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2.
Brain Behav ; 14(7): e3586, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38970230

RESUMO

BACKGROUND: Patients with myocardial infarction (MI) frequently experience a heightened incidence of depression, thereby increasing the risk of adverse cardiovascular events. Consequently, early detection and intervention in depressive symptoms among patients with MI are imperative. Shexiang Baoxin Pills (SBP), a Chinese patent medicine employed for the treatment of MI, exhibits diverse mechanisms targeting this condition. Nevertheless, its therapeutic efficacy on postmyocardial infarction depressive symptoms remains unclear. The aim of this study is to investigate the effectiveness and mechanism of SBP in managing depression during acute myocardial infarction (AMI). METHODS: A rat model combining MI and depression was established, and the rats were randomly divided into four groups: the model (MOD) group, SBP group, Fluoxetine (FLX) group, and Sham group. After 28 days of drug intervention, cardiac function was assessed using echocardiography while behavior was evaluated through sucrose preference test (SPT), forced swimming test (FST), and open-field test (OFT). Additionally, levels of inflammatory factors in serum and hippocampus were measured along with NLRP3 inflammasome-related protein expression via Western blotting and immunofluorescence. RESULTS: SBP can enhance cardiac function in rats with AMI and depression, while significantly ameliorating depressive-like behavior. Compared to the Sham group, levels of IL-1ß, IL-18, TNF-α, and other inflammatory factors were markedly elevated in the MOD group. However, expressions of these inflammatory factors were reduced to varying degrees following treatment with SBP or FLX. Analysis of NLRP3 inflammasome-related proteins in the hippocampus revealed a significant upregulation of IL-1ß, IL-18, NLRP3, ASC, caspase-1, and GSDMD in the MOD group; conversely, these measures were significantly attenuated after SBP intervention. CONCLUSION: We have observed a significant amelioration in depression-like behavior upon SBP administration during the treatment of AMI, suggesting that this effect may be attributed to the inhibition of NLRP3-mediated pyroptosis. (The main findings are summarized in the graphical abstract in the supplementary file.).


Assuntos
Antidepressivos , Depressão , Medicamentos de Ervas Chinesas , Inflamassomos , Infarto do Miocárdio , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos Sprague-Dawley , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/complicações , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/administração & dosagem , Ratos , Depressão/tratamento farmacológico , Depressão/etiologia , Antidepressivos/farmacologia , Antidepressivos/administração & dosagem , Masculino , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Modelos Animais de Doenças , Transdução de Sinais/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos
3.
Sci Total Environ ; 946: 174313, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-38964406

RESUMO

Nervous system diseases are a global health problem, and with the increase in the elderly population around the world, their incidence will also increase. Harmful substances in the environment are closely related to the occurrence of nervous system diseases. China is a large agricultural country, and thus the insecticide cyfluthrin has been widely used. Cyfluthrin is neurotoxic, but the mechanism of this injury is not clear. Inflammation is an important mechanism for the occurrence of nervous system diseases. Mitochondria are the main regulators of the inflammatory response, and various cellular responses, including autophagy, directly affect the regulation of inflammatory processes. Mitochondrial damage is related to mitochondrial quality control (MQC) and PTEN-induced kinase 1 (PINK1). As an anti-inflammatory factor, stimulator of interferon genes (STING) participates in the regulation of inflammation. However, the relationship between STING and mitochondria in the process of cyfluthrin-induced nerve injury is unclear. This study established in vivo and in vitro models of cyfluthrin exposure to explore the role of MQC and to clarify the mechanism of action of STING and PINK1. Our results showed that cyfluthrin can increase the reactive oxygen species (ROS) level, resulting in mitochondrial damage and inflammation. In this process, an imbalance in MQC leads to the aggravation of mitochondrial damage, and high STING expression drives the occurrence of inflammation. We established a differential expression model of STING and PINK1 to further determine the underlying mechanism and found that the interaction between STING and PINK1 regulates MQC to affect the levels of mitochondrial damage and inflammation. When STING and PINK1 expression are downregulated, mitochondrial damage and STING-induced inflammation are significantly alleviated. In summary, a synergistic effect between STING and PINK1 on cyfluthrin-induced neuroinflammation may exist, which leads to an imbalance in MQC by inhibiting mitochondrial biogenesis and division/fusion, and PINK1 can reduce STING-driven inflammation.


Assuntos
Mitocôndrias , Nitrilas , Proteínas Quinases , Piretrinas , Piretrinas/toxicidade , Mitocôndrias/efeitos dos fármacos , Animais , Nitrilas/toxicidade , Proteínas Quinases/metabolismo , Proteínas Quinases/genética , Doenças Neuroinflamatórias/induzido quimicamente , Inseticidas/toxicidade , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Inflamação/induzido quimicamente , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética
4.
Hortic Res ; 11(7): uhae150, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38988620

RESUMO

SHORT VEGETATIVE PHASE (SVP), a member of the MADS-box transcription factor family, has been reported to regulate bud dormancy in deciduous perennial plants. Previously, three LcSVPs (LcSVP1, LcSVP2 and LcSVP3) were identified from litchi genome, and LcSVP2 was highly expressed in the terminal buds of litchi during growth cessation or dormancy stages and down-regulated during growth stages. In this study, the role of LcSVP2 in governing litchi bud dormancy was examined. LcSVP2 was highly expressed in the shoots, especially in the terminal buds at growth cessation stage, whereas low expression was showed in roots, female flowers and seeds. LcSVP2 was found to be located in the nucleus and have transcription inhibitory activity. Overexpression of LcSVP2 in Arabidopsis thaliana resulted in a later flowering phenotype compared to the wild-type control. Silencing LcSVP2 in growing litchi terminal buds delayed re-entry of dormancy, resulting in significantly lower dormancy rate. The treatment also significantly up-regulated litchi FLOWERING LOCUS T2 (LcFT2). Further study indicates that LcSVP2 interacts with an AP2-type transcription factor, SMALL ORGAN SIZE1 (LcSMOS1). Silencing LcSMOS1 promoted budbreak and delayed bud dormancy. Abscisic acid (200 mg/L), which enforced bud dormancy, induced a short-term increase in the expression of LcSVP2 and LcSMOS1. Our study reveals that LcSVP2 may play a crucial role, likely together with LcSMOS1, in dormancy onset of the terminal bud and may also serve as a flowering repressor in evergreen perennial litchi.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38935014

RESUMO

INTRODUCTION: The aim of this study is to test the feasibility of a smartphone serious game-based intervention to promote resilience for adolescents with type 1 diabetes mellitus (T1DM). METHOD: A two-arm feasibility study was employed. Adolescents with T1DM were recruited. Adolescents in intervention group completed the serious game (named "WeCan") in one month. We evaluated feasibility and acceptability using criteria such as the recruitment response rate, the follow-up response rate, and satisfaction. RESULTS: Sixty-one adolescents with T1DM were included in this study. The study had a recruitment response rate of 62.89% (61/97) and an intervention completion rate of 64.52% (20/31). Eighty-two percent of the adolescents were satisfied with WeCan, which they perceived to have the advantages of being a lively format, attractive, and privacy, easy to operate, and improved attitude towards diabetes. CONCLUSIONS: These findings suggest that WeCan demonstrated good feasibility among the target population. However, the efficacy of health-related outcomes needs to be clarified in future studies.

6.
Cardiovasc Diabetol ; 23(1): 208, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898520

RESUMO

BACKGROUND: Triglyceride glucose (TyG) index and its related parameters have been introduced as cost-effective surrogate indicators of insulin resistance, while prospective evidence of their effects on atherosclerotic cardiovascular disease (ASCVD) remained scattered and inconsistent. We aimed to evaluate the association of TyG and its related parameters with new-onset ASCVD, and the predictive capacity were further compared. METHOD: A total of 95,342 ASCVD-free participants were enrolled from the Kailuan study. TyG and its related parameters were defined by fasting blood glucose, triglyceride, body mass index (BMI), waist circumstance (WC) and waist-to-height ratio (WHtR). The primary outcome was incident ASCVD, comprising myocardial infarction (MI) and ischemic stroke (IS). Cox proportional hazard models and restricted cubic spline (RCS) analyses were adopted to investigate the association between each index and ASCVD. The C-index, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were used for comparison of their predictive value for ASCVD. RESULTS: During a median follow-up of 15.0 years, 8,031 new cases of ASCVD were identified. The incidence rate of ASCVD increased along with elevated levels of each index, and the relationships were found to be nonlinear in the RCS analyses. The hazard ratio (HR) and 95% confidence interval (95% CI) for ASCVD was 1.39 (1.35, 1.43), 1.46 (1.41, 1.50), 1.50 (1.46, 1.55), and 1.52 (1.48, 1.57) per 1 IQR increase of baseline TyG, TyG-BMI, TyG-WC, and TyG-WHtR, respectively, and the association were more pronounced for females and younger individuals aged < 60 years (Pfor interaction<0.05). Using the updated mean or time-varying measurements instead of baseline indicators did not significantly alter the primary findings. Additionally, TyG-WC and TyG-WHtR showed better performance in predicting risk of ASCVD than TyG, with the IDI (95% CI) of 0.004 (0.001, 0.004) and 0.004 (0.001, 0.004) and the category-free NRI (95% CI) of 0.120 (0.025, 0.138) and 0.143 (0.032, 0.166), respectively. Similar findings were observed for MI and IS. CONCLUSIONS: Both the TyG index and its related parameters were significantly and positively associated with ASCVD. TyG-WC and TyG-WHtR had better performance in predicting incident ASCVD than TyG, which might be more suitable indices for risk stratification and enhance the primary prevention of ASCVD.


Assuntos
Aterosclerose , Biomarcadores , Glicemia , Triglicerídeos , Humanos , Pessoa de Meia-Idade , Feminino , Masculino , China/epidemiologia , Medição de Risco , Glicemia/metabolismo , Triglicerídeos/sangue , Incidência , Biomarcadores/sangue , Fatores de Tempo , Idoso , Prognóstico , Aterosclerose/epidemiologia , Aterosclerose/sangue , Aterosclerose/diagnóstico , AVC Isquêmico/epidemiologia , AVC Isquêmico/sangue , AVC Isquêmico/diagnóstico , Seguimentos , Adulto , Estudos Prospectivos , Índice de Massa Corporal , Fatores de Risco , Valor Preditivo dos Testes , Infarto do Miocárdio/epidemiologia , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Razão Cintura-Estatura
7.
Hellenic J Cardiol ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38838914

RESUMO

BACKGROUND: Previous studies have shown that remnant cholesterol (RC) was associated with cardiovascular disease (CVD). The study aim to identify the association of RC and the discordance between RC and lipoprotein cholesterol (LDL-C) with CVD. METHODS: Data was obtained from the Kailuan study. RC was calculated as the non high-density lipoprotein cholesterol minus LDL-C. Discordant RC and LDL-C were defined by percentile difference and clinical cutoff points. Cox proportional hazard models were used to explore the association of RC and the discordance between RC and LDL-C with CVD. RESULTS: Total of 96,769 participants were inclued, with the median age of 51.61 years, 79.56% of male. There was a significant association between RC levels and the risk of CVD, with an HR of 1.10 (95% CI, 1.08-1.13) in the continuous analysis. The discordantly high RC group had a significant increase in CVD, MI, and stroke risk, with HRs of 1.18 (95%CI, 1.10-1.26), 1.23 (1.06-1.43), and 1.15 (1.07-1.24), respectively. Compared to the group with low LDL-C and low RC, the group with low LDL-C and high RC had significantly higher incidences of CVD (HR, 1.33 [95% CI, 1.26-1.40]), MI (HR, 1.59 [95% CI, 1.41-1.80]), and stroke (HR, 1.28 [95% CI, 1.20-1.35]). CONCLUSIONS: Elevated levels of RC and discordantly high RC with LDL-C both were associated with the risk of CVD, MI, and stroke. These findings demonstrate the clinical significance of identifying residual risk related to RC.

8.
Arch Gerontol Geriatr ; 125: 105503, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38852372

RESUMO

BACKGROUND: Previous studies into relationship between high-density lipoprotein cholesterol (HDL-C) and cognitive decline were constrained to a single measurement, leaving the association between HDL-C variability and risk of cognitive decline unclear. METHODS: We identified 5930 participants from the China Health and Retirement Longitudinal Study (CHARLS) who were devoid for stroke, dementia, and memory-related diseases at baseline and underwent a minimum of 2 sequential health examinations during 2011-2015. Variability in HDL-C was defined as (1) variability independent of the mean (VIM), (2) average real variability (ARV), and (3) standard deviation (SD) of HDL-C change from baseline and follow-up visits. Cognitive function was evaluated in 2018 by Mini-mental state examination (MMSE) in the Chinese version. Logistic regression was employed to explore the association between HDL-C variability and cognitive decline. Odd ratios (OR) and 95 % confidence intervals (CI) were reported. RESULTS: The study included participants from CHARLS, mean age of 57.84±8.44 years and 44 % male. After adjustment for covariates, the highest quartile of VIM was associated with an increased risk of cognitive decline [OR:1.049, 95 %CI: 1.014-1.086] compared to the lowest quartile. For each SD increment of VIM, the OR was 1.015 (95 %CI:1.003-1.027). Strong dose-response relationships were identified (P for trend: 0.005). Consistent results were obtained for other measures of HDL-C variability (ARV and SD). Similar patterns were identified in different dimensions of cognition. CONCLUSIONS: Elevated HDL-C variability was associated with increased cognitive decline risk. Strategies to reducing HDL-C variability may lower the risks of cognitive decline among the general population.


Assuntos
HDL-Colesterol , Disfunção Cognitiva , Humanos , Masculino , Feminino , HDL-Colesterol/sangue , Disfunção Cognitiva/sangue , Disfunção Cognitiva/epidemiologia , China/epidemiologia , Pessoa de Meia-Idade , Idoso , Estudos Longitudinais , Fatores de Risco , Estudos de Coortes , Testes de Estado Mental e Demência
9.
Artigo em Inglês | MEDLINE | ID: mdl-38918056

RESUMO

BACKGROUND: Evidence on the longitudinal association of serum uric acid (SUA) with the risk of heart failure (HF) was limited and controversial. This study aimed to investigate the associations of cumulative SUA (cumSUA), incorporating its time course of accumulation, with the risk of HF. METHODS: This prospective study enrolled 54,606 participants from the Kailuan study. The magnitude of SUA accumulation was expressed as cumSUA, exposure duration, and cumulative burden from baseline to the third survey, with cumSUA, calculated by multiplying mean values between consecutive examinations by time intervals between visits, as the primary exposure. RESULTS: During a median follow-up of 10.00 years, 1,260 cases of incident HF occurred. A higher risk of HF was observed in participants with the highest versus the lowest quartile of cumSUA (adjusted hazard ratio [aHR], 1.54; 95% confidence interval [CI], 1.29-1.84), 6-years (6 years) versus 0-year exposure duration (aHR, 1.87; 95% CI, 1.43-2.45), cumulative burden >0 versus =0 (aHR, 1.55; 95 CI, 1.29-1.86), and those with a negative versus positive SUA slope (aHR, 1.12; 95% CI, 1.02-1.25). When cumSUA was incorporated with its time course, those with cumSUA≥median and a negative SUA slope had the highest risk of HF (aHR, 1.55; 95% CI, 1.29-1.86). CONCLUSIONS: Incident HF risk was associated with the magnitude and time course of cumSUA accumulation. Early accumulation resulted in a greater risk of HF than later accumulation, indicating the importance of optimal SUA control earlier in life.

10.
Orthop Surg ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38858811

RESUMO

OBJECTIVE: Although the advantages of postoperative braces have been verified in many fields, it is not clear whether postoperative braces can help reduce patients' adverse psychological emotions such as kinesiophobia, anxiety, and depression. This study aims to analyze whether the use of a postoperative brace helps reduce adverse psychological emotions in adolescent idiopathic scoliosis (AIS) patients undergoing spinal deformity surgeries. METHODS: All consecutive patients who underwent spinal corrective surgeries at our institution between April 2023 and July 2023 formed the prospective cohort. Outcome measures were collected in the preoperative period, 3 months after surgery, and 6 months after surgery. All patients were assessed using the Tampa scale for kinesiophobia (TSK), the hospital anxiety and depression scale (HADS), and the numerical rating scale (NRS). A statistical model of propensity score matching was used to eliminate potential selection bias and maintain comparability. Multivariate linear regression models were used to determine the relationship between postoperative brace and adverse psychological emotions. RESULTS: After propensity score matching, this study ultimately enrolled 150 patients. There were no significant differences between the two groups in terms of demographic and perioperative variables. The fully adjusted model showed that the TSK scores of the non-brace group at the 3-month (ꞵ = 2.50, 95% CI 0.80-4.20, p = 0.005) and 6-month follow-up (ꞵ = 2.75, 95% CI 0.75-4.74, p = 0.007) were significantly higher than those of the brace group. The HADS score of the non-brace group at the 3-month follow-up was significantly higher than that of the brace group (ꞵ = 1.75, 95% CI 0.28-3.22, p = 0.019). The NRS score of the non-brace group at the 3-month follow-up was significantly higher than that of the brace group (ꞵ = 0.69, 95% CI 0.05-1.33, p = 0.034). At the 6-month follow-up, there were no significant difference for HADS score or NRS score between the two groups. CONCLUSION: In the early postoperative period, the postoperative brace could provide AIS patients with psychological supports and help them reduce the frequency of adverse psychological emotions. The postoperative brace could continuously improve the fear of movement within 6 months after surgery, and help reduce anxiety, depression, and pain within 3 months after surgery.

11.
Transfus Med Hemother ; 51(3): 164-174, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38867809

RESUMO

Objectives: Autologous blood transfusion techniques are well applied in surgery, but the red blood cells (RBCs) collected during laparoscopic surgery may forfeit their ability to oxygenate. O3 is a potent oxidation gas. This study investigates whether O3 could improve the oxygen-carrying capacity of RBCs, reduce inflammatory reactions, and offer organ protection. Methods: We established a hemorrhagic shock model in rabbits, and simulated CO2 pneumoperitoneum and O3 were applied before autologous blood transfusion. Perioperative mean arterial pressure and arterial blood gas were recorded, blood gas and RBC morphology of collected blood were analyzed, plasma IL-6, ALT, AST, CRE, and lung histopathology POD0 and POD3 were tested, as well as postoperative survival quality. Results: Autologous blood that underwent simulated CO2 pneumoperitoneum had a lower pH and SaO2 and a higher PaCO2 than the control group. After O3 treatment, PaO2 and SaO2 increased significantly, with unchanged pH values and PaCO2. RBCs in autologous blood were drastically deformed after CO2 conditioning and then reversed to normal by O3 treatment. Rabbits that received CO2-conditioned autologous blood had a compromised survival quality after surgery, higher plasma IL-6 levels, higher lung injury scores on POD0, higher ALT and AST levels on POD3, and O3 treatment alleviated these adverse outcomes. Conclusion: O3 can restore RBC function, significantly improve blood oxygenation under simulated CO2 pneumoperitoneum, offer organ protection, and improve the postoperative survival quality in the rabbit hemorrhage shock model.

12.
Wei Sheng Yan Jiu ; 53(3): 427-434, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38839584

RESUMO

OBJECTIVE: To investigate the association between long-term fine particulate matter(PM_(2.5)) exposure and the risk of chronic kidney disease(CKD) in people with abnormal metabolism syndrome(MS) components. METHODS: Based on health checkup data from a hospital in Beijing, a retrospective cohort study was used to collect annual checkup data from 2013-2019. A questionnaire was used to obtain information on demographic characteristics and lifestyle habits. We measured blood pressure, height, weight, waist circumference, concentrations of triglycerides(TG), fasting glucose, and high-density lipoprotein cholesterol(HDL-C). Longitude and latitude were also extracted from the addresses of the study subjects for pollutant exposure data estimation. Logistic regression models were used to explore the estimated effect of long-term PM_(2.5) exposure on the risk of CKD prevalence in people with abnormal MS components. Two-pollutant and multi-pollutant models were developed to test the stability of these result. Subgroup analysis was conducted based on age, the presence of MS, individual MS component abnormalities, and dual-component MS abnormalities. RESULTS: The study included 1540 study subjects with abnormal MS components at baseline, 206 with CKD during the study period. The association between long-term PM_(2.5) exposure and increased risk of CKD in people with abnormal MS fractions was statistically significant, with a 2.26-fold increase in risk of CKD for every 10 µg/m~3 increase in PM_(2.5) exposure(OR=3.26, 95% CI 2.72-3.90). The result in the dual-pollutant models and multi-pollutant models suggested that the association between long-term PM_(2.5) exposure and increased risk of CKD in people with abnormal MS fractions remained stable after controlling for contemporaneous confounding by other air pollutants. The result of subgroup analysis revealed that individuals aged 45 or older, without MS, with TG<1.7 mmol/L, HDL-C≥1.04 mmol/L, without hypertension, and with central obesity and high blood sugar had a stronger association between PM_(2.5) exposure and CKD-related health effects. CONCLUSION: Long-term exposure to PM_(2.5) may increase the risk of CKD in people with abnormal MS components. More attention should be paid to middle-aged and elderly people aged ≥45 years, people with central obesity and hyperglycemia.


Assuntos
Exposição Ambiental , Síndrome Metabólica , Material Particulado , Insuficiência Renal Crônica , Humanos , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/epidemiologia , Síndrome Metabólica/etiologia , Síndrome Metabólica/epidemiologia , Feminino , Masculino , Material Particulado/efeitos adversos , Material Particulado/análise , Pessoa de Meia-Idade , Estudos Retrospectivos , Exposição Ambiental/efeitos adversos , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Adulto , Estudos de Coortes , Fatores de Risco , Pequim/epidemiologia , Idoso , Inquéritos e Questionários , Modelos Logísticos
13.
Neurochem Int ; 178: 105786, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38843952

RESUMO

Our previous study has identified that glutamate in the red nucleus (RN) facilitates the development of neuropathic pain through metabotropic glutamate receptors (mGluR). Here, we further explored the actions and possible molecular mechanisms of red nucleus mGluR Ⅰ (mGluR1 and mGluR5) in the development of neuropathic pain induced by spared nerve injury (SNI). Our data indicated that both mGluR1 and mGluR5 were constitutively expressed in the RN of normal rats. Two weeks after SNI, the expressions of mGluR1 and mGluR5 were significantly boosted in the RN contralateral to the nerve injury. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN contralateral to the nerve injury at 2 weeks post-SNI significantly ameliorated SNI-induced neuropathic pain. However, unilateral administration of mGluRⅠ agonist DHPG to the RN of normal rats provoked a significant mechanical allodynia, this effect could be blocked by LY367385 or MTEP. Further studies indicated that the expressions of TNF-α and IL-1ß in the RN were also elevated at 2 weeks post-SNI. Administration of mGluR1 antagonist LY367385 or mGluR5 antagonist MTEP to the RN at 2 weeks post-SNI significantly inhibited the elevations of TNF-α and IL-1ß. However, administration of mGluR Ⅰ agonist DHPG to the RN of normal rats significantly enhanced the expressions of TNF-α and IL-1ß, these effects were blocked by LY367385 or MTEP. These results suggest that activation of red nucleus mGluR1 and mGluR5 facilitate the development of neuropathic pain by stimulating the expressions of TNF-α and IL-1ß. mGluR Ⅰ maybe potential targets for drug development and clinical treatment of neuropathic pain.

14.
Brain Behav ; 14(6): e3578, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38844426

RESUMO

BACKGROUND: This study aimed to investigate sex differences in risk factors for suicide attempts in first-episode and drug naive (FEDN) major depressive disorder (MDD) with comorbid subclinical hypothyroidism (SCH). METHODS: A total of 1034 FEDN MDD patients with comorbid SCH were enrolled. The Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) positive subscale were used to assess patients' symptoms. Thyroid hormone levels and metabolic parameters were measured. RESULTS: MDD patients with SCH had a significantly higher risk of suicide attempts than those without SCH (25.4% vs. 12.2%). Logistic regression showed that HAMA score, thyroid stimulating hormone (TSH) levels, and thyroid peroxidase antibody (TPOAb) levels were significantly associated with an increased risk for suicide attempts in both male and female MDD patients comorbid SCH, while low-density lipoprotein cholesterol (LDL-C) was significantly associated with an increased risk for suicide attempts only in male patients, HAMD score and systolic blood pressure were significantly associated with an increased risk for suicide attempts only in female patients. CONCLUSION: SCH comorbidities may increase suicide attempts in MDD patients. Our results showed significant sex differences in clinical and metabolic factors associated with suicide attempts among FEDN MDD patients with comorbid SCH, highlighting appropriate sex-based preventive interventions are needed.


Assuntos
Comorbidade , Transtorno Depressivo Maior , Hipotireoidismo , Tentativa de Suicídio , Humanos , Masculino , Feminino , Transtorno Depressivo Maior/epidemiologia , Transtorno Depressivo Maior/sangue , Adulto , Estudos Transversais , Hipotireoidismo/epidemiologia , Hipotireoidismo/sangue , Tentativa de Suicídio/estatística & dados numéricos , China/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Caracteres Sexuais , Fatores Sexuais , Adulto Jovem , Tireotropina/sangue , População do Leste Asiático
15.
Redox Biol ; 73: 103206, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38796864

RESUMO

Fungal keratitis is a severely vision-threatening corneal infection, where the prognosis depends on both fungal virulence and host immune defense. Inappropriate host responses can induce substantial inflammatory damage to the cornea. Therefore, in the treatment of fungal keratitis, it is important to concurrently regulate the immune response while efforts are made to eliminate the pathogen. Ebselen is a widely studied organo-selenium compound and has been demonstrated to have antifungal, antibacterial, anti-inflammatory, and oxidative stress-regulatory properties. The effectiveness of ebselen for the treatment of fungal keratitis remains unknown. In this study, ebselen was demonstrated to produce a marked inhibitory effect on Aspergillus fumigatus (A. fumigatus), including spore germination inhibition, mycelial growth reduction, and fungal biofilm disruption. The antifungal activity of ebselen was related to the cell membrane damage caused by thioredoxin (Trx) system inhibition-mediated oxidative stress. On the contrary, ebselen enhanced the antioxidation of Trx system in mammalian cells. Further, ebselen was proven to suppress the expressions of inflammatory mediators (IL-1ß, IL-6, TNF-α, COX-2, iNOS, and CCL2) and reduce the production of oxidative stress-associated indicators (ROS, NO, and MDA) in fungi-stimulated RAW264.7 cells. In addition, ebselen regulated PI3K/Akt/Nrf2 and p38 MAPK signaling pathways, which contributed to the improvement of inflammation and oxidative stress. Finally, we verified the therapeutic effect of ebselen on mouse fungal keratitis. Ebselen improved the prognosis and reduced the fungal burden in mouse corneas. Expressions of inflammatory mediators, as well as the infiltration of macrophages and neutrophils in the cornea were also obviously decreased by ebselen. In summary, ebselen exerted therapeutic effects by reducing fungal load and protecting host tissues in fungal keratitis, making it a promising treatment for fungal infections.


Assuntos
Anti-Inflamatórios , Antifúngicos , Azóis , Isoindóis , Ceratite , Compostos Organosselênicos , Estresse Oxidativo , Compostos Organosselênicos/farmacologia , Compostos Organosselênicos/uso terapêutico , Animais , Ceratite/tratamento farmacológico , Ceratite/microbiologia , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Azóis/farmacologia , Azóis/uso terapêutico , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Células RAW 264.7 , Antioxidantes/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/metabolismo , Modelos Animais de Doenças
16.
Chin J Integr Med ; 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38816637

RESUMO

The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research. Frankincense, a widely recognized natural antitumor medicine, has undergone a systematic review encompassing its species, chemical constituents, and diverse pharmacological activities and mechanisms. The different species of frankincense include Boswellia serrata, Somali frankincense, Boswellia frereana, and Boswellia arabica. Various frankincense extracts and compounds exhibit antitumor, anti-inflammatory, and hepatoprotective properties and antioxidation, memory enhancement, and immunological regulation capabilities. They also have comprehensive effects on regulating flora. Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors. This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents, thus laying the foundations for developing effective tumor-combating targets.

17.
Insect Mol Biol ; 33(4): 312-322, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38767730

RESUMO

Bee venom serves as an essential defensive weapon for bees and also finds application as a medicinal drug. MicroRNAs (miRNAs) serve as critical regulators and have been demonstrated to perform a variety of biological functions. However, the presence of miRNAs in bee venom needs to be confirmed. Therefore, we conducted small RNA sequencing and identified 158 known miRNAs, 15 conserved miRNAs and 4 novel miRNAs. It is noteworthy that ame-miR-1-3p, the most abundant among them, accounted for over a quarter of all miRNA reads. To validate the function of ame-miR-1-3p, we screened 28 candidate target genes using transcriptome sequencing and three target gene prediction software (miRanda, PITA and TargetScan) for ame-miR-1-3p. Subsequently, we employed real-time quantitative reverse transcription PCR (qRT-PCR), Western blot and other technologies to confirm that ame-miR-1-3p inhibits the relative expression of antizyme inhibitor 1 (AZIN1) by targeting the 3' untranslated region (UTR) of AZIN1. This, in turn, caused ODC antizyme 1 (OAZ1) to bind to ornithine decarboxylase 1 (ODC1) and mark ODC1 for proteolytic destruction. The reduction in functional ODC1 ultimately resulted in a decrease in polyamine biosynthesis. Furthermore, we determined that ame-miR-1-3p accelerates cell death through the AZIN1/OAZ1-ODC1-polyamines pathway. Our studies demonstrate that ame-miR-1-3p diminishes cell viability and it may collaborate with sPLA2 to enhance the defence capabilities of honeybees (Apis mellifera L.). Collectively, these data further elucidate the defence mechanism of bee venom and expand the potential applications of bee venom in medical treatment.


Assuntos
Venenos de Abelha , Proteínas de Insetos , MicroRNAs , Animais , Abelhas/genética , Abelhas/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Venenos de Abelha/farmacologia , Proteínas de Insetos/metabolismo , Proteínas de Insetos/genética , Sobrevivência Celular , Poliaminas/metabolismo , Ornitina Descarboxilase/metabolismo , Ornitina Descarboxilase/genética
18.
Exp Eye Res ; 244: 109944, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38797260

RESUMO

Fungal keratitis (FK) is an infectious keratopathy can cause serious damage to vision. Its severity is related to the virulence of fungus and response of inflammatory. Rosmarinic acid (RA) extracted from Rosmarinus officinalis exhibits antioxidant, anti-inflammatory and anti-viral properties. The aim of this study was to investigate the effect of RA on macrophage autophagy and its therapeutic effect on FK. In this study, we demonstrated that RA reduced expression of proinflammatory cytokine, lessened the recruitment of inflammatory cells in FK. The relative contents of autophagy markers, such as LC3 and Beclin-1, were significantly up-regulated in RAW 264.7 cells and FK. In addition, RA restored mitochondrial membrane potential (MMP) of macrophage to normal level. RA not only reduced the production of intracellular reactive oxygen species (ROS) but also mitochondria ROS (mtROS) in macrophage. At the same time, RA induced macrophage to M2 phenotype and down-regulated the mRNA expression of IL-6, IL-1ß, TNF-α. All the above effects could be offset by the autophagy inhibitor 3-Methyladenine (3-MA). Besides, RA promote phagocytosis of RAW 264.7 cells and inhibits spore germination, biofilm formation and conidial adherence, suggesting a potential therapeutic role for RA in FK.


Assuntos
Aspergilose , Aspergillus fumigatus , Autofagia , Cinamatos , Depsídeos , Infecções Oculares Fúngicas , Macrófagos , Espécies Reativas de Oxigênio , Ácido Rosmarínico , Depsídeos/farmacologia , Animais , Autofagia/efeitos dos fármacos , Camundongos , Aspergilose/tratamento farmacológico , Aspergilose/microbiologia , Aspergilose/metabolismo , Infecções Oculares Fúngicas/microbiologia , Infecções Oculares Fúngicas/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/microbiologia , Cinamatos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Ceratite/microbiologia , Ceratite/tratamento farmacológico , Ceratite/metabolismo , Modelos Animais de Doenças , Células RAW 264.7 , Citocinas/metabolismo , Fagocitose/efeitos dos fármacos
19.
Endocrine ; 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38753244

RESUMO

BACKGROUND: Currently, the special blood pressure (BP) target for normotensive diabetic patients has not been recommended. We investigated the optimal systolic blood pressure (SBP) for lower cardiovascular disease (CVD) risk in normotensive diabetic patients. METHODS: In this 12-year follow-up study using the participants of the Kailuan Study, we mainly compared which SBP, 90-119 mmHg or 120-129 mmHg, had a lower risk of occurrence of CVD (stroke and myocardial infarction) in the 3072 normotensive diabetic participants and 21,532 normotensive and non-diabetic participants, respectively. The SBP was expressed as a mean time-weighted cumulative (MTWC) SBP, calculated from the multiple measurements of SBP during the follow-up. Multivariate competing risk regression analyses were used for the analysis. RESULTS: We found that in normotensive diabetic participants, MTWC SBP of 120-129 mmHg was associated with a lower risk of CVD (HR = 0.69 [0.50-0.95]), myocardial infarction (HR = 0.48 [0.24-0.96]), and trending towards lower risk of stroke (HR = 0.80 [0.55-1.16]), compared to MTWC SBP of 90-119 mmHg. Sensitivity analyses confirmed the relationship between low SBP and increased CVD risk. Whereas, in the normotensive and non-diabetic participants, MTWC SBP of 90-119 mmHg vs 120-129 mmHg did not exhibit any difference in the risk of CVD occurrence (HR = 0.99 [0.83-1.18]). CONCLUSIONS: The higher level of SBP in normotensive diabetic patients is especially associated with a lower risk of CVD occurrence.

20.
J Neuropsychol ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738605

RESUMO

Moral identity is an important moral variable which has positive moral functions, such as contributing to prosocial behaviours, reducing antisocial behaviours, and resisting the risk factors of antisocial behaviours. However, little is known about the neural correlates of moral identity and the neural basis of the effect of moral identity on the risk factors of antisocial behaviours, including moral disengagement. In this study, we explored these issues in 142 college students by estimating the regional homogeneity (ReHo) through resting-state functional magnetic resonance imaging (fMRI). The whole-brain correlation analyses found that higher internalized moral identity was correlated with higher ReHo in the precuneus. Furthermore, the ReHo in the precuneus was negatively correlated with moral disengagement, suggesting positive moral functions of the neural mechanisms of moral identity. These findings deepen our understanding of individual differences in moral identity and provide inspiration for the education of moral identity and the intervention for moral disengagement from the perspective of the brain.

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