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Chia-Sheng Yen, Cheuk-Sing Choy, Wei-Jan Huang, Shiu-Wen Huang, Pin-Ye Lai, Meng-Chieh Yu, Ching Shiue, Ya-Fen Hsu, Ming-Jen Hsu
Growing evidence shows that hydroxamate-based compounds exhibit broad-spectrum pharmacological properties including anti-tumor activity. However, the precise mechanisms underlying hydroxamate derivative-induced cancer cell death remain incomplete understood. In this study, we explored the anti-tumor mechanisms of a novel aliphatic hydroxamate-based compound, WMJ-J-09, in FaDu head and neck squamous cell carcinoma (HNSCC) cells. WMJ-J-09 induced G2/M cell cycle arrest and apoptosis in FaDu cells. These actions were associated with liver kinase B1 (LKB1), AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (p38MAPK) activation, transcription factor p63 phosphorylation, as well as modulation of p21 and survivin...
2018: Frontiers in Pharmacology
Li-Yuan Yu-Lee, Guoyu Yu, Yu-Chen Lee, Song-Chang Lin, Jing Pan, Tianhong Pan, Kai-Jie Yu, Bin Liu, Chad J Creighton, Jaime Rodriguez-Canales, Pamela Andrea Villalobos, Ignacio Ivan Wistuba, Eulàlia de Nadal, Francesc Posas, Gary E Gallick, Sue-Hwa Lin
Bone metastasis from prostate cancer (PCa) can occur years after prostatectomy, due to reactivation of dormant disseminated tumor cells (DTC) in the bone, yet the mechanism by which DTC are initially induced into a dormant state in the bone remains to be elucidated. We show here that the bone microenvironment confers dormancy to C4-2B4 PCa cells, as they become dormant when injected into mouse femurs but not under the skin. Live-cell imaging of dormant cells at the single cell level revealed that conditioned medium from differentiated, but not undifferentiated osteoblasts induced C4-2B4 cellular quiescence, suggesting that differentiated osteoblasts present locally around the tumor cells in the bone conferred dormancy to PCa cells...
March 7, 2018: Cancer Research
Ester Canto, Noriko Isobe, Alessandro Didonna, Stephen L Hauser, Jorge R Oksenberg
BACKGROUND: Multiple sclerosis (MS) is characterized by increased activation of peripheral blood mononuclear cells (PBMCs), linked to perturbations in the phosphorylation of signaling proteins. METHODS: We developed a phosphoflow cytometry protocol to assess the levels of 11 phosphorylated nuclear proteins at baseline conditions and after cell activation in distinct PBMC populations from 41 treatment-naïve relapsing-remitting (RR) MS subjects and 37 healthy controls, and in a second cohort of 9 untreated RRMS patients and 10 secondary progressive (SP) MS patients...
March 7, 2018: Journal of Neuroinflammation
Yu Zhou, Liang Zhao, Fangchao Mei, Yupu Hong, He Xia, Teng Zuo, Youming Ding, Weixing Wang
Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine involved in many acute and chronic inflammatory diseases. However, its role in acute lung injury associated with acute pancreatitis in pregnancy (APIP) has not yet been elucidated. The present study was undertaken to clarify the effect and potential mechanism of MIF antagonist (S,R)3‑(4‑hydroxyphenyl)‑4,5‑dihydro‑5‑isoxazole acetic acid methyl ester (ISO‑1) in the development of acute lung injury in rats with APIP. Eighteen late‑gestation SD rats were randomly assigned to three groups: Sham operation (SO) group, APIP group, and ISO‑1 group...
March 1, 2018: Molecular Medicine Reports
Fan Cai, Fang Wu, Jiumei Cao, Xiaonan Chen
Diabetes has been considered as an independent risk factor for cerebral infarction. However, the pathological mechanism of cerebral infarction with diabetes (DMCI) is still rarely known. In this study, we try to explore the relationship between microRNA-146b-3p (miR-146b-3p) and DMCI patients. The peripheral blood mononuclear cells were separated after the patients were selected from our hospital. Firstly, the content of IL-6 and COX-2 was detected by ELISA. Then, the total RNAs were extracted and analyzed by microRNA (miRNA) microarray...
2018: American Journal of Translational Research
Jian Song, Bin Ye, Hanghang Liu, Ruiye Bi, Nian Zhang, Jing Hu, En Luo
OBJECTIVES: To investigate the mechanism of mechanical stimulation in bone formation and regeneration during distraction osteogenesis. MATERIALS AND METHODS: In this study, microarray technology was used to investigate the time course of bone-related molecular changes in distraction osteogenesis in rats. Real-time PCR and Western-blot analyses were used to confirm the expression of genes identified in microarrays. Meanwhile, we used a lentivirus vector to inhibit Fak expression, in order to identify the osteogenic effect of Fak and Fak-Mapk pathway during distraction osteogenesis...
March 5, 2018: Cell Proliferation
Ran Deng, Feng Li, Hong Wu, Wen-Yu Wang, Li Dai, Zheng-Rong Zhang, Jun Fu
Geniposide (GE) is the extraction and purification of iridoid glycosides from the Gardenia jasminoides Ellis , which is a promising anti-inflammatory drug, but its mechanism of actions on rheumatoid arthritis (RA) has not been clarified. This study investigated the molecular mechanism behind GE reduced the high permeability of fibroblast-like synoviocytes (FLSs) derived from SD rats with adjuvant arthritis (AA), with the aims of observing the action of GE in AA rats and exploring new therapeutic strategies for RA treatment...
2018: Frontiers in Pharmacology
Xiao-Jing Wu, Hui-Min Liu, Xue-Min Song, Bo Zhao, Yan Leng, E-You Wang, Li-Ying Zhan, Qing-Tao Meng, Zhong-Yuan Xia
Blunt chest trauma with hemorrhagic shock (THS) frequently induces pulmonary inflammation that leads to acute lung injury (ALI). Penehyclidine hydrochloride (PHC) possesses anti‑inflammatory properties that may attenuate the systemic inflammatory response. The present study aimed to evaluate the molecular mechanism of PHC in modifying THS‑induced ALI in rats. Rats underwent either THS or a sham procedure. At 6 h subsequent to blunt chest trauma, arterial blood was drawn for blood gas and pro‑inflammatory factors analyses, and lung tissue samples were collected to examine pulmonary histopathological alterations, the wet/dry weight ratio, myeloperoxidase activity, and the protein expression levels of Toll-like receptor 4 (TLR4), phosphorylated (p‑)p38 mitogen‑activated protein kinase (MAPK), nuclear factor (NF)‑κB and activator protein‑1 (AP‑1)...
February 27, 2018: Molecular Medicine Reports
Ahmed A Abd-Rabou, Dhruba J Bharali, Shaker A Mousa
PURPOSE: Breast cancer is the second most common cause of mortality in women in the United States. Targeted delivery of antitumor breast cancer drugs as a drug-delivery strategy may allow direct delivery into the tumor. Currently, chemotherapy is one of the principle strategies for cancer treatment, but it can have toxic side effects. Nanotechnology attempts to resolve these challenges by loading drugs in nanoparticles, such as solid lipid nanoparticles (SLN). In response to the breast cancer drug 5-fluorouracil (5-FU), p38MAPK signaling has been investigated since the 1990s...
February 27, 2018: Pharmaceutical Research
Jossimara Polettini, Lauren S Richardson, Ramkumar Menon
OBJECTIVE: A physiologic increase of reactive oxygen species (ROS) is observed through pregnancy. ROS-induced damage to major cellular elements, specifically protein peroxidation, can lead to fetal and placental tissue senescence and inflammation often associated with normal parturition. The purpose of this study was to examine the effects of oxidative stress (OS) in inducing changes in proteins, senescence, and sterile inflammation in pregnant mice. METHODS: CD-1 mice (n = 5/group) on day 14 of gestation were subjected to minilaparotomy and the uterine horn between gestational sacs was injected with the following: saline (control), cigarette smoke extract (CSE) CSE diluted in saline and CSE + SB 203580 (SB) (a p38 mitogen-activated protein kinase (MAPK) inhibitor)...
March 2018: Placenta
Y Kim, J Y Cho, S W Oh, M Kang, S E Lee, E Jung, Y S Park, J Lee
BACKGROUND: Adiponectin is an adipocyte-derived cytokine which circulates as a full-length protein and a fragment containing the globular domain of adiponectin (gAd). A recent study has reported the anti-melanogenic effects of full-length adiponectin. OBJECTIVES: To examine the involvement of gAd in melanogenesis and its action mechanisms. METHODS: The effects of gAd on melanogenesis and its mechanism of action were investigated in human epidermal melanocytes and reconstructed epidermis, and they included the levels of melanin content, cellular tyrosinase activity, cAMP production and protein kinase A (PKA) activity, expression and phosphorylation of signaling molecules...
February 27, 2018: British Journal of Dermatology
Xin Zhao, Peng Sun, Guijie Li, Ruokun Yi, Yu Qian, Kun-Young Park
We conducted the present study to determine the gastric injury preventive effects of polyphenols in Kuding tea (KTPs) in Kunming (KM) mice through the inhibition of gastric-acid secretion and the protection of the gastric mucosa. Mice treated with a high concentration of Kuding tea polyphenols (HKTP) had lower serum levels of interleukin-6 (IL-6), IL-12, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), motilin (MOT), substance P (SP), and endothelin-1 (ET-1), and higher serum levels of somatostatin (SS) and vasoactive intestinal peptide (VIP) than did the mice in the control group...
February 27, 2018: Food & Function
Renata Gonçalves, Ana Paula Zanatta, Fernanda Carvalho Cavalari, Monica Andressa Wessner do Nascimento, Christelle Delalande-Lecapitaine, Hélène Bouraïma-Lelong, Fátima Regina Mena Barreto Silva
We investigated the acute effect of low concentrations of BPA on calcium influx and the mechanism of action of BPA in this rapid response in the rat testis. BPA increased calcium influx at 1 pM and 1 nM at 300 s of incubation, in a similar manner to that of estradiol. At 1 pM, BPA stimulated calcium influx independently of classical estrogen receptors, consistent with a G-protein coupled receptor. This effect also involves the modulation of ionic channels, such as K+ , TRPV1 and Cl- channels. Furthermore, BPA is able to modulate calcium from intracellular storages by inhibiting SERCA and activating IP3 receptor/Ca2+ channels at the endoplasmic reticulum and activate kinase proteins, such as PKA and PKC...
February 21, 2018: Reproductive Toxicology
L Xin, W Junhua, L Long, Y Jun, Y Xiaosu
The protective mechanism of exogenous hydrogen sulfide (H2S) on oxygen glucose deprivation/reoxygenation (OGD/R) at physiological doses in SH-SY5Y cells were investigated in this study. Comparing with the normal control group, the expressions of ERK3, p38MAPK and Nrf2 mRNA in other three groups were downregulated at the beginning of 24h. After 24h, the expressions of ERK3, p38MAPK and Nrf2 were upregulated significantly compared with the normal control group. When the cells were pretreated with 200μM NaHS at the beginning of 24h, the expressions of ERK3, p38MAPK and Nrf2 were decreased much more significantly than OGD/R and NaHS groups...
February 22, 2018: Current Molecular Medicine
Song Fu, Renhua Lv, Longqiang Wang, Haitao Hou, Haijun Liu, Shize Shao
Resveratrol, a polyphenol found in various plants, including grapes, plums and peanuts has shown various medIRInal properties, including antioxidant, protection of cardiovascular disease and cancer risk. However, the effects of resveratrol on spinal cord reperfusion injury have not been investigated. Hence, the present study was designed to evaluate the effect of resveratrol on nitric oxide synthase (iNOS)/p38MAPK signaling pathway and to elucidate its regulating effect on the protection of spinal cord injury...
February 2018: Saudi Journal of Biological Sciences
Layla El Moussawi, Mohamed Chakkour, Sawsan I Kreydiyyeh
Epinephrine, a key stress hormone, is known to affect ion transport in the colon. Stress has been associated with alterations in colonic functions leading to changes in water movements manifested as diarrhea or constipation. Colonic water movement is driven by the Na+-gradient created by the Na+/K+-ATPase. Whether epinephrine acts via an effect on the Na+/K+-ATPase hasn't been studied before. The aim of this work was to investigate the effect of epinephrine on the Na+/K+-ATPase and to elucidate the signaling pathway involved using CaCo-2 cells as a model...
2018: PloS One
Penghua Fang, Mei Yu, Wen Min, Dan Wan, Shiyu Han, Yizhi Shan, Rui Wang, Mingyi Shi, Zhenwen Zhang, Ping Bo
AIMS: Although baicalin could attenuate obesity-induced insulin resistance, the detailed mechanism of baicalin on glucose uptake has not been sufficiently explored as yet. The aim of this study was to survey if baicalin might facilitate glucose uptake and to explore its signal mechanisms in L6 myotubes. MATERIALS AND METHODS: L6 myotubes were treated with 100, 200, 400 μM baicalin for 6 h, 12 h and 24 h in this study. Then 2-NBDG and insulin signal protein levels in myotubes of L6 cells were examined...
March 1, 2018: Life Sciences
Qian Wang, Narayan Acharya, Zhongwei Liu, Xianmei Zhou, Meghan Cromie, Jia Zhu, Weimin Gao
ETHNOPHARMACOLOGICAL RELEVANCE: Experience-based herbal medicine as a complementary to modern western medicine has triggered an array of studies in quest of novel anticancer drugs. Scutellaria barbata D. Don (SB) is commonly used to treat different types of cancers, but its molecular mechanism of action is not clearly understood. In this study, we attempted to elucidate the mode of action of a traditional Chinese medicine prescription with a total of 14 components, named Lian-Jia-San-Jie-Fang (LJSJF, in Chinese), where SB works as the "principle" against non-small cell lung cancer (NSCLC) cells...
February 16, 2018: Journal of Ethnopharmacology
Shu-Qi Zhao, Shi-Qiang Xu, Jing Cheng, Xiao-Lu Cao, Ying Zhang, Wei-Ping Zhou, Yan-Juan Huang, Jun Wang, Xia-Min Hu
Escin, as an internally applied anti-inflammatory agent, has been widely used in the treatment of inflammation and edema resulting from trauma or operation in the clinic. However, the effect of its external use on cutaneous inflammation and edema remains unexplored. In the present study, the anti-inflammatory and anti-edematous effects of external use of escin were studied in carrageenan-induced paw edema and histamine-induced capillary permeability in rats, paraxylene-induced ear swelling in mice, and cotton pellet-induced granuloma in rats...
February 2018: Chinese Journal of Natural Medicines
Volker Spindler, Jens Waschke
Pemphigus is a severe autoimmune-blistering disease of the skin and mucous membranes caused by autoantibodies reducing desmosomal adhesion between epithelial cells. Autoantibodies against the desmosomal cadherins desmogleins (Dsgs) 1 and 3 as well as desmocollin 3 were shown to be pathogenic, whereas the role of other antibodies is unclear. Dsg3 interactions can be directly reduced by specific autoantibodies. Autoantibodies also alter the activity of signaling pathways, some of which regulate cell cohesion under baseline conditions and alter the turnover of desmosomal components...
2018: Frontiers in Immunology
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