keyword
MENU ▼
Read by QxMD icon Read
search

T cell inhibitory pathway

keyword
https://www.readbyqxmd.com/read/29784906/the-anti-cancer-activity-of-an-andrographolide-analogue-functions-through-a-gsk-3%C3%AE-independent-wnt-%C3%AE-catenin-signaling-pathway-in-colorectal-cancer-cells
#1
Somrudee Reabroi, Rungnapha Saeeng, Nittaya Boonmuen, Teerapich Kasemsuk, Witchuda Saengsawang, Kanoknetr Suksen, Weiming Zhu, Pawinee Piyachaturawat, Arthit Chairoungdua
The Wnt/β-catenin signaling pathway plays a key role in the progression of human colorectal cancers (CRCs) and is one of the leading targets of chemotherapy agents developed for CRC. The present study aimed to investigate the anti-cancer effects and molecular mechanisms of 19-O-triphenylmethyl andrographolide (RS-PP-050), an andrographolide analogue and determine its activity in the Wnt/β-catenin pathway. RS-PP-050 was found to potently inhibit the proliferation and survival of HT-29 CRC cells. It induces cell cycle arrest and promotes apoptotic cell death which was associated with the activation of PARP-1 and p53...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29778505/novel-peptide-nanoparticle-biased-antagonist-of-ccr3-blocks-eosinophil-recruitment-and-airway-hyperresponsiveness
#2
Milica Grozdanovic, Kimberly G Laffey, Hazem Abdelkarim, Ben Hitchinson, Anantha Harijith, Hyung-Geon Moon, Gye Young Park, Lee K Rousslang, Joanne C Masterson, Glenn T Furuta, Nadya I Tarasova, Vadim Gaponenko, Steven J Ackerman
BACKGROUND: Chemokine signaling through CCR3 is a key regulatory pathway for eosinophil recruitment into tissues associated with allergic inflammation and asthma. To date, none of the CCR3 antagonists have shown efficacy in clinical trials. One reason may be their unbiased mode of inhibition that prevents receptor internalization, leading to drug tolerance. OBJECTIVE: We sought to develop a novel peptide nanoparticle CCR3 inhibitor (R321) with a biased mode of inhibition that would block G-protein signaling, but enable or promote receptor internalization...
May 17, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29773813/amelioration-of-experimental-autoimmune-encephalomyelitis-and-dss-induced-colitis-by-ntg-a-009-through-the-inhibition-of-th1-and-th17-cells-differentiation
#3
Suman Acharya, Maheshwor Timilshina, Liyuan Jiang, Sabita Neupane, Dong-Young Choi, Sang Won Park, Sang Yeul Lee, Byeong-Seon Jeong, Jung-Ae Kim, Tae-Gyu Nam, Jae-Hoon Chang
CD4+ T cells are the central for the mammalian adaptive immune system. Naïve CD4+ T cells mainly differentiate in to pro-inflammatory Th1, Th2 and Th17 cells upon antigenic stimulation. IFN-γ secreting Th1 cells and IL-17 secreting Th17 cells are found to play key roles in autoimmune diseases like multiple sclerosis (MS) and ulcerative colitis (UC). In this study we found NTG-A-009, 6-aminopyridin-3-ol, has great inhibitory effect on in vitro differentiation of Th1 and Th17 cells without affecting regulatory T cells...
May 17, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29760351/leptin-aggravates-reflux-esophagitis-by-increasing-tissue-levels-of-macrophage-migration-inhibitory-factor-in-rats
#4
Tsugihiro Murata, Kiyotaka Asanuma, Nobuyuki Ara, Katsunori Iijima, Waku Hatta, Shin Hamada, Naoki Asano, Tomoyuki Koike, Akira Imatani, Atsushi Masamune, Tooru Shimosegawa
Leptin, produced primarily by the adipose tissue, acts as a pro-inflammatory modulator, thereby contributing to the development of obesity-related disease. Although high levels of leptin in the obese are closely related to gastroesophageal reflux disease, the mechanism by which leptin influences esophageal inflammation remains unknown. Macrophage migration inhibitory factor (MIF) is produced by immune cells, such as T lymphocytes and macrophages, and MIF is known to induce the production of tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and interleukin 6 (IL-6)...
2018: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/29758331/liver-regeneration-requires-yap1-tgf%C3%AE-dependent-epithelial-mesenchymal-transition-in-hepatocytes
#5
Seh-Hoon Oh, Marzena Swiderska-Syn, Mark L Jewell, Richard T Premont, Anna Mae Diehl
BACKGROUND: Chronic failure of mechanisms that promote effective regeneration of dead hepatocytes causes replacement of functional hepatic parenchyma with fibrous scar and ultimately results in cirrhosis. Therefore, defining and optimizing mechanisms that orchestrate effective regeneration might prevent cirrhosis. We hypothesized that effective regeneration of injured livers requires hepatocytes to evade the growth inhibitory actions of TGF-β since TGF-β signaling inhibits mature hepatocyte growth but drives cirrhosis pathogenesis...
May 11, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29755980/importance-of-validating-antibodies-and-small-compound-inhibitors-using-genetic-knockout-studies-t-cell-receptor-induced-cyld-phosphorylation-by-ikk%C3%AE%C2%B5-tbk1-as-a-case-study
#6
Marie Lork, Marja Kreike, Jens Staal, Rudi Beyaert
CYLD is a deubiquitinating enzyme that plays a crucial role in immunity and inflammation as a negative regulator of NF-κB transcription factor and JNK kinase signaling. Defects in either of these pathways contribute to the progression of numerous inflammatory and autoimmune disorders. Therefore, we set out to unravel molecular mechanisms that control CYLD activity in the context of T cell receptor (TCR) signaling. More specifically, we focused on CYLD phosphorylation at Ser418, which can be detected upon immunoblotting of cell extracts with phospho(Ser418)-CYLD specific antibodies...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29746601/aberrant-activity-of-nkl-homeobox-gene-nkx3-2-in-a-t-all-subset
#7
Stefan Nagel, Corinna Meyer, Maren Kaufmann, Margarete Zaborski, Roderick A F MacLeod, Hans G Drexler
T-cell acute lymphoblastic leukemia (T-ALL) is a hematopoietic malignancy originating from T-cell progenitors in which differentiation is blocked at early stages. Physiological expression of specific NKL homeobox genes obeys a hematopoietic NKL-code implicated in the process of lymphopoiesis while in differentiated T-cells these genes are silenced. We propose that this developmental expression pattern underlies the observation that NKL homeobox genes are the most ubiquitous group of transcription factors deregulated in T-ALL, including TLX1, TLX3, NKX2-5 and NKX3-1...
2018: PloS One
https://www.readbyqxmd.com/read/29743505/contrasting-roles-for-actin-in-the-cellular-uptake-of-cell-penetrating-peptide-conjugates
#8
L He, E J Sayers, P Watson, A T Jones
The increased need for macromolecular therapeutics, such as peptides, proteins and nucleotides, to reach intracellular targets necessitates more effective delivery vectors and a higher level of understanding of their mechanism of action. Cell penetrating peptides (CPPs) can transport a range of macromolecules into cells, either through direct plasma membrane translocation or endocytosis. All known endocytic pathways involve cell-cortex remodelling, a process shown to be regulated by reorganisation of the actin cytoskeleton...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29737217/update-on-fc-receptor-like-fcrl-family-new-immunoregulatory-players-in-health-and-diseases
#9
Davood Rostamzadeh, Tohid Kazemi, Zahra Amirghofran, Mahdi Shabani
Fc receptor-like (FCRL) molecules, as recently identified members of the immunoglobulin superfamily (IgSF), are preferentially expressed by B-cells. They have variable number of extracellular immunoglobulin-like domains and cytoplasmic activating ITAMs and/or inhibitory ITIMs. FCRL1-5 are dominantly expressed in different stages of B-cells development. But, FCRL6 is preferentially expressed in different subsets of T-cells and NK cells. FCRL1-5 could regulate different features of B-cell evolution such as development, differentiation, activation, antibody secretion and isotype switching...
May 10, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29737211/hepatoprotective-effect-of-wedelolactone-against-concanavalin-a-induced-liver-injury-in-mice
#10
Qingqiong Luo, Jieying Ding, Liping Zhu, Fuxiang Chen, Lili Xu
Eclipta prostrata L. is a traditional Chinese herbal medicine that has been used in the treatment of liver diseases. However, its biological mechanisms remain elusive. The current study aimed to investigate the hepatoprotective effect of wedelolactone, a major coumarin ingredient of Eclipta prostrata L., on immune-mediated liver injury. Using the well-established animal model of Concanavalin A (ConA)-induced hepatitis (CIH), we found that pretreatment of mice with wedelolactone markedly reduced both the serum levels of transaminases and the severity of liver damage...
May 8, 2018: American Journal of Chinese Medicine
https://www.readbyqxmd.com/read/29733892/suppression-of-t-lymphocyte-activation-by-3-chloro-1-2-propanediol-mono-and-di-palmitate-esters-in-vitro
#11
Guoren Huang, Jinli Xue, Xiangjun Sun, Jing Wang, Yilin Wang, Thomas T Y Wang, LucyYu Liangli
This study investigated whether and how 3-chloro-1,2-propanediol (3-MCPD) fatty acid esters, a group of food contaminants formed during processing, might inhibit the immune system through suppressing T lymphocyte activation for the first time. Three 3-MCPD esters including 1-palmitoyl-3-chloropropanediol (1-pal), 2-palmitoyl-3-chloropropanediol (2-pal), and1,2-dipalmitoyl-3-chloropropanediol (dipal) were selected as the probe compounds to test the possible effects of fatty acid structure on their potential immune inhibitory effect...
May 4, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29731749/adaptive-nkg2c-cd57-natural-killer-cell-and-tim-3-expression-during-viral-infections
#12
Hassen Kared, Serena Martelli, Shu Wen Tan, Yannick Simoni, Meng Li Chong, Siew Hwei Yap, Evan W Newell, Sylvia L F Pender, Adeeba Kamarulzaman, Reena Rajasuriar, Anis Larbi
Repetitive stimulation by persistent pathogens such as human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV) induces the differentiation of natural killer (NK) cells. This maturation pathway is characterized by the acquisition of phenotypic markers, CD2, CD57, and NKG2C, and effector functions-a process regulated by Tim-3 and orchestrated by a complex network of transcriptional factors, involving T-bet, Eomes, Zeb2, promyelocytic leukemia zinc finger protein, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, hepatitis C virus, and HIV) interferes with the functional phenotype of NK cells by modulating the Tim-3 pathway; a decrease in Tim-3 expression combined with the acquisition of inhibitory receptors skewed NK cells toward an exhausted and cytotoxic phenotype in an inflammatory environment during chronic HIV infection...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29716633/targeting-flt3-in-acute-myeloid-leukemia-using-ligand-based-chimeric-antigen-receptor-engineered-t-cells
#13
Ying Wang, Yingxi Xu, Saisai Li, Jia Liu, Yanyan Xing, Haiyan Xing, Zheng Tian, Kejing Tang, Qing Rao, Min Wang, Jianxiang Wang
BACKGROUND: Chimeric antigen receptor-engineered T (CAR-T) cells have extraordinary effect in treating lymphoblastic leukemia. However, treatment of acute myeloid leukemia (AML) using CAR-T cells remains limited to date. Leukemogenesis always relates with the abnormalities of cytogenetics, and nearly one third of AML patients have activating mutations in Fms-like tyrosine kinase 3 (FLT3) which reminded poor prognosis. Considering the FLT3 expressed in AML patients' blast cells, it may be a new candidate target for CAR-T therapy to treat FLT3+ AML, especially patients harboring FLT3-ITD mutation...
May 2, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29715548/posttranslational-regulation-of-cyp2j2-by-nitric-oxide
#14
Ji Won Park, Choon-Myung Lee, Joan S Cheng, Edward T Morgan
Nitric oxide (NO) is an essential signaling molecule in the body, regulating numerous biological processes. Beside its physiological roles, NO affects drug metabolism by modulating the activity and/or expression of cytochrome P450 enzymes. Previously, our lab showed that NO generation caused by inflammatory stimuli results in CYP2B6 degradation via the ubiquitin-proteasome pathway. In the current study, we tested the NO-mediated regulation of CYP2J2 that metabolizes arachidonic acids to bioactive epoxyeicosatrienoic acids, as well as therapeutic drugs such as astemizole and ebastine...
April 28, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29695964/root-extract-of-polygonum-cuspidatum-siebold-zucc-ameliorates-dss-induced-ulcerative-colitis-by-affecting-nf-kappab-signaling-pathway-in-a-mouse-model-via-synergistic-effects-of-polydatin-resveratrol-and-emodin
#15
Baohai Liu, Shuangdi Li, Xiaodan Sui, Lianyi Guo, Xingmei Liu, Hongmei Li, Leming Gao, Shusheng Cai, Yanrong Li, Tingting Wang, Xuehua Piao
Background: Polygonum cuspidatum Siebold & Zucc. (PCS) has antibacterial properties and may prevent Ulcerative colitis (UC) but related molecular mechanism remains unknown. NF-κB signaling pathway is associated with inflammatory responses and its inactivation may be critical for effective therapy of UC. Methods: UC mouse (C57BL/6J) model was established by using dextran sulfate sodium (DSS). The extract of PCS (PCSE) was prepared by using ethanol and its main ingredients were measured by HPLC. Thirty-two UC mice were evenly assigned into DG (received vehicle control), LG (0...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29685290/pd-1-immune-checkpoint-blockade-promotes-brain-leukocyte-infiltration-and-diminishes-cyst-burden-in-a-mouse-model-of-toxoplasma-infection
#16
Jianchun Xiao, Ye Li, Robert H Yolken, Raphael P Viscidi
Tissue cysts, the hallmark of chronic Toxoplasma gondii infection, are predominantly located in the brain making clearance of the parasite difficult. Currently available anti-T. gondii drugs are ineffective on cysts and fail to prevent reactivation of latent toxoplasmosis. We examined whether abrogation of inhibitory signaling pathways that maintain T cells in an exhausted state can be exploited for treating T. gondii tissue cysts. By using a mouse model of chronic toxoplasmosis, we showed immune checkpoint blockade directed against the programmed death-1 (PD-1) pathway results in a significant reduction in brain cyst number (77% lower)...
June 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29671161/under-evaluated-or-unassessed-pathogenic-pathways-in-autoimmune-hepatitis-and-implications-for-future-management
#17
REVIEW
Albert J Czaja
Autoimmune hepatitis is a consequence of perturbations in homeostatic mechanisms that maintain self-tolerance but are incompletely understood. The goals of this review are to describe key pathogenic pathways that have been under-evaluated or unassessed in autoimmune hepatitis, describe insights that may shape future therapies, and encourage investigational efforts. The T cell immunoglobulin mucin proteins constitute a family that modulates immune tolerance by limiting the survival of immune effector cells, clearing apoptotic bodies, and expanding the population of granulocytic myeloid-derived suppressor cells...
April 18, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29665899/-statins-regulate-the-proliferation-and-apoptosis-of-t-all-cells-through-the-inhibition-of-akt-pathway
#18
Jun-Jie Wang, Yu Tian, Kai-Lin Xu, Rui-Xue Fu, Ming-Shan Niu, Kai Zhao
OBJECTIVE: To investigate the effect of Statins on proliferation and apoptosis in human acute T lymphocytic leukemia (T-ALL) cells and its possible mechanism. METHODS: Jurkat and CCRF-CEM cells were cultured in different concentrations of Fluvastatin and Simvastatin for 24 h respectively. Then, the cell growth inhibition level was defected by CCK-8; the DNA replication was analyzed by EdU; the cell apoptosis was analyzed by Annexin V/7-AAD double labeling; the cell cycle changes were analyzed by flow cytometry; the expressions of Cyclin D1, p21, p27, BAX, BCL-2 and p-Akt were determined by Western blot...
April 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29662632/regulation-of-breast-cancer-induced-bone-disease-by-cancer-specific-ikk%C3%AE
#19
Silvia Marino, Ryan T Bishop, Mattia Capulli, Antonia Sophocleous, John G Logan, Patrick Mollat, Barbara Mognetti, Luca Ventura, Andrew H Sims, Nadia Rucci, Stuart H Ralston, Aymen I Idris
NFκB is implicated in breast cancer bone metastasis and skeletal remodelling. However, the role of IKKβ, a key component of the canonical NFκB pathway, in the regulation of breast cancer osteolytic metastasis has not been investigated. Here, we describe the cancer-specific contribution of IKKβ to bone metastasis, skeletal tumour growth and osteolysis associated with breast cancer. IKKβ is highly expressed in invasive breast tumours and its level of expression was higher in patients with bone metastasis...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29657104/inhibitory-effects-of-methyl-3-5-di-o-caffeoyl-epi-quinate-on-rankl-induced-osteoclast-differentiation
#20
Tae Hoon Kim, Hye Jung Ihn, Kiryeong Kim, Hye-Sung Cho, Hong-In Shin, Yong Chul Bae, Eui Kyun Park
In this study, we have shown that methyl-3,5-di-O-caffeoyl-epi-quinate, a naturally occurring compound isolated from Ainsliaea acerifolia, inhibits receptor activator of nuclear factor-κB ligand (RANKL)-induced formation of multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts and the expression of osteoclast marker genes. Methyl-3,5-di-O-caffeoyl-epi-quinate also inhibited RANKL-induced activation of p38, Akt and extracellular signal-regulated kinase (ERK) as well as the expression of nuclear factor of activated T-cell (NFATc1), the key regulator of osteoclast differentiation...
April 9, 2018: Bioorganic & Medicinal Chemistry Letters
keyword
keyword
115212
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"