Methane Dicarboxylic Aldehyde Research Articles

The Effect of Supplementing Tea Polyphenols in Diet of Laying Hens on Yolk Cholesterol Content and Production Performance

ABSTRACT This study was conducted to evaluate the influence of supplementing tea polyphenols (TP) in diet of laying hens on yolk cholesterol content and production performance. A total of 1800 Lohmann laying hens aged 48 weeks were randomly allocated to 6 groups. Each group consisted of 6 replicates with 50 layers. The feeding experiment was 4 weeks including one-week acclimatization. Layers fed basal diet supplemented with 0, 150, 200, 250, 300 and 350 mg TP/kg diet, respectively. The results showed that average daily feed intake (ADFI), feed conversion ratio (FCR), average egg weight (AEW), laying rate and the indicators of egg quality were not significantly affected by the diet supplemented with 300 mg/kg TP (p>0.05). However, yolk cholesterol content decreased by increasing TP concentration (p<0.01), with 18.06% reduction in layers fed diet supplemented with 300 mg TP/kg. Also, the diet supplemented with 300 mg/kg TP significantly decreased plasma triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) level (p<0.05). The activity of serum glutathione peroxidase (GSH-Px) was enhanced by increasing TP concentration, while the content of serum methane dicarboxylic aldehyde (MDA) was decreased by increasing TP concentration. The highest activity of GSH-Px and the lowest serum MDA content were both determined in 300 mg/kg TP group (p<0.01). In conclusion, this study suggests that the addition of 300 mg TP/kg basal diet had no negative effect on the production performance laying hens, yet decreased the egg yolk cholesterol content and enhanced the antioxidant capacity of laying hens at the same time.

Hepcidin Promoted Ferroptosis through Iron Metabolism which Is Associated with DMT1 Signaling Activation in Early Brain Injury following Subarachnoid Hemorrhage.

Iron metabolism disturbances play an important role in early brain injury (EBI) after subarachnoid hemorrhage (SAH), and hepcidin largely influences iron metabolism. Importantly, iron metabolism may be associated with ferroptosis, recently a nonapoptotic iron-dependent form of cell death that may have a great impact on brain injury after SAH. We investigated hepcidin on iron metabolism and ferroptosis involving divalent metal transporter 1 (DMT1), and ferroportin-1 (FPN1) in a rat model of SAH. Male Sprague-Dawley rats were subjected to the endovascular perforation to induce SAH, and treated with heparin (inhibitor of hepcidin), or oncostatin M (OSM, inducer of hepcidin), or ebselen (inhibitor of DMT1) by intracerebroventricular injections. Hepcidin, DMT1, FPN1 and glutathione peroxidase 4 (GPX4), were detected by western blot and immunofluorescence. Iron metabolism was detected through Perl's iron staining and iron content assay. Ferroptosis, the ROS production, lipid peroxidation (LPO) was evaluated by monitoring methane dicarboxylic aldehyde (MDA), glutathione (GSH), glutathione peroxidase 4 (GPX4) activity, and transmission electron microscopy. Neurological deficit scores, Evans blue staining and brain water content were also determined to detect EBI 72 h after SAH. Our results showed that inhibition of DMT1 by ebselen could suppress iron accumulation and lipid peroxidation, and thereby alleviate ferroptosis and EBI in SAH rats. Heparin downregulated the expression of hepcidin and DMT1, increased FPN1, and exerted protective effects that were equivalent to those of ebselen on ferroptosis and EBI. In addition, OSM increased the expression of hepcidin and DMT1, decreased FPN1, and aggravated ferroptosis and EBI, while the effect on ferroptosis was reversed by ebselen. Therefore, the study revealed that hepcidin could regulate iron metabolism and contribute to ferroptosis via DMT1 signaling activation in rats with EBI after SAH.

Application of pimaricin against potato white mould

AbstractThe objective of this study was to evaluate the inhibitory effect of pimaricin against Sclerotinia sclerotiorum, the causal agent of potato white mould. Field trials in 2016 and 2017 were conducted in Bahar and Lalehjin, Hamedan, Iran. Pimaricin at the concentration of 200 mg/L was able to reduce the disease incidence during field trials. The concentration of 2.5 mg/L completely inhibited the radial growth and sclerogenesis of three tested isolates of S. sclerotiorum. In addition, pimaricin at the concentration of 2.5 mg/L reduced the carpogenic germination of sclerotia in isolates 1, 2 and 3 by 100%, 88.1% and 73.9%, respectively. Treatment with pimaricin at the concentration of 2 mg/L for 160 min enhanced relative conductivity of S. sclerotiorum mycelia up to 100%. The concentration of 2 mg/L increased the cell membrane permeability of mycelia more than the concentration of 1 mg/L over 160 min. Moreover, exposure to pimaricin at the concentration of 2 mg/L for 12 hr increased carbohydrate leakage of the pathogen mycelia up to 73%. Pimaricin at the concentration of 2 mg/L markedly increased the content of methane dicarboxylic aldehyde (MDA) over time, and the highest content of MDA was recorded as 5.9 µmol/kg FW after 20 hr. The percentage of catalase activity was reduced in the pathogen mycelia by 4.1 U g−1 min−1 after exposure to pimaricin at the concentration of 2 mg/L for 20 min.

The Protective Effects of Protein-Enriched Fraction from Housefly (Musca domestica) against Aged-Related Brain Aging.

The Musca domestica larvae are well known for its multifunctions and great nutritional value. The present study aimed at investigating the beneficial effect of Musca domestica larvae extract (Mde) against memory impairment, structural damage and oxidative stress in aged rats. Twenty-month-old rats were gavaged with Mde for 2 mo. Morris Water Maze test indicated Mde prevented aging-induced spatial learning and memory dysfunction in the aged rats. Mde supply was also found to attenuate age-associated changes of brain histology that observed by light microscopy and transmission electron microscopy. Moreover, the increase of antioxidant capacity, glutathione peroxidase (GPx) activity, superoxide dismutase (SOD) activity, as well as the decreased methane dicarboxylic aldehyde (MDA) levels, were consistent with these results. Hence, we propose that oral administration of Mde could improve memory impairment via antioxidant action, and Mde has the potential to act as an excellent food supplement or medicine for the attenuation of brain aging.

Protective effect of lutein on oxidative stress damage caused by acute PM2.5 exposure in rats

Particulate matter (PM) is the sum of organic and inorganic substances suspended in air. Particles with a diameter equal to or smaller than 2.5 μm (PM2.5) can induce extensive oxidative stress damage in lung tissues. Lutein can prevent oxidative stress and the production of pro-inflammatory cytokines. However, its role in lung injury induced by PM2.5 is still unclear. This study used lutein to intervene in lung injury induced by PM2.5 in rats to confirm the protective function of lutein in PM2.5- induced lung injury. A total of 80 rats were divided into five groups according to body weight (bw). Rats in the blank control group and the PM2.5 exposure group were treated with normal saline. The low-, medium-, and high-dose lutein groups were treated with 12.5, 25.0, and 50.0 mg/kg·bw lutein continuously for 28 days. In addition, on days 22-28, 10 mg/kg PM2.5 was introduced by intratracheal instillation into the PM2.5 exposure group and all lutein dose groups continuously for 7 days to establish PM2.5 injury models. Lung tissues were collected and subjected to hematoxylin-eosin (HE) staining to observe histomorphological changes. Bronchoalveolar lavage fluid (BALF) was collected to detect the expression of cell damage indicators including lactate dehydrogenase (LDH), acidic phosphatase (ACP), alkaline phosphatase (AKP), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α). In addition, the levels of serum oxidative stress indicators in rats, including methane dicarboxylic aldehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), nitric oxide synthase (NOS), and 8-hydroxy-2'-deoxyguanosine (8-OHdG), as well as cytokines, including IL-6, IL-8, and TNF-α, were analyzed. Lung tissues of rats after PM2.5 exposure exhibited different degrees of pathological changes. In serum, oxidative damage indicators MDA, NOS, and 8-OHdG and inflammatory cytokines IL-6, IL-8, and TNF-α significantly increased whereas GSH levels significantly decreased (P<0.05). In BALF, cell damage indicators ACP and AKP and inflammatory cytokines IL-6, IL-8, and TNF-α all increased (P<0.05). After lutein intervention, oxidative damage and cellular inflammatory cytokines in serum and BALF all significantly decreased (P<0.05) whereas serum GSH levels increased (P<0.05). PM2.5 caused significant oxidative damage and inflammatory injury in rat lungs. Lutein alleviated these effects, playing a protective role in lung tissues.

Untargeted Metabolomic Analysis of the Effects and Mechanism of Nuciferine Treatment on Rats With Nonalcoholic Fatty Liver Disease.

Metabolomic analysis has been used to characterize the effects and mechanisms of drugs for nonalcoholic fatty liver disease (NAFLD) at the metabolic level. Nuciferine is an active component derived from folium nelumbinis and has been demonstrated to have beneficial effects on a high-fat diet (HFD) induced hepatic steatosis model. However, the effect of the altered metabolites of nuciferine on NAFLD has not yet been elucidated. In this study, we established a NAFLD rat model using HFD and treated with nuciferine. The lipid content levels, pro-inflammatory cytokines, and oxidative stress were investigated to access the therapeutic effects of nuciferine. Additionally, the metabolic regulatory mechanisms of nuciferine on NAFLD were analyzed using untargeted metabolomics. Gene expression of the key enzymes related to the changed metabolic pathways following nuciferine intervention was also investigated. The results showed that nuciferine treatment significantly reduced the body weight, levels of lipids, and liver enzymes in the blood and improved the hepatic steatosis in the NAFLD rat model. Nuciferine treatment also increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased the levels of methane dicarboxylic aldehyde (MDA) in the liver. Nuciferine treatment decreased the serum levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-α) and upregulated the gene expression of IL-6, IL-1β, and TNF-α in the liver. Metabolomic analysis indicated a metabolism disorder in the NAFLD rat model reflected in a dysfunction of the glycerophospholipid, linoleic acid, alpha-linolenic acid, arginine and proline metabolism. Conversely, treatment with nuciferine improved the metabolic disorder in the NAFLD rat model. Nuciferine treatment also regulated the gene expression of key enzymes related to the glycerophospholipid, linoleic acid, and alpha-linolenic acid metabolism pathways in the liver. In conclusion, our study demonstrated an amelioration of the metabolic disorders following nuciferine treatment in NAFLD rat model. Our study contributes to the understanding of the effects and mechanisms of drugs for complex diseases using metabolomic analysis and experimental approaches.

Inhibitory effect of natamycin against carrot white mold caused by Sclerotinia sclerotiorum

This study was conducted to evaluate inhibitory effect of natamycin against three isolates of Sclerotinia sclerotiorum, the causal agent of carrot white mold in postharvest phase. The results showed that natamycin was able to markedly decrease radial growth and sclerogenesis of three isolates of the pathogen. In addition, natamycin significantly reduced myceliogenic and carpogenic germinations of sclerotia in three isolates. There was a clear positive correlation between natamycin concentration and efficacy against mycelial growth, sclerogenesis, and sclerotia germinations. Application of natamycin on carrot roots 2.5 h before inoculation with the pathogen markedly reduced white mold incidence. The treatment with natamycin enhanced relative conductivity of S. sclerotiorum mycelia over time compared with control. The concentration 2 mg L−1 increased the cell membrane permeability of mycelia more than the concentration 1 mg L−1 over 160 min. Moreover, an increase of carbohydrate leakage was observed in the pathogen mycelia incubated with natamycin. The content of methane dicarboxylic aldehyde (MDA) markedly increased at 5 h and the highest MDA content was observed after 20 h. Due to exposure to natamycin, a decrease percentage of catalase activity was observed in pathogen mycelia.

Inhibitory effect of sirolimus against white rot of Brassica juncea var. tumida

White rot, caused by Sclerotinia sclerotiorum (Lib.) de Bary, has recently become a serious threat to tuber mustard (Brassica juncea var. tumida) cultivation in Hangzhou and other mustard growing parts of Zhejiang province, China. This study was conducted to evaluate the inhibitory effect of sirolimus, a natural macrolide compound, against white rot of mustard tuber caused by S. sclerotiorum in vitro and in vivo. The results showed that sirolimus was able to reduce the mycelial growth, sclerogenesis as well as myceliogenic and carpogenic germinations of three isolates of the pathogen. Application of sirolimus markedly increased activity of β-N-acetyl hexosaminidase, endochitinase and β -1,3-glucanase in plant leaves. Moreover, a significant increase was observed in the level of polyphenoloxidase and peroxidase in plant leaves two and four days after application of sirolimus. The results of in vitro tests showed that sirolimus at the concentration of 100 nM completely inhibited disease severity. The treatment with sirolimus enhanced relative conductivity of S. sclerotiorum mycelia over time compared with control. An increase of carbohydrate leakage was observed in the pathogen mycelia incubated with sirolimus. The content of methane dicarboxylic aldehyde (MDA) markedly increased at 5 h and the highest MDA content was observed after 20 h. Due to exposure to sirolimus, a decrease percentage of catalase activity was observed in pathogen mycelia. In conclusion, this study showed that sirolimus can be considered as an effective substance against white rot of tuber mustard caused by S. sclerotiorum.

Inhibitory efficacy of rapamycin against potato white mold

The inhibitory efficacy of rapamycin against potato white mold caused by Sclerotinia sclerotiorum was studied in vitro and under field conditions. The results showed that rapamycin was able to reduce radial growth, sclerogenesis as well as myceliogenic and carpogenic germinations of three isolates of the pathogen. Application of rapamycin markedly increased activity of chitin 1,4-β-chitobiosidase, endochitinase and β-1,3-glucanase in plant leaves. The treatment with rapamycin increased relative conductivity of S. sclerotiorum mycelia in different periods of time compared with the control. An increase in carbohydrate leakage was observed in the pathogen mycelia incubated with rapamycin. The content of methane dicarboxylic aldehyde (MDA) markedly increased at 5 h and the highest MDA content was observed after 20 h. Due to exposure to rapamycin, a decrease percentage of catalase activity was observed in pathogen mycelia. The results of field trials carried out over cropping seasons of 2017 and 2018 at Bahar and Lalehjin counties in Hamedan province, Iran, showed that application of rapamycin at the concentration of 100 nM has potential to markedly reduce disease severity of potato white mold as effectively as application of dichloran at 100% of the advised rate.

Optimization and mechanism of postponing aging of polysaccharides from Chinese herbal medicine formula.

To study the extraction technology of polysaccharides (AAP) from Chinese herbal medicine formula and its mechanism of delaying aging. First, L9(3)4 orthogonal test was used to optimize the optimal enzyme-assisted extraction parameters of polysaccharides. And the anti-aging effects was evaluated by detecting mitochondrial function, protein, DNA, adhesion molecules and cell cycle in aging rats. The optimal extraction process parameters were the cellulase concentration of 1.5%, the pH at 5, the enzyme temperature at 50°C and the extraction time of 180min. The anti-aging results showed that AAP can effectively increase the activities of malate dehydrogenase, succinate dehydrogenase and superoxide dismutase. It also can decrease the activity of monoamine oxidase and methane dicarboxylic aldehyde levels in the brain tissue. Meanwhile, the polysaccharides enhanced telomerase activity while reduced p16 protein expression of the brain mitochondria. In addition, the polysaccharides continued to improve heart damage and significantly lessen mitochondrial DNA concentrations. For a certain period of time, it also enhanced the activity of superoxide dismutase, reduced glutathione, glutathione peroxidase and decreased protein carbonyl and methane dicarboxylic aldehyde content of kidney in D-galactose-induced aging rats. Furthermore, the polysaccharides restored the number of cells in the peripheral blood lines and BMNC through inhibiting the drop of the number of red blood cells, white blood cells, platelets in the peripheral blood and bone marrow mononuclear cell of the aging rats. At the same time, AAP accelerated G1 phase cell to enter S phase in cell cycle in aging rats. Our research suggests that the polysaccharides may be a potential anti-aging agent and can be further developed as a functional food or new drug to delay aging or treat aging-related diseases.

The algal polysaccharide ulvan suppresses growth of hepatoma cells

AbstractTreatment for tumors depends on host immune system. The antitumor and immunoregulatory activities of Ulva lactuca polysaccharide (ULP) were evaluated in H22 tumor‐bearing mice and cyclophosphamide‐induced immunosuppressed mice, respectively. The structural properties of ULP were identified through multi‐angle laser light scattering, high‐performance liquid chromatography, Fourier‐transformed infrared, and nuclear magnetic resonance. It was composed of α‐D‐Manp‐(1→, →2,4)‐β‐L‐Rhap‐(1→, β‐D‐GlcpA‐(1→, β‐GalpA‐(1→, →2,4)‐α‐D‐Glcp‐(1→, and →6)‐β‐D‐Galp‐(1→ with the molecular weight of 1.46 × 105 Da. Its antioxidant, anti‐inflammatory, and antitumor effects were determined. Liver and tumor tissues were collected for histopathological, immunohistochemical, and western blotting analysis. ULP showed the great tumor growth inhibition of 74.41% compared with cyclophosphamide, which has side effects on immune system. ULP enhanced the expression of p53 to inhibit tumorigenesis, promoted the activation of IKKα, and inhibited the activation of p65 within the NF‐κB pathway. ULP inhibited the tumor growth through downregulating the expressions of PI3K/Akt and mTOR, and promoting BAX/Bcl‐2 ratio. The inhibition of TRAF2/TNF‐α and CD31/VEGF achieved a direct killing effect on tumor cells and inhibited tumor proliferation by inhibiting angiogenesis, respectively. Moreover, ULP increased the levels of immunoglobulin M and total superoxide dismutase, decreased the level of methane dicarboxylic aldehyde, and inhibited the activation of PI3K/AKT/mTOR/p70S6k pathways. The results showed that ULP exhibited pronounced antitumor activity and immunoregulatory effect.

Autophagy Triggered by Oxidative Stress Appears to Be Mediated by the AKT/mTOR Signaling Pathway in the Liver of Sleep-Deprived Rats.

Sleep deprivation adversely affects the digestive system. Multiple studies have suggested sleep deprivation and oxidative stress are closely related. Autophagy can be triggered by oxidative stress as a self-defense strategy to promote survival. In this study, we investigated the effects of sleep deprivation on liver functions, oxidative stress, and concomitant hepatocyte autophagy, as well as the associated pathways. Enzymatic and nonenzymatic biochemical markers in the serum were used to assess hepatic function and damage. To evaluate the occurrence of autophagy, expression of autophagy-related proteins was tested and autophagosomes were labeled. Additionally, methane dicarboxylic aldehyde (MDA), antioxidant enzymes, and the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway were analyzed using chemical methods and a Western blot. Serum alanine transaminase, aspartate aminotransferase, and alkaline phosphatase increased in sleep-deprived rats. Total protein and albumin abundance was also abnormal. Sleep deprivation induced histopathological changes in the liver. The superoxide dismutase level decreased significantly in the liver of sleep-deprived rats. In contrast, the MDA content increased in the sleep deprivation group. Moreover, the microtubule-associated protein 1 light chain 3 beta (LC3B) II/I ratio and Beclin I content increased considerably in the sleep-deprived rats, while p62 levels decreased. Sleep deprivation apparently inhibited the AKT/mTOR signaling pathway. We conclude that sleep deprivation can induce oxidative stress and ultimately cause liver injury. Autophagy triggered by oxidative stress appears to be mediated by the AKT/mTOR pathway and plays a role in relieving oxidative stress caused by sleep deprivation.

Antidepression and Prokinetic Effects of Paeoniflorin on Rats in the Forced Swimming Test via Polypharmacology.

Paeoniflorin, an organic compound extracted from the roots of the white peony (Paeonia lactiflora) plant, has previously been shown to exert antidepression and prokinetic effects. The traditional Chinese prescription Si-Ni-San, of which paeoniflorin is a constituent, is often used in treating depression and functional gastrointestinal disorders. The effectiveness of Si-Ni-San has been shown to be less effective in a paeoniflorin-deleted form. The present study further investigates whether paeoniflorin alone is as effective as herbal prescriptions in which the compound is a constituent, specifically any antidepressive and prokinetic effect on rats subjected to a forced swimming test (FST). The FST was used to establish the depression model. Sprague-Dawley rats were administrated with 10 mg/kg paeoniflorin by gastrogavage three times before the behavioral test and gastrointestinal motility tests, respectively. In antidepression studies, fluoxetine was used as the positive control. In order to determine the effect of paeoniflorin on the gastrointestinal movement, mosapride was used as the positive control. Plasma and hippocampus monoamine, hypothalamic-pituitary-adrenal axis, plasma brain-derived neurotrophic factor (BDNF), superoxide dismutase (SOD), methane dicarboxylic aldehyde (MDA), ghrelin, motilin, and hippocampus nitric oxide (NO) were assessed using an enzyme-linked immunosorbent assay (ELISA). Gastrointestinal (GI) motility was measured in vivo and in vitro. Rats subjected to FST showed decreased gastric emptying and intestinal transit in vivo, decreased plasma and hippocampus 5-hydroxytryptamine, norepinephrine, dopamine, ghrelin, motilin, and reduced plasma BDNF and SOD as well as increased plasma and hippocampus corticotropin-releasing hormone, adrenocorticotropic hormone, corticosterone, plasma MDA, and hippocampus NO. Paeoniflorin reversed these symptoms in a similar manner to fluoxetine and mosapride, respectively. In vitro, paeoniflorin can stimulate the jejunal contract of healthy rats dose-dependently. The results suggest that paeoniflorin can simultaneously exert antidepression and prokinetic effects via polypharmacology.

Study on the Material Basis of Neuroprotection of Myrica rubra Bark.

Background: Increasing attention has been given to the search for neuroprotective ingredients from natural plants. Myrica rubra bark (MRB) has been used in traditional oriental medicine for over thousand years and has potential neuroprotection. Methods and Results: Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was used to identify the compounds in MRB extract, and the MTT assay was performed to evaluate the neuroprotection of six major compounds from MRB against glutamate-induced damage in PC12 cells. The result displayed nineteen compounds were identified, and myricitrin and myricanol 11-sulfate were shown to have neuroprotection, which prevented cell apoptosis through alleviating oxidative stress by reducing the levels of reactive oxygen species and methane dicarboxylic aldehyde, as well as by enhancing the activities of superoxide dismutase. Conclusions: Several active compounds from MRB may offer neuroprotection and have the potential for the development of new drugs against central nervous system diseases.

MicroRNA-489 promotes cardiomyocyte apoptosis induced by myocardial ischemia-reperfusion injury through inhibiting SPIN1.

To investigate whether microRNA-489 could promote cardiomyocyte apoptosis through targeting inhibition of SPIN1, thus participating in the development of myocardial ischemia-reperfusion injury. MicroRNA-489 expression in H9c2 cells induced with hypoxia/reoxygenation (H/R) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). With microRNA-489 overexpression in H/R H9c2 cells, activities of lactate dehydrogenase (LDH), methane dicarboxylic aldehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) were detected using relative commercial kits, respectively. The regulatory effect of microRNA-489 on the proliferation and apoptosis of H/R H9c2 cells was assessed through cell counting kit-8 (CCK-8) assay and flow cytometry (FCM), respectively. Through conducting a dual-luciferase reporter gene assay, we evaluated the binding condition between microRNA-489 and SPIN1. Protein expressions of apoptotic genes in H/R H9c2 cells with microRNA-489 overexpression were determined by Western blot. Finally, the regulatory role of microRNA-489 in PI3K/AKT pathway was detected through Western blot. QRT-PCR data showed that microRNA-489 was highly expressed in H/R H9c2 cells than those in normoxic control. Overexpression of microRNA-489 in H/R H9c2 cells increased the activities of LDH, MDA and GSH-PX, while decreased the activities of SOD. MicroRNA-489 overexpression markedly inhibited the proliferative rate but accelerated apoptosis of H/R H9c2 cells. Western blot results indicated that protein expressions of pro-apoptotic genes Bax and cytochrome C upregulated, whereas anti-apoptotic gene Bcl-2 downregulated after overexpression of microRNA-489 in H/R H9c2 cells. We confirmed that microRNA-489 could target to SPIN1 and inhibit its expression. After overexpression of microRNA-489 in H/R H9c2 cells, PI3K/AKT pathway was inhibited, which was further reversed by PI3K/AKT pathway agonist SC79. Besides, SC79 treatment also reversed the regulatory effect of overexpressed microRNA-489 on cellular behaviors of H/R H9c2 cells. MicroRNA-489 inhibits the proliferation and accelerates apoptosis of cardiomyocytes after MIRI by targeting inhibition of SPIN1 via inactivating PI3K/AKT pathway. MicroRNA-489 may be a potential therapeutic target for MIRI.

Simvastatin Alleviates Intestinal Ischemia/Reperfusion Injury by Modulating Omi/HtrA2 Signaling Pathways

PurposeThe objective of this research was to survey the therapeutic action of simvastatin (Sim) on intestinal ischemia/reperfusion injury (II/RI) by modulating Omi/HtrA2 signaling pathways. MethodsSprague Dawley rats were pretreated with 40 mg/kg Sim and then subjected to 1 hour of ischemia and 3 hours of reperfusion. The blood and intestinal tissues were collected, pathologic injury was observed, the contents of serum tumor necrosis factor-α and interleukin–6 (IL–6) were estimated, and superoxide dismutase, methane dicarboxylic aldehyde, and cysteinyl aspartate specific proteinase–3 (caspase–3) levels, as well as the expressions of Omi/HtrA2 and caspase–3, were measured in the intestinal tissues. ResultsSim preconditioning mitigated the damnification of intestinal tissues by decreasing oxidative stress, inflammatory damage, and apoptosis and downregulating the expression of Omi/HtrA2 compared to the ischemia/reperfusion group, while Sim+Ucf–101 significantly augmented this effect. ConclusionThese results suggest that Sim may alleviate intestinal ischemia/reperfusion injury by modulating Omi/HtrA2 signaling pathways.

Fushiming Capsule Attenuates Diabetic Rat Retina Damage via Antioxidation and Anti-Inflammation.

Aims Diabetic retinopathy (DR) remains one of the leading causes of acquired blindness. Fushiming capsule (FSM), a compound traditional Chinese medicine, is clinically used for DR treatment in China. The present study was to investigate the effect of FSM on retinal alterations, inflammatory response, and oxidative stress triggered by diabetes. Main Methods Diabetic rat model was induced by 6-week high-fat and high-sugar diet combined with 35 mg/kg streptozotocin (STZ). 30 days after successful establishment of diabetic rat model, full field electroretinography (ffERG) and optical coherence tomography (OCT) were performed to detect retinal pathological alterations. Then, FSM was administered to diabetic rats at different dosages for 42-day treatment and diabetic rats treated with Calcium dobesilate (CaD) capsule served as the positive group. Retinal function and structure were observed, and retinal vascular endothelial growth factor-α (VEGF-α), glial fibrillary acidic (GFAP), and vascular cell adhesion protein-1 (VCAM-1) expressions were measured both on mRNA and protein levels, and a series of blood metabolic indicators were also assessed. Key Findings In DR rats, FSM (1.0 g/kg and 0.5 g/kg) treatment significantly restored retinal function (a higher amplitude of b-wave in dark-adaptation 3.0 and OPs2 wave) and prevented the decrease of retinal thickness including inner nuclear layer (INL), outer nuclear layer (ONL), and entire retina. Additionally, FSM dramatically decreased VEGF-α, GFAP, and VCAM-1 expressions in retinal tissues. Moreover, FSM notably improved serum antioxidative enzymes glutathione peroxidase, superoxide dismutase, and catalase activities, whereas it reduced serum advanced glycation end products, methane dicarboxylic aldehyde, nitric oxide, and total cholesterol and triglycerides levels. Significance FSM could ameliorate diabetic rat retina damage possibly via inhibiting inflammation and improving antioxidation.

Endogenous BMP-4/ROS/COX-2 Mediated IPC and Resveratrol Alleviated Brain Damage.

The objective of the study was to examine the therapeutic role of combined ischemic preconditioning (IPC) and resveratrol (RES) on brain ischemia/reperfusion injury (BI/RI) by modulating endogenous bone morphogenetic protein-4 (BMP-4)/reactive oxygen species (ROS)/cyclooxygenase-2 (COX-2) in rats. Sprague Dawley (SD) rats were pretreated with 20 mg/kg RES (20 mg/kg RES was administered once a day via intraperitoneal injection 7 days prior to the I/R procedure) and IPC (equal volumes of saline were administered once a day by intraperitoneal injection over 7 days, and the bilateral common carotid arteries were separated for clamp 5 minutes followed by 5 minutes of reperfusion prior to the I/R procedure), and then subjected to 2 hours of ischemia and 22 hours of reperfusion. Blood and cerebral tissues were collected, cerebral pathological injuries and infarct sizes were investigated, serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were measured, the activities of superoxide dismutase (SOD) and ROS were calculated, the contents of methane dicarboxylic aldehyde (MDA), IL-6, TNF-α and hemodynamic change were estimated, and expression levels of b-cell lymphoma-2 (Bcl-2), bcl-2-associated x (Bax), BMP-4 and COX-2 were assessed in cerebral tissues. IPC, RES and a combination of IPC and RES preconditioning ameliorated the pathological damage and infarct sizes, reduced cerebral oxidative stress damage, alleviated inflammatory damage, restrained apoptosis, and downregulated the expression levels of BMP-4 and COX-2 compared with those of the ischemia/reperfusion (I/R) group. This study suggested a combined strategy that could enhance protection against BI/RI in clinical brain disease.

The metabolic regulation of fenofibrate is dependent on dietary protein content in male juveniles of Nile tilapia (Oreochromis niloticus).

The fenofibrate functions in mammals could be affected by many factors such as dietary nutrient levels and physiological status. However, this phenomenon has not been well studied in fish. The goal of our study was to investigate the effect of dietary protein contents on metabolic regulation of fenofibrate in Nile tilapia. An 8-week experiment was conducted to feed fish with four diets at two protein levels (28 and 38%) with or without the supplementation of fenofibrate (200 mg/kg body weight per d). After the trial, the body morphometric parameters, plasma biochemical parameters and quantitative PCR data were examined. These results showed that fenofibrate significantly reduced the feeding intake and weight gain rate, increased the oxidative stress (increased plasma methane dicarboxylic aldehyde) and liver:body ratio (increased hepatosomatic index) in the low protein (LP)-fed fish. In contrast, fenofibrate exhibited a lipid-lowering (reduced hepatic lipid) effect and up-regulated the expressions of the genes related to lipid catabolism, transport and anabolic metabolism in the high protein (HP)-fed fish. The present study suggested that lipid-lowering effect of fenofibrate would be strengthened in the fish fed with the HP diet containing high energy, but in the fish fed with the LP diet containing low energy, the fenofibrate treatment would cause adverse effects for metabolism. Taking together, our study showed that the metabolic regulation of fenofibrate in Nile tilapia was dependent not only on feed energy content but also on dietary nutrient composition, such as dietary protein and/or lipid levels.

Blockade of Transient Receptor Potential Vanilloid 4 Enhances Antioxidation after Myocardial Ischemia/Reperfusion.

Antioxidative stress provides a cardioprotective effect during myocardial ischemia/reperfusion (I/R). Previous research has demonstrated that the blockade of transient receptor potential vanilloid 4 (TRPV4) attenuates myocardial I/R injury. However, the underlying mechanism remains unclear. The current study is aimed at investigating the antioxidative activity of TRPV4 inhibition and elucidating the underlying mechanisms in vitro and ex vivo. We found that the inhibiting TRPV4 by the selective TRPV4 blocker HC-067047 or specific TRPV4-siRNA significantly reduces reactive oxygen species (ROS) and methane dicarboxylic aldehyde (MDA) levels in H9C2 cells exposed to hypoxia/reoxygenation (H/R). Meanwhile, the activity of antioxidative enzymes, particularly superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), is enhanced. Furthermore, after H/R, HC-067047 treatment increases the expression of P-Akt and the translocation of nuclear factor E2-related factor 2 (Nrf2) and related antioxidant response element (ARE) mainly including SOD, GSH-Px, and catalase (CAT). LY294002, an Akt inhibitor, suppresses HC-067047 and specific TRPV4-siRNA-induced Nrf2 expression and its nuclear accumulation. Nrf2 siRNA attenuates HC-067047 and specific TRPV4-siRNA-induced ARE expression. In addition, treatment with LY294002 or Nrf2 siRNA significantly attenuates the antioxidant and anti-injury effects of HC-067047 in vitro. Finally, in experiments on isolated rat hearts, we confirmed the antioxidative stress roles of TRPV4 inhibition during myocardial I/R and the application of exogenous H2O2. In conclusion, the inhibition of TRPV4 exerts cardioprotective effects through enhancing antioxidative enzyme activity and expressions via the Akt/Nrf2/ARE pathway.