Abstract:
:Studies, including ours, have shown that pro-oxidative stressors, such as chemotherapeutic agents, generate oxidized lipids with agonistic platelet-activating factor (PAF) activity. Importantly, recent reports have implicated that these PAF-agonists are transported extracellularly via microvesicle particles (MVPs). While the role of PAF-receptor (PAF-R) has been implicated in mediating chemotherapy effects, its significance in chemotherapy-mediated MVP release in pancreatic cancer has not been studied. The current studies determined the functional significance of PAF-R in gemcitabine chemotherapy-mediated MVP release in human pancreatic cancer cells. Using PAF-R-expressing (PANC-1) and PAF-R-deficient (Hs766T) cells, we demonstrate that gemcitabine induces MVP release in a PAF-R-dependent manner. Blocking of PAF-R via PAF-R antagonist or inhibition of MVP generation via inhibitor of acid sphingomyelinase (aSMase) enzyme, significantly attenuated gemcitabine-mediated MVP release from PANC-1 cells, however, exerted no effects in Hs766T cells. Notably, MVPs from gemcitabine-treated PANC-1 cells, contained a measurable amount of PAF-agonists. Mechanistically, pretreatment with ERK1/2 or p38 inhibitors significantly abrogated gemcitabine-mediated MVP release, indicating the involvement of mitogen-activated protein kinase (MAPK) pathway in PAF-R-dependent gemcitabine-mediated MVP release. These findings demonstrate the significance of PAF-R in gemcitabine-mediated MVP release, as well as the rationale of evaluating PAF-R targeting agents with gemcitabine against pancreatic cancer.
journal_name
Int J Mol Scijournal_title
International journal of molecular sciencesauthors
Thyagarajan A,Kadam SM,Liu L,Kelly LE,Rapp CM,Chen Y,Sahu RPdoi
10.3390/ijms20010032subject
Has Abstractpub_date
2018-12-21 00:00:00issue
1issn
1422-0067pii
ijms20010032journal_volume
20pub_type
杂志文章abstract::The increasing prevalence of inflammatory diseases and the adverse effects associated with the long-term use of current anti-inflammatory therapies prompt the identification of alternative approaches to reestablish immune balance. Apigenin, an abundant dietary flavonoid, is emerging as a potential regulator of inflamm...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms17030323
更新日期:2016-03-01 00:00:00
abstract::Plants undergo several but very precise molecular, physiological, and biochemical modulations in response to biotic stresses. Mitogen-activated protein kinase (MAPK) cascades orchestrate multiple cellular processes including plant growth and development as well as plant responses against abiotic and biotic stresses. H...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20123023
更新日期:2019-06-20 00:00:00
abstract::Papillary thyroid cancer (PTC) is the most common tumor subtype of thyroid cancer. However, not all PTCs are responsive to current surgical and radioiodine treatment. The well-established clinical prognostic factors include tumor size, lymph node/distal metastasis, and extrathyroidal invasion. The RET/PTC-RAS-BRAF lin...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms18030636
更新日期:2017-03-15 00:00:00
abstract::Malignant gliomas are primary brain tumors with poor prognoses. These tumors are infiltrated by brain intrinsic microglia and peripheral monocytes which promote glioma cell invasion. In our previous studies, we discovered that the activation of Toll-like receptor 2 (TLR2) on microglia/brain macrophages converts them i...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21082959
更新日期:2020-04-22 00:00:00
abstract::To examine the effect of melatonin given to rats simultaneously with fructose on initial and fully developed metabolic syndrome, male Wistar rats had free access to chow and 5% or 10% fructose drinking solution for 8 weeks. As compared to controls, systolic blood pressure augmented significantly under both treatments ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms14022502
更新日期:2013-01-25 00:00:00
abstract::Idiopathic Pulmonary Arterial Hypertension (IPAH) is a deadly and disabling disease characterized by severe vascular remodeling of small pulmonary vessels by fibroblasts, myofibroblasts and vascular smooth muscle cell proliferation. Recent studies suggest that the Natriuretic Peptide Clearance Receptor (NPR-C) signali...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms20123063
更新日期:2019-06-22 00:00:00
abstract::Alternative splicing plays an important role in numerous cellular processes and aberrant splice decisions are associated with cancer. Although some studies point to a regulation of alternative splicing and its effector mechanisms in a time-dependent manner, the extent and consequences of such a regulation remains poor...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms20051182
更新日期:2019-03-08 00:00:00
abstract::Early inhibition of inflammation suppresses the carcinogenic process. Aspirin is the most commonly used non-steroid anti-inflammatory drugs (NSAIDs), and it irreversibly inhibits cyclooxygenase-1 and -2 (COX1, COX2). Multiple randomized clinical trials have demonstrated that aspirin offers substantial protection from ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms19010166
更新日期:2018-01-06 00:00:00
abstract::Extranodal NK/T-cell lymphoma, nasal type (ENKTL), is an aggressive malignancy with a poor prognosis. While the introduction of L-asparaginase in the treatment of this disease has significantly improved the prognosis, the outcome of patients relapsing after asparaginase-based chemotherapy, which occurs in up to 50% of...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms19071931
更新日期:2018-06-30 00:00:00
abstract::Deregulation of the cholesterol pathway is an anomaly observed in human diseases, many of which have in common neurological involvement and unknown pathogenesis. In this study we have used Mevalonate Kinase Deficiency (MKD) as a disease-model in order to investigate the link between the deregulation of the mevalonate ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms17030365
更新日期:2016-03-11 00:00:00
abstract::In wheat, flag leaf, stem, chaff and awns contribute to grain filling through photosynthesis and/or re-mobilization. Environmental and genetic effects on the relative contribution of each organ were examined by analyzing the consequences of sink-source manipulations (shading and excision) and by comparing carbon isoto...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19010056
更新日期:2017-12-25 00:00:00
abstract::Epidermal keratinocytes represent a rich source of C-C motif chemokine 20 (CCL20) and recruit CCR6+ interleukin (IL)-17A-producing T cells that are known to be pathogenic for psoriasis. A previous study revealed that scratch injury on keratinocytes upregulates CCL20 production, which is implicated in the Koebner pheno...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21020434
更新日期:2020-01-09 00:00:00
abstract::The immune system and the central nervous system message each other to preserving central homeostasis. Both systems undergo changes during aging that determine central age-related defects. Ellagic acid (EA) is a natural product which is beneficial in both peripheral and central diseases, including aging. We analyzed t...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21103631
更新日期:2020-05-21 00:00:00
abstract::Metacaspases, a class of cysteine-dependent proteases like caspases in animals, are important regulators of programmed cell death (PCD) during development and stress responses in plants. The present study was focused on comprehensive analyses of expression patterns of the rice metacaspase (OsMC) genes in response to a...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms160716216
更新日期:2015-07-17 00:00:00
abstract::The binding of epidermal growth factor (EGF) to EGF receptor (EGFR) stimulates cell mitogenesis and survival through various signalling cascades. EGF also stimulates rapid EGFR endocytosis and its eventual degradation in lysosomes. The immediate events induced by ligand binding include receptor dimerization, activatio...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms17081200
更新日期:2016-07-25 00:00:00
abstract::Shared metabolomic patterns at delivery have been suggested to underlie the mother-to-child transmission of adverse metabolic health. This study aimed to investigate whether mothers with gestational diabetes mellitus (GDM) and their offspring show similar metabolomic patterns several years postpartum. Targeted metabol...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21249647
更新日期:2020-12-17 00:00:00
abstract::We investigated TLR10 expression in human monocytes, THP-1 cells, cultured in hypoxia (3% O(2)). Levels of both TLR10 mRNA and protein in THP-1 cells cultured in hypoxia were significantly higher than those cultured in normoxia (20% O(2)). We examined intracellular reactive oxygen species (ROS) content in hypoxic cell...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms11103769
更新日期:2010-09-29 00:00:00
abstract::Phenolic compounds, which are secondary plant metabolites, are considered an integral part of the human diet. Physiological properties of dietary polyphenols have come to the attention in recent years. Especially, proanthocyanidins (ranging from dimers to decamers) have demonstrated potential interactions with biologi...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms18020376
更新日期:2017-02-10 00:00:00
abstract::We investigated the toxicity of benzo[a]pyrene (B[a]P), 1-nitropyrene (1-NP) and 3-nitrobenzanthrone (3-NBA) in A549 cells. Cells were treated for 4 h and 24 h with: B[a]P (0.1 and 1 μM), 1-NP (1 and 10 μM) and 3-NBA (0.5 and 5 μM). Bulky DNA adducts, lipid peroxidation, DNA and protein oxidation and mRNA expression o...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms17091393
更新日期:2016-08-26 00:00:00
abstract::Iron is an essential element for virtually all organisms. On the one hand, it facilitates cell proliferation and growth. On the other hand, iron may be detrimental due to its redox abilities, thereby contributing to free radical formation, which in turn may provoke oxidative stress and DNA damage. Iron also plays a cr...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms20020273
更新日期:2019-01-11 00:00:00
abstract::We investigated the therapeutic potential and mechanism of chitosan oligosaccharides (COS) for experimental autoimmune uveoretinitis (EAU) in mice. EAU was induced in C57/BL6 mice by injection of human interphotoreceptor retinoid-binding protein (IRBP) peptides. At the same time, a high or low dose (20 or 10 mg/kg) of...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21218326
更新日期:2020-11-06 00:00:00
abstract::The onset and selection of resistant clones during cancer treatment with chemotherapy or targeted therapy is a major issue in the clinical management of metastatic colorectal cancer patients. It is possible that a more personalized treatment selection, using reliable response-to-therapy predictive biomarkers, could le...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms18071547
更新日期:2017-07-17 00:00:00
abstract::Chemoresistance is a leading cause of morbidity and mortality in cancer and it continues to be a challenge in cancer treatment. Chemoresistance is influenced by genetic and epigenetic alterations which affect drug uptake, metabolism and export of drugs at the cellular levels. While most research has focused on tumor c...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms18071586
更新日期:2017-07-21 00:00:00
abstract::The transition from pregnancy to lactation is characterized by a progressive decrease in insulin sensitivity. Propionate increases with dietary fiber consumption and has been shown to improve insulin sensitivity. Recent studies suggest that plasma odd-chain fatty acids [OCFAs; pentadecanoic acid (C15:0) and heptadecan...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms21020635
更新日期:2020-01-18 00:00:00
abstract::Antioxidant capacity (AOC) against peroxyl radical and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) radical cation was measured for a series of p-hydroxybenzoic (HB) and p-hydroxycinnamic (HC) acids at different pH. Quantum-chemical computation was performed using Gaussian 3.0 softwa...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms150916351
更新日期:2014-09-16 00:00:00
abstract:INTRODUCTION:Studies have shown that long-term positive behavioural and physiological changes are induced in connection with vaginal, physiological birth, and skin-to-skin contact after birth in mothers and babies. Some of these effects are consistent with the effect profile of oxytocin. This scoping review explores wh...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms21249503
更新日期:2020-12-14 00:00:00
abstract::Grass carp reovirus (GCRV) causes huge economic loss to the grass carp cultivation industry but the mechanism remains largely unknown. In this study, we investigated the global and complement gene-specific DNA methylation in grass carp after GCRV infection aimed to uncover the mechanism underlying GCRV infection. The ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19041110
更新日期:2018-04-07 00:00:00
abstract::Protein hydroxylation is one type of post-translational modifications (PTMs) playing critical roles in human diseases. It is known that protein sequence contains many uncharacterized residues of proline and lysine. The question that needs to be answered is: which residue can be hydroxylated, and which one cannot. The ...
journal_title:International journal of molecular sciences
pub_type: 杂志文章
doi:10.3390/ijms19092817
更新日期:2018-09-18 00:00:00
abstract::Sarcopenia is primarily characterized by skeletal muscle disturbances such as loss of muscle mass, quality, strength, and physical performance. It is commonly seen in elderly patients with chronic diseases. The prevalence of sarcopenia in chronic heart failure (HF) patients amounts to up to 20% and may progress into c...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms21186549
更新日期:2020-09-08 00:00:00
abstract::The thymus generates central immune tolerance by producing self-restricted and self-tolerant T-cells as a result of interactions between the developing thymocytes and the stromal microenvironment, mainly formed by the thymic epithelial cells. The thymic epithelium derives from the endoderm of the pharyngeal pouches, e...
journal_title:International journal of molecular sciences
pub_type: 杂志文章,评审
doi:10.3390/ijms21165765
更新日期:2020-08-11 00:00:00