keyword
https://read.qxmd.com/read/36480602/decoding-car-t-cell-phenotype-using-combinatorial-signaling-motif-libraries-and-machine-learning
#21
JOURNAL ARTICLE
Kyle G Daniels, Shangying Wang, Milos S Simic, Hersh K Bhargava, Sara Capponi, Yurie Tonai, Wei Yu, Simone Bianco, Wendell A Lim
Chimeric antigen receptor (CAR) costimulatory domains derived from native immune receptors steer the phenotypic output of therapeutic T cells. We constructed a library of CARs containing ~2,300 synthetic costimulatory domains, built from combinations of 13 signaling motifs. These CARs promoted diverse cell fates, which were sensitive to motif combinations and configurations. Neural networks trained to decode the combinatorial grammar of CAR signaling motifs allowed extraction of key design rules. For example, non-native combinations of motifs which bind tumor necrosis factor receptor-associated factors (TRAFs) and phospholipase C gamma 1 (PLCγ1) enhanced cytotoxicity and stemness associated with effective tumor killing...
December 8, 2022: Science
https://read.qxmd.com/read/36286420/potential-of-epidermal-growth-factor-like-peptide-from-the-sea-cucumber-stichopus-horrens-to-increase-the-growth-of-human-cells-in-silico-molecular-docking-approach
#22
JOURNAL ARTICLE
Nur Shazwani Mohd Pilus, Azira Muhamad, Muhammad Ashraf Shahidan, Nurul Yuziana Mohd Yusof
The sea cucumber is prominent as a traditional remedy among Asians for wound healing due to its high capacity for regeneration after expulsion of its internal organs. A short peptide consisting of 45 amino acids from transcriptome data of Stichopus horrens (Sh-EGFl-1) shows a convincing capability to promote the growth of human melanoma cells. Molecular docking of Sh-EGFl-1 peptide with human epidermal growth factor receptor (hEGFR) exhibited a favorable intermolecular interaction, where most of the Sh-EGFl-1 residues interacted with calcium binding-like domains...
September 23, 2022: Marine Drugs
https://read.qxmd.com/read/36159417/evaluation-of-high-risk-factors-and-the-diagnostic-value-of-alpha-fetoprotein-in-the-stratification-of-primary-liver-cancer
#23
JOURNAL ARTICLE
Hong-Bin Jiao, Wei Wang, Meng-Nan Guo, Ya-Li Su, De-Quan Pang, Bao-Lin Wang, Jun Shi, Jing-Hua Wu
BACKGROUND: Alpha-fetoprotein (AFP) is one of the diagnostic standards for primary liver cancer (PLC); however, AFP exhibits insufficient sensitivity and specificity for diagnosing PLC. AIM: To evaluate the effects of high-risk factors and the diagnostic value of AFP in stratified PLC. METHODS: In total, 289 PLC cases from 2013 to 2019 were selected for analysis. First, the contributions of high-risk factors in stratifying PLC were compared according to the following criteria: Child-Pugh score, clinical stage of liver cirrhosis, tumor size, and Barcelona Clinic Liver Cancer (BCLC) stage...
September 16, 2022: World Journal of Clinical Cases
https://read.qxmd.com/read/36116562/perinatal-exposure-to-a-glyphosate-pesticide-formulation-induces-offspring-liver-damage
#24
JOURNAL ARTICLE
Carla Elise Heinz Rieg, Daiane Cattani, Nathalia Ferrazzo Naspolini, Vitoria Hayduck Cenci, Vera Lúcia de Liz Oliveira Cavalli, Amanda Virtuoso Jacques, Marcus Vinicius Pereira Dos Santos Nascimento, Eduardo Monguilhott Dalmarco, Ana Carolina Rabello De Moraes, Maria Cláudia Santos-Silva, Fátima Regina Mena Barreto Silva, Eduardo Benedetti Parisotto, Ariane Zamoner
The present study investigated the effects of perinatal exposure to glyphosate-based herbicide (GBH) in offspring's liver. Pregnant Wistar rats were exposed to GBH (70 mg glyphosate/Kg body weight/day) in drinking water from gestation day 5 to postnatal day 15. The perinatal exposure to GBH increased 45 Ca2+ influx in offspring's liver. Pharmacological tools indicated a role played by oxidative stress, phospholipase C (PLC) and Akt pathways, as well as voltage-dependent Ca2+ channel modulation on GBH-induced Ca2+ influx in offspring's liver...
September 16, 2022: Toxicology and Applied Pharmacology
https://read.qxmd.com/read/35337082/antidepressant-like-effects-of-bdnf-and-ngf-individual-loop-dipeptide-mimetics-depend-on-the-signal-transmission-patterns-associated-with-trk
#25
JOURNAL ARTICLE
Armen G Mezhlumyan, Anna V Tallerova, Polina Y Povarnina, Aleksey V Tarasiuk, Nellya M Sazonova, Tatiana A Gudasheva, Sergey B Seredenin
Neurotrophins are considered as an attractive target for the development of antidepressants with a novel mechanism of action. Previously, the dimeric dipeptide mimetics of individual loops of nerve growth factor, NGF (GK-6, loop 1; GK-2, loop 4) and brain-derived neurotrophic factor, BDNF (GSB-214, loop 1; GTS-201, loop 2; GSB-106, loop 4) were designed and synthesized. All the mimetics of NGF and BDNF in vitro after a 5-180 min incubation in a HT-22 cell culture were able to phosphorylate the tropomyosin-related kinase A (TrkA) or B (TrkB) receptors, respectively, but had different post-receptor signaling patterns...
February 24, 2022: Pharmaceuticals
https://read.qxmd.com/read/34916256/off-the-shelf-v%C3%AE-1-gamma-delta-t-cells-engineered-with-glypican-3-gpc-3-specific-chimeric-antigen-receptor-car-and-soluble-il-15-display-robust-antitumor-efficacy-against-hepatocellular-carcinoma
#26
JOURNAL ARTICLE
Amani Makkouk, Xue Cher Yang, Taylor Barca, Anthony Lucas, Mustafa Turkoz, Jonathan T S Wong, Kevin P Nishimoto, Mary M Brodey, Maryam Tabrizizad, Smitha R Y Gundurao, Lu Bai, Arun Bhat, Zili An, Stewart Abbot, Daulet Satpayev, Blake T Aftab, Marissa Herrman
BACKGROUND: Glypican-3 (GPC-3) is an oncofetal protein that is highly expressed in various solid tumors, but rarely expressed in healthy adult tissues and represents a rational target of particular relevance in hepatocellular carcinoma (HCC). Autologous chimeric antigen receptor (CAR) αβ T cell therapies have established significant clinical benefit in hematologic malignancies, although efficacy in solid tumors has been limited due to several challenges including T cell homing, target antigen heterogeneity, and immunosuppressive tumor microenvironments...
December 2021: Journal for Immunotherapy of Cancer
https://read.qxmd.com/read/34790577/anti-tumor-activity-of-azd4547-against-ntrk1-fusion-positive-cancer-cells-through-inhibition-of-ntrks
#27
JOURNAL ARTICLE
Hanna Cho, Namkyoung Kim, Takashi Murakami, Taebo Sim
Inhibitors of tropomyosin-related kinases (TRKs) display remarkable outcomes in the regression of cancers harboring the Neurotrophin Receptors Tyrosine Kinase (NTRK) fusion gene. As a result, TRKs have become attractive targets in anti-cancer drug discovery programs. Here, we demonstrate that AZD4547, a highly potent and selective inhibitor of fibroblast growth factor receptor (FGFR), displays anti-tumor activity against KM12(Luc) harboring the TPM3-NTRK1 fusion gene associated with its direct inhibition of TRKs...
2021: Frontiers in Oncology
https://read.qxmd.com/read/34482812/macrophages-target-listeria-monocytogenes-by-two-discrete-non-canonical-autophagy-pathways
#28
JOURNAL ARTICLE
Alexander Gluschko, Alina Farid, Marc Herb, Daniela Grumme, Martin Krönke, Michael Schramm
Non-canonical autophagy pathways decorate single-membrane vesicles with Atg8-family proteins such as MAP1LC3/LC3 (microtubule-associated protein 1 light chain 3). Phagosomes containing the bacterial pathogen Listeria monocytogenes (L.m.) can be targeted by a non-canonical autophagy pathway called LC3-associated phagocytosis (LAP), which substantially contributes to the anti-listerial activity of macrophages and immunity. We here characterized a second non-canonical autophagy pathway targeting L.m.-containing phagosomes, which is induced by damage caused to the phagosomal membrane by the pore-forming toxin of L...
May 2022: Autophagy
https://read.qxmd.com/read/34454048/recent-advances-in-understanding-the-molecular-role-of-phosphoinositide-specific-phospholipase-c-gamma-1-as-an-emerging-onco-driver-and-novel-therapeutic-target-in-human-carcinogenesis
#29
REVIEW
Supratim Mandal, Shrabasti Bandyopadhyay, Komal Tyagi, Adhiraj Roy
Phosphoinositide metabolism is crucial intracellular signaling system that regulates a plethora of biological functions including mitogenesis, cell proliferation and division. Phospholipase C gamma 1 (PLCγ1) which belongs to phosphoinositide-specific phospholipase C (PLC) family, is activated by many extracellular stimuli including hormones, neurotransmitters, growth factors and modulates several cellular and physiological functions necessary for tumorigenesis such as cell survival, migration, invasion and angiogenesis by generating inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG) via hydrolysis of phosphatidylinositol 4,5-biphosphate (PIP2)...
December 2021: Biochimica et Biophysica Acta. Reviews on Cancer
https://read.qxmd.com/read/33580583/oxytocin-modulates-neural-processing-of-mitral-tufted-cells-in-the-olfactory-bulb
#30
JOURNAL ARTICLE
Changcheng Sun, Zhaoyang Yin, Ben-Zheng Li, Han Du, Keke Tang, Penglai Liu, Sio Hang Pun, Tim C Lei, Anan Li
AIM: Oxytocin plays an important role in social recognition in rodents, which is mediated predominantly by the olfactory system. Although oxytocin modulates neural activity in the olfactory bulb, the underlying mechanism is largely unknown. Here, we studied how direct infusion of oxytocin into the olfactory bulb affect social interactions in mice and modulate the neural activity of mitral / tufted cells in the olfactory bulb. METHODS: A three-chamber social interaction test was used in the behavioral test...
February 13, 2021: Acta Physiologica
https://read.qxmd.com/read/33050377/significance-of-targeting-vegfr-2-and-cyclin-d1-in-luminal-a-breast-cancer
#31
JOURNAL ARTICLE
Ashraf N Abdalla, Amal Qattan, Waleed H Malki, Imran Shahid, Mohammad Akbar Hossain, Muhammad Ahmed
The hormonal luminal-A is the most pre-dominant sub type of breast cancer (BC), and it is associated with a high level of cyclin D1 in Saudi patients. Tamoxifen is the golden therapy for hormonal BC, but resistance of cancer cells to tamoxifen contributes to the recurrence of BC due to many reasons, including high levels of AIB1 and cyclin D1. Overcoming drug resistance could be achieved by exploring alternative targetable therapeutic pathways and new drugs or combinations. The objective of this study was to determine the differentially enriched pathways in 12 samples of Saudi women diagnosed with luminal-A using the PamChip peptide microarray-based kinase activity profiling, and to compare the activity of HAA2020 and dinaciclib with tamoxifen in singles and combinations in the MCF7 luminal-A cell line...
October 10, 2020: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/32787521/reelin-amplifies-gpvi-activation-and-alphaiib-beta3-integrin-outside-in-signaling-via-plc-gamma-2-and-rho-gtpases
#32
JOURNAL ARTICLE
Irena Krueger, Lothar Gremer, Lena Mangels, Meike Klier, Kerstin Jurk, Dieter Willbold, Hans H Bock, Margitta Elvers
OBJECTIVE: Reelin, a secreted glycoprotein, was originally identified in the central nervous system, where it plays an important role in brain development and maintenance. In the cardiovascular system, reelin plays a role in atherosclerosis by enhancing vascular inflammation and in arterial thrombosis by promoting platelet adhesion, activation, and thrombus formation via APP (amyloid precursor protein) and GPIb. However, the role of reelin in hemostasis and arterial thrombosis is not fully understood to date...
August 13, 2020: Arteriosclerosis, Thrombosis, and Vascular Biology
https://read.qxmd.com/read/32563953/role-of-bisphenol-a-on-calcium-influx-and-its-potential-toxicity-on-the-testis-of-danio-rerio
#33
JOURNAL ARTICLE
Hemily Batista-Silva, Keyla Rodrigues, Kieiv Resende Sousa de Moura, Glen Van Der Kraak, Christelle Delalande-Lecapitaine, Fátima Regina Mena Barreto Silva
This study investigated the acute in vitro effect of low-concentration bisphenol A (BPA) on calcium (45 Ca2+ ) influx in zebrafish (Danio rerio) testis and examined whether intracellular Ca2+ was involved in the effects of BPA on testicular toxicity. In vitro studies on 45 Ca2+ influx were performed in the testes after incubation with BPA for 30 min. Inhibitors were added 15 min before the addition of 45 Ca2+ and BPA to testes to study the mechanism of action of BPA. The involvement of intracellular calcium from stores on lactate dehydrogenase (LDH) release and on triacylglycerol (TAG) content were carried out after in vitro incubation of testes with BPA for 1 h...
October 1, 2020: Ecotoxicology and Environmental Safety
https://read.qxmd.com/read/32305757/perfluorooctane-sulfonate-acute-exposure-stimulates-insulin-secretion-via-gpr40-pathway
#34
JOURNAL ARTICLE
Lianying Zhang, Xiaoyu Duan, Weijie Sun, Hongwen Sun
Perfluoroalkyl substances (PFASs) are widely used synthetic chemicals, showing environmental/biological persistence and adverse effects on ecosystem and human health. Several epidemiological and animal studies have revealed that PFASs levels are associated with elevated serum insulin level; however, the effect of PFASs on insulin secretion and the underlying mechanism are not clear. In this study, the effect of a most concerned PFAS, perfluorooctane sulfonate (PFOS) on insulin secretion in Beta-TC-6 pancreatic cells was studied...
April 7, 2020: Science of the Total Environment
https://read.qxmd.com/read/32302608/bacterial-phytochrome-as-a-scaffold-for-engineering-of-receptor-tyrosine-kinases-controlled-with-near-infrared-light
#35
JOURNAL ARTICLE
Anna V Leopold, Sergei Pletnev, Vladislav V Verkhusha
Optically controlled receptor tyrosine kinases (opto-RTKs) allow regulation of RTK signaling using light. Until recently, the majority of opto-RTKs were activated with blue-green light. Fusing a photosensory core module of Deinococcus radiodurans bacterial phytochrome (DrBphP-PCM) to the kinase domains of neurotrophin receptors resulted in opto-RTKs controlled with light above 650 nm. To expand this engineering approach to RTKs of other families, here we combined the DrBpP-PCM with the cytoplasmic domains of EGFR and FGFR1...
April 14, 2020: Journal of Molecular Biology
https://read.qxmd.com/read/32108427/phospholipase-c-gamma-plc%C3%AE-regulates-soluble-trehalase-in-the-20e-induced-fecundity-of-apolygus-lucorum
#36
JOURNAL ARTICLE
Yong-An Tan, Xu-Dong Zhao, Hou-Jun Sun, Jing Zhao, Liu-Bin Xiao, De-Jun Hao, Yi-Pin Jiang
Apolygus lucorum is the dominant pathogenic insect attacking Bacillus thuringiensis (Bt) cotton in China. Additionally, 20-hydroxyecdysone (20E) has important functions in many biological processes, including insect reproduction. Phospholipase C (PLC), which is an essential enzyme for phosphoinositide metabolism, is involved in 20E signal transduction, but its function in 20E-mediated reproduction in A. lucorum remains unclear. In this study, 20E increased AlPLCγ transcription as well as the abundance and activity of the encoded protein during molting and metamorphosis...
February 28, 2020: Insect Science
https://read.qxmd.com/read/31918402/structural-insights-and-activating-mutations-in-diverse-pathologies-define-mechanisms-of-deregulation-for-phospholipase-c-gamma-enzymes
#37
JOURNAL ARTICLE
Yang Liu, Tom D Bunney, Sakshi Khosa, Kévin Macé, Katharina Beckenbauer, Trevor Askwith, Sarah Maslen, Christopher Stubbs, Taiana M de Oliveira, Kasim Sader, Mark Skehel, Anne-Claude Gavin, Christopher Phillips, Matilda Katan
BACKGROUND: PLCγ enzymes are key nodes in cellular signal transduction and their mutated and rare variants have been recently implicated in development of a range of diseases with unmet need including cancer, complex immune disorders, inflammation and neurodegenerative diseases. However, molecular nature of activation and the impact and dysregulation mechanisms by mutations, remain unclear; both are critically dependent on comprehensive characterization of the intact PLCγ enzymes. METHODS: For structural studies we applied cryo-EM, cross-linking mass spectrometry and hydrogen-deuterium exchange mass spectrometry...
January 6, 2020: EBioMedicine
https://read.qxmd.com/read/31362705/plc-gamma-1-phosphorylation-status-is-prognostic-of-metastatic-risk-in-patients-with-early-stage-luminal-a-and-b-breast-cancer-subtypes
#38
JOURNAL ARTICLE
Rossano Lattanzio, Manuela Iezzi, Gianluca Sala, Nicola Tinari, Marco Falasca, Saverio Alberti, Simonetta Buglioni, Marcella Mottolese, Letizia Perracchio, Pier Giorgio Natali, Mauro Piantelli
BACKGROUND: Phospholipase Cγ1 (PLCγ1) is highly expressed in human tumours. Our previous studies reported that both stable and inducible PLCγ1 down-regulation can inhibit formation of breast-cancer-derived experimental lung metastasis. Further, high expression of PLCγ1 and its constitutively activated forms (i.e., PLCγ1-pY1253, PLCγ1-pY783) is associated with worse clinical outcome in terms of incidence of distant metastases, but not of local relapse in T1-T2, N0 breast cancer patients...
July 30, 2019: BMC Cancer
https://read.qxmd.com/read/31146410/mgf-based-mutual-approximation-of-hybrid-fading-performance-of-wireless-power-line-relaying-communication-for-iot
#39
JOURNAL ARTICLE
Zhixiong Chen, Cong Ye, Jinsha Yuan, Dongsheng Han
Wireless and power line communications (PLC) are important components of distribution network communication, and have a broad application prospect in the fields of intelligent power consumption and home Internet of Things (IoT). This study mainly analyzes the performance of a dual-hop wireless/power line hybrid fading system employing an amplify-and-forward (AF) relay in terms of outage probability and average bit error rate (BER). The Nakagami-m distribution captures the wireless channel fading; whereas the PLC channel gain is characterized by the Log-normal (LogN) distribution...
May 29, 2019: Sensors
https://read.qxmd.com/read/30774272/effect-of-adipose-derived-mesenchymal-stem-cells-on-hepatocellular-carcinoma-in-vitro-inhibition-of-carcinogenesis
#40
JOURNAL ARTICLE
Rim Serhal, Nagib Saliba, George Hilal, Mayssam Moussa, Ghada S Hassan, Oula El Atat, Nada Alaaeddine
AIM: To investigate the effect of adipose-derived mesenchymal stem cells (ADMSCs) and their conditioned media (CM) on hepatocellular carcinoma (HCC) cell tumorigenesis. METHODS: The proliferation rate of HepG2 and PLC-PRF-5 HCC cancer cells was measured using the trypan blue exclusion method and confirmed using the cell-counting kit 8 (commonly known as CCK-8) assay. Apoptosis was detected by flow cytometry using annexin V-FITC. Protein and mRNA expression was quantified by ELISA and real time PCR, respectively...
February 7, 2019: World Journal of Gastroenterology: WJG
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