Superoxide Dismutase Research Articles

Differentiated management of ROS level in tumor and kidney to alleviate Cis-platinum induced acute kidney injury with improved efficacy

Cisplatin (DDP) is a prevalent chemotherapeutic agent used in tumor therapy, yet DDP-induced acute kidney injury (AKI) severely limits its clinical application. Antioxidants as reactive oxygen species (ROS) scavengers can circumvent this adverse effect while leading to the decrease of efficacy to tumor. Herein, we report ultrasmall ruthenium nanoparticles (URNPs) as switchable ROS scavengers/generators to alleviate DDP-induced AKI and improve its therapeutic efficacy. In the physiological environment of the kidney, URNPs mimic multi-enzyme activities, such as superoxide dismutase and catalase, effectively protecting the renal cell and tissue by down-regulating the increased ROS level caused by DDP and alleviating AKI. Specifically, URNPs are oxidized by high levels of H2O2 in the tumor microenvironment (TME), resulting in the generation of oxygen vacancies and Ru3+/Ru4+ ions. This unique structure transformation endows URNPs to generate singlet oxygen (1O2) under laser irradiation and hydroxyl radicals (∙OH) through a Fenton-like reaction in tumor cell and tissue. The simultaneous generation of multifarious ROS effectively improves the efficacy of DDP in vitro and in vivo. This TME-responsive ROS scavenger/generator acts as an adjuvant therapeutic agent to minimize side effects and improve the efficacy of chemotherapy drugs, providing a new avenue to chemotherapy and facilitating clinical tumor therapy.Graphical

In Situ Hydrogel with Immobilized Mn-Porphyrin for Reactive Oxygen Species Scavenging, Oxygen Generation, and Risedronate Delivery in Bone Defect Treatment.

We propose a hydrogel immobilized with manganese porphyrin (MnP), a biomimetic superoxide dismutase (SOD), and catalase (CAT) to modulate reactive oxygen species (ROS) and hypoxia that impede the repair of large bone defects. Our hydrogel synthesis involved thiolated chitosan and polyethylene glycol-maleimide conjugated with MnPs (MnP-PEG-MAL), which enabled in situ gelation via a click reaction. Through optimization, a hydrogel with mechanical properties and catalytic effects favorable for bone repair was selected. Additionally, the hydrogel was incorporated with risedronate to induce synergistic effects of ROS scavenging, O2 generation, and sustained drug release. In vitro studies demonstrated enhanced proliferation and differentiation of MG-63 cells and suppressed proliferation and differentiation of RAW 264.7 cells in ROS-rich environments. In vivo evaluation of a calvarial bone defect model revealed that this multifunctional hydrogel facilitated significant bone regeneration. Therefore, the hydrogel proposed in this study is a promising strategy for addressing complex wound environments and promoting effective bone healing.

A standardized chamuangone enriched extract from Garcinia cowa Roxb. leaves shows acute and sub-acute safety

Ethnopharmacological relevanceThe safety assessment of herbal products is critical for their appropriate pharmacological applications. Garcinia cowa Roxb., commonly known as Cha-muang in Thai, has ethnopharmacological relevance in inflammation, infectious diseases, and diabetes. The leaf extracts of G. cowa have been extensively reported for their anticancer, anti-inflammatory, antimicrobial and antioxidative effects. Notably, chamuangone is their major active constituent that contributes to various pharmacological properties. Aim of the studyThe current study aims to establish a standardized chamuangone enriched extract (CEE) and assess its acute and sub-acute toxicities in animal models. MethodologyCEE was established from G. cowa leaves using microwave-assisted extraction (MAE), followed by fractionation and enrichment through silica gel vacuum and column chromatography. The concentration of chamuangone in the leaves was quantified using validated quantitative high-performance liquid chromatography (HPLC) method. The safety profile of CEE was thoroughly evaluated in rodents according to the Organization for Economic Cooperation and Development (OECD) guidelines, specifically 425 and 407. The effect on oxidative stress markers such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) levels were also evaluated in various organs. ResultsBase on the quantitative HPLC analysis the CEE containing 73.0 ± 2% w/w of chamuangone in the extract. In the acute toxicity study, following up and down procedure the female rats were dosed with CEE at 1750 and 550 mg/kg body weight (b.w.), with CEE 1750 mg/kg b.w. identified as toxic, causing mortality, while CEE 550 mg/kg b.w. was deemed safe. The LD50 value was calculated according to the standard protocols, resulting in 970 mg/kg b.w. In histopathological examination, CEE 550 mg/kg b.w. were safe in all the selected organs while the CEE 1750 mg/kg b.w. treated rats exhibited toxic effects in histological tissues sections in the form of necrosis in brain, cardiac muscle hypertrophy, liver inflammation, mild untoward in the spleen, fibrosis in lungs, pancreatitis, pyelonephritis, and ovaries cyst. Administration of CEE at doses of 550 mg/kg b.w. (single dose) in acute and 100 mg/kg b.w. (regularly 28-days) in sub-acute toxicities studies significantly (p < 0.05) decreased levels of uric acid, triglycerides, and cholesterol. Importantly, the CEE 550 and 100 mg/kg b.w. also significantly increased the levels of antioxidant enzymes (SOD, GSH and CAT) and decreased malondialdehyde levels. Normal histopathology was observed in the sub-acute toxicity study in all treated groups. ConclusionThe study successfully concludes that CEE at a dose of 100 mg/kg b.w. is safe for therapeutic application or use as a chemo preventive functional food utilizing green extraction methods. However, chronic toxicity studies are recommended to validate safety concerns over an extended period.

Exogenously applied silver nanoparticles (AgNPs) differentially affect bacterial blight disease control in twenty-seven wheat cultivars

The bacterial blight of wheat is an important global disease causing a significant decline in crop yield. Nanotechnology offers a potential solution for managing plant diseases. Therefore, this research aimed to investigate the effectiveness of silver nanoparticles (AgNPs) in controlling bacterial blight in 27 locally grown wheat cultivars. The study examined the impact of AgNPs at three distinct time points: 1, 3, and 5 days after the onset of the disease. Biochemical assay revealed that one day after applying the disease stress, the Inia cultivar had the highest amount of soluble protein (55.60 μg.g−1FW) content in the treatment without AgNPs. The Azadi cultivar, without AgNPs treatment, had the lowest amount of soluble protein content (15.71 μg.g−1FW). The Tabasi cultivar had the highest activity of the superoxide dismutase (SOD) (61.62 mM.g−1FW) with the combination treatment of AgNPs. On the other hand, the Karchia cultivar had the lowest SOD activity (0.6 mM.g−1FW) in the treatment of disease without AgNPs. Furthermore, three days after the application of stress, the Mahdavi cultivar had the highest amount of soluble protein content (54.16 μg.g−1FW) in the treatment of disease without AgNPs. The Niknejad cultivar had the highest activity of the SOD (74.15 mM.g−1FW) with the combined treatment of the disease without AgNPs. The Kavir cultivar had the lowest SOD activity (1.95 mM.g−1FW) and the lowest peroxidase (POX) activity (0.241 mM g−1FW min−1) in the treatment of the disease with AgNPs. Five days after exposure to stress, the Mahooti cultivar had the highest SOD activity (88.12 mM.g−1FW) with the combined treatment of the disease with AgNPs, and the Karchia cultivar had the lowest SOD activity (2.39 mM.g−1FW) in the treatment of the disease with AgNPs. Further, the results indicated that exposure to AgNPs could improve the antioxidant properties of wheat seeds in blight-infected and disease-free conditions in some cultivars.

Heavy metal impacts on antioxidants in cow blood from wastewater-irrigated areas

The aim of the present research was to investigate the presence of heavy metals such as lead (Pb), copper (Cu), chromium (Cr), and cadmium (Cd) in blood samples from cows raised with irrigated wastewater, as well as in the wastewater itself, in the North-western region of Pakistan. A total of 60 blood samples were collected from five different locations in Kohat, namely Tappi Road (TR), Pindi Road (PR), Gul Malik Road (GMR), Markaz Road (MR), and a control group. The samples of both i.e. cow blood and wastewater were analyzed for the concentrations of heavy metals. The highest concentration of Cd was detected in the MR site with a mean value of 0.03 mg/L, and the highest concentration of Cu (0.04 mg/L) was recorded in the TR site, while the lowest level was found in the control group with a mean of 0.002 mg/L in blood samples. The highest Cr and Pb concentrations were found at the PR site, with mean values of 0.03 and 0.07 mg/L, respectively, whereas the control group had the lowest concentrations, with mean values of 0.002 and 0.01 mg/L. Similarly, heavy metal concentrations were analyzed in wastewater used for irrigation in the study area. Results indicated elevated concentrations of Cu and Cr in wastewater, although they remained below the World Health Organization (WHO) recommended values except for Cr (0.13 mg/L) in the GMR site, which exceeded permissible limits. Cd and Pb concentrations in wastewater were relatively low, but Cd concentration surpassed WHO limits, particularly with a mean concentration of 0.08 mg/L in the TR site. Comparison between heavy metal concentrations in blood and wastewater revealed higher values of Cd and Pb in blood samples than in wastewater, while Cu and Cr concentrations were higher in water compared to blood. Additionally, elevated levels of Super Oxide Dismutase (SOD), antioxidant enzyme Catalase (CAT), and oxidative stress marker malondialdehyde (MDA) were detected in blood samples. Cluster and principal component analyses were employed to assess heavy metal toxicity among the groups, indicating potential long-term adverse health effects on animals, transfer to humans, and toxicity in living organisms.

Ameliorative effect of nodakenin in combating TNBS-induced ulcerative colitis by suppressing NFƙB-mediated NLRP3 inflammasome pathway.

Ulcerative colitis (UC) is an enduring and complex inflammatory bowel disease that is clinically prevalent, progressive, and debilitating. As of now, the few effective medical treatments for UC have unacceptably high side effects. It is crucial to find safer and more effective UC treatments. Nodakenin possesses anti-inflammatory and antioxidant activity by suppressing several pro-inflammatory mediators. In the present study, we aimed to evaluate the colonoprotective effect of nodakenin in combating colitis through the NFƙB-mediated NLRP3 inflammasome pathway. In mice, UC was induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). Nodakenin (10, 20, and 40mg/kg) was introduced intragastrically, and disease activity index (DAI) score was calculated. Malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), nitric oxide (NO) levels, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) concentration were evaluated in colon homogenate. Colon samples were used for histopathological investigation and mRNA expression studies involving nuclear factor kappa B (NFƙB), cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), nucleotide-binding receptor domain 3 (NLRP3), interleukin-1β (IL-1β), and interleukin-18 (IL-18). Nodakenin treatment was found effective in lowering the DAI score, histological score, MPO, MDA, and NO levels while elevating SOD levels as compared to the model control group, showcasing its anti-inflammatory and antioxidant properties. Nodakenin (40mg/kg) significantly downregulated the expression of TNF-α, IL-6, NFƙB (1.24-fold), iNOS (1.2-fold), COX-2 (1.98-fold), NLRP3 (1.78-fold), IL-1β (1.29-fold), and IL-18 (1.17-fold) conferring its great anti-inflammatory potential in combating colitis. Taking together, nodakenin presumably alleviated TNBS-induced colitis by NFƙB-mediated NLRP3 inflammasome pathway and reduced colon damage by downregulating various transcriptional genes and pro-inflammatory mediators.

Effects of Melatonin Supplementation on Markers of Inflammation and Oxidative Stress in Patients with Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background & aimsDiabetes mellitus is a metabolic disorder, in which chronic systemic inflammation and oxidative stress contribute to the progression of this condition and its complications. Melatonin, a hormone known for its potent antioxidant and anti-inflammatory properties, has emerged as a potential therapeutic intervention in diabetes. This review aims to evaluate the effects of melatonin supplementation on markers of oxidative stress and inflammation in diabetic patients. MethodsA thorough literature search of databases, including PubMed, Embase, Web of Science, Cochrane Central, CNKI, and Scopus, was conducted through October 2023. We included randomized controlled trials investigating the effects of melatonin on markers of inflammation and oxidative stress, compared to placebo in patients with diabetes. The data was analyzed using the random-effects model and the summary effect size was determined using the standardized mean difference (SMD) with 95% confidence interval (CI). ResultsFourteen studies with 823 participants were included. Our analysis indicates that melatonin can lead to significant reductions in levels of C-reactive protein (CRP) [SMD = -0.75; 95% CI: -1.37, -0.12; P = 0.018], tumor necrosis factor-alpha (TNF-α) [SMD = -0.40; 95% CI: -0.64, -0.15; P = 0.001], interleukin (IL)-1 [SMD = -0.75; 95% CI: -1.03, -0.47; P < 0.0001], IL-6 [SMD = -0.79; 95% CI: -1.07, -0.51; P < 0.0001], and malondialdehyde (MDA) [SMD = -0.61; 95% CI: -0.80, -0.43; P < 0.0001]. Furthermore, we found a significant increase in levels of total antioxidant capacity (TAC) [SMD = 0.81; 95% CI: 0.12, 1.51; P = 0.021], glutathione (GSH) [SMD = 0.66; 95% CI: 0.28, 1.03; P = 0.001], and superoxide dismutase (SOD) [SMD = 1.69; 95% CI: 0.80, 2.58; P < 0.0001] following melatonin consumption in patients with diabetes. ConclusionMelatonin supplementation is a promising complementary strategy to attenuate oxidative stress and inflammation in diabetic patients.

Sodium nitroprusside as a signal molecule for up-regulating membrane characteristics, antioxidant defense system to improve flax productivity under water stress

Water stress is a critical environmental adversity that significantly impacts the growth, development, and yield of flax plants. In this study, flax seeds were cultivated under different water irrigation requirements (100%, 75%, and 50% WIR) to investigate the effects of exogenously supplied nitric oxide (NO) donor sodium nitroprusside (SNP) as foliar treatments at concentrations of 0.0 mmol/L, 0.5 mmol/L, 1.0 mmol/L, and 2.0 mmol/L. Drought stress led to a significant decrease in plant growth, photosynthetic pigments, yield components such as oil and total carbohydrate percentage. It also resulted in an increase in leaf H2O2 production, lipid peroxidation levels and activities of enzymatic antioxidants including polyphenol oxidase, superoxide dismutase, and nitrate reductase enzymes. However, foliar application of SNP improved photosynthetic pigments and antioxidant defense system which mitigated the negative impact of water stress on growth and yield productivity by reducing oxidative damage caused by reactive oxygen species accumulation. The use of SNP also decreased H2O2 accumulation levels, lipid peroxidation levels, and improved membrane stability. SNP treatment at concentration of 2 mmol/L showed superior results compared to other concentrations with extremely significant increases observed in yield characteristics such as oil content, total carbohydrate percentages, and unsaturated fatty acids to saturated fatty acids ratio.

Protective Effects of Berberine on Nonalcoholic Fatty Liver Disease in db/db Mice via AMPK/SIRT1 Pathway Activation.

Berberine (BBR) has emerged as a promising therapeutic agent for nonalcoholic fatty liver disease (NAFLD). This study aims to elucidate the underlying molecular mechanisms. In this study, db/db mice were chosen as an animal model for NAFLD. A total of 10 healthy C57BL/6J mice and 30 db/db mice were randomly allocated to one of 4 groups: the normal control (NC) group, the diabetic control (DC) group, the Metformin (MET) therapy group, and the BBR therapy group. The total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in the serum were measured. The glutathione peroxidase (GSH-Px), glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), interleukin (IL)-1β, tumor necrosis factor (TNF)-α and monocyte chemotactic protein 1 (MCP-1) levels in liver tissue were measured. Hematoxylin and eosin (H&E), acid-Schiff (PAS) and TUNEL stanning was performed for histopathological analysis. Western blotting and immunohistochemistry were conducted to detect the expression levels of key proteins in the AMPK/SIRT1 pathway. BBR could improve lipid metabolism, attenuate hepatic steatosis and alleviate liver injury significantly. The excessive oxidative stress, high levels of inflammation and abnormal apoptosis in db/db mice were reversed after BBR intervention. BBR clearly changed the expression of AMP-activated protein kinase (AMPK)/Sirtuin 1 (SIRT1), and their downstream proteins. BBR could reverse NAFLD-related liver injury, likely by activating the AMPK/SIRT1 signaling pathway to inhibit oxidative stress, inflammation and apoptosis in hepatic tissue.

Potential therapeutic properties of broccoli extract and soy isoflavones on improvement endometriosis and involved oxidative parameters.

In Endometriosis is a gynecological disorder characterized by the growth of endometrial tissue outside the uterine cavity that is associated with chronic pelvic pain and subfertility. The purpose of the study was to investigate the effect of broccoli extract (BE) alone and in combination with soy isoflavones (SI) on endometrial implants in female rat. In this study, endometriosis was induced surgically in 40 mature female rats. The rats were divided into 5 groups that were treated by oral gavage for 6weeks with 0.5 mL of saline 0.9 %/day (control group), BE (3,000 mg/kg/day), SI (50 mg/kg/day), BE/soy isoflavones (BE 3000 mg/kg/day+soy isoflavones 50 mg/kg/day) and diphereline as a standard medication (3 mg/kg) intramuscularly. At the end of treatments, the volume and histopathology of the endometrial implants were compared among the 5 groups. The serum levels of oxidative parameters including superoxide dismutase (SOD), malondialdehyde (MDA) and tumor necrosis factor alpha (TNF-α) were also compared between the groups. The volume of the implants significantly decreased in diphereline group (p=0.002). The histopathological grade of endometrial implants in BE/SI and diphereline group were significantly decreased compared to the control group (p=0.001). The serum levels of SOD in BE group were enhanced significantly in comparison to the control group (p=0.034). BE in combination with SI decreased the growth and histopathologic grades of transplanted endometrial implants. These herbal compounds may have the potential therapeutic effect to be used as an alternative medication for the treatment of endometriosis.

StSnRK1.1 protein kinase positively regulates tuber dormancy release of potato

SnRK1 is a plant-specific serine/threonine protein kinase, that plays a vital role in maintaining the energy balance, nutrient distribution, growth, and development of organisms for survival. The period of tuber dormancy seriously affects potato production. To elucidate the effect of the StSnRK1.1 gene on dormancy release, the gene was cloned from the potato cultivar 'Desiree', and the overexpression and interfering expression lines were obtained through genetic transformation. StSnRK1.1 promoted early dormancy release and sprouting of potato tubers in the overexpression line, while it delayed tuber sprouting in the StSnRK1.1-interfering expression line. In addition, it was discovered that abscisic acid (ABA) in the StSnRK1.1 overexpression line was significantly reduced compared with the wild type plants, while the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were increased. Conversely, the opposite result was found in the StSnRK1.1 gene interference expression line, which indicated that the dormancy release was accelerated, the reactive oxygen species metabolism efficiency was high, and the reactive oxygen species could be quickly removed and the accumulation of reactive oxygen species could be avoided during the dormancy release process. The positive regulatory genes StSnRK2.2 and StABI5 of ABA signal transduction were lower than those of wild type in the overexpression line and higher than that of the wild type in the interfering expression line, while the negative regulatory genes StPP2CA1 and StPP2CA3 of ABA signal transduction were higher than those of the wild type in the overexpression line and lower than that of the wild type in the interfering expression line. In summary, StSnRK1.1 affects ABA signaling by mediating the expression of StSnRK2.2, StABI5, StPP2CA1 and StPP2CA3, which provides a theoretical basis for the molecular mechanism of StSnRK1.1 to positively regulate the release of potato tuber dormancy. Through yeast two-hybrid (YH2) screening, two interacting proteins, StCAT3 and StFBA1, were identified. The interaction between StCAT3, StFBA1 and StSnRK1.1 was confirmed through bimolecular fluorescence complementation. These results provide novel information for further study on the molecular mechanism of StSnRK1.1 regulating dormancy and germination of potato tubers.

Trichoderma produces methyl jasmonate-rich metabolites in the presence of Fusarium, showing biostimulant activity and wilt resistance in tomatoes.

Bioactive secondary metabolites from fungi, including Trichoderma, are an excellent source of plant biostimulants. Although production of novel biostimulants from known microbes is critical, challenging them may produce novel bioactive compounds. With this hypothesis, the study used live Fusarium chlamydosporum (FOL7) culture as the inducer during T. harzianum (IF63) growth in broth. Plate assays and gas chromatography-mass spectrometry (GC-MS) analysis were used to characterise the metabolites. Microscopy, pot experiments and, biochemical estimations of the defence-related enzymes in tomato plants established the biostimulant activity of the induced Trichoderma metabolites. Fungal crude metabolites (FCM) obtained from IF63+FOL7 broth and its extracts (ethyl acetate) showed increased antimicrobial activity. Extracts (dissolved in methanol) of the mixed culture FCM (TF.ex), 50 μgmL-1, inhibited the FOL7 growth by 68.33% compared to the Trichoderma alone extract (T.ex). Scanning electron microscopy (SEM) revealed morphological disruption of FOL7 mycelia by TF.ex. GC-MS analysis of the extracts revealed the presence of approximately 64 compounds, of which at least 13 were detected explicitly in TF.ex. Methyl (3-oxo-2-pentylcyclopentyl) acetate (Methyl di-hydrojasmonate), a lipid functionally related to jasmonic acid, was the major metabolite (∼21%) present in TF.ex. Tomato seed dressing with TF.ex promoted plant growth and induced systemic resistance against FOL7 compared to T.ex and F.ex. The TF.ex treatment increased the superoxide dismutase (33%) and catalase activity by 2.5-fold in tomato plants. The study concludes that fungal secondary metabolites may be modulated by providing appropriate challenges to produce effective metabolite-based biostimulants for agricultural applications.

Transcriptome profiling reveals the protective mechanism of sulfated Cyclocarya paliurus polysaccharides against oxidative damage of IEC-6 cell.

Our previous studies have shown that sulfated Cyclocarya paliurus polysaccharides (SCP3) can alleviate intestinal oxidative stress (OS) damage by improving the antioxidant capacity of the intestine, but its mechanism still needs further exploration. This study aimed to reveal the possible underlying protective mechanism of SCP3 against OS damage of intestinal epithelial cells (IEC-6) based on transcriptome profiling. The results showed that SCP3 could increase the activity of superoxide dismutase and reduce the production of malondialdehyde and reactive oxygen species. In addition, the SCP3 could also alleviate the H2O2-induced high apoptosis rate and mitochondrial membrane potential decrease in IEC-6 cells. RNA-sequencing results showed that there were 2152 differentially expressed genes between the control group and the SCP3 group, and the mitogen-activated protein kinases (MAPK) and PI3K-Akt signaling pathways are the main signaling pathways that contributed to SCP3 protecting IEC-6 cells from OS damage. In summary, the SCP3 plays a role in improving intestinal cell damage by inhibiting OS, which may be closely related to the PI3K/Akt and MAPK signaling pathways. PRACTICAL APPLICATION: This study provides a theoretical basis for the practical application of Cyclocarya paliurus polysaccharides as an antioxidant ingredient in auxiliary medicines and functional foods.

Cu(II)-chelated ovalbumin mimicking the active centre of superoxide dismutase: Structure, antioxidant and antibacterial properties for food preservation application

Enzymatic browning and microbial contamination of food threaten food sensory and safety. With the development of green and healthy concepts, there is a greater need for efficient, low-carbon antioxidant and antimicrobial strategies. In this study, we designed a nano-enzyme with antioxidant activities and biocompatibility. By mimicking the active center of the natural SOD enzyme, copper (Cu) and ovalbumin (OVA) were self-assembled to form Cu-nano-polymerised sheet (Cu-NPS), in which OVA as a scaffold carries cofactors to create the active sites, making the nanoenzymes compatible with the antioxidant activity and antimicrobial properties of Cu, and at the same time possessing good stability and biocompatibility. These properties enable Cu-NPS to have a broader application range, for removing reactive oxygen species (ROS) and broad-spectrum sterilization. Subsequently, Cu-NPS was doped into carrageenan (Carr) to form a nanocomposite film, effectively inhibiting enzymatic browning and microbial contamination. In this work, protein-based mimetic enzymes as artificial nanoenzymes have advantages over natural enzymes, and the Cu-NPS with simple synthesis, high stability, and diverse properties, provides new ideas for the design of functional materials.

A blend of chitosan-vitamin C and vitamin E nanoparticles robust the immunosuppressed- status in Nile tilapia treated with salt

In aquaculture, fish are exposed to many stressors, such as climate changes and infectious diseases that affect their performance, immunity, and welfare. Freshwater fish subjected to salt bath become exhausted and stressed. In this experiment, Nile tilapia were exposed to a salt bath at a dose of 30 ppt for 30 min a day. Vitamin C and vitamin E are well-known antioxidants that are used in aquaculture. Fish received dietary nanoparticles of chitosan-vitamin C and chitosan-vitamin E (CCE-NPs) for different periods (7 and 14 days) pre- (G2) and post-salt treatment (G3). In the control fish (G1), cortisol 5.44 µg/dL and glucose 91.67 mg/dL were significantly up-regulated post-salt treatment by 1 h and 24 h, respectively, whereas those (G2) fed CCE-NPs diet had significantly lower values of 4.72 and 3.25 µg/dL; 86.3 and 84.3 mg/dL, respectively. A rapid decrease of glucose 68.3 and 66.3 mg/dL was noticed in those (G2) fed CCE-NPs diet compared to the control 84.67 mg/dL at 48 h post-stress. Regardless of the supplementation period, fish (G2) could partially restore normal food reflex at 48 h (post-salt bath) and fully restored at 72 h compared to 7 days in the control (G1). After 48 h, fish that received dietary CCE-NPs (G2 and G3) restored normal mucus lysozyme levels, whereas the control did not restore pre-treatment values till the seventh day. Mucus antibacterial activity, fish received rapid dietary CCE-NPs (G2) and partially restored average values (pre-salt bath) at 96 h. The salt treatment could provoke gene expression of pro-inflammatory cytokines interleukin (IL-1β) and tumor necrosis (TNF)-α in the head kidney of fish at 24 h post-salt bath to 5.9–8.35 fold-change, respectively, with a rapid decline in fish (G2) the gene expression. Post-salt bath (24 h), the gene expression of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) was higher in fish (G2) than in the control group (G1) regardless of the supplementation period (7 and 14 days). Bacterial infection S. agalactiae (OL471408), a significantly lower MR was recorded in G2 at 40% and 33.3% compared to the control G1 MR (53.3%), with an RPL of 24.95% and 37.5%. In conclusion, Nile tilapia treated with a 30 ppt salt became more vulnerable to S. agalactiae. Adding CCE-NPs to the Nile tilapia diet for 7- and 14-day pre-salt bath could increase immune and antioxidant-related gene expression to counteract S. agalactiae infection.

Combining In Vitro, In Vivo, and Network Pharmacology Assays to Identify Targets and Molecular Mechanisms of Spirulina-Derived Biomolecules against Breast Cancer

The current research employed an animal model of 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary gland carcinogenesis. The estrogen receptor-positive human breast adenocarcinoma cell line (MCF-7) was used for in vitro analysis. This was combined with a network pharmacology-based approach to assess the anticancer properties of Spirulina (SP) extract and understand its molecular mechanisms. The results showed that the administration of 1 g/kg of SP increased the antioxidant activity by raising levels of catalase (CAT) and superoxide dismutase (SOD), while decreasing the levels of malonaldehyde (MDA) and protein carbonyl. A histological examination revealed reduced tumor occurrence, decreased estrogen receptor expression, suppressed cell proliferation, and promoted apoptosis in SP protected animals. In addition, SP disrupted the G2/M phase of the MCF-7 cell cycle, inducing apoptosis and reactive oxygen species (ROS) accumulation. It also enhanced intrinsic apoptosis in MCF-7 cells by upregulating cytochrome c, Bax, caspase-8, caspase-9, and caspase-7 proteins, while downregulating Bcl-2 production. The main compounds identified in the LC-MS/MS study of SP were 7-hydroxycoumarin derivatives of cinnamic acid, hinokinin, valeric acid, and α-linolenic acid. These substances specifically targeted three important proteins: ERK1/2 MAPK, PI3K-protein kinase B (AKT), and the epidermal growth factor receptor (EGFR). Network analysis and molecular docking indicated a significant binding affinity between SP and these proteins. This was verified by Western blot analysis that revealed decreased protein levels of p-EGFR, p-ERK1/2, and p-AKT following SP administration. SP was finally reported to suppress MCF-7 cell growth and induce apoptosis by modulating the PI3K/AKT/EGFR and MAPK signaling pathways suggesting EGFR as a potential target of SP in breast cancer (BC) treatment.

Evaluation of Salvia officinalis in the Treatment of Acetic Acid-Induced Ulcerative Colitis in a Rat Model

Abstract Introduction Ulcerative colitis (UC) is an inflammatory bowel disease that causes long-lasting inflammation and ulcers within the digestive tract. This study aims to determine the histochemical alteration of Salvia officinalis (sage), an anti-inflammatory and antioxidant herbal agent on UC. Materials and Methods The disease was induced in 37 Sprague-Dawley rats with 2 mL of 3% acetic-acid (AA) enema. The rats were divided into five groups: a control group (AA), two 5-aminosalicylic (5-ASA) groups treated either orally (AO) or rectally (AR) with a dose of 100 mg/kg, and two salvia groups treated with 300mg/kg salvia orally (SO) or rectally (SR). Histopathological analyses of the colon were done on day 7, and markers such as C-reactive protein (CRP), superoxide dismutase (SOD), and complete blood count were measured. Result In macroscopic evaluation, the AO group demonstrated the lowest involvement, followed by the SO, SR, AR, and AA groups, respectively (p = 0.01). There was no significant difference between the SO and AO groups (p = 0.10), and the SR and AR groups (p = 0.58). Regarding microscopic histopathological findings, the AO and SO group demonstrated the most satisfactory results, with no significant difference between the AO versus SO, and AR versus SR groups. Inflammation was resolved in all of the AO and SO subjects. Conclusion Salvia can be beneficial in the treatment course of UC by inhibiting inflammatory responses, increasing the growth and viability of intestinal mucosa, and its antioxidant effects. Therefore, we propose the prescription of salvia as an adds-on or alternative therapy in the management of UC.

Unlocking Selective Anticancer Mechanisms: Dinuclear Manganese Superoxide Dismutase Mimetics Combined with Pt(II) Complexes.

We exploration the in vitro activities of the dinuclearMn2L2AcandMn2L2complexes (where HL = 2-{[di(2-pyridyl)methylamino]-methyl}phenol), possessing dual superoxide dismutase (SOD) and catalase (CAT) activity, both individually and in conjunction with various Pt(II)-complexes, either as mixtures or astheMn2-Ptadducts. Our findings revealed a notable up to 50% enhancement in the viability of healthy human breast cells, contrasted with a viability decrease as low as 50% in breast cancer cells upon combined treatments withMn2SOD mimics and Pt(II) complexes.Specifically, we synthesized and characterized the self-assembledMn2-Ptadducts(isolatedMn2L2Ptandin situMn2L2Pt'), linkingMn2L2-core with the carboxylate group ofPtDAPCl2(dichloro(2,3-diaminopropionic acid) platinum(II)). The SOD activity of the isolatedMn2L2Ptadduct (kSOD= 1.7 × 107M-1s-1) remained intact. We elucidated key mechanisms underlying the observed biological effects.We demonstrated thatMn2-containing formulations predominantly target mitochondrial processes, differently affecting the proteome of cancerous and healthy cells. They induced downregulation of H2S signaling and expression of mitochondrial complex I and III, as well as increased oxidative phosphorylation pathways and upregulation of EGFR in cancer cells. In contrast, healthy cells showed a decrease in EGFR expression and a moderate enrichment in oxidative phosphorylation pathways.

Effects of Drought Stress on Leaf Functional Traits and Biomass Characteristics of Atriplex canescens

Drought is a critical factor constraining plant growth in arid regions. However, the performance and adaptive mechanism of Atriplex canescens (A. canescens) under drought stress remain unclear. Hence, a three-year experiment with three drought gradients was performed in a common garden, and the leaf functional traits, biomass and biomass partitioning patterns of A. canescens were investigated. The results showed that drought stress had significant effects on A. canescens leaf functional traits. A. canescens maintained the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), but the peroxidase (POD) and catalase (CAT) activity decreased, and the content of proline (Pro) and soluble sugar (SS) increased only under heavy drought stress. Under drought stress, the leaves became smaller but denser, the specific leaf area (SLA) decreased, but the dry matter content (LDMC) maintained stability. Total biomass decreased 60% to 1758 g under heavy drought stress and the seed and leaf biomass was only 10% and 20% of non-stress group, but there had no significant difference on root biomass. More biomass was allocated to root under drought stress. The root biomass allocation ratio was doubled from 9.62% to 19.81% under heavy drought, and the root/shoot ratio (R/S) increased from 0.11 to 0.25. The MDA was significantly and negatively correlated with biomass, while the SPAD was significantly and positively correlated with total and aboveground organs biomass. The POD, CAT, Pro and SS had significant correlations with root and seed allocation ratio. The leaf morphological traits related to leaf shape and weight had significant correlations with total and aboveground biomass and biomass allocation. Our study demonstrated that under drought stress, A. canescens made tradeoffs between growth potential and drought tolerance and evolved with a conservative strategy. These findings provide more information for an in-depth understanding of the adaption strategies of A. canescens to drought stress and provide potential guidance for planting and sustainable management of A. canescens in arid and semi-arid regions.

Interplay of miRNAs and molecular pathways in spaceflight-induced depression: Insights from a rat model using simulated complex space environment.

Depression is a significant concern among astronauts, yet the molecular mechanisms underlying spaceflight-induced depression remain poorly understood. MicroRNAs (miRNAs) have emerged as potential regulators of neuropsychiatric disorders, including depression, but their specific role in space-induced depression remains unexplored. This study aimed to elucidate the involvement of candidate miRNAs (miR-455-3p, miR-206-3p, miR-132-3p, miR-16-5p, miR-124-3p, and miR-145-3p) and their interaction with differentially expressed genes (DEGs) in the neurobiology of spaceflight-induced depressive behavior. Using a simulated space environmental model (SCSE) for 21 days, depressive behavior was induced in rats, and candidate miRNA expressions and DEGs in the cortex region were analyzed through qRT-PCR and HPLC, respectively. Results showed that SCSE-exposed rats exhibited depressive behaviors, including anhedonia, increased immobility, and anxiousness compared to controls. Further analysis revealed increased hydrogen peroxide levels and decreased superoxide dismutase levels in the SCSE group, indicating abnormal oxidative stress in the cerebral cortex. Moreover, miRNA analysis demonstrated significant upregulation of miR-455-3p, miR-206-3p, miR-132-3p, and miR-16-5p expression. Among the DEGs identified, the in silico analysis highlighted their involvement in crucial pathways such as glutamatergic signaling, GABA synaptic pathway, and calcium signaling, implicating their role in spaceflight-induced depression. Protein-protein interaction analysis identified hub genes, including DLG4, DLG3, GRIN1, GRIN2B, GRIN2A, SYNGAP1, DLGAP1, GRIK2, and GRIN3A, impacting neuronal dysfunction functions in the cortex region of SCSE depressive rats. DLG4 emerged as a core gene regulated by miR-455-3p and miR-206-3p. Overall, this study underscores the potential of miRNAs as biomarkers for mood disorders and neurological abnormalities associated with spaceflight, advancing health sciences, and space health care.