Coceth sulfate characterization by electrospray ionization tandem mass spectrometry.

RATIONALE: The anionic surfactants, among which are alkyl ether sulfates (AESs), are the most used class of surfactants in cleansing applications. The negatively charged head group of AESs is a sulfate moiety linked with a variable number of ethylene oxide units, i.e. a polyethylene glycol chain. The hydrophobic part of an AES is constituted by a linear alkyl chain of carbon atoms, generally obtained from natural fatty acids. Coconut oil fatty acids, including the sodium salts of coceth sulfate (CES) with chemical formula Cx Hy (OCH2 CH2 )n OSO3 Na, are widely used as feedstock for AESs synthesis. CES is added to many cleaning products and detergents defined as non-aggressive. Currently, no detailed structural information concerning the alkyl chain length x and, more importantly, the degree of ethoxylation n has been reported. METHODS: A commercial standard solution of CES was characterized by tandem mass spectrometry, employing direct injection into the electrospray ionization (ESI) source of a a linear quadrupole ion trap mass spectrometer. RESULTS: Two series of oligomeric species, characterized by a C12 and C14 alkyl chains, i.e. [C12 H25 (OCH2 CH2 )nOSO3 ]- and [C14 H29 (OCH2 CH2 )n OSO3 ]- with n ranging from 0 to 7, were successfully identified. The interpretation of these data was very useful for CES identification in three commercial dishwasher cleaning products. CONCLUSIONS: Direct injection MS/MS analysis of CES revealed a well-defined molecular weight distribution and allowed the alkyl chain composition and the number of ethylene oxide units to be to identified.

Identification of a de novo NLRP3 gene variation in an Italian Behçet syndrome patient.

A novel nonsynonymous variation of NLRP3 was identified in an Italian patient with Behçet syndrome using both bioinformatics and molecular methods. This variation was a thymine to guanine polymorphism responsible for the isoleucine to serine amino acid change at position 348. The novel variation was predicted to be a pathogenic allele.

Transcriptional Regulation Factors of the Human Mitochondrial Aspartate/Glutamate Carrier Gene, Isoform 2 (SLC25A13): USF1 as Basal Factor and FOXA2 as Activator in Liver Cells.

Mitochondrial carriers catalyse the translocation of numerous metabolites across the inner mitochondrial membrane, playing a key role in different cell functions. For this reason, mitochondrial carrier gene expression needs tight regulation. The human SLC25A13 gene, encoding for the mitochondrial aspartate/glutamate carrier isoform 2 (AGC2), catalyses the electrogenic exchange of aspartate for glutamate plus a proton, thus taking part in many metabolic processes including the malate-aspartate shuttle. By the luciferase (LUC) activity of promoter deletion constructs we identified the putative promoter region, comprising the proximal promoter (-442 bp/-19 bp), as well as an enhancer region (-968 bp/-768 bp). Furthermore, with different approaches, such as in silico promoter analysis, gene silencing and chromatin immunoprecipitation, we identified two transcription factors responsible for SLC25A13 transcriptional regulation: FOXA2 and USF1. USF1 acts as a positive transcription factor which binds to the basal promoter thus ensuring SLC25A13 gene expression in a wide range of tissues. The role of FOXA2 is different, working as an activator in hepatic cells. As a tumour suppressor, FOXA2 could be responsible for SLC25A13 high expression levels in liver and its downregulation in hepatocellular carcinoma (HCC).

A novel homozygous stop-codon mutation in human HFE responsible for nonsense-mediated mRNA decay.

HFE-hemochromatosis (HH) is an autosomal disease characterized by excessive iron absorption. Homozygotes for H63D variant, and still less H63D heterozygotes, generally do not express HH phenotype. The data collected in our previous study in the province of Matera (Basilicata, Italy) underlined that some H63D carriers showed altered iron metabolism, without additional factors. In this study, we selected a cohort of 10/22 H63D carriers with severe biochemical iron overload (BIO). Additional analysis was performed for studying HFE exons, exon-intron boundaries, and untranslated regions (UTRs) by performing DNA extraction, PCR amplification and sequencing. The results showed a novel substitution (NM_000410.3:c.847C>T) in a patient exon 4 (GenBankJQ478433); it introduces a premature stop-codon (PTC). RNA extraction and reverse-transcription were also performed. Quantitative real-time PCR was carried out for verifying if our aberrant mRNA is targeted for nonsense-mediated mRNA decay (NMD); we observed that patient HFE mRNA was expressed much less than calibrator, suggesting that the mutated HFE protein cannot play its role in iron metabolism regulation, resulting in proband BIO. Our finding is the first evidence of a variation responsible for a PTC in iron cycle genes. The genotype-phenotype correlation observed in our cases could be related to the additional mutation.

Preliminary characterization of biomolecular processes related to plasticity in Acyrthosiphonpisum.

Global warming strongly impacts many organisms' development, distribution and population structure. This problem has attracted the attention of many scientists to understand and study its actual effects, especially on insects influenced by environmental temperatures. Aphids are a model for studies of the genetics and physiology of stress. Aphids are characterized by parthenogenetic reproduction, which limits the effects of recombination on evolutionary processes, and have shown resistance to various biotic and abiotic stresses. This study was based on the hypothesis that aphids have optimized, over time, genetic mechanisms capable to give them plasticity through genome modifications mediated by transposition. To understand and evaluate the effects of heat stress, the expression levels of transposases and methylases were analyzed in mothers and daughters. Our results show that after four days from the thermal shock, methylation decreases in both mothers and daughters, while transposition significantly increases in daughters, thus generating gene variability, essential for adaptation.

TNFα rs1800629 Polymorphism and Response to Anti-TNFα Treatment in Behçet Syndrome: Data from an Italian Cohort Study.

Tumor Necrosis Factor-alpha (TNFα) rs1800629 (-308G>A) is a single nucleotide polymorphism (SNP) related to variable responses to anti-TNFα therapy. This therapy is efficient in severe and refractory manifestation of Behçet syndrome (BS), an auto-inflammatory systemic vasculitis. We investigated (1) the association between rs1800629 genotypes and responses to therapy and (2) the correlation between SNP and clinical patterns in a cohort of 74 BS Italian patients receiving anti-TNFα therapy with a follow-up of at least 12 months. The rs1800629 was genotyped through amplification, direct sequencing and bioinformatics analyses. The rs1800629 GG and GA genotypes were assessed as predictors of outcomes dividing the patients between therapy responders and non-responders. The rs1800629 GG and GA genotypes were found, respectively, in 59/74 (79.7%) and 15/74 BS patients (21.3%) (p < 0.05). We identified 16/74 (21.9%) non-responder patients, of which 9/16 (56.3%) showed the GG genotype and 7/16 (43.7%) the GA genotype. A total of 50/58 (86.2%) responder patients showed the GG genotype, and 8/58 (13.8%) the GA genotype (p < 0.05). The percentage of non-responder females (68.8%) was significantly higher than non-responder males (31.2%) (p < 0.05). No correlation between SNP and clinical patterns was observed. To successfully include rs1800629 as a predictive biomarker of TNFα inhibitor response, genome-wide association studies in larger, well-characterised cohorts are required.

Effects of Extracts of Two Selected Strains of Haematococcus pluvialis on Adipocyte Function.

Recently, microalgae are arousing considerable interest as a source of countless molecules with potential impacts in the nutraceutical and pharmaceutical fields. Haematococcus pluvialis, also named Haematococcus lacustris, is the largest producer of astaxanthin, a carotenoid exhibiting powerful health effects, including anti-lipogenic and anti-diabetic activities. This study was carried out to investigate the properties of two selected strains of H. pluvialis (FBR1 and FBR2) on lipid metabolism, lipolysis and adipogenesis using an in vitro obesity model. FBR1 and FBR2 showed no antiproliferative effect at the lowest concentration in 3T3-L1 adipocytes. Treatment with FBR2 extract reduced lipid deposition, detected via Oil Red O staining and the immunocontent of the adipogenic proteins PPARγ, ACLY and AMPK was revealed using Western blot analysis. Extracts from both strains induced lipolysis in vitro and reduced the secretion of interleukin-6 and tumor necrosis factor-α. Moreover, the FBR1 and FBR2 extracts improved mitochondrial function, reducing the levels of mitochondrial superoxide anion radical and increasing mitochondrial mass compared to untreated adipocytes. These findings suggest that FBR2 extract, more so than FBR1, may represent a promising strategy in overweight and obesity prevention and treatment.

Ceratonia siliqua L. Pod Extract: From Phytochemical Characterization to Liposomal Formulation and Evaluation of Behaviour in Cells.

The formulation of plant extracts in phospholipid vesicles is a promising strategy to exploit their biological properties while solving problems related to poor solubility in water, high instability, and low skin permeation and retention time. In this study, Ceratonia siliqua ripe pods were used for the preparation of a hydro-ethanolic extract, which showed antioxidant properties owing to the presence of biologically active compounds identified by liquid chromatography-mass spectrometry (e.g., hydroxybenzoic acid and flavonoid derivatives). To improve the applicability of the extract in therapy, a topical formulation based on liposomes was explored. The vesicles were characterized by small size (around 100 nm), negative charge (-13 mV), and high entrapment efficiency (>90%). Furthermore, they displayed both spherical and elongated shapes, with oligolamellar structure. Their biocompatibility was demonstrated in cells, including erythrocytes and representative skin cell lines. The antioxidant activity of the extract was proved by the scavenging of free radicals, the reduction of ferric ions, and the protection of skin cells from oxidative damage.

Phenolic Fingerprint, Bioactivity and Nanoformulation of Prunus spinosa L. Fruit Extract for Skin Delivery.

The nanoformulation of plant extracts in phospholipid vesicles is a promising strategy to exploit the biological properties of natural bioactive substances and overcome drawbacks such as poor aqueous solubility, chemical instability, low skin permeation and retention time, which strongly limit their topical application. In this study, Prunus spinosa berries were used for the preparation of a hydro-ethanolic extract, which showed antioxidant and antibacterial properties owing to the presence of phenolic compounds. Two types of phospholipid vesicles were developed to improve the applicability as topical formulations. Liposomes and Penetration Enhancer-containing Vesicles were characterized for mean diameter, polydispersity, surface charge, shape, lamellarity, and entrapment efficiency. Additionally, their safety was assayed with different cell models, including erythrocytes and representative skin cell lines.

Immunometabolism Modulation by Extracts from Pistachio Stalks Formulated in Phospholipid Vesicles.

Several studies have demonstrated the effectiveness of plant extracts against various diseases, especially skin disorders; namely, they exhibit overall protective effects. The Pistachio (Pistacia vera L.) is known for having bioactive compounds that can effectively contribute to a person's healthy status. However, these benefits may be limited by the toxicity and low bioavailability often inherent in bioactive compounds. To overcome these problems, delivery systems, such as phospholipid vesicles, can be employed. In this study, an essential oil and a hydrolate were produced from P. vera stalks, which are usually discarded as waste. The extracts were characterized by liquid and gas chromatography coupled with mass spectrometry and formulated in phospholipid vesicles intended for skin application. Liposomes and transfersomes showed small size (<100 nm), negative charge (approximately -15 mV), and a longer storage stability for the latter. The entrapment efficiency was determined via the quantification of the major compounds identified in the extracts and was >80%. The immune-modulating activity of the extracts was assayed in macrophage cell cultures. Most interestingly, the formulation in transfersomes abolished the cytotoxicity of the essential oil while increasing its ability to inhibit inflammatory mediators via the immunometabolic citrate pathway.

Liposomal Formulations to Improve Antioxidant Power of Myrtle Berry Extract for Potential Skin Application.

Many substances in plant extracts are known for their biological activities. These substances act in different ways, exerting overall protective effects against many diseases, especially skin disorders. However, plant extracts' health benefits are often limited by low bioavailability. To overcome these limitations, drug delivery systems can be employed. In this study, we evaluated the antioxidant power of an ethanolic extract from Myrtus communis L. (myrtle) berries through colorimetric tests (DPPH and FRAP). The antioxidant activity was also verified by using fibroblast cell culture through cellular Reactive Oxygen Species (ROS) levels measurements. Moreover, the myrtle extract was formulated in phospholipid vesicles to improve its bioavailability and applicability. Myrtle liposomes were characterized by size, surface charge, storage stability, and entrapment efficiency; visualized by using cryo-TEM images; and assayed for cytocompatibility and anti-ROS activity. Our results suggest that myrtle liposomes were cytocompatible and improved the extract's antioxidant power in fibroblasts, suggesting a potential skin application for these formulations and confirming that nanotechnologies could be a valid tool to enhance plant extracts' potentialities.

Natural Polymeric Materials: A Solution to Plastic Pollution from the Agro-Food Sector.

Conventional petroleum-derived plastics represent a serious problem for global pollution because, when discarded in the environment, are believed to remain for hundreds of years. In order to reduce dependence on fossil resources, bioplastic materials are being proposed as safer alternatives. Bioplastics are bio-based and/or biodegradable materials, typically derived from renewable sources. Food waste as feedstock represents one of the recent applications in the research field of bioplastics production. To date, several food wastes have been used as raw materials for the production of bioplastics, including mostly fruit and vegetable wastes. The conversion of fruit and vegetable wastes into biomaterials could occur through simple or more complex processes. In some cases, biopolymers extracted from raw biomass are directly manufactured; on the other hand, the extracted biopolymers could be reinforced or used as reinforcing agents and/or natural fillers in order to obtain biocomposites. The present review covers available results on the application of methods used in the last 10 years for the design of biomaterials obtained from formulations made up with both fruits and vegetables by-products. Particular attention will be addressed to the waste pre-treatment, to the bioplastic formulation and to its processing, as well as to the mechanical and physical properties of the obtained materials.

Effects of astaxanthin in animal models of obesity-associated diseases: A systematic review and meta-analysis.

BACKGROUND AND AIM: Obesity is a major risk factor for several diseases, including metabolic syndrome (MetS), non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). The use of natural products, such as astaxanthin (ASX), a potent antioxidant compound produced by the freshwater green microalga Haematococcus pluvialis, has gained particular interest to reduce oxidative stress and inflammation, and to improve redox status, often associated with obesity. A systematic review and meta-analysis was performed to comprehensively examine the effects of ASX in animal models of diet induced obesity-associated diseases in order to inform the design of future human clinical studies for ASX use as supplement or nutraceutical. METHODS: Cinahl, Cochraine, MEDLINE, Scopus and Web of Science were searched for English-language manuscripts published between January 2000 and April 2020 using the following key words: astaxanthin, obesity, non-alcoholic fatty liver disease, diabetes mellitus type 2, NAFLD and metabolic. RESULTS: Seventeen eligible articles, corresponding to 21 animal studies, were included in the final quantitative analysis. ASX, at different concentrations and administered for different length of time, induced a significant reduction in adipose tissue weight (P = 0.05) and systolic blood pressure (P < 0.0001) in control animals. In animal models of T2D, ASX significantly reduced serum glucose levels (P = 0.04); whereas it improved several disease biomarkers in the blood (e.g. cholesterol, triglycerides, ALT and AST, P < 0.10), and reduced liver (P = 0.0002) and body weight (P = 0.11), in animal models of NAFLD. CONCLUSIONS: Supplementation of ASX in the diet has positive effects on symptoms associated with obesity related diseases in animals, by having lipid-lowering, hypo-insulin and hypoglycaemic capacity, protecting organs from oxidative stress and mitigating the immune system, as suggested in this review.

Exploiting the Anti-Inflammatory Potential of White Capsicum Extract by the Nanoformulation in Phospholipid Vesicles.

The peppers of the Capsicum species are exploited in many fields, as flavoring agents in food industry, or as decorative and therapeutic plants. Peppers show a diversified phytochemical content responsible for different biological activities. Synergic activity exerted by high levels of antioxidant compounds is responsible for their important anti-inflammatory property. A methanolic extract was obtained from a new pepper genotype and tested for anti-inflammatory activity. The extract was incorporated into phospholipid vesicles to increase the bioavailability of its bioactive components. Two types of phospholipid vesicles were produced, conventional liposomes and Penetration Enhancer containing Vesicles (PEVs). They were tested in human monoblastic leukemia U937 cell line, showing no cytotoxic effect. The intracellular reactive oxygen species (ROS) and nitric oxide (NO) levels were measured to value the in vitro efficacy of the vesicles in regulating inflammatory responses. Liposomal incorporation significantly reduced ROS levels in extract-treated LPS-activated cells. Furthermore, LC-MS/MS analyses demonstrated that liposomes facilitated the transport of the extract components across the cell membrane and their accumulation into the cytoplasm.

A First Step for the Molecular Characterization of Neurological Involvement of Behçet Syndrome: an Italian Pivotal Study.

Behçet syndrome (BS) is a vasculitis characterized by several clinical manifestations including the rare neurological involvement (neuro-BS, NBS). The aim of our pivotal study was to investigate the mutational status of several inflammation-related genes in a cohort of Italian patients with and without the neurological involvement (20 NBS vs 40 no-NBS patients). The preliminary in silico single nucleotide polymorphism (SNP) selection and primer design were performed by NCBI Primer-Blast tool. Genomic DNA was isolated and amplified using PCR. PCR amplicons were sequenced and bioinformatically analysed. Twelve tagSNPs were selected and genotyped: ERAP1 rs30187, rs17482078, and rs27044; IL10 rs1800872 and rs1518111, IL12A rs17810546, IL23R rs17375018, IL23R-IL12RB2 rs924080, STAT4 rs7572482, CCR1 rs7616215, KLRC4 rs2617170, and UBAC2 rs3825427. ERAP1 and IL23R SNPs showed statistically significant higher frequencies in NBS group than no-NBS. ERAP1 rs30187 AA was more common in no-NBS patients (20.0% NBS vs 47.5% no-NBS; p < 0.05), while rs17482078 GA frequency was higher in NBS patients (55.0% NBS vs 22.5% no-NBS; p < 0.05, OR: 4.21). IL23R rs17375018 GG was more frequent in NBS group (65.0% NBS vs 40.0% no-NBS; p < 0.05), according to a previous finding. No other statistically significant differences were found. In conclusion, ERAP1 and IL23R SNPs were found associated with neurological involvement of BS. Additional and larger analyses were required to verify our preliminary findings.

Detection and quantification of Covid-19 antiviral drugs in biological fluids and tissues.

Since coronavirus disease 2019 (COVID-19) started as a fast-spreading pandemic, causing a huge number of deaths worldwide, several therapeutic options have been tested to counteract or reduce the clinical symptoms of patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, no specific drugs for COVID-19 are available, but many antiviral agents have been authorised by several national agencies. Most of them are under investigation in both preclinical and clinical trials; however, pharmacokinetic and metabolism studies are needed to identify the most suitable dose to achieve the desired effect on SARS-CoV-2. Therefore, the efforts of the scientific community have focused on the screening of therapies able to counteract the most severe effects of the infection, as well as on the search of sensitive and selective analytical methods for drug detection in biological matrices, both fluids and tissues. In the last decade, many analytical methods have been proposed for the detection and quantification of antiviral compounds currently being tested for COVID-19 treatment. In this review, a critical discussion on the overall analytical procedure is provided, i.e (a) sample pre-treatment and extraction methods such as protein precipitation (PP), solid-phase extraction (SPE), liquid-liquid extraction (LLE), ultrasound-assisted extraction (UAE) and QuEChERS (quick, easy, cheap, effective, rugged and safe), (b) detection and quantification methods such as potentiometry, spectrofluorimetry and mass spectrometry (MS) as well as (c) methods including a preliminary separation step, such as high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) coupled to UV-Vis or MS detection. Further current trends, advantages and disadvantages and prospects of these methods have been discussed, to help the analytical advances in reducing the harm caused by the SARS-CoV-2 virus.

An innovative protocol to select the best growth phase for astaxanthin biosynthesis in H. pluvialis.

H. pluvialis is a green unicellular microalgae and it is the first producer of natural astaxanthin in the world if subjected to stress conditions such as high light, high salinity and nutrient starvation. Astaxanthin is a powerful antioxidant used in many fields, such as aquaculture, pharmaceutical, food supplements and cosmetic. To obtain a large amount of astaxanthin, researcher focused on the optimisation of H. pluvialis growth. H. pluvialis has four different size growth stage (macrozooids, microzooids, palmelloid and "red non-motile astaxanthin accumulated encysted"), and astaxanthin production occur in the last phase. Recent studies shown that non-motile cells can produce more astaxanthin than motile cells if subjected to light stress. For these reasons, the aim of this study is to find a new and innovative methodology to select and recovery H. pluvialis in his last growth phase thanks to an electrophoretic run, and optimize, in this way, astaxanthin production.

Phenolic Compounds of Red Wine Aglianico del Vulture Modulate the Functional Activity of Macrophages via Inhibition of NF-κB and the Citrate Pathway.

Phenolic compounds of red wine powder (RWP) extracted from the Italian red wine Aglianico del Vulture have been investigated for the potential immunomodulatory and anti-inflammatory capacity on human macrophages. These compounds reduce the secretion of IL-1ß, IL-6, and TNF-α proinflammatory cytokines and increase the release of IL-10 anti-inflammatory cytokine induced by lipopolysaccharide (LPS). In addition, RWP restores Annexin A1 levels, thus involving activation of proresolutive pathways. Noteworthy, RWP lowers NF-κB protein levels, promoter activity, and nuclear translocation. As a consequence of NF-κB inhibition, reduced promoter activities of SLC25A1-encoding the mitochondrial citrate carrier (CIC)-and ATP citrate lyase (ACLY) metabolic genes have been observed. CIC, ACLY, and citrate are components of the citrate pathway: in LPS-activated macrophages, the mitochondrial citrate is exported by CIC into the cytosol where it is cleaved by ACLY in oxaloacetate and acetyl-CoA, precursors for ROS, NO·, and PGE2 inflammatory mediators. We identify the citrate pathway as a RWP target in carrying out its anti-inflammatory activity since RWP reduces CIC and ACLY protein levels, ACLY enzymatic activity, the cytosolic citrate concentration, and in turn ROS, NO·, PGE2, and histone acetylation levels. Overall findings suggest that RWP potentially restores macrophage homeostasis by suppressing inflammatory pathways and activating proresolutive processes.

Liposome-Mediated Inhibition of Inflammation by Hydroxycitrate.

Hydroxycitrate (HCA), a main organic acid component of the fruit rind of Garcinia cambogia, is a natural citrate analog that can inhibit the ATP citrate lyase (ACLY) enzyme with a consequent reduction of inflammatory mediators (i.e., nitric oxide (NO), reactive oxygen species (ROS), and prostaglandin E2 (PGE2)) levels. Therefore, HCA has been proposed as a novel means to prevent, treat, and ameliorate conditions involving inflammation. However, HCA presents a low membrane permeability, and a large quantity is required to have a biological effect. To overcome this problem, HCA was formulated in liposomes in this work, and the enhancement of HCA cell availability along with the reduction in the amount required to downregulate NO, ROS, and PGE2 in macrophages were assessed. The liposomes were small in size (~60 nm), monodispersed, negatively charged (-50 mV), and stable on storage. The in vitro results showed that the liposomal encapsulation increased by approximately 4 times the intracellular accumulation of HCA in macrophages, and reduced by 10 times the amount of HCA required to abolish LPS-induced NO, ROS, and PGE2 increase. This suggests that liposomal HCA can be exploited to target the citrate pathway involved in inflammatory processes.

From structure to function for the characterization of ERAP1 active site in Behçet syndrome. A novel polymorphism associated with known gene variations.

INTRODUCTION: ERAP1 has been recently proposed as risk marker of Behçet syndrome (BS). Gene single nucleotide polymorphisms (SNPs) could affect the enzymatic activity and the conserved active site is pivotal for the aminopeptidase function. This study aims to characterize the ERAP1 active site in a cohort of BS patients vs healthy controls (HC) integrating genomics, transcriptomics and bioinformatics approach. MATERIALS AND METHODS: We recruited 109 consecutive Italian BS patients (63M:46 F; mean age: 45.07 ± 12.28 years) and 106 matched HC (55M:51 F; mean age: 42.57 ± 12.29 years). DNA was isolated and amplified using PCR with home made-primer pairs. PCR products were directly sequenced and computational analyses were performed to search active site SNPs (NCBI-BlastN tool), to predict SNPs functional effect (PolyPhen-2 software) and to obtain protein 3D modelling (Protean3D software). In a second phase of analysis, RNA was extracted and reverse transcribed. Quantitative Real-Time PCR (qPCR) was performed to assess ERAP1 mRNA level in presence (target) and in absence (control) of gene polymorphisms. The Fold change was calculated for the relative quantification of gene expression. RESULTS: A novel coding variation (NG_027839.1:g.25637 T > G; NP_057526.3:p.Phe360Cys, HGSV nomenclature) was found in heterozygosity state in 5/109 BS patients (4.59 % of cases) and none of HC. It was recognized in association with rs2287987, rs30187, rs17482078, and rs27044 BS-related polymorphisms for 4 out of 5 patients. All patients carrying the novel SNP were HLA-B*51-positive. The novel SNP was released in GenBank database with MK140632.1 ID. The SNP was predicted to be damaging and resides within the Zn-binding HEXXH(X)18E region of the active site, changing the structurally conserved region for the amminopeptidase function. In fact, the change in energy (ΔE) score between wild-type and SNP-containing protein showed a less stable protein in presence of p.Cys360 (ΔE:3.584) (Protean3D prediction). Preliminary qPCR results underlined a significant difference in fold change value when target and control values were compared (p < 0.05), suggesting a reduced expression of ERAP1 mRNA in presence of the novel SNP. CONCLUSIONS: Our study strengthens the association between ERAP1 and BS. The most significant point was the localization of the novel p.Phe360Cys SNP within the Zn-binding region of protein active site that was predicted to affect its function, causing protein destabilization. Our findings need to be tested in larger genetic studies.