Intervertebral disc degeneration (IDD) is a major cause of chronic low back pain, involving lipid dysregulation and cellular senescence in nucleus pulposus (NP) cells. However, the relationship between lipid accumulation and cellular senescence in IDD remain unclear. This study aims to investigate whether lipid accumulation promotes NP cell senescence and explore the role of LAMP1-mediated lipophagy in mitigating these effects.

Human and rat NP tissue samples were analyzed for lipid levels and senescence markers, including p16, p21 and p53. NP cells were treated with palmitic acid (PA) to induce lipid accumulation. Multi-omics analysis and machine learning were used to identify LAMP1 as a key regulator of lipid metabolism in NP cells. The effects of LAMP1 overexpression on lipid clearance and cellular senescence were evaluated in vitro. The natural compound sulforaphane (SFN) was applied to stimulate LAMP1-mediated lipophagy. LAMP1 knockdown was used to assess the role of LAMP1 in SFN-induced lipophagy and its impact on lipid accumulation and senescence. In vivo, SFN treatment was administered to rats with IDD induced by needle puncture. MRI, X-ray, and histological analysis were performed to evaluate the effects of SFN on disc degeneration, lipid accumulation, and senescence in NP tissue.

Excessive lipid accumulation in degenerated NP tissues was observed, along with increased expression of senescence markers. Further experiments demonstrated that LAMP1 overexpression reduced lipid accumulation and senescence in NP cells. Notably, the natural compound sulforaphane enhanced LAMP1-mediated lipophagy, promoting lipid clearance and reducing senescence. In vivo, sulforaphane treatment in a rat IDD model reduced lipid accumulation and delayed IDD.

Our findings suggest that LAMP1-mediated lipophagy plays a crucial role in inhibiting NP cell senescence and that sulforaphane can slow the progression of IDD by activating LAMP1.

This study indicates that the therapeutic effects of sulforaphane in mitigating lipid accumulation and senescence can provide an effective treatment strategy for delaying the progression of IDD in the future.

The prevalence of autism spectrum disorder (ASD), a neurodevelopmental disorder characterized by impairments in social communication and restricted/repetitive behavioral patterns, has increased significantly over the past few decades. The etiology of ASD involves a highly complex interplay of genetic, neurobiological, and environmental factors, contributing to significant heterogeneity in its clinical phenotype. In the evolving landscape of ASD research, increasing evidence suggests that oxidative stress, resulting from both intrinsic and extrinsic factors, may be a crucial pathophysiological driver in ASD, influencing neurodevelopmental processes that underlie behavioral abnormalities. Elevated levels of oxidative stress biomarkers, including lipid peroxides, protein oxidation products, and DNA damage markers, alongside deficient antioxidant enzyme activity, have been consistently linked to ASD. This may be attributed to dysregulated activity of nuclear factor erythroid 2-related factor 2 (NRF2), a pivotal transcription factor that maintains cellular redox homeostasis by orchestrating the expression of genes involved in antioxidant defenses. Here, we summarize the converging evidence that redox imbalance in ASD may result from NRF2 dysregulation, leading to reduced expression of its target genes. We also highlight the most promising antioxidant compounds under investigation, which may restore NRF2 activity and ameliorate ASD behavioral symptoms.

Mastitis is a significant concern in both human and animal medicine. The causative agent S. aureus is one of the most challenging pathogens responsible for mastitis, and the rise of its antibiotic resistance underscores the need for alternative therapies. The SESN2/Nrf2 pathway, owing to its pivotal role in regulating cellular antioxidant defenses, which are critically disrupted during ferroptosis, has recently received less attention. However, whether C3G targets the SESN2/Nrf2 pathway remains unclear, which provides a dual mechanism for treating S. aureus-induced mastitis by reducing inflammation and safeguarding mammary epithelial cells (MECs) from ferroptosis. Using a mouse mastitis and MECs model, we investigated the therapeutic potential of C3G in alleviating S. aureus-induced mastitis, focusing specifically on its role in inhibiting inflammation and modulating ferroptosis through the SESN2/Nrf2 pathway. The results demonstrated the potential antimicrobial effects of C3G against S. aureus and MRSA, suppressed inflammatory responses by downregulating pro-inflammatory markers (IL-1β, IL-6, and TNF-α), and inhibited STAT2/STAT3 signaling. Furthermore, C3G modulates ferroptosis by activating the SESN2/Nrf2 pathway, reducing oxidative stress, and protecting mammary epithelial cells from ferroptosis-induced damage. This comprehensive approach highlights C3G's potential as a novel therapeutic strategy for managing mastitis, offering an effective alternative to antibiotics in addressing both bacterial infection and inflammation.

Salinity stress severely impacts agricultural productivity by inhibiting seed germination in rice. Finding plant-derived products that can improve germination under salinity stress offers an environment-friendly approach. This study investigates the protective role of exogenous sulforaphane (SFN) in enhancing rice seed germination under salinity stress. We compared the responses of salt-sensitive (LLY-7108) and salt-tolerant (G-16) rice varieties to determine the effectiveness of SFN treatment with 150 mM NaCl stress, where LLY-7108 showed significantly higher germination inhibition under salt stress compared to G-16, while SFN application notably improved germination rate of LLY-7108 with minimal effects on G-16. Our investigation revealed that salt stress increased Na+ accumulation and Na+/K+ ratio in rice seeds, leading to elevated levels of reactive oxygen species (H2O2, O2-) and malonaldehyde (MDA). This ionic imbalance disrupted hormone homeostasis, decreasing gibberellic acid (GA) while increasing abscisic acid (ABA) levels, and inhibited α-amylase activity, thereby reducing starch hydrolysis. SFN treatment effectively mitigated these adverse effects by enhancing OsHKT1;1 and OsHKT1;5 expressions, which reduced Na+ uptake and improved ion balance. Additionally, SFN enhanced antioxidant enzyme activities (superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), regulated ABA biosynthesis genes (OsNCED1, OsNCED3), improved α-amylase activity, and increased soluble sugar content; besides it improved the cell ultrastructure and chloroplast structure versus salt treatment. These findings highlight SFN's protective role in rice germination under salinity stress through ion homeostasis regulation, reactive oxygen species (ROS) scavenging, hormone balance restoration, and enhanced starch metabolism. SFN offers a practical solution for improving direct-seeded rice germination in saline soils.

The brain accounts for about 2% of the body's weight, but it consumes about 20% of the body's energy at rest, primarily derived from ATP produced in mitochondria. The brain thus has a high mitochondrial density in its neurons because of its extensive energy demands for maintaining ion gradients, neurotransmission, and synaptic activity. The brain is also extremely susceptible to damage and dysregulation caused by inflammation (neuroinflammation) and oxidative stress. Many systemic challenges to the brain can be mitigated by the phytochemical sulforaphane (SF), which is particularly important in supporting mitochondrial function. SF or its biogenic precursor glucoraphanin, from broccoli seeds or sprouts, can confer neuroprotective and cognitive benefits via diverse physiological and biochemical mechanisms. SF is able to cross the blood-brain barrier as well as to protect it, and it mitigates the consequences of destructive neuroinflammation. It also protects against the neurotoxic effects of environmental pollutants, combats the tissue and cell damage wrought by advanced glycation end products (detoxication), and supports healthy glucose metabolism. These effects are applicable to individuals of all ages, from the developing brains in periconception and infancy, to cognitively, developmentally, and traumatically challenged brains, to those in later life as well as those who are suffering with multiple chronic conditions including Parkinson's and Alzheimer's diseases.

Oxidative stress, a pivotal driver of neurodegenerative diseases, results from an imbalance between the generation of reactive oxygen species (ROS) and cellular antioxidant defenses. This review provides a comprehensive analysis of key oxidative stress sources, focusing on NADPH oxidase (NOX) hyperactivity and mitochondrial Uncoupling Protein (UCP) downregulation. Critically, we examine the therapeutic potential of phytochemicals in mitigating NOX-mediated ROS generation through direct enzyme inhibition, including impacts on NOX subunit assembly and gene expression. Furthermore, we explore the ability of phytochemicals to bolster cellular antioxidant defenses by activating the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway, elucidating the upregulation of antioxidant genes, such as GPx, SOD, CAT, and HO-1. This review expands beyond confined overviews; emphasizes specific molecular interactions between phytochemicals and target proteins, including NOX isoforms; and provides an in-depth analysis of the specific antioxidant genes upregulated via Nrf2. This approach aims to pave the way for targeted and translatable therapeutic strategies in neurodegenerative diseases. Ultimately, this review illuminates the intricate molecular dynamics of oxidative stress in neurodegenerative diseases; underscores the potential of phytochemicals to restore redox homeostasis and reverse pathological conditions through precise modulation of key signaling pathways.

Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-activated transcription factor regulating cellular defense against oxidative stress, thereby playing a pivotal role in maintaining cellular homeostasis. Its dysregulation is implicated in the progression of a wide array of human diseases, making NRF2 a compelling target for therapeutic interventions. However, challenges persist in drug discovery and safe targeting of NRF2, as unresolved questions remain especially regarding its context-specific role in diseases and off-target effects. This comprehensive review discusses the dualistic role of NRF2 in disease pathophysiology, covering its protective and/or destructive roles in autoimmune, respiratory, cardiovascular, and metabolic diseases, as well as diseases of the digestive system and cancer. Additionally, we also review the development of drugs that either activate or inhibit NRF2, discuss main barriers in translating NRF2-based therapies from bench to bedside, and consider the ways to monitor NRF2 activation in vivo.

Sulforaphane (SFN), a natural compound found in cruciferous vegetables, possesses well-documented antitumor properties. However, the precise functions and mechanisms of SFN in cancer suppression remain poorly understood. Here we provide evidence to demonstrate that SFN exerts more pronounced antitumor effects in immunocompetent mice compared to immunodeficient mice, suggesting the involvement of the host immune system in SFN-mediated tumor suppression. Furthermore, we reveal that SFN primarily acts through CD8+ cytotoxic T lymphocytes (CTLs) to enhance antitumor immunity by blocking the IFN-γ-mediated induction of PD-L1, a critical immune checkpoint receptor expressed in cancer cells. Importantly, our findings indicate that the suppression of PD-L1 expression by SFN is independent of the NRF2 protein stabilization pathway. Instead, SFN inhibits IFN-γ-mediated activation of STAT1, a key transcription factor involved in PD-L1 induction. Mechanistically, SFN covalently modifies specific cysteine residues (C155 and C174) on STAT1, resulting in the inhibition of its transcriptional activity. Notably, SFN-mediated downregulation of PD-L1 contributes to its antitumor immune effects, as demonstrated by enhanced anti-CTLA-4-mediated cytotoxicity. These findings indicate that SFN's antitumor effect extends beyond its direct cytotoxic properties, as it also actively engages the host immune system. This underscores SFN's immense potential as an immune-modulating agent in cancer therapy.

Aging is associated with the decline of tissue and cellular functions, which can promote the development of age-related diseases like cancer, cardiovascular disease, neurodegeneration, and disorders of the musculoskeletal and immune systems. Healthspan is the length of time an individual is in good health and free from chronic diseases and disabilities associated with aging. Two modifiable factors that can influence healthspan, promote healthy aging, and prevent the development of age-related diseases, are diet and microbiota in the gastrointestinal tract (gut microbiota). This review will discuss how dietary phytochemicals and gut microbiota can work in concert to promote a healthy gut and healthy aging. First, an overview is provided of how the gut microbiota influences healthy aging through its impact on gut barrier integrity, immune function, mitochondria function, and oxidative stress. Next, the mechanisms by which phytochemicals effect gut health, inflammation, and nurture a diverse and healthy microbial composition are discussed. Lastly, we discuss how the gut microbiota can directly influence health by producing bioactive metabolites from phytochemicals in food like urolithin A, equol, hesperetin, and sulforaphane. These and other phytochemical-derived microbial metabolites that may promote healthspan are discussed. Importantly, an individual's capacity to produce health-promoting microbial metabolites from cruciferous vegetables, berries, nuts, citrus, and soy products will be dependent on the specific bacteria present in the individual's gut.

The Qidong Liver Cancer Institute (QDLCI) and the Qidong Cancer Registry were established in 1972 with input from doctors, other medical practitioners, and non-medical investigators arriving from urban centers such as Shanghai and Nanjing. Medical teams were established to quantify the extent of primary liver cancer in Qidong, a corn-growing peninsula on the north side of the Yangtze River. High rates of liver cancer were documented and linked to several etiologic agents, including aflatoxins. Local corn, the primary dietary staple, was found to be consistently contaminated with high levels of aflatoxins, and bioassays using this corn established its carcinogenicity in ducks and rats. Observational studies noted a positive association between levels of aflatoxin in corn and incidence of liver cancer across townships. Biomarker studies measuring aflatoxin B1 and its metabolite aflatoxin M1 in biofluids reflected the exposures. Approaches to decontamination of corn from aflatoxins were also studied. In 1993, investigators from Johns Hopkins University were invited to visit the QDLCI to discuss chemoprevention studies in some townships. A series of placebo-controlled clinical trials were conducted using oltipraz (a repurposed drug), chlorophyllin (an over-the-counter drug), and beverages prepared from 3-day-old broccoli sprouts (rich in the precursor phytochemical for sulforaphane). Modulation of biomarkers of aflatoxin DNA and albumin adducts established proof of principle for the efficacy of these agents in enhancing aflatoxin detoxication. Serendipitously, by 2012, aflatoxin exposures quantified using biomarker measurements documented a many hundred-fold reduction. In turn, the Cancer Registry documents that the age-standardized incidence rate of liver cancer is now 75% lower than that seen in the 1970s. This reduction is seen in Qidongese who have never received the hepatitis B vaccination. Aflatoxin mitigation driven by economic changes switched the dietary staple of contaminated corn to rice coupled with subsequent dietary diversity leading to lower aflatoxin exposures. This 50-year effort to understand the etiology of liver cancer in Qidong provides the strongest evidence for aflatoxin mitigation as a public health strategy for reducing liver cancer burden in exposed, high-risk populations. Also highlighted are the challenges and successes of international team science to solve pressing public health issues.

Ulcerative colitis (UC) can cause severe oxidative stress in the colon, which can lead to tissue damage and an imbalance in the normal gut microbiota. Ellagic acid (EA) is one of the main types of plant polyphenols with improved pharmacological effects such as antioxidant, anti-inflammatory, and antibacterial properties. However, currently, the studies on the impact of EA on the gut microbiota and its potential to alleviate UC in mice through the ROS/NLRP3 pathway are limited. In this study, dextran sodium sulfate (DSS) was used to construct a UC mouse model, which was then treated with EA as an intervention for UC. The results revealed that EA alleviated the trend of liver, spleen, and weight changes in UC mice and improved colon oxidative stress, inflammation, and pathological damage. Mechanistically, DSS-induced UC indicated a significant increase in ROS/NLRP3 pathway-related factors, whereas EA intervention activated the Nrf2 pathway to reduce these factors. Furthermore, the DSS group had a reduced abundance of Firmicutes (59.02%) and an increased abundance of Bacteroides and Proteobacterium by 1.8 times and 10.16%; however, EA intervention reversed these changes, thus alleviating UC. The findings of this study revealed that EA could significantly enhance the composition of gut microbiota in UC and reduce the inflammatory response, colonic damage as well as oxidative stress caused by DSS by regulating the ROS/NLRP3 pathway. These results provide novel perspectives on the prevention and treatment strategies of UC and highlight the therapeutic benefits of EA in managing colitis.

Helicobacter pylori (Hp) infection is highly prevalent globally and poses a significant public health challenge due to its link with chronic gastritis, peptic ulcers, and gastric malignancies. Hp's persistence within the gastric environment, particularly in case of infection with virulent strains, triggers chronic inflammatory responses and mucosal damage. Antibiotic therapy is the primary approach for Hp eradication, but antibiotic resistance and adverse effects hinder treatment efficacy. Emerging evidence suggests that Brassicaceae-derived metabolites could serve as adjunctive therapy for Hp infection, offering potential antimicrobial and anti-inflammatory benefits.

A systematic literature review was conducted following PRISMA guidelines to assess the impact of Brassicaceae-rich diets on Hp infection control. Searches were performed in MEDLINE PubMed, Web of Science, and the Cochrane Library until 18 October 2023, without language or date restrictions. Eligible studies meeting PICOS criteria were included, encompassing populations infected with Hp or Hp-infected human cell cultures, interventions involving Brassicaceae consumption or its bioactive molecules, and outcomes related to Hp infection control, antibiotic therapy interactions, reduction of antibiotic side effects, and inflammation mitigation. Animal studies, cell line experiments, reviews unrelated to the research objectives, and studies on Hp-related gastric cancer were excluded.

Available evidence indicates that Brassicaceae consumption exhibits the potential to reduce Hp colonization but achieving complete eradication of the pathogen remains challenging. Conflicting results regarding the efficacy of broccoli in Hp treatment emerge, with certain investigations suggesting limited effectiveness. Other studies point to a potential for heightened eradication rates when combined with standard triple therapy. Furthermore, promising outcomes are observed with broccoli extract supplements, indicating their role in mitigating Hp-induced gastric mucosal damage. In fact, it is noteworthy that sulforaphane and its derivatives manifest notable reductions in pro-inflammatory markers, indicative of their anti-inflammatory properties. Adverse events associated with antibiotic therapy seem unaffected by sulforaphane derivatives or probiotics. However, individual responses to these treatments vary, underscoring the unpredictability of their efficacy in ameliorating antibiotic therapy-related side effects.

Our systematic review highlights the potential of Brassicaceae-rich diets as adjunctive therapy for Hp infection, offering synergistic interactions with antibiotics and possibly mitigating antibiotic side effects and inflammation. Further research, particularly well-designed randomized trials, is warranted to elucidate the therapeutic efficacy and optimal utilization of Brassicaceae-derived metabolites in managing human Hp-related diseases.

Preclinical modelling is a crucial component of advancing the understanding of cancer biology and therapeutic development. Several models exist for understanding the pathobiology of bladder cancer and evaluating therapeutics. N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced bladder cancer is a commonly used model that recapitulates many of the features of human disease. Particularly in mice, BBN is a preferred laboratory model owing to a high level of reproducibility, high genetic fidelity to the human condition, and its relative ease of use. However, important aspects of the model are often overlooked in laboratory studies. Moreover, the advent of new models has yielded a variety of methodologies that complement the use of BBN. Toxicokinetics, histopathology, molecular genetics and sex can differ between available models and are important factors to consider in bladder cancer modelling.

This study aimed to investigate the therapeutic effects of sulforaphane and the role of the Nrf2-Keap1/HO-1/ROS pathway in AngII-induced oxidative stress in podocyte injury.

Mouse mpc5 podocytes were divided into four groups: control (Con), AngII, AngII + sulforaphane (AngII + SFN), and control + sulforaphane (Con + SFN). Western blotting was used to detect protein expression of Nrf2-Keap1, antioxidant enzyme HO-1, and apoptosis-related proteins. ROS levels were measured using a ROS assay kit, and cell survival and viability were assayed using the CCK-8 kit. Molecular interactions between Nrf2 and sulforaphane were analyzed computationally.

Compared with the Con group, podocytes treated with AngII alone exhibited inhibited proliferation, reduced cell viability, lower Bcl-2 expression, and higher cleaved caspase 3 expression. In the presence of sulforaphane, AngII group showed a mild inhibition on podocyte proliferation but did not induce the aforementioned changes in Bcl-2 and cleaved caspase 3 expression. Similarly, compared to the Con group, AngII treatment alone had lower Nrf2 expression and higher Keap1 expression in podocytes, accompanied by a significant decrease in ROS content. However, in the presence of sulforaphane, AngII failed to induce increases in Nrf2 and a decrease in Keap1 expression, as well as ROS levels. Furthermore, cells treated with sulforaphane exhibited higher HO-1 levels than control cells, and co-incubation with AngII did not alter HO-1 levels. Computational modeling revealed hydrophobic interactions between sulforaphane and the amino acid LYS-462 of Nrf2, as well as hydrogen bonding with amino acid HIS-465. The binding score between sulforaphane and Nrf2 was -4.7.

Sulforaphane alleviated AngII-induced podocyte oxidative stress injury via the Nrf2-Keap1/HO-1/ROS pathway, providing new insights into therapeutic compounds for mitigating chronic kidney disease.

Cumulative evidence has verified that persistent oxidative stress is involved in the development of various chronic diseases, including pulmonary, neurodegenerative, kidney, cardiovascular, and liver diseases, as well as cancers. Nuclear factor erythroid 2-related factor 2 (Nrf2) plays a pivotal role in regulating cellular oxidative stress and inflammatory reactions, making it a focal point for disease prevention and treatment strategies. Natural products are essential resources for discovering leading molecules for new drug research and development. In this review, we comprehensively outlined the progression of the knowledge on the Nrf2 pathway, Nrf2 activators in clinical trials, the naturally-derived Nrf2 modulators (particularly from 2014-present), as well as their effects on the pathogenesis of chronic diseases.

Inflammatory diseases, including psoriasis, atherosclerosis, rheumatoid arthritis, and ulcerative colitis, are characterized by persistent inflammation. Moreover, the existing treatments for inflammatory diseases only provide temporary relief by controlling symptoms, and treatments of unstable and expensive. Therefore, new therapeutic solutions are urgently needed to address the underlying causes or symptoms of inflammatory diseases. Inflammation frequently coincides with a high level of (reactive oxygen species) ROS activation, serving as a fundamental element in numerous physiological and pathological phenotypes that can result in serious harm to the organism. Given its pivotal role in inflammation, oxidative stress, and ferroptosis, ROS represents a focal node for investigating the (nuclear factor E2-related factor 2) Nrf2 pathway and ferroptosis, both of which are intricately linked to ROS. Ferroptosis is mainly triggered by oxidative stress and involves iron-dependent lipid peroxidation. The transcription factor Nrf2 targets several genes within the ferroptosis pathway. Recent studies have shown that Nrf2 plays a significant role in three key ferroptosis-related routes, including the synthesis and metabolism of glutathione/glutathione peroxidase 4, iron metabolism, and lipid processes. As a result, ferroptosis-related treatments for inflammatory diseases have attracted much attention. Moreover, drugs targeting Nrf2 can be used to manage inflammatory conditions. This review aimed to assess ferroptosis regulation mechanism and the role of Nrf2 in ferroptosis inhibition. Therefore, this review article may provide the basis for more research regarding the treatment of inflammatory diseases through Nrf2-inhibited ferroptosis.

There are different stress resistance among different breeds of pigs. Changes in intestinal stem cells (ISCs) are still unclear among various breeds of piglets after early weaning. In the current study, Taoyuan Black and Duroc piglets were slaughtered at 21 days of age (early weaning day) and 24 days of age (3 days after early weaning) for 10 piglets in each group. The results showed that the rate of ISC-driven epithelial renewal in local Taoyuan Black pigs hardly changed after weaning for 3 days. However, weaning stress significantly reduced the weight of the duodenum and jejunum in Duroc piglets. Meanwhile, the jejunal villus height, tight junction-related proteins (ZO-1, Occludin, and Claudin1), as well as the trans-epithelial electrical resistance (TEER) values, were down-regulated after weaning for 3 days in Duroc piglets. Moreover, compared with Unweaned Duroc piglets, the numbers of Olfm4+ ISC cells, PCNA+ mitotic cells, SOX9+ secretory progenitor cells, and Villin+ absorptive cells in the jejunum were reduced significantly 3 days after weaning. And ex vivo jejunal crypt-derived organoids exhibited growth disadvantages in weaned Duroc piglets. Notably, the Keap1/Nrf2 signaling activities and the expression of HO-1 were significantly depressed in weaned Duroc piglets compared to Unweaned Duroc piglets. Thus, we can conclude that ISCs of Duroc piglets were more sensitive to weaning stress injury than Taoyuan Black piglets, and Keap1/Nrf2 signaling is involved in this process.

Few therapeutic options are available to treat COVID-19. The KEAP1/NRF2 pathway, the major redox-responsive pathway, has emerged as a potential therapeutic target for COVID-19 as it regulates redox homeostasis and inflammation that are altered during SARS-CoV-2 infection. Here, we characterized the effects of NRF2-agonist Sulfodyne®, a stabilized natural Sulforaphane, in cellular and animal models of SARS-CoV-2 infection. In pulmonary or colonic epithelial cell lines, Sulfodyne® elicited a more efficient inhibition of SARS-CoV-2 replication than NRF2-agonists DMF and CDDO. This antiviral activity was not dependent on NRF2 but was associated with the regulation of several metabolic pathways, including the inhibition of ER stress and mTOR signaling, which are activated during SARS-CoV-2 infection. Sulfodyne® also decreased SARS-CoV-2 mediated inflammatory responses by inhibiting the delayed induction of IFNB1 and type I IFN-stimulated genes in infected epithelial cell lines and by reducing the activation of human by-stander monocytes recruited after SARS-CoV-2 infection. In K18-hACE2 mice infected with SARS-CoV-2, Sulfodyne® treatment reduced both early lung viral load and disease severity by fine-tuning IFN-beta levels. Altogether, these results provide evidence for multiple mechanisms that underlie the antiviral and anti-inflammatory activities of Sulfodyne® and pinpoint Sulfodyne® as a potent therapeutic agent against pathogenic effects of SARS-CoV-2 infection.

Autism is a neurodevelopmental disorder, the prevalence of which has increased dramatically in the United States over the past two decades. It is characterized by stereotyped behaviors and impairments in social interaction and communication. In this paper, we present evidence that autism can be viewed as a PIN1 deficiency syndrome. Peptidyl-prolyl cis/trans isomerase, NIMA-Interacting 1 (PIN1) is a peptidyl-prolyl cis/trans isomerase, and it has widespread influences in biological organisms. Broadly speaking, PIN1 deficiency is linked to many neurodegenerative diseases, whereas PIN1 over-expression is linked to cancer. Death-associated protein kinase 1 (DAPK1) strongly inhibits PIN1, and the hormone melatonin inhibits DAPK1. Melatonin deficiency is strongly linked to autism. It has recently been shown that glyphosate exposure to rats inhibits melatonin synthesis as a result of increased glutamate release from glial cells and increased expression of metabotropic glutamate receptors. Glyphosate's inhibition of melatonin leads to a reduction in PIN1 availability in neurons. In this paper, we show that PIN1 deficiency can explain many of the unique morphological features of autism, including increased dendritic spine density, missing or thin corpus callosum, and reduced bone density. We show how PIN1 deficiency disrupts the functioning of powerful high-level signaling molecules, such as nuclear factor erythroid 2-related factor 2 (NRF2) and p53. Dysregulation of both of these proteins has been linked to autism. Severe depletion of glutathione in the brain resulting from chronic exposure to oxidative stressors and extracellular glutamate leads to oxidation of the cysteine residue in PIN1, inactivating the protein and further contributing to PIN1 deficiency. Impaired autophagy leads to increased sensitivity of neurons to ferroptosis. It is imperative that further research be conducted to experimentally validate whether the mechanisms described here take place in response to chronic glyphosate exposure and whether this ultimately leads to autism.

Sulforaphane (SFN), found in cruciferous vegetables, is a known activator of NRF2 (master regulator of cellular antioxidant responses). Patients with chronic kidney disease (CKD) present an imbalance in the redox state, presenting reduced expression of NRF2 and increased expression of NF-κB. Therefore, this study aimed to evaluate the effects of SFN on the mRNA expression of NRF2, NF-κB and markers of oxidative stress in patients with CKD. Here, we observed a significant increase in the mRNA expression of NRF2 (p = 0.02) and NQO1 (p = 0.04) in the group that received 400 μg/day of SFN for 1 month. Furthermore, we observed an improvement in the levels of phosphate (p = 0.02), glucose (p = 0.05) and triglycerides (p = 0.02) also in this group. On the other hand, plasma levels of LDL-c (p = 0.04) and total cholesterol (p = 0.03) increased in the placebo group during the study period. In conclusion, 400 μg/day of SFN for one month improves the antioxidant system and serum glucose and phosphate levels in non-dialysis CKD patients.

Glucosinolate-derived isothiocyanates are valuable for human health as they exert health promoting effects. As thermal food processing could affect their levels in a structure dependent way, the stability and reactivity of 12 Brassicaceae isothiocyanates during aqueous heating at 100 °C and pH 5-8 were investigated. The formation of their corresponding amines and N,N'-dialk(en)yl thioureas was quantified. Further, the potential to form odor active compounds was investigated by HRGC-MS-olfactometry. A strong structure-reactivity relationship was found and shorter side chains and electron withdrawing groups increase the reactivity of isothiocyanates. 3-(Methylsulfonyl)-propyl isothiocyanate was least stable. The main products are the corresponding amines (up to 69% recovery) and formation of N,N'-dialk(en)yl thioureas is only relevant at neutral to basic pH values. Apart from allyl isothiocyanate also 3-(methylthio)propyl isothiocyanate is precursor to many sulfur-containing odor active compounds. Thus, the isothiocyanate-structure affects their levels but also contributes to the flavor of boiled Brassicaceae vegetables.

Nutrition has been increasingly recognized for its use in mental health. Depression is commonly observed in patients with chronic liver disease (CLD). Building on our recent findings of depression-like behaviors in mice with hepatic ischemia/reperfusion (HI/R) injury, mediated by the gut-liver-brain axis, this study explored the potential influence of dietary sulforaphane glucosinolate (SGS) on these behaviors. Behavioral assessments for depression-like behaviors were conducted 7 days post either sham or HI/R injury surgery. Dietary intake of SGS significantly prevented splenomegaly, systemic inflammation, depression-like behaviors, and downregulation of synaptic proteins in the prefrontal cortex (PFC) of HI/R-injured mice. Through 16S rRNA analysis and untargeted metabolomic analyses, distinct bacterial profiles and metabolites were identified between control + HI/R group and SGS + HI/R group. Correlations were observed between the relative abundance of gut microbiota and both behavioral outcomes and blood metabolites. These findings suggest that SGS intake could mitigate depression-like phenotypes in mice with HI/R injury, potentially through the gut-liver-brain axis. Additionally, SGS, found in crucial vegetables like broccoli, could offer prophylactic nutritional benefits for depression in patients with CLD.

Sulforaphane (SFN) is a dietary isothiocyanate, derived from glucoraphanin, present in cruciferous vegetables belonging to the Brassica genus. It is a biologically active phytochemical that acts as a nuclear factor erythroid 2-related factor 2 (Nrf2) inducer. Thus, it has been reported to have multiple protective functions including anticancer responses and protection against a toxic agent's action.

The present work systematically reviewed and synthesised the protective properties of sulforaphane against a toxic agent. This review reveals the mechanism of the action of SFN in each organ or system.

The PRISMA guideline was followed in this sequence: researched literature, organised retrieved documents, abstracted relevant information, assessed study quality and bias, synthesised data, and prepared a comprehensive report. Searches were conducted on Science Direct and PubMed using the keywords "Sulforaphane" AND ("protective effects" OR "protection against").

Reports showed that liver and the nervous system are the target organs on which attention was focused, and this might be due to the key role of oxidative stress in liver and neurodegenerative diseases. However, protective activities have also been demonstrated in the lungs, heart, immune system, kidneys, and endocrine system. SFN exerts its protective effects by activating the Nrf2 pathway, which enhances antioxidant defenses and reduces oxidative stress. It also suppresses inflammation by decreasing interleukin production. Moreover, SFN inhibits apoptosis by preventing caspase 3 cleavage and increasing Bcl2 levels. Overall, SFN demonstrates multifaceted mechanisms to counteract the adverse effects of toxic agents.

SFN has potential clinical applications as a chemoprotective agent. Nevertheless, more studies are necessary to set the safe doses of SFN in humans.

The relationship between nuclear factor erythroid 2-related factor 2 (Nrf2) and phytocannabinoids/endocannabinoids (pCBs/eCBs) has been investigated in a variety of models of peripheral illnesses, with little clarification on their interaction within the central nervous system (CNS). In this context, evidence suggests that the Nrf2-pCBs/eCBS interaction is relevant in modulating peroxidation processes and the antioxidant system. Nrf2, one of the regulators of cellular redox homeostasis, appears to have a protective role toward damaging insults to neurons and glia by enhancing those genes involved in the regulation of homeostatic processes. Specifically in microglia and macroglia cells, Nrf2 can be activated, and its signaling pathway modulated, by both pCBs and eCBs. However, the precise effects of pCBs and eCBs on the Nrf2 signaling pathway are not completely elucidated yet, making their potential clinical employment still not fully understood.

Chronic inflammation-induced diseases (CID) are the dominant cause of death worldwide, contributing to over half of all global deaths. Sulforaphane (SFN) derived from cruciferous vegetables has been extensively studied for its multiple functional benefits in alleviating CID. This work comprehensively reviewed the biosynthesis, metabolism, bioavailability, delivery, health benefits, and applications of SFN and its potential mechanisms against CID (e.g., cancer, obesity, type 2 diabetes, et al.), and neurological disorders based on a decade of research. SFN exerts its biological functions through the hydrolysis of glucosinolates by gut microbiota, and exhibits rapid metabolism and excretion characteristics via metabolization of mercapturic acid pathway. Microencapsulation is an important way to improve the stability and targeted delivery of SFN. The health benefits of SNF against CID are attributed to the multiple regulatory mechanisms including modulating oxidative stress, inflammation, apoptosis, immune response, and intestinal homeostasis. The clinical applications of SFN and related formulations show promising potential; however, further exploration is required regarding the sources, dosages, toxicity profiles, and stability of SFN. Together, SFN is a natural product with great potential for development and application, which is crucial for the development of functional food and pharmaceutical industries.

Sargassum horneri (SH) is widely consumed as a healthy seaweed food in the Asia-Pacific region. However, the bioactive components contributing to its biological activity remain unknown. Herein, we optimized multifrequency ultrasonic-assisted extraction conditions to achieve higher antioxidant activity using a response surface methodology and an artificial neural network. High-resolution mass spectrometry (HRMS; negative mode) was used to tentatively identify the secondary metabolites in the optimized SH extract, which were further tested against oxidative stress in RAW264.7 cells. Additionally, the identified compounds were analyzed in silico to determine their binding energies with the Keap1 protein (4L7B). We identified 89 compounds using HRMS, among which 19 metabolites (8 polyphenolics, 2 flavonoids, 2 lignans, 2 terpenes, 2 tannins, 2 sulfolipids, and 1 phospholipid) were putatively reported for the first time in SH. The in vitro results revealed that optimized SH extract inhibited oxidative stress via the Nrf2/MAPKs/HO-1 pathway in a dose-dependent manner. This result was validated by performing in silico simulation, indicating that sargaquinoic acid and glycitein-7-O-glucuronide had the highest binding energies (-9.20 and -9.52 Kcal/mol, respectively) toward Keap1 (4L7B). This study offers a unique approach for the scientific community to identify potential bioactive compounds by optimizing the multivariant extraction processing conditions, which could be used to develop functional and nutraceutical foods.

Cadmium (Cd) is a heavy metal that is highly toxic to humans and animals. Its adverse effects have been widely associated with mitochondrial alterations. However, there are not many treatments that target mitochondria. This study aimed to evaluate the impact of sulforaphane (SFN) pre-exposure against cadmium chloride (CdCl2)-induced toxicity and mitochondrial alterations in the nematode Caenorhabditis elegans (C. elegans), by exploring the role of the insulin/insulin-like growth factor signaling pathway (IIS). The results revealed that prior exposure to SFN protected against CdCl2-induced mortality and increased lifespan, body length, and mobility while reducing lipofuscin levels. Furthermore, SFN prevented mitochondrial alterations by increasing mitochondrial membrane potential (Δψm) and restoring mitochondrial oxygen consumption rate, thereby decreasing mitochondrial reactive oxygen species (ROS) production. The improvement in mitochondrial function was associated with increased mitochondrial mass and the involvement of the daf-16 and skn-1c genes of the IIS signaling pathway. In conclusion, exposure to SFN before exposure to CdCl2 mitigates toxic effects and mitochondrial alterations, possibly by increasing mitochondrial mass, which may be related to the regulation of the IIS pathway. These discoveries open new possibilities for developing therapies to reduce the damage caused by Cd toxicity and oxidative stress in biological systems, highlighting antioxidants with mitochondrial action as promising tools.

Changes during the production cycle of dairy cattle can leave these animals susceptible to oxidative stress and reduced antioxidant health. In particular, the periparturient period, when dairy cows must rapidly adapt to the sudden metabolic demands of lactation, is a period when the production of damaging free radicals can overwhelm the natural antioxidant systems, potentially leading to tissue damage and reduced milk production. Central to the protection against free radical damage and antioxidant defense is the transcription factor NRF2, which activates an array of genes associated with antioxidant functions and cell survival. The objective of this study was to evaluate the effect that two natural NRF2 modulators, the NRF2 agonist sulforaphane (SFN) and the antagonist brusatol (BRU), have on the transcriptome of immortalized bovine mammary alveolar cells (MACT) using both the RT-qPCR of putative NRF2 target genes, as well as RNA sequencing approaches. The treatment of cells with SFN resulted in the activation of many putative NRF2 target genes and the upregulation of genes associated with pathways involved in cell survival, metabolism, and antioxidant function while suppressing the expression of genes related to cellular senescence and DNA repair. In contrast, the treatment of cells with BRU resulted in the upregulation of genes associated with inflammation, cellular stress, and apoptosis while suppressing the transcription of genes involved in various metabolic processes. The analysis also revealed several novel putative NRF2 target genes in bovine. In conclusion, these data indicate that the treatment of cells with SFN and BRU may be effective at modulating the NRF2 transcriptional network, but additional effects associated with cellular stress and metabolism may complicate the effectiveness of these compounds to improve antioxidant health in dairy cattle via nutrigenomic approaches.

Prostate cancer (PCa) is the second most common solid cancer among men worldwide and the fifth leading cause of cancer-related deaths in men. Sulforaphane (SFN), an isothiocyanate compound, has been shown to exert inhibitory effects on a variety of cancers. However, the biological function of SFN in PCa has not been fully elucidated. The objective of this study was conducted to further investigate the possible underlying mechanism of SFN in PCa using in vitro cell culture and in vivo tumor model experiments.

Cell viability, migration, invasion, and apoptosis were analyzed by Cell Counting Kit-8 (CCK-8), wound healing assay, transwell assay, or flow cytometry. Expression of microRNA (miR)-3919 was detected by quantitative real-time polymerase chain reaction (qRT-PCR) or in situ hybridization assay. Xenograft assay was conducted to validated the antitumor effect of miR-3919. The targeting relationship between miR-3919 and DJ-1 was verified by dual-luciferase reporter assay. The level of DJ-1was measured by qRT-PCR or western blotting (WB).

In the present study, SFN downregulated mRNA and protein expression of DJ-1, an oncogenic gene. Small RNA sequencing analysis and dual-luciferase reporter assay confirmed that microRNA (miR)-3919 directly targeted DJ-1 to inhibition its expression. Furthermore, miR-3919 overexpression impeded viability, migration, and invasion and promoted apoptosis of PCa cells. Tumor growth in nude mice was also inhibited by miR-3919 overexpression, and miR-3919 expression in PCa tissues was lower than that in peritumoral tissues in an in situ hybridization assay. Transfection with miR-3919 inhibitors partially reversed the effects of SFN on cell viability, migration, invasion, and apoptosis.

Overall, the miR-3919/DJ-1 axis may be involved in the effects of SFN on the malignant biological behavior of PCa cells, which might be a new therapeutic target in PCa.

A neurodegenerative disorder (ND) refers to Huntington's disease (HD) which affects memory loss, weight loss, and movement dysfunctions such as chorea and dystonia. In the striatum and brain, HD most typically impacts medium-spiny neurons. Molecular genetics, excitotoxicity, oxidative stress (OS), mitochondrial, and metabolic dysfunction are a few of the theories advanced to explicit the pathophysiology of neuronal damage and cell death. Numerous in-depth studies of the literature have supported the therapeutic advantages of natural products in HD experimental models and other treatment approaches. This article briefly discusses the neuroprotective impacts of natural compounds against HD models. The ability of the discovered natural compounds to suppress HD was tested using either in vitro or in vivo models. Many bioactive compounds considerably lessened the memory loss and motor coordination brought on by 3-nitropropionic acid (3-NP). Reduced lipid peroxidation, increased endogenous enzymatic antioxidants, reduced acetylcholinesterase activity, and enhanced mitochondrial energy generation have profoundly decreased the biochemical change. It is significant since histology showed that therapy with particular natural compounds lessened damage to the striatum caused by 3-NP. Moreover, natural products displayed varying degrees of neuroprotection in preclinical HD studies because of their antioxidant and anti-inflammatory properties, maintenance of mitochondrial function, activation of autophagy, and inhibition of apoptosis. This study highlighted about the importance of bioactive compounds and their semi-synthetic molecules in the treatment and prevention of HD.

The nuclear factor erythroid 2-related factor 2 (NRF2) is a crucial transcription factor that plays a central role in regulating oxidative stress pathways by binding antioxidant response elements, but its involvement in early embryo development remains largely unexplored. In this study, we demonstrated that NRF2 mRNA is expressed in porcine embryos from day 2 to day 7 of development, showing a decrease in abundance from day 2 to day 3, followed by an increase on day 5 and day 7. Comparable levels of NRF2 mRNA were observed between early-cleaving and more developmental competent embryos and late-cleaving and less developmental competent embryos on day 4 and day 5 of culture. Attenuation of NRF2 mRNA significantly decreased development of parthenote embryos to the blastocyst stage. When NRF2-attenuated embryos were cultured in presence of 3.5 mM or 7 mM glucose, development to the blastocyst stage was dramatically decreased in comparison to the control group (15.9% vs. 27.8% for 3.5 mM glucose, and 5.4% vs. 25.3% for 7 mM glucose). Supplementation of melatonin moderately improved the development of NRF2-attenuated embryos cultured in presence of 0.6 mM glucose. These findings highlight the importance of NRF2 in early embryo development, particularly in embryos cultured under metabolically stressful conditions.

Adipose tissue fibrosis has been identified as a novel contributor to the pathomechanism of obesity associated metabolic disorders. Sulforaphane (SFN) has been shown to have an anti-obesity effect. However, the impact of SFN on adipose tissue fibrosis is still not well understood. In this study, obese mice induced by high-fat diets (HFD) were used to examine the effects of SFN on adipose tissue fibrosis. According to the current findings, SFN dramatically enhanced glucose tolerance and decreased body weight in diet-induced-obesity (DIO) mice. Additionally, SFN therapy significantly reduced extracellular matrix (ECM) deposition and altered the expression of genes related to fibrosis. Furthermore, SFN also reduced inflammation and promoted macrophages polarization towards to M2 phenotype in adipose tissue, which protected adipose tissue from fibrosis. Notably, SFN-mediated nuclear factor E2-related factor 2 (Nrf2) activation was crucial in decreasing adipose tissue fibrosis. These results implied that SFN had favorable benefits in adipose tissue fibrosis, which consequently ameliorates obesity-related metabolic problems. Our research provides new treatment strategies for obesity and associated metabolic disorders.

Hyperglycemia is a major risk factor for kidney diseases. Oxidative stress, caused by reactive oxygen species, is a key factor in the development of kidney abnormalities related to hyperglycemia. The nuclear factor erythroid 2-related factor-2 (Nrf2) plays a crucial role in defending cells against oxidative stress by activating genes that produce antioxidants. L-sulforaphane (SFN), a drug that activates Nrf2, reduces damage caused by hyperglycemia. Hyperglycemic Wistar rats and HEK 293 cells maintained in hyperglycemic medium exhibited decreased Nrf2 nuclear translocation and reduced expression and activity of antioxidant enzymes. SFN treatment increased Nrf2 activity and reversed decreased renal function, oxidative stress and cell death associated with hyperglycemia. To investigate mechanisms involved in hyperglycemia-induced reduced Nrf2 activity, we addressed whether Nrf2 is modified by O-linked β-N-acetylglucosamine (O-GlcNAc), a post-translational modification that is fueled in hyperglycemic conditions. In vivo, hyperglycemia increased O-GlcNAc-modified Nrf2 expression. Increased O-GlcNAc levels, induced by pharmacological inhibition of OGA, decreased Nrf2 activity in HEK 293 cells. In conclusion, hyperglycemia reduces Nrf2 activity, promoting oxidative stress, cell apoptosis and structural and functional renal damage. Pharmacological treatment with SFN attenuates renal injury. O-GlcNAcylation negatively modulates Nrf2 activity and represents a potential mechanism leading to oxidative stress and renal damage in hyperglycemic conditions.

In many famous formulas of traditional Chinese medicine (TCM), the rhizome of Ligusticum chuanxiong (L. chuanxiong) is commonly used as an ingredient for promoting blood circulation and resolving blood stasis to treat diabetic nephropathy. However, its material basis and mechanism of action are still needed to be explored.

The aim of this work is to elucidate the potential effective parts (phthalides) of L. chuanxiong responsible for renal protection and to explore the possible mechanism of renal protection.

A method based on column chromatography of macroporous resin was established to enrich an effective part (LCE70), and the composition of LCE70 was identified by HPLC-UV and UPLC-MS/MS methods. Mice model was induced by streptozotocin (STZ) to evaluate the protective effect of LCE70 on diabetic nephropathy (DN). In vitro, the suppressive effect of LCE70 on oxidative damage, inflammation and its mechanism were tested using immunoblot analysis, ELISA, etc. Cellular thermal shift assay (CETSA) was adopted to verify the interaction between the phthalides and the key targets involved in renal injury.

LCE70 displayed therapeutic potential against metabolic disorders, renal dysfunction, and fibrosis in a DN model induced by STZ in mice. Furthermore, it markedly reduced oxidative stress of the kidney in DN mice by activating Nrf2 pathway. Z-ligustilide, the main component of LCE70, reacted with Keap1, and thus promoted Nrf2 dissociating from Keap1 to activate Nrf2 pathway.

LCE70 improved hyperglycemia-induced renal function by enhancing the Nrf2 activation, reducing collagen deposition, and alleviating inflammation and oxidative stress, which suggested its potential as a therapeutic agent for DN.

Patients with chronic kidney disease (CKD) have reduced expression of erythroid nuclear factor-related factor 2 (NRF2) and increased nuclear factor κB (NF-κB). "Food as medicine" has been proposed as an adjuvant therapeutic alternative in modulating these factors. No studies have investigated the effects of sulforaphane (SFN) in cruciferous vegetables on the expression of these genes in patients with CKD.

The study aimed to evaluate the effects of SFN on the expression of NRF2 and NF-κB in patients on hemodialysis (HD).

A randomized, double-blind, crossover study was performed on 30 patients on regular HD. Fourteen patients were randomly allocated to the intervention group (1 sachet/day of 2.5 g containing 1% SFN extract with 0.5% myrosinase) and 16 patients to the placebo group (1 sachet/day of 2.5 g containing corn starch colored with chlorophyll) for 2 months. After a washout period of 2 months, the groups were switched. NRF2 and NF-κB mRNA expression was evaluated by real-time quantitative polymerase chain reaction, and tumor necrosis factor alpha and interleukin-6 levels were quantified by enzyme-linked immunosorbent assay. Malondialdehyde was evaluated as a marker of lipid peroxidation.

Twenty-five patients (17 women, 55 [interquartile range = 19] years and 55 [interquartile range = 74] months on HD) completed the study. There was no significant difference concerning the expression of mRNA NRF2 (P = .915) and mRNA NF-κB (P = .806) after supplementation with SFN. There was no difference in pro-inflammatory and oxidative stress biomarkers.

150 μmol of SFN for 2 months had no antioxidant and anti-inflammatory effect in patients with CKD undergoing HD.

Sulforaphane (SFN) is a bioactive phytonutrient found in cruciferous vegetables. There is a lack of detailed information on the lactational transfer of SFN and SFN metabolites, and potential pharmacological effects on breastfeeding infants. We carried out two maternal supplementation studies in a mouse model, wherein lactating dams received either vehicle, 300 or 600 ppm SFN from postnatal day (PND) 1 to 5, or in a second experiment, vehicle or 600 ppm SFN from PND 1 to 14. The parent compound was only detectable in milk and plasma from dams receiving 600 ppm SFN for five days. The predominant metabolite SFN-N-acetylcysteine (SFN-NAC) was readily detected in milk from dams receiving 300 and 600 ppm SFN for five days or 600 ppm for 14 days. Maternal SFN-NAC plasma levels were elevated in both 600 ppm groups. Maternal hepatic and pulmonary expression of NRF2-related genes, Nqo1, Gsta2, Gstm1, and Gstp1, were significantly increased, generally following a dose-response; however, offspring induction varied. PND5 neonates in the 600-ppm group exhibited significantly elevated expression of Nqo1, Gsta2, and Gstp1 in liver, and Gstm1 and Gstp1 in lung. Findings support maternal dietary supplementation with SFN induces NRF2-related gene expression in neonates via lactational transfer of SFN-NAC. However, NQO1 enzyme activity was not significantly elevated, highlighting the need to optimize dosing strategy. Additionally, in a pilot investigation of lactating women consuming a typical diet, without any purified SFN supplementation, 7 out of 8 breast milk samples showed SFN-NAC above the limit of quantification (LOQ). Notably, the one sample below the LOQ was collected from the only participant who reported no consumption of cruciferous vegetables in the past 24 h. The parent compound was not detected in any of the human breast milk samples. Overall, these data indicate lactational transfer of SFN-NAC at dietary relevant levels. Future studies are needed to evaluate pharmacokinetics and pharmacodynamics of lactational transfer for potential preventive or therapeutic effects in breastfeeding children.

Zinc deficiency can lead to multiple organ damage. In this study, we investigated the effects of zinc deficiency on obesity-related lung damage.

C57BL/6 J mice were fed a diet with differing amounts of zinc and fat over a 6-month period. Palmitic acid was used to stimulate A549 cells to construct a high-fat alveolar epithelial cell model. Western blotting and histopathological staining were performed on animal tissues. Nuclear expression of nuclear factor erythroid 2-related factor 2 (Nrf2) was detected in cultured cells. A reactive oxygen species (ROS) assay kit was used to detect intracellular ROS. Furthermore, Nrf2 siRNA was used to examine zinc deficiency effects on A549 cells.

Pathological results showed significant damage to the lung structure of mice in the high-fat and low-zinc diet group, with a significant increase in the expression of inflammatory (IL-6, TNF-α) and fibrosis (TGFβ1, PAI-1) factors, combined with a decrease in the expression of Nrf2, HO-1 and NQO1 in the antioxidant pathway. In A549 cells, high fat and low zinc levels aggravated ROS production. Western blot and immunofluorescence results showed that high fat and zinc deficiency inhibited Nrf2 expression. After Nrf2-specific knockout in A549 cells, the protective effect of zinc on oxidant conditions induced by high fat was reduced. Phosphorylated Akt and PI3K levels were downregulated on the high-fat and low-zinc group compared with the high-fat group.

Zinc attenuated lung oxidative damage in obesity-related lung injury and Nrf2 activation is one of the important mechanisms of this effect.

Regulating zinc homeostasis through dietary modifications or supplemental nutritional therapy can contribute to the prevention and treatment of obesity-related lung injury.

Open heart surgery is often an unavoidable procedure for the treatment of coronary artery disease. The procedure-associated reperfusion injury affects postoperative cardiac performance and long-term outcomes. We addressed here whether cardioplegia essential for cardiopulmonary bypass surgery activates Nrf2, a transcription factor regulating the expression of antioxidant and detoxification genes. With commonly used cardioplegic solutions, high K+, low K+, Del Nido (DN), histidine-tryptophan-ketoglutarate (HTK), and Celsior (CS), we found that DN caused a significant increase of Nrf2 protein in AC16 human cardiomyocytes. Tracing the ingredients in DN led to the discovery of KCl at the concentration of 20-60 mM capable of significant Nrf2 protein induction. The antioxidant response element (ARE) luciferase reporter assays confirmed Nrf2 activation by DN or KCl. Transcriptomic profiling using RNA-seq revealed that oxidation-reduction as a main gene ontology group affected by KCl. KCl indeed elevated the expression of classical Nrf2 downstream targets, including TXNRD1, AKR1C, AKR1B1, SRXN1, and G6PD. DN or KCl-induced Nrf2 elevation is Ca2+ concentration dependent. We found that KCl decreased Nrf2 protein ubiquitination and extended the half-life of Nrf2 from 17.8 to 25.1 mins. Knocking out Keap1 blocked Nrf2 induction by K+. Nrf2 induction by DN or KCl correlates with the protection against reactive oxygen species generation or loss of viability by H2O2 treatment. Our data support that high K+ concentration in DN cardioplegic solution can induce Nrf2 protein and protect cardiomyocytes against oxidative damage.NEW & NOTEWORTHY Open heart surgery is often an unavoidable procedure for the treatment of coronary artery disease. The procedure-associated reperfusion injury affects postoperative cardiac performance and long-term outcomes. We report here that Del Nido cardioplegic solution or potassium is an effective inducer of Nrf2 transcription factor, which controls the antioxidant and detoxification response. This indicates that Del Nido solution is not only essential for open heart surgery but also exhibits cardiac protective activity.