Prostate cancer (PCa) represents a major public health concern and continues to be one of the leading causes of cancer‐related mortality among men worldwide. Current epidemiological projections suggest that the incidence and associated burden of PCa are likely to increase, emphasizing the importance of advancing preventive measures, improving early diagnostic approaches, and refining targeted therapeutic strategies. While established risk factors, including age, genetic predisposition, lifestyle‐related factors, ethnicity, and androgen signaling, have been extensively studied, these factors alone do not fully explain the observed patterns of PCa development. Increasing evidence suggests that infection‐associated chronic inflammation plays a central role in prostate tumor initiation and progression. Chronic inflammation of the prostate, arising from conditions such as prostatitis, benign prostatic hyperplasia (BPH), lower urinary tract infections (UTIs), sexually transmitted infections (STIs), and prolonged or repeated catheterization, has been associated with histological and molecular changes that may predispose prostate tissue to malignant transformation. Moreover, emerging evidence suggests that alterations in the prostate microbiome may sustain inflammatory signaling, thereby influencing tumor initiation and progression. This review synthesizes current epidemiological findings and experimental evidence linking infection‐associated inflammation to the development of PCa. Particular focus is placed on inflammatory signaling pathways implicated in prostate tumorigenesis, including nuclear factor kappa B (NF‐κB), signal transducer and activator of transcription 3 (STAT3), cyclooxygenase‐2/prostaglandin E2 (COX‐2/PGE2), interleukin‐6 and interleukin‐8 signaling, Toll‐like receptor (TLR) pathways, and activation of the NLRP3 inflammasome. In addition, we discuss therapeutic strategies that are aimed at modulating these pathways and their potential relevance in PCa management. A more comprehensive understanding of the interactions between infection, chronic inflammation, and PCa development may facilitate the identification of novel biomarkers and therapeutic targets. Such advances could ultimately contribute to improved risk stratification, earlier detection, and more effective treatment of PCa.
Ensiyeh Bahadoran, Abouzar Babaei, shahla shahbazi et al.· BioMed Research Internationa...· 0 citations
Background Stenotrophomonas maltophilia is a multidrug-resistant opportunistic pathogen causing severe hospital-acquired infections, especially in immunocompromised patients. The absence of an effective vaccine and rising antibiotic resistance underscore the need for novel interventions. This study employed an integrated reverse vaccinology and computational analyses to identify new immunogenic targets, design a multi-epitope vaccine (MEV), and propose potential drug targets. Methods A comprehensive immunoinformatics pipeline was employed to assess antigenicity, allergenicity, human similarity, and physicochemical properties of S. maltophilia proteins. Both B- and T-cell epitopes were screened; however, only the top B-cell epitopes were selected for MEV construction, given the extracellular nature of S. maltophilia. MEV–TLR interactions were analyzed through molecular docking and dynamics simulations. In parallel, cytoplasmic proteins were screened via a subtractive genomics approach to identify essential, non-human homologous, and non-microbiome-similar proteins, which were further evaluated for druggability and interaction networks to propose novel therapeutic targets. Results From a total of 4111 proteins, seven potential immunogenic targets were identified: GspD (WP_108270537.1), FhuE (WP_049451370.1), fimbrial protein (WP_012479122.1), TonB-dependent receptor (WP_169448402.1), TolC family protein (WP_108270106.1), autotransporter beta-barrel OMP (WP_169448945.1), and a hypothetical protein (WP_005407892.1). Subsequently, an MEV was designed using five immunogenic epitopes derived from four of these targets: WP_005407892.1 (ADQDSSNM), WP_049451370.1 (SGKAEQ and GEESKTPS), WP_108270537.1 (GVTSTQSDSERT), and WP_169448945.1 (RELGGDRNE). Molecular docking and molecular dynamics simulations demonstrated strong, stable, and feasible interactions between the MEV and TLR-2 and TLR-4 receptors. Moreover, nine novel drug targets were predicted for S. maltophilia, providing new therapeutic insights. Conclusion The designed MEV and identified immunogenic targets represent promising vaccine candidates against S. maltophilia. Further in vitro and in vivo studies are essential to confirm their safety, immunogenicity, and protective efficacy. Additionally, subtractive genomics analysis revealed nine novel, non-homologous drug targets, offering safer and more specific therapeutic avenues.
Safoura Moradkasani, Narjes Noori Goodarzi, M. Beig et al.· Journal of Genetic Engineeri...· 1 citation
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