Proangiogenic potential of plasma exosomes from prostate cancer patients.

Angiogenesis plays a pivotal role in the progression and metastasis of solid cancers, including prostate cancer (PCa). While small extracellular vesicles derived from PCa cell lines induce a proangiogenic phenotype in vascular endothelial cells, the contribution of plasma exosomes from patients with PCa to this process remains unclear. Here, we successfully extracted and characterized plasma exosomes. Notably, a ring of PKH67-labeled exosomes was observed around the HUVEC nucleus using fluorescence microscopy, indicating the uptake of exosomes by HUVEC. At the cellular level, PCa plasma exosomes enhanced angiogenesis, proliferation, invasion, and migration of HUVEC cells. Moreover, PCa plasma exosomes promoted angiogenesis and aortic sprouting. MicroRNAs are the most common genetic material in exosomes, and to identify miRNAs associated with the angiogenic response, we performed small RNA sequencing followed by RT-qPCR and bioinformatics analysis. These analyses revealed distinct miRNA profiles in plasma exosomes from patients with PCa compared to healthy individuals. Notably, hsa-miR-184 emerged as a potential regulator implicated in the proangiogenic effects of PCa plasma exosomes.

Integrating plasma exosomal miRNAs, ultrasound radiomics and tPSA for the diagnosis and prediction of early prostate cancer: a multi-center study.

INTRODUCTION: This multi-center study aims to explore the roles of plasma exosomal microRNAs (miRNAs), ultrasound (US) radiomics, and total prostate-specific antigen (tPSA) levels in early prostate cancer detection. METHODS: We analyzed the publicly available dataset GSE112264 to identify the differentially expressed miRNAs associated with prostate cancer. Then, PyRadiomics was used to extract image features, and least absolute shrinkage and selection operator (LASSO) was used to screen the data. Subsequently, according to strict inclusion and exclusion criteria, the internal dataset (n = 199) was used to construct a diagnostic model, and the receiver operating characteristic (ROC) curve, calibration curve, decision curve analysis (DCA), and DeLong test were used to evaluate its diagnostic performance. Finally, we used an external dataset (n = 158) for further validation. RESULTS: The number of features extracted by PyRadiomics was 851, and the number of features screened by LASSO was 23. We combined the hsa-miR-320c, hsa-miR-944, radiomics, and tPSA features to construct a joint model. The area under the ROC curve of the combined model was 0.935. In the internal validation, the area under the curve (AUC) of the training set was 0.943, and the AUC of the test set was 0.946. The AUC of the external data set was 0.910. The calibration curve and decision curve were consistent with the performance of the combined model. There was a significant difference in the prediction ability between the combined prediction model and the single index prediction model, indicating the high credibility and accuracy of the combined model in predicting PCa. CONCLUSIONS: The combined prediction model, consisting of plasma exosomal miRNAs (hsa-miR-320c and hsa-miR-944), US radiomics, and clinical tPSA, can be utilized for the early diagnosis of prostate cancer.

BCI Improves Alcohol-Induced Cognitive and Emotional Impairments by Restoring pERK-BDNF.

Binge drinking causes a range of problems especially damage to the nervous system, and the specific neural mechanism of brain loss and behavioral abnormalities caused by which is still unclear. Extracellular regulated protein kinases (ERK) maintain neuronal survival, growth, and regulation of synaptic plasticity by phosphorylating specific transcription factors to regulate expression of brain-derived neurotrophic factor (BDNF). Dual-specific phosphatase 1 (DUSP1) and DUSP6 dephosphorylate tyrosine and serine/threonine residues in ERK1/2 to inactivate them. To investigate the molecular mechanism by which alcohol affects memory and emotion, a chronic intermittent alcohol exposure (CIAE) model was established. The results demonstrated that mice in the CIAE group developed short-term recognition memory impairment and anxiety-like behavior; meanwhile, the expression of DUSP1 and DUSP66 in the mPFC was increased, while the levels of p-ERK and BDNF were decreased. Micro-injection of DUSP1/6 inhibitor BCI into the medial prefrontal cortex (mPFC) restored the dendritic morphology by reversing the activity of ERK-BDNF and ultimately improved cognitive and emotional impairment caused by CIAE. These findings indicate that CIAE inhibits ERK-BDNF by increasing DUSP1/6 in the mPFC that may be associated with cognitive and emotional deficits. Consequently, DUSP1 and DUSP6 appear to be potential targets for the treatment of alcoholic brain disorders.

Advanced slime mould algorithm incorporating differential evolution and Powell mechanism for engineering design.

The slime mould algorithm (SMA) is a population-based swarm intelligence optimization algorithm that simulates the oscillatory foraging behavior of slime moulds. To overcome its drawbacks of slow convergence speed and premature convergence, this paper proposes an improved algorithm named PSMADE, which integrates the differential evolution algorithm (DE) and the Powell mechanism. PSMADE utilizes crossover and mutation operations of DE to enhance individual diversity and improve global search capability. Additionally, it incorporates the Powell mechanism with a taboo table to strengthen local search and facilitate convergence toward better solutions. The performance of PSMADE is evaluated by comparing it with 14 metaheuristic algorithms (MA) and 15 improved MAs on the CEC 2014 benchmarks, as well as solving four constrained real-world engineering problems. Experimental results demonstrate that PSMADE effectively compensates for the limitations of SMA and exhibits outstanding performance in solving various complex problems, showing potential as an effective problem-solving tool.

COVID-19 Vaccine in Renal Transplant Recipients: A Bibliometric-Based Analysis of Trends.

BACKGROUND: The global community has been affected by COVID-19, which emerged in December 2019. Since then, many studies have been conducted on kidney transplant recipients (KTRs) and COVID-19. This study aimed to perform a bibliometric and visual analysis of the published relationship between KTRs and COVID-19. OBJECTIVE: To discuss the current status, hot spots, and development trend of research on KTRs vaccination with the COVID-19 vaccine and to provide a reference for researchers in related fields. METHODS: Visual analysis of countries/regions, institutions, authors, references cited, and keywords for 2020 to 2023 via Microsoft Office Excel 2019 and CiteSpace (6.1.R6) based on the Web of Science core database. RESULTS: A total of 366 publications were included after screening, with a rapid increase in the global literature studying the COVID-19 vaccine of KTRs. The US has the highest number of publications, indicating that it is the leading country in this field of research. Charite University of Medicine Berlin and Schrezenmeier E are the most published institutions and authors, respectively. "Antibody Response After a Third Dose of the messenger RNA-1273 SARS-CoV-2 Vaccine in Kidney Transplant Recipients With Minimal Serologic Response to 2 Doses" is the most central co-cited reference; The keywords "kidney transplant recipient," "covid 19 vaccine," and "mortality" have become hot topics of research. The keywords "humoral response" and "bnt162b2" are the latest research frontiers for detecting bursts. CONCLUSIONS: This paper analyzed the current status and trends of vaccination studies in KTRs through bibliometric analysis. Several studies support the vaccination of KTRs with the COVID-19 vaccine. However, the evidence for improving vaccine efficacy by adjustment of immunosuppression is still limited, and future studies on vaccination will remain a hot topic in this field.

Multiparametric MRI radiomics in prostate cancer for predicting Ki-67 expression and Gleason score: a multicenter retrospective study.

PURPOSE: Prostate cancer (PCa) with high Ki-67 expression and high Gleason Scores (GS) tends to have aggressive clinicopathological characteristics and a dismal prognosis. In order to predict the Ki-67 expression status and the GS in PCa, we sought to construct and verify MRI-based radiomics signatures. METHODS AND MATERIALS: We collected T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and apparent diffusion coefficient (ADC) images from 170 PCa patients at three institutions and extracted 321 original radiomic features from each image modality. We used support vector machine (SVM) and least absolute shrinkage and selection operator (LASSO) logistic regression to select the most informative radiomic features and built predictive models using up sampling and feature selection techniques. Using receiver operating characteristic (ROC) analysis, the discriminating power of this feature was determined. Subsequent decision curve analysis (DCA) assessed the clinical utility of the radiomic features. The Kaplan-Meier (KM) test revealed that the radiomics-predicted Ki-67 expression status and GS were prognostic factors for PCa survival. RESULT: The hypothesized radiomics signature, which included 15 and 9 selected radiomics features, respectively, was significantly correlated with pathological Ki-67 and GS outcomes in both the training and validation datasets. Areas under the curve (AUC) for the developed model were 0.813 (95% CI 0.681,0.930) and 0.793 (95% CI 0.621, 0.929) for the training and validation datasets, respectively, demonstrating discrimination and calibration performance. The model's clinical usefulness was verified using DCA. In both the training and validation sets, high Ki-67 expression and high GS predicted by radiomics using SVM models were substantially linked with poor overall survival (OS). CONCLUSIONS: Both Ki-67 expression status and high GS correlate with PCa patient survival outcomes; therefore, the ability of the SVM classifier-based model to estimate Ki-67 expression status and the Lasso classifier-based model to assess high GS may enhance clinical decision-making.

Porphin e6 complex loaded with gold nanorod mesoporous silica enhances photodynamic therapy in ovarian cancer cells in vitro.

A growing amount of experimental evidence has proven that the application of gold nanorods (AuNRs) in photodynamic therapy (PDT) can significantly enhance its therapeutic efficacy. The aim of this study was to establish a protocol for investigating the effect of gold nanorods loaded with the photosensitizer chlorin e6 (Ce6) on photodynamic therapy in the OVCAR3 human ovarian cancer cell line in vitro and to determine whether the PDT effect was different from that of Ce6 alone. OVCAR3 cells were randomly divided into three groups: the control group, Ce6-PDT group, and AuNRs@SiO2@Ce6-PDT group. Cell viability was measured by MTT assay. The generation of reactive oxygen species (ROS) was measured by a fluorescence microplate reader. Cell apoptosis was detected by flow cytometry. The expression of apoptotic proteins was detected by immunofluorescence and western blotting. The results showed that compared with that of the Ce6-PDT group, the cell viability of the AuNRs@SiO2@Ce6-PDT group was significantly decreased (P < 0.05) in a dose-dependent manner, and ROS production increased significantly (P < 0.05). The flow cytometry results showed that the proportion of apoptotic cells in the AuNRs@SiO2@Ce6-PDT group was significantly higher than that in the Ce6-PDT group (P < 0.05). Immunofluorescence and western blot results showed that the protein expression levels of cleaved caspase-9, cleaved caspase-3, cleaved PARP, and Bax in the AuNRs@SiO2@Ce6-PDT-treated-OVCAR3 cells were higher than those in the Ce6-PDT-treated cells (P < 0.05), and the protein expression levels of caspase-3, caspase-9, PARP, and Bcl-2 were slightly lower than those in the Ce6-PDT group (P < 0.05). In summary, our results show that AuNRs@SiO2@Ce6-PDT has a significantly stronger effect on OVCAR3 cells than the effect of Ce6-PDT alone. The mechanism may be related to the expression of Bcl-2 family and caspase family in the mitochondrial pathway.

Study on the effect of 5-aminolevulinic acid-mediated photodynamic therapy combined with cisplatin on human ovarian cancer OVCAR-3 ​cells.

PURPOSE: This article explores the effect of 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) combined with cisplatin (CDDP) on the apoptosis of human ovarian cancer cells and the mechanism of action of the combination therapy. MATERIALS AND METHODS: Human ovarian cancer OVCAR-3 â€‹cells were cultured in vitro and divided into 5-ALA/PDT group, CDDP group and combined treatment group (5-ALA/PDT combined with different concentrations of CDDP). After administration of the corresponding drugs, a CCK-8 assay was used to detect the inhibition rate of cell proliferation. After Rhodamine 123 staining, mitochondrial membrane potential changes were observed under fluorescence microscopy. The apoptosis rate and reactive oxygen species (ROS) content were detected by flow cytometry. Western blotting was used to detect protein expression. RESULTS: The CCK-8 assay showed that CDDP in combination with 5-ALA/PDT significantly enhanced cytotoxicity compared to treatment with CDDP alone and that low doses of CDDP were sufficient to induce these combination effects. The mitochondrial membrane potential in each combination treatment group gradually decreased with increasing CDDP concentration, while the apoptosis rate and reactive oxygen species (ROS) content detected by flow cytometry gradually increased. Western blotting assay showed that the expression of bax, cleaved caspase-9, cleaved caspase-3, and cleaved PARP was increased, while the expression of bcl-2, caspase-9, caspase-3, and PARP was decreased, and the differences were statistically significant (P â€‹< â€‹0.05). CONCLUSIONS: In summary, 5-ALA/PDT combined with CDDP can effectively inhibit cell proliferation and promote apoptosis, and this combination may induce apoptosis by activating the mitochondrial pathway.

Effects of dexmedetomidine on cellular immunity of perioperative period in children with brain neoplasms.

OBJECTIVE: To study the effects of dexmedetomidine (Dex) on cellular immunity during the perioperative period in children with brain neoplasms. METHODS: Forty children with brain neoplasms scheduled for selective operation were recruited and divided randomly into two groups. The Dex group was given a loading dose of 1 µg*kg(-1) Dex 15 minutes before anesthesia induction followed by a continuous infusion of 0.5 µg × kg(-1) × h(-1) Dex. Patients in control group received a same volume of normal saline for a same time period. Venous blood was collected before anesthesia (T0), 1 h after operation started (T1), immediately after operation ended (T2), 1 day after operation (T3) and 3 days after operation (T4), respectively. RESULTS: CD3 (+), CD4 (+), CD4 (+)/CD8 (+), NK and B cells at T1-T3 decreased significantly (P < 0.05) in both groups compared with those at T0, while the decrease of CD3 (+), CD4 (+), CD4 (+)/CD8 (+) and NK cells at T1-T3 and B cells at T1-T2 in Dex group was significantly less than the control group (P < 0.05). All values at T4 recovered to the level before anesthesia in both groups. CONCLUSION: Dex given by a continuous intravenous infusion during general anesthesia may effectively inhibit the stress responses and reduce the inhibition of cellular immunity in children with brain neoplasms during the perioperative period.

Structural stability of different reconstruction techniques following total sacrectomy: a biomechanical study.

BACKGROUND: The biomechanical stability of spino-pelvis structure after varying reconstruction methods following total sacrectomy remains poorly defined. The objective of this study was to compare the structural stability of different reconstruction techniques. METHODS: Six fresh human cadavers (L2-pelvis-femora) were used to compare biomechanical stability after reconstruction using four different techniques: (1) sacral rod reconstruction; (2) bilateral fibular flap reconstruction; (3) four-rod reconstruction; and (4) improved compound reconstruction. After total sacrectomy, the construction was carried out using each method once in each cadaver. Structural stiffness was evaluated by linear and angular ranges of motion. L5 relative shift-down displacement, abduction angle on the coronal plane and rotation angle on the sagittal plane, were calculated based on displacement of the identification point under 500N axial loading. Overall stiffness was estimated using load displacement curve. FINDINGS: Improved compound reconstruction resulted in significantly higher stiffness than all three other techniques. The structural stability following bilateral fibular flap reconstruction was superior to that after sacral rod reconstruction. Four-rod reconstruction achieved worst stability due to the lack of anterior bracing applied in three other methods. INTERPRETATION: Improved compound reconstruction produces optimal structural stability after total sacrectomy. This finding suggests that both anterior bracing and alternation of screw trajectory are important in achieving optimal structural stability.