Search

Molecular profiles of thymomas and recurrent thymomas are far from being defined. Herein, we report an analysis of a comprehensive genetic profile (CGP) in a highly selected cohort of recurrent thymomas. Among a cohort of 426 thymomas, the tissue was available in 23 recurrent tumors for matching the biomolecular results obtained from primary and relapse samples. A control group composed of non-recurrent thymoma patients was selected through a propensity score match analysis. CGP was performed using the NGS Tru-SightOncology assay to evaluate TMB, MSI, and molecular alterations in 523 genes. CGP does not differ when comparing initial tumor with tumor relapse. A significantly higher frequency of cell cycle control genes alterations (100.0% vs. 57.1%, p = 0.022) is detected in patients with early recurrence (<32 months) compared to late recurrent cases. The CGPs were similar in recurrent thymomas and non-recurrent thymomas. Finally, based on NGS results, an off-label treatment or clinical trial could be potentially proposed in >50% of cases (oncogenic Tier-IIC variants). In conclusion, CGPs do not substantially differ between initial tumor vs. tumor recurrence and recurrent thymomas vs. non-recurrent thymomas. Cell cycle control gene alterations are associated with an early recurrence after thymectomy. Multiple target therapies are potentially available by performing a comprehensive CGP, suggesting that a precision medicine approach on these patients could be further explored. [ABSTRACT FROM AUTHOR]

Background/Objectives: The relationship between sarcoidosis and the occurrence of neoplasia deserves to be investigated, but this relation has been observed in different and heterogeneous populations, leading to conflicting data. To clarify the causal relationship between these two diseases, different risk factors (e.g., smoking), concurrent comorbidities, corticosteroid therapy, and metastasis development—as an expression of cancer aggressiveness—were investigated. Methods: In a retrospective study on 287 sarcoidosis outpatients at the Pneumological Department of the Gemelli Foundation (Rome, Italy) between 2000 and 2024, the diagnosis of cancer was recorded in 36 subjects (12.5%). Results: The reciprocal timeline of the diseases showed three different scenarios: (1) cancer preceding sarcoidosis or sarcoid-like reactions (63.8%); (2) cancer arising after sarcoidosis diagnosis (8.3%); and (3) sarcoidosis accompanying the onset of malignancy (27.8%). Only two subjects with sarcoidosis and cancer showed metastasis, and one of them was affected by lymphoma. Conclusions: These data suggest that granulomatous inflammation due to sarcoidosis may assume an ambivalent role as a "double-edged sword", according to the M1/M2 macrophage polarization model: it represents a protective shield, preventing the formation of metastasis through the induction of immune surveillance against cancer while, on the other hand, it can be a risk factor for carcinogenesis due to the persistence of a chronic active inflammatory status. Low-dose steroid treatment was administered in only 31.6% of the cancer–sarcoidosis subjects for less than six months to control inflammation activity, with no promotive effect on carcinogenesis observed. [ABSTRACT FROM AUTHOR]

Tumor heterogeneity refers to the diversity observed among tumor cells: both between different tumors (inter-tumor heterogeneity) and within a single tumor (intra-tumor heterogeneity). These cells can display distinct morphological and phenotypic characteristics, including variations in cellular morphology, metastatic potential and variability treatment responses among patients. Therefore, a comprehensive understanding of such heterogeneity is necessary for deciphering tumor-specific mechanisms that may be diagnostically and therapeutically valuable. Innovative and multidisciplinary approaches are needed to understand this complex feature. In this context, proteogenomics has been emerging as a significant resource for integrating omics fields such as genomics and proteomics. By combining data obtained from both Next-Generation Sequencing (NGS) technologies and mass spectrometry (MS) analyses, proteogenomics aims to provide a comprehensive view of tumor heterogeneity. This approach reveals molecular alterations and phenotypic features related to tumor subtypes, potentially identifying therapeutic biomarkers. Many achievements have been made; however, despite continuous advances in proteogenomics-based methodologies, several challenges remain: in particular the limitations in sensitivity and specificity and the lack of optimal study models. This review highlights the impact of proteogenomics on characterizing tumor phenotypes, focusing on the critical challenges and current limitations of its use in different clinical and preclinical models for tumor phenotypic characterization. [ABSTRACT FROM AUTHOR]

Background: Pathogenic variants in the Polycystic Kidney Disease 2 (PKD2) gene are associated with Autosomal Dominant Polycystic Kidney Disease (ADPKD) in approximately 30% of cases. In recent years, the high-throughput sequencing techniques have significantly increased the number of variants identified in affected patients. Here, we described the peculiar effect of a PKD2 splicing variant, the c.1717-2A>G, identified in an Italian male patient with ADPKD. This variant led to the unusual and rare skipping of two consecutive exons, causing a large in-frame deletion. Methods: The genetic evaluation of the patient was performed using the Next-Generation Sequencing (NGS) assay Clinical Exome Solution® (SOPHiA Genetics). Bioinformatics analysis was performed using the SOPHiA DDM platform (SOPHiA Genetics). Prediction of pathogenicity was carried out by integrating several in silico tools. RNA evaluation was performed to test the effect of the variant on the PKD2 splicing using a Reverse-Transcription PCR coupled with cDNA sequencing. Results: NGS revealed the presence of the PKD2 c.1717-2A>G variant that lies in the canonical splice site of intron 7. This rare variant was predicted to have a significant impact on the splicing, proved by the RNA-based analysis. We identified the presence of a transcript characterised by the simultaneous skipping of exons 8 and 9, with a retained reading frame and the merging of exons 7–10. Conclusions: We described for the first time a dual-exon skip event related to the presence of a single-base substitution in the PKD2 gene in an ADPKD-affected patient. We assumed that the molecular basis of such a rare mechanism lies in the specific order of intron removal. The finding represents novel evidence of an alternative and unusual splicing mechanism in the PKD2 gene, adding insights to the pathogenesis of the ADPKD. [ABSTRACT FROM AUTHOR]

Redox dysregulation, an imbalance between oxidants and antioxidants, is crucial in the pathogenesis of various neurodegenerative diseases. Within this context, the "redoxome" encompasses the network of redox molecules collaborating to maintain cellular redox balance and signaling. Among these, cysteine-sensitive proteins are fundamental for this homeostasis. Due to their reactive thiol groups, cysteine (Cys) residues are particularly susceptible to oxidative post-translational modifications (PTMs) induced by free radicals (reactive oxygen, nitrogen, and sulfur species) which profoundly affect protein functions. Cys-PTMs, forming what is referred to as "cysteinet" in the redox proteome, are essential for redox signaling in both physiological and pathological conditions, including neurodegeneration. Such modifications significantly influence protein misfolding and aggregation, key hallmarks of neurodegenerative diseases such as Alzheimer's, Parkinson's, and notably, amyotrophic lateral sclerosis (ALS). This review aims to explore the complex landscape of cysteine PTMs in the cellular redox environment, elucidating their impact on neurodegeneration at protein level. By investigating specific cysteine-sensitive proteins and the regulatory networks involved, particular emphasis is placed on the link between redox dysregulation and ALS, highlighting this pathology as a prime example of a neurodegenerative disease wherein such redox dysregulation is a distinct hallmark. [ABSTRACT FROM AUTHOR]

Mitochondrial diseases (MDs) affect 4300 individuals, with different ages of presentation and manifestation in any organ. How defects in mitochondria can cause such a diverse range of human diseases remains poorly understood. In recent years, several published research articles regarding the metabolic and protein profiles of these neurogenetic disorders have helped shed light on the pathogenetic mechanisms. By investigating different pathways in MDs, often with the aim of identifying disease biomarkers, it is possible to identify molecular processes underlying the disease. In this perspective, omics technologies such as proteomics and metabolomics considered in this review, can support unresolved mitochondrial questions, helping to improve outcomes for patients. [ABSTRACT FROM AUTHOR]

Background. The 2015 Nobel Prize in Medicine, awarded for the discovery of artemisinin in Artemisia annua, reignited interest in aromatic plants, including Artemisia absinthium L. This article delves into the historical, ethnopharmacological and medicinal significance of A. absinthium, examining its bitter taste noted since ancient Greek times and its association with medicinal properties throughout history. Despite being banned in the 20th century due to perceived health risks; recent research has led to the reconsideration of A. absinthium's potential applications. This study focuses on the prebiotic efficacy of essential oils (EOs) from two Artemisia species: A. absinthium and A. annua. Materials and methods. A broth microdilution test, growth curve test and in vivo models were used to study the impact of low doses (from 0.5% v/v to 0.00048 v/v) of Artemisia spp-EO on the three probiotic strains (Lactobacillus, Lactobacillus casei and Saccharomyces boulardii). Results. These essential oils, when used in minimal concentrations (lower than 0.06% v/v), are safe and exhibit prebiotic effects on major probiotic strains, supporting the traditional culinary use of Artemisia spp. Conclusion. This research opens avenues for potential applications in the food industry, emphasizing the need for further exploration into the prebiotic properties of Artemisia spp-EOs and their influence on the microbiota. [ABSTRACT FROM AUTHOR]

The bee gut microbiota plays an important role in the services the bees pay to the environment, humans and animals. Alongside, gut-associated microorganisms are vehiculated between apparently remote habitats, promoting microbial heterogeneity of the visited microcosms and the transfer of the microbial genetic elements. To date, no metaproteomics studies dealing with the functional bee microbiota are available. Here, we employ a metaproteomics approach to explore a fraction of the bacterial, fungal, and unicellular parasites inhabiting the bee gut. The bacterial community portrays a dynamic composition, accounting for specimens of human and animal concern. Their functional features highlight the vehiculation of virulence and antimicrobial resistance traits. The fungal and unicellular parasite fractions include environment- and animal-related specimens, whose metabolic activities support the spatial spreading of functional features. Host proteome depicts the major bee physiological activities, supporting the metaproteomics strategy for the simultaneous study of multiple microbial specimens and their host-crosstalks. Altogether, the present study provides a better definition of the structure and function of the bee gut microbiota, highlighting its impact in a variety of strategies aimed at improving/overcoming several current hot topic issues such as antimicrobial resistance, environmental pollution and the promotion of environmental health. [ABSTRACT FROM AUTHOR]

Simple Summary: Codon 61 RAS mutations are rare in metastatic colorectal cancer. Despite being associated with primary and acquired resistance to anti-EGFR agents, little is known about their phenotype and prognostic impact. We retrospectively investigated the clinicopathological features and prognoses of 50 patients with tumors harboring codon 61 RAS mutations compared to 648 codon 61 RAS wild-type tumors. We identified a significant correlation between codon 61 RAS mutations and metastatic involvement of the peritoneum and ovary and a negative prognostic impact. This is the first evidence of an impact of RAS mutational status on the metastatization pattern. These results are of great interest given the high frequency of codon 61 RAS mutations as mechanisms of secondary resistance to anti-EGFRs and the advent of RAS inhibitors. This is the widest codon 61 RAS-mutated cohort reported so far; nevertheless, these findings must be validated in larger studies. RAS mutations involving codon 61 are rare in metastatic colorectal cancer (mCRC), accounting for only 1–4%, but they have recently been identified with high frequency in the circulating tumor DNA (ctDNA) of patients with secondary resistance to anti-EGFRs. This retrospective monocentric study aimed to investigate the clinical phenotype and prognostic performance of codon 61 RAS-mutated mCRC. Fifty patients with codon 61 RAS-mutated mCRC treated at our institution between January 2013 and December 2021 were enrolled. Additional datasets of codon 61 RAS wild-type mCRCs (648 patients) were used as comparators. The endpoint for prognostic assessment was overall survival (OS). Metastatic involvement of the peritoneum or ovary was significantly more frequent in codon 61 RAS-mutated mCRC compared to codon 61 RAS wild-type (54 vs. 28.5%), non-codon 61 RAS-mutated (35.6%), BRAF V600E-mutated (25%), and RAS/BRAF wild-type (20.5%) cohorts. At a median follow up of 96.2 months, the median OS for codon 61 RAS-mutated patients was significantly shorter compared to RAS/BRAF wild-type (26.9 vs. 36.0 months, HR 0.56) patients, while no significant difference was observed compared to non-codon 61 RAS-mutated and BRAF V600E-mutated patients. We showed a negative prognostic impact and a statistically significant correlation between codon 61 RAS mutations and metastatic involvement of the peritoneum and ovary. [ABSTRACT FROM AUTHOR]

(1) Background: Preeclampsia (PE) usually presents with hypertension and proteinuria, related to poor placentation. Reduced maternal–fetal immunological tolerance is a possible trigger of inadequate placentation. Aberrant antigen expression of HLA-DR has been observed in the syncytiotrophoblast of PE patients. In this study, we analyzed plasma levels of Human Leukocyte Antigen (HLA)-DR+ syncytiotrophoblast-derived extracellular vesicles (STEVs) during the three trimesters of pregnancy in relation to PE onset. (2) Methods: Pregnant women underwent venous blood sampling during the three trimesters. STEVs were collected from plasma via ultracentrifugation (120,000 g) and characterized by Western blot, nanotracking analysis and flow cytometry for the expression of Placental Alkaline Phosphatase (PLAP), a placental-derived marker, and HLA-DR. (3) Results: Out of 107 women recruited, 10 developed PE. STEVs were detected in all three trimesters of pregnancy with a zenith in the second trimester. A significant difference was found between the non-PE and PE groups in terms of plasma levels of HLA-DR+ STEVs during all three trimesters of pregnancy. (4) Conclusions: More research is needed to investigate HLA-DR+ as a potential early marker of PE. [ABSTRACT FROM AUTHOR]

The incidence of cystic fibrosis (CF) and the spectrum of cystic fibrosis transmembrane conductance regulator (CFTR) gene variants differ among geographic regions. Differences in CF carrier distribution are also reported among Italian regions. We described the spectrum of the CFTR variants observed in a large group of subjects belonging from central–southern Italy. We also provide a predictive evaluation of the novel variants identified. CFTR screening was performed in a south–central Italian cohort of 770 subjects. We adopted a next-generation sequencing (NGS) approach using the Devyser CFTR NGS kit on the Illumina MiSeq System coupled with Amplicon Suite data analysis. Bioinformatics evaluation of the impact of novel variants was described. Overall, the presence of at least one alternative allele in the CFTR gene was recorded for 23% of the subjects, with a carrier frequency of CF pathogenic variants of 1:12. The largest sub-group corresponded to the heterozygous carriers of a variant with a conflicting interpretation of pathogenicity. The common CFTR p.(Phe508del) pathogenic variants were identified in 37% of mutated subjects. Bioinformatics prediction supported a potential damaging effect for the three novel CFTR variants identified: p.(Leu1187Phe), p.(Pro22Thr), and c.744-3C > G. NGS applied to CF screening had the benefit of: effectively identifying asymptomatic carriers. It lies in a wide overview of CFTR variants and gives a comprehensive picture of the carrier prevalence. The identification of a high number of unclassified variants may represent a challenge whilst at the same time being of interest and relevance for clinicians. [ABSTRACT FROM AUTHOR]

An altered amino acid metabolism has been described in frail older adults which may contribute to muscle loss and functional decline associated with frailty. In the present investigation, we compared circulating amino acid profiles of older adults with physical frailty and sarcopenia (PF&S, n = 94), frail/pre-frail older adults with type 2 diabetes mellitus (F-T2DM, n = 66), and robust non-diabetic controls (n = 40). Partial least squares discriminant analysis (PLS–DA) models were built to define the amino acid signatures associated with the different frailty phenotypes. PLS–DA allowed correct classification of participants with 78.2 ± 1.9% accuracy. Older adults with F-T2DM showed an amino acid profile characterized by higher levels of 3-methylhistidine, alanine, arginine, ethanolamine, and glutamic acid. PF&S and control participants were discriminated based on serum concentrations of aminoadipic acid, aspartate, citrulline, cystine, taurine, and tryptophan. These findings suggest that different types of frailty may be characterized by distinct metabolic perturbations. Amino acid profiling may therefore serve as a valuable tool for frailty biomarker discovery. [ABSTRACT FROM AUTHOR]

Altered l-arginine metabolism has been described in patients with COVID-19 and has been associated with immune and vascular dysfunction. In the present investigation, we determined the serum concentrations of l-arginine, citrulline, ornithine, monomethyl-l-arginine (MMA), and symmetric and asymmetric dimethylarginine (SDMA, ADMA) in adults with long COVID at baseline and after 28-days of l-arginine plus vitamin C or placebo supplementation enrolled in a randomized clinical trial, compared with a group of adults without previous history of SARS-CoV-2-infection. l-arginine-derived markers of nitric oxide (NO) bioavailability (i.e., l-arginine/ADMA, l-arginine/citrulline+ornithine, and l-arginine/ornithine) were also assayed. Partial least squares discriminant analysis (PLS–DA) models were built to characterize systemic l-arginine metabolism and assess the effects of the supplementation. PLS–DA allowed discrimination of participants with long COVID from healthy controls with 80.2 ± 3.0% accuracy. Lower markers of NO bioavailability were found in participants with long COVID. After 28 days of l-arginine plus vitamin C supplementation, serum l-arginine concentrations and l-arginine/ADMA increased significantly compared with placebo. This supplement may therefore be proposed as a remedy to increase NO bioavailability in people with long COVID. [ABSTRACT FROM AUTHOR]

Allergic reactions to COVID-19 vaccine components are rare but should be considered. Polyethylene glycol (PEG) is responsible for anaphylaxis in mRNA vaccines. Skin tests have been used in the allergological work-up programs for COVID-19 vaccine evaluation. However, the reproducibility of the skin prick test is time-dependent and the reactivity declines over time. Therefore, we combined the administration of the skin tests with the basophil activation test (BAT) using PEG2000, PEG4000 and DMG-PEG2000, where the BAT was considered positive when the percentage of activated basophils was higher than 6%, 5% and 6.5%, for PEG 4000, PEG2000 and DMG-PEG2000, respectively. To this end, among the subjects that underwent allergy counseling at the Allergy Unit of our Institution during the 2020/2021 vaccination campaign, 13 patients had a suggested medical history of PEG/drug hypersensitivity and were enrolled together with 10 healthy donors. Among the enrolled patients 2 out of 13 tested patients were positive to the skin test. The BAT was negative in terms of the percentages of activated basophils in all analyzed samples, but the stimulation index (SI) was higher than 2.5 in 4 out of 13 patients. These data evidenced that, when the SI is higher than 2.5, even in the absence of positivity to BAT, the BAT to PEG may be a useful tool to be coupled to skin tests to evidence even low-grade reactions. [ABSTRACT FROM AUTHOR]

Goat cheese is an important element of the Mediterranean diet, appreciated for its health-promoting features and unique taste. A pivotal role in the development of these characteristics is attributed to the microbiota and its continuous remodeling over space and time. Nevertheless, no thorough study of the cheese-associated microbiota using two metaomics approaches has previously been conducted. Here, we employed 16S rRNA gene sequencing and metaproteomics to explore the microbiota of a typical raw goat milk cheese at various ripening timepoints and depths of the cheese wheel. The 16S rRNA gene-sequencing and metaproteomics results described a stable microbiota ecology across the selected ripening timepoints, providing evidence for the microbiologically driven fermentation of goat milk products. The important features of the microbiota harbored on the surface and in the core of the cheese mass were highlighted in both compositional and functional terms. We observed the rind microbiota struggling to maintain the biosafety of the cheese through competition mechanisms and/or by preventing the colonization of the cheese by pathobionts of animal or environmental origin. The core microbiota was focused on other biochemical processes, supporting its role in the development of both the health benefits and the pleasant gustatory nuances of goat cheese. [ABSTRACT FROM AUTHOR]

Aberrant accumulation of β-catenin in the cell nucleus as a result of deregulation of the Wnt/β-catenin pathway is found in various types of cancer. Direct β-catenin targeting agents are being researched despite obstacles; however, specific β-catenin drugs for clinical treatments have not been approved so far. We focused on direct β-catenin targeting of potential therapeutic value as anticancer agents. This review provides recent advances on small molecule β-catenin agents. Structure-activity relationships and biological activities of reported inhibitors are discussed. This work provides useful knowledge in the discovery of β-catenin agents. [ABSTRACT FROM AUTHOR]

The non-orthotopic expression of olfactory receptors (ORs) includes the male reproductive system, and in particular spermatozoa; their active ligands could be essential to sperm chemotaxis and chemical sperm–oocyte communication. OR51E2 expression has been previously reported on sperm cells' surface. It has been demonstrated in different cellular models that olfactory receptor 51E2 (OR51E2) binds volatile short-chain fatty acids (SCFAs) as specific ligands. In the present research, we make use of Western blot, confocal microscopy colocalization analysis, and the calcium-release assay to demonstrate the activation of sperm cells through OR51E2 upon SCFAs stimulus. Moreover, we perform a novel modified swim-up assay to study the involvement of OR51E2/SCFAs in sperm migration. Taking advantage of computer-assisted sperm analysis (CASA system), we determine the kinematics parameters of sperm cells migrating towards SCFAs-enriched medium, revealing that these ligands are able to promote a more linear sperm-cell orientation. Finally, we obtain SCFAs by mass spectrometry in cervico-vaginal mucus and show for the first time that a direct incubation between cervical mucus and sperm cells could promote their activation. This study can shed light on the possible function of chemosensory receptors in successful reproduction activity, laying the foundation for the development of new strategies for the treatment of infertile individuals. [ABSTRACT FROM AUTHOR]

Three out of the eight proteins that significantly increased their presence on day 18 of the cycle were also identified previously by Grande et al.: small proline-rich protein 3 (SPRR3) and WAP four-disulfide core domain protein 2 (WFDC2) as constitutive proteins, and desmoglein-3 (DSG3) as an ovulatory-specific protein. [Extracted from the article]

The implementation of cancer molecular characterization in clinical practice has improved prognostic re-definition, extending the eligibility to a continuously increasing number of targeted treatments. Broad molecular profiling technologies better than organ-based approaches are believed to serve such dynamic purposes. We here present the workflow our institution adopted to run a comprehensive cancer genome profiling in clinical practice. This article describes the workflow designed to make a comprehensive cancer genome profiling program feasible and sustainable in a large-volume referral hospital. [ABSTRACT FROM AUTHOR]

21-hydroxylase deficiency (21OHD), the most common form of congenital adrenal hyperplasia (CAH), is associated with pathogenic variants in CYP21A2 gene. The clinical form of the disease ranges from classic or severe to non-classic (NC) or mild late onset. The CYP21A2 gene is located on the long arm of chromosome 6, within the RCCX region, one of the most complex loci in the human genome. The 3′untranslated sequence of CYP21A2 exon 10 overlap the last exon of TNXB gene (these genes lie on the opposite strands of DNA and have the opposite transcriptional direction) that encodes an extracellular matrix glycoprotein tenascin-X (TNX). A recombination event between TNXB and its pseudogene TNXA causes a 30 kb deletion producing a chimeric TNXA/TNXB gene (CAH-X chimera) where both CYP21A2 and TNXB genes are impaired. This genetic condition characterizes a subset of patients with 21OHD who display the hypermobility phenotype of Ehlers–Danlos syndrome (hEDS) (CAH-X Syndrome). The aim of this study was to assess the prevalence of CAH-X syndrome in an Italian cohort of patients with 21OHD. At this purpose, 196 probands were recruited. Multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing were used to identify the CAH-X genotype. Twenty-one individuals showed the heterozygous continuous deletion involving the CYP21A2 and part of the TNXB gene. EDS-related clinical manifestations were identified in most patients carrying the CAH-X chimera. A CAH-X prevalence of 10.7% was estimated in our population. [ABSTRACT FROM AUTHOR]

Several genes are involved in sport performance, especially in injuries incidence. The aim of this study was to investigate the association of ACE, ACTN3, COL1A1, and MCT1 genotypes and injuries in rugby players in order to find a genotype/phenotype correlation and provide useful information improving athletic performance. One-hundred male professional and semiprofessional rugby players were selected. Analysis was performed genotyping the genes ACE, ACTN3, COL1A1, and MCT1 as candidate gene of interest involved in athletic performance. A control group of non-athletic Italian male participants was analyzed to compare the results. We found statistical significance of MCT1 rs1049434 AA for total injuries (χ2 = 0.115; p = 0.003) and bone injuries (χ2 = 0.603; p = 0.007) in the rugby athlete population. No statistical significance was found between injury incidence and ACE, ACTN3, COL1A1 genotypes. The MCT1 AA genotype is associated with the incidence of total and bone injuries in the rugby player population. Although environmental factors such as lifestyle, diet, training, and stress can influence athletic performance, our data demonstrated the importance of genetic study in sport aimed at developing personalized training and achieving the best possible athletic excellence. [ABSTRACT FROM AUTHOR]

Athletic performance is influenced by many factors such as the environment, diet, training and endurance or speed in physical effort and by genetic predisposition. Just a few studies have analyzed the impact of genotypes on physical performance in rugby. The aim of this study was to verify the modulation of genetic influence on rugby-specific physical performance. Twenty-seven elite rugby union players were involved in the study during the in-season phase. Molecular genotyping was performed for: angiotensin-converting enzyme (ACE rs4646994), alfa-actinin-3 (ACTN3 rs1815739) and monocarboxylate transporter 1 (MCT1 rs1049434) and their variants. Lean mass index (from skinfolds), lower-limb explosive power (countermovement jump), agility (505), speed (20 m), maximal aerobic power (Yo-yo intermittent recovery test level 1) and repeated sprint ability (12 × 20 m) were evaluated. In our rugby union players ACE and ACTN3 variants did not show any influence on athletic performance. MCT1 analysis showed that TT-variant players had the highest peak vertical power (p = 0.037) while the ones with the AA genotype were the fastest in both agility and sprint tests (p = 0.006 and p = 0.012, respectively). Considering the T-dominant model, the AA genotype remains the fastest in both tests (agility: p = 0.013, speed: p = 0.017). Only the MCT1 rs1049434 A allele seems to be advantageous for elite rugby union players, particularly when power and speed are required. [ABSTRACT FROM AUTHOR]

Recurrent cystitis (RC) is a common disease, especially in females. Anatomical, behavioral and genetic predisposing factors are associated with the ascending retrograde route, which often causes bladder infections. RC seems to be mainly caused by agents derived from the intestinal microbiota, and most frequently by Escherichia coli. Intestinal contiguity contributes to the etiopathogenesis of RC and an alteration in intestinal permeability could have a major role in RC. The aim of this pilot study is to assess gut microbiome dysbiosis and intestinal permeability in female patients with RC. Patients with RC (n = 16) were enrolled and compared with healthy female subjects (n = 15) and patients with chronic gastrointestinal (GI) disorders (n = 238). We calculated the Acute Cystitis Symptom Score/Urinary Tract Infection Symptom Assessment (ACSS/UTISA) and Gastrointestinal Symptom Rating Scale (GSRS) scores and evaluated intestinal permeability and the fecal microbiome in the first two cohorts. Patients with RC showed an increased prevalence of gastrointestinal symptoms compared with healthy controls. Of the patients with RC, 88% showed an increased intestinal permeability with reduced biodiversity of gut microbiota compared to healthy controls, and 68% of the RC patients had a final diagnosis of gastrointestinal disease. Similarly, GI patients reported a higher incidence of urinary symptoms with a diagnosis of RC in 20%. Gut barrier impairment seems to play a major role in the pathogenesis of RC. Further studies are necessary to elucidate the role of microbiota and intestinal permeability in urinary tract infections. [ABSTRACT FROM AUTHOR]

The retention of a number of solutes that may cause adverse biochemical/biological effects, called uremic toxins, characterizes uremic syndrome. Uremia therapy is based on renal replacement therapy, hemodialysis being the most commonly used modality. The membrane contained in the hemodialyzer represents the ultimate determinant of the success and quality of hemodialysis therapy. Membrane's performance can be evaluated in terms of removal efficiency for unwanted solutes and excess fluid, and minimization of negative interactions between the membrane material and blood components that define the membrane's bio(in)compatibility. Given the high concentration of plasma proteins and the complexity of structural functional relationships of this class of molecules, the performance of a membrane is highly influenced by its interaction with the plasma protein repertoire. Proteomic investigations have been increasingly applied to describe the protein uremic milieu, to compare the blood purification efficiency of different dialyzer membranes or different extracorporeal techniques, and to evaluate the adsorption of plasma proteins onto hemodialysis membranes. In this article, we aim to highlight investigations in the hemodialysis setting making use of recent developments in proteomic technologies. Examples are presented of why proteomics may be helpful to nephrology and may possibly affect future directions in renal research. [ABSTRACT FROM AUTHOR]

Based on our previous proteomic study on Cavitating Ultrasound Aspirator (CUSA) fluid pools of Newly Diagnosed (ND) and Recurrent (R) glioblastomas (GBMs) of tumor core and periphery, as defined by 5-aminolevulinc acid (5-ALA) metabolite fluorescence, this work aims to apply a bioinformatic approach to investigate specifically into three sub-proteomes, i.e., Not Detected in Brain (NB), Cancer Related (CR) and Extracellular Vesicles (EVs) proteins following selected database classification. The study of these yet unexplored specific datasets aims to understand the high infiltration capability and relapse rate that characterizes this aggressive brain cancer. Out of the 587 proteins highly confidently identified in GBM CUSA pools, 53 proteins were classified as NB. Their gene ontology (GO) analysis showed the over-representation of blood coagulation and plasminogen activating cascade pathways, possibly compatible with Blood Brain Barrier damage in tumor disease and surgery bleeding. However, the NB group also included non-blood proteins and, specifically, histones correlated with oncogenesis. Concerning CR proteins, 159 proteins were found in the characterized GBM proteome. Their GO analysis highlighted the over-representation of many pathways, primarily glycolysis. Interestingly, while CR proteins were identified in ND-GBM exclusively in the tumor zones (fluorescence positive core and periphery zones) as predictable, conversely, in R-GBM they were unexpectedly characterized prevalently in the healthy zone (fluorescence negative tumor periphery). Relative to EVs protein classification, 60 proteins were found. EVs are over-released in tumor disease and are important in the transport of biological macromolecules. Furthermore, the presence of EVs in numerous body fluids makes them a possible low-invasive source of brain tumor biomarkers to be investigated. These results give new hints on the molecular features of GBM in trying to understand its aggressive behavior and open to more in-depth investigations to disclose potential disease biomarkers. [ABSTRACT FROM AUTHOR]

Background: The federalization of the Italian National Health Service (NHS) gave administrative, financial, and managerial independence to regions. They are in reciprocal competition according to the "quasi-market" model. A network of independent providers replaced the state monopoly. The NHS, based on the Beveridge model in which citizens are free to choose their place of treatment, was consolidated. The aim of our research was to analyze the fulfillment of need for hospital services on site and patients' migration to hospitals of other regions. Material and Methods: We analyzed data from 2013 to 2017 of Hospital Discharge Cards (HDCs) provided by the Ministry of Health. The subjects of the analysis (catchment areas) were the hospital networks of every Italian region. The study of flows was developed through Internal Demand Satisfaction, Attraction, Escape, Attraction, Absorption, and Escape Production indexes. Graphic representations were produced using Gandy's Nomogram and Qgis software. Results: In the studied period, the mean number of mobility admission was 678.659 ± 3.388, with an increase of 0.90%; in particular, the trend for ordinary regime increased 1.17%. Regions of central/northern Italy have attracted more than 60% of the escapes of the southern ones. Gandy's Nomogram showed that only nine regions had optimal public hospital planning (Lombardy, Autonomous Province of Bolzano, Veneto, Friuli V.G., Emilia-Romagna, Tuscany, Umbria, Latium and Molise). Conclusion: The central/northern regions appear more able to meet the care needs of their citizens and to attract patients than the southern ones. [ABSTRACT FROM AUTHOR]

The ongoing outbreak of coronavirus disease 2019 (COVID-19), which impairs the functionality of several organs, represents a major threat to human health. One of the hardest challenges in the fight against COVID-19 is the development of wide-scale, effective, and rapid laboratory tests to control disease severity, progression, and possible sudden worsening. Monitoring patients in real-time is highly demanded in this pandemic era when physicians need reliable and quantitative tools to prioritize patients' access to intensive care departments. In this regard, salivary biomarkers are extremely promising, as they allow for the fast and non-invasive collection of specimens and can be repeated multiple times. Methods: We compare salivary levels of immunoglobulin A subclasses (IgA1 and IgA2) and free light chains (kFLC and λFLC) in a cohort of 29 SARS-CoV-2 patients and 21 healthy subjects. Results: We found that each biomarker differs significantly between the two groups, with p-values ranging from 10−8 to 10−4. A Receiving Operator Curve analysis shows that λFLC level is the best-suited candidate to discriminate the two groups (AUC = 0.96), with an accuracy of 0.94 (0.87–1.00 95% CI), a precision of 0.91 (0.81–1.00 95% CI), a sensitivity of 1.00 (0.96–1.00 95% CI), and a specificity of 0.86 (0.70–1.00 95% CI). Conclusion: These results suggest λFLC as an ideal indicator of patient conditions. This hypothesis is strengthened by the consideration that the λFLC half-life (approximately 6 h) is significantly shorter than the IgA one (21 days), thus confirming the potential of λFLC for effectively monitoring patients' fluctuation in real-time. [ABSTRACT FROM AUTHOR]

Basic and preclinical research founded the progress of personalized medicine by providing a prodigious amount of integrated profiling data and by enabling the development of biomedical applications to be implemented in patient-centered care and cures. If the rapid development of genomics research boosted the birth of personalized medicine, further development in omics technologies has more recently improved our understanding of the functional genome and its relevance in profiling patients' phenotypes and disorders. Concurrently, the rapid biotechnological advancement in diverse research areas enabled uncovering disease mechanisms and prompted the design of innovative biological treatments tailored to individual patient genotypes and phenotypes. Research in stem cells enabled clarifying their role in tissue degeneration and disease pathogenesis while providing novel tools toward the development of personalized regenerative medicine strategies. Meanwhile, the evolving field of integrated omics technologies ensured translating structural genomics information into actionable knowledge to trace detailed patients' molecular signatures. Finally, neuroscience research provided invaluable models to identify preclinical stages of brain diseases. This review aims at discussing relevant milestones in the scientific progress of basic and preclinical research areas that have considerably contributed to the personalized medicine revolution by bridging the bench-to-bed gap, focusing on stem cells, omics technologies, and neuroscience fields as paradigms. [ABSTRACT FROM AUTHOR]

Simple Summary: Biofilm formation represents one of the most effective forms of bacterial persistence in surfaces where nutrients are available or in the tissues of living hosts as humans or animals. Such persistence is due to the high rate of antimicrobial resistance of this shell conformation. It often represents a burden when the pathogen colonizes niches from where it is not removable such as food facilities, farm facilities or parts of living organisms. In this study, we investigated biofilm formation mechanisms and enhanced antimicrobial resistance of 6 different S. aureus strains. The detected mechanisms were primarily related to the control of catabolites, the production of proteins with moonlighting activities and the detoxification of compounds with antimicrobial activities (i.e., alcohol). Glycolysis and aerobic metabolisms were found to be less active in the biofilm conformation. Consequently, less H2O2 production from aerobic metabolism was translated into a measurable under-representation of catalase protein. Antimicrobial resistance (AMR) represents one of the most critical challenges that humanity will face in the following years. In this context, a "One Health" approach with an integrated multidisciplinary effort involving humans, animals and their surrounding environment is needed to tackle the spread of AMR. One of the most common ways for bacteria to live is to adhere to surfaces and form biofilms. Staphylococcus aureus (S. aureus) can form biofilm on most surfaces and in a wide heterogeneity of environmental conditions. The biofilm guarantees the survival of the S. aureus in harsh environmental conditions and represents an issue for the food industry and animal production. The identification and characterization of biofilm-related proteins may provide interesting insights into biofilm formation mechanisms in S. aureus. In this regard, the aims of this study were: (i) to use proteomics to compare proteomes of S. aureus growing in planktonic and biofilm forms in order to investigate the common features of biofilm formation properties of different strains; (ii) to identify specific biofilm mechanisms that may be involved in AMR. The proteomic analysis showed 14 differentially expressed proteins among biofilm and planktonic forms of S. aureus. Moreover, three proteins, such as alcohol dehydrogenase, ATP-dependent 6-phosphofructokinase, and fructose-bisphosphate aldolase, were only differentially expressed in strains classified as high biofilm producers. Differentially regulated catabolites metabolisms and the switch to lower oxygen-related metabolisms were related to the sessile conformation analyzed. [ABSTRACT FROM AUTHOR]

Over the past 30 years a considerable amount of data has accumulated on the multifaceted role of hydrogen sulfide (H2S) in the central nervous system. Depending on its concentrations, H2S has opposite actions, ranging from neuromodulator to neurotoxic. Nowadays, accurate determination of H2S is still an important challenge to understand its biochemistry and functions. In this perspective, this study aims to explore H2S levels in cerebrospinal fluid (CSF), key biofluid for neurological studies, and to assess alleged correlations with neuroinflammatory and neurodegenerative mechanisms. A validated analytical determination combining selective electrochemical detection with ion chromatography was developed to measure free and bound sulfur forms of H2S. A first cohort of CSF samples (n = 134) was analyzed from patients with inflammatory and demyelinating disorders (acute disseminated encephalomyelitis; multiple sclerosis), chronic neurodegenerative diseases (Alzheimer disease; Parkinson disease), and motor neuron disease (Amyotrophic lateral sclerosis). Given its analytical features, the chromatographic method resulted sensitive, reproducible and robust. We also explored low molecular weight-proteome linked to sulphydration by proteomics analysis on matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). This study is a first clinical report on CSF H2S concentrations from neurological diseases and opens up new perspectives on the potential clinical relevance of H2S and its potential therapeutic application. [ABSTRACT FROM AUTHOR]

Gallbladder carcinoma (GBC) is one of the most aggressive malignancies with poor prognosis and a high fatality rate. The disease presents in advanced stages where the treatment is ineffective. Regarding GBC pathogenesis, as with other neoplasia, this tumor is a multifactorial disorder involving different causative factors such as environmental, microbial, metabolic, and molecular. Genetic alterations can be germline or somatic that involving proto-oncogenes, tumor suppressor genes, cell cycle genes, and growth factors. The ataxia telangiectasia mutated (ATM) gene, coding a serine/threonine kinase involved in the early stages of the homologous recombination (HR) mechanism, is one of the most altered genes in GBC. Here, we present the molecular characterization of a novel germline ATM large genomic rearrangement (LGR) identified by next-generation sequencing (NGS) analysis in an Italian woman diagnosed with metastatic GBC at the age of 55. The results underline the importance of expanding the NGS approach in gallbladder cancer in order to propose new molecular markers of predisposition and prognosis exploitable by novel targeted therapies that may improve the response of patients with ATM-deficient cancers. [ABSTRACT FROM AUTHOR]

Facioscapulohumeral muscular dystrophy (FSHD) is caused by a complex epigenetic mechanism finally leading to the misexpression of DUX4 in skeletal muscle. Detecting DUX4 and quantifying disease progression in FSHD is extremely challenging, thus increasing the need for surrogate biomarkers. We applied a shotgun proteomic approach with two different setups to analyze the protein repertoire of interstitial fluids obtained from 20 muscles in different disease stages classified by magnetic resonance imaging (MRI) and serum samples from 10 FSHD patients. A total of 1156 proteins were identified in the microdialysates by data independent acquisition, 130 of which only found in muscles in active disease stage. Proteomic profiles were able to distinguish FSHD patients from controls. Two innate immunity mediators (S100-A8 and A9) and Dermcidin were upregulated in muscles with active disease and selectively present in the sera of FSHD patients. Structural muscle and plasminogen pathway proteins were downregulated. Together with the upstream inhibition of myogenic factors, this suggests defective muscle regeneration and increased fibrosis in early/active FSHD. Our MRI targeted exploratory approach confirmed that inflammatory response has a prominent role, together with impaired muscle regeneration, before clear muscle wasting occurs. We also identified three proteins as tissue and possibly circulating biomarkers in FSHD. [ABSTRACT FROM AUTHOR]

Simple Summary: The biological processes responsible for the high infiltration and recurrence rate of glioblastoma multiforme, the most frequent and aggressive primary brain tumor (GBM), are still under investigation. By the original analysis of cavitating ultrasound aspirator fluid as the biological specimen, the present study aimed to preliminarily explore and compare the protein profiles of the tumor core and tumor periphery, as defined by 5-aminolevulinic acid fluorescence, in newly diagnosed and recurrent glioblastoma sampled pools. The results showed distinguished protein elements in the different tumor and peritumoral zones, as well as in the two tumor states (newly diagnosed vs recurrent), and suggested the presence of pathological aspects in the fluorescent negative periphery, possibly contributing to the comprehension of the molecular mechanisms underlying this tumor's onset and development, opening to potential clinical applications. The present investigation aimed to characterize the protein profile of cavitating ultrasound aspirator fluid of newly diagnosed and recurrent glioblastoma comparing diverse zones of collection, i.e., tumor core and tumor periphery, with the aid of 5-aminolevulinic acid fluorescence. The samples were pooled and analyzed in triplicate by LC-MS following the shotgun proteomic approach. The identified proteins were then grouped to disclose elements exclusive and common to the tumor state or tumor zones and submitted to gene ontology classification and pathway overrepresentation analysis. The proteins common to the distinct zones were further investigated by relative quantitation, following a label free approach, to disclose possible differences of expression. Nine proteins, i.e., tubulin 2B chain, CD59, far upstream element-binding, CD44, histone H1.4, caldesmon, osteopontin, tropomyosin chain and metallothionein-2, marked the core of newly diagnosed glioblastoma with respect to tumor periphery. Considering the tumor zone, including the core and the fluorescence positive periphery, the serine glycine biosynthesis, pentose phosphate, 5-hydroxytryptamine degredation, de novo purine biosynthesis and huntington disease pathways resulted statistically significantly overrepresented with respect to the human genome of reference. The fluorescence negative zone shared several protein elements with the tumor zone, possibly indicating the presence of pathological aspects of glioblastoma rather than of normal brain parenchyma. On the other hand, its exclusive protein elements were considered to represent the healthy zone and, accordingly, exhibiting no pathways overrepresentation. On the contrary to newly diagnosed glioblastoma, pathway overrepresentation was recognized only in the healthy zone of recurrent glioblastoma. The TGFβ signaling pathway, exclusively classified in the fluorescence negative periphery in newly diagnosed glioblastoma, was instead the exclusive pathway classified in the tumor core of recurrent glioblastoma. These results, preliminary obtained on sample pools, demonstrated the potential of cavitron ultrasonic surgical aspirate fluid for proteomic profiling of glioblastoma able to distinguish molecular features specific of the diverse tumor zones and tumor states, possibly contributing to the understanding of the highly infiltrative capability and recurrent rate of this aggressive brain tumor and opening to potential clinical applications to be further investigated. [ABSTRACT FROM AUTHOR]

Simple Summary: Antimicrobials represent useful tools to fight bacterial infections that could harm human and animal health. Antimicrobial resistance occurs naturally or can be induced by the misuse of antibiotics. Its occurrence limits the efficiency of antibiotics and therefore the possibility to treat infections effectively. This can lead to an increasing severity of infectious diseases in humans and animals. Here, we describe the development of a workflow that provides a qualitative representation of the antimicrobial genes that are translated into proteins. Since proteins are ultimately the real effectors, the method herein described demonstrates that those genes are effectively enhancing antimicrobial resistance (AMR). The presented method is independent of any amplification step and provides useful information on the dynamics of the biochemical functions accomplished by the raw milk bacterial consortium. The environment, including animals and animal products, is colonized by bacterial species that are typical and specific of every different ecological niche. Natural and human-related ecological pressure promotes the selection and expression of genes related to antimicrobial resistance (AMR). These genes might be present in a bacterial consortium but might not necessarily be expressed. Their expression could be induced by the presence of antimicrobial compounds that could originate from a given ecological niche or from human activity. In this work, we applied (meta)proteomics analysis of bacterial compartment of raw milk in order to obtain a method that provides a measurement of circulating AMR involved proteins and gathers information about the whole bacterial composition. Results from milk analysis revealed the presence of 29 proteins/proteoforms linked to AMR. The detection of mainly β-lactamases suggests the possibility of using the milk microbiome as a bioindicator for the investigation of AMR. Moreover, it was possible to achieve a culture-free qualitative and functional analysis of raw milk bacterial consortia. [ABSTRACT FROM AUTHOR]

Primary mitochondrial myopathies (PMM) are a group of mitochondrial disorders characterized by a predominant skeletal muscle involvement. The aim of this study was to evaluate whether the biochemical profile determined by Fourier-transform infrared (FTIR) spectroscopic technique would allow to distinguish among patients affected by progressive external ophthalmoplegia (PEO), the most common PMM presentation, oculopharyngeal muscular dystrophy (OPMD), and healthy controls. Thirty-four participants were enrolled in the study. FTIR spectroscopy was found to be a sensitive and specific diagnostic marker for PEO. In particular, FTIR spectroscopy was able to distinguish PEO patients from those affected by OPMD, even in the presence of histological findings similar to mitochondrial myopathy. At the same time, FTIR spectroscopy differentiated single mtDNA deletion and mutations in POLG, the most common nuclear gene associated with mitochondrial diseases, with high sensitivity and specificity. In conclusion, our data suggest that FTIR spectroscopy is a valuable biodiagnostic tool for the differential diagnosis of PEO with a high ability to also distinguish between single mtDNA deletion and mutations in POLG gene based on specific metabolic transitions. [ABSTRACT FROM AUTHOR]

Down syndrome (DS) is the most common chromosomal disorder and the leading genetic cause of intellectual disability in humans, which results from the triplication of chromosome 21. To search for biomarkers for the early detection and exploration of the disease mechanisms, here, we investigated the protein expression signature of peripheral blood mononuclear cells (PBMCs) in DS children compared with healthy donors (HD) by using an in-depth label-free shotgun proteomics approach. Identified proteins are found associated with metabolic pathways, cellular trafficking, DNA structure, stress response, cytoskeleton network, and signaling pathways. The results showed that a well-defined number of dysregulated pathways retain a prominent role in mediating DS pathological features. Further, proteomics results are consistent with published study in DS and provide evidences that increased oxidative stress and the increased induction of stress related response, is a participant in DS pathology. In addition, the expression levels of some key proteins have been validated by Western blot analysis while protein carbonylation, as marker of protein oxidation, was investigated. The results of this study propose that PBMCs from DS children might be in an activated state where endoplasmic reticulum stress and increased production of radical species are one of the primary events contributing to multiple DS pathological features. [ABSTRACT FROM AUTHOR]

Paratuberculosis is an infectious disease of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). MAP is an intracellular pathogen with a possible zoonotic potential since it has been successfully isolated from the intestine and blood of Crohn's disease patients.Since no cure is available, after the detection of the disease, animal culling is the sole applicable containment strategy. However, the difficult detection of the disease in its subclinical form, facilitates its spread raising the need for the development of effective diagnosis and vaccination strategies. The prompt identification and isolation of the infected animals in the subclinical stage would prevent the spread of the infection.In the present study, an immunoinformatic approach has been used to investigate the immunogenic properties of 10 MAP proteins. These proteins were chosen according to a previously published immunoproteomics approach. For each previously-described immunoreactive protein, we predicted the epitopes capable of eliciting an immune response by binding both B-cells and/or class I MHC antigens. The retrieved peptide sequences were analyzed for their specificity and cross-reactivity. The final aim is to employ the discovered peptides sequences as a filtered library useful for early-stage diagnosis and/or to be used in novel multi-subunit or recombinant vaccine formulations. [ABSTRACT FROM AUTHOR]

Ependymoma pediatric brain tumor occurs at approximate frequencies of 10–15% in supratentorial and 20–30% in posterior fossa regions. These tumors have an almost selective response to surgery and relative and confirmed resistance to radiotherapy and chemotherapic agents, respectively. Alongside histopathological grading, clinical and treatment evaluation of ependymomas currently consider the tumor localization and the genomic outlined associated molecular subgroups, with the supratentorial and the posterior fossa ependymomas nowadays considered diverse diseases. On these grounds and in trying to better understand the molecular features of these tumors, the present investigation aimed to originally investigate the proteomic profile of pediatric ependymoma tissues of different grade and localization by mass spectrometry platforms to disclose potential distinct protein phenotypes. To this purpose, acid-soluble and acid-insoluble fractions of ependymoma tumor tissues homogenates were analyzed by LC-MS following both the top-down and the shotgun proteomic approaches, respectively, to either investigate the intact proteome or its digested form. The two approaches were complementary in profiling the ependymoma tumor tissues and showed distinguished profiles for supratentorial and posterior fossa ependymomas and for WHO II and III tumor grades. Top-down proteomic analysis revealed statistically significant higher levels of thymosin beta 4, 10 kDa heat shock protein, non-histone chromosomal protein HMG-17, and mono-/uncitrullinated forms ratio of the glial fibrillary acidic protein (GFAP) fragment 388–432 in supratentorial ependymomas—the same GFAP fragment as well as the hemoglobin alpha- and the beta-chain marked grade II with respect to grade III posterior fossa ependymomas. Gene ontology classification of shotgun data of the identified cancer and the non-cancer related proteins disclosed protein elements exclusively marking tumor localization and pathways that were selectively overrepresented. These results, although preliminary, seem consistent with different protein profiles of ependymomas of diverse grade of aggressiveness and brain region development and contributed to enlarging the molecular knowledge of this still enigmatic tumor. [ABSTRACT FROM AUTHOR]

Physical frailty and sarcopenia (PF&S) are hallmarks of aging that share a common pathogenic background. Perturbations in protein/amino acid metabolism may play a role in the development of PF&S. In this initial report, 68 community-dwellers aged 70 years and older, 38 with PF&S and 30 non-sarcopenic, non-frail controls (nonPF&S), were enrolled as part as the "BIOmarkers associated with Sarcopenia and Physical frailty in EldeRly pErsons" (BIOSPHERE) study. A panel of 37 serum amino acids and derivatives was assayed by UPLC-MS. Partial Least Squares–Discriminant Analysis (PLS-DA) was used to characterize the amino acid profile of PF&S. The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classification was 76.6 ± 3.9% (75.1 ± 4.6% for enrollees with PF&S; 78.5 ± 6.0% for nonPF&S). Older adults with PF&S were characterized by higher levels of asparagine, aspartic acid, citrulline, ethanolamine, glutamic acid, sarcosine, and taurine. The profile of nonPF&S participants was defined by higher concentrations of α-aminobutyric acid and methionine. Distinct profiles of circulating amino acids and derivatives characterize older people with PF&S. The dissection of these patterns may provide novel insights into the role played by protein/amino acid perturbations in the disabling cascade and possible new targets for interventions. [ABSTRACT FROM AUTHOR]