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1.
Brain ; 147(9): 3048-3058, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-38426222

RESUMO

Frontotemporal dementia (FTD) is a disease of high heterogeneity, apathy and disinhibition present in all subtypes of FTD and imposes a significant burden on families/society. Traditional neuroimaging analysis has limitations in elucidating the network localization due to individual clinical and neuroanatomical variability. The study aims to identify the atrophy network map associated with different FTD clinical subtypes and determine the specific localization of the network for apathy and disinhibition. Eighty FTD patients [45 behavioural variant FTD (bvFTD) and 35 semantic variant progressive primary aphasia (svPPA)] and 58 healthy controls at Xuanwu Hospital were enrolled as Dataset 1; 112 FTD patients including 50 bvFTD, 32 svPPA and 30 non-fluent variant PPA (nfvPPA) cases, and 110 healthy controls from the Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) dataset were included as Dataset 2. Initially, single-subject atrophy maps were defined by comparing cortical thickness in each FTD patient versus healthy controls. Next, the network of brain regions functionally connected to each FTD patient's location of atrophy was determined using seed-based functional connectivity in a large (n = 1000) normative connectome. Finally, we used atrophy network mapping to define clinical subtype-specific network (45 bvFTD, 35 svPPA and 58 healthy controls in Dataset 1; 50 bvFTD, 32 svPPA, 30 nfvPPA and 110 healthy controls in Dataset 2) and symptom-specific networks [combined Datasets 1 and 2, apathy without depression versus non-apathy without depression (80:26), disinhibition versus non-disinhibition (88:68)]. We compare the result with matched symptom networks derived from patients with focal brain lesions or conjunction analysis. Through the analysis of two datasets, we identified heterogeneity in atrophy patterns among FTD patients. However, these atrophy patterns are connected to a common brain network. The primary regions affected by atrophy in FTD included the frontal and temporal lobes, particularly the anterior temporal lobe. bvFTD connects to frontal and temporal cortical areas, svPPA mainly impacts the anterior temporal region and nfvPPA targets the inferior frontal gyrus and precentral cortex regions. The apathy-specific network was localized in the orbital frontal cortex and ventral striatum, while the disinhibition-specific network was localized in the bilateral orbital frontal gyrus and right temporal lobe. Apathy and disinhibition atrophy networks resemble known motivational and criminal lesion networks, respectively. A significant correlation was found between the apathy/disinhibition scores and functional connectivity between atrophy maps and the peak of the networks. This study localizes the common network of clinical subtypes and main symptoms in FTD, guiding future FTD neuromodulation interventions.


Assuntos
Atrofia , Demência Frontotemporal , Imageamento por Ressonância Magnética , Humanos , Demência Frontotemporal/patologia , Demência Frontotemporal/diagnóstico por imagem , Demência Frontotemporal/fisiopatologia , Demência Frontotemporal/psicologia , Atrofia/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Imageamento por Ressonância Magnética/métodos , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/patologia , Rede Nervosa/fisiopatologia , Apatia/fisiologia , Encéfalo/patologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Conectoma
2.
Genomics ; 116(5): 110933, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39218165

RESUMO

Yaks are crucial genetic resources in the Tibetan Plateau and surrounding regions. Throughout the long process of domestication, natural and artificial selection pressures have enabled yaks to demonstrate adaptive characteristics to the environment in terms of physiological structure and genetic molecules, but no systematic cell analysis has been carried out on this phenomenon of yaks. Here, the population structure and genetic diversity of yak were studied by WGRS, and the genes related to yak adaptability were excavated. Combined with scRNA-seq method, the transcription map of yak lung tissue and skin tissue was constructed, which provided a new comprehensive insight into yak adaptability. The analysis of yak population structure showed that there was obvious genetic differentiation between TZ _ yak and other seven yak populations, while there was significant genetic exchange between PL _ yak and SB _ yak at high altitude. WGRS and scRNA-seq analysis revealed that the gene HIF1A related to high altitude adaptation was expressed in various cell types, while EPAS1 was predominantly expressed in epithelial and endothelial cells of yak lung tissue. Endothelial cells play a critical role in hypoxia-adapted VEGF signaling, which correlates closely with the high expression of KDR and VEGFA genes in endothelial cells and monocytes. Furthermore, in the selection signal of High _ yak vs Low _ yak, 19.8 % of the genes overlapped with the genes screened by skin scRNA-seq, including genes related to coat color such as RORA, BNC2, and KIT. Notably, BNC2 is a gene associated with melanin deposition and shows high expression levels in HS cells. Additionally, GRN in melanocytes and SORT1 in IRS play an important role in cell communication between melanocytes and IRS. These findings offer new insights into the natural polymorphism of yaks and provide a valuable reference for future research on high-altitude mammals, and potentially even human genetics.


Assuntos
Adaptação Fisiológica , Animais , Bovinos/genética , Adaptação Fisiológica/genética , Altitude , Seleção Genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos
3.
Genomics ; 116(4): 110872, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849017

RESUMO

Cattle-yak is a hybrid offspring resulting from the crossbreeding of yak and cattle, and it exhibits substantial heterosis in production performance. However, male sterility in cattle-yak remains a concern. Reports suggest that noncoding RNAs are involved in the regulation of spermatogenesis. Therefore, in this study, we comprehensively compared testicular transcription profiles among cattle, yak, and cattle-yak. Numerous differentially expressed genes (DEGs), differentially expressed circRNAs (DECs), and differentially expressed miRNAs (DEMs) were identified in the intersection of two comparison groups, namely cattle versus cattle-yak and yak versus cattle-yak, with the number of DEGs, DECs, and DEMs being 4968, 360, and 59, respectively. The DEGs in cattle-yaks, cattle, and yaks were mainly associated with spermatogenesis, male gamete generation, and sexual reproduction. Concurrently, GO and KEGG analyses indicated that DEC host genes and DEM source genes were involved in the regulation of spermatogenesis. The construction of a potential competing endogenous RNA network revealed that some differentially expressed noncoding RNAs may be involved in regulating the expression of genes related to testicular spermatogenesis, including miR-423-5p, miR-449b, miR-34b/c, and miR-15b, as well as previously unreported miR-6123 and miR-1306, along with various miRNA-circRNA interaction pairs. This study serves as a valuable reference for further investigations into the mechanisms underlying male sterility in cattle-yaks.


Assuntos
Redes Reguladoras de Genes , MicroRNAs , RNA Circular , RNA Mensageiro , Testículo , Bovinos/genética , Bovinos/metabolismo , Animais , Masculino , Testículo/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espermatogênese/genética , Transcriptoma , RNA Endógeno Competitivo
4.
BMC Genomics ; 25(1): 498, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773419

RESUMO

BACKGROUND: The hair follicle development process is regulated by sophisticated genes and signaling networks, and the hair grows from the hair follicle. The Tianzhu white yak population exhibits differences in hair length, especially on the forehead and shoulder region. However, the genetic mechanism is still unclear. Isoform sequencing (Iso-seq) technology with advantages in long reads sequencing. Hence, we combined the Iso-seq and RNA-seq methods to investigate the transcript complexity and difference between long-haired yak (LHY) and normal-haired yak (NHY). RESULTS: The hair length measurement result showed a significant difference between LHY and NHY on the forehead and the shoulder (P-value < 0.001). The skin samples from the forehead and the shoulder of LHY and NHY were pooled for isoform sequencing (Iso-seq). We obtained numerous long transcripts, including novel isoforms, long non-coding RNA, alternative splicing events, and alternative polyadenylation events. Combined with RNA-seq data, we performed differential isoforms (DEIs) analysis between LHY and NHY. We found that some hair follicle and skin development-related DEIs, like BMP4, KRT2, IGF2R, and COL1A2 in the forehead skin; BMP1, KRT1, FGF5, COL2A1, and IGFBP5 in the shoulder skin. Enrichment analysis revealed that DEIs in both two comparable groups significantly participated in skin and hair follicle development-related pathways, like ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathways. The results indicated that the hair follicle development of Tianzhu white yak may influence the hair length difference. Besides, the protein-protein interaction (PPI) network of DEIs showed COL2A1 and COL3A1 exhibited a high degree of centrality, and these two genes were suggested as potential candidates for the hair length growth of Tianzhu white yak. CONCLUSIONS: The results provided a comprehensive analysis of the transcriptome complexity and identified differential transcripts that enhance our understanding of the molecular mechanisms underlying the variation in hair length growth in Tianzhu white yak.


Assuntos
Cabelo , Isoformas de Proteínas , RNA-Seq , Pele , Transcriptoma , Animais , Bovinos/genética , Pele/metabolismo , Cabelo/metabolismo , Cabelo/crescimento & desenvolvimento , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Folículo Piloso/metabolismo , Folículo Piloso/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Processamento Alternativo , Análise de Sequência de RNA
5.
BMC Genomics ; 25(1): 481, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38750421

RESUMO

BACKGROUND: There is no consensus as to the origin of the domestic yak (Bos grunniens). Previous studies on yak mitochondria mainly focused on mitochondrial displacement loop (D-loop), a region with low phylogenetic resolution. Here, we analyzed the entire mitochondrial genomes of 509 yaks to obtain greater phylogenetic resolution and a comprehensive picture of geographical diversity. RESULTS: A total of 278 haplotypes were defined in 509 yaks from 21 yak breeds. Among them, 28 haplotypes were shared by different varieties, and 250 haplotypes were unique to specific varieties. The overall haplotype diversity and nucleotide diversity of yak were 0.979 ± 0.0039 and 0.00237 ± 0.00076, respectively. Phylogenetic tree and network analysis showed that yak had three highly differentiated genetic branches with high support rate. The differentiation time of clades I and II were about 0.4328 Ma, and the differentiation time of clades (I and II) and III were 0.5654 Ma. Yushu yak is shared by all haplogroups. Most (94.70%) of the genetic variation occurred within populations, and only 5.30% of the genetic variation occurred between populations. The classification showed that yaks and wild yaks were first clustered together, and yaks were clustered with American bison as a whole. Altitude had the highest impact on the distribution of yaks. CONCLUSIONS: Yaks have high genetic diversity and yak populations have experienced population expansion and lack obvious phylogeographic structure. During the glacial period, yaks had at least three or more glacial refugia.


Assuntos
Variação Genética , Genoma Mitocondrial , Haplótipos , Filogenia , Filogeografia , Animais , Bovinos/genética , Herança Materna , Feminino , DNA Mitocondrial/genética
6.
Ann Neurol ; 94(3): 442-456, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37243334

RESUMO

OBJECTIVES: Glymphatic function has not yet been explored in behavioral variant frontotemporal dementia (bvFTD). The spatial correlation between regional glymphatic function and bvFTD remains unknown. METHOD: A total of 74 patients with bvFTD and 67 age- and sex-matched healthy controls (HCs) were selected from discovery dataset and replication dataset. All participants underwent neuropsychological assessment. Glymphatic measures including choroid plexus (CP) volume, diffusion tensor imaging along the perivascular (DTI-ALPS) index, and coupling between blood-oxygen-level-dependent signals and cerebrospinal fluid signals (BOLD-CSF coupling), were compared between the two groups. Regional glymphatic function was evaluated by dividing DTI-ALPS and BOLD-CSF coupling into anterior, middle, and posterior regions. The bvFTD-related metabolic pattern was identified using spatial covariance analysis based on l8 F-FDG-PET. RESULTS: Patients with bvFTD showed higher CP volume (p < 0.001); anterior and middle DTI-ALPS (p < 0.001); and weaker anterior BOLD-CSF coupling (p < 0.05) than HCs after controlling for cortical gray matter volume in both datasets. In bvFTD from the discovery dataset, the anterior DTI-ALPS was negatively associated with the expression of the bvFTD-related metabolic pattern (r = -0.52, p = 0.034) and positively related with regional standardized uptake value ratios of l8 F-FDG-PET in bvFTD-related brain regions (r range: 0.49 to 0.62, p range: 0.017 to 0.047). Anterior and middle glymphatic functions were related to global cognition and disease severity. INTERPRETATION: Our findings reveal abnormal glymphatic function, especially in the anterior and middle regions of brain in bvFTD. Regional glymphatic dysfunction may contribute to the pathogenesis of bvFTD. ANN NEUROL 2023;94:442-456.


Assuntos
Demência Frontotemporal , Humanos , Demência Frontotemporal/patologia , Imagem de Tensor de Difusão/métodos , Fluordesoxiglucose F18 , Encéfalo/patologia , Substância Cinzenta/patologia
7.
Neuroepidemiology ; 58(5): 383-393, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38599180

RESUMO

INTRODUCTION: We aimed to investigate the risk factors associated with poststroke epilepsy (PSE) among patients with different subtypes of stroke, focusing on age-related risk and time-varying effects of stroke subtypes on PSE development. METHODS: A retrospective, nationwide, population-based cohort study was conducted using Korean National Health Insurance Service-National Sample Cohort data. Patients hospitalized with newly diagnosed stroke from 2005 to 2015 were included and followed up for up to 10 years. The primary outcome was the development of PSE, defined as having a diagnostic code and a prescription for anti-seizure medication. Multivariable Cox proportional hazard models were used to estimate PSE hazard ratios (HRs), and time-varying effects were also assessed. RESULTS: A total of 8,305 patients with ischemic stroke, 1,563 with intracerebral hemorrhage (ICH), and 931 with subarachnoid hemorrhage (SAH) were included. During 10 years of follow-up, 4.6% of patients developed PSE. Among patients with ischemic stroke, significant risk factors for PSE were younger age (HR = 1.47), living in rural areas (HR = 1.35), admission through the emergency room (HR = 1.33), and longer duration of hospital stay (HR = 1.45). Time-varying analysis revealed elevated HRs for ICH and SAH, particularly in the first 2 years following the stroke. The age-specific HRs also showed an increased risk for those under the age of 65, with a noticeable decrease in risk beyond that age. CONCLUSION: The risk of developing PSE varies according to stroke subtype, age, and other demographic factors. These findings underscore the importance of tailored poststroke monitoring and management strategies to mitigate the risk of PSE.


Assuntos
Epilepsia , Acidente Vascular Cerebral , Humanos , Masculino , Feminino , República da Coreia/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Idoso , Epilepsia/epidemiologia , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/complicações , Adulto , AVC Isquêmico/epidemiologia , AVC Isquêmico/complicações , Idoso de 80 Anos ou mais , Estudos de Coortes , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/complicações , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/complicações
8.
Cephalalgia ; 44(8): 3331024241252666, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39133176

RESUMO

BACKGROUND: In an effort to improve migraine management around the world, the International Headache Society (IHS) has here developed a list of practical recommendations for the acute pharmacological treatment of migraine. The recommendations are categorized into optimal and essential, in order to provide treatment options for all possible settings, including those with limited access to migraine medications. METHODS: An IHS steering committee developed a list of clinical questions based on practical issues in the management of migraine. A selected group of international senior and junior headache experts developed the recommendations, following expert consensus and the review of available national and international headache guidelines and guidance documents. Following the initial search, a bibliography of twenty-one national and international guidelines was created and reviewed by the working group. RESULTS: A total of seventeen questions addressing different aspects of acute migraine treatment have been outlined. For each of them we provide an optimal recommendation, to be used whenever possible, and an essential recommendation to be used when the optimal level cannot be attained. CONCLUSION: Adoption of these international recommendations will improve the quality of acute migraine treatment around the world, even where pharmacological options remain limited.


Assuntos
Transtornos de Enxaqueca , Transtornos de Enxaqueca/tratamento farmacológico , Humanos , Analgésicos/uso terapêutico , Sociedades Médicas/normas
9.
Headache ; 64(2): 149-155, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38284247

RESUMO

OBJECTIVE: To evaluate the efficacy of prednisolone in the treatment of medication-overuse headache (MOH) using data from a multicenter prospective registry (Registry for Load and Management of Medication Overuse Headache [RELEASE]). BACKGROUND: The treatment of MOH is challenging, especially when withdrawal headache manifests during the cessation of overused medication. Although systemic corticosteroids have been empirically used to reduce withdrawal headaches, their efficacy on the long-term outcomes of MOH has not been documented. METHODS: This was a post hoc analysis of the RELEASE study. The RELEASE is an ongoing multicenter observational cohort study in which patients with MOH have been recruited from seven hospitals in Korea since April 2020. Clinical characteristics, disease profiles, treatments, and outcomes were assessed at baseline and specific time points. We analyzed the effect of prednisolone on MOH reversal at 3 months. RESULTS: Among the 309 patients enrolled during the study period, prednisolone was prescribed to 59/309 (19.1%) patients at a dose ranging from 10 to 40 mg/day for 5-14 days; 228/309 patients (73.8%) completed the 3-month follow-up period. The MOH reversal rates at 3 months after baseline were 76% (31/41) in the prednisolone group and 57.8% (108/187) in the non-prednisolone group (p = 0.034). The effect of steroids remained significant (adjusted odds ratio 2.78, 95% confidence interval 1.27-6.1, p = 0.010) after adjusting for the number of monthly headache days at baseline, mode of discontinuation of overused medication, use of early preventive medications, and the number of preventive medications combined. CONCLUSIONS: Although our observational study could not draw a definitive conclusion, prednisolone may be effective in the treatment of MOH.


Assuntos
Transtornos da Cefaleia Secundários , Prednisolona , Humanos , Prednisolona/efeitos adversos , Transtornos da Cefaleia Secundários/terapia , Sistema de Registros , Cefaleia/induzido quimicamente , Analgésicos/uso terapêutico
10.
Environ Sci Technol ; 58(14): 6274-6283, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38531380

RESUMO

Microbial aerobic cometabolism is a possible treatment approach for large, dilute trichloroethene (TCE) plumes at groundwater contaminated sites. Rapid microbial growth and bioclogging pose a persistent problem in bioremediation schemes. Bioclogging reduces soil porosity and permeability, which negatively affects substrate distribution and contaminant treatment efficacy while also increasing the operation and maintenance costs of bioremediation. In this study, we evaluated the ability of acetylene, an oxygenase enzyme-specific inhibitor, to decrease biomass production while maintaining aerobic TCE cometabolism capacity upon removal of acetylene. We first exposed propane-metabolizing cultures (pure and mixed) to 5% acetylene (v v-1) for 1, 2, 4, and 8 d and we then verified TCE aerobic cometabolic activity. Exposure to acetylene overall decreased biomass production and TCE degradation rates while retaining the TCE degradation capacity. In the mixed culture, exposure to acetylene for 1-8 d showed minimal effects on the composition and relative abundance of TCE cometabolizing bacterial taxa. TCE aerobic cometabolism and incubation conditions exerted more notable effects on microbial ecology than did acetylene. Acetylene appears to be a viable approach to control biomass production that may lessen the likelihood of bioclogging during TCE cometabolism. The findings from this study may lead to advancements in aerobic cometabolism remediation technologies for dilute plumes.


Assuntos
Água Subterrânea , Tricloroetileno , Tricloroetileno/metabolismo , Acetileno/metabolismo , Biodegradação Ambiental , Bactérias/metabolismo , Biomassa
11.
Artigo em Inglês | MEDLINE | ID: mdl-39488640

RESUMO

Recent empirical findings suggest that negative symptoms are not limited to schizophrenia (SCZ) but also present in major depressive disorder (MDD) and bipolar disorder (BD) patients. Although SCZ patients generally showed a latent structure comprising the motivation and pleasure (MAP) and expression (EXP) factors, it remains unclear whether the same latent structure exists in MDD and BD patients. We administered the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS) to 179 MDD patients and 152 BD patients. Confirmatory Factor Analysis (CFA) was conducted to examine the one-factor model, the two-factor model of the MAP and the EXP domain, the five-factor model of anhedonia, avolition, asociality, alogia, and blunted affect, and the hierarchical model comprising the first-order five-factor, and the second-order two-factor (MAP and EXP factors). We further examined the correlations between demographics and the negative symptom dimensions found in the best factor model. The CFA showed that, when the CAINS and the BNSS were combined together, the two-factor model of MAP and EXP provided the best model fit than other competing models, in the MDD alone sample, BD alone sample, and the combined clinical sample. The two-factor model of the MAP and EXP appears to be a stable, transdiagnostic latent structure of negative symptoms across BD and MDD. Clarifying negative symptoms in MDD and BD can facilitate future research on the underlying neural mechanisms of the MAP and EXP dimensions.

12.
BMC Vet Res ; 20(1): 67, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38395831

RESUMO

BACKGROUND: Yaks (Bos grunniens), prized for their ability to thrive in high-altitude environments, are indispensable livestock in the plateau region. Modifying their feeding systems holds significant promise for improving their growth and meat quality. Tenderness, a key determinant of yak meat quality and consumer appeal, is demonstrably influenced by dietary regimen. Indoor feeding regimes have been shown to enhance tenderness by lowering shear stress and optimizing pH values. CircRNAs, well-known modulators of circulatory function, also play a crucial role in skeletal muscle development across various animal species. However, their functional significance in yak skeletal muscle remains largely unexplored. RESULTS: In this study, we identified a total of 5,534 circRNAs within the longissimus dorsi muscle, and we found 51 differentially expressed circRNAs (20 up-regulated and 31 down-regulated) between the two feeding groups. Constructing a comprehensive ceRNA network illuminated intricate regulatory mechanisms, with PGP and circRNA_0617 converging on bta-miR-2285q, mirrored by KLF15/circRNA_0345/bta-miR-20b and CTSF/circRNA_0348/bta-miR-146a. These findings shed light on the potential of circRNAs to influence yak muscle development and meat quality, offering valuable insights for future research. CONCLUSIONS: This investigation unraveled a complex interaction network between circRNAs、mRNAs and miRNAs in yak skeletal muscle. We further elucidated the target genes regulated by these target genes within the network, offering valuable insights into the potential regulatory mechanisms governing muscle development and meat quality-related traits in yaks.


Assuntos
MicroRNAs , RNA Circular , Bovinos/genética , Animais , RNA Circular/genética , RNA Endógeno Competitivo , MicroRNAs/genética , RNA Mensageiro/genética , Carne/análise
13.
J Nanobiotechnology ; 22(1): 291, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802919

RESUMO

BACKGROUND: Stroke is a devastating disease affecting populations worldwide and is the primary cause of long-term disability. The inflammatory storm plays a crucial role in the progression of stroke. In the acute phase of ischemic stroke, there is a transient increase in anti-inflammatory M2 microglia followed by a rapid decline. Due to the abundant phospholipid in brain tissue, lipid peroxidation is a notable characteristic of ischemia/reperfusion (I/R), constituting a structural foundation for ferroptosis in M2 microglia. Slowing down the decrease in M2 microglia numbers and controlling the inflammatory microenvironment holds significant potential for enhancing stroke recovery. RESULTS: We found that the ferroptosis inhibitor can modulate inflammatory response in MCAO mice, characterizing that the level of M2 microglia-related cytokines was increased. We then confirmed that different subtypes of microglia exhibit distinct sensitivities to I/R-induced ferroptosis. Adipose-derived stem cells derived exosome (ADSC-Exo) effectively decreased the susceptibility of M2 microglia to ferroptosis via Fxr2/Atf3/Slc7a11, suppressing the inflammatory microenvironment and promoting neuronal survival. Furthermore, through plasmid engineering, a more efficient M2 microglia-targeted exosome, termed M2pep-ADSC-Exo, was developed. In vivo and in vitro experiments demonstrated that M2pep-ADSC-Exo exhibits significant targeting specificity for M2 microglia, further inhibiting M2 microglia ferroptosis and improving neurological function in ischemic stroke mice. CONCLUSION: Collectively, we illustrated a novel potential therapeutic mechanism that Fxr2 in ADSC-Exo could alleviate the M2 microglia ferroptosis via regulating Atf3/Slc7all expression, hence inhibiting the inflammatory microenvironment, improving neurofunction recovery in cerebral I/R injury. We obtained a novel exosome, M2pep-ADSC-Exo, through engineered modification, which exhibits improved targeting capabilities toward M2 microglia. This provides a new avenue for the treatment of stroke.


Assuntos
Exossomos , Ferroptose , AVC Isquêmico , Camundongos Endogâmicos C57BL , Microglia , Animais , Exossomos/metabolismo , Microglia/metabolismo , Camundongos , AVC Isquêmico/metabolismo , AVC Isquêmico/terapia , Ferroptose/efeitos dos fármacos , Masculino , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Modelos Animais de Doenças , Citocinas/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/terapia
14.
Neurol Sci ; 45(2): 557-564, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37668827

RESUMO

BACKGROUND: The mild behavioral impairment checklist (MBI-C) designed to capture neuropsychiatric symptoms in the whole spectrum of elder with or without dementia, have been verified in mild behavioral impairment, mild cognitive impairment and Alzheimer's Disease, but never used in the behavioral variant of frontotemporal dementia (bvFTD). METHODS: Fifty-two patients with bvFTD (mild, n = 30; moderate-severe, n = 22) and 82 community-dwelling elderly individuals (HCs) were enrolled. All subjects were assessed with a full neuropsychological scale including the MBI-C, Neuropsychiatric Inventory Questionnaire (NPI-Q), and Frontal Behavioral Inventory (FBI). Receiver operating characteristic curves were drawn to analyze the sensitivity and specificity of the MBI-C, NPI-Q, and FBI, and cutoff points were determined using the Youden index. RESULTS: The MBI-C and domain scores in all patients with bvFTD were significantly higher than those in HCs. The most common symptoms of bvFTD were apathy (82.7%) and impulse dyscontrol (80.8%). The MBI-C score was positively correlated with the NPI-Q, FBI, and Activities of Daily Living. For differentiating patients with both bvFTD and mild bvFTD from HCs, the optimal MBI-C cutoff point was 5.5 with a sensitivity of 100% and specificity of 82%, and its sensitivity was higher than that of the NPI-Q and FBI. CONCLUSION: The MBI-C is a sensitive tool for screening behavioral and psychological symptoms in patients with bvFTD, even in the early stages of the disease.


Assuntos
Disfunção Cognitiva , Demência Frontotemporal , Humanos , Idoso , Demência Frontotemporal/diagnóstico , Lista de Checagem , Atividades Cotidianas , Testes Neuropsicológicos , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , China
15.
Curr Pain Headache Rep ; 28(8): 753-767, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38761296

RESUMO

PURPOSE OF REVIEW: This review aimed to investigate emerging evidence regarding the effectiveness of exercise for migraines, focusing on the results of recent trials. Additionally, it explored the possibility of exercise as a treatment for migraines. RECENT FINDINGS: Between 2020 and 2023, five, four, one, and two trials were conducted regarding the effect of aerobic exercise, anaerobic exercise, Tai Chi, and yoga, respectively, on migraine; all studies showed significant effects. Two trials on aerobic exercise showed that high-intensity exercise was similar to or slightly more effective than moderate-intensity exercise as a treatment for migraines. Three trials on anaerobic exercise reported its effectiveness in preventing migraines. Regarding efficacy, side effects, and health benefits, aerobic exercises and yoga are potentially beneficial strategies for the prevention of migraines. Further studies are needed to develop evidence-based exercise programs for the treatment of migraines.


Assuntos
Terapia por Exercício , Transtornos de Enxaqueca , Transtornos de Enxaqueca/terapia , Transtornos de Enxaqueca/prevenção & controle , Humanos , Terapia por Exercício/métodos , Ensaios Clínicos como Assunto , Yoga , Exercício Físico/fisiologia
16.
Anim Biotechnol ; 35(1): 2344213, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38669244

RESUMO

Lysozyme like 4 (LYZL4), lysozyme like 6 (LYZL6) and proliferating cell nuclear antigen (PCNA) are implicated in the regulation of testicular function, but there was no research reported available on the expression patterns of LYZL4, LYZL6 and PCNA genes at different developmental stages of yak testes. In this study, we used the qRT-PCR, western blotting and immunohistochemistry estimated the LYZL4, LYZL6 and PCNA gene expression and protein lo-calization at different developmental stages of yak testes. The qPCR results showed that the mRNA expression of LYZL4, LYZL6 and PCNA genes significantly increased with age in the testes of yaks. Western blot results showed that the protein abundance of LYZL4, LYZL6 and PCNA in yak testes was significantly higher after puberty than before puberty. Furthermore, the results of immunohistochemistry indicated that LYZL4, LYZL6 and PCNA may be involved in the regulation of spermatogonia proliferation and Leydig cell function in immature testis. In adult yak testes, LYZL4, LYZL6 and PCNA may involve in the development of round spermatids and primary spermatocytes during testicular development. Our results indicated that LYZL4, LYZL6 and PCNA may be involved in the development of Sertoli cells, Leydig cells and gonocytes in yak testes.


Assuntos
Antígeno Nuclear de Célula em Proliferação , Testículo , Animais , Masculino , Testículo/crescimento & desenvolvimento , Testículo/metabolismo , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Bovinos/genética , Bovinos/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Envelhecimento , Células Intersticiais do Testículo/metabolismo
17.
Anim Biotechnol ; 35(1): 2294785, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38193799

RESUMO

Yak is an important dominant livestock species at high altitude, and the growth performance of yak has obvious differences under different feeding methods. This experiment was conducted to compare the effects of different feeding practices on growth performance and meat quality of yaks through combined transcriptomic and metabolomic analyses. In terms of yak growth performance, compared with traditional grazing, in-house feeding can significantly improve the average daily weight gain, carcass weight and net meat weight of yaks; in terms of yak meat quality, in-house feeding can effectively improve the quality of yak meat. A combined transcriptomic and metabolomic analysis revealed 31 co-enriched pathways, among which arginine metabolism, proline metabolism and glycerophospholipid metabolism may be involved in the development of the longissimus dorsi muscle of yak and the regulation of meat quality-related traits. The experimental results increased our understanding of yak meat quality and provided data materials for subsequent deep excavation of the mechanism of yak meat quality.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Bovinos/genética , Animais , Perfilação da Expressão Gênica/veterinária , Músculo Esquelético/metabolismo , Carne/análise
18.
Ecotoxicol Environ Saf ; 283: 116798, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39083874

RESUMO

Propylparaben (PrPB) is a known endocrine disrupting chemicals that is widely applied as preservative in pharmaceuticals, food and cosmetics. PrPB has been detected in human urine samples and human serum and has been proven to cause functional decline in reproduction. However, the direct effects of PrPB on mammalian oocyte are still unknown. Here, we demonstrationed that exposure to PrPB disturbed mouse oocyte maturation in vitro, causing meiotic resumption arrest and first polar body extrusion failure. Our results indicated that 600 µM PrPB reduced the rate of oocyte germinal vesicle breakdown (GVBD). Further research revealed that PrPB caused mitochondrial dysfunction and oxidative stress, which led to oocyte DNA damage. This damage further disturbed the activity of the maturation promoting factor (MPF) complex Cyclin B1/ Cyclin-dependent kinase 1 (CDK1) and induced G2/M arrest. Subsequent experiments revealed that PrPB exposure can lead to spindle morphology disorder and chromosome misalignment due to unstable microtubules. In addition, PrPB adversely affected the attachment between microtubules and kinetochore, resulting in persistent activation of BUB3 amd BubR1, which are two spindle-assembly checkpoint (SAC) protein. Taken together, our studies indicated that PrPB damaged mouse oocyte maturation via disrupting MPF related G2/M transition and SAC depended metaphase-anaphase transition.


Assuntos
Ciclo Celular , Exposição Ambiental , Oócitos , Parabenos , Parabenos/toxicidade , Ciclo Celular/efeitos dos fármacos , Oócitos/efeitos dos fármacos , Oócitos/crescimento & desenvolvimento , Feminino , Animais , Camundongos , Disruptores Endócrinos/toxicidade , Camundongos Endogâmicos ICR , Corpos Polares/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fuso Acromático/efeitos dos fármacos , Cromossomos/efeitos dos fármacos , Microtúbulos/efeitos dos fármacos
19.
J Korean Med Sci ; 39(31): e222, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39137809

RESUMO

BACKGROUND: Migraine presents a significant global health problem that emphasizes the need for efficient acute treatment options. Triptans, introduced in the early 1990s, have substantially advanced migraine management owing to their effectiveness compared to that of traditional medications. However, data on triptan use in migraine management from Asian countries, where migraines tend to have milder symptoms than those in European and North American countries, are limited. This study aimed to identify the trends in triptan usage in Korea. METHODS: This retrospective cohort study used data from the Korean National Health Insurance Service-National Sample Cohort spanning from 2002 to 2019. Patients with migraine were identified using the International Classification of Diseases 10th revision codes, and triptan prescriptions were evaluated annually in terms of quantity, pills per patient, and associated costs. The distribution of triptan prescriptions across different medical specialties was also examined. Factors contributing to the odds of triptan use were analyzed using multivariable logistic regression. RESULTS: From 2002 to 2019, the total number of triptan tablets, prescriptions, and patients using triptans increased by 24.0, 17.1, and 13.6 times, respectively, with sumatriptan being the most frequently prescribed type of triptan. Additionally, the number of prescriptions and related costs have consistently increased despite stable pricing because of government regulation. By 2019, only approximately one-tenth of all patients with migraines had been prescribed triptans, although there was a notable increase in prescriptions over the study period. These prescription patterns varied according to the physician's specialty. After adjusting for patient-specific factors including age and sex, the odds of prescribing triptans were higher for neurologists than for internal medicine physicians (odds ratio 2.875, P < 0.001), while they were lower for general practitioners (odds ratio 0.220, P < 0.001). CONCLUSION: The findings revealed an increasing trend in triptan use among individuals with migraines in Korea, aligning with global usage patterns. Despite these increases, the overall prescription rate of triptans remains low, indicating potential underutilization and highlighting the need for improved migraine management strategies across all medical fields. Further efforts are necessary to optimize the use of triptans in treating migraines effectively.


Assuntos
Transtornos de Enxaqueca , Triptaminas , Humanos , República da Coreia , Transtornos de Enxaqueca/tratamento farmacológico , Feminino , Triptaminas/uso terapêutico , Masculino , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Idoso , Adulto Jovem , Padrões de Prática Médica/tendências , Modelos Logísticos , Bases de Dados Factuais , Prescrições de Medicamentos/estatística & dados numéricos , Sumatriptana/uso terapêutico , Estudos de Coortes , Razão de Chances , Adolescente
20.
J Korean Med Sci ; 39(38): e257, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39376188

RESUMO

BACKGROUND: Chronotype refers to individual variations in diurnal preferences that manifest as everyday behaviors, including sleep patterns. Traditionally, the Horne & Östberg Morningness-Eveningness Questionnaire (MEQ), which comprises of 19 items, has been the standard for determining chronotype. However, its length makes it cumbersome for widespread application. To address this issue, the reduced MEQ (rMEQ), a concise version containing only five items from the MEQ, was developed for a more practical approach to chronotype assessment. This study aimed to evaluate the validity and reliability of Korean version of rMEQ in a sample from the general Korean population. METHODS: The Korean version of the rMEQ comprises of items 1, 7, 10, 18, and 19 of the original MEQ. The validity of the rMEQ was assessed by correlating its scores with those of the MEQ and Munich Chronotype Questionnaire (MCTQ). Its reliability was determined by calculating internal consistency. RESULTS: A total of 3,030 individuals participated in the study, yielding an average rMEQ score of 14.0 ± 3.4. There was a substantial positive correlation between the rMEQ and MEQ scores (r = 0.859, P < 0.001). Furthermore, the rMEQ scores were significantly negatively correlated with the midpoint of sleep on free days corrected for sleep debt as measured by the MCTQ (r = -0.388, P < 0.001), indicating a robust association with chronotype. The internal consistency of rMEQ, measured using Cronbach's alpha, was 0.609. CONCLUSION: This study finds the Korean version of the rMEQ to be a valid and reliable instrument for assessing chronotype in the general population.


Assuntos
Ritmo Circadiano , Sono , Humanos , Inquéritos e Questionários , Feminino , Masculino , República da Coreia , Adulto , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sono/fisiologia , Adulto Jovem , Idoso
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