Oxygen Free Radical Scavengers Research Articles

Rapid classification of a novel ALS-causing I149S variant in superoxide dismutase-1

Variants of the oxygen free radical scavenging enzyme superoxide dismutase-1 (SOD1) are associated with the neurodegenerative disease amyotrophic lateral sclerosis (ALS). These variants occur in roughly 20% of familial ALS cases, and 1% of sporadic ALS cases. Here, we identified a novel SOD1 variant in a patient in their 50s who presented with movement deficiencies and neuropsychiatric features. The variant was heterozygous and resulted in the isoleucine at position 149 being substituted with a serine (I149S). In silico analysis predicted the variant to be destabilizing to the SOD1 protein structure. Expression of the SOD1I149S variant with a C-terminal EGFP tag in neuronal-like NSC-34 cells resulted in extensive inclusion formation and reduced cell viability. Immunoblotting revealed that the intramolecular disulphide between Cys57 and Cys146 was fully reduced for SOD1I149S. Furthermore, SOD1I149S was highly susceptible to proteolytic digestion, suggesting a large degree of instability to the protein fold. Finally, fluorescence correlation spectroscopy and native-PAGE of cell lysates showed that SOD1I149S was monomeric in solution in comparison to the dimeric SOD1WT. This experimental data was obtained within 3 months and resulted in the rapid re-classification of the variant from a variant of unknown significance (VUS) to a clinically actionable likely pathogenic variant.

Galloyl-oligochitosan nano-vehicles for effective and controlled propolis delivery targeting upgrading its antioxidant and antiproliferative potential

A new conjugate, galloyl-oligochitosan nanoparticles (GOCNPs), was fabricated and used as nano-vehicle for effective and controlled delivery of propolis extract (PE) in the form of PE#GOCNPs, targeting improving its pharmaceutical potential. H-bonding interactions between the carboxyl, amino, and hydroxyl groups of the GOCNPs and PE resulted in successful encapsulation, with an entrapment efficacy of 97.3 %. The PE#GOCNPs formulation also exhibited excellent physicochemical stability and time-triggered drug release characteristics under physiological conditions. Furthermore, PE#GOCNPs showed significant activity against MCF-7 and HEPG2 carcinoma cells by scavenging free oxygen radicals and upregulating antioxidant enzymes. Additionally, PE#GOCNPs displayed anti-inflammatory properties by increasing IL10 and reducing pro-inflammatory cytokines more effectively than celecoxib. Furthermore, PE#GOCNPs reduced the expression of epidermal growth factor receptor (EGFR) and survivin genes. Furthermore, the encapsulated PE demonstrated significant activity in suppressing sonic hedgehog protein (SHH). The use of GOCNPs in combination with propolis presents a promising new strategy for chemotherapy with reduced toxicity and enhanced biocompatibility. This novel approach has the potential to revolutionize the field of chemotherapy. Future studies should focus on the application of the encapsulated PE in various cancer cell lines, distinct gene expression factors, and cell cycles.

RESEARCH PROGRESS OF CURCUMIN IN THE TREATMENT OF SEPSIS.

Sepsis is a life-threatening organ dysfunction caused by an unregulated host response to infection. It is an important clinical problem in acute and critical care. In recent years, with the increasing research on the epidemiology, and pathogenesis, diagnostic and therapeutic strategies of sepsis, great progress has been made in clinical practice, but there is still a lack of specific and effective treatment plans. Curcuma longa , a leafy plant of the ginger family, which is a common and safe compound, has multiple pharmacological actions, including, but not limited to, scavenging of oxygen free radicals, attenuation of inflammatory response, and antifibrotic effects. Great progress has been made in the study of sepsis-associated rodent models and in vitro cellular models. However, the evidence of curcumin in the clinical management practice of sepsis is still insufficient; hence, it is very important to systematically summarize the study of curcumin and sepsis pathogenesis.

Edaravone Maintains AQP4 Polarity Via OS/MMP9/β-DG Pathway in an Experimental Intracerebral Hemorrhage Mouse Model.

Oxidative stress (OS) is the main cause of secondary damage following intracerebral hemorrhage (ICH). The polarity expression of aquaporin-4 (AQP4) has been shown to be important in maintaining the homeostasis of water transport and preventing post-injury brain edema in various neurological disorders. This study primarily aimed to investigate the effect of the oxygen free radical scavenger, edaravone, on AQP4 polarity expression in an ICH mouse model and determine whether it involves in AQP4 polarity expression via the OS/MMP9/β-dystroglycan (β-DG) pathway. The ICH mouse model was established by autologous blood injection into the basal nucleus. Edaravone or the specific inhibitor of matrix metalloproteinase 9 (MMP9), MMP9-IN-1, called MMP9-inh was administered 10min after ICH via intraperitoneal injection. ELISA detection, neurobehavioral tests, dihydroethidium staining (DHE staining), intracisternal tracer infusion, hematoxylin and eosin (HE) staining, immunofluorescence staining, western blotting, Evans blue (EB) permeability assay, and brain water content test were performed. The results showed that OS was exacerbated, AQP4 polarity was lost, drainage function of brain fluids was damaged, brain injury was aggravated, expression of AQP4, MMP9, and GFAP increased, while the expression of β-DG decreased after ICH. Edaravone reduced OS, restored brain drainage function, reduced brain injury, and downregulated the expression of AQP4, MMP9. Both edaravone and MMP9-inh alleviated brain edema, maintained blood-brain barrier (BBB) integrity, mitigated the loss of AQP4 polarity, downregulated GFAP expression, and upregulated β-DG expression. The current study suggests that edaravone can maintain AQP4 polarity expression by inhibiting the OS /MMP9/β-DG pathway after ICH.

Sanshools from Zanthoxylum genus and their antioxidant properties in vitro and in vivo

The objective of the present study was to evaluate structure–activity relationships of four sanshools on antioxidant activities. In vitro, hydroxy-α-sanshool (HAS), hydroxy-β-sanshool (HBS), and hydroxy-γ-sanshool (HRS) had stronger antioxidant capacities than hydroxy-γ-sanshool (RS), attributed to the hydroxyl group. Furthermore, HRS had the greatest oxygen radical absorbance capacities (ORAC) and free radical scavenging (DPPH and ABTS) capacities, attributed to more cis-double bonds. Sanshools could effectively decrease the level of oxidative stress in colonic tissue and HCT-116 cells, including increased enzyme activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) and decreased concentrations of malondialdehyde (MDA). After intragastric administration of sanshool, HRS increased the the level of hepatic Total antioxidant capacity (T-AOC) and colon GSH-Px and SOD. Moreover, sanshools significantly increased Nrf2, HO-1 proteins and decreased Keap1 protein. The protective effect of HRS was much higher than HAS, HBS, and RS, apparently due to its amide and hydroxyl groups. The binding energies of Nrf2 with HAS, HBS, HRS, and RS were −5.17, −5.11, −5.75, and −4.16 kcal/mol, respectively. HRS is more easily combine with Nrf2. In summary, sanshools acted as substitutes for natural antioxidants, in which HRS has the greatest antioxidant activity. This study provided a basis for future research on relationships between structure and activity.

Effect of the Novel Free Radical Scavenger 4′-Hydroxyl-2-Substituted Phenylnitronyl Nitroxide on Oxidative Stress, Mitochondrial Dysfunction and Apoptosis Induced by Cerebral Ischemia–Reperfusion in Rats

Mitochondrial dysfunction, which results in the overproduction of oxygen free radicals, is a crucial mechanism underlying cerebral ischemia–reperfusion injury. 4′-Hydroxyl-2-substituted phenylnitronyl nitroxide (HPN), which is an antioxidant and free radical scavenger, can effectively scavenge oxygen free radicals, suggesting its potential as a protective agent against cerebral ischemia–reperfusion injury. In this study, we investigated the effects of HPN on mitochondrial function and apoptosis following cerebral ischemia/reperfusion injury in rats. Healthy adult SD rats were chosen as the experimental subjects, and the rat ischemia/reperfusion injury model was generated using the modified Zea Longa method. The administration of HPN significantly enhanced the activity of endogenous antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). Additionally, HPN effectively preserved the morphology and function of mitochondria, reduced the protein and gene expression of Caspase-3 and Bax, increased the protein and gene expression of Bcl-2, mitigated neuronal apoptosis, improved neurological deficits, and decreased the volume of cerebral infarction. Of interest, the protective effect on brain tissue was more evident with increasing doses of HPN. These findings indicate that HPN can serve as an effective protective agent against cerebral ischemia–reperfusion injury.

Acetyl-L-carnitine attenuates chronic ethanol-induced oxidative stress, ER stress and apoptosis in rat gastric tissue.

Consuming alcohol affects almost all organs. Acetaldehyde, formed as the main product as a result of alcohol metabolism, causes the production of free superoxide radicals when oxidized, and accordingly oxidative and apoptotic processes are triggered. There are studies showing that carnitine has effects on oxidative and apoptotic processes that occur in various conditions. However, the mechanisms showing the effects of L-carnitine on these effects of alcohol have not been fully elucidated. In our study, the effects of acetyl-L-carnitine administration on the molecular mechanisms of oxidative stress, endoplasmic reticulum stress and apoptotic parameters in gastric tissue of rats chronically exposed to alcohol were investigated. Hematoxylin-eosin staining was used for histopathological studies. Endoplasmic reticulum stress markers were detected with immunohistochemical staining and western blotting. Apoptotic index was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Total oxidant and antioxidant status were examined by ELISA. Our results showed that chronic alcohol administration caused a significant increase in TOS levels, an indicator of oxidative stress, the levels of ER-stress-associated proteins XBP1, GRP78 and CHOP, and % apoptotic index values in rat gastric tissues. Additionally, it was determined that acetyl-L-carnitine administration caused an improvement in those values. Based on our data, we can conclude that acetyl-L-carnitine has a tissue protective effect by scavenging free oxygen radicals and reducing ER stress-related proteins XBP1, GRP78 and CHOP and apoptosis in chronic ethanol administered rats, and that this natural antioxidant may be beneficial in the treatment of oxidative stress-induced diseases.

Exploration of the effect and potential mechanism of quercetin in repairing spinal cord injury based on network pharmacology and in vivo experimental verification

Spinal cord injury (SCI) is a highly complex neurological disease, but there is no effective repair method. Quercetin is a flavonol drug and has a variety of biological activities, such as scavenging oxygen free radicals in the body to resist oxidation, inhibiting inflammation, and so on. In this study, quercetin was firstly demonstrated to reduce tissue damage, promote neuron survival and repair motor function after SCI in rats through in vivo experiments. Then, 293 potential targets of quercetin repair for SCI were predicted by network pharmacology. GO analysis revealed that the biological processes of potential targets focused mainly on signal transduction, negative regulation of the apoptotic process, protein phosphorylation, drug response, and so on. Similarly, KEGG analysis suggested that these potential targets were involved in cell growth regulation, differentiation, apoptosis, and a few metabolic pathways. PPI network analysis predicted that the key genes were EP300, CREBBP, SRC, HSP90AA1, TP53, PIK3R1, EGFR, ESR1, and CBL. Further, the molecular docking showed that quercetin binds well with these proteins. Finally, RT-qPCR and Western blotting experiments verified that quercetin downregulated the expression levels of PIK3R1 and EGFR. It is suggested that quercetin can repair SCI in rats through PI3K-AKT signaling pathway and EGFR/MAPK pathway, which may provide a new theoretical basis for the repair of spinal cord injury.

Research Progress on Skin Aging and Active Ingredients.

With the advancement of living standards in modern society and the emergence of an aging population, an increasing number of people are becoming interested in the topic of aging and anti-aging. An important feature of aging is skin aging, and women are particularly concerned about skin aging. In the field of cosmetics, the market share of anti-aging products is increasing year by year. This article reviews the research and development progress of skin aging and related active compounds both domestically and internationally in recent years. The results show that, in terms of the research on skin aging, the popular theories mainly include free radicals and oxidative stress theory, inflammation theory, photoaging theory, and nonenzymatic glycosyl chemistry theory. In terms of research on the active ingredients with anti-aging activities in the skin, there are numerous reports on related products in clinical studies on human subjects, animal experiments, and experimental studies on cell cultures, with a variety of types. Most of the compounds against skin aging are sourced from natural products and their action mechanisms are mainly related to scavenging oxygen free radicals and enhancing antioxidant defenses. This review provides important references for the future research of skin aging and the development of related products. Although there is a great progress in skin aging including related active ingredients, ideal compounds or products are still lacking and need to be further validated. New mechanisms of skin aging, new active ingredients sourced from natural and artificial products, and new pharmaceutical forms including further clinical validations should be further investigated in the future.

Hollow-polydopamine-nanocarrier-based near-infrared-light/pH-responsive drug delivery system for diffuse alveolar hemorrhage treatment.

Introduction: Diffuse alveolar hemorrhage (DAH) is a serious complication caused by systemic lupus erythematosus (SLE). Tissue damage and changes in immune response are all associated with excessive free radical production. Therefore, removing excess reactive oxygen species are considered a feasible scheme for diffuse alveolar hemorrhage treatment. Cyclophosphamide is often used as the main therapeutic drug in clinics. However, CTX carries a high risk of dose-increasing toxicity, treatment intolerance, and high recurrence rate. The combination of therapeutic drugs and functional nanocarriers may provide an effective solution. PDA is rich in phenolic groups, which can remove the reactive oxygen species generated in inflammatory reactions, and can serve as excellent free radical scavengers. Methods: We developed a hollow polydopamine (HPDA) nanocarrier loaded with CTX by ionization to prepare the novel nanoplatform, CTX@HPDA, for DAH treatment. The monodisperse silica nanoparticles were acquired by reference to the typical Stober method. PDA was coated on the surface of SiO2 by oxidation self-polymerization method to obtain SiO2@PDA NPs. Then, HPDA NPs were obtained by HF etching. Then HPDA was loaded with CTX by ionization to prepare CTX@HPDA. Then we tested the photothermal effect, animal model therapeutics effect, and biosafety of CTX@HPDA. Results: Material tests showed that the CTX@ HPDA nanoplatform had a uniform diameter and could release CTX in acidic environments. The vitro experiments demonstrated that CTX@HPDA has good photothermal conversion ability and photothermal stability. Animal experiments demonstrated that the CTX@HPDA nanoplatform had good biocompatibility. The nanoplatform can dissociate in acidic SLE environment and trigger CTX release through photothermal conversion. Combining HPDA, which scavenges oxygen free radicals, and CTX, which has immunosuppressive effect, can treat pulmonary hemorrhage in SLE. Micro-CT can be used to continuously analyze DAH severity and lung changes in mice after treatment. The pulmonary exudation in the various treatment groups improved to varying degrees. Discussion: In this study, we report a photothermal/PH-triggered nanocarrier (CTX@HPDA) for the precise treatment of SLE-DAH. CTX@HPDA is a simple and efficient nanocarrier system for DAH therapy. This work provides valuable insights into SLE treatment.

Research progress of proanthocyanidins and anthocyanidins.

Proanthocyanidins (PA) are polyphenol compounds that are widely distributed in the bark, fruit core, skin, or seeds of various plants. Anthocyanidins are water-soluble natural pigments widely found in plants. They are all flavonoids, a major coloring substance in plants and fruits. In recent years, research into PA and anthocyanins has become increasingly popular because of their excellent anti-oxidation, scavenging of reactive oxygen free radicals and other physical and chemical activities, and their anti-cancer, vision protection, aging prevention, skin beauty pharmacological, and nutraceutical effects. Especially, recent systematic reviews and meta-analyses indicate their value, safety, and efficacy in the prevention, adjuvant therapy, and management of cardiometabolic disease. Here, we summarize their research progress from the aspects of chemical structure, biosynthetic pathways, distribution, extraction and separation, coloration, efficacy, and potential. The comparison between them might provide a reference for their development and efficient utilization. However, more large-sample-size randomized controlled trials and high-quality studies are needed to firmly establish their clinical efficacy.

Novel PD-L1-Targeted Phenyl-Pyrazolone Derivatives with Antioxidant Properties.

Orally-active anticancer small molecules targeting the PD-1/PD-L1 immune checkpoint are actively searched. Phenyl-pyrazolone derivatives with a high affinity for PD-L1 have been designed and characterized. In addition, the phenyl-pyrazolone unit acts as a scavenger of oxygen free radicals, providing antioxidant effects. The mechanism is known for the drug edaravone (1) which is also an aldehyde-reactive molecule. The present study reports the synthesis and functional characterization of new molecules (2-5) with an improved anti-PD-L1 activity. The leading fluorinated molecule 5 emerges as a potent checkpoint inhibitor, avidly binding to PD-L1, inducing its dimerization, blocking PD-1/PD-L1 signaling mediated by phosphatase SHP-2 and reactivating the proliferation of CTLL-2 cells in the presence of PD-L1. In parallel, the compound maintains a significant antioxidant activity, characterized using electron paramagnetic resonance (EPR)-based free radical scavenging assays with the probes DPPH and DMPO. The aldehyde reactivity of the molecules was investigated using 4-hydroxynonenal (4-HNE), which is a major lipid peroxidation product. The formation of drug-HNE adducts, monitored by high resolution mass spectrometry (HRMS), was clearly identified and compared for each compound. The study leads to the selection of compound 5 and the dichlorophenyl-pyrazolone unit as a scaffold for the design of small molecule PD-L1 inhibitors endowed with antioxidant properties.

Sanhua decoction: Current understanding of a traditional herbal recipe for stroke.

Both thrombolytic and endovascular therapies are optimal treatment options for patients with acute ischemic stroke, but only less than half of these patients can benefit from these treatments. Traditional Chinese medicine has a long history of successfully managing ischemic stroke using both herbal and physical therapeutics. Among herbal recipes, Sanhua decoction (SHD) is one of the classical prescriptions for ischemic stroke. The present review aimed to summarize evidence from both clinical and basic research to demonstrate its efficacy in managing ischemic stroke and the potential mechanisms underlying its therapeutic effects, which will provide evidence on the therapeutic effect of this herbal recipe and guide future studies on this recipe. SHD is composed of four herbs, Rheum palmatum L. [Polygonaceae], Magnolia officinalis Rehder & E.H.Wilson [Magnoliaceae], Citrus × aurantium L. [Rutaceae], Hansenia weberbaueriana (Fedde ex H.Wolff) Pimenov & Kljuykov [Apiaceae]. We found that the majority of clinical studies on SHD are case reports and they showed positive therapeutic effect of SHD on both acute and chronic ischemic stroke. There are over 40 bioactive compounds identified in SHD, but few experimental studies have examined their individual molecular mechanisms. As an extract of SHD, it improves neurological functions through suppressing inflammation, protecting the blood brain barrier from degradation, restoring the number of neural stem cells, inhibiting apoptosis and brain edema, scavenging oxygen free radicals, and regulating the brain-gut axis. These will lay the theoretical foundation for future studies on this prescription and its clinical application. Future research may need to confirm its clinical efficacy in large-scale clinical trials and to disentangle its bioactive compounds and their potential mechanisms.

Polyphenols Mediate Neuroprotection in Cerebral Ischemic Stroke—An Update

Stroke is one of the main causes of mortality and disability, and it is due to be included in monetary implications on wellbeing frameworks around the world. Ischemic stroke is caused by interference in cerebral blood flow, leading to a deficit in the supply of oxygen to the affected region. It accounts for nearly 80-85% of all cases of stroke. Oxidative stress has a significant impact on the pathophysiologic cascade in brain damage leading to stroke. In the acute phase, oxidative stress mediates severe toxicity, and it initiates and contributes to late-stage apoptosis and inflammation. Oxidative stress conditions occur when the antioxidant defense in the body is unable to counteract the production and aggregation of reactive oxygen species (ROS). The previous literature has shown that phytochemicals and other natural products not only scavenge oxygen free radicals but also improve the expressions of cellular antioxidant enzymes and molecules. Consequently, these products protect against ROS-mediated cellular injury. This review aims to give an overview of the most relevant data reported in the literature on polyphenolic compounds, namely, gallic acid, resveratrol, quercetin, kaempferol, mangiferin, epigallocatechin, and pinocembrin, in terms of their antioxidant effects and potential protective activity against ischemic stroke.

Epigallocatechin-3-gallate enhances sterilization of irradiated whole bovine casein and protects alpha and beta caseins from gamma radiation: Depending on polyphenol/protein ratio

The increasing use of milk proteins in medicine requires developing effective processes for sterilizing milk formulations. It was found that epigallocatechin-3-gallate (EGCG) reduce bacterial flora in total casein, depending on the concentration of EGCG. Furthermore, the combination of EGCG and gamma radiation reduced the dose D10 to 0.88 kGy and 0.63 kGy with 250 and 500 μM EGCG, respectively, instead 2.01 kGy without EGCG. The effect of gamma radiation on alpha- and beta-casein in the absence and presence of epigallocatechin-3-gallate (EGCG) was also examined. Milk proteins in solution were exposed to different doses of gamma radiation with and without EGCG. Unirradiated and irradiated samples were analyzed by SDS-PAGE and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-MS). The results suggest that EGCG (10 μM) protects α- and β-casein from degradation and subsequent polymerization, possibly by scavenging oxygen and protein free radicals generated during irradiation. Although it was used a ratio of polyphenols to the protein higher for alpha-casein (1/5) than beta-casein (1/10), beta-casein was better protected with EGCG. According to previous studies, this result could be explained by differences in primary protein structure and its interaction with EGCG. The interaction of EGCG with casein is hydrophobic rather than hydrophilic, so the interaction with β-casein is more robust than with α-casein. In conclusion, the low EGCG concentrations enhance the sterilization of total casein by gamma radiation. It provided an excellent radioprotection of α- and β-casein, especially β-casein, against degradation and aggregation.

Marine halophyte derived polyphenols inhibit glioma cell growth through mitogen-activated protein kinase signaling pathway

Plants that are pharmacologically significant require intensive phytochemical characterization for bioactive profiling of the compounds, which has enabled their safe use in ayurvedic medicine. The present study is focused on the phytochemical analyses, quantitative estimation and profiling of secondary metabolites of leaf extract, as well as the antioxidant and cytotoxic activity of the potent halophytes such as Avicennia marina, Ceriops tagal, Ipomoea pes-caprae, and Sonneratia apetala. The in vitro antioxidant property was investigated using DPPH, ferric reducing antioxidant capacity (FRAP) assay. Bioactive compounds such as phenols, flavonoids, saponin and alkaloids were quantitatively estimated from the extracts of A.marina, C.tagal, I.pes-capra and S.apetala, which possessed higher phenol content than the other studied halophytes. The extracts at 200 µg/ml revealed higher antioxidant activity than the standard ascorbic acid and it functions as a powerful oxygen free radical scavenger with 77.37%, 75.35% and 72.84% for S.apetala, I.pes-caprae and C.tagal respectively and with least IC50 for I.pes-caprae (11.95 µg/ml) followed by C.tagal (49.94 µg/ml). Cell viability and anti-proliferative activity of different polyphenolic fractions of C.tagal (CT1 and CT2) and I.pes-caprae fraction (IP) against LN229, SNB19 revealed Ipomoea as the promising anti-cytotoxic fraction. IP-derived polyphenols was further subjected to apoptosis, migration assay, ROS and caspase − 3 and − 7 to elucidate its potentiality as a therapeutic drug. IP-polyphenols was found to have higher percentage of inhibition than the CT1 and CT2 polyphenols of C.tagal on comparison with TMZ. All the above-mentioned in-vitro analysis further validated the ability of IP-polyphenols inducing cell death via ROS-mediated caspase dependent pathway. Further, proteomic and phospho-proteomic analysis revealed the potential role of IP-polyphenols in the regulation of cell proliferation through MMK3, p53, p70 S6 kinase and RSK1 proteins involved in mitogen-activated protein kinase signaling pathway. Our analysis confirmed the promising role of I.pes-caprae derived polyphenols as an anti-metastatic compound against GBM cells.

Anti-Inflammatory Effect of Dendrobium Huoshanense Polysaccharides on Carrageenan-Induced Air Pouch Synovitis in Mice

Objective: The purpose was to observe the anti-inflammatory effects of Dendrobium huoshanense polysaccharides (DHPs) on carrageenan-induced sterile air pouch synovitis. Materials and Methods: A total of 30 Institute of Cancer Research (ICR) mice were randomly and equally assigned to the control, carrageenan-induced air pouch synovitis model (model), and carrageenan-induced air pouch synovitis model + DHP (200 mg/kg of body weight) (model + DHP) groups. Mice in the model + DHP group were intragastrically administered 200 mg/kg BW of DHP solution daily for 10 days. Mice in the control and model groups were intragastrically administered the same amount of distilled water. Two hours after intragastric administration on day 10, 1 mL of a 1% carrageenan solution in a sterile 0.9% saline solution was injected into the air pouch of mice in the model and model + DHP groups. Six hours later, the mice were sacrificed and 4 mL of ice-cold sterile 0.9% saline solution was injected into the air pouch to fully wash its inner wall. The lavage fluid was collected to observe the color and turbidity of the lavage fluid, as well as the appearance of the backside of the air pouch. The exudate volume, total number of leukocytes, protein content, levels of malondialdehyde (MDA), interleukin-1b (IL-1β), and tumor necrosis factor-alpha (TNF-α), and total superoxide dismutase (T-SOD) activity of the lavage fluid were analyzed. Results: The results showed that pretreatment with DHPs reduced the carrageenan-induced exudate volume (P < 0.01), total leukocytes (P < 0.05), and protein content (P < 0.01) in the air pouch lavage fluid. Furthermore, mice in the model + DHP group had significantly higher (P < 0.01) T-SOD activity and lower MDA content (P < 0.05), IL-1β (P < 0.05), and TNF-α (P < 0.01) levels in the air pouch lavage fluid compared with the model group. Conclusion: It is concluded that DHPs partially alleviated carrageenan-induced sterile inflammation, and its mechanism may be related to reducing exudation and scavenging oxygen-free radicals, inhibiting lipid peroxidation, and reducing the level of the proinflammatory factors, such as IL-1β and TNF-α.

New technology for large preparation of a series of bioactive polyphenols from by-products of vinification

Grape pomaces or vinification by-products are abundant and rich in polyphenols, particularly proanthocyanidins. During the last three decades, grape and wine polyphenols, particularly catechins (CATs) and oligomeric proanthocyanidins (OPCs) have attracted considerable attention of the international scientific community, due essentially to their potential health-beneficial effects, related to their protective action towards cardiovascular disease and the oxygen free radical scavenger capacity. Such phenolic compounds have been proved to be the key components responsible for the health-beneficial effects of red wine. Furthermore, although the most widely recognized antioxidants are Vitamins A, C, and E, scientific research has shown that OPCs are likely the most powerful antioxidants known. Although various OPCs have been available in the market, they are generally very expensive due to the high cost of their production. As a consequence, the development of efficient methods for large-scale preparation of these bioactive compounds have still a challenging task for scientists. In this communication, we will present a new and efficient technology for large preparation of bioactive polyphenols from vinification by-products (grape seed and grape skin). On one hand, polymeric proanthocyanidins were transformed into a series of low- molecule-weight bioactive compounds using various degradation methods. On the other hand, High-Speed Countcurrent Chromatography (HSCCC), as a relative new separation technology for natural product preparation, was applied to large and efficient isolation of these bioactive compounds.

Mannitol for prevention of acute kidney injury after liver transplantation: a randomized controlled trial

BackgroundAcute kidney injury (AKI) is a common complication after liver transplantation, which is associated with increased morbidity and mortality. Therefore, this study investigated mannitol as an oxygen-free radical scavenger and its role in the prevention of early AKI after living donor liver transplantation (LDLT).MethodsA total of 84 adult patients who underwent LDLT were randomly assigned to two equal groups: the M group, where patients received 1 g/kg mannitol 20%, or the S group, where patients received an equal volume of saline. The primary outcome was the incidence of early AKI, defined as a 0.3 mg/dl increase in the serum creatinine 48 h postoperatively. Laboratory assessments of the graft and creatinine were recorded until 3 months after transplantation besides the post-reperfusion syndrome and the intraoperative hemodynamic measurements.ResultsThe AKI incidence was comparable between groups (relative risk ratio of 1.285, 95% CI 0.598–2.759, P = 0.518). Moreover, AKI stages and serum creatinine 3 months after transplantation, P = 0.23 and P = 0.25, respectively. The incidence of the post-reperfusion syndrome was comparable in both groups, 29/39 (74.4%) and 31/41 (75.6%) in M and S groups, respectively, P = 0.897. The intraoperative hemodynamic parameters showed no significant difference between groups using the area under the curve.ConclusionThe current LDLT recipient sample was insufficient to demonstrate that pre-reperfusion 1 g/kg mannitol infusion would reduce the risk of early AKI or post-reperfusion syndrome.Clinical trial registration numberPan African Clinical Trials Registry (PACTR202203622900599); https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=21511.

Transcriptome and Metabolome Analysis of a Late-Senescent Vegetable Soybean during Seed Development Provides New Insights into Degradation of Chlorophyll.

(1) Background: Senescence represents the final stage of plant growth and development, which transfers nutrients to growing seeds and directly affects the yield and quality of crops. However, little is known about chlorophyll degradation in developing and maturing seeds, in contrast to leaf senescence; (2) Methods: RNA-Seq was used to analyze the differentially expressed genes of different late-senescent germplasms. A widely untargeted metabolic analysis was used to analyze differential metabolites. In addition, qRT-PCR was conducted to detect gene expression levels; (3) Results: Transcriptome analysis revealed that ZX12 seeds have a higher expression level of the chlorophyll synthesis genes in the early stage of maturity, compared with ZX4, and have a lower expression level of chlorophyll degradation genes in the late stage of maturity. Flavonoids were the primary differential metabolites, and ZX12 contains the unique and highest expression of three types of metabolites, including farrerol-7-O-glucoside, cyanidin-3-o-(6'-o-feruloyl) glucoside, and kaempferide-3-o-(6'-malonyl) glucoside. Among them, farrerol-7-O-glucoside and cyanidin-3-o-(6'-o-feruloyl) glucoside are flavonoid derivatives containing mono and dihydroxy-B-ring chemical structures, respectively; and (4) Conclusions: It is speculated that the two metabolites can slow down the degradation process of chlorophyll by scavenging oxygen-free radicals in the chloroplast.