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1.
Pediatr Investig ; 8(2): 101-107, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38910848

RESUMEN

Importance: Systemic lupus erythematosus (SLE) is a diffuse connective tissue disease with complex clinical manifestations and prolonged course. The early diagnosis and condition monitoring of SLE are crucial to disease prognosis. Objective: To assess the diagnostic value of long noncoding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) in childhood-onset SLE (cSLE). Methods: Fifty-seven children diagnosed with SLE, 40 children diagnosed with juvenile idiopathic arthritis (JIA), and 40 healthy children were included. Peripheral blood samples from each patient were collected. A quantitative polymerase chain reaction was used to confirm the expression of lncNEAT1_1 and lncNEAT1_2 in peripheral blood. Associations among parameters were analyzed using the Mann-Whitney U test or independent sample t-test. Results: The expression of both lncNEAT1_1 and lncNEAT1_2 in patients with cSLE were significantly higher than that of healthy control and patients with JIA. Receiver operating characteristic curves revealed an area under the curve (AUC) of 0.633 (95% confidence interval [CI], 0.524-0.742; P = 0.024) for lncNEAT1_1. The AUC of lncNEAT1_2 was 0.812 (95% CI, 0.727-0.897; P < 0.0001) to discriminate individuals with cSLE from health control and children with JIA with a sensitivity of 0.622 and a specificity of 0.925. Moreover, lncNEAT1_2 expression was higher in patients with cSLE presenting with fever, lupus nephritis, elevated erythrocyte sedimentation rate, active disease activity, and decreased C3 level, compared with those without these conditions. However, no similar correlation was observed for lncNEAT1_1. Interpretation: The expression of lncNEAT1_2 was significantly elevated in children with SLE, especially those with fever, renal involvement, and low C3 levels. These findings suggest that lncNEAT1_2 may represent a potential biomarker for cSLE.

2.
J Nanobiotechnology ; 22(1): 370, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38918856

RESUMEN

Parkinson's disease (PD) is the second largest group of neurodegenerative diseases, and its existing drug treatments are not satisfactory. Natural cell membrane drugs are used for homologous targeting to enhance efficacy. In this study, microfluidic electroporation chip prepared mesenchymal stem cell-derived neuron-like cell membrane-coated curcumin PLGA nanoparticles (MM-Cur-NPs) was synthesized and explored therapeutic effect and mechanism in PD. MM-Cur-NPs can protect neuron from damage, restore mitochondrial membrane potential and reduce oxidative stress in vitro. In PD mice, it also can improve movement disorders and restore damaged TH neurons. MM-Cur-NPs was found to be distributed in the brain and metabolized with a delay within 24 h. After 1 h administration, MM-Cur-NPs were distributed in brain with a variety of neurotransmitters were significantly upregulated, such as dopamine. Differentially expressed genes of RNA-seq were enriched in the inflammation regulation, and it was found the up-expression of anti-inflammatory factors and inhibited pro-inflammatory factors in PD. Mechanically, MM-Cur-NPs can not only reduce neuronal apoptosis, inhibit the microglial marker IBA-1 and inflammation, but also upregulate expression of neuronal mitochondrial protein VDAC1 and restore mitochondrial membrane potential. This study proposes a therapeutic strategy provide neuroprotective effects through MM-Cur-NPs therapy for PD.


Asunto(s)
Apoptosis , Membrana Celular , Inflamación , Células Madre Mesenquimatosas , Nanopartículas , Neuronas , Enfermedad de Parkinson , Animales , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Ratones , Apoptosis/efectos de los fármacos , Nanopartículas/química , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Membrana Celular/metabolismo , Membrana Celular/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Curcumina/farmacología , Curcumina/química , Ratones Endogámicos C57BL , Microfluídica/métodos , Masculino , Estrés Oxidativo/efectos de los fármacos
3.
Theranostics ; 14(7): 2946-2968, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38773973

RESUMEN

Recent advancements in modern science have provided robust tools for drug discovery. The rapid development of transcriptome sequencing technologies has given rise to single-cell transcriptomics and single-nucleus transcriptomics, increasing the accuracy of sequencing and accelerating the drug discovery process. With the evolution of single-cell transcriptomics, spatial transcriptomics (ST) technology has emerged as a derivative approach. Spatial transcriptomics has emerged as a hot topic in the field of omics research in recent years; it not only provides information on gene expression levels but also offers spatial information on gene expression. This technology has shown tremendous potential in research on disease understanding and drug discovery. In this article, we introduce the analytical strategies of spatial transcriptomics and review its applications in novel target discovery and drug mechanism unravelling. Moreover, we discuss the current challenges and issues in this research field that need to be addressed. In conclusion, spatial transcriptomics offers a new perspective for drug discovery.


Asunto(s)
Descubrimiento de Drogas , Perfilación de la Expresión Génica , Análisis de la Célula Individual , Transcriptoma , Descubrimiento de Drogas/métodos , Humanos , Transcriptoma/genética , Análisis de la Célula Individual/métodos , Perfilación de la Expresión Génica/métodos , Animales
4.
Cell Death Dis ; 15(4): 267, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38622131

RESUMEN

Isochlorate dehydrogenase 1 (IDH1) is an important metabolic enzyme for the production of α-ketoglutarate (α-KG), which has antitumor effects and is considered to have potential antitumor effects. The activation of IDH1 as a pathway for the development of anticancer drugs has not been attempted. We demonstrated that IDH1 can limit glycolysis in hepatocellular carcinoma (HCC) cells to activate the tumor immune microenvironment. In addition, through proteomic microarray analysis, we identified a natural small molecule, scutellarin (Scu), which activates IDH1 and inhibits the growth of HCC cells. By selectively modifying Cys297, Scu promotes IDH1 active dimer formation and increases α-KG production, leading to ubiquitination and degradation of HIF1a. The loss of HIF1a further leads to the inhibition of glycolysis in HCC cells. The activation of IDH1 by Scu can significantly increase the level of α-KG in tumor tissue, downregulate the HIF1a signaling pathway, and activate the tumor immune microenvironment in vivo. This study demonstrated the inhibitory effect of IDH1-α-KG-HIF1a on the growth of HCC cells and evaluated the inhibitory effect of Scu, the first IDH1 small molecule agonist, which provides a reference for cancer immunotherapy involving activated IDH1.


Asunto(s)
Carcinoma Hepatocelular , Glucuronatos , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Proteómica , Apigenina/farmacología , Apigenina/uso terapéutico , Ácidos Cetoglutáricos/metabolismo , Microambiente Tumoral , Isocitrato Deshidrogenasa
5.
Psychiatry Res ; 331: 115612, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38039652

RESUMEN

The epidemiology of schizophrenia has been reported in many countries. However, due to the limitations of those studies, the findings cannot be generalized to other parts of the world, especially in China. In this study, the incidence, prevalence, and mortality of schizophrenia in Shandong, China were calculated using data from the National Severe Mental Disorder Registration System collected between 2016 and 2020 and census data from 2010 to 2020. The overall incidence decreased from 9.61 per 100,000 in 2016 to 4.40 per 100,000 in 2020, the aggregate prevalence was approximately 3.20 per 1000, and the overall mortality ranged from 6.17 per 100,000 to 7.71 per 100,000. The evidence from this study indicated that the incidence, prevalence, and mortality of schizophrenia were higher in rural areas than in urban areas. Females had higher incidence, prevalence, and mortality than males. This study provided epidemiological information on schizophrenia and opened avenues for future research.


Asunto(s)
Esquizofrenia , Femenino , Masculino , Humanos , Esquizofrenia/epidemiología , Incidencia , Prevalencia , Población Rural , Población Urbana , Sistema de Registros , China/epidemiología
6.
PLoS One ; 18(11): e0289848, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37948392

RESUMEN

BACKGROUND: The top 100 ATP/WTA ranking points are a crucial indicator of entry into the high-level world of tennis players, and the number of players from a nation in this ranking reflects the overall level of their tennis. However, the growth time series characteristics of elite tennis athletes are unclear. OBJECTIVE: This study aims to examine the historical career ranking changes of elite players and provide valuable insights for aspiring young players looking to achieve success in the sport. At the same time, it is of great significance for the efficient and sustainable cultivation of Chinese tennis players. METHODS: Data on the rankings of 202 players were analyzed, Spearman and Pearson correlations were employed to investigate the association between ranking and time-use patterns. The variance test was utilized to compare disparities in time characteristics of the ranking, with a statistical significance level of p<0.05. RESULTS: There was a significant correlation between the time of entering the professional tournament ranking system and the ranking, top 100 time, top 100 age, and age of starting tennis. Top 50 ATP players are earlier than those ranked 51-100. There was a significant difference between the age of starting tennis and the time to top 10 among the ATP and WTA players. Chinese female players showed no significant differences compared to their global Top 10 counterparts in terms of time-to-success characteristics. CONCLUSION: The elite tennis players who achieve success typically start playing and competing in the sport at a young age, with professional competition often commencing around 18 years of age. Notably, these players frequently attain high rankings before reaching the age of 20. Furthermore, top 10 ATP male players tend to start tennis at an earlier age and require a shorter time to achieve a top 10 ranking compared with WTA female players.


Asunto(s)
Tenis , Humanos , Masculino , Adolescente , Femenino , Atletas , Logro , China , Adenosina Trifosfato
7.
Front Microbiol ; 14: 1192574, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38029174

RESUMEN

Introduction: Interspecies interactions are a crucial driving force of species evolution. The genes of each coexisting species play a pivotal role in shaping the structure and function within the community, but how to identify them at the genome-wide level has always been challenging. Methods: In this study, we embed the Lotka-Volterra ordinary differential equations in the theory of community ecology into the systems mapping model, so that this model can not only describe how the quantitative trait loci (QTL) of a species directly affects its own phenotype, but also describe the QTL of the species how to indirectly affect the phenotype of its interacting species, and how QTL from different species affects community behavior through epistatic interactions. Results: By designing and implementing a co-culture experiment for 100 pairs of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus), we mapped 244 significant QTL combinations in the interaction process of the two bacteria using this model, including 69 QTLs from E. coli and 59 QTLs from S. aureus, respectively. Through gene annotation, we obtained 57 genes in E. coli, among which the genes with higher frequency were ypdC, nrfC, yphH, acrE, dcuS, rpnE, and ptsA, while we obtained 43 genes in S. aureus, among which the genes with higher frequency were ebh, SAOUHSC_00172, capF, gdpP, orfX, bsaA, and phnE1. Discussion: By dividing the overall growth into independent growth and interactive growth, we could estimate how QTLs modulate interspecific competition and cooperation. Based on the quantitative genetic model, we can obtain the direct genetic effect, indirect genetic effect, and genome-genome epistatic effect related to interspecific interaction genes, and then further mine the hub genes in the QTL networks, which will be particularly useful for inferring and predicting the genetic mechanisms of community dynamics and evolution. Systems mapping can provide a tool for studying the mechanism of competition and cooperation among bacteria in co-culture, and this framework can lay the foundation for a more comprehensive and systematic study of species interactions.

8.
Arthritis Res Ther ; 25(1): 204, 2023 10 18.
Artículo en Inglés | MEDLINE | ID: mdl-37853451

RESUMEN

OBJECTIVES: Juvenile dermatomyositis (JDM) is a chronic autoimmune disease. Some patients remain in an active state even though they were administrated with a combination of corticosteroid and methotrexate. Existing research has suggested that interferon and Janus kinase played an important role in pathogenesis. Existing research has suggested the efficacy of JAK inhibitors (JAKi). Our retrospective study aimed to investigate the efficacy of tofacitinib in refractory JDM patients. METHODS: A total of eighty-eight patients in China who had been diagnosed with JDM and subjected to tofacitinib therapy for over 3 months were retrospectively analyzed. Skin and muscle manifestations were assessed using the Cutaneous Assessment Tool-binary method (CAT-BM), Childhood Myositis Assessment Scale (CMAS), and kinase. Pulmonary function was assessed using a high-resolution CT (computerized tomography) scan and pulmonary symptoms. All patients were subjected to regular follow-up, and core measures were assessed every 3 months after initiation. Furthermore, the data were analyzed using the Wilcoxon single test, Mann-Whitney U test, and chi-square test. RESULTS: Compared with the baseline data, skin and muscle manifestations were found significantly improved during the respective follow-up visit. At the most recent follow-up, nearly 50% of patients achieved a clinical complete response and six patients received tofacitinib monotherapy. Sixty percent of patients suffering from interstitial lung disease well recovered on high-resolution CT. Seventy-five percent of patients showed a reduction in the size or number of calcinosis, and 25% of patients showed completely resolved calcinosis. CONCLUSION: In this study, the result suggested that tofacitinib therapy exerted a certain effect on skin manifestations, muscle manifestations, interstitial lung disease (ILD), calcinosis, as well as downgrade of medication. In-depth research should be conducted to focus on the correlation between the pathogenesis of JDM and JAKi.


Asunto(s)
Calcinosis , Dermatomiositis , Inhibidores de las Cinasas Janus , Enfermedades Pulmonares Intersticiales , Humanos , Niño , Dermatomiositis/diagnóstico , Estudios Retrospectivos , Inhibidores de las Cinasas Janus/uso terapéutico , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/tratamiento farmacológico
9.
ACS Pharmacol Transl Sci ; 6(10): 1453-1470, 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37854614

RESUMEN

Programmed cell death protein 2-like (PDCD2L) is a shuttle protein of the nucleus and cytoplasm and is related to the ribosome biogenesis. However, there are few reports on the relationship between PDCD2L and inflammation, and the exact relationship between PDCD2L and inflammation has not been determined in vascular endothelial cells yet. Accordingly, we focus on exploring the relationship between PDCD2L and inflammation and its potential mechanisms. Our research findings suggested that PDCD2L is a proinflammatory target. The result showed that, by interfering with the expression of PDCD2L, LPS-induced inflammation of vascular endothelial cells can be reduced, such as IL-6 and IL-1ß, as well as the adhesion factor ICAM1. Meanwhile, overexpression of PDCD2L can further increase LPS-induced inflammation levels, ICAM1, and ROS production, reduce CAT, GSH/GSSG levels, and increase SOD levels. Therefore, we determined that PDCD2L has a regulatory effect on inflammation and oxidative stress of vascular endothelial cells, and its regulatory mechanism may be related to inflammatory transcription factors STAT1, NF-κB regulation, transport of inflammatory messenger mRNA, and ribosome biogenesis. Then, we screened that andrographolide (Andro) can bind to PDCD2L, thus inhibiting inflammation and endothelial cell adhesion caused by the overexpression of PDCD2L. This study reveals that PDCD2L is a potential anti-inflammatory therapeutic target, providing new exploration for the development of anti-inflammatory drugs.

10.
Lupus ; 32(14): 1675-1680, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37905512

RESUMEN

OBJECTIVE: This study aimed to analyze age-specific characteristics of childhood-onset systemic lupus erythematosus (cSLE) at a health center in China. METHODS: The children with SLE were grouped based on age at disease-onset: pre-pubertal (≤7 years), peri-pubertal (8-13 years), and adolescence (14-18 years). The retrospective study included patients with cSLE diagnosed at the Beijing Children's Hospital between 2013 and 2021. RESULTS: A total of 675 females and 178 males were eligible for inclusion in this study. Among them, 160 patients were diagnosed during pre-puberty, 635 during peri-puberty, and 58 during adolescence. The female-to-male ratio of pre-pubertal, peri-pubertal, and adolescent diagnosis was 3.5: 1, 3.6: 1, and 7.28:1, respectively. The median time from onset to diagnosis during the pre-puberal period was 3.0 (IQR 1.0-24.0 months), which was longer than that during the peri-puberal period (1.4; IQR 0.7-4) months and adolescence (1.0; IQR 0.4-2) months (p = <.0001). The proportion of LN in patients diagnosed during the peri-puberal period (304, 46.6%) and during adolescence (27, 47.9%) was higher than that of patients diagnosed during the pre-puberal period (59, 36.9%) (p = .044). 46 (28.8%), 233 (36.7%), and 32 (55.2%) of children diagnosed during the pre-pubertal period, peri-pubertal period, and adolescence, respectively, suffered from leukopenia. CONCLUSION: The proportion of renal involvement and leukopenia in the pre-pubertal group was lower than that of the pubertal group and adolescent group. More importantly, the younger the age of the patient, the more likely the diagnosis to be delayed.


Asunto(s)
Leucopenia , Lupus Eritematoso Sistémico , Niño , Adolescente , Humanos , Masculino , Femenino , Lupus Eritematoso Sistémico/diagnóstico , Estudios Retrospectivos , Diagnóstico Tardío , Edad de Inicio
11.
Sci Total Environ ; 905: 167053, 2023 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-37709070

RESUMEN

Triclosan (TCS), a widely used broad-spectrum antibacterial agent and preservative, is commonly found in products and environments. Widespread human exposure to TCS has drawn increasing attention from researchers concerning its toxicological effect. However, minimal studies have focused on the impact of TCS exposure on human stem cells. Therefore, the aim of the present study was to evaluate the effects of TCS exposure on stem cells from human exfoliated deciduous teeth (SHED) and its molecular mechanisms. A series of experimental methods were conducted to assess cell viability, morphology, proliferation, differentiation, senescence, apoptosis, mitochondrial function, and oxidative stress after SHED exposure to TCS. Furthermore, transcriptome analysis was applied to investigate the response of SHED to different concentrations of TCS exposure and to explore the molecular mechanisms. We demonstrated that TCS has a dose-dependent proliferation and differentiation inhibition of SHED, while promoting cellular senescence, mitochondrial dysfunction, endoplasmic reticulum (ER) stress, and oxidative stress, as well as significantly induces apoptosis and autophagy flux inhibition at high concentrations. Interestingly, no significant morphological changes in SHED were observed after TCS exposure. Transcriptome analysis of normal and TCS-induced SHED suggested that SHED may use different strategies to counteract stress from different concentrations of TCS and showed significant differences. We discovered that TCS mediates cellular injury of SHED by enhancing the expression of PTEN, thereby inhibiting the phosphorylation levels of PI3K and AKT as well as mTOR expression. Collectively, our findings provide a new understanding of the toxic effects of TCS on human stem cell fate, which is important for determining the risk posed by TCS to human health.


Asunto(s)
Triclosán , Humanos , Triclosán/toxicidad , Estrés Oxidativo , Fosforilación , Células Madre , Diente Primario
13.
Lipids Health Dis ; 22(1): 136, 2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37626321

RESUMEN

OBJECTIVE: The purpose of this study was to comprehensively evaluate the lipid profiles in patients with juvenile idiopathic arthritis (JIA). METHODS: The literature and relevant reviews were searched for published clinical studies on the relationship between JIA and blood lipid levels. The Newcastle-Ottawa scale (NOS) was applied to evaluate the risk and methodological value of the included case‒control and cohort studies. Standardized mean differences (SMDs) and 95% confidence intervals were derived for all variables with adequate unprocessed data. This meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. RESULTS: In total, 16 studies were incorporated through screening. The analysis findings revealed that the levels of very low-density lipoprotein cholesterol [SMD=-0.411, 95% CI (-0.774~-0.048), P = 0.026], high-density lipoprotein cholesterol [SMD=-0.528, 95% CI (-0.976~-0.079), P = 0.021], and apolipoprotein A1 [SMD=-1.050, 95% CI (-1.452~-0.647), P = 0.000] in JIA patients were statistically lower than those observed in healthy controls. The level of low-density lipoprotein cholesterol [SMD = 0.202, 95% CI (0.003 ~ 0.400), P = 0.046] was significantly higher in JIA patients than in healthy controls. In JIA patients, body mass index [SMD=-0.189, 95% CI (-0.690 ~ 0.311), P = 0.459], high-density lipoprotein [SMD =-1.235, 95% CI (-2.845 ~ 0.374), P = 0.133), low-density lipoprotein [SMD = 0.616, 95% CI (-0.813 ~ 2.046), P = 0.398), triglycerides (SMD = 0.278, 95% CI (-0.182 ~ 0.738), P = 0.236], total cholesterol [SMD=-0.073, 95% CI (-0.438 ~ 0.293), P = 0.696] and apolipoprotein B levels [SMD = 0.226, 95% CI (-0.133 ~ 0.585), P = 0.217] were not significantly different from those in healthy controls. CONCLUSIONS: The outcomes of this meta-analysis suggest that dyslipidemia is common in JIA patients compared to healthy controls. Patients with JIA have a significantly increased risk of atherosclerosis and cardiovascular disease later in life.


Asunto(s)
Artritis Juvenil , Humanos , Apolipoproteínas B , HDL-Colesterol , LDL-Colesterol , Lipoproteínas HDL
14.
Theranostics ; 13(13): 4526-4558, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37649608

RESUMEN

Drug evaluation has always been an important area of research in the pharmaceutical industry. However, animal welfare protection and other shortcomings of traditional drug development models pose obstacles and challenges to drug evaluation. Organ-on-a-chip (OoC) technology, which simulates human organs on a chip of the physiological environment and functionality, and with high fidelity reproduction organ-level of physiology or pathophysiology, exhibits great promise for innovating the drug development pipeline. Meanwhile, the advancement in artificial intelligence (AI) provides more improvements for the design and data processing of OoCs. Here, we review the current progress that has been made to generate OoC platforms, and how human single and multi-OoCs have been used in applications, including drug testing, disease modeling, and personalized medicine. Moreover, we discuss issues facing the field, such as large data processing and reproducibility, and point to the integration of OoCs and AI in data analysis and automation, which is of great benefit in future drug evaluation. Finally, we look forward to the opportunities and challenges faced by the coupling of OoCs and AI. In summary, advancements in OoCs development, and future combinations with AI, will eventually break the current state of drug evaluation.


Asunto(s)
Inteligencia Artificial , Sistemas Microfisiológicos , Animales , Humanos , Evaluación de Medicamentos , Reproducibilidad de los Resultados , Desarrollo de Medicamentos
15.
BMJ Open ; 13(7): e074046, 2023 07 30.
Artículo en Inglés | MEDLINE | ID: mdl-37518073

RESUMEN

OBJECTIVE: To investigate the association between furosemide administration and clinical outcomes in patients with sepsis-associated acute kidney injury (SAKI) receiving renal replacement therapy (RRT). DESIGN: A retrospective observational cohort study. SETTING: The data were collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, which contains clinical data from more than 380 000 patients admitted to the intensive care units (ICUs) of the Beth Israel Deaconess Medical Center from 2008 to 2019. PARTICIPANTS: All adult patients with SAKI receiving RRT were enrolled. Data for each patient within the first 24 hours of ICU admission were extracted from the MIMIC-IV database. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was in-hospital mortality, and the secondary outcome was the length of hospital stay, length of ICU stay, RRT-free time and ventilator-free time. Logistic regression was used to investigate the association between furosemide administration and in-hospital mortality. Subgroup analysis was employed to explore the potential sources of heterogeneity. RESULTS: A total of 1663 patients with SAKI receiving RRT were enrolled in the study, of whom 991 patients (59.6%) were retrospectively allocated to the Furosemide group and 672 (40.4%) patients to the non-furosemide group. Univariate and multivariate logistic regression showed that furosemide administration was associated with reduced in-hospital mortality, respectively ((OR 0.77; 95% CI 0.63 to 0.93; p=0.008 < 0.05), (OR 0.59; 95% CI 0.46 to 0.75; p<0.001)). The association remained robust to different ways of adjusting for baseline confounding (all p<0.05). Subgroup analysis suggested that AKI-stage may be a source of heterogeneity. Patients in the furosemide group also had longer RRT-free time (p<0.001) and longer ventilator-free time (p<0.001) than those in the non-furosemide group. CONCLUSIONS: Furosemide is associated with decreased in-hospital mortality, longer RRT-free time and ventilator-free time in patients with SAKI receiving RRT.


Asunto(s)
Lesión Renal Aguda , Sepsis , Adulto , Humanos , Estudios Retrospectivos , Furosemida/uso terapéutico , Terapia de Reemplazo Renal , Cuidados Críticos , Lesión Renal Aguda/etiología , Lesión Renal Aguda/terapia , Unidades de Cuidados Intensivos , Sepsis/complicaciones
16.
Exp Neurol ; 368: 114482, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37467842

RESUMEN

This study is to investigate the function of miR-34a and interactions between miR-34a, SIRT1, and p53 in sevoflurane-induced neuronal apoptosis and autophagy in neonatal mice. A mouse model was established by inhalation anesthesia with sevoflurane and injected with genetic reagents, followed by tests of learning and memory abilities and histological staining of the hippocampus. CCK-8 and AnnexinV/PI staining respectively measured the survival and apoptosis rates of primary hippocampal neurons cultured with sevoflurane. The expression levels of miR-34a, SIRT1, p53, Ac-p53, and autophagy- or apoptosis-related proteins were measured. Sevoflurane impaired the learning and memory abilities of mice, increased TUNEL-positive cells in their hippocampus, and hindered the survival of hippocampal neurons. Sevoflurane increased miR-34a, Bax, cleaved caspase-3, and the ratio of LC3-II/LC3-I and reduced SIRT1 and p62. MiR-34a overexpression promoted sevoflurane-induced neural damage, whereas SIRT1 inhibition or p53 upregulation counteracted the neuroprotection of miR-34a knockdown. SIRT1 was a target of miR-34a and promoted p53 deacetylation. MiR-34a promotes sevoflurane-stimulated neuronal apoptosis and autophagy in neonatal mice by inhibiting SIRT1 expression and subsequent p53 deacetylation.


Asunto(s)
MicroARNs , Sirtuina 1 , Ratones , Animales , Sirtuina 1/genética , Sirtuina 1/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Animales Recién Nacidos , Proteína p53 Supresora de Tumor/genética , Sevoflurano , Apoptosis/genética , Autofagia
17.
Mol Neurobiol ; 60(10): 5533-5547, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37328677

RESUMEN

Optimizing the metabolic phenotype to improve cerebral function is critical for treatment of cerebral ischemia-reperfusion (I/R) injury. Guhong injection (GHI), which comprised safflower extract and aceglutamide, is widely prescribed in Chinese medicine for the treatment of cerebrovascular diseases. In this study, a combination of LC-QQQ-MS and MALDI-MSI were utilized to explore tissue-specific metabolic alterations in the brain of I/R, as well as to evaluate the therapeutic effect of GHI. Pharmacological evaluation demonstrated that GHI can significantly improve infarction rate, neurological deficit, cerebral blood flow, and neuronal damage in I/R rats. Based on LC-QQQ-MS, 23 energy metabolites were found to be significantly altered in the I/R group compared to the sham group (P < 0.05). After GHI treatment, 12 metabolites, including G6P, TPP, NAD, citrate, succinate, malate, ATP, GTP, GDP, ADP, NADP, and FMN showed a significant tendency of returning to baseline values (P < 0.05). Based on MALDI-MSI, 4 metabolites in glycolysis and TCA, 4 metabolites in nucleic acid metabolism, 4 amino acid metabolites, and 6 metabolites were discovered and compared between the different groups in the four special regions of cortex, hippocampus, hypothalamus, and striatum. Parts of these were found to have significant changes after I/R in the special brain region, and were regulated by GHI. The study provides comprehensive and detailed information for specific metabolic reprogramming of brain tissue in rats with I/R, and the therapeutic effect of GHI. Schema describing the discovery strategies of integrated LC-MS and MALDI-MSI to identify cerebral ischemia reperfusion metabolic reprogramming and GHI therapeutic effects.


Asunto(s)
Isquemia Encefálica , Daño por Reperfusión , Ratas , Animales , Ratas Sprague-Dawley , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Infarto Cerebral , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Metabolómica , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Reperfusión
19.
Int J Rheum Dis ; 26(7): 1235-1247, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37309290

RESUMEN

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is the most common pediatric rheumatic disease, thought to be influenced by both genetics and the environment. Identifying environmental factors associated with disease risk will improve knowledge of disease mechanisms and ultimately benefit patients. This review aimed to collate and synthesize the current evidence of environmental factors associated with JIA. METHODS: MEDLINE (Ovid), EMBASE (Ovid), Cumulative Index of Nursing and Related Health Literature (EBSCOhost), science network (WOS, Clarivate Analytics), Chinese National Knowledge Infrastructure, and Chinese Biological Medical Database were systematically searched. Study quality was rated using the Newcastle-Ottawa Scale. Pooled estimates for each environmental factor were generated using a random-effects, inverse-variance method, where possible. The remaining environmental factors were synthesized in narrative form. RESULTS: This review includes environmental factors from 23 studies (6 cohorts and 17 case-control studies). Cesarean section delivery was associated with increased JIA risk (pooled relative risk [RR] 1.103, 95% CI 1.033-1.177). Conversely, maternal smoking of more than 20 cigarettes/day (pooled RR 0.650, 95% CI 0.431-0.981) and gestational smoking (pooled RR0.634, 95% CI 0.452-0.890) were associated with decreased JIA risk. CONCLUSION: This review identifies several environmental factors associated with JIA and demonstrates the huge breadth of environmental research. We also highlight the challenges of combining data collected over this period due to limited study comparability, evolution in healthcare and social practices, and changing environment, which warrant consideration when planning future studies.


Asunto(s)
Artritis Juvenil , Humanos , Niño , Embarazo , Femenino , Artritis Juvenil/diagnóstico , Artritis Juvenil/epidemiología , Artritis Juvenil/complicaciones , Cesárea , Fumar , Calidad de Vida , Estudios de Casos y Controles
20.
Risk Manag Healthc Policy ; 16: 1049-1057, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37337544

RESUMEN

Purpose: In recent years, mental health problems have become the most serious social problems worldwide. Past studies have proposed that some links exist between sunlight and mental health; however, relevant studies examining low-dose sunlight exposure populations are lacking. We conducted a study among a group of operating room nurses (ORNs) who work long hours in operating rooms and have limited sunlight exposure. We aim to add to and refine previous researches on the association between mental health and sunlight exposure in community population. Patients and Methods: A total of 787 ORNs were interviewed and analyzed. Mental health, sunlight exposure duration, sociodemographic and work-related variables, and chronic diseases were evaluated. The Kessler 10 scale (K10) was used to assess participants' mental health status, and their sunlight exposure duration was assessed using their self-reports. Multiple linear regression analysis was adopted to examine the association between sunlight exposure and mental health. Results: The average K10 score of ORNs was 25.41. ORNs exhibit poorer mental health than other populations. Poor mental health was negatively associated with greater sunlight exposure hours per day (ß=-0.378) and sleep regularity (ß=-3.341). Poor mental health was positively associated with chronic disease (ß=3.514). Conclusion: This study indicated that the positive association between sunlight exposure and mental health existed. Appropriate enhancement of sunlight exposure will be beneficial to mental health. Hospitals, related organizations and individuals should pay greater attention to ORNs' mental health and sunlight exposure conditions. More policy recommendations as well as building structure recommendations should be proposed.

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