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JNK pathway

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https://www.readbyqxmd.com/read/29150630/inhibition-of-myeloid-differentiation-primary-response-protein-88-provides-neuroprotection-in-early-brain-injury-following-experimental-subarachnoid-hemorrhage
#1
Huiying Yan, Dingding Zhang, Yongxiang Wei, Hongbin Ni, Weibang Liang, Huasheng Zhang, Shuangying Hao, Wei Jin, Kuanyu Li, Chun-Hua Hang
Accumulating of evidence suggests that activation of nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) exacerbates early brain injury (EBI) following subarachnoid hemorrhage (SAH) by provoking pro-inflammatory and pro-apoptotic signaling. Myeloid differentiation primary response protein 88 (MyD88) is an endogenous adaptor protein in the toll-like receptors (TLRs) and interleukin (IL) -1β family signaling pathways and acts as a bottle neck in the NF-κB and MAPK pathways. Here, we used ST2825, a selective inhibitor of MyD88, to clarify whether inhibiting MyD88 could provide neuroprotection in EBI following SAH...
November 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29150048/dna-dependent-protein-kinase-modulates-the-anti-cancer-properties-of-silver-nanoparticles-in-human-cancer-cells
#2
Hui Kheng Lim, Resham Lal Gurung, M Prakash Hande
Silver nanoparticles (Ag-np) were reported to be toxic to eukaryotic cells. These potentially detrimental effects of Ag-np can be advantageous in experimental therapeutics. They are currently being employed to enhance the therapeutic efficacy of cancer drugs. In this study, we demonstrate that Ag-np treatment trigger the activation of DNA-PKcs and JNK pathway at selected doses, presumably as a physiologic response to DNA damage and repair in normal and malignant cells. Ag-np altered the telomere dynamics by disrupting the shelterin complex located at the telomeres and telomere lengths...
December 2017: Mutation Research
https://www.readbyqxmd.com/read/29149759/dusp1-alleviates-cardiac-ischemia-reperfusion-injury-by-suppressing-the-mff-required-mitochondrial-fission-and-bnip3-related-mitophagy-via-the-jnk-pathways
#3
Qinhua Jin, Ruibing Li, Nan Hu, Ting Xin, Pingjun Zhu, Shunying Hu, Sai Ma, Hong Zhu, Jun Ren, Hao Zhou
Mitochondrial fission and selective mitochondrial autophagy (mitophagy) form an essential axis of mitochondrial quality control that plays a critical role in the development of cardiac ischemia-reperfusion (IR) injury. However, the precise upstream molecular mechanism of fission/mitophagy remains unclear. Dual-specificity protein phosphatase1 (DUSP1) regulates cardiac metabolism, but its physiological contribution in the reperfused heart, particularly its influence on mitochondrial homeostasis, is unknown. Here, we demonstrated that cardiac DUSP1 was downregulated following acute cardiac IR injury...
November 6, 2017: Redox Biology
https://www.readbyqxmd.com/read/29148173/metformin-protects-against-intestinal-barrier-dysfunction-via-ampk%C3%AE-1-dependent-inhibition-of-jnk-signalling-activation
#4
Jun Deng, Lishan Zeng, Xueying Lai, Jing Li, Le Liu, Qianyun Lin, Ye Chen
Disruption of the intestinal epithelial barrier, that involves the activation of C-Jun N-terminal kinase (JNK), contributes to initiate and accelerate inflammation in inflammatory bowel disease. Metformin has unexpected beneficial effects other than glucose-lowering effects. Here, we provided evidence that metformin can protect against intestinal barrier dysfunction in colitis. We showed that metformin alleviated dextran sodium sulphate (DSS)-induced decreases in transepithelial electrical resistance, FITC-dextran hyperpermeability, loss of the tight junction (TJ) proteins occludin and ZO-1 and bacterial translocation in Caco-2 cell monolayers or in colitis mice models...
November 17, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29148169/antitumor-and-anti-metastatic-mechanisms-of-rhizoma-paridis-saponins-in-lewis-mice
#5
Shuli Man, Hongyan Chai, Jingxia Cui, Jingwen Yao, Long Ma, Wenyuan Gao
Lung cancer is one of the most common causes of death in the world. Rhizoma paridis saponins (RPS) have been found to show inhibition of pulmonary adenoma in previous research. However, the detailed mechanisms of RPS from a holistic view have not been established. In this study, Lewis pulmonary adenoma mice were successfully established to analyze the pathways involved in RPS intervening tumor formation and progression. As a result, RPS inhibited levels of cytokines or receptors such as VEGFD, VEGFR3, RAGE, IL6R, IL17BR, and CXCL16 which were regarded as the initiators induced tumor cell proliferation, adhesion, angiogenesis, and invasion...
November 17, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/29147906/regulation-of-signal-transduction-by-dj-1
#6
Stephanie E Oh, M Maral Mouradian
The ability of DJ-1 to modulate signal transduction has significant effects on how the cell regulates normal processes such as growth, senescence, apoptosis, and autophagy to adapt to changing environmental stimuli and stresses. Perturbations of DJ-1 levels or function can disrupt the equilibrium of homeostatic signaling networks and set off cascades that play a role in the pathogenesis of conditions such as cancer and Parkinson's disease.DJ-1 plays a major role in various pathways. It mediates cell survival and proliferation by activating the extracellular signal-regulated kinase (ERK1/2) pathway and the phosphatidylinositol-3-kinase (PI3K)/Akt pathway...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29146495/polysaccharides-from-citrus-grandis-l-osbeck-suppress-inflammation-and-relieve-chronic-pharyngitis
#7
Liyan Chen, Yongfeng Lai, Lei Dong, Shasha Kang, Xiumei Chen
Chronic pharyngitis, a common inflammation of the pharyngeal mucosa, is often caused by bacteria, viruses, alcohol abuse, overuse of the voice and cigarettes. This study aimed to explore the effects of polysaccharides of Citrus grandis L. Osbeck (PCG) in relieving chronic pharyngitis and illustrate the underlying mechanisms. Polysaccharides were obtained from PCG by column chromatographic extraction. Six clinical symptom scores, such as the severity of itchy throat, hoarseness, pain, odynophagia, cough and otalgia were evaluated in chronic pharyngitis patients after the oral intake of PCG...
November 13, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29145158/vibrio-cholerae-ompu-induces-il-8-expression-in-human-intestinal-epithelial-cells
#8
Jae Seung Yang, Jun Ho Jeon, Mi Seon Jang, Seok-Seong Kang, Ki Bum Ahn, Manki Song, Cheol-Heui Yun, Seung Hyun Han
Although Vibrio cholerae colonizes the small intestine and induces acute inflammatory responses, less is known about the molecular mechanisms of V. cholerae-induced inflammatory responses in the intestine. We recently reported that OmpU, one of the most abundant outer membrane proteins of V. cholerae, plays an important role in the innate immunity of the whole bacteria. In this study, we evaluated the role of OmpU in induction of IL-8, a representative chemokine that recruits various inflammatory immune cells, in the human intestinal epithelial cell (IEC) line, HT-29...
November 13, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29144008/a-copper-ii-phenanthroline-metallopeptide-that-targets-and-disrupts-mitochondrial-function-in-breast-cancer-stem-cells
#9
Kristine Laws Laws, Ganka Bineva-Todd, Arvin Eskandari, Chunxin Lu, Nicola O'Reilly, Kogularamanan Suntharalingam
The breast cancer stem cell (CSC) and bulk breast cancer cell potency of a series of metallopeptides, 1-4 containing dichloro(1,10-phenanthroline) copper(II) and various organelle-targeting peptide sequences, is reported. The mitochondrial-targeting metallopeptide, 1 exploits the higher mitochondrial load in breast CSCs over corresponding non-CSCs, and the vulnerability of breast CSCs to mitochondrial damage, to potently and selectivity kill breast CSCs. Strikingly, 1 reduces the formation and size of mammospheres to a better extent than salinomycin, an established CSC-potent agent...
November 16, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/29143973/effects-of-microrna-24-targeting-c-myc-on-apoptosis-proliferation-and-cytokine-expressions-in-chondrocytes-of-rats-with-osteoarthritis-via-mapk-signaling-pathway
#10
Yuan-Hao Wu, Wei Liu, Lei Zhang, Xiao-Ya Liu, Yi Wang, Bin Xue, Bin Liu, Ran Duan, Bo Zhang, Yang Ji
OBJECTIVE: To investigate whether microRNA-24 (miR-24) targeting C-myc affects chondrocytes of rats with osteoarthritis (OA) via the MAPK signaling pathway. METHODS: Thirty rats were assigned as a sham group and an OA group (established as OA rat models by cutting the anterior cruciate ligaments and removing 1/3 medial meniscus). TUNEL staining and immunohistochemistry were conducted for cell apoptosis index (AI) and positive expression rate of C-myc protein. Enzyme-linked immuno sorbent assay (ELISA) was carried out for serum level of IL-1β and TNF-α...
November 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29143802/the-inhibitory-effects-of-cobalt-protoporphyrin-ix-and-cannabinoid-2-receptor-agonists-in-type-2-diabetic-mice
#11
Christina McDonnell, Sergi Leánez, Olga Pol
The activation of the transcription factor Nrf2 inhibits neuropathy and modulates the activity of delta-opioid receptors (DOR) in type 2 diabetic mice but the impact of Nrf2/HO-1 pathway on the antinociceptive actions of cannabinoid 2 receptors (CB2R) has not been assessed. Using male mice BKS.Cg-m+/+Leprdb/J (db/db) we investigated if treatment with cobalt protoporphyrin IX (CoPP), an HO-1 inductor, inhibited mechanical allodynia, hyperglycemia and obesity associated to type 2 diabetes. The antinociceptive effects of JWH-015 and JWH-133 (CB2R agonists) administered with and without CoPP or sulforaphane (SFN), a Nrf2 transcription factor activator, have been also evaluated...
October 28, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29142215/the-effects-of-artocarpin-on-wound-healing-in-vitro-and-in-vivo-studies
#12
Chung-Ju Yeh, Chin-Chuan Chen, Yann-Lii Leu, Ming-Wei Lin, Mei-Miao Chiu, Shu-Huei Wang
The skin protects the body against harmful substances and microorganisms. When the skin is damaged, wound healing must be finely regulated to restore the normal function of skin tissue. Artocarpin (ARTO), a prenylated flavonoid purified from the plant Artocarpus communis, has been reported to have anti-inflammatory and anti-cancer properties. The aim of the present study was to evaluate the wound healing potential and therapeutic mechanism of ARTO. Immunohistochemical staining of neutrophils and macrophages and mouse cytokine array analysis demonstrated that ARTO accelerates inflammatory progression and subsequently decreases persistent inflammation...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141222/jnk-promotes-epithelial-cell-anoikis-by-transcriptional-and-post-translational-regulation-of-bh3-only-proteins
#13
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/29138815/curcumin-reverses-tobacco-smoke%C3%A2-induced-epithelial%C3%A2-mesenchymal-transition-by-suppressing-the-mapk-pathway-in-the-lungs-of-mice
#14
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
#15
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/29138180/inhibition-of-vascular-c-jun-n-terminal-kinase-2-improves-obesity-induced-endothelial-dysfunction-after-roux-en-y-gastric-bypass
#16
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
#17
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/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
#18
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
#19
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/29136776/dihydroartemisinin-inhibits-er-stress-mediated-mitochondrial-pathway-to-attenuate-hepatocyte-lipoapoptosis-via-blocking-the-activation-of-the-pi3k-akt-pathway
#20
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
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