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Neuroprotective potential for mitigating ischemia-reperfusion-induced damage

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Neural Regeneration Research 2025年第8期20卷 2199-2217页

作者： Zi Ye Runqing Liu Hangxing Wang Aizhen Zuo Cen Jin Nan Wang Huiqi Sun Luqian Feng Hua Yang The Clinical Medical College Guizhou Medical UniversityGuiyangGuizhou ProvinceChina division of Infectious Diseases Department of Internal MedicinePeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina School of Medical Imaging Guizhou Medical UniversityGuiyangGuizhou ProvinceChina division of Gastroenterology First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina The Second Clinical Medical College Lanzhou UniversityLanzhouGansu ProvinceChina Department of Neurosurgery Affiliated Hospital of Guizhou Medical UniversityGuiyangGuizhou ProvinceChina

Reperfusion following cerebral ischemia causes both structural and functional damage to brain tissue and could aggravate a patient's condition;this phenomenon is known as cerebral ischemia-reperfusion *** studies have elucidated the neuroprotective role of the sirtuin protein family(Sirtuins)in modulating cerebral ischemia-reperfusion ***,the potential of utilizing it as a novel intervention target to influence the prognosis of cerebral ischemia-reperfusion injury requires additional *** this review,the origin and research progress of Sirtuins are summarized,suggesting the involvement of Sirtuins in diverse mechanisms that affect cerebral ischemia-reperfusion injury,including inflammation,oxidative stress,blood-brain barrier damage,apoptosis,pyroptosis,and *** therapeutic avenues related to Sirtuins that may improve the prognosis of cerebral ischemia-reperfusion injury were also investigated by modulating Sirtuins expression and affecting representative pathways,such as nuclear factor-kappa B signaling,oxidative stress mediated by adenosine monophosphate-activated protein kinase,and the forkhead box *** review also summarizes the potential of endogenous substances,such as RNA and hormones,drugs,dietary supplements,and emerging therapies that regulate Sirtuins *** review also reveals that regulating Sirtuins mitigates cerebral ischemia-reperfusion injury when combined with other risk *** Sirtuins show promise as a potential target for the treatment of cerebral ischemiareperfusion injury,most recent studies are based on rodent models with circadian rhythms that are distinct from those of humans,potentially influencing the efficacy of Sirtuinstargeting drug ***,this review provides new insights into the role of Sirtuins in the pathology and treatment of cerebral ischemia-reperfusion injury.

关键词： apoptosis autophagy blood-brain barrier dietary supplements drug hormones inflammation neuroprotection oxidative stress prognosis pyroptosis reperfusion injury risk factors RNA therapeutics

Fitting dynamic models to epidemic outbreaks with quantified uncertainty:A primer for parameter uncertainty,identifiability,and forecasts

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Infectious Disease Modelling 2017年第3期2卷 379-398页

作者： Gerardo Chowell division of Epidemiology&Biostatistics School of Public HealthGeorgia State UniversityAtlantaGAUSA division of International Epidemiology and Population studies Fogarty International CenterNational Institutes of HealthBethesdaMDUSA

Mathematical models provide a quantitative framework with which scientists can assess hypotheses on the potential underlying mechanisms that explain patterns in observed data at different spatial and temporal scales,generate estimates of key kinetic parameters,assess the impact of interventions,optimize the impact of control strategies,and generate *** review and illustrate a simple data assimilation framework for calibrating mathematical models based on ordinary differential equation models using time series data describing the temporal progression of case counts relating,for instance,to population growth or infectious disease transmission *** contrast to Bayesian estimation approaches that always raise the question of how to set priors for the parameters,this frequentist approach relies on modeling the error structure in the *** discuss issues related to parameter identifiability,uncertainty quantification and propagation as well as model performance and forecasts along examples based on phenomenological and mechanistic models parameterized using simulated and real datasets.

关键词： Parameter estimation Uncertainty quantification Bootstrap Parameter identifiability Model performance Forecasts Uncertainty propagation

Tumor necrosis factor-α inhibitor therapy and fetal risk:A systematic literature review

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World Journal of Gastroenterology 2013年第17期19卷 2591-2602页

作者： Renée M Marchioni Gary R Lichtenstein division of Gastroenterology and Hepatology University of Connecticut Health Center division of Gastroenterology Hospital of the University of Pennsylvania

Tumor necrosis factor-α inhibitors (anti-TNFs) are effective in the treatment of inflammatory bowel disease (IBD) recalcitrant to conventional medical therapy. As the peak incidence of IBD overlaps with the prime reproductive years, it is crucial to establish pharmacologic regimens for women of childbearing age that achieve effective disease control without posing significant fetal harm. A systematic literature review was performed to identify all human studies with birth outcomes data after maternal exposure to infliximab, adalimumab, or certolizumab pegol within 3 mo of conception or during any trimester of pregnancy. Live births, spontaneous abortions or stillbirths, preterm or premature births, low birth weight or small for gestational age infants, and congenital abnormalities were recorded. Fifty selected references identified 472 pregnancy exposures. The subsequent review includes general information regarding anti-TNF therapy in pregnancy followed by a summary of our findings. The benefits of biologic modalities in optimizing disease control during pregnancy must be weighed against the potential toxicity of drug exposure on the developing fetus. Although promising overall, there is insufficient evidence to prove absolute safety for use of anti-TNFs during pregnancy given the limitations of available data and lack of controlled trials.

关键词： Tumor necrosis factor-α inhibitors Pregnancy Congenital abnormalities Safety Infliximab Adalimumab Certolizumab

Molecular characterization of cyanobacterial diversity in Lake Gregory, Sri Lanka

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Chinese Journal of Oceanology and Limnology 2011年第4期29卷 898-904页

作者： Dhammika MAGANA-ARACHCHI Rasika WANIGATUNGE Madhushankha LIYANAGE Cell Biology division Institute of Fundamental Studies Hantana Road Kandy Sri Lanka

Eutrophication or the process of nutrient enrichment of stagnant waters due to excessive use of fertilizer is becoming a critical issue worldwide. Lake Gregory, an artificial lake situated in Nuwara Eliya, Sri Lanka was once a very attractive landscape feature and recreational area attracting a large number of visitors. Rapid urbanization in surrounding areas and the consequent intensification of agricultural and industrial activities led to eutrophication and siltation in the lake. Present study was conducted to detect cyanobacterial diversity and their ability to produce hepatotoxic microcystins using polymerase chain reaction (PCR)-based techniques. Twenty five water samples (surface and bottom) were collected from the lake and total nitrogen and total carbon were estimated. Cyanobacterial cultures were grown in appropriate media and microscopic observations were used to determine the morphological diversity of cyanobacteria isolated from different sites. Genomic DNA was isolated and purified from cyanobacteria using Boom's method. DNA samples were analyzed by PCR with oligonucleotide primers for 16S rRNA gene and mcyA gene of the operon that encodes a microcystin synthetase. The 16S rRNA gene sequences revealed the presences of cyanobacteria belong to Synechococcus sp., Microcystis aeruginosa, Calothrix sp., Leptolyngbya sp., Limnothrix sp., order Oscillatoriales and order Chroococcales. The sequences obtained from this study were deposited in the database under the accession numbers (GenBank: GU368104-GU368116). PCR amplification of mcyA primers indicated the potential for toxin formation of isolated M. aeruginosa from Lake Gregory. This preliminary study shows that the Lake Gregory is under the potential risk of cyanobacterial toxicity. Clearly more work is needed to extend this finding and clarify if other cyanobacterial isolates have genetic potential to produce microcystin since this lake is utilized for recreational activities.

关键词： eutrophication boom's method PCR microcystin mcyA gene

IKK inhibition prevents PM_(2.5)-exacerbated cardiac injury in mice with type 2 diabetes

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Journal of Environmental Sciences 2015年第5期27卷 98-103页

作者： Jinzhuo Zhao Cuiqing Liu Yuntao Bai Tse-yao Wang Haidong Kan Qinghua Sun Department of Environment health School of Public Health and the Key Laboratory of Public Health Safety Fudan University division of Environmental health Sciences College of Public Health The Ohio State University Davis Heart and Lung Research Institute The Ohio State University Wexner Medical Center

Epidemiological studies have found that individuals with diabetes mellitus（DM） display an increased susceptibility for adverse cardiovascular outcomes when exposed to air *** study was conducted to explore the potential mechanism linking ambient fine particles（PM2.5） and heart injury in a Type 2 DM（T2DM） animal model. The KKay mouse, an animal model of T2DM, was exposed to concentrated ambient PM2.5 or filtered air for 8 weeks via a versatile aerosol exposure and concentrator system. Simultaneously, an inhibitor of IκB kinase-2（IKK-a）（IMD-0354）, which is a blocker of nuclear factor κB（NF-κB）nuclear translocation, was administrated by intracerebroventricular injection（ICV） to regulate the NF-êB pathway. The results showed that ambient PM2.5 induced the increase of, NF-êB, cyclooxygenase-2（COX-2） and mitogen activated protein kinase（MAPK） expression in cardiac tissue, and that IMD-0354 could alleviate the inflammatory injury. The results suggested that the NF-êB pathway plays an important role in mediating the PM2.5-induced cardiovascular injury in the T2DM model. Inhibiting NFκB may be a therapeutic option in air-pollution-exacerbated cardiovascular injury in diabetes mellitus.

关键词： Fine particles Cardiovascular diseases Diabetes mellitus NFκB

Is it growing exponentially fast? -Impact of assuming exponential growth for characterizing and forecasting epidemics with initial near-exponential growth dynamics

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Infectious Disease Modelling 2016年第1期1卷 71-78页

作者： Gerardo Chowell Cecile Viboud School of Public health Georgia State UniversityAtlantaGAUSA division of International Epidemiology and Population studies Fogarty International CenterNational Institutes of HealthBethesdaMDUSA

The increasing use of mathematical models for epidemic forecasting has highlighted the importance of designing models that capture the baseline transmission characteristics in order to generate reliable epidemic *** models for epidemic forecasting could be achieved by identifying signature features of epidemic growth,which could inform the design of models of disease spread and reveal important characteristics of the transmission *** particular,it is often taken for granted that the early growth phase of different growth processes in nature follow early exponential growth *** the context of infectious disease spread,this assumption is often convenient to describe a transmission process with mass action kinetics using differential equations and generate analytic expressions and estimates of the reproduction *** this article,we carry out a simulation study to illustrate the impact of incorrectly assuming an exponential-growth model to characterize the early phase(e.g.,3e5 disease generation intervals)of an infectious disease outbreak that follows near-exponential growth ***,we assess the impact on:1)goodness of fit,2)bias on the growth parameter,and 3)the impact on short-term epidemic *** findings indicate that devising transmission models and statistical approaches that more flexibly capture the profile of epidemic growth could lead to enhanced model fit,improved estimates of key transmission parameters,and more realistic epidemic forecasts.

关键词： dynamics. process. exponential

Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

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Neural Regeneration Research 2025年第1期20卷 224-233页

作者： Yi Zhang Zhongwu Liu Michael Chopp Michael Millman Yanfeng Li Pasquale Cepparulo Amy Kemper Chao Li Li Zhang Zheng Gang Zhang Department of Neurology Henry Ford HospitalDetroitMIUSA Department of Physics Oakland UniversityRochesterMIUSA Department of Pathology Henry Ford HospitalDetroitMIUSA division of Pharmacology Department of NeuroscienceReproductive and Dentistry SciencesSchool of MedicineUniversity of Naples“Federico Ⅱ”NaplesItaly

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional *** previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic *** the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression *** EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a *** male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or *** array of behavior assays was used to measure neurological *** with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological *** vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal *** analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct *** of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of *** data provide evidence that 27a-sEVs have

关键词： axonal remodeling cerebral endothelial cells exosomes miR-27a mitochondria Semaphorin 6A small extracellular vesicles stroke

Predicting cutaneous leishmaniasis using SARIMA and Markov switching models in Isfahan, Iran: A time-series study

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Asian Pacific Journal of Tropical Medicine 2021年第2期14卷 83-93页

作者： Vahid Rahmanian Saied Bokaie Aliakbar Haghdoost Mohsen Barouni Department of Food Hygiene and Quality Control Division of Epidemiology&ZoonosesFaculty of Veterinary MedicineUniversity of TehranTehranIran HIV/STI Surveillance Research Center and WHO Collaborating Center for HIV SurveillanceInstitute for Futures Studies in HealthKerman University of Medical SciencesKermanIran health Services Management Research Center Institute for Futures Studies in HealthKerman University of Medical SciencesKermanIran

Objective:To determine the potential effect of environment variables on cutaneous leishmaniasis occurrence using time-series models and compare the predictive ability of seasonal autoregressive integrated moving average(SARIMA)models and Markov switching model(MSM).Methods:This descriptive study employed yearly and monthly data of 49364 parasitologically-confirmed cases of cutaneous leishmaniasis in Isfahan province,located in the center of Iran from January 2000 to December *** data were provided by the leishmaniasis national surveillance system,the meteorological organization of Isfahan province,and Iranian Space Agency for vegetation *** SARIMA and MSM models were implemented to examine the environmental factors of cutaneous leishmaniasis ***:The minimum relative humidity,maximum relative humidity,minimum wind speed,and maximum wind speed were significantly associated with cutaneous leishmaniasis epidemics in different lags(P<0.05).Comparing SARIMA and MSM,Akaikes information criterion(AIC),and mean absolute percentage error(MAPE)in MSM were much smaller than SARIMA models(MSM:AIC=0.95,MAPE=3.5%;SARIMA:AIC=158.93,MAPE:11.45%).Conclusions:SARIMA and MSM can be a useful tool for predicting cutaneous leishmaniasis in Isfahan *** cutaneous leishmaniasis falls into one of two states of epidemic and non-epidemic,the use of MSM(dynamic)is recommended,which can provide more information compared to models that use a single distribution for all observations(Box-Jenkins SARIMA model).

关键词： Leishmaniasis Climate factor Time series analysis Forecasting Iran

Tectonomagmatic origin of some volcanic and sub-volcanic rocks from the Lower Benue rift, Nigeria

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Chinese Journal Of Geochemistry 2011年第4期30卷 507-522页

作者： Smart C. Obiora Nirmal S. Charan Department of Geology University of Nigeria National Geophysical Research Institute Geological Studies Division

Petrological and geochemical studies on some volcanic and sub-volcanic rocks from the Lower Benue rift indicate that they are basalts, basaltic and doleritic sills, trachybasalt and trachyte which generally belong to the alkali basalt series. The alkaline affinity is clearly evident in both their normative and modal mineral compositions, as well as their chemical compositions. The generally high fractionation indices [(La/Yb)N] are 7.06 to 17.65 for the basaltic rocks and 23.59 to 135. 35 for the trachytic rocks, against low values commonly seen in subalkaline (tholeiitic) series, with strong enrichments in the incompatible elements. All this strongly supports their alkaline affinity. The basaltic rocks are generally fine-grained and porphyritic, consisting of phenocrysts of clinopyroxene and olivine in the groundmass of the same minerals together with plagioclase. The clinopyroxene is either diopside or clinoenstatite. The trachyte consists of oligoclase, orthoclase, biotite, quartz and exhibits typical trachytic, flow structure. The basaltic and doleritic sills are commonly altered, with calcite and epidote as common alteration prod-ucts. This alteration, which is reflected in the erratic behaviour of K2O, MnO and P2O5 on Harker variation diagrams, high values of LOI, strong depletions in the more mobile LILE (Rb, K, Ba and Sr) and high Th/Ta ratios, is attributed to the effects of an aqueous fluid phase and crustal contamination. On the whole, the mineralogical, as well as major-, trace-elements and REE data suggest that the rocks are co-genetic and most likely derived from differentiation of an alkali olivine-basalt magma, generating through variable low degrees of partial melting of probably an enriched lithospheric (upper) mantle following an asthenospheric uplift (mantle plume or intumescence) with HIMU signa-tures in a within-plate continental rift tectonic setting. This corroborates earlier results obtained for the intrusive rocks in the region.

关键词：次火山岩裂谷构造岩浆起源岩石学尼日利亚粗面玄武岩玄武质岩石单斜辉石