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https://www.readbyqxmd.com/read/29793020/epha2-stimulates-vcam-1-expression-through-calcium-dependent-nfat1-activity
#1
Steven Daniel Funk, Alexandra C Finney, Arif Yurdagul, Christopher B Pattillo, A Wayne Orr
Endothelial cell activation by proinflammatory stimuli drives leukocyte recruitment through enhanced expression of counter-receptors such as vascular cell adhesion molecule-1 (VCAM-1). We previously demonstrated that activation of the receptor tyrosine kinase EphA2 with its ligand ephrin-A1 induces VCAM-1 expression. Here, we sought to characterize the proinflammatory signaling pathways involved. Analysis of over-represented transcription factors in ephrin-A1-induced genes identified multiple potential transcriptional regulators, including the Rel family members nuclear factor-κB (NF-κB/p65) and nuclear factor of activated T-cells (NFAT)...
May 21, 2018: Cellular Signalling
https://www.readbyqxmd.com/read/29792947/trail-attenuates-sulforaphane-mediated-nrf2-and-sustains-ros-generation-leading-to-apoptosis-of-trail-resistant-human-bladder-cancer-cells
#2
Cheng-Yun Jin, Ilandarage Menu Neelaka Molagoda, Wisurumuni Arachchilage Hasitha Maduranga Karunarathne, Sang-Hyuck Kang, Cheol Park, Gi-Young Kim, Yung Hyun Choi
Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) can preferentially initiate apoptosis in malignant cells with minimal toxicity to normal cells. Unfortunately, many human cancer cells are refractory to TRAIL-induced apoptosis through many unknown mechanisms. Here, we report that TRAIL resistance can be reversed in human bladder cancer cell lines by treatment with sulforaphane (SFN), a well-known chemopreventive isothiocyanate in various cruciferous vegetables. Combined treatment with SFN and TRAIL (SFN/TRAIL) significantly induced apoptosis concomitant with activation of caspases, loss of mitochondrial membrane potential (MMP), Bid truncation, and induction of death receptor 5...
May 21, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29792888/oral-vitamin-a-coupled-valsartan-nanomedicine-high-hepatic-stellate-cell-receptors-accessibility-and-prolonged-enterohepatic-residence
#3
Nesrine S El-Mezayen, Wessam F El-Hadidy, Wessam M El-Refaie, Thanaa I Shalaby, Mahmoud M Khattab, Aiman S El-Khatib
So far, liver fibrosis still has no clinically-approved treatment. The loss of stored vitamin-A (VA ) in hepatic stellate cells (HSCs), the main regulators to hepatic fibrosis, can be applied as a mechanism for their targeting. Valsartan is a good candidate for this approach; it is a marketed oral-therapy with inverse- and partial-agonistic activity to the over-expressed angiotensin-II type1 receptor (AT1R) and depleted nuclear peroxisome proliferator-activated receptor-gamma (PPAR-γ), respectively, in activated HSCs...
May 21, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29792195/histamine-activates-inflammatory-response-and-depresses-casein-synthesis-in-mammary-gland-of-dairy-cows-during-sara
#4
Guangjun Chang, Lailai Wang, Nana Ma, Wenwen Zhang, Huanmin Zhang, Hongyu Dai, Xiangzhen Shen
BACKGROUND: Mounting evidences observed that subacute ruminal acidosis (SARA) induced by high concentration (HC) diet increases the translocation of histamine from digestive tract into circulation causing a diverse of diseases in dairy cows. However, it is largely unknown how it does affect the function of mammary gland and milk quality. Hence, this study aims to observe the effects of histamine derived from the digestive tract on the inflammatory response and casein synthesis in the mammary glands during SARA...
May 23, 2018: BMC Veterinary Research
https://www.readbyqxmd.com/read/29791907/toll-like-receptor-3-signaling-contributes-to-regional-neutrophil-recruitment-in-cultured-human-glomerular-endothelial-cells
#5
Qiang Liu, Tadaatsu Imaizumi, Shogo Kawaguchi, Tomomi Aizawa, Tomoh Matsumiya, Shojiro Watanabe, Koji Tsugawa, Hidemi Yoshida, Kazushi Tsuruga, Kensuke Joh, Hiroshi Kijima, Hiroshi Tanaka
BACKGROUND: Given the importance of neutrophil recruitment in the pathogenesis of glomerulonephritis (GN), the representative neutrophil chemoattractant C-X-C motif chemokine 1 (CXCL1)/GROα and the adhesion molecule E-selectin in glomerular endothelial cells (GECs) play a pivotal role in the development of GN. Endothelial Toll-like receptor 3 (TLR3) is thought to be involved in the inflammatory response via innate immunity. However, the role of endothelial TLR3 signaling in the expression of neutrophil chemoattractants and adhesion molecules remains to be elucidated...
May 23, 2018: Nephron
https://www.readbyqxmd.com/read/29791873/rhoa-rock-signaling-regulates-smooth-muscle-phenotypic-modulation-and-vascular-remodeling-via-the-jnk-pathway-and-vimentin-cytoskeleton
#6
Lian Tang, Fan Dai, Yan Liu, Xiaoqiang Yu, Chao Huang, Yuqin Wang, Wenjuan Yao
The RhoA/ROCK signaling pathway regulates cell morphology, adhesion, proliferation, and migration. In this study, we investigated the regulatory role of RhoA/ROCK signaling on PDGF-BB-mediated smooth muscle phenotypic modulation and vascular remodeling and clarified the molecular mechanisms behind these effects. PDGF-BB treatment induced the activation of RhoA, ROCK, PDGF-Rβ, and the expression of PDGF-Rβ in HA-VSMCs (human aortic vascular smooth muscle cells). PDGF-Rβ inhibition and RhoA suppression blocked PDGF-BB-induced RhoA activation and ROCK induction...
May 20, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29791844/regulation-of-pathogenic-t-helper-17-cell-differentiation-by-steroid-receptor-coactivator-3
#7
Kentaro Tanaka, Gustavo J Martinez, Xiaowei Yan, Weiwen Long, Kenji Ichiyama, Xinxin Chi, Byung-Seok Kim, Joseph M Reynolds, Yeonseok Chung, Shinya Tanaka, Lan Liao, Yoichi Nakanishi, Akihiko Yoshimura, Pan Zheng, Xiaohu Wang, Qiang Tian, Jianming Xu, Bert W O'Malley, Chen Dong
T helper 17 (Th17) cell development is programmed by the orphan nuclear receptor RORγt, but the underlying mechanism is not well understood. Nuclear receptor-mediated transcriptional activation depends on coactivators. Here, we show that steroid receptor coactivator-3 (SRC-3) critically regulates Th17 cell differentiation. Reduced incidence of experimental autoimmune encephalitis (EAE) associated with decreased Th17 cell generation in vivo was observed in mice with SRC-3 deletion specifically in T cells...
May 22, 2018: Cell Reports
https://www.readbyqxmd.com/read/29789866/role-of-peroxisome-proliferator-activated-receptors-in-non-alcoholic-fatty-liver-disease-inflammation
#8
REVIEW
Amanda Karolina Soares Silva, Christina Alves Peixoto
Overweight and obesity have been identified as the most important risk factors for many diseases, including cardiovascular disease, type 2 diabetes and lipid disorders, such as non-alcoholic fatty liver disease (NAFLD). The metabolic changes associated with obesity are grouped to define metabolic syndrome, which is one of the main causes of morbidity and mortality in industrialized countries. NAFLD is considered to be the hepatic manifestation of metabolic syndrome and is one of the most prevalent liver diseases worldwide...
May 22, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29788882/impact-of-drug-metabolism-pharmacokinetics-and-their-relevance-upon-taxus-based-drug-development
#9
Da-Cheng Hao, Guang-Bo Ge, Ping Wang, Ling Yang
Drug metabolism and pharmacokinetic (DMPK) studies of Taxus natural products, their semi-synthetic derivatives and analogs are indispensable in the optimization of lead compounds and clinical therapy. These studies can lead to development of new drug entities with improved absorption, distribution, metabolism, excretion and toxicity (ADME/T) profiles. To date, there have been no comprehensive reviews of the DMPK features of Taxus derived medicinal compounds.Natural and semi-synthetic taxanes may cause and could be affected by drug-drug interaction (DDI)...
May 22, 2018: Current Drug Metabolism
https://www.readbyqxmd.com/read/29788535/cyp2a5-promoter-based-gene-reporter-assay-a-novel-design-of-cell-based-bioassay-for-toxicity-prediction
#10
A'edah Abu-Bakar, Hao Hu, Matti A Lang
The murine cytochrome P450 2a5 (Cyp2a5) gene is regulated by complex interactions of various stress-activated transcription factors (TFs). Elevated Cyp2a5 transcription under chemical-induced stress conditions is achieved by interplay between the various TFs-including as aryl hydrocarbon receptor (AhR) and nuclear factor (erythroid-derived 2)-like 2 wild-type (Nrf2)-at the "stress-responding" cluster of response elements on the Cyp2a5 promoter, as well as through mRNA stabilisation mediated by interaction of the stress-activated heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) with the 3'UTR of the CYP2A5 mRNA...
May 22, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29788447/varicella-zoster-virus-induces-nuclear-translocation-of-the-neurokinin-1-receptor-promoting-lamellipodia-formation-and-viral-spread-in-spinal-astrocytes
#11
Andrew N Bubak, Christina N Como, Anna M Blackmon, Seth Frietze, Teresa Mescher, Dallas Jones, Randall J Cohrs, Petr Paucek, Nicholas L Baird, Maria A Nagel
Background: Varicella zoster virus (VZV) can present as a myelopathy with spinal astrocyte infection. Recent studies support a role for the neurokinin-1 receptor (NK-1R) in virus infections, as well as for cytoskeletal alterations that may promote viral spread. Thus, we examined the role of NK-1R in VZV-infected primary human spinal astrocytes (HA-sps) to shed light on the pathogenesis of VZV myelopathy. Methods: Mock- and VZV-infected HA-sps were examined for substance P (subP) production, NK-1R localization, morphological changes and viral spread in the presence or absence of NK-1R antagonists, aprepitant and rolapitant...
May 19, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29788408/effects-of-4-hydroxy-2-3-3-4-5-pentachlorobiphenyl-4-oh-cb107-on-liver-transcriptome-in-rats-implication-in-the-disruption-of-circadian-rhythm-and-fatty-acid-metabolism
#12
Mari Ochiai, Midori Iida, Tetsuro Agusa, Kohki Takaguchi, Satoshi Fujiic, Kei Nomiyama, Hisato Iwata
Polychlorinated biphenyls (PCBs) and their hydroxylated metabolites (OH-PCBs) have been detected in tissues of both wild animals and humans. Several previous studies have suggested adverse effects of OH-PCBs on the endocrine and nervous systems in mammals. However, there have been no studies on transcriptome analysis of the effects of OH-PCBs, and thus, the whole picture and mechanisms underlying the adverse effects induced by OH-PCBs are still poorly understood. We therefore investigated the mRNA expression profile in the liver of adult male Wistar rats treated with 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) to explore the genes responsive to OH-PCBs and to understand the potential effects of the chemical...
May 21, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29787950/macroporous-silica-nanoparticles-for-delivering-bcl2-function-converting-peptide-to-treat-multidrug-resistant-cancer-cells
#13
Weixia Xu, Pengjin Ge, Boning Niu, Xiaokun Zhang, Jie Liu, Jingjing Xie
The abundance of B cell lymphoma gene 2 (Bcl-2) is closely correlated with the resistance of cancer cells to chemotherapeutic agents, and a peptide derived from orphan nuclear receptor Nur77 can convert Bcl-2 from a protector to a killer of cancer cells. However, successful application of the Bcl-2-converting peptide to treat drug-resistant cancer cells depends on an efficient delivery carrier. Mesoporous silica nanoparticles (MSNs) have been extensively studied as promising candidates for small molecule drug delivery...
May 15, 2018: Journal of Colloid and Interface Science
https://www.readbyqxmd.com/read/29787749/epidermal-hmgb1-activates-dermal-fibroblasts-and-causes-hypertrophic-scar-formation-in-reduced-hydration
#14
Jingling Zhao, Jianxing Yu, Yingbin Xu, Lei Chen, Fei Zhou, Qiyi Zhai, Jun Wu, Bin Shu, Shaohai Qi
High-mobility group box 1 (HMGB1) protein is a multifunctional cytokine involved in inflammatory reactions and is known to play a key role in tissue repair and fibrosis. However, the function of HMGB1 in fibrotic skin diseases, such as hypertrophic scar formation, remains unclear. In this study, HMGB1 was detected in the nuclei of epidermal cells in normal skin and had accumulated in the cytoplasm in hypertrophic scars. By establishing a keratinocyte-fibroblast co-culture and conditional medium treatment models, we found that a reduced hydration condition increased the expression and secretion of HMGB1 in keratinocytes, subsequently activating dermal fibroblasts...
May 19, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29787037/effects-of-perinatal-exposure-to-dibutyltin-chloride-on-fat-and-glucose-metabolism-in-mice-and-molecular-mechanisms-in-vitro
#15
Raquel Chamorro-García, Bassem M Shoucri, Sigal Willner, Heidi Käch, Amanda Janesick, Bruce Blumberg
BACKGROUND: The organotin dibutyltin (DBT) is used in the manufacture of polyvinyl chloride (PVC) plastics, in construction materials, and in medical devices. Previous animal studies showed detrimental effects of DBT during in utero development at relatively high doses, but little was known about the effects of DBT exposure at environmentally relevant doses on endpoints such as obesity and metabolic disease. OBJECTIVES: We tested the potential obesogenic effects of DBT using in vitro and in vivo models...
May 2018: Environmental Health Perspectives
https://www.readbyqxmd.com/read/29786790/functional-studies-on-steroid-receptors
#16
Simon Schlanger, Hannelore V Heemers
Nuclear receptors play an important role in prostate cancer and the androgen receptor is a key transcription factor in regulation of cellular events. Androgen receptor-associated coregulators may be upregulated or downregulated in prostate cancer. Altered expression of regulators may potentiate androgen-induced proliferation, migration, and invasion. Therapies aimed to modulate the function of coregulators in prostate cancer may be based on the use of small molecule inhibitors. Expression and function of AR-associated proteins could be investigated after overexpression and gene silencing followed by hormonal treatment, real-time RT-PCR and ChIP...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29786751/inhibition-of-osteoclastogenesis-for-periprosthetic-osteolysis-therapy-through-the-suppression-of-p38-signaling-by-fraxetin
#17
Jia-Cheng Liao, Zhao-Xia Wei, Chang Zhao, Zhong-Ping Ma, Dao-Zhang Cai
Periprosthetic osteolysis belongs to osteolytic diseases, which often occur due to an imbalance between osteoclast and osteoblast number or activity. Fraxetin, a natural plant extract, inhibits osteoblast apoptosis and has therapeutic potential for treating osteolytic diseases. However, data pertaining to the effects of fraxetin on osteoclasts are limited. In the present study, it was demonstrated that the inhibition of osteoclastogenesis by fraxetin had an important role on the therapy of titanium particle‑induced osteolysis in vivo...
May 21, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29786170/immunopeptidomic-profiling-of-hla-a2-positive-triple-negative-breast-cancer-identifies-potential-immunotherapy-target-antigens
#18
Nicola Ternette, Marloes J M Olde Nordkamp, Julius Muller, Amanda P Anderson, Annalisa Nicastri, Adrian V S Hill, Benedikt M Kessler, Demin Li
The recent development in immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cells in the treatment of cancer has not only demonstrated the potency of utilising T-cell reactivity for cancer therapy, but has also highlighted the need for developing new approaches to discover targets suitable for such novel therapeutics. Here we analysed the immunopeptidomes of 6 HLA-A2-positive triple negative breast cancer (TNBC) samples by nano-ultra performance liquid chromatography tandem mass spectrometry (nUPLC-MS2 )...
May 22, 2018: Proteomics
https://www.readbyqxmd.com/read/29785433/the-immunomodulatory-activity-and-mechanism-of-docosahexenoic-acid-dha-on-immunosuppressive-mice-models
#19
Lirong Han, Huanna Lei, Ziwei Tian, Xu Wang, Dai Cheng, Chunling Wang
In this study, the immunomodulatory activity of docosahexaenoic acid (DHA) on the immunosuppressive BALB/c mice model and its molecular mechanism are elucidated. It was found that the weight indexes of the spleen and thymus were significantly increased by DHA (44.0 mg kg-1 and 88.0 mg kg-1) treatment in the prevention or cure groups. The result of macrophages showed that DHA (44.0 mg kg-1 and 88.0 mg kg-1) could promote the proliferation and phagocytosis activity of macrophages in the prevention or cure groups...
May 22, 2018: Food & Function
https://www.readbyqxmd.com/read/29785120/association-between-nr5a2-and-the-risk-of-pancreatic-cancer-especially-among-caucasians-a-meta-analysis-of-case-control-studies
#20
Qun Chen, Hao Yuan, Guo-Dong Shi, Yang Wu, Dong-Fang Liu, Yu-Ting Lin, Lei Chen, Wan-Li Ge, Kuirong Jiang, Yi Miao
Background: Previous studies have reported that nuclear receptor subfamily 5, group A, member 2 (NR5A2) polymorphisms (rs3790843 G>A, rs3790844 T>C, rs12029406 C>T) are associated with the risk of pancreatic cancer. However, the results of epidemiological investigations are still controversial. In order to explore its potential attributing factors, we pooled the updated literatures to evaluate the association between NR5A2 polymorphism and the risk of pancreatic cancer in this meta-analysis...
2018: OncoTargets and Therapy
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