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https://www.readbyqxmd.com/read/29141222/jnk-promotes-epithelial-cell-anoikis-by-transcriptional-and-post-translational-regulation-of-bh3-only-proteins
#1
Nomeda Girnius, Roger J Davis
Developmental morphogenesis, tissue injury, and oncogenic transformation can cause the detachment of epithelial cells. These cells are eliminated by a specialized form of apoptosis (anoikis). While the processes that contribute to this form of cell death have been studied, the underlying mechanisms remain unclear. Here, we tested the role of the cJUN NH2-terminal kinase (JNK) signaling pathway using murine models with compound JNK deficiency in mammary and kidney epithelial cells. These studies demonstrated that JNK is required for efficient anoikis in vitro and in vivo...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29139225/oolong-tea-prevents-cardiomyocyte-loss-against-hypoxia-by-attenuating-p-jnk-mediated-hypertrophy-and-enhancing-p-igf1r-p-akt-and-p-bad-ser136-activity-and-by-fortifying-nrf2-antioxidation-system
#2
Marthandam Asokan Shibu, Chia-Hua Kuo, Bih-Cheng Chen, Da-Tong Ju, Ray-Jade Chen, Chao-Hung Lai, Pei-Jane Huang, Vijaya Padma Viswanadha, Wei-Wen Kuo, Chih-Yang Huang
Tea, the most widely consumed natural beverage has been associated with reduced mortality risk from cardiovascular disease. Oolong tea is a partially fermented tea containing high levels of catechins, their degree of oxidation varies between 20%-80% causing differences in their active metabolites. In this study we examined the effect of oolong tea extract (OTE) obtained by oxidation at low-temperature for short-time against hypoxic injury and found that oolong tea provides cyto-protective effects by suppressing the JNK mediated hypertrophic effects and by enhancing the innate antioxidant mechanisms in neonatal cardiomyocytes and in H9c2 cells...
November 15, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29138815/curcumin-reverses-tobacco-smoke%C3%A2-induced-epithelial%C3%A2-mesenchymal-transition-by-suppressing-the-mapk-pathway-in-the-lungs-of-mice
#3
Zhaofeng Liang, Rui Wu, Wei Xie, Mingming Zhu, Chunfeng Xie, Xiaoting Li, Jianyun Zhu, Weiwei Zhu, Jieshu Wu, Shanshan Geng, Wenrong Xu, Caiyun Zhong, Hongyu Han
Tobacco smoke is a major risk factor for lung cancer. Epithelial‑mesenchymal transition (EMT) is decisive in cancer invasion and metastasis, and therefore promotes cancer progression. Mitogen‑activated protein kinase (MAPK) pathways are implicated in various aspects of cancer development and progression, including the EMT process. The chemopreventive effect of curcumin on carcinogenesis has been reported in vivo and in vitro. The present study investigated tobacco smoke‑induced alterations in the MAPK/activator protein‑1 (AP‑1) pathways, and pulmonary EMT changes in the lungs of mice, and further observed the chemopreventive effect of curcumin...
November 13, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29138678/febuxostat-modulates-mapk-nf-%C3%AE%C2%BAbp65-tnf-%C3%AE-signaling-in-cardiac-ischemia-reperfusion-injury
#4
Sana Irfan Khan, Rajiv Kumar Malhotra, Neha Rani, Anil Kumar Sahu, Ameesha Tomar, Shanky Garg, Tapas Chandra Nag, Ruma Ray, Shreesh Ojha, Dharamvir Singh Arya, Jagriti Bhatia
Xanthine oxidase and xanthine dehydrogenase have been implicated in producing myocardial damage following reperfusion of an occluded coronary artery. We investigated and compared the effect of febuxostat and allopurinol in an experimental model of ischemia-reperfusion (IR) injury with a focus on the signaling pathways involved. Male Wistar rats were orally administered vehicle (CMC) once daily (sham and IR + control), febuxostat (10 mg/kg/day; FEB10 + IR), or allopurinol (100 mg/kg/day; ALL100 + IR) for 14 days...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29138498/glutaredoxin-1-mediates-the-protective-effect-of-steady-laminar-flow-on-endothelial-cells-against-oxidative-stress-induced-apoptosis-via-inhibiting-bim
#5
Yao Li, Meng Ren, Xiaoqun Wang, Xingxing Cui, Hongmei Zhao, Chuanrong Zhao, Jing Zhou, Yanan Guo, Yi Hu, Chen Yan, Bradford Berk, Jing Wang
Endothelial cell apoptosis induced by oxidative stress is an early event in the development of atherosclerosis. Several antioxidant enzymes which can cope with oxidative stress are up-regulated by the anti-atherogenic laminar blood flow often seen in straight or unbranched regions of blood vessels. However, the molecular mechanism responsible for flow-induced beneficial effects is incompletely understood. Here we report the role of glutaredoxin 1 (Grx1), an antioxidant enzyme, in flow-mediated protective effect in endothelial cells...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138180/inhibition-of-vascular-c-jun-n-terminal-kinase-2-improves-obesity-induced-endothelial-dysfunction-after-roux-en-y-gastric-bypass
#6
Petia Doytcheva, Thomas Bächler, Erika Tarasco, Vincenzo Marzolla, Michael Engeli, Giovanni Pellegrini, Simona Stivala, Lucia Rohrer, Francesco Tona, Giovanni G Camici, Paul M Vanhoutte, Christian M Matter, Thomas A Lutz, Thomas F Lüscher, Elena Osto
BACKGROUND: Roux-en-Y gastric bypass (RYGB) reduces obesity-associated comorbidities and cardiovascular mortality. RYGB improves endothelial dysfunction, reducing c-Jun N-terminal kinase (JNK) vascular phosphorylation. JNK activation links obesity with insulin resistance and endothelial dysfunction. Herein, we examined whether JNK1 or JNK2 mediates obesity-induced endothelial dysfunction and if pharmacological JNK inhibition can mimic RYGB vascular benefits. METHODS AND RESULTS: After 7 weeks of a high-fat high-cholesterol diet, obese rats underwent RYGB or sham surgery; sham-operated ad libitum-fed rats received, for 8 days, either the control peptide D-TAT or the JNK peptide inhibitor D-JNKi-1 (20 mg/kg per day subcutaneous)...
November 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29137840/resolvin-d1-attenuates-imiquimod-induced-mice-psoriasiform-dermatitis-through-mapks-and-nf-%C3%AE%C2%BAb-pathways
#7
Juntao Xu, Xiaoru Duan, Feng Hu, Devesh Poorun, Xinxin Liu, Xin Wang, Song Zhang, Lu Gan, Mengwen He, Ke Zhu, Zhangyin Ming, Hongxiang Chen
BACKGROUND: Resolvin D1 (RvD1), a pro-resolution lipid mediator derived from docosahexaenoic acid (DHA), has been described to promote several kinds of inflammatory resolution. However, the effects and anti-inflammatory mechanisms of RvD1 on psoriasis have not been previously reported. OBJECTIVE: The present study aimed to determine the protective effects and the underlying mechanisms of RvD1 on imiquimod (IMQ)-induced psoriasiform dermatitis. METHODS: Mice were topically treated with IMQ to develop psoriasiform dermatitis on their shaved back, pretreated intraperitoneally (i...
November 11, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29137322/the-c-jun-n-terminal-kinase-plays-a-key-role-in-ocular-degenerative-changes-in-a-mouse-model-of-alzheimer-disease-suggesting-a-correlation-between-ocular-and-brain-pathologies
#8
Lucia Buccarello, Alessandra Sclip, Matteo Sacchi, Anna Maria Castaldo, Ilaria Bertani, Andrea ReCecconi, Silvia Maestroni, Gianpaolo Zerbini, Paolo Nucci, Tiziana Borsello
Recently a range of ocular manifestations such as retinal and lens amyloid-beta accumulation and retinal nerve fiber layer loss have been proposed as potential biomarkers in Alzheimer disease (AD). The TgCRND8 mouse model of AD exhibits age-dependent amyloid β (Aβ) oligomers accumulation and cognitive defects, amyloid plaques and hyperphosphorylated Tau deposition and inflammation. We proved the correlation between ocular pathologies and AD, observing increased levels of p-APP and p-Tau, accumulation of Aβ oligomers in the retina, eye, and optic nerve...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137154/two-sulfur-glycoside-compounds-isolated-from-lepidium-apetalum-willd-protect-nrk52e-cells-against-hypertonic-induced-adhesion-and-inflammation-by-suppressing-the-mapk-signaling-pathway-and-raas
#9
Peipei Yuan, Xiaoke Zheng, Meng Li, Yingying Ke, Yang Fu, Qi Zhang, Xiaolan Wang, Weisheng Feng
Lepidium apetalum Willd has been used to reduce edema and promote urination. Cis-desulfoglucotropaeolin (cis-DG) and trans-desulfoglucotropaeolin (trans-DG) were isolated from Lepidium apetalum Willd, and caused a significant increase in cell viability in a hypertonic model in NRK52e cells. In the hypertonic model, cis-DG and trans-DG significantly promoted the cell viability of NRK52e cells and inhibited the elevation of Na⁺ in the supernatant, inhibited the renin-angiotensin-aldosterone (RAAS) system, significantly reduced the levels of angiotensin II (Ang II) and aldosterone (ALD), and lowered aquaporin-2 (AQP2) and Na⁺-K⁺ ATP content in renal medulla...
November 12, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29136954/vaccaria-hypaphorine-impairs-rankl-induced-osteoclastogenesis-by-inhibition-of-erk-p38-jnk-and-nf-%C3%AE%C2%BAb-pathway-and-prevents-inflammatory-bone-loss-in-mice
#10
Hongxi Chen, Tongya Guo, Dianrong Wang, Rujie Qin
Osteoclasts are sole bone-resorbing cells which exert a profound effect on skeletal metabolism. The search for medicines that affect the differentiation and function of osteoclasts is crucial in developing therapies for osteoclast-based diseases. Vaccaria hypaphorine, the main active compound of the traditionally used Chinese herb Vaccaria segetalis, has anti-inflammatory activity. The present study demonstrated for the first time that vaccaria hypaphorine could significantly inhibit the receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastic differentiation in vitro and alleviate lipopolysaccharide (LPS)-induced bone loss in vivo...
November 10, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136950/a-novel-sesquiterpene-glycoside-from-loquat-leaf-alleviates-oleic-acid-induced-steatosis-and-oxidative-stress-in-hepg2-cells
#11
Tunyu Jian, Yuexian Wu, Xiaoqin Ding, Han Lv, Li Ma, Yuanyuan Zuo, Bingru Ren, Lei Zhao, Bei Tong, Jian Chen, Weilin Li
Loquat (Eriobotrya japonica) leaf has displayed beneficial effect on metabolic syndrome. In our previously study, total sesquiterpene glycosides (TSG) isolated from Loquat leaf exhibited therapeutic effect on Non-alcoholic fatty liver disease (NAFLD) in vivo, but the accurate active compound remains unknown. Sesquiterpene glycoside 1 (SG1) is a novel compound, which is exclusively isolated from Loquat leaf, but its biological activity has been rarely reported. The present study was designed to evaluate the pharmacological effect of SG1, the main component of TSG, in oleic acid (OA)-induced HepG2 cell model of NAFLD with its related mechanisms of action...
November 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136776/dihydroartemisinin-inhibits-er-stress-mediated-mitochondrial-pathway-to-attenuate-hepatocyte-lipoapoptosis-via-blocking-the-activation-of-the-pi3k-akt-pathway
#12
Xingran Chen, Mianli Bian, Chenxi Zhang, Jun Kai, Zhen Yao, Huanhuan Jin, Chunfeng Lu, Jiangjuan Shao, Anping Chen, Feng Zhang, Shizhong Zheng
Alcoholic liver disease (ALD), characterized by accumulation of fatty acids in liver cells, is usually caused by Chronic alcohol consumption. Our previous study has identified that DA protects against alcoholic liver injury in alcohol-fed rats through alleviating hepatocyte steatosis. It has emerged that saturated fatty acids could provoke endoplasmic reticulum (ER) stress and apoptosis in hepatocytes. This study was aimed to explore the impact of DA on ALD and further elaborate the underlying mechanisms. Results demonstrated that DA attenuates alcoholic liver injury in mice...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29136772/trimethylamine-n-oxide-promotes-atherosclerosis-via-cd36-dependent-mapk-jnk-pathway
#13
Jin Geng, Chenchen Yang, Bingjian Wang, Xiwen Zhang, Tingting Hu, Yang Gu, Ju Li
BACKGROUND: Many studies have identified trimethylamine N-oxide (TMAO) as a new risk factor of cardiovascular diseases. It has been suggested that TMAO promotes atherosclerosis development. However, the underlying mechanism is still unclear. METHODS: Apoe-/- mice were fed a high-fat diet and given water with or without TMAO for 8-week. Histological and immunohistological analyses were used to evaluate the atherogenic effect of TMAO in vivo. We also employed peritoneal elicited macrophages and RAW264...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29133184/jnk-is-antagonized-to-ensure-the-correct-number-of-interommatidial-cells-pattern-the-drosophila-retina
#14
Henry L Bushnell, Christina E Feiler, Kwami F Ketosugbo, Mark B Hellerman, Valerie L Nazzaro, Ruth I Johnson
Apoptosis is crucial during the morphogenesis of most organs and tissues, and is utilized for tissues to achieve their proper size, shape and patterning. Many signaling pathways contribute to the precise regulation of apoptosis. Here we show that Jun N-terminal Kinase (JNK) activity contributes to the coordinated removal of interommatidial cells via apoptosis in the Drosophila pupal retina. This is consistent with previous findings that JNK activity promotes apoptosis in other epithelia. However, we found that JNK activity is repressed by Cindr (the CIN85 and CD2AP ortholog) in order to promote cell survival...
November 10, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29132432/ac-93253-iodide-a-novel-src-inhibitor-suppresses-nsclc-progression-by-modulating-multiple-src-related-signaling-pathways
#15
Yi-Hua Lai, Sih-Yin Lin, Yu-Shan Wu, Huei-Wen Chen, Jeremy J W Chen
BACKGROUND: The tyrosine kinase Src is involved in the progression of many cancers. Moreover, inhibiting Src activity has been shown to obstruct several signaling pathways regulated by the EGFR. Thus, Src is a valuable target molecule in drug development. The purpose of this study was to identify compounds that directly or indirectly modulate Src to suppress lung cancer cell growth and motility and to investigate the molecular mechanisms underlying the effects of these compounds. METHODS: Human non-small cell lung cancer (NSCLC) cell lines (PC9, PC9/gef, A549, and H1975) with different EGFR statuses were tested by cytotoxicity and proliferation assays after AC-93253 iodide treatment...
November 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29131243/photodynamic-therapy-with-5-aminolevulinic-acid-suppresses-ifn-%C3%AE-induced-k17-expression-in-hacat-cells-via-mapk-pathway
#16
X-L Wang, Q Sun
OBJECTIVE: Psoriasis is a chronic inflammatory skin disorder that greatly affects the patient's quality of life. Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has recently been applied for inflammatory dermatoses including psoriasis. However, the therapeutic effect of ALA-PDT is yet to be validated, and the underlying mechanisms remain unclear. MATERIALS AND METHODS: In this study, a psoriatic model was established by treating HaCaT cells with 250 U/ml IFN-γ for 48 h...
October 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29130959/ginsenoside-rg1-protects-cardiomyocytes-against-hypoxia-reoxygenation-injury-via-activation-of-nrf2-ho-1-signaling-and-inhibition-of-jnk
#17
Qianhui Li, Yin Xiang, Yu Chen, Yong Tang, Yachen Zhang
BACKGROUND/AIMS: Excessive reactive oxygen species (ROS) disturb the physiology of H9c2 cells, which is regarded as a major cause of H9c2 cardiomyocyte apoptosis. Ginsenoside Rg1 is the main active extract of ginseng, which has important antioxidant properties in various cell models. This project investigated the role of ginsenoside Rg1 in hypoxia/reoxygenation (H/R)-induced oxidative stress injury in cultured H9c2 cells to reveal the underlying signaling pathways. METHODS: H9c2 cells were pretreated with ginsenoside Rg1 for 12 h before exposure to H/R...
November 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29129046/acebutolol-a-cardioselective-beta-blocker-promotes-glucose-uptake-in-diabetic-model-cells-by-inhibiting-jnk-jip1-interaction
#18
Yi Li, Nan-Young Jung, Jae Cheal Yoo, Yul Kim, Gwan-Su Yi
The phosphorylation of JNK is known to induce insulin resistance in insulin target tissues. The inhibition of JNK-JIP1 interaction, which interferes JNK phosphorylation, becomes a potential target for drug development of type 2 diabetes. To discover the inhibitors of JNK-JIP1 interaction, we screened out 30 candidates from 4320 compound library with In Cell Interaction Trap method. The candidates were further confirmed and narrowed down to five compounds using the FRET method in a model cell. Among those five compounds, Acebutolol showed notable inhibition of JNK phosphorylation and elevation of glucose uptake in diabetic models of adipocyte and liver cell...
November 13, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/29128906/toll-like-receptor-3-mediates-hiv-1-induced-interleukin-6-expression-in-the-human-brain-endothelium-via-tak1-and-jnk-pathways-implications-for-viral-neuropathogenesis
#19
Biju Bhargavan, Georgette D Kanmogne
HIV-1-associated neurocognitive disorders (HAND) is associated with blood-brain-barrier (BBB) inflammation, and inflammation involves toll-like receptors (TLRs) signaling. It is not known whether primary human brain microvascular endothelial cells (HBMEC), the major BBB component, express TLRs or whether TLRs are involved in BBB dysfunction and HAND. We demonstrate that HBMEC express TLR3, 4, 5, 7, 9, and 10, and TLR3 was the most abundant. HIV-1 and TLR3 activation increased endothelial TLR3 transcription and expression...
November 11, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/29128513/dihydroartemisinin-induced-caspase-dependent-apoptosis-through-inhibiting-the-specificity-protein-1-pathway-in-hepatocellular-carcinoma-sk-hep-1-cells
#20
Eunji Im, Changhwan Yeo, Hyo-Jeong Lee, Eun-Ok Lee
AIMS: Dihydroartemisinin (DHA) is a semi-synthetic derivative of artemisinin, well known for a safe and effective first-line antimalarial agent. This study investigated whether and how DHA induces apoptosis focusing on the specificity protein 1 (Sp1) pathway in hepatocellular carcinoma (HCC) SK-Hep-1 cells. MAIN METHODS: The cell viability was evaluated by MTT assay. Cell cycle analysis was performed after PI staining by flow cytometry system. Apoptosis was confirmed by DAPI staining and by detecting cytoplasmic histone-associated-DNA-fragments using a cell death detection ELISA(PLUS) kit...
November 8, 2017: Life Sciences
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