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The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) is well recognized as a critical regulator of redox, metabolic, and protein homeostasis, as well as the regulation of inflammation. An age-associated decline in NRF2 activity may allow oxidative stress to remain unmitigated and affect key features associated with the aging phenotype, including telomere shortening. Telomeres, the protective caps of eukaryotic chromosomes, are highly susceptible to oxidative DNA damage, which can accelerate telomere shortening and, consequently, lead to premature senescence and genomic instability. In this review, we explore how the dysregulation of NRF2, coupled with an increase in oxidative stress, might be a major determinant of telomere shortening and age-related diseases. We discuss the relevance of the connection between NRF2 deficiency in aging and telomere attrition, emphasizing the importance of studying this functional link to enhance our understanding of aging pathologies. Finally, we present a number of compounds that possess the ability to restore NRF2 function, maintain a proper redox balance, and preserve telomere length during aging., (© 2023. The Author(s).)

Polyunsaturated fatty acids (PUFA) are known to have a regulatory effect on oxidative and inflammatory processes. This study aimed to identify the relationship between blood PUFA status and circulatory markers of oxidative stress and inflammation in a cohort of 172 subjects. The population was divided by sex and into three age groups: adults (18-64 years old, n = 69), older adults (65-89 years old, n = 54), and long-lived individuals (LLIs, 90-111 years old, n = 49). Whole blood PUFA content was quantified using gas chromatography. Additionally, serum levels of C-reactive protein (CRP), paraoxonase (PON), Trolox equivalent antioxidant capacity (TEAC), and malondialdehyde (MDA) were measured. Our results showed that a higher omega-3 (n-3) index in adult females was a predictor of lower MDA concentrations (p = 0.038). Conversely, total n-3 PUFA and total n-6 PUFA were positively related to MDA values among older adult females and LLI men (p < 0.05), while total n-6 PUFA was inversely correlated with MDA levels in LLI females (p < 0.05). Interestingly, increased concentrations of total n-3 PUFA and n-3 index were positively correlated with higher TEAC values in LLI men (p = 0.007), while the arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio was inversely correlated with TEAC values among LLI females (p = 0.006). These findings suggest that cellular antioxidant capacity is inversely correlated with changes in the AA/EPA ratio in long-lived females, whereas n-3 PUFA may enhance blood antioxidant capacity in long-lived men. Overall, our study highlights the complex, sex-specific interactions between PUFA profiles and oxidative stress and inflammatory markers across different age groups., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Managing metabolism for optimal training, performance, and recovery in medium-to-high-level endurance runners involves enhancing energy systems through strategic nutrient intake. Optimal carbohydrate intake before, during, and after endurance running can enhance glycogen stores and maintain optimal blood glucose levels, influencing various physiological responses and adaptations, including transitory post-endurance inflammation. This randomized trial investigates the impact of a high-dose 2:1 maltodextrin-fructose supplementation to medium-to-high-level endurance runners immediately before, during, and after a 15 km run at 90% VO 2max intensity on post-exercise inflammatory stress., Methods: We evaluated inflammatory biomarkers and lipidomic profiles before the endurance tests and up to 24 h after. We focused on the effects of high-dose 2:1 maltodextrin-fructose supplementation on white blood cell count, neutrophil number, IL-6, cortisol, and CRP levels, as well as polyunsaturated fatty acids, ω-3 index, and AA/EPA ratio., Results: This supplementation significantly reduced inflammatory markers and metabolic stress. Additionally, it may enhance the post-activity increase in blood ω-3 fatty acid levels and reduce the increase in ω-6 levels, resulting in a lower trend of AA/EPA ratio at 24 h in the treated arm., Conclusions: Adequate carbohydrate supplementation may acutely mitigate inflammation during a one-hour endurance activity of moderate-to-high intensity. These effects could be beneficial for athletes engaging in frequent, high-intensity activities.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has quickly become a global health pandemic. Among the viral proteins, RNA-dependent RNA polymerase (RdRp) is responsible for viral genome replication and has emerged as a promising target against SARS-CoV-2 infection. Dietary bioactive compounds represent an important source of evolutionarily optimized molecules with antiviral properties against SARS-CoV-2 RdRp. We investigated the inhibitory potential effects of different phytochemicals against SARS-CoV-2 RdRp, including andrographolide, kaempferol, resveratrol, and silibinin. Unlike the other investigated compounds, kaempferol exhibited a significant dose-dependent in vitro inhibition of SARS-CoV-2 RdRp activity. To assess the binding interactions and stability of the SARS-CoV-2 RdRp-kaempferol complex, we performed in silico techniques, including molecular docking, quantum chemical calculation, and molecular dynamics simulations. We found strong binding affinities and stability between kaempferol and SARS-CoV-2 RdRp variants (Wuhan and Omicron). These findings provide valuable insights into the antiviral properties of kaempferol as a stable inhibitor of SARS-CoV-2 RdRp.Communicated by Ramaswamy H. Sarma.

Introduction: Managing burn injuries is a challenge in healthcare. Due to the alarming increase in antibiotic resistance, new prophylactic and therapeutic strategies are being sought. This study aimed to evaluate the potential of live Lactic Acid Bacteria for managing burn infections, using Galleria mellonella larvae as an alternative preclinical animal model and comparing the outcomes with a common antibiotic., Methods: The antimicrobial activity of LAB isolated from human breast milk was assessed in vitro against Pseudomonas aeruginosa ATCC 27853. Additionally, the immunomodulatory effects of LAB were evaluated in vivo using the G. mellonella burn wound infection model., Results and Discussion: In vitro results demonstrated the antimicrobial activity of Lactic Acid Bacteria against P. aeruginosa . In vivo results show that their prophylactic treatment improves, statistically significant, larval survival and modulates the expression of immunity-related genes, Gallerimycin and Relish/NF-κB, strain-dependently. These findings lay the foundation and suggest a promising alternative for burn wound prevention and management, reducing the risk of antibiotic resistance, enhancing immune modulation, and validating the potential G. mellonella as a skin burn wound model., Competing Interests: Authors NV, MC, IM, LP, FV, SD, GSc, GP and RM were NATIVAL s.r.l. founders at the time of the study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Guarnieri, Venditti, Cutuli, Brancazio, Salvatore, Magnifico, Pietrangelo, Falcone, Vergalito, Nicolosi, Scarsella, Davinelli, Scapagnini, Petronio Petronio and Di Marco.)

Neuropathic pain, a chronic condition resulting from nerve injury or dysfunction, presents significant therapeutic challenges and is closely associated with oxidative stress and inflammation, both of which can lead to mitochondrial dysfunction. The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, a critical cellular defense mechanism against oxidative stress, has emerged as a promising target for neuropathic pain management. Nrf2 modulators enhance the expression of antioxidant and cytoprotective genes, thereby reducing oxidative damage, inflammation, and mitochondrial impairment. This review explores the antinociceptive effects of Nrf2, highlighting how pharmacological agents and natural compounds may be used as potential therapeutic strategies against neuropathic pain. Although preclinical studies demonstrate significant pain reduction and improved nerve function through Nrf2 activation, several clinical challenges need to be addressed. However, emerging clinical evidence suggests potential benefits of Nrf2 modulators in several conditions, such as diabetic neuropathy and multiple sclerosis. Future research should focus on further elucidating the molecular role of Nrf2 in neuropathic pain to optimize its modulation efficacy and maximize clinical utility.

Sleep is a fundamental conserved physiological state across evolution, suggesting vital biological functions that are yet to be fully clarified. However, our understanding of the neural and molecular basis of sleep regulation has increased rapidly in recent years. Among various processes implicated in controlling sleep homeostasis, a bidirectional relationship between sleep and oxidative stress has recently emerged. One proposed function of sleep may be the mitigation of oxidative stress in both brain and peripheral tissues, contributing to the clearance of reactive species that accumulate during wakefulness. Conversely, reactive species, such as reactive oxygen species (ROS) and reactive nitrogen species (RNS), at physiological levels, may act as signaling agents to regulate redox-sensitive transcriptional factors, enzymes, and other effectors involved in the regulation of sleep. As a primary sensor of intracellular oxidation, the transcription factor NRF2 is emerging as an indispensable component to maintain cellular redox homeostasis during sleep. Indeed, a number of studies have revealed an association between NRF2 dysfunction and the most common sleep conditions, including sleep loss, obstructive sleep apnea, and circadian sleep disturbances. This review examines the evidence of the intricate link between oxidative stress and NRF2 function in the context of sleep, and highlights the potential of NRF2 modulators to alleviate sleep disturbances., (© 2024. The Author(s).)

Background: Cellulite represents a common multi-factorial condition that affects nearly all women and is now recognized as a clinical condition associated with systemic factors and negative psychological effects. Several noninvasive and minimally invasive treatments were developed during the last few years, but limited evidence supports many of them due to lack of evidence, insufficient participants, and potential adverse effects., Methods: This study aimed to evaluate the efficacy of a seaweed mud application in improving both the structure and function of tissues affected by cellulite. Sixty women with cellulite underwent 4-week applications of seaweed mud on the buttocks and thighs. The following assessments were performed at baseline and after the last treatment: photographic, clinical, and anthropometric evaluation; tests for elasticity and hydration; ultrasonography of cellulite nodules; and cellulite biopsies in the trochanteric region. Patient satisfaction was assessed using a 5-point Likert-scale questionnaire., Results: The treatment resulted in a significant improvement in the severity of cellulite severity between the initial assessment and the 4-week follow-up, with enhanced structure, elasticity, and hydration of the affected tissues. Microscopic analysis of the cellulite biopsies revealed a significant restoration of dermal organization with induced collagen synthesis and reduced inflammation, edema, and lipid deposition following the 4-week seaweed mud applications. Additionally, the treatment led to a remarkable improvement in comfort and satisfaction as well as a reduction in body circumferences., Conclusions: The cosmetic application of seaweed mud has proven to be a safe, non-invasive treatment for improving the tissue alterations characteristic of cellulite., (© 2024 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

The composition of polyunsaturated fatty acids (PUFA) in the cell membrane plays a crucial role in cell signaling and function. Physical activity can induce shifts in PUFA metabolism, potentially altering their membrane composition. Given the multifaceted regulatory and structural roles of PUFA, training-related fluctuations in PUFA concentrations may impact health and athletic performance in both elite and non-elite athletes, highlighting the critical role of these fatty acids' nutritional intake. The ω-3 index (O3I), a biomarker reflecting the proportion of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in red blood cell membranes, is considered a marker of cardiovascular risk, gaining increasing interest in sports medicine. Dietary interventions aimed at maintaining an optimal O3I may offer several benefits for elite and non-elite athletes, including cardiovascular health performance optimization, recovery, and injury prevention. Here, we discuss emerging evidence on the application of O3I in sports and physical exercise, highlighting its promising role as a biomarker in a wide range of sports practices.

Decreased adult neurogenesis, or the gradual depletion of neural stem cells in adult neurogenic niches, is considered a hallmark of brain aging. This review provides a comprehensive overview of the intricate relationship between aging, adult neurogenesis, and the potential neuroregenerative properties of astaxanthin, a carotenoid principally extracted from the microalga Haematococcus pluvialis. The unique chemical structure of astaxanthin enables it to cross the blood-brain barrier and easily reach the brain, where it may positively influence adult neurogenesis. Astaxanthin can affect molecular pathways involved in the homeostasis, through the activation of FOXO3-related genetic pathways, growth, and regeneration of adult brain neurons, enhancing cell proliferation and the potency of stem cells in neural progenitor cells. Furthermore, astaxanthin appears to modulate neuroinflammation by suppressing the NF-κB pathway, reducing the production of pro-inflammatory cytokines, and limiting neuroinflammation associated with aging and chronic microglial activation. By modulating these pathways, along with its potent antioxidant properties, astaxanthin may contribute to the restoration of a healthy neurogenic microenvironment, thereby preserving the activity of neurogenic niches during both normal and pathological aging.

Studies on the COVID-19 pandemic effects on gestational diabetes mellitus (GDM) remain limited and controversial. This study aimed to investigate the impact of the COVID-19 lockdown on the glycemic balance of pregnant women and GDM risk. To this aim, a single-center retrospective cohort analysis assessing glucose homeostasis using the oral glucose tolerance test in 862 pregnant women before (from March 9, 2019 to March 8, 2020 - Group 1), during (from March 9, 2020 to March 8, 2021 - Group 2), and after (from March 9, 2021 to March 8, 2022 - Group 3) the COVID-19 lockdown in Molise, a region of central Italy, was conducted. We observed that the blood glucose concentration of pregnant women was significantly lower during the COVID-19 lockdown than during the previous and following years at all time points evaluated (time 0, 60', and 120'). Specifically, at time 0, it was 82.14 mg/dl for group 2 vs 85.94 for group 1 ( p = 0.0001) and 85.87 for group 3 ( p = 0.001). Similarly, at 60', it was 121.38 mg/dl for group 2 vs 129.30 mg/dl for group 1 ( p = 0.0029) and 131.68 mg/dl for group 3 ( p = 0.0006). Moreover, at 120', it was 104.20 mg/dl for group 2 vs 111.51 mg/dl ( p = 0.0004) for group 1, and 116.06 mg/dl for group 3 ( p = 0.0001). In contrast with previous findings, the COVID-19 lockdown was associated with an improved glycemic balance. Further studies are needed to better clarify the influence of lockdown restrictions on glucose metabolism and, consequently, on GDM risk., Competing Interests: Conflict of interest: Sergio Davinelli serves as Editor in Open Medicine, but it did not affect the peer-review process. The authors have no conflicts of interest to disclose., (© 2023 the author(s), published by De Gruyter.)

The recent attention to the risk of potential permanent eye damage triggered by ocular infections has been leading to a deeper investigation of the current antimicrobials. An antimicrobial agent used in ophthalmology should possess the following characteristics: a broad antimicrobial spectrum, prompt action even in the presence of organic matter, and nontoxicity. The objective of this study is to compare the antimicrobial efficacy of widely used ophthalmic antiseptics containing povidone-iodine, chlorhexidine, and liposomes containing ozonated sunflower oil. We determined the minimum inhibitory concentration (MIC) on various microbial strains: Staphylococcus aureus (ATCC 6538), methicillin-resistant Staphylococcus aureus (ATCC 33591), Staphylococcus epidermidis (ATCC 12228), Pseudomonas aeruginosa (ATCC 9027), and Escherichia coli (ATCC 873). Furthermore, we assessed its efficacy in controlling antibiotic resistance, biofilm formation, and bacterial adhesion. All three antiseptic ophthalmic preparations showed significant anti-microbicidal and anti-biofilm activity, with the liposomes containing ozonated sunflower oil with the highest ability to control antibiotic resistance and bacteria adhesion to human corneal cells.

Dimethyl fumarate (DMF) is an FDA-approved drug for the treatment of psoriasis and multiple sclerosis. DMF is known to stabilize the transcription factor Nrf2, which in turn induces the expression of antioxidant response element genes. It has also been shown that DMF influences autophagy and participates in the transcriptional control of inflammatory factors by inhibiting NF-κB and its downstream targets. DMF is receiving increasing attention for its potential to be repurposed for several diseases. This versatile molecule is indeed able to exert beneficial effects on different medical conditions through a pleiotropic mechanism, in virtue of its antioxidant, immunomodulatory, neuroprotective, anti-inflammatory, and anti-proliferative effects. A growing number of preclinical and clinical studies show that DMF may have important therapeutic implications for chronic diseases, such as cardiovascular and respiratory pathologies, cancer, eye disorders, neurodegenerative conditions, and systemic or organ specific inflammatory and immune-mediated diseases. This comprehensive review summarizes and highlights the plethora of DMF's beneficial effects and underlines its repurposing opportunities in a variety of clinical conditions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bresciani, Manai, Davinelli, Tucci, Saso and Amadio.)

Cellular senescence has long been considered a permanent state of cell cycle arrest occurring in proliferating cells subject to different stressors, used as a cellular defense mechanism from acquiring potentially harmful genetic faults. However, recent studies highlight that senescent cells might also alter the local tissue environment and concur to chronic inflammation and cancer risk by secreting inflammatory and matrix remodeling factors, acquiring a senescence-associated secretory phenotype (SASP). Indeed, during aging and age-related diseases, senescent cells amass in mammalian tissues, likely contributing to the inevitable loss of tissue function as we age. Cellular senescence has thus become one potential target to tackle age-associated diseases as well as cancer development. One important aspect characterizing senescent cells is their telomere length. Telomeres shorten as a consequence of multiple cellular replications, gradually leading to permanent cell cycle arrest, known as replicative senescence. Interestingly, in the large majority of cancer cells, a senescence escape strategy is used and telomere length is maintained by telomerase, thus favoring cancer initiation and tumor survival. There is growing evidence showing how (poly)phenols can impact telomere maintenance through different molecular mechanisms depending on dose and cell phenotypes. Although normally, (poly)phenols maintain telomere length and support telomerase activity, in cancer cells this activity is negatively modulated, thus accelerating telomere attrition and promoting cancer cell death. Some (poly)phenols have also been shown to exert senolytic activity, thus suggesting both antiaging (directly eliminating senescent cells) and anticancer (indirectly, via SASP inhibition) potentials. In this review, we analyze selective (poly)phenol mechanisms in senescent and cancer cells to discriminate between in vitro and in vivo evidence and human applications considering (poly)phenol bioavailability, the influence of the gut microbiota, and their dose-response effects., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Accumulating evidence suggests that fatty acids (FAs) play an essential role in regulating skeletal muscle mass and function throughout life. This systematic review and meta-analysis aimed to examine the relationship between dietary or circulatory levels of monounsaturated FAs (MUFAs) and sarcopenia in observational studies. A comprehensive literature search was performed in three databases (PubMed, Scopus, and Web of Science) from inception until August 2022. Of 414 records, a total of 12 observational studies were identified for this review. Ten studies were meta-analysed, comprising a total of 3704 participants. The results revealed that MUFA intake is inversely associated with sarcopenia (standardized mean difference = - 0.28, 95% CI - 0.46 to - 0.11; p < 0.01). Despite the limited number of studies, our results suggest that lower MUFA intake is associated with a higher risk of sarcopenia. However, the available evidence is still insufficient and further investigations are needed to demonstrate this relationship., (© 2023. The Author(s).)

Estrogen deficiency is a major cause of loss of postmenopausal bone mineral density (BMD). This study aimed to evaluate the effects of equol and resveratrol on bone turnover biomarkers in postmenopausal women. Sixty healthy postmenopausal women were randomly assigned to receive 200 mg fermented soy containing 10 mg equol and 25 mg resveratrol or a placebo for 12 months. Whole-body BMD and bone turnover biomarkers, such as deoxypyridinoline (DPD), tartrate-resistant acid phosphatase 5b (TRACP-5b), osteocalcin, and bone-specific alkaline phosphatase (BAP), were measured at baseline and after 12 months of treatment. At the end of treatment, DPD, osteocalcin, and BAP significantly improved in the active group ( p < 0.0001 for all) compared to the placebo group. Conversely, TRACP-5b levels were unaffected by supplementation ( p = 0.051). Statistically significant changes in the concentrations of DPD ( p < 0.0001), osteocalcin ( p = 0.0001), and BAP ( p < 0.0001) compared to baseline were also identified. Overall, the intervention significantly increased BMD measured in the whole body ( p = 0.0220) compared with the placebo. These data indicate that the combination of equol and resveratrol may positively modulate bone turnover biomarkers and BMD, representing a potential approach to prevent age-related bone loss in postmenopausal women.

Dietary supplementation with nutraceuticals can promote optimal immune system activation, modulating different pathways that enhance immune defenses. Therefore, the immunity-boosting effects of nutraceuticals encompass not only immunomodulatory but also antioxidant, antitumor, antiviral, antibacterial, and antifungal properties, with therapeutic effects against diverse pathological conditions. However, the complexity of the pathways that regulate the immune system, numerous mechanisms of action, and heterogeneity of the immunodeficiencies, and subjects treated make their application in the clinical field difficult. Some nutraceuticals appear to safely improve immune system function, particularly by preventing viral and bacterial infections in specific groups, such as children, the elderly, and athletes, as well as in frail patients, such as those affected by autoimmune diseases, chronic diseases, or cancer. Several nutraceuticals, such as vitamins, mineral salts, polyunsaturated omega-3 fatty acids, many types of phytocompounds, and probiotic strains, have the most consolidated evidence in humans. In most cases, further large and long-term randomized clinical trials are needed to confirm the available preliminary positive data., Competing Interests: AUTHOR DISCLOSURE STATEMENT The authors declare no conflict of interest., (Copyright © 2023 by The Korean Society of Food Science and Nutrition. All rights Reserved.)

Although autism spectrum disorder (ASD) is a multifaceted neurodevelopmental syndrome, accumulating evidence indicates that oxidative stress and inflammation are common features of ASD. Flavonoids, one of the largest and best-investigated classes of plant-derived compounds, are known to exert antioxidant, anti-inflammatory, and neuroprotective effects. This review used a systematic search process to assess the available evidence on the effect of flavonoids on ASD. A comprehensive literature search was carried out in PubMed, Scopus, and Web of Science databases following the PRISMA guidelines. A total of 17 preclinical studies and 4 clinical investigations met our inclusion criteria and were included in the final review. Most findings from animal studies suggest that treatment with flavonoids improves oxidative stress parameters, reduces inflammatory mediators, and promotes pro-neurogenic effects. These studies also showed that flavonoids ameliorate the core symptoms of ASD, such as social deficits, repetitive behavior, learning and memory impairments, and motor coordination. However, there are no randomized placebo-controlled trials that support the clinical efficacy of flavonoids in ASD. We only found open-label studies and case reports/series, using only two flavonoids such as luteolin and quercetin. These preliminary clinical studies indicate that flavonoid administration may improve specific behavioral symptoms of ASD. Overall, this review is the first one to systematically report evidence for the putative beneficial effects of flavonoids on features of ASD. These promising preliminary results may provide the rationale for future randomized controlled trials aimed at confirming these outcomes.

Sirtuin 1 (SIRT1) belongs to the histone deacetylase enzyme family and its activity regulates various signaling networks associated with aging. SIRT1 is widely involved in a large number of biological processes, including senescence, autophagy, inflammation, and oxidative stress. In addition, SIRT1 activation may improve lifespan and health in numerous experimental models. Therefore, SIRT1 targeting is a potential strategy to delay or reverse aging and age-related diseases. Although SIRT1 is activated by a wide array of small molecules, only a limited number of phytochemicals that directly interact with SIRT1 have been identified. Using the Geroprotectors.org database and a literature search, the aim of this study was to identify geroprotective phytochemicals that might interact with SIRT1. We performed molecular docking, density functional theory studies, molecular dynamic simulations (MDS), and absorption, distribution, metabolism, excretion, and toxicity (ADMET) prediction to screen potential candidates against SIRT1. After the initial screening of 70 phytochemicals, crocin, celastrol, hesperidin, taxifolin, vitexin, and quercetin had significant binding affinity scores. These six compounds established multiple hydrogen-bonding and hydrophobic interactions with SIRT1 and showed good drug-likeness and ADMET properties. In particular, crocin was further analyzed using MDS to study its complex with SIRT1 during simulation. Crocin has a high reactivity to SIRT1 and can form a stable complex with it, showing a good ability to fit into the binding pocket. Although further investigations are required, our results suggest that these geroprotective phytochemicals, especially crocin, are novel interacting partners of SIRT1., Competing Interests: Conflicts of interests The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: The potential mechanisms of endocrine therapy for thrombosis remain currently unclear, and more studies are warranted for further investigation and elucidation. However, high plasma concentration of lipoprotein(a) (Lp(a)) is a recognized prothrombotic factor. The aim of our study was to systematically evaluate the effect of different anti-oestrogen therapy on plasma Lp(a) level in postmenopausal women., Methods: A systematic literature search was conducted in multiple electronic databases to identify the randomized, double-blind, placebo-controlled clinical studies on this topic. Effect size for changes in Lp(a) was expressed as mean difference (MD) and 95% confidence intervals (CI)., Results: Data were pooled from 10 clinical trials comprising 24 treatment arms, which included 2049 women (1128 women in the active-treated arms and 921 women in the control arms). Meta-analysis of data suggested that anti-oestrogen therapy in women significantly reduced Lp(a) [MD = -5.92% (95%CI: -9.05%,-2.8%)]., Conclusions: This observation is of both clinical and pathophysiological relevance, also in view that the identification of molecular determinants and cellular pathways implicated in Lp(a) synthesis and metabolism is still of concern as a critical issue in lipidology and CV prevention., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Long-lived individuals (LLIs) are considered an ideal model to study healthy human aging. Blood fatty acid (FA) profile of a cohort of LLIs (90-111 years old, n = 49) from Sicily was compared to adults (18-64 years old, n = 69) and older adults (65-89 years old, n = 54) from the same area. Genetic variants in key enzymes related to FA biosynthesis and metabolism were also genotyped to investigate a potential genetic predisposition in determining the FA profile. Gas chromatography was employed to determine the FA profile, and genotyping was performed using high-resolution melt (HRM) analysis. Blood levels of total polyunsaturated FA (PUFA) and total trans-FA decreased with age, while the levels of saturated FA (SFA) remained unchanged. Interestingly, distinctively higher circulatory levels of monounsaturated FA (MUFA) in LLIs compared to adults and older adults were observed. In addition, among LLIs, rs174537 in the FA desaturase 1/2 (FADS1/2) gene was associated with linoleic acid (LA, 18:2n-6) and docosatetraenoic acid (DTA, 22:4n-6) levels, and the rs953413 in the elongase of very long FA 2 (ELOVL2) was associated with DTA levels. We further observed that rs174579 and rs174626 genotypes in FADS1/2 significantly affect delta-6 desaturase (D6D) activity. In conclusion, our results suggest that the LLIs have a different FA profile characterized by high MUFA content, which indicates reduced peroxidation while maintaining membrane fluidity., (© 2022. The Author(s), under exclusive licence to American Aging Association.)

Adult neurogenesis deficiency has been proposed to be a common hallmark in different age-related neurodegenerative diseases. The administration of flavonoids is currently reported as a potentially beneficial strategy for preventing brain aging alterations, including adult neurogenesis decline. Flavonoids are a class of plant-derived dietary polyphenols that have drawn attention for their neuroprotective and pro-cognitive effects. Although they undergo extensive metabolism and localize in the brain at low concentrations, flavonoids are now believed to improve cerebral vasculature and interact with signal transduction cascades involved in the regulation of adult neurogenesis. Furthermore, many dietary flavonoids have been shown to reduce oxidative stress and neuroinflammation, improving the neuronal microenvironment where adult neurogenesis occurs. The overall goal of this review is to summarize the evidence supporting the role of flavonoids in modulating adult neurogenesis as well as to highlight how these dietary agents may be promising candidates in restoring healthy brain function during physiological and pathological aging., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

ABSTRACT The aim of this study was to examine the association between biomarkers of polyunsaturated fatty acids (PUFA), such as omega-3 (ω-3) index and arachidonic acid (AA; 20:4 ω-6)/eicosapentaenoic acid (EPA; 20:5ω-3) ratio (AA/EPA), and the prevalence of running-related injuries (RRI) in a cohort of recreational runners. We performed a retrospective, observational study of 275 non-elite runners (mean age: 41.20 ± 12.47 years) who were not supplemented with ω-3 fatty acids. The training characteristics and RRI were recorded over a period of 12 months through a self-reported questionnaire. Using whole blood samples collected by finger prick, PUFA were quantified by gas chromatography and ω-3 index and AA/EPA ratio measured. A total of 191 RRI cases were reported, with an injury prevalence rate of 50.9% in the overall population. The injured runners ran a significantly greater weekly distance than uninjured subjects (53.54 ± 25.27 km/week; p  = 0.007). In a multivariate regression analysis, the lowest number of RRI was associated with higher values of ω-3 index ( β  = - 0.237; 95% CI - 0.308 to - 0.164; R 2  = 0.172; p  < 0.0001), while a higher AA/EPA ratio was correlated with higher number of RRI ( β  = 0.019; 95% CI 0.007-0.031; R 2  = 0.038; p  = 0.003). This study identifies ω-3 index and AA/EPA ratio as potential parameters associated with the risk of RRI. Future research is needed to confirm these results and apply specific nutritional strategies to successfully modify these biochemical variables. Trial registration: ISRCTN.org identifier: ISRCTN12847156..

The transcription factor NRF2 and its endogenous inhibitor KEAP1 play a crucial role in the maintenance of cellular redox homeostasis by regulating the gene expression of diverse networks of antioxidant, anti-inflammatory, and detoxification enzymes. Therefore, activation of NRF2 provides cytoprotection against numerous pathologies, including age-related diseases. An age-associated loss of NRF2 function may be a key driving force behind the aging phenotype. Recently, numerous NRF2 inducers have been identified and some of them are promising candidates to restore NRF2 transcriptional activity during aging. Emerging evidence indicates that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) and their electrophilic derivatives may trigger a protective response via NRF2 activation, rescuing or maintaining cellular redox homeostasis. In this review, we provide an overview of the NRF2-KEAP1 system and its dysregulation in aging cells. We also summarize current studies on the modulatory role of n-3 PUFAs as potential agents to prevent multiple chronic diseases and restore the age-related impairment of NRF2 function., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

In recent years, the scientific community's interest in T. molitor as an insect model to investigate immunity and host-pathogen interactions has considerably increased. The reasons for this growing interest could be explained by the peculiar features of this beetle, which offers various advantages compared to other invertebrates models commonly used in laboratory studies. Thus, this review aimed at providing a broad view of the T. molitor immune system in light of the new scientific evidence on the developmental/tissue-specific gene expression studies related to microbial infection. In addition to the well-known cellular component and humoral response process, several studies investigating the factors associated with T. molitor immune response or deepening of those already known have been reported. However, various aspects remain still less understood, namely the possible crosstalk between the immune deficiency protein and Toll pathways and the role exerted by T. molitor apolipoprotein III in the expression of the antimicrobial peptides. Therefore, further research is required for T. molitor to be recommended as an alternative insect model for pathogen-host interaction and immunity studies.

Aging results from the progressive dysregulation of several molecular pathways and mTOR and AMPK signaling have been suggested to play a role in the complex changes in key biological networks involved in cellular senescence. Moreover, multiple factors, including poor nutritional balance, drive immunosenescence progression, one of the meaningful aspects of aging. Unsurprisingly, nutraceutical and pharmacological interventions could help maintain an optimal biological response by providing essential bioactive micronutrients required for the development, maintenance, and the expression of the immune response at all stages of life. In this regard, many studies have provided evidence of potential antiaging properties of resveratrol, as well as rapamycin and metformin. Indeed, in vitro and in vivo models have demonstrated for these molecules a number of positive effects associated with healthy aging. The current review focuses on the mechanisms of action of these three important compounds and their suggested use for the clinical treatment of immunosenescence and aging.

One of the characteristics of the SARS-CoV-2 infection in Italy is the significant regional difference in terms of lethality and mortality. These geographical variances were clear in the first wave and confirmed in the second one as well. The study aimed to analyze the correlation between regional differences in COVID-19 mortality and different regional care models, by retrospectively analyzing the association between the Italian COVID-19 deaths and the number of hospital beds, long-term care facilities, general practitioners (GPs), and the health expenditure per capita. The period considered was from 1 March 2020 to 1 March 2021. The number of hospital beds (p < 0.0001) and the number of GPs (p = 0.0094) significantly predicted the COVID-19 death rate. The Italian regions with a higher number of hospital beds and a lower number of GPs showed a higher number of deaths. Multivariate analyses confirmed the results. The Italian regions with a higher amount of centralized healthcare, as represented by the number of hospital beds, experienced a higher number of deaths, while the regions with greater community support, as exemplified by the number of the GPs, faced higher survival. These results suggest the need for a change in the current healthcare system organization.

Bacteria are the most common causative agents of ocular infections. Treatment with topical broad-spectrum antibiotics is recommended in severe cases. However, antibiotic resistance has become a major concern in recent years, although antibiotics are generally effective in treating ocular infections. Antibacterial compound screening is performed to identify alternative therapeutic options to antibiotics. The aim of this study was to assess the in vitro antimicrobial activity of an ophthalmic solution containing ozonated oil. Strains of bacterial species with a multidrug resistance profile, which are responsible for a large proportion of ocular infections, were isolated and selected from different biological samples. The bacterial isolates were cultured, and ozonated oil was used to evaluate the inhibition zones at different time points. The treatment exhibited antibacterial activity against all the tested species. The effect was lower against the strains of Pseudomonas aeruginosa and more evident against Staphylococcus and Streptococcus spp. Our results suggest that the administration of ozonated oil may be a candidate agent to treat some infections of the ocular surface with a potential role in antimicrobial prophylaxis., Competing Interests: Conflict of interest: Sergio Davinelli become Editor in Open Medicine from March, but this fact hasnt impacted the peer-review process., (© 2022 Giuseppe Grandi et al., published by De Gruyter.)

Background: Clinical and epidemiological studies suggest that analysis of the polyunsaturated fatty acids (PUFAs) is essential to evaluate nutritional requirements and disease risk. We describe a simple, sensitive and non-invasive method for estimating the n-3 index and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio in dried blood spots (DBSs). Experimental: After obtaining DBSs on a spot card, PUFAs were transesterified (direct, acidic transesterification) and subsequently extracted with n-hexane. Gas chromatography with flame ionization detection (GC-FID) was used to analyze the extracted PUFAs, and then n-3 index and AA/EPA ratio were calculated. Method validation showed satisfactory precision and linearity. Conclusion: This analysis is simple and reliable to estimate PUFA status, and it was successfully applied to samples from 20 subjects, demonstrating its applicability.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant outbreaks have highlighted the need of antigen-detecting rapid diagnostic tests (Ag-RDTs) that can be used at the point-of-care (POC). Although many Ag-RDTs have been approved for SARS-CoV-2 detection, studies demonstrating the clinical performance of Ag-RDTs against variants of concern, especially the new Omicron variant, are limited. The aim of this study was to evaluate the diagnostic sensitivity and specificity of the AMAZING COVID-19 Antigen Sealing Tube Test Strip (Colloidal Gold) in 584 early symptomatic and asymptomatic participants (age range 0-90 years). The performance of this Ag-RDT was assessed by comparing its results with reverse transcription RT-PCR (rRT-PCR). One hundred twenty positive samples were also analyzed with rRT-PCR to discriminate Omicron and Delta/Kappa variants (72.50% Omicron; 27.50% Delta/Kappa). Overall, the Ag-RDT showed high positive and negative percent values of 92.52% (95% CI, 86.61-95.95%) and 98.05% (95% CI, 96.41-98.95%), respectively, as well as an overall diagnostic accuracy of 96.92% (95% CI, 95.17-98.16%). Taken together, these data indicate that this inexpensive and simple-to-use Ag-RDT presents excellent analytical performance and can reliably detect Omicron and Delta/Kappa variants.

The medical community recognizes sex-related differences in pathophysiology and cardiovascular disease outcomes (CVD), culminating with heart failure. In general, pre-menopausal women tend to have a better prognosis than men. Explaining why this occurs is not a simple matter. For decades, sex hormones like estrogens (Es) have been identified as one of the leading factors driving these sex differences. Indeed, Es seem protective in women as their decline, during and after menopause, coincides with an increased CV risk and HF development. However, clinical trials demonstrated that E replacement in post-menopause women results in adverse cardiac events and increased risk of breast cancer. Thus, a deeper understanding of E-related mechanisms is needed to provide a vital gateway toward better CVD prevention and treatment in women. Of note, sphingolipids (SLs) and their metabolism are strictly related to E activities. Among the SLs, ceramide and sphingosine 1-phosphate play essential roles in mammalian physiology, particularly in the CV system, and appear differently modulated in males and females. In keeping with this view, here we explore the most recent experimental and clinical observations about the role of E and SL metabolism, emphasizing how these factors impact the CV system.

Aging induces significant shifts in the composition of gut microbiota associated with decreased microbial diversity. Age-related changes in gut microbiota include a loss of commensals and an increase in disease-associated pathobionts. These alterations are accelerated by lifestyle factors, such as poor nutritional habits, physical inactivity, and medications. Given that diet is one of the main drivers shaping the gut microbiota, nutritional interventions for restoring gut homeostasis are of great importance to the overall health of older adults. Polyphenols, ubiquitously present in fruits and vegetables, have emerged as promising anti-aging candidates because of their ability to modulate some of the common denominators of aging, including gut dysbiosis. These compounds can influence the composition of the gut microbiota, and gut bacteria metabolize polyphenols into bioactive compounds that produce relevant health effects. Although the role of polyphenols on the aging gut has not been fully characterized, accumulating evidence suggests that these compounds exert selective effects on the gut microbial community. Here, we discuss the reciprocal interactions between polyphenols and gut microbiota and summarize the latest findings on the effects of polyphenols on modulating intestinal bacteria during aging., (© 2021 International Union of Biochemistry and Molecular Biology.)

Telomeres are protective caps at the end of eukaryotic chromosomes, whose length is correlated with health and lifespan. Telomere attrition is a common feature of the aging process and can be accelerated by oxidative stress and chronic inflammation. Various nutrients influence the telomere length, partially due to their antioxidant and anti-inflammatory properties. The aim of this review was to meta-analytically assess the effect of omega-3 fatty acids on the telomere length. We searched four databases (PubMed, Web of Sciences, Scopus, and the Cochrane Library) from inception until November 2021. Of 573 records, a total of 5 clinical trials were included for the quantitative meta-analysis, comprising a total of 337 participants. The results revealed an overall beneficial effect of omega-3 fatty acids on the telomere length (mean difference = 0.16; 95% CI, 0.02, 0.30; p = 0.02). Despite a limited number of studies, the available evidence suggests that omega-3 fatty acids may positively affect the telomere length. However, larger clinical trials are needed to confirm our findings, along with studies aimed to clarify the underlying molecular mechanisms., (© 2022 Sawan Ali et al., published by De Gruyter.)

Astaxanthin (AST) is a dietary xanthophyll predominantly found in marine organisms and seafood. Due to its unique molecular features, AST has an excellent antioxidant activity with a wide range of applications in the nutraceutical and pharmaceutical industries. In the past decade, mounting evidence has suggested a protective role for AST against a wide range of diseases where oxidative stress and inflammation participate in a self-perpetuating cycle. Here, we review the underlying molecular mechanisms by which AST regulates two relevant redox-sensitive transcription factors, such as nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor κB (NF-κB). Nrf2 is a cellular sensor of electrophilic stress that coordinates the expression of a battery of defensive genes encoding antioxidant proteins and detoxifying enzymes. Likewise, NF-κB acts as a mediator of cellular stress and induces the expression of various pro-inflammatory genes, including those encoding cytokines, chemokines, and adhesion molecules. The effects of AST on the crosstalk between these transcription factors have also been discussed. Besides this, we summarize the current clinical studies elucidating how AST may alleviate the etiopathogenesis of oxidative stress and inflammation.

Telomere length (TL) is considered a biomarker of ageing although this topic is still debated. Also, sleep pattern changes are physiological part of the normal ageing process. In fact, it is widely recognized that sleep duration declines with age, leading to dysregulation of circadian rhythms. The aim of our study was to analyse the possible association of sleep duration with TL in a sample of 135 subjects with ages ranging from 20 to 111 years, recruited from Palermo and neighbouring municipalities in Sicily (Italy). Preliminary data suggest that relative TL (RTL) decreases with age in both men and women. However, at older ages, the difference between men and women tends to narrow. Nonagenarian and centenarian women do not show RTL values significantly different from those observed in adult and old women (40-89 years aged). Moreover, to analyse the relationship between TL and sleep, we stratified sleep duration into greater or lesser than 8-h periods. We found that centenarians, who daily sleep 8 hours or more, have longer RTL than centenarians who sleep fewer than 8 hours. Although the relatively small sample size of centenarians, we provide preliminary evidence that sleep duration may affect the RTL of centenarians. To the best of our knowledge, this is the first study to examine the relationship between centenarians, RTL and sleep duration. Further studies with greater sample size of centenarians are required to replicate and extend these data., Competing Interests: Conflicts of interest No conflicts of interest.., (© 2021 Università di Salerno.)

Mediterranean diet (MedDiet) is rich in fruits and vegetables associated with longevity and a reduced risk of several age-related diseases. It is demonstrated that phytochemicals in these plant products enhance the positive effects of MedDiet by acting on the inflammatory state and reducing oxidative stress. Evidence support that these natural compounds act as hormetins, triggering one or more adaptive stress-response pathways at low doses. Activated stress-response pathways increase the expression of cytoprotective proteins and multiple genes that act as lifespan regulators, essential for the ageing process. In these ways, the hormetic response by phytochemicals such as resveratrol, ferulic acid, and several others in MedDiet might enhance cells' ability to cope with more severe challenges, resist diseases, and promote longevity. This review discusses the role of MedDiet phytochemicals in healthy ageing and the prevention of age-related diseases., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The microbiota is a dynamic ecosystem that plays a major role in the host health. Numerous studies have reported that alterations in the intestinal microbiota (dysbiosis) may contribute to the pathogenesis of various common diseases such as diabetes, neuropsychiatric diseases, and cancer. However, emerging findings also suggest the existence of a gut-eye axis, wherein gut dysbiosis may be a crucial factor influencing the onset and progression of multiple ocular diseases, including uveitis, dry eye, macular degeneration, and glaucoma. Currently, supplementation with pre- and probiotics appears is the most feasible and cost-effective approach to restore the gut microbiota to a eubiotic state and prevent eye pathologies. In this review, we discuss the current knowledge on how gut microbiota may be linked to the pathogenesis of common eye diseases, providing therapeutic perspectives for future translational investigations within this promising research field.

Recent evidence suggests that diet modifies key biological factors associated with the development of depression. It has been suggested that this could be due to the high flavonoid content commonly found in many plant foods, beverages and dietary supplements. Our aim was to conduct a systematic review to evaluate the effects of dietary flavonoids on the symptoms of depression. A total of 46 studies met the eligibility criteria. Of these, 36 were intervention trials and 10 were observational studies. A meta-analysis of 36 clinical trials involving a total of 2788 participants was performed. The results showed a statistically significant effect of flavonoids on depressive symptoms (mean difference = -1.65; 95% C.I., -2.54, -0.77; p < 0.01). Five of the 10 observational studies included in the systematic review reported significant results, suggesting that a higher flavonoid intake may improve symptoms of depression. Further studies are urgently required to elucidate whether causal and mechanistic links exist, along with substantiation of functional brain changes associated with flavonoid consumption.

The human diet and dietary patterns are closely linked to the health status. High-calorie Western-style diets have increasingly come under scrutiny as their caloric load and composition contribute to the development of non-communicable diseases, such as diabetes, cancer, obesity, and cardiovascular disorders. On the other hand, calorie-reduced and health-promoting diets have shown promising results in maintaining health and reducing disease burden throughout aging. More recently, pharmacological Caloric Restriction Mimetics (CRMs) have gained interest of the public and scientific community as promising candidates that mimic some of the myriad of effects induced by caloric restriction. Importantly, many of the CRM candidates activate autophagy, prolong life- and healthspan in model organisms and ameliorate diverse disease symptoms without the need to cut calories. Among others, glycolytic inhibitors (e.g., D-allulose, D-glucosamine), hydroxycitric acid, NAD + precursors, polyamines (e.g., spermidine), polyphenols (e.g., resveratrol, dimethoxychalcones, curcumin, EGCG, quercetin) and salicylic acid qualify as CRM candidates, which are naturally available via foods and beverages. However, it is yet unclear how these bioactive substances contribute to the benefits of healthy diets. In this review, we thus discuss dietary sources, availability and intake levels of dietary CRMs. Finally, since translational research on CRMs has entered the clinical stage, we provide a summary of their effects in clinical trials., Competing Interests: FM has equity interest in and is advisor of TLL The Longevity Labs GmbH and Samsara Therapeutics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hofer, Davinelli, Bergmann, Scapagnini and Madeo.)

Data supporting the use of Tocilizumab (TCZ) in COVID-19 are contrasting and inconclusive. This meta-analysis aimed to assess TCZ effectiveness in reducing the mortality rate in COVID-19 patients. PubMed, Scopus, Embase, Cochrane, WILEY, and ClinicalTrials.gov were searched to evaluate observational studies and RCTs. The outcome was the mortality rate. Forty observational studies and seven RCTs, involving 9640 and 5556 subjects treated with Standard Therapy (ST) + TCZ or ST alone, respectively, were included. In patients treated with ST+TCZ, a higher survival (Log odds ratio = -0.41; 95% CI: -0.68 -0.14; p < 0.001) was found. Subgroups analyses were performed to better identify the possible interference of some parameters in modifying the efficacy of TCZ therapy on COVID-19 mortality. Separating observational from RCTs, no statistically significant ( p = 0.70) TCZ-related reduction of mortality regarding RCTs was found, while a significant reduction (Log odds ratio = -0.52; 95% CI: -0.82 -0.22, p < 0.001) was achieved regarding the observational studies. Stratifying for the use of Invasive Mechanic Ventilation (IMV), a higher survival was found in patients treated with TCZ in the No-IMV and IMV groups (both p < 0.001), but not in the No-IMV/IMV group. Meta-regression analyses were also performed. The meta-analysis of observational studies reveals that TCZ is associated with reducing the mortality rate in both severe and critically ill patients. Although the largest RCT, RECOVERY, is in line with this result, the meta-analysis of RCTs failed to found any difference between ST + TCZ and ST. It is crucial to personalize the therapy considering the patients' characteristics.

Frailty is a late life phenotype characterized by a decline in physiological reserve across several organ systems, resulting in the increased susceptibility to endogenous and/or exogenous stressors. Although the etiology of frailty remains poorly understood, an interconnected network of putative mechanisms linked to the ageing process has been proposed. However, frailty is a dynamic process that may be prevented, delayed, or even reversed. The syndromic nature of frailty requires a multidomain approach, such as proper nutrition, as part of modifiable environmental factors, and represents one of the most promising and least costly ways to prevent and reduce frailty among older adults. Nutrient deficiencies have been consistently associated with frailty; however, mounting evidence also supports the hypothesis that beyond the traditional nutritional value, specific dietary components may exert function-enhancing effects and mitigate the extent of frailty. Thus, further mechanistic studies, along with large clinical trials, are imperative to establish the exact role of functional nutrients in the clinical management of frailty. Here, we provide a contemporary discussion of how emerging functional nutrients may contribute to modify the trajectory of the frailty syndrome., (Copyright © 2021. Published by Elsevier B.V.)

Dry eye disease (DED) is a multifactorial condition caused by tear deficiency and accompanied by ocular surface damage. Recent data support a key role of oxidative and inflammatory processes in the pathogenesis of DED. Hyaluronic acid (HA) is widely used in artificial tears to treat DED by improving ocular hydration and reducing surface friction. Crocin (Cr), the main constituent of saffron, is a renowned compound that exhibits potent antioxidant and anti-inflammatory effects. The present study was undertaken to assess the viscosity and muco-adhesiveness of a photoactivated formulation with crosslinked HA (cHA), Cr, and liposomes (cHA-Cr-L). Our aim was also to evaluate whether cHA-Cr-L may exert cytoprotective effects against oxidative and inflammatory processes in human corneal epithelial cells (HCECs). Viscosity was measured using a rotational rheometer, and then the muco-adhesiveness was evaluated. Under hyperosmolarity (450 mOsm), the HCECs were treated with cHA-Cr-L. Interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα) were quantified by quantitative real-time polymerase chain reaction (RT-qPCR). The levels of reactive oxygen species (ROS) were measured using the DCF assay. The combined action of cHA-Cr-L produced a higher viscosity and muco-adhesiveness compared to the control. The anti-inflammatory effect of cHA-Cr-L was achieved through a significant reduction of IL-1β and TNFα ( p < 0.001). The results also showed that cHA-Cr-L reduces ROS production under conditions of hyperosmolarity ( p < 0.001). We conclude that cHA-Cr-L has potential as a therapeutic agent in DED, which should be further investigated.

Recent evidence suggests that diet can modify the risk of future cognitive impairment and dementia. A biologically plausible rationale and initial clinical data indicate that the antioxidant activities of dietary carotenoids may assist the preservation of cognitive function. A meta-analysis of randomized controlled trials was conducted to examine the relationship between carotenoid supplementation and cognitive performance. A literature search was conducted in the MEDLINE (via PubMed), Scopus, Web of Science, and Cochrane databases from their inception to July 2020. A total of 435 studies were retrieved. Abstract screening using predefined inclusion and exclusion criteria was followed by full-text screening and data extraction of study characteristics and measured outcomes. A meta-analysis of eligible trials was performed using a random-effects model to estimate pooled effect size. We identified 9 studies with a total of 4402 nondemented subjects, whose age ranged from 45 to 78 years. Results of the pooled meta-analysis found a significant effect of carotenoid intervention on cognitive outcomes (Hedge's g = 0.14; 95% confidence interval: 0.08, 0.20, p < 0.0001). There was no evidence of heterogeneity among the studies (τ2 = 0.00, I 2 = 0.00%, H 2 = 1.00) or publication bias. Although further studies are needed, our results suggest that carotenoid interventions are associated with better cognitive performance. Thus, these dietary compounds may help to reduce the risk of cognitive impairment and dementia.

The n-3 and n-6 polyunsaturated fatty acids (PUFA) are among the most studied nutrients in human metabolism. In the past few decades, prospective studies and controlled trials have supported the view that the effects of these essential fatty acids are clinically relevant. PUFA profiles in different blood compartments are reflections of both diet and metabolism, and their levels may be related to disease risk. Despite widespread interest, there is no consensus regarding which biomarkers best reflect PUFA status in the body. The measurement of PUFA levels is not straight-forward, and a wide variety of indices have been used in clinical studies, producing conflicting results. A major source of heterogeneity among studies is associated with research design, sampling, and laboratory analyses. To date, the n-3 index, n-6/n-3 ratio, and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio are the most promising biomarkers associated with PUFA metabolism. Although hotly debated, these indices may be considered at least markers, if not risk factors, for several diseases, especially cardiovascular events and brain disorders. Here, we summarize the most updated evidence of n-3 and n-6 PUFA effects on human health, reviewing current controversies on the aforementioned indices and whether they can be considered valuable predictors of clinical outcomes.