Enhanced Immunogenicity and Protective Effects against SARS-CoV-2 Following Immunization with a Recombinant RBD-IgG Chimeric Protein.

The unprecedented global impact caused by SARS-CoV-2 imposed huge health and economic challenges, highlighting the urgent need for safe and effective vaccines. The receptor-binding domain (RBD) of SARS-CoV-2 is the major target for neutralizing antibodies and for vaccine formulations. Nonetheless, the low immunogenicity of the RBD requires the use of alternative strategies to enhance its immunological properties. Here, we evaluated the use of a subunit vaccine antigen generated after the genetic fusing of the RBD with a mouse IgG antibody. Subcutaneous administration of RBD-IgG led to the extended presence of the protein in the blood of immunized animals and enhanced RBD-specific IgG titers. Furthermore, RBD-IgG immunized mice elicited increased virus neutralizing antibody titers, measured both with pseudoviruses and with live original (Wuhan) SARS-CoV-2. Immunized K18-hACE2 mice were fully resistant to the lethal challenge of the Wuhan SARS-CoV-2, demonstrated by the control of body-weight loss and virus loads in their lungs and brains. Thus, we conclude that the genetic fusion of the RBD with an IgG molecule enhanced the immunogenicity of the antigen and the generation of virus-neutralizing antibodies, supporting the use of IgG chimeric antigens as an approach to improve the performance of SARS-CoV-2 subunit vaccines.

Recombinant antigen delivery to dendritic cells as a way to improve vaccine design.

Dendritic cells are central to the development of immunity, as they are specialized in initiating antigen-specific immune responses. In this review, we briefly present the existing knowledge on dendritic cell biology and how their division in different dendritic cell subsets may impact the development of immune responses. In addition, we explore the use of chimeric monoclonal antibodies that bind to dendritic cell surface receptors, with an emphasis on the C-type lectin family of endocytic receptors, to deliver antigens directly to these cells. Promising preclinical studies have shown that it is possible to modulate the development of immune responses to different pathogens when monoclonal antibodies fused to pathogen-derived antigens are used to deliver the antigen to different subsets of dendritic cells. This approach can be used to improve the efficacy of vaccines against different pathogens.

Memory elicitation, T-cell response and antibody production: an independent study of an inactivated entire virus vaccine (Coronavac).

Health professionals working to mitigate the COVID-19 pandemic are one of the main risk groups for the disease, being prioritized for vaccination. Considering this, the aim of this study was to analyze the immune response of these professionals immunized with CoronaVac in the first and second doses. Blood samples were collected after the first and second doses of the vaccine (CoronaVac) and used to investigate hematological and biochemical parameters, analysis of immunoglobulin production, cytokines, and gene expression profile, as well as the identification of subsets of immune cells. Post-first dose immunological phenotypic memory (CD27+) profiles (T CD4+, TCD8+ and CD19+) showed a significant increase, as did Monocyte APCs (CD80+HLA-DR+) in relation to the second dose. The cytokines IL-2, IL-6 and IFN-° showed increased values in relation to the other analyzed cytokines. The Th2/Th17 profile in the second dose was characterized by gene expression analysis. The production of IgM and IgG after vaccination showed statistically significant values in the comparison between doses. CoronaVac showed activation of APCs monocytes, memory response of T and B lymphocytes, with immunoglobulins production. This set of responses is characterized by the Th2/Th17 immunological profile.

Simultaneous occurrence of Epstein-Barr virus (EBV) in periodontal pockets and in oral squamous cell carcinoma: a cross-sectional study.

OBJECTIVES: This study aimed to investigate the detection of Epstein-Barr virus (EBV) in oral squamous cell carcinoma (OSCC) and to verify the concordance of EBV-DNA frequency in subgingival sites and in the OSCC. METHODS: A cross-sectional study with 30 OSCC patients, aged from 44 to 88 years old, was conducted. Samples were collected in subgingival sites and at the OSCC, then submitted to DNA isolation, qPCR, and genotyping. Descriptive statistic was performed to report the frequency of EBV-DNA in all samples, and McNemar test was applied to verify the concordance among the EBV-DNA frequency in both sites. RESULTS: The individuals presented 62 years old in average, and the majority were male (66.6%). EBV-DNA was detected in 56.7% OSCC lesions. Among the subgroup of 19 dentate individuals, high concordance (73.7%) in both EBV-DNA detection and the absence in subgingival sites and OSCC was observed, and it was statistically significant (p < 0.05). CONCLUSIONS: We report the notable occurrence of EBV-DNA in OSCC; also, the presence of EBV in periodontal sites may contribute to find it in OSCC, although the possible contribution of EBV in the OSCC remains to be investigated. CLINICAL RELEVANCE: The identification of this easily accessible site of EBV latent infection may help to improve the patient's quality of life by maintenance of oral/periodontal health condition and preventing further possible disorders related to the virus, and also encourages new approaches for investigating EBV, periodontitis, and OSCC.

Characterization of a lignin from Crataeva tapia leaves and potential applications in medicinal and cosmetic formulations.

Lignins are phenolic macromolecules that have several applications. In this work, we examine some biological activities of a lignin-like macromolecule isolated from the Crataeva tapia leaves, not yet studied to evaluate its potential applications in medicinal and cosmetic formulations. Lignin was obtained by alkaline delignification and its physical-chemical characterization was made by means of FT-IR, UV-Vis, NMR spectroscopy, elementary analysis, molecular mass determination and thermal analysis. Lignin is of the GSH type, with levels of hydrogen (5.10%), oxygen (27.18%), carbon (67.60%), nitrogen (0.12%) and phenolic content of 189.6 ± 9.6 mg GAE/g. In addition, it is a thermally stable macromolecule with low antioxidant activity. Cytotoxicity and cytokine production were assessed by flow cytometry. The photoprotective activity was evaluated by adding different concentrations of lignin to a commercial cream. Lignin was not cytotoxic, it stimulated the production of TNF-α, IL-6 and IL-10 and did not promote a significant change in nitric oxide levels. In addition, this macromolecule was able to promote increased absorption of ultraviolet light from a commercial cream. These results reinforce the ethnopharmacological use of C. tapia leaves and suggest the need for further studies to determine the potential medicinal and cosmetic applications (sunscreen) of lignin from C. tapia leaves.

Left Ventricular Noncompaction: New Insights into a Poorly Understood Disease.

Left ventricular noncompaction (LVNC) is a congenital pathology that directly affects the lining walls of myocardial tissue, causing trabeculations with blood filling in the inner wall of the heart, concomitantly with the development of a mesocardial thinning. Although LVNC was described for the first time as long ago as 1984, our understanding of the disease with regard to its genetic pattern, diagnosis, clinical presentation and treatment is still scanty. LVNC can present as an isolated condition or associated with congenital heart disease, genetic syndromes or neuromuscular disease. This suggests that LVNC is not a distinct form of cardiomyopathy, but rather a morphological expression of different diseases. Recognition of the disease is of fundamental importance because its clinical manifestations are variable, ranging from the absence of any symptom to congestive heart failure, lethal arrhythmias and thromboembolic events. The study of this disease has emphasized its genetic aspects, as it may be of sporadic origin or hereditary, in which case it most commonly has an autosomal dominant inheritance or one linked to the X chromosome. Echocardiography is the gold standard for diagnosis, and magnetic resonance imaging may refine the identification of the disease, especially in those patients with non-conclusive echocardiography. This article sets out to review the main characteristics of LVNC and present updates, especially in the genetic pattern, diagnosis and treatment of the disease.

Lignin isolated from Caesalpinia pulcherrima leaves has antioxidant, antifungal and immunostimulatory activities.

Caesalpinia pulcherrima is a shrub with worldwide distribution used as an ornamental plant. In this study, we extracted a lignin from the C. pulcherrima leaves and investigated its biological functions. The lignin was characterized by FT-IR, UV-Vis, GPC, TGA and nuclear magnetic resonance (1H and 13C). The antioxidant activity was evaluated using phosphomolybdenum complexation methods (TAA), sequestration of DPPH and ABTS radicals, reducing power, formation of nitrite radical and iron chelating activity (Fe2 +). Antifungal activity was made using Candida spp., Aspergillus spp. and Cryptococcus neoformans strains. Cytotoxicity, oxidative stress, and cytokine production were performed using mouse splenocytes. The lignin showed maximal UV-Vis at ~280 nm, 22.27 L/g·cm of absorptivity and, 2,503 kDa of molecular weight. Phenolic compounds (41.33 ± 0.65 mg GAE/g) and indications of a guaiacyl-syringyl-hydroxyphenyl (GSH)-type composition were found. Antioxidant activities of lignin to TAA (40±1.2%) and to DPPH (16.9±0.2%) was high and showed antifungal potential, especially against Candida spp. (IC50 = 31.3 µg/mL) and C. neoformans (15.6 µg/mL). In mouse splenocytes, the lignin was not cytotoxic and stimulated the cell proliferation and cytokine release. These results indicate that C. pulcherrima lignin has the potential to be used as antifungal and immunostimulant compound.

SARS-CoV, MERS-CoV and SARS-CoV-2 infections in pregnancy and fetal development.

Recently, in China, in 2019, a new type of disease has arisen caused by a new strain of coronavirus, the SARS-CoV-2 virus, considered extremely worrying due to its high infectivity power and the easy ability to spread geographically. For patients in general, the clinical features resulting from respiratory syndromes can trigger an asymptomatic condition. However, 25 % of patients infected by SARS-CoV-2 can progress to severity. Pregnant women are an unknown field in this complex process, and although they have symptoms similar to non-pregnant women, some points should be considered, such as complications during pregnancy and postpartum. Thus, the aim of this study was to understand the consequences of pregnancy and fetal development, caused by infections by the SARS-CoV, MERS-CoV and SARS-CoV-2 viruses. Among the aforementioned infections, MERS-CoV seems to be the most dangerous for newborns, inducing high blood pressure, pre-eclampsia, pneumonia, acute renal failure, and multiple organ failure in mother. This also causes a higher occurrence of emergency cesarean deliveries and premature births, in addition, some deaths of mothers and fetuses were recorded. Meanwhile, SARS-CoV and SARS-CoV-2 appear to have less severe symptoms. Furthermore, although a study found the ACE2 receptor, used by SARS-CoV-2, widely distributed in specific cell types of the maternal-fetal interface, there is no evidence of vertical transmission for any of the coronaviruses. Thus, the limited reported obstetric cases alert to the need for advanced life support for pregnant women infected with coronaviruses and to the need for further investigation for application in clinical practice.

Tolerance of early oral feeding in patients subjected to total laryngectomy.

BACKGROUND: The purpose of this study was to assess the tolerance of early oral feeding after total laryngectomy. METHOD: A randomized multicenter study was conducted that included 89 individuals subjected to total laryngectomy. The participants were allocated to 2 groups: early (n = 44), early oral feeding; and late (n = 45), late oral feeding. The participants in the early group were assessed as to acceptance of oral feeding, and their food intake was quantified. RESULTS: In the early group, the total energy expenditure and protein needs were not met through oral feeding alone at any time during the first 7 postoperative days. The times to attain 25% and 50% of the total energy expenditure and protein needs by oral feeding after surgery were 4 and 7 days, respectively. CONCLUSION: The patients subjected to early oral feeding failed to meet their caloric and protein needs through that route alone during the first 4 postoperative days and required complementary nutrition through another route. © 2015 Wiley Periodicals, Inc. Head Neck 38: E643-E648, 2016.

Spontaneous remission of a squamous cell carcinoma of the floor of the mouth.

Spontaneous remission is a rare, but well recognized event in oncology. Certain tumours, such as melanomas, hypernephromas and neuroblastomas, are known for showing spontaneous regression. Similarly, spontaneous regression of oral lymphomas, as well as oropharyngeal and recurrent tongue carcinomas, has been reported. Here, we present a novel case of a patient with a primary squamous cell carcinoma on the floor of the mouth whose tumour regressed spontaneously in three months, without any treatment. We also review of the literature on the spontaneous remission of oral cancer and discuss possible mechanisms for this phenomenon.