Necroptosis in intestinal inflammation and cancer: new concepts and therapeutic perspectives

Necroptosis is a caspases-independent programmed cell death displaying intermediate features between necrosis and apoptosis. Albeit some physiological roles during embryonic development such tissue homeostasis and innate immune response are documented, necroptosis is mainly considered a pro-inflammatory cell death. Key actors of necroptosis are the receptor-interacting-protein-kinases, RIPK1 and RIPK3, and their target, the mixed-lineage-kinase-domain-like protein, MLKL. The intestinal epithelium has one of the highest rates of cellular turnover in a process that is tightly regulated. Altered necroptosis at the intestinal epithelium leads to uncontrolled microbial translocation and deleterious inflammation. Indeed, necroptosis plays a role in many disease conditions and inhibiting necroptosis is currently considered a promising therapeutic strategy. In this review, we focus on the molecular mechanisms of necroptosis as well as its involvement in human diseases. We also discuss the present developing therapies that target necroptosis machinery

Krill oil, vitamin D and Lactobacillus reuteri cooperate to reduce gut inflammation

Current research into original therapies to treat intestinal inflammation is focusing on no-drug therapies. KLD is a mixture of krill oil (KO), probiotic Lactobacillus reuteri (LR), and vitamin D (VitD3). The aim of this study was to assess in vitro and in vivo the potential cooperative effects of KLD in reducing gut inflammation. Colorectal adenocarcinoma cell lines, CACO2 and HT29, and C57BL/6 mice were used for in vitro and in vivo analyses, respectively. Cells were exposed to cytomix (interferon gamma + tumour necrosis factor alpha (TNF-a)) to induce inflammation or co-exposed to cytomix and KO, LR and VitD3 alone or to cytomix and KLD. Animals were treated for 7 days with dextran sodium sulphate (DSS) to induce colitis or with DSS and KLD. In vitro assays: F-actin expression was analysed by immunofluorescence; scratch test and trans-epithelial electric resistance test were performed to measure wound healing; adhesion/invasion assays of adhesive and invasive Escherichia coli (AIEC) bacteria were made; mRNA expression of TNF-α, interleukin (IL)-8 and vitamin D receptor (VDR) was detected by quantitative PCR. In vivo assays: body weight, clinical score, histological score and large intestine weight and length were estimated; mRNA expression of TNF-α, IL-1ß, IL-6, IL-10 by quantitative PCR; VDR expression was detected by quantitative PCR and immunohistochemistry. In vitro: KLD restores epithelial cell-cell adhesion and mucosal healing during inflammation, while decreases the adhesiveness and invasiveness of AIEC bacteria and TNF-α and IL-8 mRNA expression and increases VDR expression. In vivo: KLD significantly improves body weight, clinical score, histological score and large intestine length of mice with DSS-induced colitis and reduces TNF-α, IL-1ß and IL-6 mRNA levels, while increases IL-10 mRNA and VDR levels. KLD has significant effects on the intestinal mucosa, strongly decreasing inflammation, increasing epithelial restitution and reducing pathogenicity of harmful commensal bacteria

Porous dipeptide crystals as volatile-drug vessels

Anesthetic vapors find temporary hospitality in porous dipeptide crystals, which behave as biologically friendly hosts and carriers

Catheter ablation in an 80-year-old male with late-onset Wolff-Parkinson-White syndrome

Wolff-Parkinson-White syndrome is a congenital condition involving abnormal conductive cardiac tissue between atria and ventricles, that provides a pathway for a re-entrant tachycardia circuit or rapid repetitive ventricular response during atrial fibrillation. Clinical onset is usually from childhood to middle age, and symptoms vary in severity from palpitations (with or without syncope) to cardiac arrest. Presentation varies depending on the patient\u2019s age and presence of comorbidities, as arrhythmias are less tolerated in case of an associated heart disease. In individuals who do not experience symptoms, the condition may go unnoticed for years. We describe the case of an 80-year-old Caucasian male with late-onset of Wolff-Parkinson-White syndrome. He presented with a regular, hemodynamically unstable wide-complex tachycardia with left bundle branch morphology, successfully treated with medical therapy. After recurrence of tachycardia, he underwent an electrophysiological study that showed an orthodromic atrioventricular re-entrant tachycardia using a posterolateral accessory pathway and with functional left bundle branch block. Transseptal radiofrequency catheter ablation of the accessory pathway was successfully performed. After 15 months of follow-up, there was no tachycardia recurrence or findings of pre-excitation on the electrocardiogram. The treatment of both supraventricular and ventricular arrhythmias may be challenging especially in elderly patients. Catheter ablation of left accessory pathways with transseptal approach is feasible and effective in old patients with late-onset Wolff-Parkinson-White syndrome

Determination of fatty acids profile in original brown cows dairy products and relationship with alpine pasture farming system

This study aimed to evaluate the relationships between fatty acids and the pattern that most contributes to discriminate between two farming systems, in which the main difference was the practice, or not, of alpine summer-grazing. Milk and cheese were sampled every month in two farms of Original Brown cows identical under geographical location and management during no grazing season point of view in the 2018 season. Fatty acids concentrations were determined by gas chromatography. The principal component analysis extracted three components (PCs). Mammary gland de novo synthetized fatty acids (C14:0, C14:1 n9, and C16:0) and saturated and monosaturated C18 fatty acids (C18:0, C18:1 n9c) were inversely associated in the PC1; PC2 included polyunsaturated C18 fatty acids (C18:2 n6c, C18:3 n3) and C15:0 while conjugated linoleic acid (CLA n9c, n11t) and fatty acids containing 20 or more carbon atoms (C21:0, C20:5 n3) were associated in the PC3. The processes of rumen fermentation and de novo synthesis in mammary gland that are, in turn, influenced by diet, could explain the relationships between fatty acids within each PC. The discriminant analyses showed that the PC2 included the fatty acids profile that best discriminated between the two farming systems, followed by PC3 and, lastly, PC1. This model, if validated, could be an important tool to the dairy industry

Single top production at the LHC as a probe of R parity violation

We investigate the potential of the LHC to probe the R parity violating couplings involving the third generation by considering single top production. This study is based on particle level event generation for both signal and background, interfaced to a simplified simulation of the ATLAS detector.Comment: 11 pages, 5 figures, 5 tables (LaTeX, style revtex), few references adde

Summary of the SUSY Working Group of the 1999 Les Houches Workshop

The results obtained by the Working Group on Supersymmetry at the 1999 Les Houches Workshop on Collider Physics are summarized. Separate chapters treat "general" supersymmetry, R-parity violation, gauge mediated supersymmetry breaking, and anomaly mediated supersymmetry breaking.Comment: LaTeX, 110 pages with numerous .ps and .eps files. proc.tex is main tex fil

A case report of accidental intoxication following ingestion of foxglove confused with borage : high digoxinemia without major complications

Foxglove (Digitalis purpurea L.) leaves are frequently confused with borage (Borago officinalis L.), which is traditionally used as a food ingredient. Due to the presence of the cardiac glycosides, mostly digitoxin, foxglove leaves are poisonous to human and may be fatal if ingested. A 55-year-old Caucasian woman complaining weakness, fatigue, nausea, and vomiting was admitted to the Emergency Department. Her symptoms started following consumption of a home-made savory pie with 5 leaves from a plant bought in a garden nursery as borage. Digoxinemia was high (10.4\u2009\u3bcg/L). The patient was admitted to the cardiac intensive care unit for electrocardiographic monitoring. Two days after admission, a single episode of advanced atrioventricular (AV) block was recorded by telemetry, followed by a second-degree AV block episode. Plasma samples at day 11 were analysed by LC-MS spectrometry, and gitoxin was identified suggesting that this compound may be responsible for the clinical toxicity rather than digoxin. In the case of Digitalis spp. poisoning, laboratory data should be interpreted according to the clinical picture and method of analysis used since a variety of glycosides, which are chemically similar to the cardioactive glycosides but without or with fewer cardiac effects, may be incorrectly recognized as digoxin by the test, giving misleading results