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1.
Front Med (Lausanne) ; 9: 949520, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091694

RESUMO

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are rare, life-threatening immunologic reactions. Prior studies using electronic health records, registries or reporting databases are often limited in sample size or lack clinical details. We reviewed diverse detailed case reports published over four decades. Methods: Stevens-Johnson syndrome and toxic epidermal necrolysis-related case reports were identified from the MEDLINE database between 1980 and 2020. Each report was classified by severity (i.e., SJS, TEN, or SJS-TEN overlap) after being considered a "probable" or "definite" SJS/TEN case. The demographics, preconditions, culprit agents, clinical course, and mortality of the cases were analyzed across the disease severity. Results: Among 1,059 "probable" or "definite" cases, there were 381 (36.0%) SJS, 602 (56.8%) TEN, and 76 (7.2%) SJS-TEN overlap cases, with a mortality rate of 6.3%, 24.4%, and 21.1%, respectively. Over one-third of cases had immunocompromised conditions preceding onset, including cancer (n = 194,18.3%), autoimmune diseases (n = 97, 9.2%), and human immunodeficiency virus (HIV) (n = 52, 4.9%). During the acute phase of the reaction, 843 (79.5%) cases reported mucous membrane involvement and 210 (19.8%) involved visceral organs. Most cases were drug-induced (n = 957, 90.3%). A total of 379 drug culprits were reported; the most frequently reported drug were antibiotics (n = 285, 26.9%), followed by anticonvulsants (n = 196, 18.5%), analgesics/anesthetics (n = 126, 11.9%), and antineoplastics (n = 120, 11.3%). 127 (12.0%) cases reported non-drug culprits, including infections (n = 68, 6.4%), of which 44 were associated with a mycoplasma pneumoniae infection and radiotherapy (n = 27, 2.5%). Conclusion: An expansive list of potential causative agents were identified from a large set of literature-reported SJS/TEN cases, which warrant future investigation to understand risk factors and clinical manifestations of SJS/TEN in different populations.

2.
Front Pharmacol ; 13: 916421, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091794

RESUMO

Background: Due to limited time windows and technical requirements, only a small percentage of patients can receive reperfusion therapy for acute ischemic stroke (AIS). Previous studies have shown that LongShengZhi (LSZ) capsule can improve neurological outcomes in patients after AIS, yet those results have not been finally verified through rigorous randomized controlled trials. Thus, this trial was designed to further clarify the efficacy and safety of LSZ capsule for patients with AIS. Methods: LSZ capsule on Functional Recovery after Acute Ischemic Stroke (LONGAN) trial is a prospective, multicenter, randomized, placebo-controlled, double-blind, parallel-group, superiority trial that enrolls patients from stroke and rehabilitation units in China. We will enroll 1,376 patients aged 18 years or older with AIS within 7 days of symptom onset and a National Institute of Health Stroke Scale (NIHSS) score of 4-15. Eligible patients will be randomized to receive either 2 g LSZ capsules three times a day or placebo LSZ capsules for 90 days. The primary outcome is the proportion of patients with favorable outcomes, as measured by the modified Rankin Scale (mRS) 90 days after randomization. The main safety outcome is the proportion of severe adverse events. Conclusion: This study will be the first randomized, double-blind trial to evaluate the efficacy and safety of LSZ capsule in patients with AIS. In order to improve the transparency and reproducibility of the trial, the data will be analyzed in accordance with this pre-specified plan for statistical analysis to reduce bias due to selective analysis and reporting. This trial aims to provide high-quality evidence for the efficacy and safety of LSZ capsule for AIS.

3.
Front Pharmacol ; 13: 893244, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091836

RESUMO

Yuan-Zhi Decoction (YZD) is a traditional Chinese medical formulation with demonstrated clinical benefits in Alzheimer's disease (AD). We used liquid chromatography coupled with mass spectrometry to identify 27 unique chemical components of YZD. Analyzing these using network pharmacology and molecular docking models identified 34 potential interacting molecular targets involved in 26 biochemical pathways. When tested in an animal model of AD, the APP/PS1 transgenic mice showed measurable improvements in spatial orientation and memory after the administration of YZD. These improvements coincided with significantly reduced deposition of Aß plaques and tau protein in the hippocampi in the treated animals. In addition, a decreased BACE1 and beta-amyloid levels, a downregulation of the p-GSK-3ß/GSK-3ß, and an upregulation of the PI3K and p-AKT/AKT pathway was seen in YZD treated animals. These in vivo changes validated the involvement of molecular targets and pathways predicted in silico analysis of the chemical components of YZD. This study provides scientific support for the clinical use of YZD and justifies further investigations into its effects in AD. Furthermore, it demonstrates the utility of network pharmacology in elucidating the biochemical mechanisms underlying the beneficial effects of traditional Chinese medicines (TCM).

4.
Front Genet ; 13: 918858, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092908

RESUMO

Hidradenitis suppurativa (HS) is a multifactorial chronic skin disease characterized by inflammation around the hair follicles commonly affecting intertriginous areas. The underlying pathogenesis of HS and its molecular mechanisms are largely understudied. Genetic studies in families have identified variants within the γ-secretase complex associated with HS; however, no definitive genotype-phenotype correlations have been made. The lack of knowledge regarding the intersection of genetics, immunology and environmental risk factors is a major obstacle to improving treatment for patients with HS. This article provides an overview of the role of race, genetics, and immunology in HS to provide insight into the multiple factors influencing the pathophysiology of HS.

5.
Front Pharmacol ; 13: 971715, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147319

RESUMO

Background: Psoriasis represents the chronic, recurrent and inflammatory disorder. The Traditional Chinese Medicine Xiyanping injection (XYP) is extensively applied in China for treating diverse inflammatory disorders, such as bronchitis, viral pneumonia or upper respiratory tract infection. XYP may offer a potential treatment for psoriasis vulgaris (PV). This study focused on analyzing whether XYP combined with acitretin was effective and safe. Methods: The present meta-analysis was carried out in line with guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). This systematic review was registered in PROSPERO (CRD42022333273). Besides, relevant randomized controlled trials (RCTs) that compared XYP plus acitretin with acitretin alone for treating PV were searched from several databases from their inception till May 2022. In addition, this work utilized RevMan5.4 to conduct risk assessment as well as meta-analysis. Results: This meta-analysis selected altogether 10 RCTs including 815 subjects. Upon quality assessment, the RCTs mainly had low or unclear risk. According to our meta-analysis results, relative to acitretin monotherapy, XYP plus acitretin increased the total clinical effective rate, as evidenced by Psoriasis area and severity index score (PASI)-20, PASI-30 and PASI-60 in patients with PV [risk ratio (RR) = 1.23 Z = 4.87, p < 0.00001, 95% confidence interval (CI): 1.13-1.34; RR = 1.29, Z = 3.89, p = 0.009, 95% CI: 1.07 to 1.55; and RR = 1.31, Z = 3.89, p = 0.0001, 95% CI: 1.14-1.49]; the reduced levels of TNF-α, MCP-1 and RANTES, the alleviated side effects resulting from acitretin like itchiness (RR = 0.54, 95% CI: 0.4 to 0.74, Z = 3.94, p < 0.0001), and the increased levels of aminotransferases and dyslipidemia (RR = 0.5, 95%CI = 0.29, 0.86, p = 0.01; and RR = 0.41, 95% CI = 0.23, 0.75, p = 0.004). Conclusion: As suggested in the present meta-analysis, XYP combined with acitretin effectively and safely treats PV. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022333273, identifier PROSPERO 2022 CRD42022333273.

6.
iScience ; 25(10): 105065, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36147955

RESUMO

Cytomegalovirus (CMV) infection remains one of the most frequent and life-threatening infectious complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Herein, we comprehensively compared the immune cells of patients with uncontrolled and controlled CMV infection post-allo-HSCT and found that B-cells were extraordinarily insufficient because of impaired B-cells reconstitution in the uncontrolled infection group. Furthermore, in the controlled infection group, reconstructed B-cells showed signatures of mature B-cells, high expression of CXCR4 and IFITM1, and enrichment of CMV-associated B-cell receptors, which were lacking in the uncontrolled infection group. Consistently, sera from the uncontrolled infection group failed to inhibit CMV infection via neutralizing virus in vitro because of its lower content of anti-CMV-specific immunoglobulin G (IgG) than the controlled infection group. Overall, these results highlighted the contribution of B cells and anti-CMV-specific neutralizing IgGs to the restraint of CMV infection post-allo-HSCT, suggesting their potential as a supplementary treatment to improve outcomes.

7.
Front Psychiatry ; 13: 1005748, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147986

RESUMO

Objectives: Children with autism spectrum disorder (ASD) can exhibit persistent deficits in social communication, causing their mothers to experience elevated parenting stress during the childrearing process. Some internal and external psychosocial resources may mediate or moderate the mother-child relationship, though the underlying mechanisms remain unclear. This study aimed to explore the predictors of parenting stress in mothers of children with ASD and elucidate the mechanisms underlying the relationship between child social impairment and parenting stress. Methods: A cross-sectional study was conducted between October 2020 and March 2022 in Shanghai, China. Mothers of children with ASD completed a survey investigating child social impairment, parenting stress, parental self-efficacy, and social support. Results: A total of 185 mothers of children with ASD were included in the final analysis. 70.27 percent of mothers experienced a clinically significant level of parenting stress. Child social impairment (r = 0.46, P < 0.001), parental self-efficacy (r = -0.58, P < 0.001), and social support (r = -0.35, P < 0.001) were significantly correlated with parenting stress. Parental self-efficacy completely mediated the relationship between child social impairment and parenting stress (B = 0.51, P < 0.001), after controlling for socioeconomic status (SES) correlated with parenting stress. There was no significant moderating effect of social support between child social impairment and parenting stress (B = 0.01, P = 0.09). Conclusion: Future early intervention programs that focused on child's social communication skills and empowered mothers with related strategies through group-based parent training programs may help reduce parenting stress.

8.
J Hematol Oncol ; 15(1): 132, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36096856

RESUMO

Poor targeting of therapeutics leading to severe adverse effects on normal tissues is considered one of the obstacles in cancer therapy. To help overcome this, nanoscale drug delivery systems have provided an alternative avenue for improving the therapeutic potential of various agents and bioactive molecules through the enhanced permeability and retention (EPR) effect. Nanosystems with cancer-targeted ligands can achieve effective delivery to the tumor cells utilizing cell surface-specific receptors, the tumor vasculature and antigens with high accuracy and affinity. Additionally, stimuli-responsive nanoplatforms have also been considered as a promising and effective targeting strategy against tumors, as these nanoplatforms maintain their stealth feature under normal conditions, but upon homing in on cancerous lesions or their microenvironment, are responsive and release their cargoes. In this review, we comprehensively summarize the field of active targeting drug delivery systems and a number of stimuli-responsive release studies in the context of emerging nanoplatform development, and also discuss how this knowledge can contribute to further improvements in clinical practice.


Assuntos
Nanopartículas , Neoplasias , Sistemas de Liberação de Medicamentos , Humanos , Ligantes , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Microambiente Tumoral
9.
FASEB Bioadv ; 4(9): 619-631, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36089980

RESUMO

Lung endothelial permeability is a key pathological feature of acute respiratory distress syndrome. Hyaluronic acid (HA), a major component of the glycocalyx layer on the endothelium, is generated by HA synthase (HAS) during inflammation and injury and is critical for repair. We hypothesized that administration of exogenous high molecular weight (HMW) HA would restore protein permeability across human lung microvascular endothelial cells (HLMVEC) injured by an inflammatory insult via upregulation of HAS by binding to CD44. A transwell coculture system was used to study the effects of HA on protein permeability across HLMVEC injured by cytomix, a mixture of IL-1ß, TNFα, and IFNγ, with or without HMW or low molecular weight (LMW) HA. Coincubation with HMW HA, but not LMW HA, improved protein permeability following injury at 24 h. Fluorescence microscopy demonstrated that exogenous HMW HA partially prevented the increase in "actin stress fiber" formation. HMW HA also increased the synthesis of HAS2 mRNA expression and intracellular HMW HA levels in HLMVEC following injury. Pretreatment with an anti-CD44 antibody or 4-methylumbelliferone, a HAS inhibitor, blocked the therapeutic effects. In conclusion, exogenous HMW HA restored protein permeability across HLMVEC injured by an inflammatory insult in part through upregulation of HAS2.

10.
JAMA Netw Open ; 5(9): e2234194, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36173627

RESUMO

Importance: Health care systems focus on delivering routine cancer screening to eligible individuals, yet little is known about the perceptions of primary care practitioners (PCPs) about barriers to timely follow-up of abnormal results. Objective: To describe PCP perceptions about factors associated with the follow-up of abnormal breast, cervical, colorectal, and lung cancer screening test results. Design, Setting, and Participants: Survey study of PCPs from 3 primary care practice networks in New England between February and October 2020, prior to participating in a randomized clinical trial to improve follow-up of abnormal cancer screening test results. Participants were physicians and advanced practice clinicians from participating practices. Main Outcomes and Measures: Self-reported process, attitudes, knowledge, and satisfaction about the follow-up of abnormal cancer screening test results. Results: Overall, 275 (56.7%) PCPs completed the survey (range by site, 34.9%-71.9%) with more female PCPs (61.8% [170 of 275]) and general internists (73.1% [201 of 275]); overall, 28,7% (79 of 275) were aged 40 to 49 years. Most PCPs felt responsible for managing abnormal cancer screening test results with the specific cancer type being the best factor (range, 63.6% [175 of 275] for breast to 81.1% [223 of 275] for lung; P < .001). The PCPs reported limited support for following up on overdue abnormal cancer screening test results. Standard processes such as automated reports, reminder letters, or outreach workers were infrequently reported. Major barriers to follow-up of abnormal cancer screening test results across all cancer types included limited electronic health record tools (range, 28.5% [75 of 263]-36.5%[96 of 263]), whereas 50% of PCPs felt that there were major social barriers to receiving care for abnormal cancer screening test results for colorectal cancer. Fewer than half reported being very satisfied with the process of managing abnormal cancer screening test results, with satisfaction being greatest for breast cancer (46.9% [127 of 271]) and lowest for cervical (21.8% [59 of 271]) and lung cancer (22.4% [60 of 268]). Conclusions and Relevance: In this survey study of PCPs, important deficiencies in systems for managing abnormal cancer screening test results were reported. These findings suggest a need for comprehensive organ-agnostic systems to promote timely follow-up of abnormal cancer screening results using a primary care-focused approach across the range of cancer screening tests.

11.
Artigo em Inglês | MEDLINE | ID: mdl-36179787

RESUMO

OBJECTIVE: Central venous occlusion (CVO) refractory to endovascular angioplasty is a critical challenge threatening hemodialysis vascular access. The present study aimed to evaluate the efficacy and safety of tunnelled cuffed central venous catheter (tCVC) placement via percutaneous superior vena cava (SVC) puncture in patients with refractory CVO. METHODS: Maintenance hemodialysis patients with refractory CVO who received percutaneous puncture of SVC and tCVC insertion in a university-affiliated hospital from January 2016 to June 2020 were included. The patients were followed-up until May 2021. Demographic information, complications, and catheter patency were analyzed. RESULTS: A total of 205 patients were included. There were 105 females (51.2%), and the mean age was 61±15 years old. SVC puncture and tCVC insertion were successfully performed in 194 patients, achieving a technical success rate of 94.6%. A patient unfortunately encountered pleura injury and hemothorax who required urgent thoracotomy. Thirty-seven patients presented with mild chest pain and were prescribed oral NSAIDs. During the follow-up of those 194 patients with a successful procedure, catheter dysfunction due to thrombosis occurred in 66 patients, while 5 patients suffered from catheter malposition and 6 patients encountered catheter related-blood stream infection. The 3-year primary patency rate was 64.2%, and the 3-year secondary patency rate was 76.3%. CONCLUSIONS: TCVC placed through percutaneous SVC puncture had a satisfactory technical success rate and long-term patency rate in hemodialysis patients, providing optional vascular access for those with exhausted central vein resources. SVC puncture also avoided left-sided catheters and preserved central vein resources. Caution should be paid to avoid potential complications such as pleura injury and hemothorax.

12.
Clin Chim Acta ; 536: 86-93, 2022 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-36150521

RESUMO

Chronic inflammation caused by immune cells and their mediators is a characteristic of atherosclerosis. Interleukin-38 (IL-38), a member of the IL-1 family, exerts multiple anti-inflammatory effects via specific ligand-receptor interactions. Upon recognizing a specific receptor, IL-38 restrains mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NK-κB), or other inflammation-related signaling pathways in inflammatory disease. Further research has shown that IL-38 also displays anti-atherosclerotic effects and reduces the occurrence and risk of cardiovascular events. On the one hand, IL-38 can regulate innate and adaptive immunity to inhibit inflammation, reduce pathological neovascularization, and inhibit apoptosis. On the other hand, it can curb obesity, reduce hyperlipidemia, and restrain insulin resistance to reduce cardiovascular disease risk. Therefore, this article expounds on the vital function of IL-38 in the development of atherosclerosis to provide a theoretical basis for further in-depth studies of IL-38 and insights on the prophylaxis and treatment of atherosclerosis.

13.
Artigo em Inglês | MEDLINE | ID: mdl-36057059

RESUMO

Active and passive exposure to tobacco smoke may increase risk of cognitive decline. However, effects of enhanced the aging process on the association of urinary nicotine metabolites with cognitive impairment remain unclear. In this study, 6657 Chinese older adults completed the physical examinations and cognitive tests. We measured urinary nicotine metabolite levels, mitochondrial DNA copy number (mtDNA-CN), and relative telomere length (RTL) and analyzed effects of urinary nicotine metabolites and their interaction with mtDNA-CN or RTL on cognitive impairment by generalized linear models and qg-computation, respectively. Each 1-unit increase in urinary 3-OHCot, 3-OHCotGluc, CotGluc, or NicGluc levels corresponded to a 1.05-, 1.09-, 1.04-, and 0.90-fold increased risk of cognitive impairment. Each 1-quantile increment in the mixture level of 8 nicotine metabolites corresponded to an increment of 1.40- and 1.34-fold risk of cognitive impairment in individuals with longer RTL or low mtDNA-CN. Urinary 3-OHCotGluc and RTL or mtDNA-CN exhibited an additive effect on cognitive impairment in addition to the mixture of 8 nicotine metabolites and mtDNA-CN. The findings suggested that aging process may increase the risk of tobacco-related cognitive impairment.

14.
Aging (Albany NY) ; 14(undefined)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36057263

RESUMO

BACKGROUND: Colon adenocarcinoma (COAD) is a highly heterogeneous disease, which is the second most common cancer in females and third in males. Collagen type I alpha 2 (COL1A2) has been documented to be involved in the carcinogenesis of multiple tumors; however, the expression and prognostic significance of COL1A2 and its underlying mechanism in COAD remains unclarified. MATERIALS AND METHODS: The general profile of COL1A2, its expression pattern, and prognostic value were systematically assessed through various bioinformatics tools. The protein level of COL1A2 was verified in COAD patients using immunohistochemistry analysis. In addition, enrichment analyses were performed to explore the possible regulatory pathways of COL1A2 in COAD. RESULTS: The mRNA and protein levels of COL1A2 were significantly increased in COAD than that in normal tissues (P < 0.05). The COL1A2 expression tended to increase along with cancer stages and nodal metastasis status in COAD, while the promoter methylation levels of COL1A2 might negatively related to its mRNA expression. Survival analysis showed that COL1A2 was a reliable predictor for distinguishing the status of disease-specific survival (DSS), overall survival (OS), and progression-free survival (PFS), and might serve as a robust independent prognostic biomarker for DSS and OS in COAD patients (P < 0.05). The enrichment analysis showed focal adhesion as the most possible regulatory pathway by COL1A2. CONCLUSION: Collectively, COL1A2 functioned as an independent prognostic biomarker and might be a potential therapeutic target in COAD.

15.
Cell Discov ; 8(1): 89, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085197

RESUMO

Infection of human peripheral blood cells by SARS-CoV-2 has been debated because immune cells lack mRNA expression of both angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease type 2 (TMPRSS2). Herein we demonstrate that resting primary monocytes harbor abundant cytoplasmic ACE2 and TMPRSS2 protein and that circulating exosomes contain significant ACE2 protein. Upon ex vivo TLR4/7/8 stimulation, cytoplasmic ACE2 was quickly translocated to the monocyte cell surface independently of ACE2 transcription, while TMPRSS2 surface translocation occurred in conjunction with elevated mRNA expression. The rapid translocation of ACE2 to the monocyte cell surface was blocked by the endosomal trafficking inhibitor endosidin 2, suggesting that endosomal ACE2 could be derived from circulating ACE2-containing exosomes. TLR-stimulated monocytes concurrently expressing ACE2 and TMPRSS2 on the cell surface were efficiently infected by SARS-CoV-2, which was significantly mitigated by remdesivir, TMPRSS2 inhibitor camostat, and anti-ACE2 antibody. Mass cytometry showed that ACE2 surface translocation in peripheral myeloid cells from patients with severe COVID-19 correlated with its hyperactivation and PD-L1 expression. Collectively, TLR4/7/8-induced ACE2 translocation with TMPRSS2 expression makes circulating monocytes permissive to SARS-CoV-2 infection.

16.
Dis Markers ; 2022: 1664474, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046373

RESUMO

Background: Increasing evidence reveals that iron deficiency during pregnancy causes adverse pregnancy outcomes. Thus far, the mechanisms underlying iron deficiency-associated preterm birth are mostly limited to animal studies. Whether the suggested mechanisms exist in human requires further investigation. The goal of this study was to characterize the iron metabolism in both the maternal side and fetal side in pregnant women with preterm birth. Methods: Serum and placenta samples were collected from 42 pregnant women divided into four groups according to the gestational week. Indicators of iron metabolism, including serum iron, serum hepcidin, placental tissue iron, ferroportin (FPN), transferrin receptor 1 (TfR1), and ferritin, were surveyed using enzyme-linked immunosorbent assays (Elisa), Western blots, and real-time quantitative polymerase chain reactions (qRT-PCR). Results: Significant reduction of maternal serum iron was observed in women with preterm birth relative to those with full-term birth, indicative of worsen iron deficiency in those mothers with preterm birth. Meanwhile, the maternal hepcidin levels were notably diminished in women with preterm birth, whereas the fetal hepcidin levels were comparable between the two groups. Moreover, the placental iron stores were remarkably reduced in the preterm group, associated with reduced concentration of TfR1 and increased FPN concentration relative to the normal controls. In other words, the ratio of placental FPN mass to TfR1 mass (PIDI index) was strikingly increased in the preterm group. Conclusions: Dysregulated iron homeostasis in both the maternal and fetal sides was implicated in preterm births, and disordered regulations in maintaining the placental iron equilibrium were also presumed to account for the compromised fetal iron supply.


Assuntos
Deficiências de Ferro , Nascimento Prematuro , Feminino , Feto/metabolismo , Hepcidinas , Humanos , Recém-Nascido , Ferro , Placenta/metabolismo , Gravidez , Nascimento Prematuro/metabolismo
17.
Sci Rep ; 12(1): 15166, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071136

RESUMO

Estrogen can promote the acceleration of bone maturation and phthalate esters (PAEs) have estrogen-mimicking effects. We investigated whether PAEs are associated with the acceleration of bone age (BA) in girls with early onset of puberty (EOP). This case-control study enrolled 254 girls with EOP from the Endocrinology Department at Shenzhen Children's Hospital between December 2018 and August 2019. Ultra-performance liquid chromatography and tandem mass spectrometry were used to analyze the 10 metabolites of PAEs (mPAEs) in urine samples. BA was measured using an artificial intelligence system. BA exceeding the chronological age (CA) by > 2 years (BA-CA ≥ 2 years) was referred to as significant BA advancement. Participants were divided into groups A (BA-CA ≥ 2 years; case group) and B (BA-CA < 2 years; control group). Propensity score matching (PSM) was performed for both groups in a 1:2 ratio with a caliper of 0.25. To identify potential dose-response relationships between PAEs exposure and BA advancement, we grouped the participants after PSM according to the tertiles of the mPAE concentrations. After PSM, 31 and 62 girls in groups A and B were selected. The concentration of Mono-ethyl phthalate (MEP) in group A was significantly higher than in group B (11.83 µg/g vs. 7.11 µg/g, P < 0.05); there was no significant difference in the levels of other mPAEs between the groups. The degree of BA advancement and proportion of significantly advanced BA in the lowest, middle, and highest tertiles of the MEP sequentially increased, as well as in the lowest, middle, and highest tertiles of Mono-(2-ethyl-5-carboxypentyl) phthalate; however, these were only statistically different between the highest and lowest MEP tertiles (both P < 0.05). For the remaining mPAEs, differences in the degree of BA advancement among the lowest, middle, and highest tertiles, as well as differences in the proportion of significantly advanced BA among the lowest, middle, and highest tertiles, were not significant (all P > 0.05). Our findings suggested that MEP was positively associated with BA advancement in girls with EOP. Exposure to PAEs may promote accelerated bone maturation.


Assuntos
Inteligência Artificial , Puberdade Precoce , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Ésteres , Estrogênios , Feminino , Humanos , Ácidos Ftálicos , Pontuação de Propensão , Puberdade
18.
Mediators Inflamm ; 2022: 7006281, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36052309

RESUMO

The endothelial dysfunction, associated with inflammation and vascular permeability, remains the key event in the pathogenesis of cerebral ischemic stroke. Angiogenesis is essential for neuroprotection and neural repair following stroke. The neuroinflammatory reaction plays a vital role in stroke, and inhibition of inflammation contributes to establishing an appropriate external environment for angiogenesis. Exosomes are the heterogeneous population of extracellular vesicles which play critical roles in intercellular communication through transmitting various proteins and nucleic acids to nearby and distant recipient cells by body fluids and circulation. Recent reports have shown that exosomal therapy is a valuable and potential treatment strategy for stroke. In this review, we discussed the exosomes in complex interaction mechanisms of angiogenesis and inflammation following stroke as well as the challenges of exosomal studies such as secretion, uptake, modification, and application.


Assuntos
Exossomos , Acidente Vascular Cerebral , Comunicação Celular , Exossomos/metabolismo , Humanos , Inflamação/metabolismo , Neovascularização Patológica/metabolismo , Acidente Vascular Cerebral/metabolismo
19.
Food Chem ; 401: 134084, 2022 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-36115225

RESUMO

Enzyme labeled competitive molecules are generally homologous with competitors in competitive broad-spectrum enzyme-linked immunosorbent assays (ELISA). It is speculated that the detectability will be improved when the competitiveness of competitive molecule is weak. Herein, common small molecule food hazard-estrogen disrupting chemicals (EDCs) were used as target model for verification. The dual-estrogen receptor (ER) and three estrogen-enzyme conjugates with various responses were used as recognizers and competitive molecules in ELISA. ELISA based on bisphenol (BPA)-horseradish peroxidase (HRP) has the highest detectability and can screen all six EDCs, in which BPA-HRP showed the weakest ER excitatory activity (Ka = 1.39 × 10-2 nmol·L-1) among three conjugates. The proposal showed good practicability with spiked recovery of 80.0-110 % for estrogens (17ß-estradiol, 17α-estradiol, BPA) in foodstuffs, and revealed biomarkers with weak competitiveness may be applied to other competitive procedures to improve detectability, and it provides sensitive pre-screening strategy for follow-up screening tool.

20.
Huan Jing Ke Xue ; 43(9): 4697-4705, 2022 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-36096610

RESUMO

Microplastics are widely distributed in the biogeochemical cycle driven by microbes. Their surface is enriched with unique microbial communities, called plastispheres. Various redox environments that exist widely in the natural environment can affect the microbial composition in the plastisphere and the fate of the microplastics. To explore the microbial community composition and construction mechanism on the surface of microplastics in typical redox environments, three microplastics, PHA (polyhydroxyalkanoates), PLA (polylactic acid), and PVC (polyvinyl chloride), were placed in five specific redox environments:aerobic, nitrate reduction, iron oxide reduction, sulfate reduction, and methane production. The culture experiment simulated the microcosm, which was inoculum by sludge. The results showed that microplastic factors affected 18.94% and 46.67% of the microbial communities on the plastisphere in taxonomy and phylogeny, respectively. Redox factors affected 31.04% and 90.00% of the microbial communities on the plastisphere in taxonomy and phylogeny, respectively. Compared with that in sludge, the microbial community richness and diversity were reduced on the three microplastics. The most apparent reduction was found on the plastisphere of more degradable PHA. At the same time, microbial communities on the refractory PLA and PVC surfaces remained similar. Anaerocolumna (26.44%) was the dominant genus on the surface of PHA microplastics, whereas microbes related to the redox reaction were less enriched. Clostridium_sensu_stricto_7 (15.49% and 11.87%) was the dominant strain on PLA and PVC microplastics, and the microbes related to the redox reaction were significantly enriched. Thus, characteristic microbes involved in the redox reaction will be enriched in the surface of refractory microplastics, and microplastics may affect the rate of biogeochemical cycling.


Assuntos
Microbiota , Microplásticos , Oxirredução , Plásticos , Poliésteres , Cloreto de Polivinila , Esgotos
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