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Tatsuhiro Akaishi, Kazuho Abe
CNB-001, a pyrazole derivative of curcumin, has been found to exert neuroprotective and memory-enhancing effects that may be effective for the treatment of Alzheimer's disease. Since aberrant activation of microglia is involved in the pathogenesis of Alzheimer's disease, the present study was undertaken to investigate the effect of CNB-001 on microglia-mediated inflammatory responses. In primary cultured rat microglia, CNB-001 (1-10µM) suppressed the lipopolysaccharide (LPS)-induced nitric oxide (NO) production and expression of inducible NO synthase (iNOS), and the potency of CNB-001 was stronger than curcumin...
December 5, 2017: European Journal of Pharmacology
Ilaria Cervellini, Jorge Galino, Ning Zhu, Shannen Allen, Carmen Birchmeier, David L Bennett
The MAPK/ERK pathway has a critical role in PNS development. It is required for Schwann cell (SC) differentiation and myelination; sustained embryonic MAPK/ERK activation in SCs enhances myelin growth overcoming signals that normally end myelination. Excess activation of this pathway can be maladaptive as in adulthood acute strong activation of MAPK/ERK has been shown to cause SC dedifferentiation and demyelination. We used a mouse model (including male and female animals) in which gain of function Mek1DD allele produces sustained MAPK/ERK activation in adult SCs and we determined the impact of such activation on nerve repair...
December 6, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Angela Queisser, Laurence M Boon, Miikka Vikkula
The detection of somatic, activating genetic mutations to underlie development of vascular tumors and malformations led to a better understanding of their pathophysiology. Proteins encoded by the detected mutated genes activate the two major signaling pathways, also involved in cancer: the RAS/MAPK/ERK pathway and/or the PI3K/AKT/mTOR pathway. This gives a strong basis for studies to repurpose cancer therapeutics to patients with vascular tumors and malformations.
February 2018: Otolaryngologic Clinics of North America
Anusha Chidambaram, S H Kavya, Ramesh Kumar Chidambaram, Rajasekaran Subbiah, John Marshal Jayaraj, Karthikeyan Muthusamy, Ravikumar Vilwanathan
Histone deacetylase inhibitors (HDACi) are a small molecule chemotherapeutics that target the chromatin remodeling through the regulation of histone and non-histone proteins. These inhibitors directed against HDAC enzymes have become an important therapeutic tool in oncology; consequently, scientific efforts have fortified the quest for newer and novel HDACi, which forces the design of structurally innovative HDACi. Various urea containing compounds exhibited admirable anticancer activity. On the basis of these observations, we design and synthesize HDAC specific blocker molecules which are specifically besieged towards class I, class II and class IV HDAC isoforms to enhance the structural assortment for HDACi...
December 7, 2017: Journal of Cellular Physiology
Ke Wang, Yuekun Zhu
Objective To investigate the protective effects of dexmedetomidine (DEX) in oxygen-glucose deprivation/reoxygenation (OGD/R) injury, which is involved in a number of ischaemic diseases. Methods An in vitro OGD/R injury model was generated using mouse Neuro 2A neuroblastoma (N2A) cells. Different concentrations of DEX were administrated to OGD/R cells. CV-65 was used to inhibit p38 microtubule associated protein kinase/extracellular signal-regulated kinases (MAPK/ERK) signalling. Cell proliferation, cell cycle, apoptosis, and the levels of proteins related to p38 MAPK/ERK signalling and apoptosis were evaluated using Cell Counting Kit-8, flow cytometry, TdT-UTP nick end labelling and Western blot analysis, respectively...
January 1, 2017: Journal of International Medical Research
Weili Hui, Chenqi Zhao, Sylvain G Bourgoin
Lysophosphatidic acid (LPA) is a pleiotropic bioactive lysophospholipid involved in inflammatory mediator synthesis. Signaling through p38MAPK, ERK, Rho kinase, and MSK-CREB contributes to LPA-mediated IL-8 production in fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients. The study was undertaken to investigate how LPA activates MSKs and how signaling crosstalk between TNFα and LPA contributes to the super-production of cytokines/chemokines. RAFLS pretreated or not with TNFα were stimulated with LPA...
2017: Frontiers in Pharmacology
K M Suen, C C Lin, C Seiler, R George, G Poncet-Montange, A B Biter, Z Ahmed, S T Arold, J E Ladbury
Scaffold proteins play important roles in regulating signalling network fidelity, the absence of which is often the basis for diseases such as cancer. In the present work, we show that the prototypical scaffold protein Shc is phosphorylated by the extracellular signal-regulated kinase, Erk. In addition, Shc threonine phosphorylation is specifically up-regulated in two selected triple-negative breast cancer (TNBC) cell lines. To explore how Erk-mediated threonine phosphorylation on Shc might play a role in the dysregulation of signalling events, we investigated how Shc affects pathways downstream of EGF receptor...
December 2, 2017: International Journal of Biochemistry & Cell Biology
Yusuke Baba, Zenpei Shigemi, Naoko Hara, Misato Moriguchi, Marina Ikeda, Tadashi Watanabe, Masahiro Fujimuro
Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of primary effusion lymphoma (PEL) and Kaposi's sarcoma. PEL is a type of non-Hodgkin's B-cell lymphoma, affecting immunosuppressed individuals, such as post-transplant or AIDS patients. However, since PEL is resistant to chemotherapeutic regimens, new effective treatment strategies are required. Arctigenin, a natural lignan compound found in the plant Arctium lappa, has been widely investigated as a potential anticancer agent in the clinical setting...
December 1, 2017: International Journal of Oncology
Yanliang Li, Huihui Wu, Naijia Liu, Xinyi Cao, Zhen Yang, Bin Lu, Renming Hu, Xuanchun Wang, Jie Wen
The pineal hormone melatonin influences the secretion of insulin by pancreatic islets via the G‑protein‑coupled melatonin receptors 1 and 2 that are expressed in pancreatic β‑cells. Genome‑wide association studies indicate that melatonin receptor 1B (MTNR1B) single nucleotide polymorphisms are tightly associated with type 2 diabetes mellitus (T2DM). However, the underlying mechanism is unclear. Raf‑1 serves a critical role in the mitogen‑activated protein kinase (MAPK) pathways in β‑cell survival and proliferation and, therefore, may be involved in the mechanism by which melatonin impacts on T2DM through MTNR1B...
December 1, 2017: International Journal of Molecular Medicine
Dongdong Chen, Xiaoxiao Wu, Jie Zheng, Ruijie Dai, Zhichao Mo, Fahad Munir, Xiaolong Ni, Yunfeng Shan
Hepatic oval cells (HOCs) are thought to possess self‑renewal ability and a bipotential capacity for differentiation, which allows them to differentiate into hepatocytes and cholangiocytes. Autophagy serves an important role in self‑renewal and differentiation of stem cells; however, how autophagy contributes to proliferation and differentiation of hepatic progenitor cells has yet to be elucidated. In the present study, autophagy was regulated by rapamycin (Rapa) and chloroquine (Chlo) administration. The results demonstrated that Chlo‑treated HOCs exhibited decreased autophagic activity alongside a decreased tendency to proliferate, as determined by Cell Counting Kit‑8...
November 27, 2017: Molecular Medicine Reports
Jinfan Tian, Yingke Zhao, Yanfei Liu, Yue Liu, Keji Chen, Shuzheng Lyu
Diabetic cardiomyopathy is one of the major complications among patients with diabetes mellitus. Diabetic cardiomyopathy (DCM) is featured by left ventricular hypertrophy, myocardial fibrosis, and damaged left ventricular systolic and diastolic functions. The pathophysiological mechanisms include metabolic-altered substrate metabolism, dysfunction of microvascular, renin-angiotensin-aldosterone system (RAAS) activation, oxidative stress, cardiomyocyte apoptosis, mitochondrial dysfunction, and impaired Ca2+ handling...
2017: Oxidative Medicine and Cellular Longevity
Kai Kai Li, Shan Shan Shen, Xiangyi Deng, Hoi Ting Shiu, Wing Sum Siu, Ping Chung Leung, Chun Hay Ko, Bao Hui Cheng
Dihydrofisetin is a flavanonol derived from some edible wild herbs and traditional Chinese medicines. It has been found to possess many biological activities. However, the anti-inflammatory potential of Dihydrofisetin remains uncharacterized. The aim of the present study was to investigate the anti-inflammatory activity of Dihydrofisetin and its underlying mechanisms. We found that Dihydrofisetin dose-dependently inhibited lipopolysaccharide-induced productions of nitric oxide (NO) and prostaglandin E2 (PGE2) in RAW 264...
December 1, 2017: International Immunopharmacology
Chunling Du, Jinchang Lu, Lei Zhou, Bo Wu, Feng Zhou, Liang Gu, Donghui Xu, Yingxin Sun
Objective: To explore the effect of cigarette smoke (CS) on the development of squamous metaplasia in human airway epithelial cells and the role of MAPK- and FoxA2-signaling pathways in the process. Materials and methods: In an in vitro study, we treated the bronchial epithelial cell line BEAS2B with CS extract, followed by treatment with the ERK inhibitor U0126, the JNK inhibitor SP600125, or the p38 inhibitor SB203580. In vivo, we used a CS-induced rat model. After treatment with CS with or without MAPK inhibitors for 90 days, lung tissues were harvested...
2017: International Journal of Chronic Obstructive Pulmonary Disease
Hong Jin Joo, Kwan Ho Jeong, Jung Eun Kim, Hoon Kang
Background: The human dermal papilla cells (hDPCs) play an important role in regulation of hair cycling and growth. Objective: The aim of this study was to investigate the effect of different wavelengths of light-emitting diode (LED) irradiation on the proliferation of cultured hDPCs and on the growth of human hair follicles (HFs) in vitro. Methods: We examined the effect of LED irradiation on Wnt/β-catenin signaling and mitogen-activated protein kinase (MAPK) pathways in hDPCs...
December 2017: Annals of Dermatology
Sanda Win, Tin Aung Than, Jun Zhang, Christina Oo, Robert Win Maw Min, Neil Kaplowitz
Mitogen-activated protein kinase (MAPK) signaling in the liver occurs in response to physical and chemical stress, including alterations in nutrients, growth factors, cytokines, extracellular matrix, DNA damage, drugs and toxins. This signaling pathway plays a role in liver injury and diseases such as drug induced hepatotoxicity, viral hepatitis, infection and inflammation, NAFLD, NASH, ALD, ischemia/reperfusion, fibrosis, regeneration, and carcinogenesis (1-4). In mammals, three major groups of MAPK have been identified...
November 30, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Aasif Ahmad Sheikh, O K Hooda, A K Dang
Interferon tau, a 23 KDa trophoblast derived protein diffuses out from the uterus into the circulation and leads to the expression of IFNτ stimulated genes viz. ISG15 and OAS1 in blood neutrophils. The IFNτ pathway is species as well as tissue specific. To unsnarl the IFNτ downstream signaling pathway, the blood neutrophils were incubated simultaneously with 10 ng/ml of Recombinant Bovine Interferon tau and the inhibitors of JAK2 (AG490), JAK3 (CP690550), p38 (SB202190), PI3K/Akt (LY294002) and MAPK/Erk (U0126) at specific doses for 4 hour duration...
November 30, 2017: Journal of Cellular Physiology
Kati Räsänen, Kien X Dang, Harri Mustonen, Tho H Ho, Susanna Lintula, Hannu Koistinen, Ulf-Håkan Stenman, Caj Haglund, Jakob Stenman
The mitogen-activated protein kinase (MAPK) pathway plays a central role in colorectal cancers (CRC). In particular, BRAF V600E-mutant tumors, which represent around 10% of CRCs, are refractory to current therapies. Over-expression and secretion of serine peptidase inhibitor Kazal type 1 (SPINK1) is observed in around 50% of CRCs and its serum level can be used as a biomarker for poor prognosis. Utilizing a recently developed Extendable Blocking Probe assay, we analyzed the BRAF mutation status in a CRC patient cohort (N=571) using tissue-derived RNA as the starting material...
November 28, 2017: Molecular Oncology
Junfei Gu, Shulan Su, Jianming Guo, Yue Zhu, Ming Zhao, Jin-Ao Duan
OBJECTIVE: This study was performed to assess the anti-inflammatory and anti-apoptotic effects of the combination of Ligusticum chuanxiong and Radix Paeoniae (XS) on focal cerebral ischaemic stroke. METHODS: MCAO rats were used to evaluate the effect of XS on stroke. Cerebral water content was measured, and the levels of IFN-γ, IL-1β, IL-6 and IL-12 in serum and brain were assessed by ELISA kits. Protein expressions including p-p38, p-38, TLR-4, p-ERK, ERK, TLR-5, NF-κBp65, Myd88, Caspase-3 and Caspase-12 were examined by WB and IHC...
November 28, 2017: Journal of Pharmacy and Pharmacology
K Nonaka, Y Kajiura, M Bando, E Sakamoto, Y Inagaki, J H Lew, K Naruishi, T Ikuta, K Yoshida, T Kobayashi, H Yoshie, T Nagata, J Kido
BACKGROUND AND OBJECTIVES: Diabetes mellitus (DM) is a risk factor for periodontal diseases and may exacerbate the progression of the pathogenesis of periodontitis. Advanced glycation end-products (AGEs) cause DM complications relative to levels of glycemic control and larger amounts accumulate in the periodontal tissues of patients with periodontitis and DM. In the present study, we investigated the effects of AGEs on the expression of inflammation-related factors in human gingival fibroblasts (HGFs) to elucidate the impact of AGEs on DM-associated periodontitis...
November 30, 2017: Journal of Periodontal Research
Chien-Min Chen, Shu-Ching Hsieh, Chia-Liang Lin, Yu-Syun Lin, Jen-Pi Tsai, Yi-Hsien Hsieh
BACKGROUND/AIMS: α-mangostin has anti-carcinogenic effects against several cancers. We investigated the molecular mechanism of this compound on the metastasis of human renal carcinoma cells. METHODS: Cell viability was measured using the MTT assay, and cell cycle distribution using flow cytometry. A Matrigel-based assay was used to measure in vitro cell migration and invasion. MAPK-related proteins and matrix metalloproteinase (MMP)-9 and MMP-2 expression were measured by western blotting, and MMP2/-9 activities were determined by gelatin zymography...
December 1, 2017: Cellular Physiology and Biochemistry
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