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Consequences of the disease produced by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have led to an urgent search for preventive and therapeutic strategies. Besides drug treatments, proposals have been made for supplementation with biomolecules possessing immunomodulatory and antioxidant properties. The objective of this study was to review published evidence on the clinical usefulness of supplementation with vitamin D, antioxidant vitamins (vitamin A, vitamin E, and vitamin C), melatonin, lactoferrin and natural products found in food (curcumin, luteolin, ginger, allicin, magnesium and zinc) as supplements in SARS-CoV-2 infection. In general, supplementation of conventional treatments with these biomolecules has been found to improve the clinical symptoms and severity of the coronavirus disease (COVID-19), with some indications of a preventive effect. In conclusion, these compounds may assist in preventing and/or improving the symptoms of COVID-19. Nevertheless, only limited evidence is available, and findings have been inconsistent. Further investigations are needed to verify the therapeutic potential of these supplements.

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 apoptosis; 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., (© 2023. The Author(s).)

Fibroblasts contribute to maintaining tissue integrity and homeostasis and are a key cell population in wound healing. This cell population can be stimulated by some bioactive compounds such as extra virgin olive oil (EVOO) polyphenols. The aim of this study was to determine the effects of hydroxytyrosol (htyr), tyrosol (tyr), and oleocanthal (ole) phenolic compounds present in EVOO on the proliferation, migration, cell cycle, and antigenic profile of cultured human fibroblasts. CCD-1064Sk human fibroblast cells were treated for 24 h with each polyphenol at doses ranging 10 -5 to 10 -9 M. Cell proliferation was evaluated using the MTT spectrophotometric technique, migration capacity by culture insert assay, and cell cycle and antigenic profile with flow cytometry. Cell proliferation was significantly increased by treatment with all compounds. The highest increases followed treatments with htyr or tyr at doses of 10 -5 or 10 -6 M and with ole at 10 -6 and 10 -7 M, and these compounds and doses were used for assays of antigenic profile, cell cycle, and migration. During the first few hours after treatment, increased fibronectin and α-actin expressions and greater cell migration were observed, with no cell cycle changes. In conclusion, these in vitro results suggest that phenolic compounds in EVOO might contribute to wound healing through action on fibroblasts related to tissue regeneration.

Bone effects attributed to bisphenols (BPs) include the inhibition of growth and differentiation. This study analyzes the effect of BPA analogs (BPS, BPF, and BPAF) on the gene expression of the osteogenic markers RUNX2, osterix (OSX), bone morphogenetic protein-2 (BMP-2), BMP-7, alkaline phosphatase (ALP), collagen-1 (COL-1), and osteocalcin (OSC). Human osteoblasts were obtained by primary culture from bone chips harvested during routine dental work in healthy volunteers and were treated with BPF, BPS, or BPAF for 24 h at doses of 10 -5 , 10 -6 , and 10 -7 M. Untreated cells were used as controls. Real-time PCR was used to determine the expression of the osteogenic marker genes RUNX2, OSX, BMP-2, BMP-7, ALP, COL-1, and OSC. The expression of all studied markers was inhibited in the presence of each analog; some markers (COL-1; OSC, BMP2) were inhibited at all three doses and others only at the highest doses (10 -5 and 10 -6 M). Results obtained for the gene expression of osteogenic markers reveal an adverse effect of BPA analogs (BPF, BPS, and BPAF) on the physiology of human osteoblasts. The impact on ALP, COL-1, and OSC synthesis and therefore on bone matrix formation and mineralization is similar to that observed after exposure to BPA. Further research is warranted to determine the possible contribution of BP exposure to the development of bone diseases such as osteoporosis.

The olive tree and its derivatives are of great interest in the field of biomedicine due to their numerous health properties. The aim of the present study was to identify the effects of the use of olive products, extra virgin olive oil (EVOO) and products derived from its extraction, on the skin. Numerous studies have pointed out the protective effect of olive compounds on skin ageing, thanks to their role in the different mechanisms involved in the ageing process, such as reducing oxidative stress, increasing cell viability and decreasing histological alterations. With regard to their photoprotective effect, the olive tree and its fruit contain phenolic compounds which have a protective effect against radiation, such as low ultraviolet absorption and high antioxidant activity, acting as a protective factor against photocarcinogenesis. Similarly, the anti-tumour effects of olives have been studied at the level of the different compounds and extracts obtained from them, and their ability to selectively attack human melanoma cells has been observed. They have also shown antibacterial activity against microorganisms particularly implicated in skin infections, such as Escherichia coli , Candida albicans , Staphylococcus aureus , Staphylococcus epidermidis , Enterococcus faecalis , Pseudomonas aeruginosa and Proteus spp. Likewise, on healthy tissue, they have shown the ability to stimulate growth, migration and the expression of genes involved in cell differentiation, which favours the regeneration of skin wounds. According to the results included in this review, the olive tree and its derivatives could be useful in the treatment of many skin conditions.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new disease that has led to a worldwide pandemic, resulting in millions of deaths and a high economic burden. Here, we analyze the current status of preventive vaccines authorized by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA). Published clinical trials have shown the effectiveness of mRNA (BNT162b2 and Spikevax), adenovirus vector-based (Ad26.COV2.S and ChAdOx1 nCoV-19), and recombinant protein S (NVX-CoV2373) vaccines to be between 52.9% and 100%. The most-frequent adverse effects include local pain, fatigue, headache, or chills. Serious events are associated with Ad26.COV2.S and ChAdOx1 nCoV-19 vaccines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Antiseptics are used for the cleansing of acute or chronic wounds to eliminate micro-organisms from the wound bed. However, they have effects on the skin cells., Aim: To determine the effects of hexetidine, povidone-iodine (PI), undecylenamidopropyl-betaine/polyhexanide (UBP), chlorhexidine, disodium eosin and hydrogen peroxide on human skin fibroblasts., Methods: CCD-1064Sk cells were treated with hexetidine, PI, UBP, chlorhexidine, disodium eosin or hydrogen peroxide. Spectrophotometry was used to measure cell viability and flow cytometry was used to study apoptosis and necrosis after the treatment. In vitro wound scratch assays were performed to determine the gap closure., Results: All antiseptics significantly reduced the viability of human skin fibroblasts compared with controls. The percentage wound closure was lower with hexetidine, PI and UBP. The scratch assay could not be measured after treatments with chlorhexidine, disodium eosin or hydrogen peroxide, owing to their cytotoxicity. The apoptosis/necrosis experiments evidenced a significant reduction in viable cells compared with controls. An increased percentage of apoptotic cells was observed after treatment with all antiseptics. Compared with controls, the percentage of necrotic cells was significantly increased with all antiseptics except for hexetidine., Conclusion: The proliferation, migration and viability of human skin fibroblasts are reduced by treatment with hexetidine, PI, UBP, chlorhexidine, disodium eosin and hydrogen peroxide., (© 2022 The Authors. Clinical and Experimental Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

The success of regenerative medicine in various clinical applications depends on the appropriate selection of the source of mesenchymal stem cells (MSCs). Indeed, the source conditions, the quality and quantity of MSCs, have an influence on the growth factors, cytokines, extracellular vesicles, and secrete bioactive factors of the regenerative milieu, thus influencing the clinical result. Thus, optimal source selection should harmonize this complex setting and ensure a well-personalized and effective treatment. Mesenchymal stem cells (MSCs) can be obtained from several sources, including bone marrow and adipose tissue, already used in orthopedic regenerative applications. In this sense, for bone, dental, and oral injuries, MSCs could provide an innovative and effective therapy. The present review aims to compare the properties (proliferation, migration, clonogenicity, angiogenic capacity, differentiation potential, and secretome) of MSCs derived from bone marrow, adipose tissue, and dental tissue to enable clinicians to select the best source of MSCs for their clinical application in bone and oral tissue regeneration to delineate new translational perspectives. A review of the literature was conducted using the search engines Web of Science, Pubmed, Scopus, and Google Scholar. An analysis of different publications showed that all sources compared (bone marrow mesenchymal stem cells (BM-MSCs), adipose tissue mesenchymal stem cells (AT-MSCs), and dental tissue mesenchymal stem cells (DT-MSCs)) are good options to promote proper migration and angiogenesis, and they turn out to be useful for gingival, dental pulp, bone, and periodontal regeneration. In particular, DT-MSCs have better proliferation rates and AT and G-MSC sources showed higher clonogenicity. MSCs from bone marrow, widely used in orthopedic regenerative medicine, are preferable for their differentiation ability. Considering all the properties among sources, BM-MSCs, AT-MSCs, and DT-MSCs present as potential candidates for oral and dental regeneration.

(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.

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.

Purpose: The objective of this study was to determine the effect of two antibiotics (amoxicillin and clindamycin) and one antiseptic (chlorhexidine digluconate [CHX]) on the growth and differentiation capacity of primary human osteoblasts., Materials and Methods: Osteoblast proliferation was determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) technique after a 1-minute treatment with 400 μg/mL amoxicillin or 150 μg/mL clindamycin or CHX (0.12% or 0.2%). Flow cytometry was used for apoptosis/necrosis analysis. The study of cell differentiation was performed using a mineralization medium and staining of the nodules formed using red alizarin at 15 and 22 days of treatment with 400 μg/mL amoxicillin or 150 μg/mL clindamycin. Spectrophotometry was used to determine alkaline phosphatase (ALP) activity after 1 minute of treatment., Results: Treatment of osteoblasts with 0.12% and 0.2% CHX for 1 minute induced a strong dose-dependent reduction in cell proliferation (P < .001) with a significant increase in the percentage of apoptotic cells (P = .004 and < .001, respectively). However, cell proliferation significantly increased (P < .05) after treatment with 150 μg/mL clindamycin. Treatment of the osteoblasts with 150 μg/mL clindamycin for 1 minute significantly increased the expression of ALP (P = .002). Calcium deposition was significantly higher (P < .001) in the 150 μg/mL clindamycin group., Conclusion: These data support the use of low doses of clindamycin and amoxicillin for intraoral bone graft decontamination and raise questions about the use of CHX. Osteoblast growth and differentiation may be favored by low doses of clindamycin, and it may be the decontaminant of choice for intraoral bone grafts, while CHX is shown as a less bone-friendly agent.

Mesenchymal stromal cells (MSCs) have evidenced considerable therapeutic potential in numerous clinical fields, especially in tissue regeneration. The immunological characteristics of this cell population include the expression of Toll-like receptors and mannose receptors, among others. The study objective was to determine whether MSCs have phagocytic capacity against different target particles. We isolated and characterized three human adipose tissue MSC (HAT-MSC) lines from three patients and analysed their phagocytic capacity by flow cytometry, using fluorescent latex beads, and by transmission electron microscopy, using Escherichia coli, Staphylococcus aureus and Candida albicans as biological materials and latex beads as non-biological material. The results demonstrate that HAT-MSCs can phagocyte particles of different nature and size. The percentage of phagocytic cells ranged between 33.8% and 56.2% (mean of 44.37% ± 11.253) according to the cell line, and a high phagocytic index was observed. The high phagocytic capacity observed in MSCs, which have known regenerative potential, may offer an advance in the approach to certain local and systemic infections., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Alzheimer's disease (AD) is the most common cause of dementia. It is characterized by cognitive decline and progressive memory loss. The aim of this review was to update the state of knowledge on the pathophysiological mechanisms, diagnostic methods and therapeutic approach to AD. Currently, the amyloid cascade hypothesis remains the leading theory in the pathophysiology of AD. This hypothesis states that amyloid-β (Aβ) deposition triggers a chemical cascade of events leading to the development of AD dementia. The antemortem diagnosis of AD is still based on clinical parameters. Diagnostic procedures in AD include fluid-based biomarkers such as those present in cerebrospinal fluid and plasma or diagnostic imaging methods. Currently, the therapeutic armory available focuses on symptom control and is based on four pillars: pharmacological treatment where acetylcholinesterase inhibitors stand out; pharmacological treatment under investigation which includes drugs focused on the control of Aβ pathology and tau hyperphosphorylation; treatment focusing on risk factors such as diabetes; or nonpharmacological treatments aimed at preventing development of the disease or treating symptoms through occupational therapy or psychological help. AD remains a largely unknown disease. Further research is needed to identify new biomarkers and therapies that can prevent progression of the pathology.

Oral squamous cell carcinoma (OSCC) is the most prevalent oral malignant tumor worldwide. An early diagnosis can have a major positive impact on its prognosis. Human saliva contains cytokines, DNA and RNA molecules, circulating cells, and derivatives of tissues and extracellular vesicles, among other factors that can serve as biomarkers. Hence, the analysis of saliva may provide useful information for the early diagnosis of OSCC for its prognosis. The objective of this review was to determine the potential usefulness of salivary biomarkers (cytokines and microRNA) to diagnose OSCC and improve its prognosis. A combination of salivary miRNA and proteomic data could allow a definitive and early diagnosis to be obtained. However, there remains a need to optimize and standardize the protocols used to quantify miRNAs.

Plastic is a synthetic or semisynthetic polymer with numerous physicochemical properties, and its fragmentation can give rise to microplastics (MPs) and nanoplastics (NPs). These particles can enter our ecosystem, where a process of constant degradation facilitates their dispersion and absorption by different species, affecting multiple organs and systems. The objective of this review was to provide an update on the potential health effects of MPs and NPs indicated by in vitro and in vivo studies. In vitro studies have described the absorption of plastic particles of different sizes and have documented their proinflammatory effects and genotoxicity, which can lead to the structural alteration of cells. MPs and NPs have also been implicated in the development of antibiotic resistance. In vivo studies have demonstrated that MPs and NPs can access organisms via dietary and respiratory pathways and through the epidermis. Their reported effects include: changes in microbiota and digestive enzyme production; inflammatory processes at respiratory level; circulatory and reproductive system disorders; and neurotoxicity, inducing behavioral changes. In vitro and in vivo studies have evidenced detrimental effects in different organs and systems as a function of the dose, size, and chemical properties of plastic particles. Further research is warranted to determine the effects on human health of these particles at environmental doses., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Some micronutrients of vegetable origin are considered potentially useful as wound-healing agents because they can increase fibroblast proliferation and differentiation., The Aim of This Study: was to evaluate the regenerative effects of selected olive oil phenolic compounds on cultured human fibroblasts and explore their antimicrobial properties., Material and Methods: The CCD-1064Sk fibroblast line was treated for 24 h with 10 -6 M luteolin, apigenin, ferulic, coumaric acid or caffeic acid, evaluating the effects on cell proliferation by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) spectrophotometric assay; the migratory capacity by the scratch assay and determining the expression of Fibroblast Growth Factor (FGF), Vascular Endothelial Growth Factor (VEGF), Transforming Growth Factor- β1 (TGFβ1), Platelet Derived Growth Factor (PDGF), and Collagen Type I (COL-I) genes by real-time polymerase chain reaction. The antimicrobial capacity of the polyphenols was evaluated by the disc diffusion method., Results: All compounds except for ferulic acid significantly stimulated the proliferative capacity of fibroblasts, increasing their migration and their expression of the aforementioned genes. With respect to their antimicrobial properties, treatment with the studied compounds inhibited the growth of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Proteus spp., and Candida Albicans., Conclusions: The phenolic compounds in olive oil have a biostimulatory effect on the regeneration capacity, differentiation, and migration of fibroblasts and exert major antibacterial activity. According to the present findings, these compounds may have a strong therapeutic effect on wound recovery., (Copyright © 2021 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.)

The treatment of tissue damage produced by physical, chemical, or mechanical agents involves considerable direct and indirect costs to health care systems. Wound healing involves a series of molecular and cellular events aimed at repairing the defect in tissue integrity. These events can be favored by various natural agents, including the polyphenols in extra virgin olive oil (EVOO). The objective of this study was to review data on the potential effects of different phenolic compounds that can also be found in EVOO on wound healing and closure. Results of in vitro and animal studies demonstrate that polyphenols from different plant species, also present in EVOO, participate in different aspects of wound healing, accelerating this process through their anti-inflammatory, antioxidant, and antimicrobial properties and their stimulation of angiogenic activities required for granulation tissue formation and wound re-epithelialization. These results indicate the potential usefulness of EVOO phenolic compounds for wound treatment, either alone or in combination with other therapies. Human studies are warranted to verify this proposition.

Objectives: To analyze how novel developed silicon dioxide composite membranes, functionalized with zinc or doxycycline, can modulate the expression of genes related to the osteogenic functional capacity of osteoblastic cells., Methods: The composite nanofibers membranes were manufactured by using a novel polymeric blend and 20 nm silicon dioxide nanoparticles (SiO 2 -NPs). To manufacture the membranes, 20 nm SiO 2 -NPs were added to the polymer solution and the resulting suspension was processed by electrospinning. In a second step, the membranes were functionalized with zinc or doxycycline. Then, they were subjected to MG63 osteoblast-like cells culturing for 48 h. After this time, real-time quantitative polymerase chain reaction (RT-qPCR) was carried out to study the expression of Runx-2, OSX, ALP, OSC, OPG, RANKL, Col-I, BMP-2, BMP-7, TGF-β1, VEGF, TGF-βR1, TGF- βR2, and TGF-βR3. Mean comparisons were conducted by One-way ANOVA and Tukey tests (p < 0.05)., Results: In general, the blending of SiO 2 -NPs in the tested non-resorbable polymeric scaffold improves the expression of osteogenic genes over the control membranes. Doxycycline doping of experimental scaffolds attained the best results, encountering up-regulation of BMP-2, ALP, OPG, TGFβ-1 and TGFβ-R1. Membranes with zinc induced a significant increase in the expression of Col-I, ALP and TGF β1. Both, zinc and doxycycline functionalized membranes enormously down-regulated the expression of RANKL., Conclusions: Zinc and doxycycline doped membranes are bioactive inducing overexpression of several osteogenic gene markers., Clinical Significance: Doxycycline doped membranes may be a potential candidate for use in GBR procedures in several challenging pathologies, including periodontal diseases., (Copyright © 2021. Published by Elsevier Ltd.)

Polymeric membranes are employed in guided bone regeneration (GBR) as physical barriers to facilitate bone in-growth. A bioactive and biomimetic membrane with the ability to participate in the healing and regeneration of the bone is necessary. The aim of the present study was to analyze how novel silicon dioxide composite membranes functionalized with zinc or doxycycline can modulate the osteoblasts' proliferation, differentiation, and expression of selected antigenic markers related to immunomodulation. Nanostructured acrylate-based membranes were developed, blended with silica, and functionalized with zinc or doxycycline. They were subjected to MG63 osteoblast-like cells culturing. Proliferation was assessed by MTT-assay, differentiation by evaluating the alkaline phosphatase activity by a spectrophotometric method and antigenic phenotype was assessed by flow cytometry for selected markers. Mean comparisons were conducted by one-way ANOVA and Tukey tests ( p < 0.05). The blending of silica nanoparticles in the tested non-resorbable polymeric scaffold improved the proliferation and differentiation of osteoblasts, but doxycycline doped scaffolds attained the best results. Osteoblasts cultured on doxycycline functionalized membranes presented higher expression of CD54, CD80, CD86, and HLA-DR, indicating a beneficial immunomodulation activity. Doxycycline doped membranes may be a potential candidate for use in GBR procedures in several challenging pathologies, including periodontal disease.

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.

Fibromyalgia (FM) is a highly prevalent syndrome that impairs the quality of life of the patients; however, its diagnosis is complex and mainly centered on pain symptoms. The study of salivary biomarkers has proven highly useful for the diagnosis and prognosis of numerous diseases. The objective of this review was to gather published data on the utilization of salivary biomarkers to facilitate and complement the diagnosis of FM. Salivary biomarkers used in FM diagnosis include cortisol; calgranulin; and the enzymes α-amylase, transaldolase, and phosphoglycerate mutase. Increased serum levels of C-reactive protein, cytokines interleukin 1-β, interleukin 6, interleukin 8, interleukin 10, interleukin 17, tumor necrosis factor α, and various chemokines may serve as salivary biomarkers, given observations of their increased serum levels in patients with FM. Further research is warranted to study in depth the role and performance of biomarkers currently used in FM diagnosis/prognosis and to identify novel salivary biomarkers for this disease.

Obesity is one of the main public health problems of the 21 st century resulting from an imbalance between calorie intake and energy expenditure. Currently, the search for new treatments against this pathology has become a priority. One of the therapeutic strategies against obesity could be the activation of brown adipose tissue through different molecules such as the phenolic compounds of extra virgin olive oil (EVOO). The objective of this review was to provide an update of scientific knowledge on the relationship between EVOO phenolic compounds and brown adipose tissue.According to this review, it has been demonstrated that extra virgin olive oil phenolic compounds can have beneficial effects on obesity by activating brown adipose tissue and enhance thermogenesis through different signaling pathways mediated by molecules such as AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α) or sirtuin 1 (Sirt1).

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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Saliva is a highly versatile biological fluid that is easy to gather in a non-invasive manner-and the results of its analysis complement clinical and histopathological findings in the diagnosis of multiple diseases. The objective of this review was to offer an update on the contribution of salivary biomarkers to the diagnosis and prognosis of diseases of the oral cavity, including oral lichen planus, periodontitis, Sjögren's syndrome, oral leukoplakia, peri-implantitis, and medication-related osteonecrosis of the jaw. Salivary biomarkers such as interleukins, growth factors, enzymes, and other biomolecules have proven useful in the diagnosis and follow-up of these diseases, facilitating the early evaluation of malignization risk and the monitoring of disease progression and response to treatment. However, further studies are required to identify new biomarkers and verify their reported role in the diagnosis and/or prognosis of oral diseases.

Systemic lupus erythematosus (SLE) is an autoimmune chronic inflammatory disease of unknown etiology, although genetic and environmental factors appear to contribute to its pathogenesis. Specifically, infectious processes are associated with SLE onset and exacerbation. However, we are far from a complete understanding of the interactions between infectious agents and the host, explaining the interest in gathering updated scientific information on this topic. According to the literature, the pathogens most frequently associated with SLE are viruses, notably human endogenous retroviruses, Epstein-Barr virus, parvovirus B19, cytomegalovirus and human immunodeficiency virus type 1, alongside certain bacterial components that can also trigger activation of the immune system. The mechanisms underlying autoreactivity remain unclear but various explanations have been proposed, including immunological changes responsible for infectious processes or molecular mimicry between host structures and those of infectious agents., (© 2019 John Wiley & Sons Ltd.)

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 -9 M) of each BP but was not affected at the higher doses (10 -5 and 10 -7 M). The proliferation increase may be related to the rise in TGF-β1 and TGFβR1 expression detected after the treatment of cells with 10 -9 M 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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Non-steroidal anti-inflammatory drugs (NSAIDs), including cyclooxygenase-2 (COX-2)-selective NSAIDs, are associated with adverse effects on bone tissue. These drugs are frequently the treatment of choice but are the least studied with respect to their repercussion on bone. The objective of this study was to determine the effects of celecoxib on cultured human osteoblasts. Human osteoblasts obtained by primary culture from bone samples were treated with celecoxib at doses of 0.75, 2, or 5μM for 24 h. The MTT technique was used to determine the effect on proliferation; flow cytometry to establish the effect on cell cycle, cell viability, and antigenic profile; and real-time polymerase chain reaction to measure the effect on gene expressions of the differentiation markers RUNX2, alkaline phosphatase (ALP), osteocalcin (OSC), and osterix (OSX). Therapeutic doses of celecoxib had no effect on osteoblast cell growth or antigen expression but had a negative impact on the gene expression of RUNX2 and OSC, although there was no significant change in the expression of ALP and OSX. Celecoxib at therapeutic doses has no apparent adverse effects on cultured human osteoblasts and only inhibits the expression of some differentiation markers. These characteristics may place this drug in a preferential position among NSAIDs used for analgesic and anti-inflammatory therapy during bone tissue repair., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

The prevalence of autoimmune diseases (ADs) has increased over the past few decades. Vitamin D deficiency is a common factor in many of these diseases, whose etiology remains poorly understood. The objective of this study was to review published data on the role of vitamin D in ADs. Vitamin D insufficiency has been described as an important factor in the development of some ADs, generally attributed to the key role of this vitamin in the immune system. Most studies show that adequate supplementation can prevent and improve the development of some of these diseases, although the optimal vitamin D dose remains controversial. We highlight the importance of measuring serum vitamin D levels of the population and developing strategies to improve and maintain levels with no health risks., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Pressure ulcers represent a major challenge to patient safety in the health care context, presenting high incidence (from 7% to 14% in Spain) and increased financial costs (€400-600 million/year) in medical treatment. Moreover, they are a significant predictor of mortality. The prevention of pressure ulcers in long-term care centers and patients' own homes is proposed as a priority indicator of health care quality. Early stage risk assessment and database recording are both crucial aspects of prevention, classification, diagnosis, and treatment., Objective: This project proposes a 3-year study of immobilized patients residing in the Granada-Metropolitan Primary Healthcare District (DSGM) and monitored via the Pressure Ulcer Information and Registration System (SIRUPP, Spanish initials). The project aims to estimate the incidence of PUs among immobilized elderly patients, analyze the health-related quality of life of these patients by using the Pressure Ulcer Quality of Life (PU-QoL) instrument in a sample of 250 patients, determine the average time to complete wound healing, estimate the rate of pressure ulcers-associated mortality, and assess the predictive value of the Braden and Mini Nutritional Assessment risk measurement scales in a sample of 1700 patients., Methods: The DSGM runs SIRUPP, which is linked to patients' electronic health records. Currently, 17,104 immobilized patients are monitored under this system. Health-related quality of life will be measured by patient self-reports using the Spanish Pressure Ulcer Quality of Life questionnaire, following cross-cultural adaptation and psychometric validation with respect to the English-language version., Results: The project commenced in June 2017 and is expected to conclude in April 2020., Conclusions: This study addresses two main health outcomes-the time needed for wound healing and the mortality associated with pressure ulcers-both of which might be accounted for by variations in clinical practice and the health-related quality of life of patients with pressure ulcers., International Registered Report Identifier (irrid): DERR1-10.2196/13701., (©Eugenio Vera-Salmerón, Claudia Rutherford, Carmen Dominguez-Nogueira, María Pilar Tudela-Vázquez, Victor J Costela-Ruiz, Basilio Gómez-Pozo. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 12.08.2019.)

Autoimmune diseases result from an immune response against structures of the organism itself. Their etiology is unknown, although they have been associated with genetic and environmental factors and the participation of mast cells has recently been proposed. The objective of this review was to provide an update on the role of mast cells in these diseases. According to the literature, mast cells not only intervene in immune processes as a defense mechanism but are also involved in the development of disease. Thus, mast cells may participate in important ways in autoimmune diseases through the secretion of cytokines or release of enzymes from their cytoplasmic granules or through the activity of proinflammatory mediators released by these cells. Further research is warranted to elucidate the role of mast cells in autoimmune diseases., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently used in clinical practice, which can have adverse effects on the osteoblast. The objective of this study was to determine the effect of NSAIDs on the osteoblast by analyzing the gene expression of different markers related to osteoblast maturation and function when treated in vitro with different NSAIDs., Methods: Three human osteoblast lines from bone samples of three healthy volunteers were treated with 10 µM acetaminophen, indomethacin, ketoprofen, diclofenac, ibuprofen, ketorolac, naproxen, and piroxicam. The gene expression of different markers (run related transcription factor 2 [ RUNX-2 ], type 1 collagen [ COL-I ], osterix [ OSX ], osteocalcin [ OSC ], bone morphogenetic protein 2 [ BMP-2 ] and 7 [ BMP-7 ], transforming growth factor β 1 [ TGF- β 1 ], and TGF β receptors [ TGF β R1, TGF β R2; TGFBR3 ]) were analyzed by real-time PCR at 24 h of treatment., Results: Expression of RUNX-2, COL-I, OSX , was reduced by treatment with all studied NSAIDs, OSC expression was reduced by all NSAIDs except for ketoprofen, naproxen, or piroxicam. Expression of BMP-7 was reduced by all NSAIDs; BMP-2 was reduced by all except for naproxen. In general, NSAID treatment increased the expression of TGF- β 1 , but not of its receptors ( TGF β -R1, TGF β -R2, and TFG β -R3 ), which was either unchanged or reduced by the treatment., Conclusion: These data confirm that NSAIDs can affect osteoblast physiology, suggesting their possible impact on bone., Competing Interests: The authors declare there are no competing interests.

Objective: To determine the effect of different nonsteroidal anti-inflammatory drugs (NSAIDs) on vascular endothelial growth factor (VEGF) gene expression in two osteoblast cell populations., Design: Osteoblasts obtained by primary culture (HOp) and human osteosarcoma cell line MG63 (MG-63), which were treated with 10 μM doses of acetaminophen, indomethacin, ketoprofen, diclofenac, ibuprofen, ketorolac, naproxen or piroxicam. At 24 h of treatment, their gene expression of VEGF was evaluated by real-time polymerase chain reaction (RT-PCR) and compared with the expression in untreated cells (control group)., Results: The treatment with the different NSAIDs significantly reduced VEGF expression regardless of the cell line and NSAID studied., Conclusion: The results of this study suggest that these drugs may have undesirable effects on the osteoblast and its bone-forming capacity, given the effect of this growth factor on these cells. Further studies are warranted to determine their repercussions on bone tissue and to elucidate the cell signaling mechanism/s involved., (Copyright © 2018 Elsevier Ltd. All rights reserved.)