Oral organic nanovaccines against bacterial and viral diseases.

Vaccines have saved millions of humans and animals from deadly diseases. Many vaccines are still under development to fight against lethal diseases. Indeed, subunit vaccines are a versatile approach with several advantageous attributes, but they lack strong immunogenicity. Nanotechnology is an avenue to vaccine development because nanoparticles may serve as nanocarriers and adjuvants, which are critical aspects for oral vaccines. This review provides an update of oral organic nanovaccines, describing suitable nanomaterials for oral vaccine design and recent (last five-year view) oral nanovaccine developments to fight against those principal pathogens causing human and animal diseases.

COVID-19 susceptibility and severity risks in a cross-sectional survey of over 500 000 US adults.

OBJECTIVES: The enormous toll of the COVID-19 pandemic has heightened the urgency of collecting and analysing population-scale datasets in real time to monitor and better understand the evolving pandemic. The objectives of this study were to examine the relationship of risk factors to COVID-19 susceptibility and severity and to develop risk models to accurately predict COVID-19 outcomes using rapidly obtained self-reported data. DESIGN: A cross-sectional study. SETTING: AncestryDNA customers in the USA who consented to research. PARTICIPANTS: The AncestryDNA COVID-19 Study collected self-reported survey data on symptoms, outcomes, risk factors and exposures for over 563 000 adult individuals in the USA in just under 4 months, including over 4700 COVID-19 cases as measured by a self-reported positive test. RESULTS: We replicated previously reported associations between several risk factors and COVID-19 susceptibility and severity outcomes, and additionally found that differences in known exposures accounted for many of the susceptibility associations. A notable exception was elevated susceptibility for men even after adjusting for known exposures and age (adjusted OR=1.36, 95% CI=1.19 to 1.55). We also demonstrated that self-reported data can be used to build accurate risk models to predict individualised COVID-19 susceptibility (area under the curve (AUC)=0.84) and severity outcomes including hospitalisation and critical illness (AUC=0.87 and 0.90, respectively). The risk models achieved robust discriminative performance across different age, sex and genetic ancestry groups within the study. CONCLUSIONS: The results highlight the value of self-reported epidemiological data to rapidly provide public health insights into the evolving COVID-19 pandemic.

C-type lectin 17A and macrophage-expressed receptor genes are magnified by fungal ß-glucan after Vibrio parahaemolyticus infection in Totoaba macdonaldi cells.

C-type lectins are a principal carbohydrate recognition mechanism as glucans on cell surfaces. This study identified and investigated molecular characterization and immune roles of a novel c-type lectin 17A from Totoaba macdonaldi (TmCLEC17A), which were described in head-kidney leukocytes after immunostimulation with fungal ß-glucan 197A and Vibrio parahaemolyticus infection. This nucleotide sequence from totoaba was acquired using NGS and bioinformatics tools. Its full-length cDNA sequence consisted of 1128 bp (including the stop codon) and an open reading frame (ORF) of 771 bp encoding a 256 amino acid protein, 5´-UTR of 48 bp and 3´-UTR of 309 bp. The TmCLEC17A protein revealed a C-terminal-C-type lectin (CTL, also named carbohydrate-recognition domain, CRD), a N-terminal trans-membrane domain and a coiled coil motif, showing the highest similarity (80%) and identity (96%) with Larimichthys crocea. Fungal ß-glucan 197A plus V. parahaemolyticus enhanced transcriptions of CLEC17A and TLR2 significantly besides the macrophage receptors, such as macrophage mannose receptor 1 and macrophage colony-stimulating factor 1 receptor 2. In addition, natural resistance-associated macrophage protein 2 was significantly up-regulated in leukocytes challenged with live V. parahaemolyticus. Overall, these results indicated that CLEC17A might be implicated in T. macdonaldi innate immunity as a pattern recognition receptor; fungal ß-glucan 197A could stimulate cellular immune mechanisms in head-kidney leukocytes; and it could be used as potential immunostimulant in fish aquaculture.

Biosynthesis of ß-d-glucan­gold nanoparticles, cytotoxicity and oxidative stress in mouse splenocytes.

This study reports biosynthesis of gold-nanoparticles (AuNPs) by using ß-d-glucans isolated from the yeast Yarrowia lypolitica D1. ß-d-glucans serve as reducing and stabilizing mediators that induce the formation of AuNPs on the outer surface of the own ß-d-glucan. The systems were physicochemically characterized by ultraviolet visible (UV-Vis) spectroscopy, high-resolution transmission electron microscopy (HR-TEM), scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), and dynamic light scattering (DLS) analyses. The results revealed the generation of AuNPs with quasi-spherical shape or large one dimension (1D) gold-nanostructures (AuNSs) depending on the HAuCl4 concentration. A cytotoxic study was assessed in mouse splenocytes. Contrary to that expected, important cytotoxicity was found in all ß-d-gluc+AuNPs systems by an oxidative stress increase. This study discusses the cytotoxic mechanism, suggesting that the resulting ß-d-gluc+AuNPs systems may not be candidates for the formulation of immunostimulants or nanocarriers for biomedical applications.

Caspase -1, -3, -8 and antioxidant enzyme genes are key molecular effectors following Vibrio parahaemolyticus and Aeromonas veronii infection in fish leukocytes.

Caspases are a family of proteases involved in many important biological processes including apoptosis and inflammation. In order to get insights into the caspase gene family and antioxidant enzymes in Totoaba macdonaldi during bacterial infection, an in vitro assay was performed involving three different types of caspases (Casp-1, Casp-3 and Casp-8) and antioxidant enzymes (catalase, gluthathione peroxidase 1 and 4) after Vibrio parahaemolyticus and Aeromonas veronii infection, using head-kidney and spleen leukocytes from the teleost fish totoaba at 12 and 24 h post-exposure. Characterization of caspases by bioinformatics analyses showed that TmCas-1, TmCas-3 and TmCas-8 shared overall sequence identities of 82-61%, 85-97% and 77-63%, respectively, with other teleost fish. Caspase-1, -3 and -8 proteins revealed a conserved penta-peptide sequence at the catalytic site and three amino acid residues involved in the catalysis (H, G and C), as well as two conserved domains. The expression levels of the three caspases were detected in a wide range of fish tissues; however, they varied among tissues and caspases, which were highly up-regulated in immune organs, such as head-kidney, liver and/or spleen. The pathogen-induced gene expression pattern revealed two interesting facts; first, that the expression of all the caspase genes and antioxidant enzyme genes evaluated in this study were strongly induced following V. parahaemolyticus infection; second, these up-regulations reached a maximum level at 24 h post-infection in head-kidney whereas in spleen leukocytes, it was observed at 6-h post-infection. In conclusion, based on these observations, the acute toxic effects of V. parahaemolyticus are associated to cell death and release of free radicals. This information provides a better understanding of the effects and nature of early immune response against common bacterial infections in totoaba leukocytes.

Predicción de mortalidad en pacientes oncológicos en terapia intensiva. Un estudio de centro único / Mortality prediction in cancer patients in intensive care. A single center study

In troducción:La mortalidad de los pacientes con cáncer,ingresados en unaunidad de terapia intensiva puede ser estimada usando las escalas de sepsis. El objetivo del presente estudio fue realizar una prueba diagnóstica entre las principales escalas en un grupo de pacientes oncológicos de un centro de referencia de Guayaquil-Ecuador.Met odología: Se realizó un estudio transversal, en la unidad de terapia intensiva del Instituto Oncológico Nacional "Dr Juan Tanca Marengo" de SOLCA-Guayaquil, en el período octubre 2019a noviembre del 2020. La muestrafue probabilística, de pacientes con diagnóstico oncológicos clínicos ingresado en UCI. Se registró edad, tipo de cáncer, antecedentes familiares, mortalidad y las escalas SOFA y APACHE II. Se utiliza estadística descriptiva, se realiza una prueba diagnóstica y un análisis de supervivencia.R esultados: Se analizan 99 casos, de 57 ± 16 añosde edad, 37 hombres (37.4%). Con Hipertensión arte-rial (39.4%) y diabetes mellitus tipo 2 (17.1%). 12.1 %casos de linfoma no Hodgkiny cáncer intestinal 11.1%; 17 fallecimientos (17.2%). La puntuación global SOFA fue de 6.8 ± 3.0. La puntuación global APACHE II de 18.6 ± 7.0. El riesgo de mortalidad fue estadísticamente significativo a partir del 5to día. La puntuación SOFA >6 tuvo una sensibilidad del 88.24 %, valor predictivo (VP) positivo fue muy bajo, así como la especificidad; el VP negativo fue de 97%. La escala APACHE II, tuvo una sensibilidad del 94.12 %, con una especificidad de 96.34 %; VP positivo, comparada a la escala SOFA fue el doble.Co nclusión: La escala APACHE II en pacientes oncológicos clínicos ingresados en UCI predice de la ma-nera más exacta la mortalidad cuando la puntuación es mayor a 18

Debaryomyces hansenii up regulates superoxide dismutase gene expression and enhances the immune response and survival in Pacific red snapper (Lutjanus peru) leukocytes after Vibrio parahaemolyticus infection.

Application of yeast is increasing to improve welfare and promotes growth in aquaculture. The halotolerant yeast Debaryomyces hansenii is normally a non-pathogenic yeast with probiotic properties and potential source of antioxidant enzymes as superoxide dismutase. Here, first, we characterized the sequence features of MnSOD and icCu/ZnSOD from Pacific red snapper, and second, we evaluated the potential antioxidant immune responses of the marine yeast Debaryomyces hansenii strain CBS004 in leukocytes which were then subjected to Vibrio parahaemolyticus infection. In silico analysis revealed that LpMnSOD consisted of 1186 bp, with an ORF of 678 bp encoding a 225 amino acid protein and LpicCu/ZnSOD consisted of 1090 bp in length with an ORF of 465 bp encoding a 154 amino acid protein. Multiple alignment analyzes revealed many conserved regions and active sites among its orthologs. In vitro assays using head-kidney and spleen leukocytes immunostimulated with D. hansenii and zymosan in response to V. parahaemolyticus infection reveled that D. hansenii strain CBS004 significantly increased transcriptions of MnSOD and icCu/ZnSOD genes. Flow cytometry assay showed that D. hansenii was able to inhibit apoptosis caused by V. parahaemolyticus in the Pacific red snapper leukocytes and enhanced the phagocytic capacity in head-kidney leukocytes. Immunological assays reveled an increased in superoxide dismutase and peroxidase activities, as well as, in nitric oxide production and reactive oxygen species production (respiratory burst) in fish stimulated with D. hansenii. Finally, our results. These results strongly support the idea that marine yeast Debaryomyces hansenii strain CBS004 can stimulate the antioxidant immune mechanism in head-kidney and spleen leukocytes.

Role of cytokines in the pathophysiology of systemic lupus erythematosus / Papel de las citocinas en la fisiopatología del lupus eritematoso sistémico

ABSTRACT The physiological mechanism in systemic lupus erythematosus is not yet fully elucidated. It is currently known that it is a multifactorial autoimmune disease which includes genetic, environmental and immune factors. Over the years it has been reported that cytokines play a predominant role during the course of the disease. In this review some findings reported in recent years were reviewed and the most important cytokines in SLE were considered; and we analyzed how the levels of each cytokine have been found in patients and how each of them can contribute to the proposed mechanisms and the relationship with the disease, as well as their possible effects on the triggering and control of systemic lupus erythematosus. The aimed of this article is to provide a focused review of the current knowledge of cytokines in SLE.

RESUMEN Los mecanismos fisiopatológicos en el lupus eritematoso sistémico (LES) aún no están completamente elucidados. Actualmente se sabe que es una enfermedad autoinmune multifactorial que comprende factores genéticos, ambientales e inmunes. A lo largo de los años se ha reportado que las citocinas tienen un papel preponderante durante el curso de la enfermedad. En esta revisión, algunos hallazgos reportados durante los últimos años fueron revisados para algunas de las citocinas más importantes descritas en el lupus, se analizó cómo se han encontrado los niveles de cada citocina en los pacientes y cómo cada una de ellas puede contribuir a los mecanismos propuestos, también se abordó su relación con la enfermedad, así como sus posibles efectos en el desencadenamiento y control del LES. El propósito de este artículo es brindar una revisión focalizada en el conocimiento actual de las citocinas en el LES.