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Obiettivi dello studio sono stati: 1) valutare la possibile influenza del polimorfismo dei geni GSTM1, GSTT1 e NQO1 sui livelli di biomarcatori urinari dell'esposizione a benzene rappresentati dall'acido trans, trans-muconico (t,t-MA) e dall'acido S-fenilmercapturico (SPMA); 2) utilizzare i risultati dell'analisi genotipica per indirizzare su un numero ridotto di soggetti la valutazione del danno al DNA per studiare il possibile effetto protettivo di NQO1. Sono stati reclutati 331 lavoratori del settore petrolchimico di cui 201 esposti, sottoposti a sorveglianza sanitaria obbligatoria, e 130 controlli. Su tutti i soggetti è stata effettuata l'analisi genotipica per i geni GSTM1, GSTT1 e NQO1. Lo studio ha evidenziato un significativo (p<0.001) effetto modulante del polimorfismo del gene GSTT1 sui livelli di escrezione di S-PMA in soggetti fumatori e non fumatori e di GSTM1 (p<0.001) solo in quello dei fumatori. Contrariamente a quanto descritto in alcuni lavori, i nostri dati non dimostrano la presenza di livelli più bassi di metaboliti urinari nei soggetti con almeno un allele mutato nel gene NQO1 (genotipi NQO1 Pro/Ser e NQO1 Ser/Ser) rispetto agli omozigoti non mutati (Pro/Pro). Viene presentata una proposta metodologica per orientare le successive analisi del danno genotossico/ossidativo al DNA su un numero ridotto di soggetti, con un significativo risparmio di risorse, che potrebbe fornire un modello utile per lo studio di indicatori di suscettibilità con bassa frequenza, quali il polimorfismo del gene NQO1. [ABSTRACT FROM AUTHOR]

Biofilm formation in common public places and hospitals is of great concern. Active antimicrobial coatings can prevent the formation of bacterial biofilms and the spreading of primary and secondary infections caused by contagious bacteria and viruses. In the present work, we report a simple spray coating process using copper oxide (CuO) nanoparticles (NPs) dispersed in a titanium dioxide (TiO 2 ) sol, where CuONPs act as the active antimicrobial agent and TiO 2 as the inorganic binder. Homogeneous CuONPs/TiO 2 coating was obtained on polypropylene substrates by spraying the CuO/TiO 2 sol using a commercial air gun, followed by drying at 80 °C. The amount of CuONPs loading in the coating was adjusted by controlling the number of coated layers. CuONPs and CuONPs/TiO 2 coatings were characterized by XRD, BET, X-ray fluorescence spectroscopy, AFM, and field emission scanning electron microscopy techniques. All of the coated films showed dual activity, i.e., antimicrobial and superhydrophobicity. A high bactericidal effect against both Escherichia coli and Staphylococcus aureus was observed for the coated substrates. Coatings with higher CuONPs showed greater antibacterial activity, reaching R value >6, and no bacterial colonies were detected after 24 h of incubation. An increasing trend of water contact angle was observed with the increasing amount of CuONP loading., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

In our continuing search for new polymer composites with antimicrobial activity, we observed that even unmodified epoxy resins exhibit significant activity. Considering their widespread use as starting materials for the realization of multifunctional nanocomposites with excellent chemical and mechanical properties, it was deemed relevant to uncover these unexpected properties that can lead to novel applications. In fact, in places where the contact with human activities makes working surfaces susceptible to microbial contamination, thus jeopardizing the sterility of the environment, their biological activity opens the way to their successful application in minimizing healthcare-associated infections. To this end, three commercial and widely used epoxy resins (DGEBA/Elan-TechW 152LR, 1 ; EPIKOTE TM Resin MGS ® /EPIKURE TM RIM H 235, 2 and MC152/EW101, 3 ) have been investigated to determine their antibacterial and antiviral activity. After 24 h, according to ISO 22196:2011, resins 1 and 2 showed a high antibacterial efficacy (R value > 6.0 log reduction) against Staphylococcus aureus and Escherichia coli . Resin 2 , prepared according to the ratio epoxy/hardener indicated by the supplier (sample 2a ) and with 10% w / w hardener excess (sample 2b ), exhibited an intriguing virucidal activity against Herpes Simplex Virus type-1 and Human Coronavirus type V-OC43 as a surrogate of SARS-CoV-2.

Cystatin B (CSTB), an inhibitor of the cysteine proteases, belongs to the cathepsin family and it is known to interact with a number of proteins involved in cytoskeletal organization. CSTB has an intrinsic tendency to form aggregates depending on the redox environment. The gene encoding for CSTB is frequently mutated in association with the rare neurodegenerative condition progressive myoclonus epilepsy. Increased levels of CSTB have been observed in the spinal cord of transgenic mice modeling SOD1-linked familial amyotrophic lateral sclerosis, a fatal neurodegenerative disease affecting motoneurons. In the present study, we have investigated the relationship occurring between the expression of SOD1 and CSTB either wild-type or double-cysteine substitution mutant (Cys 3 and Cys 64). Whether or not there is a physical interaction between the two proteins was also investigated in overexpression experiments using a human neuroblastoma cell line and mouse-immortalized motoneurons. Here we report evidences for a reciprocal influence of CSTB and SOD1 at the gene expression level and for a direct interaction of the two proteins.

The Herlitz junctional epidermolysis bullosa (H-JEB) subtype usually presents as a severe lethal inherited variant of epidermolysis bullosa (EB) caused by a homozygous mutation in the genes LAMA3, LMAB3, or LAMAC3. Each gene encodes one of the three chains of heterotrimer laminin-332 proteins (including the alpha-3 chain, beta-3 chain and gamma-2-chain) responsible for the adherence of the epidermis to the underlying dermis. The aim of this report is to add to the existing knowledge about EB by describing a novel mutation in a gene responsible for genodermatosis. A case of a Jordanian male neonate, born to healthy, first cousin consanguineous parents, who developed nonhealing blistering skin and mucous membrane lesions, crusted erosions with significant granulation tissue and dystrophic nails immediately after birth is described. The patient was diagnosed as having a novel LAMA3 mutation causing (H-JEB) by immunofluorescence mapping and molecular analysis. Both parents and this baby's sibling were shown to be heterozygous carriers of the same mutation. Pre-implantation diagnosis using molecular analysis for subsequent pregnancies in this family is crucial for managing any new pregnancy., (© 2012 The Authors Australasian Journal of Dermatology © 2012 The Australasian College of Dermatologists.)

cis-Diamminedichloroplatinum(II) (cisplatin) is able to interact with human superoxide dismutase (hSOD1) in the disulfide oxidized apo form with a dissociation constant of 37 ± 3 μM through binding cysteine 111 (Cys111) located at the edge of the subunit interface. It also binds to Cu(2)-Zn(2) and Zn(2)-Zn(2) forms of hSOD1. Cisplatin inhibits aggregation of demetalated oxidized hSOD1, and it is further able to dissolve and monomerize oxidized hSOD1 oligomers in vitro and in cell, thus indicating its potential as a leading compound for amyotrophic lateral sclerosis.

Increasing evidence indicates that the accumulation and aggregation of mutant Cu,Zn superoxide dismutase (mutSOD1) in spinal cord mitochondria is implicated in the pathogenesis of familial amyotrophic lateral sclerosis (FALS). Although the mechanisms underlying this effect are only partially understood, a deficit in the import mechanism of mutSOD1 and/or in its folding and maturation inside mitochondria is likely involved. To investigate this issue, we overexpressed mitochondria-targeted wild-type and mutSOD1s in neuronal cell lines. Mitochondria-targeted G93A mutSOD1 induces a significant impairment of mitochondrial morphology and metabolism, resulting in caspase-3 activation and cell death. These effects are paralleled by the formation of disulfide-linked, insoluble oligomers of mutSOD1 inside mitochondria. Overexpression of the copper chaperone for SOD1 (CCS) improves the solubility of cytosolic mutSOD1s, but has no effect or even worsens the insolubility of mitochondria-targeted G93A mutSOD1, indicating that CCS may increase the availability of an aggregating form of mutSOD1. Interestingly, prevention of the formation of such aggregates by removal of disulfide-bonded cysteines counteracts the effects produced by mutSOD1 accumulated inside mitochondria. Overall, our results demonstrate for the first time that aggregation of mutSOD1s into mitochondria is important for mutSOD1 to induce damage, although other forms of misfolded SOD1s might be involved.

Converging evidence indicates that aberrant aggregation of mutant Cu,Zn-superoxide dismutase (mutSOD1) is strongly implicated in familial amyotrophic lateral sclerosis (FALS). MutSOD1 forms high molecular weight oligomers, which disappear under reducing conditions, both in neural tissues of FALS transgenic mice and in transfected cultured cells, indicating a role for aberrant intermolecular disulfide cross-linking in the oligomerization and aggregation process. To study the contribution of specific cysteines in the mechanism of aggregation, we mutated human SOD1 in each of its four cysteine residues and, using a cell transfection assay, analyzed the solubility and aggregation of those SOD1s. Our results suggest that the formation of mutSOD1 aggregates are the consequence of covalent disulfide cross-linking and non-covalent interactions. In particular, we found that the removal of Cys-111 strongly reduces the ability of a range of different FALS-associated mutSOD1s to form aggregates and impair cell viability in cultured NSC-34 cells. Moreover, the removal of Cys-111 impairs the ability of mutSOD1s to form disulfide cross-linking. Treatments that deplete the cellular pool of GSH exacerbate mutSOD1s insolubility, whereas an overload of intracellular GSH or overexpression of glutaredoxin-1, which specifically catalyzes the reduction of protein-SSG-mixed disulfides, significantly rescues mutSOD1s solubility. These data are consistent with the view that the redox environment influences the oligomerization/aggregation pathway of mutSOD1 and point to Cys-111 as a key mediator of this process.