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Phytochemicals as inhibitors of tumor necrosis factor alpha and neuroinflammatory responses in neurodegenerative diseases

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Neural Regeneration Research 2022年第8期17卷 1675-1684页

作者： Fatemeh Zahedipour Seyede Atefe Hosseini Neil C.Henney George E.Barreto Amirhossein Sahebkar Department of Medical Biotechnology School of MedicineMashhad University of Medical SciencesMashhadIran Student Research Committee Faculty of MedicineMashhad University of Medical SciencesMashhadIran Pharmacy&Biomolecular Sciences Liverpool John Moores UniversityLiverpoolUK Department of Biological Sciences University of LimerickLimerickIreland Health Research Institute University of LimerickLimerickIreland Applied Biomedical Research Center Mashhad University of Medical SciencesMashhadIran Biotechnology Research Center Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran Polish Mother’s Memorial Hospital Research Institute(PMMHRI) LodzPoland School of Pharmacy Mashhad University of Medical SciencesMashhadIran

Inflammatory processes and proinflammatory cytokines have a key role in the cellular processes of neurodegenerative diseases and are linked to the pathogenesis of functional and mental health disorders.Tumor necrosis factor alpha has been reported to play a major role in the central nervous system in Alzheimer’s disease,Parkinson’s disease and amyotrophic lateral sclerosis and many other neurodegenerative diseases.Therefore,a potent proinflammatory/proapoptotic tumor necrosis factor alpha could be a strong candidate for targeted therapy.Plant derivatives have now become promising candidates as therapeutic agents because of their antioxidant and chemical characteristics,and anti-inflammatory features.Recently,phytochemicals including flavonoids,terpenoids,alkaloids,and lignans have generated interest as tumor necrosis factor alpha inhibitor candidates for a number of diseases involving inflammation within the nervous system.In this review,we discuss how phytochemicals as tumor necrosis factor alpha inhibitors are a therapeutic strategy targeting neurodegeneration.

关键词： brain central nervous system cytokine herbal medicine inflammation neurodegenerative diseases phytochemicals tumor necrosis factor-alpha

Neuroprotective effects of minocycline on focal cerebral ischemia injury: a systematic review

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Neural Regeneration Research 2020年第5期15卷 773-782页

作者： Yazdan Naderi Yunes Panahi george e. barreto Amirhosein Sahebkar Chemical Injuries Research Center Systems Biology and Poisonings InstituteBaqiyatallah University of Medical SciencesTehranIran Pharmacotherapy Department Faculty of PharmacyBaqiyatallah University of Medical SciencesTehranIran Department of Biological Sciences University of LimerickLimerickIreland Halal Research Center of IRI FDATehranIran Biotechnology Research Center Pharmaceutical Technology InstituteMashhad University of Medical SciencesMashhadIran Neurogenic Inflammation Research Center Mashhad University of Medical SciencesMashhadIran

To review the neuroprotective effects of minocycline in focal cerebral ischemia in animal models.By searching in the databases of PubMed,ScienceDirect,and Scopus,and considering the inclusion and exclusion criteria of the study.Studies were included if focal cerebral ischemia model was performed in mammals and including a control group that has been compared with a minocycline group.Written in languages other than english;duplicate data;in vitro studies and combination of minocycline with other neuroprotective agents were excluded.Neurological function of patients was assessed by National Institute of Health Stroke Scale,modified Rankin Scale,and modified Barthel Index.Neuroprotective effects were assessed by detecting the expression of inflammatory cytokines.We examined 35 papers concerning the protective effects of minocycline in focal cerebral ischemia in animal models and 6 clinical trials which had evaluated the neuroprotective effects of minocycline in ischemic stroke.These studies revealed that minocycline increases the viability of neurons and decreases the infarct volume following cerebral ischemia.The mechanisms that were reported in these studies included anti-inflammatory,antioxidant,as well as anti-apoptotic effects.Minocycline also increases the neuronal regeneration following cerebral ischemia.Minocycline has considerable neuroprotective effects against cerebral ischemia-induced neuronal damages.However,larger clinical trials may be required before using minocycline as a neuroprotective drug in ischemic stroke.

关键词： ischemic stroke minocycline neuronal regeneration neuroprotection stroke

Systematic review and meta-analysis of the impact of deviations from a clinical pathway on outcomes following pancreatoduodenectomy

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World Journal of Clinical Cases 2021年第13期9卷 3024-3037页

作者： Monish Karunakaran Pavan Kumar Jonnada Savio George.barreto Department of Gastrointestinal Surgery Gastrointestinal Oncologyand Bariatric SurgeryMedanta Institute of Digestive and Hepatobiliary SciencesGurgaon 122001HaryanaIndia Department of Liver Transplantation and Regenerative Medicine Medanta-The MedicityGurgaon 122001HaryanaIndia Surgical Oncology Kidwai Memorial Institute of OncologyBengaluru 560029KarnatakaIndia Division of Surgery and Perioperative Medicine Flinders Medical CenterBedford Park 5042South AustraliaAustralia College of Medicine and Public Health Flinders UniversityBedford Park 5042South AustraliaAustralia

BACKGROUND enhanced recovery after surgery is steadily gaining importance in patients undergoing pancreatic surgery,including pancreatoduodenectomy(PD).While clinical pathways targeting enhanced-recovery can achieve their intended outcome in reducing length of stay,compliance to these pathways,and their relevance is poorly understood.The aim of this systematic review was to assess the impact of deviations from/non-compliance to a clinical pathway on post-PD outcomes.AIM To assess the impact of deviations from/non-compliance to a clinical pathway on post-PD outcomes.MeTHODS A systematic review of major reference databases was undertaken,according to preferred reporting items for systematic reviews and meta-analysis guidelines,between January 2000 and November 2020 relating to compliance with clinical pathways and its impact on outcomes in patients undergoing PD.A meta-analysis was performed using fixed-effects or random-effects models.ReSULTS eleven studies including 1852 patients were identified.Median overall compliance to all components of the clinical pathway was 65.7%[interquartile range(IQR):62.7%-72.3%]with median compliance to post-operative parameters of the clinical pathway being 44%(IQR:34.5%-52.25%).Meta-analysis using a fixed-effects model showed that≥50%compliance to a clinical pathway predicted significantly fewer post-operative complications[pooled odds ratio(OR):9.46,95%confidence interval(CI):5.00-17.90;Per length of hospital stay[pooled mean difference(MD):4.32,95%CI:-3.88 to-4.75;Pe which was associated with significantly fewer post-operative complications(pooled OR:11.25,95%CI:4.71-26.84;Per hospital stay(pooled MD of 4.66,95%CI:2.81-6.51;Pe to post-PD clinical pathways remains low.Deviations are associated with an increased risk of complications and length of hospital stay.Understanding the relevance of deviations to clinical pathways post-PD presents pancreatic surgeons with opportuniti

关键词： Outcomes Morbidity Mortality Quality Surgery Recovery

Repair and regeneration of peripheral nerve injuries that ablate branch points

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Neural Regeneration Research 2023年第12期18卷 2564-2568页

作者： JuliAnne e.Allgood george D.Bittner Jared S.Bushman Division of Pharmaceutical Sciences University of WyomingLaramieWYUSA Department of Neuroscience The University of Texas at AustinAustinTXUSA

The peripheral nervous system has an extensive branching organization, and peripheral nerve injuries that ablate branch points present a complex challenge for clinical repair. Ablations of linear segments of the PNS have been extensively studied and routinely treated with autografts, acellular nerve allografts, conduits, wraps, and nerve transfers. In contrast, segmental-loss peripheral nerve injuries, in which one or more branch points are ablated so that there are three or more nerve endings, present additional complications that have not been rigorously studied or documented. This review discusses:(1) the branched anatomy of the peripheral nervous system,(2) case reports describing how peripheral nerve injuries with branched ablations have been surgically managed,(3) factors known to influence regeneration through branched nerve structures,(4) techniques and models of branched peripheral nerve injuries in animal models, and(5) conclusions regarding outcome measures and studies needed to improve understanding of regeneration through ablated branched structures of the peripheral nervous system.

关键词： allograft animal model branched injuries femoral nerve peripheral nerve injury peripheral nervous system regeneration repair sciatic nerve surgical repair

evaluation of disinfection byproducts for their ability to affect mitochondrial function

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Journal of environmental Sciences 2022年第7期34卷 295-304页

作者： george William Kajjumba Rachael e.Bokota Matias Attene-Ramos erica J.Marti Department of Civil and environmental engineering University of NevadaLas VegasNVUSA Department of environmental and Occupational Health Milken Institute School of Public HealthGeorge Washington UniversityWashington DCUSA

In the race to deliver clean water to communities through potable water reuse, disinfection and water quality assessment are and will continue to be fundamental factors. There are over 700 disinfection byproducts(DBPs) in water;evaluating each compound is practically impossible and very time consuming. A bioanalytical approach could be an answer to this challenge. In this work, the response of four major classes of DBPs toward mitochondrial membrane potential( Δψm) and cytoplasmic adenosine triphosphate(C-ATP) was investigated with human carcinoma(Hep G2) cells. Within 90 min of cell exposure, only the haloacetic acid(HAA) mixture caused a cytotoxic response as measured by C-ATP. All four groups(haloacetonitriles(HANs), trihalomethanes(THMs), nitrosamines(NOAs), and HAAs) responded well to Δψm, R 2 > 0.70. Based on the half-maximum concentration that evoked a 50% response in Δψm, the response gradient was HANs >> HAAs ~ THM > NOAs. The inhibition of the Δψm by HANs is driven by dibromoacetonitrile(DBAN), while dichloroacetonitrile(DCAN) did not cause a significant change in the Δψm at less than 2000 μM. A mixture of HANs exhibited an antagonistic behavior on the Δψm compared to individual compounds. If water samples are concentrated to increase HAN concentrations, especially DBAN, then Δψm could be used as a biomonitoring tool for DBP toxicity.

关键词： Disinfection byproducts Toxicity Mitochondrial membrane potential Dose-response curve In vitro bioassay emerging contaminants

Borderline resectable pancreatic tumors:Is there a need for further refinement of this stage?

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Hepatobiliary & Pancreatic Diseases International 2011年第3期10卷 319-324页

作者： Shailesh V Shrikhande Supreeta Arya Savio George.barreto Sachin Ingle Melroy A D'Souza Rohini Hawaldar Parul J Shukla Department of Hepato-Pancreato-Biliary Surgical Oncology Department of Radiology Tata Memorial Hospital Department of Surgery Royal Adelaide Hospital Clinical Research Secretariat

BACKGROUND:The ideal treatment of patients with 'borderline resectable pancreatic tumors (BRTs)' needs to be established.Current protocols advise neoadjuvant chemo(radio)therapy,although some patients may appear to have BRT on preoperative imaging and a complete resection may be achieved without the need for vascular resection.The aim of the present study was to identify specific findings on preoperative imaging that could help predict in which patients with BRT a complete resection,with or without vascular resection (VR),could be achieved.MeTHODS:Twelve patients with BRTs were identified.Tumor location,maximum degree of circumferential contact (CC),length of contact of the tumor with major vessels (LC),and luminal narrowing of vessels at the point of contact with the tumor (venous deformity,VD) were graded on preoperatively acquired multidetector computed tomography (MDCT) images and then compared with the intraoperative findings and need for VR.ReSULTS:A complete resection (R0) was achieved in 10 patients with 2 having microscopic positive margins (R1) on histopathology at the uncinate margin.Four of the 10 patients required VR (40%).In 3 of the 4 patients whose tumors required VRs,CC was ≥grade III and VD was grade 2.LC did not influence the need for VR.CONCLUSIONS:It is possible to achieve a complete resection at the first instance in patients found to have BRTs on preoperative imaging.Preoperative MDCT-based grading systems and our proposed criteria may help identify such patients,thus avoiding any delay in curative resections in such patients.

关键词： pancreatic head carcinoma pancreatic cancer pancreatic neoplasms resection

Does orthotics use improve comfort,speed,and injury rate during running?A randomised control trial

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World Journal of Orthopedics 2023年第5期14卷 348-361页

作者： Alice e Fortune Jonathan M G Sims george Ampat School of Medicine University of LiverpoolLiverpool L693GEUnited Kingdom Research Unit Talita Cumi Ltd.SouthportPR83NSUnited Kingdom School of Medicine University of LiverpoolLiverpool L693GEMerseysideUnited Kingdom

BACKGROUND Running is a hugely popular sport.Unfortunately,running-related injury(RRI)rates are high,particularly amongst amateur and recreational runners.Finding ways to reduce RRI rates and maximise comfort and performance for runners is important.evidence regarding whether orthotics can successfully improve these parameters is limited and contradicting.Further research is required to provide runners with clearer guidance on the usefulness of orthotics.AIM To investigate the effect of Aetrex Orthotics on comfort,speed and RRI rates during recreational running.MeTHODS One hundred and six recreational runners were recruited on a voluntary basis via running clubs and social media pages and randomised into either the intervention or control group.Participants in the intervention group ran with Aetrex L700 Speed Orthotics inserted in their usual running shoes,whilst participants in the control group ran in their usual running shoes with no orthotics.The study ran for an 8-wk period.Participants provided data relating to running comfort,distance,and time during weeks 3-6.Participants provided data relating to any RRIs they sustained during all 8 wks.Running distance and time were used to calculate running speed in miles per hour(mph).For each outcome variable,95%confidence intervals and P values were calculated to assess the statistical significance between the groups.For comfort and speed data,univariate multi-level analysis was performed,and for outcome variables with significant between group differences,multi-level multivariate analysis was performed to evaluate any confounding effects of gender and age.ReSULTS Ninety-four participants were included in the final analysis(drop-out rate=11%).Comfort and speed from 940 runs and 978 injury data reports were analysed.Participants who ran with orthotics reported,on average,speeds 0.30 mph faster(P=0.20)and comfort scores 1.27 points higher(P≤0.001)than participants who ran with no orthotics.They were also 2.22 times less likely to sustain an injury(P=0.08)than particip

关键词： Running Foot orthoses Running related injuries Pain Patient comfort Athletic performance

Late Cryogenian glaciation in South Australia:Fluctuating ice margin and no extreme or rapid post-glacial sea-level rise

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Geoscience Frontiers 2019年第4期10卷 1397-1408页

作者： george e.Williams Victor A.Gostin Department of earth Sciences University of Adelaide

Postulated extreme sea-level rise of up to 1-1.5 km with the late Cryogenian Ghaub deglaciation in Namibia is contentious,as is the great rapidity(<104 yr)of the sea-level rise.Such extreme glacioeustatic events,if re... 详细信息

Postulated extreme sea-level rise of up to 1-1.5 km with the late Cryogenian Ghaub deglaciation in Namibia is contentious,as is the great rapidity(e sea-level rise.Such extreme glacioeustatic events,if real,would have been global and affected all continents.In South Australia,up to six glacial advances and retreats during the late Cryogenian elatina glaciation indicate a fluctuating ice margin.The latter stage of the elatina glaciation and the immediate post-glacial environment are examined here for evidence of extreme and rapid sea-level rise.In the central Adelaide Rift Complex,diamictite with faceted and striated clasts occurs at the top of the elatina Formationeneath the early ediacaran Nuccaleena Formation’cap carbonate’.One hundred kilometres to the south,~30 m of siltstone and sandstone followed by^6 m of clast-poor diamictite with clasts 10+cm long occur between tidal rhythmites and the cap carbonate.Three hundred kilo metres further south,~70 m of siltsto ne,dolo mitic siltstone and minor dolomite separate tidal rhythmites and early ediacaran strata.Hence the rhythmites were deposited during a high stand(interstadial or interglacial),not during post-glacial sea-level rise.Storm-generated erosional surfaces within tidal rhythmites at Warren Gorge indicate intermittent rhythmite deposition,and water depth and other palaeoenvironmental factors are uncertain,casting doubt on a published estimate of rapid sea-level rise during rhythmite deposition.The lack of late Cryogenian deeply incised valleys and thick valley-fill deposits in South Australia and central Australia argues against extreme sea-level variations.A hiatus occurred between elatina deglaciation and deposition of the Nuccaleena cap carbonate,and three palaeomagnetic polarity chrons identified in the cap carbonate imply slow deposition spanning 10^5-10^6 yr.This is supported by independent evidence from magnetic chronostratigraphy for ediacaran strata in South Australia and California,and by stratigraphic and sedimentological a

关键词： Late Cryogenian glaciation Sea level Adelaide Rift Complex elatina Formation Nuccaleena Formation

Al-Cu-Mg合金在氯化钠溶液浸泡过程中萌生于单个和簇状金属间化合物粒子的局部溶解（英文）

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Transactions of Nonferrous Metals Society of China 2016年第11期26卷 2800-2809页

作者：骆晨 Xiaorong ZHOU george e.THOMPSON 中航工业北京航空材料研究院航空材料先进腐蚀与防护航空科技重点实验室北京100095 School of Materials The University of Manchester

为了深刻理解AA2024-T3 铝合金暴露在含氯水介质中金属间化合物相的响应方式,运用扫描电镜获得腐蚀试验前后合金表面的形貌信息,进行能谱分析确定金属间化合物粒子的成分变化,使用原子力显微镜检测金属间化合物相电化学反应所引起的高... 详细信息

为了深刻理解AA2024-T3 铝合金暴露在含氯水介质中金属间化合物相的响应方式,运用扫描电镜获得腐蚀试验前后合金表面的形貌信息,进行能谱分析确定金属间化合物粒子的成分变化,使用原子力显微镜检测金属间化合物相电化学反应所引起的高度变化,并对去合金金化的Al2CuMg 粒子及其周边区域进行透射电镜分析.研究发现,去合金化Al2CuMg 粒子为由5-20 nm 大小的体心立方铜粒子组成的多孔多晶体结构;在去合金化早期,铝基体就开始在Al2CuMg 粒子周边出现沟槽状腐蚀;Al-Cu-Fe-Mn.（Si）粒子周边沟槽状腐蚀的发展不均匀且比Al2CuMg 去合金化需要更长时间萌生;由Al2CuMg 和Al2Cu 组成的粒子簇的局部腐蚀主要与Al2CuMg 粒子相关.

关键词：铝合金金属间化合物粒子局部溶解去合金化沟槽状腐蚀