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Microglial senescence in neurodegeneration:insights,implications,and therapeutic opportunities

Neuroprotection 2024年第3期2卷 182-195页

作者： Tobiloba Samuel olajide Toheeb o.oyerinde omolabake i.omotosho oritoke M.okeowo olayemi J.olajide omamuyouwi M.ijomone Laboratory for Experimental and Translational Neurobiology University of Medical SciencesOndoOndoNigeria Department of Physiology School of Basic Medical ScienceFederal University of TechnologyAkureOndoNigeria Center for Studies in Behavioral Neurobiology Department of PsychologyConcordia UniversityMontrealQuebecCanada Division of Neurobiology Department of AnatomyFaculty of Basic Medical SciencesUniversity of IlorinIlorinKwaraNigeria Department of Molecular Pharmacology Albert Einstein College of MedicineBronxNew YorkUSA

The existing literature on neurodegenerative diseases(NDDs)reveals a common pathological feature:the accumulation of misfolded ***,the heterogeneity in disease onset mechanisms and the specific brain regions affected complicates the understanding of the diverse clinical manifestations of individual ***,a hallmark symptom across various NDDs,serves as a multifaceted denominator,contributing to the clinical manifestations of these *** is a compelling hypothesis that therapeutic strategies capable of mitigating misfolded protein accumulation and disrupting ongoing pathogenic processes may slow or even halt disease *** research has linked disease-associated microglia to their transition into a senescent state—characterized by irreversible cell cycle arrest—in aging populations and *** senescent microglia are consistently observed in NDDs,few studies have utilized animal models to explore their role in disease *** evidence from experimental rat models suggests that disease-associated microglia exhibit characteristics of senescence,indicating that deeper exploration of microglial senescence could enhance our understanding of NDD pathogenesis and reveal novel therapeutic *** review underscores the importance of investigating microglial senescence and its potential contributions to the pathophysiology of NDDs,including Alzheimer's disease,Parkinson's disease,Huntington's disease,and amyotrophic lateral ***,it highlights the potential of targeting microglial senescence through iron chelation and senolytic therapies as innovative approaches for treating age-related NDDs.

关键词： aging ferritin microglia neurodegenerative diseases senescence-associated secretory phenotype senescent

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Connexins in neurons and glia: targets for intervention in disease and injury

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Neural Regeneration Research 2015年第7期10卷 1013-1017页

作者： Keith B.Moore John o'Brien Richard S.Ruiz M.D.Department of Ophthalmology & Visual Science The University of Texas Health Science Center at Houston The University of Texas Graduate School of Biomedical Sciences

Both neurons and glia throughout the central nervous system are organized into networks by gap junctions. Among glia, gap junctions facilitate metabolic homeostasis and intercellular communication. Among neurons, gap junctions form electrical synapses that function primarily for communication. However, in neurodegenerative states due to disease or injury gap junctions may be detrimental to survival. Electrical synapses may facilitate hyperactivity and bystander killing among neurons, while gap junction hemichannels in glia may facilitate inflammatory signaling and scar formation. Advances in understanding mechanisms of plasticity of electrical synapses and development of molecular therapeutics to target glial gap junctions and hemichannels offer new hope to pharmacologically limit neuronal degeneration and enhance recovery.

关键词： ischemia retinal degeneration amacrine cells astrocytes dopamine receptors adenosine receptors NMDA receptors connexin mimetic peptides

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impact of radiotherapy on the immune landscape in oesophageal adenocarcinoma

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World Journal of Gastroenterology 2022年第21期28卷 2302-2319页

作者： Noel E Donlon Maria Davern Fiona o'Connell Andrew Sheppard Aisling Heeran Anshul Bhardwaj Christine Butler Ravi Narayanasamy Claire Donohoe James J Phelan Niamh Lynam-Lennon Margaret R Dunne Stephen Maher Jacintha o'Sullivan John V Reynolds Joanne Lysaght Department of Surgery Trinity Translational Medicine InstituteSt James HospitalDublin D08Ireland

BACKGRoUND in the contemporary era of cancer immunotherapy,an abundance of clinical and translational studies have reported radiotherapy(RT)and immunotherapies as a viable option for immunomodulation of many cancer subtypes,with many related clinical trials *** locally advanced disease,chemotherapy or chemoradiotherapy followed by surgical excision of the tumour remain the principal treatment strategy in oesophageal adenocarcinoma(oAC),however,the use of the host immune system to improve anti-tumour immunity is rapidly garnering increased support in the curative *** To immunophenotype oAC patients’immune checkpoint(iC)expression with and without radiation and evaluate the effects of checkpoint blockade on cell *** in the contemporary era of cancer immunotherapy,an abundance of studies have demonstrated that combination RT and iC inhibitors(iCis)are effective in the immunomodulation of many cancer subtypes,with many related clinical trials *** surgical excision and elimination of tumour cells by chemotherapy or chemoradiotherapy remains the gold standard approach in oAC,the propagation of anti-tumour immune responses is rapidly garnering increased support in the curative *** aim of this body of work was to immunophenotype oAC patients’iC expression with and without radiation and to establish the impact of checkpoint blockade on cell *** study was a hybrid combination of in vitro and ex vivo *** of serum immune proteins was performed by enzyme-linked immunosorbent *** cytometry staining was performed to evaluate iC expression for in vitro oAC cell lines and ex vivo oAC *** viability in the presence of radiation with and without iC blockade was assessed by a cell counting kit-8 *** We identified that conventional dosing and hypofractionated approaches resulted in increased iC expression(PD-1,PD-L1,TiM3,TiGiT)in vitro and ex vivo in *** were two distinct subco

关键词： oesophageal Cancer Radiotherapy immunotherapy immunology Surgery oncology

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The economic impacts of cataract surgery on sustainable vision and quality of life in Katsina state

Health Care Science

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Health Care Science 2023年第2期2卷 112-119页

作者： Mansur M.Rabiu Manal o.Taryam Muhammad Yusuf ibrahim Kabiru Maji Department of Programmes and Research Noor Dubai FoundationDubaiUAE Department of Economics Air Force Institute of TechnologyKadunaNigeria Department of Economics Nigerian Army UniversityBiuNigeria

Background:This study investigates the economic impacts of eye care interventions on the quality of life in Katsina *** care intervention is a requirement for equitable and inclusive development in the ***:The study used a survey method and 5-point Likert scale questionnaire to collect data.A multistage sampling strategy was employed to select 300 beneficiaries from the existing beneficiaries of Noor Dubai Foundation(NDF)eye care ***:The findings show that cataract surgery interventions improve economic benefits and quality of life of beneficiaries in Katsina *** results show that productivity,income,employability,dignity and skills of beneficiaries have improved significantly after the cataract ***,96.2%of the beneficiaries agree that their productivity has improved;99.6%of the beneficiaries revealed that their income has improved;99%of respondents evidence that their employability has improved;90%of beneficiaries have experienced an improvement in their dignity;while 97%agreed that their skills have ***:The implication of these findings is that poor eye health is negatively related to economic benefits and quality of life while good eye health is a vital determinant of standard of *** good eye health,it is hard to participate in the labour force,produce goods and earn ***,the Katsina state government should further improve awareness of good eye health to mitigate preventable cases of blindness for equitable and inclusive development.

关键词： cataract economic effects surgery sustainability vision

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ice-templated porous tungsten and tungsten carbide inspired by natural wood

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Journal of Materials Science & Technology 2020年第10期42卷 187-197页

作者： Yuan Zhang Guoqi Tan Da Jiao Jian Zhang Shaogang Wang Feng Liu Zengqian Liu Longchao Zhuo Zhefeng Zhang Sylvain Deville Robert o.Ritchie Laboratory of Fatigue and Fracture for Materials Institute of Metal Research.Chinese Academy of SciencesShenyang 110016China School of Mechanical Engineering Liaoning Shihua UniversityFushun 113001China School of Materials Science and Engineering University of Science and Technology of ChinaHefei 230026China School of Materials Science and Engineering Xi'an University of TechnologyXi'an710048China Laboratoire De Synthese Et Fonctionnalisation Des Ceramiques UMR3080 CNRS/Saint-Gobain CREESaint-Gobain Research ProvenceCavaillon 84306France Department ofMateriab Science and Engineering University of California BerkeleyBerkeleyCA 94720USA

The structures of tungsten and tungsten carbide scaffolds play a key role in determining the properties of their infiltrated composites for multifunctional ***,it is challenging to construct and control the architectures by means of self-assembly in W/WC systems because of their large *** we present the development of unidirectionally porous architectures,with high porosities exceeding 65 vol.%,for W and WC scaffolds which in many respects reproduce the design motif of natural wood using a direct ice-templating *** was achieved by adjusting the viscosities of suspensions to retard sedimentation during *** processing,structural characteristics and mechanical properties of the resulting scaffolds were investigated with the correlations between them *** relationships were established to describe their strengths based on the mechanics of cellular solids by taking into account both inter-and intra-lamellar *** fracture mechanisms were also identified,especially in light of the *** study extends the effectiveness of the ice-templating technique for systems with large densities or particle *** further provides preforms for developing new natureinspired multifunctional materials,as represented by W/WC-Cu composites.

关键词： ice-templating Tungsten Scaffolds Fracture mechanisms Bioinspired materials

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Geological,Structural and Mineralogical Approach to investigate the Evolution of Low-and very Low-Grade Metamorphic Units from the intra-Pontide Suture Zone,Central Pontides,Turkey

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Journal of Earth Science 2021年第6期32卷 1512-1527页

作者： Alessandro Ellero Chiara Frassi Mehmet Cemal Göncüoğlu Marco Lezzerini Michele Marroni Giuseppe ottria Luca Pandolfi Kaan Sayit Marco Tamponi istituto di Geoscienze e Georisorse-CNR Via G.Moruzzi 156124PisaItaly Dipartimento di Scienze della Terra Universitàdi PisaVia S.Maria 5356126PisaItaly Department of Geological Engineering Middle East Technical University06800AnkaraTurkey

A multidisciplinary approach combining multiscale geological-structural analyses(from field to microscale) and clay mineral transformations(clay mineralogy, illite and chlorite "crystallinity" and b cell dimension(b_(0)) of K-white mica) was adopted to unravel the tectono-metamorphic evolution of low-and very low-grade tectono-metamorphic units from the intra-Pontide suture zone in northern Turkey. The mineralogical study allowed to better evaluate the structural stacking outlined during the geological mapping, leading to distinguish three tectono-metamorphic units, two in epizone(Daday and Emirkoy units) and one in anchizone(Cifter Unit) metamorphic conditions. The mesostructural and microstructural analyses suggest a polyphase tectonic-metamorphic evolution. The different macroscopic features observed between the two units characterized by the same epizone metamorphism, can be justified by the evidence that these metamorphic conditions were acquired during the last stages of exhumation in the Daday Unit, while they constrained the metamorphic-peak conditions in the Emirkoy Unit. Contemporary analyses and comparison between structural and mineralogical data have thus proven to be a powerful tool to investigate the low-grade and very low-grade metamorphic environments, allowing at the same time to solve the apparent contradictions deriving from the mineralogical study and to significantly improve the detail of the geological mapping in the field.

关键词： clay minerals structural analyses low-temperature metamorphism epizone anchizone diagenesis intra-Pontide suture zone Turkey

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Functional groups of Sahelian trees in a semiarid agroforestry system of Senegal

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Journal of Plant Ecology 2018年第3期11卷 375-384页

作者： Joseph S.Diémé Mayécor Diouf Cristina Armas Graciela MRusch Francisco i.Pugnaire Estación Experimental de ZonasÁridas Consejo Superior de Investigaciones CientíficasCtra.de Sacramento s/n04120 La CañadaAlmeríaSpain Centre National de Recherches Forestières Institut Sénégalais de Recherches Agricoles(CNRF/ISRA)DakarSenegal Norwegian institute for Nature Research TrondheimNorway

Aims Addressing plant responses to water stress is critical to understand the structure of plant communities in water-limited environments and to forecast their resilience to future changes in *** a semiarid agroforestry system in the Sahelian savannah of Leona(Senegal),we selected nine common tree species and explored their stress-resistance *** species represent a variety of life forms and are of high regional socio-economic *** hypothesized that different species would show different suites of traits to cope with water stress and expected to identify functional groups differing in strategies to withstand water *** Along a dry and a wet season,we monitored four traits reflecting above-and below-ground strategies of resource acquisition such as predawn leaf water potential(ψpd),specific leaf area(SLA),leaf thickness and leaf area index(LAi).We also measured two mor-phological traits:trunk diameter and tree *** andψpd were measured six times during the dry and rainy seasons,and the other traits were measured *** Findings We identified two functional classes subdivided into two func-tional groups of each *** first class included deciduous and semi-deciduous species that generally had large SLA,low leaf thickness and small-to-intermediate inter-seasonal varia-tions inψ*** second class included evergreen species of two functional groups that differ in SLA,leaf thickness and the mag-nitude of inter-seasonal variations ofψpd throughout the *** four functional groups identified in this study represent plant strategies differing in their response to changing environmental conditions.

关键词： Acacia tortilis Adansonia digitata Balanites aegyptiaca Celtis integrifolia Combretum glutinosum Faidherbia albida functional traits Neocarya macrophyla Sclerocarya birrea Tamarindus indica water stress

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Effects of holistic grazing management on milk production,weight gain,and visitation to grazing areas by livestock and wildlife in Laikipia County,Kenya

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Ecological Processes 2016年第1期5卷 216-227页

作者： Priscilla K.Lalampaa oliver V.Wasonga Daniel i.Rubenstein Jesse T.Njoka Faculty of Agriculture Department of Land Resource Management and Agricultural TechnologyUniversity of NairobiP.O.Box 29053-00625NairobiKenya Princeton University PrincetonNJ 08544-2016USA

Background:Grazing is an important management tool for maintaining healthy ecosystems and improving rangelands ***,its effectiveness for this purpose is dependent on timing and frequency of grazing,as well as the type of *** the effects of grazing management on rangeland ecosystems is critical in ensuring sustainable use of grazing resources and enhanced livestock *** study assessed the effects of holistic grazing on animal productivity and range use pattern in Laikipia County of ***:The results revealed that the average milk yields(106±20.1)of animals in holistic grazing areas(HGA)were significantly(pigher than those in traditional grazing areas(TGA)(101±20.1).Weight gain of animals in HGA was significantly(0.13±0.01)higher as compared to those in TGA(0.07±0.01).The number of livestock grazing was significantly(pigher in HGA(74±10%)than those in TGA(57±10%).in addition,the number of wildlife grazing was significantly(pigher in HGA(74±18%)than in TGA(32±18%).Conclusions:The results indicate that holistic grazing management has the potential to improve animal performance,as well as condition of range areas as evident in the preference shown by frequent visits to HGA by both livestock and wildlife.

关键词： Camera traps Continuous grazing Animal performance Rest periods Wildlife visits

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Mass and chemical changes of immobile elements in Yamaghan occurrence, Zanjan Province, iran

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中国有色金属学会会刊：英文版 2001年第4期11卷 617-622页

作者： i.Vosoughi Niri (institute of Applied Geophysics, Central South University, Changsha 410083, P.R.China) Cent S Univ Inst Appl Geophys Changsha 410083 Peoples R China

Using mass and chemical changes, behavior of some elements have been evaluated in the study area, Yamaghan occurrence. The techniques using immobile elements can precisely identify altered volcanic rock precursors and measure material changes. The rocks of the study area were affected by hydrothermal alteration. Testing of some compatible incompatible and compatible compatible immobile pairs indicates that Al 2o 3 is the most immobile component in the study area. it means that during the three main stages of hydrothermal alteration (phyllic, intermediate argillic and propylitic) aluminum was the most immobile and titanium was slightly immobile. increases in mass mostly result from mineralization, silicification or carbonatization as voids and other open space fillings and may have replaced the part of glassy matrix. Mass addition has diluted the immobile elements at constant rates. Mass loss is commonly due to leaching of Si, Ca and Na 2o during chloritization and sericitization. The mass loss is recognized by increased proportions of inert minerals such as chlorite and sericite. Mineralographic studies in the study area shows the existence of a supergene zone. Calcocite and covellite are considered enriched minerals. Considering this evidence and mass change results, the enrichment of copper in the circulating fluid is suspected with occasional sulfide precipitation.

关键词： mass and chemical changes immobile elements lithogeochemical Yamaghan

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Genistein improves the vaginal epithelium thickness in a rat model of vaginal atrophy through modulation of hormone and heat shock protein 70 levels

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Asian pacific Journal of Reproduction 2020年第4期9卷 192-196页

作者： Pribakti Budinurdjaja i Wayan Arsana Wiyasa ika Kustiyah oktaviyanti Djanggan Sargowo Doctoral Program in Medicine Faculty of MedicineUniversitas BrawijayaMalangEast JavaIndonesia Department of obstetric and Gynecology Faculty of Medicine Universitas Lambung Mangkurat/Ulin General HospitalBanjarmasinSouth KalimantanIndonesia Department of obstetric and Gynecology Faculty of Medicine Universitas Brawijaya/dr.Saiful Anwar General HospitalMalangEast JavaIndonesia Department of Cardiology and Vascular Medicine Faculty of Medicine Universitas Brawijaya/dr.Saiful Anwar General HospitalMalangEast JavaIndonesia

objective: To investigate whether administration of genistein can improve hormonal changes [estradiol and follicle stimulating hormone (FSH)] , heat shock protein 70 (Hsp70) expression, and thickness of vaginal epithelial cells in a rat model of vaginal atrophy. Methods: Twenty-five multiparous female rats were divided into five groups, namely the control group (without ovariectomy), the ovariectomy only group, and the ovariectomy groups 1, 2 and 3 receiving genistein at the doses of 0.045, 0.090 and 0.180 mg/kg body weight/day, respectively. Estradiol, FSH, and Hsp70 expression were analyzed by using the immunoassay technique. Analysis of the thickness of the vaginal epithelium was performed by histology. Results: ovariectomy significantly decreased estradiol levels compared to the control group (Poses of genistein significantly increased levels of estradiol in rats with vaginal atrophy compared to the ovariectomy only group (Povariectomy significantly increased FSH levels compared to the control group (Poses of genistein restored FSH levels comparable to those in the control group (P>0.05). ovariectomy significantly increased parabasal cell Hsp70 expression compared to the control group (Pof all the genistein doses, only the dose at 0.045 mg/kg body weight/day restored the expression of Hsp70 to levels in the control group (P>0.05). Conclusions: Genistein is able to increase the thickness of the vaginal epithelium through hormone modulation and cellular stress suppression. Genistein is beneficial in the form of a herbal or alternative food for improvement of vaginal atrophy due to menopause.

关键词： Vagina Cellular stress Hypoestrogen Pelvic organ prolapse

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