Selenium (Se), a critically essential trace element, plays a crucial role in diverse physiological processes within the human body, such as oxidative stress response, inflammation regulation, apoptosis, and lipid metabolism. Organ fibrosis, a pathological condition caused by various factors, has become a significant global health issue. Numerous studies have demonstrated the substantial impact of Se on fibrotic diseases. This review delves into the latest research advancements in Se and Se-related biological agents for alleviating fibrosis in the heart, liver, lungs, and kidneys, detailing their mechanisms of action within fibrotic pathways. Additionally, the article summa-rizes some of the anti-fibrotic drugs currently in clinical trials for the aforementioned organ fibroses.

H2Se is the precursor for the biosynthesis of selenocompounds and is a potential gasotransmitter. Chemical tools for H2Se delivery and detection are important for Se-related biology research. Key challenges in the field include developing compound platforms that are triggered to release H2Se under various stimuli and developing fluorogenic donors that allow for real-time tracking of H2Se delivery. Here we report a new general platform for triggered H2Se donors based on controllable deprotection of a thiol, which can quickly activate an intramolecular arylselenoamide (t1/2 < 1 min) to release H2Se efficiently. Furthermore, we leverage this platform to develop the first examples of fluorogenic H2Se donors, which can be used to monitor H2Se release by fluorescence in real time. We anticipate that the well-defined donation chemistries will significantly advance the development of H2Se donors and stimulate further in-depth studies of H2Se biomedicine.

Sepsis is a life-threatening organ dysfunction caused by the dysregulated response of the host to an infection, and treatments are limited. Recently, a novel selenium source, selenium-enriched Cardamine violifolia (SEC) has attracted much attention due to its anti-inflammatory and antioxidant properties, but little is known about its role in the treatment of sepsis. Here, we found that SEC alleviated LPS-induced intestinal damage, as indicated by improved intestinal morphology, and increased disaccharidase activity and tight junction protein expression. Moreover, SEC ameliorated the LPS-induced release of pro-inflammatory cytokines, as indicated by decreased IL-6 level in the plasma and jejunum. Moreover, SEC improved intestinal antioxidant functions by regulating oxidative stress indicators and selenoproteins. In vitro, TNF-α-challenged IPEC-1 cells were examined and showed that selenium-enriched peptides, which are the main functional components extracted from Cardamine violifolia (CSP), increased cell viability, decreased lactate dehydrogenase activity and improved cell barrier function. Mechanistically, SEC ameliorated LPS/TNF-α-induced perturbations in mitochondrial dynamics in the jejunum and IPEC-1 cells. Moreover, CSP-mediated cell barrier function is primarily dependent on the mitochondrial fusion protein MFN2 but not MFN1. Taken together, these results indicate that SEC mitigates sepsis-induced intestinal injury, which is associated with modulating mitochondrial fusion.

Broiler chicks are fast-growing and susceptible to dietary selenium (Se) deficiency. This study sought to reveal the underlying mechanisms of how Se deficiency induces key organ dysfunctions in broilers. Day-old male chicks (n=6 cages/diet, 6 chicks/cage) were fed with a Se-deficient diet (Se-Def, 0.047 mg Se/kg) or the Se-Def+0.3 mg Se/kg (Control, 0.345 mg Se/kg) for 6 weeks. The serum, liver, pancreas, spleen, heart, and pectoral muscle of the broilers were collected at week 6 to assay for Se concentration, histopathology, serum metabolome, and tissue transcriptome. Compared with the Control group, Se deficiency induced growth retardation and histopathological lesions and reduced Se concentration in the five organs. Integrated transcriptomics and metabolomics analysis revealed that dysregulation of immune and redox homeostasis related biological processes and pathways contributed to Se deficiency-induced multiple tissue damage in the broilers. Meanwhile, four metabolites in the serum, daidzein, epinephrine, L-aspartic acid and 5-hydroxyindoleacetic acid, interacted with differentially expressed genes with antioxidative effects and immunity among all the five organs, which contributed to the metabolic diseases induced by Se deficiency. Overall, this study systematically elucidated the underlying molecular mechanisms in the pathogenesis of Se deficiency-related diseases, which provides a better understanding of the significance of Se-mediated heath in animals.

Selenium was one of the essential trace elements that played a pivotal role in human health. Although previous studies have investigated the relationship between selenium and non-alcoholic fatty liver disease (NAFLD) and fibrosis, these findings were still inconclusive. Our study was aimed to explore the association between blood selenium level and NAFLD and advanced liver fibrosis diagnosed by vibration controlled transient elastography (VCTE) in US adults.

All data were extracted from National Health and Nutrition Examination Survey database (2017-2018). Participants were divided into four groups according to quartile of blood selenium level. Liver stiffness and controlled attenuation parameter (CAP) were measured by VCTE. Multiple logistic regression models and subgroup analyses were conducted to determine the association between blood selenium level and NAFLD and advanced liver fibrosis diagnosed by a variety of methods.

A total of 3336 participants were enrolled in main analysis. In multiple logistic regression models, the higher blood selenium level (>205.32, ≤453.62 μg/L) had a significant positive association with NAFLD (β = 1.31). Moreover, high blood selenium level had significantly inversely association to advanced liver fibrosis (β = 0.61). In subgroup analysis, the main inversely correlation between blood selenium and advanced liver fibrosis was found in males with high blood selenium level. Despite dietary selenium intake being adjusted or in different subgroups, the associations between blood selenium level and NAFLD/advanced liver fibrosis remained significant.

This study showed that blood selenium level were positively association with NAFLD among US population. Participants with lower blood selenium level showed a higher percentage of advanced liver fibrosis. Blood selenium is more likely to cause NAFLD and liver fibrosis due to imbalances in selenium homeostasis rather than dietary selenium intake.Key messagesHigh blood selenium level was association with NAFLD diagnosed by vibration controlled transient elastography.Participants with lower blood selenium level had high percentage of advanced liver fibrosis.NAFLD and liver fibrosis are caused by an imbalance of selenium homeostasis, not by dietary selenium intake.

Selenium (Se) is an essential element for human health as it is involved in different physiological functions. Moreover, a great number of Se compounds can be considered potential agents in the prevention and treatment of some diseases. It is widely recognized that Se activity is related to multiple factors, such as its chemical form, dose, and its metabolism. The understanding of its complex biochemistry is necessary as it has been demonstrated that the metabolites of the Se molecules used to be the ones that exert the biological activity. Therefore, the aim of this review is to summarize the recent information about its most remarkable metabolites of acknowledged biological effects: hydrogen selenide (HSe-/H2Se) and methylselenol (CH3SeH). In addition, special attention is paid to the main seleno-containing precursors of these derivatives and their role in different pathologies.

The importance of selenium (Se) in biology and health has become increasingly clear. Hydrogen selenide (H₂Se), the biologically available and active form of Se, is suggested to be an emerging nitric oxide (NO)-like signaling molecule. Nevertheless, the research on H₂Se chemical biology has technique difficulties due to the lack of well-characterized and controllable H₂Se donors under physiological conditions, as well as a robust assay for direct H₂Se quantification. Motivated by these needs, here, we demonstrate that selenocyclopropenones and selenoamides are tunable donor motifs that release H₂Se upon reaction with cysteine (Cys) at pH 7.4 and that structural modifications enable the rate of Cys-mediated H₂Se release to be tuned. We monitored the reaction pathways for the H₂Se release and confirmed H₂Se generation qualitatively using different methods. We further developed a quantitative assay for direct H₂Se trapping and quantitation in an aqueous solution, which should also be operative for investigating future H₂Se donor motifs. In addition, we demonstrate that arylselenoamide has the capability of Cys-mediated H₂Se release in cellular environments. Importantly, mechanistic investigations and density functional theory (DFT) calculations illustrate the plausible pathways of Cys-activated H₂Se release from arylselenoamides in detail, which may help understand the mechanistic issues of the H₂S release from pharmacologically important arylthioamides. We anticipate that the well-defined chemistries of Cys-activated H₂Se donor motifs will be useful for studying Se biology and for development of new H₂Se donors and bioconjugate techniques.