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Inhibitory receptor

Olga Volotskova, Larisa Dubrovsky, Michael Keidar, Michael Bukrinsky
Cold atmospheric plasma (CAP) is a specific type of partially ionized gas that is less than 104°F at the point of application. It was recently shown that CAP can be used for decontamination and sterilization, as well as anti-cancer treatment. Here, we investigated the effects of CAP on HIV-1 replication in monocyte-derived macrophages (MDM). We demonstrate that pre-treatment of MDM with CAP reduced levels of CD4 and CCR5, inhibiting virus-cell fusion, viral reverse transcription and integration. In addition, CAP pre-treatment affected cellular factors required for post-entry events, as replication of VSV-G-pseudotyped HIV-1, which by-passes HIV receptor-mediated fusion at the plasma membrane during entry, was also inhibited...
2016: PloS One
John P Veluchamy, A Marijne Heeren, Jan Spanholtz, Jaap D H van Eendenburg, Daniëlle A M Heideman, Gemma G Kenter, Henk M Verheul, Hans J van der Vliet, Ekaterina S Jordanova, Tanja D de Gruijl
Down-regulation of HLA in tumor cells, low numbers and dysfunctionality of NK cells are commonly observed in patients with end-stage cervical cancer. Adoptive transfer of high numbers of cytotoxic NK cells might be a promising treatment approach in this setting. Here, we explored the cytotoxic efficacy on ten cervical cancer cell lines of activated allogeneic NK cells from two sources, i.e., peripheral blood (PBNK) with and without cetuximab (CET), a tumor-specific monoclonal antibody directed against EGFR, or derived from umbilical cord blood (UCB-NK)...
October 25, 2016: Cancer Immunology, Immunotherapy: CII
Youping Wu, Chun-Shiang Chung, Yaping Chen, Sean Farrell Monaghan, Sima Patel, Xin Huang, Daithi Seamus Heffernan, Alfred Ayala
Studies imply that intestinal barrier dysfunction is a key contributor to morbid events associated with sepsis. Recently, co-inhibitory molecule, programmed death-ligand1 (PD-L1) has been shown to be involved in the regulation of intestinal immune tolerance and/or inflammation. Our previous studies showed that PD-L1 gene deficiency reduced sepsis-induced intestinal injury morphologically. However, it isn't known how PD-L1 expression impacts intestinal barrier dysfunction during sepsis. Here we tested the hypothesis that PD-L1 expressed on intestinal epithelial cells (IECs) has a role in sepsis-induced intestinal barrier dysfunction...
October 25, 2016: Molecular Medicine
Zhen Zhang, Dongmei Zhao, Yang Dai, Maosheng Cheng, Meiyu Geng, Jingkang Shen, Yuchi Ma, Jing Ai, Bing Xiong
Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazole derivatives as potent FGFR inhibitors. The compound 6-(2,6-dichloro-3,5-dimethoxyphenyl)-N-phenyl-1H-indazole-4-carboxamide (10a) was identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that 6-(2,6-dichloro-3,5-dimethoxyphenyl)-N-(3-(4-methylpiperazin-1-yl)phenyl)-1H-indazole-4-carboxamide (13a) is the most potent FGFR1 inhibitor in this series, with an enzyme inhibitory activity IC50 value of about 30...
October 23, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Samra Khalid, Rumeza Hanif, Samar H K Tareen, Amnah Siddiqa, Zurah Bibi, Jamil Ahmad
BACKGROUND: Breast cancer (BC) is one of the leading cause of death among females worldwide. The increasing incidence of BC is due to various genetic and environmental changes which lead to the disruption of cellular signaling network(s). It is a complex disease in which several interlinking signaling cascades play a crucial role in establishing a complex regulatory network. The logical modeling approach of René Thomas has been applied to analyze the behavior of estrogen receptor-alpha (ER-α) associated Biological Regulatory Network (BRN) for a small part of complex events that leads to BC metastasis...
2016: PeerJ
I Rostás, J Tenk, A Mikó, N Füredi, S Soós, M Solymár, A Lengyel, M Székely, B Gaszner, D Feller, E Pétervári, M Balaskó
Leptin is a key catabolic regulator of food intake (FI) and energy expenditure. Both aging and obesity have been shown to induce leptin-resistance. The present study aimed to analyze age-related changes in the anorexigenic and hypermetabolic responsiveness to acute intracerebroventricular leptin administration in different age-groups of normally fed male Wistar rats (adult and old rats from 3 to 24months of age, NF3 to NF24, respectively). The expressions of the long form of the leptin receptor (Ob-Rb) and inhibitory SOCS3 genes were also assessed by quantitative RT-PCR in the arcuate nucleus (ARC)...
October 22, 2016: Experimental Gerontology
Mingzhou Yuan, Junmin Chen, Zhiyong Zeng
Patients with multiple myeloma (MM) often develop myeloma bone disease (MBD). The development of MBD from MM is considered to be caused by an abnormal bone marrow microenvironment. Macrophage inhibitory cytokine-1 (MIC-1) is a member of the transforming growth factor‑β superfamily. In patients with MM, MIC‑1 is expressed at high levels, however, whether this increased expression of MIC‑1 is associated with the development of MBD from MM remains to be elucidated. The present study investigated whether MIC‑1 is essential for the osteoclastic differentiation of peripheral blood mononuclear cells (PBMNCs) by using a co‑culture system, in which the PBMNCs were co‑cultured with RPMI‑8226 cells...
October 24, 2016: Molecular Medicine Reports
Diogo M Rombo, Joaquim A Ribeiro, Ana M Sebastião
Physiological network functioning in the hippocampus is dependent on a balance between glutamatergic cell excitability and the activity of diverse local circuit neurons that release the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Tuners of neuronal communication such as adenosine, an endogenous modulator of synapses, control hippocampal network operations by regulating excitability. Evidence has been recently accumulating on the influence of adenosine on different aspects of GABAergic transmission to shape hippocampal function...
October 25, 2016: Journal of Neurochemistry
Yamila Sol Rocca, María Paula Roberti, Estefanía Paula Juliá, María Betina Pampena, Luisina Bruno, Sergio Rivero, Eduardo Huertas, Fernando Sánchez Loria, Alejandro Pairola, Anne Caignard, José Mordoh, Estrella Mariel Levy
The clinical outcome of colorectal cancer (CRC) is associated with the immune response; thus, these tumors could be responsive to different immune therapy approaches. Natural killer (NK) cells are key antitumor primary effectors that can eliminate CRC cells without prior immunization. We previously determined that NK cells from the local tumor environment of CRC tumors display a profoundly altered phenotype compared with circulating NK cells from healthy donors (HD). In this study, we evaluated peripheral blood NK cells from untreated patients and their possible role in metastasis progression...
2016: Frontiers in Immunology
Yong-Kang Yang, Chao Yang, Waipan Chan, Zhaoquan Wang, Katelynn E Deibel, Joel L Pomerantz
The activation of NF-κB downstream of T Cell Receptor (TCR) engagement is a key signaling step required for normal lymphocyte function during the adaptive immune response. During TCR signaling, the adaptor protein Bcl10 is inducibly recruited to the CARD11 scaffold protein as part of a multicomponent complex that induces IKK kinase activity and NF-κB activation. Here we show that a consequence of this recruitment is the TCR-induced conjugation of Bcl10 with linear-linked polyubiquitin chains, to generate the signaling intermediate Lin(Ub)n-Bcl10, which is required for the association of Bcl10 with the NEMO subunit of the IKK complex...
October 24, 2016: Journal of Biological Chemistry
Quan Feng Liu, Haemin Jeong, Jang Ho Lee, Yoon Ki Hong, Youngje Oh, Young-Mi Kim, Yoon Seok Suh, Semin Bang, Hye Sup Yun, Kyungho Lee, Sung Man Cho, Sung Bae Lee, Songhee Jeon, Young-Won Chin, Byung-Soo Koo, Kyoung Sang Cho
Alzheimer's disease (AD), the most common neurodegenerative disease, has a complex and widespread pathology that is characterized by the accumulation of amyloid [Formula: see text]-peptide (A[Formula: see text]) in the brain and various cellular abnormalities, including increased oxidative damage, an amplified inflammatory response, and altered mitogen-activated protein kinase signaling. Based on the complex etiology of AD, traditional medicinal plants with multiple effective components are alternative treatments for patients with AD...
October 25, 2016: American Journal of Chinese Medicine
Pleun Hombrink, Christina Helbig, Ronald A Backer, Berber Piet, Anna E Oja, Regina Stark, Giso Brasser, Aldo Jongejan, René E Jonkers, Benjamin Nota, Onur Basak, Hans C Clevers, Perry D Moerland, Derk Amsen, René A W van Lier
Tissue-resident memory T cells (TRM cells) in the airways mediate protection against respiratory infection. We characterized TRM cells expressing integrin αE (CD103) that reside within the epithelial barrier of human lungs. These cells had specialized profiles of chemokine receptors and adhesion molecules, consistent with their unique localization. Lung TRM cells were poised for rapid responsiveness by constitutive expression of deployment-ready mRNA encoding effector molecules, but they also expressed many inhibitory regulators, suggestive of programmed restraint...
October 24, 2016: Nature Immunology
Marta Pardo, Eleonore Beurel, Richard S Jope
Cotinine is the major metabolite of nicotine and has displayed some capacity for improving cognition in mouse models following chronic administration. We tested if acute cotinine treatment is capable of improving cognition in the mouse model of Fragile X syndrome, Fmr1(-/-) knockout mice, and if this is related to inhibition by cotinine treatment of glycogen synthase kinase-3β (GSK3β), which is abnormally active in Fmr1(-/-) mice. Acute cotinine treatment increased the inhibitory serine-phosphorylation of GSK3β and the activating phosphorylation of AKT, which can mediate serine-phosphorylation of GSK3β, in both wild-type and Fmr1(-/-) mouse hippocampus...
October 24, 2016: European Journal of Neuroscience
Yingguo Ren, Baochao Zhang, Dongpei Jia, Ke Hu
Objective To investigate the effects of tetramethylpyrazine (TMP) on experimental autoimmune myasthenia gravis (EAMG) in rats and explore the possible immune regulation mechanism. Methods Lewis rats were randomly divided into 4 groups: control group, EAMG group, TMP low-dose group (TMP-L, 10 mg/kg) and TMP high-dose group (TMP-H, 20 mg/kg). Except the control group, the other 3 groups were subjected to EAMG modeling. The body mass was determined and the symptoms of muscular weakness in rats were scored by Lennon EAMG criteria...
November 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
Alina Kurolap, Anja Armbruster, Tova Hershkovitz, Katharina Hauf, Adi Mory, Tamar Paperna, Ewald Hannappel, Galit Tal, Yusif Nijem, Ella Sella, Muhammad Mahajnah, Anat Ilivitzki, Dov Hershkovitz, Nina Ekhilevitch, Hanna Mandel, Volker Eulenburg, Hagit N Baris
Glycine is a major neurotransmitter that activates inhibitory glycine receptors and is a co-agonist for excitatory glutamatergic N-methyl-D-aspartate (NMDA) receptors. Two transporters, GLYT1 and GLYT2, regulate extracellular glycine concentrations within the CNS. Dysregulation of the extracellular glycine has been associated with hyperekplexia and nonketotic hyperglycinemia. Here, we report four individuals from two families who presented at birth with facial dysmorphism, encephalopathy, arthrogryposis, hypotonia progressing to hypertonicity with startle-like clonus, and respiratory failure...
October 18, 2016: American Journal of Human Genetics
Junji Uno, Keisuke Obara, Hiroko Suzuki, Satomi Miyatani, Daisuke Chino, Takashi Yoshio, Yoshio Tanaka
BACKGROUND/AIMS: To investigate the potential inhibitory effects of 18 clinically available antidepressants on acetylcholine (ACh)-induced contractions in guinea pig urinary bladder smooth muscle (UBSM) in order to predict whether they may induce voiding impairment. METHODS: Concentration-response curves for ACh-induced contractions in guinea pig UBSM strips were obtained in the absence or presence of selected antidepressants. When inhibitory effects indicated competitive antagonism, pA2 values against ACh were calculated and compared to plausible antidepressant blood concentrations...
October 22, 2016: Pharmacology
Michiko Nanao-Hamai, Bo-Kyung Son, Tsuyoshi Hashizume, Sumito Ogawa, Masahiro Akishita
Vascular calcification is one of the major complications of cardiovascular disease and is an independent risk factor for myocardial infarction and cardiac death. Postmenopausal women have a higher prevalence of vascular calcification compared with premenopausal women, suggesting protective effects of estrogen (E2). However, the underlying mechanisms of its beneficial effects remain unclear. In the present study, we examined the inhibitory effects of E2 on vascular smooth muscle cell (VSMC) calcification, and found that growth arrest-specific gene 6 (Gas6), a crucial molecule in vascular calcification, is transactivated by estrogen receptor α (ERα) in response to E2...
October 19, 2016: Biochemical and Biophysical Research Communications
Ge Shi, Ting-Ting Wang, Juan-Hua Quan, Shi-Jie Li, Man-Feng Zhang, Pei-Yu Liao, Yi-Ming Fan
BACKGROUND: The transcription factor Sox9 is pivotal in the morphogenesis of hair follicles, but its role in sebocytes is poorly understood. OBJECTIVE: We investigated the effect of Sox9 on human sebocyte proliferation, differentiation and lipogenesis. METHODS: Sox9 expression was detected by immunohistochemistry in normal skin and acne lesion. Primary cultured human sebocytes were transfected with adenovirus expressing GFP-Sox9 or Sox9 microRNA...
October 13, 2016: Journal of Dermatological Science
Andrei Tsentsevitsky, Leniz Nurullin, Evgeny Nikolsky, Artem Malomouzh
There is some evidence that glutamate (Glu) acts as a signaling molecule at vertebrate neuromuscular junctions where acetylcholine (ACh) serves as a neurotransmitter. In this study, performed on the cutaneous pectoris muscle of the frog Rana ridibunda, Glu receptor mechanisms that modulate ACh release processes were analyzed. Electrophysiological experiments showed that Glu reduces both spontaneous and evoked quantal secretion of ACh and synchronizes its release in response to electrical stimulation. Quisqualate, an agonist of ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptors and metabotropic Group I mGlu receptors, also exerted Glu-like inhibitory effects on the secretion of ACh but had no effect on the kinetics of quantal release...
October 22, 2016: Journal of Neuroscience Research
Xuehua Piao, Soh Yamazaki, Sachiko Komazawa-Sakon, Sanae Miyake, Osamu Nakabayashi, Takeyuki Kurosawa, Tetsuo Mikami, Minoru Tanaka, Nico Van Rooijen, Masaki Ohmuraya, Akira Oikawa, Yuko Kojima, Soichiro Kakuta, Yasuo Uchiyama, Masato Tanaka, Hiroyasu Nakano
: Tissue-resident macrophages and bone marrow (BM)-derived monocytes play a crucial role in the maintenance of tissue homeostasis; however, their contribution to recovery from acute tissue injury is not fully understood. To address this issue, we generated an acute murine liver injury model using hepatocyte-specific Cflar-deficient (Cflar(Hep-low) ) mice. Cellular FLICE-inhibitory protein (cFLIP) expression was downregulated in Cflar-deficient hepatocytes, which thereby increased susceptibility of hepatocytes to death receptor-induced apoptosis...
October 22, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
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