RESUMEN
OBJECTIVES: Stroke is a leading cause of death in Taiwan. Poor public knowledge of stroke may lead to delays in prehospital arrival, resulting in unfavorable prognoses. Studies have investigated public knowledge of stroke and highlighted the importance of stroke education, however, few such studies have been conducted in Taiwan. This study assessed the changes in public knowledge of stroke between 2012 and 2020 by conducting a survey during two World Stroke Day events. Furthermore, this study identified areas where educational efforts may have been insufficient. MATERIALS & METHODS: Questionnaires were distributed to the participants of 2012 and 2020 World Stroke Day events in Taiwan. In total, 328 and 336 questionnaires were completed, respectively. Stroke literacy and knowledge were analyzed between 2012 and 2020. Data were analyzed using the chi-square test or independent t-test. p < 0.05 indicates statistical significance. RESULTS: Hypertension was the most recognized risk factor for stroke in both years (p < 0.001), and recognition of most of the given risk factors significantly increased. In addition, recognition of more than half of the stroke warning signs significantly increased, awareness of the correct acute stroke response also increased (p < 0.001), and overall stroke literacy in Taiwan increased (p = 0.001). CONCLUSION: Stroke literacy and knowledge in Taiwan have improved significantly between 2012 and 2020, but many people still lack adequate stroke knowledge and awareness. Government health department must take this sort of intervention continually (campaigns) and novel approaches (e.g. board game ) to improve stroke literacy and knowledge in public health. REGISTRATION ID: N202109072, approved by the Joint Institutional Review Board of Taipei Medical University on 2021/11/02.
RESUMEN
Sepsis is a critical medical condition associated with high mortality for patients. Current pharmacological strategies for sepsis management or prevention had not achieved satisfactory results. The omega-3 fatty acids, with anti-inflammatory benefits, are considered to be promising agents for sepsis management/prevention. The aim of this network meta-analysis (NMA) is to compare the efficacy of various dosages and formulations of fish oil supplements for sepsis management and sepsis prevention. The current NMA consisted of two parts: (1) sepsis management and (2) sepsis prevention. The PubMed, ClinicalKey, Embase, ProQuest, Cochrane CENTRAL, ScienceDirect, Web of Science, and ClinicalTrials.gov databases were systematically searched to date of February 22nd, 2024 for relevant randomized controlled trials (RCTs). RCTs were eligible for inclusion if they enrolled participants with a diagnosis of sepsis or who with high risk for sepsis. All NMA procedures were conducted under the frequentist model. The primary outcomes assessed are (1) mortality rate in sepsis treatment or (2) incidence of sepsis in sepsis prevention. Our NMA, based on 28 RCTs and 1718 participants (mean age=51.6 years, mean female proportion=35.6 %), showed that (1) high dose parenteral fish oil supplement yield the lowest mortality rate in sepsis management in adult patients, and (2) high dose enteral fish oil supplement yield the lowest incidence of sepsis in pediatric patients. This study provides compelling evidence that high-dose fish oil supplements provide beneficial effects for both sepsis management and sepsis prevention. Our findings provide a preliminary rationale for future large-scale RCTs to investigate the role of fish oil supplementation in sepsis management or prevention.
RESUMEN
This study reports the design, synthesis, and comprehensive biological evaluation of 13 benzodioxolane derivatives, derived from the core structure of piperine, a natural product with established antitumor properties. Piperine, primarily found in black pepper, has been noted for its diverse pharmacological activities, including anti-inflammatory, antioxidant, and anticancer effects. Leveraging piperine's antitumor potential, we aimed to enhance its efficacy through structural modifications. Among the synthesized compounds, HJ1 emerged as the most potent, exhibiting a 4-fold and 10-fold increase in inhibitory effects on HeLa and MDA-MB-231 cell lines, respectively, compared to piperine. Furthermore, HJ1 demonstrated a favorable safety profile, characterized by significantly lower cytotoxicity towards the human normal cell line 293T. Mechanistic investigations revealed that HJ1 markedly inhibited clonogenicity, migration, and adhesion of HeLa cells. In vivo studies utilizing the chick embryo chorioallantoic membrane (CAM) model substantiated the robust antitumor activity of HJ1, evidenced by its ability to suppress tumor angiogenesis and reduce tumor weight. These results suggest that HJ1 holds significant promise as a lead compound for the development of novel antitumor therapies.
Asunto(s)
Antineoplásicos , Proliferación Celular , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Relación Estructura-Actividad , Animales , Proliferación Celular/efectos de los fármacos , Estructura Molecular , Benzodioxoles/farmacología , Benzodioxoles/síntesis química , Benzodioxoles/química , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Células HeLa , Movimiento Celular/efectos de los fármacos , Embrión de PolloRESUMEN
The United Nations Sustainable Development Goals call for innovative proposals to ensure access to clean water and sanitation. While significant strides have been made in enhancing drinking water purification technologies, the role of drinking water distribution systems (DWDS) in maintaining water quality safety has increasingly become a focal point of concern. The presence of scale within DWDS can impede the secure and efficient functioning of the drinking water supply system, posing risks to the safety of drinking water quality. Previous research has identified that the primary constituents of scale in DWDS are insoluble minerals, such as calcium and magnesium carbonate. Elevated levels of hardness and alkalinity in the water can exacerbate scale formation. To address the scaling issue, softening technologies like induced crystallization, nanofiltration/reverse osmosis, and ion exchange are currently in widespread use. These methods effectively mitigate the scaling in DWDS by reducing the water's hardness and alkalinity. However, the application of softening technologies not only alters the hardness and alkalinity but also induces changes in the fundamental characteristics of water quality, leading to transition effects within the DWDS. This article reviews the impact of various softening technologies on the intrinsic properties of water quality and highlights the merits of electrochemical characteristic indicators in the assessment of water quality stability. Additionally, the paper delves into the factors that influence the transition effects in DWDS. It concludes with a forward-looking proposal to leverage artificial intelligence, specifically machine learning and neural networks, to develop an evaluation and predictive framework for the stability of drinking water quality and the transition effects observed in DWDS. This approach aims to provide a more accurate and proactive method for managing and predicting the impacts of water treatment processes on distribution system integrity and water quality over time.
Asunto(s)
Agua Potable , Purificación del Agua , Calidad del Agua , Abastecimiento de Agua , Agua Potable/química , Purificación del Agua/métodosRESUMEN
The influences of landscape pattern on water quality are dependent on spatial-temporal scales. However, the effects of landscape composition, landscape configuration, and landscape slope metrics on seasonal water quality at different spatial scales remain unclear. Based on the total nitrogen, total phosphorus, nitrate-N, and ammonium-N data from 26 sampling sites in the Qingshan Lake watershed, this study coupled landscape pattern analysis, redundancy analysis, and partial redundancy analysis to quantify the spatiotemporal scale effects of landscape pattern on riverine nitrogen ï¼Nï¼ and phosphorus ï¼Pï¼ concentrations. The results showed thatï¼ â The explanatory ability of landscape pattern at the sub-watershed scale on riverine N and P concentrations was 6.8%-8.4% higher than that at the buffer scale, and this effect was more obvious in the dry season. â¡ At the sub-watershed scale, the percentage of forestland and the interspersion and juxtaposition degree of residential land had a greater influence on riverine N and P concentrations. At the buffer scale, the slope of farmland and residential land and the aggregation degree of forestland patches were the key factors affecting riverine N and P concentrations. ⢠The contribution rate of landscape configuration to riverine N and P concentration variations ï¼20.1%-36.5%ï¼ was the highest. The sensitivity of the effect of landscape configuration on riverine N and P concentrations to seasonal changes was the highest, and the effect of landscape slope on riverine N and P concentrations had the highest sensitivity to spatial scale changes. Therefore, landscape pattern-regulated non-point source pollution should be considered from a multi-scale perspective. These results can provide scientific basis for the formulation of landscape pattern optimization measures aiming at non-point source pollution control.
RESUMEN
Androgen deprivation therapy (ADT) is the primary treatment for advanced prostate cancer (PCa). However, prolonged ADT inevitably results in therapy resistance with the emergence of the castration-resistant PCa phenotype (CRPC). Hence, there is an urgent need to explore new treatment options capable of delaying PCa progression. Hispidin (HPD) is a natural polyketide primarily derived from plants and fungi. HPD has been shown to have a diverse pharmacological profile, exhibiting anti-inflammatory, antiviral, cardiovascular and neuro-protective activities. However, there is currently no research regarding its properties in the context of PCa treatment. This research article seeks to evaluate the anti-cancer effect of HPD and determine the underlying molecular basis in both androgen-sensitive PCa and CRPC cells. Cell growth, migration, and invasion assays were performed via the MTS method, a wound healing assay and the transwell method. To investigate if HPD affected the expression of proteins, Western blot analysis was conducted. Furthermore, apoptosis was assessed by Annexin V-FITC/PI staining and Western blot analyses. HPD exhibited a favorable pharmaceutical profile to inhibit cell growth; disrupt the cell cycle; attenuate wound healing, migration and invasion; and induce apoptosis in PCa cells in vitro. The mechanistic results demonstrated that HPD reduced AR, MMP-2 and MMP-9 expression and activated the caspase-related pathway, leading to programmed cell death in PCa cells. We showed the anti-cancer effect of HPD on PCa cells and confirmed its feasibility as a novel therapeutic agent. This study provides significant insights into the delineation of the molecular mechanism of HPD in PCa cells and the development of an effective and safe therapy using HPD to eliminate PCa progression.
Asunto(s)
Apoptosis , Movimiento Celular , Proliferación Celular , Neoplasias de la Próstata , Humanos , Masculino , Apoptosis/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Antineoplásicos/farmacología , Ciclo Celular/efectos de los fármacos , Neoplasias de la Próstata Resistentes a la Castración/tratamiento farmacológico , Neoplasias de la Próstata Resistentes a la Castración/metabolismo , Neoplasias de la Próstata Resistentes a la Castración/patología , Policétidos/farmacología , Policétidos/químicaRESUMEN
Valproic acid (VPA) is one of the most effective antiepileptic drugs, and exposing animals to VPA during gestation has been used as a model for autism spectrum disorder (ASD). Numerous studies have shown that impaired synaptic transmission in the cerebellar cortical circuits is one of the reasons for the social deficits and repetitive behavior seen in ASD. In this study, we investigated the effect of VPA exposure during pregnancy on tactile stimulation-evoked cerebellar mossy fiber-granule cell (MF-GC) synaptic transmission in mice anesthetized with urethane. Three-chamber testing showed that mice exposed to VPA mice exhibited a significant reduction in social interaction compared with the control group. In vivo electrophysiological recordings revealed that a pair of air-puff stimulation on ipsilateral whisker pad evoked MF-GC synaptic transmission, N1, and N2. The evoked MF-GC synaptic responses in VPA-exposed mice exhibited a significant increase in the area under the curve (AUC) of N1 and the amplitude and AUC of N2 compared with untreated mice. Cerebellar surface application of the selective N-methyl-D-aspartate (NMDA) receptor blocker D-APV significantly inhibited facial stimulation-evoked MF-GC synaptic transmission. In the presence of D-APV, there were no significant differences between the AUC of N1 and the amplitude and AUC of N2 in the VPA-exposed mice and those of the untreated mice. Notably, blockade of the GluN2A subunit-containing, but not the GluN2B subunit-containing, NMDA receptor, significantly inhibited MF-GC synaptic transmission and decreased the AUC of N1 and the amplitude and AUC of N2 in VPA-exposed mice to levels similar to those seen in untreated mice. In addition, the GluN2A subunit-containing NMDA receptor was expressed at higher levels in the GC layer of VPA-treated mice than in control mice. These results indicate that gestational VPA exposure in mice produces ASD-like behaviors, accompanied by increased cerebellar MF-GC synaptic transmission and an increase in GluN2A subunit-containing NMDA receptor expression in the offspring.
Asunto(s)
Trastorno del Espectro Autista , Modelos Animales de Enfermedad , Efectos Tardíos de la Exposición Prenatal , Receptores de N-Metil-D-Aspartato , Transmisión Sináptica , Ácido Valproico , Animales , Receptores de N-Metil-D-Aspartato/metabolismo , Ácido Valproico/farmacología , Embarazo , Femenino , Ratones , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Transmisión Sináptica/efectos de los fármacos , Trastorno del Espectro Autista/inducido químicamente , Masculino , Cerebelo/efectos de los fármacos , Cerebelo/metabolismo , Anticonvulsivantes/farmacologíaRESUMEN
In this editorial, we comment on the article by Chen et al. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a global public health burden whose incidence has risen concurrently with overweight and obesity. Given its detrimental health impact, early identification of at-risk individuals is crucial. MAFLD diagnosis is based on evidence of hepatic steatosis indicated by liver biopsy, imaging, or blood biomarkers, and one of the following conditions: Overweight/ obesity, type 2 diabetes mellitus, or metabolic dysregulation. However, in large-scale epidemiological studies, liver biopsies are not feasible. The application of techniques such as ultrasonography, computed tomography, magnetic resonance imaging, and magnetic resonance spectroscopy is restricted by their limited sensitivity, low effectiveness, high costs, and need for specialized software. Blood biomarkers offer several advantages, particularly in large-scale epidemiological studies or clinical scenarios where traditional imaging techniques are impractical. Analysis of cumulative effects of excess high-normal blood alanine aminotransferase (ALT) levels of blood ALT levels could facilitate identification of at-risk patients who might not be detected through conventional imaging methods. Accordingly, investigating the utility of blood biomarkers in MAFLD should enhance early detection and monitoring, enabling timely intervention and management and improving patient outcomes.
Asunto(s)
Alanina Transaminasa , Biomarcadores , Humanos , Biomarcadores/sangre , Alanina Transaminasa/sangre , Hígado/diagnóstico por imagen , Hígado/patología , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/sangre , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Factores de Riesgo , Obesidad/complicaciones , Obesidad/diagnóstico , Obesidad/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Diagnóstico PrecozRESUMEN
N-glycosylation is a highly conserved glycan modification that plays crucial roles in various physiological processes, including protein folding, trafficking, and signal transduction. Porcine deltacoronavirus (PDCoV) poses a newly emerging threat to the global porcine industry. The spike protein of PDCoV exhibits a high level of N-glycosylation; however, its role in viral infection remains poorly understood. In this study, we applied a lentivirus-based entry reporter system to investigate the role of N-glycosylation on the viral spike protein during PDCoV entry stage. Our findings demonstrate that N-glycosylation at positions 652 and 661 of the viral spike protein significantly reduces the infectivity of PDCoV pseudotyped virus. Overall, our results unveil a novel function of N-glycosylation in PDCoV infection, highlighting its potential for facilitating the development of antiviral strategies.
RESUMEN
Rheumatoid arthritis (RA) is a chronic autoimmune disease. Targeting NLRP3 inflammasome, specifically its interaction with NEK7 via the LRR domain of NLRP3, is a promising therapeutic strategy. Our research aimed to disrupt this interaction by focusing on the LRR domain. Through virtual screening, we identified five compounds with potent anti-inflammatory effects and ideal LRR binding affinity. Lead compound C878-1943 underwent structural optimization, yielding pyridoimidazole derivatives with different anti-inflammatory activities. Compound I-19 from the initial series effectively inhibited caspase-1 and IL-1ß release in an adjuvant-induced arthritis (AIA) rat model, significantly reducing joint swelling and spleen/thymus indices. To further enhance potency and extend in vivo half-life, a second series including II-8 was developed, demonstrating superior efficacy and longer half-life. Both I-19 and II-8 bind to the LRR domain, inhibiting NLRP3 inflammasome activation. These findings introduce novel small molecule inhibitors targeting the LRR domain of NLRP3 protein and disrupt NLRP3-NEK7 interaction, offering a novel approach for RA treatment.
Asunto(s)
Artritis Experimental , Artritis Reumatoide , Quinasas Relacionadas con NIMA , Proteína con Dominio Pirina 3 de la Familia NLR , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Quinasas Relacionadas con NIMA/antagonistas & inhibidores , Quinasas Relacionadas con NIMA/metabolismo , Animales , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Humanos , Ratas , Artritis Experimental/tratamiento farmacológico , Descubrimiento de Drogas , Relación Estructura-Actividad , Masculino , Inflamasomas/metabolismo , Inflamasomas/antagonistas & inhibidores , Simulación del Acoplamiento Molecular , Antirreumáticos/farmacología , Antirreumáticos/química , Antirreumáticos/síntesis química , Antirreumáticos/uso terapéuticoRESUMEN
The prevalence of pediatric constipation ranges from 0.7 to 29.6% across different countries. Functional constipation accounts for 95% of pediatric constipation, and the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. We aimed to compare the efficacy and acceptability of different probiotic supplements for pediatric functional constipation. The current frequentist model-based network meta-analysis (NMA) included RCTs of probiotic supplements for functional constipation in children. The primary outcome was changes in bowel movement or stool frequency; acceptability outcome was all-cause discontinuation. Nine RCTs were included (N = 710; mean age = 5.5 years; 49.4% girls). Most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives (standardized mean difference (SMD) = 1.87, 95% confidence interval (95% CI) = 0.85 to 2.90) were associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments (SMD = 1.37, 95% CI: 0.32 to 2.43). All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments. Conclusion: The results of our NMA support the application of an advanced combination of probiotics and laxatives for pediatric functional constipation if there is no concurrent contraindication. Registration: PROSPERO (CRD42022298724). What is Known: ⢠Despite of the high prevalence of pediatric constipation, which ranges from 0.7% to 29.6%, the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. The widely heterogeneous strains of probiotics let the traditional meta-analysis, which pooled all different strains into one group, be nonsense and insignificant. What is New: ⢠By conducting a comprehensive network meta-analysis, we aimed to compare the efficacy and acceptability of different strains of probiotic supplements for pediatric functional constipation. Network meta-analysis of nine randomized controlled trials revealed that the most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives was associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments. All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.
Asunto(s)
Estreñimiento , Laxativos , Metaanálisis en Red , Probióticos , Ensayos Clínicos Controlados Aleatorios como Asunto , Niño , Preescolar , Femenino , Humanos , Masculino , Estreñimiento/terapia , Estreñimiento/tratamiento farmacológico , Laxativos/uso terapéutico , Probióticos/uso terapéutico , Resultado del Tratamiento , Aceptación de la Atención de Salud/estadística & datos numéricosRESUMEN
In this work, a magnetic adsorption material based on metal-organic framework (Fe3O4@ZnAl-LDH@MIL-53(Al)) was synthesized and used as an adsorbent in the process of magnetic solid phase extraction. Then, a high-performance liquid chromatograph was used to quantitatively detect triazole fungicides in samples. In order to verify the successful preparation of the material, a series of characterization analyses were carried out. Besides, the key parameters that may affect the extraction efficiency have been optimized, and under optimal conditions the three triazole fungicides showed good linearity in the range of 10-1000 µg/L (R2 ≥ 0.9796); Limit of detections were ranged from 0.013 to 0.030 µg/mL. Finally, the established method was applied to the detection of triazole fungicides in four fresh juice samples. The results showed that the target analyte was not detected in all the test samples. By detecting the recoveries (73.3-104.3%) and coefficient variation (RSD ≤ 6.8%) of triazole fungicides in fortified samples, it proved that this established method meets the requirements of pesticide residue analysis and showed excellent application potential.
RESUMEN
INTRODUCTION: Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta-analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management. METHODS: We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason). RESULTS: We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high-frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms, including depression and anxiety symptoms, and overall PTSD severity. CONCLUSIONS: This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms. TRIAL REGISTRATION: PROSPERO CRD42023391562.
Asunto(s)
Metaanálisis en Red , Ensayos Clínicos Controlados Aleatorios como Asunto , Trastornos por Estrés Postraumático , Estimulación Transcraneal de Corriente Directa , Estimulación Magnética Transcraneal , Humanos , Aceptación de la Atención de Salud , Trastornos por Estrés Postraumático/terapia , Estimulación Transcraneal de Corriente Directa/métodos , Estimulación Magnética Transcraneal/métodos , Resultado del Tratamiento , Estimulación del Nervio Vago/métodosRESUMEN
Nonischemic cardiomyopathy (NICM) is a major cause of advanced heart failure, and the morbidity and mortality associated with NICM are serious medical problems. However, the etiology of NICM is complex and the related mechanisms involved in its pathogenesis remain unclear. The microarray datasets GSE1869 and GSE9128 retrieved from the Gene Expression Omnibus database were used to identify differentially expressed genes (DEGs) between NICM and normal samples. The co-expressed genes were identified using Venn diagrams. Kyoto Encyclopedia of Genes and Genomes pathway analyses and gene ontology enrichment were used to clarify biological functions and signaling pathways. Analysis of protein-protein interaction networks using Search Tool for the Retrieval of Interacting Genes/Proteins online to define the hub genes associated with NICM pathogenesis. A total of 297 DEGs were identified from GSE1869, 261 of which were upregulated genes and 36 were downregulated genes. A total of 360 DEGs were identified from GSE9128, 243 of which were upregulated genes and 117 were downregulated genes. In the 2 datasets, the screening identified 36 co-expressed DEGs. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis showed that DEGs were mainly enriched in pantothenate and CoA biosynthesis, beta-alanine metabolism, kinetochore, G-protein beta/gamma-subunit complex, and other related pathways. The PPI network analysis revealed that DUSP6, EGR1, ZEB2, and XPO1 are the 4 hub genes of interest in the 2 datasets. Bioinformatics analysis of hub genes and key signaling pathways is an effective way to elucidate the mechanisms involved in the development of NICM. The results will facilitate further studies on the pathogenesis and therapeutic targets of NICM.
Asunto(s)
Cardiomiopatías , Biología Computacional , Mapas de Interacción de Proteínas , Cardiomiopatías/genética , Humanos , Biología Computacional/métodos , Mapas de Interacción de Proteínas/genética , Perfilación de la Expresión Génica/métodos , Redes Reguladoras de Genes , Transducción de Señal/genética , Ontología de Genes , Bases de Datos GenéticasRESUMEN
Etomidate (ET) is a widely used intravenous imidazole general anesthetic, which depresses the cerebellar neuronal activity by modulating various receptors activity and synaptic transmission. In this study, we investigated the effects of ET on the cerebellar climbing fiber-Purkinje cells (CF-PC) plasticity in vitro in mice using whole-cell recording technique and pharmacological methods. Our results demonstrated that CF tetanic stimulation produced a mGluR1-dependent long-term depression (LTD) of CF-PC excitatory postsynaptic currents (EPSCs), which was enhanced by bath application of ET (10 µM). Blockade of mGluR1 receptor with JNJ16259685, ET triggered the tetanic stimulation to induce a CF-PC LTD accompanied with an increase in paired-pulse ratio (PPR). The ET-triggered CF-PC LTD was abolished by extracellular administration of an N-methyl-(D)-aspartate (NMDA) receptor antagonist, D-APV, as well as by intracellular blockade of NMDA receptors activity with MK801. Furthermore, blocking cannabinoids 1 (CB1) receptor with AM251 or chelating intracellular Ca2+ with BAPTA, ET failed to trigger the CF-PC LTD. Moreover, the ET-triggered CF-PC LTD was abolished by inhibition of protein kinase A (PKA), but not by inhibition of protein kinase C inhibiter. The present results suggest that ET acts on postsynaptic NMDA receptor resulting in an enhancement of the cerebellar CF-PC LTD through CB1 receptor/PKA cascade in vitro in mice. These results provide new evidence and possible mechanism for ET anesthesia to affect motor learning and motor coordination by regulating cerebellar CF-PC LTD.
Asunto(s)
Etomidato , Ratones , Animales , Etomidato/farmacología , Receptor Cannabinoide CB1/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Depresión Sináptica a Largo Plazo/fisiología , Sinapsis/fisiología , Cerebelo/fisiología , Plasticidad Neuronal/fisiología , Células de Purkinje/fisiología , Transmisión Sináptica , Anestésicos Intravenosos/farmacologíaRESUMEN
Periodontitis has recently been defined as a dysbiotic disease caused by an imbalanced oral microbiota. The transition from commensal microbial communities to periodontitis-associated ones requires colonization by specific pathogens, including Porphyromonas gingivalis. We previously reported an antagonistic relationship between Streptococcus cristatus and P. gingivalis. To determine the role of S. cristatus in altering the interactions of P. gingivalis with other oral bacteria in a complex context, we collected dental plaque samples from patients with periodontitis and assigned them to two groups based on the ratios of S. cristatus and P. gingivalis. We then characterized the microbial profiles of the dental plaque samples using shotgun metagenomic sequencing and compared the oral microbial composition and functional capabilities of the group with high S. cristatus-P. gingivalis ratios with the low ratio group. Taxonomic annotation revealed significant differences in the microbial composition at both the genus and species levels between the low and high S. cristatus-P. gingivalis ratio groups. Notably, a higher microbial diversity was observed in the samples with low S. cristatus-P. gingivalis ratios. Furthermore, the antibiotic resistance gene profiles of the two groups were also distinct, with a significantly increased abundance of the genes in the dental plaque samples with low S. cristatus-P. gingivalis ratios. It, therefore, indicates that the S. cristatus-P. gingivalis ratios influenced the virulence potential of the oral microbiome. Our work shows that enhancing the S. cristatus-P. gingivalis ratio in oral microbial communities can be an attractive approach for revising the dysbiotic oral microbiome.IMPORTANCEPeriodontitis, one of the most common chronic diseases, is linked to several systemic diseases, such as cardiovascular disease and diabetes. Although Porphyromonas gingivalis is a keystone pathogen that causes periodontitis, its levels, interactions with accessory bacteria and pathobionts in the oral microbiome, and its association with the pathogenic potential of the microbial communities are still not well understood. In this study, we revealed the role of Streptococcus cristatus and the ratios of S. cristatus and P. gingivalis in modulating the oral microbiome to facilitate a deeper understanding of periodontitis and its progression. The study has important clinical implications as it laid a foundation for developing novel non-antibiotic therapies against P. gingivalis and improving the efficiency of periodontal treatments.
Asunto(s)
Placa Dental , Microbiota , Periodontitis , Streptococcus , Humanos , Porphyromonas gingivalis/genéticaRESUMEN
Surface-enhanced Raman scattering (SERS) technology has unique advantages in the rapid detection of pesticides in plant-derived foods, leading to reduced detection limits and increased accuracy. Plant-derived Chinese herbal medicines have similar sources to plant-derived foods; however, due to the rough surfaces and complex compositions of herbal medicines, the detection of pesticide residues in this context continues to rely heavily on traditional methods, which are time consuming and laborious and are unable to meet market demands for portability. The application of flexible nanomaterials and SERS technology in this realm would allow rapid and accurate detection in a portable format. Therefore, in this review, we summarize the underlying principles and characteristics of SERS technology, with particular focus on applications of SERS for the analysis of pesticide residues in agricultural products. This paper summarizes recent research progress in the field from three main directions: sample pretreatment, SERS substrates, and data processing. The prospects and limitations of SERS technology are also discussed, in order to provide theoretical support for rapid detection of pesticide residues in Chinese herbal medicines.
RESUMEN
Objective: Children born small for gestational age (SGA) are at a greater risk of developing insulin resistance, type 2 diabetes, and cardiovascular disease in adulthood. Gastrointestinal peptides, some secreted by intestinal L cells, regulate glucose and lipid metabolism and act on the hypothalamus to regulate energy homeostasis. The aim of this study was to explore whether gastrointestinal peptides are involved in metabolic disorders in SGA, which remains unclear. Methods: The secretion of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) were investigated in prepubertal children born SGA, the differences between catch-up growth and persistent short stature were compared, and correlation with glucose and lipid metabolism was analyzed. GLP-1, PYY, insulin-like growth factor 1, glucose, insulin, and lipid concentrations were analyzed in prepubertal children aged 4-10 years, stratified into three groups: short-SGA (SGA-s), catch-up growth SGA, and normal growth appropriate for gestational age (AGA). Results: Fasting GLP-1 and PYY concentrations were significantly lower in the SGA group than in the AGA group (p<0.05), and the GLP-1 level in infants born SGA with catch-up growth was lower than that in the SGA-s group (p<0.05). In the SGA population, GLP-1 showed a weak negative correlation with catch-up growth (r=-0.326) and positive correlation with fasting insulin (r=0.331). Conclusion: Lower GLP-1 concentrations may be associated with abnormal glucose metabolism in prepubertal children born SGA with catch-up growth. This is indirect evidence that impaired intestinal L cell function may be involved in the development of metabolic complications in SGA children.
Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Niño , Recién Nacido , Humanos , Péptido YY , Edad Gestacional , Recién Nacido Pequeño para la Edad Gestacional , Insulina , Glucosa , Péptido 1 Similar al GlucagónRESUMEN
OBJECTIVE: Focusing on the relationship between unpaid labor and the occurrence of depressive symptoms, this study aimed to explore the factors influencing the inequality of depressive symptoms and their contribution among Chinese urban and rural employed people. METHODS: This study utilized the 2020 China Family Panel Studies' national resampling data. Multivariate logistic regression was used to explore the factors influencing the occurrence of depressive symptoms among employed persons in urban and rural areas in China, respectively. Fairlie decomposition was used to explore the contribution of influencing factors such as unpaid labor to the difference in the occurrence of depressive symptoms between urban and rural areas. RESULTS: About 2,136 (21.70%) participants had depressive symptoms, of which 1,197 (24.75%) rural employed people had depressive symptoms and 939 (18.75%) urban employed people had depressive symptoms. The results of Fairlie decomposition analysis showed that 70.51% of the differences in depressive symptoms between urban and rural Chinese employed people could be explained by the covariates included in this study, including education level (52.44%), age (-11.91%), housework time (10.42%), self-rated health status (10.22%), self-rated income status (2.53%), exercise (2.36%), job satisfaction status (1.99%), chronic disease status (1.90%), and marital status (1.79%). CONCLUSION: This study found that the proportion of depressive symptoms was lower among urban employed residents than among rural employed residents. This difference was mainly caused by unpaid labor time, socioeconomic status, personal lifestyle, and health status. Housework, which is one of the unpaid labor, contributed to this depressive symptom difference in the third place.
Asunto(s)
Depresión , Estado de Salud , Humanos , Depresión/epidemiología , Factores Socioeconómicos , Estudios Longitudinales , Población Rural , China/epidemiología , Población UrbanaRESUMEN
BACKGROUND: Adolescents often carry their depression well into their adulthood. This creates perpetual difficulties for their family and society. Research on the relationship between positive parenting and adolescent depressive symptoms is rare. The protective effect of positive parenting on adolescent depressive symptoms also remains underexplored. Parents are a vital source of feedback that shapes adolescents' self-view in crucial ways. AIMS: This study examines the latent relationships between four factors related to positive parenting and adolescent depressive symptoms. METHOD: Using data from the Chinese Family Panel Studies (CFPS), Stata MP 17.0 was used for preliminary data processing and descriptive statistics. The structural equation model (SEM) was adopted to test the seven proposed hypotheses. RESULTS: The study participants were 2,816 adolescents (52.34% male). The SEM showed that positive communication and parental praise can directly reduce depressive symptoms in adolescents (path coefficients of -0.24 and -0.13 [p < .001], respectively). Additionally, both positive communication and positive parent-adolescent interactions can reduce adolescents' depressive symptoms by heightening the intermediate factor of parental praise (path coefficients of 0.30 and 0.44 [p < .001], respectively). Conversely, positive parent-adolescent interactions did not negatively affect adolescents' depressive symptoms, as we hypothesized. CONCLUSIONS: High level of positive parenting negatively predicts the level of depressive symptoms among adolescents. Specifically, positive communication, positive parent-adolescent communication, and parental praise are the main protective factors related to positive parenting for adolescents' depressive symptoms.