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1.
J Neurosci ; 43(45): 7554-7564, 2023 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-37940582

RESUMO

The cerebellum, traditionally associated with motor coordination and balance, also plays a crucial role in various aspects of higher-order function and dysfunction. Emerging research has shed light on the cerebellum's broader contributions to cognitive, emotional, and reward processes. The cerebellum's influence on autonomic function further highlights its significance in regulating motivational and emotional states. Perturbations in cerebellar development and function have been implicated in various neurodevelopmental disorders, including autism spectrum disorder and attention deficit hyperactivity disorder. An increasing appreciation for neuropsychiatric symptoms that arise from cerebellar dysfunction underscores the importance of elucidating the circuit mechanisms that underlie complex interactions between the cerebellum and other brain regions for a comprehensive understanding of complex behavior. By briefly discussing new advances in mapping cerebellar function in affective, cognitive, autonomic, and social processing and reviewing the role of the cerebellum in neuropathology beyond the motor domain, this Mini-Symposium review aims to provide a broad perspective of cerebellar intersections with the limbic brain in health and disease.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Espectro Autista , Transtornos do Neurodesenvolvimento , Humanos , Cognição/fisiologia , Cerebelo/fisiologia , Transtornos do Neurodesenvolvimento/patologia
2.
Cell Commun Signal ; 22(1): 368, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030571

RESUMO

BACKGROUND: Painful diabetic neuropathy (PDN) is closely linked to inflammation, which has been demonstrated to be associated with pyroptosis. Emerging evidence has implicated TANK-binding kinase 1 (TBK1) in various inflammatory diseases. However, it remains unknown whether activated TBK1 causes hyperalgesia via pyroptosis. METHODS: PDN mice model of type 1 or type 2 diabetic was induced by C57BL/6J or BKS-DB mice with Lepr gene mutation. For type 2 diabetes PDN model, TBK1-siRNA, Caspase-1 inhibitor Ac-YVAD-cmk or TBK1 inhibitor amlexanox (AMX) were delivered by intrathecal injection or intragastric administration. The pain threshold and plantar skin blood perfusion were evaluated through animal experiments. The assessments of spinal cord, dorsal root ganglion, sciatic nerve, plantar skin and serum included western blotting, immunofluorescence, ELISA, and transmission electron microscopy. RESULTS: In the PDN mouse model, we found that TBK1 was significantly activated in the spinal dorsal horn (SDH) and mainly located in microglia, and intrathecal injection of chemically modified TBK1-siRNA could improve hyperalgesia. Herein, we described the mechanism that TBK1 could activate the noncanonical nuclear factor κB (NF-κB) pathway, mediate the activation of NLRP3 inflammasome, trigger microglia pyroptosis, and ultimately induce PDN, which could be reversed following TBK1-siRNA injection. We also found that systemic administration of AMX, a TBK1 inhibitor, could effectively improve peripheral nerve injury. These results revealed the key role of TBK1 in PDN and that TBK1 inhibitor AMX could be a potential strategy for treating PDN. CONCLUSIONS: Our findings revealed a novel causal role of TBK1 in pathogenesis of PDN, which raises the possibility of applying amlexanox to selectively target TBK1 as a potential therapeutic strategy for PDN.


Assuntos
Neuropatias Diabéticas , Microglia , Proteínas Serina-Treonina Quinases , Piroptose , Animais , Masculino , Camundongos , Aminopiridinas/farmacologia , Aminopiridinas/uso terapêutico , Neuropatias Diabéticas/patologia , Modelos Animais de Doenças , Hiperalgesia/patologia , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Microglia/patologia , Microglia/efeitos dos fármacos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/genética , Piroptose/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/genética
3.
Epidemiol Infect ; 150: e43, 2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-35105410

RESUMO

This review aimed to compare the clinical features and CT imaging features between patients with pulmonary tuberculosis (PTB) and lung cancer and patients with PTB alone. That would help to analyse the differences between the two and consequently providing a theoretical basis for the clinical diagnosis and treatment for the patients. Relevant case-control studies focusing on the clinical and CT imaging characteristics between PTB with lung cancer and PTB alone were systematically searched from five electronic databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for comparison. As of 2021-07-06, a total of 1735 articles were retrieved. But only 15 articles were finally included for meta-analysis. The results showed a higher proportion of irritable cough, haemorrhagic pleural effusion and lower proportion of night sweating in PTB patients with lung cancer than in PTB patients, and the differences were statistically significant (irritable cough: OR 2.43, 95% CI 1.43-4.11; haemorrhagic pleural effusion: OR 5.73, 95% CI 1.63-20.12; night sweating: OR 0.56, 95% CI 0.36-0.87). In addition, there are many differences in the imaging characteristics of the two types of patients. In conclusion, this review summarises the similarities and differences in clinical symptoms and imaging features between patients with PTB and lung cancer and patients with PTB alone, suggesting that we should be alert to the occurrence of lung cancer in patients with obsolete PTB relapse.


Assuntos
Neoplasias Pulmonares , Derrame Pleural , Tuberculose Pulmonar , Estudos de Casos e Controles , Tosse , Humanos , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/diagnóstico por imagem , Derrame Pleural/complicações , Tuberculose Pulmonar/complicações , Tuberculose Pulmonar/diagnóstico por imagem
4.
BMC Womens Health ; 22(1): 87, 2022 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-35321721

RESUMO

BACKGROUND: Pregnancy has been considered a risk factor for the development of osteoporosis. Despite much research in this field, the relationship between parity and bone mineral density (BMD) is still controversial. Therefore, we conducted this study to investigate whether there was an association between parity and BMD of the femoral neck and lumbar spine in postmenopausal women. METHODS: Cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES). Three linear regression models, Model 1 (unadjusted), Model 2 (adjusted for age and body mass index (BMI)), and Model 3 (adjusted for all covariates), were established to evaluate the relationship between parity and BMD. In addition, the p value trend of BMD in the different parity groups was mutually verified with the results of multiple regression. Multiple logistic regression models were used to assess the relationship between parity and osteoporosis. RESULTS: In total, 924 postmenopausal women aged 45-65 years were eligible for this study. After adjustment for potential confounders, women with ≥ 6 parities had significantly lower lumbar spine BMD than women with 1-2 parities (ß = - 0.072, 95% CI: - 0.125, - 0.018, P = 0.009). However, there was no correlation between parity and femoral neck BMD in any of the three regression models. Furthermore, ≥ 6 parities were associated with a significantly higher prevalence of lumbar spine osteoporosis compared with 1-2 parities (OR = 3.876, 95% CI: 1.637, 9.175, P = 0.002). CONCLUSIONS: After adjustment for BMD-related risk factors, ≥ 6 parities were associated with decreased lumbar spine BMD but not femoral neck BMD in postmenopausal women. This suggests that postmenopausal women with high parity are at increased risk of lumbar osteoporotic fractures and should pay more attention to their bone health.


Assuntos
Osteoporose Pós-Menopausa , Osteoporose , Absorciometria de Fóton/efeitos adversos , Densidade Óssea , Estudos Transversais , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Inquéritos Nutricionais , Osteoporose/epidemiologia , Osteoporose Pós-Menopausa/diagnóstico por imagem , Osteoporose Pós-Menopausa/epidemiologia , Paridade , Pós-Menopausa , Gravidez
5.
Cerebellum ; 20(6): 836-852, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33661502

RESUMO

Topographic organization of the cerebellum is largely segregated into the anterior and posterior lobes that represent its "motor" and "non-motor" functions, respectively. Although patients with damage to the anterior cerebellum often exhibit motor deficits, it remains unclear whether and how such an injury affects cognitive and social behaviors. To address this, we perturbed the activity of major anterior lobule IV/V in mice by either neurotoxic lesion or chemogenetic excitation of Purkinje cells in the cerebellar cortex. We found that both of the manipulations impaired motor coordination, but not general locomotion or anxiety-related behavior. The lesioned animals showed memory deficits in object recognition and social-associative recognition tests, which were confounded by a lack of exploration. Chemogenetic excitation of Purkinje cells disrupted the animals' social approach in a less-preferred context and social memory, without affecting their overall exploration and object-based memory. In a free social interaction test, the two groups exhibited less interaction with a stranger conspecific. Subsequent c-Fos imaging indicated that decreased neuronal activities in the medial prefrontal cortex, hippocampal dentate gyrus, parahippocampal cortices, and basolateral amygdala, as well as disorganized modular structures of the brain networks might underlie the reduced social interaction. These findings suggest that the anterior cerebellum plays an intricate role in processing motor, cognitive, and social functions.


Assuntos
Cerebelo , Animais , Ansiedade , Vermis Cerebelar , Córtex Cerebral , Humanos , Camundongos , Células de Purkinje
6.
Mol Psychiatry ; 25(9): 2017-2035, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-30224722

RESUMO

Principal neurons encode information by varying their firing rate and patterns precisely fine-tuned through GABAergic interneurons. Dysregulation of inhibition can lead to neuropsychiatric disorders, yet little is known about the molecular basis underlying inhibitory control. Here, we find that excessive GABA release from basket cells (BCs) attenuates the firing frequency of Purkinje neurons (PNs) in the cerebellum of Fragile X Mental Retardation 1 (Fmr1) knockout (KO) mice, a model of Fragile X Syndrome (FXS) with abrogated expression of the Fragile X Mental Retardation Protein (FMRP). This over-inhibition originates from increased excitability and Ca2+ transients in the presynaptic terminals, where Kv1.2 potassium channels are downregulated. By paired patch-clamp recordings, we further demonstrate that acutely introducing an N-terminal fragment of FMRP into BCs normalizes GABA release in the Fmr1-KO synapses. Conversely, direct injection of an inhibitory FMRP antibody into BCs, or membrane depolarization of BCs, enhances GABA release in the wild type synapses, leading to abnormal inhibitory transmission comparable to the Fmr1-KO neurons. We discover that the N-terminus of FMRP directly binds to a phosphorylated serine motif on the C-terminus of Kv1.2; and that loss of this interaction in BCs exaggerates GABA release, compromising the firing activity of PNs and thus the output from the cerebellar circuitry. An allosteric Kv1.2 agonist, docosahexaenoic acid, rectifies the dysregulated inhibition in vitro as well as acoustic startle reflex and social interaction in vivo of the Fmr1-KO mice. Our results unravel a novel molecular locus for targeted intervention of FXS and perhaps autism.


Assuntos
Proteína do X Frágil da Deficiência Intelectual , Síndrome do Cromossomo X Frágil , Animais , Modelos Animais de Doenças , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Síndrome do Cromossomo X Frágil/genética , Interneurônios/metabolismo , Camundongos , Camundongos Knockout , Transmissão Sináptica , Ácido gama-Aminobutírico
7.
Int J Clin Pract ; 75(12): e14944, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34605145

RESUMO

BACKGROUND: Gestational diabetes mellitus (GDM) is the most common pregnancy-related disease that increases the risk of metabolic disorders for the pregnancies and their offspring. GDM could be effectively prevented by early diagnosis and timely treatment. METHODS: 120 patients with GDM and 108 gestational week-matched pregnancies with normal glucose tolerance (NGT) were enrolled in our study. Their blood samples were collected, and demographic characteristics were analysed. RESULTS: Compared to NGT pregnancies, patients with GDM had increased the secretions of interleukin (IL)-33, soluble suppression of tumorigenicity 2 (sST2), IL-6 and tumour necrosis factor-α (TNF-α) in their plasma with elevated homeostatic model assessment (HOMA). Moreover, IL-33/sST2 was positively correlated with HOMA, IL-6 and TNF-α levels in the plasma of patients with GDM respectively. CONCLUSION: IL-33/sST2 might serve as a novel potential biomarker for early diagnosis of GDM.


Assuntos
Diabetes Gestacional , Resistência à Insulina , Complicações na Gravidez , Diabetes Gestacional/diagnóstico , Feminino , Humanos , Interleucina-33 , Gravidez , Fator de Necrose Tumoral alfa
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(3): 238-241, 2021 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-33751532

RESUMO

OBJECTIVE: To explore the genetic basis for a patient featuring developmental delay. METHODS: The patient and her parents were subjected to G- and C-banded chromosomal karyotyping analysis. The proband was also analyzed by single nucleotide polymorphism microarray (SNP-array). The result was verified by using fluorescence quantitative PCR (qPCR). RESULTS: The proband's karyotype was ascertained as 46,XX, r(15)(p11.2q26.3)[92]/45,XX,-15[9]/46,XX, dic r(15)(p11.2q26.3;p11.2q26.3)[4]. SNP-array revealed that she has carried a de novo deletion at 15q26.3 (98 957 555-102 429 040) spanning approximately 3.4 Mb, which encompassed the IGF1R gene. qPCR has confirmed haploinsufficiency of exons 3, 10 and 20 of the IGF1R gene. Both of her parents had a normal karyotype. CONCLUSION: The abnormal phenotype of the proband may be attributed to the microdeletion at 15q26.3, in particular haploinsuffiency of the IGF1R gene and instability of the ring chromosome. Cytogenetic method combined with SNP-array and qPCR can efficiently delineate chromosomal aberrations and provide accurate information for clinical diagnosis and genetic counseling.


Assuntos
Aconselhamento Genético , Cariotipagem , Cromossomos em Anel , Deleção Cromossômica , Análise Citogenética , Feminino , Humanos , Fenótipo
9.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(8): 867-870, 2020 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-32761597

RESUMO

OBJECTIVE: To explore the genetic basis for a child with developmental delay and mental retardation. METHODS: Chromosomal karyotype of the child was analyzed by G-, C- and N-banding techniques. Her genome DNA was analyzed with single nucleotide polymorphisms array (SNP array). The result was validated by fluorescence quantitative polymerase chain reaction (PCR). RESULTS: The karyotype of the child was ascertained as 46,XX,r(22)(p12q13). SNP array has revealed a deletion of approximately 1.4 Mb at 22q13.33 (49 802 963-51 197 766). The deletion has encompassed the SHANK3, a crucial gene for the development of nervous system. Fluorescence quantitative PCR has confirmed the deletion of exons 7, 19 and 22 of the SHANK3 gene. CONCLUSION: The phenotype of the patient may be attributed to the microdeletion at 22q13.33. Cytogenetic methods combined with SNP array and fluorescence quantitative PCR can identify aberrant chromosomes and provide accurate information for the clinical diagnosis and genetic counseling.


Assuntos
Análise Citogenética , Deficiências do Desenvolvimento/genética , Deficiência Intelectual , Criança , Bandeamento Cromossômico , Deleção Cromossômica , Cromossomos Humanos Par 22 , Feminino , Humanos , Deficiência Intelectual/genética , Cariotipagem , Polimorfismo de Nucleotídeo Único
10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(12): 1171-1174, 2019 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-31813140

RESUMO

OBJECTIVE: To apply high-throughput whole genome sequencing (WGS) and short tandem repeat (STR) typing to detect aneuploidies, heteroploidies and copy number variations(CNVs) in spontaneous abortic tissues. METHODS: Chorionic villus samples from 145 patients with spontaneous abortion were subjected to detection of aneuploidies, heteroploidies and copy number variations by WGS and STR typing. RESULTS: All testing was successful and the rate of chromosomal abnormalities among the patients was 22.07%. Among these, there were 11 trisomies, 3 monosomies, 2 triploidies, 5 autosomal mosaicisms, 4 sex chromosomal mosaicisms, 7 structural abnormalities (including 1 mosaicism). In 89 cases, there were 130 CNVs of uncertain significance, 47 likely benign CNVs, and 2 loss of one copy of pathogenic AR gene. One sample contained 6 fragment duplications and deletions. Only 24 samples had no abnormal finding. CONCLUSION: The most important reason for spontaneous abortions is embryonic chromosomal abnormality. Combined STR typing and WGS is both comprehensive and fast, and may become a major means for the detection of chorionic villi tissue from spontaneous abortions.


Assuntos
Aborto Espontâneo/genética , Coreia/genética , Repetições de Microssatélites , Sequenciamento Completo do Genoma , Aberrações Cromossômicas , Variações do Número de Cópias de DNA , Feminino , Humanos , Gravidez
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 35(6): 852-855, 2018 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-30512162

RESUMO

OBJECTIVE: To explore the genetic cause for a child featuring growth and mental retardation. METHODS: Following conventional karyotyping analysis of the trio family, next generation sequencing (NGS) was carried out to explore the origin of the supernumerary marker chromosome. Fluorescence in situ hybridization (FISH) was used to confirm the result. RESULTS: The karyotypes of both parents were normal, while the proband was found to be 47,XX,+mar. NGS showed that the supernumerary marker has originated from chromosome 9p13.1p24.3 with a size of 39.77 Mb. FISH has confirmed the above finding. CONCLUSION: The 9p13.1-p24.3 trisomy probably underlies the abnormal phenotypes of the child. Cytogenetic analysis combined with NGS and FISH can provide accurate diagnosis for such disorders.


Assuntos
Cromossomos Humanos Par 9/genética , Sequenciamento de Nucleotídeos em Larga Escala , Trissomia , Criança , Análise Citogenética , Humanos , Hibridização in Situ Fluorescente , Cariotipagem
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 34(6): 835-838, 2017 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-29188611

RESUMO

OBJECTIVE: To assess the value of next generation sequencing (NGS) for the analysis of spontaneous abortion samples. METHODS: The NGS analysis was carried out on 85 chorionic villi samples (taken between 42 days to 12 weeks of gestation) for which conventional cell culture has failed or chromosomal karyotyping has yielded normal or uncertain result. RESULTS: Among 68 samples with a normal karyotype, the NGS analysis has identified 2 copy number variations (CNVs) and 2 chimeras. For 16 cases with failed cell culture, the NGS has identified 4 chromosomal abnormalities including 1 copy number variation and 3 numerical chromosomal aberrations. For 1 remaining case with uncertain karyotyping result, the NGS analysis has verified it as 46,XX,del(4) (p15.1p16.3).seq[GRCh37/hg19] (57 549 - 32 371 364)×1. CONCLUSION: The NGS analysis is capable of identifying novel CNVs in samples for which conventional cell culture may fail or karyotyping analysis may yield a normal result.


Assuntos
Aborto Espontâneo/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Adolescente , Adulto , Células Cultivadas , Variações do Número de Cópias de DNA , Feminino , Humanos , Cariotipagem , Pessoa de Meia-Idade , Gravidez , Adulto Jovem
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 33(6): 829-832, 2016 Dec 10.
Artigo em Chinês | MEDLINE | ID: mdl-27984615

RESUMO

OBJECTIVE: To analyze the genetic cause for a child with growth retardation and mental retardation and discuss the application of array-based comparative genomic hybridization (aCGH) in its molecular genetic diagnosis. METHODS: Conventional karyotyping of peripheral blood for the family was carried out. aCGH was performed to further ascertain the size and origin of the additional chromosome fragments. RESULTS: In the trio family here, the karyotype of the father was normal, the karyotype of the mother was 46,XX, t(6;9)(q26;q21)and the proband child's was 47,XX,+der(9)?t(6;9)(q26;q21). aCGH showed that the extra chromosomal fragments originated from chromosome 9p24.3-q21.13 and the size was 78.26 Mb, and the repeat region included the 9p trisomy's clinical area. At the same time, it was confirmed that 6q26-q27 was trisomic and the fragment that related to development delay was 6.6 Mb. We determined that the proband's karyotype was 47,XX,+der(9)t(6;9)(q26;q21.13)mat finally. CONCLUSION: The patient's abnormal chromosome has originated from her mother with balance translocation. The duplications of 9p24.3-q21.13 and 6q26-q27 may lead to growth retardation and mental retardation. Accompanied with the cytogenetic methods, aCGH can accurately identify the origin and size of the abnormal chromosomes, contributing to the genetic analysis.


Assuntos
Transtornos Cromossômicos/genética , Trissomia/genética , Pré-Escolar , Cromossomos Humanos Par 6/genética , Cromossomos Humanos Par 9/genética , Hibridização Genômica Comparativa/métodos , Feminino , Humanos
14.
Artigo em Chinês | MEDLINE | ID: mdl-30124254

RESUMO

In recent years, gold nanoparticles (GNPs) have attracted more and more attention for their unique physical, chemical and biological properties, and are emerging as optical probes and biocompatibility materials for use. With the application of nanogold labeling technology in the medical field, detection techniques using GNPs as immune markers will become a major labeling technique, and will have wide applications in basic and clinical medicine. In this article, recent research progress on the applications of GNPs in the detection of pathogens, nucleic acids, and proteins and in the preparation of biosensors is reviewed.


Assuntos
Nanopartículas Metálicas , Técnicas Biossensoriais , Biotecnologia , Ouro
15.
J Neurosci ; 33(15): 6460-8, 2013 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-23575844

RESUMO

The cyclic adenosine monophosphate (cAMP), mitogen-activated protein kinase (MAPK), and cAMP response element-binding protein (CREB) transcriptional pathway is required for consolidation of hippocampus-dependent memory. In mice, this pathway undergoes a circadian oscillation required for memory persistence that reaches a peak during the daytime. Because mice exhibit polyphasic sleep patterns during the day, this suggested the interesting possibility that cAMP, MAPK activity, and CREB phosphorylation may be elevated during sleep. Here, we report that cAMP, phospho-p44/42 MAPK, and phospho-CREB are higher in rapid eye movement (REM) sleep compared with awake mice but are not elevated in non-REM sleep. This peak of activity during REM sleep does not occur in mice lacking calmodulin-stimulated adenylyl cyclases, a mouse strain that learns but cannot consolidate hippocampus-dependent memory. We conclude that a preferential increase in cAMP, MAPK activity, and CREB phosphorylation during REM sleep may contribute to hippocampus-dependent memory consolidation.


Assuntos
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/fisiologia , AMP Cíclico/fisiologia , Memória/fisiologia , Proteína Quinase 1 Ativada por Mitógeno/fisiologia , Proteína Quinase 3 Ativada por Mitógeno/fisiologia , Sono REM/fisiologia , Adenilil Ciclases/genética , Adenilil Ciclases/fisiologia , Animais , Aprendizagem da Esquiva/fisiologia , Condicionamento Psicológico/fisiologia , AMP Cíclico/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/fisiologia , Eletroencefalografia/métodos , Eletroencefalografia/psicologia , Eletromiografia/métodos , Eletromiografia/psicologia , Hipocampo/metabolismo , Hipocampo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação , Transdução de Sinais/fisiologia , Sono REM/genética
16.
Artigo em Chinês | MEDLINE | ID: mdl-25065215

RESUMO

OBJECTIVE: To investigated the intermediate hosts of Angiostrongylus cantonensis in three plateau lakes of Yunnan Province, and analyze the effect of temperature on A. cantonensis during 1991-2010. METHODS: An epidemiological investigation of angiostrongyliasis cantonensis in Erhai Lake, Fuxian Lake and Xingyun Lake was conducted from April to September in 2012. Snails were examined for the third stage larvae by enzyme digestion or lung examination. Rodents were captured in the fields, and their hearts and lungs were dissected for adult worms. The potential distribution of A. cantonensis and its main intermediate host Pomacea canaliculata were predicted based on degree-day models using GIS technique. RESULTS: A total of 4 950 snails were collected, belonging to 4 species, P. canaliculata, Cipangopaludina chinensis, Bellamya aeruginosa, and B. quadrata. 174 rodents were captured, belonging to 5 species. No positive samples were found. The potential distribution map showed that the distribution of A. cantonensis and P. canaliculata in Yunnan would expand with the rise of temperature, and with the passage of time they could complete one generation in the region which couldn't finish one generation in one year along with time passing. CONCLUSION: A. cantonensis are not found in the hosts. The natural environment and ecological system of the three lakes match the condition of A. cantonensis transmission.


Assuntos
Angiostrongylus cantonensis , Animais , China , Lagos , Larva , Roedores , Caramujos , Temperatura
17.
Neurosci Biobehav Rev ; 157: 105523, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38142983

RESUMO

The circadian rhythm affects multiple physiological processes, and disruption of the circadian system can be involved in a range of disease-related pathways. The genetic underpinnings of the circadian rhythm have been well-studied in model organisms. Significant progress has been made in understanding how clock genes affect the physiological functions of the nervous system. In addition, circadian timing is becoming a key factor in improving drug efficacy and reducing drug toxicity. The circadian biology of the target cell determines how the organ responds to the drug at a specific time of day, thus regulating pharmacodynamics. The current review brings together recent advances that have begun to unravel the molecular mechanisms of how the circadian clock affects neurophysiological and behavioral processes associated with human brain diseases. We start with a brief description of how the ubiquitous circadian rhythms are regulated at the genetic, cellular, and neural circuit levels, based on knowledge derived from extensive research on model organisms. We then summarize the latest findings from genetic studies of human brain disorders, focusing on the role of human clock gene variants in these diseases. Lastly, we discuss the impact of common dietary factors and medications on human circadian rhythms and advocate for a broader application of the concept of chronomedicine.


Assuntos
Relógios Circadianos , Neurociências , Humanos , Neurofisiologia , Ritmo Circadiano/genética , Relógios Circadianos/genética
18.
Comput Biol Med ; 178: 108759, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38917530

RESUMO

BACKGROUND: The retinal vasculature, a crucial component of the human body, mirrors various illnesses such as cardiovascular disease, glaucoma, and retinopathy. Accurate segmentation of retinal vessels in funduscopic images is essential for diagnosing and understanding these conditions. However, existing segmentation models often struggle with images from different sources, making accurate segmentation in crossing-source fundus images challenging. METHODS: To address the crossing-source segmentation issues, this paper proposes a novel Multi-level Adversarial Learning and Pseudo-label Denoising-based Self-training Framework (MLAL&PDSF). Expanding on our previously proposed Multiscale Context Gating with Breakpoint and Spatial Dual Attention Network (MCG&BSA-Net), MLAL&PDSF introduces a multi-level adversarial network that operates at both the feature and image layers to align distributions between the target and source domains. Additionally, it employs a distance comparison technique to refine pseudo-labels generated during the self-training process. By comparing the distance between the pseudo-labels and the network predictions, the framework identifies and corrects inaccuracies, thus enhancing the accuracy of the fine vessel segmentation. RESULTS: We have conducted extensive validation and comparative experiments on the CHASEDB1, STARE, and HRF datasets to evaluate the efficacy of the MLAL&PDSF. The evaluation metrics included the area under the operating characteristic curve (AUC), sensitivity (SE), specificity (SP), accuracy (ACC), and balanced F-score (F1). The performance results from unsupervised domain adaptive segmentation are remarkable: for DRIVE to CHASEDB1, results are AUC: 0.9806, SE: 0.7400, SP: 0.9737, ACC: 0.9874, and F1: 0.8851; for DRIVE to STARE, results are AUC: 0.9827, SE: 0.7944, SP: 0.9651, ACC: 0.9826, and F1: 0.8326. CONCLUSION: These results demonstrate the effectiveness and robustness of MLAL&PDSF in achieving accurate segmentation results from crossing-domain retinal vessel datasets. The framework lays a solid foundation for further advancements in cross-domain segmentation and enhances the diagnosis and understanding of related diseases.


Assuntos
Vasos Retinianos , Humanos , Vasos Retinianos/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Algoritmos
19.
Clin Interv Aging ; 18: 619-627, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37096217

RESUMO

Background: Vitamin D status is indicated by serum 25-hydroxyvitamin D [25(OH)D] levels, and the positive effects of high levels of vitamin D on bone mineral density (BMD) have not been ascertained. Therefore, we performed a study to analyze the association between serum 25(OH)D levels and osteoporosis in postmenopausal women. Methods: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES). Multiple logistic regression was used to explore the relationship between serum 25(OH)D and osteoporosis of total femur, femoral neck and lumbar spine, with stratified analyses for age (<65 and ≥65 years), BMI (<25, 25 to <30, ≥30 kg/m2) and survey months (winter months and summer months). Results: In total, 2058 participants were enrolled in our study. In the fully adjusted model, compared with serum 25(OH)D levels <50 nmol/L, the odds ratios (ORs) and 95% confidence intervals (CIs) of serum 25(OH)D 50-<75 nmol/L and ≥75 nmol/L were 0.274 (0.138, 0.544) and 0.374 (0.202, 0.693) in osteoporosis of total femur, 0.537 (0.328, 0.879) and 0.583 (0.331, 1.026) in osteoporosis of femoral neck, and 0.614 (0.357, 1.055) and 0.627 (0.368, 1.067) in osteoporosis of lumbar spine, respectively. The protective effect of high 25(OH)D was observed at all three skeletal sites in those ≥65 years of age, whereas it was observed only in the total femur in those <65 years of age. Conclusion: In conclusion, adequate vitamin D may reduce the risk of osteoporosis in postmenopausal women in the United States, especially in those aged 65 years and older. More attention should be given to serum 25 (OH) D levels to prevent osteoporosis.


Assuntos
Osteoporose Pós-Menopausa , Osteoporose , Deficiência de Vitamina D , Feminino , Humanos , Idoso , Inquéritos Nutricionais , Pós-Menopausa , Estudos Transversais , Vitamina D , Calcifediol , Densidade Óssea , Vitaminas , Vértebras Lombares
20.
J Orthop Surg Res ; 18(1): 51, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650576

RESUMO

BACKGROUND: Age at menarche (AAM) directly affects female estrogen levels, which play a vital role in bone metabolism. The exact relationship between bone mineral density (BMD) and AAM remains controversial. Thus, this study aimed to determine the association between AAM and lumbar spine (LS) BMD in postmenopausal women. METHODS: Our data were based on the National Health and Nutrition Examination Survey (NHANES) 2011-2018. AAM was divided into three categories including ≤ 12, 13-15, and ≥ 16 years, and the ≤ 12 years old category was used as the reference group. To examine the association between AAM and LS BMD, we used three weighted linear regression models, Model 1 (without adjustment), Model 2 (with adjustment for age, race, and body mass index [BMI]), and Model 3 (with adjustment for all covariates). RESULTS: This study included 1195 postmenopausal women aged 40-59 years. In the unadjusted model, a menarche age of ≥ 16 years compared with a menarche age of ≤ 12 years was associated with lower LS BMD (ß = - 0.083, 95% CI - 0.117, - 0.048, P < 0.001). After adjusting for potential confounding factors, there was still a negative correlation in model 2 (ß = - 0.078, 95% CI - 0.113, - 0.042, P < 0.001) and model 3 (ß = - 0.065, 95% CI - 0.096, - 0.033, P < 0.001). Moreover, this significant relationship persisted after excluding participants who used female hormones (ß = - 0.053, 95% CI - 0.089, - 0.016, P = 0.006). CONCLUSION: Our study found that postmenopausal women with a menarche age of ≥ 16 years had significantly lower LS BMD than that had by those with a menarche age of ≤ 12 years. As a result of this study, postmenopausal women with a late menarche age may have a higher risk of lumbar osteoporotic fractures and need better bone health care.


Assuntos
Densidade Óssea , Osteoporose Pós-Menopausa , Feminino , Humanos , Criança , Inquéritos Nutricionais , Menarca , Pós-Menopausa , Vértebras Lombares/diagnóstico por imagem , Absorciometria de Fóton
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