Plasma Biomarker Screening Based on Proteomic Signature of Patients with Resistant Hypertension.

Resistant hypertension (RH) poses a significant health challenge, yet its underlying pathogenesis remains unclear. This study employs untargeted proteomic techniques to analyze the plasma of patients with RH and controlled hypertension (CH), identifying 157 differentially expressed proteins, with TGFB1 emerging as a key candidate. Through gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, Protein-Protein Interaction Networks (PPI) topological analysis, TGFB1's differential regulation in RH is established. ELISA verification solidifies TGFB1's role, marking it as a potential biological target for early RH diagnosis and treatment. The study underscores the importance of proteomic approaches in enhancing our understanding of RH and improving therapeutic strategies. These findings carry implications for advancing RH diagnostics and treatment modalities, addressing a critical gap in current knowledge.

Development and Application of a Physiologically Based Pharmacokinetic Model for Elagolix in the Adult and Adolescent Population.

INTRODUCTION: Endometriosis, a common and distressing gynecological condition, affects fertility and causes pain, is often managed with medications such as Elagolix. The present study aimed to construct a physiologically based pharmacokinetic (PBPK) model for elagolix to predict its pharmacokinetics in different populations, including those with special conditions, to enhance treatment strategies for endometriosis. METHODS: The PBPK model was optimized using observational data based on the oral administration of elagolix in a healthy Chinese population under fasting conditions. Model accuracy was further verified by comparing the predicted postprandial elagolix concentration data for healthy Chinese individuals with observed data and by comparing these values with the predicted values in a US population model with renal injury or following multiple-dose administration. RESULTS: Elagolix pharmacokinetic (PK) profiles in the Chinese and American populations exhibited no differences that were attributable to ethnicity. The model predicted in vivo PK in adolescents aged 14-18 years, revealing no clinically significant differences in the effects of elagolix between adolescents and adults. In addition, no predicted PK differences in individuals with overweight were observed. However, notable variations emerged in those classified as obesity class 2 and above compared to healthy individuals. CONCLUSION: Our study presents a novel PBPK model for elagolix in healthy Chinese women, addressing a clinical data gap for its use in adolescents and obese patients. By validating the model with real-world factors, including diet and renal impairment, we provide initial pharmacokinetic predictions for these populations, contributing to a more informed clinical approach.

Research on Classification of Grassland Degeneration Indicator Objects Based on UAV Hyperspectral Remote Sensing and 3D_RNet-O Model.

Real-time and high-precision land cover classification is the foundation for efficient and quantitative research on grassland degradation using remote sensing techniques. In view of the shortcomings of manual surveying and satellite remote sensing, this study focuses on the identification and classification of grass species indicating grassland degradation. We constructed a UAV-based hyperspectral remote sensing system and collected field data in grassland areas. By applying artificial intelligence technology, we developed a 3D_RNet-O model based on convolutional neural networks, effectively addressing technical challenges in hyperspectral remote sensing identification and classification of grassland degradation indicators, such as low reflectance of vegetation, flat spectral curves, and sparse distribution. The results showed that the model achieved a classification accuracy of 99.05% by optimizing hyperparameter combinations based on improving residual block structures. The establishment of the UAV-based hyperspectral remote sensing system and the proposed 3D_RNet-O classification model provide possibilities for further research on low-altitude hyperspectral remote sensing in grassland ecology.

WITHDRAWN: Cinobufagin induced cell apoptosis and protective autophagy through the ROS/MAPK signaling pathway.

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Influence of Flue Gas Injection on the Long-Term Durability of a Natural Draft Concrete Cooling Tower.

The article undertakes the very important topic of the long-term durability of concrete in a natural draft concrete cooling tower with flue gas injection. The corrosive conditions, including temperature, relative humidity, and CO2 and SO2 gas concentrations, near the inner wall of a cooling tower with flue gas injection were monitored in real time to obtain the long-term durability performance of concrete. The pH and chemical compositions of the condensed liquid that adhered to the tower's inner face and the macromorphology, compressive strength, and neutralization depth of in situ specimens were tested periodically. In addition, a finite element numerical simulation was conducted to simulate and verify the concentration distributions of CO2 and SO2 in the flue gas in the cooling tower. The results showed that the cleaned flue gas was enveloped, diluted, and uplifted by hot vapor in the cooling tower, and its concentration decreased. Meanwhile, the effective diffusion radius increased gradually as the flue gas rose. With the same elevation in the cooling tower, the concentration of flue gas decreased rapidly from the central point to the surrounding area. The air near the inner surface of the cooling tower was merely dampened air with a low concentration of acidic gas due to the gigantic diameter of the cooling tower. As a result, the injection of cleaned flue gas will not evidently increase the corrosion risk in a natural draft concrete cooling tower.

Upregulation of CASC2 sensitized glioma to temozolomide cytotoxicity through autophagy inhibition by sponging miR-193a-5p and regulating mTOR expression.

OBJECTIVE: Numerous studies suggested autophagy was involved in temozolomide (TMZ) resistance in glioma. Long non-coding RNA (lncRNA) CASC2 was shown to be downregulated in glioma tissues and cell lines, and was related to the TMZ resistance. However, whether CASC2 affects TMZ resistance through regulating autophagy is unknown. The aim of this study was to assess the role and mechanism of CASC2 in TMZ-induced drug resistance in glioma cells. METHODS: Glioma and the adjacent non-cancerous tissues from 32 patients were collected. The expressions of CASC2 and miR-193a-5p were determined by PCR, and their correlation was analyzed. The correlation between CASC2 expression and the clinical characteristics of patients was also studied. Glioma cells were treated with TMZ to acquire the TMZ-resistant cell lines in which the expressions of CASC2, miR-193a-5p, and mTOR were measured. The regulatory roles of CASC2, miR-193a-5p, and mTOR were defined through the loss of function and luciferase reporter assays. Autophagy was inhibited by autophagy inhibitor 3-MA, CASC2 and mTOR overexpression, or miR-193a-5p inhibitor, and the effect of which on cell viability, apoptosis, and migration of TMZ-resistant glioma cells was evaluated. RESULTS: CASC2 downregulation and miR-193a-5p upregulation was found to be associated with advanced clinical stage and TMZ response in patients with glioma. CASC2 negatively regulates miR-193a-5p expression by direct interaction in glioma cells. Overexpression of CASC2 or inhibition of miR-193a-5p reduced TMZ-induced autophagy via mTOR upregulation, which makes the glioma cells become sensitive to TMZ cytotoxicity. CONCLUSION: CASC2 is downregulated in gliomas, resulting in increased miR-193a-5p level and a decrease in mTOR expression, which further induces protective autophagy, leading to TMZ resistance. Inhibition of autophagy helps to increase the efficacy of TMZ.

MicroRNA-564 is downregulated in glioblastoma and inhibited proliferation and invasion of glioblastoma cells by targeting TGF-ß1.

Increasing evidence has indicated that aberrant expression of miRNAs has been shown to be strongly implicated in the initiation and progression of glioblastoma. Here, we identified a novel tumor suppressive miRNA, miR-564, and investigated its role and therapeutic effect for glioblastoma. We showed that miR-564 was down-regulated in human glioblastoma tissues and cell lines. Introduction of miR-564 dramatically inhibited cell growth and invasion in glioblastoma cells. Subsequent experiments revealed that Transforming growth factor-ß1 (TGF-ß1) was a direct and functional target of miR-564 in glioblastoma cells. Furthermore, overexpression of miR-564 decreased p-SMAD and SMAD4 expression, which are the downstream signaling molecules of TGF-ß. Meanwhile, ectopic of miR-564 reduced the messenger RNA (mRNA) and protein expression of epidermal growth factor receptor (EGFR) and MMP9. Furthermore, the upregulation of miR-564 suppressed TGF-ß-mediated U87 proliferation and migration. The expression of EGFR and MMP9 was upregulated in glioblastoma tissues compared to their normal tissues. The EGFR and MMP9 expression levels were inverse correlated with the expression of miR-564. miR-564 suppressed the growth of U87-engrafted tumors. These findings reveal that miR-564/TGF-ß1 signaling that may be required for glioblastoma development and may consequently serve as a new therapeutic target for the treatment of glioblastoma.

DNA repair gene ERCC1 polymorphisms and glioma susceptibility among Chinese population: a meta-analysis.

BACKGROUND: Excision repair cross complementation group 1 (ERCC1) has been shown to be involved in the progression of glioma susceptibility. However, the results remain conflict. The aim of this study was to systematically review and evaluate the role of ERCC1 C118T and C8092A polymorphisms in glioma risk among Chinese population. METHODS: Related case-control studies were searched in online electronic databases. Odds ratio (OR) with its 95% confidence interval (CI) were employed to calculate the extracted data. RESULTS: Total seven articles were retrieved, including 4426 subjects (1926 were glioma patients and 2500 were matched controls). No significant heterogeneity was found between studies (I(2)=0%, P>0.01). Our results demonstrated that A allele and AA genotype of ERCC1 C8092A polymorphism have a positive association with increasing the risk of glioma in the fixed-effect model (A vs. C: OR=1.13, 95% CI=1.02-1.25, P=0.02; AA vs. CC: OR=1.29, 95% CI=1.04-1.61, P=0.02; AA vs. CA+CC: OR=1.25, 95% CI=1.01-1.55, P=0.04). However, no significant relationship was found between C118T variant and glioma susceptibility. CONCLUSIONS: Our results indicated that ERCC1 C8092A, not C118T polymorphism might be a biomarker for patients with glioma among Chinese population. Future studies with more ethnicities are needed to explore the precise association.

Plasma copeptin levels are associated with prognosis of severe acute pancreatitis.

Copeptin reflects the individual stress level, and is correlated with outcomes of critical illness. This study was designed to evaluate its relationship with disease severity, local complications, organ failure and mortality of severe acute pancreatitis (SAP). Seventy-eight SAP patients and 78 sex- and age-matched healthy individuals were recruited. Plasma samples were obtained on admission from SAP patients and at study entry from healthy individuals. Copeptin concentration was determined using enzyme-linked immunosorbent assay. Plasma copeptin level was obviously higher in patients than in healthy individuals, was identified as an independent predictor of local complications, organ failure and in-hospital mortality, was highly associated with traditional predictors of disease severity and mortality including the Acute Physiology and Chronic Health Care Evaluation II score, Ranson score, multiple organ dysfunction score, sequential organ failure assessment score, and predicted local complications, organ failure, and in-hospital mortality of SAP patients with high areas under receiver operating characteristic curve. Furthermore, its predictive value was similar to the traditional predictors'. However, it could not improve these traditional predictors' predictive values. Therefore, increased plasma copeptin level is associated with disease severity and identified as a novel prognostic marker of local complications, organ failure and mortality after SAP.

Relationship between plasma copeptin levels and complications of community-acquired pneumonia in preschool children.

High plasma copeptin level has been associated with clinical outcomes after acute illness. The present study was undertaken to investigate the plasma copeptin concentrations in preschool children with community-acquired pneumonia (CAP) and to analyze the correlations of copeptin with CAP-related complications and pleural effusion. Plasma copeptin concentrations of 100 healthy children and 165 preschool children with CAP were measured. 35 children (21.2%) presented with complicated CAP and 28 children (17.0%) presented with pleural effusion. The admission copeptin levels were significantly increased in all patients (49.7 ± 21.4 pmol/L), children with complicated CAP (73.0 ± 16.9 pmol/L), those with uncomplicated CAP (43.4 ± 17.8 pmol/L), those with pleural effusion (70.9 ± 17.4 pmol/L) and those without pleural effusion (45.3 ± 19.5 pmol/L) compared with healthy control individuals (9.0 ± 2.7 pmol/L, all P<0.001). Multivariate logistic regression analysis showed that plasma copeptin levels were independently related to CAP-related complications (odds ratio 1.214, 95% confidence interval 1.104-1.872, P<0.001) and pleural effusion (odds ratio 1.226, 95% confidence interval 1.109-1.917, P<0.001). A receiver operating characteristic curve analysis showed plasma copeptin level better predicted CAP-related complications (area under curve 0.876, 95% confidence interval 0.815-0.922) and pleural effusion (area under curve 0.831, 95% confidence interval 0.765-0.885). Thus, plasma copeptin level may represent a novel biomarker for predicting CAP-related complications in preschool children.

[Effects of recombinant human erythropoietin on serum levels of neuron-specific enolase, S-100ß protein and myelin basic protein in rats following status epilepticus].

OBJECTIVE: This study examined the effect of recombinant human erythropoietin (r-HuEPO) on the serum levels of neuron-specific enolase (NSE), S-100ß protein and myelin basic protein (MBP) in young rats 24 hrs after lithium-pilocarpine-induced status epilepticus (SE) in order to study the potential role of r-HuEPO in epileptic brain damage. METHODS: Forty 19-21-day-old male Sprague-Dawley (SD) rats were randomly divided into four groups (n=10): normal control group, SE, r-HuEPO pretreated-SE and r-HuEPO. SE was induced by lithium-pilocarpine. R-HuEPO (500 IU/kg) was intraperitoneally injected in the r-HuEPO pretreated-SE and r-HuEPO groups 4 hrs before SE. Serum levels of NSE, S-100ß and MBP were determined 24 hrs after the SE event. RESULTS: Serum levels of NSE, S-100ß and MBP in the SE group increased significantly compared with those in the normal control and the r-HuEPO groups (P＜0.05). The r-HuEPO pretreated-SE group showed significantly decreased serum levels of NSE, S-100ß and MBP compared with the SE group (P＜0.05). CONCLUSIONS: r-HuEPO may reduce the expression of NSE, S-100ß and MBP and thus might provide an early protective effect against epileptic brain injury.

[Expression and clinical significance of surfactant protein D mRNA in peripheral blood of lung cancer patients].

BACKGROUND AND OBJECTIVES: The sensitive detection of circulating tumor cells in lung cancer patients is very important for prognosis and selection of appropriate treatment modalities. Based on recent promising data, the authors established reverse transcriptase (RT)-PCR with primers specific for surfactant protein D (SP-D) gene to detect circulating tumor cells in the peripheral blood of lung cancer patients, and to initiatively discuss its clinical significance. METHODS: The expression of SP-D mRNA was analyzed by an improved nested RT-PCR in the peripheral blood of 26 lung cancer patients with metastases, 37 lung cancer patients without metastases, 15 benign pneumonia patients, and 15 healthy volunteers. RESULTS: 1) The sensitivity of the method was 1 x 10(-6), with high level of specificity. 2) Using this method, the positive detection rate of the expression of SP-D mRNA was 92.3% (24/26) and 24.3% (9/37) in the peripheral blood of lung cancer patients with and without metastases, respectively. While no sample was positive for SP-D mRNA expression in the benign pneumonia patients and in the healthy volunteers. CONCLUSIONS: SP-D mRNA might be a valuable marker to detect circulating tumor cells in the peripheral blood of lung cancer patients. This method may be a valuable tool for early identification of metastases in asymptomatic lung cancer patients. Furthermore, it can also provide important clinical information for the evaluation of prognosis and in the selection of appropriate treatment strategies.