Modulation of the Senescence-Associated Inflammatory Phenotype in Human Fibroblasts by Olive Phenols

Senescent cells display an increase in the secretion of growth factors, inflammatory cytokines and proteolytic enzymes, termed the “senescence-associated-secretory-phenotype” (SASP), playing a major role in many age-related diseases. The phenolic compounds present in extra-virgin olive oil are inhibitors of oxidative damage and have been reported to play a protective role in inflammation-related diseases. Particularly, hydroxytyrosol and oleuropein are the most abundant and more extensively studied. Pre-senescent human lung (MRC5) and neonatal human dermal (NHDF) fibroblasts were used as cellular model to evaluate the effect of chronic (4–6 weeks) treatment with 1 μM hydroxytyrosol (HT) or 10 μM oleuropein aglycone (OLE) on senescence/inflammation markers. Both phenols were effective in reducing β-galactosidase-positive cell number and p16 protein expression. In addition, senescence/inflammation markers such as IL-6 and metalloprotease secretion, and Ciclooxigenase type 2 (COX-2) and α-smooth-actin levels were reduced by phenol treatments. In NHDF, COX-2 expression, Nuclear Factor κ-light-chain-enhancer of activated B cells (NFκB) protein level and nuclear localization were augmented with culture senescence and decreased by OLE and HT treatment. Furthermore, the inflammatory effect of Tumor Necrosis Factor α (TNFα) exposure was almost completely abolished in OLE- and HT-pre-treated NHDF. Thus, the modulation of the senescence-associated inflammatory phenotype might be an important mechanism underlying the beneficial effects of olive oil phenols

Surgical approach to multifocal hepatocellular carcinoma with portal vein thrombosis and arterioportal shunt leading to portal hypertension and bleeding: a case report

It is reported the case of a 69 years man who presented to the Emergency Room because of pain and abdominal distension from ascites. After admission and paracentesis placement, he developed a digestive hemorrhage due to oesophageal varices from portal ipertension secondary to the formation of a portal shunt concomitant with a multifocal HepatoCellular Carcinoma (HCC) with portal vein thrombosis (PVT). The patient underwent endoscopic varices ligation, twice transarterial embolization (TAE) of arterial branches feeding the shunt and subsequent left hepatectomy. During the postoperative course he developed mild and transient signs of liver failure and was discharged in postoperative day 16. He is alive and disease free 8 months after surgery

New Treatment Options for Hyperkalemia in Patients with Chronic Kidney Disease

Hyperkalemia may cause life-threatening cardiac and neuromuscular alterations, and it is associated with high mortality rates. Its treatment includes a multifaceted approach, guided by potassium levels and clinical presentation. In general, treatment of hyperkalemia may be directed towards stabilizing cell membrane potential, promoting transcellular potassium shift and lowering total K+ body content. The latter can be obtained by dialysis, or by increasing potassium elimination by urine or the gastrointestinal tract. Until recently, the only therapeutic option for increasing fecal K+ excretion was represented by the cation-exchanging resin sodium polystyrene sulfonate. However, despite its common use, the efficacy of this drug has been poorly studied in controlled studies, and concerns about its safety have been reported. Interestingly, new drugs, namely patiromer and sodium zirconium cyclosilicate, have been developed to treat hyperkalemia by increasing gastrointestinal potassium elimination. These medications have proved their efficacy and safety in large clinical trials, involving subjects at high risk of hyperkalemia, such as patients with heart failure and chronic kidney disease. In this review, we discuss the mechanisms of action and the updated data of patiromer and sodium zirconium cyclosilicate, considering that the availability of these new treatment options offers the possibility of improving the management of both acute and chronic hyperkalemia

Pooled Genome-Wide Analysis to Identify Novel Risk Loci for Pediatric Allergic Asthma

BACKGROUND: Genome-wide association studies of pooled DNA samples were shown to be a valuable tool to identify candidate SNPs associated to a phenotype. No such study was up to now applied to childhood allergic asthma, even if the very high complexity of asthma genetics is an appropriate field to explore the potential of pooled GWAS approach. METHODOLOGY/PRINCIPAL FINDINGS: We performed a pooled GWAS and individual genotyping in 269 children with allergic respiratory diseases comparing allergic children with and without asthma. We used a modular approach to identify the most significant loci associated with asthma by combining silhouette statistics and physical distance method with cluster-adapted thresholding. We found 97% concordance between pooled GWAS and individual genotyping, with 36 out of 37 top-scoring SNPs significant at individual genotyping level. The most significant SNP is located inside the coding sequence of C5, an already identified asthma susceptibility gene, while the other loci regulate functions that are relevant to bronchial physiopathology, as immune- or inflammation-mediated mechanisms and airway smooth muscle contraction. Integration with gene expression data showed that almost half of the putative susceptibility genes are differentially expressed in experimental asthma mouse models. CONCLUSION/SIGNIFICANCE: Combined silhouette statistics and cluster-adapted physical distance threshold analysis of pooled GWAS data is an efficient method to identify candidate SNP associated to asthma development in an allergic pediatric population

Wine, spirits, and beer intake and endometriosis risk among infertile women: results from a case control study

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Trend of change of sperm count and concentration over the last two decades: A systematic review and meta‐regression analysis

Background: Since the 1970s, several studies found that sperm concentration (SC) and total sperm count (TSC) constantly worsened over time, mainly in high-income countries. Objectives: To evaluate whether the decreasing trend in sperm count is continuing in Western European countries and USA, we performed a systematic review and meta-regression analysis. Materials and methods: Embase and Pubmed/Medline were searched papers published in English in the 2000-2020 period limiting the search to data collected in the USA and Western European countries. Results: We identified 62 articles and pooled information on 24,196 men (range 10-2,523), collected from 1993 to 2018. Considering all the studies, random-effects meta-regression analyses showed no significant trend for SC (slope per year -0.07 mil/mL, p-value = 0.86). Negative trends of SC were detected in Scandinavian countries (slope per year -1.11 mil/mL, 95% CI: -2.40 to +0.19; p-value = 0.09), but the findings were statistically not significant. No significant trends of SC were detected in Central Europe (slope per year +0.23, 95% CI -2.51 to +2.96; p-value = 0.87), the USA (slope per year +1.08, 95% CI -0.42 to +2.57; p-value = 0.16), and Southern Europe (slope per year +0.19, 95% CI -0.99 to +1.37; p-value = 0.75). We have analyzed separately findings from studies including sperm donors, fertile men, young unselected men (unselected men, study mean age < 25 years) and unselected men (unselected men, study mean age ≥ 25 years). No significant trends of SC were observed among sperm donors (slope per year -2.80, 95% CI -6.76 to +1.17; p-value 0.16), unselected men (slope per year -0.23, 95% CI -1.58 to +1.12; p-value 0.73), young unselected men (slope per year -0.49, 95% CI -1.76 to +0.79; p-value 0.45), fertile men (slope per year +0.29, 95% CI -1.09 to +1.67; p-value 0.68). Discussion and conclusion: The results of this analysis show no significant trends in SC, in USA, and selected Western European countries