A novel N95 respirator with chitosan nanoparticles: mechanical, antiviral, microbiological and cytotoxicity evaluations.

BACKGROUND: It is known that some sectors of hospitals have high bacteria and virus loads that can remain as aerosols in the air and represent a significant health threat for patients and mainly professionals that work in the place daily. Therefore, the need for a respirator able to improve the filtration barrier of N95 masks and even inactivating airborne virus and bacteria becomes apparent. Such a fact motivated the creation of a new N95 respirator which employs chitosan nanoparticles on its intermediate layer (SN95 + CNP). RESULTS: The average chitosan nanoparticle size obtained was 165.20 ± 35.00 nm, with a polydispersity index of 0.36 ± 0.03 and a zeta potential of 47.50 ± 1.70 mV. Mechanical tests demonstrate that the SN95 + CNP respirator is more resistant and meets the safety requisites of aerosol penetration, resistance to breath and flammability, presenting higher potential to filtrate microbial and viral particles when compared to conventional SN95 respirators. Furthermore, biological in vitro tests on bacteria, fungi and mammalian cell lines (HaCat, Vero E6 and CCL-81) corroborate the hypothesis that our SN95 + CNP respirator presents strong antimicrobial activity and is safe for human use. There was a reduction of 96.83% of the alphacoronavirus virus and 99% of H1N1 virus and MHV-3 betacoronavirus after 120 min of contact compared to the conventional respirator (SN95), demonstrating that SN95 + CNP have a relevant potential as personal protection equipment. CONCLUSIONS: Due to chitosan nanotechnology, our novel N95 respirator presents improved mechanical, antimicrobial and antiviral characteristics.

Two Years into the COVID-19 Pandemic: Lessons Learned.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible and virulent human-infecting coronavirus that emerged in late December 2019 in Wuhan, China, causing a respiratory disease called coronavirus disease 2019 (COVID-19), which has massively impacted global public health and caused widespread disruption to daily life. The crisis caused by COVID-19 has mobilized scientists and public health authorities across the world to rapidly improve our knowledge about this devastating disease, shedding light on its management and control, and spawned the development of new countermeasures. Here we provide an overview of the state of the art of knowledge gained in the last 2 years about the virus and COVID-19, including its origin and natural reservoir hosts, viral etiology, epidemiology, modes of transmission, clinical manifestations, pathophysiology, diagnosis, treatment, prevention, emerging variants, and vaccines, highlighting important differences from previously known highly pathogenic coronaviruses. We also discuss selected key discoveries from each topic and underline the gaps of knowledge for future investigations.

Widespread contamination of SARS-CoV-2 on highly touched surfaces in Brazil during the second wave of the COVID-19 pandemic.

Although SARS-CoV-2 surface contamination has been investigated in health care settings, little is known about the SARS-CoV-2 surface contamination in public urban areas, particularly in tropical countries. Here, we investigated the presence of SARS-CoV-2 on high-touch surfaces in a large city in Brazil, one of the most affected countries by the COVID-19 pandemic in the world. A total of 400 surface samples were collected in February 2021 in the City of Recife, Northeastern Brazil. A total of 97 samples (24.2%) tested positive for SARS-CoV-2 by RT-qPCR using the CDC-USA protocol. All the collection sites, except one (18/19, 94.7%) had at least one environmental surface sample contaminated. SARS-CoV-2 positivity was higher in public transport terminals (47/84, 55.9%), followed by health care units (26/84, 30.9%), beach areas (4/21, 19.0%), public parks (14/105, 13.3%), supply centre (2/21, 9.5%), and public markets (4/85, 4.7%). Toilets, ATMs, handrails, playgrounds and outdoor gyms were identified as fomites with the highest rates of SARS-CoV-2 detection. Taken together, our data provide a real-world picture of SARS-CoV-2 dispersion in highly populated tropical areas and identify critical control points that need to be targeted to break SARS-CoV-2 transmission chains.

High FUT3 expression is a marker of lower overall survival of breast cancer patients.

The complex enzyme network responsible for glycan synthesis suffers significant changes during the first steps of tumor development, leading to the early formation of tumor-associated glycan signatures. Among the glycosylation pathways, changes in fucosylation emerged as one of most important features in cancer. Αlpha-1,3/4-fucosyltransferase (FUT3) has been linked to pro-tumor and anti-tumor pathways depending on the cancer type. The present study aimed to understand the gene and protein expression profiles of FUT3 in three different and independent cohorts composed by invasive breast cancer patients: Local Brazilian population, METABRIC and TCGA. FUT3 transcripts and protein were measured in the Brazilian population by real-time PCR and Western blotting, respectively. Clinical records and FUT3 levels from public METABRIC and TCGA cohorts were accessed through CBioPortal database. FUT3 expression was analyzed in each cohort using the appropriated statistic tools. Survival meta-analysis in triple negative patients was performed using five independent cohorts including GSE41119, GSE47994 and GSE86945, data obtained from GEO repository available at NCBI database, and METABRIC and TCGA. Our analysis showed that high FUT3 levels were consistently associated to reduced invasive breast cancer patients overall survival. This finding is particularly significant in triple negative patients. These results together with the previously knowledge regarding the involvement of FUT3 in pro-tumor and anti-tumor mechanisms led us to purpose a model for FUT3 expression regulation throughout breast cancer establishment and progression.

The challenge of determining the impact of FUT3 tumor-associated polymorphism rs2306969 (-6951 C> T) in invasive breast cancer cells.

FUT3 gene is responsible for encode an homonymous α1,3/4-fucosyltransferase involved in the synthesis of sialyl-Lewis antigens. FUT3-fucosylated glycoconjugates play key roles in pathways involved in tumor biology and metastasis, such as cellular ligation to E-selectins, TGF-ß-induced epithelial-mesenchymal transition, NK cell-mediated tumor cytotoxicity and apoptosis. Tumor-associated FUT3 promoter polymorphism rs2306969 (-6951 C> T, position related to the gene's translation start site) has been linked to breast, ovarian and intestinal gastric cancer. Although non-coding polymorphisms accounts for the majority of variations founded in breast cancer, their functional roles are still poorly understood. This study aimed to investigate the impact of different alleles for this variation in FUT3 expression of invasive breast tumors. A luciferase reporter assay was performed using two breast tumor cell lines to evaluate respectively the impact of FUT3 rs2306969 (-6951 CC) and (-6951 TT) on protein expression. Gene and protein expressions were also measured in twenty-nine fresh biopsies of invasive breast tumors. Rs2306969 did not significantly influence FUT3 expression in both used systems. However, this study is defiant since the biological role of this polymorphism in breast cancer and other tumor types could be linked to cis/trans modulation of other genes, respond to different environmental stimuli or impact gene expression only in association with other variations. Rs2306969 did not modulate FUT3 expression in breast tumors under non-stimulated conditions. Nevertheless, our study contributes to the notably challenging task that is to understand how non-coding polymorphisms can drive the overall risk in cancer development.

Molecular modeling, docking and dynamics simulations of the Dioclea lasiophylla Mart. Ex Benth seed lectin: An edematogenic and hypernociceptive protein.

Lectins are proteins, or glycoproteins, capable of reversibly binding to specific mono- or oligosaccharides via a noncatalytic domain. The Diocleinae subtribe presents lectins with high structural similarity, but different effects based on biological activity assays. This variability results from small structural differences. Therefore, in this context, the present study aimed to perform a structural analysis of the lectin from Dioclea lasiophylla Mart. ex Benth seeds (DlyL) and evaluate its inflammatory effect. To accomplish this, DlyL was purified in a single step by affinity chromatography on Sephadex® G-50 matrix. DlyL primary structure was determined through a combination of tandem mass spectrometry and DNA sequencing. DlyL showed high similarity with other species from the same genus. Its theoretical three-dimensional structure was predicted by homology modelling, and the protein was subjected to ligand screening with monosaccharides, oligosaccharides and complex N-glycans by molecular docking. Stability and binding of the lectin with α-methyl-d-mannoside were assessed by molecular dynamics. DlyL showed acute inflammatory response with hypernociceptive effect in the paw edema model, possibly by interaction with glycans present at the cell surface.

Fut3 role in breast invasive ductal carcinoma: Investigating its gene promoter and protein expression.

Fucosylated glycans synthesized by α1,3/4-fucosyltransferase (FUT3) enzyme play an important role in breast cancer prognosis and metastasis, being involved in the binding of circulating tumor cells to the endothelium and being related to tumor stage, metastatic potential and chemoresistance. Despite the pro-tumor action of this enzyme, studies have demonstrated its role in natural killer-induced cytotoxicity through the recognition of sialyl Lewis X by C-type lectin receptors and through extrinsic apoptosis pathway triggered by Apo2L-TRAIL. This study aimed to investigate the expression pattern of FUT3 in invasive breast carcinoma (IDC) from patients of Pernambuco state, Northeast of Brazil, and genotype FUT3 promoter region to identify possible SNPs that could be associated with variations in FUT3 expression. Immunohistochemistry assay was used to access the FUT3 expression in normal (n=11) and tumor tissues (n=85). DNA sequencing was performed to genotype the FUT3 promoter region in patients with IDC (n=109) and healthy controls (n=110). Our results demonstrated that the absence of FUT3 enzyme is related to breast's IDC. The non-expression of FUT3 was more frequent in larger lesions and also in HER2 negative IDC tumors. Genomic analysis showed that two variations localized in FUT3 promoter region are possibly associated with IDC. Our results suggest that minor allele T of SNP rs73920070 (-6933 C>T) confers protection whereas minor allele T of SNP rs2306969 (-6951 C>T) triggers to susceptibility to IDC in the population of Pernambuco state, Northeast of Brazil.