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https://www.readbyqxmd.com/read/28652577/human-in-vitro-induced-regulatory-t-cells-display-dlgh1dependent-and-pkc-%C3%AE-restrained-suppressive-activity
#1
Alexandra Zanin-Zhorov, Sudha Kumari, Keli L Hippen, Sarah C Merkel, Margaret L MacMillan, Bruce R Blazar, Michael L Dustin
In vitro induced human regulatory T cells (iTregs) have demonstrated in vivo therapeutic utility, but pathways regulating their function have not been elucidated. Here, we report that human iTregs generated in vitro from naïve cord blood cells preferentially recruit Disc large homolog 1 (Dlgh1) and exclude protein kinase C (PKC)-θ from immunological synapses formed on supported lipid bilayers with laterally mobile ICAM-1 and anti-CD3 mAb. Also, iTregs display elevated Dlgh1 overall and Dlgh1-dependent p38 phosphorylation, higher levels of phosphatase and tensin homolog (PTEN), and diminished Akt phosphorylation...
June 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28648820/selective-erasure-of-distinct-forms-of-long-term-synaptic-plasticity-underlying-different-forms-of-memory-in-the-same-postsynaptic-neuron
#2
Jiangyuan Hu, Larissa Ferguson, Kerry Adler, Carole A Farah, Margaret H Hastings, Wayne S Sossin, Samuel Schacher
Generalization of fear responses to non-threatening stimuli is a feature of anxiety disorders. It has been challenging to target maladaptive generalized memories without affecting adaptive memories. Synapse-specific long-term plasticity underlying memory involves the targeting of plasticity-related proteins (PRPs) to activated synapses. If distinct tags and PRPs are used for different forms of plasticity, one could selectively remove distinct forms of memory. Using a stimulation paradigm in which associative long-term facilitation (LTF) occurs at one input and non-associative LTF at another input to the same postsynaptic neuron in an Aplysia sensorimotor preparation, we found that each form of LTF is reversed by inhibiting distinct isoforms of protein kinase M (PKM), putative PRPs, in the postsynaptic neuron...
June 12, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28648552/epigenetic-induction-of-melatonin-mt1-receptors-by-valproate-neurotherapeutic-implications
#3
Sarra G Bahna, Lennard P Niles
We have reported that the anticonvulsant/mood stabilizer and histone deacetylase (HDAC) inhibitor valproate (VPA) induces expression of melatonin receptors both in vitro and in vivo, but the mechanisms involved were not known. Here we show that pharmacological inhibition of CREB, PKC, PI3K, or GSK3β signaling pathways, which are known targets for VPA, do not prevent its upregulation of melatonin MT1 receptors in rat C6 glioma cells. M344, an HDAC inhibitor unrelated to VPA, mimics the effects of VPA on MT1 expression, whereas valpromide, a VPA derivative lacking HDAC inhibitory activity, does not...
June 22, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28647652/kinase-activity-in-recurring-primary-skull-base-chordomas-and-chondrosarcomas-identification-of-novel-pathways-of-oncogenesis-and-potential-drug-targets
#4
Philip Tatman, Joshua Osbun, Youssef Yakkioui, Sumanpret Kaur, Carolina Parada, Tina Busald, Donald Born, Owais Ahmad, Jing Zhang, Manuel Ferreira
OBJECTIVE: Chordomas and chondrosarcomas are tumors that can occur in the skull base. Currently, 45% of chordomas and 56% of chondrosarcomas recur within five years of surgery. The role of adjuvant therapy is highly debated. No pharmacotherapies have been approved by the FDA for chordomas or chondrosarcomas. The high propensity for recurrence and lack of definitive adjuvant therapy necessitates additional basic science research to identify molecular anomalies associated with recurrent disease...
June 21, 2017: World Neurosurgery
https://www.readbyqxmd.com/read/28645780/salvia-miltiorrhiza-bunge-danshen-extract-attenuates-permanent-cerebral-ischemia-through-inhibiting-platelet-activation-in-rats
#5
Yu-Xiang Fei, Si-Qi Wang, Li-Jian Yang, Yan-Ying Qiu, Yi-Ze Li, Wen-Yuan Liu, Tao Xi, Wei-Rong Fang, Yun-Man Li
ETHNOPHARMACOLOGICAL RELEVANCE: Danshen is a crude herbal drug isolated from dried roots of Salvia miltiorrhiza Bunge. This plant is widely used in oriental medicine for the treatment of cardiovascular and cerebrovascular diseases. The supercritical CO2 extract from Danshen (SCED) (57.85%, 5.67% and 4.55% for tanshinone IIA, tanshinone I and cryptotanshinone respectively) was studied in this article, whose potential molecular mechanism remains unclear, especially in anti-thrombosis. AIM OF THE STUDY: The present study was designed to observe the protective effect of SCED on ischemic stroke in rats and to explore the underlying anti-thrombosis mechanism...
June 20, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28645106/phorbol-esters-dppa-dpa-promote-furin-expression-involving-transcription-factor-cebp%C3%AE-in-neuronal-cells
#6
Jing-Si Zha, Bing-Lin Zhu, Lu Liu, Yu-Jie Lai, Yan Long, Xiao-Tong Hu, Xiao-Juan Deng, Xue-Feng Wang, Zhen Yan, Guo-Jun Chen
Using high-throughput small molecule screening targeting furin gene, we identified that phorbol esters dPPA (12-Deoxyphorbol 13-phenylacetate 20-acetate) and dPA (12-Deoxyphorbol 13-acetate) significantly increased furin protein and mRNA expression in SH-SY5Y cells. This effect was prevented by PKC (protein kinase C) inhibitor calphostin C but not Ro318220, suggesting that the C1 domain, rather than the catalytic domain of PKC plays an important role. Luciferase assay revealed that nucleotides -7925 to -7426 were sufficient to mediate dPPA/dPA enhancement of furin P1 promoter activity...
June 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/28644870/effects-of-nicotine-on-corneal-wound-healing-following-acute-alkali-burn
#7
Jong Won Kim, Chae Woong Lim, Bumseok Kim
Epidemiological studies have indicated that smoking is a pivotal risk factor for the progression of several chronic diseases. Nicotine, the addictive component of cigarettes, has powerful pathophysiological properties in the body. Although the effects of cigarette smoking on corneal re-epithelialization have been studied, the effects of nicotine on corneal wound healing-related neovascularization and fibrosis have not been fully demonstrated. The aim of this study was to evaluate the effects of chronic administration of nicotine on corneal wound healing following acute insult induced by an alkali burn...
2017: PloS One
https://www.readbyqxmd.com/read/28644030/a-plc-%C3%AE-1-feedback-pathway-regulates-lck-substrate-phosphorylation-at-the-t-cell-receptor-and-slp-76-complex
#8
Judson Belmont, Tao Gu, Ashley Marie Mudd, Arthur R Salomon
Phospholipase C gamma 1 (PLC-γ1) occupies a critically important position in the T cell signaling pathway. While its functions as a regulator of both Ca2+ signaling and PKC-family kinases are well characterized, PLC-γ1's role in the regulation of early T cell receptor signaling events is incompletely understood. Activation of the T cell receptor leads to the formation of a signalosome complex between SLP-76, LAT, PLC-γ1, Itk, and Vav1. Recent studies have revealed the existence of both positive and negative feedback pathways from SLP-76 to the apical kinase in the pathway, Lck...
June 23, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28642707/tetrandrine-an-activator-of-autophagy-induces-autophagic-cell-death-via-pkc-%C3%AE-inhibition-and-mtor-dependent-mechanisms
#9
Vincent Kam Wai Wong, Wu Zeng, Juan Chen, Xiao Jun Yao, Elaine Lai Han Leung, Qian Qian Wang, Pauline Chiu, Ben C B Ko, Betty Yuen Kwan Law
Emerging evidence suggests the therapeutic role of autophagic modulators in cancer therapy. This study aims to identify novel traditional Chinese medicinal herbs as potential anti-tumor agents through autophagic induction, which finally lead to autophagy mediated-cell death in apoptosis-resistant cancer cells. Using bioactivity-guided purification, we identified tetrandrine (Tet) from herbal plant, Radix stephaniae tetrandrae, as an inducer of autophagy. Across a number of cancer cell lines, we found that breast cancer cells treated with tetrandrine show an increase autophagic flux and formation of autophagosomes...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28642580/a-snake-venom-group-iia-pla2-with-immunomodulatory-activity-induces-formation-of-lipid-droplets-containing-15-d-pgj2-in-macrophages
#10
Karina Cristina Giannotti, Elbio Leiguez, Ana Eduarda Zulim de Carvalho, Neide Galvão Nascimento, Márcio Hideki Matsubara, Consuelo Latorre Fortes-Dias, Vanessa Moreira, Catarina Teixeira
Crotoxin B (CB) is a catalytically active group IIA sPLA2 from Crotalus durissus terrificus snake venom. In contrast to most GIIA sPLA2s, CB exhibits anti-inflammatory effects, including the ability to inhibit leukocyte functions. Lipid droplets (LDs) are lipid-rich organelles associated with inflammation and recognized as a site for the synthesis of inflammatory lipid mediators. Here, the ability of CB to induce formation of LDs and the mechanisms involved in this effect were investigated in isolated macrophages...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28638804/pkc-%C3%AE-marcks-signaling-promotes-intracellular-survival-of-unopsonized-burkholderia-thailandensis
#11
Sofiya N Micheva-Viteva, Yulin Shou, Kumkum Ganguly, Terry H Wu, Elizabeth Hong-Geller
Pathogenic Burkholderia rely on host factors for efficient intracellular replication and are highly refractory to antibiotic treatment. To identify host genes that are required by Burkholderia spp. during infection, we performed a RNA interference (RNAi) screen of the human kinome and identified 35 host kinases that facilitated Burkholderia thailandensis intracellular survival in human monocytic THP-1 cells. We validated a selection of host kinases using imaging flow cytometry to assess efficiency of B. thailandensis survival in the host upon siRNA-mediated knockdown...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28638377/a-novel-bromodomain-inhibitor-reverses-hiv-1-latency-through-specific-binding-with-brd4-to-promote-tat-and-p-tefb-association
#12
Huachao Huang, Shuai Liu, Maxime Jean, Sydney Simpson, He Huang, Mark Merkley, Tsuyoshi Hayashi, Weili Kong, Irene Rodríguez-Sánchez, Xiaofeng Zhang, Hailemichael O Yosief, Hongyu Miao, Jianwen Que, James J Kobie, James Bradner, Netty G Santoso, Wei Zhang, Jian Zhu
While combinatory antiretroviral therapy (cART) can effectively reduce HIV-1 viremia, it cannot eliminate HIV-1 infection. In the presence of cART, viral reservoirs remain latent, impeding the cure of HIV-1/AIDS. Recently, latency-reversing agents (LRAs) have been developed with the intent of purging latent HIV-1, providing an intriguing strategy for the eradication of the residual viral reservoirs. Our earlier studies show that the first-generation, methyl-triazolo bromodomain, and extra-terminal domain inhibitor (BETi), JQ1, facilitates the reversal of HIV-1 latency...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28636947/assembly-secretory-pathway-trafficking-and-surface-delivery-of-kainate-receptors-is-regulated-by-neuronal-activity
#13
Ashley J Evans, Sonam Gurung, Kevin A Wilkinson, David J Stephens, Jeremy M Henley
Ionotropic glutamate receptor (iGluR) trafficking and function underpin excitatory synaptic transmission and plasticity and shape neuronal networks. It is well established that the transcription, translation, and endocytosis/recycling of iGluRs are all regulated by neuronal activity, but much less is known about the activity dependence of iGluR transport through the secretory pathway. Here, we use the kainate receptor subunit GluK2 as a model iGluR cargo to show that the assembly, early secretory pathway trafficking, and surface delivery of iGluRs are all controlled by neuronal activity...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28634451/berberine-ameliorates-diabetes-associated-cognitive-decline-through-modulation-of-aberrant-inflammation-response-and-insulin-signaling-pathway-in-dm-rats
#14
Qingjie Chen, Ran Mo, Ninghua Wu, Xin Zou, Cai Shi, Jing Gong, Jingbin Li, Ke Fang, Dingkun Wang, Deshen Yang, Kaifu Wang, Juan Chen
Background: Memory-impairment was one of the common characteristics in patients with diabetes mellitus. The release of chronic inflammation mediators and insulin resistance in diabetic brain gave rise to the generation of toxic factor Aβ42 which was the marker of Alzheimer's disease. In addition, the impairment of memory in diabetes mellitus was also correlated predominantly with uptake/metabolism of glucose in medial prefrontal cortex (mPFC). Previously, anti-inflammation and hypoglycemic effects of berberine (BBr) have been described in peripheral tissues...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28629334/protein-kinase-c-%C3%AE-pkc%C3%AE-modulates-cell-apoptosis-by-stimulating-nuclear-translocation-of-nf-kappa-b-p65-in-urothelial-cell-carcinoma-of-the-bladder
#15
Jin Zheng, Chuize Kong, Xiaoxi Yang, Xiaolu Cui, Xuyong Lin, Zhe Zhang
BACKGROUND: The protein kinase C (PKC) family comprises central regulators of multiple signal transduction processes and is involved in the progression of many cancers. Nuclear factor Kappa-B (NF-κB) is constitutively expressed in cancer tissues and stimulates the transcription of various tumor-related genes. The present study aims to investigate the clinical significance of PKCα and NF-κB p65 in bladder cancer tissues and the mechanism underlying PKCα induction of bladder cancer cell apoptotic resistance through stimulation of p65 nuclear translocation...
June 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28627240/quercetin-has-antimetastatic-effects-on-gastric-cancer-cells-via-the-interruption-of-upa-upar-function-by-modulating-nf-%C3%AE%C2%BAb-pkc-%C3%AE-erk1-2-and-ampk%C3%AE
#16
Hai Li, Chen Chen
Gastric cancer (GC) is a malignancy with few effective treatment options after metastasis occurs. Quercetin (Qu) intake has been associated with reduced incidence and slow development of GC, probably due to its anti-proliferative and apoptotic effects, but it is unclear whether Qu can inhibit the metastatic activity. The urokinase plasminogen activator (uPA)/uPA receptor (uPAR) system plays an important role in cancer metastasis. In this study, we measured both uPA activity and uPAR expression in GC and pericarcinous tissues, and we investigated the correlation between uPAR expression and the migratory and invasive activities of various GC cell lines...
March 1, 2017: Integrative Cancer Therapies
https://www.readbyqxmd.com/read/28624831/chelerythrine-attenuates-renal-ischemia-reperfusion-induced-myocardial-injury-by-activating-cse-h2s-via-pkc-nf-%C3%AE%C2%BAb-pathway-in-diabetic-rats
#17
Bo Hu, Guangtao Xu, Yongxia Zheng, Fei Tong, Ping Qian, Xiaoyan Pan, Xinmei Zhou, Ruilin Shen
BACKGROUND/AIMS: Chelerythrine (CHE), a benzophenanthridine alkaloid, is a potent, selective, and cell-permeable protein kinase C (PKC) inhibitor. The purpose of the present study was to evaluate the effect of CHE on myocardial recovery after renal ischemia/reperfusion (I/R)-induced myocardial injury (RI/RMI) in a streptozocin (STZ)-induced diabetic rat model. METHODS: Diabetes mellitus (DM) rats preconditioned with CHE and D, L-propargylglycine (PAG) were subjected to renal I/R...
2017: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/28623716/aldose-reductase-inhibitors-attenuate-%C3%AE-amyloid-induced-tnf-%C3%AE-production-in-microlgia-via-ros-pkc-mediated-nf-%C3%AE%C2%BAb-and-mapk-pathways
#18
Xiao-Min Song, Qian Yu, Xin Dong, Hyun Ok Yang, Ke-Wu Zeng, Jun Li, Peng-Fei Tu
Microglia-mediated neuroinflammation is a key risk factor to the development of Alzheimer' disease (AD). Aldose reductase (AR) has been found to be widely involved in inflammation-related diseases; however, whether aldose reductase inhibitors (ARIs) could be used to treat neuroinflammation is rarely reported. This study aims to evaluate the anti-neuroinflammatory effects of two major ARIs of Sorbinil (Sor) and Zopolrestat (Zol) in β-amyloid protein (Aβ)-induced microglia (BV-2). We find that Sor and Zol significantly inhibit TNF-α, IL-1β, IL-6 production from microglia in response to Aβ stimulation...
June 14, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28620161/different-signaling-patterns-contribute-to-loss-of-keratinocyte-cohesion-dependent-on-autoantibody-profile-in-pemphigus
#19
Elias Walter, Franziska Vielmuth, Lukas Rotkopf, Miklós Sárdy, Orsolya N Horváth, Matthias Goebeler, Enno Schmidt, Rüdiger Eming, Michael Hertl, Volker Spindler, Jens Waschke
Pemphigus is an autoimmune blistering skin disease caused primarily by autoantibodies against desmoglein (Dsg)1 and 3. Here, we characterized the mechanisms engaged by pemphigus IgG from patients with different clinical phenotypes and autoantibody profiles. All pemphigus vulgaris (PV) and pemphigus foliaceus (PF) IgG and AK23, a monoclonal mouse antibody against Dsg3, caused loss of cell cohesion, cytokeratin retraction and p38MAPK activation. Strong alterations in Dsg3 distribution were caused by mucosal (aDsg3 antibodies), mucocutaneous (aDsg1 + aDsg3) as well as atypical (aDsg3) PV-IgG...
June 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28618084/ccl20-promotes-migration-and-invasiveness-of-human-cancerous-breast-epithelial-cells-in-primary-culture
#20
Antonella Muscella, Carla Vetrugno, Santo Marsigliante
The relation between the tumor and its microenvironment is one of the most interesting and less understood issues. Recently, we showed a role of CCL20 chemokine in proning the healthy tissue neighbouring the tumor to carcinogenesis. Besides, tumor-secreted CCL20 induced proliferation, migration and EMT of healthy cells. In this context, we have studied here if CCL20 had effects on the migration of cancer cells and the intracellular pathways used in breast epithelial cells in primary culture. Using molecular (siRNA) and pharmacological (inhibitors) techniques, we found multiple signaling kinases to be activated and involved in CCL20-induced tumor breast cell migration...
June 15, 2017: Molecular Carcinogenesis
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