Prostate cancer (PCa) is the most prevalent cancer (20%) in males and is accountable for a fifth (6.8%) cancer-related deaths in males globally. Smoking, obesity, race/ethnicity, diet, age, chemicals and radiation exposure, sexually transmitted diseases, etc. are among the most common risk factors for PCa. However, the basic change at the molecular level is the manifested confirmation of PCa. Thus, this study aims to evaluate the molecular signature for PCa in comparison to benign prostatic hyperplasia (BPH). Additionally, representation of differentially expressed genes (DEGs) are conducted with the help of some bioinformatics tools like DAVID, STRING, GEPIA, Cytoscape. The gene expression profile for the four data sets GSE55945, GSE104749, GSE46602, and GSE32571 was downloaded from NCBI, Gene Expression Omnibus (GEO). For the extracted DEGs, different types of analysis including functional and pathway enrichment analysis, protein–protein interaction (PPI) network construction, survival analysis and transcription factor (TF) prediction were conducted. We obtained 633 most significant upregulated genes and 1219 downregulated genes, and a sum total of 1852 DEGs were found from all four datasets after assessment. The key genes, including EGFR, MYC, VEGFA, and PTEN, are targeted by TF such as AR, Sp1, TP53, NF-KB1, STAT3, RELA. Moreover, miR-21-5p also found significantly associated with all the four key genes. Further, The Cancer Genome Atlas data (TCGA) independent database was used for validation of key genes EGFR, MYC, VEGFA, PTEN expression in prostate adenocarcinoma. All four key genes were found to be significantly correlated with overall survival in PCa. Therefore, the therapeutic target may be determined by the information of these key gene’s findings for the diagnosis, prognosis and treatment of PCa.

Hypertension stands as the leading global cause of mortality, affecting one billion individuals and serving as a crucial risk indicator for cardiovascular morbidity and mortality. Elevated salt intake triggers inflammation and hypertension by activating antigen-presenting cells (APCs). We found that one of the primary reasons behind this pro-inflammatory response is the epithelial sodium channel (ENaC), responsible for transporting sodium ions into APCs and the activation of NADPH oxidase, leading to increased oxidative stress. Oxidative stress increases lipid peroxidation and the formation of pro-inflammatory isolevuglandins (IsoLG). Long noncoding RNAs (lncRNAs) play a crucial role in regulating gene expression, and MALAT1, broadly expressed across cell types, including blood vessels and inflammatory cells, is also associated with inflammation regulation. In hypertension, the decreased transcriptional activity of nuclear factor erythroid 2-related factor 2 (Nrf2 or Nfe2l2) correlates with heightened oxidative stress in APCs and impaired control of various antioxidant genes. Kelch-like ECH-associated protein 1 (Keap1), an intracellular inhibitor of Nrf2, exhibits elevated levels of hypertension. Sodium, through an increase in Sp1 transcription factor binding at its promoter, upregulates MALAT1 expression. Silencing MALAT1 inhibits sodium-induced Keap1 upregulation, facilitating the nuclear translocation of Nrf2 and subsequent antioxidant gene transcription. Thus, MALAT1, acting via the Keap1-Nrf2 pathway, modulates antioxidant defense in hypertension. This review explores the potential role of the lncRNA MALAT1 in controlling the Keap1-Nrf2-antioxidant defense pathway in salt-induced hypertension. The inhibition of MALAT1 holds therapeutic potential for the progression of salt-induced hypertension and cardiovascular disease (CVD).

Plasma microRNAs (miRNAs) have recently garnered attention for their potential as stable biomarkers in the context of Prostate Cancer (PCa), demonstrating established associations with tumor grade, biochemical recurrence (BCR), and metastasis. This study seeks to assess the utility of plasma miRNAs as prognostic indicators for distinguishing between high-grade and low-grade PCa, and to explore their involvement in PCa pathogenesis. We conducted miRNA profiling in both plasma and tissue specimens from patients with varying PCa grades. Subsequently, the identified miRNAs were validated in a substantial independent PCa cohort. Furthermore, we identified and confirmed the gene targets of these selected miRNAs through Western blot analysis. In our plasma profiling investigation, we identified 98, 132, and 154 differentially expressed miRNAs (DEMs) in high-grade PCa vs. benign prostatic hyperplasia (BPH), low-grade PCa vs. BPH, and high-grade PCa vs. low-grade PCa, respectively. Our tissue profiling study revealed 111, 132, and 257 statistically significant DEMs for the same comparisons. Notably, miR-373-3p emerged as the sole consistently dysregulated miRNA in both plasma and tissue samples of PCa. This miRNA displayed significant overexpression in plasma and tissue samples, with fold changes of 3.584 ± 0.5638 and 8.796 ± 1.245, respectively. Furthermore, we observed a significant reduction in KPNA2 protein expression in PCa. Our findings lend support to the potential of plasma miR-373-3p as a valuable biomarker for predicting and diagnosing PCa. Additionally, this miRNA may contribute to the progression of PCa by inhibiting KPNA2 expression, shedding light on its role in the disease.

Background: Ulcerative colitis (UC) is a prevalent inflammatory bowel disease primarily impacting the mucosa of the colon. It is characterized by recurring and incurable symptoms and causes immense suffering and significant economic burden due to limited treatment options. Typical symptoms of UC include diarrhea, alterations in bowel patterns, bleeding from the rectum, rectal pain or urgency, anemia, and tiredness. Therefore, developing novel and effective treatment strategies for UC is imperative. Purpose: This review aimed to explain how macrophage polarization contributes to UC development and compiled information on natural compounds with promising therapeutic potential that can target the macrophage phenotype and shed light on its potential mode of action. Results: The phenotypic alteration of macrophages profoundly affects the development of UC, and these cells are essential for preserving intestinal immunological homeostasis. Evidence from research suggests that one effective method for UC prevention and therapy is to guide macrophage polarization toward the M2 phenotype. Phytochemicals, which are compounds extracted from plants, possess a wide array of biological activities. For example: Ginsenoside Rg1 emerges as a crucial regulator of macrophage polarization, promoting the M2 phenotype while inhibiting the M1 phenotype. Notably, their low toxicity and high effectiveness render them promising candidates for therapeutic interventions. These compounds have demonstrated encouraging protective effects against inflammation in the colon. Conclusions: Exploring phytochemicals as a therapeutic avenue targeting macrophage polarization presents an innovative approach to treating UC.

BACKGROUND: Salt-sensitivity of blood pressure is an independent risk factor for cardiovascular diseases, yet the molecular pathways linking dietary sodium to immune activation and hypertension remain poorly defined. We previously demonstrated that sodium entry into antigen-presenting cells via the ENaC (epithelial sodium channel) promotes inflammation and salt-sensitivity of blood pressure. AP-1 (activator protein-1; c-FOS, FOSB, c-JUN, JUNB, JUND) regulates inflammatory signaling, but its role in salt-sensitivity of blood pressure has not been elucidated. We hypothesized that high salt drives AP-1-mediated inflammatory activation in antigen-presenting cells, contributing to immune dysfunction and hypertension. METHODS: Using SV129 salt-sensitive mice, we assessed blood pressure responses and profiled immune cell phenotypes under normal- and high-salt conditions by flow cytometry. RNA-seq was performed on human monocytes exposed to high salt in vitro. In a clinical study, we enrolled prehypertensive subjects and performed an inpatient salt-loading/depletion protocol to characterize AP-1 gene expression signatures in salt-sensitive versus salt-resistant individuals. To test causality, we adoptively transferred PBMCs from salt-sensitive, salt-resistant, and salt-sensitive individuals pretreated with T5224 (a selective AP-1 inhibitor) into immunodeficient NSG-( K ^b D ^b ) ^null ( IA ) ^null humanized mice, followed by assessment of blood pressure, vascular reactivity, kidney function, and immune infiltration. RESULTS: High salt robustly induced AP-1 gene expression in murine monocytes. In humans, salt-sensitive but not salt-resistant subjects exhibited concordant increases in AP-1 gene expression and blood pressure during salt loading. PBMCs from salt-sensitive individuals promoted greater tissue infiltration, AP-1 activation, and immune-mediated renal and vascular dysfunction in humanized mice compared with PBMCs from salt-resistant individuals. Strikingly, pretreatment of salt-sensitive PBMCs with T5224 abrogated these effects, preserving normal renal and vascular function despite high-salt exposure. CONCLUSIONS: These findings identify AP-1 as a key transcriptional driver linking dietary sodium, immune activation, and salt-sensitivity of blood pressure. Targeting AP-1 signaling mitigates immune-mediated renal and vascular injury, highlighting a novel mechanistic pathway and a therapeutic target for salt-sensitive hypertension.