Inverse correlation between the expression of AMPK/SIRT1 and NAMPT in psoriatic skin: A pilot study

PurposeEpidermal hyperplasia and the involvement of immune cells characterize the clinical picture of psoriasis. Among the several factors involved, attention has been focused on sirtuin 1 (SIRT1) - a deacetylase endowed with a variety of functions including the control of metabolic and inflammatory processes-, and on nicotinamide phosphoribosyltransferase (NAMPT), important for SIRT1 activation and involved in inflammatory events. The aim of the study was to analyze changes of SIRT1 and NAMPT expression in psoriatic skin.Patients and methodsSamples from healthy controls and psoriatic patients were subjected to immunohistochemical analysis.ResultsA strong downregulation of SIRT1 expression was observed in skin samples from psoriatic patients compared to healthy controls. This was accompanied by a parallel reduction of adenosine monophosphate-activated kinase (AMPK) expression and, more strikingly, by the disappearance of cells immunolabeled for its active, phosphorylated form (pAMPK). In both cases, analysis of the distribution of immunopositive cells revealed a shift towards reduced intensity of staining. In contrast, NAMPT expression was upregulated in psoriatic samples in line with its pro-inflammatory role. This was again more visible with an intensity-based distribution analysis that evidenced a shift towards more intensely immunostained cell populations.ConclusionsThe present data correlate in the same samples the expression of SIRT1, pAMPK/AMPK and NAMPT in psoriasis and open the way for novel pharmacological targets in the treatment of the disease.     

Cancer Stem Cells and Circulatory Tumor Cells Promote Breast Cancer Metastasis

Breast cancer (BC) is a highly metastatic, pathological cancer that significantly affects women worldwide. The mortality rate of BC is related to its heterogeneity, aggressive phenotype, and metastasis. Recent studies have highlighted that the tumor microenvironment (TME) is critical for the interplay between metastasis mediators in BC. BC stem cells, tumor-derived exosomes, circulatory tumor cells (CTCs), and signaling pathways dynamically remodel the TME and promote metastasis. This review examines the cellular and molecular mechanisms governing the epithelial to mesenchymal transition (EMT) that facilitate metastasis. This review also discusses the role of cancer stem cells (CSCs), tumor-derived exosomes, and CTs in promoting BC metastasis. Furthermore, the review emphasizes major signaling pathways that mediate metastasis in BC. Finally, the interplay among CSCs, exosomes, and CTCs in mediating metastasis have been highlighted. Therefore, understanding the molecular cues that mediate the association of CSCs, exosomes, and CTCs in TME helps to optimize systemic therapy to target metastatic BC.     

Adherence to a Mediterranean Lifestyle and Changes in Frequency,Severity, and Localization of Pain in Older Adults

ObjectiveTo assess the association between adherence to a Mediterranean lifestyle and changes in pain, and its characteristics over time in older adults.Patients and MethodsWe analyzed data from 864 and 862 community-dwelling individuals aged 65+ years from the Study on Cardiovascular Health, Nutrition and Frailty in Older Adults in Spain (Seniors-ENRICA) Seniors-ENRICA-1 (2008–2010 to 2012) and Seniors-ENRICA-2 (2015–2017 to 2019) cohorts, with a median follow-up of 2.8 and 2.4 years, respectively. Adherence to a Mediterranean lifestyle was assessed at baseline with the 27-item Mediterranean lifestyle (MEDLIFE) index. Pain changes over time were calculated with a pain scale that assessed the frequency, severity, and the number of pain locations both at baseline and follow-up. Multivariable-adjusted relative risk ratios (RRRs) were obtained using multinomial logistic regression.ResultsIn the pooled cohorts, after a median follow-up of 2.6 years, pain worsened for 697 participants, improved for 734, and did not change for 295. Compared with the lowest category of MEDLIFE adherence, those in the highest category showed an RRR of improvement vs worsening of overall pain of 1.85 (95% CI, 1.28 to 2.67; P-trend<.001). MEDLIFE adherence was also linked to improvement in pain frequency (RRR, 1.98; 95% CI, 1.31 to 3.01; P-trend=.001), pain severity (RRR, 2.00; 95% CI, 1.33 to 3.00; P-trend=.001), and a reduction in the number of pain locations (RRR, 1.68; 95% CI, 1.13 to 2.50; P-trend=.004). Limitations of this study are the use of self-reported lifestyle data.ConclusionA Mediterranean lifestyle was associated with improvement of pain characteristics in older adults. Experimental studies should assess the efficacy of an integral lifestyle approach for the management of pain in older adults.