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1.
Can J Aging ; : 1-8, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38757195

RESUMEN

BACKGROUND: Immigrant caregivers support the aging population, yet their own needs are often neglected. Mobile technology-facilitated interventions can promote caregiver health by providing easy access to self-care materials. OBJECTIVE: This study employed a design thinking framework to examine Chinese immigrant caregivers' (CICs) unmet self-care needs and co-design an app for promoting self-care with CICs. METHODS: Nineteen semi-structured interviews were conducted in conceptual design and prototype co-design phases. FINDINGS: Participants reported unmet self-care needs influenced by psychological and social barriers, immigrant status, and caregiving tasks. They expressed the need to learn to keep healthy boundaries with the care recipient and respond to emergencies. Gaining knowledge was the main benefit that drew CICs' interest in using the self-care app. However, potential barriers to use included issues of curriculum design, technology anxiety, limited free time, and caregiving burdens. DISCUSSION: The co-design process appears to be beneficial in having participants voice both barriers and preferences.

2.
Sci Total Environ ; 934: 173009, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38734111

RESUMEN

OBJECTIVE: Air pollution has been linked to multiple psychiatric disorders, but little is known on its long-term association with schizophrenia. The interaction between air pollution and genetic susceptibility on incident schizophrenia has never been reported. We aimed to explore the associations between long-term air pollution exposure and late-onset schizophrenia and evaluate whether genetic susceptibility could modify the association. METHODS: This population-based prospective cohort study included 437,802 middle-aged and elderly individuals free of schizophrenia at baseline in the UK Biobank. Land use regression models were applied in the estimation of the annual average concentrations of nitrogen dioxide (NO2), nitrogen oxides (NOx), fine particulate matter (PM2.5), and inhalable particulate matter (PM10) at residence. The associations between air pollutants and schizophrenia were evaluated by using Cox proportional hazard models. A polygenic risk score of schizophrenia was constructed for exploring potential interaction of air pollutants with genetic susceptibility. RESULTS: An interquartile range increase in PM2.5, PM10, NO2, and NOx was associated with the hazard ratios (HR) for incident schizophrenia at 1.19, 1.16, 1.22, and 1.09, respectively. The exposure-response curves for the association of air pollution with incident schizophrenia were approximately linear. There are additive interactions of air pollution score (APS), PM10, NO2, and NOx with genetic risk. Specifically, compared with participants with low genetic susceptibility and low APS, the HR was 3.23 for individuals with high genetic risk and high APS, among which 0.49 excess risk could be attributed to the additive interaction, accounting for 15 % of the schizophrenia risk. CONCLUSION: This large-scale, prospective cohort study conveys the first-hand evidence that long-term air pollution exposure could elevate schizophrenia incidence in later life, especially for individuals with higher genetic risks. The findings highlight the importance of improving air quality for preventing the late-onset schizophrenia in an aging era, especially among those with high genetic risks.

3.
Comput Biol Med ; 175: 108532, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38703547

RESUMEN

BACKGROUND: Glioma is a malignant brain tumor originating from glial cells, and there still a challenge to accurately predict the prognosis. Programmed cell death (PCD) plays a key role in tumorigenesis and immune response. However, the crosstalk and potential role of various PCDs in prognosis and tumor microenvironment remains unknown. Therefore, we comprehensively discussed the relationship between different models of PCD and the prognosis of glioma and provided new ideas for the optimal targeted therapy of glioma. MATERIALS AND METHODS: We compared and analyzed the role of 14 PCD patterns on the prognosis from different levels. We constructed the cell death risk score (CDRS) index and conducted a comprehensive analysis of CDRS and TME characteristics, clinical characteristics, and drug response. RESULTS: Effects of different PCDs at the genomic, functional, and immune microenvironment levels were discussed. CDRS index containing 6 gene signatures and a nomogram were established. High CDRS is associated with a worse prognosis. Through transcriptome and single-cell data, we found that patients with high CDRS showed stronger immunosuppressive characteristics. Moreover, the high-CDRS group was resistant to the traditional glioma chemotherapy drug Vincristine, but more sensitive to the Temozolomide and the clinical experimental drug Bortezomib. In addition, we identified 19 key potential therapeutic targets during malignant differentiation of tumor cells. CONCLUSION: Overall, we provide the first systematic description of the role of 14 PCDs in glioma. A new CDRS model was built to predict the prognosis and to provide a new idea for the targeted therapy of glioma.


Asunto(s)
Neoplasias Encefálicas , Glioma , Microambiente Tumoral , Humanos , Glioma/genética , Glioma/tratamiento farmacológico , Glioma/inmunología , Glioma/patología , Glioma/mortalidad , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Pronóstico , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Resistencia a Antineoplásicos , Transcriptoma , Apoptosis/efectos de los fármacos
4.
Phytomedicine ; 128: 155502, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38489889

RESUMEN

BACKGROUND: Jaceosidin (JA) is a natural flavone extracted from Artemisia that is used as a food and traditional medicinal herb. It has been reported to possess numerous biological activities. However, the regulatory mechanisms underlying amelioration of hepatic fibrosis remain unclear. HYPOTHESIS/PURPOSE: We hypothesized that jaceosidin acid (JA) modulates hepatic fibrosis and inflammation. METHODS: Thioacetamide (TAA) was used to establish an HF mouse model. In vitro, mouse primary hepatocytes and HSC-T6 cells were induced by TGF-ß, whereas mouse peritoneal macrophages received a treatment lipopolysaccharide (LPS)/ATP. RESULTS: JA decreased serum transaminase levels and improved hepatic histological pathology in TAA-treated mice stimulated by TAA. Moreover, the expression of pro-fibrogenic biomarkers associated with the activation of liver stellate cells was downregulated by JA. Likewise, JA down-regulated the expression of vestigial-like family member 3 (VGLL3), high mobility group protein B1 (HMGB1), toll-like receptors 4 (TLR4), and nucleotide-binding domain-(NOD-) like receptor protein 3 (NLRP3), thereby inhibiting the inflammatory response and inhibiting the release of mature-IL-1ß in TAA-stimulated mice. Additionally, JA suppressed HMGB1 release and NLRP3/ASC inflammasome activation in LPS/ATP-stimulated murine peritoneal macrophages. JA decreases the expression of pro-fibrogenic biomarkers related to liver stellate cell activation and inhibits inflammasome activation in mouse primary hepatocytes. It also down-regulated α-SMA and VGLL3 expressions and also suppressed inflammasome activation in HSC-T6 cells. VGLL3 and α-SMA expression levels were decreased in TGF-ß-stimulated HSC-T6 cells following Vgll3 knockdown. In addition, the expression levels of NLRP3 and cleaved-caspase-1 were decreased in Vgll3-silenced HSC-T6 cells. JA enhanced the inhibitory effects on Vgll3-silenced HSC-T6 cells. Finally, Vgll3 overexpression in HSC-T6 cells affected the expression levels of α-SMA, NLRP3, and cleaved-caspase-1. CONCLUSION: JA effectively modulates hepatic fibrosis by suppressing fibrogenesis and inflammation via the VGLL3/HMGB1/TLR4 axis. Therefore, JA may be a candidate therapeutic agent for the management of hepatic fibrosis. Understanding the mechanism of action of JA is a novel approach to hepatic fibrosis therapy.


Asunto(s)
Proteína HMGB1 , Cirrosis Hepática , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR , Transducción de Señal , Receptor Toll-Like 4 , Animales , Masculino , Ratones , Línea Celular , Células Estrelladas Hepáticas/efectos de los fármacos , Células Estrelladas Hepáticas/metabolismo , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Proteína HMGB1/metabolismo , Lipopolisacáridos , Hígado/efectos de los fármacos , Hígado/metabolismo , Cirrosis Hepática/tratamiento farmacológico , Cirrosis Hepática/inducido químicamente , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Transducción de Señal/efectos de los fármacos , Tioacetamida , Receptor Toll-Like 4/metabolismo
5.
Sci Total Environ ; 926: 171831, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38521267

RESUMEN

In Great Britain, limited studies have employed machine learning methods to predict air pollution especially ozone (O3) with high spatiotemporal resolution. This study aimed to address this gap by developing random forest models for four key pollutants (fine and inhalable particulate matter [PM2.5 and PM10], nitrogen dioxide [NO2] and O3) by integrating multiple-source predictors at a daily level and 1-km resolution. The out-of-bag R2 (root mean squared error, RMSE) between predictions from models and measurements from monitoring stations in 2006-2013 was 0.85 (3.63 µg/m3) for PM2.5, 0.77 (6.00 µg/m3) for PM10, 0.85 (9.71 µg/m3) for NO2, and 0.85 (9.39 µg/m3) for maximum daily 8-h average (MDA8) O3 at daily level, and the predicting accuracy was higher at monthly and annual level. The high-resolution predictions captured characterized spatiotemporal patterns of the four pollutants. Higher concentrations of PM2.5, PM10, and NO2 were distributed in densely populated southern regions of Great Britain while O3 showed an inverse spatial pattern in general, which could not be fully depicted by monitoring stations. Therefore, predictions produced in this study could improve exposure assessment with less exposure misclassification and flexible exposure windows for future epidemiological studies to investigate the impact of air pollution across Great Britain.

6.
J Ethnopharmacol ; 326: 117996, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38431110

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis, the dried and ripe fruit of the magnolia family plant Schisandra chinensis (Turcz.) Baill, was commonly used in traditional analgesic prescription. Studies have shown that the extract of Schisandra chinensis (SC) displayed analgesic activity. However, the analgesic active component and the exact mechanisms have yet to be revealed. AIM OF THE STUDY: The present study was to investigate the anti-nociceptive constituent of Schisandra chinensis, assess its analgesic effect, and explore the potential molecular mechanisms. MATERIALS AND METHODS: The effects of a series of well-recognized compounds from SC on glycine receptors were investigated. The analgesic effect of the identified compound was evaluated in three pain models. Mechanistic studies were performed using patch clamp technique on various targets expressed in recombinant cells. These targets included glycine receptors, Nav1.7 sodium channels, Cav2.2 calcium channels et al. Meanwhile, primary cultured spinal dorsal horn (SDH) neurons and dorsal root ganglion (DRG) neurons were also utilized. RESULTS: Schisandrin B (SchB) was a positive allosteric modulator of glycine receptors in spinal dorsal horn neurons. The EC50 of SchB on glycine receptors in spinal dorsal horn neurons was 2.94 ± 0.28 µM. In three pain models, the analgesic effect of SchB was comparable to that of indomethacin at the same dose. Besides, SchB rescued PGE2-induced suppression of α3 GlyR activity and alleviated persistent pain. Notably, SchB could also potently decrease the frequency of action potentials and inhibit sodium and calcium channels in DRG neurons. Consistent with the data from DRG neurons, SchB was also found to significantly block Nav1.7 sodium channels and Cav2.2 channels in recombinant cells. CONCLUSION: Our results demonstrated that, Schisandrin B, the primary lignan component of Schisandra chinensis, may exert its analgesic effect by acting on multiple ion channels, including glycine receptors, Nav1.7 channels, and Cav2.2 channels.


Asunto(s)
Lignanos , Compuestos Policíclicos , Schisandra , Receptores de Glicina , Lignanos/farmacología , Dolor , Canales de Calcio Tipo N , Analgésicos/farmacología , Analgésicos/uso terapéutico , Canales de Sodio , Ciclooctanos
7.
Environ Pollut ; 345: 123540, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38341067

RESUMEN

Gout is a chronic disorder characterized by the accumulation of uric acid in the body, leading to recurrent episodes of joint inflammation and pain. There remains a lack of studies investigating the association between long-term exposure to ambient air pollution and the incidence of gout. We conducted this prospective cohort study involving participants aged 38-70 from the UK Biobank who were enrolled in 2006-2010 and followed until 2023. Baseline residential concentrations of fine particulate matter (PM2.5), inhalable particulate matter (PM10), nitrogen dioxide (NO2) and nitrogen oxides (NOx) were predicted using land-use regression models. Cox proportional hazards models were employed to examine the relationship between air pollution and incident gout events. A total of 443,587 individuals were included in the analyses and a total of 6589 incident gout cases were identified over a follow-up of 6,130,439 person-years. There were significant associations between higher levels of air pollution and an increased incidence risk of gout. Higher risk of incident gout was associated with each interquartile range increase in concentrations of PM2.5 (hazard ratio:1.05, 95% confidence intervals: 1.02-1.09), PM10 (1.04, 1.00-1.07), NO2 (1.08, 1.05-1.12) and NOx (1.04, 1.02-1.07). The magnitude of associations was larger at higher concentrations. The association was more prominent among older adults, smokers, and individuals with lower and moderate physical activity. This prospective cohort study provides novel and compelling evidence of increased risk of incident gout associated with long-term air pollution exposures.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Gota , Humanos , Anciano , Dióxido de Nitrógeno/análisis , Contaminantes Atmosféricos/análisis , Estudios Prospectivos , Biobanco del Reino Unido , Bancos de Muestras Biológicas , Estudios de Cohortes , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Material Particulado/análisis , Gota/epidemiología , Gota/inducido químicamente
8.
Psychol Res Behav Manag ; 17: 691-703, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38410378

RESUMEN

Background: There is substantial evidence from previous studies that abnormalities in sleep parameters associated with depression are demonstrated in almost all stages of sleep architecture. Patients with symptoms of sleep-wake disorders have a much higher risk of developing major depressive disorders (MDD) compared to those without. Objective: The aim of the present study is to establish and compare the performance of different machine learning models based on sleep-wake disorder symptoms data and to select the optimal model to interpret the importance of sleep-wake disorder symptoms to predict MDD occurrence in adolescents. Methods: We derived data for this work from 2020 to 2021 Assessing Nocturnal Sleep/Wake Effects on Risk of Suicide Phase I Study from National Sleep Research Resource. Using demographic and sleep-wake disorder symptoms data as predictors and the occurrence of MDD measured base on the center for epidemiologic studies depression scale as an outcome, the following six machine learning predictive models were developed: eXtreme Gradient Boosting model (XGBoost), Light Gradient Boosting mode, AdaBoost, Gaussian Naïve Bayes, Complement Naïve Bayes, and multilayer perceptron. The models' performance was assessed using the AUC and other metrics, and the final model's predictor importance ranking was explained. Results: XGBoost is the optimal predictive model in comprehensive performance with the AUC of 0.804 in the test set. All sleep-wake disorder symptoms were significantly positively correlated with the occurrence of adolescent MDD. The insomnia severity was the most important predictor compared with the other predictors in this study. Conclusion: This machine learning predictive model based on sleep-wake disorder symptoms can help to raise the awareness of risk of symptoms between sleep-wake disorders and MDD in adolescents and improve primary care and prevention.

9.
10.
J Affect Disord ; 350: 513-520, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38244790

RESUMEN

BACKGROUND: The popularity of digital devices seems to provide a new observational variable for early identification and prevention of suicide with the development of the information technology era. Nevertheless, whether it is the use of digital devices that alters suicide risk or suicide risk manifests itself through change digital device use needs to be further explored. METHODS: Bidirectional Mendelian randomization (MR) analysis was used to explore potential causal relationships in the perspective of genetic prediction. We collected publicly available digital device use and suicide risk summary statistics genome-wide association data from UK Biobank, Neale Lab and FinnGen genetic databases. We used inverse variance weighting methods to assess MR estimates. For robustness of the results, we performed further tests of heterogeneity and pleiotropy. RESULTS: In the Phase 1 results, we did not observe any effect of the length of digital device use on the suicide risk, while the results of Phase 2 suggested a significant positive association between suicide risk and the length of mobile phone use (IVW OR, 1.04; 95%CI, 1.01-1.06; P = 0.002), but this significance disappeared after adjusting for confounders of mental and affective disorders. CONCLUSIONS: In this bidirectional MR analysis, we observed that People at high risk of suicide may be more addicted to digital device use, but more detailed GWAS data and research methods to validate this finding are required.


Asunto(s)
Uso del Teléfono Celular , Suicidio , Humanos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Causalidad
11.
Sci Total Environ ; 912: 169145, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38061653

RESUMEN

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of legal blindness. It remains unclear whether and to what extent the ambient ozone pollution could increase the risk of AMD. METHODS: A nationwide cross-sectional survey was conducted in 129 major cities in 27 of 31 provincial regions across China from 2018 to 2021. Data in relation to demographics, residential address, and medical histories were collected. The exposure-response relationship between ozone exposure and AMD was explored using the restricted cubic splines. A piecewise logistic regression model was used to examine the magnitudes of the association, after adjusting demographic, social-economic and co-pollutants. Residential ozone exposures were estimated using a satellite-based model. RESULTS: A total of 624,167 middle-aged and older participants were included in the final analyses, the overall prevalence of AMD was 16.76 %. The risk of AMD was consistently increasing with higher warm-season ozone concentration, and the risk became much larger after the cut-off of 110 µg/m3 (approximately 50 ppb). Every 10 µg/m3 increment in warm-season ozone concentration, the adjusted odds ratio (OR) for AMD were 1.15 (1.13, 1.16) and 1.66 (1.63, 1.69) when the warm-season ozone concentration was below or above 110 µg/m3, respectively. CONCLUSION: This large-scale nationwide study provides the first epidemiological evidence demonstrating significant associations between long-term residential ozone exposure and AMD prevalence. Based on our findings, in conjunction with WHO global air quality guidelines, we suggest that a warm-season ozone of 110 µg/m3 should be adopted for middle-aged and older populations to reduce the risk of AMD. Ongoing efforts to reduce ozone exposure in communities through improved air quality regulations and public education are essential for the improvement of public health.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Ozono , Persona de Mediana Edad , Humanos , Anciano , Ozono/análisis , Contaminantes Atmosféricos/análisis , Estudios Transversales , Material Particulado/análisis , Exposición a Riesgos Ambientales/análisis , China/epidemiología
12.
Sleep Med ; 113: 6-12, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37976908

RESUMEN

BACKGROUND: Observational findings suggest that patients with narcolepsy are at higher risk for cardiovascular diseases (CVDs), but the potential causal relationship between narcolepsy and CVDs is unclear. Therefore, Mendelian randomization (MR) was used to explore the association between narcolepsy and CVDs. METHODS: Summary statistics related to narcolepsy, coronary artery disease (CAD), myocardial infarction (MI), heart failure (HF), any stroke (AS), and any ischemic stroke (AIS) were extracted from the public database of relevant published genome-wide association studies (GWAS). Independent single nucleotide polymorphisms were selected as instrumental variables under strict quality control criteria. Inverse variance-weighted (IVW) was the main analytical method to assess causal effects. In addition, we conducted MR pleiotropy residual sum and outlier (MR-PRESSO), weighted median, MR-Egger, and leave-one-out sensitivity analysis to verify the robustness and reliability of the results. RESULTS: The results of the MR study revealed that narcolepsy was significantly associated with an increased risk of HF (OR = 1.714; 95%CI [1.031-2.849]; P = 0.037), CAD (OR = 1.702; 95%CI [1.011-2.864]; P = 0.045). There was no statistically significant causal association between narcolepsy and MI, AS, and AIS. In addition, further sensitivity analysis showed robust results. CONCLUSIONS: The results of the two-sample MR study reveal a potential causal relationship between the increased risk of HF and CAD in narcolepsy. These findings emphasize the importance of early monitoring and assessment of cardiovascular risk in patients with narcolepsy.


Asunto(s)
Enfermedades Cardiovasculares , Enfermedad de la Arteria Coronaria , Insuficiencia Cardíaca , Infarto del Miocardio , Narcolepsia , Humanos , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Reproducibilidad de los Resultados , Narcolepsia/genética
13.
J Gerontol Soc Work ; 67(2): 188-206, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37477277

RESUMEN

This study investigated how older Chinese immigrants in affordable senior housing facilities (ASHs) appraise and cope with anti-Asian discrimination and related stress during the COVID-19 pandemic. Qualitative interviews were conducted with 26 participants aged over 65, analyzing verbatim transcripts and field notes using thematic analysis. Four major domains were identified: (1) discriminatory experience, (2) appraisals of discrimination stress, (3) coping strategies, and (4) rationales behind coping. Among the participants, 11 (42%) reported experiencing discrimination either personally or by someone they know. Participants' appraisals of discrimination stress varied, and most of them opted for disengagement coping strategies (e.g., avoidance, rationalization) attributing them to health concerns, individual characteristics, environmental and societal factors, and low acculturation. The findings suggest the need for more social and community resources to enhance coping capacity and resilience in this vulnerable population.


Asunto(s)
COVID-19 , Emigrantes e Inmigrantes , Anciano , Humanos , Adaptación Psicológica , COVID-19/epidemiología , Hogares para Ancianos , Pandemias , China/epidemiología
14.
Chemosphere ; 349: 140828, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38040257

RESUMEN

Kawasaki disease (KD) is an acute, systemic vasculitis that primarily affects children aged under the age of 5. While environmental factors have been linked to the development of KD, the specific role of ozone (O3) pollution in triggering the disease onset remains uncertain. This study aimed to examine the associations between short-term O3 exposure and KD onset in children. Utilizing a satellite-based model with a spatial resolution of 1 × 1 km, we matched 1808 KD patients (out of a total of 6115 eligible individuals) to pre-onset ozone exposures based on their home addresses in East China between 2013 and 2020. Our findings revealed a significant association of O3 exposure with KD onset on the day of onset (lag 0 day). However, this association attenuated and became statistically insignificant on lag 1 and lag 2 days. Each interquartile range (52.32 µg/m3) increase in O3 concentration at lag 0 day was associated with a 16.2% (95% CI: 3.6%, 30.3%) increased risk of KD onset. The E-R curve for O3 exhibited a plateau at low concentrations and then increased rapidly at concentrations ≥75 µg/m3. Notably, these associations were stronger in male children, younger children (<2 years of age) and patients experiencing KD onset during the warm season. This study provides novel epidemiological evidence indicating that short-term O3 exposure is associated with an increased risk of childhood KD onset. These findings emphasized the importance of considering this environmental risk factor in KD prevention strategies.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Síndrome Mucocutáneo Linfonodular , Ozono , Niño , Humanos , Masculino , Preescolar , Ozono/análisis , Contaminación del Aire/análisis , Contaminantes Atmosféricos/toxicidad , Contaminantes Atmosféricos/análisis , Estudios Cruzados , Síndrome Mucocutáneo Linfonodular/inducido químicamente , Síndrome Mucocutáneo Linfonodular/epidemiología , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , China/epidemiología , Material Particulado/análisis
15.
Acta Pharmacol Sin ; 45(3): 465-479, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38017298

RESUMEN

Epilepsy is a prevalent and severe neurological disorder and approximately 30% of patients are resistant to existing medications. It is of utmost importance to develop alternative therapies to treat epilepsy. Schisandrin B (SchB) is a major bioactive constituent of Schisandra chinensis (Turcz.) Baill and has multiple neuroprotective effects, sedative and hypnotic activities. In this study, we investigated the antiseizure effect of SchB in various mouse models of seizure and explored the underlying mechanisms. Pentylenetetrazole (PTZ), strychnine (STR), and pilocarpine-induced mouse seizure models were established. We showed that injection of SchB (10, 30, 60 mg/kg, i.p.) dose-dependently delayed the onset of generalized tonic-clonic seizures (GTCS), reduced the incidence of GTCS and mortality in PTZ and STR models. Meanwhile, injection of SchB (30 mg/kg, i.p.) exhibited therapeutic potential in pilocarpine-induced status epilepticus model, which was considered as a drug-resistant model. In whole-cell recording from CHO/HEK-239 cells stably expressing recombinant human GABAA receptors (GABAARs) and glycine receptors (GlyRs) and cultured hippocampal neurons, co-application of SchB dose-dependently enhanced GABA or glycine-induced current with EC50 values at around 5 µM, and application of SchB (10 µM) alone did not activate the channels in the absence of GABA or glycine. Furthermore, SchB (10 µM) eliminated both PTZ-induced inhibition on GABA-induced current (IGABA) and strychnine (STR)-induced inhibition on glycine-induced current (Iglycine). Moreover, SchB (10 µM) efficiently rescued the impaired GABAARs associated with genetic epilepsies. In addition, the homologous mutants in both GlyRs-α1(S267Q) and GABAARs-α1(S297Q)ß2(N289S)γ2L receptors by site-directed mutagenesis tests abolished SchB-induced potentiation of IGABA and Iglycine. In conclusion, we have identified SchB as a natural positive allosteric modulator of GABAARs and GlyRs, supporting its potential as alternative therapies for epilepsy.


Asunto(s)
Epilepsia , Lignanos , Compuestos Policíclicos , Receptores de Glicina , Ratones , Animales , Humanos , Pilocarpina/efectos adversos , Estricnina/farmacología , Estricnina/uso terapéutico , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Receptores de GABA-A , Glicina/farmacología , Hipnóticos y Sedantes , Ácido gamma-Aminobutírico , Ciclooctanos
16.
Gerontologist ; 64(4)2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-37935416

RESUMEN

BACKGROUND AND OBJECTIVES: Social isolation is a risk factor for cognitive decline and dementia. We conducted a randomized controlled clinical trial (RCT) of enhanced social interactions, hypothesizing that conversational interactions can stimulate brain functions among socially isolated older adults without dementia. We report topline results of this multisite RCT (Internet-based conversational engagement clinical trial [I-CONECT]; NCT02871921). RESEARCH DESIGN AND METHODS: The experimental group received cognitively stimulating semistructured conversations with trained interviewers via internet/webcam 4 times per week for 6 months (induction) and twice per week for an additional 6 months (maintenance). The experimental and control groups both received weekly 10 minutes telephone check-ins. Protocol modifications were required due to the coronavirus disease 2019 pandemic. RESULTS: A total of 186 participants were randomized. After the induction period, the experimental group had higher global cognitive test scores (Montreal Cognitive Assessment [primary outcome]; 1.75 points [p = .03]) compared with the control group. After induction, experimental group participants with normal cognition had higher language-based executive function (semantic fluency test [secondary outcome]; 2.56 points [p = .03]). At the end of the maintenance period, the experimental group of mild cognitive impairment subjects had higher encoding function (Craft Story immediate recall test [secondary outcome]; 2.19 points [p = .04]). Measure of emotional well-being improved in both control and experimental groups. Resting-state functional magnetic resonance imaging showed that the experimental group had increased connectivity within the dorsal attention network relative to the control group (p = .02), but the sample size was limited. DISCUSSION AND IMPLICATIONS: Providing frequent stimulating conversational interactions via the internet could be an effective home-based dementia risk-reduction strategy against social isolation and cognitive decline. CLINICAL TRIALS REGISTRATION NUMBER: NCT02871921.


Asunto(s)
Disfunción Cognitiva , Demencia , Humanos , Anciano , Disfunción Cognitiva/psicología , Cognición , Función Ejecutiva
17.
ACS Appl Mater Interfaces ; 15(38): 45158-45166, 2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37708412

RESUMEN

Modification of the molecular packing of nonfullerene acceptors through fluorination represents one of the most promising strategies to achieve highly efficient organic solar cells (OSCs). In this work, three nonfused electron acceptors, namely, DTCBT-Fx (x = 0, 5, 9) with precisely controlled amounts of fluorine atoms in the side chains are designed and synthesized, and the effect of side chain fluorination is systematically studied. The results demonstrate that the light absorption, energy levels, molecular ordering, and film morphology could be effectively tuned by precisely controlling the side chain fluorination. DTCBT-F5 with an appropriate fluorine functionalization exhibits suitable miscibility with the donor polymer (PM6), leading to diminished charge recombination and improved charge carrier mobility. Consequently, a promising power conversion efficiency of 12.7% was obtained for DTCBT-F5-based solar cells, which outperforms those OSCs based on DTCBT-F0 (11.4%) and DTCBT-F9 (11.6%), respectively. This work demonstrates that precise control of the fluorine functionalization in side chains of nonfused electron acceptors is an effective strategy for realizing highly efficient OSCs.

18.
Nat Commun ; 14(1): 5556, 2023 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-37689690

RESUMEN

Chemicals or drugs can accumulate within biomolecular condensates formed through phase separation in cells. Here, we use super-resolution imaging to search for chemicals that induce phase transition within chromatin at the microscale. This microscopic screening approach reveals that adriamycin (doxorubicin) - a widely used anticancer drug that is known to interact with chromatin - specifically induces visible local condensation and global conformational change of chromatin in cancer and primary cells. Hi-C and ATAC-seq experiments systematically and quantitatively demonstrate that adriamycin-induced chromatin condensation is accompanied by weakened chromatin interaction within topologically associated domains, compartment A/B switching, lower chromatin accessibility, and corresponding transcriptomic changes. Mechanistically, adriamycin complexes with histone H1 and induces phase transition of H1, forming fibrous aggregates in vitro. These results reveal a phase separation-driven mechanism for a chemotherapeutic drug.


Asunto(s)
Condensados Biomoleculares , Cromatina , Secuenciación de Inmunoprecipitación de Cromatina , Doxorrubicina/farmacología , Perfilación de la Expresión Génica
19.
Molecules ; 28(13)2023 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-37446706

RESUMEN

This study aimed to explore the applicability of DNA barcoding for assessing the authenticity of caviar on the Chinese market. A set of universal COI primers and two sets of designed primers based on COI and D-loop genes were used to identify maternal species of samples from 21 batches of caviar. The results showed that the PCR products from three sets of primers had more than 98% similarity to the sequences in database. The COI gene could not distinguish sturgeons with closed genetic relationships, while D-loop gene could effectively improve the accuracy of DNA barcoding and was more suitable to the identification of interspecific sturgeon than the COI gene. The neighbor-joining dendrogram further confirmed the applicability and accuracy of COI and D-loop genes in identifying maternal relatives of caviar (Acipenser baerii/Acipenser gueldenstaedtii/Acipenser schrenckii/Huso dauricus/Huso huso). Despite the limitations of mitochondrial DNA in identifying hybrid sturgeon species, the presence of counterfeit caviar of non-sturgeon ingredients could be excluded. All the caviar samples were identified successfully as sturgeon species, but the mislabeling rate of species was 33.4%, indicating that there were illegal phenomena such as disorderly labeling, mislabeling, and adulteration on the market.


Asunto(s)
Código de Barras del ADN Taxonómico , ADN Mitocondrial , Animales , ADN Mitocondrial/genética , Peces/genética , Reacción en Cadena de la Polimerasa/métodos , Cartilla de ADN
20.
J Colloid Interface Sci ; 647: 467-477, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37271091

RESUMEN

An abundance of early warning graphene-based nano-materials and sensors have been developed to avoid and prevent the critical fire risk of combustible materials. However, there are still some limitations that should be addressed, such as the black color, high-cost and single fire warning response of graphene-based fire warning materials. Herein, we report an unexpected montmorillonite (MMT)-based intelligent fire warning materials that have excellent fire cyclic warning performance and reliable flame retardancy. Combining phenyltriethoxysilane (PTES) molecules, poly(p-phenylene benzobisoxazole) nanofiber (PBONF), and layers of MMT to form a silane crosslinked 3D nanonetwork system, the homologous PTES decorated MMT-PBONF nanocomposites are designed and fabricated via a sol-gel process and low temperature self-assembly method. The optimized nanocomposite paper shows good mechanical flexibility (good recovery after kneading or bending process), high tensile strength of âˆ¼81 MPa and good water resistance. Furthermore, the nanocomposite paper exhibits high-temperature flame resistance (almost unchanged structure and size after 120 s combustion), sensitive flame alarm response (∼0.3 s response once exposure onto a flame), cyclic fire warning performance (>40 cycles), and adaptability to complex fire situations (several fire attack and evacuation scenarios), showing promising applications for monitoring the critical fire risk of combustible materials. Therefore, this work paves a rational way for design and fabrication of MMT-based smart fire warning materials that combine excellent flame shielding and sensitive fire alarm functions.

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