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Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infection.

The terms deodorants and antiperspirants very frequently used interchangeably despite the fact that they employ completely different active substances and mechanisms of action. Antiperspirants are necessarily deodorants due to the lack of substrate to decompose. They nevertheless represent a group of very specific substances that create particular problems due to the presence of aluminium chlorohydrate, or ACH, (Al2(OH)5Cl, 2H2O), aluminium sesquichlorohydrate and aluminium-zirconium complex, which, after hydrolysis, causes intense acidification of the skin, hence the importance of inclusion of emollients and pH regulators in formulations. Moreover, systemic aluminium is thought to be genotoxic and to promote breast cancer, and it is thus at the centre of numerous scientific controversies. Nevertheless, its potential toxicity following topical application is related to its ability to penetrate skin, which is as yet poorly understood but considered very low, a fact that may provide some degree of reassurance regarding its use in cosmetic products. Its role in Alzheimer's disease has not been proven. On the other hand, zirconium salts are considered toxic and are partly regulated in Europe. The problems associated with deodorants are those arising from the presence of antiseptics (triclosan, usnic acid) capable of inducing bacterial resistance, but more particularly, the presence of axillary dermatitis due to the allergenic potential of the fragrances and essential oils used (e.g. isoeugenol, citronellal, lyral, cinnamic aldehyde, etc.).

Highlights • Recent advances in Zika virus drug discovery efforts. • Drug repositioning and computationally guided compounds. • New inhibitors and promising ZIKV molecular targets. • Promising host cell targets for ZIKV drug design. • Lessons learned from ZIKV drug discovery., Despite the recent outbreak of Zika virus (ZIKV), there are still no approved treatments, and early-stage compounds are probably many years away from approval. A comprehensive A–Z review of the recent advances in ZIKV drug discovery efforts is presented, highlighting drug repositioning and computationally guided compounds, including discovered viral and host cell inhibitors. Promising ZIKV molecular targets are also described and discussed, as well as targets belonging to the host cell, as new opportunities for ZIKV drug discovery. All this knowledge is not only crucial to advancing the fight against the Zika virus and other flaviviruses but also helps us prepare for the next emerging virus outbreak to which we will have to respond., Teaser Zika clinical outcomes might be nefarious impacting newborns for a lifetime. There is still no drug available to cure Zika. We provide guidance to help understand and advance the search for a cure.

Made available in DSpace on 2020-12-12T02:25:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-09-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Fundo de Apoio ao Ensino, à Pesquisa e Extensão, Universidade Estadual de Campinas Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes and macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor-1α (HIF-1α) and consequently promotes glycolysis. HIF-1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19. Diabetic people with uncontrolled blood glucose levels have a greater risk to develop severe COVID-19 disease. Codo et al. show that elevated glucose levels and glycolysis promote SARS-CoV-2 (CoV-2) replication and cytokine production in monocytes through a mitochondrial ROS/hypoxia-inducible factor-1α dependent pathway, resulting in T cell dysfunction and epithelial cell death. Laboratory of Immunometabolism Department of Genetics Evolution Microbiology and Immunology Institute of Biology University of Campinas Department of Genetics Evolution Microbiology and Immunology Institute of Biology University of Campinas Department of Biochemistry and Tissue Biology Institute of Biology University of Campinas Department of Genetics at Ribeirao Preto Medical School University of Sao Paulo, Ribeirao Preto Department of Clinical and Toxicological analyses School of Pharmaceutical Sciences University of São Paulo Brazilian Biosciences National Laboratory (LNBio), Campinas Department of Animal Biology Institute of Biology University of Campinas, Campinas Department of Internal Medicine School of Medical Sciences University of Campinas, Campinas Department of Clinical Medicine School of Medical Sciences University of Campinas, Campinas Hematology and Hemotherapy Center University of Campinas, Campinas Obesity and Comorbidities Research Center (OCRC) University of Campinas Experimental Medicine Research Cluster (EMRC) University of Campinas Department of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP), Botucatu D'Or Institute for Research and Education (IDOR) Instituto Nacional de Biomarcadores em Neuropsiquiatria Conselho Nacional de Desenvolvimento Científico e Tecnológico Department of Structural and Functional Biology Institute of Biosciences São Paulo State University (UNESP), Botucatu FAPESP: 20/04579-7 FAPESP: 2015/15626-8 FAPESP: 2016/18031-8 FAPESP: 2016/23328-0 FAPESP: 2017/01184-9 FAPESP: 2018/22505-0 FAPESP: 2019/00098-7 FAPESP: 2019/06372-3 FAPESP: 2020/04522-5 FAPESP: 2020/04558-0 FAPESP: 2020/04583-4 FAPESP: 2020/04746-0 FAPESP: 2020/04919-2 Fundo de Apoio ao Ensino, à Pesquisa e Extensão, Universidade Estadual de Campinas: 2274/20

COVID-19 can result in severe lung injury. It remained to be determined why diabetic individuals with uncontrolled glucose levels are more prone to develop the severe form of COVID-19. The molecular mechanism underlying SARS-CoV-2 infection and what determines the onset of the cytokine storm found in severe COVID-19 patients are unknown. Monocytes/macrophages are the most enriched immune cell types in the lungs of COVID-19 patients and appear to have a central role in the pathogenicity of the disease. These cells adapt their metabolism upon infection and become highly glycolytic, which facilitates SARS-CoV-2 replication. The infection triggers mitochondrial ROS production, which induces stabilization of hypoxia-inducible factor- 1α (HIF - 1α) and consequently promotes glycolysis. HIF- 1α-induced changes in monocyte metabolism by SARS-CoV-2 infection directly inhibit T cell response and reduce epithelial cell survival. Targeting HIF-1 ɑ may have great therapeutic potential for the development of novel drugs to treat COVID-19.

Practically all currently available self-tanning products have as their active ingredient dihydroxyacetone (DHA), which may or may not be combined with erythrulose, tyrosine derivatives, and occasionally a naphthoquinone. The resulting skin tone, which resembles a natural tan, is due to chemical combination of the DHA with amino acids in the skin through the Maillard reaction. Polymer pigments known as melanoidins are formed and are fixed in the stratum corneum, where they remain until corneocyte desquamation occurs. The colouring thus achieved is semi-permanent and is well tolerated by skin. While the formulation of such products is complex and their storage difficult, no other substances provide more satisfactory or more lasting results.

I termini deodoranti e antitraspiranti sono molto spesso confusi, mentre i meccanismi di azione degli uni e degli altri, cosi come gli ingredienti attivi utilizzati, sono completamente differenti. E certo che gli antitraspiranti sono inevitabilmente deodoranti per l’assenza di substrato da decomporre. Rappresentano, tuttavia, un gruppo di prodotti molto particolari che generano dei problemi specifici a causa della presenza di alluminio cloridrato o ACH (Al 2 (OH) 5 Cl, 2H 2 O), di alluminio sesquicloridrato o del complesso di alluminio-zirconio, che provocano, dopo l’idrolisi, un’acidificazione intensa della cute. Da cio deriva l’importanza degli emollienti e dei regolatori del pH nelle formulazioni. Inoltre, l’alluminio e accusato di essere genotossico e di accelerare la comparsa del cancro della mammella. La sua eventuale tossicita per via topica e legata alla sua capacita di penetrazione cutanea, ancora poco conosciuta ma ritenuta molto modesta. La sua incidenza nella malattia di Alzheimer non e stata ancora provata. Viceversa, i sali di zirconio sono considerati tossici e sono severamente regolamentati in Europa. I problemi posti dai deodoranti sono le resistenze batteriche talvolta indotte dalla presenza di antisettici (triclosan, acido usnico), ma anche le dermatiti ascellari dovute al potenziale allergenico dei componenti dei profumi e degli olii essenziali (isoeugenolo, citronella, liral, aldeide cinnamica, ecc.).

I prodotti per il trucco del viso comprendono rossetti, fondotinta, polveri, fard, cosi come i prodotti per il trucco degli occhi, quali eyeliner, ombretti, mascara, matite e khol. Tutti questi prodotti contengono grandi quantita di coloranti di origine naturale e sintetica sotto forma insolubile di pigmenti o di lacche. Sono spiegate la natura, la legislazione e la denominazione dei coloranti, come anche la composizione dei differenti prodotti che li contengono. Sono ricordati la tollerabilita, la conservazione e gli eventuali controlli di ogni tipo di prodotto. Infine, il mercato francese dell’insieme dei prodotti per il trucco e confrontato con il mercato cosmetico globale.

I prodotti di gommage meccanico sono di natura principalmente cosmetica. Essi promuovono un’esfoliazione dolce che permette l’eliminazione delle cellule cornee desquamanti. Su basi emulsionate o gelificate, gli ingredienti attivi piu o meno abrasivi sono di origine vegetale (come le polveri di noccioli), minerale (come i microcristalli di alluminio) o sintetica (per esempio, microsfere di polietilene). La loro efficacia e in funzione della granulometria delle polveri e della forma delle particelle. Sono utilizzati nell’invecchiamento cutaneo, nella cura delle cuti nere, nell’eliminazione delle macchie senili, nell’eliminazione delle parti cornee dei talloni e dei gomiti e nella preparazione per le cure di bellezza.

Gli agenti autoabbronzanti attualmente sul mercato sono praticamente tutti basati sul diidrossiacetone (DHA), associato o meno all⬢eritrulosio, a derivati della tirosina e, a volte, a un naftochinone. La colorazione ottenuta, vicina all⬢abbronzatura naturale, e dovuta alla combinazione chimica del DHA con gli aminoacidi della pelle secondo la reazione di Maillard. Vi sara, dunque, la formazione di melanoidine, pigmenti polimerici, fissati nello strato corneo, che vi rimangono fino alla desquamazione dei corneociti. Questo colore e semipermanente e ben tollerato dalla pelle. La formulazione dei prodotti e delicata e la loro conservazione e difficile, ma nessun⬢altra sostanza fornisce risultati piu soddisfacenti e duraturi.

I principi specifici piu utilizzati nei prodotti cosmetici sono spiegati nei particolari della loro natura chimica, delle loro proprieta e della loro efficacia e tollerabilita. Vengono forniti alcuni esempi commerciali. Vengono presi in considerazione i prodotti idratanti (occlusivi, igroscopici, filmogeni idrofili, filmogeni idrofobi, regolatori del flusso idrico) gli antirughe o antieta (favorenti la desquamazione, schermi e filtri solari, antiradicali liberi, stimolanti cellulari, antielastasi, antiglicazione, tensori, rassodanti), gli antinfiammatori o lenitivi, gli immunoregolatori, i seboregolatori, gli antistress, i dimagranti, gli abbronzanti artificiali, i depigmentanti.

I cosmetici sono costituiti per il 20% da prodotti totalmente anidrici e per il 20% di circa da prodotti totalmente acquosi; il resto e rappresentato da prodotti emulsionati. Gli eccipienti saranno dunque divisi in due gruppi: lipofili e idrofili. Gli eccipienti lipofili sono: idrocarburi, siliconi, trigliceridi, cere, alcoli grassi, acidi grassi, esteri grassi, gelificanti lipofili. Gli eccipienti idrofili sono: acqua, umidificanti, gelificanti idrofili. E possibile aggiungere a questo insieme le polveri organiche e minerali, insolubili in entrambe le fasi quali gli ossidi minerali; la silice e i silicati quali il talco e il caolino, le polveri di poliamide e d’amido. Gli additivi quali i coloranti e i conservanti non sono compresi in questo capitolo, e nemmeno i tensioattivi.