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BACKGROUND: To investigate the feasibility of Diffusion Kurtosis Imaging (DKI) in assessing renal interstitial fibrosis induced by hyperuricemia. METHODS: A hyperuricemia rat model was established, and the rats were randomly split into the hyperuricemia (HUA), allopurinol (AP), and AP + empagliflozin (AP + EM) groups (n = 19 per group). Also, the normal rats were selected as controls (CON, n = 19). DKI was performed before treatment (baseline) and on days 1, 3, 5, 7, and 9 days after treatment. The DKI indicators, including mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) of the cortex (CO), outer stripe of the outer medulla (OS), and inner stripe of the outer medulla (IS) were acquired. Additionally, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and nuclear factor kappa B (NF-κB) immunostaining were used to reveal renal histopathological changes at baseline, 1, 5, and 9 days after treatment. RESULTS: The HUA, AP, and AP + EM group MKOS and MKIS values gradually increased during this study. The HUA group exhibited the highest MK value in outer medulla. Except for the CON group, all the groups showed a decreasing trend in the FA and MD values of outer medulla. The HUA group exhibited the lowest FA and MD values. The MKOS and MKIS values were positively correlated with Masson's trichrome staining results (r = 0.687, P < 0.001 and r = 0.604, P = 0.001, respectively). The MDOS and FAIS were negatively correlated with Masson's trichrome staining (r = -626, P < 0.0014 and r = -0.468, P = 0.01, respectively). CONCLUSION: DKI may be a non-invasive method for monitoring renal interstitial fibrosis induced by hyperuricemia.
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Hiperuricemia , Ratos , Animais , Hiperuricemia/diagnóstico por imagem , Rim/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Imagem de Difusão por Ressonância Magnética/métodos , FibroseRESUMO
Breast cancer is one of the leading cancer deaths around the world. Targeted drugs have greatly increased the survival rate of breast cancer patients in recent years. But in some patients, the current regimen is still ineffective. Therefore, more therapeutic targets for treating breast cancer are demanding. The core heterochromatin-related genes of breast cancer were identified by utilizing prognostic survival analysis and multivariate Cox hazard proportional regression analysis. Both breast cancer and adjacent normal tissue were collected and analyzed with western blot and immunohistochemistry. Colony formation assay, CCK-8 assay, and EdU assay were used to measure the effect of CBX3 on breast cancer cell growth, wound-healing assay and Transwell assay were used to analyze the effect of CBX3 on breast cancer cell migration and invasion. Flow cytometry assay and western blot were used to study the molecular mechanism of CBX3 in breast cancer. High expression of heterochromatin-related proteins CBX3, H2AFY, and SULF1 showed a poor prognosis in patients in both TCGA dataset and GEO datasets. Western blot demonstrated that the expression level of CBX3 was significantly higher in breast cancer than that in adjacent normal tissues. Colony formation assay, CCK-8 assay, and EdU assay showed that the knockdown of CBX3 could significantly inhibit breast cancer cell growth, and the overexpression of CBX3 could promote the growth of breast cancer cells. Transwell assay and wound healing assay showed that knockdown of CBX3 inhibited breast cancer cell migration and invasion, and the overexpression of CBX3 promoted breast cancer cell migration and invasion. Western blot showed that CBX3 might promote breast cancer cell proliferation, invasion, and migration in breast cancer by modulating the ERK1/2 signaling pathway and epithelial-mesenchymal transition (EMT)-related genes. CBX3 was a biomarker of poor prognosis in breast cancer patients. CBX3 promoted the proliferation of breast cancer cells through the ERK signaling pathway, and migration and invasion of breast cancer cells through EMT-related genes. The CBX3/p-ERK1/2 signaling axis might provide a new therapeutic method against breast cancer.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/metabolismo , Heterocromatina , Linhagem Celular Tumoral , Movimento Celular/genética , Prognóstico , Transformação Celular Neoplásica/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Proteínas Cromossômicas não Histona/genéticaRESUMO
Background: Angiotensin receptor neprilysin inhibition (ARNI) is superior to enalapril in reducing the risk of cardiovascular death and heart failure hospitalization (HFH). However, whether prescription pattern is associated with heart failure outcome is unknown. Methods: This is a retrospective study of 153 patients who received ARNI in a tertiary medical center in Taiwan. We analyzed the impact of dose up-titration and prescription timing including during initial admission, within 3 months after initial HFH discharge, and at outpatient clinics without prior HFH. The primary endpoint was the composite of cardiovascular death and HFH. Results: After a mean follow-up period of 287 ± 197 days, the primary endpoint occurred in 43 (28.1%) subjects. Patients without and with a primary endpoint significantly differed in terms of history of valvular heart disease (VHD, p = 0.006), ventricular tachyarrhythmia (VT, p = 0.043), percutaneous coronary intervention (p = 0.007), coronary artery bypass grafting (p = 0.002), chronic kidney disease (p = 0.002), age (p = 0.002), diastolic blood pressure (p = 0.025), and prescription timing (p = 0.002). Kaplan-Meier analysis showed ARNI up-titration and prescription timing had a significant association with primary endpoint-free survival (Breslow test; p = 0.032, and log-rank test; p = 0.001, respectively). Cox regression analysis showed that independent predictors for the primary endpoint were ARNI up-titration [hazard ratio (HR): 0.41, p = 0.024], non-hospital ARNI versus hospital ARNI (HR: 0.41, p = 0.009), VHD (HR: 2.71, p = 0.013), VT (HR: 3.09, p = 0.02), and age (HR: 1.03, p = 0.033). Conclusions: The prescription pattern of ARNI could be associated with heart failure events.
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Metabolic-associated fatty liver disease (MAFLD) is the most common metabolic disease with a global prevalence of 25%. While MAFLD is serious and incurable at the later stage, it can be controlled or reversed at the early stage of hepatosteatosis originating from unhealthy diets. Recent laboratory evidence implicates a critical role of the mammalian target of rapamycin (mTOR)-autophagy signaling pathway in the pathogenesis of MAFLD induced by a high-fructose diet mimicking the overconsumption of sugar in humans. This review discusses the possible molecular mechanisms of mTOR-autophagy-endoplasmic reticulum (ER) stress in MAFLD. Based on careful analysis of recent studies, we suggest possible new therapeutic concepts or targets that can be explored for the discovery of new anti-MAFLD drugs.
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Autofagia , Frutose/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Estresse do Retículo Endoplasmático , Frutose/efeitos adversos , Humanos , Transdução de SinaisRESUMO
BACKGROUND: Depression is a heterogeneous disorder, with the exact neuronal mechanisms causing the disease yet to be discovered. Recent work suggests it is accompanied by neuro-inflammation, characterized, in particular, by microglial activation. However, microglial activation and its involvement in neuro-inflammation and stress-related depressive disorders are far from understood. METHODS: We utilized multiple detection methods to detect the neuro-inflammation in the hippocampus of rats after exposure to chronic mild stress (CMS). Male Sprague Dawley (SD) rats were subjected to chronic mild stressors for 12 weeks. Microglial activation and hippocampal neuro-inflammation were detected by using a combinatory approach of in vivo [18F] DPA-714 positron emission computed tomography (PET) imaging, ionized calcium-binding adapter molecule 1 and translocator protein (TSPO) immunohistochemistry, and detection of NOD-like receptor protein 3 (NLRP3) inflammasome and some inflammatory mediators. Then, the rats were treated with minocycline during the last 4 weeks to observe its effect on hippocampal neuro-inflammation and depressive-like behavior induced by chronic mild stress. RESULTS: The results show that 12 weeks of chronic mild stress induced remarkable depressive- and anxiety-like behavior, simultaneously causing hippocampal microglial activation detected by PET, immunofluorescence staining, and western blotting. Likewise, activation of NLRP3 inflammasome and upregulation of inflammatory mediators, such as interleukin-1ß (IL-1ß), IL-6, and IL-18, were also observed in the hippocampus after exposure to chronic stress. Interestingly, the anti-inflammatory mediators, such as IL-4 and IL-10, were also increased in the hippocampus following chronic mild stress, which may hint that chronic stress activates different types of microglia, which produce pro-inflammatory cytokines or anti-inflammatory cytokines. Furthermore, chronic minocycline treatment alleviated the depressive-like behavior induced by chronic stress and significantly inhibited microglial activation. Similarly, the activation of NLRP3 inflammasome and the increase of inflammatory mediators were not exhibited or significantly less marked in the minocycline treatment group. CONCLUSION: These results together indicate that microglial activation mediates the chronic mild stress-induced depressive- and anxiety-like behavior and hippocampal neuro-inflammation.
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Ansiedade/metabolismo , Depressão/metabolismo , Mediadores da Inflamação/metabolismo , Microglia/metabolismo , Estresse Psicológico/metabolismo , Animais , Ansiedade/psicologia , Doença Crônica , Depressão/psicologia , Modelos Animais de Doenças , Hipocampo/metabolismo , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/psicologiaRESUMO
Allergic rhinitis (AR) represents a clinical health issue affecting approximately 500 million people worldwide. This study aimed to explore the effects of airborne fine particulate matter (PM2.5) on the nasal mucosa of rats with AR. Seventy-five healthy male SD rats were included and randomly divided into the normal, model, low-concentration, middle-concentration, and high-concentration groups (15 rats each group). AR rat models were established using sensitized mixture and were stimulated using different concentrations of PM2.5. Sneeze and nose-scratching events were observed. Automatic hematology analyzer was utilized to count white blood cells (WBCs). The serum IgE, ICAM-1, and VCAM-1 expressions, eosinophil (EOS) infiltration, and IFN-γ, IL-4, IL-5, IL-33, and TSLP expressions were detected by ELISA, HE staining, and qRT-PCR. Greater numbers of WBCs, increased IgE level, elevated levels of ICAM-1, VCAM-1, EOS, IFN-γ, IL-4, IL-5, IL-33, and TSLP in the model, low-concentration, middle-concentration, and high-concentration groups than the normal group. The same trend also exhibited in rats of the middle-concentration and high-concentration groups than that of the model and low-concentration groups. Comparisons between normal rats and AR rats indicated that AR rats exhibit remarkably higher cytokine expression levels of IFN-γ, IL-4, IL-5, TSLP, and IL-33. The study revealed that as stimulation is triggered by PM2.5, AR rats result in increased levels of adhesion molecules and inflammatory cytokine expressions in a concentration-dependent manner. Analyses of PM2.5 as well as, its effects on AR are crucial in the continued drive for both prevention and management of the disease.
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Citocinas/análise , Interferon gama/análise , Interleucinas/análise , Mucosa Nasal/metabolismo , Material Particulado , Rinite Alérgica , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Animais , Modelos Animais de Doenças , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Tamanho da Partícula , Material Particulado/efeitos adversos , Material Particulado/análise , Ratos , Ratos Sprague-Dawley , Rinite Alérgica/etiologia , Rinite Alérgica/metabolismo , Estatística como Assunto , Linfopoietina do Estroma do TimoRESUMO
Background: Due to the variations in surgical approaches and prognosis between intraspinal schwannomas and meningiomas, it is crucial to accurately differentiate between the two prior to surgery. Currently, there is limited research exploring the implementation of machine learning (ML) methods for distinguishing between these two types of tumors. This study aimed to establish a classification and regression tree (CART) model and a random forest (RF) model for distinguishing schwannomas from meningiomas. Methods: We retrospectively collected 88 schwannomas (52 males and 36 females) and 51 meningiomas (10 males and 41 females) who underwent magnetic resonance imaging (MRI) examinations prior to the surgery. Simple clinical data and MRI imaging features, including age, sex, tumor location and size, T1-weighted images (T1WI) and T2-weighted images (T2WI) signal characteristics, degree and pattern of enhancement, dural tail sign, ginkgo leaf sign, and intervertebral foramen widening (IFW), were reviewed. Finally, a CART model and RF model were established based on the aforementioned features to evaluate their effectiveness in differentiating between the two types of tumors. Meanwhile, we also compared the performance of the ML models to the radiologists. The receiver operating characteristic (ROC) curve, accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were used to evaluate the models and clinicians' discrimination performance. Results: Our investigation reveals significant variations in ten out of 11 variables in the training group and five out of 11 variables in the test group when comparing schwannomas and meningiomas (P<0.05). Ultimately, the CART model incorporated five variables: enhancement pattern, the presence of IFW, tumor location, maximum diameter, and T2WI signal intensity (SI). The RF model combined all 11 variables. The CART model, RF model, radiologist 1, and radiologist 2 achieved an area under the curve (AUC) of 0.890, 0.956, 0.681, and 0.723 in the training group, and 0.838, 0.922, 0.580, and 0.659 in the test group, respectively. Conclusions: The RF prediction model exhibits more exceptional performance than an experienced radiologist in discriminating intraspinal schwannomas from meningiomas. The RF model seems to be better in discriminating the two tumors than the CART model.
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BACKGROUND: The aim of this study was to investigate the effects and safety of 120 watt PVP surgery for the high risk prostate hyperplasia patients. METHODS: 120 watt PVP surgery was performed on 120 cases of high risk prostate hyperplasia patients. The assessment included the operation time, energy consumed, hemoglobin changes, and serum salt concentration, whether to keep urinary catheter, hospitalization time, and complications after the operation. International Prostate Symptom Scoring (IPSS), the maximum urine flow rate (Qmax) and residual urine volume (RUV) were conducted preoperatively and postoperatively for the patients. RESULTS: There were 30% of patients taking oral anti-coagulant drug (n = 36), 88 cases with abnormal ECGs. All the patient's internal diseases, include the cardiovascular disease (42/120), the hypertension (56/120), the respiratory system diseases (51/120), the cerebrovascular diseases (39/120), anemia (24/120), liver or kidney dysfunction (16/120), diabetes (18/120), hypoproteinemia (15/120) were under controlled. The average age, prostate volume and energy consumed was 82.8 ± 8.6 (70-96) years, 66.1 ± 25.3 (30-160) ml, and 224 ± 85 (31-596) kJ respectively. The average follow-up time was 20.8 ± 3.2 (18-24) months. The incidence of bladder neck contracture and urethral stricture were 1.7% and 0.8% respectively, no prostate cancer occurred during the subsequent follow-up period. CONCLUSIONS: 120 watt PVP surgery can safely and effectively alleviate the urination parameters of high risk prostate hyperplasia patients. The surgical process is safe and effective, and is not affected by the various internal diseases or the use of oral anti-coagulant drugs.
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Terapia a Laser/estatística & dados numéricos , Sintomas do Trato Urinário Inferior/epidemiologia , Sintomas do Trato Urinário Inferior/prevenção & controle , Complicações Pós-Operatórias/epidemiologia , Hiperplasia Prostática/epidemiologia , Hiperplasia Prostática/cirurgia , Doenças Urológicas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China , Comorbidade , Humanos , Masculino , Prevalência , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the effects of electromyography on the clinical manifestations and prognosis after posterior lumbar interbody fusion(PLIF) of degenerative lumbar diseases. METHODS: A retrospective analysis was performed on 68 patients with degenerative lumbar diseases, including 29 males and 39 females, aged 21 to 84 years old, who underwent electromyogram (EMG) from January 2018 to October 2019. The patients were divided into negative and positive groups according to whether theresults of EMG was normal or abnormal, PLIF surgery was performed in both groups. The preoperative duration of illness, postoperative recovery time, operative time, intraoperative blood loss, postoperative ambulation time and length of postoperative hospital stay were recorded. The clinical efficacy was evaluated by visual analogue scale(VAS) of low back and lower limb, the Japanese Orthopedic Association(JOA) score before and after operation. RESULTS: All patients were follow-up from 26 to 39 months. The subjective symptoms, clinical signs, daily activities and JOA total scores after operation in two groups were significantly higher than those before preoperation(P<0.05);the clinical signs score and total JOA score in the negative group at 3 months after operation were higher than those in the positive group(P<0.05). The VAS score of leg pain in the negative group after 1 and 3 months was less than that in the positive group(P<0.05). Patients 's illness time, postoperative recovery time, hospitalization time and implantation time in the negative group were shorter than those in the positive group(P<0.05). At other time points, there was no significant difference in low pain VAS, leg pain VAS, JOA scores in the two groups(P>0.05). There was no significant difference in the operation time and intraoperative bleeding volume between the two groups(P>0.05). CONCLUSION: Patients with normal electromyography had shorter disease duration than ones with abnormal electromyography in lumbar degenerative disease;after PLIF, patients with normal electromyography recovered faster than ones with abnormal electromyography, but the results of electromyography had no effect on the final prognosis of PLIF surgery.
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Fusão Vertebral , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Fusão Vertebral/métodos , Vértebras Lombares/cirurgia , Resultado do Tratamento , DorRESUMO
Objective: To investigate the reason for fungal balls (FBs) being localized in paranasal sinuses, we analyzed the clinical presentations of patients with FB rhinosinusitis (FBS). Methods: Clinical data, anatomical variation (ie, nasal septal deviation, concha bullosa, and Haller cell), as well as measurements of nasal resistance (NR), nasal cavity volume (NCV), and nasal cross-sectional area (NCA) using active anterior rhinomanometry and acoustic rhinometry were collected from FBS patients hospitalized in our hospital between January 2021 and December 2022. A retrospective analysis was conducted using IBM SPSS 19.0 to perform the Shapiro-Wilk test, t-test and logistic regression analysis. Results: A total of 95 FBS patients, including 33 male and 62 female patients, were included in this study. FBs in maxillary sinus were the most common (83, 87.4%), followed by sphenoid sinus (9, 9.5%). Logistic multivariate regression analysis revealed that a higher left-to-right NR ratio was associated with an increased likelihood of FBs being present in the left sinus [Odds ratios (OR) = 0.185; 95% CI, 0.061-0.558; P < .01]. When the ratio of the left-to-right second-minimum NCA was higher and the FB was more in the right sinus (OR = 3.194; 95% CI, 1.593-6.405; P = .001). Additionally, when the difference between left and right NCV was greater and FB occurred more commonly in the right sinus (OR = 1.435; 95% CI, 1.196-1.721; P < .001). Nonetheless, the presence of nasal septum deviation and concha bullosa did not significantly contribute to FB formation. Conclusions and significance: The differences in NR, NCA, and NCV between the affected and unaffected sides of nasal cavity are risk factors for the FB formation. To reduce FBS recurrence, it is important to focus on improving nasal ventilation during the surgical treatment.
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BACKGROUND: Glucose metabolism disorder is a common feature in cancer. Cancer cells generate much energy through anaerobic glycolysis, which promote the development of tumors. However, long non-coding RNA may play an important role in this process. Our aim is to explore a prognostic risk model based on the glucose metabolism-related lncRNAs which provides clues that lncRNAs predict a clinical outcome through glucose metabolism in breast cancer. METHODS: 1222 RNA-seq were extracted from the TCGA database, and 74 glucose metabolism-related genes were loaded from the GSEA website. Then, 7 glucose metabolism-related lncRNAs risk score model was developed by univariate, Lasso, and multivariate regression analysis. The lncRNA risk model showed that high-risk patients predict a poor clinical outcome with high reliability (P=2.838×10-6). Univariate and multivariate independent prognostic analysis and ROC curve analysis proved that the risk score was an independent prognostic factor in breast cancer with an AUC value of 0.652. Finally, Gene set enrichment analysis showed that cell cycle-related pathways were significantly enriched in a high-risk group. RESULTS: Our results showed that glucose metabolism-related lncRNAs can affect breast cancer progression. 7 glucose metabolism-related lncRNAs prognostic signature was established to evaluate the OS of patients with breast cancer. PICSAR, LINC00839, AP001505.1, LINC00393 were risk factors and expressed highly in the high-risk group. A Nomogram was made based on this signature to judge patients' living conditions and prognosis. CONCLUSION: 7 glucose metabolism-related lncRNAs risk score model had a high prognostic value in breast cancer. PICSAR, LINC00839, AP001505.1, LINC00393 were risk factors. AP001505.1 expression was increased in most triple-negative breast cancer cells treated with high glucose, which may also take part in breast cancer progression and potential therapeutic targets.
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RNA Longo não Codificante , Neoplasias de Mama Triplo Negativas , Humanos , RNA Longo não Codificante/genética , Amigos , Reprodutibilidade dos Testes , GlucoseRESUMO
OBJECTIVE: To explore the influence and the underlying mechanism of vaspin (visceral adipose tissue-derived serpin) on the development of triple-negative breast malignancy. METHODS: First, we analyzed medical records and screened out 22 breast cancer patients with different BMI according to inclusion and exclusion criterion, and measured serum vaspin of those patients. Then we studied the effects of vaspin on TNBC cell lines by using EdU assay, colony formation, transwell and wound-healing assay. Later, we used bioinformatics analysis to identify downstream effectors and verify with qRT-PCR, luciferase assay, western blot, etc. RESULTS: We found the vaspin level was positively correlated with BMI in breast malignant patients and vaspin could significantly enhance the proliferation, infiltration and transferring of triple-negative breast cancer cells by restraining the expression of miR-33a-5p. By using bioinformatic analysis and luciferase assay, we identified miR-33a-5p directly regulating ABHD2. CONCLUSION: Vaspin, as a cancer-promoting cytokine, may inhibit miR-33a-5p thus increasing the level of ABHD2 to promote the development of the triple-negative breast cancer.
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MicroRNAs , Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , HidrolasesRESUMO
The purpose of the present study was to investigate whether catalpol exhibited neuroprotective effects in chronic unpredictable mild stress (CUMS) mice through oxidative stress-mediated nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin-domain-containing 3 (NLRP3) inflammasome and neuroinflammation. Deficits in behavioral tests, including open field test (OFT), forced swim test (FST), and elevated plus-maze test (EPM), were ameliorated following catalpol administration. To study the potential mechanism, western blots, quantitative real-time PCR (qRT-PCR) analysis and immunofluorescence imaging were performed on the hippocampus samples. We found that the defects of behavioral tests induced by CUMS could be reversed by the absence of NLRP3 and NLRP3 inflammasome might be involved in the antidepressant effects of catalpol on CUMS mice. Similar to the NLRP3 inflammasome, the expression of interleukin-1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), and inducible nitride oxide synthase (iNOS) were increased after CUMS. The current study demonstrated that catalpol possessed anti-inflammatory effect on CUMS mice and inhibited microglial polarization to the M1 phenotype. In addition, the activity of mitochondrial oxidative stress might be involved in the NLRP3 activation, which was proved by the downregulation of NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and cleaved IL-1ß, after the administration of mitochondrion-targeted antioxidant peptide SS31. Taken together, we provided evidence that catalpol exhibited antidepressive effects on CUMS mice possibly via the oxidative stress-mediated regulation of NLRP3 and neuroinflammation.
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Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Animais , Depressão/tratamento farmacológico , Glucosídeos Iridoides , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo , Estresse Psicológico/complicações , Estresse Psicológico/tratamento farmacológicoAssuntos
Surtos de Doenças , Leptospirose/epidemiologia , Chuva , Adolescente , Adulto , Idoso , Criança , China/epidemiologia , Feminino , Humanos , Leptospirose/mortalidade , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto JovemRESUMO
Postmenopausal depression has been shown to be related to the reduction of ovarian hormones produced as a woman transitions from a menopausal to a post-menopausal stage. What remains to be known is which type of estrogen receptor plays a key role in estrogen neuroprotection, a process that may be mediated by potentiating brain mitochondrial function and inhibiting mitochondria-associated apoptosis. In order to better imitate the condition of postmenopause, we conducted our research on aged female rats. Plasma estrogen levels declined significantly in ovariectomized rats and 16-month-old female rats, while anxiety and depression-like behavior increase. Moreover, ERα, ERß, GPER, Bcl2 and UCP2 expression decreased significantly in hippocampus in female rats following ovariectomy. In our study, the anxiety and depression-like behavior in aged female rats were significantly relieved after the treatment of G-1, the GPER agonist. Furthermore, G-1 could reverse the reduction of ERα, ERß, GPER, Bcl2 and UCP2 expression within the hippocampus. Mitochondrial JC-1 staining indicated that mitochondrial membrane potential increased after G-1 treatment. In addition, total antioxidant capacity (TAC) and superoxide dismutase activity (SOD) were found to be elevated in aged female rats following G-1 treatment. Taken together, estrogen receptors, especially GPER, may activate anti-apoptotic signaling and accelerate mitochondrial function. Therefore, GPER could be the potential therapeutic target for estrogen deficiency-related affective disorders.
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Envelhecimento/efeitos dos fármacos , Ciclopentanos/farmacologia , Hipocampo/efeitos dos fármacos , Transtornos do Humor/tratamento farmacológico , Oxirredução/efeitos dos fármacos , Quinolinas/farmacologia , Receptores de Estrogênio/metabolismo , Animais , Modelos Animais de Doenças , Estrogênios/sangue , Comportamento Exploratório/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/ultraestrutura , Aprendizagem em Labirinto/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Ovariectomia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Natação/psicologiaRESUMO
Ghrelin, a peptide derived from stomach, is an endogenous ligand for growth hormone secretagogue receptor (GHSR). So far, the exact role of ghrelin in depression and anxiety is still being debated. The p38 mitogen-activated protein kinase (p38-MAPK) is known to be activated in response to various stress stimuli. Thus, we hypothesize that ghrelin has an antidepressant effect, to which the p38-MAPK signaling pathway significantly contributes. To test this hypothesis, chronic social defeat stress (CSDS) was used as a model of depression. We employed the adeno-associated virus-mediated siRNA approach to down-regulate GHSR expression in the hippocampus of mice in vivo. Both ghrelin and the p38 inhibitor, SB203580, were administered to identify the effect of ghrelin on depressive-like behavior of stressed mice and to better assess the role of the p38-MAPK signaling pathway in this process. We found that CSDS activated the endogenous ghrelin-GHSR in hippocampal neurons, which possibly resulted in opposing the formation of depression- and anxiety-like behaviors in mice. Furthermore, the p38-MAPK signaling pathway had an important role in the antidepressant effect of ghrelin. Therefore, we conclude that ghrelin may reduce CSDS-induced depression- and anxiety-like behaviors via inhibiting the p38-MAPK signaling pathway in hippocampal neurons of mice.
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Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Grelina/farmacologia , Hipocampo/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Técnicas de Silenciamento de Genes , Hipocampo/metabolismo , Imidazóis/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Piridinas/farmacologiaRESUMO
Depression is the second leading cause of disability worldwide. The effects of clinical depression may be mediated by neuroinflammation such as activation of microglia and high levels of proinflammatory cytokines in certain brain areas. Traditional Chinese medicine techniques such as electro-acupuncture (EA) are used extensively in Asia to treat mental health disorders. However, EA has not been rigorously studied in treatment of depression. This study was designed to assess the effectiveness of EA on depressive-like behavior and explore the role of hippocampal neuroinflammation in the potential antidepressant effect of EA. In this study, we used six chronic unpredictable stressors daily in a random sequence for 10 weeks. EA were performed on "Bai-Hui" (Du-20) (+) and "Yang-Ling-Quan" (GB-34, the right side; -) acupoints by an EA apparatus (HANS Electronic Apparatus, LH202H, 2/100 Hz, 0.3 mA) for 30 min once every other day for last 4 weeks. The behavior tests including open field test and forced swimming test, which are widely used to assess depressive and anxiety-like behavior were performed on the Monday and Tuesday of the eleventh week. The results showed that 10 week of chronic unpredictable stress (CUS) caused behavioral deficits in rats and neuroinflammation in hippocampus, such as increased expression of NLRP3 inflammasome components, upregulated mRNA level of IL-1ß and the protein level of IL-1ß mature form (p17) and activation of microglia. Moreover, 4 weeks of EA treatment significantly attenuated behavioral deficits caused by CUS. EA's antidepressant effect was accompanied by markedly decreased expression of certain NLRP3 inflammasome components and matured IL-1ß. Meanwhile, EA treatment can significantly reverse CUS-induced increases in P2X7 receptor, Iba-1, IL-18, TNFα and IL-6 expression and decreases in GFAP expression. In conclusion, EA exhibited the antidepressant effect and alleviated the hippocampal neuroinflammation. These findings may provide insight into the role of hippocampal neuroinflammation in the antidepressant effect of EA.
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Toxoplasma gondii is an important food-borne zoonotic protozoan parasite, which can infect endothermic animals, including pigs. However, data on T. gondii in slaughter pigs in Shaanxi Province were still lacking. To detect the seroprevalence and analyze the risk factors of T. gondii infection in slaughter pigs in Shaanxi Province, Northwestern China, a total of 784 serum samples were collected from four administrative regions and detected by indirect hemagglutination test for T. gondii infection. Antibodies to T. gondii were found in 19.9% (156/784) slaughter pigs. Moreover, the seropositive rate was different among rearing systems (31% in nonintensive pig farms and 6.7% in intensive pig farms), genders (19.8% in male and 20.0% in female), and regions (ranging from 6.7% in Shenmu to 38.2% in Zhouzhi). Rearing system and region were identified as risk factors for T. gondii infection. These results showed that T. gondii is highly prevalent in slaughter pigs in Shaanxi Province, and it could cause a serious risk to public health. This study provided fundamental information for the prevention and control of T. gondii infection in slaughter pigs in China.
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Doenças dos Suínos/parasitologia , Toxoplasma/isolamento & purificação , Toxoplasmose Animal/sangue , Animais , China/epidemiologia , Fatores de Risco , Estudos Soroepidemiológicos , Suínos , Doenças dos Suínos/epidemiologia , Toxoplasmose Animal/epidemiologia , ZoonosesRESUMO
As a regulator of food intake, ghrelin also plays a key role in mood disorders. Previous studies reported that acute ghrelin administration defends against depressive symptoms of chronic stress. However, the effects of long-term ghrelin on rodents under chronic stress hasn't been revealed. In this study, we found chronic peripheral administration of ghrelin (5nmol/kg/day for 2 weeks, i.p.) could alleviate anxiety- and depression-like behaviors induced by chronic unpredictable mild stress (CUMS). The depression-like behaviors were assessed by the forced swimming test (FST), and anxiety-like behaviors were assessed by the open field test (OFT) and the elevated plus maze test (EPM). Meanwhile, we observed that peripheral acylated ghrelin, together with gastral and hippocampal ghrelin prepropeptide mRNA level, were significantly up-regulated in CUMS mice. Besides, the increased protein level of growth hormone secretagogue receptor (GHSR) in hippocampus were also detected. These results suggested that the endogenous ghrelin/GHSR pathway activated by CUMS plays a role in homeostasis. Further results showed that central treatment of ghrelin (10µg/rat/day for 2 weeks, i.c.v.) or GHRP-6 (the agonist of GHSR, 10µg/rat/day for 2 weeks, i.c.v.) significantly alleviated the depression-like behaviors induced by CUMS in FST and sucrose preference test (SPT). Based on these results, we concluded that central GHSR is involved in the antidepressant-like effect of exogenous ghrelin treatment, and ghrelin/GHSR may have the inherent neuromodulatory properties against depressive symptoms.
Assuntos
Ansiedade/tratamento farmacológico , Comportamento Animal , Depressão/tratamento farmacológico , Grelina/metabolismo , Grelina/farmacologia , Hipocampo/metabolismo , Oligopeptídeos/farmacologia , Receptores de Grelina/metabolismo , Estresse Psicológico/metabolismo , Animais , Ansiedade/etiologia , Comportamento Animal/efeitos dos fármacos , Depressão/etiologia , Grelina/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oligopeptídeos/administração & dosagem , Ratos , Ratos Sprague-Dawley , Receptores de Grelina/agonistas , Estresse Psicológico/complicaçõesRESUMO
While social stress exposure is a common risk factor for affective disorders, most individuals exposed to it can maintain normal physical and psychological functioning. However, factors that determine susceptibility vs. resilience to social stress remain unclear. Here, the resident-intruder model of social defeat was used as a social stressor in male C57BL/6J mice to investigate the difference between susceptibility and resilience. As depression is often characterized by hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis, we conducted the present study to further investigate the individual differences in the HPA axis response and glucocorticoid receptor (GR) protein expression and translocation between susceptible mice and resilient mice. We found that hypercortisolemia, induced by social defeat stress occurred in susceptible mice, but not in resilient mice. Moreover, susceptible mice exhibited significantly less GR protein expression and nuclear translocation in the hippocampus than resilient mice. Treatment with escitalopram could decrease the serum corticosterone (CORT), increase GR protein expression as well as nuclear translocation in the hippocampus and ultimately reverse social withdrawal behaviors in susceptible mice. These results indicate that the up-regulation of GR and the enhancement of GR nuclear translocation in the hippocampus play an important role in resilience to chronic social defeat stress.