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Purpose: The purpose of this study was to evaluate the efficacy of recombinant human superoxide dismutase (rhSOD) enemas in radiation-induced acute rectal injury (RARI) in patients with locally advanced cervical cancer., Methods and Materials: In this phase 3, randomized, open-label trial (NCT04819685) conducted across 14 medical centers in China from June 2021 to August 2023, all patients received concurrent chemoradiation therapy (CCRT). The experimental group was treated with a rhSOD enema during chemoradiation therapy, and the control group had no enema. The Common Terminology Criteria for Adverse Events (version 5.0) was used to evaluate radiation therapy-induced side effects. Endoscopic appearance was assessed using the Vienna Rectoscopy Score. The primary endpoint in the acute phase was the occurrence rate and duration of grade ≥1 (≥G1) diarrhea during CCRT. Secondary endpoints included the occurrence rate and duration of ≥G2 and ≥G3 diarrhea, ≥G1 and ≥G2 diarrhea lasting at least 3 days, and damage to the rectal mucosa due to radiation therapy measured by endoscopy., Results: Two hundred and eighty-three patients were randomly divided into the experimental (n = 141) or control group (n = 142). The mean number of ≥G1 and ≥G2 diarrhea days were significantly lower in the experimental group than in the control group (3.5 and 0.8 days vs 14.8 and 4.5 days, respectively; P < .001). The incidence of ≥G2 diarrhea decreased from 53.6% to 24.1% when rhSOD enemas were used. Use of antidiarrheals was lower in the experimental group (36.2% vs 55.7%, P < .001). Three patients felt intolerable or abdominal pain after rhSOD enema. RARI grades in the experimental group tended to be lower than those in the control group (P = .061). Logistic regression analysis revealed that rhSOD enema was associated with a lower occurrence rate of ≥G1/2 diarrhea for at least 3 days (P < .001)., Conclusions: The results of this study suggest that rhSOD enema is safe and significantly reduces the incidence, severity, and duration of RARI, protecting the rectal mucosa., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Superoxide dismutase (SOD), a natural enzyme with high antioxidant activity, reduces injury and accelerates wound healing by scavenging superoxide radicals. This enzyme plays an important role in cellular defense against oxidative stress such as burn injury. The aim of this study was to load SOD into solid lipid nanoparticles for the treatment of rat burn wounds., Methods: Solid lipid nanoparticles were prepared by Solvent Emulsification Diffusion method and evaluated for particle size, enzyme activity and enzyme entrapment efficiency. Twenty-seven rats in 3 different groups were induced with deep second-degree burns and then treated with SOD-loaded solid lipid nanoparticles, solid lipid nanoparticles without enzyme, or SOD solution. After the treatment period, the wounds were evaluated macroscopically for the area of healing and microscopically for indices of re-epithelialization, granulation tissue and angiogenesis., Results: The optimized SOD-loaded solid lipid nanoparticles showed a particle size of 35-85 ± 2.41 nm, 78.4 ± 4.31 % entrapment efficiency and 90 % initial enzyme activity. Macroscopic examination showed that the best recovery rate belonged to the solid lipid nanoparticle group. Pathological studies also showed that angiogenesis and granulation tissue were significantly better in this group. Compared to the other two groups, SOD-loaded solid lipid nanoparticles showed a significant improvement in pathological factors, particularly angiogenesis and granulation tissue, as well as a faster reduction in the number of inflammatory cells., Conclusion: Based on this study, solid lipid nanoparticles could be used as an effective delivery system for SOD in the treatment of second-degree burns., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest in this study., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Objective: To examine the therapeutic effects of vitamin E combined with recombinant human epidermal growth factor on recurrent oral ulcers as well as on the levels of serum superoxide dismutase (SOD), interleukin-10 (IL-10), and tumor necrosis factor- (TNF-α), to provide evidence to facilitate medical management., Method: From June 2021 to May 2022, 84 patients with recurrent oral ulcers assessed and treated in our hospital were assigned to the control group and observation group with 42 cases in each group. Vitamin E was administered to the control group, while recombinant human epidermal growth factor and vitamin E were administered to the observation group. The clinical efficacy, serum SOD level, inflammatory factor level (IL-10, TNF-α), immune function index, clinical symptom improvement, pain disappearance time, healing time of ulcer surface, and adverse reactions were examined., Results: Clinical efficacy of the observation group (92.86%) was considerably greater than the control group (73.81%), (P < .05). Following treatment, the observation group had comparatively higher levels of serum SOD and significantly decreased TNF-α and IL-10 concentrations compared to the control group (P < .05). Similarly, post-treatment, the observation group had substantially higher CD3+, CD4+, and CD4+/CD8+ concentrations and lower CD8+ concentrations compared to the normal control (P < .05). In contrast to the control group, the observation group's pain degree score, ulcer diameter, duration for pain relief, and ulcer surface healing time duration were reduced substantially (P < .05). Notably, the incidence of adverse reactions was fairly similar in both groups (P > .05)., Conclusion: Vitamin E combined with recombinant human epidermal growth factor has a significant clinical effect on recurrent oral ulcers, can achieve rapid improvement of symptoms in patients, and is relatively safe to be used as a clinical therapy.

Background: Chronic prostatitis demonstrates a prevalence rate of nearly 5%-10% among young and middle-aged individuals, significantly affecting their daily lives. Researchers have obtained significant outcomes investigating the anti-inflammatory properties of itaconic acid (IA) and its derivative, 4-Octyl itaconate (4-OI), against diverse chronic inflammatory disorders, such as osteoarthritis and airway inflammation. Nevertheless, whether IA can also exert anti-inflammatory effects in chronic prostatitis requires extensive research and validation., Methods: Human prostate tissues obtained through transurethral prostate resection (TURP) from individuals were divided into three groups based on different levels of inflammation using hematoxylin and eosin staining (H&E). Subsequently, immunohistochemistry (IHC) was employed to detect the expression of immune-responsive gene 1 (IRG-1) in these different groups. The animal experiment of this study induced experimental autoimmune prostatitis (EAP) in nonobese diabetic mice through intradermal prostate antigen injection and complete Freund's adjuvant. Then, the experimental group received intraperitoneal injections of different doses of 4-OI, while the control group received injections of saline. Western blot (WB), H&E staining, and TUNEL staining helped analyze the prostate tissues, while enzyme-linked immunosorbent assay (ELISA) helped evaluate serum inflammatory factors. Reactive oxygen species, superoxide dismutase (SOD), and malondialdehyde (MDA) were assessed for oxidative stress across experimental groups., Results: IHC analysis of human prostate tissue depicts that IRG-1 expression enhances as prostate inflammation worsens, highlighting the critical role of IA in human prostatitis. The application of 4-OI increased Nrf2/HO-1 expression while inhibited NLRP3 expression following the WB results, and its application resulted in a decrease in cell pyroptosis in prostate tissue, demonstrated by the results of TUNEL staining. Administering a Nrf2 inhibitor ML385 1 h before intraperitoneal injection of 50 mg/kg 4-OI reversed the previous conclusion, further confirming the above conclusion from another perspective. Meanwhile, the ELISA results of serum inflammatory factors (IL-1β, IL-6, and TNF-α), as well as the measurements of oxidative stress markers MDA and SOD, further confirmed the specific anti-inflammatory effects of 4-OI in EAP., Conclusions: The present study indicates that 4-OI can alleviates EAP by inhibiting the NLRP3 inflammasome-induced pyroptosis through activating Nrf2/HO-1 pathway, which may facilitate a novel approach toward prostatitis treatment., (© 2023 Wiley Periodicals LLC.)

Background: Sepsis is a life-threatening condition characterized by acute organ dysfunction, which frequently leads to acute lung injury (ALI) in approximately 40% of cases. Isoegomaketone (IK) is a constituent of essential oil found in P. frutescens , known for its diverse biological properties, including anti-inflammatory and antitumor effects. However, the regulatory impact of IK on ALI in the context of sepsis remains poorly understood., Methods: Pathological alterations in lung tissues were assessed using hematoxylin and eosin staining. Enumeration of total leukocytes and neutrophils in bronchoalveolar lavage fluid (BALF) was performed using a hematocytometer, while the levels of interleukin (IL)-6, IL-1β, IL-10, and IL-17 in BALF were quantified using enzyme-linked immunosorbent serological assay. In addition, the levels of malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and glutathione (GSH) in lung tissues were assessed using respective commercial kits; cell apoptosis was evaluated using the terminal deoxynucleotide transferase--mediated dUTP nick end-labeling assay, and protein expressions were determined through Western blot analysis., Results: Our findings revealed that cecal ligation and puncture (CLP) treatment in mice induced severe lung injury, characterized by increased lung injury scores, significant bleeding, neutrophil infiltration, and alveolar edema. However, treatment with IK at a dose of 10 mg/kg ameliorated CLP-induced lung injury, while IK dose of 5 mg/kg showed no significant effect. Additionally, IK treatment at 10 mg/kg reduced CLP-induced inflammation by decreasing levels of IL-6, IL-1β, IL-10, and IL-17. Furthermore, IK at 10 mg/kg attenuated CLP-induced oxidative stress by modulating levels of MDA, MPO, SOD, and GSH. Moreover, IK treatment with a dose of 10 mg/kg activated the nuclear factor erythroid 2-related factor 2-heme oxygenase-1 (Nrf2-HO-1) pathway by enhancing the protein expressions of Nrf2 and HO-1., Conclusion: This study demonstrates that IK could mitigate the inflammatory response and oxidative stress associated with sepsis-induced ALI, supporting IK as a promising therapeutic agent for the treatment of sepsis-associated ALI., Competing Interests: The authors stated that there were no conflict of interest to disclose.

Toxic signaling by extrasynaptic NMDA receptors (eNMDARs) is considered an important promoter of amyotrophic lateral sclerosis (ALS) disease progression. To exploit this therapeutically, we take advantage of TwinF interface (TI) inhibition, a pharmacological principle that, contrary to classical NMDAR pharmacology, allows selective elimination of eNMDAR-mediated toxicity via disruption of the NMDAR/TRPM4 death signaling complex while sparing the vital physiological functions of synaptic NMDARs. Post-disease onset treatment of the SOD1 G93A ALS mouse model with FP802, a modified TI inhibitor with a safe pharmacology profile, stops the progressive loss of motor neurons in the spinal cord, resulting in a reduction in the serum biomarker neurofilament light chain, improved motor performance, and an extension of life expectancy. FP802 also effectively blocks NMDA-induced death of neurons in ALS patient-derived forebrain organoids. These results establish eNMDAR toxicity as a key player in ALS pathogenesis. TI inhibitors may provide an effective treatment option for ALS patients., Competing Interests: Declaration of interests H.B. and J.Y. are named inventors of the patent application for a novel class of neuroprotectants (PCT/EP2018/078577); H.B. is co-founder of FundaMental Pharma GmbH, Heidelberg, Germany, which licenses FP802; H.B. and J.Y. are shareholders of FundaMental Pharma GmbH., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ginger (Gin) has numerous therapeutic properties. One of Gin's most potent components is 6-gingerol, a naturally occurring phenol. This study aimed to investigate the therapeutic impact of gingerol and/or sorafenib on the ATG4/CASP3 and COIIV/COX-2/NF-B Expression as a potential therapy for DAB-induced HCC. Gin was administered to HCC mice induced by p-Dimethylaminoazobenzene (DAB) alone or combined with sorafenib (Sor). Superoxide dismutase (SOD), catalase (CAT), and oxidative stress malondialdehyde (MDA), as well as biochemical markers including AST, ALT, ALP, Albumin, and Bilirubin, were examined. The expression of oncogenes (COIIV, COX-2, NF-κB, and survivin) and tumor suppressor genes (ATG4 and CASP3) was evaluated using qPCR. According to the results, the levels of MDA have been markedly decreased, while SOD and CAT have been increased. Further, the expression levels of tumor suppressor genes were upregulated, whereas the expression levels of oncogene genes were downregulated. Furthermore, in a dose-dependent manner, gingerol has shown the potential to alleviate hepatic portal vein (PV) dilatation and could offer a reliable therapy for HCC. This suggests combining the two compounds may be more effective than alone and that Gin could be a promising therapeutic option for HCC. The binding of Gin and Sor to the active sites of the target genes prevents them from functioning normally, which in turn stops the pathways from carrying out their oncogenic functions. Additionally, COX-2 inhibition reduces the production of certain pro-inflammatory compounds, which further averts oncogenesis. Conclusively, this study indicated that Gin has cytoprotective properties and anti-cancer activity that may be related to controlling oxidative stress. This effect may be achieved by suppressing the COIIV/COX-2/NF-κB pathway and upregulating the ATG4 /CASP3 pathways., (© 2024. The Author(s).)

Amyotrophic lateral sclerosis (ALS) is a devastating fatal neurodegenerative disease with no cure. Receptor-interacting protein kinase 1 (RIPK1) has been proposed to mediate pathogenesis of ALS. Primidone has been identified as an old drug that can also inhibit RIPK1 kinase. We conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1 G93A mice and ALS patients. SOD1 G93A mice treated with primidone showed significant delay of symptomatic onset and improved motor performance. One-hundred-sixty-two ALS participants dosed daily with primidone (62.5 mg) completed 24-week follow-up. A significant reduction was showed in serum levels of RIPK1 and IL-8, which were significantly higher in ALS patients than that of healthy controls (P < 0.0001). Serum RIPK1 levels were correlated positively with the severity of bulbar symptoms (P < 0.05). Our study suggests that serum levels of RIPK1 and IL-8 in peripheral can be used as clinical biomarkers for the activation of RIPK1 in central nervous system in human ALS patients. Repurposing primidone may provide a promising therapeutic strategy for ALS. The effect of primidone for the treatment of other inflammatory diseases may also be considered, since the activation of RIPK1 has been implicated in mediating a variety of inflammatory diseases including COVID-19-associated cytokine release syndrome (CRS). (ChiCTR2200060149)., (© 2023. The Author(s).)

Objectives: Oxidative stress is one of the carcinogenic mechanisms underlying the development of glioblastoma multiforme (GBM), a highly aggressive brain tumor type associated with poor prognosis. Curcumin is known to be an efficient antioxidant, anti-inflammatory, and anticancer compound. However, its poor solubility in water, inappropriate pharmacokinetics, and low bioavailability limit its use as an antitumor drug. We prepared PLGA-based curcumin nanoparticles changed with folic acid and chitosan (curcumin-PLGA-CS-FA) and evaluated its effects on GBM tumor cells' redox status., Methods: The nanoprecipitation method was used to synthesize CU nanoparticles (CU-NPs). The size, morphology, and stability were characterized by DLS, SEM, and zeta potential analysis, respectively. The CU-NPs' toxic properties were studied by MTT assay and measuring the intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) concentrations. The study was completed by measuring the gene expression levels and activity of superoxide dismutase, catalase, glutaredoxin, and thioredoxin antioxidant enzymes., Results: The size, polydispersity index, and zeta potential of CU-NPs were 77.27 nm, 0.29, and -22.45 mV, respectively. The encapsulation efficiency was approximately 98%. Intracellular ROS and MDA levels decreased after CU-NP treatment. Meanwhile, the CU-NPs increased gene expression and activity of superoxide dismutase, catalase, glutaredoxin, and thioredoxin antioxidant enzymes., Conclusion: CU-NPs might be effective in the prevention and treatment of glioblastoma cancer by modulating the antioxidant-oxidant balance., (© 2023 John Wiley & Sons Ltd.)

Background: Inflammation and oxidative stress (OS) are major causes of aneurysmal subarachnoid hemorrhage (aSAH)-induced early brain injury (EBI). Eriocitrin (EC), a flavonoid compound, has anti-inflammatory and antioxidant actions. However, there is still no relevant studies on the role of EC in SAH. Accordingly, this research aims to clarify the anti-OS and anti-inflammatory efficacy of EC in SAH., Method: Rat SAH model was established in vivo and administered with Eriocitrin (25 mg/kg). In vitro , BV2 cells were exposed to oxyhemoglobin (OxyHb) for 24 hours and pretreated with Eriocitrin (1 uM/mL, 2 uM/mL, 4 uM/mL) for 30 minutes. Water maze experiments and neurological function scores were conducted to assess cognitive and motor function. TdT-mediated dUTP Nick-End Labeling (TUNEL) staining was used to detect cortical cell apoptosis. Enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR) were used to detect the inflammatory factors and malondialdehyde (MDA), as well as the expression of superoxide dismutase (SOD) and glutathione peroxidase (GSH-px). Western blots were used to semi quantify nuclear factor erythroid-2-related factor 2 (Nrf2), nuclear factor-κB (NF-κB), dual specificity phosphatase 14 (DUSP14) expression., Results: The findings suggest that EC (25 mg/kg) reduced SAH-induced central nervous system (CNS) damage, neuronal apoptosis, inflammatory reactions and OS. Regarding a mechanistic study, EC enhanced Nrf2 and NF-κB by increasing DUSP14 activation, thereby reducing the inflammatory cytokines interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-6. In addition, EC decreased MDA while markedly elevating SOD and enhancing GSH-px. Furthermore, specifically inhibiting DUSP14 expression via using protein-tyrosine-phosphatase (PTP) inhibitor IV, neutralized the protective action of EC and aggravated inflammation and OS. In vitro experiments of OxyHb-induced BV2 cells revealed that EC promoted Nrf2 while markedly suppressing NF-κB by increasing DUSP14 activation, thereby reducing the concentrations of the above inflammatory cytokines. Moreover, EC decreased MDA while evidently increasing SOD and GSH-px., Conclusion: In summary, this paper lays a theoretical grounding for EC treatment of SAH-induced inflammatory reactions and OS by regulating DUSP14.

Introduction: Environmental chemicals have been associated with the regulation of oxidative stress markers, which have the potential for the development of bladder cancer. However, limited studies on the function of oxidative stress parameters and nonmuscle invasive bladder cancer (NMIBC) in therapy response are available. Here we studied the oxidative stress parameters in response to BCG immunotherapy in NMIBC patients., Material and Methods: A total of 120 patients with NMIBC and treatment with BCG were enrolled and categorized into 2 groups on BCG response, 50 patients were BCG-responsive (BCG-R) and 70 were BCG-nonresponsive (BCG-N). BCG-R have no evidence of tumor recurrence or advancement after 1 year of BCG immunotherapy, but BCG-N has a recurrence of tumor after 3 to 6 months cycles of BCG instillation, as determined by cystoscopy. In all groups, we measured the levels of oxidative stress markers- malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and catalase (CAT)., Results: The levels of oxidative stress markers viz. MDA, NO, and SOD in the BCG-N group were significantly higher (P < 0.001) than in the BCG-R group. Furthermore, the data demonstrated a significant correlation between oxidative stress marker and NMIBC T1 high grade and tumor size >2.5 cm. However, no statistically significant difference was found between studied groups with CAT., Conclusion: The findings suggest that the carcinogenesis of NMIBC is associated with oxidative damage of biomolecules and indicates the involvement of oxidative stress markers in the development and recurrence of NMIBC.; Therefore, it is critical to ensure the management for T1 high grade and tumor size of >2.5 cm for antioxidant protection., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pelvic inflammatory disease (PID) is commonly encountered in gynecological practice. Kangfuxiaomi suppository, made from the compound extract of Periplaneta Americana, is a Traditional Chinese Medicine remedy widely used for the treatment of gynecological disorders. This study aimed to preliminarily explore the therapeutic effect of Kangfuxiaomi suppository in a rat model of PID established by chemical injury and pathogen infection. The key parameters assessed were vulvar inflammation score, vaginal + uterine organ index, and serum levels of interleukin (IL)- 8; tumor necrosis factor (TNF)-α; C-reactive protein (CRP); superoxide dismutase (SOD); and malondialdehyde (MDA). In addition, levels of IL-6, cyclooxygenase (COX)- 2, and IL-2 in cervical tissues as well as that of IL-1β and prostaglandin E-2 (PGE2) in uterine tissues were measured. The expression levels of nuclear factor-kappa B (NF-κB) p65 and Toll-like receptor 4 (TLR4) in uterine tissues were detected by immunohistochemical method. After Kangfuxiaomi suppository treatment, the vulva inflammation score and histopathological score of PID rats showed a tendency to decrease. Serum IL-8, TNF-α, CRP, and MDA levels were reduced, while SOD levels were significantly increased. Levels of IL-6, IL-2, and COX-2 in cervical tissues were somewhat decreased, and PGE2 and IL-1β levels in uterine tissue were significantly decreased. Moreover, the levels of NF-κB p65 and TLR4 protein expression were also decreased. These findings demonstrated the therapeutic effect of Kangfuxiaomi suppository in PID rats. The underlying mechanism may involve enhanced antioxidant capacity and decreased secretion of proinflammatory factors via the NF-κB/TLR4 signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To study the effects of grape seed proanthocyanidins (GSP) combined with allicin on serum lipids level and vascular damage in a rat model of hyperlipidemia., Materials and Methods: SD rats(male, 170-220 gn= 40) were randomized into five groups (n = 8/group): modelhigh fat and cholesterol diet; controlnormal diet; model+low-dose (GSP+allicin )(GSP 45mg/kg, allicin 30mg/kg, orally); model+high-dose (GSP+allicin) (GSP180mg/kg, allicin 90mg/kg, orally) and positive control (model+simvastatin (4 mg/kg)). Normal control group was fed conventionally, and remaining four groups were fed high cholesterol and fat food to replicate the high fat model. After 9 weeks, the normal control group continued to receive regular feeding, while the other groups continued to receive high-fat feeding. At the same time, model and normal control groups were given equal volume of physiological saline by gavage, and the other treatment groups began to receive corresponding drugs by gavage once a day. After 4 weeks, serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) as well as high-density lipoprotein cholesterol (HDL-C) in rats were determined. And the body weight of rat, total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA)in serum were identified. The level of endothelin-1(ET-1) was quantitative analysis by ELISA assay., Results: In comparison to normal controls, the model group displayed a marked rise in body weight, an increment in serum concentrations of LDL-C, TG and TC, as well as a decline in HDL (P<0.01), demonstrating successful model replication; All doses of GSP in combination with allicin resulted in a reduction in TG, LDL-C, and TC and an enhancement in HDL-C in contrast to the model control (all P<0.05). High-dose (GSP+allicin ) decreased MDA, and increased T-AOC and SOD activity(all P<0.01). All doses of GSP combined with allicin decreased ET-1 (all P<0.05). In addition, the protective effect of GSP combined with allicin was dose-dependent., Conclusions: Studies have shown that GSP combined with allicin can significantly improve blood lipids in hyperlipidemic rats, and this mechanism may be related to antioxidants and reduced endothelial damage.

Objective: This study aims to explore the potential biomarkers in the development of diabetes mellitus (DM) into diabetic retinopathy (DR)., Methods: Systematic review of diabetic metabolomics was used to screen the differential metabolites and related pathways during the development of DM. Non-targeted lipidomics of rat plasma was performed to explore the differential metabolites in the development of DM into DR in vivo. To verify the effects of differential metabolites in inducing retinal microvascular endothelial cells (RMECs) injury by increasing oxidative stress, high glucose medium containing differential metabolites was used to induce rat RMECs injury and cell viability, malondialdehyde (MDA) contents, superoxide dismutase (SOD) activities, reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were evaluated in vitro. Network pharmacology was performed to explore the potential mechanism of differential metabolites in inducing DR., Results: Through the systematic review, 148 differential metabolites were obtained and the sphingolipid metabolic pathway attracted our attention. Plasma non-targeted lipidomics found that sphingolipids were accompanied by the development of DM into DR. In vitro experiments showed sphinganine and sphingosine-1-phosphate aggravated rat RMECs injury induced by high glucose, further increased MDA and ROS levels, and further decreased SOD activities and MMP. Network pharmacology revealed sphinganine and sphingosine-1-phosphate may induce DR by regulating the AGE-RAGE and HIF-1 signaling pathways., Conclusions: Integrated systematic review, lipidomics and experiment verification reveal that abnormal sphingolipid metabolism facilitates DR by inducing oxidative stress on RMECs. Our study could provide the experimental basis for finding potential biomarkers for the diagnosis and treatment of DR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Free oxygen radicals have been implicated in the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants. Superoxide dismutase (SOD) is a naturally occurring enzyme which provides a defense against such oxidant injury. Providing supplementary SOD has been tested in clinical trials to prevent BPD in preterm infants., Objectives: To determine the efficacy and safety of SOD in the prevention and treatment of BPD on mortality and other complications of prematurity in infants at risk for, or having BPD., Search Methods: We searched CENTRAL, PubMed, Embase, and three trials registers on 22 September 2022 together with reference checking, citation searching and contact with study authors to identify additional studies., Selection Criteria: Randomized, quasi-randomized and cluster-randomized controlled trials (RCTs) where the participants were preterm infants who had developed, or were at risk of developing BPD, and who were randomly allocated to receive either SOD (in any form, by any route, any dose, anytime) or placebo, or no treatment., Data Collection and Analysis: We used standard Cochrane methods. Our primary outcomes were BPD defined as an oxygen requirement at 28 days, BPD defined as oxygen at 36 weeks' postmenstrual age, neonatal mortality, mortality prior to discharge, and BPD or death at 36 weeks' postmenstrual age. We reported risk ratio (RR) and risk difference (RD) with 95% confidence intervals (CIs) for the dichotomous outcomes. We used GRADE to assess certainty of evidence for each outcome., Main Results: We included three RCTs (380 infants) on SOD administration in preterm infants at risk for BPD, and no studies in preterm infants with evolving BPD / early respiratory insufficiency. The evidence is very uncertain about the effect of SOD on BPD defined as an oxygen requirement at 28 days (RR 1.09, 95% CI 0.94 to 1.26; RD 0.06, 95% CI -0.05 to 0.16, 1 study, 302 infants; I 2 for RR and RD not applicable), BPD defined as oxygen at 36 weeks' postmenstrual age (RR 0.96, 95% CI 0.72 to 1.29; RD -0.01, 95% CI -0.11 to 0.09, 2 studies, 335 infants; I 2 for RR and RD = 0%), neonatal mortality (RR 0.98, 95% CI 0.57 to 1.68; RD -0.00, 95% CI -0.08 to 0.07, 2 studies, 335 infants; I 2 for RR and RD = 0%), and mortality prior to discharge (RR 1.20, 95% CI 0.53 to 2.71; RD 0.04, 95% CI -0.14 to 0.23, 2 studies, 78 infants; I 2 for RR and RD = 0%). No studies reported BPD or death at 36 weeks' postmenstrual age. The evidence is very uncertain about the effect of SOD on retinopathy of prematurity any stage (RR 0.95, 95% CI 0.78 to 1.15; RD -0.03, 95% CI -0.15 to 0.08, 2 studies, 335 infants; I 2 for RR = 0%, I 2 for RD = 8%), and severe retinopathy of prematurity (ROP) (RR 0.97, 95% CI 0.57 to 1.65; RD -0.01, 95% CI -0.10 to 0.09, 1 study, 244 infants; I 2 for RR and RD not applicable). No studies reported moderate to severe neurodevelopmental outcome at 18 to 24 months. Certainty of evidence was very low for all outcomes. We identified no ongoing trials., Authors' Conclusions: The evidence is very uncertain about the effect of SOD on BPD defined as an oxygen requirement at 28 days, BPD defined as oxygen at 36 weeks' postmenstrual age, neonatal mortality and mortality prior to discharge compared to placebo. No studies reported BPD or death at 36 weeks' postmenstrual age and need for supplemental oxygen. The evidence is very uncertain about the effect of SOD on retinopathy of prematurity any stage and severe retinopathy of prematurity. No studies reported moderate to severe neurodevelopmental outcome at 18 to 24 months. The effects of SOD in preterm infants has not been reported in any trial in the last few decades, considering that the most recent trial on SOD in preterm infants was conducted in 1997/1998, and no new studies are ongoing. In the light of the limited available evidence, new data from preclinical and observational studies are needed to justify the conduction of new RCTs. Observational studies might report how SOD is administered, including indication, dose and association with relevant outcomes such as mortality, BPD and long-term neurodevelopment., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory failure syndrome with diverse etiologies characterized by increased permeability of alveolar-capillary membranes, pulmonary edema, and acute onset hypoxemia. During the ARDS acute phase, neutrophil infiltration into the alveolar space results in uncontrolled release of reactive oxygen species (ROS) and proteases, overwhelming antioxidant defenses and causing alveolar epithelial and lung endothelial injury. Objectives: To investigate the therapeutic potential of a novel recombinant human Cu-Zn-superoxide dismutase (SOD) fusion protein in protecting against ROS injury and for aerosolized SOD delivery to treat Escherichia coli induced ARDS. Methods: Fusion proteins incorporating human Cu-Zn-SOD (hSOD1), with (pep1-hSOD1-his) and without (hSOD1-his) a fused hyaluronic acid-binding peptide, were expressed in E. coli . Purified proteins were evaluated in in vitro assays with human bronchial epithelial cells and through aerosolized delivery to the lung of an E. coli -induced ARDS rat model. Results: SOD proteins exhibited high SOD activity in vitro and protected bronchial epithelial cells from oxidative damage. hSOD1-his and pep1-hSOD1-his retained SOD activity postnebulization and exhibited no adverse effects in the rat. Pep1-hSOD1-his administered through instillation or nebulization to the lung of an E. coli -induced pneumonia rat improved arterial oxygenation and lactate levels compared to vehicle after 48 hours. Static lung compliance was improved when the pep1-hSOD1-his protein was delivered by instillation. White cell infiltration to the lung was significantly reduced by aerosolized delivery of protein, and reduction of cytokine-induced neutrophil chemoattractant-1, interferon-gamma, and interleukin 6 pro-inflammatory cytokine concentrations in bronchoalveolar lavage was observed. Conclusions: Aerosol delivery of a novel recombinant modified SOD protein reduces oxidant injury and attenuates E. coli induced lung injury in rats. The results provide a strong basis for further investigation of the therapeutic potential of hSOD1 in the treatment of ARDS.

Background and Objectives: Myocardial ischemia-reperfusion injury (MIRI) threatens global health and lowers people's sense of happiness. Till now, the mechanism of MIRI has not been well-understood. Therefore, this study was designed to explore the role of UBIAD1 in MIRI as well as its detailed reaction mechanism., Methods: The mRNA and protein expressions of UBIAD1 before or after transfection were measured using RT-qPCR and western blot. Western blot was also adopted to measure the expressions of signaling pathway-, mitochondrial damage- and apoptosis-related proteins. Moreover, mitochondrial membrane potential and ATP level were verified by JC-1 immunofluorescence and ATP kits, respectively. With the application of CCK-8, LDH and CK-MB assays, the cell viability, LDH and CK-MB levels were evaluated, respectively. In addition, the cell apoptosis was detected using TUNEL. Finally, the expressions of ROS, SOD, MDA and CAT were measured using DCFH-DA, SOD, MDA and CAT assays, respectively., Results: In the present study, we found that UBIAD1 was downregulated in hypoxia-reoxygenation (H/R) -induced H9C2 cells and its upregulation could activate SIRT1/PGC1α signaling pathway. It was also found that UBIAD1 regulated mitochondrial membrane potential and ATP level via activating SIRT1/PGC1α signaling pathway. In addition, the injury of H/R-induced H9C2 cells could be relieved by UBIAD1 through the activation of SIRT1/PGC1α signaling pathway. Moreover, UBIAD1 exhibited inhibitory effects on apoptosis and oxidative stress of H/R-induced H9C2 cells through activating SIRT1/PGC1α signaling pathway., Conclusion: To sum up, UBIAD1 could alleviate apoptosis, oxidative stress and H9C2 cell injury by activating SIRT1/PGC1α, which laid experimental foundation for the clinical treatment of MIRI.

The loss and progressive dysfunction of neurons are hallmarks of neurodegenerative diseases. The aim of the current study is to explore the effects of photobiomodulation at 460-660 nm (100-1000 lux units) on the progression of scopolamine-induced cognitive dysfunctions in Wistar male rats. Photobiomodulation (PBM) is defined as "the use of monochromatic or quasi-monochromatic light from a low-power laser or light-emitting diode (LED) source to modify or modulate biological functions." Neuroprotective activity was assessed by in vivo models such as the Morris water maze, the elevated plus maze (EPM), and the T-maze. After using scopolamine (1 mg/kg/day) as a dementia induction model for 21 days, the induction was primarily due to impairments in cholinergic transmission, oxidative stress, and inflammation. The in vitro determinations, including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), reduced glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor-alpha (TNF-α), Interleukin 1 beta (IL-1β), and alkaline phosphatase (ALP), were assessed biochemicals and biomarkers. The structural and morphological integrity of the cortex and hippocampus was investigated through histopathology. In vivo studies of exteroceptive behavior models such as the Morris water maze, the EPM, and the T-maze revealed that administration of scopolamine resulted in enhanced escape latency time (ELT), transfer latency (TL), and decreased percentage alternation, respectively. The levels of AChE, BChE, reduced, GSH, SOD, TNF-α, IL-1β and ALP were increased, while MDA level was decreased. In contrast to normal and control groups with treatment groups, histopathology of the cortex and hippocampus examination revealed the maintenance of structural integrity and densities of CA1 and CA3 neuronal cells. However, network pharmacology predicted Ca +2 modulation of various pathways, among the treatments with red LED light showed highly significant amelioration compared with normal and control groups. Photobiomodulation by hormesis, chromophores in cells, and tissues excitation can influence neuroprotective effect mainly by scavenging of ROS, variation in the level of GSH MDA and SOD mitochondrial electron transfer, the improved abscopal effects on improved in gut microbiome by resembles the of fecal ALP level correlation of intestinal microbiome, cholinergic neurotransmissions, anti-inflammatory, and antioxidant activities., (© 2023 Wiley-VCH GmbH.)

This study aimed to evaluate the effects of the repeated administration of tramadol subcutaneously on postoperative analgesia, liver, kidneys, and oxidative status in the postoperative period of cats undergoing ovariohysterectomy. Thirty-seven cats were randomly assigned to 5 groups, according to the postoperative analgesic treatment: NaCl 0.9%, GC; tramadol at 2 mg/kg, T2B (q12h) and T2T (q8h); or 4 mg/kg, T4B (q12h) and T4T (q8h). Oxidative status was assessed at baseline, 12 hours and 24 hours after the final administration of tramadol by the activity of superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), butyrylcholinesterase (BuChE), and lipoperoxidation (MDA). Total blood count, serum biochemistry and urinalysis were compared between baseline and 12 hours posttramadol. Postoperative pain was evaluated by applying the Glasgow Feline Composite Measure Pain Scale at baseline, 3 (T3), 6 (T6), 8 (T8), 12 (T12), 24 (T24) e 36 (T36) hours after extubation. No side effects were observed. Tramadol increased SOD activity while CAT varied among groups in all time points but not over time. MDA levels increased from baseline to 12 hours in all groups but T4T. MPO activity decreased from baseline to 24 hours in some groups, including GC. Creatinine and phosphatase alkaline decreased in T2T, T4B, and T4T at 12 hours. Higher pain scores were observed from T3 to T8, except for GC. Rescue analgesia was administered only at T3. No difference in pain scores was observed from T8 onwards. Based on the findings, it is suggested that tramadol at 2 mg/kg every 8 hours is recommended for postoperative analgesia of cats undergoing ovariohysterectomy., Competing Interests: Declaration of Competing Interest None of the authors of this article has a financial or personal relationship with other people or organizations that may influence the content of the article, declaring any potential conflict of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: The objective of this study was to use a novel combined pharmacoepidemiologic and amyotrophic lateral sclerosis (ALS) mouse model approach to identify potential motor neuron protective medications., Methods: We constructed a large, population-based case-control study to investigate motor neuron disease (MND) among US Medicare beneficiaries aged 66 to 90 in 2009. We included 1,128 incident MND cases and 56,400 age, sex, race, and ethnicity matched controls. We calculated MND relative risk for >1,000 active ingredients represented in Part D (pharmacy) claims in 2006 to 2007 (>1 year before diagnosis/reference). We then applied a comprehensive screening approach to select medications for testing in SOD1 G93A mice: sulfasalazine, telmisartan, and lovastatin. We treated mice with the human dose equivalent of the medication or vehicle via subcutaneous osmotic pump before onset of weakness. We then assessed weight, gait, and survival. In additional mice, we conducted histological studies., Results: We observed previously established medical associations for MND and an inverse dose-response association between lovastatin and MND, with 28% reduced risk at 40 mg/day. In SOD1 G93A mouse studies, sulfasalazine and telmisartan conferred no benefit, whereas lovastatin treatment delayed onset and prolonged survival. Lovastatin treated mice also had less microgliosis, misfolded SOD1, and spinal motor neuron loss in the ventral horn., Interpretation: Lovastatin reduced the risk of ALS in humans, which was confirmed in an ALS mouse model by delayed symptom onset, prolonged survival, and preservation of motor neurons. Although further studies to understand the mechanism are required, lovastatin may represent a potential neuroprotective therapy for patients with ALS. These data demonstrate the utility of a combined pharmacoepidemiologic and mouse model approach. ANN NEUROL 2023;93:881-892., (© 2023 American Neurological Association.)

Diabetic peripheral neuropathy (DPN) is a complex disorder caused by long-standing diabetes. Oxidative stress was considered the critical creed in this DPN pathophysiology. Hydrogen has antioxidative effects on diabetes mellitus and related complications. However, there is still no concern on the beneficial effects of hydrogen in DPN. This paper aimed to evaluate the effects of exogenous hydrogen to reduce the severity of DPN in streptozotocin-induced diabetic rats. Compared with hydrogen-rich saline treatment, hydrogen inhalation significantly reduced blood glucose levels in diabetic rats in the 4 th and 8 th weeks. With regard to nerve function, hydrogen administration significantly attenuated the decrease in the velocity of motor nerve conduction in diabetic animals. In addition, hydrogen significantly attenuated oxidative stress by reducing the level of malondialdehyde, reactive oxygen species, and 8-hydroxy-2-deoxyguanosine and meaningfully enhanced the antioxidant capability by partially restoring the activities of superoxide dismutase. Further studies showed that hydrogen significantly upregulated the expression of nuclear factor erythroid-2-related factor 2 and downstream proteins such as catalase and hemeoxygenase-1 in the nerves of diabetic animals. Our paper showed that hydrogen exerts significant protective effects in DPN by downregulating oxidative stress via the pathway of nuclear factor erythroid-2-related factor 2, which suggests its potential value in clinical applications., Competing Interests: None

There is significant evidence demonstrating the influence of oxidative stress on atherosclerosis and cardiovascular diseases (CVD). However, oxidative biomarkers have not been applied to follow patients under primary or secondary prevention. Many factors can explain this paradox: the higher complexity of the methods applied to quantify oxidative markers, the high variability observed among the studies, the lack of reference values, and the weak correlation with clinical endpoints. This review presents the role of the major reactive oxygen species (ROS) involved in cardiovascular pathophysiology and how they can be neutralized by endogenous and exogenous antioxidants based on classical and recent studies, highlighting the importance of the secondary products of fatty acid oxidation as potential biomarkers. Furthermore, we discuss the great variability of oxidative stress biomarkers, using as an example data obtained from 55 studies. Among the molecules directly formed from lipid oxidation, such as malondialdehyde (MDA), oxidized LDL (oxLDL), and isoprostanes (F 2 -IsoP), and those associated with general oxidative conditions (ferric-reducing antioxidant power (FRAP), superoxide dismutase (SOD), glutathione (GSH)), MDA was the most lipid biomarker evaluated in the treatments and proved to be an independent factor compared with traditional markers used in the algorithms to stratify the patient's risk. Finally, this review suggests four steps to follow, aiming to include MDA in the algorithms applied to estimate CVD risk., Competing Interests: Conflict of interest statement Conflict of interest statement, (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Introduction: Nicotinamide mononucleotide (NMN) is a nucleotide that is commonly recognized for its role as an intermediate of nicotinamide adenine dinucleotide (NAD + ) biosynthesis with multiple pharmacological effects. The purpose of this study was to evaluate the protective effect of nicotinamide mononucleotide (NMN) against lipopolysaccharide (LPS)-induced acute lung injury (ALI)., Methods: We investigated the effect of NMN on ALI-induced inflammatory response, oxidative stress, and cell apoptosis. The ALI mouse model was performed by injecting LPS intratracheally at a dose of 10 mg/kg in 50 μL saline. Flow cytometry was used to detect neutrophil infiltration in bronchoalveolar lavage fluid (BALF), and ELISA was used to detect the contents of inflammatory cytokines TNF-α, IL-1β and IL-6 in BALF. Oxidative stress was evaluated by determining the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in lung tissue. ROS formation was analyzed by immunofluorescence. Western blotting was performed to detect apoptotic levels and p38MAPK/NF-κB phosphorylation levels in lung tissue., Results: In the ALI mouse model, NMN showed a significant therapeutic effect compared to the LPS group. NMN attenuated the pathological damage and cell apoptosis in lung tissue, decreased the levels of TNF-α, IL-1β, and IL-6 in BALF, and reduced the number of total cells and neutrophils in BALF. In addition, NMN attenuated the LPS-induced elevation of dry-to-wet ratio, MDA content, p38 MAPK and p65 NF-κB phosphorylation levels, and the SOD activity was increased by NMN treatment., Conclusions: In conclusion, the present study showed that NMN exerted a protective effect on LPS-induced ALI with anti-inflammatory, antioxidative, and antiapoptotic effects., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The rise of antibiotic resistance and dearth of novel antibiotics have posed a serious health crisis worldwide. In this study, we screened a combination of antibiotics and nonantibiotics providing a viable strategy to solve this issue by broadening the antimicrobial spectrum. We found that chenodeoxycholic acid (CDCA), a cholic acid derivative of the traditional Chinese medicine (TCM) Tanreqing (TRQ), synergizes with amikacin against Staphylococcus aureus in vitro , and this synergistic killing was effective against diverse methicillin-resistant S. aureus (MRSA) variants, including small-colony variants (SCVs), biofilm strains, and persisters. The CDCA-amikacin combination protects a mouse model from S. aureus infections. Mechanistically, CDCA increases the uptake of aminoglycosides in a proton motive force-dependent manner by dissipating the chemical potential and potentiates reactive oxygen species (ROS) generation by inhibiting superoxide dismutase activity. This work highlights the potential use of TCM components in treating S. aureus-associated infections and extend the use of aminoglycosides in eradicating Gram-positive pathogens. IMPORTANCE Multidrug resistance (MDR) is spreading globally with increasing speed. The search for new antibiotics is one of the key strategies in the fight against MDR. Antibiotic resistance breakers that may or may not have direct antibacterial action and can either be coadministered or conjugated with other antibiotics are being studied. To better expand the antibacterial spectrum of certain antibiotics, we identified one component from a traditional Chinese medicine, Tanreqing (TRQ), that increased the activity of aminoglycosides. We found that this so-called agent, chenodeoxycholic acid (CDCA), sensitizes Staphylococcus aureus to aminoglycoside killing and protects a mouse model from S. aureus infections. CDCA increases the uptake of aminoglycosides in a proton motive force-dependent manner by dissipating the chemical potential and potentiates ROS generation by inhibiting superoxide dismutase activity in S. aureus. Our work highlights the potential use of TCM or its effective components, such as CDCA, in treating antibiotic resistance-associated infections.

Background: Sepsis is a complex syndrome which comes out after infection, characterized by activation of inflammation and infection and has a high morbidity and mortality. Sildenafil (SLD) is a selective phosphodiesterase Type 5 enzyme inhibitor and is used in the treatment of erectile dysfunction effectively all over the world. In this study, we investigated whether SLD had protective effect or not by studying the effect of SLD on reactive oxygen species and antioxidants in cecal ligation and puncture (CLP) polymicrobial sepsis model in rat liver histopathologically and biochemically., Methods: Rats were divided into four groups: (1) 10 mg/kg SLD given CLP group; (2) 20 mg/kg SLD given CLP group; (3) CLP group; and (4) SHAM operated group. CLP polymicrobial sepsis model was applied to the rats. All rats in our study were sacrificed by overdose general anesthetic after 16 h (thiopental sodium, 50 mg/kg). Specimens of rat liver were analyzed histopathologically and biochemically. In the study, superoxide dismutase (SOD) and glutathione (GSH) parameters were measured to indicate the antioxidant activity in liver during sepsis. To evaluate the oxidant activity, myeloperoxidase (MPO) and lipid peroxidation (LPO) parameters were measured in liver tissue., Results: SOD and MPO activities and GSH and LPO levels were high in CLP polymicrobial sepsis model when compared to SHAM group (p<0.05). In all SLD groups, GSH levels were high when compared to CLP group. In 20 mg/kg SLD given sepsis group, high GSH levels were observed according to SHAM group. In addition, while all SLD dose groups had a significant decrease versus CLP group in LPO levels (p<0.05), they had a significant increase in MPO activities. In 20 mg/kg SLD administrated rats, an improvement observed in biochemical parameters. In this study, SOD and MPO activities which were low in SHAM group increased in CLP polymicrobial sepsis model. When SLD administrated, MPO activity increased in both SHAM and CLP groups. In this study, GSH and LPO levels also increase in septic liver tissue. When SLD administrated to SHAM group, it increased VI protective GSH level and decreased detrimental LPO level. In histopathological examination, it was observed that 10 mg/kg SLD administration had a curative effect in liver tissue partly., Conclusion: It was shown that acute SLD administration decreased liver damage in septic rats dose-dependently in this study. In addition, it was observed that it corrected the broken oxidant-antioxidant balance. This might mediate the protective effect of SLD in liver. However, we believe that new experimental and clinical studies should be in the future to understand the protective effect of SLD in liver.

Background: Uterine ischemia/reperfusion (I/R) injury often occurs during many complex surgical procedures, such as uterus transplantation, cesarean, and myomectomy, which may lead to the loss of uterine function and failure of the operation. Crocetin (CRO), as one of the major active constituents from saffron extract, shows protective effects against reactive oxygen species, inflammation, and apoptosis. However, the role of CRO in protecting the uterus against I/R-induced injury has never been investigated. This study aims to clarify the protective role of CRO against I/R injury and the underlying mechanisms., Materials and Methods: Sprague-Dawley rats were randomly divided into five groups: the control group, I/R group, 20 mg/kg CRO-treated I/R group, 40 mg/kg CRO-treated I/R group, and 80 mg/kg CRO-treated I/R group. Rats were given daily gavages with different doses of CRO or vehicle for five consecutive days. The rat uterine I/R model was created by routine method with 1h ischemia and 3h reperfusion. The serum and uterine tissues were collected, the changes in malondialdehyde (MDA) level and superoxide dismutase (SOD) activity, the mRNA and protein levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and IL-10, the protein levels of B-cell chronic lymphocytic leukemia/lymphoma (Bcl)-2, Bcl-2-associated X protein (Bax), caspase-3, nuclear factor erythroid 2-related factor (Nrf)-2, and heme oxygenase (HO)-1, were measured. The histological changes were examined by HE staining. The number of apoptotic cells was analyzed by flow cytometry., Results: Uterine I/R significantly induced MDA level, suppressed SOD activity, upregulated levels of pro-inflammatory cytokines, down-regulated level of the antiinflammatory cytokine, induced caspase-3-dependent apoptosis, activated the protein expression of Nrf-2 and HO-1, and caused uterine damage. However, pre-administration of CRO effectively reversed I/R-induced above changes and further enhanced Nrf-2/HO- 1 activation in a dose-dependent manner., Conclusion: Pre-administration of CRO effectively alleviates I/R-induced oxidative stress, inflammation, apoptosis, and tissue injury probably through activating the Nrf- 2/HO-1 pathway, suggesting a protective role of CRO in I/R-induced uterus injury., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Diseases caused by protozoa are one of the leading causes of death worldwide, especially in tropical regions such as Brazil. Chagas disease, leishmaniasis, and malaria are responsible for around 234 million cases and more than 400,000 deaths worldwide. Despite this scenario, drugs for these diseases have several limitations, which justifies the search for new treatments. Iron superoxide dismutase is a promising target for the drug design to treat patients with these diseases. It is a validated target and protects against oxidative stress., Aim: Thus, this systematic review aimed to synthesize evidence on the importance of superoxide dismutase in the drug design to treat patients with this protozoosis., Methods: A search was performed for in vitro and in vivo studies, without publication and language restrictions, in MEDLINE (PubMed), LILACS (BVS), Science Direct, and EMBASE (Elsevier). Studies that pointed to the relationship between the reduction or increase in superoxide dismutase activity and the diseases were included. 23 studies were selected for the qualitative synthesis., Results: The results showed that the inhibition or reduction of the enzyme activity decreases the degree of infection and reinfection and improves the results in treating these diseases. In contrast, the increase in activity caused a high degree of survival and resistance of the parasites., Conclusion: However, the overall quality of evidence is low and more studies with methodological rigor are provided., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objectives: There is overwhelming evidence of the relationship between smoking and schizophrenia (SZ). Tobacco smoke is considered to ameliorate the symptoms and reduce the side effects of antipsychotics in SZ patients. However, the underlying biological mechanism by which tobacco smoke improves symptoms in SZ remains unclear. This study was designed to examine the effects of tobacco smoke on antioxidant enzyme activities and psychiatric symptoms after receiving 12-week risperidone monotherapy., Methods: Two hundred and fifteen antipsychotic-naïve first-episode (ANFE) patients were recruited and treated with risperidone for 3 months. The severity of the patient's symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS) at baseline and at post-treatment. Plasma SOD, GSH-Px, and CAT activities were determined at baseline and follow-up., Results: Relative to nonsmoking patients with ANFE SZ, patients who smoked had higher baseline CAT activity. In addition, among non-smokers with SZ, baseline GSH-Px was associated with clinical symptom improvement, while baseline CAT was associated with positive symptom improvement in smokers with SZ., Conclusion: Our findings demonstrate that smoking affects the predictive role of baseline SOD, GSHPx, and CAT activities on clinical symptom improvement in patients with SZ., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The aim of this study is to investigate the effect of Tianjiang Xueshuantong Wan pills on reperfusion injury after venous thrombolysis in acute cerebral infarction., Methods: The strategy used in this study is a randomised controlled clinical trial. In total, 72 cases were included, with 36 in the trial group and 36 in the control group, with a 1:1 ratio. Both groups were given standardised treatment for acute cerebral infarction. Based on the rt-PA intravenous thrombolysis, the test group took Tianjiang Xueshuantong Wan pills orally, whereas the control group solely utilised rt-PA for intravenous thrombolysis and did not take the test medicine orally. The patients' intracranial hemorrhage was clarified by head CT scan, and the occurrence of reperfusion injury was recorded during the entire trial., Results: There were no significant differences in serum IL-6, MDA, SOD and TNF concentrations and NIHSS scores between the two groups before therapy (P > 0.05). After treatment, the serum concentrations of IL-6, MDA and TNF in the experimental group were significantly decreased compared with the control group, while the serum concentrations of SOD were significantly increased compared with the control group, with statistical significance (P > 0.05). After seven days of treatment, the total effective rate in the experimental group was 88.89%, while the data in the control group was 75%. There was a statistically significant difference between the experimental and control groups., Conclusion: Tianjiang Xueshuantong Wan pills can effectively prevent reperfusion injury following intravenous thrombolysis in individuals with cerebral infarction while improving patients' neurological deficits., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Quercetin (3,3',4',5,7-pentahydroxyflavone) is a dietary flavonoid with good antioxidant and anti-inflammatory properties., Aims: The present study aims to determine these effects in peripheral blood mononuclear cells (PBMCs) evoked by lipopolysaccharides (LPS)., Methods: The mRNA expression and protein secretion of inflammatory mediators were evaluated by enzyme- linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (PCR), respectively. Western blotting was utilized for assessing p65-NF-κB phosphorylation. Ransod kits evaluated the glutathione peroxidase (GPx) and superoxide dismutase (SOD) activity in the cell lysates. Ultimately, the molecular docking approach was performed to investigate the biological activity of Quercetin against NF-κB pathway proteins and antioxidant enzymes., Results: The findings revealed that quercetin significantly attenuated the expression and secretion of inflammatory mediators and p65-NF-κB phosphorylation in LPS-induced PBMCs. Additionally, quercetin dose-dependently improved the activities of SOD and GPx enzymes and decreased LPS-mediated oxidative stress in PBMCs. Moreover, quercetin has a considerable binding affinity to IκKb, the core element of the NF-κB pathway and the antioxidant enzyme SOD., Conclusion: The data show that quercetin plays a vital role in ameliorating inflammation and oxidative stress caused by LPS in PBMCs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: This study aimed to ascertain the effects of astaxanthin (ASX) in an experimental necrotizing enterocolitis (NEC) model using rat pups., Study Design: Forty-two pups born from five Wistar albino rats were randomly divided into three groups as the control group, NEC + placebo (saline), and NEC + ASX. Pups in the NEC + ASX group were given 100 mg/kg/day oral ASX from day 1 to day 4 of the study. Saline of 2 mL/kg was given to the NEC + placebo group. Histopathological, immunohistochemical (caspase-3), and biochemical evaluations including the total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), glutathione (GSH), lipid hydroperoxide (LPO), 8-hydroxydeoxyguanosine (8-OHdG), advanced oxidation protein products (AOPP), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and nuclear factor erythroid 2-related factor 2 (Nfr-2) activities were all performed., Results: A better survival rate and weight gain were demonstrated in the NEC + ASX group ( p  < 0.05). In the histopathological evaluation, the severity of intestinal damage was significantly reduced in the NEC + ASX group, as well as decreased apoptosis (enzyme-linked immunosorbent assay [ELISA] for caspase-3; p  = 0.001). The biochemical analyses of intestinal tissue TOS, oxidative stress index (OSI; TOS/TAS), IL-1β, LPO, 8-OHdG, AOPP, caspase-3 ( p  < 0.001 for all), and TNF-α and MPO ( p  = 0.001 for both parameters) levels were lower in the NEC + ASX group than in the NEC + placebo group. Nrf-2, TAS, GSH, and SOD levels were higher in the NEC + ASX group than in the NEC + placebo group ( p  = 0.001, 0.001, <0.001, and 0.01, respectively)., Conclusion: ASX treatment has been shown to effectively reduce the severity of intestinal damage in NEC due to its antioxidant, anti-inflammatory, and antiapoptotic properties., Key Points: · NEC causes extremely high morbidity and mortality, as well as many complications.. · We investigated the effectiveness of ASX in the experimental NEC model created in rat pups.. · First study examining the effect of ASX on the experimental NEC rat model.., Competing Interests: None declared., (Thieme. All rights reserved.)

Schistosomiasis is still a major health problem affecting nearly 250 million people worldwide and causes approximately 280,000 deaths per year. The disease causes a serious granulomatous inflammatory response that produces significant mortality. Plumbagin reportedly displays anti-inflammatory, anti-fibrotic, antioxidant and anthelmintic properties. This study further elucidates these properties. Mice were infected with schistosomes and divided into five groups: non-infected untreated (C); infected untreated (IU); non-infected treated with plumbagin (P); infected treated with plumbagin (PI) and infected treated with praziquantel (PZ). Mice treated with 20 mg plumbagin/kg body weight showed reduction of 64.28% and 59.88% in male and female animals, respectively. Also, the number of eggs/g tissue was reduced 69.39%, 68.79% and 69.11% in liver, intestine and liver/intestine combined, respectively. Plumbagin alleviated schistosome-induced hepatosplenomegaly and reduced hepatic granuloma and liver collagen content by 62.5% and 35.26%, respectively while PZQ reduced hepatic granuloma and liver collagen content by 41.11% and 11.21%, respectively. Further, plumbagin treatment significantly (p < .001) reduced IL-4, IL-13, IL-17, IL-37, IFN-γ, TGF-β and TNF-α levels and significantly (p < .001) upregulated IL-10. Plumbagin treatment restored hepatic enzymes activity to nearly normal levels and induced an increase in catalase, SOD, GSH, total thiol and GST in liver tissue homogenate. NO and LPO content was, however, decreased. Moreover, serum IgG levels significantly increased. The present study is the first to report immunomodulatory and schistosomicidal activities of plumbagin in schistosomiasis., (© 2022 John Wiley & Sons Ltd.)

Diabetes is accompanied by inflammation and oxidation. Supplementation of anti-inflammatory and antioxidant compounds can prevent the progression of diabetes. This study aimed to investigate the effects of supplementation of Nannochloropsis oculata microalgae (NOM) on the inflammatory and antioxidant responses in diabetic rats. Sixty male rats were divided into six groups as diabetic and non-diabetic rats receiving 0, 10 and 20 mg/kg of body weight of NOM daily for 21 days. Body weight, the serum concentrations of insulin and glucose and the tissue concentrations of interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), interleukin-6 (IL-6), malondialdehyde (MDA), ferric reducing antioxidant power (FRAP), superoxide dismutase (SOD), glutathione peroxidase (GPx) were assessed. The results showed that induction of diabetes significantly reduced the body weight, the serum concentrations of insulin and the tissue concentrations of SOD, FRAP and GPx while increasing the concentrations of glucose, MDA, IL-1β, IL-6, NF-κB and TNF-α. Daily oral administration of NOM (10 and 20 mg/kg) significantly maintained the body weight, the serum concentrations of insulin and the tissue concentrations of SOD, FRAP and GPx while preventing the increase in the concentrations of glucose, MDA, IL-1β and TNF-α. In conclusion, diabetes caused inflammation and oxidation while NOM worked as a natural anti-inflammatory and antioxidant compound., (© 2022 Ali Fereidouni et al., published by De Gruyter.)

Tardive dyskinesia (TD) is a prevalent movement disorder that significantly impacts patients with schizophrenia (SCZ) due to extended exposure to antipsychotics (AP). Several genetic polymorphisms, including superoxide dismutase (SOD) and DRD3 9ser, have been suggested as explanations why some patients suffer from TD. Methods . A PubMed search was used to search relevant articles using the following keywords: "Tardive Dyskinesia and Superoxide Dismutase". Fifty-eight articles were retrieved. Among them, 16 were included in this review. Results . Overall, 58 studies were retrieved from PubMed. Most studies investigated the association between TD and the SOD-related polymorphisms. In addition, previous studies reported an association between TD occurrence and other genetic polymorphisms. Conclusion . This study found that the risk of TD is associated with altered SOD levels and several genetic polymorphisms, including VAL 66 Met and DRD3 9ser., Competing Interests: The authors have no conflict of interest to declare., (Copyright © 2022 Kadir Uludag et al.)

Objective: To analyze the effects of modified Duhuo Jisheng Decoction combined with arthroscopic surgery on bone metabolism, oxidative stress, and serum TLR4 and TGF- β 1 in patients with knee osteoarthritis (KOA)., Methods: Prospectively select 82 patients with KOA from January 2020 to January 2022 in our hospital and divide them into the control group and observation group according to the random number table method, with 41 patients in each group. The control group was treated with arthroscopic surgery alone and routine anti-infection after operation. The observation group was treated with Duhuo Jisheng Decoction on the basis of the treatment of the control group. The patients in the two groups were treated continuously for 4 weeks. The improvement of patients' symptoms was evaluated by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Before treatment and 4 weeks after treatment, the scores of traditional Chinese medicine (TCM) symptoms, bone metabolism indicators (cartilage oligomeric matrix protein (COMP), collagen type II carboxy terminal peptide (ctx-II), and matrix metalloproteinase-3 (MMP-3)), oxidative stress indicators (superoxide dismutase (SOD), glutathione peroxidase (GSHPx), malondialdehyde (MDA), nitric oxide (NO)), serum Toll-like receptor 4 (TLR4), and transforming growth factor β (TGF- β ) level were compared between the two groups., Results: After treatment, the WOMAC score of the two groups decreased (42.45 ± 10.83) in the observation group and (67.81 ± 14.63) in the control group. The WOMAC score of the observation group was lower than that of the control group ( P < 0.05). After treatment, the levels of COMP, CTX-II, and MMP-3 in the two groups decreased, and the levels of COMP, CTX-II, and MMP-3 in the observation group were lower than those in the control group ( P < 0.05). After treatment, the levels of SOD and GSHPx increased, while the levels of MDA and NO decreased in the two groups. The levels of SOD and GSHPx in the observation group were higher than those in the control group, while the levels of MDA and NO were lower than those in the control group ( P < 0.05). After treatment, the TLR4 level in the observation group was lower than that of the control group, and the level of TGF- β in the observation group was higher than that of the control group ( P < 0.05)., Conclusion: Compared with arthroscopic surgery alone, combined with modified Duhuo Jisheng Decoction can better alleviate the clinical symptoms of patients with KOA, improve their bone metabolism, oxidative stress indicators, and serum TLR4 and TGF- β 1 level, and reduce the inflammatory injury of knee joint., Competing Interests: The authors declare no conflict of interest, financial, or otherwise., (Copyright © 2022 Xiangjing Zeng et al.)

Objective: To systematically assess effectiveness and safety of Bifidobacterium quadruple viable bacteria combined with mesalamine against ulcerative colitis (UC) in the Asian population., Methods: An electronic search was conducted in PubMed, Embase, Cochrane Library, CNKI, VIP, and Wanfang databases for a random collection of controlled trials of Bifidobacterium quadruple viable bacteria combined with mesalamine against UC. Following data screening and extraction, a Cochrane risk assessment tool was adopted to evaluate the quality of the included studies, and RevMan 5.3 and Stata/SE 15.1 software were used for meta-analysis., Results: Nineteen articles which enrolled 1,707 subjects were included ultimately in this study. The experimental group performed better than the control group in improving the Mayo score (MD = -1.94, 95% CI = (-2.69, -1.19), P < 0.00001), increasing the total clinical efficiency (OR = 5.10, 95% CI (3.53, 7.38), P < 0.00001), reducing the levels of IL-8 (SMD = -1.79, 95% CI (-2.36, -1.12), P < 0.00001), increasing the levels of IL-4 (SMD = 1.00, 95% CI (0.60, 1.41), P < 0.00001), and reducing the levels of hsCRP (MD = -3.26, 95% CI (-4.28, -2.25), P < 0.00001), TNF- α (MD = -7.11, 95% CI (-9.23, -5.00), P < 0.00001), ox-LDL (MD = -14.46, 95% CI (-17.20, -11.72), P < 0.00001), and LPO (MD = -3.55, 95% CI (-4.70, -2.39), P < 0.0001) as well as increasing SOD level (SMD = 1.68, 95% CI (1.02, 2.35), P < 0.00001), and adverse reactions were substantially less than that of control (OR = 0.43, 95% CI = (0.28, 0.66), P = 0.0001)., Conclusion: In conclusion, the current meta-analysis shows that Bifidobacterium quadruple viable bacterium combined with mesalamine has a satisfactory effect in the treatment of UC in China, and its safety is better than that of mesalamine or Bifidobacterium quadruple viable bacteria alone. However, randomized controlled trials with standardized designs and large sample sizes are still needed for further validation., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Fei Xie et al.)

Objectives: Hyperhomocysteinemia (HHcy) can induce vascular inflammatory and oxidative damage and accelerate intimal hyperplasia. This study investigated the protective effect of pirfenidone (PFD) on the recovery process of injured endothelial arteries during HHcy., Materials and Methods: Thirty rabbits were randomly separated into three groups: A control group (n=10, standard rabbit chow), a model group (n=10, control diet plus 30 g methionine/kg food), and a PFD group (n=10, model diet plus oral administration of 90 mg/day of PFD). After 14 weeks of arterial injury, histopathological changes were determined. Plasma homocysteine (Hcy) concentrations, lipid profiles and oxidant and antioxidant status were evaluated. Macrophage infiltration was assessed using immunohistochemical staining., Results: PFD supplementation decreased macrophage infiltration of iliac artery significantly without changes in blood lipids and Hcy concentrations. Compared with the model group, PFD restored superoxide dismutase and glutathione peroxidase activities and reduced malondialdehyde and reactive oxygen species levels. A high-methionine diet significantly increased neointimal area and the ratio between neointimal and media area. Systemic administration of PFD inhibited neointimal formation., Conclusions: PFD can partly alleviate intimal hyperplasia by inhibiting inflammatory and oxidative stress response induced by HHcy during endothelial injury. It may be a potential therapeutic agent for the prevention and treatment of endothelial injury-associated diseases such as atherosclerosis., (Copyright © 2022 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Ischemia-reperfusion (IR) injury is induced by an interrupted blood flow and succeeding blood restoration, which is common in the operation of liver transplantation. Serious IR injury is a major reason leading to transplant failure. Hepatic IR is featured by excessive inflammatory response, oxidative stress, and apoptosis. Sinomenine (SIN) is derived from the herb Sinomeniumacutum and shows properties of anti-inflammation and antiapoptosis in multiple IR-induced organ injuries. However, the effect of SIN in hepatic IR has not been investigated., Methods: This study aims to investigate impacts of SIN on hepatic IR and the involved signaling pathway. An in vivo rat model of syngeneic orthotopic liver transplantation was constructed to induce the hepatic IR injury., Results: Results showed that SIN pretreatment provided a significant prevention against IR-induced hepatic injury as manifested by the downregulated activities of serum alanine aminotransferase, aspartate aminotransferase, and lactate dehydrogenase, the alleviatedoxidative stress as shown by increased activities of serum superoxide dismutase and glutathione peroxidase, and decreased serum level of malondialdehyde, the suppressed inflammatory responses as shown by downregulated serum tumor necrosis factor-α, interleukin (IL)-6, IL-8 levels, and upregulated IL-10 level, as well as attenuated apoptosis as shown by decreased protein expression of cleaved caspase-3 and -9. In line with these results, SIN pretreatment also alleviatedthe hepatic histopathological changes in IR rats and induced Nrf-2/HO-1 activation. The use of brusatol, a selective inhibitor for Nrf-2, effectively reversed SIN-induced above effects., Conclusions: Altogether, our results demonstrate that SIN might be a useful therapeutic drug for preventing hepatic IR-induced injury during clinical liver transplantation., (© 2022 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) is rapidly growing in China, especially in patients with type 2 diabetes mellitus (T2DM). Weight loss strategies have been shown to treat NAFLD effectively. We conducted a 24-week, prospective, randomized study in T2DM patients with NAFLD to evaluate the effects of a 5:2 fasting diet on liver fat content. Methods: Sixty-one T2DM patients with NAFLD were enrolled and randomly divided into a 5:2 fasting diet intervention group (5:2 diet group, n  = 31) and 1.8 mg/day liraglutide intervention group (Lira group, n  = 30). The study was performed for 24 weeks. Data of the body weight, waist circumference, plasma lipids and glucose profile, fasting plasma insulin, and liver function parameters were collected. Controlled attenuation parameter (CAP) was measured to assess the liver fat content. Superoxide dismutase (SOD) and malondialdehyde (MDA) were measured to evaluate oxidative stress status. Results: At 24 weeks after intervention, compared with those at baseline, CAP was significantly decreased in both the 5:2 diet group and Lira group, which was 7.4% and 5.5%, respectively. Body weight, plasma lipids and glucose profile, and liver function parameters improved significantly, while homeostasis model assessment-β (HOMA-β) was significantly increased in both groups (all P  < 0.05). Stepwise linear regression showed that increased HOMA-β and SOD, as well as reduced body mass index (BMI), were the independent predictors of CAP decrease in the Lira group ( P  = 0.000, 0.000, 0.015). In contrast, reduced BMI and MDA were the independent influencing factors of CAP decrease in the 5:2 diet group ( P  = 0.011, 0.043). The common side effects in the 5:2 diet group were hunger (60%), weakness (10%), and constipation (0.3%). Conclusions: A 5:2 fasting diet achieved comparable effects with liraglutide on liver fat content in patients with T2DM with NAFLD by reducing BMI and oxidative stress. Both treatment strategies were safe and effective for glucose control.

Present research was planned to assess the in vitro and in vivo anti-arthritic potential of Caralluma tuberculata N. E. Brown. methanolic (CTME) and aqueous (CTAQ) extracts. Chemical characterization was done by high-performance liquid chromatography and gas chromatography−mass spectrometry analysis. The Complete Freund’s Adjuvant (CFA) was injected in left hind paw of rat at day 1 and dosing at 150, 300 and 600 mg/kg was started on the 8th day via oral gavage in all groups except normal and disease control rats (which were given distilled water), whereas methotrexate (intraperitoneal; 1 mg/kg/mL) was administered to standard control. The CTME and CTAQ exerted significant (p < 0.01−0.0001) in vitro anti-arthritic action. Both extracts notably reduced paw edema, and restored weight loss, immune organs weight, arthritic score, RBCs, ESR, platelet count, rheumatoid factor (RF), C-reactive protein, and WBCs in treated rats. The plant extracts showed significant (p < 0.05−0.0001) downregulation of tumor necrosis factor-α, Interleukin-6, -1β, NF-κB, and cyclooxygenase-2, while notably upregulated IL-4, IL-10, I-κBα in contrast to disease control rats. The plant extracts noticeably (p < 0.001−0.0001) restored the superoxide dismutase and catalase activities and MDA levels in treated rats. Both extracts exhibited significant anti-arthritic potential. The promising potential was exhibited by both extracts probably due to phenolic, and flavonoids compounds.

Objective: Mutations in the copper-zinc superoxide dismutase (SOD1) gene cause familial amyotrophic lateral sclerosis (ALS), a progressive fatal neuromuscular disease characterized by motor neurons death and severe skeletal muscle degeneration. However, there is no effective treatment for this debilitating disease, since the underlying cause for the pathogenesis remains poorly understood. Here, we investigated a role of acyl-CoA:lysocardiolipin acyltransferase 1 (ALCAT1), an acyltransferase that promotes mitochondrial dysfunction in age-related diseases by catalyzing pathological remodeling of cardiolipin, in promoting the development of ALS in the SOD1 G93A transgenic mice., Methods: Using SOD1 G93A transgenic mice with targeted deletion of the ALCAT1 gene and treated with Dafaglitapin (Dafa), a very potent and highly selective ALCAT1 inhibitor, we determined whether ablation or pharmaceutical inhibition of ALCAT1 by Dafa would mitigate ALS and the underlying pathogenesis by preventing pathological remodeling of cardiolipin, oxidative stress, and mitochondrial dysfunction by multiple approaches, including lifespan analysis, behavioral tests, morphological and functional analysis of skeletal muscle, electron microscopic and Seahorse analysis of mitochondrial morphology and respiration, western blot analysis of the SOD1 G93A protein aggregation, and lipidomic analysis of cardiolipin content and acyl composition in mice spinal cord., Results: ALCAT1 protein expression is potently upregulated in the skeletal muscle of the SOD1 G93A mice. Consequently, ablation or pharmacological inhibition of ALCAT1 by Dafa attenuates motor neuron dysfunction, neuronal inflammation, and skeletal muscle atrophy in SOD1 G93A mice by preventing SOD1 G93A protein aggregation, mitochondrial dysfunction, and pathological CL remodeling, leading to moderate extension of lifespan in the SOD1 G93A transgenic mice., Conclusions: ALCAT1 promotes the development of ALS by linking SOD1 G93A protein aggregation to mitochondrial dysfunction, implicating Dafa as a potential treatment for this debilitating disorder., (Copyright © 2022 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: We aimed to compare biochemical and histopathological findings of astaxanthin's potential effects on oxidative stress in ischemia/reperfusion damage (I/R)., Methods: Thirty-two rats were randomly divided into four groups: control group; I/R group; I/R + treatment group; drug group. Astaxanthin was orally administered to groups C and D for 14 days. In groups B and C, the femoral artery was clamped for 2 h to form ischemia. The clamp was opened, and reperfusion was performed for 1 h. In all groups, 4 ml of blood sample through intracardiac puncture and gastrocnemius muscle tissue samples were collected. Serum and tissue samples were analyzed by measuring malondialdehyde (MDA), superoxide dismutase (SOD), total antioxidant capacity (TAC), and total oxidative level (TOL). Necrosis, inflammation, and caspase-3 in muscle tissue collected for histopathological examination were evaluated., Results: Tissue MDA, SOD and TOL values significantly differed between groups. Serum MDA, SOD, TOL and TAC values significantly differed between groups. On necrosis examination, there was a significant difference between groups B and C. Although signs of inflammation significantly differed between groups, there was no significant difference between groups A and C and groups A and D. Although there was a significant difference in caspase-3 results between groups, there was no significant difference between groups A and C., Conclusions: The use of astaxanthin before and after surgery showed preventive or therapeutic effects against I/R damage., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Background: Oxidative stress plays an important role in weight gain induced by antipsychotics in schizophrenia (SCZ). However, little is known about how antioxidant enzymes are involved in weight gain caused by risperidone monotherapy in antipsychotics-naïve first-episode (ANFE) patients with SCZ. Therefore, the main purpose of this study was to investigate the effects of risperidone on several antioxidant enzymes in patients with ANFE SCZ and the relationship between weight gain and changes in antioxidant enzyme activities., Objective: The activities of plasma superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as the levels of malondialdehyde (MDA) were measured in 225 ANFE patients and 125 healthy controls., Methods: Patients were treated with risperidone monotherapy for 12 weeks. Clinical symptoms, antioxidant enzyme activities, and MDA levels were measured at baseline and during follow-up., Results: Compared with healthy controls, the patients showed higher activities of SOD and CAT but lower MDA levels and GPx activity. At baseline, the CAT activity was associated with body weight or BMI. Further, based on a 7% weight increase from baseline to follow-up, we found 75 patients in the weight gain (WG) group and 150 patients in the non-WG group. Comparing SOD, CAT, GPx activities and MDA levels between the WG group and the non-WG group at baseline and during the 12-week follow-up, it was found that after treatment, the SOD activity in the WG group increased while the MDA level decreased in the non-WG group. Moreover, baseline SOD and GPx activities were predictors of weight gain at 12-week follow-up., Conclusion: These results suggest that the antioxidant defense system may have predictive value for the weight gain of ANFE SCZ patients after risperidone treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background & Aims: Ghrelin, a gut hormone with pleiotropic effects, may act as a protective signal in parenchymal cells. Hepatic ischemia-reperfusion injury (HIRI) causes acute-on-chronic liver failure and induces transformation of acute to chronic injury. HIRI model of mice was established by a semi-hepatic blocking method and treated with Ghrelin. This process is involved in inflammation, oxidative stress damage and apoptosis, and is associated with the expansion and activation of fibrotic haematopoietic stem cells (HSCs) which express and secrete high levels of collagen that induces liver fibrosis. Therefore, we investigated the effects of Ghrelin during transformation of HIRI to liver fibrosis, and explored the molecular mechanism of Ghrelin's action based on Smad and ERK pathways., Methods: Hepatic injury was detected by plasma ALT levels. The hepatic histology and collagen were elucidated by HE staining and Masson staining, respectively. Liver inflammation levels and inflammatory cell counts were assessed by MPO and HE staining, respectively. The antioxidant capacity of plasma was evaluated based on the levels of SOD, MDA, and XOD. The mRNA or protein expression levels of genes related to apoptosis, fibrosis, Smad, and ERK pathways were assessed by real-time quantitative PCR (RT-qPCR), ELISA, or western blotting., Results: The HIRI model was established to investigate the effects of the liver injury transformed to liver fibrosis. Ghrelin exhibited good hepatic protection by ameliorating liver histological changes and decreasing plasma ALT levels. Ghrelin significantly decreased the expression of MPO than that in model group, suggesting that Ghrelin blocked the inflammatory response in the HIRI liver tissue; this supports the anti-inflammatory effects of Ghrelin. Ghrelin significantly decreased apoptosis (enhanced Bcl-2 expression, and down-regulated Bax and Caspase 3). Ghrelin exhibited anti-oxidative effects as it inhibited plasma MDA levels, and promoted plasma SOD and XOD levels. Moreover, Ghrelin inhibited activation of hepatic stellate cells, blocked traditional fibrotic Smad and ERK signalling pathways, and reduced hepatic fibrosis by stimulating degradation of extracellular matrices (ECMs; such as collagen I, collagen III, HA, and LN)., Conclusions: This study demonstrates that Ghrelin delays the transformation of HIRI to liver fibrosis process which is correlated to its anti-apoptotic, anti-inflammatory, and anti-oxidative effects. Moreover, Ghrelin alleviates HIRI-mediated liver fibrosis, inhibits activation of HSCs, and reduces accumulation of ECM via inhibition of Smad and ERK signalling pathways., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Purpose: To evaluate the effects of manganese superoxide dismutase (Mn-SOD) from thermophilic bacterium HB27 (name as Tt-SOD) on chemical cystitis., Methods: Control and experimental rats were infused by intravesical saline or hydrochloric acid (HCl) on the first day of the experiments. Saline, sodium hyaluronate (SH) or Tt-SOD were infused intravesically once a day for three consequent days. On the fifth day, the rats were weighted and sacrificed following a pain threshold test. The bladder was harvested for histological and biochemical analyses., Results: Tt-SOD could reduce the bladder index, infiltration of inflammatory cells in tissues, serum inflammatory factors and SOD levels, mRNA expression of inflammatory factors in tissues, and increase perineal mechanical pain threshold and serum MDA and ROS levels in HCl-induced chemical cystitis. Furthermore, Tt-SOD alleviated inflammation and oxidative stress by the negative regulation of the NF-κB p65 and p38 MAPK signaling pathway., Conclusions: Intravesical instillation of Tt-SOD provides protective effects against HCl-induced cystitis., (© 2021. The Author(s).)

Objectives: Omega 3 polyunsaturated fatty acids are dietary factors with several beneficial cardiovascular effects. This study aimed to assess the possible protective effect of omega 3 fatty acids on early doxorubicin-induced cardiac toxicity in children with acute lymphoblastic leukemia (ALL)., Patients and Methods: Sixty children of newly diagnosed ALL were randomized into two groups: group I (n = 30) who received omega 3 fatty acids 1000 mg/day for 6 months in addition to their usual protocol of chemotherapy including doxorubicin; and group II (n = 30) who received their usual doxorubicin protocol during the period from February 2020 till August 2021. Echocardiographic examinations were performed before and after the treatment. Glutathione, malondialdehyde (MDA), superoxide dismutase (SOD), troponin I, creatine kinase MB (CK-MB), and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured also before and after omega 3 treatment., Results: After 6 months of omega 3 administration, group I had a significantly lower MDA level and a significantly higher glutathione and SOD levels than group II. Similarly, the levels of troponin I, CK-MB, and NT-proBNP were significantly high in group II, whereas they were unchanged in group I after treatment. Similarly, systolic function (presented with peak mitral annular systolic velocity and two-dimensional global longitudinal strain) of the heart was preserved in omega 3-treated patients, unlike the control group that showed significant impairment of left ventricular function after 6 months., Conclusion: Omega 3 fatty acids may decrease early cardiac injury and doxorubicin-induced cardiotoxicity in children with ALL., (© 2021 Wiley Periodicals LLC.)

Background: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is the most prevalent type of ACLF in China. The mortality rate of HBV-ACLF has decreased in recent years due to advances in treatment therapies; however, it is still above 50%. Many cases of HBV-ACLF are caused by HBV reactivation due to discontinuation of nucleoside analog treatment. The present study focused on plasma levels of superoxide dismutase (SOD) in HBV-ACLF patients and investigated whether the plasma level of SOD is a useful biomarker in assessing disease severity and predicting outcomes of HBV-ACLF patients, including patients treated with Entecavir (ETV) and patients who were withdrawn from ETV treatment., Methods: Plasma samples and clinical data from 200 HBV-ACLF patients and from age- and sex-matched cirrhotic and healthy controls were collected and analyzed. Plasma levels of SOD were measured using an ELISA commercial kit., Results: Among the HBV-ACLF patients, in the ETV withdrawal group, the mortality rate was higher than in the ETV group (69.95% vs 46.71%, P < 0.05). Moreover, HBV-DNA and SOD plasma levels were higher in the ETV withdrawal group than in the ETV group (Log 10 (HBV-DNA): 6.49 ± 0.24 vs 4.79 ± 0.14, P < 0.01; SOD: 463.1 ± 27.61 U/mL vs 397.2 ± 10.97 U/mL, P < 0.05). The mortality and liver transplantation rates were significantly higher in HBV-ACLF patients with plasma levels of SOD > 428 U/mL than in patients with plasma SOD levels ≤ 428 U/mL., Conclusions: Reactivation of HBV and elevated oxidative stress caused by discontinuation of ETV treatment are crucial factors in the pathogenesis of HBV-ACLF. Plasma level of SOD may serve as a useful biomarker in estimating disease severity and predicting outcomes of HBV-ACLF patients who stop ETV treatment., (© 2022. The Author(s).)

Codonolactone is the main biologically active ingredient in Atractylodes lancea Studies have shown various functions of codonolactone, while its protective effect against neurotoxicity caused by ischemic stroke is unclear. This study investigated the roles of codonolactone in inflammation, oxidative stress and apoptosis after cerebral ischemia-reperfusion (I/R) injury. Rats with codonolactone treatment, I/R treatment and the sham operation group were used in this study. After reperfusion for 24 hours, nerve damage was detected by nerve staining, and the neurological deficits of the rats were analyzed. The contents of superoxide dismutase (SOD), malondialdehyde (MDA), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in rat brain tissues were also determined. Western blot analysis was performed to determine the expression levels of Akt/Nrf2 pathway-associated proteins. Compared with the I/R group, the cerebral blood flow, infarct volume, brain water content, coronary blood flow and neurological deficits in the codonolactone treatment group, especially with the 80 mg/kg dosage, were significantly reduced. Codonolactone could significantly reduce the expression levels of caspase-3 and Bax, and significantly increase the expression levels of Bcl-2 after I/R. In addition, codonolactone could significantly reduce MDA content and the expression levels of TNF-α and IL-1β in ischemic brain tissues. It also significantly increased SOD activity, the expression levels of heme oxygenase-1 (HO-1) and the phosphorylation of Akt and Nrf2. Codonolactone ameliorated the cerebral I/R injury by improving anti-oxidant, anti-inflammatory activities and reducing apoptosis. Besides, the Akt/Nrf2 pathway was involved in the pharmacological action of the codonolactone., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Asparaginase is an integral component of acute lymphoblastic leukemia (ALL) 3 treatment. Hepatotoxicity related to asparaginase is one of the most common treatment-related toxicities in ALL therapy. Hispanic children are at higher risk of developing ALL, and toxicities from ALL therapy. The rs4880 variant in the superoxide dismutase 2 (SOD2) 4 gene, a critical mitochondrial enzyme that protects cells against oxidative stress, was found to be associated with increased incidence of asparaginase-related hepatotoxicity in adult cohort of largely White non-Hispanics patients with ALL. The risk genotype (rs4880-CC) is more frequent among adult Hispanic patients with ALL. To assess the prevalence of hepatotoxicity and risk genotype among pediatric patients with ALL, particularly of Hispanic ethnicity, we conducted a prospective study of 143 pediatric patients with ALL (62.2% Hispanic). Bilirubin and hepatic transaminase levels were collected at different times during multiagent therapy including asparaginase treatment. Germline DNA blood samples were genotyped for the SOD2 rs4880. We found that the frequency of hepatotoxicity and the rs4880-CC risk genotype are higher in Hispanic patients than non-Hispanic. Patients with the CC genotype exhibit higher bilirubin and hepatic transaminase levels compared with patients with the TT and CT genotypes. In a multivariate Cox analysis, Hispanic ethnicity was identified as a strong predictor of hepatotoxicity (hazard ratio [HR] = 1.9, 95% confidence interval [95% CI] 1.0-3.5, p = 0.05). Altogether, these findings demonstrate that hepatotoxicity is highly prevalent among Hispanic pediatric patients with ALL, and those with rs4880-CC genotype., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Melasma is present in 40% of cases in Southeast Asia. The condition is often unresponsive to therapy; treatment has variable success rates, and melasma has high recurrence rates. Lycopene-rich tomato extract is needed to avoid oxidative stress due to ultraviolet rays that cause melasma through the melanogenesis pathway. The aim of this study was to evaluate the effectiveness of an oral tomato extract supplement as an adjuvant for melasma therapy., Methods: The study recruited 62 subjects with melasma to a true-experimental clinic with a double-blind, randomized, pre and post-test control design over 12 weeks at the Diponegoro National Hospital, Indonesia. The subjects received an oral tomato extract supplement contains lycopene 30 mg (placebo). All subjects applied topical sunscreen and hydroquinone-4%-cream. Subjects were assessed by superoxide dismutase (SOD) and melasma area and severity index (MASI)., Results: Fifty-nine patients completed the research. The serum SOD levels in the treatment group (tomato extract supplementation) were higher than in the control group given the placebo, with delta SOD (P<0.05). The difference in MASI Scores after therapy in the treatment group had a significant decrease compared to the control group, with statistical review results suggesting that the difference was significant (P<0.05)., Conclusions: Supplementation of tomato extract as an adjuvant therapy can increase serum SOD levels and improve melasma severity.