Antimicrobial and mechanical properties of functionalized textile by nanoarchitectured photoinduced Ag@polymer coating.

The control of microbial proliferation is a constant battle, especially in the medical field where surfaces, equipment, and textiles need to be cleaned on a daily basis. Silver nanoparticles (AgNPs) possess well-documented antimicrobial properties and by combining them with a physical matrix, they can be applied to various surfaces to limit microbial contamination. With this in mind, a rapid and easy way to implement a photoinduced approach was investigated for textile functionalization with a silver@polymer self-assembled nanocomposite. By exposing the photosensitive formulation containing a silver precursor, a photoinitiator, and acrylic monomers to a UV source, highly reflective metallic coatings were obtained directly on the textile support. After assessing their optical and mechanical properties, the antimicrobial properties of the functionalized textiles were tested against Escherichia coli (E. coli) and Candida albicans (C. albicans) strains. In addition to being flexible and adherent to the textile substrates, the nanocomposites exhibited remarkable microbial growth inhibitory effects.

Fluorescent bioinspired albumin/polydopamine nanoparticles and their interactions with Escherichia coli cells.

Inspired by the eumelanin aggregates in human skin, polydopamine nanoparticles (PDA NPs) are promising nanovectors for biomedical applications, especially because of their biocompatibility. We synthesized and characterized fluorescent PDA NPs of 10-25 nm diameter based on a protein containing a lysine-glutamate diad (bovine serum albumin, BSA) and determined whether they can penetrate and accumulate in bacterial cells to serve as a marker or drug nanocarrier. Three fluorescent PDA NPs were designed to allow for tracking in three different wavelength ranges by oxidizing BSA/PDA NPs (Ox-BSA/PDA NPs) or labelling with fluorescein 5-isothiocyanate (FITC-BSA/PDA NPs) or rhodamine B isothiocyanate (RhBITC-BSA/PDA NPs). FITC-BSA/PDA NPs and RhBITC-BSA/PDA NPs penetrated and accumulated in both cell wall and inner compartments of Escherichia coli (E. coli) cells. The fluorescence signals were diffuse or displayed aggregate-like patterns with both labelled NPs and free dyes. RhBITC-BSA/PDA NPs led to the most intense fluorescence in cells. Penetration and accumulation of NPs was not accompanied by a bactericidal or inhibitory effect of growth as demonstrated with the Gram-negative E. coli species and confirmed with a Gram-positive bacterial species (Staphylococcus aureus). Altogether, these results allow us to envisage the use of labelled BSA/PDA NPs to track bacteria and carry drugs in the core of bacterial cells.

Assessment of plasma Catestatin in COVID-19 reveals a hitherto unknown inflammatory activity with impact on morbidity-mortality.

Introduction: Neuroendocrine cells release Catestatin (CST) from Chromogranin A (CgA) to regulate stress responses. As regards COVID-19 patients (COVID+) requiring oxygen supply, to date nobody has studied CST as a potential mediator in the regulation of immunity. Patients & Methods: Admission plasma CST and CgA - its precursor - concentrations were measured (ELISA test) in 73 COVID+ and 27 controls. Relationships with demographics, comorbidities, disease severity and outcomes were analysed (Mann-Whitney, Spearman correlation tests, ROC curves). Results: Among COVID+, 49 required ICU-admission (COVID+ICU+) and 24 standard hospitalization (COVID+ICU-). Controls were either healthy staff (COVID-ICU-, n=11) or COVID-ICU+ patients (n=16). Median plasma CST were higher in COVID+ than in controls (1.6 [1.02; 3.79] vs 0.87 [0.59; 2.21] ng/mL, p<0.03), with no difference between COVID+ and COVID-ICU+. There was no difference between groups in either CgA or CST/CgA ratios, but these parameters were lower in healthy controls (p<0.01). CST did not correlate with either hypoxia- or usual inflammation-related parameters. In-hospital mortality was similar whether COVID+ or not, but COVID+ had longer oxygen support and more complications (p<0.03). CST concentrations and the CST/CgA ratio were associated with in-hospital mortality (p<0.01) in COVID+, whereas CgA was not. CgA correlated with care-related infections (p<0.001). Conclusion: Respiratory COVID patients release significant amounts of CST in the plasma making this protein widely available for the neural regulation of immunity. If confirmed prospectively, plasma CST will reliably help in predicting in-hospital mortality, whereas CgA will facilitate the detection of patients prone to care-related infections.

The Catestatin-Derived Peptides Are New Actors to Fight the Development of Oral Candidosis.

Resistance to antifungal therapy of Candida albicans and non-albicans Candida strains, frequently associated with oral candidosis, is on the rise. In this context, host-defense peptides have emerged as new promising candidates to overcome antifungal resistance. Thus, the aim of this study was to assess the effectiveness against Candida species of different Catestatin-derived peptides, as well as the combined effect with serum albumin. Among Catestatin-derived peptides, the most active against sensitive and resistant strains of C. albicans, C. tropicalis and C. glabrata was the D-isomer of Cateslytin (D-bCtl) whereas the efficiency of the L-isomer (L-bCtl) significantly decreases against C. glabrata strains. Images obtained by transmission electron microscopy clearly demonstrated fungal membrane lysis and the leakage of the intracellular material induced by the L-bCtl and D-bCtl peptides. The possible synergistic effect of albumin on Catestatin-derived peptides activity was investigated too. Our finding showed that bovine serum albumin (BSA) when combined with the L- isomer of Catestatin (L-bCts) had a synergistic effect against Candida albicans especially at low concentrations of BSA; however, no synergistic effect was detected when BSA interacted with L-bCtl, suggesting the importance of the C-terminal end of L-bCts (GPGLQL) for the interaction with BSA. In this context in vitro D-bCtl, as well as the combination of BSA with L-bCts are potential candidates for the development of new antifungal drugs for the treatment of oral candidosis due to Candida and non-Candida albicans, without detrimental side effects.

Catestatin in innate immunity and Cateslytin-derived peptides against superbugs.

Chromogranin A (CgA) is the precursor of several antimicrobial peptides, such as Catestatin (Cts, bovine CgA344-364), initially described as a potent inhibitor of catecholamines. This peptide displays direct antimicrobial activities and contributes to immune system regulation. The aim of the present study is to investigate a designed peptide based on Cts to fight infections against superbugs and more particularly Staphylococcus aureus. In addition to Cateslytin (Ctl, bovine CgA344-358), the active domain of Catestatin, several peptides including dimers, D-isomer and the new designed peptide DOPA-K-DOPA-K-DOPA-TLRGGE-RSMRLSFRARGYGFR (Dopa5T-Ctl) were prepared and tested. Cateslytin is resistant to bacterial degradation and does not induce bacterial resistance. The interaction of Catestatin with immune dermal cells (dendritic cells DC1a, dermal macrophages CD14 and macrophages) was analyzed by using confocal microscopy and cytokine release assay. The dimers and D-isomer of Ctl were tested against a large variety of bacteria showing the potent antibacterial activity of the D-isomer. The peptide Dopa5T-Ctl is able to induce the self-killing of S. aureus after release of Ctl by the endoprotease Glu-C produced by this pathogen. It permits localized on-demand delivery of the antimicrobial drug directly at the infectious site.

Dual role of tannic acid and pyrogallol incorporated in plaster of Paris: Morphology modification and release for antimicrobial properties.

The design of bioactive plasters is of major interest for the amelioration of dental and bone cements. In this article, a one pot and environmentally friendly strategy based on the addition of a cheap polyphenol-tannic acid (TA) or the main phenolic constituent of TA, namely pyrogallol (PY)- able to interact with calcium sulfate is proposed. Tannic acid and pyrogallol not only modify the morphology of the obtained plaster+TA/PY composites but a part of it is released and provides strong-up to twenty fold- antibacterial effect against Staphylococcus aureus. It is shown that the higher antibacterial efficiency of PY is related to a greater release compared to TA even if in solution the antibacterial effect of PY is lower than that of TA when reported on the basis of the molar concentration in PY units.

Adrenal gland-released vasostatin-I is a myocardial depressant factor.

Pheochromocytoma crisis is an exceptional consequence of the release of storage vesicles of the adrenal medulla. It is complicated by fulminant adrenergic myocarditis. It offers a unique opportunity to detect inotropic negative factors from neuroendocrine origin. Our objectives were (a) to describe a pheochromocytoma crisis, (b) to investigate in vivo myocardial depressant activities for the N-terminal 1-76 Chromogranin A-derived peptide, vasostatin-I (VS-I). A patient with a pheochromocytoma crisis was treated, including extracorporeal membrane oxygenation, until mass resection. Plasma concentrations of VS-I were time-dependently assessed with a specific immunoassay; correlations with invasive cardiovascular parameters were investigated. Increased VS-I concentrations were observed over 7 days until tumour resection. VS-I concentrations correlated positively with Chromogranin A levels, negatively with cardiac output and left ventricular stroke work index, but not with heart rate. This case illustrates the pharmacokinetics of VS-I in a pheochromocytoma crisis. It highlights myocardial depressant activity for this peptide at high concentrations.

A Pilot Study on Continuous Infusion of 4% Albumin in Critically Ill Patients: Impact on Nosocomial Infection via a Reduction Mechanism for Oxidized Substrates.

Care-related infections affect up to 11% of ICU patients. Running therapeutic albumin is sometimes associated to less infection: whether a specific method of its infusion is of any interest to modulate innate defense is unknown. Our objectives were: 1) to test whether the method for albumin infusion is important to prevent care-related infections and 2) to analyze in vitro the antioxidative role of albumin on host defense proteins during shock (using vasostatin-I as an example). DESIGN: In a prospective, randomized, open-label trial, shock patients were allocated to receive either continuously 4% albumin or intermittently 20% albumin, as long as they were infused with norepinephrine. A translational study including in vivo and in vitro analyses of albumin-vasostatin-I interactions is reported. SETTING: A tertiary ICU caring for 1,000 patients per year. PATIENTS: Fifty shock patients with serum albumin less than 20 g/L. INTERVENTIONS: In vivo colonization and nosocomial infections were recorded and time-dependent changes in serum albumin, chromogranin A, and vasostatin-I concentrations as well. In vitro, we studied biochemical albumin-vasostatin-I relationship using biochemical methods. MEASUREMENTS AND MAIN RESULTS: Over 18 days, we recorded a decrease in colonization (four vs 12 episodes; p = 0.035) and nosocomial infection frequency (two vs 13 episodes; p = 0.002) in patients infused continuously 4% albumin versus controls. In vitro, albumin interacts with the disulfide loop vasostatin-I (residues 17-40) and continuous 4% albumin infusion restores its oxidative status required for antimicrobial activity. CONCLUSIONS: Continuous 4% albumin is effective in reducing care-related infections in shock patients by increasing the availability of antimicrobial vasostatin-I. This might guide future care of shock patients.

In Trauma Patients, the Occurrence of Early-Onset Nosocomial Infections is Associated With Increased Plasma Concentrations of Chromogranin A.

In previously healthy persons suffering from acute illnesses, nosocomial infections (NIs) are frequent. Their prevalence suggests the existence of as yet unknown conditions that may promote care-related infection. This study assessed whether the measurement of plasma chromogranin A, a stress-related protein involved in innate defense, is related to NI risk, and whether any chromogranin A-derived fragment included in vasostatin-I displays immunosuppressive activities related to AP-1 or NF-kappa B downregulation. At the clinical level, trauma patients and healthy controls were recruited to be eligible. Clinical histories were recorded, and standard biological tests (including plasma chromogranin A) were performed. For 9 randomly chosen patients and 16 controls, the time-dependent concentrations of chromogranin A (CGA) were assessed twice a day over 66 h. The data show that trauma patients present a higher value of CGA concentration during 66 h in comparison with healthy controls. In addition, patients maintaining this significant increase in CGA readily develop NIs. We therefore studied the effects of chromogranin A-derived peptides on monocytes, focusing on transcription factors that play a central role in inflammation. In vitro assay demonstrated that a chromogranin A-derived fragment (CGA47-70) displays a significant inhibition of NF-kappa B and AP-1 transcriptional activities in these cells. In conclusion, the occurrence of NI in trauma patients is associated with significantly increased plasma CGA concentrations. Downregulation of the two transcription factors by CGA47-70 might induce early acquired immune defect after a serious medical stress.

Exome sequencing identifies mutations in LZTFL1, a BBSome and smoothened trafficking regulator, in a family with Bardet--Biedl syndrome with situs inversus and insertional polydactyly.

BACKGROUND: Bardet--Biedl Syndrome (BBS) is an emblematic recessive genetically highly heterogeneous ciliopathy characterised mainly by polydactyly, retinitis pigmentosa, obesity, cognitive impairment, and kidney dysfunction. The 16 BBS genes known to date are implied in the primary cilia related cellular pathways. METHODS AND RESULTS: Single nucleotide polymorphism (SNP) array analysis followed by exome sequencing was performed in a consanguineous family diagnosed with BBS with unusual developmental features, namely situs inversus and insertional polydactyly. A homozygous 5 bp deletion (NM_020347.2:c.402-406del, p.Pro136ThrfsX5) in LZTFL1 was identified. No LZTFL1 transcript was found in the patient's fibroblasts and no protein could be detected. The sonic hedgehog (Shh) pathway analysis conducted on the patient's fibroblast showed a significant increase in Smo. Patched1 as well as the downstream target GLI2 were also found to be upregulated, indicating an overall massive activation of the Shh signalling in the absence of LZTFL1. CONCLUSION: LZTFL1, encoding the human leucine zipper transcription factor like 1, has been recently shown to be an important negative regulator of BBSome ciliary trafficking and Shh signalling. This study shows that absence of LZTFL1 leads to a BBS phenotype with enhanced developmental abnormalities associated with cellular Shh dysfunction. LZTFL1 is a novel BBS gene (BBS17).

A novel TFAP2A mutation in familial Branchio-Oculo-Facial Syndrome with predominant ocular phenotype.

INTRODUCTION: Branchio-Oculo-Facial Syndrome (BOFS) is a rare autosomal dominant congenital disorder defined by branchial defects, ocular anomalies and craniofacial malformations, including variable degrees of cleft lip with or without cleft palate. In addition, temporal bone anomalies, renal and ectodermal manifestations can be present. Mutations in the TFAP2A gene have been reported in patients with BOFS, prompting phenotype-genotype studies because of the variable clinical spectrum. MATERIALS AND METHODS: We report on a family (a mother, her daughter and son) with BOFS and significant variability in clinical expression. The daughter presents predominantly with an ocular phenotype of unilateral microphthalmia and bilateral chorioretinal colobomas, whereas her brother is more severely affected contrasting with the paucisymptomatic mother. TFAP2A molecular analysis revealed a novel frameshift mutation. DISCUSSION: We confirm the wide clinical spectrum of BOFS. The importance of upper lip examination in mild and paucisymptomatic cases is underlined. TFAP2A mutation spectrum is discussed and broadened by the report of the second frameshift mutation in this gene. CONCLUSION: Patients with BOFS and predominant ocular phenotypes can be underdiagnosed. In such cases, upper lip examination can be of important diagnostic value. TFAP2A analysis provides diagnostic confirmation and improves genetic counselling.

Molecular diagnosis reveals genetic heterogeneity for the overlapping MKKS and BBS phenotypes.

Hydrometrocolpos and polydactyly diagnosed in the prenatal period or early childhood may raise diagnostic dilemmas especially in distinguishing McKusick-Kaufman syndrome (MKKS) and the Bardet-Biedl syndrome (BBS). These two conditions can initially overlap. With time, the additional features of BBS appearing in childhood, such as retinitis pigmentosa, obesity, learning disabilities and progressive renal dysfunction allow clear differentiation between BBS and MKKS. Genotype overlap also exists, as mutations in the MKKS-BBS6 gene are found in both syndromes. We report 7 patients diagnosed in the neonatal period with hydrometrocolpos and polydactyly who carry mutations in various BBS genes (BBS6, BBS2, BBS10, BBS8 and BBS12), stressing the importance of wide BBS genotyping in patients with this clinical association for diagnosis, prognosis and genetic counselling.