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Multimodal comparison of plasma proteins associated with blood-brain barrier impairment in Alzheimer’s disease

Aging Communications 2024年第1期6卷 1-9页

作者： Elisa Giunti Roberto Collu Joel Reisman Jong Soo Lee Noureddine Melikechi Weiming Xia Geriatric Research Education and Clinical Center Bedford VA Healthcare SystemBedfordMA 01730U.S.A Department of pharmacology Physiology and BiophysicsBoston University Chobanian&Avedisian School of MedicineBostonMA 02118U.S.A Center for Healthcare Organization and Implementation Research Bedford VA Healthcare SystemBedfordMA 01730U.S.A Kennedy College of Science University of Massachusetts LowellLowellMA 01854U.S.A.

Background:Vascular impairment is one of the major contributors to *** aimed to identify blood biomarkers suggestive of potential impairment of the blood-brain barrier(BBB)in subjects with Alzheimer’s disease(AD).Methods:We used administrative data from the VA Informatics and Computing Infrastructure Resource Center to study both inpatients and outpatients with *** samples from healthy control and AD individuals were analyzed using enzyme-linked immunosorbent assay and proteomics approaches to identify differentially expressed *** analysis was applied to explore significantly enriched ***:In the same cohort of patients with AD,we found twice number of subjects with cerebral amyloid angiopathy in the two-year period after the onset of AD,compared to the number of subjects with cerebral amyloid angiopathy in the two-year period prior to AD *** pathways related to BBB,like cell adhesion,extracellular matrix organization and Wnt signaling,were activated and differentially expressed proteins such as ADAM22,PDGFR-α,DKK-4,Neucrin and RSOP-1 were ***,matrix metalloproteinase-9,which is implicated in causing degradation of basal lamina and BBB disruption,was significantly increased in the plasma of AD ***:Alteration of proteins found in AD subjects could provide new insights into biomarkers regulating permeability and BBB integrity.

关键词： Alzheimer’s disease blood-brain barrier peripheral biomarkers matrix metalloproteinases cerebral amyloid angiopathy

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Protective effects of a polysaccharide from Spirulina platensis on dopaminergic neurons in an MPT-Pinduced Parkinson's disease model in C57BL/6J mice

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Neural Regeneration Research 2015年第2期10卷 308-313页

作者： Fang Zhang Jian Lu Ji-guo Zhang Jun-xia Xie Department of pharmacology Medical College of Qingdao University Department of Pharmacy Xianyang Central Hospital Department of pharmacology Taishan Medical College Department of physiology Medical College of Qingdao University

The present study aimed to determine whether a polysaccharide obtained fromSpirulina platensis shows protective effects on dopaminergic neurons. A Parkinson’s disease model was established through the intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyr-idine （MPTP） in C57BL/6J mice. Prior to the MPTP injection, some mice were pretreated with intraperitoneal injections of a polysaccharide derived fromSpirulina platensis once daily for 10 days. The results showed that the immunoreactive staining and mRNA expression of the dopa-mine transporter and tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis, in the substantia nigra, were signiifcantly increased in mice pretreated with 800 mg/kg of the poly-saccharide compared with those in MPTP-treated mice. The activities of superoxide dismutase and glutathione peroxidase in the serum and midbrain were also increased signiifcantly in mice injected with MPTP after pretreatment with the polysaccharide fromSpirulina platensis. By con-trast, the activity of monoamine oxidase B in serum and midbrain maintained unchanged. These experimental ifndings indicate that the polysaccharide obtained fromSpirulina platensis plays a protective role against the MPTP-induced loss of dopaminergic neurons in C57BL/6J mice, and that the antioxidative properties of this polysaccharide likely underlie its neuroprotective effect.

关键词： nerve regeneration polysaccharide from Spirulina platensis Parkinson’s disease MPTP dopaminergic neurons antioxidation neural regeneration

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Fractalkine: multiple strategies to counteract glutamate receptors activation leading to neuroprotection

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Neural Regeneration Research 2015年第8期10卷 1214-1215页

作者： Clotilde Lauro Department of physiology and pharmacology Istituto Pasteur Fondazione Cenci Bolognetti Sapienza University of Rome

Glutamate（Glu）is the main excitatory amino acid in the brain and plays a pivotal role in many neurophysiological ***,an excess and prolonged exposure to Glu determines the overactivation of glutamate receptors（Glu... 详细信息

关键词： glutamate excitatory impairment homeostasis neuronal Glutamate NMDAR intracellular adenosine microglia

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White adipose tissue browning and obesity

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The Journal of Biomedical Research 2017年第1期31卷 1-2页

作者： Xiao-Bing Cui Shi-You Chen Department of physiology & pharmacology University of Georgia Athens GA 30602 USA

Obesity and metabolic disorders are major health concems worldwide. Although a range of therapies have been developed, these pharmaceutical treatments often have adverse side effects or limited efficacy. Therefore, there is a growing need of novel therapeutics to prevent or treat obesity. Obesity is thought to be caused by an imbalance between energy intake and energy consumption. Increasing energy consumption is considered as a potential therapeutic strategy to treat obesity and its related disorders.

关键词： obesity adipose pharmaceutical intake imbalance metabolism embryonic uncoupling downstream brown

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Antidiarrheal and protein conservative activities of Psidium guajava in diarrheal rats

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Journal of Integrative Medicine 2019年第1期17卷 57-65页

作者： Khaled M.M.Koriem Mahmoud S.Arbidb Hend N.Saleh Department of Medical physiology National Research Centre Department of pharmacology National Research Centre Faculty of Pharmacy Cairo University

Objective: Psidium guajava occurs worldwide in tropical and subtropical areas. It has been used to treat inflammation, diabetes, fever, hypertension and ulcers. However, its antidiarrheal and protein conservative activities still need to be ***: Fifty-four male rats were divided into normal and diarrheal rats. The normal rats were divided into 4 groups: control, low-dose P. guajava leaf extract(50 mg/kg), high-dose P. guajava leaf extract(100 mg/kg) and gallic acid. Treatments were administrated orally in 1 mL saline for a 1-month *** diarrheal rats were divided into 5 groups: desmopressin(0.2 mg/kg) drug, low-dose P. guajava leaf extract(50 mg/kg), high-dose P. guajava leaf extract(100 mg/kg), gallic acid and an untreated *** were given daily for a 1-month period while the untreated control received no ***: Diarrhea was responsible for an observed decline in kidney weight and serum sodium, potassium and chloride. Further, diarrhea was positively correlated with a significant increase in urine volume, and excretion of electrolytes, serum urea, creatinine and uric acid in the urine. In contrast, there was a proportional increase in the lipid peroxidation value in diarrhea and a significant decline was observed in serum superoxide dismutase, glutathione peroxidase and glutathione levels in diarrhea. Also, diarrhea inhibited blood proteins. The oral intake of P. guajava leaf extract by diarrheal rats restored all of these parameters to near normal levels. High-dose P. guajava leaf extract was more effective than the same compound at a low ***: P. guajava leaf extract elicited antidiarrheal and protein conservative effects.

关键词： Psidium guajava Myrtaceae Diarrhea Proteins Antioxidant

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S100B protein in the gut:The evidence for enteroglial-sustained intestinal inflammation

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World Journal of Gastroenterology 2011年第10期17卷 1261-1266页

作者： Carla Cirillo Giovanni Sarnelli Giuseppe Esposito Fabio Turco Luca Steardo Rosario Cuomo Department of Clinical and Experimental Medicine University of Naples "Federico Ⅱ" Department of Human physiology and pharmacology University of Rome "La Sapienza"

Glial cells in the gut represent the morphological and functional equivalent of astrocytes and microglia in the central nervous system （CNS）. In recent years, the role of enteric glial cells （EGCs） has extended from that of simple nutritive support for enteric neurons to that of being pivotal participants in the regulation of inflammatory events in the gut. Similar to the CNS astrocytes, the EGCs physiologically express the SIOOB protein that exerts either trophic or toxic effects depending on its concentration in the extracellular milieu. In the CNS, SIOOB overexpression is responsible for the initiation of a gliotic reaction by the release of pro-inflammatory mediators, which may have a deleterious effect on neighboring cells. SlOOB-mediated pro-inflammatory effects are not limited to the brain： SIOOB overexpression is associated with the onset and maintenance of inflammation in the human gut too. In this review we describe the major features of EGCs and SIOOB protein occurring in intestinal inflammation deriving from such.

关键词： Enteric glial cells Nitric oxide Intestinaldiseases

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From nerve to blood vessel:a new role of Olfm2 in smooth muscle differentiation from human embryonic stem cell-derived mesenchymal cells

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The Journal of Biomedical Research 2015年第4期29卷 261-263页

作者： Ning Shi Shi-You Chen Department of physiology & pharmacology University of Georgia

Vascular smooth muscle cell （SMC） differentiation is an important process in vasculogenesis and angio- genesis during embryonic development. The altera- tions in the differentiated state in SMCs contribute to a variety of major cardiovascular diseases such as atherosclerosis, hypertension, restenosis and vascular aneurysm . A better understanding of the cellular and molecular mechanisms that control SMC differen-tiation is essential to help develop new approaches to both prevent and treat these diseases. Therefore, development of reliable and reproducible in vitro cellular models in order to study the differentiation mechanisms is important although it has been challenging because of intrinsic peculiarities of SMC.

关键词： From nerve to blood vessel cell stem SMC

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Okadaic acid: a tool to study regulatory mechanisms for neurodegeneration and regeneration in Alzheimer's disease

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Neural Regeneration Research 2015年第3期10卷 365-367页

作者： Pradip Kumar Kamat Chandishwar Nath Division of physiology and Biophysics University of LouisvilleSchool of Medicine Division of pharmacology Central Drug Research Institute(CDRI)

Okadaic acid： Okadaic acid （OKA）, a polyether （C38 fatty acid） toxin, is a potent and selective inhibitor of protein phosphatase, PP1 and protein phosphatase 2A （PP2A）. It is mainly extracted from a black sponge Hallichondria okadaii and has been suggested to play a potent probe for studying the various molecular, cellular, biochemical and mechanism of neurotoxicity. It is known as a selective and potent in- hibitor of serine/threonine phosphatases 1 and 2A induces hyperphosphorylation of tau in vitro and in vivo. It has been reported that Alzheimer＇s disease （AD） is a complex multi- factorial neurodegenerative disorder and hyperphosphor- ylated tau protein is a major pathological hallmark of AD. The reduced activity of phosphatases like, PP2A has been implicated in the brain of AD patients. OKA also induced inhibition of protein phosphatases cause neurofibrillary tangles （NFTs） like pathological changes and tau hyperphos- phorylation seen in AD pathology. Our and others reports inferred that OKA induces neurodegeneration along with tau hyperphosphorylation, GSK3β activation, oxidative stress, neuroinflammation and neurotoxicity which are char- acteristic of AD pathology （Figure 1）.

关键词： a tool to study regulatory mechanisms for neurodegeneration and regeneration in Alzheimer’s disease Okadaic acid AD

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Epigenetic effects of ethanol on liver and gastrointestinal injury

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World Journal of Gastroenterology 2006年第33期12卷 5265-5271页

作者： Shivendra D Shukla Annayya R Aroor Department of Medical pharmacology & physiology University of Missouri School of Medicine Columbia Missouri 65212 United States

Alcohol consumption causes cellular injury. Recent developments indicate that ethanol induces epigenetic alterations, particularly acetylation, methylation of histones, and hypo- and hypermethylation of DNA. This has opened up a new area of interest in ethanol research and is providing novel insight into actions of ethanol at the nucleosomal level in relation to gene expression and patho-physiological consequences. The epigenetic effects are mainly attributable to ethanol metabolic stress (Emess), generated by the oxidative and non-oxidative metabolism of ethanol, and dysregulation of methionine metabolism. Epigenetic changes are important in ethanol-induced hepatic steatosis, fibrosis, carcinoma and gastrointestinal injury. This editorial highlights these new advances and its future potential.

关键词： Alcohol Alcoholic liver disease DNA methylation Epigenetics Ethanol Gastrointestinal injury Histone modifications Liver injury

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Comparison of the effects of carbamyl-β-methylcholine chloride ad ministered by intravenous,intramuscular and intra-acupuncture point injections

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Journal of Traditional Chinese Medicine 2012年第1期32卷 93-98页

作者：王玉敏高俊虹逯波彭娟范斌崔晶晶王洪新马琰岩喻晓春 Department of physiology Experimental Research CenterChina Academy of Chinese Medical Sciences Department of physiology Institute of Acupuncture and MoxibustionChina Academy of Chinese Medical Sciences Department of pharmacology Liaoning Medical College

OBJECTIVE:To compare the effects of carbamylβ-methylcholine chloride(CMCC) administered by intra-acupuncture point injection(IAI),intramuscular injection(IMI),and intravenous injection(IVI),and to analyze the ***:In the IAI group,CMCC was injected into the Zusanli acupoint(ST 36) immediately after 30-min stimulation by electro-acupuncture(EA) at the acupoints,and into the femoral vein and skeletal muscle in IVI and IMI groups,***-gastric pressure was *** plasma concentration of CMCC was measured at various ***:The gastric effect of CMCC in the IVI group was enhanced and attenuated more rapidly than in the other *** the IAI group,this effect was significantly stronger than that in the IMI group at 2 min and 15 min,but not significantly different between the two groups at 5 min and 30 *** concentration of CMCC in the IAI group was similar to that in the IVI group at 2 min,but higher than that in the IMI *** concentration in the IAI group was higher than that in the IV group and similar to that in the IMI group at 5,15 and 30 min,indicating rapid increase and slower reduction of the plasma concentration of the drug in the IAI *** was a positive correlation between the plasma concentration of CMCC and intragastric pressure in all ***:The effect of IAI with CMCC was stronger than that of IMI and longer-lasting than that of IVI,which correlated with the blood concentration of CMCC.

关键词： Acupuncture Intra-acupuncture point injection Synergistic effect Plasma concentration

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