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https://www.readbyqxmd.com/read/29148173/metformin-protects-against-intestinal-barrier-dysfunction-via-ampk%C3%AE-1-dependent-inhibition-of-jnk-signalling-activation
#1
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/29146153/the-stress-kinase-jnk-regulates-gap-junction-cx43-gene-expression-and-promotes-atrial-fibrillation-in-the-aged-heart
#2
Jiajie Yan, Justin K Thomson, Weiwei Zhao, Xiaomin Wu, Xianlong Gao, Dominic DeMarco, Wei Kong, Min Tong, Jun Sun, Mamdouh Bakhos, Vladimir G Fast, Qingrong Liang, Sumanth D Prabhu, Xun Ai
BACKGROUND: The stress kinase c-jun N-terminal kinase (JNK) is critical in the pathogenesis of cardiac diseases associated with an increased incidence of atrial fibrillation (AF), the most common arrhythmia in the elderly. We recently discovered that JNK activation is linked to the loss of gap junction connexin43 (Cx43) and enhanced atrial arrhythmogenicity. However, direct evidence for JNK-mediated impairment of intercellular coupling (cell-cell communication) in the intact aged atrium is lacking, as is evidence for whether and how JNK suppresses Cx43 in the aged human atrium...
November 13, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29145888/tgf-%C3%AE-2-initiates-autophagy-via-smad-and-non-smad-pathway-to-promote-glioma-cells-invasion
#3
Chao Zhang, Xin Zhang, Ran Xu, Bin Huang, An-Jing Chen, Chao Li, Jian Wang, Xin-Gang Li
BACKGROUND: Glioblastoma multiforme (GBM) is characterized by lethal aggressiveness and patients with GBM are in urgent need for new therapeutic avenues to improve quality of life. Current studies on tumor invasion focused on roles of cytokines in tumor microenvironment and numerous evidence suggests that TGF-β2 is abundant in glioma microenvironment and vital for glioma invasion. Autopagy is also emerging as a critical factor in aggressive behaviors of cancer cells; however, the relationship between TGF-β2 and autophagy in glioma has been poorly understood...
November 16, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29144206/c-jun-expression-in-lichen-planus-psoriasis-and-cutaneous-squamous-cell-carcinoma-an-immunohistochemical-study
#4
Asmaa Gaber Abdou, Alaa Hassan Marae, Mohammed Shoeib, Ghada Dawood, Enas Abouelfath
The AP-1 transcription factor complex is a key player in regulating inflammatory processes, cell proliferation, differentiation and cell transformation. The aim of the present study is to investigate C-Jun (one of AP-1complex) expression and its proliferative role in skin samples of lichen planus, psoriasis as common inflammatory skin diseases and squamous cell carcinoma using immunohistochemical method. The present study was carried out on skin biopsies of 15 psoriatic patients, 15 lichen planus patients, 15 SCC and 15 normal skin biopsies...
November 16, 2017: Journal of Immunoassay & Immunochemistry
https://www.readbyqxmd.com/read/29143802/the-inhibitory-effects-of-cobalt-protoporphyrin-ix-and-cannabinoid-2-receptor-agonists-in-type-2-diabetic-mice
#5
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/29142417/inhibition-of-phosphorylated-c-jun-nh-2-terminal-kinase-by-2-4-dihydroxy-6-methoxy-3-5-dimethylchalcone-isolated-from-eugenia-aquea-burm-f-leaves-in-jurkat-t-cells
#6
Melisa I Barliana, Ajeng Diantini, Anas Subarnas, Rizky Abdulah, Takashi Izumi
Background: Indonesian medicinal plants have been used for their anticancer activity for decades. However, the therapeutic effects of medicinal plants have not been fully examined scientifically. As cancer is a major health problem worldwide, searching for a new anticancer compound has attracted considerable attention. Our previous study found that 2',4'-dihydroxy-6-methoxy-3,5-dimethylchalcone, an active compound isolated from leaves of Indonesian medicinal plants Eugenia aquea Burm f...
October 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/29141367/-differentiation-of-induced-pluripotent-stem-cells-into-neural-stem-cells-induced-by-brain-derived-neurotrophic-factor-via-wnt-%C3%AE-catenin-and-extracellular-signal-regulated-kinase-mitogen-activated-protein-kinases-signal-pathway
#7
S Q Chen, M Huang, C L Liu, Y Y Shen, Q Cai, P J Wang
Objective: To investigate the mechanism of brain-derived neurotrophic factor (BDNF) promoting induced pluripotent stem cells (iPSCs) to differentiate into neural stem cells (NSCs) via Wnt/β-catenin and extracellular signal-regulated kinase/mitogen-activated protein kinases (ERK/MAPK) signal pathways. Methods: iPSCs were cultured and identified. The iPSCs were induced to differentiate into NSCs by BDNF and retinoic acid (RA). Nestin was detected by immunofluorescence and flow cytometry after iPSCs differentiated...
November 7, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/29138854/ng25-an-inhibitor-of-transforming-growth-factor%C3%A2-%C3%AE-%C3%A2-activated-kinase-1-ameliorates-neuronal-apoptosis-in-neonatal-hypoxic%C3%A2-ischemic-rats
#8
Hua Wang, Zhong Chen, Yu Li, Qiaoyun Ji
Transforming growth factor (TGF)‑β‑activated kinase 1 (TAK1) was found to be activated by TGF‑β and acts as a central regulator of cell death in various types of disease. However, the expression and function of TAK1 in the neonatal brain following hypoxia‑ischemia (HI) remains unclear. In the present study, western blotting and immunofluorescence were employed to determine the expression and distribution of TAK1 in the brain cortex of a perinatal HI rat model. In addition, the specific inhibitor of TAK1, NG25 was administered via intracerebroventricular injection, prior to insult of the neonatal rat brains, for neuroprotection...
November 10, 2017: Molecular Medicine 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
#9
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/29138180/inhibition-of-vascular-c-jun-n-terminal-kinase-2-improves-obesity-induced-endothelial-dysfunction-after-roux-en-y-gastric-bypass
#10
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/29138007/rbm4-srsf3-map4k4-splicing-cascade-modulates-the-metastatic-signature-of-colorectal-cancer-cell
#11
Jung-Chun Lin, Yuan-Chii Lee, Tse-Hua Tan, Yu-Chih Liang, Huai-Chia Chuang, Yang C Fann, Kory R Johnson, Ying-Ju Lin
Alternative splicing (AS) of pre-messenger (m)RNA is a pivotal mechanism in expanding proteomic diversity, which determines the functions of mammalian cells. By conducting transcriptome analyses to profile splicing events in human colorectal cancer (CRC) tissues compared to adjacent normal counterparts, we noted differential splicing profiles of serine/arginine-rich splicing factor 3 (SRSF3) and mitogen-activated protein 4 kinase 4 (MAP4K4) in cancerous tissues of CRC compared to adjacent normal tissues. In addition to SRSF3-mediated autoregulation, RNA-binding motif protein 4 (RBM4) constituted another mechanism in reprogramming the splicing profile of SRSF3...
November 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29137866/development-of-noviomimetics-that-modulate-molecular-chaperones-and-manifest-neuroprotective-effects
#12
Leah K Forsberg, Mercy Anyika, Zhenyuan You, Sean Emery, Mason McMullen, Rick T Dobrowsky, Brian S J Blagg
Heat shock protein 90 (Hsp90) is a chaperone under investigation for the treatment of cancer and neurodegenerative diseases. Neuroprotective Hsp90 C-terminal inhibitors derived from novobiocin (novologues) include KU-32 and KU-596. These novologues modulate molecular chaperones and result in an induction of Heat Shock Protein 70 (Hsp70). "Noviomimetics" replace the synthetically complex noviose sugar with a simple cyclohexyl moiety to maintain biological efficacy as compared to novologues KU-596 and KU-32...
October 18, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29137840/resolvin-d1-attenuates-imiquimod-induced-mice-psoriasiform-dermatitis-through-mapks-and-nf-%C3%AE%C2%BAb-pathways
#13
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/29137357/akr7a3-suppresses-tumorigenicity-and-chemoresistance-in-hepatocellular-carcinoma-through-attenuation-of-erk-c-jun-and-nf-%C3%AE%C2%BAb-signaling-pathways
#14
Raymond Kwok Kei Chow, Sarah Tsz-Kwan Sin, Ming Liu, Yan Li, Tim Hon Man Chan, Yangyang Song, Leilei Chen, Dora Lai-Wan Kwong, Xin-Yuan Guan
Hepatocellular carcinoma (HCC), which accounts for 85-90% of primary liver cancer, is now the second leading cause of cancer-related mortality worldwide. Here we reported that Aldo-Keto Reductase family 7A isoform 3 (AKR7A3) is frequently down-regulated in HCC, associating with poor overall survival rate, elevated serum α-fetoprotein (AFP) and poor differentiation of HCC. The promoter region of AKR7A3 was detected to be hypermethylated. Loss of heterozygosity (LOH) was also detected in AKR7A3. Functional assays on both AKR7A3 overexpressed and knockdown cells, including foci formation, colony formation in soft agar, migration, invasion and tumor formation in nude mice, demonstrated the strong tumor suppressive functions of AKR7A3...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137326/overexpression-of-carbonic-anhydrase-ix-induces-cell-motility-by-activating-matrix-metalloproteinase-9-in-human-oral-squamous-cell-carcinoma-cells
#15
Jia-Sin Yang, Chiao-Wen Lin, Yi-Hsien Hsieh, Ming-Hsien Chien, Chun-Yi Chuang, Shun-Fa Yang
Oral cancer is a solid malignant tumor that is prone to occur following hypoxia. There are no clear studies showing a link between hypoxia and oral carcinogenesis. Carbonic anhydrase IX (CAIX), which is a hypoxia-induced transmembrane protein, is highly expressed in various types of human cancer. However, the effects of CAIX on the metastasis of human oral cancer cells and the underlying molecular mechanisms have not been clarified. In this study, we observed that CAIX overexpression increased the migratory and invasive abilities of SCC-9 and SAS cells...
October 10, 2017: Oncotarget
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
#16
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/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
#17
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
#18
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/29133791/network-pharmacology-exploration-reveals-endothelial-inflammation-as-a-common-mechanism-for-stroke-and-coronary-artery-disease-treatment-of-danhong-injection
#19
Ming Lyu, Chun-Lin Yan, Hai-Xin Liu, Tai-Yi Wang, Xin-Hui Shi, Jin-Ping Liu, John Orgah, Guan-Wei Fan, Ji-Hong Han, Xiao-Ying Wang, Yan Zhu
Although Danhong injection (DHI) is the most widely prescribed Chinese medicine for both stroke and coronary artery disease (CAD), its underlying common molecular mechanisms remain unclear. An integrated network pharmacology and experimental verification approach was used to decipher common pharmacological mechanisms of DHI on stroke and CAD treatment. A compound-target-disease & function-pathway network was constructed and analyzed, indicating that 37 ingredients derived from DH (Salvia miltiorrhiza Bge., Flos Carthami tinctorii and DHI) modulated 68 common targets shared by stroke and CAD...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133030/20-s-protopanaxadiol-ppd-alleviates-scopolamine-induced-memory-impairment-via-regulation-of-cholinergic-and-antioxidant-systems-and-expression-of-egr-1-c-fos-and-c-jun-in-mice
#20
Cong Lu, Liming Dong, Jingwei Lv, Yan Wang, Bei Fan, Fengzhong Wang, Xinmin Liu
20(S)-protopanaxadiol (PPD) possesses various biological properties, including anti-inflammatory, antitumor and anti-fatigue properties. Recent studies found that PPD functioned as a neurotrophic agent to ameliorate the sensory deficit caused by glutamate-induced excitotoxicity through its antioxidant effects and exhibited strong antidepressant-like effects in vivo. The objective of the present study was first to investigate the effect of PPD in scopolamine (SCOP)-induced memory deficit in mice and the potential mechanisms involved...
November 10, 2017: Chemico-biological Interactions
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