Selenium (Se) is an essential trace element crucial for human health that primarily functions as an immunonutrient. It is incorporated into polypeptides such as selenocysteine (SeC) and selenomethionine (SeMet), two key amino acids involved in various biochemical processes. All living organisms can convert inorganic Se into biologically active organic forms, with SeMet being the predominant form and a precursor for SeC production in humans and animals. The human genome encodes 25 selenoprotein genes, which incorporate low-molecular-weight Se compounds in the form of SeC. Organic Se, especially in the form of selenoproteins, is more efficiently absorbed than inorganic Se, driving the demand for selenoprotein-based health products, such as functional foods. Se-enriched functional foods offer a practical means of delivering bioavailable Se and are associated with enhanced antioxidant properties and various health benefits. Recent advancements in selenoprotein synthesis have improved our understanding of their roles in antioxidant defense, cancer prevention, immune regulation, anti-inflammation, hypoglycemia, cardiovascular health, Alzheimer's disease, fertility, and COVID-19. This review highlights key selenoproteins and their biological functions, biosynthetic pathways, and emerging applications while highlighting the need for further research.

Sequence analysis of the Zaire ebolavirus (EBOV) polymerase (L gene) mRNA, using online tools, identified a highly ranked -1 programmed ribosomal frameshift (FS) signal including an ideal slippery sequence heptamer (UUUAAAA), with an overlapping coding region featuring two tandem UGA codons, immediately followed by an RNA region that is the inverse complement (antisense) to a region of the mRNA of the selenoprotein iodothyronine deiodinase II (DIO2). This antisense interaction was confirmed in vitro via electrophoretic gel shift assay, using cDNAs at the EBOV and DIO2 segments. The formation of a duplex between the two mRNAs could trigger the ribosomal frameshift, by mimicking the enhancing role of a pseudoknot structure, while providing access to the selenocysteine insertion sequence (SECIS) element contained in the DIO2 mRNA. This process would allow the -1 frame UGA codons to be recoded as selenocysteine, forming part of a C-terminal module in a low abundance truncated isoform of the viral polymerase, potentially functioning in a redox role. Remarkably, 90 bases downstream of the -1 FS site, an active +1 FS site can be demonstrated, which, via a return to the zero frame, would enable the attachment of the entire C-terminal of the polymerase protein. Using a construct with upstream and downstream reporter genes, spanning a wildtype or mutated viral insert, we show significant +1 ribosomal frameshifting at this site. Acting singly or together, frameshifting at these sites (both of which are highly conserved in EBOV strains) could enable the expression of several modified isoforms of the polymerase. The 3D modeling of the predicted EBOV polymerase FS variants using the AI tool, AlphaFold, reveals a peroxiredoxin-like active site with arginine and threonine residues adjacent to a putative UGA-encoded selenocysteine, located on the back of the polymerase "hand". This module could serve to protect the viral RNA from peroxidative damage.

Background and Objectives: Mammary gland surgery has become very common, but there are complications of these operations, including the concept of breast implant illness (BII) in women with silicone gel breast implants (SBI), who suffer from various symptoms such as myalgia, arthralgia, fatigue, fever, dry eyes, or dry mouth. Silicone biomaterials are synthetic polymers that have their own physical and chemical properties and can exert their effect at the site of use and possibly on the general status of the body, causing inflammation and oxidative stress signs. The aim of the study was to examine components of the blood antioxidant system (AOS) of the mastopexy and breast augmentation patients before the operation, on the first post-op day, and 6 months after surgery. Materials and Methods: Healthy breast surgery patients (women aged 31 to 60 years without visible pathologies) were selected for the study and formed 2 groups: breast lift-mastopexy without silicone biomaterials (I group, 30 patients) and breast augmentation using silicone biomaterials (II group, 28 patients). All patients underwent standard preoperative tests. Glutathione peroxidase (GPxSe) and gamma-glutamyl transferase (GGT) in blood, selenium (Se), selenium protein P (SelPP), and total antioxidant status (TAS) in plasma were measured as AOS parameters. The concentration of vitamin D was also determined. A total of 174 blood tests were performed. Results: Overall, there were no differences in both groups in measured antioxidant system indicators over time; neither changes in objective nor subjective status were observed. However, baseline activity of GPxSe was relatively high but restored to normal values 6 months after surgery. In the mastopexy group, GPxSe decreased from 12,961.7 U/L by 18.9% to 10,513.4 U/L, and in the breast augmentation group, from 15,505.0 U/L by 25.1% to 11,265.5 U/L, which is a decrease of 18.9% and 25.1%, respectively. The patients did not note any complaints; other indicators of standard biochemical tests were within normal limits. Conclusions: The two types of surgical interventions, breast mastopexy and augmentation of the mammary glands, do not significantly impact blood AOS and are physiological in nature.

The authors of this Comment are longstanding selenium investigators with a total of 200 or more published articles on selenium; the corresponding author (Margaret P [...].

Micronutrient deficiencies can develop in critically ill patients, arising from factors such as decreased intake, increased losses, drug interactions, and hypermetabolism. These deficiencies may compromise important immune functions, with potential implications for patient outcomes. Alternatively, micronutrient blood levels may become low due to inflammation-driven redistribution rather than consumption. This explorative pilot study investigates blood micronutrient concentrations during the first three weeks of ICU stay in critically ill COVID-19 patients and evaluates the impact of additional micronutrient administration. Moreover, associations between inflammation, disease severity, and micronutrient status were explored. We measured weekly concentrations of vitamins A, B6, D, and E; iron; zinc; copper; selenium; and CRP as a marker of inflammation state and the SOFA score indicating disease severity in 20 critically ill COVID-19 patients during three weeks of ICU stay. Half of the patients received additional (intravenous) micronutrient administration. Data were analyzed with linear mixed models and Pearson's correlation coefficient. High deficiency rates of vitamins A, B6, and D; zinc; and selenium (50-100%) were found at ICU admission, along with low iron status. After three weeks, vitamins B6 and D deficiencies persisted, and iron status remained low. Plasma levels of vitamins A and E, zinc, and selenium improved. No significant differences in micronutrient levels were found between patient groups. Negative correlations were identified between the CRP level and levels of vitamins A and E, iron, transferrin, zinc, and selenium. SOFA scores negatively correlated with vitamin D and selenium levels. Our findings reveal high micronutrient deficiency rates at ICU admission. Additional micronutrient administration did not enhance levels or expedite their increase. Spontaneous increases in vitamins A and E, zinc, and selenium levels were associated with inflammation resolution, suggesting that observed low levels may be attributed, at least in part, to redistribution rather than true deficiencies.

Selenium has been proven to influence several biological functions, showing to be an essential micronutrient. The functional studies demonstrated the benefits of a balanced selenium diet and how its deficiency is associated with diverse diseases, especially cancer and viral diseases. Selenium is an antioxidant, protecting the cells from damage, enhancing the immune system response, preventing cardiovascular diseases, and decreasing inflammation. Selenium can be found in its inorganic and organic forms, and its main form in the cells is the selenocysteine incorporated into selenoproteins. Twenty-five selenoproteins are currently known in the human genome: glutathione peroxidases, iodothyronine deiodinases, thioredoxin reductases, selenophosphate synthetase, and other selenoproteins. These proteins lead to the transport of selenium in the tissues, protect against oxidative damage, contribute to the stress of the endoplasmic reticulum, and control inflammation. Due to these functions, there has been growing interest in the influence of polymorphisms in selenoproteins in the last two decades. Selenoproteins' gene polymorphisms may influence protein structure and selenium concentration in plasma and its absorption and even impact the development and progression of certain diseases. This review aims to elucidate the role of selenoproteins and understand how their gene polymorphisms can influence the balance of physiological conditions. In this polymorphism review, we focused on the PubMed database, with only articles published in English between 2003 and 2023. The keywords used were "selenoprotein" and "polymorphism". Articles that did not approach the theme subject were excluded. Selenium and selenoproteins still have a long way to go in molecular studies, and several works demonstrated the importance of their polymorphisms as a risk biomarker for some diseases, especially cardiovascular and thyroid diseases, diabetes, and cancer.

Cadmium (Cd), being a highly toxic heavy metal, significantly impacts plant growth and development by altering nutrient uptake and causing oxidative and structural damage, resulting in reduced yield. To combat Cd toxicity and accumulation in wheat, it was hypothesized that co-application of Selenium (Se) and Silicon (Si) can reduce the adverse effect of Cd and regulate Cd resistance while improving Se fortification in wheat. Therefore, this study evaluated the comparative effect of Se and Si on the growth and antioxidant defense systems of wheat plants grown in a hydroponic setup. Briefly, the plants were acclimatized to the hydroponic solution for 1 week and then exposed to 10 µmol Cd. Afterwards, the treatments, including 0.2 mmol Si and 1.5 µmol Se, were applied as a root and foliar application, respectively. Plants supplemented with both Se and Si showed improved biomass and other physiological growth attributes, and this response was associated with improved activity/contents of antioxidants, including glutathione (GSH) content, glutathione reductase (GR), ascorbate peroxidase (APX), and catalase (CAT), with related lowering of hydrogen peroxide, malondialdehyde content, and structural damages. Moreover, by Se + Si supplementation, a decrease in total S levels in plant tissues was observed, whereas an increase in total protein concentration and GSH indicated a different and novel mechanism of Cd tolerance and S homeostasis in the plant. It was observed that Si was more involved in significantly reducing Cd translocation by stabilizing Cd in the root and reducing its content in the soluble fraction in both the root and shoot. Whereas Se was found to play the main role in reducing the oxidative damage caused by Cd, and the effect was more profound in the shoot. In addition, this study also observed a positive correlation between Si and Se for relative uptake, which had not been reported earlier. Our findings show that the Se and Si doses together benefit growth regulation and nutrient uptake; additionally, their combinations support the Cd resistance mechanism in wheat through upregulation of the antioxidant system and control of Cd translocation and subcellular distribution, ultimately contributing to the nutritional quality of wheat produced. Thus, it is concluded that the co-application of Se and Si has improved the nutritional quality while reducing the Cd risk in wheat and therefore needs to be employed as a potential strategy to ensure food safety in a Cd-contaminated environment.

Living organisms use selenium mainly in the form of selenocysteine in the active site of oxidoreductases. Here, selenium's unique chemistry is believed to modulate the reaction mechanism and enhance the catalytic efficiency of specific enzymes in ways not achievable with a sulfur-containing cysteine. However, despite the fact that selenium/sulfur have different physicochemical properties, several selenoproteins have fully functional cysteine-containing homologues and some organisms do not use selenocysteine at all. In this review, selected selenocysteine-containing proteins will be discussed to showcase both situations: (i) selenium as an obligatory element for the protein's physiological function, and (ii) selenium presenting no clear advantage over sulfur (functional proteins with either selenium or sulfur). Selenium's physiological roles in antioxidant defence (to maintain cellular redox status/hinder oxidative stress), hormone metabolism, DNA synthesis, and repair (maintain genetic stability) will be also highlighted, as well as selenium's role in human health. Formate dehydrogenases, hydrogenases, glutathione peroxidases, thioredoxin reductases, and iodothyronine deiodinases will be herein featured.

Zinc, an essential trace element that serves as a cofactor for numerous cellular and viral proteins, plays a central role in the dynamics of HIV-1 infection. Among the viral proteins, the nucleocapsid NCp7, which contains two zinc finger motifs, is abundantly present viral particles and plays a crucial role in coating HIV-1 genomic RNA, thus concentrating zinc within virions. In this study, we investigated whether HIV-1 virus production impacts cellular zinc homeostasis and whether isotopic fractionation occurs between the growth medium, the producing cells, and the viral particles. We found that HIV-1 captures a significant proportion of cellular zinc in the neo-produced particles. Furthermore, as cells grow, they accumulate lighter zinc isotopes from the medium, resulting in a concentration of heavier isotopes in the media, and the viruses exhibit a similar isotopic fractionation to the producing cells. Moreover, we generated HIV-1 particles in HEK293T cells enriched with each of the five zinc isotopes to assess the potential effects on the structure and infectivity of the viruses. As no strong difference was observed between the HIV-1 particles produced in the various conditions, we have demonstrated that enriched isotopes can be accurately used in future studies to trace the fate of zinc in cells infected by HIV-1 particles. Comprehending the mechanisms underlying zinc absorption by HIV-1 viral particles offers the potential to provide insights for developing future treatments aimed at addressing this specific facet of the virus's life cycle.

COVID-19 patients suffer from the detrimental effects of cytokine storm and not much success has been achieved to overcome this issue. We sought to test the ability of selenium to reduce the impact of two important cytokine storm players: IL-6 and TNF-α. The effects of four selenium compounds on the secretion of these cytokines from THP-1 macrophages were evaluated in vitro following an LPS challenge. Also, the potential impact of methylseleninic acid (MSeA) on Nrf2 and IκBα was determined after a short treatment of THP-1 macrophages. MSeA was found to be the most potent selenium form among the four selenium compounds tested that reduced the levels of IL-6 and TNF-α secreted by THP-1 macrophages. In addition, an increase in Nrf2 and decrease in pIκBα in human macrophages was observed following MSeA treatment. Our data indicate that COVID-19 patients might benefit from the addition of MSeA to the standard therapy due to its ability to suppress the key players in the cytokine storm.

In recent times, the emergence of viral infections, including the SARS-CoV-2 virus, the monkeypox virus, and, most recently, the Langya virus, has highlighted the devastating effects of viral infection on human life. There has been significant progress in the development of efficacious vaccines for the prevention and control of viruses; however, the high rates of viral mutation and transmission necessitate the need for novel methods of control, management, and prevention. In recent years, there has been a shift in public awareness on health and wellbeing, with consumers making significant dietary changes to improve their immunity and overall health. This rising health awareness is driving a global increase in the consumption of functional foods. This review delves into the benefits of functional foods as potential natural means to modulate the host immune system to enhance defense against viral infections. We provide an overview of the functional food market in Europe and discuss the benefits of enhancing immune fitness in high-risk groups, including the elderly, those with obesity, and people with underlying chronic conditions. We also discuss the immunomodulatory mechanisms of key functional foods, including dairy proteins and hydrolysates, plant-based functional foods, fermentates, and foods enriched with vitamin D, zinc, and selenium. Our findings reveal four key immunity boosting mechanisms by functional foods, including inhibition of viral proliferation and binding to host cells, modulation of the innate immune response in macrophages and dendritic cells, enhancement of specific immune responses in T cells and B cells, and promotion of the intestinal barrier function. Overall, this review demonstrates that diet-derived nutrients and functional foods show immense potential to boost viral immunity in high-risk individuals and can be an important approach to improving overall immune health.

The primary objective of this study was to compare the plasma levels of copper, selenium, and zinc between critically ill COVID-19 patients and less severe COVID-19 patients. The secondary objective was to investigate the association of these trace element levels with adverse outcomes, including the duration of mechanical ventilation, occurrence of septic shock, and mortality in critically ill COVID-19 patients. All COVID-19 patients admitted to the ICU of the Geneva University Hospitals between 9 March 2020 and 19 May 2020 were included in the study. Plasma levels of copper, selenium and zinc were measured on admission to the ICU and compared with levels measured in COVID-19 patients hospitalized on the ward and in non-hospitalized COVID-19 patients. To analyze the association of trace elements with clinical outcomes, multivariate linear and logistic regressions were performed. Patients in the ICU had significantly lower levels of selenium and zinc and higher levels of copper compared to COVID-19 patients hospitalized on the ward and in non-hospitalized COVID-19 patients. In ICU patients, lower zinc levels tended to be associated with more septic shock and increased mortality compared to those with higher zinc levels (p = 0.07 for both). Having lower copper or selenium levels was associated with a longer time under mechanical ventilation (p = 0.01 and 0.04, respectively). These associations remained significant in multivariate analyses (p = 0.03 for copper and p = 0.04 for selenium). These data support the need for interventional studies to assess the potential benefit of zinc, copper and selenium supplementation in severe COVID-19 patients.

Selenium is a main group element and an essential trace element in human health. It was discovered in selenocysteine (SeC) by Stadtman in 1974. SeC is an encoded natural amino acid hailed as the 21st naturally occurring amino acid (U) present in several enzymes and which exquisitely participates in redox biology. As it turns out, selenium bears a U-shaped toxicity curve wherein too little of the nutrient present in biology leads to disorders; concentrations that are too great, on the other hand, pose toxicity to biological systems. In light of many excellent previous reviews and the corpus of literature, we wanted to offer this current review, in which we present aspects of the clinical and biological literature and justify why we should further investigate Se-containing species in biological and medicinal contexts, especially small molecule-containing species in biomedical research and clinical medicine. Of central interest is how selenium participates in biological signaling pathways. Several clinical medical cases are recounted; these reports are mainly pertinent to human cancer and changes in pathology and cases in which the patients are often terminal. Selenium was an option chosen in light of earlier chemotherapeutic treatment courses which lost their effectiveness. We describe apoptosis, and also ferroptosis, and senescence clearly in the context of selenium. Other contemporary issues in research also compelled us to form this review: issues with CoV-2 SARS infection which abound in the literature, and we described findings with human patients in this context. Laboratory scientific studies and clinical studies dealing with two main divisions of selenium, organic (e.g., methyl selenol) or inorganic selenium (e.g., sodium selenite), are discussed. The future seems bright with the research and clinical possibilities of selenium as a trace element, whose recent experimental clinical treatments have so far involved dosing simply and inexpensively over a set of days, amounts, and time intervals.

Agronomic biofortification with selenium (Se) effectively reduces hidden hunger and increases the nutritional intake of Se in people and animals. Because sorghum is a staple diet for millions of people and is used in animal feed, it becomes a crop with biofortification potential. Consequently, this study aimed to compare organoselenium compounds with selenate, which is effective in numerous crops, and to assess grain yield, the effect in the antioxidant system, and macronutrient/micronutrient contents of different sorghum genotypes treated with Se, via foliar spray. The trials used a 4 × 8 factorial design, with four Se sources (control-without Se supply, sodium selenate, potassium hydroxy-selenide, acetylselenide) and eight genotypes (BM737, BRS310, Enforcer, K200, Nugrain320, Nugrain420, Nugrain430, and SHS410). The Se rate used was 0.125 mg plant^-1. All genotypes reacted effectively to foliar fertilization with Se through sodium selenate. In this experiment, potassium hydroxy-selenide and acetylselenide showed low Se levels and lower Se uptake and absorption efficiency than selenate. Selenium fertilization increased grain yield and altered lipid peroxidation by malondialdehyde content, hydrogen peroxide content, catalase activity, ascorbate peroxidase, superoxide dismutase, and macronutrients and micronutrients content of the studied genotypes. In sum, biofortification with selenium led to an overall yield increase of sorghum plants and supplementation with selenium through sodium selenate was more efficient than organoselenium compounds, yet acetylselenide had a positive effect on the antioxidant system. Sorghum can be effectively biofortified through the foliar application of sodium selenate; however, studying the interaction between organic and inorganic Se compounds in plants is necessary.

Since the coronavirus disease 2019 (COVID-19) pandemic appeared, both governments and the scientific community have focused their efforts on the search for prophylactic and therapeutic alternatives in order to reduce its effects. Vaccines against SARS-CoV-2 have been approved and administered, playing a key role in the overcoming of this situation. However, they have not reached the whole world population, and several doses will be needed in the future in order to successfully protect individuals. The disease is still here, so other strategies should be explored with the aim of supporting the immune system before and during the infection. An adequate diet is certainly associated with an optimal inflammatory and oxidative stress status, as poor levels of different nutrients could be related to altered immune responses and, consequently, an augmented susceptibility to infections and severe outcomes derived from them. Minerals exert a wide range of immune-modulatory, anti-inflammatory, antimicrobial, and antioxidant activities, which may be useful for fighting this illness. Although they cannot be considered as a definitive therapeutic solution, the available evidence to date, obtained from studies on similar respiratory diseases, might reflect the rationality of deeper investigations of the use of minerals during this pandemic.

The purpose of this review is to systematically examine the scientific evidence investigating selenium's relationship with COVID-19, aiming to support, or refute, the growing hypothesis that supplementation could prevent COVID-19 etiopathogenesis. In fact, immediately after the beginning of the COVID-19 pandemic, several speculative reviews suggested that selenium supplementation in the general population could act as a silver bullet to limit or even prevent the disease. Instead, a deep reading of the scientific reports on selenium and COVID-19 that are available to date supports neither the specific role of selenium in COVID-19 severity, nor the role of its supplementation in the prevention disease onset, nor its etiology.

Oxidative stress (OS) could cause various COVID-19 complications. Recently, we have developed the Pouvoir AntiOxydant Total (PAOT®) technology for reflecting the total antioxidant capacity (TAC) of biological samples. We aimed to investigate systemic oxidative stress status (OSS) and to evaluate the utility of PAOT® for assessing TAC during the recovery phase in critical COVID-19 patients in a rehabilitation facility.

In a total of 12 critical COVID-19 patients in rehabilitation, 19 plasma OSS biomarkers were measured: antioxidants, TAC, trace elements, oxidative damage to lipids, and inflammatory biomarkers. TAC level was measured in plasma, saliva, skin, and urine, using PAOT and expressed as PAOT-Plasma, -Saliva, -Skin, and -Urine scores, respectively. Plasma OSS biomarker levels were compared with levels from previous studies on hospitalized COVID-19 patients and with the reference population. Correlations between four PAOT scores and plasma OSS biomarker levels were analyzed.

During the recovery phase, plasma levels in antioxidants (γ-tocopherol, β-carotene, total glutathione, vitamin C and thiol proteins) were significantly lower than reference intervals, whereas total hydroperoxides and myeloperoxidase (a marker of inflammation) were significantly higher. Copper negatively correlated with total hydroperoxides (r = 0.95, p = 0.001). A similar, deeply modified OSS was already observed in COVID-19 patients hospitalized in an intensive care unit. TAC evaluated in saliva, urine, and skin correlated negatively with copper and with plasma total hydroperoxides. To conclude, the systemic OSS, determined using a large number of biomarkers, was always significantly increased in cured COVID-19 patients during their recovery phase. The less costly evaluation of TAC using an electrochemical method could potentially represent a good alternative to the individual analysis of biomarkers linked to pro-oxidants.

Nutrients and diets have an important impact on our immune system and infection risk and a huge number of papers have been published dealing with various aspects of nutrition in relation to SARS-CoV-2 infection risk or COVID-19 severity. This narrative review aims to give an update on this association and tries to summarize some of the most important findings after three years of pandemic. The analysis of major studies and systematic reviews leads to the conclusion that a healthy plant-based diet reduces the risks for SARS-CoV-2 infection and especially COVID-19 severity. Regarding micronutrients, vitamin D is to the fore, but also zinc, vitamin C and, to some extent, selenium may play a role in COVID-19. Furthermore, omega-3-fatty acids with their anti-inflammatory effects also deserve attention. Therefore, a major aim of societal nutritional efforts in future should be to foster a high quality plant-based diet, which not only exerts beneficial effects on the immune system but also reduces the risk for non-communicable diseases such as type 2 diabetes or obesity which are also primary risk factors for worse COVID-19 outcomes. Another aim should be to focus on a good supply of critical immune-effective nutrients, such as vitamin D and zinc.

Excessive inflammatory response has been implicated in severe respiratory forms of coronavirus disease 2019 (COVID-19). Trace elements such as zinc, selenium, and copper are known to modulate inflammation and immunity. This study aimed to assess the relationships between antioxidant vitamins and mineral trace elements levels as well as COVID-19 severity in older adults hospitalized. In this observational retrospective cohort study, the levels of zinc, selenium, copper, vitamin A, β-carotene, and vitamin E were measured in 94 patients within the first 15 days of hospitalization. The outcomes were in-hospital mortality secondary to COVID-19 or severe COVID-19. A logistic regression analysis was conducted to test whether the levels of vitamins and minerals were independently associated with severity. In this cohort (average age of 78 years), severe forms (46%) were associated with lower zinc (p = 0.012) and β-carotene (p < 0.001) concentrations, and in-hospital mortality (15%) was associated with lower zinc (p = 0.009), selenium (p = 0.014), vitamin A (p = 0.001), and β-carotene (p = 0.002) concentrations. In regression analysis, severe forms remained independently associated with lower zinc (aOR 2.13, p = 0.018) concentrations, and death was associated with lower vitamin A (aOR = 0.165, p = 0.021) concentrations. Low plasma concentrations of zinc and vitamin A were associated with poor prognosis in older people hospitalized with COVID-19.

Long-term neurological complications, persisting in patients who cannot fully recover several months after severe SARS-CoV-2 coronavirus infection, are referred to as neurological sequelae of the long COVID syndrome. Among the numerous clinical post-acute COVID-19 symptoms, neurological and psychiatric manifestations comprise prolonged fatigue, "brain fog", memory deficits, headache, ageusia, anosmia, myalgias, cognitive impairments, anxiety, and depression lasting several months. Considering that neurons are highly vulnerable to inflammatory and oxidative stress damages following the overproduction of reactive oxygen species (ROS), neuroinflammation and oxidative stress have been suggested to dominate the pathophysiological mechanisms of the long COVID syndrome. It is emphasized that mitochondrial dysfunction and oxidative stress damages are crucial for the pathogenesis of neurodegenerative disorders. Importantly, antioxidant therapies have the potential to slow down and prevent disease progression. However, many antioxidant compounds display low bioavailability, instability, and transport to targeted tissues, limiting their clinical applications. Various nanocarrier types, e.g., liposomes, cubosomes, solid lipid nanoparticles, micelles, dendrimers, carbon-based nanostructures, nanoceria, and other inorganic nanoparticles, can be employed to enhance antioxidant bioavailability. Here, we highlight the potential of phytochemical antioxidants and other neuroprotective agents (curcumin, quercetin, vitamins C, E and D, melatonin, rosmarinic acid, N-acetylcysteine, and Ginkgo Biloba derivatives) in therapeutic strategies for neuroregeneration. A particular focus is given to the beneficial role of nanoparticle-mediated drug-delivery systems in addressing the challenges of antioxidants for managing and preventing neurological disorders as factors of long COVID sequelae.

Selenium is an important dietary supplement and an essential trace element incorporated into selenoproteins with growth-modulating properties and cytotoxic mechanisms of action. However, different compounds of selenium usually possess a narrow nutritional or therapeutic window with a low degree of absorption and delicate safety margins, depending on the dose and the chemical form in which they are provided to the organism. Hence, selenium nanoparticles (SeNPs) are emerging as a novel therapeutic and diagnostic platform with decreased toxicity and the capacity to enhance the biological properties of Se-based compounds. Consistent with the exciting possibilities offered by nanotechnology in the diagnosis, treatment, and prevention of diseases, SeNPs are useful tools in current biomedical research with exceptional benefits as potential therapeutics, with enhanced bioavailability, improved targeting, and effectiveness against oxidative stress and inflammation-mediated disorders. In view of the need for developing eco-friendly, inexpensive, simple, and high-throughput biomedical agents that can also ally with theranostic purposes and exhibit negligible side effects, biogenic SeNPs are receiving special attention. The present manuscript aims to be a reference in its kind by providing the readership with a thorough and comprehensive review that emphasizes the current, yet expanding, possibilities offered by biogenic SeNPs in the biomedical field and the promise they hold among selenium-derived products to, eventually, elicit future developments. First, the present review recalls the physiological importance of selenium as an oligo-element and introduces the unique biological, physicochemical, optoelectronic, and catalytic properties of Se nanomaterials. Then, it addresses the significance of nanosizing on pharmacological activity (pharmacokinetics and pharmacodynamics) and cellular interactions of SeNPs. Importantly, it discusses in detail the role of biosynthesized SeNPs as innovative theranostic agents for personalized nanomedicine-based therapies. Finally, this review explores the role of biogenic SeNPs in the ongoing context of the SARS-CoV-2 pandemic and presents key prospects in translational nanomedicine.

Targeted therapeutics made significant advances in the treatment of patients with advanced clear cell renal cell carcinoma (ccRCC). Resistance and serious adverse events associated with standard therapy of patients with advanced ccRCC highlight the need to identify alternative 'druggable' targets to those currently under clinical development. Although the Von Hippel-Lindau (VHL) and Polybromo1 (PBRM1) tumor-suppressor genes are the two most frequently mutated genes and represent the hallmark of the ccRCC phenotype, stable expression of hypoxia-inducible factor-1α/2α (HIFs), microRNAs-210 and -155 (miR_S), transforming growth factor-beta (TGF-ß), nuclear factor erythroid 2-related factor 2 (Nrf2), and thymidine phosphorylase (TP) are targets overexpressed in the majority of ccRCC tumors. Collectively, these altered biomarkers are highly interactive and are considered master regulators of processes implicated in increased tumor angiogenesis, metastasis, drug resistance, and immune evasion. In recognition of the therapeutic potential of the indicated biomarkers, considerable efforts are underway to develop therapeutically effective and selective inhibitors of individual targets. It was demonstrated that HIF_S, miR_S, Nrf2, and TGF-ß are targeted by a defined dose and schedule of a specific type of selenium-containing molecules, seleno-L-methionine (SLM) and methylselenocystein (MSC). Collectively, the demonstrated pleiotropic effects of selenium were associated with the normalization of tumor vasculature, and enhanced drug delivery and distribution to tumor tissue, resulting in enhanced efficacy of multiple chemotherapeutic drugs and biologically targeted molecules. Higher selenium doses than those used in clinical prevention trials inhibit multiple targets altered in ccRCC tumors, which could offer the potential for the development of a new and novel therapeutic modality for cancer patients with similar selenium target expression. Better understanding of the underlying mechanisms of selenium modulation of specific targets altered in ccRCC could potentially have a significant impact on the development of a more efficacious and selective mechanism-based combination for the treatment of patients with cancer.

Selenium-containing agents are more and more considered as an innovative potential treatment option for cancer. Light is shed not only on the considerable advancements made in understanding the complex biology and chemistry related to selenium-containing small molecules but also on Se-nanoparticles. Numerous Se-containing agents have been widely investigated in recent years in cancer therapy in relation to tumour development and dissemination, drug delivery, multidrug resistance (MDR) and immune system-related (anti)cancer effects. Despite numerous efforts, Se-agents apart from selenocysteine and selenomethionine have not yet reached clinical trials for cancer therapy. The purpose of this review is to provide a concise critical overview of the current state of the art in the development of highly potent target-specific Se-containing agents.

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has affected millions of people globally. It was declared a pandemic by the World Health Organization in March 2020. The hyperinflammatory response to the entry of SARS-CoV-2 into the host through angiotensin-converting enzyme 2 is the result of a "cytokine storm" and the high oxidative stress responsible for the associated symptomatology. Not only respiratory symptoms are reported, but gastrointestinal symptoms (diarrhea, vomiting, and nausea) and liver abnormalities (high levels of aspartate aminotransferase, alanine aminotransferase transaminases, and bilirubin) are observed in at least 30% of patients. Reduced food intake and a delay in medical services may lead to malnutrition, which increases mortality and poor outcomes. This review provides some strategies to identify malnutrition and establishes nutritional approaches for the management of COVID-19 and liver injury, taking energy and nutrient requirements and their impact on the immune response into account. The roles of certain phytochemicals in the prevention of the disease or as promising target drugs in the treatment of this disease are also considered.

Melatonin is an important and widespread plant hormone. However, the underlying physiological and molecular mechanisms of melatonin as a secondary messenger in improving cold tolerance by selenium are limited. This study investigated the effects of selenite on the cold stress of cucumber seedlings. The results showed that exogenous application of selenite improved the cold tolerance of cucumber seedlings, which was dependent on the concentration effect. In the present experiment, 1 μM of selenite showed the best effect on alleviating cold stress. Interestingly, we found that in the process of alleviating cold stress, selenite increased the content of endogenous melatonin by regulating the expression of melatonin biosynthesis genes (TDC, T5H, SNAT, and COMT). To determine the interrelation between selenite and melatonin in alleviating cold stress, melatonin synthesis inhibitor p-chlorophenylalanine and melatonin were used for in-depth study. This study provides a theoretical basis for cucumber cultivation and breeding.