Polymorphisms of an Innate Immune Gene, Toll-Like Receptor 4, and Aggressive Prostate Cancer Risk: A Systematic Review and Meta-Analysis

Background: Toll-like receptor 4 (TLR4) is one of the best known TLR members expressed on the surface of several leukocytes and tissue cells and has a key function in detecting pathogen and danger-associated molecular patterns. The role of TLR4 in the pathophysiology of several age-related diseases is also well recognized, such as prostate cancer (PCa). TLR4 polymorphisms have been related to PCa risk, but the relationship between TLR4 genotypes and aggressive PCa risk has not been evaluated by any systematic reviews. Methods: We performed a systematic review and meta-analysis of candidate-gene and genome-wide association studies analyzing this relationship and included only white population. Considering appropriate criteria, only nine studies were analyzed in the meta-analysis, including 3,937 aggressive PCa and 7,382 controls. Results: Using random effects model, no significant association was found in the ten TLR4 SNPs reported by at least four included studies under any inheritance model (rs2737191, rs1927914, rs10759932, rs1927911, rs11536879, rs2149356, rs4986790, rs11536889, rs7873784, and rs1554973). Pooled estimates from another ten TLR4 SNPs reported by three studies also showed no significant association (rs10759930, rs10116253, rs11536869, rs5030717, rs4986791, rs11536897, rs1927906, rs913930, rs1927905, and rs7045953). Meta-regression revealed that study type was not a significant source of between-study heterogeneity. Conclusions: TLR4 polymorphisms were not significantly associated with the risk of aggressive PCa

Cellular Senescence and Inflammaging in Age-Related Diseases

none4sirestrictedOlivieri, Fabiola; Prattichizzo, Francesco; Grillari, Johannes; Balistreri, Carmela R.*Olivieri, Fabiola; Prattichizzo, Francesco; Grillari, Johannes; Balistreri, Carmela R

Are Endothelial Progenitor Cells the Real Solution for Cardiovascular Diseases? Focus on Controversies and Perspectives

Advanced knowledge in the field of stem cell biology and their ability to provide a cue for counteracting several diseases are leading numerous researchers to focus their attention on “regenerative medicine” as possible solutions for cardiovascular diseases (CVDs). However, the lack of consistent evidence in this arena has hampered the clinical application. The same condition affects the research on endothelial progenitor cells (EPCs), creating more confusion than comprehension. In this review, this aspect is discussed with particular emphasis. In particular, we describe biology and physiology of EPCs, outline their clinical relevance as both new predictive, diagnostic, and prognostic CVD biomarkers and therapeutic agents, discuss advantages, disadvantages, and conflicting data about their use as possible solutions for vascular impairment and clinical applications, and finally underline a very crucial aspect of EPCs “characterization and definition,” which seems to be the real cause of large heterogeneity existing in literature data on this topic

Can the TLR-4-Mediated Signaling Pathway Be “A Key Inflammatory Promoter for Sporadic TAA”?

Thoracic aorta shows with advancing age various changes and a progressive deterioration in structure and function. As a result, vascular remodeling (VR) and medial degeneration (MD) occur as pathological entities responsible principally for the sporadic TAA onset. Little is known about their genetic, molecular, and cellular mechanisms. Recent evidence is proposing the strong role of a chronic immune/inflammatory process in their evocation and progression. Thus, we evaluated the potential role of Toll like receptor- (TLR-) 4-mediated signaling pathway and its polymorphisms in sporadic TAA. Genetic, immunohistochemical, and biochemical analyses were assessed. Interestingly, the rs4986790 TLR4 polymorphism confers a higher susceptibility for sporadic TAA (OR=14.4, P=0.0008) and it represents, together with rs1799752 ACE, rs3918242 MMP-9, and rs2285053 MMP-2 SNPs, an independent sporadic TAA risk factor. In consistency with these data, a significant association was observed between their combined risk genotype and sporadic TAA. Cases bearing this risk genotype showed higher systemic inflammatory mediator levels, significant inflammatory/immune infiltrate, a typical MD phenotype, lower telomere length, and positive correlations with histopatological abnormalities, hypertension, smoking, and ageing. Thus, TLR4 pathway should seem to have a key role in sporadic TAA. It might represent a potential useful tool for preventing and monitoring sporadic TAA and developing personalized treatments

Is the Serum N Terminal Pro-Brain Natriuretic Peptide the Best Candidate Biomarker for Long-term Prognosis in Patients with Prosthesis-patient Mismatch after Mitral Valve Replacement?

AGE8. Is the Serum N Terminal Pro-Brain Natriuretic Peptide the Best Candidate Biomarker for Long-term Prognosis in Patients with Prosthesis-patient Mismatch after Mitral Valve Replacement? C. R. Balistreri1, C. Pisano1, R. Franchino1, S.R. Vacirca1, F. Crapanzano1, O. F. Triolo1, C. Palmeri1, G. Ruvolo1 1University Of Palermo, Palermo, Italy Background: Natriuretic peptides (NPs) are released from the heart in response to pressure and volume overload. Among these, B-NP and Nterminal- proBNP (NT-proBNP) have become important diagnostic tools for the management of heart failure. However, B-NP and NT-proBNP levels reflect complications of systolic and diastolic function as well as alteration of right ventricular and valvular function. In addition, their serum levels have a prognostic value in multiple clinical settings. Based on these observations, we sought to evaluate the relationship between prosthesis patient mismatch (PPM) and serum NT-pro-BNP levels after mitral valve replacement (MVR). PPM following MVR has been less investigated and it seems to mediate deleterious effects on long-term survival, even if contrasting opinions and data exist in the literature. Methods: A total of 100 patients that have undergone this surgical treatment will be enrolled, and opportune clinical data and peripheral blood samples will be collected. Blood samples are utilized to analyze clinical conditions and serum NT-proBNP levels. Evaluation of hemodynamic performances before or under dobutamine infusion is also being assessed. Results: The preliminary data on the serum NT-proBNP levels obtained seem to be interesting and promising, as well as their correlations with hemodynamic performances. Conclusions: The demonstration of negative effects on tricuspid valve and pulmonary hypertension and consequently on survival induced by PPM after MVR through the serum quantification of NT-proBNP levels might lead to consider it as an optimal biomarker to evaluate patients’ long-term prognosis and optimize surgical recommendations (i.e. tricuspid valve repair during mitral valve surgery in patients with moderate-severe mismatch)