Investigation of Serum Endocan Levels in SARS-CoV-2 Patients.

Endocan is an endothelial-cell-specific proteoglycan (ESM-1) and has emerged as an endothelial dysfunction and inflammatory marker in recent years. Endocan can be used as a marker of inflammatory endothelial dysfunction in endothelium-dependent disease: cardiovascular disease, sepsis, lung and kidney disease and malignancies. Recent data suggest that endothelial dysfunction is a key mechanism in COVID-19 pathogenesis. Endotheliitis and thrombo-inflammation are associated with severe forms of SARS-CoV-2 infection, and endocan is currently under investigation as a potential diagnostic and prognostic marker. The aim of this study was to determine serum endocan levels in patients with COVID-19 to evaluate the correlation between endocan levels and clinical disease diagnosis and prognosis. This study enrolled 56 patients, divided into three groups depending on disease severity: mild (15), moderate (25) and severe (16). The biochemical, demographic, clinical and imagistic data were collected and evaluated in correlation with the endocan levels. Serum endocan levels were significantly higher in the COVID-19 patients compared to the control group; also, endocan concentration correlated with vaccination status. The results revealed significantly elevated serum endocan levels in COVID-19 patients compared to the control group, with a correlation observed between endocan concentration and vaccination status. These findings suggest that endocan may serve as a novel biomarker for detecting inflammation and endothelial dysfunction risk in COVID-19 patients. There was no significant relationship between serum endocan levels and disease severity or the presence of cardiovascular diseases. Endocan can be considered a novel biomarker for the detection of inflammation and endothelial dysfunction risk in COVID-19 patients.

Exploring the therapeutic potential of quercetin: A focus on its sirtuin-mediated benefits.

As the global population ages, preventing lifestyle- and aging-related diseases is increasing, necessitating the search for safe and affordable therapeutic interventions. Among nutraceuticals, quercetin, a flavonoid ubiquitously present in various plants, has garnered considerable interest. This review aimed to collate and analyze existing literature on the therapeutic potentials of quercetin, especially its interactions with SIRTs and its clinical applicability based on its bioavailability and safety. This narrative review was based on a literature survey spanning from 2015 to 2023 using PUBMED. The keywords and MeSH terms used were: "quercetin" AND "bioavailability" OR "metabolism" OR "metabolites" as well as "quercetin" AND "SIRTuin" OR "SIRT*" AND "cellular effects" OR "pathway" OR "signaling" OR "neuroprotective" OR "cardioprotective" OR "nephroprotective" OR "antiatherosclerosis" OR "diabetes" OR "antidiabetic" OR "dyslipidemia" AND "mice" OR "rats". Quercetin demonstrates multiple therapeutic activities, including neuroprotective, cardioprotective, and anti-atherosclerotic effects. Its antioxidant, anti-inflammatory, antiviral, and immunomodulatory properties are well-established. At a molecular level, it majorly interacts with SIRTs, particularly SIRT1 and SIRT6, and modulates numerous signaling pathways, contributing to its therapeutic effects. These pathways play roles in reducing oxidative stress, inflammation, autophagy regulation, mitochondrial biogenesis, glucose utilization, fatty acid oxidation, and genome stability. However, clinical trials on quercetin's effectiveness in humans are scarce. Quercetin exhibits a wide range of SIRT-mediated therapeutic effects. Despite the compelling preclinical data, more standardized clinical trials are needed to fully understand its therapeutic potential. Future research should focus on addressing its bioavailability and safety concerns.

Circadian Rhythms, Chrononutrition, Physical Training, and Redox Homeostasis-Molecular Mechanisms in Human Health.

A multitude of physiological processes, human behavioral patterns, and social interactions are intricately governed by the complex interplay between external circumstances and endogenous circadian rhythms. This multidimensional regulatory framework is susceptible to disruptions, and in contemporary society, there is a prevalent occurrence of misalignments between the circadian system and environmental cues, a phenomenon frequently associated with adverse health consequences. The onset of most prevalent current chronic diseases is intimately connected with alterations in human lifestyle practices under various facets, including the following: reduced physical activity, the exposure to artificial light, also acknowledged as light pollution, sedentary behavior coupled with consuming energy-dense nutriments, irregular eating frameworks, disruptions in sleep patterns (inadequate quality and duration), engagement in shift work, and the phenomenon known as social jetlag. The rapid evolution of contemporary life and domestic routines has significantly outpaced the rate of genetic adaptation. Consequently, the underlying circadian rhythms are exposed to multiple shifts, thereby elevating the susceptibility to disease predisposition. This comprehensive review endeavors to synthesize existing empirical evidence that substantiates the conceptual integration of the circadian clock, biochemical molecular homeostasis, oxidative stress, and the stimuli imparted by physical exercise, sleep, and nutrition.

The Beneficial Effects of Dietary Interventions on Gut Microbiota-An Up-to-Date Critical Review and Future Perspectives.

Different dietary interventions, especially intermittent fasting, are widely used and promoted by physicians; these regimens have been studied lately for their impact on the gut microbiota composition/function and, consequently, on the general physiopathological processes of the host. Studies are showing that dietary components modulate the microbiota, and, at the same time, the host metabolism is deeply influenced by the different products resulting from nutrient transformation in the microbiota compartment. This reciprocal relationship can potentially influence even drug metabolism for chronic drug regimens, significantly impacting human health/disease. Recently, the influence of various dietary restrictions on the gut microbiota and the differences between the effects were investigated. In this review, we explored the current knowledge of different dietary restrictions on animal and human gut microbiota and the impact of these changes on human health.

Intermittent Fasting on Human Health and Disease.

Chronic non-communicable diseases (NCDs) are the leading cause of morbidity and mortality worldwide, but most of all in industrialized countries, and are fundamentally correlated to improper nutrition and impaired lifestyle behaviours [...].

Cetirizine and Levetiracetam as Inhibitors of Monoacylglycerol Lipase: Investigating Their Repurposing Potential as Novel Osteoarthritic Pain Therapies.

Osteoarthritis is characterized by progressive articular cartilage degradation, subchondral bone changes, and synovial inflammation, and affects various joints, causing pain and disability. Current osteoarthritis therapies, primarily focused on pain management, face limitations due to limited effectiveness and high risks of adverse effects. Safer and more effective treatments are urgently needed. Considering that the endocannabinoid 2-arachidonoyl glycerol is involved in pain processing, increasing its concentration through monoacylglycerol lipase (MAGL) inhibition reduces pain in various animal models. Furthermore, drug repurposing approaches leverage established drug safety profiles, presenting a cost-effective route to accelerate clinical application. To this end, cetirizine and levetiracetam were examined for their MAGL inhibitory effects. In vitro studies revealed that cetirizine and levetiracetam inhibited MAGL with IC50 values of 9.3931 µM and 3.0095 µM, respectively. In vivo experiments demonstrated that cetirizine, and to a lesser extent levetiracetam, reduced mechanical and thermal nociception in complete Freund adjuvant (CFA)-induced osteoarthritis in rats. Cetirizine exhibited a notable anti-inflammatory effect, reducing CFA-induced inflammation, as well as the inflammatory infiltrate and granuloma formation in the affected paw. These findings suggest that cetirizine may serve as a promising starting point for the development of novel compounds for osteoarthritis treatment, addressing both pain and inflammation.

Sirtuins, resveratrol and the intertwining cellular pathways connecting them.

Sirtuins are a family of NAD+-dependent deacylases with numerous physiological and pathological implications, which lately became an attractive therapeutic target. Sirtuin-activating compounds (STACs) could be useful in disease prevention and treatment. Despite its bioavailability issues, resveratrol exerts a myriad of beneficial effects, known as the "resveratrol paradox". Modulation of sirtuins' expression and activity may, in fact, underlie many of resveratrol revered actions; however, the cellular pathways affected by modulating the activity of each sirtuin isoform, in different physio-pathological conditions, are not fully known. The purpose of this review was to summarize recent reports concerning the effects of resveratrol on the activity of sirtuins in different experimental settings, focusing on in vitro and in vivo preclinical studies. Most reports concern SIRT1, however recent studies dive into the effects initiated via other isoforms. Numerous cellular signaling pathways were reported to be modulated by resveratrol in a sirtuin-dependent manner (increased phosphorylation of MAPKs, AKT, AMPK, RhoA, BDNF, decreased activation of NLRP3 inflammasome, NF-κB, STAT3, upregulation of SIRT1/SREBP1c pathway, reduced ß-amyloid via SIRT1-NF-κB-BACE1 signaling and counteracting mitochondrial damage by deacetylating PGC-1α). Thus, resveratrol may be the ideal candidate in the search for STACs as a tool for preventing and treating inflammatory and neurodegenerative diseases.

Exploring the potential impact of probiotic use on drug metabolism and efficacy.

Probiotics are frequently consumed as functional food and widely used as dietary supplements, but are also recommended in treating or preventing various gastrointestinal diseases. Therefore, their co-administration with other drugs is sometimes unavoidable or even compulsory. Recent technological developments in the pharmaceutical industry permitted the development of novel drug-delivery systems for probiotics, allowing their addition to the therapy of severely ill patients. Literature data regarding the changes that probiotics could impose on the efficacy or safety of chronic medication is scarce. In this context, the present paper aims to review probiotics currently recommended by the international medical community, to evaluate the relationship between gut microbiota and various pathologies with high impact worldwide and, most importantly, to assess the literature reports concerning the ability of probiotics to influence the pharmacokinetics/pharmacodynamics of some widely used drugs, especially for those with narrow therapeutic indexes. A better understanding of the potential influence of probiotics on drug metabolism, efficacy and safety could contribute to improving therapy management, facilitating individualized therapy and updating treatment guidelines.

Vaccine development for zoonotic viral diseases caused by positive­sense single­stranded RNA viruses belonging to the Coronaviridae and Togaviridae families (Review).

Outbreaks of zoonotic viral diseases pose a severe threat to public health and economies worldwide, with this currently being more prominent than it previously was human history. These emergency zoonotic diseases that originated and transmitted from vertebrates to humans have been estimated to account for approximately one billion cases of illness and have caused millions of deaths worldwide annually. The recent emergence of severe acute respiratory syndrome coronavirus-2 (coronavirus disease 2019) is an excellent example of the unpredictable public health threat causing a pandemic. The present review summarizes the literature data regarding the main vaccine developments in human clinical phase I, II and III trials against the zoonotic positive-sense single-stranded RNA viruses belonging to the Coronavirus and Alphavirus genera, including severe acute respiratory syndrome, Middle east respiratory syndrome, Venezuelan equine encephalitis virus, Semliki Forest virus, Ross River virus, Chikungunya virus and O'nyong-nyong virus. That there are neither vaccines nor effective antiviral drugs available against most of these viruses is undeniable. Therefore, new explosive outbreaks of these zoonotic viruses may surely be expected. The present comprehensive review provides an update on the status of vaccine development in different clinical trials against these viruses, as well as an overview of the present results of these trials.

Cerebrolysin Alleviating Effect on Glutamate-Mediated Neuroinflammation Via Glutamate Transporters and Oxidative Stress.

Glutamate, one of the most important excitatory neurotransmitters, acts as a signal transducer in peripheral tissues and endocrine cells. Excessive glutamate secretion has been shown to cause excitotoxicity and neurodegenerative disease. Cerebrolysin is a mixture of enzymatically treated peptides derived from pig brain including neurotrophic factors, like brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), nerve growth factor (NGF), and ciliary neurotrophic factor (CNTF). The present study investigated the protective effects of cerebrolysin on glutamate transporters (EAAT 1, EAAT 2) and cytokines (IL-1ß and IL-10) activity in glutamate-mediated neurotoxicity. Primary cortex neuron culture was exposed to glutamate and successively treated with various cerebrolysin concentrations for 24 and 48 h. Our data showed that cerebrolysin primarily protects neurons by decreasing glutamate concentration in the synaptic cleft. In addition, Cerebrolysin can decrease oxidative stress and neuron cell damage by increasing antioxidant activity and decreasing inflammation cytokine levels.

Effects of boric acid and potassium metaborate on cytokine levels and redox stress parameters in a wound model infected with methicillin­resistant Staphylococcus aureus.

Methicillin­resistant Staphylococcus aureus (MRSA) infections are usually found in hospital settings and, frequently, in patients with open wounds. One of the most critical virulence factors affecting the severity and recurrence of infections is the biofilm; increasing antibiotic resistance due to biofilm formation has led to the search for alternative compounds to antibiotics. The present study aimed to use boric acid and potassium metaborate against MRSA infection in a fibroblast wound model. For this purpose, a two­part experiment was designed: First, MRSA strains were used for the test, and both boric acid and potassium metaborate were prepared in microdilution. In the second step, an MRSA wound model was prepared using a fibroblast culture, and treatments with boric acid and potassium metaborate were applied for 24 h. For the evaluation of the effects of treatment, cell viability assay (MTT assay), analysis of redox stress parameters, including total oxidant status and total antioxidant capacity analyses, lactate dehydrogenase analysis and immunohistochemical staining were performed. In addition, IL­1ß and IL­10 gene expression levels were assayed. According to the results, potassium metaborate was more effective and exhibited a lower toxicity to fibroblast cells compared to boric acid; moreover, potassium metaborate decreased the level of prooxidant species and increased the antioxidant status more effectively than boric acid. The IL­1ß level in the bacteria group was high; however, boric acid and potassium metaborate significantly decreased the expression levels of inflammatory markers, exhibiting the potential to improve the resolution of the lesion. On the whole, the findings of the present study suggest that boric acid and potassium metaborate may be effective on the tested microorganisms.

Regulation of Gene Expression through Food-Curcumin as a Sirtuin Activity Modulator.

The sirtuin family comprises NAD+-dependent protein lysine deacylases, mammalian sirtuins being either nuclear (SIRT1, SIRT2, SIRT6, and SIRT7), mitochondrial (SIRT3, SIRT4, and SIRT5) or cytosolic enzymes (SIRT2 and SIRT5). They are able to catalyze direct metabolic reactions, thus regulating several physiological functions, such as energy metabolism, stress response, inflammation, cell survival, DNA repair, tissue regeneration, neuronal signaling, and even circadian rhythms. Based on these data, recent research was focused on finding molecules that could regulate sirtuins' expression and/or activity, natural compounds being among the most promising in the field. Curcumin (1,7-bis-(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) can induce, through SIRT, modulation of cancer cell senescence, improve endothelial cells protection against atherosclerotic factors, enhance muscle regeneration in atrophy models, and act as a pro-longevity factor counteracting the neurotoxicity of amyloid-beta. Although a plethora of protective effects was reported (antioxidant, anti-inflammatory, anticancer, etc.), its therapeutical use is limited due to its bioavailability issues. However, all the reported effects may be explained via the bioactivation theory, which postulates that curcumin's observed actions are modulated via its metabolites and/or degradation products. The present article is focused on bringing together the literature data correlating the ability of curcumin and its metabolites to modulate SIRT activity and its consequent beneficial effects.

Interleukins and redox impairment in type 2 diabetes mellitus: mini-review and pilot study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) represents a leading cause of morbidity and premature mortality, low-grade inflammation being acknowledged as a key contributor to its development and progression. A tailored therapeutic approach, based on sensitive and specific biomarkers, could allow a more accurate analysis of disease susceptibility/prognostic and of the response to treatment. OBJECTIVES: This mini-review and pilot study had two main goals: (1) reviewing the most recent literature encompassing the use of interleukins as inflammatory markers influenced by the redox imbalances in T2DM and (2) assessing parameters that conjunctly evaluate the redox impairment and inflammatory burden of T2DM patients, taking into consideration smoking status, as such group-specific biomarkers are scarcely reported in literature. METHODS: Firstly, PubMed database was surveyed to select and review the relevant studies employing interleukins as T2DM biomarkers and to assess if studies using combined inflammatory-redox indices were reported. Then, routine biochemical parameters were assessed in a pilot study -T2DM patients with 3 subgroups: non-smokers, smokers and ex-smokers, were compared to a control group of non-diabetic, apparently healthy non-smokers. Protein (AOPPs, AGEs), lipid/HDL (Amplex Red-based method) oxidative damage and inflammatory status (CRP, IL-1ß, IL-6, IL-10) biomarkers were assessed. Cytokine ratios and 2 oxidative-inflammatory status indices were developed (IH1 and IH2) and evaluated. RESULTS: We observed significant differences in terms of serum redox and inflammatory status (AOPPs, AGEs, CRP, CRP/HDL, CRP/IL-6, IL-10/IL-6, IH1) between T2DM patients compared to control and, moreover, between the subgroups formed considering smoking status (CRP, CRP/HDL, IH1). Glycemic control strongly influenced inflammatory status biomarkers: glycemia was positively correlated with the inflammatory parameters (CRP/IL-10) and inversely with the anti-inflammatory ones (IL-10, IL-10/IL-1ß ratio). CONCLUSIONS: Several of the assessed parameters may possess prognostic value for diabetics, especially when comparing subgroups with a different smoking history and could prove useful in clinical practice for assessing disease progress and therapeutic efficacy.

Metabolic and Metabolomic Insights Regarding the Omega-3 PUFAs Intake in Type 1 Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) is currently considered an autoimmune disease characterized by the destruction of pancreatic ß-cells, insulin deficiency, and dysglycemia. Dietary factors, including omega-3 polyunsaturated fatty acids (ω-3 PUFAs), were reported to influence T1DM. Therefore, a better understanding of the potential role of ω-3 PUFAs in the development and progression of T1DM will help to improve the clinical management of the disease. In this review, we explored the current understanding of molecular mechanisms and signaling pathways induced by ω-3 PUFAs and the beneficial effects of ω-3 PUFAs intake in the prevention and treatment of T1DM, as well as the underlying possible metabolomic (lipidomics) changes.

Identification of Novel Antistaphylococcal Hit Compounds Targeting Sortase A.

Staphylococcus aureus (S. aureus) is a causative agent of many hospital- and community-acquired infections with the tendency to develop resistance to all known antibiotics. Therefore, the development of novel antistaphylococcal agents is of urgent need. Sortase A is considered a promising molecular target for the development of antistaphylococcal agents. The main aim of this study was to identify novel sortase A inhibitors. In order to find novel antistaphylococcal agents, we performed phenotypic screening of a library containing 15512 compounds against S. aureus ATCC43300. The molecular docking of hits was performed using the DOCK program and 10 compounds were selected for in vitro enzymatic activity inhibition assay. Two inhibitors were identified, N,N-diethyl-N'-(5-nitro-2-(quinazolin-2-yl)phenyl)propane-1,3-diamine (1) and acridin-9-yl-(1H-benzoimidazol-5-yl)-amine (2), which decrease sortase A activity with IC50 values of 160.3 µM and 207.01 µM, respectively. It was found that compounds 1 and 2 possess antibacterial activity toward 29 tested multidrug resistant S. aureus strains with MIC values ranging from 78.12 to 312.5 mg/L. These compounds can be used for further structural optimization and biological research.

Zinc status, insulin resistance and glycoxidative stress in elderly subjects with type 2 diabetes mellitus.

Zinc deficiencies have been reported in numerous pathologies, such as diabetes mellitus, but also in the physiological process of ageing. Similarly, the end products of glycoxidation processes, advanced glycation end products (AGEs), are damaging compounds, a myriad of reports linking them to the development and progression of several age-associated chronic diseases. The aim of the present study was to analyze the relationships between zinc status, glycoxidative stress and insulin resistance (IR) in elderly subjects with type 2 diabetes mellitus (T2DM). A group of 52 non-smoking subjects (9 men and 43 women, aged 65-83 years) were enrolled in this cross-sectional study: 27 patients with T2DM, and 25 apparently healthy control subjects. Serum zinc (Zn) levels were assessed using a commercial kit based on an end-point colorimetric method, and serum AGEs were evaluated with a fluorimetric analytic procedure. The calculated glucose-to-zinc ratio (Gly/Zn), insulin-to-zinc ratio (Ins/Zn) and insulin-zinc resistance index (HOMA-IR/Zn) were further used to study the associations between serum Zn levels, secretory function of ß-pancreatic cells and AGEs. T2DM patients presented significantly higher serum insulin and Zn levels, as compared to the controls. We found a significant inverse correlation between Zn and AGEs, and a strong positive correlation between AGEs and the Gly/Zn ratio, suggesting that both Zn and AGEs are biomarkers that could reflect the persistence of hyperglycemia. We identified new surrogate biomarkers useful for the assessment of glycemic control with great potential for the development of preventive and therapeutic strategies for elderly diabetics, based on the evaluation of serum Zn levels.

Apoptosis is induced by sub-acute exposure to 3-MCPD and glycidol on Wistar Albino rat brain cells.

3-chloropropane-1,2-diol (3-MCPD) and its toxic metabolite glycidol were classified by the International Agency for Research on Cancer (IARC) as belonging to group 2B and 2A for humans. This study aimed to determine the sub-acute toxicity of these agents. Rats were exposed to 3-MCPD at 0.87 and 10 mg/kg/bw and glycidol (2,4 and 37,5 mg/kg/bw) for 90 days. miR-21 gene expression levels significantly decreased in all group's cerebellar tissues compared with control. Exposure to 10 mg/kg/bw 3-MCPD showed significant increases in PTEN in brain as compared to control group. The Akt gen expressions were significantly decreased in 3-MCPD and glycidol groups when compared to control group brains. Additionally, Caspase 3 and AIF immunopositivity significantly increased in 3-MCPD high dose and glycidol high dose groups in cerebellum granular layers compared to control. The results of the present study conclude that 3-MCPD and glycidol can induce apoptosis in rat brain tissue.

Procaine-The Controversial Geroprotector Candidate: New Insights Regarding Its Molecular and Cellular Effects.

Since its discovery in 1905 and its employment in everyday medical practice as a local anesthetic, to its highly controversial endorsement as an "anti-aging" molecule in the sixties and seventies, procaine is part of the history of medicine and gerontoprophylaxis. Procaine can be considered a "veteran" drug due to its long-time use in clinical practice, but is also a molecule which continues to incite interest, revealing new biological and pharmacological effects within novel experimental approaches. Therefore, this review is aimed at exploring and systematizing recent data on the biochemical, cellular, and molecular mechanisms involved in the antioxidant and potential geroprotective effects of procaine, focusing on the following aspects: (1) the research state-of-the-art, through an objective examination of scientific literature within the last 30 years, describing the positive, as well as the negative reports; (2) the experimental data supporting the beneficial effects of procaine in preventing or alleviating age-related pathology; and (3) the multifactorial pathways procaine impacts oxidative stress, inflammation, atherogenesis, cerebral age-related pathology, DNA damage, and methylation. According to reviewed data, procaine displayed antioxidant and cytoprotective actions in experimental models of myocardial ischemia/reperfusion injury, lipoprotein oxidation, endothelial-dependent vasorelaxation, inflammation, sepsis, intoxication, ionizing irradiation, cancer, and neurodegeneration. This analysis painted a complex pharmacological profile of procaine: a molecule that has not yet fully expressed its therapeutic potential in the treatment and prevention of aging-associated diseases. The numerous recent reports found demonstrate the rising interest in researching the multiple actions of procaine regulating key processes involved in cellular senescence. Its beneficial effects on cell/tissue functions and metabolism could designate procaine as a valuable candidate for the well-established Geroprotectors database.

Targeting Bacterial Sortases in Search of Anti-Virulence Therapies with Low Risk of Resistance Development.

Increasingly ineffective antibiotics and rapid spread of multi- and pan-resistant bacteria represent a global health threat; hence, the need of developing new antimicrobial medicines. A first step in this direction is identifying new molecular targets, such as virulence factors. Sortase A represents a virulence factor essential for the pathogenesis of Gram-positive pathogens, some of which have a high risk for human health. We present here an exhaustive collection of sortases inhibitors grouped by relevant chemical features: vinyl sulfones, 3-aryl acrylic acids and derivatives, flavonoids, naphtoquinones, anthraquinones, indoles, pyrrolomycins, isoquinoline derivatives, aryl ß-aminoethyl ketones, pyrazolethiones, pyridazinones, benzisothiazolinones, 2-phenyl-benzoxazole and 2-phenyl-benzofuran derivatives, thiadiazoles, triazolothiadiazoles, 2-(2-phenylhydrazinylidene)alkanoic acids, and 1,2,4-thiadiazolidine-3,5-dione. This review focuses on highlighting their structure-activity relationships, using the half maximal inhibitory concentration (IC50), when available, as an indicator of each compound effect on a specific sortase. The information herein is useful for acquiring knowledge on diverse natural and synthetic sortases inhibitors scaffolds and for understanding the way their structural variations impact IC50. It will hopefully be the inspiration for designing novel effective and safe sortase inhibitors in order to create new anti-infective compounds and to help overcoming the current worldwide antibiotic shortage.

Vitamin E beyond Its Antioxidant Label.

Vitamin E, comprising tocopherols and tocotrienols, is mainly known as an antioxidant. The aim of this review is to summarize the molecular mechanisms and signaling pathways linked to inflammation and malignancy modulated by its vitamers. Preclinical reports highlighted a myriad of cellular effects like modulating the synthesis of pro-inflammatory molecules and oxidative stress response, inhibiting the NF-κB pathway, regulating cell cycle, and apoptosis. Furthermore, animal-based models have shown that these molecules affect the activity of various enzymes and signaling pathways, such as MAPK, PI3K/Akt/mTOR, JAK/STAT, and NF-κB, acting as the underlying mechanisms of their reported anti-inflammatory, neuroprotective, and anti-cancer effects. In clinical settings, not all of these were proven, with reports varying considerably. Nonetheless, vitamin E was shown to improve redox and inflammatory status in healthy, diabetic, and metabolic syndrome subjects. The anti-cancer effects were inconsistent, with both pro- and anti-malignant being reported. Regarding its neuroprotective properties, several studies have shown protective effects suggesting vitamin E as a potential prevention and therapeutic (as adjuvant) tool. However, source and dosage greatly influence the observed effects, with bioavailability seemingly a key factor in obtaining the preferred outcome. We conclude that this group of molecules presents exciting potential for the prevention and treatment of diseases with an inflammatory, redox, or malignant component.