicitis without requiring additional tests,thus reducing the cost and loss of time.

关键词： Appendicitis Diagnosis Platelet function test Plat

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Resection and primary anastomosis with or without modified blow-hole colostomy for sigmoid volvulus

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World Journal of Gastroenterology 2008年第36期14卷 5590-5594页

作者： Sacid Coban Mehmet Yilmaz Alpaslan Terzi Fahrettin Yildiz Dincer Ozgor Cengiz Ara Saim Yologlu Vedat Kirimlioglu department of general surgery Gaziantep University School of Medicine Gaziantep 27310 Turkey department of general surgery Inonu University School of Medicine Malatya 44280 Turkey department of general surgery Harran University School of Medicine Sanliurfa 63200 Turkey department of Biostatistics Inonu University School of Medicine Malatya 44280 Turkey

AIM: To evaluate the efficacy of resection and primary anastomosis (RPA) and RPA with modified blow-hole colostomy for sigmoid volvulus. METHODS: From March 2000 to September 2007, 77 patients with acute sigmoid volvulus were treated. A total of 47 patients underwent RPA or RPA with modified blow-hole colostomy. Twenty-five patients received RPA (Group A), and the remaining 22 patients had RPA with modified blow-hole colostomy (Group B). The clinical course and postoperative complications of the two groups were compared. RESULTS: The mean hospital stay, wound infection and mortality did not differ significantly between the groups. Superficial wound infection rate was higher in group A (32% vs 9.1%). Anastomotic leakage was observed only in group A, with a rate of 6.3%. The difference was numerically impressive but was statistically not significant. CONCLUSION: RPA with modified blow-hole colostomy provides satisfactory results. It is easy to perform and may become a method of choice in patients with sigmoid volvulus. Further studies are required to further establish its role in the treatment of sigmoid volvulus.

关键词： Acute sigmoid volvulus Anastomosis Primary resection Surgical technique

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Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

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Neural Regeneration Research 2025年第3期20卷 873-886页

作者： Ying Wang Xiang Zhang Henrik Biverstål Nicolas GBazan Shuai Tan Nailin Li Makiko Ohshima Marianne Schultzberg Xiaofei Li department of Neurobiology Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden department of Neurology Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina department of Physiology and Pharmacology Karolinska InstitutetStockholmSweden department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden Neuroscience Center of Excellence Louisiana State UniversityNew OrleansLAUSA department of Medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β maresin microglia monocyte neuroinflammation resolution RNA-sequencing specialized pro-resolving lipid mediator

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Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

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Neural Regeneration Research 2025年第9期20卷 2727-2736页

作者： Yujia Liu Xue Han Yan Su Yiming Zhou Minhui Xu Jiyan Xu Zhengliang Ma Xiaoping Gu Tianjiao Xia department of Anesthesiology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina Medical School Nanjing UniversityNanjingJiangsu ProvinceChina Jiangsu Key Laboratory of Molecular Medicine Nanjing UniversityNanjingJiangsu ProvinceChina state Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjingJiangsu ProvinceChina department of Anesthesiology Zhongshan HospitalFudan UniversityShanghaiChina

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of *** date,there are no viable treatment options for postoperative cognitive *** identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future *** identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial *** dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub ***,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re *** were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning *** addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western *** with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expr

关键词： Chil1 hippocampus learning and memory M2 microglia neuroinflammation postoperative cognitive dysfunction(POCD) recombinant CHI3L1

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Current status of drug therapy for chronic hepatitis B

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World Journal of Gastroenterology 2025年第2期31卷 1-12页

作者： Chuang Jiang Zhi-Hong Zhang Jia-Xin Li Division of Liver surgery Department of General Surgery and Laboratory of Liver Surgeryand State Key Laboratory of Biotherapy and Collaborative Innovation Center of BiotherapyWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina department of general surgery Dafang County People's HospitalBijie 551600Guizhou ProvinceChina

In this editorial,we comment on the article by Meng et *** hepatitis B(CHB)is a significant global health problem,particularly in developing *** B virus(HBV)infection is one of the most important risk factors for cirrhosis and hepatocellular *** and treatment of HBV are key measures to reduce *** present,drug therapy can effectively control virus replication and slow disease progression,but completely eliminating the virus remains a ***-HBV treatment is a long-term process,and there are many kinds of antiviral drugs with different mechanisms of action,it is essential to evaluate the safety and efficacy of these drugs to reduce side effects and improve patients’*** will summarize the current status of CHB drug treatment,hoping to provide a reference for the selection of clinical antiviral drugs.

关键词： Chronic hepatitis B Hepatitis B virus Anti virus Drug treatment Therapy

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Acute pancreatitis at the beginning of the 21st century: The state of the art

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World Journal of Gastroenterology 2009年第24期15卷 2945-2959页

作者： Alfredo F Tonsi Matilde Bacchion Stefano Crippa Giuseppe Malleo Claudio Bassi department of general surgery East Surrey Hospital department of surgery University of Verona

Acute pancreatitis is an acute inflammatory disease of the pancreas which can lead to a systemic inflammatory response syndrome with significant morbidity and mortality in 20% of patients. Gallstones and alcohol consumption are the most frequent causes of pancreatitis in adults. The treatment of mild acute pancreatitis is conservative and supportive; however severe episodes characterized by necrosis of the pancreatic tissue may require surgical intervention. Advanced understanding of the pathology, and increased interest in assessment of disease severity are the cornerstones of future management strategies of this complex and heterogeneous disease in the 21st century.

关键词： Acute necrotizing pancreatitis Systemic inflammatory response syndrome surgery Pancreatectomy Minimal surgical procedures

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Microglia:a promising therapeutic target in spinal cord injury

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Neural Regeneration Research 2025年第2期20卷 454-463页

作者： Xiaowei Zha Guoli Zheng Thomas Skutella Karl Kiening Andreas Unterberg Alexander Younsi department of Neurosurgery Heidelberg University HospitalHeidelbergGermany department of Neuroanatomy Institute for Anatomy and Cell BiologyHeidelberg UniversityHeidelbergGermany

Microglia are present throughout the central nervous system and are vital in neural repair,nutrition,phagocytosis,immunological regulation,and maintaining neuronal *** a healthy spinal cord,microglia are accountable for immune surveillance,however,when a spinal cord injury occurs,the microenvironment drastically changes,leading to glial scars and failed axonal *** this context,microglia vary their gene and protein expression during activation,and proliferation in reaction to the injury,influencing injury responses both favorably and unfavorably.A dynamic and multifaceted injury response is mediated by microglia,which interact directly with neurons,astrocytes,oligodendrocytes,and neural stem/progenitor *** a clear understanding of their essential nature and origin,the mechanisms of action and new functions of microglia in spinal cord injury require extensive *** review summarizes current studies on microglial genesis,physiological function,and pathological state,highlights their crucial roles in spinal cord injury,and proposes microglia as a therapeutic target.

关键词： astrocytes cytokines functional recovery immune regulation M1/M2 activation macrophages microglia neuroinflammation spinal cord injury therapy

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