scholarly journals MiR-203-3p inhibits the oxidative stress, inflammatory responses and apoptosis of mice podocytes induced by high glucose through regulating Sema3A expression

2020 ◽  
Vol 15 (1) ◽  
pp. 939-950
Author(s):  
Jingfu Chen ◽  
Qing Xu ◽  
Wei Zhang ◽  
YuLan Zhen ◽  
Fei Cheng ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
High Glucose ◽  
Renal Injury ◽  
Inflammatory Responses ◽  
Cell Model ◽  
The Body ◽  
Enzyme Linked Immunosorbent Assay ◽  
Podocyte Injury

AbstractDiabetic nephropathy (DN) is the most serious long-term microvascular complication of diabetes, which mainly causes podocyte injury. Many studies have shown that microRNAs play a vital role in the development of DN. Studies have shown that miR-203-3p is involved in mesangial cell proliferation and apoptosis of DN mice. Therefore, we speculated that miR-203-3p might be related to the development of DN, but our study does not provide any evidence. In animal experiments, diabetic mice (db/db) were transfected with iR-203-3p overexpression lentiviral vectors (LV-miR-203-3p) and their control (LV-miR-con), with normal mice (db/m) being used as the control. High glucose (HG)-induced podocytes were used to construct a DN cell model in vitro. The expression levels of miR-203-3p, Semaphorin 3A (Sema3A) and inflammatory cytokines were detected by quantitative real-time polymerase chain reaction. Also, serum creatinine and blood urea nitrogen levels were used to evaluate the degree of renal injury in DN mice. Sema3A and apoptosis-related protein levels were assessed by the western blot analysis. Enzyme-linked immunosorbent assay was used to determine the different oxidative stress-related indicators and inflammatory cytokines. Flow cytometry and caspase-3 activity detection were used to analyze the degree of podocyte apoptosis. Our results suggested that the expression of miR-203-3p was lower in DN mice and in HG-induced podocytes. Overexpression of miR-203-3p reduced the body weight, blood glucose and renal injury of DN mice in vivo, as well as relieve the oxidative stress, inflammatory response and apoptosis of HG-induced podocytes in vitro. Functionally, Sema3A was a target of miR-203-3p, and Sema3A overexpression reversed the inhibitory effect of miR-203-3p on HG-induced podocyte injury. Our findings revealed that miR-203-3p alleviated the podocyte injury induced by HG via regulating Sema3A expression, suggesting that miR-203-3p might be a new therapeutic target to improve the progression of DN.

scholarly journals Improved Promotion of M2 Microglial Polarization by Zuogui Jiangtang Jieyu Formulation in Diabetes-Related Depression

2021 ◽  
Author(s):  
xiuli zhang ◽  
Dahua Wu ◽  
Dandan Li ◽  
Jian Liu ◽  
Chang Lei ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
High Glucose ◽  
Neuroprotective Effect ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mild Stress ◽  
Microglial Polarization ◽  
M2 Polarization ◽  
M1 Polarization

Abstract Background Zuogui Jiangtang Jieyu formulation (ZGJTJY) is a Chinese polyherbal prescription for diabetes-related depression (DD). The mechanism underlying hippocampal M1/M2 polarization in DD and the ZGJTJY treatment effects remain unclear. This study aimed to investigate M1/M2 microglial polarization in the hippocampus of DD rats and HAPI (highly aggressively proliferating immortalized) cells simulating the DD state, as well as to examine the ZGJTJY intervention effects, both in vivo and in vitro. Methods We subjected Sprague Dawley rats to a high-fat diet, streptozotocin, and unpredictable chronic mild stress; subsequently, we orally administered ZGJTJY. HAPI cells were induced using high glucose and corticosterone; subsequently, ZGJTJY-containing serum was added to examine changes in M1/M2 microglial polarization. Moreover, metformin combined with fluoxetine (DMGB/F) was used as a positive drug for evaluating the ZGJTJY intervention. Laser confocal scanning was used to examine the microglial morphology. Further, real-time PCR was used to determine M1 markers (MHCII, iNOS, MCP-1, CD11b), M2 markers (Arg1, Mrc1, Ym1), pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and anti-inflammatory cytokines (IL-4, IL-10). Additionally, an enzyme-linked immunosorbent assay was used to examine inflammatory cytokines. Results There was significant activation of M1 polarization in the hippocampus of DD rats and HAPI cells induced using high glucose and corticosterone. Compared with DMGB/F, ZGJTJY inhibited and promoted M1 and M2 polarization, respectively; moreover, it decreased the M1-to-M2 polarization ratio both in vivo and in vitro. Conclusions The study indicated that hippocampal M1 polarization is crucially involved in DD pathogenesis; moreover, there is a need for further research on the neuroprotective effect of Chinese medicine associated with M2-polarized microglia.

scholarly journals L-Theanine Reduced the Development of Knee Osteoarthritis in Rats via Its Anti-Inflammation and Anti-Matrix Degradation Actions: In Vivo and In Vitro Study

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1988 ◽  
Author(s):  
Hui Bai ◽  
Zhiheng Zhang ◽  
Yue Li ◽  
Xiaopeng Song ◽  
Tianwen Ma ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Quantitative Polymerase Chain Reaction ◽  
Hydrolytic Enzyme ◽  
Enzyme Linked Immunosorbent Assay ◽  
Matrix Degradation ◽  
In Vivo Animal Model

The etiology of osteoarthritis (OA) is multifactorial, with no effective disease-modifying-drugs. L-theanine has been reported to inhibit inflammatory responses in some diseases and this study aimed to investigate the effect of L-theanine on Interleukin-1(IL-1)β-stimulated chondrocytes, and in an injury-induced OA rat model. Primary chondrocytes were stimulated by IL-1β (10 ng/mL) for 24 h and then co-cultured with L-theanine for 24 h. The effects of L-theanine on IL-1β-stimulated expression of pro-inflammatory cytokines and hydrolytic enzyme were analyzed using Western blotting, quantitative polymerase chain reaction (q-PCR) and enzyme-linked immunosorbent assay (ELISA) kits. An immunofluorescence assay was used to detect nuclear factor kappa B (NF-κB) phosphorylation. OA was induced by anterior cruciate ligament transection (ACLT) surgery in rats and celecoxib was used as a positive control. OA severity was measured using the Osteoarthritis Research Society International (OARSI) grading system to describe histological changes. The results showed that L-theanine decreased the expression of pro-inflammatory mediators, including cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE-2), inducible nitric oxide synthase (iNOS), and nitric oxide (NO), both in vivo and in vitro. L-theanine treatment inhibited IL-1β-induced upregulation of matrix metalloproteinases (MMP)-3 and MMP-13, as well as inhibited NF-κB p65 activation. In vivo animal model showed that L-theanine administration (200 mg/kg) significantly alleviated OA lesions and decreased OARSI score. Our data indicated that L-theanine decreased inflammatory cytokines and protected extracellular matrix degradation through inhibition of the NF-κB pathway, and L-theanine may be considered a promising therapeutic strategy in OA prevention.

miR‐15b‐5p ameliorated high glucose‐induced podocyte injury through repressing apoptosis, oxidative stress, and inflammatory responses by targeting Sema3A

2019 ◽  
Vol 234 (11) ◽  
pp. 20869-20878 ◽  
Author(s):  
Yanqin Fu ◽  
Chongxian Wang ◽  
Dongming Zhang ◽  
Xiaojing Chu ◽  
Yuanyuan Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
High Glucose ◽  
Inflammatory Responses ◽  
Podocyte Injury

Long noncoding RNA OIP5-AS1 overexpression promotes viability and inhibits high glucose-induced oxidative stress of cardiomyocytes by targeting microRNA-34a/SIRT1 axis in diabetic cardiomyopathy

2020 ◽  
Vol 21 ◽  
Author(s):  
Haiyun Sun ◽  
Chong Wang ◽  
Ying Zhou ◽  
Xingbo Cheng
Keyword(s):  
Oxidative Stress ◽  
Protein Expression ◽  
Diabetic Cardiomyopathy ◽  
High Glucose ◽  
Long Noncoding Rna ◽  
Noncoding Rna ◽  
Luciferase Reporter ◽  
H9c2 Cells ◽  
Promoting Effect

Objective: Diabetic cardiomyopathy (DCM) is an important complication of diabetes. This study was attempted to discover the effects of long noncoding RNA OIP5-AS1 (OIP5-AS1) on the viability and oxidative stress of cardiomyocyte in DCM. Methods: The expression of OIP5-AS1 and microRNA-34a (miR-34a) in DCM was detected by qRT-PCR. In vitro, DCM was simulated by high glucose (HG, 30 mM) treatment in H9c2 cells. The viability of HG (30 mM)-treated H9c2 cells was examined by MTT assay. The reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were used to evaluate the oxidative stress of HG (30 mM)-treated H9c2 cells. Dual-luciferase reporter assay was used to confirm the interactions among OIP5-AS1, miR-34a and SIRT1. Western blot was applied to analyze the protein expression of SIRT1. Results: The expression of OIP5-AS1 was down-regulated in DCM, but miR-34a was up-regulated. The functional experiment stated that OIP5-AS1 overexpression increased the viability and SOD level, while decreased the ROS and MDA levels in HG (30 mM)-treated H9c2 cells. The mechanical experiment confirmed that OIP5-AS1 and SIRT1 were both targeted by miR-34a with the complementary binding sites at 3′UTR. MiR-34a overexpression inhibited the protein expression of SIRT1. In the feedback experiments, miR-34a overexpression or SIRT1 inhibition weakened the promoting effect on viability, and mitigated the reduction effect on oxidative stress caused by OIP5-AS1 overexpression in HG (30 mM)-treated H9c2 cells. Conclusions: OIP5-AS1 overexpression enhanced viability and attenuated oxidative stress of cardiomyocyte via regulating miR-34a/SIRT1 axis in DCM, providing a new therapeutic target for DCM.

scholarly journals Fucoxanthin Ameliorates Oxidative Stress and Airway Inflammation in Tracheal Epithelial Cells and Asthmatic Mice

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1311
Author(s):  
Shu-Ju Wu ◽  
Chian-Jiun Liou ◽  
Ya-Ling Chen ◽  
Shu-Chen Cheng ◽  
Wen-Chung Huang
Keyword(s):  
Oxidative Stress ◽  
Epithelial Cells ◽  
Airway Inflammation ◽  
Inflammatory Cytokines ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Eosinophil Infiltration ◽  
Tracheal Epithelial Cells ◽  
Tracheal Epithelial ◽  
And Oxidative Stress

Fucoxanthin is isolated from brown algae and was previously reported to have multiple pharmacological effects, including anti-tumor and anti-obesity effects in mice. Fucoxanthin also decreases the levels of inflammatory cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. The purpose of the present study was to investigate the effects of fucoxanthin on the oxidative and inflammatory responses in inflammatory human tracheal epithelial BEAS-2B cells and attenuated airway hyperresponsiveness (AHR), airway inflammation, and oxidative stress in asthmatic mice. Fucoxanthin significantly decreased monocyte cell adherence to BEAS-2B cells. In addition, fucoxanthin inhibited the production of pro-inflammatory cytokines, eotaxin, and reactive oxygen species in BEAS-2B cells. Ovalbumin (OVA)-sensitized mice were treated by intraperitoneal injections of fucoxanthin (10 mg/kg or 30 mg/kg), which significantly alleviated AHR, goblet cell hyperplasia and eosinophil infiltration in the lungs, and decreased Th2 cytokine production in the BALF. Furthermore, fucoxanthin significantly increased glutathione and superoxide dismutase levels and reduced malondialdehyde (MDA) levels in the lungs of asthmatic mice. These data demonstrate that fucoxanthin attenuates inflammation and oxidative stress in inflammatory tracheal epithelial cells and improves the pathological changes related to asthma in mice. Thus, fucoxanthin has therapeutic potential for improving asthma.

scholarly journals Circ-ACTR2 aggravates the high glucose-induced cell dysfunction of human renal mesangial cells through mediating the miR-205-5p/HMGA2 axis in diabetic nephropathy

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jie Yun ◽  
Jinyu Ren ◽  
Yufei Liu ◽  
Lijuan Dai ◽  
Liqun Song ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetic Nephropathy ◽  
High Glucose ◽  
Cell Injury ◽  
Mesangial Cells ◽  
Protein Detection ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Dysfunction

Abstract Background Circular RNAs (circRNAs) have been considered as pivotal biomarkers in Diabetic nephropathy (DN). CircRNA ARP2 actin-related protein 2 homolog (circ-ACTR2) could promote the HG-induced cell injury in DN. However, how circ-ACTR2 acts in DN is still unclear. This study aimed to explore the molecular mechanism of circ-ACTR2 in DN progression, intending to provide support for the diagnostic and therapeutic potentials of circ-ACTR2 in DN. Methods RNA expression analysis was conducted by the quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Cell growth was measured via Cell Counting Kit-8 and EdU assays. Inflammatory response was assessed by Enzyme-linked immunosorbent assay. The protein detection was performed via western blot. Oxidative stress was evaluated by the commercial kits. The molecular interaction was affirmed through dual-luciferase reporter and RNA immunoprecipitation assays. Results Circ-ACTR2 level was upregulated in DN samples and high glucose (HG)-treated human renal mesangial cells (HRMCs). Silencing the circ-ACTR2 expression partly abolished the HG-induced cell proliferation, inflammation and extracellular matrix accumulation and oxidative stress in HRMCs. Circ-ACTR2 was confirmed as a sponge for miR-205-5p. Circ-ACTR2 regulated the effects of HG on HRMCs by targeting miR-205-5p. MiR-205-5p directly targeted high-mobility group AT-hook 2 (HMGA2), and HMGA2 downregulation also protected against cell injury in HG-treated HRMCs. HG-mediated cell dysfunction was repressed by miR-205-5p/HMGA2 axis. Moreover, circ-ACTR2 increased the expression of HMGA2 through the sponge effect on miR-205-5p in HG-treated HRMCs. Conclusion All data have manifested that circ-ACTR2 contributed to the HG-induced DN progression in HRMCs by the mediation of miR-205-5p/HMGA2 axis.

scholarly journals Selenium deficiency induces spleen pathological changes in pigs by decreasing selenoprotein expression, evoking oxidative stress, and activating inflammation and apoptosis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shuang Li ◽  
Wenjuan Sun ◽  
Kai Zhang ◽  
Jiawei Zhu ◽  
Xueting Jia ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
The Body ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Antioxidant Systems ◽  
Tunel Staining ◽  
White Pulp ◽  
Sibling Pairs ◽  
Se Deficiency ◽  
Spleen Index

Abstract Background The immune system is one aspect of health that is affected by dietary selenium (Se) levels and selenoprotein expression. Spleen is an important immune organ of the body, which is directly involved in cellular immunity. However, there are limited reports on Se levels and spleen health. Therefore, this study established a Se-deficient pig model to investigate the mechanism of Se deficiency-induced splenic pathogenesis. Methods Twenty-four pure line castrated male Yorkshire pigs (45 days old, 12.50 ± 1.32 kg, 12 full-sibling pairs) were divided into two equal groups and fed Se-deficient diet (0.007 mg Se/kg) or Se-adequate diet (0.3 mg Se/kg) for 16 weeks. At the end of the trial, blood and spleen were collected to assay for erythroid parameters, the osmotic fragility of erythrocytes, the spleen index, histology, terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining, Se concentrations, the selenogenome, redox status, and signaling related inflammation and apoptosis. Results Dietary Se deficiency decreased the erythroid parameters and increased the number of osmotically fragile erythrocytes (P < 0.05). The spleen index did not change, but hematoxylin and eosin and TUNEL staining indicated that the white pulp decreased, the red pulp increased, and splenocyte apoptosis occurred in the Se deficient group. Se deficiency decreased the Se concentration and selenoprotein expression in the spleen (P < 0.05), blocked the glutathione and thioredoxin antioxidant systems, and led to redox imbalance. Se deficiency activated the NF-κB and HIF-1α transcription factors, thus increasing pro-inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17, and TNF-α), decreasing anti-inflammatory cytokines (IL-10, IL-13, and TGF-β) and increasing expression of the downstream genes COX-2 and iNOS (P < 0.05), which in turn induced inflammation. In addition, Se-deficiency induced apoptosis through the mitochondrial pathway, upregulated apoptotic genes (Caspase3, Caspase8, and Bak), and downregulated antiapoptotic genes (Bcl-2) (P < 0.05) at the mRNA level, thus verifying the results of TUNEL staining. Conclusions These results indicated that Se deficiency induces spleen injury through the regulation of selenoproteins, oxidative stress, inflammation and apoptosis.

scholarly journals Camu-Camu Fruit Extract Inhibits Oxidative Stress and Inflammatory Responses by Regulating NFAT and Nrf2 Signaling Pathways in High Glucose-Induced Human Keratinocytes

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3174
Author(s):  
Nhung Quynh Do ◽  
Shengdao Zheng ◽  
Bom Park ◽  
Quynh T. N. Nguyen ◽  
Bo-Ram Choi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathways ◽  
High Glucose ◽  
Skin Diseases ◽  
Inflammatory Responses ◽  
Human Keratinocytes ◽  
Related Factor ◽  
Nuclear Factor ◽  
Fruit Extract ◽  
Activated T Cells

Myrciaria dubia (HBK) McVaugh (camu-camu) belongs to the family Myrtaceae. Although camu-camu has received a great deal of attention for its potential pharmacological activities, there is little information on the anti-oxidative stress and anti-inflammatory effects of camu-camu fruit in skin diseases. In the present study, we investigated the preventative effect of 70% ethanol camu-camu fruit extract against high glucose-induced human keratinocytes. High glucose-induced overproduction of reactive oxygen species (ROS) was inhibited by camu-camu fruit treatment. In response to ROS reduction, camu-camu fruit modulated the mitogen-activated protein kinases (MAPK)/activator protein-1 (AP-1), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and nuclear factor of activated T cells (NFAT) signaling pathways related to inflammation by downregulating the expression of proinflammatory cytokines and chemokines. Furthermore, camu-camu fruit treatment activated the expression of nuclear factor E2-related factor 2 (Nrf2) and subsequently increased the NAD(P)H:quinone oxidoreductase1 (NQO1) expression to protect keratinocytes against high-glucose-induced oxidative stress. These results indicate that camu-camu fruit is a promising material for preventing oxidative stress and skin inflammation induced by high glucose level.

scholarly journals Enhancing the Nrf2 Antioxidant Signaling Provides Protection Against Trichloroethene-mediated Inflammation and Autoimmune Response

2020 ◽  
Vol 175 (1) ◽  
pp. 64-74 ◽  
Author(s):  
Nivedita Banerjee ◽  
Hui Wang ◽  
Gangduo Wang ◽  
M Firoze Khan
Keyword(s):  
Oxidative Stress ◽  
T Cells ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Autoimmune Response ◽  
Mediated Effects ◽  
Antioxidant Gene Expression ◽  
Responsive Element

Abstract Trichloroethene (trichloroethylene, TCE) and one of its reactive metabolites dichloroacetyl chloride (DCAC) are associated with the induction of autoimmunity in MRL+/+ mice. Although oxidative stress plays a major role in TCE-/DCAC-mediated autoimmunity, the underlying molecular mechanisms still need to be delineated. Nuclear factor (erythroid-derived 2)-like2 (Nrf2) is an oxidative stress-responsive transcription factor that binds to antioxidant responsive element (ARE) and provides protection by regulating cytoprotective and antioxidant gene expression. However, the potential of Nrf2 in the regulation of TCE-/DCAC-mediated autoimmunity is not known. This study thus focused on establishing the role of Nrf2 and consequent inflammatory responses in TCE-/DCAC-mediated autoimmunity. To achieve this, we pretreated Kupffer cells (KCs) or T cells with/without tert-butylhydroquinone (tBHQ) followed by treatment with DCAC. In both KCs and T cells, DCAC treatment significantly downregulated Nrf2 and HO-1 expression along with induction of Keap-1 and caspase-3, NF-κB (p65), TNF-α, and iNOS, whereas pretreatment of these cells with tBHQ attenuated these responses. The in vitro findings were further verified in vivo by treating female MRL+/+ mice with TCE along with/without sulforaphane. TCE exposure in mice also led to reduction in Nrf2 and HO-1 but increased phospho-NF-κB (p-p65) and iNOS along with increased anti-dsDNA antibodies. Interestingly, sulforaphane treatment led to amelioration of TCE-mediated effects, resulting in Nrf2 activation and reduction in inflammatory and autoimmune responses. Our results show that TCE/DCAC mediates an impairment in Nrf2 regulation. Attenuation of TCE-mediated autoimmunity via activation of Nrf2 supports that antioxidants sulforaphane/tBHQ could be potential therapeutic agents for autoimmune diseases.

The protective effects of carvacrol and thymol against paracetamol–induced toxicity on human hepatocellular carcinoma cell lines (HepG2)

2016 ◽  
Vol 35 (12) ◽  
pp. 1252-1263 ◽  
Author(s):  
SS Palabiyik ◽  
E Karakus ◽  
Z Halici ◽  
E Cadirci ◽  
Y Bayir ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Cytokines ◽  
Hepg2 Cells ◽  
Folk Medicine ◽  
Hepatoprotective Activity ◽  
High Dose ◽  
Protective Effects ◽  
And Oxidative Stress ◽  
Pro Inflammatory Cytokines

Acetaminophen (APAP) overdose could induce liver damage and lead to acute liver failure. The treatment of APAP overdoses could be improved by new therapeutic strategies. Thymus spp., which has many beneficial effects and has been used in folk medicine, is one such potential strategy. In the present study, the hepatoprotective activity of the main constituents of Thymus spp., carvacrol and thymol, were evaluated in light of APAP-induced hepatotoxicity. We hoped to understand the hepatoprotective mechanism of these agents on the antioxidant system and pro-inflammatory cytokines in vitro. Dose-dependent effects of thymol and carvacrol (25, 50, and 100 µM) were tested on cultured HepG2 cells. N-Acetylcysteine (NAC) was tested as positive control. We showed that APAP inhibited HepG2 cell growth by inducing inflammation and oxidative stress. Incubating APAP-exposed HepG2 cells with carvacrol and thymol for 24 h ameliorated this inflammation and oxidative stress. We also evaluated alanine transaminase and lactate dehydrogenase levels of HepG2 cells. We found that thymol and carvacrol protected against APAP-induced toxicity in HepG2 cells by increasing antioxidant activity and reducing pro-inflammatory cytokines, such as tumor necrosis factor α and interleukin 1β. Taking together high-dose thymol and carvacrol treatment has an effect close to NAC treatment in APAP toxicity, but thymol has better treatment effect than carvacrol.

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