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Prostate adenocarcinoma (PRAD), driven by both genetic and epigenetic factors, is a common malignancy that affects men worldwide. We aimed to identify and characterize differentially expressed epigenetic-related genes (ERGs) in PRAD and investigate their potential roles in disease progression and prognosis. We used PRAD samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to identify prognosis-associated ERGs. Thirteen ERGs with two distinct expression profiles were identified through consensus clustering. Gene set variation analysis highlighted differences in pathway activities, particularly in the Hedgehog and Notch pathways. Higher epigenetic scores correlated with favorable prognosis and improved immunotherapeutic response. Experimental validation underscored the importance of CBX3 and KAT2A, suggesting their pivotal roles in PRAD. This study provides crucial insights into the epigenetic scoring approach and presents a promising prognostic tool, with CBX3 and KAT2A as key players. These findings pave the way for targeted and personalized interventions for the treatment of PRAD.
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Benign prostatic hyperplasia (BPH) is a multifactorial disease in which abnormal growth factor activation and embryonic reawakening are considered important factors. Here we demonstrated that the aberrant activation of transforming growth factor ß (TGF-ß)/Rho kinase 1 (ROCK1) increased the stemness of BPH tissue by recruiting mesenchymal stem cells (MSCs), indicating the important role of embryonic reawakening in BPH. When TGF-ß/ROCK1 is abnormally activated, MSCs are recruited and differentiate into fibroblasts/myofibroblasts, leading to prostate stromal hyperplasia. Further research showed that inhibition of ROCK1 activation suppressed MSC migration and their potential for stromal differentiation. Collectively, our findings suggest that abnormal activation of TGF-ß/ROCK1 regulates stem cell lineage specificity, and the small molecule inhibitor GSK269962A could target ROCK1 and may be a potential treatment for BPH.
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Células-Tronco Mesenquimais , Hiperplasia Prostática , Fator de Crescimento Transformador beta , Quinases Associadas a rho , Quinases Associadas a rho/metabolismo , Masculino , Hiperplasia Prostática/patologia , Hiperplasia Prostática/metabolismo , Humanos , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/patologia , Fator de Crescimento Transformador beta/metabolismo , Animais , Diferenciação Celular , Próstata/patologia , Próstata/metabolismo , Movimento Celular , Camundongos , Células Estromais/metabolismo , Células Estromais/patologiaRESUMO
Benign prostatic hyperplasia (BPH) is a prevalent disease among middle-aged and elderly males, but its pathogenesis remains unclear. Dysbiosis of the microbiome is increasingly recognized as a significant factor in various human diseases. Prostate tissue also contains a unique microbiome, and its dysbiosis has been proposed to contribute to prostate diseases. Here, we obtained prostate tissues and preoperative catheterized urine from 24 BPH individuals, and 8 normal prostate samples as controls, which followed strict aseptic measures. Using metagenomic next-generation sequencing (mNGS), we found the disparities in the microbiome composition between normal and BPH tissues, with Pseudomonas significantly enriched in BPH tissues, as confirmed by fluorescence in situ hybridization (FISH). Additionally, we showed that the prostate microbiome differed from the urine microbiome. In vitro experiments revealed that lipopolysaccharide (LPS) of Pseudomonas activated NF-κB signalling, leading to inflammation, proliferation, and EMT processes, while inhibiting apoptosis in prostatic cells. Overall, our research determines the presence of microbiome dysbiosis in BPH, and suggests that Pseudomonas, as the dominant microflora, may promote the progression of BPH through LPS activation of NF-κB signalling.
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Microbiota , Hiperplasia Prostática , Masculino , Pessoa de Meia-Idade , Idoso , Humanos , Hiperplasia Prostática/patologia , NF-kappa B/genética , Pseudomonas , Disbiose , Hibridização in Situ Fluorescente , LipopolissacarídeosRESUMO
The research of the human microbiome in the preceding decade has yielded novel perspectives on human health and diseases. Benign prostatic hyperplasia (BPH) is a common disease in middle-aged and elderly males, which negatively affects the life quality. Existing evidence has indicated that the human microbiome, including urinary, intra-prostate, gut, oral and blood microbiome may exert a significant impact on the natural progression of BPH. The dysbiosis of the microbiome may induce inflammation at either a local or systemic level, thereby affecting the BPH. Moreover, metabolic syndrome (MetS) caused by the microbiome can also be involved in the development of BPH. Additionally, alterations in the microbiome composition during the senility process may serve as another cause of the BPH. Here, we summarize the influence of human microbiome on BPH and explore how the microbiome is linked to BPH through inflammation, MetS, and senility. In addition, we propose promising areas of investigation and discuss the implications for advancing therapeutic approaches.
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Síndrome Metabólica , Microbiota , Hiperplasia Prostática , Masculino , Idoso , Pessoa de Meia-Idade , Humanos , Hiperplasia Prostática/etiologia , Hiperplasia Prostática/metabolismo , Inflamação , Síndrome Metabólica/complicaçõesRESUMO
PURPOSE: To determine the difference in the burden of benign prostatic hyperplasia (BPH) between China and the United States from 1990 to 2019. METHODS: The prevalence, incidence, Years Lived with Disability (YLD), and their age-standardized rates for BPH in China and USA from 1990 to 2019 were based on the Global Burden of Disease Study 2019 (GBD 2019). The annual percentage changes (APC) of the age-standardized incidence rate (ASIR) and the age-standardized YLD rates (ASYR) were calculated using joinpoint regression analysis. The YLD numbers of six urinary tract diseases were also compared in both countries. RESULTS: The absolute burden of BPH increased continuously in both countries, but it was much higher in China than in the United States. The ASIR and ASYR of BPH decreased in China but remained stable or decreased slightly in the United States. BPH incidence and YLD rates decreased in all age groups in China from 1990 to 2019. In the USA, they varied by age group. BPH caused more YLD number than any other urinary tract disease in China. In the USA, prostate cancer (PCa) caused more YLDs than BPH. CONCLUSIONS: This research reveals marked BPH burden differences between China and the US (1990-2019). China's higher burden necessitates targeted interventions, while unique trends in both countries demand tailored strategies. These insights enhance understanding of BPH dynamics, informing effective interventions across diverse contexts.
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Carga Global da Doença , Hiperplasia Prostática , Masculino , Humanos , Estados Unidos/epidemiologia , Hiperplasia Prostática/epidemiologia , Incidência , Prevalência , China/epidemiologia , Anos de Vida Ajustados por Qualidade de VidaRESUMO
In this experiment, a gas-liquid two-phase discharge water treatment inverse device was designed independently to treat the actual workshop intermediate dye wastewater from a chemical plant. Firstly, the effects of initial concentration of wastewater, initial pH, circulation flow rate of solution, content of Fe2+, content of H2O2, and addition of tert-butanol on the organic removal rate and decolorization rate of dye wastewater treatment were investigated. The results showed that Fe2+ and tert-butanol would react with the active particles (H2O2, ·OH) and inhibit the degradation of the dye wastewater, resulting in the decrease of both organic matter degradation rate and decolorization rate. The experimentally degraded dye wastewater mainly contained benzoic acid and its derivatives in addition to dye molecules, thus the degradation mechanism of benzoic acid was mainly analyzed. Then, the actual dye wastewater treated by low-temperature plasma was combined with the traditional biological treatment technology. The biochemical properties of the wastewater treated by low-temperature plasma technology were greatly improved, and the B/C was increased from the initial 0.17 to 0.33. The effluent after the combined biological method could meet the effluent discharge standard, and the final CODcr reached 198 mg/L, BOD5 reached 65 mg/L, and pH and chromaticity reached 6.39 and 50, respectively.
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Águas Residuárias , Poluentes Químicos da Água , Eliminação de Resíduos Líquidos/métodos , Peróxido de Hidrogênio/química , terc-Butil Álcool , Biotecnologia , Poluentes Químicos da Água/química , Corantes/químicaRESUMO
Coronavirus Disease 2019 (COVID-19), instigated by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has hugely impacted global public health. To identify and intervene in critically ill patients early, this paper proposes an efficient, intelligent prediction model based on the machine learning approach, which combines the improved whale optimization algorithm (RRWOA) with the k-nearest neighbor (KNN) classifier. In order to improve the problem that WOA is prone to fall into local optimum, an improved version named RRWOA is proposed based on the random contraction strategy (RCS) and the Rosenbrock method. To verify the capability of the proposed algorithm, RRWOA is tested against nine classical metaheuristics, nine advanced metaheuristics, and seven well-known WOA variants based on 30 IEEE CEC2014 competition functions, respectively. The experimental results in mean, standard deviation, the Friedman test, and the Wilcoxon signed-rank test are considered, proving that RRWOA won first place on 18, 24, and 25 test functions, respectively. In addition, a binary version of the algorithm, called BRRWOA, is developed for feature selection problems. An efficient prediction model based on BRRWOA and KNN classifier is proposed and compared with seven existing binary metaheuristics based on 15 datasets of UCI repositories. The experimental results show that the proposed algorithm obtains the smallest fitness value in eleven datasets and can solve combinatorial optimization problems, indicating that it still performs well in discrete cases. More importantly, the model was compared with five other algorithms on the COVID-19 dataset. The experiment outcomes demonstrate that the model offers a scientific framework to support clinical diagnostic decision-making. Therefore, RRWOA is an effectively improved optimizer with efficient value.
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Benign prostatic hyperplasia (BPH) is a common disease among aging males. We obtained BPH transcriptional signatures by high-throughput RNA sequencing analysis. Accordingly, we determined the differentially expressed RNAs (DERNAs) between BPH tissues and normal prostate tissues. WebGestalt and R package (clusterprofiler) was used to enrichment analysis. Clinical correlations were analyzed using Spearman's coefficient. TargetScan, ENCORI, miRNet, and miRDB databases were used to predict targets' relationships in ceRNA networks. Immunofluorescence staining and qRT-PCR analyses were performed to validate the findings. Microarray analysis of the datasets showed 369 DElncRNAs, 122 DEpseudogenes, 6 DEmiRNAs and 1358 DEmRNAs. DEmRNAs were particularly enriched in the autophagy-related pathways. Following the screening of DEmRNAs and autophagy-related genes (ARGs), 50 DEARGs were selected. MCODE analysis on Cytoscape was performed for the 50 DEARGs, and 3 hub genes (ATF4, XBP1, and PPP1R15A) were obtained. Spearman's correlation analysis showed that the mRNA expression of XBP1 correlated positively with age, total score, and storage score, but negatively with the maximum flow rate. Subsequently, the pseudogene/lncRNA- hsa-miR-222-3p-XBP1 pathway was identified. Our findings elucidate that the pseudogene/lncRNA-hsa-miR-222-3p-XBP1 pathway may play a regulatory role in the occurrence of BPH through autophagy.
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MicroRNAs , Hiperplasia Prostática , RNA Longo não Codificante , Masculino , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Hiperplasia Prostática/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Redes Reguladoras de GenesRESUMO
Uncontrolled epithelial cell proliferation in the prostate transition zone and the hyper-accumulation of mesenchymal-like cells derived from the epithelial-mesenchymal transition (EMT) of prostatic epithelium are two key processes in benign prostatic hyperplasia (BPH). m6A RNA modification affects multiple cellular processes, including cell proliferation, apoptosis, and differentiation. In this study, the aberrant up-regulation of methylase METTL3 in BPH samples suggests its potential role in BPH development. Elevated m6A modification in the prostate of the BPH rat was partially reduced by METTL3 knockdown. METTL3 knockdown also partially reduced the prostatic epithelial thickness and prostate weight, significantly improved the histological features of the prostate, inhibited epithelial proliferation and EMT, and promoted apoptosis. In vitro, METTL3 knockdown decreased TGF-ß-stimulated BPH-1 cell proliferation, m6A modification, and EMT, whereas promoted cell apoptosis. METTL3 increased the m6A modification of PTEN and inhibited its expression through the reading protein YTHDF2. PTEN knockdown aggravated the molecular, cellular, and pathological alterations in the prostate of BPH rats and amplified TGF-ß-induced changes in BPH-1 cells. More importantly, PTEN knockdown partially abolished the improving effects of METTL3 knockdown both in vivo and in vitro. In conclusion, the level of m6A modification is elevated in BPH; the METTL3/YTHDF2/PTEN axis disturbs the balance between epithelial proliferation and apoptosis, promotes EMT, and accelerates BPH development in an m6A modification-related manner.