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https://www.readbyqxmd.com/read/28822034/microrna-expression-target-genes-and-signaling-pathways-in-infants-with-a-ventricular-septal-defect
#1
Hui Chai, Zhaoyuan Yan, Ke Huang, Yuanqing Jiang, Lin Zhang
This study aimed to systematically investigate the relationship between miRNA expression and the occurrence of ventricular septal defect (VSD), and characterize the miRNA target genes and pathways that can lead to VSD. The miRNAs that were differentially expressed in blood samples from VSD and normal infants were screened and validated by implementing miRNA microarrays and qRT-PCR. The target genes regulated by differentially expressed miRNAs were predicted using three target gene databases. The functions and signaling pathways of the target genes were enriched using the GO database and KEGG database, respectively...
August 18, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28821884/the-atopic-dermatitis-blood-signature-is-characterized-by-increases-in-inflammatory-and-cardiovascular-risk-proteins
#2
Patrick M Brunner, Mayte Suárez-Fariñas, Helen He, Kunal Malik, Huei-Chi Wen, Juana Gonzalez, Tom Chih-Chieh Chan, Yeriel Estrada, Xiuzhong Zheng, Saakshi Khattri, Nancy Dattola, James G Krueger, Emma Guttman-Yassky
Beyond classic "allergic"/atopic comorbidities, atopic dermatitis (AD) emerges as systemic disease with increased cardiovascular risk. To better define serum inflammatory and cardiovascular risk proteins, we used an OLINK high-throughput proteomic assay to analyze moderate-to-severe AD (n = 59) compared to psoriasis (n = 22) and healthy controls (n = 18). Compared to controls, 10 proteins were increased in serum of both diseases, including Th1 (IFN-γ, CXCL9, TNF-β) and Th17 (CCL20) markers. 48 proteins each were uniquely upregulated in AD and psoriasis...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821818/an-essential-role-for-tagln2-in-phagocytosis-of-lipopolysaccharide-activated-macrophages
#3
Hye-Ran Kim, Hyun-Su Lee, Kyung-Sik Lee, In Duk Jung, Min-Sung Kwon, Chang-Hyun Kim, Seong-Min Kim, Myung-Han Yoon, Yeong-Min Park, Sang-Myeong Lee, Chang-Duk Jun
Activated macrophages have a greater ability of phagocytosis against pathogens that is mediated by large-scale actin rearrangement. However, molecular machineries that conduct this task have not been fully identified. Here, we demonstrate an unanticipated role of TAGLN2, a 22-kDa actin-binding protein, in Toll-like receptor (TLR)-stimulated phagocytosis. TAGLN2 was greatly induced in macrophages in response to lipopolysaccharide (LPS), a ligand for TLR4, partly via the NF-κB pathway. TAGLN2-deficient macrophages (TAGLN2 (-/-)) showed defective phagocytic functions of IgM- and IgG-coated sheep red blood cells as well as bacteria...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821645/mutant-huntingtin-is-secreted-via-a-late-endosomal-lysosomal-unconventional-secretory-pathway
#4
Katarina Trajkovic, Hyunkyong Jeong, Dimitri Krainc
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG triplet in the gene encoding for huntingtin. The resulting mutant protein huntingtin (mHtt) with extended polyglutamine (polyQ) sequence at the N-terminus leads to neuronal degeneration both in cell-autonomous and non-cell-autonomous manners. Recent studies identified mHtt in the extracellular environment and suggested that its spreading contributes to toxicity, but the mechanism of mHtt release from the cell of origin remains unknown...
August 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28812425/nasunin-inhibits-the-lipopolysaccharide-induced-pro-inflammatory-mediator-production-in-raw264-mouse-macrophages-by-suppressing-ros-mediated-activation-of-pi3%C3%A2-k-akt-nf-%C3%AE%C2%BAb-and-p38-signaling-pathways
#5
Wataru Komatsu, Kazuko Itoh, Satomi Akutsu, Hisashi Kishi, Shuji Ohhira
Nasunin is a major anthocyanin in eggplant peel. The purpose of this study was to examine the anti-inflammatory effects of nasunin in lipopolysaccharide (LPS)-stimulated RAW264 macrophages and to identify the molecular mechanisms underlying these effects. We found that nasunin reduced the LPS-induced secretion of tumor necrosis factor-α, interleukin-6 and nitric oxide, and expression of inducible nitric oxide synthase in a dose-dependent manner. Nasunin diminished LPS-induced nuclear factor-κB (NF-κB) activation by suppressing the degradation of inhibitor of κB-α and nuclear translocation of p65 subunit of NF-κB...
August 16, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28810530/caspase-dependent-and-caspase-independent-induction-of-apoptosis-in-breast-cancer-by-fucoidan-via-the-pi3k-akt-gsk3%C3%AE-pathway-in-vivo-and-in-vitro
#6
Meilan Xue, Xinqiang Ji, Chuanxing Xue, Hui Liang, Yinlin Ge, Xinjia He, Li Zhang, Kang Bian, Lichen Zhang
Purpose Fucoidan, a complex, sulfated polysaccharide obtained from brown seaweed, exerted anticancer activity through the down-regulation of β-catenin signaling in mouse breast cancer cells in our previous study. This study examines the anti-cancer effects of fucoidan as well as its underlying molecular mechanisms in the human triple negative breast cancer (TNBC) cell line and in 7,12-dimethylbenz[a]anthracene (DMBA)-induced experimental mammary carcinogenesis in rats. Methods in vitro studies, fluorescent staining, flow cytometry and Western blotting were performed to analyze apoptosis and protein expression in human breast cancer MDA-MB-231 cells...
August 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28810254/insulin-influences-lps-induced-tnf-%C3%AE-and-il-6-release-through-distinct-pathways-in-mouse-macrophages-from-different-compartments
#7
Fernando H G Tessaro, Thais S Ayala, Eduardo L Nolasco, Leonardo M Bella, Joilson O Martins
BACKGROUND/AIMS: Diabetic subjects are more susceptible to infections, which is partially due to insulin deficiency and hyperglycemia. We hypothesized that insulin influences cytokine release by macrophages from diabetic C57BL/6 mice stimulated with lipopolysaccharides (LPS). METHODS: Bone marrow-derived macrophages (BMDM) and tissue-specific macrophages from diabetic (alloxan 60 mg/kg, i.v.) male C57BL/6 mice were stimulated by LPS (100 ng/mL) and/or treated by insulin (1 mU/mL)...
August 15, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28807675/substantial-protection-against-mptp-associated-parkinson-s-neurotoxicity-in-vitro-and-in-vivo-by-anti-cancer-agent-su4312-via-activation-of-mef2d-and-inhibition-of-mao-b
#8
Baojian Guo, Shengquan Hu, Chengyou Zheng, Hongyu Wang, Fangcheng Luo, Haitao Li, Wei Cui, Xifei Yang, Guozhen Cui, Shinghung Mak, Tony Chung-Lit Choi, Edmond Dik-Lung Ma, Yuqiang Wang, Simon Ming Yuen Lee, Zaijun Zhang, Yifan Han
We have previously demonstrated the unexpected neuroprotection of the anti-cancer agent SU4312 in cellular models associated with Parkinson's disease (PD). However, the precise mechanisms underlying its neuroprotection are still unknown, and the effects of SU4312 on rodent models of PD have not been characterized. In the current study, we found that the protection of SU4312 against 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neurotoxicity in PC12 cells was achieved through the activation of transcription factor myocyte enhancer factor 2D (MEF2D), as evidenced by the fact that SU4312 stimulated myocyte enhancer factor 2 (MEF2) transcriptional activity and prevented the inhibition of MEF2D protein expression caused by MPP(+), and that short hairpin RNA (ShRNA)-mediated knockdown of MEF2D significantly abolished the neuroprotection of SU4312...
August 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28797056/anaplasma-phagocytophilum-infection-modulates-expression-of-megakaryocyte-cell-cycle-genes-through-phosphatidylinositol-3-kinase-signaling
#9
Supreet Khanal, Hameeda Sultana, John D Catravas, Jason A Carlyon, Girish Neelakanta
Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis infects neutrophils and other cells from hematopoietic origin. Using human megakaryocytic cell line, MEG-01, we show that expression of cell cycle genes in these cells are altered upon A. phagocytophilum infection. Expression of several cell cycle genes in MEG-01 cells was significantly up regulated at early and then down regulated at later stages of A. phagocytophilum infection. Lactate dehydrogenase (LDH) assays revealed reduced cellular cytotoxicity in MEG-01 cells upon A...
2017: PloS One
https://www.readbyqxmd.com/read/28792498/4-hydroxywogonin-suppresses-lipopolysaccharide-induced-inflammatory-responses-in-raw-264-7-macrophages-and-acute-lung-injury-mice
#10
Chao Fan, Le-Hao Wu, Gu-Fang Zhang, Fangfang Xu, Shuo Zhang, Xiuli Zhang, Lei Sun, Yang Yu, Yan Zhang, Richard D Ye
4'-Hydroxywogonin (4'-HW), a flavonoid, has been isolated from various plants and shown to inhibit NO production in macrophages. However, the molecular mechanisms and its in vivo activity have not been determined. Our study aimed to investigate the mechanisms underlying the anti-inflammatory effects of 4'-HW in vitro and in vivo. We showed that 4'-HW potently reduced the expression levels of COX-2 and iNOS as well as their products, prostaglandin E2 (PGE2) and nitric oxide (NO) respectively, in LPS-stimulated RAW 264...
2017: PloS One
https://www.readbyqxmd.com/read/28791774/n-substituted-hydroxynapthalene-imino-oxindole-derivatives-as-new-class-of-pi3-kinase-inhibitor-and-breast-cancer-drug-molecular-validation-and-structure-activity-relationship-studies
#11
M Rajesh Kumar, Manikandan Alagumuthu, V Violet Dhayabaran
N-substituted hydroxynapthalene imino-oxindole derivatives (5a-g) were emerged as the inhibitors of the phosphoinositide 3-kinase (PI3K) which is a crucial regulator of apoptosis or programmed cell death. Electron donor/acceptor substituted indole-imine (5a-g) were achieved and the structures were elucidated by FTIR, 1H NMR, 13C NMR, and HRMS. PI3Ks inhibition potency was assessed by competitive ELISA. Subsequently, an anticancer activity against breast cancer (MCF-7) cell lines was evaluated. In both activities, compounds 5c, 5d, 5f and were showed most potent activities...
August 9, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28768233/identification-of-transcriptome-signature-for-myocardial-reductive-stress
#12
Justin M Quiles, Madhusudhanan Narasimhan, Timothy Mosbruger, Gobinath Shanmugam, David Crossman, Namakkal S Rajasekaran
The nuclear factor erythroid 2 like 2 (Nfe2l2/Nrf2) is a master regulator of antioxidant gene transcription. We recently identified that constitutive activation of Nrf2 (CaNrf2) caused reductive stress (RS) in the myocardium. Here we investigate how chronic Nrf2 activation alters myocardial mRNA transcriptome in the hearts of CaNrf2 transgenic (TG-low and TG-high) mice using an unbiased integrated systems approach and next generation RNA sequencing followed by qRT-PCR methods. A total of 246 and 1031 differentially expressed genes (DEGs) were identified in the heart of TGL and TGH in relation to NTG littermates at ~ 6 months of age...
July 24, 2017: Redox Biology
https://www.readbyqxmd.com/read/28766166/rhpdgf-bb-combined-with-adscs-in-the-treatment-of-achilles-tendinitis-via-mir-363-pi3%C3%A2-k-akt-pathway
#13
Qiao-Jie Chen, Liang Chen, Shao-Kun Wu, Yao-Jun Wu, Qing-Jiang Pang
To investigate the mechanism of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and human adipose-derived stem cells (hADSCs) in the treatment of Achilles tendinitis. Biomechanical indices of stiffness, stress, and maximum load-to-failure were detected by biomechanical test. mRNA and protein levels of miR-363, p-PI3K/AKT, tendon-related genes Collagen I, Scleraxis (Scx), and Tenascin C (TNC) were measured by qRT-PCR and western blot. The proliferation of hADSCs was accessed by MTT assay. Biomechanical indices of stiffness, stress, and maximum load-to-failure, and mRNA and protein levels of tendon-related genes could be improved by rhPDGF-BB or hADSCs alone, and could be further improved by rhPDGF-BB + hADSCs...
August 1, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28751862/utp-gated-signaling-pathways-of-5-ht-release-from-bon-cells-as-a-model-of-human-enterochromaffin-cells
#14
Andromeda Liñán-Rico, Fernando Ochoa-Cortes, Alix Zuleta-Alarcon, Mazin Alhaj, Esmerina Tili, Josh Enneking, Alan Harzman, Iveta Grants, Sergio Bergese, Fievos L Christofi
Background: Enterochromaffin cells (EC) synthesize and release 5-HT and ATP to trigger or modulate gut neural reflexes and transmit information about visceral/pain sensation. Alterations in 5-HT signaling mechanisms may contribute to the pathogenesis of IBD or IBS, but the pharmacologic or molecular mechanisms modulating Ca(2+)-dependent 5-HT release are not understood. Previous studies indicated that purinergic signaling via ATP and ADP is an important mechanism in modulation of 5-HT release. However, EC cells also respond to UTP and UDP suggesting uridine triphosphate receptor and signaling pathways are involved as well...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28747555/tripchlorolide-induces-autophagy-in-lung-cancer-cells-by-inhibiting-the-pi3k-akt-mtor-pathway-and-improves-cisplatin-sensitivity-in-a549-ddp-cells
#15
Li-Min Chen, Tian-Jiao Song, Jian-Hong Xiao, Zheng-Hui Huang, Yong Li, Ting-Yan Lin
Tripchlorolide (T4) has been shown to induce A549 lung cancer cell death predominantly by activating an autophagy pathway. However, the underlying mechanism remains unclear. Herein, we demonstrated that compared with T4 treatment alone, pretreatment with wortmannin (an inhibitor of phosphatidylinositol 3-kinase), perifosine (an inhibitor of AKT) or rapamycin (an inhibitor of mTOR) combined with a subsequent T4 treatment significantly impaired the cell viability of A549 and A549/DDP lung cancer cells. We found that either treatment scheme markedly reduced the activity of P13K and AKT...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28744222/presence-of-functional-neurotrophin-trkb-receptors-in-the-rat-superior-cervical-ganglion
#16
Pablo Valle-Leija, Angeles Cancino-Rodezno, Berardo M Sánchez-Tafolla, Erwin Arias, Diana Elinos, Jessica Feria, María E Zetina, Miguel A Morales, Fredy Cifuentes
Sympathetic neurons express the neurotrophin receptors TrkA, p75NTR, and a non-functional truncated TrkB isoform (TrkB-Tc), but are not thought to express a functional full-length TrkB receptor (TrkB-Fl). We, and others, have demonstrated that nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) modulate synaptic transmission and synaptic plasticity in neurons of the superior cervical ganglion (SCG) of the rat. To clarify whether TrkB is expressed in sympathetic ganglia and contributes to the effects of BDNF upon sympathetic function, we characterized the presence and activity of the neurotrophin receptors expressed in the adult SCG compared with their presence in neonatal and cultured sympathetic neurons...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28743213/kallikrein-related-peptidase-4-contributes-to-the-tumor-metastasis-of-oral-squamous-cell-carcinoma
#17
Zhi Cui, Ye Cui, Gan Luo, Shuting Yang, Xinlian Ling, Yixin Lou, Xinhua Sun
Oral squamous cell carcinoma (OSCC) is a disfiguring malignancy and significantly impacts the quality of patient's life. Kallikrein-related peptidase 4 (KLK4), which is closely related to cancers, is highly expressed in OSCC. To explore the biological function of KLK4 in OSCC, a KLK4-specific shRNA was used to silence its endogenous expression, and then the migration and invasion of OSCC cells were explored. Results of our study showed that silencing KLK4 inhibited the migration and invasion of OSCC cells. The protein levels of epithelial mesenchymal transition-associated markers and proteases were also altered by KLK4 silencing...
September 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28724384/deficiency-of-pi3-kinase-catalytic-isoforms-p110%C3%AE-and-p110%C3%AE-in-mice-enhances-the-il-17-g-csf-axis-and-induces-neutrophilia
#18
Kirsten Bucher, Fee Schmitt, Benedikt Mothes, Carolin Blumendeller, Daniel Schäll, Roland Piekorz, Emilio Hirsch, Bernd Nürnberg, Sandra Beer-Hammer
BACKGROUND: Phosphoinositide 3-kinase γ (PI3Kγ) and PI3Kδ are second messenger-generating enzymes with key roles in proliferation, differentiation, survival, and function of leukocytes. Deficiency of the catalytic subunits p110γ and p110δ of PI3Kγ and PI3Kδ in p110γ/δ(-/-) mice leads to defective B- and T-cell homeostasis. Here we examined the role of p110γ and p110δ in the homeostasis of neutrophils by analyzing p110γ(-/-), p110δ(-/-) and p110γ/δ(-/-) mice. METHODS: Neutrophils and T cells in leukocyte suspensions from the bone marrow (BM), blood, spleen and lung were analyzed by flow cytometry...
July 19, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28718684/role-of-gsk-3%C3%AE-in-regulation-of-canonical-wnt-%C3%AE-catenin-signaling-and-pi3-k-akt-oncogenic-pathway-in-colon-cancer
#19
Shelly Jain, Preety Ghanghas, Chandan Rana, S N Sanyal
Non-steroidal anti-inflammatory drugs (NSAIDs) are emerging as novel chemopreventive agents because of their ability in blocking cellular proliferation, and thereby tumor development, and also by promoting apoptosis. GSK-3β, a serine threonine kinase and a negative regulator of the oncogenic Wnt/β-catenin signaling pathway, plays a critical role in the regulation of oncogenesis. Celecoxib and etoricoxib, the two cyclooxygenase-2 (COX-2) selective NSAIDs, and Diclofenac, a preferential COX-2 inhibitory NSAID, had shown uniformly the chemopreventive and anti-neoplastic effects in the early stage of colon cancer by promoting apoptosis as well as an over-expression of GSK-3β while down-regulating the PI3-K/Akt oncogenic pathway...
July 18, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28716954/synaptically-driven-phosphorylation-of-ribosomal-protein-s6-is-differentially-regulated-at-active-synapses-versus-dendrites-and-cell-bodies-by-mapk-and-pi3k-mtor-signaling-pathways
#20
Patricia Salgado Pirbhoy, Shannon Farris, Oswald Steward
High-frequency stimulation of the medial perforant path triggers robust phosphorylation of ribosomal protein S6 (rpS6) in activated dendritic domains and granule cell bodies. Here we dissect the signaling pathways responsible for synaptically driven rpS6 phosphorylation in the dentate gyrus using pharmacological agents to inhibit PI3-kinase/mTOR and MAPK/ERK-dependent kinases. Using phospho-specific antibodies for rpS6 at different sites (ser235/236 versus ser240/244), we show that delivery of the PI3-kinase inhibitor, wortmannin, decreased rpS6 phosphorylation throughout the somatodendritic compartment (granule cell layer, inner molecular layer, outer molecular layer), especially in granule cell bodies while sparing phosphorylation at activated synapses (middle molecular layer)...
August 2017: Learning & Memory
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