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2.
Free Radic Biol Med ; 172: 578-589, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34242792

RESUMO

Acetaminophen (APAP) is the leading cause of acute liver failure (ALF), which is characterized by GSH depletion, oxidative stress and mitochondrial dysfunction. However, the specific mechanism of APAP-induced ALF remains to be clarified. In this study, we demonstrated that indoleamine 2,3-dioxygenase 1 (IDO1) aggravated APAP-induced ALF associated with excess lipid peroxidation, which was reversed by lipid peroxidation inhibitor (ferrostatin-1). Meanwhile, IDO1 deficiency effectively decreased the accumulation of reactive nitrogen species. Additionally, IDO1 deficiency prevented against APAP-induced liver injury through suppressing the activation of macrophages, thereby reduced their iron uptake and export, eventually reduced iron accumulation in hepatocytes through transferrin and transferrin receptor axis. In summary, our study confirmed that APAP-induced IDO1 aggravated ALF by triggering excess oxidative and nitrative stress and iron accumulation in liver. These results offer new insights for the clinical treatment of ALF or iron-dysregulated liver diseases in the future.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Dioxigenases , Falência Hepática Aguda , Acetaminofen/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Dioxigenases/metabolismo , Hepatócitos , Ferro/metabolismo , Fígado/metabolismo , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo
3.
PLoS One ; 16(7): e0255224, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34320040

RESUMO

Training individuals to interpret ambiguous information in positive ways might be an effective method of reducing social anxiety. However, little research had been carried out in Chinese samples, and the effect of interpretation training on other processes such as attentional bias also remained unclear. This study examined the effect of interpretation bias modification program (IMP) on interpretation bias, social anxiety and attentional bias, and the possible mediation effects. 51 healthy adults were randomly assigned to either a 5-session IMP training that guided them to endorse benign interpretation in ambiguous scenarios or an interpretation control condition (ICC). Self-reported measures of social anxiety symptoms, attentional bias and interpretation bias were evaluated before and after training. Results showed that compared to control group, IMP group generated more positive interpretations and less negative interpretations after training (F(1,49) = 7.65, p<0.01, ηp2 = 0.14; F(1,49) = 14.60, p<0.01, ηp2 = 0.23respectively). IMP yielded greater interpretation bias reduction (F(1,49) = 12.84, p<0.01, ηp2 = 0.21) and social anxiety reduction (F(1,49) = 21.39, p<0.01, ηp2 = 0.30) than ICC, but change in attentional bias was not significant between IMP and the control group. Change in interpretation bias did not show a significant mediation effect in the relationship between training condition and social anxiety reduction. This study provided preliminary evidence for the efficacy of the Chinese version of IMP training. Possible methodological issues and interpretations underlying the findings were discussed. This study was registered in Chinese Clinical Trial Registry (www.chitr.org.cn), a WHO approved registry. The title of registration trial was "A Study on the efficiency of cognitive bias and attentional bias training on fear and phobia" and the registration number was ChiCTR2100045670.


Assuntos
Ansiedade/psicologia , Viés de Atenção , China , Feminino , Humanos , Masculino , Interpretação Psicanalítica , Autorrelato , Tradução , Adulto Jovem
4.
Front Psychiatry ; 12: 666789, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34108897

RESUMO

Introduction: One year after the Coronavirus disease 2019 (COVID-19) outbreak, China has made substantial progress in the prevention and control of the pandemic, while the epidemic situation remains grim in China since virus may easily survive with the falling temperature in winter. The present study aimed to compare the prevalence and associated factors of anxiety between high-risk and low-risk nurses 1 year after the COVID-19 outbreak, and examine the association between resilience and anxiety and its underlying mechanisms. Method: Connor-Davidson Resilience scale, Perceived Social Support Scale and Generalized Anxiety Disorder Scale were administrated to 701 nurses from Jiangsu Province, China, 1 year after the COVID-19 outbreak. The mediating effect was examined by Mackinnon's four-step procedure, while the moderated mediation model was tested by Hayes PROCESS macro. Results: The findings presented the prevalence of anxiety among nurses was 21.4% 1 year after the COVID-19 pandemic. High-risk nurses presented a higher prevalence of anxiety (24.5 vs. 19.3%) than low-risk nurses. Age and professional title were significantly associated with anxiety only in high-risk nurses (all P < 0.05). Perceived social support mediated the association between resilience and anxiety and the indirect effect was stronger for high-risk nurses than low-risk nurses. Conclusion: Anxiety remains prevalent among nurses 1 year after the COVID-19 outbreak, and resilience plays a protective role against anxiety. Programs that enhance resilience and social support should be designed and special attention should be paid to nurses from high-risk units.

5.
Psychol Health Med ; : 1-12, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33906519

RESUMO

Healthcare workers (HCWs) exposed to Coronavirus disease 2019 (COVID-19) are not immune to stressors. This study aimed to explore the prevalence of posttraumatic stress symptoms (PTSS) among HCWs during the COVID-19 epidemic and investigate the associations among negative coping, fatigue and PTSS. A total of 507 HCWs from Anhui province enrolled in the study and completed the cross-sectional survey including demographic data, Simplified Coping Style Questionnaire (SCSQ), 14-item Fatigue Scale (FS-14), and PTSD Checklist-civilian Version (PCL-C). Univariate linear regression, Pearson correlation and Mackinnon's four-step procedure were performed in the statistical analysis. Results indicated that the prevalence of PTSS among HCWs during the pandemic was 24%. Univariate linear regression showed HCWs aged 31-40 years exhibited significantly higher scores of PTSS than those aged 51-60 (ß = 0.20, 95% CI: 0.59 to 9.41). Having at least one child was associated with a higher risk of developing PTSS (ß = 0.01, 95% CI: 0.36 to 5.45). Negative coping and fatigue were positively correlated with all three PTSS (all P < 0.001), including re-experiencing, avoidance and hyper-arousal. Fatigue has mediated the association between negative coping and PTSS among HCWs during the pandemic (ab = 0.09, SE = 0.03, bootstrap 95% CI: 0.04 to 0.14). A considerable proportion of HCWs was traumatized during the COVID-19 outbreak. Hence, the institutions should screen out and pay close attention to HCWs who tend to use negative coping (e.g., withdrawal thinking, distraction and blaming others) and arrange work scientifically to avoid overfatigue and PTSS amid the public health crisis.

6.
Aging (Albany NY) ; 13(4): 5875-5891, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33591947

RESUMO

Indoleamine 2, 3-dioxygenase 1 (IDO1) has been implicated in the pathogenesis of depression, though its molecular mechanism is still poorly understood. We investigated the molecular mechanism of IDO1 in depression by using the chronic unpredictable mild stress (CUMS) model in Ido1-/- mice and WT mice. The brain blood oxygen level dependent (BOLD) signals in mice were collected by functional magnetic resonance imaging (fMRI) technology. IDO1 inhibitor INCB024360 was intervened in dorsal raphe nucleus (DRN) through stereotactic injection. We found an elevation of serum IDO1 activity and decreased 5-HT in CUMS mice, and the serum IDO1 activity was negatively correlated with 5-HT level. Consistently, IDO1 was increased in hippocampus and DRN regions, accompanied by a reduction of hippocampal BDNF levels in mice with CUMS. Specifically, pharmacological inhibition of IDO1 activity in the DRN alleviated depressive-like behaviour with improving hippocampal BDNF expression and neurogenesis in CUMS mice. Furthermore, ablation of Ido1 exerted stress resistance and decreased the sensitivity of depression in CUMS mice with the stable BOLD signals, BDNF expression and neurogenesis in hippocampus. Thus, IDO1 hyperactivity played crucial roles in modulating 5-HT metabolism and BDNF function thereby impacting outcomes of hippocampal neurogenesis and BOLD signals in depressive disorder.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/metabolismo , Hipocampo/metabolismo , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Triptofano/metabolismo , Animais , Depressão/diagnóstico por imagem , Depressão/tratamento farmacológico , Depressão/etiologia , Núcleo Dorsal da Rafe/metabolismo , Avaliação Pré-Clínica de Medicamentos , Hipocampo/diagnóstico por imagem , Hipocampo/efeitos dos fármacos , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Imageamento por Ressonância Magnética , Camundongos Endogâmicos C57BL , Neurogênese/efeitos dos fármacos , Oximas/farmacologia , Oximas/uso terapêutico , Estresse Psicológico/complicações , Estresse Psicológico/metabolismo , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Triptofano Hidroxilase/metabolismo
7.
Cell Death Dis ; 12(1): 16, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33414436

RESUMO

Liver fibrosis is a course of chronic liver dysfunction, can develop into cirrhosis and hepatocellular carcinoma. Inflammatory insult owing to pathogenic factors plays a crucial role in the pathogenesis of liver fibrosis. Indoleamine 2,3-dioxygenase 1 (IDO1) can affect the infiltration of immune cells in many pathology processes of diseases, but its role in liver fibrosis has not been elucidated completely. Here, the markedly elevated protein IDO1 in livers was identified, and dendritic cells (DCs) immune-phenotypes were significantly altered after BDL challenge. A distinct hepatic population of CD11c+DCs was decreased and presented an immature immune-phenotype, reflected by lower expression levels of co-stimulatory molecules (CD40, MHCII). Frequencies of CD11c+CD80+, CD11c+CD86+, CD11c+MHCII+, and CD11c+CD40+ cells in splenic leukocytes were reduced significantly. Notably, IDO1 overexpression inhibited hepatic, splenic CD11c+DCs maturation, mature DCs-mediated T-cell proliferation and worsened liver fibrosis, whereas above pathological phenomena were reversed in IDO1-/- mice. Our data demonstrate that IDO1 affects the process of immune cells recruitment via inhibiting DCs maturation and subsequent T cells proliferation, resulting in the promotion of hepatic fibrosis. Thus, amelioration of immune responses in hepatic and splenic microenvironment by targeting IDO1 might be essential for the therapeutic effects on liver fibrosis.


Assuntos
Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Cirrose Hepática/enzimologia , Cirrose Hepática/patologia , Animais , Ductos Biliares/enzimologia , Ductos Biliares/patologia , Ductos Biliares/cirurgia , Diferenciação Celular/fisiologia , Hepatócitos/enzimologia , Hepatócitos/metabolismo , Hepatócitos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
8.
PLoS One ; 15(12): e0243884, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33301523

RESUMO

PURPOSES: Since a considerable number of health care workers (HCWs) were sent to Wuhan to aid COVID-19 control during the epidemic, non-frontline HCWs who stayed in local hospitals had to work overload to provide daily health care services for other health issues, which makes them more vulnerable to experience fatigue. Self-efficacy is suggested as a protective factor for fatigue. Nonetheless, less is known regarding the underlying mechanisms. This research aimed to explore the prevalence of fatigue among non-frontline HCWs during the pandemic, investigate the mediating effect of posttraumatic stress disorder (PTSD) symptoms and moderating effect of negative coping in the association between self-efficacy and fatigue. METHODS: General Self-Efficacy Scale, PTSD Checklist-Civilian Version, Simplified Coping Style Questionnaire and 14-item Fatigue Scale were administrated to 527 non-frontline HCWs from Anhui Province, China. The mediating effect was examined by Mackinnon's four-step procedure, while Hayes PROCESS macro was used to test the moderated mediation model. RESULTS: The prevalence of fatigue among non-frontline HCWs was 56.7%. The effect of self-efficacy on fatigue was partially mediated by PTSD symptoms (ab = -0.146, SE = 0.030, 95% CI = [-0.207, -0.095]). Additionally, negative coping moderated both the direct effect of self-efficacy on fatigue (ß = -0.158, P<0.001) and the mediating effect of PTSD symptoms (ß = 0.077, P = 0.008). When the standard score of negative coping increased to 1.49 and over, the direct association between self-efficacy and fatigue became insignificant. Likewise, the effect of self-efficacy on PTSD symptoms had no statistical significance when the standard score of negative coping was -1.40 and lower. CONCLUSIONS: More than half non-frontline HCWs suffered from fatigue during COVID-19. For those who tend to use negative coping, it might be crucial to design programs combining the enhancement of self-efficacy, preventions for PTSD symptoms and interventions for fatigue.


Assuntos
Adaptação Psicológica , COVID-19/epidemiologia , Fadiga/epidemiologia , Pessoal de Saúde , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adulto , China/epidemiologia , Estudos Transversais , Surtos de Doenças , Fadiga/psicologia , Feminino , Pessoal de Saúde/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Autoeficácia , Transtornos de Estresse Pós-Traumáticos/psicologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Adulto Jovem
9.
Medicine (Baltimore) ; 99(47): e23340, 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33217874

RESUMO

Although social anxiety as a ubiquitous emotion impacting people's social behaviors has aroused much researchers' interest in exploring its cognitive behavioral model, no previous study has focused on soldiers with different social anxiety within the context of the specific military environment.To explore the associations between social anxiety and interpersonal information processing concerted on interpretation and judgment, the study may provide an intervention point for soldiers to ameliorate social anxiety and accommodate to the military-life environment.A self-reported questionnaire and 2 behavioral tasks were conducted in the cross-section study to explore the associations.Seventy-four soldiers were randomly recruited from a naval base. The Interpersonal Anxiety Scale was used to assess social anxiety of soldiers. Two behavioral tasks were designed to test the characteristics of interpersonal information processing, one for interpretation bias and the other for judgment bias.This cross-sectional study showed social anxiety had a significant negative correlation with interpretation bias and abidance (as judgment bias), signaling that soldiers with higher levels of social anxiety had a stronger tendency to negative interpretation bias and showed lower abidance. The mediating effect analysis showed the interpretation bias could indirectly affect the soldier's abidance through social anxiety. Notably, none of the interaction effects of social anxiety and social information types were statistically significant; therefore, the level of social anxiety predetermined the abidance of soldiers.Soldiers' social anxiety has an influence on processing military-life interpersonal information, and it plays a certain intermediary role in the associations between low abidance and negative interpretation bias. The stronger negative interpretation bias than positive bias of soldiers, the higher social anxiety they could show with the less possibility to abide, which might result in behaviors against the military collective requirements. Social anxiety has the primary effect on the abidance of soldiers; hence, in the future, the interpretation bias modification could be a plausible cognitive-behavior therapy to help soldiers ameliorate social anxiety, thus contributing to enhancing their sense of belonging to the troops and accommodation to military life.


Assuntos
Ansiedade/psicologia , Julgamento , Militares/psicologia , Autoimagem , Adulto , China , Estudos Transversais , Emoções , Humanos , Masculino , Inquéritos e Questionários
10.
PLoS One ; 15(10): e0241301, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33125424

RESUMO

PURPOSES: Evidence suggests evening-type individuals have a higher risk of reporting psychological distress than morning-type individuals. However, less is known regarding the underlying processes that might mediate or moderate this association among Chinese rural population. This study aimed to evaluate the prevalence of psychological distress, investigate whether sleep quality would mediate the association between chronotype and psychological distress and explore whether age would moderate the direct or indirect effect of the mediation model. METHODS: The cross-sectional study utilized a sample of 884 rural residents from rural regions in Anqing City, Anhui Province, China. Morningness-Eveningness Questionnaire (MEQ), Pittsburgh Sleep Quality Index (PSQI) and 21-item Depression Anxiety Stress Scale (DASS-21) were used to measure chronotype, sleep quality and psychological distress, respectively. MacKinnon's four-step procedure was employed to examine the mediation effect, while Hayes PROCESS macro (model 59) was used to perform the moderated mediation analysis. RESULTS: The prevalence of psychological distress among Chinese rural population was 33.4%. The association between chronotype and psychological distress was partially mediated by sleep quality (indirect effect = - 0.05, 95% CI = [-0.08, -0.03]). In addition, age moderated the first stage (sleep quality-psychological distress) of the indirect effect, with the indirect effect being attenuated for older rural residents. As suggested by Johnson-Neyman technique, the association between sleep quality and psychological distress was only significant when the age of the participant was lower than 48.59. CONCLUSIONS: The incidence of psychological distress among Chinese rural residents cannot be neglected. Interventions for the enhancement of sleep quality to prevent and reduce psychological distress should be prioritized to rural residents who are prone to eveningness, especially those who are younger.


Assuntos
Angústia Psicológica , Sono/fisiologia , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático/psicologia , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Rural/estatística & dados numéricos , Fatores Socioeconômicos , Inquéritos e Questionários , Adulto Jovem
11.
Free Radic Biol Med ; 160: 178-190, 2020 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-32771520

RESUMO

Liver fibrosis can develop into liver cirrhosis and hepatocellular carcinoma substantially without effective available treatment currently due to rarely characterized molecular pathogenesis. Indoleamine 2,3-dioxygenase 1(IDO1) can be detected on antigen-presenting cells (APCs) and modulates various immune responses. However, the role of IDO1 in the regulation of dendritic cells (DCs) during liver fibrosis is rarely reported. Here, we found that hepatic IDO1 was up-regulated during CCL4-induced liver fibrosis, which accompanied by a significant decrease in the frequencies of CD11c+CD80+, CD11c+CD86+, CD11c+CD40+ and CD11c+MHCII+ cells and a reduction in the subsequent T cell proliferation rate, whereas these changes were reversed significantly in IDO1-/- mice. Overexpressing IDO1 by adeno-associated viral vector serotype 9 (AAV9) significantly inhibited the maturation status of DCs, worsened fibrosis. In vitro studies showed that significantly elevated CD80, CD86, CD40 and MHCII expression were observed in BMDCs derived from IDO1-/- mice. Moreover, the maturation of BMDCs derived from WT mice were significantly increased after stimulated with IDO1 inhibitor (1-methyl- D -tryptophan). Nuclear factor E2-related factor 2 (Nrf2), a key regulator of the cellular adaptive response to oxidative insults and inflammation, exhibited a markedly decrease in the liver of WT fibrotic mice, nevertheless, knockout of IDO1 enhanced the protein level of Nrf2. Moreover, the expression of IDO1 and Nrf2 exhibited inverse colocalization pattern suggesting that ectopically expressed IDO1 down-regulated Nrf2. Additionally, up-regulation of IDO1 was also observed in the livers of Nrf2-/- fibrotic mice. Taken together, these data uncovered mutual antagonism between IDO1 and Nrf2 on the maturation status of DCs during hepatic fibrosis.


Assuntos
Indolamina-Pirrol 2,3,-Dioxigenase , Cirrose Hepática , Fator 2 Relacionado a NF-E2 , Animais , Células Dendríticas , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Cirrose Hepática/genética , Camundongos , Fator 2 Relacionado a NF-E2/genética , Triptofano
13.
Biochem Pharmacol ; 180: 114153, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32679126

RESUMO

Caveolin-1 (Cav-1) is a multifunctional protein and critical for the production of nitric oxide (NO) in intestinal physiological and pathological conditions, but its role in the inflammatory bowel disease(IBD) are still controversial. In this study we tested the hypothesis that Cav-1 could be an important cellular defense against IBD through inhibiting nitrosative stress and mucosal barrier damage. Male wild-type mice and Cav-1 knockout (Cav-1-/-) mice were subjected to 3% dextran sodium sulfate(DSS) for 7d to establish the experimental colitis model. A representative iNOS inhibitor (1400 W) was adopted to suppress the activity of iNOS in parallel group. Body weight and disease activity index were monitored. The colon tissues were evaluated through histological analysis. We found Cav-1 was down-regulated in the colon tissue and accompanied with the increase of iNOS and NO levels after DSS administration. Cav-1-/- mice were greatly increased susceptibility to DSS-induced colitis with the more weight loss and higher disease score than WT mice. Ablation of Cav-1gene significantly resulted in RNS overproduction, tight junctions impaired and inflammation elevated, which aggravated the severity of the intestinal damages. Furthermore, pharmacologic inhibition of iNOS by 1400 W significantly attenuated DSS-induced colitis in both WT and Cav-1-/- groups. Our results revealed an important role of Cav-1 in preventing intestinal nitrosative stress and mucosal barrier damage in the development of DSS-induced colitis.


Assuntos
Caveolina 1/deficiência , Colite/induzido quimicamente , Colite/metabolismo , Sulfato de Dextrana/toxicidade , Mucosa Intestinal/metabolismo , Estresse Nitrosativo/fisiologia , Animais , Colite/prevenção & controle , Mucosa Intestinal/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Nitrosativo/efeitos dos fármacos
14.
PLoS One ; 15(5): e0233831, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32470007

RESUMO

PURPOSES: During the outbreak of Coronavirus Disease 2019 (COVID-19) all over the world, the mental health conditions of health care workers are of great importance to ensure the efficiency of rescue operations. The current study examined the effect of social support on mental health of health care workers and its underlying mechanisms regarding the mediating role of resilience and moderating role of age during the epidemic. METHODS: Social Support Rating Scale (SSRS), Connor-Davidson Resilience scale (CD-RISC) and Symptom Checklist 90 (SCL-90) were administrated among 1472 health care workers from Jiangsu Province, China during the peak period of COVID-19 outbreak. Structural equation modeling (SEM) was used to examine the mediation effect of resilience on the relation between social support and mental health, whereas moderated mediation analysis was performed by Hayes PROCESS macro. RESULTS: The findings showed that resilience could partially mediate the effect of social support on mental health among health care workers. Age group moderated the indirect relationship between social support and mental health via resilience. Specifically, compared with younger health care workers, the association between resilience and mental health would be attenuated in the middle-aged workers. CONCLUSIONS: The results add knowledge to previous literature by uncovering the underlying mechanisms between social support and mental health. The present study has profound implications for mental health services for health care workers during the peak period of COVID-19.


Assuntos
Infecções por Coronavirus/epidemiologia , Pessoal de Saúde/psicologia , Pneumonia Viral/epidemiologia , COVID-19 , China/epidemiologia , Medicina de Desastres , Humanos , Serviços de Saúde Mental , Pandemias , Escalas de Graduação Psiquiátrica , Resiliência Psicológica , Apoio Social
15.
Asian J Psychiatr ; 51: 102111, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32361388

RESUMO

The spread of Corona Virus Disease 2019 (COVID-19) has become a global major public health event, threatening people's physical and mental health and even life safety. This study is to investigate the psychological abnormality in health care workers battling the COVID-19 epidemic and to explore the associations among social support, resilience and mental health. A total of 1521 health care workers, of whom 147 had public health emergency experience while 1374 showed no experience, completed the Symptom Check-List-90 (SCL-90), Chinese version of Connor-Davidson resilience scale (CD-RISC) and Social Support Rating Scale (SSRS). χ2 test, t test and multiple regression analyses were used in statistical analysis. The results showed that people without public health emergency treatment experience showed worse performance in mental health, resilience and social support, and tended to suffer from psychological abnormality on interpersonal sensitivity and photic anxiety. This finding suggested that high levels of training and professional experience, resilience and social support were necessary to health care workers who are first taking part in public health emergence.


Assuntos
Sintomas Comportamentais/epidemiologia , Infecções por Coronavirus/terapia , Pessoal de Saúde/estatística & dados numéricos , Pneumonia Viral/terapia , Competência Profissional , Resiliência Psicológica , Apoio Social , Adulto , COVID-19 , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias
16.
Biomed Pharmacother ; 126: 110092, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32203890

RESUMO

Actinidia chinensis Planch (ACP) was the kiwifruit plant Chinese kiwifruit Actinidia chinensis Planch Root, which had been approved to be an anti-tumor drug widespread in clinical. However, the specific mechanism of ACP in resistance to gastric cancer remained unclear. Therefore, our study was dedicated to investigate the anti-proliferation and anti-migration effects of ACP on gastric cancer cells and its molecular mechanisms. Firstly, we utilized HPLC-MS to analyze the composition of ACP decoction, the results showed that ACP contained two main anti-tumor components, Ursolic acid and Oleanolic acid. The proliferation and migration ability of HGC-27 were examined by CCK-8 and cell scratch tests respectively. In addition, we also investigated HGC-27 cells apoptosis, mesenchymal phenotype and ferroptosis after ACP rat drug-containing serum (ACPs) treatment. EGFP-expressing lentiviral vectors were utilized to construct HGC-27 cells which containing green fluorescence. Then we take advantages of containing green fluorescence cells to establish a zebrafish xenograft model in vivo. The CCK-8 and cell scratch experiments verified that ACPs significantly inhibited proliferation and migration of HGC-27 in vitro. ACPs increased cells apoptosis rate, while were rescued by apoptosis inhibitor Z-VAD-FMK. Furthermore, ACPs downregulated the expression levels of Vimentin protein and Snail protein markedly. Intriguingly, ACPs increased the accumulation of ROS via inhibited the glutathione peroxidase 4 (GPx4) and xCT (SLC7A11) proteins, while were inhibited by Ferrostatin-1 (Fer-1) significantly. Furthermore, the zebrafish xenograft study further confirmed that administration of ACP suppressed the xenograft growth and metastasis of transplanted HGC-27 cells in vivo. In conclusion, ACP was a promising antineoplastic agent for the treatment of gastric cancer by regulating apoptosis, ferroptosis and mesenchymal phenotype.


Assuntos
Actinidia/química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Biomarcadores , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Humanos , Espectrometria de Massas , Camundongos , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Ratos , Espécies Reativas de Oxigênio
17.
Medicine (Baltimore) ; 99(3): e18746, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011456

RESUMO

Converging evidence reveals the negative interpretation bias in anxiety. Given that anxiety is a severe psychological problem among Chinese military personnel, the present study examined whether high trait anxiety military personnel showed negative interpretation bias in real-world situations and whether their interpretations were influenced by self-relevance.The sample included 24 high trait anxiety (H-TA) and 22 low trait anxiety (L-TA) Chinese military servicemen. Participants completed 20 open-ended ambiguous scenarios by deciding how much they believed in the positive and negative ending of each sentence. The 20 scenarios were designed according to real life in military and half of them were self-relevant and the others were non-self-relevant.A 2(group) ×2(self-relevance) ANOVA of positive and negative endings revealed that compared to L-TA, H-TA believed more in negative continuations and less in positive continuations. Moderate correlations were found between samples' believes in positive and negative endings and their trait anxiety scores. Military personnel showed more positive interpretation biases in non-self-relevant scenarios than in self-relevant scenarios.These findings are the first to show interpretation bias in military situations, and interventional strategies to modify servicemen's interpretation bias could be designed according to military situations.


Assuntos
Transtornos de Ansiedade/psicologia , Militares/psicologia , Adaptação Psicológica , Adolescente , Adulto , China , Humanos , Masculino , Testes Neuropsicológicos , Repressão Psicológica
18.
Free Radic Biol Med ; 152: 668-679, 2020 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-31945497

RESUMO

Ferroptosis is a recently recognized form of regulated cell death that is characterized by lipid peroxidation. However, the molecular mechanisms of ferroptosis in acute immune hepatitis (AIH) are largely unknown. In this study, we investigated the classical ferroptotic events in the livers of mice with concanavalin A (ConA) to induce AIH. The dramatically upregulated gene indoleamine 2, 3-dioxygenase 1 (IDO1) was identified with AIH, and its role in generation of ferroptosis and reactive nitrogen species (RNS) was assessed both in vitro and in vivo by genetic deletion or pharmacologic inhibition of IDO1. We observed that ferroptosis contributed to the ConA-induced hepatic damage, which was confirmed by the therapeutical effects of ferroptosis inhibitor (ferrostatin-1). Noteworthy, upregulation of hepatic IDO1 and nitrative stress in ConA-induced hepatic damage were also remarkably inhibited by the ferroptosis abolishment. Additionally, IDO1 deficiency contributed to ferroptosis resistance by activating solute carrier family 7 member 11 (SLC7A11; also known as xCT) expression, accompanied with the reductions of murine liver lesions and RNS. Meanwhile, IDO inhibitor 1-methyl tryptophan alleviated murine liver damage with the reduction of inducible nitric oxide synthase and 3-nitrotyrosine expression. Consistent with the results in vivo, hepatocytes-specific knockdown of IDO1 led to ferroptosis resistance upon exposure to ferroptosis-inducing compound (Erastin) in vitro, whereas IDO1 overexpression aggravated the classical ferroptotic events, and the RNS stress. Overall, these results revealed a novel molecular mechanism of ferroptosis with the key feature of nitrative stress in ConA-induced liver injury, and also identified IDO1-dependent ferroptosis as a potential target for the treatment of AIH.


Assuntos
Ferroptose , Hepatite , Animais , Hepatócitos , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Camundongos
19.
Free Radic Biol Med ; 148: 151-161, 2020 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-31877357

RESUMO

Ferroptosis is a new regulated cells death manner defined as results of iron-dependent accumulation of lipid peroxidation. However, the specific mechanisms of regulating ferroptosis remain unclear. In our present study, we demonstrated that Caveolin-1 (Cav-1) played a central role in protecting hepatocytes against ferroptosis in autoimmunity-mediated hepatitis (AIH). The down-regulated Cav-1 in liver tissues, accompanied by ferroptotic events and RNS production, were contributed to the outcome of ConA-induced hepatic damage, which were rescued by ferrostatin-1 (an inhibitor of ferroptosis) in vivo and in vitro. Additionally, Cav-1 deficiency aggravated ConA-induced hepatocellular death and ferroptosis associated with excessive nitrogen stress response. Short hairpin RNA of Cav-1 in hepatocytes promoted ferroptosis and nitrative stress in response to erastin in vitro, which was ameliorated by Cav-1 over-expression. Meanwhile, administration of the iNOS inhibitor (1400W) or ONOO- scavenger (Fe-TMPyP), diminished reactive nitrogen species (RNS), remarkably reduced hepatocytes ferroptosis and attenuated ConA-induced liver damage. Furthermore, immune inhibition by gadolinium chloride (GdCl3), a well-known Kupffer cell depletor, elevated hepatic Cav-1 but inhibited ferroptosis and nitrative stress under ConA exposure. In conclusion, these data revealed a novel molecular mechanism of ferroptosis with the Cav-1 regulation was essential for pathogenesis of ConA-induced hepatitis. Downstream of Cav-1, RNS-mediated ferroptosis was a pivotal step that drives the execution of acute immune-mediated hepatic damage.


Assuntos
Ferroptose , Caveolina 1/genética , Hepatócitos , Peroxidação de Lipídeos , Nitrogênio
20.
Life Sci ; 216: 305-312, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30031061

RESUMO

AIMS: Alcoholic liver disease (ALD) is a leading health risk worldwide, which can induce hepatic steatosis, progressive fibrosis, cirrhosis and even carcinoma. As a potential therapeutic drug for ALD, naringin, an abundant flavanone in grapefruit, could improve resistance to oxidative stress and inflammation and protects against multiple organ injury. However, the specific mechanisms responsible for protection against alcoholic injury remain not fully understood. In this study, we aim to investigate the effect and the regulatory mechanisms of naringin in the liver and whole body after alcohol exposure under zebrafish larvae system. MAIN METHODS: At 96 h post fertilization (hpf), larvae from wild-type (WT) and transgenic zebrafish, with liver-specific eGFP expression (Tg(lfabp10α:eGFP)), were exposed to 2% ethanol for 32 h to establish an ALD model. Different endpoints, such as morphological changes in liver shape and size, histological changes, oxidative stress-related free radical levels, apoptosis and the expression of certain genes, were chosen to verify the essential impact of naringin in alcohol-induced liver lesions. KEY FINDINGS: Subsequent experiments, including Oil red O, Nile red, pathological hematoxylin and eosin (H&E), and TUNEL staining and qPCR, revealed that naringin treatment reduced alcoholic hepatic steatosis, and this inhibitory effect was dose dependent. Specifically, a 25 mg/L dose resulted in an almost normal response. SIGNIFICANCE: This finding suggested that naringin may inhibit alcoholic-induced liver steatosis and injury by attenuating lipid accumulation and reducing oxidative stress and apoptosis.


Assuntos
Fígado Gorduroso Alcoólico/prevenção & controle , Flavanonas/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Hepatopatias Alcoólicas/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Animais , Animais Geneticamente Modificados , Apoptose/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etanol/efeitos adversos , Flavanonas/administração & dosagem , Proteínas de Fluorescência Verde/genética , Marcação In Situ das Extremidades Cortadas , Larva , Reação em Cadeia da Polimerase em Tempo Real , Peixe-Zebra
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