Extra Virgin Olive Oil Phenolic Compounds Modulate the Gene Expression of Biomarkers Involved in Fibroblast Proliferation and Differentiation.

Extra virgin olive oil phenolic compounds have been identified as possible biostimulant agents against different pathological processes, including alterations in healing processes. However, there is little evidence on the molecular mechanisms involved in this process. The aim was to analyse the effect of hydroxytyrosol, tyrosol, and oleocanthal on fibroblast gene expression. PCR was used to determine the expression of different differentiation markers, extracellular matrix elements, and growth factors in cultured human fibroblasts CCD-1064Sk treated with different doses of hydroxytyrosol (10-5 M and 10-6 M), tyrosol (10-5 M and 10-6 M), and oleocanthal (10-6 M and 10-7 M). After 24 h of hydroxytyrosol treatment, increased expression of connective tissue growth factor, fibroblast growth factor (FGF), platelet-derived growth factor, vascular endothelial growth factor, transforming growth factor ß1 (TGF-ß1), and their receptors was observed. Tyrosol and olecanthal modulated the expression of FGF and TGFßR1. All phytochemicals tested modified the expression of differentiation markers and extracellular matrix elements, increasing gene expression of actin, fibronectin, decorin, collagen I, and III. Phenolic compounds present in extra virgin olive could have a beneficial effect on tissue regeneration by modulating fibroblast physiology.

Physiological Mechanisms Inherent to Diabetes Involved in the Development of Dementia: Alzheimer's Disease.

Type 2 diabetes mellitus (T2D) is a metabolic disease reaching pandemic levels worldwide. In parallel, Alzheimer's disease (AD) and vascular dementia (VaD) are the two leading causes of dementia in an increasingly long-living Western society. Numerous epidemiological studies support the role of T2D as a risk factor for the development of dementia. However, few basic science studies have focused on the possible mechanisms involved in this relationship. On the other hand, this review of the literature also aims to explore the relationship between T2D, AD and VaD. The data found show that there are several alterations in the central nervous system that may be promoting the development of T2D. In addition, there are some mechanisms by which T2D may contribute to the development of neurodegenerative diseases such as AD or VaD.

The Benefits of Olive Oil for Skin Health: Study on the Effect of Hydroxytyrosol, Tyrosol, and Oleocanthal on Human Fibroblasts.

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.

Amyotrophic Lateral Sclerosis and Serum Lipid Level Association: A Systematic Review and Meta-Analytic Study.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown etiology. Many metabolic alterations occur during ALS progress and can be used as a method of pre-diagnostic and early diagnosis. Dyslipidemia is one of the physiological changes observed in numerous ALS patients. The aim of this study is to analyze the possible relationship between the rate of disease progression (functional rating scale (ALS-FRS)) and the plasma lipid levels at the early stage of ALS. A systematic review was carried out in July 2022. The search equation was "Triglycerides AND amyotrophic lateral sclerosis" and its variants. Four meta-analyses were performed. Four studies were included in the meta-analysis. No significant differences were observed between the lipid levels (total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol) and the ALS-FRS score at the onset of the disease. Although the number of studies included in this research was low, the results of this meta-analytic study suggest that there is no clear relationship between the symptoms observed in ALS patients and the plasma lipid levels. An increase in research, as well as an expansion of the geographical area, would be of interest.

Current Treatments and New, Tentative Therapies for Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative pathology, the origin of which is associated with the death of neuronal cells involved in the production of dopamine. The prevalence of PD has increased exponentially. The aim of this review was to describe the novel treatments for PD that are currently under investigation and study and the possible therapeutic targets. The pathophysiology of this disease is based on the formation of alpha-synuclein folds that generate Lewy bodies, which are cytotoxic and reduce dopamine levels. Most pharmacological treatments for PD target alpha-synuclein to reduce the symptoms. These include treatments aimed at reducing the accumulation of alpha-synuclein (epigallocatechin), reducing its clearance via immunotherapy, inhibiting LRRK2, and upregulating cerebrosidase (ambroxol). Parkinson's disease continues to be a pathology of unknown origin that generates a significant social cost for the patients who suffer from it. Although there is still no definitive cure for this disease at present, there are numerous treatments available aimed at reducing the symptomatology of PD in addition to other therapeutic alternatives that are still under investigation. However, the therapeutic approach to this pathology should include a combination of pharmacological and non-pharmacological strategies to maximise outcomes and improve symptomatological control in these patients. It is therefore necessary to delve deeper into the pathophysiology of the disease in order to improve these treatments and therefore the quality of life of the patients.

Modulation of Osteogenic Gene Expression by Human Osteoblasts Cultured in the Presence of Bisphenols BPF, BPS, or BPAF.

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.

Therapeutic potential of antimicrobial peptides for treatment of wound infection.

Healing of cutaneous wounds is a fundamental process required to re-establish tissue integrity, repair skin barrier function, and restore skin homeostasis. Chronic wound infection, exacerbated by the growing development of resistance to conventional therapies, hinders the skin repair process and is a serious clinical problem affecting millions of people worldwide. In the past decade, the use of antimicrobial peptides (AMPs) has attracted increasing attention as a potential novel strategy for the treatment of chronic wound infections due to their unique multifaceted mechanisms of action, and AMPs have been demonstrated to function as potent host-defense molecules that can control microbial proliferation, modulate host-immune responses, and act as endogenous mediators of wound healing. To date over 3,200 AMPs have been discovered either from living organisms or through synthetic derivation, some of which have progressed to clinical trials for the treatment of burn and wound injuries. However, progress to routine clinical use has been hindered due to AMPs' susceptibility to wound and environmental factors including changes in pH, proteolysis, hydrolysis, oxidation, and photolysis. This review will discuss the latest research focused on the development and applications of AMPs for wound infections using the latest nanotechnological approaches to improve AMP delivery, and stability to present effective combinatorial treatment for clinical applications.

Effect of Punicalagin and Ellagic Acid on Human Fibroblasts In Vitro: A Preliminary Evaluation of Their Therapeutic Potential.

BACKGROUND: Pomegranate is a fruit that contains various phenolic compounds, including punicalagin and ellagic acid, which have been attributed to anti-inflammatory, antioxidant, and anticarcinogenic properties, among others. OBJECTIVE: To evaluate the effect of punicalagin and ellagic acid on the viability, migration, cell cycle, and antigenic profile of cultured human fibroblasts (CCD-1064Sk). MTT spectrophotometry was carried out to determine cell viability, cell culture inserts were used for migration trials, and flow cytometry was performed for antigenic profile and cell cycle analyses. Cells were treated with each phenolic compound for 24 h at doses of 10-5 to 10-9 M. RESULTS: Cell viability was always significantly higher in treated versus control cells except for punicalagin at 10-9 M. Doses of punicalagin and ellagic acid in subsequent assays were 10-6 M or 10-7 M, which increased the cell migration capacity and upregulated fibronectin and α-actin expression without altering the cell cycle. CONCLUSIONS: These in vitro findings indicate that punicalagin and ellagic acid promote fibroblast functions that are involved in epithelial tissue healing.

Biological effects of the olive tree and its derivatives on the skin.

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.

The current status of COVID-19 vaccines. A scoping review.

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.

Therapeutic Approach to Alzheimer's Disease: Current Treatments and New Perspectives.

Alzheimer's disease (AD) is the most common cause of dementia. The pathophysiology of this disease is characterized by the accumulation of amyloid-ß, leading to the formation of senile plaques, and by the intracellular presence of neurofibrillary tangles based on hyperphosphorylated tau protein. In the therapeutic approach to AD, we can identify three important fronts: the approved drugs currently available for the treatment of the disease, which include aducanumab, donepezil, galantamine, rivastigmine, memantine, and a combination of memantine and donepezil; therapies under investigation that work mainly on Aß pathology and tau pathology, and which include γ-secretase inhibitors, ß-secretase inhibitors, α-secretase modulators, aggregation inhibitors, metal interfering drugs, drugs that enhance Aß clearance, inhibitors of tau protein hyperphosphorylation, tau protein aggregation inhibitors, and drugs that promote the clearance of tau, and finally, other alternative therapies designed to improve lifestyle, thus contributing to the prevention of the disease. Therefore, the aim of this review was to analyze and describe current treatments and possible future alternatives in the therapeutic approach to AD.

Different Sources of Mesenchymal Stem Cells for Tissue Regeneration: A Guide to Identifying the Most Favorable One in Orthopedics and Dentistry Applications.

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.

Analysis of the Lifestyle of Spanish Undergraduate Nursing Students and Comparison with Students of Other Degrees.

BACKGROUND: Nursing students are exposed to concepts of healthy lifestyles while they are attending university. OBJECTIVE: The aim of this study was to analyze whether nursing students have a healthier lifestyle than non-nursing students and to determine whether their behaviour is consistent with their beliefs. METHODS: A cross-sectional study, with 293 university students was performed by using a validated questionnaire to measure beliefs and behaviour regarding health. RESULTS: The lifestyle pattern of the nursing students evaluated was characterised by a high percentage of nurses with low levels of physical activity, poor balanced diet and smoking habits. The comparative analysis showed no significant differences between nursing students and students from other degrees. CONCLUSIONS: Students have a positive attitude and knowledge about healthy lifestyle, but do not transfer it to their own lives. Nurses' lifestyle can unintentionally affect the behaviour of other people through their own behaviour and beliefs because they serve as a model for a healthy lifestyle. These findings support that nurse educators have an active role as promoter of health by using lessons to modify the behaviour of their students.

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.

Effect of the most common wound antiseptics on human skin fibroblasts.

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.

The Effect of Chlorhexidine, Amoxicillin, and Clindamycin on the Growth and Differentiation of Primary Human Osteoblasts.

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.

Biological properties and therapeutic applications of garlic and its components.

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.

Human adipose tissue-derived mesenchymal stromal cells and their phagocytic capacity.

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.

Current Understanding of the Physiopathology, Diagnosis and Therapeutic Approach to Alzheimer's Disease.

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-ß (Aß) 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 Aß 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.

Potential Effects of Phenolic Compounds That Can Be Found in Olive Oil on Wound Healing.

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.