Expression Of Superoxide Dismutase Research Articles

Efficacy and safety of a SOD1-targeting artificial miRNA delivered by AAV9 in mice are impacted by miRNA scaffold selection

Toxic gain-of-function mutations in superoxide dismutase 1 (SOD1) contribute to approximately 2%-3% of all amyotrophic lateral sclerosis (ALS) cases. Artificial microRNAs (amiRs) delivered by adeno-associated virus (AAV) have been proposed as a potential treatment option to silence SOD1 expression and mitigate disease progression. Primary microRNA (pri-miRNA) scaffolds are used in amiRs to shuttle a hairpin RNA into theendogenous miRNA pathway, but it is unclear whether different primary miRNA (pri-miRNA) scaffolds impact the potency and safety profile of the expressed amiR invivo. In our process to develop an AAV amiR targeting SOD1, we performed a preclinical characterization of two pri-miRNA scaffolds, miR155 and miR30a, sharing the same guide strand sequence. We report that, while the miR155-based vector, compared with the miR30a-based vector, leads to a higher level of the amiR and more robust suppression of SOD1 invitro and invivo, it also presents significantly greater risks for CNS-related toxicities invivo. Despite miR30a-based vector showing relatively lower potency, it can significantly delay the development of ALS-like phenotypes in SOD1-G93A mice and increase survival in a dose-dependent manner. These data highlight the importance of scaffold selection in the pursuit of highly efficacious and safe amiRs for RNA interference gene therapy.

Gut Bacteria Promote Phosphine Susceptibility of Tribolium castaneum by Aggravating Oxidative Stress and Fitness Costs.

Knowledge about resistance mechanisms can provide ideas for pesticide resistance management. Although several studies have unveiled the positive or negative impacts of gut microbes on host pesticide resistance, minimal research is available regarding the association between gut microbes and host phosphine resistance. To explore the influence of gut bacteria on host phosphine susceptibility and its molecular basis, mortality, fitness, redox responses, and immune responses of adult Tribolium castaneum were determined when it was challenged by phosphine exposure and/or gut bacteria inoculation. Five cultivable gut bacteria were excised from a population of phosphine-resistant T. castaneum. Among them, only Enterococcus sp. inoculation significantly promoted host susceptibility to phosphine, while inoculation of any other gut bacteria had no significant effect on host phosphine susceptibility. Furthermore, when T. castaneum was exposed to phosphine, Enterococcus sp. inoculation decreased the female fecundity, promoted host oxidative stress, and suppressed the expression and activity of host superoxide dismutase, catalase, and peroxidase. In the absence of phosphine, Enterococcus sp. inoculation also elicited overactive immune responses in T. castaneum, including the immune deficiency and Toll signaling pathways and the dual oxidase-reactive oxygen species system. These results indicate that Enterococcus sp. likely promotes host phosphine susceptibility by aggravating oxidative stress and fitness costs.

Effect of tamoxifen treatment on catalase (CAT) and superoxide dismutase (SOD) expression and localization in the hen oviduct

The imbalance between free reactive oxygen species (ROS) generation and removal (e.g., by antioxidative enzymes) leads to the damage of important biomolecules and cells. Earlier studies in hens showed that treatment with tamoxifen (TMX; estrogen receptor inhibitor) modulates oxidative stress and causes the reproductive system regression realized by cell apoptosis. The aim of the present study was, therefore, to examine the expression and immunolocalization of the key enzymatic antioxidants, i.e. catalase (CAT) and superoxide dismutase (SOD), in the chicken oviduct following TMX treatment. Laying hens were treated daily with TMX until a pause in egg-laying occurred and then euthanized on day 8 of the experiment. Quantitative real-time PCR and western blot analyses showed the presence of CAT and SOD transcripts and proteins, respectively, in all oviductal segments, i.e., the infundibulum, magnum, isthmus, shell gland and vagina. In control hens (laying), the mRNA expression of CAT was the highest in the shell gland, lower in the isthmus and the lowest in other oviductal parts, whereas protein expression was the highest in the magnum, lower in the isthmus and the lowest in other segments. The SOD transcript and protein abundances only were lower in the magnum than in other segments. Immunoreactive CAT and SOD products were localized in all layers of the oviductal wall, but the intensity of staining depended on the cell type. TMX treatment affected CAT and SOD expression and the effect of TMX depended on gene, protein, cell type and oviductal part. Generally, CAT expression was elevated, while SOD expression was decreased under TMX treatment. These results point to the importance of CAT and SOD in the maintenance of proper oviduct health and function. Changes in ROS scavenging enzymes after estrogen receptor blockage indicate the significance of estrogen in the regulation of oxidative status in the avian oviduct.

Ferroptosis preceded the onset of oxidative stress under acute ammonia exposure and quercetin relieved ammonia-induced ferroptosis of yellow catfish (Pelteobagrus fulvidraco)

Ammonia is the most common pollutant and stressor in the aquaculture environment and can cause massive fish mortality. Its toxicity in fish is mainly related to the generation of oxidative stress, but the mechanisms are not well understood. Ferroptosis is a unique cell death pathway characterized by iron-dependent lipid peroxidation. However, little information is available regarding the association between oxidative stress and ferroptosis under ammonia stress and mitigation measures in fish. This study was divided into two parts. In the first part of the study, yellow catfish were exposed to three levels of ammonia (0 mg L−1, 5.7 mg L−1, 28.5 mg L−1) for 96 h. Results showed that ammonia poisoning could result in a decrease in survival rates, elevation of blood ammonia levels, ferroptosis activation (iron accumulation, reduced glutathione depletion, upregulation of transferrin receptor 1 and 15B-lipoxygenase, first increased then a decreased expression of glutamate/cystine antiporter system xc– and glutathione peroxidase 4) and oxidative stress (first increased and then decreased expression of superoxide dismutase and catalase). In the second part of the study, primary head-kidney macrophages were used for investigating the underlying mechanism of quercetin in protecting against ammonia-induced ferroptosis in vitro. Results showed that quercetin could decrease the production of reactive oxygen species, increase GSH contents, suppress the expression of TFR1 and LOX-15B, and upregulate the expression levels of FER, system xc– as well as GPX4. The results of this study suggested that oxidative stress induced by ferroptosis might be a prominent mechanism behind ammonia-induced cytotoxicity and quercetin exhibited good protective effects against macrophage ferroptosis under ammonia stress.

Biochemical and gene expression alterations due to individual exposure of atrazine, dichlorvos, and imidacloprid and their combination in zebrafish.

In environmental toxicology, combined toxicity has emerged as an important concern. Atrazine (ATZ), dichlorvos (DIC), and imidacloprid (IMD) are the major pesticides, extensively used to control insect, flies, mosquitoes, and weed. Here, we investigate whether the exposure to three different types of pesticides individually and in combination for 24h alters antioxidant enzyme responses in zebrafish (Danio rerio). Oxidative stress parameters (biochemical and mRNA expression), acetylcholinesterase (AChE) activity, and Metallothionein-II (MT-II) mRNA expression levels were measured. Present work includes toxicological assessment of individual and combined (CMD) exposure of ATZ (185.4µM), DIC (181µM), IMD (97.8 µ), and CMD (ATZ 92.7µM + DIC 90.5µM + IMD 48.9µM), in the liver, kidney, and brain of adult zebrafish. Lipid peroxidation (LPO), glutathione (GSH) content, AChE, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activity along with mRNA expression of SOD, CAT, GPx, and MT-II were evaluated. Briefly, LPO, GSH content, the activity of AChE, and all antioxidant enzymes enhanced significantly in individual exposure, which was further altered in the CMD group. The mRNA expression of SOD, CAT, GPx, and MT-II in the liver and kidney showed significant down-regulation in all exposed groups. In the brain, significant upregulation in mRNA expression of SOD, CAT, GPx, and MT-II was observed in DIC and IMD groups, while ATZ and CMD showed significant downregulation except for GPx. Findings postulate that the CMD group exhibits synergistic toxic manifestation. The present study provides the baseline data on the combined toxic effects of pesticides and suggests regulating the use of pesticides.

Interleukin-1β triggers muscle-derived extracellular superoxide dismutase expression and protects muscles from doxorubicin-induced atrophy.

Doxorubicin, a conventional chemotherapeutic agent prescribed for cancer, causes skeletal muscle atrophy and adversely affects mobility and strength. Given that doxorubicin-induced muscle atrophy is attributable primarily to oxidative stress, its effects could be mitigated by antioxidant-focused therapies; however, these protective therapeutic targets remain ambiguous. The aim of this study was to demonstrate that doxorubicin triggers severe muscle atrophy via upregulation of oxidative stress (4-hydroxynonenal and malondialdehyde) and atrogenes (atrogin-1/MAFbx and muscle RING finger-1) in association with decreased expression of the antioxidant enzyme extracellular superoxide dismutase (EcSOD), in cultured C2C12myotubes and mouse skeletal muscle. Supplementation with EcSOD recombinant protein elevated EcSOD levels on the cellular membrane of cultured myotubes, consequently inhibiting doxorubicin-induced oxidative stress and myotube atrophy. Furthermore, doxorubicin treatment reduced interleukin-1β (IL-1β) mRNA expression in cultured myotubes and skeletal muscle, whereas transient IL-1β treatment increased EcSOD protein expression on the myotube membrane. Notably, transient IL-1β treatment of cultured myotubes and local administration in mouse skeletal muscle attenuated doxorubicin-induced muscle atrophy, which was associated with increased EcSOD expression. Collectively, these findings reveal that the regulation of skeletal muscle EcSOD via maintenance of IL-1β signalling is a potential therapeutic approach to counteract the muscle atrophy mediated by doxorubicin and oxidative stress. KEY POINTS: Doxorubicin, a commonly prescribed chemotherapeutic agent for patients with cancer, induces severe muscle atrophy owing to increased expression of oxidative stress; however, protective therapeutic targets are poorly understood. Doxorubicin induced muscle atrophy owing to increased expression of oxidative stress and atrogenes in association with decreased protein expression of extracellular superoxide dismutase (EcSOD) in cultured C2C12myotubes and mouse skeletal muscle. Supplementation with EcSOD recombinant protein increased EcSOD levels on the cellular membrane of cultured myotubes, resulting in inhibition of doxorubicin-induced oxidative stress and myotube atrophy. Doxorubicin treatment decreased interleukin-1β (IL-1β) expression in cultured myotubes and skeletal muscle, whereas transient IL-1β treatment in vivo and in vitro increased EcSOD protein expression and attenuated doxorubicin-induced muscle atrophy. These findings reveal that regulation of skeletal muscle EcSOD via maintenance of IL-1β signalling is a possible therapeutic approach for muscle atrophy mediated by doxorubicin and oxidative stress.

Changes in the expression of oxidative stress genes in toxic hepatitis of different etiologies and their correction

The study aims to study of changes in transcriptional activity of oxidative stress genes in acute toxic hepatitis. Materials and methods. The study material was white mongrel male rats weighing 180-200 grams. The studied toxicants were: carbon tetrachloride, ethanol, acetaminophen. As hepatoprotectors were introduced: oxymethyluracil, ademethionine and ethylmethylhydroxypyridine succinate. RNA was isolated, which was subjected to reverse transcription. RT-PCR was performed using a real-time PCR system in the presence of SYBR Green. GAPDH was used as a normalized control. The expression of the studied genes was evaluated by PCR analysis using pre-selected primers. Statistical significance was checked using IBM SPSS Statistics software. Results. In comparison of experimental groups, statistically significant differences were found in the level of expression of the CASP7 gene. Transcriptional activity of the CHEK gene (k=11.25; p=0.024). The GCLC gene (k=21.70; p=0.001) reached its minimum value of -3.6 [-3.72; -3.32] in the Mexidol group. The multiplicity of expression of the GSTM1 gene (k=15.54; p=0.004) had the highest value -0.14 [-1.11; 1] in the group that did not receive TCM. The NQO1 gene achieved its statistical significance in a 72-hour experiment (p=0.005). Statistical analysis of the RIPK gene showed significant differences. The expression level of the GSTP1 gene (k=10.39; p=0.034) reached its maximum value in the untreated group of 0.03 [-0.74; 0.48]. Expression of the NFE2L2 gene with acetaminophen administration showed the following results (k=13.64; p=0.009). Glutathione activity (k=10.29; p=0.036) reached its minimum value in the group receiving Mexidol -1.6 [-1.7; -1.29]. The multiplicity of superoxide dismutase expression showed statistical significance (p=0.003). Conclusions. Markers of the clinical course, prognosis and outcomes of toxic hepatitis were found. These data make it possible to determine the severity of the disease at the stage of early molecular response, when active clinical symptoms have not yet developed, which makes it possible to prescribe targeted therapy and adjust treatment tactics.

Protective effect of eriodictyol against hyperglycemia-induced diabetic nephropathy in rats entails antioxidant and anti-inflammatory effects mediated by activating Nrf2

The pathogenesis of diabetic nephropathy (DN) involves cellular activation of oxidative stress and inflammation. Eriodictyol is a citrus-derived flavonoid with multiple pharmacological and protective effects in various conditions. The protective role of Eriodictyol against diabetes and diabetic nephropathy is less investigated. The current research aimed to explore the role of eriodictyol in protecting against DN prompted by streptozotocin in male rats and investigate some possible mechanisms of action. Diabetes was brought about in rats by an i.p injection of a lone dose (65 mg/kg). Five groups of rats were included (n = 8 each) as control (non-diabetic), eriodictyol (20 mg/kg, orally), STZ-diabetic, STZ + eriodictyol (20 mg/kg, orally), and STZ + eriodictyol (20 mg/kg, orally) + ML385 (30 µg/kg, i.p.). Kidney histology and the levels of some markers of kidney function, renal oxidative stress, and renal inflammation were analyzed in all groups of rats. Treatment with eriodictyol prevented the damage in the renal glomeruli and tubules and reduced renal immune cell infiltration in STZ-treated animals. It also spiked urinary creatinine excretion and reduced urine volume and urinary levels of albumin, monocyte chemoattractant protein 1 (MCP-1), urinary kidney injury molecule-1 (KIM-1), and nephrin in these diabetic rats. In addition, eriodictyol stimulated the nuclear protein accumulation of Nrf2 and boosted the expression of superoxide dismutase (SOD), glutathione (GSH), heme oxygenase-1 (HO-1), and catalase (CAT) in the diabetic rat kidneys. In concomitance, it reduced the nuclear levels of NF-κB and levels of interleukine-6 (IL-6), malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) and attenuated the reduction in renal ATP levels and the increase in the mitochondria transition pore opening (mtTPT). However, the administration of eriodictyol did not affect rats’ body weights and fasting glucose and insulin levels but significantly reduced serum levels of cholesterol, triglycerides, LDL-c, and oxidized LDL-c (ox-LDL-c). In conclusion, eriodictyol prevents STZ-induced nephropathy by a hypolipidemic effect and concomitant antioxidant and anti-inflammatory effects mediated by activating Nrf2/NF-κB/antioxidant axis.

Sperm quality of Litopenaeus vannamei fed fresh or experimental food in two culture systems

AbstractThe growth of shrimp production through aquaculture has led to efforts to optimize processes such as nutrition during the prematuration and reproductive phases. This study sought an optimal culture system and diet to enhance the reproductive characteristics of male Litopenaeus vannamei during prematuration: this compared biofloc with clear water, and an experimental pellet (EP) with a mix of fresh food. Effects were measured in terms of shrimp survival, sperm quality, immunological parameters including prophenoloxidase (ProPO) and hemocyte count, nutritional condition measured as metabolites in hemolymph, hepatopancreas, and reproductive tract, oxidative stress biomarkers in the hepatopancreas and reproductive tract, and relative expression of superoxide dismutase, catalase, glutathione peroxidase, ProPO, alpha2‐macroglobulin and caspase in reproductive tract. Survival was higher with pellets (100%) than with fresh food (87%). Shrimp that were fed pellets had a higher hepatosomatic index, higher nutrient concentration in the hepatopancreas, and a higher antioxidant activity in the reproductive tract. Notably, sperm quality remained similar regardless of culture system or diet. These promising results should be ratified with a bioeconomic study to check the feasibility of hatcheries to use monosex tanks and feeding the males with EPs.

The genetic variation in drought resistance in eighteen perennial ryegrass varieties and the underlying adaptation mechanisms

BackgroundDrought resistance is a complex characteristic closely related to the severity and duration of stress. Perennial ryegrass (Lolium perenne L.) has no distinct drought tolerance but often encounters drought stress seasonally. Although the response of perennial ryegrass to either extreme or moderate drought stress has been investigated, a comprehensive understanding of perennial ryegrass response to both conditions of drought stress is currently lacking.ResultsIn this study, we investigated the genetic variation in drought resistance in 18 perennial ryegrass varieties under both extreme and moderate drought conditions. The performance of these varieties exhibited obvious diversity, and the survival of perennial ryegrass under severe stress was not equal to good growth under moderate drought stress. ‘Sopin’, with superior performance under both stress conditions, was the best-performing variety. Transcriptome, physiological, and molecular analyses revealed that ‘Sopin’ adapted to drought stress through multiple sophisticated mechanisms. Under stress conditions, starch and sugar metabolic enzymes were highly expressed, while CslA was expressed at low levels in ‘Sopin’, promoting starch degradation and soluble sugar accumulation. The expression and activity of superoxide dismutase were significantly higher in ‘Sopin’, while the activity of peroxidase was lower, allowing for ‘Sopin’ to maintain a better balance between maintaining ROS signal transduction and alleviating oxidative damage. Furthermore, drought stress-related transcriptional and posttranscriptional regulatory mechanisms, including the upregulation of transcription factors, kinases, and E3 ubiquitin ligases, facilitate abscisic acid and stress signal transduction.ConclusionOur study provides insights into the resistance of perennial ryegrass to both extreme and moderate droughts and the underlying mechanisms by which perennial ryegrass adapts to drought conditions.

Calpain inhibition decreases oxidative stress via mitochondrial regulation in a swine model of chronic myocardial ischemia

IntroductionCalpain overexpression is implicated in mitochondrial damage leading to tissue oxidative stress and myocardial ischemic injury. The aim of this study was to determine the effects of calpain inhibition (CI) on mitochondrial impairment and oxidative stress in a swine model of chronic myocardial ischemia and metabolic syndrome. MethodsYorkshire swine were fed a high-fat diet for 4 weeks to induce metabolic syndrome then underwent placement of an ameroid constrictor to the left circumflex artery. Three weeks later, animals received: no drug (control, “CON”; n= 7); a low-dose calpain inhibitor (0.12 mg/kg; “LCI”, n= 7); or high-dose calpain inhibitor (0.25 mg/kg; “HCI”, n=7). Treatment continued for 5 weeks, followed by tissue harvest. Cardiac tissue was assayed for protein carbonyl content, as well as antioxidant and mitochondrial protein expression. Reactive oxygen species (ROS) and mitochondrial respiration was measured in H9c2 cells following exposure to normoxia or hypoxia (1%) for 24 h with or without CI. ResultsIn ischemic myocardial tissue, CI was associated with decreased total oxidative stress compared to control. CI was also associated with increased expression of mitochondrial proteins superoxide dismutase 1, SDHA, and pyruvate dehydrogenase compared to control. 100 nM of calpain inhibitor decreased ROS levels and respiration in both normoxic and hypoxic H9c2 cardiomyoblasts. ConclusionsIn the setting of metabolic syndrome, CI improves oxidative stress in chronically ischemic myocardial tissue. Decreased oxidative stress may be via modulation of mitochondrial proteins involved in free radical scavenging and production.

Nimbolide Inhibits SOD2 to Control Pancreatic Ductal Adenocarcinoma Growth and Metastasis.

Reactive oxygen species are frequently associated with various cancers including pancreatic ductal adenocarcinomas (PDACs). Superoxide dismutase 2 (SOD2) is an enzyme that plays an important role in reactive oxygen species (ROS) signaling. Investigating the molecular function and biological functions of SOD2 can help us develop new therapeutic options and uncover new biomarkers for PDAC diagnosis and prognosis. Here, we show that nimbolide (NB), a triterpene limonoid, effectively blocks the growth and metastasis of PDACs by suppressing the expression and activity of SOD2. To identify the role of SOD2 in NB-induced anticancer activity, we used RNA interference to silence and plasmid transfection to overexpress it. Silencing SOD2 significantly reduced the growth and metastatic characteristics like epithelial-to-mesenchymal transition, invasion, migration, and colony-forming capabilities of PDACs, and NB treatment further reduced these characteristics. Conversely, the overexpression of SOD2 enhanced these metastatic characteristics. ROS signaling has a strong feedback mechanism with the PI3K/Akt signaling pathway, which could be mediated through SOD2. Finally, NB treatment to SOD2-overexpressing PDAC xenografts resulted in significant inhibition of tumor growth and metastasis. Overall, this work suggests that NB, a natural and safe phytochemical that silences SOD2 to induce high levels of ROS generation, results in increased apoptosis and reduced growth and progression of PDACs. The role of SOD2 in regulating NB-induced ROS generation presents itself as a therapeutic option for PDACs.

Schefflera arboricola Tablets Relieve Diabetic Neuropathic Pain: Involvement of Oxidative Stress and Inflammation

Background Diabetic neuropathic pain (DNP) is a serious chronic complication of diabetes mellitus. Oxidative stress and inflammation are considered the central mechanisms of its pathogenesis. Schefflera arboricola (SA) is a Schefflera plant of the Araliaceae family that has the effect of pain relief. In this study, the effect of SA on DNP was first investigated. Materials and Methods Diabetic neuropathy in rats was induced by a single injection of streptozotocin (60 mg/kg). Three weeks later, SA (100 mg/kg, 300 mg/kg) or gabapentin (100 mg/kg) was given once a day for a week. Blood glucose, body weight, and thermal withdrawal latency in DNP rats were measured. The morphology of the sciatic nerve was observed by light microscopy and toluidine blue staining. Semiquantitative analysis of myelin basic protein (MBP) of the sciatic nerve was performed by immunohistochemistry. IL-1β, tumor necrosis factor-alpha (TNF-α), and IL-6 were detected by enzyme-linked immunosorbent assay. Commercial reagent kits were used to detect inducible nitric oxide synthase, superoxide dismutase (SOD), and malondialdehyde (MDA). The expression levels of nuclear factor erythroid-2-related factor 2 (Nrf2) and nuclear factor-kappa B (NF-κB) were detected by Western blot. Results DNP rat model was successfully constructed. SA and gabapentin could alleviate the thermal sting pain of DNP rats, increase the expression of MBP and SOD, and decrease the expression of proinflammatory agents and MDA. Moreover, SA could reverse the upregulation of NF-κB and the downregulation of Nrf2. Conclusion SA has a significant protective effect on DNP, manifesting in the improvement of allodynia and sciatic nerve pathology, inhibition of neuroinflammation, reduction of oxidative stress, enhancement of Nrf2, and inhibition of NF-κB.

Genetic polymorphisms in Nrf2 and FoxO1: implications for antioxidant enzyme activity in diabetes

In diabetes, persistent hyperglycemia generates excess reactive oxygen species (ROS), leading to oxidative stress (OS). In response to OS, transcription factors (TFs) Nrf2 and FoxO1 get activated, which induce the expression of antioxidant enzymes catalase (CAT) and superoxide dismutase (SOD). It is well documented that the antioxidant response in diabetic individuals is very low. Since Nrf2 and FoxO1 are the major TFs activating these genes, we were interested in determining if single nucleotide polymorphisms (SNPs) in genes for these TFs have any association with lowered antioxidant enzyme activity in diabetic individuals. The activity of CAT and SOD and total antioxidant capacity (TAC) were quantified from the serum samples of diabetic (n = 98) and non-diabetic (n = 90) individuals. Genomic DNA was isolated, and Nrf2 and FoxO1 were amplified and sequenced by Illumina NextSeq500. Data were screened for SNPs in amplified regions. An independent samples t-test to find an association between CAT, SOD, and TAC and allele frequency of SNP with the diabetic condition was carried out. We found decreased CAT and SOD activity and significantly low TAC in diabetic individuals. Thirty-two and thirty-four SNPs and Single-nucleotide variants (SNVs) were observed in Nrf2 and FoxO1, respectively. However, a statistically significant difference in the allele frequency distribution between study groups was observed only in two intronic SNPs, rs17524059:A > C and rs60373589:Indel(A) of Nrf2 and FoxO1, respectively. SNPs, rs17524059 in the Nrf2 and rs60373589 of FoxO1, were not associated with reduced CAT and SOD activity and level of TAC in Indian diabetic individuals. Communicated by Ramaswamy H. Sarma

Alleviating Effects of Ovatodiolide and Antcin K Supplements on High-Fat Diet-Induced Cardiovascular Dysfunction in ApoE-Knockout Mice by Attenuating Oxidative Stress.

A high-fat diet (HFD) is a major risk factor for cardiovascular diseases. Many pure compounds have been demonstrated to be effective in treating cardiovascular diseases. In this study, we investigated the alleviating effects of oral ovatodiolide and antcin K (OAK) supplements on HFD-induced cardiovascular dysfunction in apolipoprotein E (ApoE)-knockout mice. Cardiovascular dysfunction was induced in ApoE-knockout mice by feeding them an HFD for 12 weeks. The degree of cardiovascular dysfunction was assessed through echocardiography, hematological and biochemical analyses, and immunofluorescence and immunohistochemical staining. The HFD-fed mice exhibited cardiovascular dysfunction-abnormal blood biochemical index. The arterial wall tissue exhibited the marked deposition of lipids, upregulated expression of vascular cell adhesion molecule-1 and CD36 receptors, and downregulated expression of the ABCA1 receptor. Macrophages isolated from the peritoneal cavity of the mice exhibited increased levels of lipid accumulation, reactive oxygen species, and CD11b expression but reduced mitochondrial membrane potential. The expression of superoxide dismutase 2 was downregulated and that of tumor necrosis factor-α was upregulated in the myocardial tissue. Oral OAK supplements twice a day for 12 weeks significantly mitigated HFD-induced cardiovascular dysfunction in the experimental mice. Oral OAK supplements appear to be a promising strategy for treating HFD-induced cardiovascular dysfunction. The underlying mechanisms may involve the reduction of lipid accumulation in the artery and oxidative stress and inflammation in the cardiovascular tissue.

SiJunZi decoction ameliorates bone quality and redox homeostasis and regulates advanced glycation end products/receptor for advanced glycation end products and WNT/β-catenin signaling pathways in diabetic mice

Ethnopharmacological relevanceSiJunZi decoction (SJZD), one of the traditional Chinese medicine formulas, has been clinically and traditionally used to improve glucose and lipid metabolism and promote bone remodeling. Aim of the studyTo study the actions and mechanisms of SJZD on bone remodeling in a type 2 diabetes mouse model. Materials and methodsDiabetic mice generated with a high-fat diet (HFD) and streptozotocin (STZ) were subjected to SJZD treatment for 8 weeks. Blood glucose and lipid profile, redox status and bone metabolism were determined by ELISA or biochemical assays. Bone quality was evaluated by micro-CT, three-point bending assay and Fourier transform infrared spectrum (FTIR). Bone histomorphometry alterations were evaluated by Hematoxylin-Eosin (H&E), tartrate resistant acid phosphatase (TRAP) staining and Safranin O-fast green staining. The expressions of superoxide dismutase 1 (SOD1), advanced glycation end products (AGEs), receptor for advanced glycosylation end products (RAGE), phosphorylated nuclear factor kappa-B (p–NF–κB), NF-κB, cathepsin K, semaphorin 3A (Sema3A), insulin-like growth factor 1 (IGF1), p-GSK-3β, (p)-β-catenin, Runt-related transcription factor 2 (Runx2) and Cyclin D1 in the femurs and/or tibias were examined by Western blot or immunohistochemical staining. The main constituents in the SJZD aqueous extract were characterized by a HPLC/MS. ResultsSJZD intervention improved glucose and lipid metabolism and preserved bone quality in the diabetic mice, in particular glucose tolerance, lipid profile, bone microarchitecture, strength and material composition. SJZD administration to diabetic mice preserved redox homeostasis in serum and bone marrow, and prevented an increase in AGEs, RAGE, p–NF–κB/NF-κB, cathepsin K, p-GSK-3β, p-β-catenin expressions and a decrease in Sema3A, IGF1, β-catenin, Runx2 and Cyclin D1 expressions in tibias and/or femurs. Thirteen compounds were identified in SJZD aqueous extract, including astilbin, liquiritin apioside, ononin, ginsenoside Re, Rg1, Rb1, Rb2, Ro, Rb3, Rd, notoginsenoside R2, glycyrrhizic acid, and licoricesaponin B2. ConclusionsSJZD ameliorates bone quality in diabetic mice possibly via maintaining redox homeostasis. The mechanism governing these alterations are possibly related to effects on the AGEs/RAGE and Wnt/β-catenin signaling pathways. SJZD may offer a novel source of drug candidates for the prevention and treatment of type 2 diabetes and osteoporosis.

Supplementation with kefir improves metabolism and liver inflammation in malnourished mice

BackgroundMalnutrition causes several changes in body composition and physiological liver function and is commonly related to systemic inflammation, cognitive deficits, and metabolic changes. Kefir is a symbiotic association of yeast and bacteria fermenting milk, used as food supplementation, and is now recognized for its beneficial health properties. In this context, the present study aims to verify the effects promoted by Kefir supplementation in a model of mice malnutrition, evaluating its metabolic effects and liver modulation. MethodsMale Swiss mice were divided into four groups with 8 animals each. After the adaptation period, the animals were subjected to two phases of treatment: the caloric restriction phase to promote malnutrition and the renutrition phase. A calorie restriction of 20 % compared to the control group was adopted. Metabolic profile, adipose tissue, liver, biochemical parameters, and gene expression of CAT and SOD were evaluated. ResultsThe main findings demonstrate an improvement in body weight and biochemical parameters followed by a greater recovery of adipocyte area in the (FR + Kefir) group when compared to the malnourished (FR) group. The data showed an increase in the expression of genes associated with oxidative stress suppression such as superoxide dismutase (SOD) and catalase (CAT) in the groups supplemented with kefir. ConclusionsOral supplementation was able to increase body weight recovery, and adiposity, enabling improvements in metabolism and reducing liver inflammation.

A Second Life for Seafood Waste: Therapeutical Promises of Polyhydroxynapthoquinones Extracted from Sea Urchin by-Products.

Coping with a zero-waste, more sustainable economy represents the biggest challenge for food market nowadays. We have previously demonstrated that by applying smart multidisciplinary waste management strategies to purple sea urchin (Paracentrotus lividus) food waste, it is possible to obtain both a high biocompatible collagen to produce novel skin substitutes and potent antioxidant pigments, namely polyhydroxynapthoquinones (PHNQs). Herein, we have analyzed the biological activities of the PHNQs extract, composed of Spinochrome A and B, on human skin fibroblast cells to explore their future applicability in the treatment of non-healing skin wounds with the objective of overcoming the excessive oxidative stress that hinders wound tissue regeneration. Our results clearly demonstrate that the antioxidant activity of PHNQs is not restricted to their ability to scavenge reactive oxygen species; rather, it can be traced back to an upregulating effect on the expression of superoxide dismutase 1, one of the major components of the endogenous antioxidant enzymes defense system. In addition, the PHNQs extract, in combination with Antimycin A, displayed a synergistic pro-apoptotic effect, envisaging its possible employment against chemoresistance in cancer treatments. Overall, this study highlights the validity of a zero-waste approach in the seafood chain to obtain high-value products, which, in turn, may be exploited for different biomedical applications.

Polyphosphate promotes oxidation resistance of ppk-expressing transgenic rice in low phosphorus culture

Phosphorus (P) plays a crucial role in plant growth. Insufficient availability of inorganic phosphate (Pi) can significantly impact crop yields. To address this, we previously developed transgenic rice expressing the low polyphosphate kinase gene (ppk) - known as ETRS - to enhance the efficiency of P resource utilization. Previous studies have shown that ETRS thrives and presents high yields in the low P culture. ETRS and wild-type rice (WT) were cultivated to the heading stage at 15 μM of P in the low P (LP) culture and 300 μM of P in the normal culture (CK) to identify the molecular pathways behind low P tolerance. Our findings revealed that polyphosphate (polyP) significantly enhanced the growth performance of ETRS in the LP culture. This enhanced tolerance can be attributed to polyP's capacity to mitigate oxidative damage induced by LP. This was evidenced by the reduction in levels of superoxide radicals, hydrogen peroxide, and malondialdehyde. PolyP also improved the antioxidant capacity of ETRS under LP stress by regulating enzymatic antioxidants viz., superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), as well as non-enzymatic antioxidants such as ascorbate (AsA) and glutathione (GSH). In addition, transcriptomics analysis suggested that polyP synthesis positively promoted the expressions of SOD, POD, and CAT related genes and played an active role in regulating the expression of AsA-GSH cycle system related genes in ETRS in the LP culture. These results strongly support the notion that polyP within ETRS mitigates oxidative damage through enhancement of the antioxidant system, ultimately bolstering tolerance to LP conditions.

Involvement of the Sch9/Rim15/Msn2 signaling pathway in the anti-aging activity of dendrobine from Dendrobium nobile Lindl. via modification of oxidative stress and autophagy

BackgroundAging is an important pathogenic factor of age-related diseases and has brought huge health threat and economic burden to the society. Dendrobium nobile Lindl., a valuable herb in China, promotes longevity according to the record of ancient Chinese materia medica. This study aimed to discover the material basis of D. nobile as an anti-aging herb and elucidate its action mechanism.MethodsK6001 yeast replicative lifespan assay was used to guide the isolation of D. nobile. The chronological lifespan assay of YOM36 yeast was further conducted to confirm the anti-aging activity of dendrobine. The mechanism in which dendrobine exerts anti-aging effect was determined by conducting anti-oxidative stress assay, quantitative real-time PCR, Western blot, measurements of anti-oxidant enzymes activities, determination of nuclear translocation of Rim15 and Msn2, and replicative lifespan assays of Δsod1, Δsod2, Δcat, Δgpx, Δatg2, Δatg32, and Δrim15 yeasts.ResultsUnder the guidance of K6001 yeast replicative lifespan system, dendrobine with anti-aging effect was isolated from D. nobile. The replicative and chronological lifespans of yeast were extended upon dendrobine treatment. In the study of action mechanism, dendrobine improved the survival rate of yeast under oxidative stress, decreased the levels of reactive oxygen species and malondialdehyde, and enhanced the enzyme activities and gene expression of superoxide dismutase and catalase, but it failed to elongate the replicative lifespans of Δsod1, Δsod2, Δcat, and Δgpx yeast mutants. Meanwhile, dendrobine enhanced autophagy occurrence in yeast but had no effect on the replicative lifespans of Δatg2 and Δatg32 yeast mutants. Moreover, the inhibition of Sch9 phosphorylation and the promotion of nuclear translocation of Rim15 and Msn2 were observed after treatment with denrobine. However, the effect of dendrobine disappeared from the Δrim15 yeast mutant after lifespan extension, oxidative stress reduction, and autophagy enhancement.ConclusionsDendrobine exerts anti-aging activity in yeast via the modification of oxidative stress and autophagy through the Sch9/Rim15/Msn2 signaling pathway. Our work provides a scientific basis for the exploitation of D. nobile as an anti-aging herb.