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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

Diagnostic yield of EUS-FNA of small(≤15 mm) solid pancreatic lesions using a 25-gauge needle

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Hepatobiliary & Pancreatic Diseases International 2018年第1期17卷 70-74页

作者： Stefano Francesco Crinò Maria Cristina Conti Bellocchi Laura Bernardoni Erminia Manfrin Alice Parisi Antonio Amodio Nicolò De Pretis Luca Frulloni Armando gabbrielli gastroenterology and Digestive Endoscopy Unit The Pancreas Institute University of Verona G.B. Rossi University Hospital department of pathology University of Verona G.B. Rossi University Hospital

Background: Early detection of small solid pancreatic lesions is increasingly common. To date, few and contradictory data have been published about the relationship between lesion size and endoscopic ultrasound-guided fine needle aspiration(EUS-FNA) diagnostic yield. The aim of this study was to assess the relation between the size of solid pancreatic lesions and the diagnostic yield of EUS-FNA using a 25-gauge needle in a center without available rapid on-site ***: In the retrospective cohort study, we selected patients who underwent EUS-FNA for solid pancreatic lesions with a 25-gauge needle from October 2014 to October 2015. Patients were divided into three groups(≤15 mm, 16–25 mm and >25 mm), and the outcomes were ***: We analyzed 163 patients. Overall adequacy, sensitivity, specificity and accuracy were 85.2%,81.8%, 93.7%, and 80.4%, respectively. When stratified by size, the sensitivity and accuracy correlated with size(P = 0.016 and P = 0.042, respectively). Multivariate analysis showed that lesion size was the only independent factor(P = 0.019, OR = 4.76) affecting accuracy. The role of size as an independent factor affecting accuracy was confirmed in a separate multivariate analysis, where size was included in the model as a covariate(P = 0.018, OR = 1.08).Conclusion: Our study demonstrates that, in the absence of rapid on-site evaluation, mass size affects the accuracy of EUS-FNA of solid pancreatic lesions.

关键词： Endoscopic ultrasound Endoscopic ultrasound-guided fine needle aspiration Pancreatic cancer Benign pancreatic tumors Pancreatic neoplasms

Histopathology of hepatocellular carcinoma

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World Journal of gastroenterology 2014年第43期20卷 15955-15964页

作者： Manuel Schlageter Luigi Maria Terracciano Salvatore D'Angelo Paolo Sorrentino department of pathology University Hospital Basel Liver Unit Clinical and Experimental HepatologyS.G.Moscati General Hospital

Hepatocellular carcinoma(HCC)is currently the sixth most common type of cancer with a high mortality rate and an increasing incidence *** etiology is usually linked to environmental,dietary or lifestyle *** most commonly arises in a cirrhotic liver but interestingly an increasing proportion of HCCs develop in the non-fibrotic or minimal fibrotic liver and a shift in the underlying etiology can be *** this process is yet to be completely understood,this changing scenario also has impact on the material seen by pathologists,presenting them with new diagnostic *** criteria for diagnosing classical,progressed HCC are well established and known,but with an increase in detection of small and early HCCs due to routine screening programs,the diagnosis of these small lesions in core needle biopsies poses a difficult *** lesions can be far more difficult to distinguish from one another than progressed HCC,which is usually a clear cut hematoxylin and eosin *** lesions thought to derive from progenitor cells have recently been reclassified in the *** review summarizes recent developments and tries to put new HCC biomarkers in context with the WHOs *** it also addresses the group of tumors known as combined hepatocellular-cholangiocellular carcinomas.

关键词： Histology pathology Hepatocellular carinoma

Effects of intraocular rifampicin on retinal ganglion cell structure:a stereological and histopathological study

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International Journal of Ophthalmology(English edition) 2013年第5期6卷 596-599页

作者： zgür Cakici Selina Aksak Deniz Unal Sare Sipal Sadullah Keles Talha Dumlu Murat Karamese department of Ophthalmology Erzurum Research and Education Hospital department of cytology and Histology Faculty of MedicineAtaturk University department of pathology Faculty of SciencesAtaturk University department of Ophthalmology Faculty of MedicineAtaturk University department of Chest Diseases Horasan Government Hospital department of Microbiology Faculty of MedicineAtaturk University

AIM:To determine the histopathological changes of rifampicin applied intravitreally on retinal ganglion cells by means of stereological and histopathological ***:For this study twenty-four New Zealand adult rabbits were divided into four groups(n=6 for each group).50μg/0.1mL(group 1),100μg/0.1mL(group 2),150μg/0.1mL(group 3) and 200μg/0.1mL(group 4),rifampicin were injected into the vitreous of the right eyes of animals,their left eyes were used as control(group 5).After the 28thday of application,animals were anesthetised with xylazine(8mg/kg,IM) and then their eyes were enucleated *** were taken away and eyes were prepared for both stereological and electromicroscopic ***:Depending on the high dose of rifampicin,some histopathological changes such as cytoplasmic dilatation and damaged membrane were observed on the electromicroscopic *** quantitative examination,which was done at the light microscopic level,it was shown that the number of neurons decreased linearly as rifampicin dose increased when compared with the control ***:Based on these findings,low-dose rifampicin(50μg/0.1mL) may be useful for treatment of the ocular diseases.

关键词： rifampicin stereology histopathology ganglion cells

Esophageal subepithelial lesion diagnosed as malignant gastrointestinal neuroectodermal tumor

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World Journal of gastroenterology 2015年第18期21卷 5739-5743页

作者： Sung Bum Kim Si Hyung Lee Mi Jin gu department of Internal Medicine Yeungnam University Hospital department of pathology Yeungnam University Hospital

A 21-year-old male visited our hospital with a complaint of aggravating dysphagia and odynophagia for a few *** showed huge bulging mucosa with an intact surface causing luminal narrowing at 35 cm from the incisor *** ultrasonography showed an about 35 mm sized irregular margined in-homogenous hypoechoic lesion with an obscure layer of *** ultrasonography fine needle aspiration revealed spindle cell proliferation without immunoreactivity for CD117,SMA,and *** patient underwent excision of the subepithelial lesion at the distal *** pathologic examination of the specimen,the tumor was composed of short fascicles of oval to spindle cells with eosinophilic and clear cytoplasm and vesicular *** tumor cells were positive for S-100 and SOX10and negative for CD117,SMA,HMB-45,melan-A,cytokeratin,and *** split-apart signal was detected in EWSR1 on FISH,suggesting a malignant gastrointestinal neuroectodermal *** the time of writing,the patient is on radiation therapy at the operated site of esophagus and doing well,with no recurrence for three *** gastrointestinal neuroectodermal tumor is a rare gastrointestinal tumor with features of clear cell sarcoma,without melanocytic differentiation,and shows a poor *** is the first reported case of malignant gastrointestinal neuroectodermal tumor arising as subepithelial lesion in the esophagus.

关键词： Subepithelial lesion Esophagus Malignant gastrointestinal neuroectodermal tumor Ewing sarcoma break point region 1 gene Fluorescence in situ hybridization

Prevalence and Prognosis of Relapse of Nephroblastoma at the Pediatric Oncology Unit of Bamako

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Open Journal of Pediatrics 2019年第4期9卷 317-325页

作者： F. L. F. Diakité P. Togo A. K. Doumbia F. Traoré M. Traoré K. Sacko C. O. Coulibaly N. L. Traoré A. Touré B. Maiga L. N. Sidibé D. Konaté A. Diall A. Dembélé C. B. Traoré B. Togo department of Pediatrics CHU Gabriel Toure Bamako Mali department of Pediatric Surgery CHU Gabriel Toure Bamako Mali department of pathology anatomy and cytology CHU Point G Bamako Mali

The nephroblastoma is the third pediatric cancer in Mali, this study aimed to describe the prevalence and prognosis of nephroblastoma relapses. Methods: It was a descriptive retrospective study over a 10-year period from January 2005 to March 2015. We collected children aged 0 to 15 years followed for relapse of nephroblastoma in the pediatric oncology unit of university hospital center (UHC) gabriel Toure. Results: The frequency of relapse of nephroblastoma was 7.4% (19 cases) whose mean age was 42 months with a sex ratio of 1.3. The relapse occurred before the end of the postoperative course in 16% of cases (3 patients). It was local recurrence in 52% of cases (10 patients), pulmonary 16% (3 patients), and hepatic 11% (2 patients). According to the SIOP classification, 47% of patients were diagnosed in stage III (9 patients) and 21% (4 patients) in stage IV. The tumor was high risk in 37%. Palliative chemotherapy was performed in 63% of the patients (12 patients) and the remaining seven were put on a high risk diet. The overall survival at 5 years was 21% or 4 patients. Conclusion: Our results showed all the difficulties in the management of nephroblastoma relapses in our context.

关键词： Nephroblastoma Relapse Mali

Targets and beyond:cancer stem cell elimination

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Science Bulletin 2017年第16期62卷 1104-1105页

作者： Anqi Wu guang Shu Jing Wang gang Yin department of pathology Xiangya HospitalCentral South University department of pathology School of Basic Medicine SciencesCentral South University

Cancer stem cells(CSCs)have been reported in various cancer types.A small portion of tumor cells that possess tumor initiation capacity,resist conventional drug treatment and correlate with poor prognosis are believed to be essential to drive tumor progression and ***,successfully targeting CSCs is a promising strategy of cancer treatment.

关键词：肿瘤干细胞癌症治疗肿瘤细胞药物治疗

Inhibitory effects of dobutamine on human gastric adenocarcinoma

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World Journal of gastroenterology 2014年第45期20卷 17092-17099页

作者： Hui-Xia Zheng Li-Na Wu Hong Xiao Qian Du Jian-Fang Liang department of pathology The First Hospital Shanxi Medical University

AIM: To explore the inhibitory effects of dobutamine on gastric adenocarcinoma cells.

关键词： Dobutamine gastric adenocarcinoma cells Yes-associated protein Hippo pathway Human gastric adenocarcinoma cell line SgC-7901 Therapy

Hypoxia-stressed cardiomyocytes promote early cardiac differentiation of cardiac stem cells through HIF-1α/Jagged1/Notch1 signaling

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Acta Pharmaceutica Sinica B 2018年第5期8卷 795-804页

作者： Keke Wang Ranran Ding Yanping Ha Yanan Jia Xiaomin Liao Sisi Wang Rujia Li Zhihua Shen Hui Xiong Junli guo Wei Jie department of pathology Guangdong Medical University department of pathology Union Hospital Tongji Medical College Huazhong University of Science and Technology Cardiovascular Institute of First Affiliated hospital Hainan Medical University

Hypoxia is beneficial for the differentiation of stem cells transplanted for myocardial injury,but mechanisms underlying this benefit remain unsolved. Here, we report the impact of hypoxia-induced Jagged1 expression in cardiomyocytes(CMs) for driving the differentiation of cardiac stem cells(CSCs).Forced hypoxia-inducible factor 1α(HIF-1α) expression and physical hypoxia(5% O_2) treatment could induce Jagged1 expression in neonatal rat CMs. Pharmacological inhibition of HIF-1α by YC-1 attenuated hypoxia-promoted Jagged1 expression in CMs. An ERK inhibitor(PD98059), but not inhibitors of JNK(SP600125), Notch(DAPT), NF-κB(PTDC), JAK(Ag490), or STAT3(Stattic) suppressed hypoxiainduced Jagged1 protein expression in CMs. c-Kit^+ CSCs isolated from neonatal rat hearts using a magnetic-activated cell sorting method expressed gATA4, SM22α or vWF, but not Nkx2.5 and ***, 87.3% of freshly isolated CSCs displayed Notch1 receptor expression. Direct co-culture of CMs with BrdU-labeled CSCs enhanced CSCs differentiation, as evidenced by an increased number of BrdU^+/Nkx2.5^+ cells, while intermittent hypoxia for 21 days promoted co-culture-triggered differentiation of CSCs into CM-like cells. Notably, YC-1 and DAPT attenuated hypoxia-induced *** results suggest that hypoxia induces Jagged1 expression in CMs primarily through ERK signaling,and facilitates early cardiac lineage differentiation of CSCs in CM/CSC co-cultures via HIF-1α/Jagged1/Notch signaling.

关键词： Cardiac stem cell Cardiomyocyte,Co-culture Hypoxia Notch1 signaling Cell differentiation