Nitric Oxide Synthase Content Research Articles

유용미생물에 의한 저이용 산채류의 복합발효 중 생리활성 성분 및 항염증 변화

It was confirmed that complex fermentation (CF) was more efficient than single-strain fermentations in inducing changes in the contents of phenolic compounds of Maclura tricuspidate and Pyrus Montana Nakai. A mixture of Maclura tricuspidata, Pyrus montana Nakai, Platycodon grandiflorum and Codonopsis lanceolata were fermented in CF using Aspergillus shirousamii (koji), yeast, and lactic acid bacteria (LAB) for 24 days, and the pH, °Brix, total acidity, anti-oxidant activity, polyphenol content, nitric oxide (NO), and Western blotting of inducible nitric oxide synthase (iNOS), cyclo-oxygenase-2 (COX-2), and tumor necrosis factor-α (TNF-α) of the sample were determined. There was no significant change in pH and total acidity. °Brix significantly decreased from day 6 onwards. HPLC confirmed that the concentrations of chlorogenic acid, 4-hydrobenzoic acid, vanillic acid, and caffeic acid significantly increased from day 18 during the fermentation. Additionally, DPPH, ABTS radical scavenging activity, total phenol, and total flavonoid were confirmed to be increased until 18 days. NO was significantly inhibited from day 6, along with significant inhibition of iNOS, COX-2, and TNF-a. In conclusion, this study confirmed that CF of low-use (or underutilized) wild vegetables enhances phenolic compounds. It effectively suppresses NO, iNOS, COX-2, and TNF-α, markers of inflammation-related pathogenesis. Altogether, our results suggest that CF of the above plants has a potential anti-inflammatory effect.

Protective effect of alizarin on vascular endothelial dysfunction via inhibiting the type 2 diabetes-induced synthesis of THBS1 and activating the AMPK signaling pathway

BackgroundIn this study, we investigated the protective effects of alizarin (AZ) on endothelial dysfunction (ED). AZ has inhibition of the type 2 diabetes mellitus (T2DM)-induced synthesis of thrombospondin 1 (THBS1). Adenosine 5‘-monophosphate- activated protein kinase (AMPK), particularly AMPKα2 isoform, plays a critical role in maintaining cardiac homeostasis. PurposeThe aim of this study was to investigate the ameliorative effect of AZ on vascular injury caused by T2DM and to reveal the potential mechanism of AZ in high glucose (HG)-stimulated human umbilical vein endothelial cells (HUVECs) and diabetic model rats. Study designHUVECs, rats and AMPK-/- transgenic mice were used to investigate the mitigating effects of AZ on vascular endothelial dysfunction caused by T2DM and its in vitro and in vivo molecular mechanisms. MethodsIn type 2 diabetes mellitus rats and HUVECs, the inhibitory effect of alizarin on THBS1 synthesis was verified by immunohistochemistry (IHC), immunofluorescence (IF) and Western blot (WB) so that increase endothelial nitric oxide synthase (eNOS) content in vitro and in vivo. In addition, we verified protein interactions with immunoprecipitation (IP). To probe the mechanism, we also performed AMPKα2 transfection. AMPK's pivotal role in AZ-mediated prevention against T2DM-induced vascular endothelial dysfunction was tested using AMPKα2-/- mice. ResultsWe first demonstrated that THBS1 and AMPK are targets of AZ. In T2DM, THBS1 was robustly induced by high glucose and inhibited by AZ. Furthermore, AZ activates the AMPK signaling pathway, and recoupled eNOS in stressed endothelial cells which plays a protective role in vascular endothelial dysfunction. ConclusionsThe main finding of this study is that AZ can play a role in different pathways of vascular injury due to T2DM. Mechanistically, alizarin inhibits the increase in THBS1 protein synthesis after high glucose induction and activates AMPKα2, which increases NO release from eNOS, which is essential in the prevention of vascular endothelial dysfunction caused by T2DM.

The regulation effect of Atractylodis macrocephalae polysaccharides on the growth performance, antioxidant capacity and immune function in Litopenaeus vannamei

This study aims to investigate the effects of Atractylodis macrocephalae polysaccharides (AMP) on the growth performance, antioxidant capacity and non-specific immune function in Litopenaeus vannamei. Accordingly, three experimental diets including 0 (control group), 0.05% and 0.5% AMP were formulated and fed for 3 weeks. The result showed that compared with the control group, dietary 0.5% AMP supplementation significantly increased the weight gain (P < 0.05), serum biochemical indices (albumin, glutamate-pyruvate transaminase, glutamate-oxalacetate transaminase, glucose, triglyceride and total cholesterol) while 0.05% AMP supplementation had no significant influence on the above index (P > 0.05). Dietary 0.05% and 0.5% AMP supplementation significantly increased total antioxidant capacity (P < 0.05), superoxide dismutase, and glutathione peroxidase in tissues (hemolymph, hepatopancreas and intestine) while there was a decreasing trend on the malondialdehyde content with the increased AMP supplementation (P < 0.05). Tissue lysozyme, alkaline phosphatase, acid phosphatase and total nitric oxide synthase content were significantly increased with increased AMP levels in the diets and reached the highest values in the 0.5% AMP supplementation group (P < 0.05). Similar trends were observed in the further antioxidant and immune-related gene expression analysis. Gene expression of inflammatory signaling pathways (toll-like receptor 4/myeloid differentiation factor 88) and inflammatory cytokines (Tumour necrosis factor-α, apoptosis-inducing factor, member RAS oncogene family) was reduced with AMP supplementation in the diets. In conclusion, dietary AMP supplementation could improve growth performance, antioxidant ability and immune function in shrimp, and recommended dosage for safety was 0.05%.

Guanxining injection alleviates fibrosis in heart failure mice and regulates SLC7A11/GPX4 axis.

Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Lamiaceae, Danshen in Chinese) and Chuanxiong Rhizoma (rhizomes of Ligusticum chuanxiong Hort., Apiaceae, Chuanxiong in Chinese) both are important traditional Chinese medicine (TCM) for activating blood and eliminating stasis. Danshen-chuanxiong herb pair has been used for more than 600 years in China. Guanxinning injection (GXN) is a Chinese clinical prescription refined from aqueous extract of Danshen and Chuanxiong at the ratio of 1:1 (w/w). GXN has been mainly used in the clinical therapy of angina, heart failure (HF) and chronic kidney disease in China for almost twenty years. This study aimed to explore the role of GXN on renal fibrosis in heart failure mice and the regulation of GXN on SLC7A11/GPX4 axis. The transverse aortic constriction model was used to mimic HF accompanied by kidney fibrosis model. GXN was administrated by tail vein injection in dose of 12.0, 6.0, 3.0mL/kg, respectively. Telmisartan (6.1mg/kg, gavage) was used as a positive control drug. Cardiac ultrasound indexes of ejection fraction (EF), cardiac output (CO), left ventricle volume (LV Vol), HF biomarker of pro-B type natriuretic peptide (Pro-BNP), kidney function index of serum creatinine (Scr), kidney fibrosis index of collagen volume fraction (CVF) and connective tissue growth factor (CTGF) were evaluated and contrasted. Metabolomic method was employed to analyze the endogenous metabolites changes in kidneys. Besides, contents of catalase (CAT), xanthine oxidase (XOD), nitricoxidesynthase (NOS), glutathione peroxidase 4 (GPX4), the x(c)(-) cysteine/glutamate antiporter (SLC7A11) and ferritin heavy chain (FTH1) in kidney were quantitatively analyzed. In addition, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the chemical composition of GXN and network pharmacology was used to predict possible mechanisms and the active ingredients of GXN. The cardiac function indexes of EF, CO and LV Vol, kidney functional indicators of Scr, the degree of kidney fibrosis indicators CVF and CTGF were all relieved to different extent for the model mice treated with GXN. 21 differential metabolites involved in redox regulation, energy metabolism, organic acid metabolism, nucleotide metabolism, etc were identified. Aspartic acid, homocysteine, glycine, and serine, methionine, purine, phenylalanine and tyrosine metabolism were found to be the core redox metabolic pathways regulated by GXN. Furthermore, GXN were found to increase CAT content, upregulate GPX4, SLC7A11 and FTH1 expression in kidney significantly. Not only that, GXN also showed good effect in down-regulating XOD and NOS contents in kidney. Besides, 35 chemical constituents were initially identified in GXN. Active ingredients of GXN-targets-related enzymes/transporters-metabolites network was established to find out that GPX4 was a core protein for GXN and the top 10 active ingredients with the most relevant to renal protective effects of GXN were rosmarinic acid, caffeic acid, ferulic acid, senkyunolide E, protocatechualdehyde, protocatechuic acid, danshensu, L-Ile, vanillic acid, salvianolic acid A. GXN could significantly maintain cardiac function and alleviate the progression of fibrosis in the kidney for HF mice, and the mechanisms of action were related to regulating redox metabolism of aspartate, glycine, serine, and cystine metabolism and SLC7A11/GPX4 axis in kidney. The cardio-renal protective effect of GXN may be attributed to multi-components like rosmarinic acid, caffeic acid, ferulic acid, senkyunolide E, protocatechualdehyde, protocatechuic acid, danshensu, L-Ile, vanillic acid, salvianolic acid A et al.

Involvement of nitrergic neurons in colonic motility in a rat model of ulcerative colitis.

BACKGROUNDThe mechanisms underlying gastrointestinal (GI) dysmotility with ulcerative colitis (UC) have not been fully elucidated. The enteric nervous system (ENS) plays an essential role in the GI motility. As a vital neurotransmitter in the ENS, the gas neurotransmitter nitric oxide (NO) may impact the colonic motility. In this study, dextran sulfate sodium (DSS)-induced UC rat model was used for investigating the effects of NO by examining the effects of rate-limiting enzyme nitric oxide synthase (NOS) changes on the colonic motility as well as the role of the ENS in the colonic motility during UC.AIMTo reveal the relationship between the effects of NOS expression changes in NOS-containing nitrergic neurons and the colonic motility in a rat UC model. METHODSMale rats (n = 8/each group) were randomly divided into a control (CG), a UC group (EG1), a UC + thrombin derived polypeptide 508 trifluoroacetic acid (TP508TFA; an NOS agonist) group (EG2), and a UC + NG-monomethyl-L-arginine monoacetate (L-NMMA; an NOS inhibitor) group (EG3). UC was induced by administering 5.5% DSS in drinking water without any other treatment (EG1), while the EG2 and EG3 were gavaged with TP508 TFA and L-NMMA, respectively. The disease activity index (DAI) and histological assessment were recorded for each group, whereas the changes in the proportion of colonic nitrergic neurons were counted using immunofluorescence histochemical staining, Western blot, and enzyme linked immunosorbent assay, respectively. In addition, the contractile tension changes in the circular and longitudinal muscles of the rat colon were investigated in vitro using an organ bath system. RESULTSThe proportion of NOS-positive neurons within the colonic myenteric plexus (MP), the relative expression of NOS, and the NOS concentration in serum and colonic tissues were significantly elevated in EG1, EG2, and EG3 compared with CG rats. In UC rats, stimulation with agonists and inhibitors led to variable degrees of increase or decrease for each indicator in the EG2 and EG3. When the rats in EGs developed UC, the mean contraction tension of the colonic smooth muscle detected in vitro was higher in the EG1, EG2, and EG3 than in the CG group. Compared with the EG1, the contraction amplitude and mean contraction tension of the circular and longitudinal muscles of the colon in the EG2 and EG3 were enhanced and attenuated, respectively. Thus, during UC, regulation of the expression of NOS within the MP improved the intestinal motility, thereby favoring the recovery of intestinal functions.CONCLUSIONIn UC rats, an increased number of nitrergic neurons in the colonic MP leads to the attenuation of colonic motor function. To intervene NOS activity might modulate the function of nitrergic neurons in the colonic MP and prevent colonic motor dysfunction. These results might provide clues for a novel approach to alleviate diarrhea symptoms of UC patients.

Diapocynin neuroprotective effects in 3-nitropropionic acid Huntington’s disease model in rats: emphasis on Sirt1/Nrf2 signaling pathway

Background and AimHuntington's disease (HD) is a rare inherited disease portrayed with marked cognitive and motor decline owing to extensive neurodegeneration. NADPH oxidase is considered as an important contributor to the oxidative injury in several neurodegenerative disorders including HD. Thus, the present study explored the possible neuroprotective effects of diapocynin, a specific NADPH oxidase inhibitor, against 3-nitropropionic acid (3-NP) model of HD in rats.MethodsAnimals received diapocynin (10 mg/kg/day, p.o), 30 min before 3-NP (10 mg/kg/day, i.p) over a period of 14 days.ResultsDiapocynin administration attenuated 3-NP-induced oxidative stress with significant increase in reduced glutathione, glutathione-S-transferase, nuclear factor erythroid 2-related factor 2, and brain-derived neurotrophic factor striatal contents contrary to NADPH oxidase (NOX2; gp91phox subunit) diminished expression. Moreover, diapocynin mitigated 3-NP-associated neuroinflammationand glial activation with prominent downregulation of nuclear factor-Кβ p65 and marked decrement of inducible nitric oxide synthase content in addition to decreased immunoreactivity of ionized calcium binding adaptor molecule 1 and glial fibrillary acidic protein; markers of microglial and astroglial activation, respectively. Treatment with diapocynin hindered 3-NP-induced apoptosis with prominent decrease in tumor suppressor protein and Bcl-2-associated X protein contents whereas the anti-apoptotic marker; B-cell lymphoma-2 content was noticeably increased. Diapocynin neuroprotective effects could be attributed to silent information regulator 1 upregulation which curbed 3-NP-associated hazards resulting in improved motor functions witnessed during open field, rotarod, and grip strength tests as well as attenuated 3-NP-associated histopathological derangements.ConclusionThe present findings indicated that diapocynin could serve as an auspicious nominee for HD management.Graphical abstract

Effect and mechanism of Jingqi Yukui Capsules on gastric ulcer mucosa healing quality: based on network pharmacology and animal experiment

This study aims to identify the active components and the mechanism of Jingqi Yukui Capsules(JQYK) in the treatment of gastric ulcer based on network pharmacology, and verify some key targets and signaling pathways through animal experiment. To be specific, first, the active components and targets of JQYK were retrieved from a Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM) and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the targets of gastric ulcer from GeneCards and Online Mendelian Inheritance in Man(OMIM) with the search term &quot;gastric ulcer&quot;. The common targets of the two were the potential targets of the prescription for the treatment of the di-sease. Then, protein-protein interaction(PPI) network of key targets were constructed based on STRING and Cytoscape 3.7.2, followed by Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment by matescape database and pathway visualization by Omicshare. For the animal experiment, the improved method of Okabe was used to induce gastric ulcer in rats, and the model rats were classified into the model group, JQYK high-dose(JQYK-H), medium-dose(JQYK-M), and low-dose(JQYK-L) groups, Anweiyang Capsules(WYA) group, and Rabeprazole Sodium Enteric Capsules(RBPZ) group. Normal rats were included in the blank group. Rats in the blank group and model group were given distilled water and those in the administration groups received corresponding drugs. Then gastric ulcer healing in rats was observed. The changes of the gastric histomorphology in rats were evaluated based on hematoxylin-eosin(HE) staining, and the content of inducible nitric oxide synthase(iNOS) in rat gastric tissue was detected with Coomassie brilliant blue method. The mRNA and protein levels of some proteins in rat gastric tissue were determined by real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot(WB) to further validate some key targets and signaling pathways. A total of 206 active components and 535 targets of JQYK, 1 305 targets of gastric ulcer, and 166 common targets of the disease and the drug were yielded. According to PPI analysis and KEGG pathway enrichment analysis, multiple key targets, such as interleukin-6(IL-6), tumor necrosis factor(TNF), mitogen-activated protein kinase 1(MAPK1), MAPK3, and MAPK14, as well as nuclear factor kappa-B(NF-κB) signaling pathway, IL-17 signaling pathway, and leukocyte transendothelial migration in the top 20 key signaling pathways were closely related to inflammation. The key protein p38 MAPK and NF-κB signaling pathway were selected for further verification by animal experiment. The gastric ulcer in the JQYK-H group recovered nearly to the level in the blank group, with significant decrease in the content of iNOS in rat gastric tissue and significant reduction in the mRNA and phosphorylation levels of p38 MAPK and the mRNA and protein levels of NF-κB p65 in rat gastric tissue. The results indicated that JQYK can inhibit the phosphorylation of the key protein p38 MAPK and the expression of NF-κB p65 in the NF-κB signaling pathway, thereby exerting the anti-inflammatory effect and effectively improving the quality of gastric ulcer healing in rats. Thus, the animal experiment result verifies some predictions of network pharmacology.

Geraniin Protects against Cerebral Ischemia/Reperfusion Injury by Suppressing Oxidative Stress and Neuronal Apoptosis via Regulation of the Nrf2/HO-1 Pathway.

Geraniin, a polyphenol isolated from Phyllanthus amarus, possesses extensive biological and pharmaceutical activities. In this study, we investigated the protective effect against cerebral ischemia/reperfusion (I/R) injury of geraniin and explored its potential mechanism. Middle cerebral artery occlusion/reperfusion (MCAO/R) was used to simulate cerebral I/R injury in vivo, and oxygen-glucose deprivation/reoxygenation (OGD/R) was applied to establish an in vitro model of cerebral I/R injury. In this study, we performed TTC and HE staining and adopted a neurological score method to evaluate the neuroprotective effect of geraniin in vivo and used the CCK-8 assay to assess this effect in vitro. Indices of reactive oxidation capacity were measured in vivo and in vitro to verify the antioxidant capacity of geraniin. TUNEL staining and flow cytometry were applied to measure the apoptosis rate, and Western blotting was performed to assess the expression of apoptosis-related proteins. Finally, the expression of Nrf2 and HO-1 was evaluated in vivo and in vitro by Western blotting. Geraniin significantly reduced the infarct volume, decreased neurological deficit scores, alleviated pathological changes in neurons, and increased the cell survival rate. Geraniin increased the activity of superoxide dismutase (SOD) and decreased the activity of lactate dehydrogenase (LDH) and the contents of malondialdehyde (MDA), nitric oxide (NO), and neuronal nitric oxide synthase (nNOS) in vivo and in vitro. In addition, geraniin significantly reduced the apoptosis. Furthermore, geraniin also evidently increased Nrf2 (total and nuclear) and HO-1 protein expression in vivo and in vitro. Collectively, these results imply that geraniin may exert a protective effect against cerebral I/R injury by suppressing oxidative stress and neuronal apoptosis. The mechanism underlying the protective effect of geraniin is associated with activation of the Nrf2/HO-1 pathway. Our results indicate that geraniin may be a potential drug candidate for the treatment of ischemic stroke.

Citronellal alleviate macro- and micro-vascular damage in high fat diet / streptozotocin - Induced diabetic rats via a S1P/S1P1 dependent signaling pathway

Citronellal (CT) is an acyclic monoterpene aldehyde isolated from lemon citronella, which could ameliorate vascular endothelial dysfunction in atherosclerosis in our previous study, however, whether CT can alleviate vascular endothelial dysfunction related with type 2 diabetes (T2DM) is still unknown. So, we investigated the role of CT in vascular dysfunction related to T2DM and the mechanism involved. T2DM rat model was induced by a single intraperitoneal injection of low-dose streptozotocin (STZ) (60 mg/kg) to rats fed with high-fat diet (HFD) (4 weeks). After treated with CT (150 mg/kg/d), both the thoracic aorta injury and micro-vascular pathological injury in T2DM rats ex vivo were alleviated, and the oxidative stress in T2DM rats treated with CT were attenuated, manifested as increased content of endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD), and decreased content of malondialdehyde (MDA). Furthermore, CT (15 μg/L) increased the migration capacity of human umbilical vein endothelial cells (HUVECs) under high glucose circumstance (30 mM), and increased the endothelial-dependent relaxation in thoracic aorta isolated from T2DM rats in vitro. Finally, all of these effects of CT were blocked by fingolimod (FTY720), a sphingosine-1-phosphate receptor agonist, and the expression of sphingosine-1-phosphate receptor 1 (S1P1) was increased by CT. In conclusion, CT improved vascular function through S1P/S1P1 signaling pathway.

Histone deacetylase inhibitor attenuates intestinal mucosal injury in fatally scalded rats.

BackgroundSevere burns, trauma and shock can cause intestinal epithelial barrier dysfunction, which can lead to intestinal endotoxemia and even sepsis and multi-organ dysfunction. Many studies have shown that histone deacetylase inhibitors (HDACIs) can improve cell tolerance to hypoxia and inflammation, thus protecting the functions of important organs in the body, and at the same time, inhibiting the degradation of tight junction (TJ) proteins, protecting the intercellular barrier, and reducing tissue edema and organ damage. However, the mechanism is unclear.MethodsEighty male Sprague-Dawley rats (weighing 280–300 g) with a 50% total body surface area full-thickness dermal burn were randomly assigned to 4 groups (20 rats/group): sham control (SC group), scald + normal saline (SN group), scald + 2-methyl-2pentenoic acid (2M2P group), and scald + valproic acid (VPA group). After scalding, we measured the following parameters at various time intervals postburn injury: intestinal mucosal injury score, diamine oxidase (DAO) activity, intestinal protein expression of acetyl histone H3 at K9 (Ac-H3K9), hypoxia inducible factor 1α (HIF-1α), erythropoietin (EPO), zonula occludens-1 (ZO-1), endothelial nitric oxide synthase (eNOS) content, nitric oxide (NO) content, and intestinal mucosal blood flow (IMBF).ResultsIntestinal mucosa showed significant morphologic injury at 4 and 8 hours after scalding that was attenuated by VPA. DAO activity in the VPA group was significantly decreased compared with the other scald groups. At 4 and 8 hours after scalding, VPA enhanced Ac-H3K9 and ZO-1 expression and decreased HIF-1α and EPO expression in the intestine compared with the other scald groups. At 4 and 8 hours after scalding, eNOS and NO protein content and IMBF in the VPA group were markedly increased compared with the other scald groups.ConclusionsHDACIs attenuated intestinal mucosal injury in fatally scalded rats. This may have involved VPA enhancing Ac-H3K9 and ZO-1 expression, inhibiting HIF-1α and EPO expression and inducing eNOS and NO increments.

Idarubicin-induced oxidative stress and apoptosis in cardiomyocytes: An in vitro molecular approach.

Idarubicin (IDA) is an anthracycline antibiotic, frequently used for the treatment of various human cancers. In vivo rodent model studies have identified a variety of possible adverse outcomes from IDA including heart effects like increased heart weights, myocardial histopathological injury, electrocardiogram abnormalities, and cardiac dysfunction. Despite significant investigations, the molecular mechanisms responsible for the cardiotoxicity of IDA have not been fully clarified. The aim of the current study was to investigate the effects of IDA on the HL-1 cardiac muscle cell. Different concentrations of IDA (10-6, 10-5, 10-4, and 10-3M) were used at different time (6, 12, 24, and 48 h) periods, and the Cell Counting Kit-8 (CCK-8); 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) probe method; and enzyme-linked immunosorbent assay (ELISA) were used to detect the oxidative stress level. In addition, we used network analysis to predict IDA-induced cardiotoxicity. The TUNEL assay, qRT-PCR, ELISA assay, and Western blotting detection of related apoptotic factors including caspase family, Bax, and Bcl-2. Overall, we found that IDA was generally more toxic at high concentrations or extended durations of exposure. At the same time, IDA can increase the content of reactive oxygen species (ROS), malondialdehyde (MDA), and decrease the level of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) in cells, and increase the content of lactate dehydrogenase (LDH) and nitric oxide synthase (NOS) in the medium. Network analysis showed that the apoptosis signaling pathway was activated; specifically, the caspase family was involved in the signal pathway. The results of the TUNEL assay, qRT-PCR, ELISA, and Western blot found that IDA can activate apoptotic factors. The mechanism may be related to the activation of apoptosis signaling pathway. These results indicate that the cardiotoxic effects of IDA are most likely associated with oxidative stress and ROS formation, which finally ends in apoptotic factors' activation and induction of cell apoptosis.

Selenium Deficiency Aggravates Heat Stress Pneumonia in Chickens by Disrupting the M1/M2 Balance

Selenium (Se) is an essential trace element found in the body. Se deficiency and M1/M2 imbalance are closely related to inflammation. Heat stress can decrease immune function and cause inflammation. In order to investigate whether Se deficiency can aggravate pneumonia caused by heat stress and the role of M1/M2 imbalance in the occurrence of pneumonia, 100 AA broilers were divided into two groups and fed the conventional diet (0.2mg/kg Se) and the Se-deficient diet (0.03mg/kg Se). After 40days of feeding, the normal feeding group was randomly divided into a control group and a heat stress group. At the same time, the Se-deficient diet feeding group was randomly divided into a low Se group and a low Se heat stress group, with 25 chickens in each group. The model was established by exposure at 40℃. Six hours later, broilers were euthanized, and their lung tissues were collected. Hematoxylin and eosin staining, immunofluorescence, quantitative real-time PCR, and western blotting were used to detect lung histopathological changes and the expression of M1/M2 markers, nuclear receptor-κB (NF-κB) pathway genes, and heat shock proteins. Meanwhile, the activity and content of oxidative stress-related indices were also detected. We found that the expression of interleukin-1β, interleukin-6, interleukin-12, and tumor necrosis factor-α was upregulated and the expression of interleukin-2, interleukin-10, and interferon-γ was downregulated. Immunofluorescence showed that the expression of CD16 was increased, the expression of CD163 was weakened, and the M1/M2 imbalance was present. In addition, the NF-κB pathway was activated by the increased expressions of heat shock proteins and oxidative stress. There was an increase in malondialdehyde, nitric oxide, and inducible nitric oxide synthase content, while the activity of total antioxidant capacity, glutathione peroxidase, catalase, and superoxide dismutase decreased, and the expression of NF-κB and cyclooxygenase-2 increased. These results suggest that low Se induces M1/M2 imbalance through oxidative stress activation of the NF-κB pathway and aggravates lung tissue inflammation caused by heat stress. This study offers a theoretical basis for exploring the pathogenesis of various kinds of inflammation induced by Se deficiency from the perspective of M1/M2 and provides a reference for the prevention of such diseases.

Carvacrol hinders the progression of hepatic fibrosis via targeting autotaxin and thioredoxin in thioacetamide-induced liver fibrosis in rat.

Fibrosis is a common outcome of nearly all chronic diseases of liver that results in changes of its functions which requires medical attention. The current research aims to investigate the potential anti-fibrotic efficacy of Carvacrol against thioacetamide (TAA)-induced liver fibrosis in male rats using Ursodeoxycholic acid (UDCA) as a reference anti-fibrotic product. Carvacrol (25 and 50 mg/kg) markedly declined TAA-increased serum liver enzymes; alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) as well as total bilirubin (TB) and direct bilirubin (DB) levels as well as increased levels of total protein (TP) and albumin. Carvacrol significantly reduced glutathione depletion (GSH), Nitric oxide (NOX) and malondialdehyde (MDA) accumulation in liver tissue. Additionally, its anti-oxidant effect brightened up via affecting markers of stress found in the cell as nuclear factor erythroid 2-related factor 2 (Nrf-2) where it still had high content and decreased Thioredoxin (Trx) level. The anti-inflammatory effect of Carvacrol was confirmed by decreasing nuclear factor kappa B (NF-κB), interleukin-1beta (IL-1β) and inducible nitric oxide synthase (iNOS) contents. Carvacrol showed anti-fibrotic effect clarified by turning down fibrosis-related markers; TGF-β1, matrix metalloproteinase-3 and 9 (MMP-3 and 9) and Autotaxin (ATX) contents. Furthermore, it decreased alpha smooth muscle actin (α-SMA) and caspase-3 immune-expression. The overall outcome of aforementioned markers results showed that Carvacrol suppresses the progression of liver fibrosis via its anti-oxidant, anti-inflammatory, anti-apoptotic effect and its ability in lowering Thioredoxin and Autotaxin; hence it can be categorized as a hepatoprotective natural substance.

Hepatoprotective effect of Saccharomyces Cervisciae Cell Wall Extract against thioacetamide-induced liver fibrosis in rats

Fibrosis represents a common outcome of almost all chronic liver diseases and leads to an impairment of liver function that requires medical intervention. The current study aimed to evaluate the potential anti-fibrotic effect of Saccharomyces cervisciae cell wall extract (SCCWE) against thioacetamide (TAA)-induced liver fibrosis in rats (200mg/kg b.w. i.p. twice weekly for 6 weeks) using Ursodeoxycholic acid (UDCA) as a reference anti-fibrotic product. SCCWE at two doses (50 and 100 mg/kg) significantly ameliorated the rise in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamide transferase (GGT) activities, total bilirubin and direct bilirubin, increased total protein and albumin. SCCWE significantly reduced glutathione depletion (GSH), Nitric oxide (NOx) and malondialdehyde (MDA), thioredoxin (Trx) contents and elevated nuclear factor erythroid 2–related factor 2 (Nrf-2) content. Its anti-inflammatory effects were confirmed by observing a decrease in nuclear factor-κB (NF- κβ), interleukin-1b (IL-1β) and inducible nitric oxide synthase (iNOS) content. The anti-fibrotic effects of SCCWE were explored by assessing fibrosis related markers as it significantly reduced transform growth factor-β (TGF-β) and autotaxin (ATX) contents. Administration of SCCWE significantly decreased matrix metalloproteinase-3 and 9 (MMP-3 and -9). Furthermore, it also decreased alpha smooth muscle actin (α-SMA) and caspase-3 as assessed immunohistochemically those results were similar to that of the standard drug UDCA. This study shows that SCCWE protects against TAA-induced liver fibrosis in rats, through attenuating oxidative stress, and inflammation, ameliorating MMPs, combating apoptosis and thereby fibrotic biomarkers in addition to improving histopathological changes.

THE ROLE OF VASODILATION FACTORS IN THE PATHOGENESIS OF CHRONIC HEART FAILURE OF ISCHEMIC ORIGIN IN ATRIAL FIBRILLATION

The purpose of the study is to study the possible role of vasodilation factors in the pathogenesis of chronic heart failure (CHF) in persistent atrial fibrillation (AF) in patients with stable coronary heart disease. Materials and methods. A survey of 86 patients with stable coronary heart disease complicated by CHF II-III FC according to the NYHA classification. There was 1 group - 22 patients with CHF with reduced LV EF ≤ 40.0% and AF; I (comparative group) - 20 patients with CHF with reduced LV EF without AF; 2-nd group - 24 patients with preserved LV EF ≥ 40.1% and AF and II (comparative group) - 20 patients with CHF with preserved LV EF without AF. The content of endothelial nitric oxide synthase (eNOS), nitrites (NO2-) and nitrates (NO3-) was determined. All patients underwent electrocardiographic examination (ECG) for the initial screening of arrhythmias and conduction, diagnosis of focal changes in the ventricular myocardium. Structural and hemodynamic characteristics of the heart muscle were determined by echocardiography.Results. In the examined patients of the 1st group with CHF of ischemic origin and reduced LV EF ≤ 40.0% and AF in comparison with the 2nd group of patients with CHF with preserved LV EF and AF, a significant increase in the values of ICO, ICD, IMML, the size of LA and a decrease in LV EF (p &lt;0.01), indicating the development of LVH (remodeling) and a decrease in isotropic heart function. When comparing the levels of vasodilation factors in patients with CHF with low LV EF and AF and data from the CHF comparison group without AF, a significant decrease in eNOS by 96.8% (almost twice) and a significant decrease in serum nitrite and nitrate levels (p &lt; 0.01), indicating the development of endothelial dysfunction. Conclusions. In patients with CHF of ischemic origin in the development of persistent forms of AF pathogenetic role is played by a significant decrease in vasodilating factors (content of eNOS, nitrites and nitrates). At decrease in EF of LV ≤ 40,0% there is a significant decrease in vasodilating factors, as a result of disturbance of endothelial function that testifies to need of correction of the revealed changes directed on slowing down of disease progression.

Study on different pathogenic factors in different disease stages of patients with Wilson disease

To investigate in different stages of patients with Wilson disease (WD), there are different pathogenic factors such as metal deposition, oxidative stress, and inflammatory response in the brain. A total of 32 untreated WD patients and 10 normal controls were enrolled in the study. The neurological symptoms were evaluated using the modified Young scale. Liver function, metal metabolism, susceptibility-weighted imaging (SWI), diffusion tensor imaging (DTI), and magnetic resonance spectroscopy (MRS) examination were done. The clinical disease stages were divided into metal deposition period, fiber damage period, and neuronal necrosis period according to the imaging results. The content of 24-h urine copper, serum copper, and serum iron; and the levels of catalase (CAT), glutathione peroxidase (GSH-PX), malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), interleukin (IL-1), and tumor necrosis factor alpha (TNF-α) were detected. The contents of urinary copper in WD patients at neuronal necrosis stage were lower than those in patients at the metal deposition stage (P = 0.011) and fiber injury stage (P = 0.023). The contents of NOS (P = 0.039) and NO (P = 0.047) in WD patients at the stage of fiber injury were higher than those of the normal control, while GSH-PX (P = 0.025) and CAT (P = 0.041) were lower in the neuronal necrosis stage. In the stage of neuronal necrosis, the levels of IL-1 (P = 0.030) and TNF-α were higher than those of the normal control (P = 0.042). The neurological symptom scores in patients with fiber injury (P = 0.013) and neuron injury were higher than those with metal deposition (P = 0.026). There are different pathogenic factors in different stages of WD. At the neuronal necrosis stage, copper deposition was decreased in WD patients. In the stage of fiber injury and neuronal necrosis, there is oxidative stress injury in WD patients. In the neuronal necrosis phase, WD patients have an inflammatory response.

Study on the Mechanism of Protective Effect of Tannic Acid on the Myocardial Hypertrophy Induced By Pressure Overload

Cardiac hypertrophy was a compensatory response to normal cardiac pressure overload, which eventually leads to heart failure. Therefore, the research of new drugs for the treatment of cardiac hypertrophy was one of the hotspots. In this paper, we explore the protective effect of tannic acid on myocardial hypertrophy and its potential mechanism. The rat model of cardiac hypertrophy was established by abdominal aortic banding. According to the random control principle, the rats treated with sham operation were used as the control group. Abdominal aortic banding rats were treated with tannic acid (20 and 40 mg/kg) or captopril and divided into low dose tannic acid group, high dose tannic acid group, and captopril group. The hemodynamic parameters of rats in each group were detected respectively, and then the related proteins and tissues were detected after the rats were killed. The results showed that the cardiac morphology and pathology of abdominal aortic banding rats treated with tannic acid were significantly improved, myocardial hypertrophy and apoptosis were decreased and the overexpression of Angiotensin II type 1 receptor and Angiotensin II type 2 receptor was decreased. In addition, the messenger Ribonucleic acid expression of extracellular signal regulated kinase 1/2, transforming growth factor-β and matrix metalloproteinase-9 decreased. At the same time, tannic acid treatment decreased the activity and content of malondialdehyde and endothelin-1, and increased the content of superoxide dismutase, catalase, glutathione peroxidase, nitric oxide, and endothelial nitric oxide synthase. In addition, tannic acid downregulated the expression of tumor necrosis factor-α, interleukin-1 β, B-cell lymphoma-2 associated X protein and cysteine-dependent aspartate specific proteases-3 and up-regulated the expression of B-cell lymphoma-2. Tannic acid treatment can improve abdominal aortic banding induced cardiac hypertrophy effectively. Its cardioprotective effect is partly attributed to the reduction of myocardial oxidative stress, inhibition of inflammation, inhibition of fibrosis, reduction of apoptosis, increase of nitric oxide level, decrease of endothelin-1 level, and down-regulation of Angiotensin II type 1 receptor.

Antihypertensive effect of rapeseed peptides and their potential in improving the effectiveness of captopril.

The main objective of this study was to evaluate the safety and antihypertensive activity of rapeseed peptides and to investigate their potential synergy with captopril. The peptides were nontoxic with the maximum tolerated dose exceeding 25 g kg-1 BW d-1 for mice and they had angiotensin converting enzyme (ACE) inhibitory activity with IC50 value of 1.27 mg mL-1 . Rapeseed peptides did not have a synergistic effect with captopril on inhibiting ACE activity in simulated digestion tests in vitro. But in vivo they could synergistically augment the amplitude range of lowering blood pressure with captopril by approximately 9% and prolong the antihypertensive effect duration time by over 20% in antihypertension tests of spontaneously hypertensive rats. In addition, the inhibiting effect of rapeseed peptides on ACE activity was noticeable in some rat organs in vivo. Nevertheless, when compared to captopril group, the potential synergy of rapeseed peptides with captopril did not cause a further decrease in ACE activity in the organs but their synergy further improved levels of NO (12.7%) and endothelial nitric oxide synthase (74.1%) in rat serum. Further studies of some peptides identified from rapeseed peptides showed that some of the rapeseed peptides (Cys-Leu, Val-Ala-Pro) could markedly increase contents of NO and endothelial nitric oxide synthase. Rapeseed peptides have antihypertensive activity and they showed potential synergy with captopril in antihypertensive performance in vivo. The synergy was not from ACE inhibition but from other pathways, like improvement in endogenous vasodilator contents. © 2020 Society of Chemical Industry.

Stress Associated with Simulated Transport, Changes Serum Biochemistry, Postmortem Muscle Metabolism, and Meat Quality of Broilers.

Simple SummaryThe objective of this study was to investigate the effects of the transportation on broilers through the use of a vibration and motion simulation machine. Short-term transport stress induced significant physiological changes in broiler chickens. Simulation of the vibration and motion associated transport for 2 h altered hormonal secretion and blood biochemical characteristics. However, after 4 h, the birds appear to regain homeostatic equilibrium. Despite this, the stress activated antioxidant defenses, acidified muscles and increased peroxidation, as well as decreasing the meat quality of broilers. This study supports and extends previous work that identified transportation as a major risk in relation to bird welfare and meat quality.Many factors contribute to the stress of transporting broilers from the farm to the processing plant. Using a motion simulation machine, a total of 144 male broilers were employed to determine the effect of motion, vibration, and feed withdrawal during transportation on serum biochemical parameters, postmortem muscle metabolism, and meat quality of broilers. The results indicated that transportation did not affect the activity of lactate dehydrogenase, γ-glutamyl transferase, aspartate aminotransferase, creatine kinase, and glucose in the serum, glutathione peroxidase in the breast and thigh muscle, nitric oxide synthase (NOS) in the breast, and heat stress protein 70 mRNA expression level in the liver (p > 0.05). Serum triiodothyronine, thyroxine, and insulin concentration declined with 2 h transportation (p < 0.05) and recovered with 4 h transportation (p < 0.05). NOS concentration in the thigh increased with 2 h transportation (p < 0.05) and recovered with 4 h transportation (p < 0.05). Two-hour and 4 h transportation increased the activity of superoxide dismutase in both muscles. Malondialdehyde, lactic acid, and drip loss24 h in both thigh and breast muscles increased, and glycogen in both muscles decreased with increasing transportation times (p < 0.05). Two-hour transportation did not influence pH45 min and pH24 h in the breast and thigh muscle, but these indexes decreased with 4 h transportation. This experiment supports and extends previous work that identified transportation as a major risk in relation to bird welfare and meat quality.

Melatonin modulates acute cardiac muscle damage induced by carbon tetrachloride - involvement of oxidative damage, glutathione, and arginine and nitric oxide metabolism.

The present study was designed to evaluate the cardioprotective effects of melatonin (a single dose of 50 mg·kg-1), a naturally occurring polypharmacological molecule, in Wistar rats acutely exposed to carbon tetrachloride (CCl4). This was done for the first time by tracking different biochemical parameters that reflect rat heart antioxidative and oxidative capacities, nitric oxide and arginine metabolism, and the glutathione cycle. Additionally, the extrinsic apoptosis pathway related parameters were studied. Acute exposure to CCl4 led to an increase in the studied tissue oxidant parameters (hydrogen peroxide, malondialdehyde, and carbonylated protein content), as well as the activity alteration of antioxidant (catalase, superoxide dismutase, and peroxidase) and glutathione-metabolizing (glutathione peroxidase, S-transferase, and reductase) enzymes. Furthermore, CCl4 caused a disturbance in the tissue myeloperoxidase, nitric oxide, citrulline, arginase, and inducible nitric oxide synthase content and activities and in two apoptosis-related parameters, caspase-3 and FAS ligand. Melatonin as a post-treatment prevented the changes induced by CCl4 to a differing extent, and in some cases, it was so potent that it completely abolished any tissue disturbances. This study is a promising starting point for further research directed to the development of melatonin treatment in cardiac tissue associated diseases.