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Excitatory amino acid transporters (EAATs) are responsible for excitatory amino acid transportation and are associated with auto-immune diseases in the central nervous system and peripheral tissues. However, the subcellular location and function of EAAT2 in macrophages are still obscure. In this study, we demonstrated that LPS stimulation increases expression of EAAT2 (coded by Slc1a2) via NF-κB signaling. EAAT2 is necessary for inflammatory macrophage polarization through sustaining mTORC1 activation. Mechanistically, lysosomal EAAT2 mediates lysosomal glutamate and aspartate efflux to maintain V-ATPase activation, which sustains macropinocytosis and mTORC1. We also found that mice with myeloid depletion of Slc1a2 show alleviated inflammatory responses in LPS-induced systemic inflammation and high-fat diet induced obesity. Notably, patients with type II diabetes (T2D) have a higher level of expression of lysosomal EAAT2 and activation of mTORC1 in blood macrophages. Taken together, our study links the subcellular location of amino acid transporters with the fate decision of immune cells, which provides potential therapeutic targets for the treatment of inflammatory diseases.
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Transportador 2 de Aminoácido Excitatório , Inflamação , Lisossomos , Macrófagos , Alvo Mecanístico do Complexo 1 de Rapamicina , Animais , Macrófagos/metabolismo , Macrófagos/imunologia , Macrófagos/efeitos dos fármacos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Transportador 2 de Aminoácido Excitatório/metabolismo , Transportador 2 de Aminoácido Excitatório/genética , Lisossomos/metabolismo , Inflamação/metabolismo , Inflamação/imunologia , Humanos , Lipopolissacarídeos/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/imunologia , Ácido Glutâmico/metabolismo , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Ácido Aspártico/metabolismo , Masculino , Obesidade/metabolismo , Obesidade/imunologia , Transdução de Sinais , Dieta Hiperlipídica/efeitos adversos , Pinocitose/efeitos dos fármacosRESUMO
PURPOSE: This study aims to appraise the therapeutic effectiveness of intravitreal injections anti-vascular endothelial growth factor (anti-VEGF) vs alternative therapies in managing radiation retinopathy (RR). DESIGN: Systematic review and meta-analysis. METHODS: We obtained comprehensive data retrieval using PubMed, Embase, Web of Science, Scopus, and the Cochrane Library from their inception until December 15, 2023. This review included randomized controlled trials (RCTs) and nonrandomized studies (NRSs) reporting on best-corrected visual acuity (BCVA) among RR patients treated with intravitreal anti-VEGF. Study selection and data extraction were meticulously performed by 2 independent reviewers. The Cochrane Risk of Bias Tool 2.0 (RoB 2.0) and Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) scales were utilized for bias risk assessment. Quantification of heterogeneity was executed using Q, H, and I2 statistics. The primary endpoint was the BCVA at the final observation point of each study. Secondary endpoints included central retinal thickness (CRT), foveal avascular zone (FAZ) area, and capillary density (CD) at the level of superficial capillary plexus. Subgroup analyses were undertaken to explore potential heterogeneity sources possibly due to treatment duration and study design. Sensitivity analyses were conducted to ascertain result stability. RESULTS: This analysis incorporated 7 studies (including 3 RCTs) encompassing 922 patients afflicted with RR. Relative to other treatment modalities, intravitreal anti-VEGF therapy was associated with a statistically significant mean decrease in BCVA of -0.34 logMAR (95% CI, -0.39 to -0.30 logMAR; I2 = 87.70%; P < .001), and a substantial reduction in CRT of -34.65 µm (95% CI, -50.70 to -18.60 µm; I2 = 30.40%; P < .001). Additionally, a reduction in the FAZ area by -0.69 mm² (95% CI, -0.91 to -0.46 mm², I2 = 0%; P < .001) was observed. A positive tendency was noted in CD at the superficial capillary plexus between anti-VEGF and other therapeutic interventions. CONCLUSIONS: Intravitreal anti-VEGF injections, in comparison to other treatments, demonstrate superior efficacy in enhancing BCVA and reducing CRT, thereby underscoring the potential of anti-VEGF in ameliorating radiation retinopathy outcomes. However, the conclusions are constrained by the incorporation of data from some NRSs and the small sample sizes.
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Inibidores da Angiogênese , Injeções Intravítreas , Lesões por Radiação , Doenças Retinianas , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual , Humanos , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Lesões por Radiação/tratamento farmacológico , Acuidade Visual/fisiologia , Doenças Retinianas/tratamento farmacológico , Resultado do Tratamento , Tomografia de Coerência ÓpticaRESUMO
Background: Most pregnant women do not reach the recommendation for physical activity (PA). As a subcategory of PA, exercise is also essential. Evidence on pregnant women's attitudes and barriers to PA and exercise self-efficacy in China is scarce. Aim: To explore the levels and influencing factors of attitudes and barriers to PA and exercise self-efficacy among pregnant women. Methods: A cross-sectional study of 311 pregnant women was conducted from August to December 2022. Individual characteristics, pregnant women's attitudes toward exercise, barriers to prenatal PA and exercise, and exercise self-efficacy were measured using the self-designed demographic questionnaire, pregnant women's attitudes toward exercise questionnaire, barriers to prenatal PA and exercise questionnaire, and the pregnancy exercise self-efficacy scale, respectively. Results: More than 90% of pregnant women believed exercise benefits themselves and their babies, and 40.8% of pregnant women did not know how to exercise. Women encounter different types of barriers to PA and exercise. Intrapersonal barriers included the proportion of feelings of tiredness (56.6%), low energy (54.7%), lack of interest or motivation (49.2%), feelings of illness and morning sickness (46.6%), and large body weight (43.7%). Interpersonal barriers included pregnant women being advised to avoid PA and exercise (49.2%), lack of clear advice about the intensity and dose of exercise (41.8%), no one to exercise with (38.9%), and lack of advice from healthcare professionals (38.6%). Weather conditions were the most significant environmental barriers (41.2%). The total score of pregnancy exercise self-efficacy was (38.50±7.33). Education level, parity, and attitudes toward exercise independently predict pregnant women's attitudes toward exercise, barriers to prenatal PA and exercise, and exercise self-efficacy, respectively. Conclusion: Pregnant women have a favorable attitude toward exercise and relatively good exercise self-efficacy but lack knowledge of exercise. They face numerous barriers. Medical professionals should encourage pregnant women with lower levels of education to exercise and assist multipara in overcoming obstacles.
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Body image (BI) is a multidimensional construct that refers to one's perceptions of and attitudes toward one's own physical characteristics. Adolescence is a critical developmental stage in which concerns about BI increase. Therefore, the present cross-sectional study aimed to evaluate body image and aesthetic body shape standards in a sample of middle school students living in China. The researchers gathered demographic information, as well as height and weight data, for their study. They used a body silhouette to assess body image perception and body shape aesthetics and calculated two indexes: BIP, which measures the accuracy of self-perception and the estimation of bodily dimensions, and BIS, which indicates the difference between an individual's perceived and ideal body images. A total of 1585 students in three grades at two middle schools were included in the study (759 = female, mean age = 13.67 ± 0.90; 839 = male, mean age = 13.70 ± 0.90). The results showed that the BIP bias rate of middle school students was 55.7%, and the BI dissatisfaction rate was 81.0%. Females tended to overestimate their body shape and desire to be thinner compared to males. Students with a higher BMI grading were more prone to underestimating their body shape and aspiring to be thinner. Furthermore, 8.6% of students chose underweight as the ideal body type for boys, while 22.6% chose underweight as the ideal body type for girls. In conclusion, there are significant gender differences in the aesthetic standards of body shape, and adolescents believe that for women, a thin body shape is beautiful.
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OBJECTIVE: To translate the English version Child Food Neophobia Scale (CFNS) into the Chinese version and test its reliability and validity in preschool children. METHODS: To create the Chinese version of the CFNS, it was translated, back-translated, and cross-culturally adapted. The use of the Chinese version of CFNS by 575 parents of preschool children in two kindergartens in Yangzhou City was investigated using cluster sampling to assess the reliability and validity of the scale. RESULTS: The Chinese version of CFNS has nine items in total. The scale-level average content validity index (S-CVI/Ave) is 0.983. Exploratory factor analysis (EFA) extracted 2 common factors, and the cumulative variance contribution rate was 49.437%. Confirmatory factor analysis (CFA) showed that the 2-factor model was well fitted. The Cronbach'α coefficient of the scale was 0.759, the Cronbach'α coefficients of the two factors were 0.735 and 0.713, the split-half reliability was 0.788, and the test-retest reliability was 0.756. CONCLUSION: The Chinese version of the Child Food Neophobia Scale has good reliability and validity in preschool children and can be used as an assessment tool for food neophobia in preschool children in China. PRACTICE IMPLICATIONS: This study has gone through a rigorous translation process, and the CFNS may support future exploration of food neophobia in preschool children. Food allergy factors in the results may be the next step in the research, and several studies are still needed to understand the relationship between food allergy and food neophobia.
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Transtorno Alimentar Restritivo Evitativo , Pré-Escolar , Humanos , Transtorno Alimentar Restritivo Evitativo/diagnóstico , Transtorno Alimentar Restritivo Evitativo/etnologia , China , Psicometria/métodos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Tradução , População do Leste Asiático , Comparação TransculturalRESUMO
AIM: To review and analyse the evidence on the efficacy and safety of non-pharmacological interventions for preterm infants to relieve endotracheal suctioning (ES) pain. DESIGN: A systematic review per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. METHODS: Six databases were searched with a retrieval strategy. Parallel and crossover randomized controlled trials reporting non-pharmacological interventions for relieving ES pain in preterm infants were identified from inception to 1 September 2021. The protocol was published in PROSPERO (CRD42021276058). RESULTS: Ten studies were retrieved, including nine different non-pharmacological interventions. Seven studies reported that non-pharmacological interventions in relieving pain were more effective than conventional care during ES, and three trials reported its safety. Due to the heterogeneity of pain assessment tools, time of assessment and population, only Facilitated tucking had sufficient evidence that it is a safe and effective non-pharmacological intervention.
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Recém-Nascido Prematuro , Dor , Lactente , Humanos , Recém-Nascido , Dor/prevenção & controle , Manejo da Dor/métodos , Sucção/efeitos adversos , Sucção/métodosRESUMO
PURPOSE: Postoperative urinary retention (POUR) is a common complication following colorectal surgery. The incidence of POUR among colorectal surgery patients varies widely, and the risk factors and outcomes of POUR are also debatable. This meta-analysis aims to systematically evaluate the risk factors for POUR in patients after colorectal surgery. METHODS: PubMed, Web of Science, the Cochrane Library, Embase, Medline, and Chinese databases (CBM, CNKI, and WanFang Databases) were searched to identify relevant cohort studies (from inception to August 2022). Two researchers independently conducted literature quality evaluation and data extraction. All data were analyzed by using the Review Manager 5.4 software. RESULTS: Nineteen studies with 101,025 patients were included in this meta-analysis. The risk factors for POUR in colorectal surgery patients were male sex, older age, diabetes mellitus, urological diseases, tumor location in the lower rectum, APR, laparoscopic surgery, operation time ≥ 4 h, postoperative date of urinary catheter removal, excessive intraoperative intravenous fluid volume, and postoperative ileus. The postoperative anastomotic leak, on the other hand, was not a risk factor for POUR. CONCLUSIONS: Multiple risk factors influence the incidence of POUR in patients undergoing colorectal surgery. To reduce the incidence of POUR in colorectal surgery patients, medical staff should identify risk factors early and enforce interventions to prevent them.
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Cirurgia Colorretal , Procedimentos Cirúrgicos do Sistema Digestório , Retenção Urinária , Humanos , Masculino , Feminino , Retenção Urinária/epidemiologia , Retenção Urinária/etiologia , Cirurgia Colorretal/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco , Estudos RetrospectivosRESUMO
Background: Maternal role competence is an important marker of achievement in the role of the mother, but parenting sense of competence (PSOC) among puerperal women is not high. Psychosocial factors, particularly social support, postnatal depression and resilience, have been identified as significant predictors of maternal role competence. However, information is limited regarding the mechanisms through which these psychosocial factors affect maternal role competence. Objective: To evaluate the multiple mediators of resilience and postpartum depression (PPD) in the relationship between social support and PSOC in puerperal women. Methods: A cross-sectional study was performed in a tertiary general hospital in Yangzhou, China. A total of 234 puerperal women at 6-8 weeks after birth completed the socio-demographic questionnaires, Social Support Rating Scale, Connor-Davidson Resilience Scale, Edinburgh Postnatal Depression Scale, and PSOC Scale. Results: Resilience and PPD mediated the relationship between social support and PSOC. The mediation effect of resilience and PPD and the total mediation effect were significant, individually accounting for 22.96, 21.70, and 44.65%, respectively, of the total effect. Moreover, pairwise contrast between the two indirect effects was not significant. The difference between the two pathways suggests that resilience and PPD play different roles in the relationship between social support and PSOC. Conclusions: This study showed that social support may exert its effects on PSOC in puerperal women with multiple mediators of resilience and PPD. This therefore highlights potential intervention targets to improve PSOC.
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Recent compelling results indicate possible links between neurotransmitters, intestinal mucosal IgA+ B cell responses, and immunoglobulin A nephropathy (IgAN) pathogenesis. Here, we demonstrated that γ-amino butyric acid (GABA) transporter-2 (GAT-2) deficiency induces intestinal germinal center (GC) B cell differentiation and worsens the symptoms of IgAN in a mouse model. Mechanistically, GAT-2 deficiency enhances GC B cell differentiation through activation of GABA-mammalian target of rapamycin complex 1 (mTORC1) signaling. In addition, IgAN patients have lower GAT-2 expression but higher activation of mTORC1 in blood B cells, and both are correlated with kidney function in IgAN patients. Collectively, this study describes GABA signaling-mediated intestinal mucosal immunity as a previously unstudied pathogenesis mechanism of IgAN and challenges the current paradigms of IgAN.
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Glomerulonefrite por IGA , Camundongos , Animais , Ácido gama-Aminobutírico/metabolismo , Imunoglobulina A/metabolismo , Centro Germinativo/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Diferenciação Celular , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , MamíferosRESUMO
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is highly contagious and has resulted in a protracted pandemic. Infections caused by new coronavirus strains, primarily Delta and Omicron and currently highly prevalent globally. In response to the epidemic, countries, and cities implemented isolation and quarantine guidance, such as limiting social contact, which have affected the lifestyles and quality of life of the population. Parental feeding behaviors may vary as a result of factors such as prolonged home isolation of parents and children, lack of supplies during isolation, and stress. This study was designed to assess the available evidence and its implications for parental feeding practices in the context of COVID-19. We screened and reviewed research published in five electronic databases between 2020 and 2022, and eight studies met the selection criteria. Parents were observed to use a variety of feeding practices, including high levels of coercive control and reduction of rules and limits according to Vaughn's food parenting constructs. The findings suggest that parental feeding practices are changing as a result of the pandemic and that more research is needed to further explore how to provide supportive feeding guidance to parents during emergencies in order to jointly promote child health.
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COVID-19 , Pandemias , Criança , Comportamento Alimentar , Humanos , Pandemias/prevenção & controle , Pais , Qualidade de Vida , SARS-CoV-2RESUMO
Accumulating evidence shows that nervous system governs host immune responses; however, how γ-aminobutyric acid (GABA)ergic system shapes the function of innate immune cells is poorly defined. Here, we demonstrate that GABA transporter (GAT2) modulates the macrophage function. GAT2 deficiency lowers the production of interleukin-1ß (IL-1ß) in proinflammatory macrophages. Mechanistically, GAT2 deficiency boosts the betaine/S-adenosylmethionine (SAM)/hypoxanthine metabolic pathway to inhibit transcription factor KID3 expression through the increased DNA methylation in its promoter region. KID3 regulates oxidative phosphorylation (OXPHOS) via targeting the expression of OXPHOS-related genes and is also critical for NLRP3-ASC-caspase-1 complex formation. Likewise, GAT2 deficiency attenuates macrophage-mediated inflammatory responses in vivo, including lipopolysaccharide-induced sepsis, infection-induced pneumonia, and high-fat diet-induced obesity. Together, we propose that targeting GABAergic system (e.g., GABA transporter) could provide previously unidentified therapeutic opportunities for the macrophage-associated diseases.
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Lipopolissacarídeos , Macrófagos , Caspases/metabolismo , Proteínas da Membrana Plasmática de Transporte de GABA/genética , Proteínas da Membrana Plasmática de Transporte de GABA/metabolismo , Expressão Gênica , Interleucina-1beta/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/metabolismoRESUMO
The γ-amino butyric acid (GABA)ergic system shapes the activation and function of immune cells. The present study was conducted to explore the regulation of GABA transporter (GAT)-2 on the differentiation of Th17 cells. Here we found that Th17 cells show higher abundance of GAT-2, and have distinct cellular metabolic signatures, such as the GABA shunt pathway, as compared to naïve T cells. GAT-2 deficiency had little effect on the metabolic signature in naïve T cells, but impaired the GABA uptake and GABA shunt pathway in Th17 cells. GAT-2 deficiency had little effect on T cell development and peripheral T cell homeostasis; however, its deficiency promoted Th17 cell differentiation in vitro. Mechanistically, GAT-2 deficiency promoted differentiation of Th17 cells through activation of GABA-mTOR signaling. In a mouse model of intestinal infection and inflammation, GAT-2 deficiency promoted Th17 responses. Collectively, GAT-2 deficiency promotes Th17 cell responses through activation of GABA-mTOR signaling.
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Citrobacter rodentium/fisiologia , Infecções por Enterobacteriaceae/imunologia , GABAérgicos/imunologia , Proteínas da Membrana Plasmática de Transporte de GABA/metabolismo , Intestinos/imunologia , Células Th17/imunologia , Ácido gama-Aminobutírico/metabolismo , Animais , Diferenciação Celular , Células Cultivadas , Proteínas da Membrana Plasmática de Transporte de GABA/genética , Homeostase , Intestinos/microbiologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
Type VI secretion system (T6SS) is a secretory system found in Gram-negative bacteria. One of the main structures for T6SS is Hcp (hemolysin co-regulation protein) pipeline. To investigate the role of Hcp major sub-unit genes hcp1 and hcp2 , we deleted hcp1 and hcp2 genes for constructing the in-frame gene deletion mutants. The properties of biofilm formation and the adhesion to chicken embryo fibroblasts cells (DF1 cells) were reduced in the hcp2 mutant. The knockout of hcp1 and hcp2 genes reduced the ability of the avian pathogenic Escherichia coli (APEC) strain CE129 to infect developing chicken embryos. The expression of quorum sensing (QS)-associated genes luxS, lsrR, and pfs were down-regulated in the hcp1 mutant, and the expression of type 1 fimbriae gene fimA and the adhesion-related genes fimC and papC were decreased in the hcp2 mutant, as well as the expression of anti-serum survival factor genes ompA and iss were inhibited in both hcp1 and hcp2 mutants. These results described above from this study help to further elaborate the role of HCP in APEC.
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Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/metabolismo , Escherichia coli/genética , Sistemas de Secreção Tipo VI/metabolismo , Fatores de Virulência/metabolismo , Animais , Aderência Bacteriana/genética , Carga Bacteriana , Biofilmes/crescimento & desenvolvimento , Linhagem Celular , Embrião de Galinha , Galinhas , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/patogenicidade , Proteínas de Escherichia coli/genética , Fímbrias Bacterianas/genética , Deleção de Genes , Regulação Bacteriana da Expressão Gênica , Percepção de Quorum/genética , Sistemas de Secreção Tipo VI/genética , Virulência/genética , Fatores de Virulência/genéticaRESUMO
Plants rich in luteolin have been used as Chinese traditional medicines for inflammatory diseases, hypertension, and cancer. However, little is known about the effect of luteolin on the apoptosis or autophagy of the macrophages. In this study, mouse macrophage ANA-1 cells were incubated with different concentrations of luteolin. The viability of the cells was determined by an MTT assay, apoptosis was determined by flow cytometric analysis, the level of cell autophagy was observed by confocal microscopy, and the expression levels of apoptotic or autophagic and antiapoptotic or antiautophagic proteins were detected by Western blot analysis. The results showed that luteolin decreased the viability of ANA-1 cells and induced apoptosis and autophagy. Luteolin induced apoptosis accompanied by downregulation of the expression of Bcl-2 and upregulation of the expression of caspase 3 and caspase 8. And luteolin increased FITC-LC3 punctate fluorescence accompanied by the increased expression levels of LC3-I, ATG7, and ATG12, while it suppressed the expression level of Beclin-1. Luteolin treatment resulted in obvious activation of the p38, JNK, and Akt signaling pathways, which is important in modulating apoptosis and autophagy. Thus, we concluded that luteolin induced the apoptosis and autophagy of ANA-1 cells most likely by regulating the p38, JNK, and Akt pathways, inhibiting the activity of Bcl-2 and Beclin-1 and upregulating caspase 3 and caspase 8 expression. These results provide novel insights into a therapeutic strategy to prevent and possibly treat macrophage-related diseases through luteolin-induced apoptosis and autophagy.
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Luteolina/farmacologia , Macrófagos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Animais , Apoptose , Autofagia , Caspase 3/metabolismo , Caspase 8/metabolismo , Linhagem Celular , Citometria de Fluxo , Regulação da Expressão Gênica , Macrófagos/fisiologia , Medicina Tradicional Chinesa , Camundongos , Microscopia Confocal , Transdução de SinaisRESUMO
OBJECTIVE: To compare the effect differences between auricular intradermal needling combined with erjian (HX6,7i) bloodletting and oral administration of western medicine, and to explore the efficacy of neuroendocrine level in patients with perimenopausal insomnia. METHODS: Ninety patients were randomized into an observation group and a control group, 45 cases in each one. In the observation group, auricular intradermal needling combined with erjian (HX6,7i) bloodletting were adopted alternately in the two ears. The auricular points were shen (CO10), xin (CO15), gan (CO12), shenmen (TF4), jiaogan (AH6a), neifenmi (CO18) and erjian (HX6,7i). The treatment was required once 3 days on the auricular points of one side alternatively. Oral administration of estazolam (1mg each day) was applied in the control group for 2 courses, 4 weeks as 1 course, once a day. The scores of Pittsburgh sleep quality index (PSQI), the levels of serum estrogen (E2), 5-hydroxy tryptamine (5-HT) and norepinephrine (NE) were valuated in the two groups before and after treatment. RESULTS: After treatment, the total scores of PSQI reduced in the two groups (both P<0.05), and the improvements of sleeping quality, sleeping time, sleeping difficulty, daytime dysfunction and the total PSQI score in the observation group were superior to those in the control group (all P<0.05). There was no significant difference in serum E2 before and after treatment in the two groupsï¼and between the two groups after treatment (all P>0.05). After treatment, 5-HT contents increased and NE levels decreased in the two groups (all P<0.05), with better results in the observation group (both P<0.05). The total effective rate was 95.6% (43/45) in the observation group, which was higher than 82.2% (37/45) in the control group (P<0.05). CONCLUSION: Auricular intradermal needling combined with erjian (HX6,7i) bloodletting can improve the sleep quality of patients with perimenopausal insomnia, and adjust the neurotransmitter level, which achieves better effect than western medication.
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Terapia por Acupuntura , Distúrbios do Início e da Manutenção do Sono , Pontos de Acupuntura , Sangria , Humanos , Perimenopausa , Distúrbios do Início e da Manutenção do Sono/terapia , Resultado do TratamentoRESUMO
Accumulating evidence implicates monopolar spindle-one-binder protein (MOB)2 as an inhibitor of nuclear-Dbf2-related kinase (NDR) by competing with MOB1 for interaction with NDR1/2. NDR/large tumor suppressor (LATS) kinases may function similarly to yes-associated protein (YAP) kinases and be considered as members of the Hippo core cassette. MOB2 appears to serve roles in cell survival, cell cycle progression, responses to DNA damage and cell motility. However, the underlying mechanisms involved remain unclarified. In the present study, it was demonstrated that the knockout of MOB2 by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 promoted migration and invasion, induced phosphorylation of NDR1/2 and decreased phosphorylation of YAP in SMMC-7721 cells when compared with the blank vector-transduced cells. By contrast, the overexpression of MOB2 resulted in the opposite results. Mechanistically, MOB2 regulated the alternative interaction of MOB1 with NDR1/2 and LATS1, which resulted in increased phosphorylation of LATS1 and MOB1 and thereby led to the inactivation of YAP and consequently inhibition of cell motility. The results of the present study provide evidence of MOB2 serving a positive role in LATS/YAP activation by activating the Hippo signaling pathway.
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Adherent-invasive Escherichia coli (AIEC) has recently attracted more attention because it is closely related to the pathogenicity of human inflammatory bowel disease (IBD). AIEC possesses a multitude of virulence factors. Considering these virulence factors belonging to various virulence groups, including adhesins, invasins, toxins, protectins, and siderophore-mediated iron acquisition, this review summarizes the current knowledge of how the major virulence factors assisting in AIEC survive in, adhere to, and invade host cells. A comprehensive understanding of the interaction of virulence factors with host cells will provide us a new therapeutic strategy for IBD prevention and treatment.
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Proteínas de Escherichia coli/metabolismo , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/patogenicidade , Doenças Inflamatórias Intestinais/microbiologia , Doenças Inflamatórias Intestinais/patologia , Fatores de Virulência/metabolismo , HumanosRESUMO
OBJECTIVE: To measure the amount of physical activity (PA) among obese adults, investigate the association between plasma orexin-A level and PA patterns, and explore the effect of orexin on the prevention and control of obesity. METHODS: Interviews were conducted in 218 participants (106 obese; 73 overweight; and 39 normal) who ranged in age between 18 and 70 years using a survey that included sociodemographic variables. The International Physical Activity Questionnaire (IPAQ-long version) was used to measure PA. A total of 178 participants agreed to submit blood sample collections, and plasma orexin-A content was measured by ELISA testing. RESULTS: The average level of orexin-A was 85.34 ± 42.85 ng/L in the obese group, 97.38 ± 36.72 ng/L in the overweight group, and 106.56 ± 52.09 ng/L in the control group, which was significantly different (P = 0.03). The concentration of plasma orexin-A correlated with the total PA (P = 0.000), moderate PA (obese = 0.007; overweight: P = 0.000; control: P = 0.000), and walking PA (P = 0.000) in all three groups. Working and domestic PAs were significantly associated with the plasma orexin-A level (P < 0.0001). CONCLUSIONS: The plasma orexin-A level was associated with PA in obese and overweight people, including many aspects of daily life, such as working, domestic work, and walking especially.
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Exercício Físico/fisiologia , Obesidade/sangue , Orexinas/sangue , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Adulto JovemRESUMO
Human immediate early response 2 (IER2) has been reported to function as a potential transcriptional factor or transcriptional coactivator and seems to play a pivotal role in tumor cell motility and metastasis, however, its role and underlying mechanisms in hepatocellular carcinoma (HCC) remain unknown. Herein, we demonstrated that overexpression of IER2 in HCC cells increased cell adhesion to fibronectin, migration and invasion, whereas knockdown of IER2 displayed the opposite effects. In agreement with this phenotype, IER2 expression was positively correlated with the metastatic potential and integrin ß1 (ITGB1) expression in HCC cell lines. Moreover, we demonstrated a critical role for IER2 in regulation of HCC cellextracellular matrix (ECM) adhesion and motility by the transcriptionally promoted ITGB1. Furthermore, we showed that ITGB1focal adhesion kinase (FAK)Srcpaxillin signal pathway activated by IER2 may contribute to the HCC cellECM adhesion and motility. These results demonstrated that IER2 promoted HCC cell adhesion and motility probably by directly increasing ITGB1 expression and subsequently activating the ITGB1FAKSrcpaxillin signal pathway.
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Carcinoma Hepatocelular/patologia , Proteínas Imediatamente Precoces/metabolismo , Integrina beta1/metabolismo , Neoplasias Hepáticas/patologia , Transativadores/metabolismo , Carcinoma Hepatocelular/metabolismo , Adesão Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Quinase 1 de Adesão Focal/genética , Quinase 1 de Adesão Focal/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Proteínas Imediatamente Precoces/genética , Neoplasias Hepáticas/metabolismo , Paxilina/genética , Paxilina/metabolismo , Transdução de Sinais , Transativadores/genéticaRESUMO
Human immediate early response 2 (IER2) has been characterized as a putative nuclear protein that functions as a transcription factor or transcriptional coactivator in the regulation of cellular responses, and may be involved in the regulation of tumor progression and metastasis. Data from our previous gene expression profile of the human microvascular endothelial cells during capillary morphogenesis showed a significant alteration of IER2 expression, suggesting that IER2 may participate in the regulation of the endothelial cell morphogenesis and angiogenesis. The aim of the present study was to investigate the role of IER2 in cell motility, cellmatrix adhesion and in vitro capillarylike structures formation of the human umbilical vein endothelium cells (HUVECs). IER2 was constitutively expressed in HUVECs, and lentiviralmediated depletion of IER2 significantly reduced the cell motility, cellmatrix adhesion and capillarylike structures formation of HUVECs. Results also showed that depletion and overexpression of IER2 altered the actin cytoskeleton rearrangement in HUVECs. Furthermore, results from western blot analysis showed that the activity of the focal adhesion kinase (FAK) can be regulated by IER2. These results indicated that IER2 regulates endothelial cell motility, adhesion on collagen type I matrix and the capillary tube formation, as the result of the regulation of the actin cytoskeleton rearrangement presumably via a FAKdependent mechanism.