Inflammation and physical activity in multiple sclerosis patients. A systematic review and meta-analysis.

OBJECTIVES: Due to the inflammatory nature of multiple sclerosis (MS), the most widely used therapeutic approach targets the immune response but can comprise side effects (e.g. secondary immunosuppression). For these reasons, among non-pharmaceutical interventions without known side effects, physical activity (PA) gained importance because it is feasible, safe and a supportive complementary treatment strategy to alleviate symptoms in MS subjects. Consequently, the main aim of this systematic review is to analyze the effect of PA protocols, as a complementary therapy, on inflammatory status in MS patients. METHODS: Four electronic databases (PubMed, Embase, CINAHL, and Cochrane CENTRAL) were systematically searched up to 01 June 2023 (Prospero Protocol ID=CRD42021244418). The refined search strategy was based on three concepts: "MULTIPLE SCLEROSIS" AND "PHYSICAL ACTIVITY" AND "INFLAMMATION". RESULTS: three main findings emerged: 1) untrained subjects showed a negative modulation of inflammatory biomarkers concentrations when compared to trained people (-0.74, 95 %C.I.-1.16, -0.32); 2) training modulated positively inflammatory biomarkers (+0.47, 95 %C.I. 0.24,0.71); 3) Aerobic PA protocol enhance higher positive influence on inflammation. CONCLUSIONS: Persistent, low-grade inflammation in MS could be upregulated by non-pharmacological complementary therapies, in particular by regular aerobic PA that could reduce and positively modulate inflammation.

Daily music listening to reduce work-related stress: a randomized controlled pilot trial.

BACKGROUND: Literature shows that music can reduce stress conditions. This pilot study investigated the effects of music listening on work-related stress and well-being in healthcare professionals. METHOD: A total of 45 subjects were randomly assigned to three treatment groups: No Music, Individualized Music and Melomics-Health Listening. Music groups experienced a daily 30-min-playlist listening for 3 weeks at home. The Maugeri Stress Index-Revised (MASI-R) and the Psychological General Well-Being Index (PGWBI) were administered at baseline, after 3 weeks and after 7 weeks (follow-up). Longitudinal data were analyzed by means of a nested ANOVA model, testing the main effects of time and treatment and the interaction between them. RESULTS: MASI-R scores showed a positive trend in music groups and a worsening in the control group. Only the interaction time/treatment emerged as supporting a trend toward statistical significance (P = 0.07). PGWBI showed a stability in music groups and a clear decline in controls, without significant effects. CONCLUSIONS: Results from the study support the need for a larger clinical trial: it is suggested that daily music listening could be implemented to reduce work-related stress and that the effects may be related, not only to individual musical preferences and familiarity, but also to specific music structures and parameters.

Heat shock protein 70-hom gene polymorphism and protein expression in multiple sclerosis.

Immune-mediated and neurodegenerative mechanisms are involved in multiple sclerosis (MS). Growing evidences highlight the role of HSP70 genes in the susceptibility of some neurological diseases. In this explorative study we analyzed a polymorphism (i.e. HSP70-hom rs2227956) of the gene HSPA1L, which encodes for the protein hsp70-hom. We sequenced the polymorphism by polymerase chain reaction (PCR), in 191 MS patients and 365 healthy controls. The hsp70-hom protein expression was quantified by western blotting. We reported a strong association between rs2227956 polymorphism and MS risk, which is independent from the association with HSP70-2 rs1061581, and a significant link between hsp70-hom protein expression and MS severity.

ß-Boswellic acid, a bioactive substance used in food supplements, inhibits protein synthesis by targeting the ribosomal machinery.

The Boswellia gum resin extracts have been used in traditional medicines because of their remarkable anti-inflammatory properties. Nowadays, these extracts are on the market as food supplements. ß-Boswellic acid (ßBA) is one of the main pentacyclic triterpene components, among the family of BAs, of the Boswellia gum resins. BAs have been broadly studied and are well known for their wide anti-inflammatory and potential anticancer properties. In this paper, a mass spectrometry-based chemoproteomic approach has been applied to characterize the whole ßBA interacting profile. Among the large numbers of proteins fished out, proteasome, 14-3-3 and some ribosomal proteins were considered the most interesting targets strictly connected to the modulation of the cancer progression. In particular, because of their recent assessment as innovative chemotherapeutic targets, the ribosomal proteins were considered the most attractive ßBA partners, and the biological role of their interaction with the natural compound has been evaluated. Copyright © 2016 John Wiley & Sons, Ltd.

Theonellasterone, a steroidal metabolite isolated from a Theonella sponge, protects peroxiredoxin-1 from oxidative stress reactions.

Peroxiredoxin-1, a key enzyme in the cellular detoxification pathway, has been identified through a chemoproteomic approach as the main partner of theonellasterone, a marine bioactive metabolite. A combination of chemical and biochemical assays disclosed its mechanism of action at the molecular level.

In cell scalaradial interactome profiling using a bio-orthogonal clickable probe.

A bio-orthogonal click-chemistry procedure was developed to allow the in cell interactome profiling of scalaradial, an anti-inflammatory marine natural product. The results were validated through the application of the classical in vitro chemical proteomics and several bio-physical methods; peroxiredoxins, 14-3-3 isoforms and proteasomes were recognized as main scalaradial targets.

Targeting the immunogenetic diseases with the appropriate HLA molecular typing: critical appraisal on 2666 patients typed in one single centre.

We compared the immunogenetic data from 2666 patients affected by HLA-related autoimmune diseases with those from 4389 ethnically matched controls (3157 cord blood donors CBD, 1232 adult bone marrow donors BMD), to verify the appropriateness of HLA typing requests received in the past decade. The frequency of HLA-B∗27 phenotype was 10.50% in 724 ankylosing spondylitis, 16.80% in 125 uveitis (3.41% BMD, 4.24% CBD, P < 0.0001); HLA-B∗51 allele was 15.57% in 212 Behçet's disease (12.91% BMD, 9.88% CBD, P < 0.0001); the HLA-DRB1-rheumatoid arthritis (RA) shared epitope was 13.72% in 554 RA (10.85% BMD, 13.48% CBD, P = 0.016); the carriers of almost one of HLA-DQB1 susceptibility alleles were 84.91% in 795 celiac disease (CD) and 59.37% in 256 insulin-dependent diabetes mellitus (IDDM) (46.06% in 875 CBD, 42.75% in 662 BMD P < 0.0001). Overall, our results show that the HLA marker frequencies were higher in patients than controls, but lower than expected from the literature data (excluding CD and IDDM) and demonstrate that, in complex immunogenetic conditions, a substantial number of genetic analyses are redundant and inappropriate, burdening to the public health costs. For this reason, we suggest the Italian Scientific Society of Immunogenetics to establish guidelines to improve the appropriateness of typing requests.

HLA class I and II alleles are associated with microvascular complications of type 1 diabetes.

Although HLA alleles are associated with type 1 diabetes, association with microvascular complications remains controversial. We tested HLA association with complications in multiplex type 1 diabetes families. Probands from 425 type 1 diabetes families from the Human Biological Data Interchange (HBDI) collection were analyzed. The frequencies of specific HLA alleles in patients with complications were compared with the frequencies in complications-free patients. The complications we examined were: retinopathy, neuropathy, and nephropathy. We used logistic regression models with covariates to estimate odds ratios. We found that the DRB1*03:01 allele is a protective factor for complications (OR=0.58; p=0.03), as is the DQA1*05:01-DQB1*02:01 haplotype found in linkage disequilibrium with DRB1*03:01 (OR=0.59; p=0.031). The DRB1*04:01 allele showed no evidence of association (OR=1.13; p=0.624), although DRB1*04:01 showed suggestive evidence when the carriers of the protective DRB1*03:01 were removed from the analysis. The class II DQA1*03:01-DQB1*03:02 haplotype was not associated with complications, but the class I allele B*39:06 (OR=3.27; p=0.008) suggested a strong positive association with complications. Our results show that in type 1 diabetes patients, specific HLA alleles may be involved in susceptibility to, or protection from, microvascular complications.

Estrogen receptor alpha and APOEepsilon4 polymorphisms interact to increase risk for sporadic AD in Italian females.

Alzheimer's disease (AD) is a progressive neurodegenerative disease that affects both sexes, with a higher prevalence in women. Declining estrogen levels after menopause may render estrogen target neurons in the brain more susceptible to age or disease-related processes such as AD. To investigate the role of two single nucleotide polymorphisms in the first intron of the ER-alpha gene, denominated PvuII and XbaI, and their interaction with the known AD susceptibility gene APOE, we examined 131 patients with sporadic AD and 109 healthy control subjects. In multinomial logistic regression analysis, a significantly increased risk of sporadic AD because of interaction between the ER-alpha p allele and APOE epsilon4 allele was observed in women, taking subjects who had neither the p allele nor epsilon4 as reference [odds ratio (OR) 7.24; 95% CI, 2.22-23.60]. For women carrying the ER-alpha x allele together with APOE epsilon4, the risk of sporadic AD was similarly elevated (OR 8.33; 95% CI, 1.73-40.06). The data suggest that the p and x alleles of polymorphic ER-alpha gene interact synergistically with the APOE epsilon4 allele to increase the risk of AD in women but not in men in this Italian cohort.

Bayesian mapping of multiple sclerosis prevalence in the province of Pavia, northern Italy.

The geographical analysis of a disease risk is particularly difficult when the disease is non-frequent and the area units are small. The practical use of the Bayesian modelling, instead of the classical frequentist one, is applied to study the geographical variation of multiple sclerosis (MS) across the province of Pavia, Northern Italy. 464 MS-affected individuals resident in the province of Pavia were identified on December 31st 2000. The overall prevalence was 94 per 100,000 inhabitants. This estimate indicates an increasing MS prevalence in the province, in accordance with the vast majority of the Italian areas where prevalence studies have been repeated. We mapped the geographical variation of MS prevalence across the 190 communes of the province both with a classical approach and a Bayesian approach. The frequentist approach produced an extremely dishomogeneous map, while the Bayesian map was much smoother and more interpretable. Our study underlines the usefulness of Bayesian methods to obtain reliable maps of disease prevalence and to identify possible clusters of disease where to carry out further epidemiological investigations.

PLA2-mediated catalytic activation of its inhibitor 25-acetyl-petrosaspongiolide M: serendipitous identification of a new PLA2 suicide inhibitor.

25-Acetyl-petrosaspongiolide M (PMAc) (1), a mild non-covalent PLA(2) inhibitor, unexpectedly recovers, after incubation with bvPLA(2), the ability to covalently modify the enzyme target. This study demonstrates the catalytic effect of bvPLA(2) in converting 1 in its deacetylated congener petrosaspongiolide M (PM) (2), a strong covalent PLA(2) inhibitor whose molecular mechanism of inhibition has already been clarified. Moreover, our findings outline the potential role of PMAc as anti-inflammatory pro-drug, by virtue of its ability of delivering the active PM agent at the site of inflammation, functioning as a suicide inhibitor.

Familial aggregation of blood pressure in a paediatric population.

Familial aggregation of blood pressure in childhood and the difference between males and females were studied in a random sample of a nursery and school-age population in Milan. Age, sex, height, weight, skinfold thicknesses and heart rate were obtained. Blood pressure was measured in accordance with the recommendations of the Task Force of Blood Pressure Control in Children. After adjusting for age, significant correlation coefficients were found between mother and son (r = 0.17 and r = 0.11), mother and daughter (r = 0.11 and r = 0.15), and father and son (r = 0.16 and r = 0.17) for systolic and diastolic pressure, respectively; the father-daughter correlations were not statistically different (r = 0.08 and r = 0.03). Multiple regression analysis underlined the difference between males and females; height was an important determinant in the males and body weight in the females. In conclusion, anthropometric measurements should be considered in evaluations of blood pressure status. Our results suggest important differences between males and females. The BP pattern of the parents also seems more important for sons, and there seems to be a lower correlation between fathers and daughters.