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1.
Environ Geochem Health ; 46(5): 173, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592592

RESUMO

Nitrate pollution in aquatic ecosystems has received growing concern, particularly in fragile karst basins. In this study, hydrochemical compositions, multiple stable isotopes (δ2H-H2O, δ18Ο-Η2Ο, δ15Ν-ΝΟ3-, and δ18Ο-ΝΟ3-), and Bayesian stable isotope mixing model (MixSIAR) were applied to elucidate nitrate pollution sources in groundwater of the Yangzhuang Basin. The Durov diagram identified the dominant groundwater chemical face as Ca-HCO3 type. The NO3- concentration ranged from 10.89 to 90.45 mg/L (average 47.34 mg/L), showing an increasing trend from the upstream forest and grassland to the downstream agricultural dominant area. It is worth noting that 47.2% of groundwater samples exceeded the NO3- threshold value of 50 mg/L for drinking water recommended by the World Health Organization. The relationship between NO3-/Cl- and Cl- ratios suggested that most groundwater samples were located in nitrate mixed endmember from agricultural input, soil organic nitrogen, and manure & sewage. The Self-Organizing Map (SOM) and Pearson correlations analysis further indicated that the application of calcium fertilizer, sodium fertilizer, and livestock and poultry excrement in farmland elevated NO3- level in groundwater. The output results of the MixSIAR model showed that the primary sources of NO3- in groundwater were soil organic nitrogen (55.3%), followed by chemical fertilizers (28.5%), sewage & manure (12.7%), and atmospheric deposition (3.4%). Microbial nitrification was a dominant nitrogen conversion pathway elevating NO3- levels in groundwater, while the denitrification can be neglectable across the study area. The human health risk assessment (HHRA) model identified that about 88.9%, 77.8%, 72.2%, and 50.0% of groundwater samples posing nitrate's non-carcinogenic health hazards (HQ > 1) through oral intake for infants, children, females, and males, respectively. The findings of this study can offer useful biogeochemical information on nitrogen pollution in karst groundwater to support sustainable groundwater management in similar human-affected karst regions.


Assuntos
Água Subterrânea , Nitratos , Criança , Feminino , Lactente , Masculino , Humanos , Teorema de Bayes , Ecossistema , Fertilizantes , Esterco , Esgotos , China , Isótopos , Nitrogênio , Solo
2.
Nat Aging ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594460

RESUMO

Limited understanding exists regarding how aging impacts the cellular and molecular aspects of the human ovary. This study combines single-cell RNA sequencing and spatial transcriptomics to systematically characterize human ovarian aging. Spatiotemporal molecular signatures of the eight types of ovarian cells during aging are observed. An analysis of age-associated changes in gene expression reveals that DNA damage response may be a key biological pathway in oocyte aging. Three granulosa cells subtypes and five theca and stromal cells subtypes, as well as their spatiotemporal transcriptomics changes during aging, are identified. FOXP1 emerges as a regulator of ovarian aging, declining with age and inhibiting CDKN1A transcription. Silencing FOXP1 results in premature ovarian insufficiency in mice. These findings offer a comprehensive understanding of spatiotemporal variability in human ovarian aging, aiding the prioritization of potential diagnostic biomarkers and therapeutic strategies.

3.
Chem Biol Drug Des ; 103(4): e14520, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38570710

RESUMO

Quercetin, a bioactive natural compound renowned for its potent anti-inflammatory, antioxidant, and antiviral properties, has exhibited therapeutic potential in various diseases. Given that bronchopulmonary dysplasia (BPD) development is closely linked to inflammation and oxidative stress, and quercetin, a robust antioxidant known to activate NRF2 and influence the ferroptosis pathway, offers promise for a wide range of age groups. Nonetheless, the specific role of quercetin in BPD remains largely unexplored. This study aims to uncover the target role of quercetin in BPD through a combination of network pharmacology, molecular docking, computer analyses, and experimental evaluations.


Assuntos
Displasia Broncopulmonar , Ferroptose , Hiperóxia , Animais , Recém-Nascido , Humanos , Displasia Broncopulmonar/tratamento farmacológico , Displasia Broncopulmonar/metabolismo , Hiperóxia/tratamento farmacológico , Hiperóxia/metabolismo , Quercetina/farmacologia , Quercetina/uso terapêutico , Simulação de Acoplamento Molecular , Ciclo-Oxigenase 2 , Animais Recém-Nascidos , Antioxidantes , Farmacologia em Rede
5.
Appl Opt ; 63(9): 2156-2166, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38568567

RESUMO

Free space optical (FSO) communication systems experience turbulence-induced fading. As a possible solution, adaptive transmission, which adjusts transmitter parameters based on instantaneous channel state information (CSI), can be used. Most of the existing channel estimation methods ignore the impact of detection noise at the receiver, which will lead to additional estimation errors. In this paper, a joint estimation model based on convolutional neural networks (CNNs) is proposed to estimate detection noise and turbulence fading parameters. We obtained turbulence channel simulation data sets considering the background of detection noise based on the edge probability distribution function of the receive signal. The training of the CNN estimator is carried out through maximum pooling, adaptive learning rate, and regularization, ultimately accurately estimating channel characteristics based on the optimal output results of the network. The simulation results show that the proposed CNN joint estimator performs better in high-detection-noise environments compared with traditional maximum likelihood estimators, and it has better generalization ability in different real atmospheric environments.

6.
EPMA J ; 15(1): 53-66, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38463627

RESUMO

Background/aims: The reciprocal promotion of cancer and stroke occurs due to changes in shared risk factors, such as metabolic pathways and molecular targets, creating a "vicious cycle." Cancer plays a direct or indirect role in the pathogenesis of ischemic stroke (IS), along with the reactive medical approach used in the treatment and clinical management of IS patients, resulting in clinical challenges associated with occult cancer in these patients. The lack of reliable and simple tools hinders the effectiveness of the predictive, preventive, and personalized medicine (PPPM/3PM) approach. Therefore, we conducted a multicenter study that focused on multiparametric analysis to facilitate early diagnosis of occult cancer and personalized treatment for stroke associated with cancer. Methods: Admission routine clinical examination indicators of IS patients were retrospectively collated from the electronic medical records. The training dataset comprised 136 IS patients with concurrent cancer, matched at a 1:1 ratio with a control group. The risk of occult cancer in IS patients was assessed through logistic regression and five alternative machine-learning models. Subsequently, select the model with the highest predictive efficacy to create a nomogram, which is a quantitative tool for predicting diagnosis in clinical practice. Internal validation employed a ten-fold cross-validation, while external validation involved 239 IS patients from six centers. Validation encompassed receiver operating characteristic (ROC) curves, calibration curves, decision curve analysis (DCA), and comparison with models from prior research. Results: The ultimate prediction model was based on logistic regression and incorporated the following variables: regions of ischemic lesions, multiple vascular territories, hypertension, D-dimer, fibrinogen (FIB), and hemoglobin (Hb). The area under the ROC curve (AUC) for the nomogram was 0.871 in the training dataset and 0.834 in the external test dataset. Both calibration curves and DCA underscored the nomogram's strong performance. Conclusions: The nomogram enables early occult cancer diagnosis in hospitalized IS patients and helps to accurately identify the cause of IS, while the promotion of IS stratification makes personalized treatment feasible. The online nomogram based on routine clinical examination indicators of IS patients offered a cost-effective platform for secondary care in the framework of PPPM. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00354-8.

7.
Am J Cancer Res ; 14(2): 507-525, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455419

RESUMO

Arsenic trioxide (ATO) is well known for its inhibitory effects on cancer progression, including lung adenocarcinoma (LUAD), but the molecular mechanism remains elusive. This study aimed to investigate the roles of ATO in regulating LUAD stem cells (LASCs) and the underlying mechanisms. To induce LASCs, cells cultured in an F12 medium, containing B27, epidermal growth factor, and basic fibroblast growth factor, induced LASCs. LASCs stemness was assessed through tumor sphere formation assay, and percentages of CD133+ cells were detected by flow cytometry. The Cell Counting Kit-8 method was used to assess LASCs viability, while reactive oxygen species (ROS) and iron ion levels were quantitated by fluorescence microscopy and spectrophotometry, respectively, and total m6A levels were measured by dot blot. Additionally, LASCs mitochondrial alterations were analyzed via transmission electron microscopy. Finally, the tumorigenicity of LASCs was assessed using a cancer cell line-based xenograft model. Tumor sphere formation and CD133 expression were used to validate the successful induction of LASCs from A549 and NCI-H1975 cells. ATO significantly inhibited proliferation, reduced ZC3H13 expression and total m6A modification levels, and increased ROS and iron ion content, but repressed sphere formation and CD133 expression in LASCs. ZC3H13 overexpression or ferrostatin-1 treatment abrogated LASCs stemness inhibition caused by ATO treatment, and interference with ZC3H13 inhibited LASCs stemness. Furthermore, the promotion of LASCs ferroptosis by ATO was effectively mitigated by ZC3H13 overexpression, while interference with ZC3H13 further promoted ferroptosis. Moreover, si-ZC3H13 promoted ferroptosis and impaired stemness in LASCs, which ferrostatin-1 abrogated. Finally, ZC3H13 overexpression alleviated the inhibitory effects of ATO on LASCs tumorigenicity. Taken together, ATO treatment substantially impaired the stemness of LUAD stem cells by promoting the ferroptosis program, which was mediated by its ZC3H13 gene expression inhibition to suppress m6A medication.

8.
Clin Kidney J ; 17(3): sfae037, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38455522

RESUMO

Background: Disruptions in gene expression associated with the glomerular basement membrane (GBM) could precipitate glomerular dysfunction. Nevertheless, a comprehensive understanding of the characterization of GBM components within pediatric glomerular diseases and their potential association with glomerular function necessitates further systematic investigation. Methods: We conducted a systematic analysis focusing on the pathological transformations and molecular attributes of key constituents within the GBM, specifically Collagen IV α3α4α5, Laminin α5ß2γ1, and Integrin α3ß1, across prevalent pediatric glomerular diseases. Results: We observed upregulation of linear expression levels of COL4A3/4/5 and Laminin 5α proteins, along with a partial reduction in the linear structural expression of Podocin in idiopathic nephrotic syndrome (INS), encompassing minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS), but showing a reduction in IgA nephropathy (IgAN), IgA vasculitis nephritis (IgAVN) and lupus nephritis (LN). Furthermore, our study revealed reductions in Laminin ß2γ1 and Integrin α3ß1 in both primary and secondary childhood glomerular diseases. Conclusion: In INS, notably MCD and FSGS, there is a notable increase in the linear expression levels of COL4A3/4/5 and Laminin 5α proteins. In contrast, in IgAN, IgAVN, and LN, there is a consistent reduction in the expression of these markers. Furthermore, the persistent reduction of Laminin ß2γ1 and Integrin α3ß1 in both primary and secondary childhood glomerular diseases suggests a shared characteristic of structural alterations within the GBM across these conditions.

9.
Sensors (Basel) ; 24(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38475171

RESUMO

Wood surface broken defects seriously damage the structure of wooden products, these defects have to be detected and eliminated. However, current defect detection methods based on machine vision have difficulty distinguishing the interference, similar to the broken defects, such as stains and mineral lines, and can result in frequent false detections. To address this issue, a multi-source data fusion network based on U-Net is proposed for wood broken defect detection, combining image and depth data, to suppress the interference and achieve complete segmentation of the defects. To efficiently extract various semantic information of defects, an improved ResNet34 is designed to, respectively, generate multi-level features of the image and depth data, in which the depthwise separable convolution (DSC) and dilated convolution (DC) are introduced to decrease the computational expense and feature redundancy. To take full advantages of two types of data, an adaptive interacting fusion module (AIF) is designed to adaptively integrate them, thereby generating accurate feature representation of the broken defects. The experiments demonstrate that the multi-source data fusion network can effectively improve the detection accuracy of wood broken defects and reduce the false detections of interference, such as stains and mineral lines.

10.
Toxicol Res ; 40(2): 189-202, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38525134

RESUMO

Chronic renal failure (CRF) resulting in vascular calcification, which does damage to blood vessels and endothelium, is an independent risk factor for stroke. It has been reported that cilostazol has a protective effect on the focal cerebral ischemic infarct. However, its impact on vascular injury in CRF combined stroke and its molecular protection mechanism have not been investigated. In this study, we carried out the effect of cilostazol on CRF combined stroke rats, and the results confirmed that it improved the neurobehavior, renal function as well as pathologic changes in both the kidney and brain. In addition, the inflammation and oxidative stress factors in the kidney and brain were suppressed. Moreover, the rates of brain edema and infarction were decreased. The injured brain-blood barrier (BBB) was recovered with less Evans blue extravasation and more expressions of zonula occludens-1(ZO-1) and occludin. More cerebral blood flow (CBF) in the ipsilateral hemisphere and more expression of CD31 and vascular endothelial growth factor (VEGF) in brain and kidney were found in the cilostazol group. Furthermore, cell apoptosis and cell autophagy became less, on the contrary, proteins of vascular endothelial growth factor receptor 2 (VEGFR2) after the cilostazol treatment were increased. More importantly, this protective effect is related to the pathway of Janus Kinase (JAK)/signal transducer and activator of transcription 3 (STAT3), mammalian target of rapamycin (mTOR), and the hypoxia inducible factor-1α (HIF-1α). In conclusion, our results confirmed that cilostazol exerted a protective effect on the brain and kidney function, specifically in vascular injury, oxidative stress, cell apoptosis, cell autophagy, and inflammation response in CRF combined with stroke rats which were related to the upregulation of JAK/STAT3/mTOR signal pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00217-w.

11.
Food Funct ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38526548

RESUMO

Changes in the chemical composition of white tea during storage have been studied extensively; however, whether such chemical changes impact the efficacy of white tea in ameliorating colitis remains unclear. In this study, we compared the effects of new (2021 WP) and 10-year-old (2011 WP) white tea on 3% dextrose sodium sulfate (DSS)-induced ulcerative colitis in mice by gavaging mice with the extracts at 200 mg kg-1 day-1. Chemical composition analysis showed that the levels of 50 compounds, such as flavanols, dimeric catechins, and amino acids, were significantly lower in the 2011 WP extract than in the 2021 WP extract, whereas the contents of 21 compounds, such as N-ethyl-2-pyrrolidinone-substituted flavan-3-ols, theobromine, and (-)-epigallocatechin-3-(3''-O-methyl) gallate, were significantly higher. Results of the animal experiments showed that 2011 WP ameliorated the pathological symptoms of colitis, which was superior to the activity of 2021 WP, and this effect was likely enhanced based on the decreasing of the relative abundance of the g_bacteroides and g_Escherichia-Shigella flora in mice with colitis and promoting the conversion of primary bile acids to secondary bile acids in the colon. These results will facilitate the development of novel functional products from white tea.

12.
J Pain Res ; 17: 1091-1105, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510563

RESUMO

Chronic pain (CP) is a leading cause of disability and a potential factor that affects biological processes, family relationships, and self-esteem of patients. However, the need for treatment of CP is presently unmet. Current methods of pain management involve the use of drugs, but there are different degrees of concerning side effects. At present, the potential mechanisms underlying CP are not completely clear. As research progresses and novel therapeutic approaches are developed, the shortcomings of current pain treatment methods may be overcome. In this review, we discuss the retinal photoreceptors and brain regions associated with photoanalgesia, as well as the targets involved in photoanalgesia, shedding light on its potential underlying mechanisms. Our aim is to provide a foundation to understand the mechanisms underlying CP and develop light as a novel analgesic treatment has its biological regulation principle for CP. This approach may provide an opportunity to drive the field towards future translational, clinical studies and support pain drug development.

13.
Cardiovasc Res ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38546342

RESUMO

AIMS: Alteplase is a cornerstone thrombolytic agent in clinical practice, but presents a potential bleeding risk. Stroke patients need pre-screening to exclude hemorrhagic stroke before using Alteplase. In this study, we develop a new thrombolytic agent citPA5, characterized by an enhanced safety profile and minimal bleeding tendency. METHODS AND RESULTS: A clot lysis agent, named citPA5, is developed based on rtPA with point mutations to completely suppress its proteolytic activity in the absence of fibrin. In the presence of fibrin, citPA5 exhibited significantly higher fibrinolytic activity (a 15.8-fold increase of kcat/Km). Furthermore, citPA5 showed resistance to endogenous fibrinolysis inhibitor, PAI-1, resulting in enhanced potency. In a series of safety evaluation experiments, including thrombelastography (TEG) assay, mice tail bleeding assay, and a murine intracerebral hemorrhage (ICH) model, citPA5 did not cause systemic bleeding or worsen intracerebral hemorrhage compared to Alteplase. This highlights the low risk of bleeding associated with citPA5. Finally, we found that citPA5 effectively improved cerebral blood flow and reduced infarct volume in a carotid embolism-induced stroke (CES) model. CONCLUSIONS: This clot lysis agent, citPA5, not only exhibits a low risk of bleeding but also demonstrates highly effective thrombolysis capabilities. As a result, citPA5 shows great potential for administration prior to the classification of stroke types, making it possible for use in ambulances at the onset of stroke when symptoms are identified. The findings presented in this study also suggest that this strategy could be applied to develop a new generation of fibrinolytic drugs that offer greater safety and specificity in targeting fibrin.

14.
Pak J Med Sci ; 40(4): 663-668, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38544987

RESUMO

Objective: To evaluate the effects of comprehensive nursing intervention on the quality of life and clinical outcomes of patients with thyroid nodules treated by ultrasound-guided microwave ablation. Methods: This was a prospective study conducted from December 2020 to December 2022 at The Fifth Medical Center of Chinese PLA General Hospital. One hundred and twenty patients with benign thyroid nodules undergoing microwave ablation were included. Patients were randomly divided into control group and experimental group. Patients in the control group were given conventional intervention mode during the perioperative period, while those in the experimental group were given comprehensive nursing intervention mode on the basis of the control group. The differences in quality of life, cognitive level before and after intervention and satisfaction between the two groups were compared and analyzed. Results: The SF-36 scores in the experimental group were significantly higher than that in the control group after intervention. After the intervention, the SAS and SDS scores in the experimental group were significantly lower than those in the control group, with a statistically significant difference. The VAS scores in the experimental group were better than those in the control group at six, twelve and twenty four hour after operation, with statistically significant differences. After the intervention, the cognitive score of the experimental group was significantly higher than that of the control group. Conclusion: Comprehensive nursing intervention is worthy of clinical promotion in the treatment of patients with thyroid nodules treated by ultrasound-guided microwave ablation, leading to various benefits such as effectively improving patients' quality of life and relieving pain.

15.
Exp Gerontol ; 188: 112393, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38458480

RESUMO

Diabetic kidney disease (DKD) is leading causes and one of the fastest growing causes of chronic kidney disease worldwide, and leads to high morbidity and mortality. Emerging evidences have revealed gut microbiota dysbiosis and related metabolism dysfunction play a dominant role in DKD progression and treatment through modulating inflammation. Our previous studies showed that Tangshen Formula (TSF), a Chinese herbal prescription, exhibited anti-inflammatory effect on DKD, but underlying mechanism that involved gut microbiota and related metabolism in aged model remained obscure. Here, BTBR ob/ob mice were used to establish aged DKD model, and 16S rRNA sequence and untargeted metabolomic analyses were employed to investigate the correlation between colonic microbiota and serum metabolism. The aged ob/ob mice exhibited obvious glomerular and renal tubule injury and kidney function decline in kidney, while TSF treatment significantly attenuated these abnormalities. TSF also exhibited potent anti-inflammatory effect in aged ob/ob mice indicating by reduced proinflammatory factor IL-6 and TNF-α, MCP-1 and COX-2 in serum, kidney and intestine, which suggested the involvement of gut microbiota with TSF effect. The 16S rDNA sequencing of the colonic microbiome and untargeted serum metabolomics analysis revealed significant differences in gut microbiota structure and serum metabolomic profiles between WT and ob/ob mice. Notably, TSF treatment reshaped the structure of gut microbiota and corrected the disorder of metabolism especially tryptophan metabolism and arginine biosynthesis. TSF increased Anaeroplasma and Barnesiella genera and decreased Romboutsia, Akkermansia, and Collinsella genera, and further elevated tryptophan, 5-hydroxyindoleacetate, glutamic acid, aspartate and reduced 4-hydroxy-2-quinolinecarboxylic acid, indole-3-acetic acid, xanthurenic acid, glutamine. Further correlation analysis indicated that disturbed gut microbiota was linked to tryptophan metabolism and arginine biosynthesis to regulate inflammation in aged DKD. Our data revealed that TSF attenuated renal inflammation by modulating gut microbiota and related amino acid metabolism in aged DKD model, highlighting gut microbiota and related metabolism functioned as potential therapeutic target for DKD in elderly patients.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Microbioma Gastrointestinal , Humanos , Idoso , Camundongos , Animais , Nefropatias Diabéticas/tratamento farmacológico , RNA Ribossômico 16S/genética , Triptofano , Inflamação/tratamento farmacológico , Anti-Inflamatórios/uso terapêutico , Arginina
16.
Stroke ; 55(4): 883-892, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38465591

RESUMO

BACKGROUND: The efficacy of thrombolysis (IVT) in minor stroke (National Institutes of Health Stroke Scale score, 0-5) remains inconclusive. The aim of this study is to compare the effectiveness and safety of IVT with best medical therapy (BMT) by means of a systematic review and meta-analysis of randomized controlled trials and observational studies. METHODS: We searched the PubMed, Embase, Cochrane Library, and Web of Science databases to obtain articles related to IVT in minor stroke from inception until August 10, 2023. The primary outcome was an excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 at 90 days. The associations were calculated for the overall and preformulated subgroups by using the odds ratios (ORs). This study was registered with PROSPERO (CRD42023445856). RESULTS: A total of 20 high-quality studies, comprised of 13 397 patients with acute minor ischemic stroke, were included. There were no significant differences observed in the modified Rankin Scale scores of 0 to 1 (OR, 1.10 [95% CI, 0.89-1.37]) and 0 to 2 (OR, 1.16 [95% CI, 0.95-1.43]), mortality rates (OR, 0.67 [95% CI, 0.39-1.15]), recurrent stroke (OR, 0.89 [95% CI, 0.57-1.38]), and recurrent ischemic stroke (OR, 1.09 [95% CI, 0.68-1.73]) between the IVT and BMT group. There were differences between the IVT group and the BMT group in terms of early neurological deterioration (OR, 1.81 [95% CI, 1.17-2.80]), symptomatic intracranial hemorrhage (OR, 7.48 [95% CI, 3.55-15.76]), and hemorrhagic transformation (OR, 4.73 [95% CI, 2.40-9.34]). Comparison of modified Rankin Scale score of 0 to 1 remained unchanged in subgroup patients with nondisabling deficits or compared with those using antiplatelets. CONCLUSIONS: These findings indicate that IVT does not yield significant improvement in the functional prognosis of patients with acute minor ischemic stroke. Additionally, it is associated with an increased risk of symptomatic intracranial hemorrhage when compared with the BMT. Moreover, IVT may not have superiority over BMT in patients with nondisabling deficits or those using antiplatelets.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Ativador de Plasminogênio Tecidual/uso terapêutico , Fibrinolíticos/uso terapêutico , Terapia Trombolítica/efeitos adversos , Isquemia Encefálica/terapia , Resultado do Tratamento , Acidente Vascular Cerebral/terapia , Hemorragias Intracranianas/induzido quimicamente , Trombectomia , AVC Isquêmico/tratamento farmacológico , Estudos Observacionais como Assunto
17.
Ecotoxicol Environ Saf ; 274: 116212, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38489900

RESUMO

Evidence of the potential causal links between long-term exposure to particulate matters (PM, i.e., PM1, PM2.5, and PM1-2.5) and T2DM mortality based on large cohorts is limited. In contrast, the existing evidence usually suffers from inherent bias with the traditional association assessment. A prospective cohort of 580,757 participants in the southern region of China were recruited during 2009 and 2015 and followed up through December 2020. PM exposure at each residential address was estimated by linking to the well-established high-resolution simulation dataset. Hazard ratios (HRs) were calculated using time-varying marginal structural Cox models, an established causal inference approach, after adjusting for potential confounders. During follow-up, a total of 717 subjects died from T2DM. For every 1 µg/m3 increase in PM2.5, the adjusted HRs and 95% confidence interval (CI) for T2DM mortality was 1.036 (1.019-1.053). Similarly, for every 1 µg/m3 increase in PM1 and PM1-2.5, the adjusted HRs and 95% CIs were 1.032 (1.003-1.062) and 1.085 (1.054-1.116), respectively. Additionally, we observed a generally more pronounced impact among individuals with lower levels of education or lower residential greenness which as measured by the Normalized Difference Vegetation Index (NDVI). We identified substantial interactions between NDVI and PM1 (P-interaction = 0.003), NDVI and PM2.5 (P-interaction = 0.019), as well as education levels and PM1 (P-interaction = 0.049). The study emphasizes the need to consider environmental and socio-economic factors in strategies to reduce T2DM mortality. We found that PM1, PM2.5, and PM1-2.5 heighten the peril of T2DM mortality, with education and green space exposure roles in modifying it.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Diabetes Mellitus Tipo 2 , Humanos , Material Particulado/efeitos adversos , Material Particulado/análise , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Prospectivos , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise , China/epidemiologia , Poluentes Atmosféricos/efeitos adversos , Poluentes Atmosféricos/análise , Poluição do Ar/efeitos adversos
18.
BMJ Open ; 14(3): e081731, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553066

RESUMO

INTRODUCTION: Urinary incontinence (UI) is one of the most common chronic diseases among women, which can endanger their physical and mental health and incur a heavy financial burden on both individuals and society. Web-based interventions (WBIs) have been applied to manage women's UI, but their effectiveness has remained inconclusive. This systematic review and meta-analysis aims to explore the effectiveness of WBIs on self-reported symptom severity, condition-specific quality of life, adherence to pelvic floor muscle training (primary outcomes) and other extensive secondary outcomes among women with UI. We also aimed to investigate whether intervention characteristics (format, interactivity and main technology) have impacts on the effectiveness of primary outcomes. METHODS AND ANALYSIS: This systematic review protocol was developed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. 10 electronic databases will be comprehensively searched from their inception to 1 May 2024, along with grey literature searches and manual reviews of relevant reference lists to identify eligible randomised controlled trials. The methodological quality of the included studies will be assessed by two reviewers based on the Cochrane Risk of Bias Tool. Meta-analyses will be conducted via Stata V.12.0. Leave-one-out sensitivity analyses will be performed, and publication bias will be evaluated using funnel plots and Egger's test. Subgroup analyses regarding intervention format, interactivity and main technology will be carried out. ETHICS AND DISSEMINATION: No ethics approval is needed for this review since no primary data are to be collected. The results of this review will help develop an optimal WBI for women with UI, thereby providing them with maximum benefits. The findings will be disseminated via a peer-reviewed journal or conference presentation. PROSPERO REGISTRATION NUMBER: CRD42023435047.


Assuntos
Intervenção Baseada em Internet , Incontinência Urinária , Feminino , Humanos , Qualidade de Vida , Revisões Sistemáticas como Assunto , Metanálise como Assunto , Incontinência Urinária/terapia , Literatura de Revisão como Assunto
19.
ACS Appl Mater Interfaces ; 16(13): 15701-15717, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38507687

RESUMO

Although topical application of minoxidil is a widely used, FDA-approved therapy for androgenetic alopecia (AGA) treatment, it suffers from low bioavailability, the requirement for frequent long-term use, and side effects. With a similar structure as minoxidil, kopexil and kopyrrol are less toxic and have been commercialized, but show an inferior hair regeneration effect compared to minoxidil. Herein, we developed a hyaluronic acid (HA)-based dissolvable microneedles (MNs) delivery platform integrated with kopexil and kopyrrol coencapsulated nanoliposomes (KK-NLPs) to effectively and safely treat AGA. Facilitated by nanoliposomes and MNs, the encapsulated KK-NLPs performed efficient skin penetration and enhanced cellular internalization into human dermal papilla cells. Furthermore, within the target cells, the codelivered kopexil and kopyrrol show synergistic effects by orchestrating an upregulation in the expression of Ki67, ß-catenin, vascular endothelial growth factor (VEGF), and CD31. These molecular responses collectively foster cell proliferation, migration, and antioxidative effects, thereby facilitating the expedited progression of hair follicles (HFs) into the anagen phase and promoting peripheral angiogenesis. Notably, the KK-NLPs-integrated MNs treatment group exhibits noteworthy enhanced hair regeneration in vivo, with identical or superior therapeutic effects at a much lower dosage than that of minoxidil. These results suggest the great potential of this kopexil and kopyrrol codelivery nanoliposomes-integrated MNs platform for AGA treatment in a safe and efficient way.


Assuntos
Minoxidil , Fator A de Crescimento do Endotélio Vascular , Humanos , Minoxidil/farmacologia , Minoxidil/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Alopecia/tratamento farmacológico , Alopecia/induzido quimicamente , Alopecia/metabolismo , Cabelo , Folículo Piloso , Resultado do Tratamento
20.
Front Biosci (Landmark Ed) ; 29(3): 109, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38538266

RESUMO

BACKGROUND: Severe neurological condition like Alzheimer's disease (AD) has a significantly negative impact on families and society, wherein there is no proven cure. As one of the principal active constituents of Achyranthes bidentata Blume, ecdysterone (ECR) has demonstrated antioxidant and cognitive dysfunction improvement effects. Nonetheless, the mechanism underlying the improvement of cognitive dysfunction by ECR remains unclear. This study sought to ascertain whether ECR may allebviate cognitive impairment by reducing oxidative stress via activation of the nuclear factor erythroid-2-related factor-2 (Nrf2) antioxidant system through Akt/GSK3ß pathway. METHODS: In terms of the experimental procedure, we determined the neuroprotective benefits of ECR in vivo via a cognitive impairment model of senescence-accelerated mouse prone 8 (SAMP8), we performed procedures such as behavioral testing, biochemical assaying, Nissl and TUNEL stainings, as well as flow cytometry, immunohistochemistry and western blotting. Furthermore, we investigated the underlying mechanistic action of ECR by activating PC12 cells with ß-amyloid peptide fragment 25-35 (Aß25-35). RESULTS: In vivo studies showed that ECR effectively improved cognitive impairment in SAMP8 via enhancement of learning and memory capabilities, but decreased oxidative stress, apoptosis and neuronal damage in the hippocampus. During the in vitro study, we observed that ECR dose-dependently reduced the oxidative stress and apoptosis that were induced in PC12 cells by Aß25-35. Additionally, the use of Akt inhibitors further established the potential of ECR to control Nrf2 through activation of the Akt/GSK3ß pathway and protect the PC12 cells from Aß25-35 induced damage. CONCLUSIONS: These findings offer proof that ECR reduces cognitive impairment by triggering the Nrf2 antioxidant system via the Akt/GSK3ß pathway and offer fresh information on ECR's potential as a promising therapeutic development candidate for AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Fármacos Neuroprotetores , Humanos , Ratos , Camundongos , Animais , Glicogênio Sintase Quinase 3 beta/metabolismo , Antioxidantes/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Ecdisterona/farmacologia , Ecdisterona/uso terapêutico , Estresse Oxidativo , Transdução de Sinais , Peptídeos beta-Amiloides/toxicidade , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/tratamento farmacológico , Disfunção Cognitiva/tratamento farmacológico , Cognição , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
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