Query: siRNA

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FSTL1 Promotes Inflammatory Reaction and Cartilage Catabolism through Interplay with NF κB Signaling Pathways in an In Vitro ONFH Model
AbstractOsteonecrosis of the femoral head (ONFH) usually occurs in young people and is closely associated with autoimmune reactions. Follistatin-like 1 (FSTL1) was recently proven to participate in several inflammation-related diseases. The role of FSTL1 in ONFH is still unclear. Serum levels of FSTL1 were not significantly different in ONFH patients and healthy individuals. In contrast, elevated expression levels of FSTL1 were observed in degraded cartilage and synovial fluid in ONFH patients and in a cultured human primary chondrocyte model treated with interleukin-1 beta (IL-1 β) and tumor necrosis factor-alpha (TNF-α...
Source: Inflammation - April 22, 2019 Category: Allergy & Immunology Source Type: research

NAK α2 inhibits fibrosis formation and protects against cardiomyocyte hypertrophy by suppressing hypertrophy associated molecules and activating LTCC/NCX signaling pathway.
CONCLUSIONS: Over-expression of NKAα2 suppressed fibrosis formation and protected against cardiomyocyte hypertrophy by inhibiting hypertrophy associated molecules, alleviating apoptosis and activating LTCC/NCX signaling pathway. PMID: 31002153 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - April 21, 2019 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Astrocytes induce proliferation of oligodendrocyte progenitor cells via connexin 47-mediated activation of Chi3l1 expression.
CONCLUSIONS: Cx47/Chi3l1 plays an important role in the promotion of OPCs proliferation by ASTs. ASTs can promote the expression of Chi3l1 via Cx47 in OPCs, and then activate the expression of cyclin D1 and regulate the cell cycle of OPCs, thereby promoting cell proliferation. This study provides a new target for the treatment of neurodegenerative diseases. PMID: 31002152 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - April 21, 2019 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

LncRNA PVT1 knockdown affects proliferation and apoptosis of uveal melanoma cells by inhibiting EZH2.
CONCLUSIONS: LncRNA PVT1 knockdown in UM cells can repress the proliferation of UM cells and promote their apoptosis by regulating EZH2 expression. PMID: 31002139 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - April 21, 2019 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

LncRNA DANCR accelerates the development of multidrug resistance of gastric cancer.
CONCLUSIONS: Upregulation of DANCR can accelerate the MDR development of GC, which may become a potential target for treating GC with MDR. PMID: 31002130 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - April 21, 2019 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

HCP5 promotes colon cancer development by activating AP1G1 via PI3K/AKT pathway.
CONCLUSIONS: HCP5 was significantly increased in CC and enhanced the proliferation and migration of CC cells by inhibiting the AP1G1 expression. HCP5 promoted CC development by activating the PI3K/AKT pathway. PMID: 31002129 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - April 21, 2019 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

MicroRNA-448 inhibits the regeneration of spinal cord injury through PI3K/AKT/Bcl-2 axis.
CONCLUSIONS: MicroRNA-448 is upregulated after SCI, which may be involved in the regenerative process of spinal motor nerves by regulating PI3K/AKT/Bcl-2 axis. PMID: 31002121 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - April 21, 2019 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

ARPC2 promotes breast cancer proliferation and metastasis.
Authors: Cheng Z, Wei W, Wu Z, Wang J, Ding X, Sheng Y, Han Y, Wu Q Abstract Actin-related protein 2/3 complex (ARPC2) is an actin‑binding component involved in the regulation of actin polymerization. It mediates the formation of branched actin networks and contacts the mother actin filament. Migration and invasion are key processes which enable tumor cells to infiltrate blood vessels or lymphatic vessels, and the actin pathway plays a very important role. Given that ARPC2 is critical to this progression, the present study focused on ARPC2 activity in breast cancer (BrCa) cell invasion and migration. Limited data...
Source: Oncology Reports - April 21, 2019 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

Follicle-stimulating hormone promoted pyruvate kinase isozyme type M2-induced glycolysis and proliferation of ovarian cancer cells
ConclusionsCollectively, the findings of this study indicated that FSH promoted glycolysis in epithelial ovarian cancer cells. Knockdown of PKM2 inhibited aerobic glycolysis and cell proliferation induced by FSH.
Source: Archives of Gynecology and Obstetrics - April 20, 2019 Category: OBGYN Source Type: research

GSE130071 Vestigial-like 1 promotes malignancy in gastric cancer by PI3K/AKT/ β-catenin and TGF-β/ERK/RSK2 axes
Contributor : Bo K KimSeries Type : Expression profiling by arrayOrganism : Homo sapiensVGLL1 is involved in the regulation of proliferation and metastasis in gastric cancer cells and in vivo mouse models. To understand the downstream regulation of VGLL1, we conducted a microarray analysis of VGLL1 siRNA-treated NUGC3 cells.
Source: GEO: Gene Expression Omnibus - April 20, 2019 Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research

Long Non-Coding RNA BANCR Is Overexpressed in Patients with Diabetic Retinopathy and Promotes Apoptosis of Retinal Pigment Epithelial Cells.
CONCLUSIONS lncRNA BANCR is overexpressed in patients with diabetic retinopathy and can promote apoptosis of retinal pigment epithelial cells. PMID: 30996220 [PubMed - in process]
Source: Medical Science Monitor - April 20, 2019 Category: Research Tags: Med Sci Monit Source Type: research

053 Molecular mechanism of miR-145/Smad3 pathway mediated by active vitamin D in Lupus Nephritis
To elucidate the roles of 1,25(OH)2D3 and VDR in the pathogenesis of Lupus Nephritis (LN) by regulating miR-145 expression through TGF- β1-dependent Smad3 signaling pathway.From January 1, 2012 to January 1, 2017, 49 children (11 males and 38 females) with LN and 50 healthy controls were selected in this study. CD4+Tcells treated with different concentrations of 1,25(OH)2D3(1×10-6mmol/L,1×10-7mmol/L,1×10-8mmol/L).VDR-siRNA inter ference vector and human VDR overexpression vector were constructed. CD4+T cells in logarithmic growth phase were divided into 6 groups: the normal control group, the normal negative control (N...
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: Y. Ding, X. He Tags: Adaptive and Auto-Immunity Source Type: research

375 The chromatin architectural protein CTCF regulates expression of pro-inflammatory cytokines in the skin cells
Increased evidence suggests that alterations in chromatin structure result in aberrant pro-inflammatory cytokines expression that leads to prolonged inflammatory responses. CCCTC-binding factor (CTCF) is a transcriptional repressor that insulates the expression of neighbouring genes and is involved in chromatin interactions between distal and proximal gene regulatory elements. However, the role of CTCF in the control of pro-inflammatory cytokines expression in the skin cells remains unknown. Here, we show that CTCF is expressed in the nuclei of normal human epidermal keratinocytes (NHEK) and dermal fibroblasts (DF), while ...
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: M. Boboljova, I. Asamaowei, V. Botchkarev, M. Fessing, A.N. Mardaryev Tags: Genetic Disease, Gene Regulation, and Gene Therapy Source Type: research

477 Identification of host cell factors involved HIV-1 trans-infection in dendritic cells
Dendritic cells (DC) are antigen presenting cells responsible for processing and presenting antigenic material to T-cells leading to the initiation of an adaptive immune response. DC are one of the first cells to encounter Human Immunodeficiency Virus-1 (HIV-1) transmitted via the sub-mucosal route. DC act as a ‘Trojan horse’ delivering the virus to an infectious synapse (IS), subsequently infecting target CD4+ T-cells. How HIV-1 is trafficked in DC to the IS is still unclear, therefore we conducted a siRNA screen in monocyte derived dendritic cells targeting 140 membrane trafficking genes with the aim of identifying h...
Source: Journal of Investigative Dermatology - April 20, 2019 Category: Dermatology Authors: R.J. Bayliss, J. Wheeldon, S. Caucheteux, C.M. Niessen, V. Piguet Tags: Innate Immunity, Microbiology, and Microbiome Source Type: research

The histone demethylase Kdm4 suppresses activation of hepatic stellate cell by inducing MiR-29 transcription.
In conclusion, our data delineate a novel epigenetic mechanism underlying HSC activation. Targeting this axis may yield potential therapeutics against liver fibrosis. PMID: 31014673 [PubMed - as supplied by publisher]
Source: Biochemical and Biophysical Research communications - April 20, 2019 Category: Biochemistry Authors: Kong M, Wu J, Fan Z, Chen B, Wu T, Xu Y Tags: Biochem Biophys Res Commun Source Type: research

EP1 receptor is involved in prostaglandin E2-induced osteosarcoma growth.
Authors: Niu JC, Ma N, Liu W, Wang PJ Abstract Recent studies showed that the activation of prostaglandin (PG) receptor EP1 promotes cell migration and invasion in different cancers. The aim of this study was to investigate the role of EP1 in the proliferation of osteosarcoma (OS) cells in vitro and in vivo. EP1 mRNA and protein levels were analyzed by real-time RT-PCR and Western blot, respectively in human OS cell lines MG63, OS732, U-2OS, HOS and SAOS-2 compared to human fetal osteoblastic hFOB 1.19 cells. MG63 cells were treated with PGE2, EP1 specific agonist 17-PT-PGE2, 17-PT-PGE2 + EP1 specific antagonist SC...
Source: Bosnian Journal of Basic Medical Sciences - April 19, 2019 Category: General Medicine Tags: Bosn J Basic Med Sci Source Type: research

Synergistic effects of 7-O-geranylquercetin and siRNAs on the treatment of human breast cancer
Publication date: Available online 19 April 2019Source: Life SciencesAuthor(s): Jiaxin Zuo, Yameng Jiang, Enxia Zhang, Yuling Chen, Ze Liang, Jie Zhu, Yinan Zhao, Hong Xu, Guoliang Liu, Jiasi Liu, Wei Wang, Shubiao Zhang, Yuhong ZhenAbstractAimsTo investigate the antitumor effect of 7-O-geranylquercetin (GQ) combining with survivin siRNA (siSuvi) or IL-10 siRNA (siIL-10) to breast cancer.Main methodsXenograft tumor model was established by subcutaneously inoculating human breast cancer MCF-7 cells in BALB/c nude mice. Transfection efficiency of siRNA mediated by cationic liposome CDO14 in MCF-7 cells and tumor bearing mice...
Source: Life Sciences - April 19, 2019 Category: Biology Source Type: research

Regulation of human inducible nitric oxide synthase expression by an upstream open reading frame
Publication date: Available online 18 April 2019Source: Nitric OxideAuthor(s): Fabian Gather, Katja Schmitz, Kathrin Koch, Lea-Marie Vogt, Andrea Pautz, Hartmut KleinertAbstractThe human inducible nitric oxide synthase (iNOS) gene contains an upstream open reading frame (uORF) in its 5′-untranslated region (5′-UTR) implying a translational regulation of iNOS expression. Transfection experiments in human DLD-1 cells revealed that the uORF although translatable seems not to inhibit the translation start at the bona fide ATG. Our data clearly show that human iNOS translation is cap-dependent and that the 5′-UTR of the...
Source: Nitric Oxide - April 19, 2019 Category: Chemistry Source Type: research

Cancers, Vol. 11, Pages 562: Dual Targeting of Y-Box Binding Protein-1 and Akt Inhibits Proliferation and Enhances the Chemosensitivity of Colorectal Cancer Cells
In this study, the effects of oncogenic mutated KRAS(G12V) and KRAS(G13D) on YB-1 phosphorylation were investigated in CRC cells. The effects of the inhibition of p90 ribosomal S6 kinase (RSK) on YB-1 phosphorylation, cell proliferation and survival were tested with and without treatment with 5-fluorouracil using pharmacological inhibitors and siRNA. YB-1 phosphorylation status and subcellular distribution in CRC patient tissues were determined by immunofluorescence staining and confocal microscopy. Endogenous expression of mutated KRAS(G13D) and conditional expression of KRAS(G12V) significantly stimulated YB-1 phosphoryl...
Source: Cancers - April 19, 2019 Category: Cancer & Oncology Authors: Maier Attenberger Tiwari Lettau Rebholz Fehrenbacher Schaller Gani Toulany Tags: Article Source Type: research

The YB-1/EZH2/amphiregulin signaling axis mediates LPA-induced breast cancer cell invasion.
Abstract Lysophosphatidic acid (LPA) has been known to induce epithelial-mesenchymal transition (EMT) to stimulate cancer cell invasion, and resveratrol (3,5,4'-trans-trihydroxystilbene; REV) suppresses the invasion and metastasis of various cancers. The current study aimed to identify the underlying mechanism by which LPA aggravates breast cancer cell invasion and the reversal of this phenomenon. Immunoblotting and quantitative RT-PCR analysis revealed that LPA induces amphiregulin (AREG) expression. Silencing of Y-box binding protein 1 (YB-1) or enhancer of zeste homolog 2 (EZH2) expression efficiently inhibited...
Source: Archives of Pharmacal Research - April 19, 2019 Category: Drugs & Pharmacology Authors: Cho KH, Jeong BY, Park CG, Lee HY Tags: Arch Pharm Res Source Type: research

Silencing FOXO1 attenuates dexamethasone-induced apoptosis in osteoblastic MC3T3-E1 cells.
Abstract Dexamethasone (DEX), a widely used glucocorticoid with strong anti-inflammatory and immunosuppressive activities, has been reported to induce apoptosis in osteoblasts, but the underlying mechanisms are still not comprehensively investigated. FOXO1 plays an important role in the regulation of cell proliferation and apoptosis. Our study aims to explore the role of FOXO1 in DEX-induced apoptosis of osteoblastic MC3T3-E1 cells through bioinformatics and experiments. We first employed bioinformatics to identify DEX-related genes and revealed their functions by GO enrichment analysis including FOXO1 associated ...
Source: Biochemical and Biophysical Research communications - April 19, 2019 Category: Biochemistry Authors: Xing L, Zhang X, Feng H, Liu S, Li D, Hasegawa T, Guo J, Li M Tags: Biochem Biophys Res Commun Source Type: research

Cyclophilin B promotes cell proliferation, migration, invasion and angiogenesis via regulating the STAT3 pathway in non-small cell lung cancer
This study aimed to investigate the role and regulatory mechanism of CypB in NSCLC progression. The expression levels of CypB was detected in NSCLC samples and cell lines by ELISA, western blot and immunohistochemistry assay. In addition, CCK8, colony formation, scratch and transwell assays were used to evaluate the proliferation, migration and invasion of A549 cells with CypB silencing. The expression of angiogenesis related proteins and pathway-related factors were detected by western blot. In NSCLC samples, CypB expression was upregulated. The expression of CypB was significantly reduced in the siRNA-cyclophilin B group...
Source: Pathology Research and Practice - April 18, 2019 Category: Pathology Source Type: research

Epigenetic Regulation of Diabetogenic Adipose Morphology
ConclusionCpG methylation could be influential in determining adipose morphology and thereby constitute a novel antidiabetic target. We identified C14orf180 as a novel regulator of adipocyte lipid storage and possibly differentiation.
Source: Molecular Metabolism - April 18, 2019 Category: Endocrinology Source Type: research

Multifunctional drug carrier based on PEI derivatives loaded with small interfering RNA for therapy of liver cancer
Publication date: Available online 17 April 2019Source: International Journal of PharmaceuticsAuthor(s): Yarong Zhao, Robert J. Lee, Luotong Liu, Shiyan Dong, Jing Zhang, Yu Zhang, Yicheng Yao, Jiahui Lu, Qingfan Meng, Jing Xie, Lesheng TengAbstractGene therapy strategies for liver cancer have broad application prospects but still lack a stable and efficient delivery vehicle. To overcome this obstacle, we designed a multifunctional gene delivery vector, sTPssOLP, which was based on oleylamine (OA)-modified disulfide-containing polyethylenimine (PEI) and incorporated into lipids to prepare a lipid nanoparticle. sTPssOLP con...
Source: International Journal of Pharmaceutics - April 18, 2019 Category: Drugs & Pharmacology Source Type: research

Modeling Modulation of the Tick Regulome in Response to Anaplasma phagocytophilum for the Identification of New Control Targets
Conclusion Our modeling of the modulation of the tick regulome in response to A. phagocytophilum infection provided new insights into the mechanisms that target specific functions in different tick tissues. These results supported the use of network analysis for the study of regulome response to infection. Although general mechanisms affected by A. phagocytophilum infection may be conserved even between tick and human cells (de la Fuente et al., 2016b), the effect of vector-pathogen co-evolution on pathogen isolates adaptation to grow in tick cells (Alberdi et al., 2015) may result in differences between isolates in the m...
Source: Frontiers in Physiology - April 18, 2019 Category: Physiology Source Type: research

TonEBP Suppresses the HO-1 Gene by Blocking Recruitment of Nrf2 to Its Promoter
Discussion Dynamic changes in the functional phenotype of macrophages are associated with pathogenesis of inflammatory diseases (5–7). TonEBP primes macrophages toward an M1 phenotype, which has pro-inflammatory properties. TonEBP does this by promoting expression of pro-inflammatory genes via interaction with NF-κB (36) and by binding directly to the promoter (37, 64). In addition, TonEBP suppresses expression of the anti-inflammatory cytokine IL-10 by limiting chromatin access to the promoter (37). The pro-inflammatory function of TonEBP suggests that inhibiting its expression or activation could suppres...
Source: Frontiers in Immunology - April 18, 2019 Category: Allergy & Immunology Source Type: research

Myeloid Derived Suppressor Cells Interactions With Natural Killer Cells and Pro-angiogenic Activities: Roles in Tumor Progression
Conclusions MDSC are major players in the immunosuppressive scenario in cancer, thanks to their phenotype heterogeneity and critical interaction with several innate immune cells, thus representing a crucial target in oncology. Here we reviewed the interactions of MDSCs with NK cells. The contribution of key cytokines, chemokines and mediators active in this process have been discussed. We also described the contribution of MDSC on angiogenesis directly or indirectly through interactions with NK and immunosuppressive activities. A parallel of the cancer associated to the decidual counterpart of these cells is discussed, a...
Source: Frontiers in Immunology - April 18, 2019 Category: Allergy & Immunology Source Type: research

Increasing Upstream Chromatin Long –Range Interactions May Favor Induction of Circular RNAs in LysoPC-Activated Human Aortic Endothelial Cells
We examined the sponging potential of all significantly changed circRNAs using the CircInteractome database (Montefiori et al., 2018), recording two miRNAs with four or more predicted binding sites in a single circRNA transcript, a threshold above which meaningful sponging activity is likely to occur Memczak et al. (2013). Another four significantly changed circRNAs are experimentally shown to sponge miRNAs (Dudekula et al., 2016; Chen et al., 2017; Yan et al., 2017; Wang et al., 2018), for six total circRNAs with miRNA sponging activity including miR125, miR143, miR1272, miR153, miR515-5p, and miR196a-5p (Table 4). In Fig...
Source: Frontiers in Physiology - April 18, 2019 Category: Physiology Source Type: research

P2Y4/TSP-1/TGF- β1/pSmad2/3 pathway contributes to acute generalized seizures induced by kainic acid.
P2Y4/TSP-1/TGF-β1/pSmad2/3 pathway contributes to acute generalized seizures induced by kainic acid. Brain Res Bull. 2019 Apr 18;: Authors: Zhang Y, Zhu W, Yu H, Yu J, Zhang M, Pan X, Gao X, Wang Q, Sun H Abstract Epilepsy is accompanied by angiogenesis and blood-brain barrier (BBB) disruption. The transforming growth factor-β1 (TGF-β1)/phosphorylated small mothers against decapentaplegic 2 and 3 (pSmad2/3)/vascular endothelial growth factor (VEGF) pathway, activated by thrombospondin-1 (TSP-1), which is further regulated by Y type P2 purinergic receptor activity, may participate in angiogenesis. W...
Source: Brain Research Bulletin - April 18, 2019 Category: Neurology Authors: Zhang Y, Zhu W, Yu H, Yu J, Zhang M, Pan X, Gao X, Wang Q, Sun H Tags: Brain Res Bull Source Type: research

High-Throughput Characterization of Viral and Cellular Protein Expression Patterns During JC Polyomavirus Infection
Discussion The study of viral infections in vitro has provided innumerable advances to the field of virology. However, the lack of rapid and efficient screening tools has hindered research progress for some viruses, like JCPyV (Houff et al., 1983; Zu Rhein, 1983; Assetta and Atwood, 2017). To overcome this challenge, the development of high-throughput analyses is needed to help aid in the production of large data sets and generation of multiple lines of inquiry. Current methodologies for analyzing JCPyV infectivity predominantly rely on manual quantitation of infection by indirect immunodetection of viral proteins by epif...
Source: Frontiers in Microbiology - April 17, 2019 Category: Microbiology Source Type: research

FGF21 as Modulator of Metabolism in Health and Disease
In conclusion, FGF21 belongs to a promising class of cytokines that are induced in response to stress and that can be used as a drug, drug target, or through a biomarker, depending on the physio-pathological context. All these findings will become clear when FGF21 will be used as a therapeutic molecule, exploiting the beneficial effects of FGF21 for treating metabolic disease or when it will be blocked to ameliorate disease progression and the onset of disease. Author Contributions CT and MS wrote the manuscript. VR contributed to the discussion. Funding This work was supported from the AFM-Telethon (19524), Italian Mi...
Source: Frontiers in Physiology - April 17, 2019 Category: Physiology Source Type: research

Sanguinarine Induces Apoptosis Pathway in Multiple Myeloma Cell Lines via Inhibition of the JaK2/STAT3 Signaling
In this study, we aimed to investigate the potential anti-proliferative and pro-apoptotic activities of SNG in a panel of MM cell lines (U266, IM9, MM1S, and RPMI-8226). SNG treatment of MM cells resulted in a dose-dependent decrease in cell viability through mitochondrial membrane potential loss and activation of caspase 3, 9, and cleavage of PARP. Pre-treatment of MM cells with a universal caspase inhibitor, Z-VAD-FMK, prevented SNG mediated loss of cell viability, apoptosis, and caspase activation, confirming that SNG-mediated apoptosis is caspase-dependent. The SNG-mediated apoptosis appears to be resulted from suppres...
Source: Frontiers in Oncology - April 17, 2019 Category: Cancer & Oncology Source Type: research

PGC1 β Regulates Breast Tumor Growth and Metastasis by SREBP1-Mediated HKDC1 Expression
Conclusions: PGC1β regulates breast cancer tumor growth and metastasis by SREBP1-mediated HKDC1 expression. This provides a novel therapeutic strategy through targeting the PGC1β/HKDC1 signaling pathway for breast cancer treatment. Introduction Breast cancer is a very common cancer with significant premature mortality in women. Around 12% of women in USA will have chance to be diagnosed with breast cancer during their lifetimes (1, 2). The development of breast cancer is regulated by many factors, and even as average survival rates have increased significantly as a result of many advanced treatments...
Source: Frontiers in Oncology - April 17, 2019 Category: Cancer & Oncology Source Type: research

Transport Mechanisms for the Nutritional Supplement β-Hydroxy-β-Methylbutyrate (HMB) in Mammalian Cells
ConclusionHMB uptake in C2C12 and MCF7 cells is primarily H+-coupled and inhibited by lactate, but MCT1 –4 are only partly responsible for HMB uptake. SMCT1 also transports HMB, but in a Na+-coupled manner. Other, yet unidentified, transporters mediate the major portion of HMB uptake in C2C12 and MCF7 cells.
Source: Pharmaceutical Research - April 17, 2019 Category: Drugs & Pharmacology Source Type: research

CDK9 modulates circadian clock by attenuating REV-ERB α activity.
CDK9 modulates circadian clock by attenuating REV-ERBα activity. Biochem Biophys Res Commun. 2019 Apr 17;: Authors: Ou J, Li H, Qiu P, Li Q, Chang HC, Tang YC Abstract Circadian clock and cell cycle are vital cellular programs acting in a timely-regulated, cyclic manner. The two cellular oscillators are coupled in various ways to facilitate biological processes. Here we report CDK9, a kinase belongs to the CDK family in regulating cell cycle and RNA Pol II activity, can serve as a modulator for circadian clock. We identified CDK inhibitor LY2857785 potently blocked PER2:LUC expression in MEFs from a ...
Source: Biochemical and Biophysical Research communications - April 17, 2019 Category: Biochemistry Authors: Ou J, Li H, Qiu P, Li Q, Chang HC, Tang YC Tags: Biochem Biophys Res Commun Source Type: research

Molecular characterization and expression of SiFad1 in the sea urchin (Strongylocentrotus intermedius).
In this study, we cloned the full-length sequence of the SiFad1 gene (SiFad1) and analyzed its expression profiles during different developmental stages and in different tissues of Strongylocentrotus intermedius. The full-length cDNA of SiFad1 is composed of 1086 bp, with a putative open reading frame of 885 bp encoding a polypeptide of 294 amino acid (AA) residues. The predicted molecular mass of SiFad1 is 34.67 kDa and its theoretical pI is 8.41. The presence of conserved motifs including three histidine boxes (HXXXH, HXXHH, XXXHH), a FA_desaturases domain and three transmembrane domains suggests that SiFad1 belong...
Source: Gene - April 17, 2019 Category: Genetics & Stem Cells Authors: Han L, Ding J, Wang H, Zuo R, Quan Z, Fan Z, Liu Q, Chang Y Tags: Gene Source Type: research

Chlorogenic acid promotes the Nrf2/HO-1 anti-oxidative pathway by activating p21Waf1/Cip1 to resist dexamethasone-induced apoptosis in osteoblastic cells.
Abstract In a previous study, p21Waf1/Cip1 (p21) promoted activation of the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, which has an important role in regulating apoptosis triggered by oxidative stress and inhibiting development of osteoporosis. Chlorogenic acid (CGA) has a strong protective effect on osteoporosis, closely related to activating the Nrf2/HO-1 pathway. However, whether CGA can resist apoptosis by regulating p21 and consequently promote activation of the Nrf2/HO-1 pathway needs further investigation. MC3T3-E1 cells were treated with dexamethasone (Dex), with or without ...
Source: Free Radical Biology and Medicine - April 17, 2019 Category: Biology Authors: Han D, Gu X, Gao J, Wang Z, Liu G, Barkema HW, Han B Tags: Free Radic Biol Med Source Type: research

Genetic Regulation of Liver Metabolites and Transcripts Linking to Biochemical-Clinical Parameters
Conclusion In summary, this study is the first to combine metabolomics, transcriptomics, and genome-wide association studies in a porcine model. Our results improve understanding of the genetic regulation of metabolites which link to transcripts and finally biochemical-clinical parameters. Further, high-performance profiling of metabolites as intermediate phenotypes is a potentially powerful approach to uncover how genetic variation affects metabolic and health status. Our results advance knowledge in areas of biomedical and agricultural interest and identify potential correlates of biomarkers, SNPs-metabolites, SNPs-tran...
Source: Frontiers in Genetics - April 17, 2019 Category: Genetics & Stem Cells Source Type: research

A multifunctional persistent luminescent nanoprobe for imaging guided dual-stimulus responsive and triple-synergistic therapy of drug resistant tumor cells.
We report the design and fabrication of a multifunctional persistent luminescent nanoprobe for imaging guided dual-stimulus responsive and triple-synergistic therapy of drug resistant tumor. The integration of the dual-stimulus of an acidic microenvironment and laser irradiation with the triple-synergistic therapy of doxorubicin, photothermal and siRNA offers excellent therapeutic performance for drug resistant tumor cells with high specificity and little side effects. PMID: 30993283 [PubMed - as supplied by publisher]
Source: Chemical Communications - April 17, 2019 Category: Chemistry Authors: Su FX, Zhao X, Dai C, Li YJ, Yang CX, Yan XP Tags: Chem Commun (Camb) Source Type: research

Activation of STAT1 by the FRK tyrosine kinase is associated with human glioma growth
ConclusionsOur findings highlighted a critical role of FRK in tumor suppression ability through promoting STAT1 activation, and provided a potential therapeutic target for glioma.
Source: Journal of Neuro-Oncology - April 16, 2019 Category: Cancer & Oncology Source Type: research

Non-canonical Notch Signaling Regulates Actin Remodeling in Cell Migration by Activating PI3K/AKT/Cdc42 Pathway
In conclusion, our research results indicate that DAPT activates PI3K/AKT/Cdc42 signaling by non-canonical Notch pathway, and the activated Cdc42 promotes the filopodia formation and inhibits lamellipodia assembly, resulting in reduced migration of breast cancer cells. The results imply that non-canonical Notch signaling may play a very important role in the rapid response of cells to the extracellular signals. Author Contributions LG, JD, and LL designed the study and wrote and revised the manuscript. LL and LZ performed most of the experiments and data analysis. SZ, X-YZ, P-XM, Y-DM, Y-YW, YC, S-JT, and Y-JZ assisted i...
Source: Frontiers in Pharmacology - April 16, 2019 Category: Drugs & Pharmacology Source Type: research

Autophagy Is a Defense Mechanism Inhibiting Invasion and Inflammation During High-Virulent Haemophilus parasuis Infection in PK-15 Cells
In this study, we sought to investigate whether SH0165 (serovar 5, high-virulent strain) and HN0001 (serovar 6, non-virulent strain) infection induces autophagy and the specific role of autophagy in bacterial invasion and inflammation during H. parasuis infection. Moreover, we explored the mechanism underlying autophagy regulated inflammation through inflammatory signaling cascades during H. parasuis infection. This observation could provide useful information for further understanding the role of autophagy in H. parasuis infection and improve our knowledge of new strategies against this pathogen. Materials and Methods B...
Source: Frontiers in cellular and infection microbiology - April 16, 2019 Category: Microbiology Source Type: research

IFIT5 Participates in the Antiviral Mechanisms of Rainbow Trout Red Blood Cells
We described a new defense mechanism based on IFIT5 antiviral activity in nucleated RBCs that appeared to contribute to halting the VHSV infection. This finding sheds light into novel antiviral therapeutics to mitigate the economic losses and social impact caused by viral infections in the aquaculture industry. This work broadens the knowledge of fish nucleated RBCs functions and their role in the immune response to viral infections. Ethics Statement Experimental protocols and methods relating to experimental animals were reviewed and approved by the Animal Welfare Body and the Research Ethics Committee at the University...
Source: Frontiers in Immunology - April 16, 2019 Category: Allergy & Immunology Source Type: research

NF κB and Kidney Injury
Conclusion As a critical regulator of inflammation and cell survival, the NFκB pathway is a promising target for diagnosing and treating kidney diseases. For modulation of the NFκB pathway in the clinic, a number of molecules can effectively inhibit NFκB signaling by targeting the receptors, associated adaptors, IKKs, IκBs and transcriptional regulators (144). There is further clinical evidence on small-molecule inhibitors of IKKα and NIK from recent trials on anti-cancer therapies (145). These clinical trials showed that the cancer-selective pharmacodynamic response of DTP3, the co...
Source: Frontiers in Immunology - April 16, 2019 Category: Allergy & Immunology Source Type: research

Midkine silencing enhances the anti –prostate cancer stem cell activity of the flavone apigenin: cooperation on signaling pathways regulated by ERK, p38, PTEN, PARP, and NF-κB
In conclusion, MK-regulated events are different between PCSCs, and when combined with apigenin plus MK silencing, docetaxel treatment may be a valuable approach for the eradication of PCSCs.
Source: Investigational New Drugs - April 16, 2019 Category: Drugs & Pharmacology Source Type: research

Systems Biology Approaches and Precision Oral Health: A Circadian Clock Perspective
Conclusion Most head and neck pathologies show a broad cellular heterogeneity making it difficult to achieve an accurate diagnosis and efficient treatment (Graf and Zavodszky, 2017; Lo Nigro et al., 2017). Single cell analysis of circadian omics (Lande-Diner et al., 2015; Abraham et al., 2018), may be a crucial tool needed in the future to fully understand the circadian control of head and neck diseases. It becomes more obvious that there is only a small genetic component but a largely unknown epigenetics and/or environmental component for most of the head and neck pathologies (Moosavi and Motevalizadeh Ardekani, 2016; He...
Source: Frontiers in Physiology - April 16, 2019 Category: Physiology Source Type: research

lncRNA ZEB1-AS1 Mediates Oxidative Low-Density Lipoprotein-Mediated Endothelial Cells Injury by Post-transcriptional Stabilization of NOD2
Conclusion We report the discovery that ZEB1-AS1 functionally participates in ox-LDL-induced ECs injury via LRPPRC-mediated stabilization of NOD2. Uncovering the precise role of ZEB1-AS1/LRPPRC/NOD2 pathway in the progression of ox-LDL-induced ECs death and AS will not only increase our knowledge of ox-LDL-induced AS, but also enable the development of novel therapeutic strategies to overcome oxidation product-induced diseases. Author Contributions XX and CL designed and mainly did the study. CM, ZD, and YD helped and did the study. Conflict of Interest Statement The authors declare that the research was conducted in ...
Source: Frontiers in Pharmacology - April 16, 2019 Category: Drugs & Pharmacology Source Type: research

TLR2 and TLR4 mediate an activation of adipose tissue renin-angiotensin system induced by uric acid.
In conclusion, TLR2/4 mediated adipose inflammation plays a key role in RAS activation induced by uric acid in adipose tissue. PMID: 31002842 [PubMed - as supplied by publisher]
Source: Biochimie - April 16, 2019 Category: Biochemistry Authors: Zhang J, Diao B, Xue Lin, Xu J, Tang F Tags: Biochimie Source Type: research

Ribavirin sensitizes nasopharyngeal carcinoma to 5-fluorouracil through suppressing 5-fluorouracil-induced ERK-dependent-eIF4E activation.
Abstract Although overexpression of eukaryotic translation initiation factor 4E (eIF4E) is associated with enhanced growth and poor prognosis in nasopharyngeal carcinoma (NPC), the function of eIF4E in NPC response to chemotherapy has not been revealed. In this work, we demonstrate that eIF4E inhibition using both ribavirin and siRNA targets NPC cells and enhances the efficacy of 5-fluorouracil (5-FU). Mechanism studies indicate that 5-FU treatment increases phosphorylation of eIF4E in NPC cells, and this is dependent on ERK activation. eIF4E inhibition thus significantly sensitizes NPC cell response to 5-FU. Of n...
Source: Biochemical and Biophysical Research communications - April 16, 2019 Category: Biochemistry Authors: Hu Z, Zhen L, Li Q, Han Q, Hua Q Tags: Biochem Biophys Res Commun Source Type: research

Luteolin Ameliorates Testis Injury and Blood –Testis Barrier Disruption through the Nrf2 Signaling Pathway and by Upregulating Cx43
ConclusionLuteolin is identified as a novel active ingredient that contributes to the protective activity in testicular damage through activating the Nrf2 signaling pathway and by upregulating Cx43.
Source: Molecular Nutrition and Food Research - April 16, 2019 Category: Food Science Authors: Bo Ma, Jie Zhang, Zhiming Zhu, Ang Zhao, Yanfen Zhou, Hanjie Ying, Qi Zhang Tags: Research Article Source Type: research