RESUMO
BACKGROUND: Numerous studies have found that inhibiting the expression of NLRP3 inflammasome can significantly improve depressive-like behaviors in mice, but the research on its effect on cognitive decline in depression and its mechanism is still lacking. This study aimed to elucidate the role of NLRP3 inflammasome in cognitive decline in depression and explore the common neuro-immunological mechanisms of depression and Alzheimer's disease (AD). METHODS: Male C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS) for 5 weeks, treatment group was administered with the NLRP3 inhibitor MCC950 (10 mg/kg, i.p.), fluoxetine served as positive control. Then, the mice were assessed for cognitive behaviors and depression-like behaviors, and changes of microglia and neurons in hippocampus and levels of Aß metabolic pathway and tau protein were measured. To explore the mechanism of NLRP3 activation on neurons, we performed in vitro studies using BV2 microglia and mouse primary neurons. Furthermore, we focused on the role of NLRP3 inflammasome in the function of neurons and the expression of AD pathological indicators. RESULTS: CUMS induced depressive-like behaviors and cognitive decline in mice, which could be reversed by inhibiting NLRP3 inflammasome. MCC950, a specific NLRP3 inhibitor, alleviated CUMS-induced neuron injury and AD-like pathological changes, including the abnormal expression of Aß metabolic pathway and the hyper-phosphorylation of tau protein. LPS (1 µg/mL) + ATP (1 mM) treatment activated the expression of NLRP3 inflammasome and IL-1ß in vitro. In vitro experiment also proved that inhibiting the expression of NLRP3 inflammasome in microglia can restore the Aß metabolic pathway to normal, decrease neuronal tau protein phosphorylation and protect neurons. CONCLUSIONS: Inhibition of NLRP3 inflammasome effectively alleviated CUMS-induced depressive-like behaviors and cognitive decline in mice, and inhibited the activation of AD physiological indicators.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Camundongos , Masculino , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doença de Alzheimer/metabolismo , Proteínas tau , Camundongos Endogâmicos C57BL , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologiaRESUMO
BACKGROUND: The COVID-19 pandemic has lasted for more than 1 year, causing far-reaching and unprecedented changes in almost all aspects of society. This study aimed to evaluate the long-term consequences of the COVID-19 pandemic on depression and anxiety, and explore the factors associated with it. METHODS: A cross-sectional study using an online survey was conducted to assess mental health problems from February 2 to February 9, 2021 by using patient health questionnaire-9 (PHQ-9) and generalized anxiety disorder-7 (GAD-7). The insomnia severity index (ISI), demographic data and COVID-19 related variables were measured by a self-designed questionnaire. The factors associated with depressive and anxiety symptoms were identified by Pearson chi-square test and binary logistic regression analysis. RESULTS: In the study that 1171 participants enrolled, the overall prevalence of depressive and anxiety symptoms among general people was 22.6 and 21.4% respectively in the present study. Living alone was a potential risk factor for depressive symptoms, while regular exercises was a potential protective factor. The prevalence of depressive and anxiety symptoms was significantly associated with the severity of insomnia symptoms and the negative feelings about pandemic. CONCLUSION: COVID-19 pandemic- related chronic stress has brought about profound impacts on long-term mental health in the general population. The level of insomnia and a negative attitude towards the pandemic are significantly correlated with unfavorable mental health. However, we failed to found a significant association of age and gender with the mental health symptoms, although they were recognized as well-established risk factors during the outbreak by some other studies. This discrepancy may be because the acute and chronic effects of the pandemic are influenced by different factors, which reminds that more attention should be paid to the intrinsic psychological factors and physical reactions towards COVID-19.
Assuntos
COVID-19 , Pandemias , Ansiedade/epidemiologia , Transtornos de Ansiedade/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Humanos , Prevalência , SARS-CoV-2RESUMO
This study examined the impact of brief mindfulness meditation (BMM) training on attention function and dispositional mindfulness in young males. 126 male participants aged 18-26 from the security industry were recruited, with 66 participants (M = 22.84, SD = 2.41) undergoing 4-week mindfulness meditation training and 60 participants (M = 23.07, SD = 2.29) in the active control group. The intervention was integrated into the participants' schedules. Measures included Five Facets Mindfulness Questionnaires (FFMQ), concentration and assignment attention tasks, Attention Network Test (ANT), and saliva cortisol concentration. Findings indicate that brief mindfulness meditation training led to significant improvements in participants' FFMQ scores), with marginally significant enhancements in the executive control network. However, it had no discernible effect on alertness and orientation networks. Additionally, brief mindfulness meditation training enhanced attention allocation to light stimulation and prolonged individual attention. Surprisingly, there was no observed decrease in saliva cortisol concentration among meditation training participants. However, this study did not find a decrease in saliva cortisol concentration in the brief mindfulness meditation group. In conclusion, this study highlights the potential of a 4-week brief mindfulness meditation training program to enhance dispositional mindfulness and specific aspects of attention function in young men, offering practical insights into the benefits of mindfulness meditation practices for this demographic.
Assuntos
Atenção , Hidrocortisona , Meditação , Atenção Plena , Saliva , Humanos , Masculino , Atenção Plena/métodos , Atenção/fisiologia , Adulto Jovem , Hidrocortisona/metabolismo , Adulto , Saliva/metabolismo , Adolescente , Função Executiva/fisiologiaRESUMO
OBJECTIVE: To examine whether contrast-enhanced ultrasound (CEUS) parameters in patients with advanced pancreatic cancer could be used to assess response to treatment with pulsed-wave high intensity focused ultrasound (PW-HIFU). METHODS: We prospectively recorded the pretreatment and posttreatment CEUS related parameters, CA19-9, pain scores of 30 patients with advanced pancreatic cancer treated with PW-HIFU treatment. Correlation of clinical parameters, tumor characteristics, and PW-HIFU treatment energy with CEUS parameters were analyzed. RESULTS: Pain score decreased after treatment (from 4.80±2.14 to 3.28±1.93, pâ=â0.001). CA19-9 dropped in RT decreased group, 4 weeks after one session PW-HIFU, compared with prolonged group (pâ=â0.013). According to the display of blood vessels in the mass by CEUS, tumors were classified by vessel grade (VG), VG1: no vessel can be seen; VG 2: vessels diameter <â5âmm; VG 3: vessels diameter >â5âmm. VGs were different between increased and decreased relative rise intensity (rRI) groups (pâ=â0.008). VG1 group shown a decreased rRI after treatment, while VG3 group showed the opposite trend (pâ=â0.006). CONCLUSIONS: CEUS can evaluating response to PW-HIFU in advanced pancreatic cancer. Quantitative analysis may help to assess the short-term efficacy of patients and help for individualized treatment.
Assuntos
Tratamento por Ondas de Choque Extracorpóreas , Ablação por Ultrassom Focalizado de Alta Intensidade , Neoplasias Pancreáticas , Antígeno CA-19-9 , Meios de Contraste/uso terapêutico , Humanos , Dor , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/terapia , Resultado do Tratamento , Neoplasias PancreáticasRESUMO
INTRODUCTION: This study aimed to test the efficacy of an oral-intake Chinese herbal medicine in enhancing the cognitive and emotional functions of individuals in a simulated microgravity condition. The herbal medicine consisted of ingredients that may enhance cognitive and emotional functions in an extreme environment. METHODS: There were 14 healthy male subjects who were randomly assigned to a Chinese medicine (CMG) or a control (CG) group and underwent a 60-d 6 degree head-down bed-rest protocol. Testing was conducted before (Day -3), throughout (Days 3, 7, 20, 40, 57), and after (Days +3, +10) the bedrest protocol. The Arrow Test, Balloon Analog Risk Task (BART), Dual Task, and Affect Grid were administered on all testing days. RESULTS: The CMG demonstrated consistently higher scores on the BART (Days 20 to 40; Mean: CMG, 43.0 to 46.2 and CG, 30.2 to 25.5) and lower levels of arousal on the Affect Grid (Days 7 to 40; Mean: CMG, 6.9 to 6.7 and CG, 8.1 to 8.0) than did the CG. The CMG showed significantly higher performance on the Arrow Test (incompatible condition) at the beginning of the bed-rest period (Day 3 to 7; Mean: 799.5 ms and 763.1 ms, respectively) which was not observed in the CG. DISCUSSIONS: Results suggest that the Chinese herbal medicine may calm subjects' emotions by lowering the arousal level. At the same time, it may have produced positive effects in enhancing advantageous risk-taking and to a lesser extent self-regulatory behaviors (in the early phase).
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Psicotrópicos/uso terapêutico , Contramedidas de Ausência de Peso , Simulação de Ausência de Peso/psicologia , Adulto , Atenção , Repouso em Cama , Cognição , Tomada de Decisões , Decúbito Inclinado com Rebaixamento da Cabeça , Humanos , Masculino , Testes Neuropsicológicos , Assunção de Riscos , Adulto JovemRESUMO
This study assessed the biological functions of LIM-domain-only 4 (LMO4) in gastric cancer (GC) and investigated the underlying molecular mechanisms. It was found that the expression of LMO4 was significantly upregulated in GC tissues and closely associated with clinicopathological factors, overall survival and disease-free survival of patients. After knockdown of LMO4 in MGC-803 and SGC-7901 cells, invasion and proliferation were obviously suppressed. Furthermore, LMO4 knockdown suppressed the phosphorylation of phosphatidylinositol 3-kinase (PI3K), Akt and mammalian target of rapamycin (mTOR). Miltefosine, the inhibitor of PI3K/Akt, and dactolisib, the inhibitor of mTOR, abrogated recombinant LMO4-induced GC cell invasion and proliferation. These results suggest that LMO4 promotes GC cell invasion and proliferation mainly through PI3K-Akt-mTOR signaling. LMO4 may serve as a potential therapeutic target for GC in the future.
RESUMO
BACKGROUND: Decoy receptor 3 (DcR3) binds to Fas ligand (FasL) and inhibits FasL-induced apoptosis. The receptor is overexpressed in hepatocellular carcinoma (HCC), and it is associated with the growth and metastatic spread of tumors. DcR3 holds promises as a new target for the treatment of HCC, but little is known regarding the molecular mechanisms underlying the oncogenic properties of DcR3. The present work, therefore, examined the role of DcR3 in regulating the growth and invasive property of liver cancer cell HepG2. METHODS: HepG2 cells were stably transfected with lentivirus-based short hairpin RNA vector targeting DcR3. After the knockdown of DcR3 was confirmed, cell proliferation, clone formation, ability of migrating across transwell membrane, and wound healing were assessed in vitro. Matrix metalloproteinase-9 (MMP 9) and vascular epithelial growth factor (VEGF)-C and D expressions of the DcR3 knockdown were also studied. Comparisons between multiple groups were done using one-way analysis of variance (ANOVA), while pairwise comparisons were performed using Student's t test. P< 0.05 was regarded statistically significant. RESULTS: DcR3 was overexpressed in HepG2 compared to other HCC cell lines and normal hepatocyte Lo-2. Stable knockdown of DcR3 slowed down the growth of HepG2 (P < 0.05) and reduced the number of clones formed by 50% compared to those without DcR3 knockdown (P < 0.05). The knockdown also reduced the migration of HepG2 across transwell matrix membrane by five folds compared to the control (P < 0.05) and suppressed the closure of scratch wound (P < 0.05). In addition, the messenger RNA levels of MMP 9, VEGF-C, and VEGF-D were significantly suppressed by DcR3 knockdown by 90% when compared with the mock control (P < 0.05). CONCLUSIONS: Loss of DcR3 impaired the growth and invasive property of HCC cell line of HepG2. Targeting DcR3 may be a potential therapeutic approach for the treatment of HCC.
Assuntos
Membro 6b de Receptores do Fator de Necrose Tumoral/metabolismo , Análise de Variância , Movimento Celular/genética , Movimento Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Células Hep G2 , Humanos , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , RNA Interferente Pequeno/genética , Membro 6b de Receptores do Fator de Necrose Tumoral/genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
PURPOSE: The aim of this study was to evaluate the effects of an aquatic exercise program designed to enhance muscular strength in paretic lower limbs in subacute stroke patients. METHOD: Thirty-six subacute stroke patients were randomly divided to a conventional or an aquatic group (n = 18 each). Outcome measures were assessed at baseline and after 8 wks of training. For the paretic lower limbs, maximum isometric voluntary contraction strength of the rectus femoris and biceps femoris caput longus and the tibialis anterior and lateral gastrocnemius was measured. Cocontraction ratios during knee extension and flexion and ankle dorsiflexion and plantarflexion were calculated respectively. In addition, Modified Ashworth Scale, Functional Ambulation Category, and Barthel Index were assessed. RESULTS: Compared with the conventional intervention, the aquatic intervention resulted in significantly higher knee extension (P = 0.002) and ankle plantarflexion torque (P = 0.002), accompanied with a significantly lower knee extension cocontraction ratio in the paretic limb (P = 0.000). Functional Ambulation Category (P = 0.009) and Barthel Index (P = 0.024) were greater in aquatic group than conventional group posttreatment. Modified Ashworth Scale scores did not show any differences between groups. CONCLUSIONS: Aquatic exercise enhanced muscle strength in paretic lower limbs and improved muscle cocontraction without increasing spasticity in subacute stroke patients.