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Fan Wu, Jinying Zhang
Epidemiological studies have confirmed that ambient fine particulate matter (PM2.5 ) exposure is associated with cardiovascular disease (CVD). However, the underlying mechanisms in PM2.5 exposure-induced heart injury are largely unknown. It has been acknowledged that NADPH oxidase (Nox) 4 plays a critical role in CVD development. To investigate the acute effects of PM2.5 on the mouse heart and the role of Nox4 in PM2.5 exposure-induced cardiac injury, C57BL/6J mice were instilled with saline or 1.5, 3.0, 6...
2018: Journal of Toxicological Sciences
Silvia Revoltella, Giorgia Baraldo, Birgit Waltenberger, Stefan Schwaiger, Philipp Kofler, Julia Moesslacher, Astrid Huber-Seidel, Konrad Pagitz, Roland Kohl, Pidder Jansen-Duerr, Hermann Stuppner
NADPH oxidase 4 (Nox4) has recently been implicated as driving force in cellular senescence. Thus, there is growing interest to develop Nox4 inhibitors, which might be valuable agents for cosmeceutical applications. Alpine plants represent a valuable source for the identification of novel bioactive natural products with anti-ageing effects, especially substances that protect plants against UV radiation, which is also known to contribute to the ageing of human skin. Therefore, the aim of this study was to identify novel Nox4 inhibitors from alpine plants...
March 14, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Rima S Zahr, Prasanthi Chappa, Hong Yin, Lou A Brown, Kenneth I Ataga, David R Archer
Recent studies have demonstrated pleiotropic effects of statins in various mouse models of kidney disease. In this study, Townes humanized sickle cell mice were treated for 8 weeks with atorvastatin at a dose of 10 mg/kg/day starting at 10 weeks of age. Treatment with atorvastatin significantly reduced albuminuria, and improved both urine concentrating ability and glomerular filtration rate. Atorvastatin also decreased markers of kidney injury and endothelial activation, and ameliorated oxidant stress in renal tissues and peripheral macrophages...
March 12, 2018: British Journal of Haematology
Ying Huang, Gui-Quan Cai, Jian-Ping Peng, Chao Shen
Based on the results from our previous study, dexamethasone (Dex) increases reactive oxygen species (ROS) levels and subsequently induces cell death and matrix catabolism in chondrocytes. Nevertheless, the mechanism underlying this phenomenon remains unclear. Nicotinamide adenine dinucleotide (phosphate) (NADPH) oxidase 4 (NOX4) is one of the major enzymes responsible for intracellular ROS production during the inflammatory process. The objective of the current study was to investigate the role of NOX4 in Dex-induced ROS over-production...
March 8, 2018: Journal of Steroid Biochemistry and Molecular Biology
Xueling Li, Weijing Cai, Kyung Lee, Bohan Liu, Yueyi Deng, Yiping Chen, Xianwen Zhang, John Cijiang He, Yifei Zhong
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
March 6, 2018: Scientific Reports
Yong Liang, Jing Xu, Yu Wang, Jia-Yu Tang, Song-Lin Yang, Hong-Guang Xiang, Shi-Xing Wu, Xiao-Juan Li
BACKGROUND/AIMS: Cerebral ischemia-reperfusion (I/R) injury involves multiple independently fatal terminal pathways. CK2α/NADPH oxidase is an important signaling pathway associated with ischemia-reperfusion injury, and miR-125b can regulate oxidative stress-related injury. In this study, we investigated whether the effect of miR-125b in rat brain I/R injury occurs through its modulation of the CK2α/NADPH oxidase pathway. METHODS: Rats were subjected to 2 h of cerebral ischemia followed by 24 h of reperfusion to establish an I/R injury model...
February 28, 2018: Cellular Physiology and Biochemistry
Jaishabanu Ameeramja, Ekambaram Perumal
Fluorosis (fluoride toxicity) seems to be reduced by plant secondary metabolites. Tamarind seed coat extract (TSCE), a mixture of procyanidins and polyphenols, possesses numerous pharmacological activities. Regardless of its beneficial properties, the underlying molecular mechanism against chronic fluorosis in vivo is not known. Hence, the present study is aimed to investigate the efficacy of TSCE against fluoride (F- )-induced pulmonary toxicity in rats. Female Wistar rats were randomly divided into four groups and treated with NaF (300 ppm in drinking water) and TSCE (100 mg/kg/bw by oral intubation) alone and in combination daily for 30 days...
March 5, 2018: Inflammation
Jing Li, Shuai Wang, Jie Bai, Xiao-Lei Yang, Yun-Long Zhang, Yi-Lin Che, Hui-Hua Li, Yan-Zong Yang
Angiotensin II (Ang II) and inflammation are associated with pathogenesis of atrial fibrillation (AF), but the underlying molecular mechanisms of these events remain unknown. The immunoproteasome has emerged as a critical regulator of inflammatory responses. Here, we investigated its role in Ang II-induced AF in immunosubunit PSMB10 (also known as β2i or LMP10) knockout (KO) mice. AF was induced by Ang II infusion (2000 ng/min per kg). PSMB10 expression and trypsin-like activity were increased in atrial tissues and serum from Ang II-treated mice or serum from patients with AF...
March 5, 2018: Hypertension
Hyun-Kyoung Kim, Geum-Hwa Lee, Kashi Raj Bhattarai, Raghu Patil Junjappa, Hwa-Young Lee, Mallikarjun Handigund, Anu Marahatta, Bidur Bhandary, In-Hwan Baek, Jae Sung Pyo, Hye-Kyung Kim, Ok Hee Chai, Hyung-Ryong Kim, Yong-Chul Lee, Han-Jung Chae
Hyperactivation of phosphoinositol 3-kinase (PI3K) has been suggested to be a potential mechanism for endoplasmic reticulum (ER) stress-enhanced airway hyperresponsiveness, and PI3K inhibitors have been examined as asthma therapeutics. However, the regulatory mechanism linking PI3K to ER stress and related pathological signals in asthma have not been defined. To elucidate these pathogenic pathways, we investigated the influence of a selective PI3Kδ inhibitor, IC87114, on airway inflammation in an ovalbumin/lipopolysaccharide (OVA/LPS)-induced asthma model...
February 16, 2018: Experimental & Molecular Medicine
Fabiana Blanco, Suvi E Heinonen, Erika Gurzeler, Lisa M Berglund, Anna-Maria Dutius Andersson, Olga Kotova, Ann-Cathrine Jönsson-Rylander, Seppo Ylä-Herttuala, Maria F Gomez
AIMS: Despite vast clinical experience linking diabetes and atherosclerosis, the molecular mechanisms leading to accelerated vascular damage are still unclear. Here, we investigated the effects of nuclear factor of activated T-cells inhibition on plaque burden in a novel mouse model of type 2 diabetes that better replicates human disease. METHODS & RESULTS: IGF-II/LDLR-/- ApoB100/100 mice were generated by crossbreeding low-density lipoprotein receptor-deficient mice that synthesize only apolipoprotein B100 (LDLR-/- ApoB100/100 ) with transgenic mice overexpressing insulin-like growth factor-II in pancreatic β cells...
March 1, 2018: Diabetes & Vascular Disease Research
Chao-Tao Tang, Xiao-Lu Lin, Shan Wu, Qian Liang, Li Yang, Yun-Jie Gao, Zhi-Zheng Ge
NADPH Oxidase 4 (NOX4), a member of the NOX family, has emerged as a significant source of reactive oxygen species, playing an important role in tumor cell proliferation, apoptosis, and other physiological processes. However, the potential function of NOX4 in gastric cancer (GC) cell proliferation is yet unknown. The aim of this study was to illustrate whether NOX4 plays a role in regulating gastric cancer cell growth. First, the clinical information from 90 patients was utilized to explore the clinical value of NOX4 as a predictive tool for tumor size and prognosis...
February 26, 2018: Cellular Signalling
Qian Shi, Suryavathi Viswanadhapalli, William E Friedrichs, Chakradhar Velagapudi, Cédric Szyndralewiez, Shweta Bansal, Manzoor A Bhat, Goutam Ghosh Choudhury, Hanna E Abboud
The mechanism by which TSC2 inactivation or deficiency contributes to the pathology of tuberous sclerosis complex (TSC) is not fully clear. We show that renal angiomyolipomas from TSC patients and kidney cortex from Tsc2+/- mice exhibit elevated levels of reactive oxygen species (ROS). Downregulation of tuberin (protein encoded by TSC2 gene) in renal proximal tubular epithelial cells significantly increased ROS concomitant with enhanced Nox4. Similarly, we found elevated levels of Nox4 in the renal cortex of Tsc2+/- mice and in the renal angiomyolipomas from TSC patients...
February 28, 2018: Scientific Reports
Xiaoyan Zhou, Jie Weng, Jing Xu, Qiulin Xu, Weiju Wang, Weijin Zhang, Qiaobing Huang, Xiaohua Guo
BACKGROUND/AIMS: Disruption of endothelial barrier integrity in response to advanced glycation end products (AEGs) stimulation contributes to vasculopathy associated with diabetes mellitus. Mammalian diaphanous-related formin (mDia1) has been reported to bind to the cytoplasmic domain of the receptor for advanced glycation end products (RAGE), which induces a series of cellular processes. This study directly evaluated the participation of mDia1 in AGE-induced hyperpermeability and revealed the precise intracellular signal transductions of this pathological process...
February 23, 2018: Cellular Physiology and Biochemistry
Ying Meng, Miao-Xia Pan, Bo-Jun Zheng, Yan Chen, Wei Li, Qian-Jie Yang, Ze-Mao Zheng, Na-Na Sun, Yue Zhang, Xu Li
<b><i>Aims:</i></b> The NLRP3 (NOD-like receptor family pyrin domain containing 3) inflammasome, which is activated by reactive oxygen species (ROS) and respressed by autophagy, has been identified as a novel agent of pulmonary fibrosis. Angiotensin II (AngII), the bioactive pro-oxidant in the renin-angiotensin system (RAS), aggravates lung fibrosis. However, the effect of AngII on NLRP3 inflammasome and autophagy in lung fibrosis remains unknown. <i><b>Objective:</b></i> To investigate a potential link between AngII, redox balance, autophagy and the NLRP3 inflammasome, which determines extracellular matrix accumulation in lung fibrosis...
February 27, 2018: Antioxidants & Redox Signaling
Jia-Fu Ji, Wan-Zhen Jiao, Yan Cheng, Hua Yan, Fan Su, Li-Li Chi
BACKGROUND/AIMS: Nonalcoholic steatohepatitis includes steatosis along with liver inflammation, hepatocyte injury and fibrosis. In this study, we investigated the protective role and the potential mechanisms of a traditional Chinese medicine ShenFu (SF) preparation in an in vitro hepatic steatosis model. METHODS: In palmitic acid (PA)-induced murine hepatic AML12 cell injury, effects of SF preparation on cellular apoptosis and intracellular triglyceride (iTG) level were assessed using TUNEL and TG Colorimetric Assay...
February 21, 2018: Cellular Physiology and Biochemistry
Jingjing Ma, Min Shi, Xiangcheng Zhang, Xiaoning Liu, Juan Chen, Ridong Zhang, Xingzhou Wang, Hong Zhang
The present study aimed to investigate the mechanism of glucagon‑like peptide‑1 receptor (GLP‑1R) agonists in the progression of diabetic peripheral neuropathy (DPN) in streptozotocin (STZ)‑induced diabetic rats, through inflammatory signaling pathways. The DPN rat model was generated by intraperitoneal injection of STZ and then treated with the GLP‑1R agonist liraglutide or saline for 8 weeks. These animals were randomly divided into 4 groups (10 rats in each): The normal control + saline group, the normal control + liraglutide group, the diabetic + saline (DM) group and the diabetic + liraglutide (DML) group...
February 23, 2018: International Journal of Molecular Medicine
Keerati Wanchai, Sakawdaurn Yasom, Wannipa Tunapong, Titikorn Chunchai, Parameth Thiennimitr, Chaiyavat Chaiyasut, Anchalee Pongchaidecha, Varanuj Chatsudthipong, Siriporn Chattipakorn, Nipon Chattipakorn, Anusorn Lungkaphin
Obesity is health issue worldwide, which can lead to kidney dysfunction. Prebiotics are non-digestible foods that have beneficial effects on health. This study aimed to investigate the effects of xylooligosaccharide (XOS) on renal function, renal organic anion transporter 3 (Oat3) and the mechanisms involved. High-fat diet was provided for 12 weeks in male Wistar rats. After that, the rats were divided into normal diet (ND); normal diet treated with XOS (NDX); high-fat diet (HF) and high-fat diet treated with XOS (HFX)...
April 2018: Journal of Endocrinology
Jaya Gautam, Suhrid Banskota, Sajita Shah, Jun-Goo Jee, Eunju Kwon, Ying Wang, Dong Young Kim, Hyun Wook Chang, Jung-Ae Kim
BACKGROUND AND PURPOSE: In this study, we examined that 4-hydroxynonenal (4-HNE) acts as a ligand for GPR109A, which elicits both anti-inflammatory and cell death responses. EXPERIMENTAL APPROACH: Agonistic activity of 4-HNE was determined by observing the inhibition of cAMP generation in CHO-K1-GPR109A-Gi cell line, surface plasmon resonance (SPR) binding assay, and competition binding assay with [3 H]niacin. 4-HNE-mediated signaling pathways and cellular responses were investigated in GPR109A-expressing and -non-expressing cells...
February 23, 2018: British Journal of Pharmacology
Francesc Jiménez-Altayó, Thayna Meirelles, Eva Crosas-Molist, M Alba Sorolla, Darya Gorbenko Del Blanco, Judit López-Luque, Aleksandra Mas-Stachurska, Ana-Maria Siegert, Fabio Bonorino, Laura Barberà, Carolina García, Enric Condom, Marta Sitges, Fernando Rodríguez-Pascual, Francisco Laurindo, Katrin Schröder, Joaquim Ros, Isabel Fabregat, Gustavo Egea
Marfan syndrome (MFS) is characterized by the formation of ascending aortic aneurysms resulting from altered assembly of extracellular matrix fibrillin-containing microfibrils and dysfunction of TGF-β signaling. Here we identify the molecular targets of redox stress in aortic aneurysms from MFS patients, and investigate the role of NOX4, whose expression is strongly induced by TGF-β, in aneurysm formation and progression in a murine model of MFS. Working models included aortae and cultured vascular smooth muscle cells (VSMC) from MFS patients, and a NOX4-deficient Marfan mouse model (Fbn1C1039G/+ -Nox4-/- )...
February 19, 2018: Free Radical Biology & Medicine
Chengfang Yang, Li Li, Zuheng Ma, Yujuan Zhong, Wenxiao Pang, Meili Xiong, Shuping Fang, Yongwen Li
The present study aimed to investigate the hepatoprotective effects of methyl ferulic acid (MFA) against oxidative stress and apoptosis in acute liver injury induced by carbon tetrachloride (CCl4 ) in rats, as well as the underlying mechanisms. Sprague Dawley rats were treated with CCl4 after oral administration of MFA (25, 50, and 100 mg/kg) or dimethyl diphenyl bicarboxylate (200 mg/kg) for 7 days. The hepatoprotective effects of MFA were determined by analyzing serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities as well as changes of oxidant parameters...
March 2018: Experimental and Therapeutic Medicine
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