Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.938
Filtrar
1.
BMJ Open ; 14(4): e080211, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589256

RESUMO

OBJECTIVES: The elimination of mother-to-child transmission (MTCT) of syphilis has been set as a public health priority. However, an instrument to predict the MTCT of syphilis is not available. We aimed to develop and validate an intuitive nomogram to predict the individualised risk of MTCT in pregnant women with syphilis in China. DESIGN: Retrospective cohort study. SETTING: Data was acquired from the National Information System of Prevention of MTCT of Syphilis in Guangdong province between 2011 and 2020. PARTICIPANTS: A total of 13 860 pregnant women with syphilis and their infants were included and randomised 7:3 into the derivation cohort (n=9702) and validation cohort (n=4158). PRIMARY OUTCOME MEASURES: Congenital syphilis. RESULTS: Among 13 860 pregnant women with syphilis and their infants included, 1370 infants were diagnosed with congenital syphilis. Least absolute shrinkage and selection operator regression and multivariable logistic regression showed that age, ethnicity, registered residence, marital status, number of pregnancies, transmission route, the timing of syphilis diagnosis, stage of syphilis, time from first antenatal care to syphilis diagnosis and toluidine red unheated serum test titre were predictors of MTCT of syphilis. A nomogram was developed based on the predictors, which demonstrated good calibration and discrimination with an area under the curve of the receiver operating characteristic of 0.741 (95% CI: 0.728 to 0.755) and 0.731 (95% CI: 0.710 to 0.752) for the derivation and validation cohorts, respectively. The net benefit of the predictive models was positive, demonstrating a significant potential for clinical decision-making. We have also developed a web calculator based on this prediction model. CONCLUSIONS: Our nomogram exhibited good performance in predicting individualised risk for MTCT of syphilis, which may help guide early and personalised prevention for MTCT of syphilis.


Assuntos
Complicações Infecciosas na Gravidez , Sífilis Congênita , Sífilis , Lactente , Gravidez , Feminino , Humanos , Gestantes , Sífilis/diagnóstico , Sífilis/epidemiologia , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/tratamento farmacológico , Sífilis Congênita/diagnóstico , Sífilis Congênita/prevenção & controle , Nomogramas , Estudos Retrospectivos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle
2.
Front Pharmacol ; 15: 1372950, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38590638

RESUMO

Bariatric surgeries are becoming more prevalent as obesity rates continue to rise. Being that it is an effective weight-loss procedure, it can induce significant anatomical, physiological, and metabolic alterations, which affect the pharmacokinetics of various medications. Cytochrome (CYP) P450 is a group of enzymes that are primarily responsible for metabolizing most medications. Bariatric surgery may affect CYP activity and consequently alter metabolism of various medications, and the resulting weight loss may influence the metabolism of various drugs. This study investigates the impact of bariatric surgery on which CYP enzymes are affected and their effects medications. Authors of this study did an extensive literature review and research in databases including PubMed and EMBASE. The evidence was gathered for medication efficacy influenced by enzyme fluctuations to advocate for further studies for patients that undergo bariatric surgery. The search was limited to English-language results and is deemed up to date as of September 2023. There are numerous studies that indicated alterations of the CYP enzyme activity, which affects the pharmacokinetics of medications used to treat acute and chronic conditions after bariatric surgery. There are various mechanisms involved in CYP enzyme activity leading to fluctuations and the clearance of medications and subsequently compromising the efficacy and safety of these agents. It is imperative to conduct more prospective randomized control studies with longer duration to guide clinicians on how to manage medications with various CYP activity for patients' post-bariatric surgery.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38575819

RESUMO

Antibiotics have been widely detected in aquatic environments, and fungal biotransformation receives considerable attention for antibiotic bioremediation. Here, a fungus designated Cladosporium cladosporioides 11 (CC11) with effective capacity to biotransform fluoroquinolones was isolated from aquaculture pond sediments. Enrofloxacin (ENR), ciprofloxacin (CIP) and ofloxacin (OFL) were considerably abated by CC11, and the antibacterial activities of the fluoroquinolones reduced significantly after CC11 treatment. Transcriptome analysis showed the removal of ENR, CIP and OFL by CC11 is a process of enzymatic degradation and biosorption which consists well with ligninolytic enzyme activities and sorption experiments under the same conditions. Additionally, CC11 significantly removed ENR in zebrafish culture water and reduced the residue of ENR in zebrafish. All these results evidenced the potential of CC11 as a novel environmentally friendly process for the removal of fluoroquinolones from aqueous systems and reduce fluoroquinolone residues in aquatic organisms.

4.
J Xray Sci Technol ; 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38457139

RESUMO

BACKGROUND: The error magnitude is closely related to patient-specific dosimetry and plays an important role in evaluating the delivery of the radiotherapy plan in QA. No previous study has investigated the feasibility of deep learning to predict error magnitude. OBJECTIVE: The purpose of this study was to predict the error magnitude of different delivery error types in radiotherapy based on ResNet. METHODS: A total of 34 chest cancer plans (172 fields) of intensity-modulated radiation therapy (IMRT) from Eclipse were selected, of which 30 plans (151 fields) were used for model training and validation, and 4 plans including 21 fields were used for external testing. The collimator misalignment (COLL), monitor unit variation (MU), random multi-leaf collimator shift (MLCR), and systematic MLC shift (MLCS) were introduced. These dose distributions of portal dose predictions for the original plans were defined as the reference dose distribution (RDD), while those for the error-introduced plans were defined as the error-introduced dose distribution (EDD). Different inputs were used in the ResNet for predicting the error magnitude. RESULTS: In the test set, the accuracy of error type prediction based on the dose difference, gamma distribution, and RDD + EDD was 98.36%, 98.91%, and 100%, respectively; the root mean squared error (RMSE) was 1.45-1.54, 0.58-0.90, 0.32-0.36, and 0.15-0.24; the mean absolute error (MAE) was 1.06-1.18, 0.32-0.78, 0.25-0.27, and 0.11-0.18, respectively, for COLL, MU, MLCR and MLCS. CONCLUSIONS: In this study, error magnitude prediction models with dose difference, gamma distribution, and RDD + EDD are established based on ResNet. The accurate prediction of the error magnitude under different error types can provide reference for error analysis in patient-specific QA.

5.
Int J Med Sci ; 21(4): 765-774, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38464823

RESUMO

Introduction: Epidermal growth factor receptor (EGFR) mutation is common in Chinese patients with lung adenocarcinoma (LUAD). Brain metastases (BMs) is high and associated with poor prognosis. Identification of EGFR-mutant patients at high risk of developing BMs is important to reduce or delay the incidence of BMs. Currently, there is no literature on the prediction and modeling of EGFR brain metastasis at the proteinomics level. Methods: We conducted a retrospective study of BMs in postoperative recurrent LUAD with EGFR mutation in the First Affiliated Hospital of Guangzhou Medical University. Tissue proteomic analysis was applied in the primary tumors of resected LUAD in this study using liquid chromatography-mass spectrometry (LC-MS/MS). To identify potential markers for predicting LUAD BM, comparative analyses were performed on different groups to evaluate proteins associated with high risk of BMs. Results: A combination of three potential marker proteins was found to discriminate well between distal metastasis (DM) and local recurrence (LR) of postoperative LUAD with EGFR mutation. Gene Ontology (GO) analysis of significantly altered proteins between BM and non-BM (NBM) indicated that lipid metabolism and cell cycle-related pathways were involved in BMs of LUAD. And the enriched pathways correlated with BMs were found to be quite different in the comparison groups of postoperative adjuvant therapy, tyrosine kinase inhibitor (TKI), and chemotherapy groups. Finally, we developed a random forest algorithm model with eight proteins (RRS1, CPT1A, DNM1, SRCAP, MLYCD, PCID2, IMPAD1 and FILIP1), which showed excellent predictive value (AUC: 0.9401) of BM in patients with LUAD harboring EGFR mutation. Conclusions: A predictive model based on protein markers was developed to accurately predict postoperative BM in operable LUAD harboring EGFR mutation.


Assuntos
Adenocarcinoma de Pulmão , Adenocarcinoma , Neoplasias Encefálicas , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/patologia , Proteômica , Estudos Retrospectivos , Cromatografia Líquida , Mutação , Recidiva Local de Neoplasia/genética , Espectrometria de Massas em Tandem , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Receptores ErbB/metabolismo , Fatores de Risco , Proteínas Nucleares/genética
6.
Transl Cancer Res ; 13(2): 542-557, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38482426

RESUMO

Background: Young breast cancer (YBC) patients demonstrate a heightened propensity for regional lymph node metastasis (RLNM) in contrast to cohorts across varying age demographics. The aim of our study was to identify clinicopathologic prognostic variables in YBC patients with RLNM and construct a practical and reliable nomogram for the prediction of overall survival (OS) using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Young individuals (≤40 years) with a diagnosis of breast cancer with RLNM were recognized from the SEER database between 2010 and 2015, and further randomly split into two cohorts: the training set (n=4,497) and the validation set (n=1,927). We first performed univariate and multivariate Cox regression analyses to confirm independent survival predictors of OS. A novel prognostic nomogram was developed and evaluated using Harrell's concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). To make a clear distinction between high- and low-risk patients in terms of patient survival, Kaplan-Meier survival curves were assessed using the log-rank test. Results: Nine risk factors were found as independent prognostic variables in predicting OS, including race, grade, histology, surgery, radiation, molecular subtype, American Joint Committee on Cancer (AJCC) stage 7th edition, T stage, and N stage. The C-index values of our nomogram were 0.786 [95% confidence interval (CI): 0.767-0.805] and 0.791 (95% CI: 0.760-0.822) in our training and validation groups, respectively. The ROC curves demonstrated sufficient discriminating ability, while the predicted and real survival rates were fairly consistent, as shown by the calibration plots. The prediction model had a higher net benefit and acceptable clinical value, as shown by the DCA curves. Conclusions: In YBC patients with RLNM, we successfully established a unique nomogram to forecast the 2-, 3-, and 5-year OS. Clinicians may utilize this nomogram to pinpoint patients at higher risk and provide them with appropriate customized therapies.

7.
Clin Cardiol ; 47(3): e24247, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38450794

RESUMO

BACKGROUND: Previous studies show that using 12-lead electrocardiogram (ECG) or 24-h ECG monitor for the detection of cardiac arrhythmia events in patients with stroke or syncope is ineffective. HYPOTHESIS: The 14-day continuous ECG patch has higher detection rates of arrhythmias compared with conventional 24-h ECG monitoring in patients with ischemic stroke or syncope. METHODS: This cross-sectional study of patients with newly diagnosed ischemic stroke or syncope received a 24-h ECG monitoring and 14-day continuous cardiac monitoring patch and the arrhythmia events were measured. RESULTS: This study enrolled 83 patients with ischemic stroke or syncope. The detection rate of composite cardiac arrhythmias was significantly higher for the 14-day ECG patch than 24-h Holter monitor (69.9% vs. 21.7%, p = .006). In patients with ischemic stroke, the detection rates of cardiac arrhythmias were 63.4% for supraventricular tachycardia (SVT), 7% for ventricular tachycardia (VT), 5.6% for atrial fibrillation (AF), 4.2% for atrioventricular block (AVB), and 1.4% for pause by 14-day ECG patch, respectively. The significant difference in arrhythmic detection rates were found for SVT (45.8%), AF (6%), pause (1.2%), AVB (2.4%), and VT (9.6%) by 14-day ECG patch but not by 24-h Holter monitor in patients with ischemic stroke or syncope. CONCLUSIONS: A 14-day ECG patch can be used on patients with ischemic stroke or syncope for the early detection of AF or other cardiac arrhythmia events. The patch can be helpful for physicians in planning medical or mechanical interventions of patients with ischemic stroke and occult AF.


Assuntos
Fibrilação Atrial , Bloqueio Atrioventricular , AVC Isquêmico , Taquicardia Ventricular , Humanos , Estudos Transversais , Síncope/diagnóstico , Síncope/etiologia , Eletrocardiografia
8.
Infect Dis Ther ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38489119

RESUMO

INTRODUCTION: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) has been increasingly replaced by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in the treatment of human immunodeficiency virus (HIV) owing to its more favorable pharmacokinetics and fewer drug-drug interactions. However, the effect of this switch on plasma lipids and lipidomic profiles remains poorly characterized. METHODS: HIV infected patients on an E/C/F/TAF regimen were recruited into the study and followed up every 12 weeks. Participants were divided into E/C/F/TAF and B/F/TAF groups depending on whether they were switched to B/F/TAF during follow-up. Clinical information and blood samples were collected at 0, 12, and 24 weeks, and lipidomic analysis was performed using liquid chromatography mass spectrometry. RESULTS: No significant differences were observed between the groups at baseline. At week 24, patients switched to B/F/TAF had lower triglyceride [mmol/L; 1.23 (0.62) versus 2.03 (0.75), P = 0.001] and very low-density lipoprotein cholesterol [mmol/L; 0.64 (0.26) versus 0.84 (0.32), P = 0.037) compared with patients who continued E/C/F/TAF therapy. Small decrease from baseline in Framingham general cardiovascular risk score (FRS) was observed in the B/F/TAF arm [week (W) 0: 2.59 (1.57) versus W24: 2.18 (1.01), P = 0.043]. Lipidomic analysis indicated that E/C/F/TAF treatment increased the levels of several diglycerides (DGs), triacylglycerols (TAGs), and lyso-phosphatidylcholines (LPCs), whereas switching to B/F/TAF led to increased sphingolipids and glycerophospholipids. After adjusting for demographic and clinical parameters, only DG (16:0/18:2), DG (18:2/22:6), DG (18:3/18:2), DG (20:5/18:2), TAG (18:3/18:2/21:5), TAG (20:5/18:2/22:6), and LPC (22:6) were found to be significantly associated with FRS (regression coefficient of 0.17-6.02, P < 0.05). Most of these FRS associate lipid species were significantly elevated in individuals treated with E/C/F/TAF instead of individuals treated with B/F/TAF. CONCLUSION: E/C/F/TAF promotes the accumulation of lipid species closely associated with cardiovascular disease (CVD) risk among people living with HIV, whereas B/F/TAF has a decreased impact on CVD-related lipid profile and is associated with lower CVD risk. A graphical abstract is available with this article. TRIAL REGISTRATION: ClinicalTrials.gov; identifier, NCT06019273.

9.
Discov Oncol ; 15(1): 76, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38492016

RESUMO

PURPOSE: To explore the impact of excluding the external iliac node (EIN) from the clinical target volume (CTV) during preoperative radiotherapy in T4b rectal cancer with anterior structure invasion. METHODS: We retrospectively identified 132 patients with T4b rectal cancer involving the anterior structures who received radiotherapy followed by surgery between May 2010 and June 2019. Twenty-nine patients received EIN irradiation (EIN group), and 103 did not (NEIN group). Failure patterns, survival and toxicities were compared between the two groups. RESULTS: The most common failure was distant metastasis (23.5%). 11 (8.3%) patients developed locoregional recurrence, 10 (9.7%) patients were in the NEIN group, and 1 (3.4%) was in the EIN group (P = 0.34). The EIN region failure was rare (1/132, 0.8%). The locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS) and progression-free survival (PFS) rates were 96.3% vs. 90.5%, 82.1% vs.73.7%, 75.9% vs. 78.0% and 72.4% vs. 68.3% (all P > 0.05) for the EIN group and NEIN group, respectively. The incidence of grade 3-4 acute toxicity in the lower intestine was significantly higher in the EIN group than in the NEIN group (13.8% vs. 1.9%, P = 0.02). The Dmax, V35 and V45 of the small bowel was decreased in the NEIN group compared to the EIN group. CONCLUSIONS: Exclusion of the EIN from the CTV in T4b rectal cancer with anterior structure invasion could reduce lower intestinal toxicity without compromising oncological outcomes. These results need further evaluation in future studies.

10.
J Transl Med ; 22(1): 287, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493183

RESUMO

BACKGROUND: Protein cysteine oxidation is substantially involved in various biological and pathogenic processes, but its implications in pancreatic cancer development remains poorly understood. METHODS AND RESULTS: In this study, we performed a global characterization of protein oxidation targets in PDAC cells through iodoTMT-based quantitative proteomics, which identified over 4300 oxidized cysteine sites in more than 2100 proteins in HPDE6c7 and PANC-1 cells. Among them, 1715 cysteine residues were shown to be differentially oxidized between HPDE6c7 and PANC-1 cells. Also, charged amino acids including aspartate, glutamate and lysine were significantly overrepresented in flanking sequences of oxidized cysteines. Differentially oxidized proteins in PANC-1 cells were enriched in multiple cancer-related biological processes and signaling pathways. Specifically, the HIF-1 signaling proteins exhibited significant oxidation alterations in PANC-1 cells, and the reduced PHD2 oxidation in human PDAC tissues was correlated with lower survival time in pancreatic cancer patients. CONCLUSION: These investigations provided new insights into protein oxidation-regulated signaling and biological processes during PDAC pathogenesis, which might be further explored for pancreatic cancer diagnosis and treatment.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Cisteína/metabolismo , Proteômica , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Oxirredução , Linhagem Celular Tumoral
11.
BMC Cancer ; 24(1): 368, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38519974

RESUMO

OBJECTIVE: This study aimed to develop and validate an artificial intelligence radiopathological model using preoperative CT scans and postoperative hematoxylin and eosin (HE) stained slides to predict the pathological staging of gastric cancer (stage I-II and stage III). METHODS: This study included a total of 202 gastric cancer patients with confirmed pathological staging (training cohort: n = 141; validation cohort: n = 61). Pathological histological features were extracted from HE slides, and pathological models were constructed using logistic regression (LR), support vector machine (SVM), and NaiveBayes. The optimal pathological model was selected through receiver operating characteristic (ROC) curve analysis. Machine learnin algorithms were employed to construct radiomic models and radiopathological models using the optimal pathological model. Model performance was evaluated using ROC curve analysis, and clinical utility was estimated using decision curve analysis (DCA). RESULTS: A total of 311 pathological histological features were extracted from the HE images, including 101 Term Frequency-Inverse Document Frequency (TF-IDF) features and 210 deep learning features. A pathological model was constructed using 19 selected pathological features through dimension reduction, with the SVM model demonstrating superior predictive performance (AUC, training cohort: 0.949; validation cohort: 0.777). Radiomic features were constructed using 6 selected features from 1834 radiomic features extracted from CT scans via SVM machine algorithm. Simultaneously, a radiopathomics model was built using 17 non-zero coefficient features obtained through dimension reduction from a total of 2145 features (combining both radiomics and pathomics features). The best discriminative ability was observed in the SVM_radiopathomics model (AUC, training cohort: 0.953; validation cohort: 0.851), and clinical decision curve analysis (DCA) demonstrated excellent clinical utility. CONCLUSION: The radiopathomics model, combining pathological and radiomic features, exhibited superior performance in distinguishing between stage I-II and stage III gastric cancer. This study is based on the prediction of pathological staging using pathological tissue slides from surgical specimens after gastric cancer curative surgery and preoperative CT images, highlighting the feasibility of conducting research on pathological staging using pathological slides and CT images.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Inteligência Artificial , Algoritmos , Amarelo de Eosina-(YS) , Tomografia Computadorizada por Raios X
12.
Gastroenterol Rep (Oxf) ; 12: goae012, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38510669

RESUMO

Background: Radiation-induced colorectal fibrosis (RICF) is a common pathological alteration among patients with rectal cancer undergoing neoadjuvant chemoradiotherapy (nCRT). Anastomotic stenosis (AS) causes symptoms and negatively impacts patients' quality of life and long-term survival. In this study, we aimed to evaluate the fibrosis signature of RICF and develop a nomogram to predict the risk of AS in patients with rectal cancer undergoing nCRT. Methods: Overall, 335 pairs of proximal and distal margins were collected and randomly assigned at a 7:3 ratio to the training and testing cohorts. The RICF score was established to evaluate the fibrosis signature in the anastomotic margins. A nomogram based on the RICF score for AS was developed and evaluated by using the area under the curve, decision curve analysis, and the DeLong test. Results: The training cohort included 235 patients (161 males [68.51%]; mean age, 59.61 years) with an occurrence rate of AS of 17.4%, whereas the testing cohort included 100 patients (72 males [72.00%]; mean age, 57.17 years) with an occurrence rate of AS of 11%. The RICF total score of proximal and distal margins was significantly associated with AS (odds ratio, 3.064; 95% confidence interval [CI], 2.200-4.268; P < 0.001). Multivariable analysis revealed that the RICF total score, neoadjuvant radiotherapy, and surgical approach were independent predictors for AS. The nomogram demonstrated good discrimination in the training cohort (area under the receiver-operating characteristic curve, 0.876; 95% CI, 0.816-0.937), with a sensitivity of 68.3% (95% CI, 51.9%-81.9%) and a specificity of 85.5% (95% CI, 78.7%-89.3%). Similar results were observed in the testing cohort. Conclusions: This study results suggest that the RICF total score of anastomotic margins is an independent predictor for AS. The prediction model developed based on the RICF total score may be useful for individualized AS risk prediction in patients with rectal cancer undergoing nCRT and sphincter-preserving surgery.

13.
J Integr Neurosci ; 23(3): 65, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38538216

RESUMO

BACKGROUND: It has been reported that ferroptosis participates in the pathophysiological mechanism of spinal cord injury (SCI). Our preliminary experiments verified that dendrobium nobile polysaccharide (DNP) improved the behavioral function of SCI rats. Therefore, the purpose of this study was to examine the role of DNP on ferroptosis and its neuroprotective mechanism in SCI rats. METHODS: Adult female sprague dawley (SD) rats were exposed to SCI by Allen's method, followed by an intragastric injection of 100 mg/kg DNP per day for 2 weeks. Behavioral features were verified by the Basso-Beattie-Bresnahan (BBB) scale and footprint evaluation. Iron content and glutathione (GSH) were assessed spectrophotometrically. Mitochondrial morphology was examined by transmission electron microscopy. The expression of ferroptosis-related genes, including System Xc- light chain (xCT), G-rich RNA sequence binding Factor 1 (GRSF1) and glutathione peroxidase 4 (Gpx4), was examined by real-time polymerase chain reaction (PCR) and western blot. The spinal cavity was defined using hematoxylin-eosin (HE) staining, and neuronal modifications were detected by immunofluorescence. RESULTS: Compared with the SCI group, the BBB score of rats in the DNP group increased at 7 d, 14 d, 21 d, and 28 d. The differences between the two groups were statistically significant. At 12 h post-injury the iron content began to decrease. At 24 h post-injury the iron content decreased significantly in the DNP group. The morphological changes of the mitochondrial crest and membrane in the DNP group were ameliorated within 24 h. Compared with the sham group, the expression of xCT, GSH, Gpx4, and GRSF1 were significantly reduced after SCI. After DNP treatment, the expression of xCT, Gpx4, and GSH were higher. The tissue cavity area was significantly reduced and the amount of NeuN+ cells was increased in the DNP group at 14 d and 28 d after SCI. CONCLUSIONS: DNP facilitated the post-injury recovery in SCI rats via the inhibition of ferroptosis.


Assuntos
Dendrobium , Ferroptose , Traumatismos da Medula Espinal , Ratos , Feminino , Animais , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/metabolismo , Ratos Sprague-Dawley , Ferro/metabolismo
14.
J Geriatr Cardiol ; 21(2): 219-231, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38544498

RESUMO

BACKGROUND: Myocardial infarction (MI) is a critical cardiovascular event with multifaceted etiology, involving several genetic and environmental factors. It is essential to understand the function of plasma metabolites in the development of MI and unravel its complex pathogenesis. METHODS: This study employed a bidirectional Mendelian randomization (MR) approach to investigate the causal relationships between plasma metabolites and MI risk. We used genetic instruments as proxies for plasma metabolites and MI and conducted MR analyses in both directions to assess the impact of metabolites on MI risk and vice versa. In addition, the large-scale genome-wide association studies datasets was used to identify genetic variants associated with plasma metabolite (1400 metabolites) and MI (20,917 individuals with MI and 440,906 individuals without MI) susceptibility. Inverse variance weighted was the primary method for estimating causal effects. MR estimates are expressed as beta coefficients or odds ratio (OR) with 95% CI. RESULTS: We identified 14 plasma metabolites associated with the occurrence of MI (P < 0.05), among which 8 plasma metabolites [propionylglycine levels (OR = 0.922, 95% CI: 0.881-0.965, P < 0.001), gamma-glutamylglycine levels (OR = 0.903, 95% CI: 0.861-0.948, P < 0.001), hexadecanedioate (C16-DC) levels (OR = 0.941, 95% CI: 0.911-0.973, P < 0.001), pentose acid levels (OR = 0.923, 95% CI: 0.877-0.972, P = 0.002), X-24546 levels (OR = 0.936, 95% CI: 0.902-0.971, P < 0.001), glycine levels (OR = 0.936, 95% CI: 0.909-0.964, P < 0.001), glycine to serine ratio (OR = 0.930, 95% CI: 0.888-0.974, P = 0.002), and mannose to trans-4-hydroxyproline ratio (OR = 0.912, 95% CI: 0.869-0.958, P < 0.001)] were correlated with a decreased risk of MI, whereas the remaining 6 plasma metabolites [1-palmitoyl-2-arachidonoyl-GPE (16:0/20:4) levels (OR = 1.051, 95% CI: 1.018-1.084, P = 0.002), behenoyl dihydrosphingomyelin (d18:0/22:0) levels (OR = 1.076, 95% CI: 1.027-1.128, P = 0.002), 1-stearoyl-2-docosahexaenoyl-GPE (18:0/22:6) levels (OR = 1.067, 95% CI: 1.027-1.109, P = 0.001), alpha-ketobutyrate levels (OR = 1.108, 95% CI: 1.041-1.180, P = 0.001), 5-acetylamino-6-formylamino-3-methyluracil levels (OR = 1.047, 95% CI: 1.019-1.076, P < 0.001), and N-acetylputrescine to (N (1) + N (8))-acetylspermidine ratio (OR = 1.045, 95% CI: 1.018-1.073, P < 0.001)] were associated with an increased risk of MI. Furthermore, we also observed that the mentioned relationships were unaffected by horizontal pleiotropy (P > 0.05). On the contrary, MI did not lead to significant alterations in the levels of the aforementioned 14 plasma metabolites (P > 0.05 for each comparison). CONCLUSIONS: Our bidirectional MR study identified 14 plasma metabolites associated with the occurrence of MI, among which 13 plasma metabolites have not been reported previously. These findings provide valuable insights for the early diagnosis of MI and potential therapeutic targets.

15.
Mitochondrion ; 76: 101875, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38499131

RESUMO

Pentatricopeptide repeat proteins are involved in mitochondrial both transcriptional and posttranscriptional regulation. Schizosaccharomyces pombe Ppr2 is a general mitochondrial translation factor that plays a critical role in the synthesis of all mitochondrial DNA-encoded oxidative phosphorylation subunits, which are essential for mitochondrial respiration. Our previous analysis showed that ppr2 deletion resulted in increased expression of iron uptake genes and caused ferroptosis-like cell death in S. pombe. In the present work, we showed that deletion of ppr2 reduced viability on glycerol- and galactose-containing media.Php4 is a transcription repressor that regulates iron homeostasis in fission yeast. We found that in the ppr2 deletion strain, Php4 was constitutively active and accumulated in the nucleus in the stationary phase. We also found that deletion of ppr2 decreased the ferroptosis-related protein Gpx1 in the mitochondria. Overexpression of Gpx1 improves the viability of Δppr2 cells. We showed that the deletion of ppr2 increased the production of ROS, downregulated heme synthesis and iron-sulfur cluster proteins, and induced stress proteins. Finally, we observed the nuclear accumulation of Pap1-GFP and Sty1-GFP, suggesting that Sty1 and Pap1 in response to cellular stress in the ppr2 deletion strain. These results suggest thatppr2 deletion may cause mitochondrial dysfunction, which is likely to lead to iron-sensing defect and iron starvation response, resulting in perturbation of iron homeostasis and increased hydroxyl radical production. The increased hydroxyl radical production triggers cellular responses in theppr2 deletion strain.

16.
Vaccine ; 42(9): 2181-2190, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38458870

RESUMO

A central goal of vaccine research is to characterize and validate immune correlates of protection (CoPs). In addition to helping elucidate immunological mechanisms, a CoP can serve as a valid surrogate endpoint for an infectious disease clinical outcome and thus qualifies as a primary endpoint for vaccine authorization or approval without requiring resource-intensive randomized, controlled phase 3 trials. Yet, it is challenging to persuasively validate a CoP, because a prognostic immune marker can fail as a reliable basis for predicting/inferring the level of vaccine efficacy against a clinical outcome, and because the statistical analysis of phase 3 trials only has limited capacity to disentangle association from cause. Moreover, the multitude of statistical methods garnered for CoP evaluation in phase 3 trials renders the comparison, interpretation, and synthesis of CoP results challenging. Toward promoting broader harmonization and standardization of CoP evaluation, this article summarizes four complementary statistical frameworks for evaluating CoPs in a phase 3 trial, focusing on the frameworks' distinct scientific objectives as measured and communicated by distinct causal vaccine efficacy parameters. Advantages and disadvantages of the frameworks are considered, dependent on phase 3 trial context, and perspectives are offered on how the frameworks can be applied and their results synthesized.


Assuntos
Eficácia de Vacinas , Vacinas , Projetos de Pesquisa , Biomarcadores/análise , Causalidade , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
Biochem Pharmacol ; 223: 116156, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38518996

RESUMO

The skin, lung, and gut are important barrier organs that control how the body reacts to environmental stressors such as ultraviolet (UV) radiation, air pollutants, dietary components, and microorganisms. The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that plays an important role in maintaining homeostasis of barrier organs. AhR was initially discovered as a receptor for environmental chemical carcinogens such as polycyclic aromatic hydrocarbons (PAHs). Activation of AhR pathways by PAHs leads to increased DNA damage and mutations which ultimately lead to carcinogenesis. Ongoing evidence reveals an ever-expanding role of AhR. Recently, AhR has been linked to immune systems by the interaction with the development of natural killer (NK) cells, regulatory T (Treg) cells, and T helper 17 (Th17) cells, as well as the production of immunosuppressive cytokines. However, the role of AhR in carcinogenesis is not as straightforward as we initially thought. Although AhR activation has been shown to promote carcinogenesis in some studies, others suggest that it may act as a tumor suppressor. In this review, we aim to explore the role of AhR in the development of cancer that originates from barrier organs. We also examined the preclinical efficacy data of AhR agonists and antagonists on carcinogenesis to determine whether AhR modulation can be a viable option for cancer chemoprevention.

18.
J Neuroendocrinol ; 36(4): e13381, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38468159

RESUMO

Hematological indicators of chronic systemic inflammation are significant biomarkers for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). We performed a systematic review and meta-analysis to assess the impact of certain factors on the overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) of patients with GEP-NENs. These factors include the neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and C-reactive protein (CRP) levels. After searching the Medline, Embase, and Cochrane Library databases from January 1, 2000 to October 20, 2022 and the American Society of Clinical Oncology conference proceedings from January 1, 2017, hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted. Subgroup analyses were conducted to identify the origins of heterogeneity and examine the impact of factor grouping. The effects of the cut-off values and sample size were assessed by meta-regression. The results revealed that higher NLRs, PLRs, and CRP levels were associated with shorter OS (HR = 2.09, 95% CI = 1.55-2.8; HR = 1.79, 95% CI = 1.40-2.28; and HR = 2.88, 95% CI = 2.09-3.95, respectively; all p < 0.001). Higher NLRs and lower LMRs were associated with shorter DFS (HR = 3.34, 95% CI = 2.11-5.29 and HR = 2.71, 95% CI = 2.27-3.24, respectively; both p < 0.001). Higher PLRs and CRP levels were correlated with shorter PFS (HR = 3.48, 95% CI = 1.34-9.03, p = 0.01 and HR = 3.14, 95% CI = 1.63-6.08, p = 0.001). As demonstrated in the research, hematological indicators of systemic inflammation are promising biomarkers for GEP-NEN assessment.


Assuntos
Linfócitos , Tumores Neuroendócrinos , Humanos , Prognóstico , Biomarcadores/metabolismo , Linfócitos/metabolismo , Inflamação/metabolismo , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/metabolismo
19.
PLoS One ; 19(3): e0301287, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38547305

RESUMO

Urban agglomerations are emerging as new regional units for national participation in global competition and the international division of labor. However, they face increasingly severe resource and eco-environment pressures during urbanization. The coordination of the relationship between urbanization and the eco-environment has attracted global attention. In this study, we used Coupling Coordination Degree and Vector Autoregression models to examine the dynamic evolution, coupling relationships, coordinated development patterns, and interaction mechanisms between urbanization and the eco-environment. The results indicate that: (1) The level of urbanization in the Chengdu-Chongqing Urban agglomeration was relatively low, and the region showed a good eco-environment background. However, rapid urbanization is gradually straining the carrying capacity of the eco-environment. (2) A close and stable coupling relationship exists between urbanization and the eco-environment, which has reached an advanced coupling stage. The status of coordinated development among cities differs considerably, and multiple stable forms may exist simultaneously. (3) Urbanization has a substantial impact on environmental changes, whereas the restrictive effect of the eco-environment on urbanization development is not particularly notable. (4) Various interactive relationships exist between the urbanization and eco-environment subsystems, including positive promotion and negative constraint effects. The positive promotion effect mainly manifests between the economic, social, and ecological response subsystems, while the negative constraint effect is most evident in the mutual coercion and inhibition between the regional urbanization, economic urbanization, ecological status, and ecological pressure subsystems. These findings have important policy implications for decision makers exploring the path of coordinated and sustainable development in urbanization and the eco-environment in Urban agglomerations.


Assuntos
Conservação dos Recursos Naturais , Urbanização , Cidades , Desenvolvimento Sustentável , Desenvolvimento Econômico , China
20.
J Alzheimers Dis ; 98(2): 563-577, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427493

RESUMO

Background: Transcranial direct current stimulation (tDCS) is considered a potential therapeutic instrument for Alzheimer's disease (AD) because it affects long-term synaptic plasticity through the processes of long-term potentiation and long-term depression, thereby improving cognitive ability. Nevertheless, the efficacy of tDCS in treating AD is still debated. Dorsal lateral prefrontal cortex is the main role in executive functions. Objective: We investigate the cognitive effects of tDCS on AD patients. Methods: Thirty mild AD patients aged 66-86 years (mean = 75.6) were included in a double-blind, randomized, sham-controlled crossover study. They were randomly assigned to receive 10 consecutive daily sessions of active tDCS (2 mA for 30 min) or a sham intervention and switched conditions 3 months later. The anodal and cathodal electrodes were placed on the left dorsal lateral prefrontal cortex and the right supraorbital area, respectively. Subjects underwent various neuropsychological assessments before and after the interventions. Results: The results showed that tDCS significantly improved Cognitive Abilities Screening Instrument scores, especially on the items of "concentration and calculation", "orientation", "language ability", and "categorical verbal fluency". Mini-Mental State Examination and Wisconsin Card Sorting Test scores in all domains of "concept formation", "abstract thinking", "cognitive flexibility", and "accuracy" also improved significantly after tDCS. For the sham condition, no difference was found between the baseline scores and the after-intervention scores on any of the neuropsychological tests. Conclusion: >: Using tDCS improves the cognition of AD patients. Further large size clinical trials are necessary to validate the data.


Assuntos
Doença de Alzheimer , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Córtex Pré-Frontal Dorsolateral , Doença de Alzheimer/terapia , Estudos Cross-Over , Cognição , Método Duplo-Cego , Córtex Pré-Frontal/fisiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...