Reduction Of Oxidative Stress Research Articles

Abstract 4114198: Humanin Level is Inversely Correlated with NT-proBNP Level and Mortality in Heart Failure with Reduced Ejection Fraction

Background: Mitochondrial dysfunction contributes to heart failure (HF) progression via diminished energy supply, release of reactive oxygen species, and increased cell death. However, there has yet to be clinically relevant biomarkers that address mitochondrial-mediated cardiac injury in patients. Humanin (HN) is a mitochondria-derived peptide that protects cells through the interference of apoptosis and reduction of oxidative stress. The objectives of our study were to measure circulating plasma HN levels in patients with HF with reduced ejection fraction and describe the relationship of HN to validated, clinically relevant measures of HF. Methods: We conducted a prospective cohort study. To be included in the study, patients must have: 1) left ventricular ejection fraction <40%, 2) high risk of future clinical instability, 3) medication and device treatment according to guidelines, and 4) stable medical therapy for at least 30 days prior to screening. Plasma HN levels were measured at time of study enrollment by an enzyme-linked immunoassay. Statistical analyses were performed to evaluate the relationships between HN levels and demographic variables, quantitative measures of HF, and clinical outcomes. Results: 54 HF patients were included in the study. Age and sex were not significantly associated with HN level. There was a significant difference in mean HN level by race with highest HN level seen in Caucasians and the lowest HN level seen in Hispanics (1310 pg/ml vs. 630 pg/ml, p=0.012). There was a significant inverse correlation between NT-proBNP level and HN level (r=-0.46, p <0.001). After adjusting for race, higher NT-proBNP level, as both a continuous and categorical variable, was significantly associated with lower HN level. Furthermore, HN level was significantly lower in patients who died within 6 months compared to those who did not (520.7 pg/ml vs. 1146.9 pg/ml, p=0.013). After adjusting for race, lower HN level was significantly associated with increased odds of 6-month mortality (OR=0.784, 95% CI 0.620-0.943, p=0.018). Conclusions: To the best of our knowledge, this is the first study to describe plasma HN levels in HF patients. Its significant correlation with mortality and NT-proBNP level supports a potential role for HN as a novel prognostic biomarker in HF with reduced ejection fraction.

Therapeutic effects of pentoxifylline in propionic acid‐induced autism symptoms in rat models: A behavioral, biochemical, and histopathological study

AbstractObjectiveThe role of propionic acid (PPA) in eliciting behaviors analogous to autism in rat models is a documented phenomenon. This study examines the therapeutic implications of pentoxifylline—an agent traditionally used for peripheral vascular diseases—on these autism‐like behaviors by modulating brain proteins and reducing pro‐inflammatory cytokines like tumor necrosis factor‐α (TNF‐α) in a rat model.MethodsThis research involved 30 male Wistar albino rats, which were divided into three distinct groups: a baseline control set, a PPA‐treated cluster receiving a 250 mg/kg/day dose of PPA via intraperitoneal injection for a span of five days followed by saline orally, and a PPA group administered an oral dose of pentoxifylline at 300 mg/kg/day over 15 days. Subsequent to the treatment phase, euthanasia was carried out for the extraction of brain and blood samples, which were then analyzed for histopathological and biochemical markers.ResultsThe pentoxifylline‐treated subjects demonstrated a significant mitigation in the manifestation of autistic‐like behaviors, as assessed through a triad of social interaction tests. A noteworthy decline in TNF‐α levels was observed, alongside a significant rise in the concentration of adenosine triphosphate and nerve growth factor in brain tissue (p < 0.05). Histopathological analysis underscored a reduction in oxidative stress and a significant preservation of neuronal cell types, specifically pyramidal neurons in the hippocampal CA1 and CA3 regions and Purkinje cells in the cerebellum (p < 0.001).ConclusionPentoxifylline treatment has been found to effectively reduce the behavioral symptoms associated with autism, as well as biochemical and histopathological disruptions induced by PPA in rat models, highlighting its potential as a neurotherapeutic agent.

Metformin (The Miracle Drug) Kinetics in Different Diseases such as Cancer

: Metformin, a miracle drug that was introduced a century ago, could be considered for various aspects of diseases such as diabetes (type 1 and 2), cancer prevention or chemotherapy, metabolic and neurodegenerative disease. It is well known that the frequency of cancer is higher in patients with type 2 diabetes mellitus. This review aims to provide updated information regarding clinical pharmacokinetics and the mechanism of action of Metformin in different diseases such as cancer. Diabetes type 1 is another chronic autoimmune disease detected usually in early childhood due to immune-mediated devastation of insulin-producing pancreatic beta-cells. Because of the lack of effective therapeutic approaches, its prevalence is increasing. Regarding cancer, an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths were reported in 2020 worldwide. By 50-60% bioavailability, the main route of metformin excretion is through urine. Its mechanism of action is based on 1) initiation of adenosine monophosphate-activated kinase, 2) block proinflammatory paths in perivascular adipose tissue, 3) decrease in monocyte-to-macrophage differentiation in vascular tissues, and 4) improvement in endothelial function. Metformin induces adenosine monophosphate-activated protein kinase signaling and suppresses gluconeogenesis. Antitumor properties of Metformin include a decrease in reactive oxygen species generation and inducing autophagy. In addition to glucose-lowering effects, Metformin has moderate anti-inflammatory and antioxidative effects. It could improve lipid profile and reduce overweight individuals' body mass and arterial blood pressure. In type 1 diabetes, Metformin reduces the requirement for daily insulin and improves glycemia. Its long-term use decreases cardiovascular events. In addition to inhibiting the synthesis of lipids via a reduction in oxidative stress, Metformin inhibits inflammation and increases energy metabolism. Finally, by reducing micro- and macro-vascular consequences, mortality-related diabetes and cancer decline by metformin administration. Therefore, in addition to diabetes, Metformin could reduce the proliferation of cancer cells and the possibility of malignancies in different types of cancer.

Taurine Reverses Arsenic-Induced Inhibition of Hippocampal Neurogenesis and Depression-Like Behavior in Mice.

Arsenic exposure results in damage to the neurological system. We previously demonstrated the arsenic-induced inhibition of hippocampal neurogenesis and its reversibility after exposure is terminated. The present study aimed to reveal whether arsenic-induced inhibition of hippocampal neurogenesis was ameliorated when taurine was co-administered, and we also investigated depression-like behavioral changes using the forced swim test. Mice were randomly divided into four groups. The first group received distilled water only for 4 months (control group), the second group received 4.0 mg/L As2O3 via drinking water for 4 months (arsenic group), the third group received 4.0 mg/L As2O3 and taurine (150 mg/kg body weight, by gavage, twice a week) for 4 months (arsenic + taurine group), and the fourth group received taurine only by gavage for 4 months (taurine group). The percentage of new mature neurons decreased in the arsenic group compared with the control group (64% ± 0.90% vs. 76% ± 1.9%, p < 0.01); however, this percentage was reversed to control levels in the arsenic + taurine group (76% ± 1.4%, p > 0.05). In the forced swim test, the immobility time during the last 4 min was significantly increased in the arsenic group, but restored to control levels in the arsenic + taurine group. The possible mechanisms of this taurine amelioration of hippocampal damage were further investigated, and included a reduction in oxidative stress as indicated by carbonyl content, inflammation, and aquaporin1, 4, and 8 expressions, as well as an increase in Wnt3a and brain-derived neurotrophic factor expression in western blot analyses.

Assessment of protective effect of Vitamin E supplementation on oxidative damage of diabetic rat spleen induced by Streptozotocin

AimsIncreased oxidative stress in diabetes mellitus may lead to splenic damage, contributing to decreased immunity. This study aims to evaluate the potential of vitamin E supplements as a protective agent against spleen injury by examining physiological, hematological, biochemical, and histological changes in diabetic rat model. MethodsDiabetes was induced in male wistar albino rats through an intraperitoneal injection of 50mg/kg Streptozotocin, and the rats were randomly divided into five groups. The rats were then administered varying doses of vitamin E for 14 consecutive days. Assessments included renal function tests, blood glucose levels, complete blood counts, lipid profiles, tissue oxidative stress and spleen histology. An acute toxicity study was also conducted on normal rats. ResultsVitamin E supplementation did not result in any mortality up to 5000mg/kg body weight. The treated diabetic group showed improved metabolic characteristics, such as normal body weight, food and water intake and a reduced spleen index compared to the untreated diabetic group. Significant improvements were observed in hematological parameters like packed cell volume (PCV), hemoglobin concentration, RBC (red blood cells) and WBC (white blood cells) counts. HCA (Hierarchical Cluster Analysis) of these parameters indicated that doses of 100mg/kg and 150mg/kg were most similar to normal condition. Catalase and MDA (Malondialdehyde) assays showed a substantial reduction in oxidative stress in spleen tissue and histopathological examination revealed significant regenerative effects. ConclusionThis study demonstrated that vitamin E supplementation significantly enhanced various metabolic, hematological, biochemical, and histological parameters in the diabetic group compared to those who did not receive the treatment. Among the doses tested, 100mg/kg and 150mg/kg body weight were found to yield the most favorable outcomes.

CB1 Receptor Activation Provides Neuroprotection in an Animal Model of Glutamate-Induced Excitotoxicity Through a Reduction of NOX-2 Activity and Oxidative Stress.

Excitotoxicity is a process in which NADPH oxidase-2 (NOX-2) plays a pivotal role in the generation of reactive oxygen species (ROS). Oxidative stress influences the expression of Aquaporin 4 (AQP4), a water channel implicated in blood-brain barrier (BBB) permeability and edema formation. The endocannabinoid system is widely distributed in the brain, particularly through the cannabinoid receptor type 1 (CB1) and type 2 (CB2), which have been shown to have a neuroprotective function in brain injury. Given the significant involvement of NOX-2 in ROS production during excitotoxicity, our research aims to assess the participation of NOX-2 in the neuroprotective effect of the cannabinoid receptor agonist WIN55,212-2 against glutamate-induced excitotoxicity damage in the striatum using invivo model. Wild-type mice (C57BL/6) and NOX-2 KO (gp91Cybbtm1Din/J) were stereotactically injected in the striatum with monosodium glutamate or vehicle. Subsequently, a group of mice was administered an intraperitoneal dose of WIN55,212-2, AM251, or AM251/WIN55,212-2 following the intracerebral injection. Motor activity was assessed, and the lesion was examined through histological sections stained with cresyl violet. Additionally, brain water content and Evans blue assay were conducted. The activity of NOX was quantified, and the protein expression of CB1, gp91phox, AQP4, Iba-1, TNF-α, and NF-κB was analyzed using Western blot. Furthermore, ROS formation was measured through the DHE assay. The activation of the endocannabinoid receptors demonstrated a neuroprotective response during excitotoxicity, meditated by NOX-2. The reduction in ROS production led to a decrease in neuroinflammation, and AQP4 expression, resulting in reduced edema formation, and BBB permeability. During excitotoxic damage, WIN55,212-2 inhibits NOX-2-induced ROS production, reducing brain injury.

Probiotic and Rice-Derived Compound Combination Mitigates Colitis Severity

Background: This study investigated the ability of Enterococcus lactis (E. lactis) and Hasawi rice protein lysate (HPL) to suppress colitis induced by dextran sulfate sodium (DSS) in miceColitis is characterized by inflammation of the colon, and exploring potential therapeutic agents could lead to improved management strategies. Methods: Male mice were subjected to DSS treatment to induce colitis, followed by supplementation with E. lactis and/or HPL. The study assessed various parameters, including disease activity index (DAI) scores, gut permeability measured using FITC-dextran, and superoxide dismutase (SOD) activity in excised colon tissues from both treated and untreated control groups. Results: E. lactis supplementation significantly alleviated DSS-induced colitis, as evidenced by improved DAI scores and enhanced gut permeability. Notably, E. lactis combined with HPL (0.1 mg/108) exhibited superior tolerance to a 0.5% pancreatin solution compared to E. lactis alone. Both E. lactis and the combination treatment significantly increased SOD activity (5.6 ± 0.23 SOD U/mg protein for E. lactis and 6.7 ± 0.23 SOD U/mg protein for the combination) relative to the Azoxymethane (AOM)/DSS group, suggesting a reduction in oxidative stress. Additionally, pro-inflammatory markers were significantly reduced in the group receiving both E. lactis and HPL compared to the E. lactis-only group. Levels of proteins associated with cell death, such as PCNA, PTEN, VEGF, COX-2, and STAT-3, were significantly decreased by 14.8% to 80% following E. lactis supplementation, with the combination treatment showing the most pronounced effects. Conclusions: These findings suggest E. lactis supplementation may be beneficial for colitis, with HPL potential to enhance its effectiveness.

Neuroprotective effect of chelidonic acid through oxidative stress reduction in paclitaxel-induced peripheral neuropathy in rats.

The present study evaluated the effect of chelidonic acid on paclitaxel-induced neuropathy in male Wistar rats. Neuropathy was induced by administering paclitaxel (2mg/kg, i.p.) on 0, 2, 4, and 6days of the protocol. Chelidonic acid treatment (at doses of 10, 20, and 40mg/kg orally, for 21days) was initiated simultaneously with paclitaxel administration. After completion of the protocol, mechanical allodynia, hyperalgesia, and thermal hyperalgesia were measured. Additionally, nerve conduction velocity was assessed. The study investigated inflammatory cytokines, oxidative stress, and histological changes in the sciatic nerve. Furthermore, the Nrf2 was measured, and the protein expression of pAMPK and HIF-1α was assessed using western blotting. The results showed that chelidonic acid significantly normalized mechanical allodynia, hyperalgesia, and thermal hyperalgesia. It also led to a significant improvement in motor and sensory nerve conduction velocity and reduced oxidative stress compared with paclitaxel alone. Inflammatory markers such as TNF-alpha, IL-6, and IL-1β concentrations, as well as nitric oxide and C-reactive protein, were significantly decreased in the chelidonic acid-treated group. Histopathological examination revealed reduced neuronal damage, demyelination, and leukocyte infiltration with chelidonic acid treatment. Chelidonic acid treatment also resulted in a considerable rise in Nrf2 levels (p < 0.001) and increased protein expression of pAMPK in the sciatic nerve. Conversely, HIF-1α expression was significantly declined in the chelidonic acid treatment. Overall, the findings suggest that chelidonic acid treatment attenuates paclitaxel-induced neuropathic pain.

Enoxaparin Protects C6 Glioma Cells from Glutamate-Induced Cytotoxicity by Reducing Oxidative Stress and Apoptosis.

Recent studies suggest enoxaparin may protect the central nervous system (CNS) from damage. However, its specific effects on glial cells and the underlying mechanisms involving cell death and oxidative stress require further investigation. Therefore, this research investigated enoxaparin's potential to safeguard C6 glioma cells against glutamate-induced cytotoxicity, specifically focusing on its influence on oxidative stress and apoptotic mechanisms. To investigate the neuroprotective effects of enoxaparin against glutamate-induced cytotoxicity in C6 cells, four groups were established: a control group, a group exposed to 10mM glutamate, a group treated with enoxaparin at concentrations ranging from 25 to 200µM, and a group receiving both 10mM glutamate and enoxaparin at concentrations ranging from 25 to 200µM. Cell viability was measured using an XTT assay. To evaluate the effects of enoxaparin on oxidative stress, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured using ELISA, along with total antioxidant status (TAS) and total oxidant status (TOS). Apoptosis was evaluated using flow cytometry, and caspase-3 activity, a key marker of apoptosis, was assessed using caspase-3 immunofluorescence staining. Enoxaparin at 50, 100, and 200µM markedly increased cell viability in the enoxaparin + glutamate group. Enoxaparin treatment in the enoxaparin + glutamate group also significantly elevated levels of SOD and TAS, while concurrently decreasing MDA and TOS levels. These changes indicate a reduction in oxidative stress. Enoxaparin treatment further resulted in a significant decline in cleaved caspase-3 levels, a marker of apoptosis. Enoxaparin pre-treatment reduced cell death according to flow cytometry analysis. This study suggests enoxaparin's potential to shield C6 glioma cells from glutamate-induced cell death by mitigating both oxidative stress and apoptotic pathways. More research is needed to confirm this effect.

Biocompatible Metal-Organic Framework-Based Fabric Composite as an Efficient Personal Protective Equipment for Particulate Matter-Induced Pulmonary Injury.

Efficient personal protection has emerged as a crucial approach for reducing pulmonary injury induced by particulate matter (PM). However, current personal protective equipments usually lack essential biosafety concerns and fail to own adsorbing/antioxidant/antibacterial function together, making it a challenge to develop an integrated platform with the above characteristics. Herein, a facile oxygen-free hydrothermal strategy is proposed to synthesize new copper-based metal-organic frameworks, Cu-HHTPs, (HHTP: 2,3,6,7,10,11-hexahydroxytriphenylene), with great adsorbing/antioxidant/antibacterial activity and high biosafety. The Cu-HHTPs can serve as an efficient additive incorporated with various fabrics including cellulose acetate (CA) membrane to achieve novel fabric composites, such as CA@Cu-HHTPs, with ideal scavenging outcome for the main components of PM. Evidenced by the animal experiments, CA@Cu-HHTPs can highly mitigate PM-induced adverse effects via adsorbing PM, scavenging ROS, and killing bacteria, leading to a significant reduction in lung permeability, inflammation and oxidative stress, and pulmonary infection. Last but not least, a two-week exposure of CA@Cu-HHTPs exhibits no obvious damage toward the animals by examining their long-term toxicity. Collectively, this study not only highlights the potential of Cu-HHTPs as attractive additives for the preparation of fabric composites, but also lays out a new concept toward the development of new-generation multifunctional personal protective equipment against PM.

Ameliorative Potential of Menstrual Blood-derived Endometrial Stem Cells in Alcohol-Induced Fatty Liver Disease

Background: Alcohol-induced fatty liver disease (AFLD) begins with steatosis and may progress to a range of pathological liver changes, including fibrosis, cirrhosis, and complications. Menstrual blood-derived endometrial stem cells (MenSCs) have shown potential therapeutic effects against various types of liver damage. However, the liver-protective effects of MenSCs in AFLD are not well understood. This study aimed to evaluate the therapeutic effects of MenSCs on AFLD progression. Methods: MenSCs were sourced from women in good health (N=5, 25-34 years old). Male C57BL/6 mice were separated into three distinct groups to establish the mouse models. The AH/- MenSCs group received MenSCs (5×105 cells/mouse) transplantation through tail injection on the 7th and 13th days following the initiation of the alcohol-induced fatty liver model. The therapeutic effects of MenSCs transplantation in AFLD mouse models were subsequently explored using qPCR, Western blotting, histopathological examination, and mRNA sequencing analysis. Results: MenSCs significantly improved liver function and reduced lipid accumulation in AFLD. Treatment with MenSCs was also found to reduce the expression levels of inflammatory cytokines and profibrotic markers in the liver tissues of the mouse model. Additionally, the MenSCs- treated group demonstrated a significant reduction in endoplasmic reticulum (ER) stress and oxidative stress, along with an increase in autophagic activity. Conclusion: The findings provided preliminary evidence of the multifaced protective effects of MenSCs in AFLD.

Ivabradine prevents doxorubicin-induced cardiotoxicity via attenuating mitochondrial dysfunction and mitochondrial dynamic imbalance in H9C2 cells and rats

Abstract Background Doxorubicin (DOX) is a widely used chemotherapeutic agent, and cardiotoxicity is one of its well-known side effects, which is mediated by cardiac mitochondrial dysfunction. Ivabradine (IVA), a heart rate reduction drug, exerts benefits in various cardiac diseases as shown in both preclinical and clinical studies. However, its roles on DOX-induced cardiotoxicity have never been investigated. Purpose We determined whether IVA reduces DOX-induced cardiotoxicity by directly promoting mitochondrial function and maintaining mitochondrial dynamic balance. Methods H9C2 cells were divided into 4 groups: 1) Control, 2) DOX (10 μM, 25 h), 3) IVA (3 μM, 25 h), 4) Pretreatment with IVA (3 μM, 1 h), followed by DOX treatment (10 μM, 24 h). Then, cell viability and mitochondrial function were determined. In animal study, male Wistar rats were divided into 4 groups: 1) Control, 2) IVA (10 mg/kg/d, PO), 3) DOX (3 mg/kg/d, 6 doses, IP), 4) Co-treatment with IVA (10 mg/kg/d, PO) and DOX (3 mg/kg/d, 6 doses, IP) for 30 days. Then, heart rate, cardiac function, and cardiac mitochondrial dynamic proteins were determined. Result DOX reduced %cell viability of H9C2 cells via increasing cellular and mitochondrial oxidative stress, and reducing mitochondrial respiration (Figure 1A, B). Under DOX-induced cellular injury condition, pretreatment with IVA resulted in increasing %cell viability by 11%, decreasing cellular and mitochondrial oxidative stress; however, IVA did not affect mitochondrial respiration. Consistent with in vitro study, DOX induced cardiac dysfunction as indicated by reduced heart rate and ejection fraction, impaired mitochondrial function and mitochondrial dynamics balance (Figure 1C, D). Co-treatment with DOX and IVA had no further impact on heart rate. DOX-IVA attenuated cardiac mitochondrial dysfunction and mitochondrial dynamics imbalance, thus prevented cardiac dysfunction. Conclusion IVA effectively protected against DOX-induced cardiotoxicity through improvement of mitochondrial function, mitochondrial dynamics, and reduction of oxidative stress. These findings suggest the therapeutic potential of IVA in preventing Dox-induced cardiotoxicity.

Dietary supplementation of probiotic Lactobacillus modulates metabolic dysfunction-associated steatotic liver disease and intestinal barrier integrity in obesity-induced mice.

The impact of Lacticaseibacillus paracasei NWAFU334 and Limosilactobacillus fermentum NWAFU0035 on the amelioration of liver function, oxidative stress reduction, and lipid metabolism modulation in mice subjected to an obesity-inducing high-fat diet (HFD) model was investigated. L. paracasei NWAFU334 and L. fermentum NWAFU0035 supplementations over 12weeks have been shown to have numerous beneficial effects in mice with induced obesity. These effects comprise the restoration of liver function and the reduction of oxidative stress within the liver. Furthermore, the supplementation led to a decreased content of fat accumulation in the liver, mitigation of the expression of inflammatory cytokines in the liver and colon, and a decrease in the expression levels of tight-junction proteins, for example, claudin-1, PPARγ, occludin, and ZO-1. Additionally, a notable improvement in the colonic expression proteins, including IL-6, TNF-α, IL-1β, Muc-2, Muc-3, Zo-1, claudin-1, and occludin. These proposed strains considerably decreased proinflammatory cytokines and influenced the regulation of lipid metabolism in the liver. These findings indicate that the potential mechanisms, primarily the impact of L. paracasei NWAFU334 and L. fermentum NWAFU0035 on obesity-induced liver function in mice, involve two regulated pathways: downregulation of lipogenesis and upregulation of gene expression related to fatty acid oxidation and lipolysis. In other words, these probiotic bacterial strains might be beneficial in reducing fat production and increasing fat breakdown in the liver. They may serve as effective therapeutic supplements for alleviating abnormalities induced by an HFD.

Genetic iron overload aggravates, and pharmacological iron restriction improves, MDS pathophysiology in a preclinical study

AbstractAlthough iron overload is a common feature in myelodysplastic syndromes (MDSs), it remains unclear how iron excess is detrimental for disease pathophysiology. Taking advantage of complementary approaches, we analyzed the impact of iron overload and restriction achieved through genetic activation of ferroportin (FPN) via the C326S mutation (FPNC326S) and pharmacologic inhibition (vamifeport) of the iron exporter FPN, respectively, in a MDS mouse model. Although FPNC326S-induced iron overload did not significantly improve the late stages of erythroid maturation, vamifeport-mediated iron restriction ameliorated anemia and red blood cell maturation in MDS mice, through the reduction of oxidative stress and apoptosis in erythroid progenitors. Iron overload aggravated, and restriction alleviated, reactive oxygen species formation, DNA damage, and cell death in hematopoietic stem and progenitor cells, resulting in altered cell survival and quality. Finally, myeloid bias, indicated by expanded bone marrow myeloid progenitors and circulating immature myeloid blasts, was exacerbated by iron excess and attenuated by iron restriction. Overall, vamifeport treatment resulted in improved anemia and significant survival increment in MDS mice. Interestingly, the combined therapy with vamifeport and the erythroid maturation agent luspatercept has superior effect in improving anemia and myeloid bias as compared with single treatments and offers additive beneficial effects in MDS. Our results prove, to our knowledge, for the first time in a preclinical model, that iron plays a pathologic role in transfusion-independent MDS. This is likely aggravated by transfusional iron overload, as suggested by observations in the FPNC326SMDS model. Ultimately, the beneficial effects of pharmacologic FPN inhibition uncovers the therapeutic potential of early prevention of iron toxicity in transfusion-independent MDS.

Honokiol protects against diabetic retinal microvascular injury via sirtuin 3-mediated mitochondrial fusion

IntroductionMitochondrial dysfunction and oxidative stress play important roles in diabetic retinal vascular injuries. Honokiol (HKL) is a small-molecule polyphenol that exhibits antioxidant effects and has a beneficial effect in diabetes. This study aimed to explore the potential ability of HKL to ameliorate vascular injury in diabetic retinopathy (DR) and its possible mechanisms of action.MethodsThe effect of HKL was evaluated in vascular injury in an in vivo type 2 diabetic (db/db) mouse model. In vitro, retinal microvascular endothelial cells were treated with high glucose (HG) to simulate the pathological diabetic environment. Cell viability, expression of apoptosis-related proteins, cellular reactive oxygen species, mitochondrial membrane potential, and morphological changes in the mitochondria were examined.ResultsThe diabetic mice exhibited severe retinal vascular damage, including vascular leakage in vivo and capillary endothelial cell apoptosis in vitro. HKL reversed the retinal vascular leakage in the diabetic mice. In vitro, HKL improved retinal capillary endothelial cell viability, decreased apoptosis, and reversed the HG-induced increased cellular oxidative stress and mitochondrial fragmentation. The sirtuin 3 (SIRT3) inhibitor 3-TYP blocked all the in vivo and in vitro protective effects of HKL against diabetic retinal vascular leakage and capillary endothelium and eliminated the decrease in oxidative stress levels and reduction of mitochondrial fragmentation.DiscussionIn conclusion, these findings suggest that HKL inhibits vascular injury in DR, which was likely achieved through SIRT3-mediated mitochondrial fusion. This study provides a potential new strategy for the treatment of DR.

Reduction of Blood Oxidative Stress Following Colorectal Cancer Resection

Background: Colorectal cancer is a major global health burden, with surgical resection being the standard treatment aimed at curative tumor removal. Oxidative stress plays a crucial role in colorectal cancer progression and prognosis. This study hypothesized that physical removal of colorectal cancer, a primary source of oxidative stress, would reduce blood levels of reactive oxygen metabolite derivatives (d-ROMs), a marker of oxidative stress, and biologic antioxidant potential (BAP) levels, a marker of antioxidant potential. Methods: This study included 123 patients who underwent radical resection for colorectal cancer. d-ROM and BAP levels were measured before and one month after surgery. Results: The clinicopathological analysis showed a correlation between preoperative d-ROM levels and tumor size (p &lt; 0.001). This study confirmed a significant reduction in d-ROM levels following tumor resection, indicating reduced systemic oxidative stress. The reduction was significant in stages II and III, but not in stage I. The d-ROM ratio before and after tumor resection was significantly higher in cases with positive lymph node metastasis and larger tumor size. BAP levels showed no significant changes post-surgery. Conclusions: These results suggest that d-ROMs could serve as a valuable biomarker for monitoring tumor burden and surgical efficacy in patients with colorectal cancer.

Ameliorating arsenic and PVC microplastic stress in barley (Hordeum vulgare L.) using copper oxide nanoparticles: an environmental bioremediation approach

The present study investigates the impact of varying concentrations of PVC microplastics (PVC–MPs) – specifically 0 (no PVC–MPs), 2, and 4 mg L− 1 –alongside different arsenic (As) levels of 0 (no As), 150, and 300 mg kg− 1 in the soil, with the concurrent application of copper oxide–nanoparticles (CuO–NPs) at 0 (no CuO –NPs), 25 and 50 µg mL− 1 to barley (Hordeum vulgare L.) plants. This research primarily aims to assess plant growth and biomass, photosynthetic pigments and gas exchange characteristics, oxidative stress indicators, as well as the response of various antioxidants (both enzymatic and non-enzymatic) and their relevant genes expression, proline metabolism, the AsA–GSH cycle, and cellular fractionation within the plants. The findings showed that increased levels of PVC–MPs and As stress in the soil significantly reduced plant growth and biomass, photosynthetic pigments, and gas exchange characteristics. Additionally, PVC–MPs and As stress increased oxidative stress in the roots and shoots, as evidenced by elevated levels of malondialdehyde (MDA), hydrogen peroxide (H2O2), and electrolyte leakage (EL), which in turn stimulated the production of various enzymatic and non-enzymatic antioxidants, gene expression, and sugar content. Furthermore, a notable increase in proline metabolism, the AsA–GSH cycle, and cellular pigmentation was observed. Conversely, the application of CuO–NPs resulted in a substantial improvement in plant growth and biomass, gas exchange characteristics, and the activity of enzymatic and non-enzymatic antioxidants, along with a reduction in oxidative stress. Additionally, CuO–NPs enhanced cellular fractionation while decreasing proline metabolism and the AsA-GSH cycle in H. vulgare plants. These outcomes provide new insights into sustainable agricultural practices and offer significant potential in addressing the critical challenges of heavy metal contamination in agricultural soils.

GLP-1 receptor agonists as promising anti-inflammatory agents in heart failure with preserved ejection fraction.

Heart Failure with Preserved Ejection Fraction (HFpEF) represents a significant challenge in modern cardiovascular medicine, characterized by diastolic dysfunction and a chronic pro-inflammatory milieu. The high prevalence of comorbidities such as diabetes, visceral obesity, and aging, which contribute to systemic inflammation, plays a pivotal role in the pathogenesis and progression of HFpEF. Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs), a class of glucose-lowering drugs, have demonstrated a wide range of pleiotropic effects that extend beyond glycaemic control. These effects include the reduction of inflammation and oxidative stress, vasodilation, decreased arterial stiffness, and a reduction in myocardial fibrosis-key factors in the pathophysiology of HFpEF. Recent evidence from the STEP-HFpEF and STEP-HFpEF-DM trials provides the first robust data supporting the efficacy of GLP-1 RAs, specifically semaglutide, in improving the quality of life in obese patients with HFpEF. These trials also demonstrated a significant reduction in C-Reactive Protein (CRP) levels, reinforcing the hypothesis that suppressing the pro-inflammatory state may yield substantial clinical benefits in this patient population. These findings suggest that GLP-1 RAs could play a crucial role in the management of HFpEF, particularly in patients with obesity, by targeting the underlying inflammatory processes and contributing to better overall cardiovascular outcomes.

Assessment of sweet whey fortified with Bifidobacteria and selenium on reduction of pesticide liver toxicity in albino rats

Deltamethrin (DLM) represents one of the most commonly used pesticides. It passes through milk, vegetables, and fruits to humans or through animals (veterinary drugs and feeding on contaminated forage) to milk; it can escape from skin to blood and be secreted in breast milk in lactating women. It is believed to have neurotoxic, nephrotoxic, and hepatotoxic properties. To investigate deltamethrin-induced hepatotoxicity, 64 rats were divided into eight groups. The control group did not receive any treatment. The groups were as follows: D 30 mg DLM/kg body weight (BW) dissolved in corn oil; B 1 mL whey (1010 cfu/mL of Bifidobacterium longum ATCC 15707); S 1 mL whey (0.5 ppm selenium); BS 1 mL whey (1010 cfu/mL of B. longum ATCC 15707 + 0.5 ppm selenium); BD 1 mL whey (1010 cfu/mL of B. longum ATCC 15707 + DLM); SD 1 mL whey (0.5 ppm selenium) + DLM; and BSD 1 mL whey (1010 cfu/mL of B. longum ATCC 15707) + 0.5 ppm selenium + DLM. Results revealed that the manipulation of Bifidobacteria with selenium triggered a significant improvement in AST (U/mL), ALT (U/mL), GSH (mg/g), TNF-α (pg/mL), NF-κB (ng/mL), and BCL2 (ng/mL) from 166.7 ± 6.42, 30.67 ± 0.55, 0.252 ± 0.005, 17.18 ± 0.42, 1.14 ± 0.10, and 1.77 ± 0.06 versus 334.9 ± 4.7, 72.83 ± 2.49, 0.108 ± 0.005, 33.57 ± 0.59, 2.58 ± 0.05, and 1.04 ± 0.04, respectively, compared to DLM group. As well as reduction in histopathological necrosis, congestion, and degradation. Whey beverages fortified with B. longum and selenium implicated a reduction in oxidative stress and histopathological degradation that accomplished DLM toxicity. The utilization of whey (a byproduct of cheese making) is considered a recycling process that supports eco-friendly practices and sustainability, thus encouraging its use as a protective tool in animal feed or manipulation by humans, especially workers in pesticide plants.

Selenium participates in the formation of kidney stones by alleviating endoplasmic reticulum stress and apoptosis of renal tubular epithelial cells

ABSTRACT Objectives: To investigate the role of selenium and selenium-containing proteins in the etiology and pathogenesis of kidney stones. Methods: The HK-2 cell line was subjected to supersaturation oxalate treatment to establish an in vitro model of calcium oxalate kidney stones, while SD rats were administered with ethylene glycol to establish an in vivo model of calcium oxalate kidney stones. qPCR analysis was employed to investigate the alterations in selenoproteins within the models, and subsequently, genes exhibiting significant changes were identified. Subsequently, based on the functions of these genes, their regulatory effects on endoplasmic reticulum stress (ERS) and apoptosis during the disease progression were examined both in HK-2 cells and rat kidneys. Finally, Selenomethionine (SeMet) supplementation was introduced to explore its therapeutic potential for kidney stone management. Results: The involvement of Selenoprotein K in the pathogenesis of calcium oxalate kidney stone disease has been confirmed, exhibiting significant alterations. Manipulation of its expression levels through overexpression and knockdown techniques resulted in a corresponding reduction or increase in oxidative stress, ERS, and apoptosis within renal tubular epithelial cells. SelK regulates ERS and apoptosis by controlling the IRE1-ASK1-JNK pathway. In addition, SeMet treatment, which contains selenium, effectively reduced the levels of oxidative stress, ERS, and apoptosis in vivo and in vitro models, thereby alleviating tubular epithelial cell damage and reducing the formation of kidney stones in experimental rats. Discussion: Selenium is involved in the occurrence and development of kidney stones by regulating oxidative damage to renal tubular epithelial cells. The results suggest that dietary selenium supplementation in daily life may be of great significance for the prevention and treatment of kidney stones.