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https://www.readbyqxmd.com/read/28944853/kisspeptin-inhibits-cancer-growth-and-metastasis-via-activation-of-eif2ak2
#1
Tae-Hun Kim, Sung-Gook Cho
Kisspeptin is a protein encoded by the KISS1 gene, which has been reported to suppress the metastatic capabilities of various types of cancer cells, through the activation of its G‑protein coupled receptor GPR54. However, the molecular mechanisms underlying the involvement of kisspeptin‑mediated signaling in the inhibition of cancer cell migration and invasion have yet to be elucidated. The present in vitro cell proliferation, migration and invasion assays and in vivo experimental metastasis studies demonstrated that kisspeptin‑induced eukaryotic translation initiation factor 2α kinase 2 (EIF2AK2) activation suppressed the metastatic capabilities of several types of cancer cells...
September 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28944833/low-doses-of-co-nanoparticles-induce-death-and-regulate-osteogenic-differentiation-in-mg%C3%A2-63-cells
#2
Qinglin Han, Fan Liu
The aim of the present study was to investigate the effects of cobalt nanoparticles (CoNPs) on the proliferation and differentiation of human osteoblasts in vitro, and to investigate the molecular mechanisms via which CoNPs affect proliferation and differentiation of osteoblasts. The MG‑63 human osteoblast cell line was treated with different concentrations of CoNPs for 12 to 48 h in vitro. At each time point, cell morphology was observed and an MTT assay was performed to assess cell viability. Alkaline phosphatase (ALP), osteocalcin (BGLAP), collagen I (COL I), osteoprotegerin (OPG) and receptor activator of nuclear factor κ‑B ligand mRNA expression levels, and ALP, BGLAP and COL protein expression levels, were assessed by reverse transcription‑quantitative polymerase chain reaction and western blotting, respectively...
September 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28944454/an-inhibitory-epitope-of-human-toll-like-receptor-4-resides-on-leucine-rich-repeat-13-and-is-recognized-by-a-monoclonal-antibody
#3
Hiroki Tsukamoto, Yuki Yamagata, Ippo Ukai, Shino Takeuchi, Misaki Okubo, Yohei Kobayashi, Sao Kozakai, Kanae Kubota, Muneo Numasaki, Yoshitomi Kanemitsu, Yotaro Matsumoto, Yoshihisa Tomioka
No abstract text is available yet for this article.
September 2017: FEBS Letters
https://www.readbyqxmd.com/read/28944167/regulation-of-cytotoxic-t-cell-responses-by-p53-in-cancer
#4
Mitchell W Braun, Tomoo Iwakuma
An intriguing aspect of the tumor suppressor p53 is its ability to communicate to the adaptive immune system and control the cytotoxic T-lymphocyte (CTL) response to cancer cells. Wild-type p53 (wtp53) communicates with CTLs through proteins involved in the major histocompatibility complex (MHC) class I antigen presentation pathway [e.g., transporter associated with antigen processing 1 (TAP1) and endoplasmic reticulum amino peptidase 1 (ERAP1)], the apoptosis signal receptor Fas/APO-1, and the inhibitory immune-checkpoint programmed death-ligand 1 (PD-L1)...
December 2016: Translational Cancer Research
https://www.readbyqxmd.com/read/28943409/interleukin-1-%C3%AE-induced-smad2-3-linker-modifications-are-tak1-dependent-and-delay-tgf%C3%AE-signaling-in-primary-human-mesenchymal-stem-cells
#5
Guus G van den Akker, Henk M van Beuningen, Elly L Vitters, Marije I Koenders, Fons A de Loo, Peter L van Lent, Esmeralda N Blaney Davidson, Peter M van der Kraan
BACKGROUND: Chondrogenic differentiation of mesenchymal stem cells (MSC) requires transforming growth factor beta (TGFβ) signaling. TGFβ binds to the type I receptor activin-like kinase (ALK)5 and results in C-terminal SMAD2/3 phosphorylation (pSMAD2/3C). In turn pSMAD2/3C translocates to the nucleus and regulates target gene expression. Inflammatory mediators are known to exert an inhibitory effect on MSC differentiation. In this study we investigated the effect of interleukin 1 β (IL1β) on SMAD2/3 signaling dynamics and post-translational modifications...
September 21, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28943093/naturak-killer-cell-immunotherapies-against-cancer-checkpoint-inhibitors-and-more
#6
REVIEW
Laura Chiossone, Margaux Vienne, Yann M Kerdiles, Eric Vivier
After many years of research, recent advances have shed new light on the role of the immune system in advanced-stage cancer. Various types of immune cells may be useful for therapeutic purposes, along with chemical molecules and engineered monoclonal antibodies. The immune effectors suitable for manipulation for adoptive transfer or drug targeting in vivo include natural killer (NK) cells. These cells are of particular interest because they are tightly regulated by an array of inhibitory and activating receptors, enabling them to kill tumor cells while sparing normal cells...
September 21, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28942638/inhibitory-effects-of-north-american-wild-rice-on-monocyte-adhesion-and-inflammatory-modulators-in-ldl-receptor-knockout-mice
#7
Mohammed H Moghadasian, Ruozhi Zhao, Nora Ghazzawi, Khuong Le, Franklin B Apea-Bah, Trust Beta, Garry Shen
The present study examined the effects of wild rice on monocyte adhesion, inflammatory and fibrinolytic mediators in low-density lipoprotein receptor-knockout (LDLr-KO) mice. Male LDLr-KO mice received cholesterol (0.06%, w/w) supplemented diet with or without white rice or wild rice (60%, w/w) for 20 weeks. White rice significantly increased monocyte adhesion, abundances of monocyte chemoattractant protein-1, tissue necrosis factor-α, intracellular cell adhesion molecule-1, plasminogen activator inhibitor-1, urokinase plasminogen activator (uPA), and uPA receptor in aortae and hearts of LDLr-KO mice compared to control diet...
September 25, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28942113/novel-serms-based-on-3-aryl-4-aryloxy-2h-chromen-2-one-skeleton-a-possible-way-to-dual-er%C3%AE-vegfr-2-ligands-for-treatment-of-breast-cancer
#8
Guoshun Luo, Xinyu Li, Guoqing Zhang, Chengzhe Wu, Zhengpu Tang, Linyi Liu, Qidong You, Hua Xiang
There is considerable interest in developing new SERMs as multifunctional agents in women's health. Development of dual selective estrogen receptor modulators/VEGFR-2 inhibitors (SERMs/V-2I) has been an attractive strategy for the discovery of new breast cancer therapeutic agents. Our previous efforts led to the preparation of a series of 3-aryl-4-anilino-2H-chromen-2-ones endowed with potent estrogen receptor binding affinity and anti-proliferative efficacy. In this study, various structurally related 3-aryl-4-anilino/aryloxy-2H-chromen-2-one analogues were rationally designed, synthesized and evaluated as a new chemo-type of dual ERα and VEGFR-2 inhibitors...
September 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28941256/distinct-protein-kinase-c-isoenzyme-mediates-inhibitory-effects-of-different-g-protein-coupled-receptors-on-cardiac-rapidly-activating-delayed-rectifier-k-current
#9
Xueli Liu, Yuhong Wang, Hua Zhang, Li Shen, Yanfang Xu
BACKGROUND AND PURPOSE: Elevated angiotensin II (Ang II) and sympathetic activity contributes to high risk of ventricular arrhythmias in heart diseases. The rapidly activating delayed rectifier K(+) current (IKr ) carried by the hERG protein plays a critical role in cardiac repolarization; and a reduction of IKr is involved in increased cardiac arrhythmogenicity. Studies have shown that stimulation of α1A -adrenoreceptors (α1A AR) or Ang II type 1 receptor (AT1 R) inhibits IKr via protein kinase C (PKC)...
September 23, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28941191/activating-%C3%AE-7-nicotinic-acetylcholine-receptor-inhibits-nlrp3-inflammasome-through-regulation-of-%C3%AE-arrestin-1
#10
Ping Ke, Bo-Zong Shao, Zhe-Qi Xu, Xiong-Wen Chen, Wei Wei, Chong Liu
AIMS: To evaluate whether activating α7 nicotinic acetylcholine receptor (α7nAChR) could inhibit the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome through regulation of β-arrestin-1 in monocyte/macrophage system, thus contributing to the control of neuroinflammation. METHODS: The protein levels of NLRP3, caspase-1 (Casp-1) p20 and proCasp-1, interleukin-1β (IL-1β) p17 and proIL-1β, IL-18 and proIL-18 were measured using Western blotting...
September 21, 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/28940989/amino-acid-modulation-of-dopamine-in-the-nucleus-accumbens-mediates-sex-differences-in-nicotine-withdrawal
#11
Luis M Carcoba, Rodolfo J Flores, Luis A Natividad, Laura E O'Dell
The aversive effect of nicotine withdrawal is greater in female versus male rats, and we postulate that this sex difference is mediated in the nucleus accumbens (NAc). Nicotine withdrawal induces decreases in NAc dopamine and increases in acetylcholine (ACh) levels in male rats. To our knowledge, these neurochemical markers of nicotine withdrawal have not been compared in female versus male rats. Given the role of amino acids in modulating NAc dopaminergic and cholinergic transmission, concomitant measures of gamma-aminobutyric acid (GABA) and glutamate levels were also compared across sex...
September 22, 2017: Addiction Biology
https://www.readbyqxmd.com/read/28940446/the-pd-1-and-pd-l1-pathway-in-recurrent-respiratory-papillomatosis
#12
Julie Ahn, Justin A Bishop, Richard B S Roden, Clint T Allen, Simon R A Best
OBJECTIVES/HYPOTHESIS: Generation of an immunosuppressive microenvironment may enable a persistent human papillomavirus infection in the setting of an otherwise normal immune system. We hypothesized that expression of the T-lymphocyte co-inhibitory receptor programmed death 1 (PD-1) and its ligand PD-L1 would be increased in the recurrent respiratory papillomatosis (RRP) microenvironment compared to normal controls. STUDY DESIGN: Case-control study. METHODS: Formalin-fixed paraffin-embedded respiratory papilloma and normal controls were obtained under institutional review board approval, stained for CD4, CD8, FoxP3, and PD-1, and scored by automated cell count...
September 22, 2017: Laryngoscope
https://www.readbyqxmd.com/read/28939592/%C3%AE-ketoglutarate-prevents-skeletal-muscle-protein-degradation-and-muscle-atrophy-through-phd3-adrb2-pathway
#13
Xingcai Cai, Yexian Yuan, Zhengrui Liao, Kongping Xing, Canjun Zhu, Yaqiong Xu, Lulu Yu, Lina Wang, Songbo Wang, Xiaotong Zhu, Ping Gao, Yongliang Zhang, Qingyan Jiang, Pingwen Xu, Gang Shu
Skeletal muscle atrophy due to excessive protein degradation is the main cause for muscle dysfunction, fatigue, and weakening of athletic ability. Endurance exercise is effective to attenuate muscle atrophy, but the underlying mechanism has not been fully investigated. α-Ketoglutarate (AKG) is a key intermediate of tricarboxylic acid cycle, which is generated during endurance exercise. Here, we demonstrated that AKG effectively attenuated corticosterone-induced protein degradation and rescued the muscle atrophy and dysfunction in a Duchenne muscular dystrophy mouse model...
September 22, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28939533/comparative-mapping-of-on-targets-and-off-targets-for-the-discovery-of-anti-trypanosomatid-folate-pathway-inhibitors
#14
Joanna Panecka-Hofman, Ina Pöhner, Francesca Spyrakis, Talia Zeppelin, Flavio Di Pisa, Lucia Dello Iacono, Alessio Bonucci, Antonio Quotadamo, Alberto Venturelli, Stefano Mangani, Maria Paola Costi, Rebecca C Wade
BACKGROUND: Multi-target approaches are necessary to properly analyze or modify the function of a biochemical pathway or a protein family. An example of such a problem is the repurposing of the known human anti-cancer drugs, antifolates, as selective anti-parasitic agents. This requires considering a set of experimentally validated protein targets in the folate pathway of major pathogenic trypanosomatid parasites and humans: (i) the primary parasite on-targets: pteridine reductase 1 (PTR1) (absent in humans) and bifunctional dihydrofolate reductase-thymidylate synthase (DHFR-TS), (ii) the primary off-targets: human DHFR and TS, and (iii) the secondary on-target: human folate receptor β, a folate/antifolate transporter...
September 20, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28939255/inhibition-of-quorum-sensing-related-virulence-factors-of-pseudomonas-aeruginosa-by-pyridoxal-lactohydrazone
#15
Azam Heidari, Nader Noshiranzadeh, Fakhri Haghi, Rahman Bikas
Pseudomonas aeruginosa quorum sensing (QS) system is a cell to cell signaling mechanism that regulates virulence factors and pathogenicity. Therefore, the QS system in P. aeruginosa may be an important target for pharmacological intervention. The present study aimed to investigate the effects of sub-MIC concentrations of (S,E)-2-hydroxy-N-(3-hydroxy-5-(hydroxymethyl)-2-methylpyridin-4-yl)propane hydrazide (pyridoxal lactohydrazone) against P. aeruginosa QS related virulence factors. We investigated the effect of sub-MIC concentrations of chiral pyridoxal lactohydrazone, which formed by the reaction of chiral lactic acid hydrazide and pyridoxal (one form of Vitamin B6) as bioactive reagents, on virulence factors...
September 19, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28938487/regulation-of-endogenous-male-rodent-glp-1-secretion-and-human-islet-insulin-secretion-by-antagonism-of-somatostatin-receptor-5
#16
Thomas B Farb, Marta Adeva, Thomas J Beauchamp, Over Cabrera, David A Coates, Tamika DeShea Meredith, Brian A Droz, Alexander Efanov, James V Ficorilli, Susan L Gackenheimer, Maria A Martinez-Grau, Victoriano Molero, Gema Ruano, Michael A Statnick, Todd M Suter, Samreen K Syed, Miguel A Toledo, Francis S Willard, Xin Zhou, Krister B Bokvist, David G Barrett
Incretin and insulin responses to nutrient loads are suppressed in persons with diabetes, resulting in decreased glycemic control. Whereas agents including sulfonylureas and Dipeptidyl peptidase-4 inhibitors (DPP4i) partially reverse these effects and provide therapeutic benefit, their modes of action limit efficacy. Because somatostatin (SST) has been shown to suppress both insulin and GLP-1 secretion through the Gi-coupled SST receptor 5 (SSTR5) isoform in vitro, antagonism of SSTR5 may improve glycemic control via intervention in both pathways...
September 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938189/the-potent-suppressive-effect-of-%C3%AE-d-mannuronic-acid-m2000-on-molecular-expression-of-the-tlr-nf-kb-signaling-pathway-in-ankylosing-spondylitis-patients
#17
Maryam Roozbehkia, Mahdi Mahmoudi, Somaye Aletaha, Nima Rezaei, Mohammad Javad Fattahi, Fahimeh Jafarnezhad-Ansariha, Anis Barati, Abbas Mirshafiey
Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease characterized by the inflammation of sacroiliac joints and axial skeleton. A combination of genetic, environmental and immunological factors are involved in AS's pathogenesis. TLRs are type I transmembrane glycoproteins that play a crucial role in the innate immune responses against invading pathogens. Observational studies have demonstrated a possible association between TLR dysregulation and AS. The β-d-mannuronic acid (M2000), as a novel NSAID with immunosuppressive property, has shown an inhibitory effect on Toll-like receptor (TLR) 2, 4 signaling in HEK293 cells...
September 19, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28938084/the-evolving-understanding-of-dopamine-neurons-in-the-substantia-nigra-and-ventral-tegmental-area
#18
Stephanie C Gantz, Christopher P Ford, Hitoshi Morikawa, John T Williams
In recent years, the population of neurons in the ventral tegmental area (VTA) and substantia nigra (SN) has been examined at multiple levels. The results indicate that the projections, neurochemistry, and receptor and ion channel expression in this cell population vary widely. This review centers on the intrinsic properties and synaptic regulation that control the activity of dopamine neurons. Although all dopamine neurons fire action potentials in a pacemaker pattern in the absence of synaptic input, the intrinsic properties that underlie this activity differ considerably...
September 22, 2017: Annual Review of Physiology
https://www.readbyqxmd.com/read/28937296/comparison-of-e-cadherin-with-stat3-and-apoptosis-regulators-bak-and-bcl-xl-in-endometrioid-adenocarcinomas-of-different-er-alpha-immunoprofile
#19
Urszula Sulkowska, Andrzej Wincewicz, Luiza Kanczuga-Koda, Mariusz Koda, Stanislaw Sulkowski
E-cadherin is a factor of good prognosis in endometrioid adenocarcinomas, while STAT3 is an oncogenic driver of carcinogenesis. E-cadherin, Bak, Bcl-xL and STAT3 were immunohistochemically detected in 78 human endometrioid adenocarcinomas. E-cadherin correlated with STAT3 (p <. 001, r = 0.537) as well as Bak (p = .005, r = 0.314) and Bcl-xL (p = .002, r = 0.340) in the whole study group. In G2 tumors, E-cadherin associated with Bak (p = .021, r = 0.319), Bcl-xL (p = .026, r = 0...
September 22, 2017: Gynecological Endocrinology
https://www.readbyqxmd.com/read/28935720/suppression-of-store-operated-ca-2-entry-by-activation-of-gper-contribution-to-a-clamping-effect-on-endothelial-ca-2-signaling
#20
Lara E Terry, Mark VerMeer, Jennifer Giles, Quang-Kim Tran
The G Protein-coupled Estrogen Receptor 1 (GPER, formerly a.k.a. GPR30) modulates many Ca(2+)-dependent activities in endothelial cells. However, the underlying mechanisms are poorly understood. We recently reported that GPER acts to prolong cytoplasmic Ca(2+) signals by interacting with and promoting inhibitory phosphorylation of the plasma membrane Ca(2+)-ATPase. In this study, we examined the role of GPER activation in modulating store-operated Ca(2+) entry (SOCE) via effects on the Stromal Interaction Molecule 1 (STIM1)...
September 21, 2017: Biochemical Journal
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