N-terminal cleavage of cyclophilin D boosts its ability to bind F-ATP synthase.

Cyclophilin (CyP) D is a regulator of the mitochondrial F-ATP synthase. Here we report the discovery of a form of CyPD lacking the first 10 (mouse) or 13 (human) N-terminal residues (ΔN-CyPD), a protein region with species-specific features. NMR studies on recombinant human full-length CyPD (FL-CyPD) and ΔN-CyPD form revealed that the N-terminus is highly flexible, in contrast with the rigid globular part.

Suppression of the - axis shifts arginine into the phosphocreatine energy system in pancreatic cancer cells.

In pancreatic ductal adenocarcinomas (PDAC), the axis controls cellular functions such as redox homeostasis and metabolism. Disruption of this axis through suppression of leads to profound reprogramming of metabolism. Unbiased transcriptome and metabolome analyses showed that PDAC cells with disrupted signaling ( cells) shift from aerobic glycolysis to metabolic pathways fed by amino acids.

E40 glutenase detoxification capabilities of residual gluten immunogenic peptides in gastrointestinal digesta of food matrices made of soft and durum wheat.

Gluten degrading enzymes, which are commonly referred to as "glutenases," represent attractive candidates for the development of a pharmacological treatment of gluten related disorders, such as coeliac disease (CeD). Endoprotease-40 (E40), a novel glutenase secreted by the actinomycete A8 and recombinantly produced in TK24, was shown to be active at pH 3 to 6 (optimum pH 5), resistant to pepsin and trypsin degradation, able to destroy immunotoxicity of both gliadin 33-mer peptide and whole proteins and to strongly reduce the response of specific T cells when added to gliadin in gastrointestinal digestion. This study aims to functionally assess the capabilities of Endoprotease-40 (E40) to detoxify residual gluten immunogenic peptides in gastrointestinal digesta of food matrices made of soft and durum wheat.

Peripheral impairments of oxidative metabolism after a 10-day bed rest are upstream of mitochondrial respiration.

In order to identify peripheral biomarkers of impaired oxidative metabolism during exercise following a 10-day bed rest, 10 males performed an incremental exercise (to determine peak pulmonary V̇O (V̇O p)) and moderate-intensity exercises, before (PRE) and after (POST) bed rest. Blood flow response was evaluated in the common femoral artery by Eco-Doppler during 1 min of passive leg movements (PLM). The intramuscular matching between O delivery and O utilization was evaluated by near-infrared spectroscopy (NIRS).

Assessment of the Exposure to Gradient Magnetic Fields Generated by MRI Tomographs: Measurement Method, Verification of Limits and Clearance Areas through a Web-Based Platform.

This work is the result of a campaign of measures of exposure levels to magnetic field gradients (GMF) generated by magnetic resonance imaging (MRI) tomographs, to which both healthcare staff and any persons accompanying patients who remain inside the magnet room are exposed while performing a diagnostic Investigation. The study was conducted on three MRI tomographs with a static magnetic induction field up to 1.5 T installed in two hospitals of Lombardy.

Rhythm dynamics of the aging heart: an experimental study using conscious, restrained mice.

Heart rate variability (HRV) is a measure of variation in time interval between heartbeats and reflects the influence of autonomic nervous system and circulating/locally released factors on sinoatrial node discharge. Here, we tested whether electrocardiograms (ECGs) obtained in conscious, restrained mice, a condition that affects sympathovagal balance, reveal alterations of heart rhythm dynamics with aging. Moreover, based on emergence of sodium channels as modulators of pacemaker activity, we addressed consequences of altered sodium channels on heart rhythm.

Effects of 3-month high-intensity interval training vs. moderate endurance training and 4-month follow-up on fat metabolism, cardiorespiratory function and mitochondrial respiration in obese adults.

Purpose: The purpose of this study was to investigate, in obese adults, changes in body composition, physical capacities, fat oxidation and ex vivo mitochondrial respiration induced by a 3-month either moderate-intensity continuous training (MICT) or high-intensity interval training (HIIT); afterwards, the patients were followed for four months.

Methods: Thirty-two patients (mean age 39 years; mean body mass index [BMI] 36 kg∙m) participated in this study attending ~ 34 sessions of training. At baseline (PRE), at the end of the program (POST) and after follow-up, body composition, peak O uptake (V'Opeak) and fat oxidation rate were measured.

Mixed hemodiafiltration reduces erythropoiesis stimulating agents requirement in dialysis patients: a prospective randomized study.

Background: Improved responsiveness to erythropoiesis stimulating agents (ESAs) in patients on on-line post-dilution hemodiafiltration (Post-HDF) compared with conventional hemodialysis (HD) was reported by some authors but challenged by others. This prospective, cross-over randomized study tested the hypothesis that an alternative infusion modality of HDF, mixed-dilution HDF (Mixed HDF), could further reduce ESAs requirement in dialysis patients compared to the traditional Post-HDF.

Methods: One-hundred-twenty prevalent patients from 6 Dialysis Centers were randomly assigned to two six-months treatment sequences: A-B and B-A (A, Mixed HDF; B, Post-HDF).

GSK3β is a key regulator of the ROS-dependent necrotic death induced by the quinone DMNQ.

Signaling pathways controlling necrosis are still mysterious and debated. We applied a shRNA-based viability screen to identify critical elements of the necrotic response. We took advantage from a small molecule (G5) that makes covalent adducts with free thiols by Michael addition and elicits multiple stresses.

Inhibition of APE1-endonuclease activity affects cell metabolism in colon cancer cells via a p53-dependent pathway.

The pathogenesis of colorectal cancer (CRC) involves different mechanisms, such as genomic and microsatellite instabilities. Recently, a contribution of the base excision repair (BER) pathway in CRC pathology has been emerged. In this context, the involvement of APE1 in the BER pathway and in the transcriptional regulation of genes implicated in tumor progression strongly correlates with chemoresistance in CRC and in more aggressive cancers.

Mitochondrial Adaptations in Elderly and Young Men Skeletal Muscle Following 2 Weeks of Bed Rest and Rehabilitation.

The aim of the study was to evaluate the expression levels of proteins related to mitochondrial biogenesis regulation and bioenergetics in muscle biopsies from 16 elderly and 7 young people subjected to 14 days of bed-rest, causing atrophy, and subsequent 14 days of exercise training. Based on quantitative immunoblot analyses, in both groups a reduction of two key regulators of mitochondrial biogenesis/remodeling and activity, namely PGC-1α and Sirt3, was revealed during bed-rest, with a subsequent up-regulation after rehabilitation, indicating an involvement of PGC-1α-Sirt3 axis in response to the treatments. A difference was observed comparing the young and elderly subjects as, for both proteins, the abundance in the elderly was more affected by immobility and less responsive to exercise.

Pharmacogenomic Approach to Selecting Antiplatelet Therapy in Patients With Acute Coronary Syndromes: The PHARMCLO Trial.

Background: Although clopidogrel is still frequently used in patients with acute coronary syndromes (ACS), its efficacy is hampered by interpatient response variability caused by genetic polymorphisms associated with clopidogrel's metabolism.

Objectives: The goal of this study was to evaluate whether selecting antiplatelet therapy (clopidogrel, prasugrel, or ticagrelor) on the basis of a patient's genetic and clinical characteristics leads to better clinical outcomes compared with the standard of care, which bases the selection on clinical characteristics alone.

Methods: Patients hospitalized for ACS were randomly assigned to standard of care or the pharmacogenomic arm, which included the genotyping of ABCB1, CYP2C19*2, and CYP2C19*17 using an ST Q3 system that provides data within 70 min at each patient's bedside.

Mitochondrial energy metabolism and signalling in human glioblastoma cell lines with different PTEN gene status.

Glioblastomas epidemiology and aggressiveness demand for a well characterization of biochemical mechanisms of the cells. The discovery of oxidative tumours related to chemoresistance is changing the prevalent view of dysfunctional mitochondria in cancer cells. Thus, glioblastomas metabolism is now an area of intense research, wherein was documented a high heterogeneity in energy metabolism and in particular in mitochondrial OxPhos.

Exercise training in Tgα*44 mice during the progression of chronic heart failure: cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism.

Cardiac function, skeletal (soleus) muscle oxidative metabolism, and the effects of exercise training were evaluated in a transgenic murine model (Tgα*44) of chronic heart failure during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e., from 10 to 12 mo of age).

Psychomotor Development in Cri du Chat Syndrome: Comparison in Two Italian Cohorts with Different Rehabilitation Methods.

The Cri du Chat syndrome (CdC) is a rare genetic disorder caused by variable size deletions of the short arm of chromosome 5 (5p-). It is well known that home-reared patients show better performances as compared to institutionalised cases, and it was reported that continuous educational intervention can ameliorate their performances. To assess the efficacy of educational intervention and to develop new CdC oriented programs of rehabilitation, we compare the results obtained for many developmental skills in two groups of CdC patients undergoing two different rehabilitation programs.

A comparison of methods for the analysis of binomial clustered outcomes in behavioral research.

Background: In behavioral research, data consisting of a per-subject proportion of "successes" and "failures" over a finite number of trials often arise. This clustered binary data are usually non-normally distributed, which can distort inference if the usual general linear model is applied and sample size is small. A number of more advanced methods is available, but they are often technically challenging and a comparative assessment of their performances in behavioral setups has not been performed.

Transformation by different oncogenes relies on specific metabolic adaptations.

Metabolic adaptations are emerging as common traits of cancer cells and tumor progression. In vitro transformation of NIH 3T3 cells allows the analysis of the metabolic changes triggered by a single oncogene. In this work, we have compared the metabolic changes induced by H-RAS and by the nuclear resident mutant of histone deacetylase 4 (HDAC4).

Can supplementation of phytoestrogens/insoluble fibers help the management of duodenal polyps in familial adenomatous polyposis?

Familial adenomatous polyposis (FAP) is an autosomal dominant inherited disorder, and prophylactic colectomy has been shown to decrease the incidence of colorectal cancer (CRC). Duodenal cancer and desmoids are now the leading causes of death in FAP. We evaluate whether 3 months of oral supplementation with a patented blend of phytoestrogens and indigestible insoluble fibers (ADI) help the management of FAP patients with ileal pouch-anal anastomosis (IPAA).

Long-term facial improvement after repeated BoNT-A injections and mirror biofeedback exercises for chronic facial synkinesis: a case-series study.

Background: Only few studies have considered the effects of the combined treatment with onabotulinumtoxinA (BoNT-A) injections and biofeedback (BFB) rehabilitation in the recovery of postparetic facial synkinesis (PPFS).

Aim: To explore the presence of a persistent improvement in facial function out of the pharmacological effect of BoNT-A in subjects with established PPFS, after repeated sessions of BoNT-A injections combined with an educational facial training program using mirror biofeedback (BFB) exercises. Secondary objective was to investigate the trend of the presumed persistent improvement.

The Prognosis of Patients with Liver Metastases from Colorectal Cancer still Depends on Anatomical Presentation more than on Treatments.

Background: The best management of liver metastases from colorectal cancer is still debated and little is known about the true impact of treatments on survival.

Materials And Methods: The study involved 122 patients (77 males), aged 64.0 ± 11.

F1FO ATP Synthase Is Expressed at the Surface of Embryonic Rat Heart-Derived H9c2 Cells and Is Affected by Cardiac-Like Differentiation.

Taking advantage from the peculiar features of the embryonic rat heart-derived myoblast cell line H9c2, the present study is the first to provide evidence for the expression of F1FO ATP synthase and of ATPase Inhibitory Factor 1 (IF1) on the surface of cells of cardiac origin, together documenting that they were affected through cardiac-like differentiation. Subunits of both the catalytic F1 sector of the complex (ATP synthase-β) and of the peripheral stalk, responsible for the correct F1-FO assembly/coupling, (OSCP, b, F6) were detected by immunofluorescence, together with IF1. The expression of ATP synthase-β, ATP synthase-b and F6 were similar for parental and differentiated H9c2, while the levels of OSCP increased noticeably in differentiated cells, where the results of in situ Proximity Ligation Assay were consistent with OSCP interaction within ecto-F1FO complexes.

Quantification of upper limb skills in elderly rehabilitative inpatients: a controlled study.

Background: Aging has a recognized degenerative effect on the functionality of the hand in terms of strength and dexterity. Despite this, there are few studies in literature that quantify the upper limb skills in the elderly.

Aim: The aim was to present quantitative data regarding upper limb functionality in the elderly and to quantify the effect of aging on them, considering the influence of the comorbidities, of the global level of autonomy, of the cognitive status and of the mood, which are typically compromised in the elderly.

Genotype-phenotype correlation in Pompe disease, a step forward.

Background: Pompe's disease is a progressive myopathy caused by mutations in the lysosomal enzyme acid alphaglucosidase gene (GAA). A wide clinical variability occurs also in patients sharing the same GAA mutations, even within the same family.

Methods: For a large series of GSDII patients we collected some clinical data as age of onset of the disease, presence or absence of muscular pain, Walton score, 6-Minute Walking Test, Vital Capacity, and Creatine Kinase.

Silver sucrose octasulfate (IASOS™) as a valid active ingredient into a novel vaginal gel against human vaginal pathogens: in vitro antimicrobial activity assessment.

This in vitro study assessed the antimicrobial properties of a novel octasilver salt of Sucrose Octasulfate (IASOS) as well as of an innovative vaginal gel containing IASOS (SilSOS Femme), against bacterial and yeast pathogens isolated from human clinical cases of symptomatic vaginal infections. In BHI and LAPT culture media, different ionic silver concentrations and different pHs were tested. IASOS exerted a strong antimicrobial activity towards all the pathogens tested in both culture media.