SARS-CoV2 infection: the role of cytokines in COVID-19 disease

Elsevier concede permiso para que toda su investigación relacionada con COVID-19 que esté disponible en el centro de recursos COVID-19 -incluido el contenido de esta investigación- esté inmediatamente disponible en PubMed Central y otros repositorios financiados con fondos públicos, como la base de datos COVID de la OMS, con derechos para su reutilización y análisis de investigación sin restricciones en cualquier forma o por cualquier medio con reconocimiento de la fuente original. Estos permisos son concedidos gratuitamente por Elsevier mientras permanezca activo el centro de recursos COVID-19.COVID-19 disease, caused by infection with SARS-CoV-2, is related to a series of physiopathological mechanisms that mobilize a wide variety of biomolecules, mainly immunological in nature. In the most severe cases, the prognosis can be markedly worsened by the hyperproduction of mainly proinflammatory cytokines, such as IL-1, IL-6, IL-12, IFN-γ, and TNF-α, preferentially targeting lung tissue. This study reviews published data on alterations in the expression of different cytokines in patients with COVID-19 who require admission to an intensive care unit. Data on the implication of cytokines in this disease and their effect on outcomes will support the design of more effective approaches to the management of COVID-19.Este estudio ha contado con el apoyo del grupo de investigación BIO277 (Junta de Andalucía) y del Departamento de Enfermería de la Universidad de Granada

Evaluating Membranes for Bone Regeneration

This work was supported by: 1)the Ministry of Economy and Competitiveness and European Regional Development Fund [Project MAT2017-85999-P MINECO/AEI/FEDER/UE],2) University of Granada/Regional Government of Andalusia Research Fund from Spain and European Regional Development Fund (A-BIO-157-UGR-18/FEDER).This research is part of M.T-O.’s PhD research study.Objectives:Maxillofacial bone defectsare the main hindering conditions for traditional dental implant strategies. Guided Bone Regeneration (GBR) is used to handle this situation. The principle of GBR is to use a membrane to prevent the colonization of soft tissue cells of the bone defect and favors the migration of osteogenic linages. Currentmembranes do not completely fulfill the requirements that an optimal membrane should have, sometimes resulting in non-predictable results. Thus, the need to develop an ideal membrane to perform this duty is clear. Recent developments in bio-manufacturing are driving innovations in membranes technology permitting the active participation of the membrane in the healing and regenerative process trough native tissue mimicking, drug-delivery and cells interaction, away from being a passive barrier. New membranes features need specific evaluation techniques, beyond the International Standard for membrane materials (last reviewed in 2004), being this the rationale for the present review.Nanotechnology application has completely shifted the way of analyzing structural characterization. New progresses on osteoimmmunomodulation have also switched the understanding of cells-membranes interaction. Data and Sources:To propose an updated protocol for GBR membranes evaluation, critical reading of therelevant published literature was carried out after a MEDLINE/PubMed database search. Conclusions:The main findings are that a potential active membrane should be assessed in its nanostructure, physicochemical and nanomechanical properties,bioactivityand antibacterial,osteoblasts proliferation, differentiation and mineralization. Immunomodulationtesting for macrophages recruitmentand M2 phenotype promotion in osteoblasts co-culture has to beachieved to completely analyze membranes/tissue interactions.Ministry of Economy and Competitiveness and European Regional Development Fund [Project MAT2017-85999-P MINECO/AEI/FEDER/UE]University of Granada/Regional Government of Andalusia Research Fund from Spain and European Regional Development Fund (A-BIO-157-UGR-18/FEDER

Biological properties and therapeutic applications of garlic and its components

This study was supported by research group BIO277 (Junta de Andalucia) and Department of Nursing (University of Granada).Garlic is one of the most widely employed condiments in cooking. It has also been used since ancient times in traditional plant-based medicine, largely based on its organosulfur compounds. The objective of this study was to provide updated information on the biological and therapeutic garlic properties. Garlic has been found to possess important biological properties with high therapeutic potential, which is influenced by the mode of its utilization, preparation, and extraction. It has been attributed with antioxidant, anti-inflammatory, and immunomodulatory capacities. Garlic, in particular its organosulfur compounds, can maintain immune system homeostasis through positive effects on immune cells, especially by regulating cytokine proliferation and expression. This may underlie their usefulness in the treatment of infectious and tumor processes. These compounds can also offer vascular benefits by regulating lipid metabolism or by exerting antihypertensive and antiaggregant effects. However, further clinical trials are warranted to confirm the therapeutic potential of garlic and its derivatives.Department of Nursing (University of Granada)Junta de Andaluci

Role of Vitamin D in the Metabolic Syndrome

This study was supported by research group BIO277 (Junta de Andalucía) and the Department of Nursing (University of Granada).The prevalence of hypovitaminosis D has risen in developed countries over the past few years in association with lifestyle changes and an increase in unhealthy habits. Vitamin D deficiency has been implicated in various diseases, including metabolic syndrome (MetS), which is clinically defined by a set of metabolic and vascular disorders. The objective of this study was to review scientific evidence on the relationship between MetS and vitamin D deficiency to support the development of prevention strategies and health education programs. An inverse relationship has been reported between plasma vitamin D concentrations and the features that define MetS, i.e., elevated serum concentrations of glucose, total cholesterol, low-density lipoproteins, triglycerides, glycosylated hemoglobin, and a high body mass index. Numerous studies have described the benefits of vitamin D supplementation to improve outcomes in individuals with MetS. Interventions to maintain optimal vitamin D concentrations are proposed as a preventive strategy against MetS.Junta de AndaluciaDepartment of Nursing (University of Granada

Impact of bisphosphonates on the proliferation and gene expression of human fibroblasts

The aim of this study was to elucidate the role of fibroblasts in bisphosphonate-related osteonecrosis of the jaw (BRONJ), evaluating the effect of zoledronate, alendronate, and ibandronate on the proliferation of fibroblasts and on their expression of genes essential for fibroblast physiology. Human CCD-1064Sk epithelial fibroblast cells were incubated in culture medium with 10-5, 10-7, or 10-9 M zoledronate, alendronate, or ibandronate. The proliferative capacity of fibroblasts was determined by spectrophotometry (MTT) at 24 of culture. Real-time polymerase chain reaction (RT-PCR) was used to study the effects of BPs at a dose of 10-9 M on the expression of FGF, CTGF, TGF-β1, TGFβR1, TGFβR2, TGFβR3, DDR2, α-actin, fibronectin, decorin, and elastin. Fibroblasts proliferation was significantly increased at the lowest dose (10-9M) of each BP but was not affected at the higher doses (10-5 and 10-7M). The proliferation increase may be related to the rise in TGF-β1 and TGFβR1 expression detected after the treatment of cells with 10-9M of zoledronate, alendronate, or ibandronate. However, the expression of CTGF, DDR2, α-actin, fibronectin, and decorin decreased versus controls. The results of this in vitro study indicate that a very low BP dose (10-9 M) can significantly affect the physiology of fibroblasts, increasing their proliferative capacity and modulating the expression of multiple genes involved in their growth and differentiation

Effects of bisphenol F, bisphenol S, and bisphenol AF on cultured human osteoblasts

Bisphenol A (BPA) analogs, like BPA, could have adverse effects on human health including bone health. The aim was to determine the effect of BPF, BPS and BPAF on the growth and differentiation of cultured human osteoblasts. Osteoblasts primary culture from bone chips harvested during routine dental work and treated with BPF, BPS, or BPAF for 24 h at doses of 10 –5 , 10 –6 , and 10 –7 M. Next, cell proliferation was studied, apoptosis induction, and alkaline phosphatase (ALP) activity. In addition, mineralization was evaluated at 7, 14, and 21 days of cell culture in an osteogenic medium supplemented with BP analog at the studied doses. BPS treatment inhibited proliferation in a dose-dependent manner at all three doses by inducing apoptosis; BPF exerted a significant inhibitory effect on cell proliferation at the highest dose alone by an increase of apopto- sis; while BPAF had no effect on proliferation or cell viability. Cell differentiation was adversely affected by treatment with BPA analogs in a dose-dependent, observing a reduction in calcium nodule formation at 21 days. According to the results obtained, these BPA analogs could potentially pose a threat to bone health, depending on their concentration in the organism.Funding for open access publishing: Universidad de Granada/ CBU

Characterization of the GGPP synthase gene family in Arabidopsis thaliana

Geranylgeranyl diphosphate (GGPP) is a key precursor of various isoprenoids that have diverse functions in plant metabolism and development. The annotation of the Arabidopsis thaliana genome predicts 12 genes to encode geranylgeranyl diphosphate synthases (GGPPS). In this study we analyzed GGPPS activity as well as the subcellular localization and tissue-specific expression of the entire protein family in A. thaliana. GGPPS2 (At2g18620), GGPPS3 (At2g18640), GGPPS6 (At3g14530), GGPPS7 (At3g14550), GGPPS8 (At3g20160), GGPPS9 (At3g29430), GGPPS10 (At3g32040) and GGPPS11 (At4g36810) showed GGPPS activity in Escherichia coli, similar to activities reported earlier for GGPPS1 (At1g49530) and GGPPS4 (At2g23800) (Zhu et al. in Plant Cell Physiol 38(3):357-361, 1997a; Plant Mol Biol 35(3):331-341, b). GGPPS12 (At4g38460) did not produce GGPP in E. coli. Based on DNA sequence analysis we propose that GGPPS5 (At3g14510) is a pseudogene. GGPPS-GFP (green fluorescent protein) fusion proteins of the ten functional GGPP synthases localized to plastids, mitochondria and the endoplasmic reticulum, with the majority of the enzymes located in plastids. Gene expression analysis using quantitative real time-PCR, GGPPS promoter-GUS (β-glucuronidase) assays and publicly available microarray data revealed a differential spatio-temporal expression of GGPPS genes. The results suggest that plastids and mitochondria are key subcellular compartments for the synthesis of ubiquitous GGPP-derived isoprenoid species. GGPPS11 and GGPPS1 are the major isozymes responsible for their biosynthesis. All remaining paralogs, encoding six plastidial isozymes and two cytosolic isozymes, were expressed in specific tissues and/or at specific developmental stages, suggesting their role in developmentally regulated isoprenoid biosynthesis. Our results show that of the 12 predicted GGPPS encoded in the A. thaliana genome 10 are functional proteins that can synthesize GGPP. Their specific subcellular location and differential expression pattern suggest subfunctionalization in providing GGPP to specific tissues, developmental stages, or metabolic pathway

Repercussions of Bisphenol A on the Physiology of Human Osteoblasts

(1) Background: Bisphenol A (BPA) is an endocrine disruptor that is widely present in the environment and exerts adverse effects on various body tissues. The objective of this study was to determine its repercussions on bone tissue by examining its impact on selected functional parameters of human osteoblasts. (2) Methods: Three human osteoblast lines were treated with BPA at doses of 10(-5), 10(-6), or 10(-7) M. At 24 h post-treatment, a dose-dependent inhibition of cell growth, alkaline phosphatase activity, and mineralization was observed. (4) Results: The expression of CD54 and CD80 antigens was increased at doses of 10(-5) and 10(-6) M, while the phagocytic capacity and the expression of osteogenic genes (ALP, COL-1, OSC, RUNX2, OSX, BMP-2, and BMP-7) were significantly and dose-dependently reduced in the presence of BPA. (5) Conclusions: According to these findings, BPA exerts adverse effects on osteoblasts by altering their differentiation/maturation and their proliferative and functional capacity, potentially affecting bone health. Given the widespread exposure to this contaminant, further human studies are warranted to determine the long-term risk to bone health posed by BPA