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Cognitive disorder and dementia in type 2 diabetes mellitus

World Journal of Diabetes 2022年第4期13卷 319-337页

作者： Genaro G Ortiz Miguel Huerta Héctor A González-Usigli Erandis D Torres-sánchez Daniela LC Delgado-Lara fermín p pacheco-moisés Mario A Mireles-Ramírez Blanca MG Torres-Mendoza Roxana I Moreno-Cih Irma E Velázquez-Brizuela Department of philosophical and Methodological Disciplines University Health Sciences CenterUniversity of GuadalajaraGuadalajara 44340JaliscoMexico Department of neurology Movement Disorders ClinicSub-Specialty Medical UnitNational Western Medical CenterMexican Social Security Institute(IMSS)Guadalajara 44340JaliscoMexico University Biomedical Research Center University of ColimaColima 28040Mexico Department of Medical and Life sciences University Center of‘La Ciénega’University of GuadalajaraOcotlán 47810JaliscoMexico Department of Chemistry University Center of Exact Sciences and EngineeringUniversity of GuadalajaraGuadalajara 44340JaliscoMexico Division of neurosciences Western Biomedical Research CenterMexican Social Security Institute(IMSS)Guadalajara 44340JaliscoMexico Gerontology postgraduate program Public Health DepartmentUniversity Health Sciences CenterUniversity of GuadalajaraGuadalajara 44340JaliscoMexico

Insulin,a key pleiotropic hormone,regulates metabolism through several signaling pathways in target tissues including skeletal muscle,liver,and *** the brain,insulin modulates learning and memory,and impaired insulin signaling is associated with metabolic dysregulation and neurodegenerative *** the receptor level,in aging and Alzheimer’s disease(AD)models,the amount of insulin receptors and their functions are *** and animal model studies suggest that memory improvements are due to changes in insulin ***,diabetes mellitus(DM)and insulin resistance are associated with age-related cognitive decline,increased levels ofβ-amyloid peptide,phosphorylation of tau protein;oxidative stress,pro-inflammatory cytokine production and dyslipidemia. Recent evidence shows that deleting brain insulin receptors leads to mildobesity and insulin resistance without influencing brain size and apoptosis ***, deleting insulin-like growth factor 1 receptor (IGF-1R) affects brain size anddevelopment, and contributes to behavior changes. Insulin is synthesized locally in the brain andis released from the neurons. Here, we reviewed proposed pathophysiological hypotheses toexplain increased risk of dementia in the presence of DM. Regardless of the exact sequence ofevents leading to neurodegeneration, there is strong evidence that mitochondrial dysfunctionplays a key role in AD and DM. A triple transgenic mouse model of AD showed mitochondrialdysfunction, oxidative stress, and loss of synaptic integrity. These alterations are comparable tothose induced in wild-type mice treated with sucrose, which is consistent with the proposal thatmitochondrial alterations are associated with DM and contribute to AD development. Alterationsin insulin/IGF-1 signaling in DM could lead to mitochondrial dysfunction and low antioxidantcapacity of the cell. Thus, insulin/IGF-1 signaling is important for increased neural processing andsystemic metabolism, a

关键词： Alzheimer´s disease Diabetes mellitus Insulin Vascular dementia Cognitive decline

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Impacts of pI3K/protein kinase B pathway activation in reactive astrocytes: from detrimental effects to protective functions

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neural Regeneration Research 2025年第4期20卷 1031-1041页

作者： Ramón pérez-núñez María Fernanda González Ana María Avalos Lisette Leyton Cellular Communication Laboratory Programa de Biología Celular y MolecularCenter for Studies on ExerciseMetabolism and Cancer(CEMC)Instituto de Ciencias Biomédicas(ICBM)Facultad de MedicinaUniversidad de ChileSantiagoChile Advanced Center for Chronic Diseases(ACCDis) Faculty of Chemical and Pharmaceutical Sciences&Faculty of MedicineUniversidad de ChileSantiagoChile Instituto de Ciencias Biomédicas Facultad de Ciencias de la SaludUniversidad Autónoma de ChileSantiagoChile

Astrocytes are the most abundant type of glial cell in the central nervous *** injury and inflammation,astrocytes become reactive and undergo morphological and functional *** on their phenotypic classification as A1 or A2,reactive astrocytes contribute to both neurotoxic and neuroprotective responses,***,this binary classification does not fully capture the diversity of astrocyte responses observed across different diseases and *** analysis has revealed that reactive astrocytes have a complex landscape of gene expression profiles,which emphasizes the heterogeneous nature of their *** actively participate in regulating central nervous system inflammation by interacting with microglia and other cell types,releasing cytokines,and influencing the immune *** phosphoinositide 3-kinase(pI3K)/protein kinase B(AKT)signaling pathway is a central player in astrocyte reactivity and impacts various aspects of astrocyte behavior,as evidenced by in silico,in vitro,and in vivo *** astrocytes,inflammatory cues trigger a cascade of molecular events,where nuclear factor-κB serves as a central mediator of the pro-inflammatory ***,we review the heterogeneity of reactive astrocytes and the molecular mechanisms underlying their *** highlight the involvement of various signaling pathways that regulate astrocyte reactivity,including the pI3K/AKT/mammalian target of rapamycin(mTOR),αvβ3 integrin/pI3K/AKT/connexin 43,and notch/pI3K/AKT *** targeting the inactivation of the pI3K/AKT cellular signaling pathway to control reactive astrocytes and prevent central nervous system damage,evidence suggests that activating this pathway could also yield beneficial *** dual function of the pI3K/AKT pathway underscores its complexity in astrocyte reactivity and brain function *** review emphasizes the importance of employing astrocyte-exclusive models to underst

关键词： inflammation integrins neuroprotective neurotoxic phosphatidylinositol 3-kinase reactive astrocytes signal transduction Thy-1(CD90)

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From single to combinatorial therapies in spinal cord injuries for structural and functional restoration

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neural Regeneration Research 2025年第3期20卷 660-670页

作者： Ernesto Doncel-pérez Gabriel Guízar-sahagún Israel Grijalva-Otero Hospital nacional de parapléjicos de Toledo Servicio de Salud de Castilla La Mancha(SESCAM)ToledoSpain Medical Research Unit for neurological Diseases UMAE Hospital de EspecialidadesCentro Médico Nacional Siglo XXIIMSSCiudad de MéxicoMéxico

spinal cord injury results in paralysis, sensory disturbances, sphincter dysfunction, and multiple systemic secondary conditions, most arising from autonomic dysregulation. All this produces profound negative psychosocial implications for affected people, their families, and their communities;the financial costs can be challenging for their families and health institutions. Treatments aimed at restoring the spinal cord after spinal cord injury, which have been tested in animal models or clinical trials, generally seek to counteract one or more of the secondary mechanisms of injury to limit the extent of the initial damage. Most published works on structural/functional restoration in acute and chronic spinal cord injury stages use a single type of treatment: a drug or trophic factor, transplant of a cell type, and implantation of a biomaterial. Despite the significant benefits reported in animal models, when translating these successful therapeutic strategies to humans, the result in clinical trials has been considered of little relevance because the improvement, when present, is usually insufficient. Until now, most studies designed to promote neuroprotection or regeneration at different stages after spinal cord injury have used single treatments. Considering the occurrence of various secondary mechanisms of injury in the acute and sub-acute phases of spinal cord injury, it is reasonable to speculate that more than one therapeutic agent could be required to promote structural and functional restoration of the damaged spinal cord. Treatments that combine several therapeutic agents, targeting different mechanisms of injury, which, when used as a single therapy, have shown some benefits, allow us to assume that they will have synergistic beneficial effects. Thus, this narrative review article aims to summarize current trends in the use of strategies that combine therapeutic agents administered simultaneously or sequentially, seeking structural and functional restoratio

关键词： neural regeneration neuroprotection spinal cord injury repair spinal cord injury treatments structural restoration of spinal cord injury

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Unlocking hypoglycemia–associated brain microvascular dysfunction:critical insights from proteomic analysis

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neural Regeneration Research 2025年第6期20卷 1707-1708页

作者： siva s.V.p.sakamuri Anil sakamuri Department of Chemistry Auburn University at MontgomeryMontgomeryALUSA Vascular Biology Center and Department of Medicine Medical College of Georgia at Augusta UniversityAugustaGAUSA

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose levels below sta nda rd physiological *** hypoglycemia,classified as level 1 hypoglycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate *** hypoglycemia,denoted by blood glucose levels less than 54 mg/dL,poses a life-threatening risk if left *** with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

关键词： impaired intake critical

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The short form of the sUR1 and its functional implications in the damaged brain

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neural Regeneration Research 2022年第3期17卷 488-496页

作者： Iván Alquisiras-Burgos Javier Franco-pérez moisés Rubio-Osornio penélope Aguilera Laboratorio de patología Vascular Cerebral Instituto Nacional de Neurología y Neurocirugía“Manuel Velasco Suárez”CDMXMexico Laboratorio de Formación Reticular Instituto Nacional de Neurología y Neurocirugía“Manuel Velasco Suárez”CDMXMexico Laboratorio Experimental de Enfermedades neurodegenerativas Instituto Nacional de Neurología y Neurocirugía“Manuel Velasco Suárez”CDMXMexico.

sulfonylurea receptor(sUR) belongs to the adenosine 5′-triphosphate(ATp)-binding cassette(ABC) transporter family;however,sUR is associated with ion channels and acts as a regulatory subunit determining the opening or closing of the ***8 and Abcc9 genes code for the proteins sUR1 and sUR2,*** sUR1 transcript encodes a protein of 1582 amino acids with a mass around 140–177 k Da expressed in the pancreas,brain,heart,and other *** is well known that sUR1 assembles with Kir6.2 and TRpM4 to establish K_(ATp) channels and non-selective cation channels,***8 and 9 are alternatively spliced,and the resulting transcripts encode different isoforms of sUR1 and sUR2,which have been detected by different experimental ***,the use of binding assays to sulfonylureas and Western blotting has allowed the detection of shorter forms of sUR(-65 k Da).Identity of the sUR1 variants has not been clarified,and some authors have suggested that the shorter forms are ***,immunoprecipitation assays have shown that sUR2 short forms are part of a functional channel even coexisting with the typical forms of the receptor in the *** evidence confirms that the structure of the short forms of the sURs is fully functional and does not lose the ability to interact with the *** structural changes in short forms of sUR modify its affinity to ATp,regulation of its expression might represent an advantage in pathologies where ATp concentrations decrease and a therapeutic target to induce ***,the expression of sUR1 variants might be induced by conditions associated to the decrease of energetic substrates in the brain(*** stroke and epilepsy).In this review,we want to contribute to the knowledge of sUR1 complexity by analyzing evidence that shows the existence of short sUR1 variants and its possible implications in brain function.

关键词： brain edema epilepsy parkinson's disease stroke sulfonylurea receptor 1 sUR1 traumatic brain injury TRpM4

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Data-driven drug repositioning using olfactory omics profiles:challenges and perspectives in neurodegeneration

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neural Regeneration Research 2025年第7期20卷 1997-1998页

作者： paz Cartas-Cejudo Adriana Cortés Mercedes Lachén-Montes Elena Anaya-Cubero Joaquín Fernández-Irigoyen Enrique santamaría Clinical neuroproteomics Unit Proteomics PlatformNavarrabiomedHospitalario Universitario de Navarra(HUN)Universidad Pública de Navarra(UPNA)IdiSNANavarra Institute for Health ResearchPamplonaSpain

Data-driven drug repositioning using olfactory omics profiles-challenges and perspectives in neurodegeneration:neurodegenerative diseases are characterized by progressive degeneration and loss of neuronal function in the central nervous *** diseases are often characterized as proteinopathies,which are disorders primarily driven by the aggregation or misfolding of specific amyloid proteins within cells,leading to their dysfunction and eventual *** the gain-of-function hypothesis related to the aggregation of these proteins,recently,an alternative hypothesis regarding the loss-of-function of the soluble monomeric proteins during the process of aggregation into amyloids is gaining *** last event is called proteinopenia and refers to conditions characterized by a deficiency or decrease in the levels of specific soluble proteins in the body(Ezzat et al.,2023).It has been demonstrated that levels of soluble proteins involved in neurodegenerative diseases are decreased.

关键词： diseases drug amyloid

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Brain-derived neurotrophic factor signaling in the neuromuscular junction during developmental axonal competition and synapse elimination

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neural Regeneration Research 2025年第2期20卷 394-401页

作者： Josep Tomàs Víctor Cilleros-Mañé Laia Just-Borràs Marta Balanyà-segura Aleksandra polishchuk Laura nadal Marta Tomàs Carolina silvera-simón Manel M.santafé Maria A.Lanuza Unitat d’Histologia i neurobiologia(UHneurob) Facultat de Medicina i Ciències de la SalutUniversitat Rovira i VirgiliReusSpain

During the development of the nervous system,there is an overproduction of neurons and *** competition between neighboring nerve endings and synapses performing different activity levels leads to their elimination or *** have extensively studied the involvement of the brain-derived neurotrophic factor-Tropomyosin-related kinase B receptor neurotrophic retrograde pathway,at the neuromuscular junction,in the axonal development and synapse elimination process versus the synapse *** purpose of this review is to describe the neurotrophic influence on developmental synapse elimination,in relation to other molecular pathways that we and others have found to regulate this *** particular,we summarize our published results based on transmitter release analysis and axonal counts to show the different involvement of the presynaptic acetylcholine muscarinic autoreceptors,coupled to downstream serine-threonine protein kinases A and C(pKA and pKC)and voltage-gated calcium channels,at different nerve endings in developmental *** dynamic changes that occur simultaneously in several nerve terminals and synapses converge across a postsynaptic site,influence each other,and require careful studies to individualize the mechanisms of specific *** describe an activity-dependent balance(related to the extent of transmitter release)between the presynaptic muscarinic subtypes and the neurotrophin-mediated TrkB/p75nTR pathways that can influence the timing and fate of the competitive interactions between the different axon *** downstream displacement of the pKA/pKC activity ratio to lower values,both in competing nerve terminals and at postsynaptic sites,plays a relevant role in controlling the elimination of supernumerary ***,calcium entry through L-and p/Q-subtypes of voltage-gated calcium channels(both channels are present,together with the n-type channel in developing nerve terminals)contributes to red

关键词： acetylcholine release adenosine receptors axonal competition brain-derived neurotrophic factor calcium channels motor end-plate muscarinic acetylcholine receptors postnatal synapse elimination serine kinases tropomyosin-related kinase receptorB

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Lipschitz Algebras and peripherally-multiplicative Maps

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Acta Mathematica sinica,English series 2008年第8期24卷 1233-1242页

作者： A.JIM■nEZ-VARGAs moisés VILLEGAs-VALLECILLOs Departamento de■lgebray Análisis Matemático Universidad de Almería04071AlmeríaSpain

Let X be a compact metric space and let Lip（X） be the Banach algebra of all scalar- valued Lipschitz functions on X, endowed with a natural norm. For each f ∈ Lip（X）, σπ（f） denotes the peripheral spectrum of f. We state that any map Φ from Lip（X） onto Lip（Y） which preserves multiplicatively the peripheral spectrum： σπ（Φ（f）Φ（g）） = σπ（fg）, A↓f, g ∈ Lip（X） is a weighted composition operator of the form Φ（f） = τ· （f °φ） for all f ∈ Lip（X）, where τ ： Y → {-1, 1} is a Lipschitz function and φ ： Y→ X is a Lipschitz homeomorphism. As a consequence of this result, any multiplicatively spectrum-preserving surjective map between Lip（X）-algebras is of the form above.

关键词： Lipschitz algebra peripherally-multiplicative map spectrum-preserving map peaking function peripheral spectrum

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Toluene Alkylation to selective Formation of p-Xylene over Co-Crystalline ZsM-12/ZsM-5 Catalyst

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Journal of natural Gas Chemistry 2007年第1期16卷 37-41页

作者： p.n.Joshi p.s.niphadkar p.A.Desai R.patil V.V.Bokade Catalysis Division National Chemical LaboratoryPune-411008India

The alkylation of toluene with methanol to selective formation of p-xylene has been systematically studied. ZsM-12 （MTW）/ZsM-5 co-crystalline zeolite in 40：60 proportions have been synthesized by the same molar gel composition, but at different temperatures and periods than that of ZsM-12 and ZsM-5, separately. All the prepared samples are characterized by XRD, sEM, BET, and XRF. The activity of toluene alkylation was investigated with a mixture of toluene and methanol as a feed over the ZsM-12, ZsM-12/ZsM-5 co-crystalline, ZsM-5, and physical mixture of ZsM-12/ZsM-5. From characterization, it is observed that the ZsM-12/ZsM-5 co-crystalline material is different from that of ZsM-12, ZsM-5, and their physical mixture. Further, the ZsM-12/ZsM-5 co-crystalline zeolite produces the highest content of xylene and has better selectivity for p-xylene than ZsM-12, ZsM-5, and their physical mixture.

关键词： ZsM-12 ZsM-5 co-crystalline toluene alkylation p-xylene

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Leveraging ROTI map derived from Indonesian Gnss receiver network for advancing study of Equatorial plasma Bubble in southeast/East Asia

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Earth and planetary physics 2025年第1期9卷 101-116页

作者： prayitno Abadi Ihsan n.Muafiry Teguh n.pratama Angga Y.putra suraina Gatot H.pramono sidik T.Wibowo Febrylian F.Chabibi Umar A.Ahmad Wildan p.Tresna Asnawi Research Center for Climate and Atmosphere Indonesian National Research and Innovation Agency(BRIN)BandungIndonesia school of Electrical Engineering Telkom UniversityBandungIndonesia Directorate of Laboratory Management Facilities and science and Technology park Indonesian National Research and Innovation Agency(BRIN)PontianakIndonesia Geophysics Laboratory Master Program in PhysicsUniversitas Gadjah Mada(UGM)YogyakartaIndonesia Research Center for space Indonesian National Research and Innovation Agency(BRIN)BandungIndonesia Indonesian Geospatial Information Agency(BIG) JakartaIndonesia Research Center for photonics Indonesian National Research and Innovation Agency(BRIN)Tangerang SelatanIndonesia Department of Earth and planetary sciences Hokkaido UniversitySapporoJapan

This paper highlights the crucial role of Indonesia’s Gnss receiver network in advancing Equatorial plasma Bubble(EpB)studies in southeast and East Asia,as ionospheric irregularities within EpB can disrupt Gnss signals and degrade positioning *** by the Indonesian Geospatial Information Agency(BIG),the Indonesia Continuously Operating Reference station(Ina-CORs)network comprises over 300 Gnss receivers spanning equatorial to southern low-latitude ***-CORs is uniquely situated to monitor EpB generation,zonal drift,and dissipation across southeast *** provide a practical tool for EpB research,by sharing two-dimensional rate of Total Electron Content(TEC)change index(ROTI)derived from this *** generate ROTI maps with a 10-minute resolution,and samples from May 2024 are publicly available for further scientific *** preliminary findings from the ROTI maps of Ina-CORs are ***,the Ina-CORs ROTI maps reveal that the irregularities within a broader EpB structure persist longer,increasing the potential for these irregularities to migrate farther ***,we demonstrate that combined ROTI maps from Ina-CORs and Gnss receivers in East Asia and Australia can be used to monitor the development of ionospheric irregularities in southeast and East *** have demonstrated the combined ROTI maps to capture the development of ionospheric irregularities in the southeast/East Asian sector during the G5 Geomagnetic storm on May 11,*** observed simultaneous ionospheric irregularities in Japan and Australia,respectively propagating northwestward and southwestward,before midnight,whereas southeast Asia’s equatorial and low-latitude regions exhibited irregularities *** sharing ROTI maps from Indonesia and integrating them with regional Gnss networks,researchers can conduct comprehensive EpB studies,enhancing the understanding of EpB behavior across southeast and East Asia and contributing significantly to ionosphe

关键词： Equatorial plasma Bubble(EpB) Gnss receivers’network Indonesia Continuously Operating Reference station(Ina-CORs) ionospheric map Rate of TEC change index(ROTI)map

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