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The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

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Neural Regeneration Research 2025年第2期20卷 402-415页

作者： Xiaorong Zhang Zhiying Chen Yinyi Xiong Qin Zhou Ling-Qiang Zhu Dan Liu Department of pathology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Jiujiang Clinical Precision Medicine Research center JiujiangJiangxi ProvinceChina center for Cognitive Science and Transdisciplinary Studies Jiujiang UniversityJiangxi ProvinceChina Department of Neurology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Department of Rehabilitation Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic ***,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia *** in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive *** oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous ***,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular *** review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular ***,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

关键词： endoplasmic reticulum stress endothelial nitric oxide synthase gene therapy nitric oxide NO-sGC-cGMP pathway synaptic dysfunction vascular dementia

miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells

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Neural Regeneration Research 2025年第1期20卷 277-290页

作者： Meng Cong Jing-Jing Hu Yan Yu Xiao-Li Li Xiao-Ting Sun Li-Ting Wang Xia Wu Ling-Jie Zhu Xiao-Jia Yang Qian-Ru He Fei Ding Hai-Yan Shi School of Medicine Nantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education and Coinnovation center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Physiology Jiangsu Health Vocational CollegeNanjingJiangsu ProvinceChina Department of pathology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina Jiangsu Clinical Medicine center of Tissue Engineering and Nerve Injury Repair Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve ***-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular ***,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain *** investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose *** mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest *** performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest ***,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded ***,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously *** findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in ***-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell *** helps to explain the mechanism of action of the secretome and e

关键词： axotomy cell-free therapy conditioned medium extracellular vesicles hypoxic preconditioning microRNA oxygen-glucose deprivation peripheral nerve injury Schwann cell precursors

Unveiling the impact:COVID-19's influence on bacterial resistance in the Kingdom of Bahrain

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World Journal of Virology 2025年第1期14卷 83-98页

作者： Nermin K Saeed Safiya K Almusawi Noor A Albalooshi Mohammed Al-Beltagi Medical Microbiology Section Department of PathologySalmaniya Medical ComplexGovernmental HospitalsManama 12Bahrain Medical Microbiology Section Department of PathologyRoyal College of Surgeons in Ireland-Medical University of BahrainBusaiteen 15503MuharraqBahrain Department of Paediatrics Faculty of MedicineTanta UniversityTanta 31511AlghrabiaEgypt Department of Pediatric University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671AlgharbiaBahrain

BACKGROUND Antibiotic resistance is a growing global health threat,and understanding local trends in bacterial isolates and their susceptibility patterns is crucial for effective infection control and antimicrobial *** coronavirus disease 2019(COVID-19)pandemic has introduced additional complexities,potentially influencing these *** To analyze trends in bacterial isolates and their antibiotic susceptibility patterns at Salmaniya Medical Complex from 2018 to 2023,with a specific focus on the impact of the COVID-19 pandemic on these *** A retrospective analysis of microbiological data was conducted,covering the period from 2018 to *** study included key bacterial pathogens such as Escherichia coli(***),Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa,and Staphylococcus aureus,among *** antibiotic susceptibility profiles of these isolates were assessed using standard laboratory *** contextualize the findings,the findings were compared with similar studies from other regions,including China,India,Romania,Saudi Arabia,the United Arab Emirates,Malaysia,and United *** The study revealed fluctuating trends in the prevalence of bacterial isolates,with notable changes during the COVID-19 *** example,a significant increase in the prevalence of Staphylococcus aureus was observed during the pandemic years,while the prevalence of *** showed a more variable *** resistance rates varied among the different pathogens,with a concerning rise in resistance to commonly used antibiotics,particularly among Klebsiella pneumoniae and ***,the study identified an alarming increase in the prevalence of multidrug-resistant(MDR)strains,especially within Klebsiella pneumoniae and *** *** impact of the COVID-19 pandemic on these trends was evident,with shifts in the frequency,resistance patterns,and the emergence of MDR bacteria among several key ***

关键词： Multidrug-resistant organisms Antibiotic susceptibility COVID-19 pandemic Antimicrobial stewardship Bacterial isolates Salmaniya Medical Complex Bahrain

Primary peritoneal carcinoma metastasizing to breast: a single case report and literature review from clinic to biology

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Cancer Biology & Medicine 2016年第3期13卷 389-395页

作者： Ji-Yuan Sun Wondwossen Gebre Yi-Min Dong Xiao Shaun Rachel Robbins Alida Podrumar Department of Internal Medicine Nassau University Medical Center Department of pathology Nassau University Medical Center Department of pathology University of Arizona

Primary peritoneal carcinoma(PPC) is a type of rare malignant epithelial tumor. Metastasis from PPC to breast has been rarely reported. PPC originates de novo from the peritoneal tissues rather than invasion or metastasis from adjacent or remote *** have been implicated in many cases of carcinomas of unknown primary origin. It is similar to ovarian cancer(Ov Ca),because it shares the same common embryonic origin, the coelomic epithelium(mesodermal origin). The mechanism of oncogenesis remains elusive. In this article, we report a rare case of PPC in a patient 10 years after total abdominal hysterectomy and bilateral salpingooophorectomy for uterine leiomyoma, which was widely spread in the abdomen and metastasized to the colon, liver and distant organs including breast. The treatment is similar to that of primary ovarian cancer. We also reviewed the primary peritoneal cancer metastatic to breast and discuss the possible mechanisms and biology of primary peritoneal cancer,using experimental and animal model.

关键词： Primary peritoneal cancer breast cancer metastasis WT1 differential diagnosis

Neuroendocrine and squamous colonic composite carcinoma:Case report with molecular analysis

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World Journal of Gastroenterology 2011年第42期17卷 4729-4733页

作者： Sabrina C Wentz Cindy Vnencak-Jones William V Chopp Department of pathology Vanderbilt University Medical Center Molecular Genetics Laboratory Vanderbilt University Medical Center Department of pathology Veterans Affairs Medical Center

Composite colorectal carcinomas are rare. There are amodest number of cases in the medical literature,with even fewer cases describing composite carcinoma with neuroendocrine and squamous components. There areto our knowledge no reports of composite carcinomamolecular alterations. We present a case of composite carcinoma of the splenic flexure in a 33 year-old Cau-casian male to investigate the presence and prognos-tic significance of molecular alterations in rare coloniccarcinoma subtypes. Formalin-fixed paraffin-embedded(FFPE) tissue was hematoxylin and eosin- and mucicar-mine-stained according to protocol,and immuno-stained with cytokeratin(CK) 7,CK20,CDX2,AE1/AE3,chromo-granin-A and synaptophysin. DNA was extracted from FFPE tissues and molecular analyses were performed according to lab-developed methods,followed by capil-lary electrophoresis. Hematoxylin and eosin staining showed admixed neuroendocrine and keratinized squamous cells. Positive nuclear CDX2 expression confirme dintestinal derivation. CK7 and CK20 were *** cells stained positively for synaptophysin and AE1/AE3 and negatively for chromogranin and mucicarmine. Hepatic metastases showed a similar immunohistochemical profile. Molecular analysis revealeda G13D KRAS mutation. BRAF mutational testing wasnegative and microsatellite instability was not *** patient had rapid disease progression on chemotherapy and died 60 d after presentation. Although theG13D KRAS mutation normally predicts an intermed iateoutcome,the aggressive tumor behavior suggests other modifying factors in rare types of colonic carcinomas.

关键词： Composite carcinoma Neuroendocrine Squamous KRAS BRAF Microsatellite instability

Alcohol,nutrition and liver cancer:Role of Toll-like receptor signaling

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World Journal of Gastroenterology 2010年第11期16卷 1344-1348页

作者： Samuel W French Joan Oliva Barbara A French Fawzia Bardag-Gorce Department of pathology Harbor-UCLA Medical Center

This article reviews the evidence that ties the development of hepatocellular carcinoma (HCC) to the natural immune pro-inflammatory response to chronic liver disease, with a focus on the role of Toll-like receptor (TLR) signaling as the mechanism of liver stem cell/progenitor transformation to HCC. Two exemplary models of this phenomenon are reviewed in detail. One model applies chronic ethanol/lipopolysaccharide feeding to the activated TLR4 signaling pathway. The other applies chronic feeding of a carcinogenic drug, in which TLR2 and 4 signaling pathways are activated. In the drug-induced model, two major methyl donors, S-adenosylmethionine and betaine, prevent the upregulation of the TLR signaling pathways and abrogate the stem cell/progenitor proliferation response when fed with the carcinogenic drug. This observation supports a nutritional approach to liver cancer prevention and treatment. The observation that upregulation of the TLR signaling pathways leads to liver tumor formation gives evidence to the popular concept that the chronic pro-inflammatory response is an important mechanism of liver oncogenesis. It provides a nutritional approach, which could prevent HCC from developing in many chronic liver diseases.

关键词： Toll-like receptor Hepatocellular carcinoma Methyl donors, Epigenetic processes Inflammation Alcohol Drug toxicity Lipopolysaccharides

Effects of ethanol on the proteasome interacting proteins

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World Journal of Gastroenterology 2010年第11期16卷 1349-1357页

作者： Fawzia Bardag-Gorce Department of pathology LABioMed at Harbor-UCLA Medical Center

Proteasome dysfunction has been repeatedly reported in alcoholic liver disease. Ethanol metabolism endproducts affect the structure of the proteasome, and, therefore, change the proteasome interaction with its regulatory complexes 19S and PA28, as well as its interacting proteins. Chronic ethanol feeding alters the ubiquitin-proteasome activity by altering the interaction between the 19S and the 20S proteasome interaction. The degradation of oxidized and damaged proteins is thus decreased and leads to accumulation of insoluble protein aggregates, such as Mallory-Denk bodies. Ethanol also affects the immunoproteasome formation. PA28a/b interactions with the 20S proteasome are decreased in the proteasome fraction isolated from the liver of rats fed ethanol chronically, thus affecting the cellular antigen presentation and defense against pathogenic agents. Recently, it has been shown that ethanol also affects the proteasome interacting proteins (PIPs). Interaction of the proteasome with Ecm29 and with deubiquitinating enzymes Rpn11, UCH37, and Usp14 has been found to decrease. However, the two UBL-ubiquitin-associated domain (UBA) PIPs p62 and valosin-containing protein are upregulated when the proteasome is inhibited. The increase of these UBL-UBA proteins, as well as the increase in Hsp70 and Hsp25 levels, compensated for the proteasome failure and helped in the unfolding/docking of misfolded proteins. Chronic alcohol feeding to rats causes a significant inhibition of the proteasome pathway and this inhibition results from a decreases of the interaction between the 20S proteasome and the regulatory complexes, PIPs, and the ubiquitin system components.

关键词： Alcoholic liver diseases Proteasome Proteasome interacting proteins

Primary leiomyosarcoma of the thyroid gland with prior malignancy and radiotherapy:A case report and review of literature

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World Journal of Clinical Cases 2019年第4期7卷 473-481页

作者： Snezana Vujosevic Djordjije Krnjevic Milan Bogojevic Ljiljana Vuckovic Aleksandar Filipovic Du?ko Dun?erovi? Jelena Sopta Endocrinology Clinical Center of Montenegro Internal Medicine Clinic Clinical Center of Montenegro Institute of pathology Clinical Center of Montenegro Surgery Clinical Center of Montenegro Institute of pathology University of Belgrade

BACKGROUND Leiomyosarcoma(LMS) of the thyroid gland is a rarely presented tumor that offers poor prognosis. To the best of the authors' knowledge, there currently exist only 28 known cases described in the literature(limited to English).CASE SUMMARY Herein a case is reported of a 60-year-old female patient who had an LMS of the thyroid, which was accompanied by periodic dysphonia and breathing disorder as well as the feeling of pressure in the chest and neck. At the time the disease was diagnosed, no metastases were detected. Prior to the diagnosis, the patient experienced a uterine adenocarcinoma that had been treated by surgical procedure and radiotherapy. For the LMS, a total thyroidectomy was performed,followed by radiotherapy. Since metastases were also discovered in the lungs,sternum, and femur, chemotherapy was administered as ***, the tumor cells in the thyroid indicated positively for alpha smooth muscle actin, calponin, and H-caldesmon, but were negative for CD34, p63, estrogen receptor, progesterone receptor, and Epstein-Barr *** Although the etiology of the LMS is as of yet unknown, prior malignancy and radiation should be considered as risk factors.

关键词： Thyroid Leiomyosarcoma Smooth muscle tumor Radiotherapy Thyroidectomy Case report

Role of Leptin in Immunity

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Cellular & Molecular Immunology 2007年第1期4卷 1-13页

作者： Queenie Lai Kwan Lam Department of pathology and center of Infection and Immunology The University of Hong Kong

Leptin, a protein hormone produced by the adipocytes, has long been recognized to regulate metabolism, neuroendorine and other physiological functions. Early findings of increased leptin production during infection and inflammation and dysregulated immune response in leptin signaling-deficient mice provide strong evidence for the involvement of leptin in the immune responses. Recent data have established the regulatory function for leptin in immunity similar to the function of a pro-inflammatory cytokine, while gene-targeting studies also demonstrated an essential role of leptin in regulating hematopoiesis and lymphopoiesis. Moreover, there has been increasing evidence that leptin is involved in the pathogenesis of various autoimmune diseases. This review discusses recent advances in understanding the role of leptin in immunity and leptin-signaling pathways involved in modulating immune homeostasis and autoimmune pathogenesis. Cellular ＆ Molecular Immunology. 2007;4（1）：1-13.

关键词： leptin leptin signaling pro-inflammatory cytokine immune response autoimmune disease