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Gut microbiota-astrocyte axis: new insights into age-related cognitive decline

Neural Regeneration Research 2025年第4期20卷 990-1008页

作者： Lan Zhang Jingge Wei Xilei Liu Dai Li Xiaoqi Pang Fanglian Chen Hailong Cao Ping Lei Haihe Laboratory of Cell Ecosystem Department of GeriatricsTianjin Medical University General HospitalTianjinChina Tianjin Geriatrics Institute Tianjin Medical University General HospitalTianjinChina Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalNational Key Clinical SpecialtyTianjin Institute of Digestive DiseasesTianjin Key Laboratory of Digestive DiseasesTianjinChina Department of Urology Tianjin Medical University General HospitalTianjinChina Tianjin Neurological Institution Tianjin Medical University General HospitalTianjinChina

With the rapidly aging human population,age-related cognitive decline and dementia are becoming increasingly prevalent *** is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota,microbial metabolites,and the functions of *** microbiota–gut–brain axis has been the focus of multiple studies and is closely associated with cognitive *** article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative *** article also summarizes the gut microbiota components that affect astrocyte function,mainly through the vagus nerve,immune responses,circadian rhythms,and microbial ***,this article summarizes the mechanism by which the gut microbiota–astrocyte axis plays a role in Alzheimer’s and Parkinson’s *** findings have revealed the critical role of the microbiota–astrocyte axis in age-related cognitive decline,aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

关键词： age aging Alzheimer’s disease astrocytes cognitive decline dementia gut microbiota gut–brain axis microbial metabolites neuroinflammation Parkinson’s disease

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Therapeutic potential of exercise-hormone irisin in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1555-1564页

作者： Eunhee Kim Rudolph ETanzi Se Hoon Choi Genetics and Aging Research Unit MassGeneral Institute for Neurodegenerative DiseaseDepartment of NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMAUSA McCance Center for Brain Health Massachusetts General HospitalBostonMAUSA

Irisin is a myokine that is generated by cleavage of the membrane protein fibronectin type Ⅲ domain-containing protein 5(FNDC5) in response to physical exercise. Studies reveal that irisin/FNDC5 has neuroprotective functions against Alzheimer's disease, the most common form of dementia in the elderly, by improving cognitive function and reducing amyloid-β and tau pathologies as well as neuroinflammation in cell culture or animal models of Alzheimer's disease. Although current and ongoing studies on irisin/FNDC5 show promising results, further mechanistic studies are required to clarify its potential as a meaningful therapeutic target for alleviating Alzheimer's disease. We recently found that irisin treatment reduces amyloid-β pathology by increasing the activity/levels of amyloid-β-degrading enzyme neprilysin secreted from astrocytes. Herein, we present an overview of irisin/FNDC5's protective roles and mechanisms against Alzheimer's disease.

关键词： Alzheimer's disease exercise fibronectin typeⅢdomain-containing protein 5(FNDC5) irisin

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Non-coding RNAs in acute ischemic stroke:from brain to periphery

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Neural Regeneration Research 2025年第1期20卷 116-129页

作者： Shuo Li Zhaohan Xu Shiyao Zhang Huiling Sun Xiaodan Qin Lin Zhu Teng Jiang Junshan Zhou Fuling Yan Qiwen Deng Department of Neurology Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Neurology Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsu ProvinceChina general Clinical Research Center Nanjing First HospitalNanjing Medical UniversityNanjingJiangsu ProvinceChina

Acute ischemic stroke is a clinical emergency and a condition with high morbidity,mortality,and *** predictive,diagnostic,and prognostic biomarkers and effective therapeutic targets for acute ischemic stroke remain *** innovations in high-throughput gene sequencing analysis,many aberrantly expressed non-coding RNAs(ncRNAs)in the brain and peripheral blood after acute ischemic stroke have been found in clinical samples and experimental *** expressed ncRNAs in the post-stroke brain were demonstrated to play vital roles in pathological processes,leading to neuroprotection or deterioration,thus ncRNAs can serve as therapeutic targets in acute ischemic ***,distinctly expressed ncRNAs in the peripheral blood can be used as biomarkers for acute ischemic stroke prediction,diagnosis,and *** particular,ncRNAs in peripheral immune cells were recently shown to be involved in the peripheral and brain immune response after acute ischemic *** this review,we consolidate the latest progress of research into the roles of ncRNAs(microRNAs,long ncRNAs,and circular RNAs)in the pathological processes of acute ischemic stroke–induced brain damage,as well as the potential of these ncRNAs to act as biomarkers for acute ischemic stroke prediction,diagnosis,and *** from this review will provide novel ideas for the clinical application of ncRNAs in acute ischemic stroke.

关键词： acute ischemic stroke apoptosis blood–brain barrier damage circular RNAs excitatory toxicity long non-coding RNAs microRNAs neuroinflammation non-coding RNAs oxidative stress

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Exploring the novel role of oligodendrocyte precursor cells in phagocytosis:beyond myelinogenesis

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Neural Regeneration Research 2025年第2期20卷 473-474页

作者： Gen Hamanaka Ken Arai Neuroprotection Research Laboratories Departments of Radiology and NeurologyMassachusetts General Hospital and Harvard Medical SchoolCharlestownMAUSA

Roles of oligodendrocyte precursor cells in the central nervous system:Oligodendrocyte precursor cells(OPCs)have long been recognized for their critical role as precursors to oligodendrocytes,the primary myelin-producing *** precursors,OPCs mature and differentiate into oligodendrocytes,which contribute significantly to the formation of myelin sheaths around *** myelination,which is critical for the conduction of salutatory nerve impulses in the cerebral white matter,underscores the classical role of oligodendrocytes in central nervous system(CNS)***,because oligodendrocytes are differentiated cells that cannot proliferate.

关键词： critical system conduction

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Human-induced pluripotent stem cell-derived neural stem cell exosomes improve blood-brain barrier function after intracerebral hemorrhage by activating astrocytes via PI3K/AKT/MCP-1 axis

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Neural Regeneration Research 2025年第2期20卷 518-532页

作者： Conglin Wang Fangyuan Cheng Zhaoli Han Bo Yan Pan Liao Zhenyu Yin Xintong Ge Dai Li Rongrong Zhong Qiang Liu Fanglian Chen Ping Lei Department of Geriatrics Tianjin Medical University General HospitalTianjinChina School of Medicine Nankai UniversityTianjinChina Tianjin Neurological Institute TianjinChina

Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor ***-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system *** this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying *** results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral ***,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory *** sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier *** with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these *** summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.

关键词： AKT astrocyte blood-brain barrier cerebral edema exosomes human-induced pluripotent stem cells intracerebral hemorrhage neural stem cells neuroinflammation PI3K

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Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury

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Neural Regeneration Research 2025年第5期20卷 1416-1430页

作者： Mou Gao Qin Dong Dan Zou Zhijun Yang Lili Guo Ruxiang Xu Department of Neurosurgery Sichuan Academy of Medical Sciences and Sichuan Provincial People’s HospitalSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Department of Neurosurgery Chinese PLA General HospitalBeijingChina Department of Neurology Fu Xing HospitalCapital Medical UniversityBeijingChina

Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and *** previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological ***,the mechanism of CXCR4 upregulation in induced neural stem cells remains *** this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 ***,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial *** agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury ***,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head *** conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neura

关键词： Akt signaling cerebral edema closed head injury Crry CXCR4 induced neural stem cell microglia neuroinflammation

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Ninety-day readmissions after inpatient cholecystectomy: A 5-year analysis

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World Journal of Gastroenterology 2017年第16期23卷 2972-2977页

作者： Alba Manuel-Vázquez Raquel Latorre-Fragua Carmen Ramiro-Pérez Aylhin López-Marcano Farah Al-Shwely Roberto De la Plaza-Llamas JoséManuel Ramia Department of general and Digestive Surgery University Hospital of Guadalajara19002 GuadalajaraSpain

AIM To determine the incidence of readmission after cholecystectomy using 90 d as a time limit. METHODS We retrospectively reviewed all patients undergoing cholecystectomy at the general Surgery and Digestive System Service of the University hospital of guadalajara, Spain. We included all patients undergoing cholecystectomy for biliary pathology who were readmitted to hospital within 90 d. We considered readmission to any hospital service as cholecystectomyrelated complications. We excluded ambulatory cholecystectomy, cholecystectomy combined with other procedures, oncologic disease active at the time of cholecystectomy, finding of malignancy in the resection specimen, and scheduled re-admissions for other unrelated pathologies. RESULTS We analyzed 1423 patients. There were 71 readmissions in the 90 d after discharge, with a readmission rate of4.99%. Sixty-four point seven nine percent occurred after elective surgery(cholelithiasis or vesicular polyps) and 35.21% after emergency surgery(acute cholecystitis or acute pancreatitis). Surgical non-biliary causes were the most frequent reasons for readmission, representing 46.48%; among them, intra-abdominal abscesses were the most common. In second place were non-surgical reasons, at 29.58%, and finally, surgical biliary reasons, at 23.94%. Regarding time for readmission, almost 50% of patients were readmitted in the first week and most second readmissions occurred during the second month. Redefining the readmissions rate to 90 d resulted in an increase in re-hospitalization, from 3.51% at 30 d to 4.99% at 90 d. CONCLUSION The use of 30-d cutoff point may underestimate the incidence of complications. The current tendency is to use 90 d as a limit to measure complications associated with any surgical procedure.

关键词： Cholecystectomy 90-d hospital readmission Readmission rate Cholelithiasis

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Postoperative complications in gastrointestinal surgery: A “hidden” basic quality indicator

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World Journal of Gastroenterology 2019年第23期25卷 2833-2838页

作者： Roberto De la Plaza Llamas JoséM Ramia Department of general and Digestive Surgery Hospital Universitario de GuadalajaraGuadalajara 19002Spain

Postoperative complications represent a basic quality indicator for measuring outcomes at surgical units. At present, however, they are not systematically measured in all surgical procedures. A more accurate assessment of their impact could help to evaluate the real morbidity associated with different surgical interventions, establish measures for improvement, increase efficiency and identify benchmarking services. The Clavien-Dindo Classification is the most widely used system worldwide for assessing postoperative ***, the postoperative period is summarized by the most serious complication without taking into account others of lesser magnitude. Recently,two new scoring systems have emerged, the Comprehensive Complication Index and the Complication Severity Score, which include all postoperative complications and quantify them from 0(no complications) to 100(patient’s death), These allow the comparison of results. It is important to train surgical staff to report and classify complications and to record 90-d morbidity rates in all patients. Comparisons with other services must take into account patient comorbidities and the complexity of the particular surgical procedure. To avoid subjectivity and bias, external audits are necessary. In addition, ensuring transparency in the reporting of the results is an urgent obligation.

关键词： Morbidity Postoperative complications Health policy Comprehensive Complication Index Clavien-Dindo Classification Complication Severity Score

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Laparoscopic gastrojejunostomy for gastric outlet obstruction in patients with unresectable hepatopancreatobiliary cancers: A personal series and systematic review of the literature

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World Journal of Gastroenterology 2018年第18期24卷 1978-1988页

作者： Alba Manuel-Vázquez Raquel Latorre-Fragua Carmen Ramiro-Pérez Aylhin López-Marcano Roberto De la Plaza-Llamas José Manuel Ramia Department of general and Digestive Surgery University Hospital of Guadalajara

The major symptoms of advanced hepatopancreaticbiliary cancer are biliary obstruction, pain and gastric outlet obstruction(GOO). For obstructive jaundice, surgical treatment should de consider in recurrent stent complications. The role of surgery for pain relief is marginal nowadays. On the last, there is no consensus for treatment of malignant GOO. Endoscopic duodenal stents are associated with shorter length of stay and faster relief to oral intake with more recurrent symptoms. Surgical gastrojejunostomy shows better long-term results and lower re-intervention rates, but there are limited data about laparoscopic approach. We performed a systematic review of the literature, according PRISMA guidelines, to search for articles on laparoscopic gastrojejunostomy for malignant GOO treatment. We also report our personal series, from 2009 to 2017. A review of the literature suggests that there is no standardized surgical technique either standardized outcomes to report. Most of the studies are case series, so level of evidence is low. Decisionmaking must consider medical condition, nutritional status, quality of life and life expectancy. Evaluation ofthe patient and multidisciplinary expertise are required to select appropriate approach. Given the limited studies and the difficulty to perform prospective controlled trials, no study can answer all the complexities of malignant GOO and more outcome data is needed.

关键词： Duodenal obstruction Gastrojejunostomy Gastroenterosmy Gastric outlet obstruction Gastric bypass Laparoscopy Laparoscopic surgery Sytematic review

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Cost of postoperative complications:How to avoid calculation errors

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World Journal of Gastroenterology 2020年第21期26卷 2682-2690页

作者： Roberto De la Plaza Llamas JoséM Ramia Department of general and Digestive Surgery Hospital Universitario de GuadalajaraGuadalajara 19002Spain

Postoperative complications(PC)are a basic health outcome,but no surgery service in the world records and/or audits the PC associated with all the surgical procedures it *** studies that have assessed the cost of PC suffer from poor quality and a lack of transparency and *** payment system in place often rewards the volume of services provided rather than the quality of patients’clinical *** a thorough registration of PC,the economic costs involved cannot be *** accurate,reliable appraisal would help identify areas for investment in order to reduce the incidence of PC,improve surgical results,and bring down the economic *** article describes how to quantify and classify PC using the Clavien-Dindo classification and the comprehensive complication index,discusses the perspectives from which economic evaluations are performed and the minimum postoperative follow-up established,and makes various *** availability of accurate and impartially audited data on PC will help reduce their incidence and bring down ***,the health authorities,and society as a whole are sure to benefit.

关键词： Morbidity Postoperative complications Costs and cost analysis Economic evaluation Healthcare costs Opportunity cost Clavien-Dindo classification Comprehensive complication index

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