RESUMO
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as icotinib, osimertinib, and aumolertinib have emerged as promising treatment options for EGFR mutated Non-small cell lung cancer (NSCLC) patients. Additionally, anlotinib, an anti-angiogenic agent targeting VEGFR, FGFR, and PDGFR, has been used in combination with EGFR-TKIs in NSCLC cases. A method utilizing ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated for quantifying icotinib, osimertinib, aumolertinib and anlotinib simultaneously in clinical TDM. The chromatographic separation was performed using a Kinetex C18 column (100â¯mm × 2.1â¯mm) and an elution gradient of ammonium acetate in water acidified with 0.1â¯% formic acid and in acetonitrile. The assay was validated over a linear range of 4-2000â¯ng/mL for icotinib, 2-1000â¯ng/mL for osimertinib, 1-500â¯ng/mL for aumolertinib, and 0.8-400â¯ng/mL for anlotinib, following the guidelines on bioanalytical methods by FDA. The quantification method exhibited satisfactory performance in terms of selectivity, accuracy (from 91.3â¯% to 107â¯%), precision (intra- and inter-day coeffficients of variation ranged from 0.944â¯% to 7.48â¯%), linearity, recovery (from 86.0â¯% to 91.9â¯%), matrix effect (IS-normalized matrix factors were from 96.7â¯% to 102â¯%), and stability. Overall, the method proved to be sensitive, reliable, and straightforward, enabling successful simultaneous determination of blood concentrations of icotinib, osimertinib, aumolertinib, and anlotinib in patients. The validity of the method has been confirmed across various instruments.
RESUMO
BACKGROUND: Exposure to light at night (LAN) has been associated with multiple adverse health outcomes. However, evidence is limited regarding the impacts of LAN exposure on human inflammation. OBJECTIVES: To examine the association between real-ambient bedroom LAN exposure with systemic inflammation and circadian rhythm of inflammatory markers. METHODS: Using data from a prospective cohort study of Chinese young adults. At baseline, bedroom LAN exposure was measured with a portable illuminance meter; fasting blood sample for high-sensitivity C-reactive protein (hs-CRP) assay was collected. At 3-year follow-up, 20 healthy young adults (10 LANavg < 5â¯lx, 10 LANavg ≥ 5â¯lx) were recruited from the same cohort; time-series venous blood samples were sampled every 4â¯h over a 24â¯h-cycle for the detection of 8 inflammatory markers. Circadian rhythm of inflammatory markers was assessed using cosinor analysis. RESULTS: At baseline, the average age of the 276 participants was 18.7 years, and 33.3â¯% were male. Higher levels of bedroom LAN exposure were significantly associated with increased hs-CRP levels. The association between bedroom LAN exposure and systemic inflammation was only significant in the inactive group (MVPA < 2â¯h/d) but not in the physically active group (MVPA ≥ 2â¯h/d). In addition, exposure to higher levels of nighttime light (LANavg ≥ 5â¯lx) disrupted circadian rhythms (including rhythmic expression, circadian amplitude and circadian phase) of some inflammatory cytokines and inflammatory balance indicators. CONCLUSION: Exposure to bedroom nighttime light increases systemic inflammation and disrupts circadian rhythm of inflammatory markers. Keep bedroom darkness at night may represent important strategies for the prevention of chronic inflammation. Additionally, for people living a community with higher nighttime light pollution, regular physical activity may be a viable option to counteract the negative impacts of LAN exposure on chronic inflammation.
Assuntos
Biomarcadores , Proteína C-Reativa , Ritmo Circadiano , Inflamação , Luz , Humanos , Masculino , Inflamação/sangue , Feminino , Biomarcadores/sangue , Adulto Jovem , Estudos Prospectivos , Adolescente , Luz/efeitos adversos , Proteína C-Reativa/análise , Iluminação/efeitos adversos , China , AdultoRESUMO
OBJECTIVE: To evaluate the causal relationship between sleep fragmentation (SF) parameters with general and abdominal obesity in free-living conditions. METHODS: SF parameters were assessed by ActiGraph accelerometers for 7 consecutive days. Obesity was measured at baseline and 1-year follow-up with InBody S10 body composition analyzer. RESULTS: At baseline, the mean age of the study population was 18.7 years old (SD = 0.9) and 139 (35.7%) were male. Each 1-unit increase of baseline sleep fragmentation index (SFI) was associated with 0.08 kg/m2-increase of body mass index (BMI) (95% CI: 0.03, 0.14), 0.20%-increase of percentage of body fat (PBF) (95% CI: 0.07, 0.32), 0.15 kg-increase of fat mass (FM) (95% CI: 0.03, 0.27), 0.15 cm-increase of waist circumference (WC) (95% CI: 0.03, 0.26) and 0.91 cm2-increase of visceral fat area (VFA) (95% CI: 0.36, 1.46) at the 1-year follow-up. In addition, each 1-unit increase of baseline SFI was associated with 15% increased risk of general obesity (OR = 1.15, 95% CI = 1.04-1.28; p = 0.006) and 7% increased risk of abdominal obesity (OR = 1.07, 95% CI = 1.01-1.13; p = 0.021) in the following year. CONCLUSIONS: Fragmented sleep is independently associated with an increased risk of both general and abdominal obesity. The result highlights SF as a modifiable risk factor for the prevention and treatment of obesity.
Assuntos
Obesidade Abdominal , Privação do Sono , Humanos , Masculino , Obesidade Abdominal/epidemiologia , Obesidade Abdominal/complicações , Obesidade Abdominal/fisiopatologia , Estudos Longitudinais , Feminino , Privação do Sono/complicações , Privação do Sono/fisiopatologia , Privação do Sono/epidemiologia , Adolescente , Índice de Massa Corporal , Circunferência da Cintura , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/fisiopatologia , Adulto Jovem , AdultoRESUMO
Parkinson's disease (PD), as a neurologically implemented disease with complex etiological factors, has a complex and variable pathogenesis. Accompanying further research, neuroinflammation has been found to be one of the possible factors in its pathogenesis. Microglia, as intrinsic immune cells in the brain, play an important role in maintaining microenvironmental homeostasis in the brain. However, over-activation of neurotoxic microglia in PD promotes neuroinflammation, which further increases dopaminergic (DA) neuronal damage and exacerbates the disease process. Therefore, targeting and regulating the functional state of microglia is expected to be a potential avenue for PD treatment. In addition, plant extracts have shown great potential in the treatment of neurodegenerative disorders due to their abundant resources, mild effects, and the presence of multiple active ingredients. However, it is worth noting that some natural products have certain toxic side effects, so it is necessary to pay attention to distinguish medicinal ingredients and usage and dosage when using to avoid aggravating the progression of diseases. In this review, the roles of microglia with different functional states in PD and the related pathways inducing microglia to transform into neuroprotective states are described. At the same time, it is discussed that abscisic acid (ABA) may regulate the polarization of microglia by targeting them, promote their transformation into neuroprotective state, reduce the neuroinflammatory response in PD, and provide a new idea for the treatment of PD and the selection of drugs.
Assuntos
Ácido Abscísico , Microglia , Doenças Neuroinflamatórias , Doença de Parkinson , Microglia/efeitos dos fármacos , Microglia/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Humanos , Ácido Abscísico/metabolismo , Ácido Abscísico/farmacologia , Animais , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/etiologia , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêuticoRESUMO
Pulmonary tuberculosis (TB) can result in irreversible damage and lead to tuberculous destructive lung (TDL), a severe chronic lung disease that is associated with a high mortality rate. Additionally, pulmonary hypertension (PH) is a hemodynamic disorder that can be caused by lung diseases. The objective of this study is to investigate the risk factors associated with PH in active TB patients diagnosed with TDL. We conducted a retrospective review of the medical records of 237 patients who were diagnosed with TDL, active pulmonary tuberculosis, and underwent echocardiography at the Third People' Hospital of Shenzhen from January 1, 2016, to June 30, 2023. Univariate and multivariate logistic regression analyses were performed to identify factors that correlated with the development of pulmonary hypertension. Univariate and multivariate logistic regression analyses revealed that several factors were associated with an increased risk of pulmonary hypertension (PH) in individuals with tuberculosis destroyed lung (TDL). These factors included age (OR = 1.055), dyspnea (OR = 10.728), D-dimer (OR = 1.27), PaCO2 (OR = 1.040), number of destroyed lung lobes (OR = 5.584), bronchiectasis (OR = 3.205), and chronic pleuritis (OR = 2.841). When age, D-dimer, PaCO2, and number of destroyed lung lobes were combined, the predictive value for PH in patients with TDL was found to be 80.6% (95% CI 0.739-0.873),with a sensitivity of 76.6% and specificity of 73.2%. Advanced age, elevated D-dimer levels, hypercapnia, and severe lung damage were strongly correlated with the onset of PH in individuals with active pulmonary tuberculosis (PTB) and TDL. Furthermore, a model incorporating age, D-dimer, PaCO2, and the number of destroyed lung lobes might be valuable in predicting the occurrence of PH in patients with active PTB and TDL.
Assuntos
Hipertensão Pulmonar , Tuberculose Pulmonar , Humanos , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Estudos Retrospectivos , Tuberculose Pulmonar/complicações , Adulto , Pulmão/patologia , Pulmão/diagnóstico por imagem , Idoso , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismoRESUMO
As a kind of biosurfactants, iturin A has attracted people's wide attentions due to their features of biodegradability, environmentally friendly, etc.; however, high production cost limited its extensive application, and the aim of this research wants to improve iturin A production in Bacillus amyloliquefaciens. Firstly, dual promoter was applied to strengthen iturin A synthetase expression, and its yield was increased to 1.25 g/L. Subsequently, original 5'-UTRs of downstream genes (ituA, ituB, and ituC) in iturin A synthetase cluster were optimized, which significantly increased mRNA secondary stability, and iturin A yield produced by resultant strain HZ-T3 reached 2.32 g/L. Secondly, synthetic pathway of α-glucosidase inhibitor 1-deoxynojirimycin was blocked to improve substrate corn starch utilization, and iturin A yield was increased by 34.91% to 3.13 g/L. Thirdly, efficient precursor (fatty acids, Ser, and Pro) supplies were proven as the critical role in iturin A synthesis, and 5.52 g/L iturin A was attained by resultant strain, through overexpressing yngH, serC, and introducing ocD. Meanwhile, genes responsible for poly-γ-glutamic acid, extracellular polysaccharide, and surfactin syntheses were deleted, which led to a 30.98% increase of iturin A yield. Finally, lipopeptide transporters were screened, and iturin A yield was increased by 17.98% in SwrC overexpression strain, reached 8.53 g/L, which is the highest yield of iturin A ever reported. This study laid a foundation for industrial production and application development of iturin A, and provided the guidance of metabolic engineering breeding for efficient production of other metabolites synthesized by non-ribosomal peptide synthetase. KEY POINTS: ⢠Optimizing 5'-UTR is an effective tactics to regulate synthetase cluster expression. ⢠Blocking 1-DNJ synthesis benefited corn starch utilization and iturin A production. ⢠The iturin A yield attained in this work was the highest yield reported so far.
Assuntos
Bacillus amyloliquefaciens , Engenharia Metabólica , Tensoativos , Bacillus amyloliquefaciens/genética , Bacillus amyloliquefaciens/metabolismo , Engenharia Metabólica/métodos , Tensoativos/metabolismo , Peptídeos Cíclicos/biossíntese , Peptídeos Cíclicos/genética , Peptídeos Cíclicos/metabolismo , Regiões Promotoras Genéticas , Ligases/genética , Ligases/metabolismoRESUMO
Background: The exact causal mechanisms of depression remain unclear due to the complexity of the triggers, which has led to limitations in treating depression using modern drugs. High-intensity interval training (HIIT) is as effective as medication in treating depression without toxic side effects. Typically, HIIT requires less time commitment (i.e., shorter exercise duration) and exhibits pronounced benefits on depressive symptoms than other forms of physical exercise. This review summarizes the risk reduction and clinical effects of HIIT for depression and discusses the underlying mechanisms, providing a theoretical basis for utilizing HIIT in treating depression. Methods: A database search was conducted in PubMed, Embase, Web of Science, and Scopus from inception up to October 2022. The methodological quality of the included literature was evaluated by the physiotherapy evidence database (PEDro) scale criteria. The review focused on evaluating the changes in depression risk or symptoms of HIIT interventions in healthy individuals, patients with depression, and patients with other disorders co-morbid with depression. Consequently, the mechanisms associated with depression related HIIT were summarized. Results: A total of 586 participants (52 % female; mean age: 43.58±8.93 years) from 22 studies were included. Implementing HIIT using different exercise types alleviates depressive symptoms in individuals with depression and in individuals with depression who have exhibited comorbidities and reduced depression scale scores in subjects immediately after acute exercise. In addition, the long-interval HIIT and short-interval HIIT in the treatment of patients with cardiovascular or psychiatric disorders may reduce depressive symptoms via complex exercise-related changes on several levels, including by effecting the following measures: releasing monoamines, reducing neuronal death, inducing neurogenesis, modulating the functional...(AU)
Assuntos
Humanos , Masculino , Feminino , Depressão , Inflamação/reabilitação , Fatores de Crescimento Neural , Sistema Hipotálamo-Hipofisário , Treinamento Intervalado de Alta Intensidade , Tratamento FarmacológicoRESUMO
BACKGROUND: Light at night (LAN) have attracted increased research attention on account of its widespread health hazards. However, the underlying mechanism remains unknown. The objective of this study was to investigate the effects of real-ambient bedroom LAN exposure on circadian rhythm among young adults and potential sex differences. METHODS: Bedroom LAN exposure was measured at 60-s intervals for 2 consecutive days using a portable illuminance meter. Circadian phase was determined by the dim light melatonin onset (DLMO) time in 7 time-series saliva samples. RESULTS: The mean age of the 142 participants was 20.7 ± 0.8 years, and 59.9% were women. The average DLMO time was 21:00 ± 1:11 h, with men (21:19 ± 1:12 h) later than women (20:48 ± 1:07 h). Higher level of LAN intensity (LANavg ≥ 3lx vs. LANavg < 3lx) was associated with an 81.0-min later in DLMO time (95% CI: 0.99, 1.72), and longer duration of nighttime light intensity ≥ 5lx (LAN5; LAN5 ≥ 45 min vs. LAN5 < 45 min) was associated with a 51.6-min later in DLMO time (95% CI: 0.46, 1.26). In addition, the delayed effect of LAN exposure on circadian phase was more pronounced in men than in women (all P-values <0.05). CONCLUSIONS: Overall, bedroom LAN exposure was significantly associated with delayed circadian rhythm. Additionally, the delayed effect is more significant in men. Keeping bedroom dark at night may be a practicable option to prevent circadian disruption and associated health implications. Future studies with more advanced light measurement instrument and consensus methodology for DLMO assessment are warranted.
Assuntos
Ritmo Circadiano , Luz , Melatonina , Humanos , Masculino , Feminino , Adulto Jovem , Estudos Transversais , China , Iluminação , Saliva/química , Saliva/efeitos da radiação , Adulto , População do Leste AsiáticoRESUMO
Background: The exact causal mechanisms of depression remain unclear due to the complexity of the triggers, which has led to limitations in treating depression using modern drugs. High-intensity interval training (HIIT) is as effective as medication in treating depression without toxic side effects. Typically, HIIT requires less time commitment (i.e., shorter exercise duration) and exhibits pronounced benefits on depressive symptoms than other forms of physical exercise. This review summarizes the risk reduction and clinical effects of HIIT for depression and discusses the underlying mechanisms, providing a theoretical basis for utilizing HIIT in treating depression. Methods: A database search was conducted in PubMed, Embase, Web of Science, and Scopus from inception up to October 2022. The methodological quality of the included literature was evaluated by the physiotherapy evidence database (PEDro) scale criteria. The review focused on evaluating the changes in depression risk or symptoms of HIIT interventions in healthy individuals, patients with depression, and patients with other disorders co-morbid with depression. Consequently, the mechanisms associated with depression related HIIT were summarized. Results: A total of 586 participants (52 % female; mean age: 43.58±8.93 years) from 22 studies were included. Implementing HIIT using different exercise types alleviates depressive symptoms in individuals with depression and in individuals with depression who have exhibited comorbidities and reduced depression scale scores in subjects immediately after acute exercise. In addition, the long-interval HIIT and short-interval HIIT in the treatment of patients with cardiovascular or psychiatric disorders may reduce depressive symptoms via complex exercise-related changes on several levels, including by effecting the following measures: releasing monoamines, reducing neuronal death, inducing neurogenesis, modulating the functional homeostasis of the HPA axis, and enhancing the level of inflammation in the body. Conclusion: HIIT is a relatively safe and effective antidepressant, which may involve multiple neurobiological mechanisms (release of monoamines, reducing neuronal death, inducing neurogenesis, modulating the functional homeostasis of the HPA axis, and enhancing the level of inflammation in the body), thereby reducing the risk or symptoms of depression in participants.
RESUMO
PURPOSE: To investigate the cross-sectional associations between real-world multiperiod bedroom light at night and sleep parameters among 365 Chinese young adults. METHODS: Bedroom light exposure was estimated at the individual level for two consecutive days using a portable illuminance meter. Subjective sleep parameters were measured with the Pittsburgh Sleep Quality Index, and objective sleep parameters were assessed by wrist-worn ActiGraph accelerometers for seven consecutive days. RESULTS: Compared with the low-exposure group (average light intensity < 3lx), the high-exposure group (average light intensity ≥ 3lx) was associated with decreased 1.15% in sleep efficiency (sleep efficiency, 95% CI: -1.78, -0.52; p < .001), increased 3.94 minutes in wake after sleep onset (wake after sleep onset, 95% CI: 1.55, 6.33; p = .001), increased 1.05 unit in movement index (95% CI: 0.20, 1.89; p = .015), and increased 2.16 unit in sleep fragmentation index ( 95% CI: 0.63, 3.68; p = .006). In comparison, each interquartile increase in 2h-average and 1h-average intensity of preawake light (PAL) (PAL-2h and PAL-1h) was associated with 7.04 minutes of increases in total sleep time (95% CI: 0.87, 13.22; p = .025) and 6.69 minutes of increases in total sleep time (95% CI: 0.51, 12.87; p = .034), respectively. DISCUSSION: Altogether, our results support the role of bedroom light exposure in sleep and imply the importance of bedroom light exposure management as a potential strategy to reduce the public health burden of sleep problems. Keeping the bedroom environment dark at night and allowing moderate morning light exposure may be important measures for improving the sleep quality of young adults.
Assuntos
Poluição Luminosa , Sono , Humanos , Adulto Jovem , Estudos Transversais , Polissonografia , ChinaRESUMO
OBJECTIVE: Accelerated female reproductive events represent the early onset of reproductive events involving puberty, menarche, pregnancy loss, first sexual intercourse, first birth, parity, and menopause. This study aimed to explore the association between childhood adversity and accelerated female reproductive events. DATA SOURCES: PubMed, Web of Science, and Embase were systematically searched from September 22, 2022 to September 23, 2022. STUDY ELIGIBILITY CRITERIA: Observational cohort, cross-sectional, and case-control studies in human populations were included if they reported the time of reproductive events for female individuals with experience of childhood adversity and were published in English. METHODS: Two reviewers independently screened studies, obtained data, and assessed study quality, and conflicts were resolved by a third reviewer. Dichotomous outcomes were evaluated using meta-analysis, and pooled odds ratios and 95% confidence intervals were generated using random-effects models. Moderation analysis and meta-regression were used to investigate heterogeneity. RESULTS: In total, 21 cohort studies, 9 cross-sectional studies, and 3 case-control studies were identified. Overall, female individuals with childhood adversity were nearly 2 times more likely to report accelerated reproductive events than those with no adversity exposure (odds ratio, 1.91; 95% confidence interval, 1.33-2.76; I2=99.6%; P<.001). Moderation analysis indicated that effect sizes for the types of childhood adversity ranged from an odds ratio of 1.61 (95% confidence interval, 1.23-2.09) for low socioeconomic status to 2.13 (95% confidence interval, 1.14-3.99) for dysfunctional family dynamics. Among the 7 groups based on different reproductive events, including early onset of puberty, early menarche, early sexual initiation, teenage childbirth, preterm birth, pregnancy loss, and early menopause, early sexual initiation had a nonsignificant correlation with childhood adversity (odds ratio, 2.70; 95% confidence interval, 0.88-8.30; I2=99.9%; P<.001). Considerable heterogeneity (I2>75%) between estimates was observed for over half of the outcomes. Age, study type, and method of data collection could explain 35.9% of the variance. CONCLUSION: The literature tentatively corroborates that female individuals who reported adverse events in childhood are more likely to experience accelerated reproductive events. This association is especially strong for exposure to abuse and dysfunctional family dynamics. However, the heterogeneity among studies was high, requiring caution in interpreting the findings and highlighting the need for further evaluation of the types and timing of childhood events that influence accelerated female reproductive events.
Assuntos
Experiências Adversas da Infância , Nascimento Prematuro , Adolescente , Criança , Feminino , Humanos , Gravidez , Estudos Transversais , Parto , ReproduçãoRESUMO
Light at night (LAN) is a significant but underappreciated risk factor contributing to cardiometabolic disease (CMD). We therefore conducted the review examining the relationship of LAN exposure with CMD in order to investigate the effects of LAN exposure on CMD. We searched PubMed, Web of Science, Embase, and Scopus for eligible studies published from database inception to August 17, 2023. The pooled effect size was calculated using random-effects models. Heterogeneity among the studies was quantified by Cochran's Q test and I2 statistic. A total of 1,019,739 participants from 14 studies (5 cohort studies and 9 cross-sectional) were included. Among the 14 eligible studies, 9 on obesity, 4 on diabetes, 2 on hypertension, 1 on dyslipidemia, and 1 on coronary heart disease. Exposure to higher levels of LAN were associated with 21% higher risk of CMD (Summary risk ratio, SRR: 1.21, 95% CI = 1.16-1.27), accompanied by substantial heterogeneity (I2 = 61%; tau2 = 0.004; Cochran's Q = 41.02). Specifically, individuals in the highest category of LAN exposure exhibited 23% higher risk of obesity (SRR: 1.23, 95% CI = 1.14-1.32), 46% higher risk of diabetes (SRR: 1.46, 95% CI = 1.05-2.03) and 21% higher risk of other CMDs (SRR: 1.21, 95% CI = 1.10-1.34). Subgroup analyses revealed that the pooled-effect size of LAN and CMD was higher for indoor LAN than outdoor LAN (indoor LAN: SRR = 1.36; outdoor LAN: SRR = 1.17, P = 0.03). The overall quality was rated as moderate using GRADE guideline. Our study strengthens the evidence on the increase in CMD risk due to LAN exposure. Findings from this study have important implications for identifying modifiable risk factor of CMD, future prevention strategy development, and resource allocation for high-risk group.
Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Humanos , Estudos Transversais , Obesidade , Fatores de Risco , Diabetes Mellitus/epidemiologia , Doenças Cardiovasculares/epidemiologiaRESUMO
Persistent oxidative stress and endoplasmic reticulum (ER) stress are the primary mechanisms of age-related cardiovascular diseases. Although exercise training is viewed as an effective anti-aging approach, further exploration is needed to identify the mechanisms and functional targets. In this study, the impact of resistance training (RT) on the expression of Smyd1, the levels of reactive oxygen species (ROS) and the expression of ER stress-related protein in the hearts of mice of different ages were assessed. In addition, the role of Smyd1 in the aging-induced oxidative stress and ER stress were evaluated in d-galactose (D-gal)-treated H9C2 cells. We demonstrated that RT in middle age increased the expression of Smyd1 and restricted heart aging-induced ER stress. Overexpression of Smyd1 restrained oxidative stress and ER stress in D-gal-treated H9C2 cells, while the inhibition of Nrf2 and Smyd1 escalated ER stress. These findings demonstrate that Smyd1 has significant impact in regulating age-related ER stress. RT in middle age can up-regulates Smyd1 expression and inhibits oxidative stress and ER stress in the heart.
Assuntos
Treinamento Resistido , Humanos , Camundongos , Animais , Coração , Estresse do Retículo Endoplasmático/genética , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Apoptose , Proteínas de Ligação a DNA/metabolismo , Proteínas Musculares/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Objective@#To explore the association between bedroom light at night (LAN) exposure and body mass index (BMI) in children at 1 year follow up, so as to provide new strategies for obesity prevention.@*Methods@#From December 2021 to May 2022, cluster random sampling was conducted, involving 648 children from two primary schools in Tianchang, Chuzhou City, Anhui Province, China, to assess bedroom LAN exposure of children during sleep. A questionnaire survey and physical examination were carried out in May 2022. Multivariate linear regression was performed to analyze the correlation between bedroom LAN exposure and BMI variable quantity at 1 year follow up (May, 2023).@*Results@#The median intensity of bedroom LAN exposure during the sleep episode was [1.11(0.35,3.24)lx] in children. The proportion of the sample exposed to an average light intensity of ≥3 lx was 27.5%, while 19.0% was exposed to a LAN intensity of ≥5 lx during the sleep episode. In the multivariable linear regression, after adjusting for covariates, including sex, baseline age, sleep duration, family monthly income, and maternal education level, exposure to a 1 h-average post bedtime LAN intensity of ≥3 lx ( β=0.25, 95%CI =0.05-0.44) and LAN≥5 lx ( β=0.34, 95% CI = 0.12-0.55) was associated with a gain of 0.25 and 0.34 kg/m 2, respectively, in the children s BMI at the 1 year follow up ( P < 0.05).@*Conclusions@#A positive correlation was found between bedroom LAN exposure and BMI variable quantity at 1 year follow up in children. Thus, reduced bedroom LAN exposure might be useful for interventions aimed at obesity prevention.
RESUMO
Purpose: To develop an UPLC-MS/MS method for the quantitative analysis of pentoxifylline in beagle dog plasma and apply it to a pharmacokinetic study of food effect. Methods: Sample separation was achieved using a Kinetex Phenyl-Hexyl column (50 × 2.1 mm, 1.7 µm) with a gradient elution program in 5.5 min after a simple protein precipitation with methanol. Using the mobile phase that made up by 0.2% formic acid and 5mM ammonium formate water (A) and methanol (B). Quantitation was carried out using the positive ionization mode with multiple reaction monitoring (MRM). A randomized, single-dose, two-period crossover study was conducted in six fasted or fed beagles that received 400 mg pentoxifylline sustained-release tablets (Brand name: Shuanling™, CSPC Pharmaceutical Group). WinNonlin® software was used to calculate pharmacokinetic parameters. Results: The linear calibration range was 2-1000 ng/mL (r2> 0.99). Both intra- and inter-batch precision were less than 6.27%, and the accuracy ranged from 88.65% to 97.18%. Pentoxifylline was readily absorbed in fasted and fed dogs administered a dose of 400 mg (tmax:1.54h vs 1.83h). Compared to the fasted group, the AUC0ât and Cmax in the fed group increased by 1.71-fold and 1.30-fold, respectively. In the fasted group, the AUC0ât and Cmax values were 4684.08 hâ¢ng/mL and 2402.33 ng/mL, respectively. In the fed group, these values were 8027.75 hâ¢ng/mL and 3119.67 ng/mL. The difference in AUC0-t between the fed and fasted group was statistically significant. Conclusion: The novel optimized UPLC-MS/MS assay is an effective tool for the determination of pentoxifylline and has been successfully applied in pharmacokinetic studies of pentoxifylline in beagle dogs. The administration of pentoxifylline sustained-release tablets with food significantly increased the area under the time curve, and it is recommended that they should be administered during or shortly after feeding.
Assuntos
Pentoxifilina , Espectrometria de Massas em Tandem , Animais , Cães , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Estudos Cross-Over , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/análise , Preparações de Ação Retardada/farmacocinética , Metanol , Pentoxifilina/administração & dosagem , Pentoxifilina/sangue , Pentoxifilina/farmacocinética , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodosRESUMO
Parkinson's disease (PD) is the second most common rapidly progressive neurodegenerative disease and has serious health and socio-economic consequences. Mitochondrial dysfunction is closely related to the onset and progression of PD, and the use of mitochondria as a target for PD therapy has been gaining traction in terms of both recognition and application. The disruption of mitochondrial proteostasis in the brain tissue of PD patients leads to mitochondrial dysfunction, which manifests as mitochondrial unfolded protein response, mitophagy, and mitochondrial oxidative phosphorylation. Physical exercise is important for the maintenance of human health, and has the great advantage of being a non-pharmacological therapy that is non-toxic, low-cost, and universally applicable. In this review, we investigate the relationships between exercise, mitochondrial proteostasis, and PD and explore the role and mechanisms of mitochondrial proteostasis in delaying PD through exercise.
Assuntos
Doenças Neurodegenerativas , Doença de Parkinson , Humanos , Doença de Parkinson/metabolismo , Proteostase , Doenças Neurodegenerativas/metabolismo , Mitocôndrias/metabolismo , Exercício FísicoRESUMO
In Parkinson's disease (PD), neurotoxic microglia, Th1 cells, and Th17 cells are overactivated. Overactivation of these immune cells exacerbates the disease process and leads to the pathological development of pro-inflammatory cytokines, chemokines, and contact-killing compounds, causing the loss of dopaminergic neurons. So far, we have mainly focused on the role of the specific class of immune cells in PD while neglecting the impact of interactions among immune cells on the disease. Therefore, this review demonstrates the reciprocal interplays between microglia and T cells and the associated subpopulations through cytokine and chemokine production that impair and/or protect the pathological process of PD. Furthermore, potential targets and models of PD neuroinflammation are highlighted to provide the new ideas/directions for future research.
Assuntos
Doença de Parkinson , Humanos , Animais , Doença de Parkinson/patologia , Microglia/patologia , Citocinas , Quimiocinas , Neurônios Dopaminérgicos/patologia , Modelos Animais de DoençasRESUMO
BACKGROUND: Autosomal dominant lateral temporal epilepsy (ADLTE) is an inherited syndrome caused by mutations in the leucine-rich glioma inactivated 1 (LGI1) gene. It is known that functional LGI1 is secreted by excitatory neurons, GABAergic interneurons, and astrocytes, and regulates AMPA-type glutamate receptor-mediated synaptic transmission by binding ADAM22 and ADAM23. However, > 40 LGI1 mutations have been reported in familial ADLTE patients, more than half of which are secretion-defective. How these secretion-defective LGI1 mutations lead to epilepsy is unknown. RESULTS: We identified a novel secretion-defective LGI1 mutation from a Chinese ADLTE family, LGI1-W183R. We specifically expressed mutant LGI1W183R in excitatory neurons lacking natural LGI1, and found that this mutation downregulated Kv1.1 activity, led to neuronal hyperexcitability and irregular spiking, and increased epilepsy susceptibility in mice. Further analysis revealed that restoring Kv1.1 in excitatory neurons rescued the defect of spiking capacity, improved epilepsy susceptibility, and prolonged the life-span of mice. CONCLUSIONS: These results describe a role of secretion-defective LGI1 in maintaining neuronal excitability and reveal a new mechanism in the pathology of LGI1 mutation-related epilepsy.
RESUMO
Objective@#To explore the association between exposure to bedroom night light during sleep and emotional symptoms in children and provide a scientific basis for subsequent effective prevention and intervention.@*Methods@#In December 2021, 1 926 students from grades 4 to 6 were recruited to conduct a student questionnaire survey in two primary schools in Tianchang of Chuzhou City, Anhui Province. The data, including general demographic information, use of night lights and curtains, emotional symptoms, and other information, was collected. Binary Logistic regression analysis was used to examine the correlation between night light use and children s emotional symptoms.@*Results@#The reporting rates of depression symptoms, generalized anxiety symptoms, social phobia, and obsessive compulsive symptoms of the children were 2.5%, 2.6%, 3.4% and 2.5%, respectively. About 12.6% of children often sleep with a night light on, and 22.0% of children did not close the curtains. Binary Logistic regression analysis revealed that frequent sleep with night lights was associated with an increased risk of depression symptoms( OR=2.29, 95%CI = 1.04- 5.03), social phobia ( OR=1.93, 95%CI =1.02-3.64) and obsessivecompulsive symptoms ( OR=3.44, 95%CI =1.72-6.88) in children( P < 0.05).@*Conclusion@#There is a positive correlation between bedroom night light exposure during sleep and the detection rate of children s emotional symptoms. The attention should be paid to bedroom light environment of children during sleep to reduce the adverse effects of night light exposure on the mental health.
RESUMO
BACKGROUND: Accumulating evidence have investigated the effects of nighttime light exposure on sleep problems. Nevertheless, the evidence of the relationship between light at night (LAN) and sleep problems remains scarce and inconsistent. OBJECTIVE: Conducted a systematic review and meta-analysis based on observational studies to examine the association between LAN exposure and sleep problems among human subjects. METHODS: We systematically searched three databases (PubMed, Web of Science, and Embase) to identify potentially eligible studies through May 25, 2022. The risk of bias and the quality of the generated evidence were assessed by two authors using the National Toxicology Program's Office of Health Assessment and Translation (OHAT) risk of bias rating tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guideline. Random-effects model was applied to synthesize the risk estimates across eligible studies. The heterogeneity of included studies was quantified by the statistics of I2. RESULTS: A total of 7 cross-sectional studies comprising 577,932 participants were included. Individuals with higher levels of LAN exposure were associated with a 22 % (Summary Odds Ratio, SOR: 1.22, 95 %CI: 1.13-1.33) increased prevalence of sleep problems. The pooled effect size of indoor LAN exposure (SOR: 1.74, 95%CI: 1.27-2.37) associated with sleep problems was significantly higher than outdoor LAN exposure (SOR: 1.19, 95%CI: 1.11-1.29; P = 0.022). Additionally, dose-response analysis demonstrated that LAN intensity threshold exceeding 5.8 nW/cm2/sr (SOR: 1.04, 95%CI: 1.01-1.07) had a significant effect on sleep problems and the prevalence of sleep problems was increasing with increase in LAN intensity. CONCLUSIONS: Overall, our findings support the detrimental effects of LAN exposure on sleep. Maintaining bedroom darkness at night may be a feasible measure to reduce the prevalence of sleep problems. Future longitudinal studies with more advanced LAN assessment methods are required to move the field forward.