Generation Of Oxygen Free Radicals Research Articles

Evaluate the effect of exercise core strength training on antioxidant enzyme activity in women from a biomechanical perspective

At present, the incidence rate of chronic diseases is increasing year by year. A variety of antioxidant enzymes in the human body, such as Superoxide Dismutase (SOD), Nitric Oxide Synthase (NOS), Glutathione Peroxidase (GSH Px), Malonic Dialdehyde (MDA) and Catalase (CAT), help to inhibit the generation of oxygen free radicals and play a certain role in preventing the occurrence of chronic diseases. The research on the activity of antioxidant enzymes and the delivery of antioxidant drugs has gradually become the focus of relevant scholars. The physical quality of women is lower than that of men, so it is of great practical significance to study the antioxidant enzyme activity of women. Therefore, this paper explores the influence of exercise core strength training on women’s antioxidant enzyme activity from a biomechanical perspective and concludes that core strength training can improve female students’ SOD content level by 2.58%, and can improve female students’ NOS content level, GSH-Px content level, and MDA content level. Sports core strength training has a positive impact on women’s antioxidant enzyme activity.

Synergistic effect of curcumin and Piperine loaded Niosomal nanoparticles on acute pulmonary toxicity induced by Paraquat in mice.

Paraquat (PQ), a widely used non-selective herbicide, induces severe lung toxicity by promoting cell death and tissue necrosis through the generation of reactive oxygen species (ROS) and free radicals. This study aimed to develop and evaluate novel niosomal nanoparticles (NPs) encapsulating curcumin and piperine to mitigate PQ-induced acute pulmonary toxicity in Balb/c mice. The NPs were prepared using non-ionic surfactants and cholesterol via the thin film hydration method. Characterization revealed high encapsulation efficiency (>85%), proper particle sizes (264-286nm), narrow polydispersity index (PDI) (0.19±0.04 to 0.23±0.02), and good stability over 90days. Thermal analysis confirmed successful encapsulation of curcumin and piperine within the niosomal NPs. In vivo studies showed that PQ exposure significantly elevated ROS, lipid peroxidation (LPO), and protein carbonylation (PC) levels, while reducing glutathione (GSH) levels and impairing mitochondrial function (P<0.001). However, co-treatment with curcumin- and piperine-loaded niosomal NPs effectively reversed these effects (P<0.001), improving mitochondrial function. The combined formulation of curcumin and piperine in niosomal NPs offers a promising therapeutic strategy for treating PQ-induced pulmonary toxicity, likely due to enhanced bioavailability and potent antioxidant activity.

Electrospun nanofibrous scaffolds reinforced with therapeutic lithium/manganese-doped calcium phosphates: Advancing skin cancer therapy through apoptosis induction

In the current study we fabricated potent materials by incorporating therapeutic elements into calcium phosphates (CPs) to combat cancer. This involved synthesizing manganese (Mn)- and lithium (Li)-doped CPs and loading them into electrospun nanofibers (NFs) composed of chitosan (CS) and polyethylene oxide (PEO). The characterized CPs exhibited excellent properties, including a particle size of 47–75 nm, surface charge of –(30−56) mV, and specific surface area of 75–266 m2/g. The electrochemical analysis revealed that Mn and Mn/Li-doped CPs are promising for generating oxygen free radicals and H2O2, crucial for cancer therapy. Biological evaluation showcased the outstanding performance of the developed materials. MTT assay revealed a cytotoxic effect of nano-constructs on melanoma A375 cell line without adverse effects on normal L929 cells over 72 h. Annexin V/PI apoptosis assay indicated substantial apoptosis rates in A375 cells treated with PC-20 % (62.55 ± 4.59 %). The obtained data of qPCR analysis of pro-apoptotic and anti-apoptotic genes (P53, Bax, Bcl-2) in A375 cells treated with different CP nanoparticles (NPs) showed a significant increase in P53 and Bax gene expression, indicating high levels of A375 cell apoptosis. Additionally, the samples containing Mn ion exhibited high reactive oxygen species (ROS) generation. In conclusion, the fabricated NFs scaffolds hold promising potential for cancer therapy.

Effect of interval hypoxytherapy on the immune status of hypertensive patients

In recent years, the role of sluggish nonspecific inflammation in the pathogenesis of hypertension has been proven. Oxidative stress that develops in hypertension leads to damage of endothelial glycocalyx with impaired barrier and adaptive functions of endothelium. Activation of transcription factor NF-kB leads to increased synthesis of free oxygen radicals, adhesion molecules (VCAM-1, ICAM-1, P-selectin, E-selectin) and proinflammatory cytokines (TNFα, IL-1, IL-6), triggering the inflammatory process in the endothelium. Modern antihypertensive drugs, affecting various pathogenetic mechanisms of arterial hypertension development, do not fully affect the immune component of arterial hypertension. Therefore, the search for various methods affecting the immunologic reactivity of hypertensive patients remains relevant in our time. The aim of the study was to reveal the effect of interval hypoxytherapy on the state of immunologic reactivity of patients with hypertension stage I. One hundred seventy male patients of 30-45 years old (mean age 38.36±1.64 years) with hypertension stage I (n = 170) who underwent combined treatment including drug therapy and normobaric interval hypoxic therapy in hypoxia-normoxia mode (oxygen content in hypoxic gas mixture was 20.9%) were examined. Indices of redox status and immunologic reactivity before and after interval hypoxytherapy were studied. Having a significant antioxidant effect, interval hypoxytherapy led to the subsidence of oxidative stress, which was indicated by an increase in the activity of superoxide dismutase and glutathione peroxidase in blood erythrocytes and a decrease in the content of malonic dialdehyde in blood as a result of a decrease in the generation of free oxygen radicals and suppression of lipid peroxidation processes. Interval hypoxytherapy resulted in a statistically significant increase in the initially decreased content of CD3+T lymphocytes (p 0.05), CD3+CD4+T lymphocytes (p 0.02), CD3+CD8+T lymphocytes (p 0.02). Initially increased number of B-lymphocytes CD19+, CD16+ lymphocytes, CD95+ lymphocytes significantly decreased. An important result of interval hypoxytherapy was a pronounced anti-inflammatory effect: statistically significant decrease in the content of pro-inflammatory interleukins IL-1β (p 0.02), IL-6 (p 0.01) and increase in the content of anti-inflammatory cytokines IL-4 (p 0.005) and IL-10 (p 0.005), which led to the subsidence of sluggish nonspecific inflammation. Suppression of oxidative stress and normalization of immunological reactivity of hypertensive patients after interval hypoxytherapy led to the subsidence of sluggish nonspecific inflammation, reduction of endothelial dysfunction and restoration of the structure and tone of the vascular wall with a decrease in blood pressure and improvement of the clinical course of hypertension.

A feasible strategy of Ag nanoparticles-sodium alginate-polyacrylamide-polyvinyl alcohol hydrogel coatings for preventing catheter-associated urinary tract infections

Catheter-associated urinary tract infections (CAUTIs) pose a significant clinical challenge, potentially resulting in complications such as bacteriuria and mortality. Developing coatings with antibacterial and antiadhesive properties for urinary catheters is essential to address these issues. In this study, a novel hydrogel coating composed of silver nanoparticles (Ag NPs), sodium alginate (SA), polyacrylamide (PAAm), and polyvinyl alcohol (PVA) was prepared on polydopamine (PDA)-modified latex urinary catheters using a simple dipping method. The Ag NPs were synthesized via an in-situ reduction of AgNO3 with SA, eliminating the need for additional chemical reductants. The Ag NPs-SA-PAAm-PVA hydrogel-coated urinary catheter demonstrated superior antibacterial and antiadhesive characteristics compared to the bare urinary catheter. The antiadhesive properties of the hydrogel-coated urinary catheter were attributed to its hydrophilicity and lubricity, while the antibacterial effects were linked to the penetration of Ag NPs and Ag+ ions into bacterial structures, disrupting bacterial metabolism through the generation of reactive oxygen species (ROS) and free radicals upon attachment of Ag+ ions to cell walls and membranes. Furthermore, the hydrogel coatings exhibited remarkable mechanical properties, along with good biocompatibility and hemocompatibility. The exceptional antibacterial and antiadhesive properties of the hydrogel-coated urinary catheter hold promise for reducing CAUTIs.

Effects of UV radiation on human skin and its microbiota: a review on microbial UV sunscreens

Solar ultraviolet (UV) radiation is the culprit for molecular and genetic changes that occur to the skin. This effect can be direct or indirect through the generation of reactive oxygen species and free radicals. So, it is important to find potential molecules that can reduce both effects. In this review, we explored the contributions of microbial-originated UV sunscreens, particularly by mycosporines and mycosporines-like amino acids (MAA). These natural molecules are capable UV ray absorbers and antioxidant health protectors, given that they are eco-friendly, have strong photostability and are non-toxic. Furthermore, microorganisms are known for producing their compounds to survive harsh environments which in turn is beneficial to humans too. The reason behind it is the reduction of production cost as it has a simple growth culture and useful genetic manipulation. Thus, the knowledge regarding the synthesis pathway and therapeutic advantages of mycosporines of microbial origin is essential to be improved. Currently, only mycosporines production of marine life have been investigated, the remaining are unclear. We aimed to search more into the impacts of UV radiation on human skin and its microbiota and the microbial-based approaches to counter UV-induced damages.

Oxygen-Independent Radiodynamic Therapy: Radiation-Boosted Chemodynamics for Reprogramming the Tumor Immune Environment and Enhancing Antitumor Immune Response.

Radiodynamic therapy (RDT) has emerged as a promising modality for cancer treatment, offering notable advantages such as deep tissue penetration and radiocatalytic generation of oxygen free radicals. However, the oxygen-dependent nature of RDT imposes limitations on its efficacy in hypoxic conditions, particularly in modulating and eliminating radioresistant immune suppression cells. A novel approach involving the creation of a "super" tetrahedron polyoxometalate (POM) cluster, Fe12-POM, has been developed for radiation boosted chemodynamic catalysis to enable oxygen-independent RDT in hypoxic conditions. This nanoscale cluster comprises four P2W15 units functioning as energy antennas, while the Fe3 core serves as an electron receptor and catalytic center. Under X-ray radiation, a metal-to-metal charge transfer phenomenon occurs between P2W15 and the Fe3 core, resulting in the valence transition of Fe3+ to Fe2+ and a remarkable 139-fold increase in hydroxyl radical generation compared to Fe12-POM alone. The rapid generation of hydroxyl radicals, in combination with PD-1 therapy, induces a reprogramming of the immune environment within tumors. This reprogramming is characterized by upregulation of CD80/86, downregulation of CD163 and FAP, as well as the release of interferon-γ and tumor necrosis factor-α. Consequently, the occurrence of abscopal effects is facilitated, leading to significant regression of both local and distant tumors in mice. The development of oxygen-independent RDT represents a promising approach to address cancer recurrence and improve treatment outcomes.

The Influence of Circadian Rhythm on the Antioxidant Capacity of Saliva in Periodontal Diseases.

Background Saliva has a powerful antioxidant activity proposing that it might have a protective role in the oral cavity. It is yet unclear, how circadian rhythm might affect this activity. Objective The main goal of this study was to compare the antioxidant status of saliva in patients with periodontal diseases (PD) to that of healthy people on a diurnal basis. Material and methods A total of 18 periodontal healthy individuals and 18 patients with chronic periodontitis were chosen. Samples of saliva were collected in the morning between 6:00 and 8:00 and in the evening between 6:00 and 8:00 (both stimulated and non-stimulated). The amount of glutathione (GSH), malondialdehyde (MDA), and total antioxidant status (TAS) in the salivary samples were analyzed, and its flow was also assessed. In addition, the scavenging capacity of saliva was tested in three systems generating oxygen free radicals. Results Results showed that GSH and TAS concentrations in the evening saliva of healthy subjects were significantly higher than those in the morning saliva, while MDA levels decreased (p<0.05). Conversely, there was no significant increase in GSH and TAS levels in the evening saliva of subjects with PD, and lipid peroxidation remained constant. On the other hand, the evening saliva of healthy subjects but not of subjects with PD was significantly more potent in scavenging free radicals in vitro than the morning saliva, especially for the superoxide (O2.-)radical (p<0.05). Moreover, scavenging activity was higher in stimulated than non-stimulated saliva. This activity was higher in evening saliva compared to the morning one and greater in healthy subjects compared to patients with PD (p<0.05). Conclusion A balance exists between oxidative stress and antioxidant mechanisms to maintain homeostasis in the oral cavity. This balance is deregulated in patients with PD as their saliva is unable to properly scavenge free radicals that might potentially increase over the day. Antioxidant supplements may be used in accordance with the circadian rhythm to minimize oxidative damage.

Abatacept: A Promising Repurposed Solution for Myocardial Infarction-Induced Inflammation in Rat Models.

Myocardial infarction (MI) is irreversible damage to the myocardial tissue caused by prolonged ischemia/hypoxia, subsequently leading to loss of contractile function and myocardial damage. However, after a perilous period, ischemia-reperfusion (IR) itself causes the generation of oxygen free radicals, disturbance in cation homeostasis, depletion of cellular energy stores, and activation of innate and adaptive immune responses. The present study employed Abatacept (ABT), which is an anti-inflammatory drug, originally used as an antirheumatic response agent. To investigate the cardioprotective potential of ABT, primarily, the dose was optimized in a chemically induced model of myocardial necrosis. Thereafter, ABT optimized the dose of 5 mg/kg s.c. OD was investigated for its cardioprotective potential in a surgical model of myocardial IR injury, where animals (n = 30) were randomized into five groups: Sham, IR-C, Telmi10 + IR (Telmisartan, 10 mg/kg oral OD), ABT5 + IR, ABT perse. ABT and telmisartan were administered for 21 days. On the 21st day, animals were subjected to LAD coronary artery occlusion for 60 min, followed by reperfusion for 45 min. Further, the cardioprotective potential was assessed through hemodynamic parameters, oxidant-antioxidant biochemical enzymatic parameters, cardiac injury, inflammatory markers, histopathological analysis, TUNEL assay, and immunohistochemical evaluation, followed by immunoblotting to explore signaling pathways. The statistics were performed by one-way analysis of variance, followed by the Tukey comparison post hoc tests. Noteworthy, 21 days of ABT pretreatment amended the hemodynamic and ventricular functions in the rat models of MI. The cardioprotective potential of ABT is accompanied by inhibiting MAP kinase signaling and modulating Nrf-2/HO-1 proteins downstream signaling cascade. Overall, the present work bolsters the previously known anti-inflammatory role of ABT in MI and contributes a mechanistic insight and application of clinically approved drugs in averting the activation of inflammatory response.

Long-term intake of sulforaphene alleviates D-galactose-induced skin senescence by activating AMPK-Sirt 1 pathway.

D-Galactose (D-gal) accumulation triggers the generation of oxygen free radicals, resulting in skin aging. Sulforaphene (SFE), an isothiocyanate compound derived from radish seeds, possesses diverse biological activities, including protective effects against inflammation and oxidative damage. This investigation delves into the antioxidant impact of SFE on age-related skin injury. In vivo experiments demonstrate that SFE treatment significantly improves the macro- and micro-morphology of dorsal skin. It effectively diminishes the elevation of oxidative stress biomarkers in mice skin tissue treated with D-gal, concurrently enhancing the activity of antioxidant enzymes. Additionally, SFE mitigates collagen mRNA degradation, lowers pro-inflammatory cytokine levels, and downregulates MAPK-related protein expression in the skin. Moreover, SFE supplementation reduces lipid metabolite levels and elevates amino acid metabolites, such as L-cysteine and L-histidine. These findings suggest that SFE holds promise as a natural remedy to mitigate aging induced by oxidative stress.

Dual-Responsive Near-Infrared BODIPY-Based Fluorescent Probe for the Detection of F- and HClO in Organisms.

Fluoride anions (F-) play a crucial role in human physiological processes. However, excessive intake of F- would affect oxygen metabolism and promote the generation of oxygen-free radicals. Hence, it is essential to develop a precise and efficient fluorescent probe for visualizing F--induced oxidative stress. In this work, we developed the first bifunctional BODIPY-based fluorescent probe dfBDP with p-tert-butyldimethylsilanolate benzyl thioether as the sensing site for the detection of F- and HClO via two distinct reactions, the self-immolative removal and the thioether oxidation, which generate the sensing products with two nonoverlap fluorescence bands: 800-1200 and 500-750 nm, respectively. The probe dfBDP displays rapid response, high specificity, and sensitivity for the detection of F- (LOD, 316.2 nM) and HClO (LOD, 33.9 nM) in vitro. Cellular imaging reveals a correlation between F--induced oxidative stress and the upregulation of HClO. Finally, probe dfBDP was employed to detect F- and HClO in mice under the stimulation of F-. The experimental results display that the level of HClO elevates in the liver of mice.

Construction of Pd/Mn3O4 heterojunction catalyst for efficient photothermal synergetic catalytic propane total oxidation

Photothermal synergistic low-temperature catalytic volatile organic compounds (VOCs) degradation has an advantage on energy efficiency and reduction of carbon emissions. Herein, an impregnation-pyrolysis-oxidation strategy was adopted to synthesize Pd/Mn3O4 heterojunction catalyst. Under photothermal synergistic conditions, 0.60Pd/Mn3O4 catalyst exhibited an excellent activity for propane total oxidation, with a T90 value of 219.1 ℃, which was 115.3 ℃ lower than that of Mn3O4. Enhancement effect of the heterojunction structure on photothermal synergy was detected by various characterization techniques and density functional theory calculation. The presence of Pd species enhanced the low-temperature reducibility of Mn3O4. Meanwhile, O2 molecules were more easily activated at the Pd sites and overflow to the surface of Mn3O4 for reaction. Besides, the formation of p-n junction between Pd species and Mn3O4 in heterojunction structure promoted the charge separation and the migration of carriers, and boosted the generation of oxygen free radical, resulting in a significant improvement in photothermal catalytic activity. Overall, this study provided new strategy and deep insight for constructing heterojunction to enhance photothermal catalytic performance of VOC elimination.

Physiological and transcriptomic analyses of leaves from Gardenia jasminoides Ellis under waterlogging stress.

Gardenia jasminoides Ellis is a Chinese herbal medicine with medicinal and economic value, but its mechanism of response to waterlogging stress remains unclear. In this study, the "double pots method" was used to simulate the waterlogging stress of Gardenia jasminoides Ellis to explore its physiological and transcriptomic response mechanism. We found no significant damage to Gardenia jasminoides Ellis membrane lipid during stress. POD played a vital antioxidant role, KEGG enrichment showed that secondary metabolites such as flavonoids might also play an antioxidant role, and PRO played a significant osmotic adjustment. Endogenous hormones regulate the Gardenia jasminoides Ellis's growth and development and play a role in signal transduction. Among them, light waterlogging stress is delayed. At the same time, there were 19631, 23693, and 15045 differentially expressed genes on the 5th, 10d, and 15d of Gardenia jasminoides Ellis under waterlogging stress. These genes were closely associated with the proteasome, endopeptidase, ribosome, MAPK signal transduction, and endogenous hormone signal transduction, plant-pathogen interaction and phenylpropanoid biosynthesis and other physiological and metabolic pathways, which regulate the turnover and transportation of protein, the reinforcement and adhesion of cell walls, the induction of stomatal closure, allergic reactions, defense reactions, leaf movements and others. It also can absorb ultraviolet rays to reduce the generation of oxygen free radicals, change the way of energy utilization and adjust the osmotic pressure of plant cells.

A Comprehensive Prognostic Model for Colon Adenocarcinoma Depending on Nuclear-Mitochondrial-Related Genes.

Background: Colon adenocarcinoma (COAD) has increasing incidence and is one of the most common malignant tumors. The mitochondria involved in cell energy metabolism, oxygen free radical generation, and cell apoptosis play important roles in tumorigenesis and progression. The relationship between mitochondrial genes and COAD remains largely unknown. Methods: COAD data including 512 samples were set out from the UCSC Xena database. The nuclear mitochondrial-related genes (NMRGs)-related risk prognostic model and prognostic nomogram were constructed, and NMRGs-related gene mutation and the immune environment were analyzed using bioinformatics methods. Then, a liver metastasis model of colorectal cancer was constructed and protein expression was detected using Western blot assay. Results: A prognostic model for COAD was constructed. Comparing the prognostic model dataset and the validation dataset showed considerable correlation in both risk grouping and prognosis. Based on the risk score (RS) model, the samples of the prognostic dataset were divided into high risk group and low risk group. Moreover, pathologic N and T stage and tumor recurrence in the two risk groups were significantly different. The four prognostic factors, including age and pathologic T stage in the nomogram survival model also showed excellent predictive performance. An optimal combination of nine differentially expressed NMRGs was finally obtained, including LARS2, PARS2, ETHE1, LRPPRC, TMEM70, AARS2, ACAD9, VARS2, and ATP8A2. The high-RS group had more inflamed immune features, including T and CD4+ memory cell activation. Besides, mitochondria-associated LRPPRC and LARS2 expression levels were increased in vivo xenograft construction and liver metastases assays. Conclusion: This study established a comprehensive prognostic model for COAD, incorporating nine genes associated with nuclear-mitochondrial functions. This model demonstrates superior predictive performance across four prognostic factors: age, pathological T stage, tumor recurrence, and overall prognosis. It is anticipated to be an effective model for enhancing the prognosis and treatment of COAD.

Synergistic toxicity of NiO nanoparticles and benzo[a]pyrene co-exposure in liver cells: Role of free oxygen radicals induced oxidative stress

Current attention has been given on health effects of combined exposure of nanoscale materials and organic pollutants. Nickel (II) oxide nanoparticles (NiO NPs) displays exceptional properties and is being used in various areas such as batteries, diesel–fuel additives, and biomedicals. Benzo[a]pyrene (BaP) is a ubiquitous pollutant. Cigarette smoke, diesel exhaust, and grilled foods are main sources of BaP exposure. Therefore, combined exposure of NiO NPs and BaP to humans is unavoidable. There is a dearth of knowledge on combined effects of NiO NPs and BaP in humans. This study was aimed to investigate co-exposure effects of NiO NPs and BaP in human liver cells (HepG2) and primary rat hepatocytes. We observed that individual and co-exposure of NiO NPs and BaP induced cytotoxicity, lactate dehydrogenase leakage, lipid peroxidation, depletion of mitochondrial membrane potential, and activation of caspases (-3 and -9) in both types of cells. Individual and co-exposure of NiO NPs and BaP further accelerated the generation of free oxygen radicals (reactive oxygen species and hydrogen peroxide) and depletion of antioxidants (glutathione and various antioxidant enzymes). Remarkably, NiO NPs and BaP exerted synergistic toxicity to both HepG2 cells and primary rat hepatocytes. Moreover, combined toxicity of NiO NPs and BaP in both cells was mediated through free oxygen radicals induced oxidative stress. This work warrants further research on risk assessment of co-exposure effects NiO NPs and BaP in an appropriate in vivo model.

Neurological-Type Wilson Disease: Epidemiology, Clinical Manifestations, Diagnosis, and Management.

Wilson disease (WD) is a complex metabolic disorder caused by disruptions to copper regulation within the body, leading to an unregulated accumulation of copper within various tissues. A less understood organ affected by the collection of copper is the brain, which further leads to the generation of oxygen-free radicals and resultant demyelination. Healthcare providers must keep the neurological form of WD in their list of differentials when patients present with diverse neurological manifestations. The initial step to diagnosis will be to distinguish the characteristic disease presentation with a thorough history and physical and neurological examination. A high clinical disease suspicion of WD should warrant further investigation by laboratory workup and imaging modalities to support the clinical findings and confirm the diagnosis of WD. Once a WD diagnosis is established, the healthcare provider should treat the underlying biological process of WD symptomatically. This review article discusses the epidemiology and pathogenesis of the neurological form of WD, its clinical and behavioral implications, diagnostic features, and treatment modalities (current and emerging therapies), further aiding healthcare professionals in early diagnosis and management strategies.

Hypothermic Oxygenated Machine Perfusion Promotes Mitophagy Flux against Hypoxia-Ischemic Injury in Rat DCD Liver

Hypothermic oxygenated machine perfusion (HOPE) can enhance organ preservation and protect mitochondria from hypoxia-ischemic injury; however, an understanding of the underlying HOPE mechanism that protects mitochondria is somewhat lacking. We hypothesized that mitophagy may play an important role in HOPE mitochondria protection. Experimental rat liver grafts were exposed to 30 min of in situ warm ischemia. Then, grafts were procured, followed by cold storage for 3 or 4 h to mimic the conventional preservation and transportation time in donation after circulatory death (DCD) in clinical contexts. Next, the grafts underwent hypothermic machine perfusion (HMP) or HOPE for 1 h through portal vein only perfusion. The HOPE-treated group showed a better preservation capacity compared with cold storage and HMP, preventing hepatocyte damage, nuclear injury, and cell death. HOPE can increase mitophagy marker expression, promote mitophagy flux via the PINK1/Parkin pathway to maintain mitochondrial function, and reduce oxygen free radical generation, while the inhibition of autophagy by 3-methyladenine and chloroquine could reverse the protective effect. HOPE-treated DCD liver also demonstrated more changes in the expression of genes responsible for bile metabolism, mitochondrial dynamics, cell survival, and oxidative stress. Overall, HOPE attenuates hypoxia-ischemic injury in DCD liver by promoting mitophagy flux to maintain mitochondrial function and protect hepatocytes. Mitophagy could pave the way for a protective approach against hypoxia-ischemic injury in DCD liver.

Combined effect of succinic acid, riboxin, nicotinamide, riboflavin for the treatment of chronic brain ischaemia

Introduction. Сhronicbrain ischaemiais associated with the generation of oxygen free radicals resulting in a condition of oxidativestress. Various studies have investigated that antioxidant compounds can neutralize reactive oxygen species and free radicals.Aim. To evaluate effect of Cytoflavin (INN: inosine + nicotinamide + riboflavin + succinic acid) for the treatment of chronic brain ischemia.Materialy and methods. In a double-blind, placebo-controlled clinical study 50 patients aged 61 ± 9 years with chronic brain ischemia (vascular cognitive impairment), were randomized into Cytoflavin (n = 32) group or placebo (n = 18) group. The sealed envelopes system was used to randomize patients; 10.0 ml of the compound were infused by drops intravenously for 10-day period. During the course of treatment, therapy with vasoactive, nootropic and psychotropic drugs was excluded. In addition to clinical evaluation were carried outa comprehensive neuropsychological testing of cognitive functions, registration of cognitive induced potentials (IP) P300 and study of cerebral hemoperfusion using single photon emission computed tomography. To assess the intensity of lipid peroxidation we estimated several kinetic parameters of ferrous iron-induced chemiluminescence.Results. Prevalence of good and excellent results of treatment was registered in patients treated with Cytoflavin comparing with those placebo (56% vs. 22%; р = 0.036). Psychological examination showed more expressed positive dynamics of physic activity rate in treatment with the active preparation comparing with those placebo (972 ± 184 sec vs. 1 251 ± 449 sec; р = 0.005). In the group of patients treated with Cytoflavin IP P300 showed the increase of P300 peak amplitude (before treatment 5.2 ± 1.2 mV, after treatment 7.2 ± 2.1 mV; р = 0.035). The biochemical basis of the therapeutic action of Cytoflavin was its antioxidant activity: Cytoflavin increased the endogenous antioxidant background (before treatment 46.8 ± 16.1 sec, after treatment 62.4 ± 13.6 sec, р = 0.004).Conclusions. Cytoflavin produces positive effects on the main symptoms in patients with chronic brain ischaemia, increases endogenous antioxidant background and possesses certain neurotropic activity.

Effect of Date Palm (Phoenix dactylifera) Phytochemicals on Aβ1-40 Amyloid Formation: An in-silico Analysis.

Alzheimer's disease (AD) is a neurodegenerative disease and the most prevalent form of dementia. The generation of oxygen free radicals and oxidative damage is believed to be involved in the pathogenesis of AD. It has been suggested that date palm, a plant rich in phenolic compounds and flavonoids, can provide an alternative treatment to fight memory loss and cognitive dysfunction due to its potent antioxidant activity. Thus, we studied the effect of flavonoids present in date palm on Aβ1−40 amyloid formation using molecular docking and molecular dynamics simulation. AutoDock. Myricetin was used as a positive control drug. The flavonoids Diosmetin, Luteolin, and Rutin were found to be potent inhibitors of aggregation (docking energies ≤ −8.05 kcal mol−1) targeting Aβ1−40 fibrils (both 2LMO and 6TI5), simultaneously. Further screening by physicochemical properties and drug-likeness analysis suggested that all flavonoids except Rutin followed Lipinski's rule of five. Rutin was, thus, taken as a negative control (due to its violation of Lipinski's rule) to compare its dynamics with Diosmetin. Diosmetin exhibited the highest positive scores for drug likeness. Since Luteolin exhibited moderate drug-likeness and better absorption properties, it was also included in molecular dynamics simulation. Molecular dynamics of shortlisted compounds (Rutin, Diosmetin, and Luteolin) were performed for 200 ns, and the results were analyzed by monitoring root mean square deviations (RMSD), root mean square fluctuation (RMSF) analysis, the radius of gyration (Rg), and solvent accessible surface area (SASA). The results proved the formation of a stable protein-compound complex. Based on binding energies and non-bonded interactions, Rutin and Luteolin emerged as better lead molecules than Diosmetin. However, high MW (610.5), lowest absorption rate (16.04%), and more than one violation of Lipinski's rule make Rutin a less likely candidate as an anti-amyloidogenic agent. Moreover, among non-violators of Lipinski's rule, Diosmetin exhibited a greater absorption rate than Luteolin as well as the highest positive scores for drug-likeness. Thus, we can conclude that Diosmetin and Luteolin may serve as a scaffold for the design of better inhibitors with higher affinities toward the target proteins. However, these results warrant in-vitro and in-vivo validation before practical use.

Ubiquitin-specific protease 7 regulates myocardial ischemia/reperfusion injury by stabilizing Keap1

Myocardial ischemia/reperfusion (I/R) injury is a complex pathological process that is still not fully understood. The oxidative stress response has a critical role in the occurrence and progression of myocardial ischemia/reperfusion injury. This study investigated the specific mechanism of ubiquitin-specific protease 7 (USP7) regulation of myocardial ischemia/reperfusion injury from the perspective of proteasome degradation and its relation with the Keap1 pathway, a vital regulator of cytoprotective responses to endogenous and exogenous stress induced by reactive oxygen species (ROS) and electrophiles. Our data indicated that USP7 expression is increased during myocardial ischemia/reperfusion injury in mice, while its inhibiting suppressed the generation of oxygen free radicals and myocardial cell apoptosis, reduced myocardial tissue damage, and improved heart function. Mechanistically, USP7 stabilizes Keap1 by regulating its ubiquitination. Taken together, these findings demonstrate the potential therapeutic effect of USP7 on myocardial ischemia/reperfusion injury.