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1.
BMC Neurol ; 22(1): 47, 2022 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130874

RESUMO

BACKGROUND: Hereditary spastic paraplegia 49 (HSP49) is an autosomal recessive genetic disease first discovered in 2012; and which the mutation primarily affects Bukharian Jewish patients. CASE PRESENTATION: The present case reports the first instance of HSP49 detected in China. The patient had normal mental development and good athletic ability before 10 years old and presented with instable temperature, mental retardation, spastic ataxia, and paroxysmal convulsions. Genetic diagnosis was based on detection of whole exons and two heterozygous variants in the exon region of the TECPR2 gene: c.1729C > T and c.4189G > A. Mutations at these two sites have not been previously reported. CONCLUSIONS: This case expands the gene mutation spectrum and clinical phenotypic characteristics of autosomal recessive HSP in China; moreover, it indicates differences in the clinical phenotype of HSP49 in different ethnicities. In addition, this reported provides further evidence regarding the effectiveness of targeted next-generation sequencing technology in improving the efficiency and diagnostic rate of genetic diagnosis of HSP.


Assuntos
Atrofia Óptica , Paraplegia Espástica Hereditária , Ataxias Espinocerebelares , Povo Asiático/genética , Proteínas de Transporte , Criança , Humanos , Mutação , Proteínas do Tecido Nervoso , Linhagem , Paraplegia Espástica Hereditária/genética
2.
Int J Mol Sci ; 23(10)2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35628519

RESUMO

Fragrant woodfern (Dryopteris fragrans) is a medicinal plant rich in terpenoids. Ultraviolet-B (UV-B) light could increase concentration of terpenoids. The aim of this study was to analyze how UV-B regulates the terpenoid synthesis of the molecular regulatory mechanism in fragrant woodfern. In this study, compared with the control group, the content of the terpenes was significantly higher in fragrant woodfern leaves under UV-B treatment for 4 days (d). In order to identify how UV-B regulates the terpenoid metabolic mechanism in fragrant woodfern, we examined the mRNAs and small RNAs in fragrant woodfern leaves under UV-B treatment. mRNA and miRNA-seq identified 4533 DEGs and 17 DEMs in the control group compared with fragrant woodfern leaves under UV-B treatment for 4 d. mRNA-miRNA analysis identified miRNA target gene pairs consisting of 8 DEMs and 115 miRNAs. The target genes were subjected to GO and KEGG analyses. The results showed that the target genes were mainly enriched in diterpene biosynthesis, terpenoid backbone biosynthesis, plant hormone signal transduction, MEP pathway and MVA pathway, in which miR156 and miR160 regulate these pathways by targeting DfSPL and DfARF, respectively. The mRNA and miRNA datasets identified a subset of candidate genes. It provides the theoretical basis that UV-B regulates the terpenoid synthesis of the molecular regulatory mechanism in fragrant woodfern.


Assuntos
Dryopteris , MicroRNAs , Perfumes , Dryopteris/genética , Perfilação da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Terpenos/metabolismo
3.
Neurochem Res ; 46(5): 1058-1067, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33761044

RESUMO

Albicanol is a natural terpenoid derived from Dryopteris fragrans. Herein, we assessed the ability of Albicanol to protect against oxidative stress-induced senescence. Using a murine model of D-galactose (D-gal)-induced aging, we determined that Albicanol treatment can reverse D-gal-mediated learning impairments and behavioral changes, while also remediating brain tissue damage in treated mice. We found that serum SOD, CAT, GSH-Px, and T-AOC levels were significantly decreased in aging mice, and that Albicanol treatment significantly increased the serum levels of these antioxidant enzymes. We additionally evaluated the impact of Albicanol treatment on the Keap1/Nrf2/ARE signaling pathway, and found that it was able to decrease Keap1 expression while increasing the expression of Nrf2, thereby activating this signaling pathway, suppressing oxidative damage, and enhancing the expression of downstream target genes including SOD, GSH, GST, HO-1, and NQO1 in this murine aging model system. Albicanol treatment also inhibited the secretion of inflammatory TNF-a and IL-1b. Together, these data indicated that Albicanol can activate Nrf2 pathway-related genes, thereby inhibition of delayed aging by alleviating oxidative stress-induced damage.


Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/uso terapêutico , Galactose/farmacologia , Naftalenos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Sesquiterpenos/uso terapêutico , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/patologia , Expressão Gênica/efeitos dos fármacos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Camundongos , Teste do Labirinto Aquático de Morris/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Aprendizagem Espacial/efeitos dos fármacos , Memória Espacial/efeitos dos fármacos
4.
Neuroepidemiology ; 52(1-2): 25-31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30476921

RESUMO

BACKGROUND/AIMS: The burden of dementia among women in China, especially among women from rural areas, has increased due to their longevity and lower education levels compared with that among men. Thus, we aimed to assess sex differences in the prevalence of cognitive impairment and its relevant determinants among rural residents in North China. METHODS: Adults aged 60 years and older with cognitive impairment no dementia (CIND) were recruited to this study. Demographic characteristics, traditional risk factors, and lifestyle characteristics were obtained and analyzed on the basis of sex. RESULTS: There were 1,295 individuals with CIND (489 [37.8%] men and 806 [62.2%] women). The prevalence of CIND was 23.3% overall (19.8% for men, 26.1% for women; p < 0.001). Age, education level, history of stroke, and social activity were significantly associated with CIND for both men and women. Widowed status compared to married status was an independent risk factor for CIND in men (OR [95% CI] 1.50 [1.14-1.98]; p = 0.004). CONCLUSION: These findings suggest that it is crucial to address the secondary prevention of stroke and to consider the psychological status among the elderly with low educational attainment in order to reduce the burden of CIND in China.


Assuntos
Disfunção Cognitiva/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Disfunção Cognitiva/etiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prevalência , Fatores de Risco , População Rural , Caracteres Sexuais , Fatores Sexuais
5.
Neuroepidemiology ; 49(3-4): 165-173, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29169179

RESUMO

BACKGROUND AND PURPOSE: Subjective cognitive decline (SCD) is a condition associated with increased risk of Alzheimer's disease. This study performs a meta-analysis to estimate the prevalence of the Apolipoprotein E e4 (APOE e4) allele in SCD and the association of APOE e4 with SCD. METHODS: The MEDLINE, EMBASE, and Cochrane Library databases were searched. Meta-analyses were conducted using STATA 12.0 software. When significant heterogeneity was present (I2 >50% and p < 0.05), we conducted stratified and meta-regression analyses to explore possible reasons for heterogeneity. RESULTS: We selected a total of 28 studies that were conducted in Australia, the United States, northern Europe, middle Europe, southern Europe, and Asia. The sample size of the SCD group was 6,044. Thirteen studies included a healthy control group (total control cohort of 3,822), whereas the remaining 15 studies were single-arm studies of SCD groups. The APOE e4 allele was associated with SCD (OR 1.12 [1.00-1.25]; p = 0.04). The pooled estimate for APOE e4 carrier prevalence was 32% (95% CI 28-35). Due to the significant heterogeneity in prevalence estimates, we performed stratified and meta-regression analyses and found that age and northern European residency were significantly associated with heterogeneity. CONCLUSION: The results of this meta-analysis indicate a weak association between APOE e4 and SCD. Age and northern European residency are the critical factors that determine heterogeneity in the APOE e4-associated prevalence of SCD.


Assuntos
Apolipoproteína E4/genética , Disfunção Cognitiva/genética , Alelos , Apolipoproteína E4/sangue , Ásia , Austrália , Disfunção Cognitiva/sangue , Europa (Continente) , Humanos , Estados Unidos
6.
Aging Ment Health ; 21(6): 651-657, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-26882509

RESUMO

BACKGROUND AND AIMS: Caregivers of individuals with neurodegenerative diseases, including frontotemporal dementia (FTD), Lewy body dementia (DLB), and Alzheimer's disease (AD), experience high levels of psychological and physical stress, likely due to behavioral and psychological symptoms of dementia (BPSD). This study is the first to simultaneously evaluate the effects of BPSD on caregiver burden in these three types of dementia. METHOD: A total of 214 dementia patients, including probable FTD (n = 82), DLB (n = 22), and AD (n = 110), as well as their primary caregivers, were assessed using psychological inventories and cognitive evaluation. The FTD group was further divided into the three established clinical variants: behavioral variant frontotemporal dementia (bvFTD, n = 51), non-fluent variant primary progressive aphasia (nfvPPA, n = 15), and semantic variant primary progressive aphasia (svPPA, n = 16). Cognitive impairment and neuropsychiatric symptoms were assessed using the Mini Mental State Examination, Montreal Cognitive Assessment, Clock Drawing Test, and Neuropsychiatric Inventory (NPI), respectively. Caregiver burden was assessed using the Zarit Burden Inventory (ZBI). RESULTS: FTD patients had higher NPI and ZBI scores than DLB and AD patients, whose scores were similar. Logistic regression analysis revealed that the factors influencing caregiver burden for each group were: FTD: total NPI scores, agitation, and aberrant motor behavior; bvFTD: total NPI scores; DLB: total NPI scores; and AD: total NPI scores, onset age, apathy, and ADL. Caregivers of bvFTD patients had the highest levels of burden, which were significantly greater than for caregivers of nfvPPA, svPPA, DLB, and AD patients. CONCLUSION: BPSD was highly correlated with emotional burden in caregivers of FTD, DLB, and AD patients. The highest burden was observed in bvFTD caregivers.


Assuntos
Doença de Alzheimer/psicologia , Cuidadores/psicologia , Demência Frontotemporal/psicologia , Doença por Corpos de Lewy/psicologia , Estresse Psicológico/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/terapia , Disfunção Cognitiva , Feminino , Demência Frontotemporal/terapia , Humanos , Doença por Corpos de Lewy/terapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Índice de Gravidade de Doença , Inquéritos e Questionários
7.
J Headache Pain ; 17(1): 83, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27619363

RESUMO

BACKGROUND: Primary headache disorders are among the most common neurological complaints worldwide, and are significant causes of disability. Data are limited on the prevalence of primary headaches among individuals aged 60 years and older in China. The purpose of our study was to investigate the prevalence and characteristics of primary headaches among people aged 60 years and older in a rural area of northern China. METHODS: A door-to-door survey was conducted in Ji County of Tianjin Province. A total of 5248 residents aged 60 years and older were visited from 2014 to 2015, unannounced, and basic sociodemographic and headache diagnostic information was collected via a questionnaire. Primary headache was classified tension-type headaches, migraines, chronic headache, and unclassified headache. RESULTS: The 1-year prevalence for primary headaches in Ji county is 10.30 %. The 1-year prevalence of tension-type headaches, migraines, chronic headache, and unclassified headache is 2.02 %, 0.85 %, 3.79 %, and 3.63 %. The 1-year prevalence of primary headache was higher in women than in men. The 1-year prevalence of primary headache was decreased with increasing age. The 1-year prevalence of tension-type headaches and chronic headache were decreased with higher education. Headache in the elderly was mild to moderate and not serious. CONCLUSIONS: In a population older than 60 years of age in rural, northern China, we found the 1-year prevalence of primary headache was 10.30 %, of tension-type headaches was 2.02 %, of migraines was 0.85 %, of chronic headache was 3.79 %, and of unclassified headache was 3.63 %. The prevalence of all of these was much lower than those observed in previous studies examining prevalence rates in the general population. The results of our study also indicated that women are more likely to have primary headache than men. We also found that chronic headache was frequent among the elderly. Participants with higher education levels were more predisposed than healthy participants to tension-type headaches. We also found that respondents who did not participate in social activities had a decreased predisposition for primary headache in general, as well as for unclassified headache. Lastly, we found that participants who had heart disease were more likely than healthy participants to experience primary headache, tension-type headache, chronic headache, and unclassified headache.


Assuntos
Transtornos da Cefaleia Primários/epidemiologia , População Rural/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/epidemiologia , Prevalência , Cefaleia do Tipo Tensional/epidemiologia
8.
Stroke ; 46(9): 2419-25, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26199315

RESUMO

BACKGROUND AND PURPOSE: Total homocysteine (tHcy) levels are associated with secondary vascular events and mortality after stroke. The aim of this study was to investigate whether tHcy levels in the acute phase of a stroke contribute to the recurrence of cerebro-cardiovascular events and mortality. METHODS: A total of 3799 patients were recruited after hospital admission for acute ischemic stroke. Levels of tHcy were measured within 24 hours after primary admission. Patients were followed for a median of 48 months. RESULTS: During the follow-up period, 233 (6.1%) patients died. After adjustment for age, smoking status, diabetes mellitus, and other cardiovascular risk factors, patients in the highest tHcy quartile (>18.6 µmol/L) had a 1.61-fold increased risk of death (adjusted hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.03-2.53) compared with patients in the lowest quartile (≤10 µmol/L). Further subgroup analysis showed that this correlation was only significant in the large-artery atherosclerosis stroke subtype (adjusted HR, 1.80; 95% CI, 1.05-3.07); this correlation was not significant in the small-vessel occlusion subtype (adjusted HR, 0.80; 95% CI, 0.30-2.12). The risk of stroke-related mortality was 2.27-fold higher for patients in the third tHcy quartile (adjusted HR, 2.27; 95% CI, 1.06-4.86) and 2.15-fold more likely for patients in the fourth quartile (adjusted HR, 2.15; 95% CI, 1.01-4.63) than for patients in the lowest tHcy quartile. The risk of cardiovascular-related mortality and the risk of recurrent ischemic stroke were not associated with tHcy levels. CONCLUSIONS: Our findings suggest that elevated tHcy levels in the acute phase of an ischemic stroke can predict mortality, especially in stroke patients with the large-vessel atherosclerosis subtype.


Assuntos
Isquemia Encefálica/sangue , Isquemia Encefálica/mortalidade , Homocisteína/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/mortalidade , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva
9.
Commun Biol ; 7(1): 827, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38972908

RESUMO

The "hologenome" concept is an increasingly popular way of thinking about microbiome-host for marine organisms. However, it is challenging to track hologenome dynamics because of the large amount of material, with tracking itself usually resulting in damage or death of the research object. Here we show the simple and efficient holo-2bRAD approach for the tracking of hologenome dynamics in marine invertebrates (i.e., scallop and shrimp) from one holo-2bRAD library. The stable performance of our approach was shown with high genotyping accuracy of 99.91% and a high correlation of r > 0.99 for the species-level profiling of microorganisms. To explore the host-microbe association underlying mass mortality events of bivalve larvae, core microbial species changed with the stages were found, and two potentially associated host SNPs were identified. Overall, our research provides a powerful tool with various advantages (e.g., cost-effective, simple, and applicable for challenging samples) in genetic, ecological, and evolutionary studies.


Assuntos
Organismos Aquáticos , Animais , Organismos Aquáticos/genética , Invertebrados/genética , Invertebrados/fisiologia , Microbiota , Polimorfismo de Nucleotídeo Único
10.
Curr Top Med Chem ; 23(8): 618-626, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36650652

RESUMO

BACKGROUND: The small sample problem widely exists in the fields of the chemical industry, chemistry, biology, medicine, and food industry. It has been a problem in process modeling and system optimization. The aim of this study is to focus on the problems of small sample size in modeling, the process parameters in the ultrasonic extraction of botanical medicinal materials can be obtained by optimizing the extraction rate model. However, difficulty in data acquisition results in problem of small sample size in modeling, which eventually reduces the accuracy of modeling prediction. METHODS: A virtual sample generation method based on full factorial design (FFD) is proposed to solve the problem ofa small sample size. The experiments are first conducted according to the Box- Behnken Design (BBD) to obtain small-size samples, and the response surface function is established accordingly. Then, virtual sample inputs are obtained by the FFD, and the corresponding virtual sample outputs are calculated by the response surface function. Furthermore, a screening method of virtual samples is proposed based on an extreme learning machine (ELM). The connection weights of ELM are used for further optimization and screening of the generated virtual samples. RESULT: The results show that virtual sample data can effectively expand the sample size. The precision of the model trained on semi-synthetic samples (small-size experimental simples and virtual samples) is higher than the model trained merely on small-size experimental samples. CONCLUSION: The virtual sample generation and screening methods proposed in this paper can effectively solve the modeling problem of small samples. The reliable process parameters can be obtained by optimizing the model trained by the semi-synthetic samples.

11.
Chem Biol Interact ; 384: 110710, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37716421

RESUMO

Poloxamer 188 is a widely used pharmaceutical excipient, which can be found in a variety of drug formulations. In this study, a novel self-assembled nanoplatform was developed for active targeting of folate receptor-overexpressing triple-negative breast cancer. This platform, FPP NPs, was prepared by the retrofitted poloxamer 188 derivatives, resulting in nanoparticles with an appropriate size (< 100 nm), good stability, and satisfactory biocompatibility. Cellular uptake and in vivo distribution studies showed that the FPP NPs had strong tumor cell uptake and active targeting capabilities. Furthermore, docetaxel (DTX) was loaded into FPP NPs in this research. The resulting DTX/FPP NPs exhibited high drug encapsulation efficiency and drug loading capacity, and could rapidly release DTX under slightly acidic conditions, significantly increasing the antitumor activity of the encapsulated drug both in vitro and in vivo. In addition, DTX/FPP NPs could significantly decrease the hepatotoxicity and nephrotoxicity of DTX. Therefore, this drug delivery nanoplatform, based on retrofitted poloxamer 188 with self-assembly properties in aqueous solution and active targeting capabilities to tumors, may provide a promising approach for targeted treatment of triple-negative breast cancer.

12.
Front Immunol ; 14: 1258579, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37701436

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often absent or at low levels in the cerebrospinal fluid (CSF) of patients with previous SARS-CoV-2-associated Guillain-Barré syndrome (GBS). This has led to speculation that SARS-CoV-2-associated GBS is more likely mediated by post-infectious immunity or a parainfection. This understanding has influenced the development of treatment regimens for SARS-CoV-2-associated GBS. This paper reports our experience with four Chinese patients with SARS-CoV-2-associated GBS who tested positive for SARS-CoV-2 RNA in the CSF. They developed symptoms of peripheral nerve damage 4-15 days after fever and confirmed SARS-CoV-2 infection, all of whom presented with progressive weakness of both lower limbs; three with autonomic nerve function impairment such as constipation and urination disorder; and one with polycranial neuritis and Miller-Fisher syndrome. Three patients were tested for anti-ganglioside antibodies, and one tested positive for GD1a-IgG. Four patients recovered well after treatment with anti-viral drugs combined with intravenous immunoglobulin. The present results showed that SARS-CoV-2 RNA can be detected via mNGS in the CSF of some patients with SARS-CoV-2-associated GBS, suggesting that SARS-CoV-2-associated GBS may have multiple pathogeneses.


Assuntos
COVID-19 , Síndrome de Guillain-Barré , Humanos , SARS-CoV-2 , Síndrome de Guillain-Barré/diagnóstico , RNA Viral/genética , Estudos Retrospectivos , COVID-19/complicações , COVID-19/diagnóstico , China , Sequenciamento de Nucleotídeos em Larga Escala
13.
Int J Gen Med ; 15: 7449-7457, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36172083

RESUMO

Objective: Stroke is the leading cause of mortality and disability worldwide. However, there is no study on the relationship between red blood cell distribution width and the prognosis of small artery occlusion, which is a stroke subtype. This study aimed to assess the association of red blood cell distribution width at admission with outcomes among patients with small artery occlusion. Methods: In this hospital-based follow-up study, all included patients were diagnosed with small artery occlusion. Outcomes included death, recurrence, and dependency at 3, 12, and 36 months after stroke onset. Multivariate analysis was performed to explore the association of red blood cell distribution width with stroke outcomes. Results: This study included 1576 patients with small artery occlusion who were followed up at 3, 12, and 36 months. For every unit increase in red blood cell distribution width, the risk of stroke recurrence and dependency increased by 5.1% (95% CI 1.002-1.102, P=0.039) at 3 months after stroke onset. At the 12-month follow-up, for every unit increase in red blood cell distribution width, the risk of stroke recurrence increased by 3.4% (95% CI 1.000-1.069, P=0.047). However, the relationship between red blood cell distribution width and mortality rate was not significant at 36 months after stroke onset after adjustment of covariates. Conclusion: Red blood cell distribution width is an important hematological index of small artery occlusion. It may be used to predict the recurrence of acute ischemic stroke in small artery occlusion. Therefore, patients with higher baseline values of red blood cell distribution width may need more risk factor control to reduce recurrence and dependency.

14.
Food Funct ; 12(4): 1757-1768, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33502412

RESUMO

Cadmium (Cd) induces hepatocyte injury by oxidative stress. Albicanol is a sesquiterpenoid extracted from the medicinal plant Dryopteris fragrans that has previously been shown to exhibit anti-aging and antioxidant activity. In this study, we explored the mechanism of albicanol inhibition of the Cd-induced apoptosis of chicken hepatoma cells (LMH) by treating these cells with CdCl2 (25 µM) and/or albicanol (2.5 × 10-5 µg mL-1) for 24 h. Under Cd treatment, the research results showed that the apoptosis rate markedly increased in LMH cells. In addition, the iNOS activity and NO content increased significantly, which promoted the expressions of genes associated with the mitochondrial apoptosis pathway (Bax, CytC, Caspase-3 and Caspase-9) and inhibited the expression of Bcl-2 in this pathway. However, Cd + albicanol co-treatment significantly reduced the apoptosis rate and the expressions of iNOS and genes associated with the mitochondrial apoptosis pathway (Bax, CytC, Caspase-3 and Caspase-9), and promoted the expression of Bcl-2 in this pathway. In addition, molecular docking supported a link between the albicanol ligand and the iNOS receptor. These results indicated that albicanol can inhibit Cd-induced apoptosis by regulating the NO/iNOS-mediated mitochondrial pathway.


Assuntos
Apoptose/efeitos dos fármacos , Cádmio/toxicidade , Hepatócitos , Mitocôndrias , Naftalenos/farmacologia , Sesquiterpenos/farmacologia , Animais , Linhagem Celular Tumoral , Galinhas , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo/efeitos dos fármacos
15.
Biomed Res Int ; 2021: 6692974, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34697589

RESUMO

Alzheimer's disease (AD) and epilepsy are neurological disorders that affect a large cohort of people worldwide. Although both of the two diseases could be influenced by genetic factors, the shared genetic mechanism underlying the pathogenesis of them is still unclear. In this study, we aimed to identify the shared genetic networks and corresponding hub genes for AD and epilepsy. Firstly, the gene coexpression modules (GCMs) were constructed by weighted gene coexpression network analysis (WGCNA), and 16 GCMs were identified. Through further integration of GCMs, genome-wide association studies (GWASs), and expression quantitative trait loci (eQTLs), 4 shared GCMs of AD and epilepsy were identified. Functional enrichment analysis was performed to analyze the shared biological processes of these GCMs and explore the functional overlaps between these two diseases. The results showed that the genes in shared GCMs were significantly enriched in nervous system-related pathways, such as Alzheimer's disease and neuroactive ligand-receptor interaction pathways. Furthermore, the hub genes of AD- and epilepsy-associated GCMs were captured by weighted key driver analysis (wKDA), including TRPC1, C2ORF40, NR3C1, KIAA0368, MMT00043109, STEAP1, MSX1, KL, and CLIC6. The shared GCMs and hub genes might provide novel therapeutic targets for AD and epilepsy.


Assuntos
Doença de Alzheimer/genética , Epilepsia/genética , Doença de Alzheimer/patologia , Biologia Computacional/métodos , Bases de Dados Genéticas , Epilepsia/enfermagem , Epilepsia/patologia , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Mapas de Interação de Proteínas , Locos de Características Quantitativas
16.
Sci Total Environ ; 771: 145407, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33548704

RESUMO

Hydrogen sulfide (H2S) is an environmental contaminant to cause the airway damage. The release of macrophage extracellular traps (METs) is the mechanism of immune protection to harmful stimulation via microRNAs, but excessive METs cause the injury. However, few studies have attempted to interpret the mechanism of an organism injury due to H2S via METs in chickens. Here, we investigated the transcriptome profiles, pathological morphologic changes and METs release from chicken trachea after H2S exposure. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that 10 differentially expressed genes were related to the METs release, the MAPK and insulin signaling pathways. Morphological and immunofluorescence analysis showed that H2S caused airway injury and MET release. H2S activated the targeting effect of miRNA-15b-5p on activating transcription factor 2 (ATF2). Western blotting and real time quantitative PCR results showed that H2S down-regulated the levels of dual specificity protein phosophatase1 (DUSP1) but up-regulated p38 MAP Kinase (p38) in the MAPK signal pathway. And the expression of phosphoinositide-dependent protein kinase 1 (PDK1), serine/threonine kinase (Akt), and protein kinase ζ subtypes (PKCζ) in the insulin signal pathway were increased after H2S exposure. These promoted the release of myeloperoxidase (MPO) and degradation histone 4 (H4) to induce the release of METs. Taken together, miR-15b-5p targeted ATF2 to mediate METs release, which triggered trachea inflammatory injury via MAPK and insulin signals after H2S exposure. These results will provide new insights into the toxicological mechanisms of H2S and environmental ecotoxicology.


Assuntos
Armadilhas Extracelulares , Sulfeto de Hidrogênio , MicroRNAs , Animais , Galinhas , Sulfeto de Hidrogênio/toxicidade , Insulina , Macrófagos , Traqueia
17.
Postgrad Med ; 133(5): 581-586, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33866924

RESUMO

Objective: Small-vessel occlusions are the most common causes of mild strokes and, in China, account for approximately 27.3% of ischemic stroke cases. However, the factors associated with short- and long-term outcomes appear contradictory. Thus, we assessed the factors related to outcomes 3 years after small-vessel occlusion among patients aged 18 to 55 years.Methods: Between 2007 and 2014, we recruited patients who experienced small-vessel occlusion (according to Trial of Org 10,172 in Acute Stroke Treatment [TOAST] classification) aged 18 to 55 years and conducted a hospital-based follow-up study. The assessed outcomes were mortality, recurrence, and dependency within 3 years after the initial stroke. The outcome determinants were assessed using a multivariate logistic regression analysis.Results: A total of 276 patients (men, 76.09%) with small-vessel occlusions were enrolled in this study. In addition, 85.1% of the patients had strokes between the ages of 45 and 55 years. The risk of recurrence within 3 years was higher for patients who had moderate strokes than for those who had mild events (relative risk [RR], 3.09; 95% confidence interval [CI], 1.14-8.34; P < 0.05). Further, the risk of dependency within 3 years was 2.61 times higher in obese patients than in non-obese patients (RR, 2.61; 95% CI, 1.00-6.79; P < 0.05). The risks of recurrence and dependency within 3 years increased by 17% and 18%, respectively, for each 1-unit increase in fasting plasma glucose levels (RR, 1.17; 95% CI, 1.05-1.30 and RR, 1.18; 95% CI, 1.06-1.32, respectively; both P < 0.05).Conclusion: Our findings suggest that small-vessel occlusions cause the heaviest disease burden in patients aged 45 to 55 years. To reduce stroke recurrence, young and middle-aged patients with small-vessel occlusions should control their fasting plasma glucose levels and manage their weight.


Assuntos
Arteriopatias Oclusivas/complicações , Isquemia Encefálica/etiologia , Hospitais , Sistema de Registros , Medição de Risco/métodos , Adolescente , Adulto , Isquemia Encefálica/epidemiologia , China/epidemiologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
18.
Medicine (Baltimore) ; 100(13): e25343, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33787634

RESUMO

ABSTRACT: This study was carried out to estimate the incidence and to determine socio-demographic risk factors for dementia among individuals residing in rural northern China.The current prospective, population-based study was conducted between 2011 and 2016. Follow-up interviews were conducted annually from 2014 to 2016. The study involved 1511 dementia-free individuals aged 60 years or above from rural China. Standard criteria were used to make diagnoses for dementia and Alzheimer disease (AD).At least one follow up survey was completed with 1181 study participants. At the 5-year follow-up, 127 individuals had developed dementia, 75 had developed AD, and 32 had developed vascular dementia (VaD). With a total of 5649.2 risk years for the sample, the estimated incidence rates per 1000 person-years were 22.48 (95% CI: 18.62, 26.35) for dementia and 13.28 (95% CI: 10.29, 16.26) for AD. Incidence rates for dementia and AD increased with age across the 10-year age groups. Poor education (illiteracy) was an independent risk factor for both AD and VaD. Being engaged in social activities was an independent protective factor for VaD.The incidence of dementia in rural China was found to be higher than previously reported. Incidence of dementia increased with age, and AD was the most frequent type of dementia. Poor education was associated with a higher risk of VaD and AD. Engagement in social activities was an independent protective factor for VaD.


Assuntos
Doença de Alzheimer/epidemiologia , Demência Vascular/epidemiologia , População Rural/estatística & dados numéricos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , China/epidemiologia , Demência Vascular/diagnóstico , Escolaridade , Feminino , Seguimentos , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Proteção , Fatores de Risco , Fatores Sexuais , Participação Social
19.
World J Clin Cases ; 8(12): 2603-2609, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32607338

RESUMO

BACKGROUND: Anti-N-methyl-D-aspartate-receptor (NMDAR) encephalitis is a common type of autoimmune encephalitis characterized by complex clinical signs and variable imaging manifestations. The pathogenesis of the disease is unclear. Syphilis is an infectious disease caused by Treponema pallidum that can invade the nervous and immune systems and cause systemic symptoms. There are few reports of anti-NMDAR encephalitis with syphilis, and the association between them is unknown; both diseases are related to immune system damage. We report a case of anti-NMDAR encephalitis with syphilis. CASE SUMMARY: A 32-year-old man was admitted to our hospital with complaints of cognitive decline, diplopia, and walking instability during the previous 6 mo. He developed dysarthria, difficulty swallowing, and involuntary shaking of his head, neck, and limbs during the month prior to presentation. Cranial magnetic resonance imaging showed symmetrical abnormal signals in the pons, midbrain, and bilateral basal ganglia, and inflammatory demyelination was considered. The diagnosis of syphilis was confirmed based on the syphilis diagnosis test and the syphilis rapid test. He was given anti-syphilis treatment, but the above symptoms gradually worsened. Anti-NMDAR antibody was positive in cerebrospinal fluid but was negative in serum. Due to the cerebrospinal fluid findings, anti-NMDAR encephalitis was a consideration. According to the patient's weight, he was treated with intravenous methylprednisolone 1 g QD for 5 d, with the dose gradually decreased for 6 mo, and immunoglobulin 25 g QD for 5 d; his symptoms improved after treatment. CONCLUSION: This case shows that anti-NMDAR encephalitis may be combined with syphilis, which should be recognized to avoid misdiagnosis and treatment delay.

20.
Sci Rep ; 9(1): 2834, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808986

RESUMO

Small artery occlusion (SAO) is responsible for 31.3% of all ischemic strokes in China. However, reports regarding the recurrence rate of SAO in China are rare. We aimed to assess the recurrence rate and factors associated with SAO in China. All consecutive patients with SAO hospitalized at Tianjin Huanhu Hospital from 2005 to 2014 were recruited. We assessed the association between stroke subtype, severity, and disease history with recurrence at 3, 12, and 36 months of onset using multivariate logistic regression analysis. A total of 2,524 SAO patients were included in this study, including 1696 (67.2%) men and 828 (32.8%) women. The recurrence rates were 3.1% at 3 months, 12.7% at 12 months, and 36.5% at 36 months. Compared with women, men had a higher risk of recurrence at 3 months after SAO (P = 0.003). Old age and severity of stroke were also associated with a higher risk of recurrence (P < 0.05). Patients with an elevated C-reactive protein had a higher risk of recurrence at 12 months (P = 0.003). On the other hand, the risk of recurrence at 12 months was 39% lower in patients who consumed alcohol than in those who did not (P = 0.037). Hypertension, atrial fibrillation, and obesity were independent risk factors of recurrence at 36 months. These findings suggest that modification of risk factors in patients with SAO, particularly men, is essential for reducing the rate of recurrence and the overall burden of stroke in China.


Assuntos
Arteriopatias Oclusivas/complicações , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial , Isquemia Encefálica , China/epidemiologia , Feminino , Humanos , Hipertensão , Masculino , Pessoa de Meia-Idade , Obesidade , Recidiva , Fatores de Risco , Acidente Vascular Cerebral/etiologia
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