scholarly journals HDL Inhibited Atherosclerosis Induced by Radiation Injury

2020 ◽  
Author(s):  
Jin Xie ◽  
Ke Zhu ◽  
Qingya Wang ◽  
Pei Zhao ◽  
Lihua Pan ◽  
...  
Keyword(s):  
Western Blotting ◽  
Cell Damage ◽  
Blood Lipid ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Uvb Radiation ◽  
Aortic Endothelial Cells ◽  
Akt Phosphorylation ◽  
Apoptosis Protein ◽  
Apoptosis Process

Abstract Background- HDL inhibits atherosclerosis development from radiation damage, nonetheless, the underlying mechanism is yet to be defined.Methods-This study used radiation patients along with cultured mouse aortic endothelial cells (MAECs) to investigate the process. Firstly, 158 patients from the oncology department of Jingzhou hospital who received radiation after neck cancers participated, and their arterial function was monitored by B ultrasound. Similarly, HDL and other blood lipid indexes were also tested. Then, MAECs were isolated and cultured and passed through MTT assay to test the HDL protective role on UVB radiation along with western blotting to test some apoptosis protein expression and possible molecules.Results-Firstly, those patients with high HDL levels were less likely to develop atherosclerosis, with statistical differences. We observed that MAECs treated with UVB were damaged significantly however HDL reversed the cell damage in a dose-depended manner. In the meantime, the apoptosis process was assessed and found that HDL inhibited the apoptosis caused by UVB. Western blotting results showed that HDL enhanced phosphatidylinositol 3-kinase (PI3K) in addition to Akt phosphorylation in MAECs.Conclusion-These results suggest that HDL protected UVB-mediated apoptosis by activation of a mechanism involving PI3K/Akt signaling pathway.

scholarly journals HDL Inhibited Atherosclerosis Induced by Radiation Injury

2020 ◽  
Author(s):  
Jin Xie ◽  
Ke Zhu ◽  
Qingya Wang ◽  
Pei Zhao ◽  
Lihua Pan ◽  
...  
Keyword(s):  
Western Blotting ◽  
Cell Damage ◽  
Blood Lipid ◽  
Protective Role ◽  
Uvb Radiation ◽  
Phosphatidylinositol 3 Kinase ◽  
Aortic Endothelial Cells ◽  
Akt Phosphorylation ◽  
Atherosclerosis Development ◽  
Apoptosis Process

Abstract Background- HDL inhibits atherosclerosis development from radiation damage; however, the mechanism for this process has not been fully defined. Methods- This study used radiation patients and cultured mouse aortic endothelial cells (MAECs) to investigate the process. Firstly, 158 patients from oncology department of Jingzhou hospital who have got radiation after neck cancers, the arterial function was monitored by B ultrasound, HDL and other blood lipid indexes were tested.Then, MAECs were isolated and cultured, MTT assay was used to test the HDL protective role on UVB radiation, along with this, western blotting was proceed to test some apotosis protein expression and possible molecular.Results- Firstly, those patients with high HDL levels were less likely to develop atherosclerosis, with statistical differences. We observed that MAECs treated with UVB was damaged significantly; HDL reversed the cell damage as dose-depended manner. At mean time, the apoptosis process was assessed and found that HDL inhibited the apoptosis caused by UVB. Western blotting results showed that HDL enhanced phosphatidylinositol 3-kinase (PI3K) and Akt phosphorylation in MAECs.Conclusion- These results suggest that HDL protected UVB-mediated appotosis by activation of a mechanism involving PI3K/Akt signal pathway.

Nitric Oxide in Life and Death of Neutrophils

2019 ◽  
Vol 26 (31) ◽  
pp. 5764-5780 ◽  
Author(s):  
Svetlana I. Galkina ◽  
Ekaterina A. Golenkina ◽  
Galina M. Viryasova ◽  
Yulia M. Romanova ◽  
Galina F. Sud’ina
Keyword(s):  
Nitric Oxide ◽  
Cell Damage ◽  
Protective Role ◽  
Neutrophil Apoptosis ◽  
High Biological Activity ◽  
Life And Death ◽  
Signalling Molecule ◽  
Activated Neutrophils ◽  
Cell Death Mechanisms ◽  
Prostacyclin Synthase

Background: Nitric Oxide (NO) is a key signalling molecule that has an important role in inflammation. It can be secreted by endothelial cells, neutrophils, and other cells, and once in circulation, NO plays important roles in regulating various neutrophil cellular activities and fate. Objective: To describe neutrophil cellular responses influenced by NO and its concomitant compound peroxynitrite and signalling mechanisms for neutrophil apoptosis. Methods: Literature was reviewed to assess the effects of NO on neutrophils. Results: NO plays an important role in various neutrophil cellular activities and interaction with other cells. The characteristic cellular activities of neutrophils are adhesion and phagocytosis. NO plays a protective role in neutrophil-endothelial interaction by preventing neutrophil adhesion and endothelial cell damage by activated neutrophils. NO suppresses neutrophil phagocytic activity but stimulates longdistance contact interactions through tubulovesicular extensions or cytonemes. Neutrophils are the main source of superoxide, but NO flow results in the formation of peroxynitrite, a compound with high biological activity. Peroxynitrite is involved in the regulation of eicosanoid biosynthesis and inhibits endothelial prostacyclin synthase. NO and peroxynitrite modulate cellular 5-lipoxygenase activity and leukotriene synthesis. Long-term exposure of neutrophils to NO results in the activation of cell death mechanisms and neutrophil apoptosis. Conclusion: Nitric oxide and the NO/superoxide interplay fine-tune mechanisms regulating life and death in neutrophils.

Nano-Curcumin Regulates p53 Phosphorylation and PAI-1 Expression during Bleomycin Induced Injury in Alveolar Basal Epithelial Cells

2020 ◽  
Vol 16 (1) ◽  
pp. 85-89
Author(s):  
Mahesh M. Gouda ◽  
Ashwini Prabhu ◽  
Varsha Reddy S.V. ◽  
Rafa Jahan ◽  
Yashodhar P. Bhandary
Keyword(s):  
Epithelial Cells ◽  
Lung Injury ◽  
Molecular Mechanisms ◽  
A549 Cells ◽  
Plasminogen Activator Inhibitor ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Alveolar Epithelial Cells ◽  
Cellular Damage

Background: Bleomycin (BLM) is known to cause DNA damage in the Alveolar Epithelial Cells (AECs). It is reported that BLM is involved in the up-regulation of inflammatory molecules such as neutrophils, macrophages, chemokines and cytokines. The complex underlying mechanism for inflammation mediated progression of lung injury is still unclear. This investigation was designed to understand the molecular mechanisms associated with p53 mediated modulation of Plasminogen Activator Inhibitor-I (PAI-I) expression and its regulation by nano-curcumin formulation. Methods: A549 cells were treated with BLM to cause the cellular damage in vitro and commercially available nano-curcumin formulation was used as an intervention. Cytotoxic effect of nano-curcumin was analyzed using Methyl Thiazolyl Tetrazolium (MTT) assay. Protein expressions were analyzed using western blot to evaluate the p53 mediated changes in PAI-I expression. Results: Nano-curcumin showed cytotoxicity up to 88.5 % at a concentration of 20 μg/ml after 48 h of treatment. BLM exposure to the cells activated the phosphorylation of p53, which in turn increased PAII expression. Nano-curcumin treatment showed a protective role against phosphorylation of p53 and PAI-I expression, which in turn regulated the fibro-proliferative phase of injury induced by bleomycin. Conclusion: Nano-curcumin could be used as an effective intervention to regulate the severity of lung injury, apoptosis of AECs and fibro-proliferation during pulmonary injury.

scholarly journals ANXA4 promotes trophoblast invasion via the PI3K/Akt/eNOS pathway in preeclampsia

2019 ◽  
Vol 316 (4) ◽  
pp. C481-C491 ◽  
Author(s):  
Yalan Xu ◽  
Lili Sui ◽  
Bintao Qiu ◽  
Xiuju Yin ◽  
Juntao Liu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Western Blotting ◽  
Underlying Mechanism ◽  
Trophoblast Invasion ◽  
Pathological Examination ◽  
Trophoblast Cells ◽  
Human Trophoblast ◽  
Annexin A4 ◽  
Extravillous Cytotrophoblasts ◽  
Phosphoinositide 3 Kinase

The inadequate trophoblast invasion is associated with the development of preeclampsia (PE). Considering that annexin A4 (ANXA4) enhances tumor invasion, we aimed to explore the functional role of ANXA4 in trophoblast cells and to examine the underlying mechanism. ANXA4 expression in PE placentas was analyzed using immunohistochemistry and Western blotting. Cell proliferation, invasion, and apoptosis were determined using a MTT assay, Transwell assay, and flow cytometry, respectively. The expression levels of matrix metalloproteinase (MMP)-2, MMP-9, phosphoinositide 3-kinase (PI3K), Akt, phosphorylated (p)-Akt, and phosphorylated endothelial nitric oxide synthase (p-eNOS) were detected by Western blotting. Placentas were prepared for pathological examination using hematoxylin and eosin staining and apoptosis determination using the TUNEL method. Expression of ANXA4, PI3K, p-Akt and p-eNOS was downregulated in human PE placentas and PE placenta-derived extravillous cytotrophoblasts (EVCTs). Furthermore, ANXA4 overexpression promoted cell proliferation and invasion, inhibited cell apoptosis, and upregulated protein expression of PI3K, p-Akt, and p-eNOS in human trophoblast cells HTR-8/SVneo and JEG-3. By contrast, ANXA4 knockdown exerted the opposite effects. Furthermore, inhibition of the PI3K/Akt pathway by LY294002 abrogated the ANXA4 overexpression-mediated effects on trophoblast behavior. Furthermore, eNOS knockdown abrogated the ANXA4 overexpression-induced promotion of cell invasion and MMP2/9 expression. Additionally, in N-nitro-l-arginine methyl ester (l-NAME)-induced PE rats, ANXA4 overexpression alleviated PE progression, accompanied by an increase in expression of PI3K, p-Akt, and p-eNOS in rat placentas. Our findings demonstrate that ANXA4 expression is downregulated in PE. ANXA4 may promote trophoblast invasion via the PI3K/Akt/eNOS pathway.

scholarly journals Structure based pharmacophore modeling, virtual screening, molecular docking and ADMET approaches for identification of natural anti-cancer agents targeting XIAP protein

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Firoz A. Dain Md Opo ◽  
Mohammed M. Rahman ◽  
Foysal Ahammad ◽  
Istiak Ahmed ◽  
Mohiuddin Ahmed Bhuiyan ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Md Simulation ◽  
Pharmacophore Model ◽  
Pharmacophore Modeling ◽  
Drug Candidate ◽  
Inhibitor Of Apoptosis ◽  
Inhibitor Of Apoptosis Protein ◽  
Apoptosis Protein ◽  
Apoptosis Process

AbstractX-linked inhibitor of apoptosis protein (XIAP) is a member of inhibitor of apoptosis protein (IAP) family responsible for neutralizing the caspases-3, caspases-7, and caspases-9. Overexpression of the protein decreased the apoptosis process in the cell and resulting development of cancer. Different types of XIAP antagonists are generally used to repair the defective apoptosis process that can eliminate carcinoma from living bodies. The chemically synthesis compounds discovered till now as XIAP inhibitors exhibiting side effects, which is making difficulties during the treatment of chemotherapy. So, the study has design to identifying new natural compounds that are able to induce apoptosis by freeing up caspases and will be low toxic. To identify natural compound, a structure-based pharmacophore model to the protein active site cavity was generated following by virtual screening, molecular docking and molecular dynamics (MD) simulation. Initially, seven hit compounds were retrieved and based on molecular docking approach four compounds has chosen for further evaluation. To confirm stability of the selected drug candidate to the target protein the MD simulation approach were employed, which confirmed stability of the three compounds. Based on the finding, three newly obtained compounds namely Caucasicoside A (ZINC77257307), Polygalaxanthone III (ZINC247950187), and MCULE-9896837409 (ZINC107434573) may serve as lead compounds to fight against the treatment of XIAP related cancer, although further evaluation through wet lab is necessary to measure the efficacy of the compounds.

MyD88-Dependent Glucose Restriction and Itaconate Production Control Brucella Infection

2021 ◽  
Author(s):  
Carolyn A. Lacey ◽  
Bárbara Ponzilacqua-Silva ◽  
Catherine A. Chambers ◽  
Alexis S. Dadelahi ◽  
Jerod A. Skyberg
Keyword(s):  
Glucose Transporter ◽  
Production Control ◽  
Brucella Melitensis ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Ifn Γ ◽  
Glucose Restriction ◽  
Myd88 Signaling

Brucellosis is one of the most common global zoonoses and is caused by facultative intracellular bacteria of the genus Brucella . Numerous studies have found that MyD88 signaling contributes to protection against Brucella , however the underlying mechanism has not been entirely defined. Here we show that MyD88 signaling in hematopoietic cells contributes both to inflammation and to control of Brucella melitensis infection in vivo . While the protective role of MyD88 in Brucella infection has often been attributed to promotion of IFN-γ production, we found that MyD88 signaling restricts host colonization by B. melitensis even in the absence of IFN-γ. In vitro , we show that MyD88 promotes macrophage glycolysis in response to B. melitensis . Interestingly, a B. melitensis mutant lacking the glucose transporter, GluP, was more highly attenuated in MyD88 -/- than in WT mice, suggesting MyD88 deficiency results in an increased availability of glucose in vivo which Brucella can exploit via GluP. Metabolite profiling of macrophages identified several metabolites regulated by MyD88 in response to B. melitensis , including itaconate. Subsequently, we found that itaconate has antibacterial effects against Brucella and also regulates the production of pro-inflammatory cytokines in B. melitensis -infected macrophages. Mice lacking the ability to produce itaconate were also more susceptible to B. melitensis in vivo . Collectively, our findings indicate that MyD88-dependent changes in host metabolism contribute to control of Brucella infection.

scholarly journals Protective role of ABCG2 against oxidative stress in colorectal cancer and its potential underlying mechanism

2018 ◽  
Author(s):  
Shuang Nie ◽  
Yaqing Huang ◽  
Mengyue Shi ◽  
Xuetian Qian ◽  
Hongzhen Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Underlying Mechanism ◽  
Protective Role

scholarly journals Ferulic Acid Attenuates TGF-β1-Induced Renal Cellular Fibrosis in NRK-52E Cells by Inhibiting Smad/ILK/Snail Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Ming-gang Wei ◽  
Wei Sun ◽  
Wei-ming He ◽  
Li Ni ◽  
Yan-yu Yang
Keyword(s):  
Ferulic Acid ◽  
Western Blotting ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Underlying Mechanism ◽  
Tubular Epithelial Cell ◽  
Epithelial Cell Line ◽  
Proximal Tubular ◽  
Mesenchymal Transformation ◽  
E Cadherin

Renal fibrosis is a common cause of renal dysfunction with chronic kidney disease. Central to this process is epithelial-mesenchymal transformation (EMT) of proximal tubular epithelial cells driven by transforming growth factor-β1 (TGF-β1) signaling. The present study aimed to investigate the effect of Ferulic acid (FA) on EMT of renal proximal tubular epithelial cell line (NRK-52E) induced by TGF-β1 and to elucidate its underlying mechanism against EMT related to TGF-β1/Smads pathway. The NRK-52E cells were treated for 48 h with TGF-β1 (5 ng/mL) in different concentrations of FA (0 to 200 µM). Fibronectin, a mesenchymal marker, was assessed by western blotting. Western blotting was also used to examine the EMT markers (E-cadherin, andα-smooth muscle actin (α-SMA)), signal transducer (p-Smad2/3), and EMT initiator (Snail). ILK was also assayed by western blotting. The results showed that TGF-β1 induced spindle-like morphological transition in NRK-52E cells. Smad2/3 signaling pathway activation, increased fibronectin,α-SMA, ILK, and Snail expression, and decreased E-cadherin expression in TGF-β1-treated NRK-52E cells. FA efficiently blocked P-Smad2/3 activation and attenuated all these EMT changes induced by TGF-β1. These findings suggest that FA may serve as a potential fibrosis antagonist for renal proximal tubule cells by inhibiting EMT process.

scholarly journals Micronized Palmitoylethanolamide Ameliorates Methionine- and Choline-Deficient Diet–Induced Nonalcoholic Steatohepatitis via Inhibiting Inflammation and Restoring Autophagy

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiaji Hu ◽  
Hanglu Ying ◽  
Jie Yao ◽  
Longhe Yang ◽  
Wenhui Jin ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Hepatocellular Injury ◽  
Deficient Diet ◽  
Neuroprotective Effects ◽  
Pathway Activation ◽  
Elevated Expression ◽  
Anti Inflammatory

Nonalcoholic steatohepatitis (NASH) has become one of the serious causes of chronic liver diseases, characterized by hepatic steatosis, hepatocellular injury, inflammation and fibrosis, and lack of efficient therapeutic agents. Palmitoylethanolamide (PEA) is an endogenous bioactive lipid with various pharmacological activities, including anti-inflammatory, analgesic, and neuroprotective effects. However, the effect of PEA on nonalcoholic steatohepatitis is still unknown. Our study aims to explore the potential protective role of PEA on NASH and to reveal the underlying mechanism. In this study, the C57BL/6 mice were used to establish the NASH model through methionine- and choline-deficient (MCD) diet feeding. Here, we found that PEA treatment significantly improved liver function, alleviated hepatic pathological changes, and attenuated the lipid accumulation and hepatic fibrosis in NASH mice induced by MCD diet feeding. Mechanistically, the anti-steatosis effect of PEA may be due to the suppressed expression of ACC1 and CD36, elevated expression of PPAR-α, and the phosphorylation levels of AMPK. In addition, hepatic oxidative stress was greatly inhibited in MCD-fed mice treated with PEA via enhancing the expression and activities of antioxidant enzymes, including GSH-px and SOD. Moreover, PEA exerted a clear anti-inflammatory effect though ameliorating the expression of inflammatory mediators and suppressing the NLRP3 inflammasome pathway activation. Furthermore, the impaired autophagy in MCD-induced mice was reactivated with PEA treatment. Taken together, our research suggested that PEA protects against NASH through the inhibition of inflammation and restoration of autophagy. Thus, PEA may represent an efficient therapeutic agent to treat NASH.

scholarly journals Protective role of eclipta alba against hyperlipidemia induced by high-fat diet in albino rats

2019 ◽  
Vol 10 (2) ◽  
pp. 1181-1184
Author(s):  
Satheesh Naik K ◽  
Gurushanthaiah M ◽  
Nagesh Raju G ◽  
Lokanadham S ◽  
Seshadri Reddy V
Keyword(s):  
High Fat Diet ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Albino Rats ◽  
High Fat ◽  
Serum Glutamic Oxaloacetic Transaminase ◽  
Eclipta Alba ◽  
Wistar Strain

Eclipta Alba has been used in traditional and folklore medicine to treat Hyperlipidemia and hepatic disorders. The present study was aimed to investigate the Antihyperlipidemic and hepatoprotective potentials of Eclipta Alba in high-fat diet -induced Albino rats and to determine the underlying mechanism.  A total of 30 adult albino rats of Wistar strain weighing 165–215 g were utilized. Animals were treated with high-fat diet for 8 weeks followed by post-treatment of E. Alba for 1 week, 2 weeks, and 3 weeks, respectively. After 12 h of fasting on the last day of the experiment, serum blood samples were collected in EDTA vials and processed for biochemical analysis.  A significant decrease in levels of total cholesterol and triglycerides was noted on animals treated with E. alba compared to high-fat diet animals. Treatment of hypercholesterolemic rats with E. Alba showed a marked decrease of serum low-density lipoprotein (LDL) and very LDL cholesterol concentrations compared to the hypercholesterolemic rats. High-fat diet feeding worsened the levels of serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and alkaline phosphatase enzymes, whereas the same markers were significantly improved by supplementation with E. alba compared to the normal group.  E. alba acts as an antihyperlipidemic agent in hyperlipidemic conditions and helps for better health.

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