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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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Glia-to-neuron reprogramming to the rescue?

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Neural Regeneration Research 2025年第5期20卷 1395-1396页

作者： Jack W.Hickmott Cindi M.Morshead Department of surgery University of TorontoTorontoONCanada Donnelly Centre for Cellular and Biomolecular Research TorontoONCanada institute of Biomedical Engineering University of TorontoTorontoONCanada The KITE Research institute Toronto Rehabilitation InstituteUniversity Health NetworkTorontoONCanada

Over the last two decades,the dogma that cell fate is immutable has been increasingly challenged,with important implications for regenerative *** brea kth rough discovery that induced pluripotent stem cells could be generated from adult mouse fibroblasts is powerful proof that cell fate can be *** exciting extension of the discovery of cell fate impermanence is the direct cellular reprogram ming hypothesis-that terminally differentiated cells can be reprogrammed into other adult cell fates without first passing through a stem cell state.

关键词： programming passing proof

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Pancreatic adenosquamous carcinoma and intraductal papillary mucinous neoplasm in a CDKN2A germline mutation carrier

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World Journal of Gastrointestinal Oncology 2017年第9期9卷 390-396页

作者： Fernando Martínez de Juan María Reolid Escribano Carmen Martínez Lapiedra Fernanda Maia de Alcantara María Caballero Soto Ana Calatrava Fons Isidro Machado Gastroenterology and digestive Endoscopy Department Valencian Institute of Oncology digestive surgery Department Valencian Institute of Oncology Pathology Department Valencian Institute of Oncology

A 69-year-old woman from a kindred with familial atypical multiple mole melanoma and carrier of a germline mutation in CDKN2A, presented with abdominal pain caused by a solid-cystic pancreatic mass. The patient had an abdominal computed tomography three years before in which there was no evidence of pancreatic lesion. The endoscopic ultrasound guided fine needle aspiration showed adenocarcinoma with squamous component. After surgical resection the final diagnosis was adenosquamous pancreatic carcinoma(ASPC) arising in an intraductal papillar mucinous neoplasm(IPMN). Adenosquamous carcinomas are uncommon in the pancreas and have rarely been described in association with IPMNs. It has worse prognosis than the ordinary pancreatic ductal adenocarcinoma and some distinct features. We review the clinical, imaging, pathologic and molecular aspects of ASPC. Differential diagnosis with contamination, squamous metaplasia and pancreatic metastases from a distant squamous carcinoma is discussed. Besides, the case is an accelerated model of the adenoma(IPMN)-carcinoma sequence probably due to the CDKN2A ger-mline mutation. Somatic CDKN2A mutations are commonevents in the early steps of sporadic pancreatic cancer, but germline mutation carriers have a significantly higher risk of pancreatic carcinoma.

关键词： Intraductal papillary mucinous neoplasia Melanoma-pancreatic cancer syndrome Adenosquamous carcinoma Pancreatic carcinoma CDKN2A

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Search for microglia-specific peptides:advances in the discovery toolbox

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Neural Regeneration Research 2025年第2期20卷 471-472页

作者： Ivan Sarabia Kyle M.Koss Department of surgery University of ArizonaTucsonAZUSA

Uncontrolled and chronic inflammatory states in the central nervous system(CNS)are the hallmark of neurodegenerative pathology and every injury or stroke-related *** key mediators of these neuroinflammatory states are glial cells known as microglia,the resident immune cell at the core of the inflammatory event,and astroglia,which encapsulate inflammatory insults in proteoglycan-rich scar *** gliotic scar blocks significant portions of healthy axonal networking,preventing *** most neuroinflammation is exclusively based on the responses of said microglia,their phenotypes are suggested to follow those of macrophages;M1 and M2 are opposites of pro-and ***,microglial phenotypes have been identified to be on an inflammatory spectrum encompassing developmental,homeostatic,and reparative behaviors as opposed to their ability to affect devastating cell death cascades and scar tissue formation.

关键词： inflammation pathology death

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Understanding the link between type 2 diabetes mellitus and Parkinson's disease:role of brain insulin resistance

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Neural Regeneration Research 2025年第11期20卷 3113-3123页

作者： Theodora Ntetsika Sergiu-Bogdan Catrina Ioanna Markaki Department of Clinical Neuroscience Karolinska InstituteStockholmSweden Department of Neurology Karolinska University HospitalStockholmSweden Department of Molecular Medicine and surgery Karolinska InstituteStockholmSweden Center for Diabetes Academic Specialist CenterStockholmSweden Center for Neurology Academic Specialist CenterStockholmSweden

Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic *** data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular *** insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological *** contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.

关键词： brain insulin resistance brain insulin signaling diabetes type 2 GLP-1 receptor agonists GLP-1 signaling insulin resistance insulin signaling neurodegeneration Parkinson's disease targeted therapy

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Tumor heterogeneity of gastric cancer: From the perspective of tumor-initiating cell

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World Journal of Gastroenterology 2018年第24期24卷 2567-2581页

作者： Jian-Peng Gao Wei Xu Wen-Tao Liu Min Yan Zheng-Gang Zhu Department of surgery Shanghai Institute of Digestive SurgeryRuijin HospitalShanghai Jiao Tong University

Gastric cancer(GC) remains one of the most common and malignant types of cancer due to its rapid progression, distant metastasis, and resistance to conventional chemotherapy, although efforts have been made to understand the underlying mechanism of this resistance and to improve clinical outcome. It is well recognized that tumor heterogeneity, a fundamental feature of malignancy, plays an essential role in the cancer development and chemoresistance. The model of tumor-initiating cell(TIC) has been proposed to explain the genetic, histological, and phenotypical heterogeneity of GC. TIC accounts for a minor subpopulation of tumor cells with key characteristics including high tumorigenicity, maintenance of self-renewal potential, giving rise to both tumorigenic and non-tumorigenic cancer cells, and resistance to chemotherapy. Regarding tumor-initiating cell of GC(GATIC), substantial studies have been performed to(1) identify the putative specific cell markers for purification and functional validation of GATICs;(2) trace the origin of GATICs; and(3) decode the regulatory mechanism of GATICs. Furthermore, recent studies demonstrate the plasticity of GATIC and the interaction between GATIC and its surrounding factors(TIC niche or tumor microenvironment). All these investigations pave the way for the development of GATIC-targeted therapy, which is in the phase of preclinical studies and clinical trials. Here, we interpret the heterogeneity of GC from the perspectives of TIC by reviewing the above-mentioned fundamental and clinical studies of GATICs. Problems encountered during the GATIC investigations and the potential solutions are also discussed.

关键词： Gastric cancer Tumor heterogeneity Tumor-initiating cell

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Management of colorectal neoplasia during pregnancy and in the postpartum period

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World Journal of Gastrointestinal Oncology 2016年第7期8卷 550-554页

作者： Erman Aytac Gokhan Ozuner Ozgen Isik Emre Gorgun Luca Stocchi Department of Colorectal surgery Digestive Disease Institute Cleveland Clinic

AIM: To report our experience on management of colorectal neoplasia during pregnancy and in the postpartum ***: Patients who were diagnosed with colorectal cancer during pregnancy or in the postpartum period(surgery was 36 mo. Median duration of symptoms before diagnosis was 16 wk. Three patients were diagnosed with colorectal cancer during pregnancy and underwent surgery prior to delivery. None of the patients received adjuvant treatment during pregnancy. Five patients were diagnosed with colorectal cancer within a median of 2.1 mo after delivery and underwent surgery. No adverse neonatal outcomes were noted. All deliveries were at term(2 cesarean sections) except for one preterm delivery following low anterior resection on the 34 th week of ***: There has been a significant delay in the diagnosis of colorectal cancer which is probably due to overlap of symptoms and signs between these tumors and a normal pregnancy. surgery for colorectal cancer during pregnancy can be performed safely without compromisingmaternal and fetal outcomes.

关键词： Colorectal cancer Pregnancy Postpartum Neoplasia

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Value of routine stool testing for pathogenic bacteria in the evaluation of symptomatic patients with ileal pouches

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Gastroenterology Report 2018年第2期6卷 93-100,I0001页

作者： Amandeep Singh Jean Ashburn Gursimran Kochhar Rocio Lopez Tracy L.Hull Bo Shen Department of Gastroenterology&Hepatology Digestive Disease and Surgery InstituteThe Cleveland Clinic FoundationClevelandOHUSA Department of Colorectal surgery Digestive Disease and Surgery InstituteThe Cleveland Clinic FoundationClevelandOHUSA Department of Quantitative Health Sciences Digestive Disease and Surgery InstituteThe Cleveland Clinic FoundationClevelandOHUSA

Background:In symptomatic patients with an ileal pouch,stool studies are often sent to diagnose enteric *** of this study is to find the value of routine stool studies in the evaluation of symptomatic patients and the clinical implications of such pathogens in patients with ileal ***:Consecutive ileal pouch-anal anastomosis(IPAA)patients who had stool tests out of a 2283-case registry from 2002 to 2015 were included in the *** with positive stool cultures were compared with controls(symptomatic without positive stool culture)in a 1:4 *** to antibiotic therapy,recurrence rate and rate of hospitalization at 1 and 3 months were ***:A total of 643(28%)had stool cultures done and only 1.7%(11/643)were found to be positive for stool *** spp.(45%)was the most common pathogen followed by Aeromonas spp.(36%).Non-smokers and patients without any antibiotic use in the last 3 months were found to have higher prevalence of positive stool cultures than controls(p<0.001 and p¼0.023).Patients with pathogenic bacteria were found to have a higher risk of acute kidney injury(27.3%vs 4.5%,p¼0.049),hospitalization within 3 months of initial stool testing(36.4%vs 6.8%,p¼0.009)and mortality(18.2%vs 0%,p¼0.040).However,there were no statistically significant differences in the clinical outcomes in patients with positive stool cultures who received pathogen-directed ***:We found that the yield of stool tests for bacterial pathogens in symptomatic pouch patients was extremely low and the treatment of detected pathogens had a minimum impact on the disease course of *** clinical utility of routine stool culture in those patients warrants further study.

关键词： pouchitis ileal pouch enteric pathogens stool culture

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Liver transplantation in patients with incidental hepatocellular carcinoma/cholangiocarcinoma and intrahepatic cholangiocarcinoma： a single-center experience

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Hepatobiliary & Pancreatic Diseases International 2017年第3期16卷 264-270页

作者： Mohammed Elshamy Naftali Presser Abdulrahman Y Hammad Daniel J Firl Christopher Coppa John Fung Federico N Aucejo Hepatobiliary and Transplant surgery Digestive Disease and Surgery Institute Cleveland Clinic Cleveland OH USA Imaging institute Cleveland Clinic Cleveland OH USA

BACKGROUND： Reports of fiver transplantation （LT） in patients with mixed hepatocellular carcinoma/cholangiocarcinoma （HCC/CC） and intrahepatic cholangiocarcinoma （ICC） are modest and have been mostly retrospective after pathological categorization in the setting of presumed HCC. Some studies suggest that patients undergoing LT with small and unifocal ICC or mixed HCC/CC can achieve about 40%-60% 5-year post-transplant survival. The study aimed to report our experience in patients undergoing LT with explant pathology revealing HCC/CC and ICC. METHODS： From a prospectively maintained database, we performed cohort analysis. We identified 13 patients who underwent LT with explant pathology revealing HCC/CC or ICC. RESULTS： The observed recurrence rate post-LT was 31% （4/13） and overall survival was 85%, 51%, and 51% at 1, 3 and 5 years, respectively. Disease-free survival was 68%, 51%, and 41% at 1, 3 and 5 years, respectively. In our cohort, four patients would have qualified for exception points based on updated HCC Organ Procurement and Transplantation Network imaging guidelines. CONCLUSIONS： Lesions which lack complete imaging characteristics of HCC may warrant pre-LT biopsy to fully elucidate their pathology. Identified patients with early HCC/CC or ICC may benefit from LT if unresectable. Additionally, incorporating adjunctive perioperative therapies such as in the case of patients undergoing LT with hilar cholangiocarcinoma may improve outcomes but this warrants further investigation.

关键词： mixed hepatocellular carcinoma/ cholangiocarcinoma liver transplantation survival outcomes

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Hepatocellular carcinoma beyond Milan criteria: Management and transplant selection criteria

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World Journal of Hepatology 2016年第21期8卷 874-880页

作者： Mohammed Elshamy Federico Aucejo KV Narayanan Menon Bijan Eghtesad Hepato-biliary and Transplant surgery Digestive Disease and Surgery InstituteCleveland Clinic Foundation Gastroenterology and Hepatology Digestive Disease and Surgery InstituteCleveland Clinic Foundation

Liver transplantation(LT) for hepatocellular carcinoma(HCC) has been established as a standard treatment in selected patients for the last two and a half decades. After initially dismal outcomes, the Milan criteria(MC)(single HCC ≤ 5 cm or up to 3 HCCs ≤ 3 cm) have been adopted worldwide to select HCC patients for LT, however cumulative experience has shown that MC can be too strict. This has led to the development of numerous expanded criteria worldwide. Morphometric expansions on MC as well as various criteria which incorporate biomarkers as surrogates of tumor biology have been described. HCC that presents beyond MC initially can be downstaged with locoregional therapy(LRT). Post-LRT monitoring aims to identify candidates with favorable tumor behavior. Similarly, tumor marker levels as response to LRT has been utilized as surrogate of tumor biology. Molecular signatures of HCC have also been correlated to outcomes; these have yet to be incorporated into HCC-LT selection criteria formally. The ongoing discrepancy between organ demand and supply makes patient selection the most challenging element of organ allocation. Further validation of extended HCCLT criteria models and pre-LT treatment strategies are required.

关键词： Hepatocellular carcinoma Milan criteria Liver transplantation Expanded criteria Locoregional therapy Down staging

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