Query: siRNA

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Ascl1 Regulates Electric Field-Induced Neuronal Differentiation through PI3K/Akt Pathway
In this study, siRNA transfection of Achaete-scute homolog 1 (Ascl1) in NPCs or NPCs was followed by direct current stimulation at 150 mV/mm. Neuronal differentiation rate and protein expression level were analyzed after 7 or 14 days of electrical stimulation. The data showed that the expression level of Ascl1 was enhanced by electrical stimulation and positively correlated to EF strength. Moreover, we identified that the expression of Ascl1 positively regulated neuronal differentiation of NPCs and can be up-regulated by EF-stimulation through the activation of PI3K/Akt pathway. Therefore, this study provides new insig...
Source: Neuroscience - February 14, 2019 Category: Neuroscience Source Type: research

Effects of Tec Tyrosine Kinase Inhibition on the Inflammatory Response of Severe Acute Pancreatitis-Associated Acute Lung Injury in Mice
ConclusionsTec tyrosine kinase plays a key role in PALI, and is therefore a potential target for clinical treatment.
Source: Digestive Diseases and Sciences - February 14, 2019 Category: Gastroenterology Source Type: research

Transcription factor TFAP2B up-regulates human corneal endothelial cell-specific genes during corneal development and maintenance Cell Biology
The corneal endothelium, which originates from the neural crest via the periocular mesenchyme (PM), is crucial for maintaining corneal transparency. The development of corneal endothelial cells (CECs) from the neural crest is accompanied by the expression of several transcription factors, but the contribution of some of these transcriptional regulators to CEC development is incompletely understood. Here, we focused on activating enhancer-binding protein 2 (TFAP2, AP-2), a neural crest–expressed transcription factor. Using semiquantitative/quantitative RT-PCR and reporter gene and biochemical assays, we found that, within...
Source: Journal of Biological Chemistry - February 14, 2019 Category: Chemistry Authors: Susumu Hara, Satoshi Kawasaki, Masahito Yoshihara, Andrew Winegarner, Caleb Busch, Motokazu Tsujikawa, Kohji Nishida Tags: Gene Regulation Source Type: research

BOLA3 Deficiency Controls Endothelial Metabolism and Glycine Homeostasis in Pulmonary Hypertension.
CONCLUSIONS: BOLA3 acts as a crucial lynchpin connecting Fe-S-dependent oxidative respiration and glycine homeostasis with endothelial metabolic re-programming critical to PH pathogenesis. These results provide a molecular explanation for the clinical associations linking PH with hyperglycinemic syndromes and mitochondrial disorders. These findings also identify novel metabolic targets, including those involved in epigenetics, iron-sulfur biogenesis, and glycine biology, for diagnostic and therapeutic development. PMID: 30759996 [PubMed - as supplied by publisher]
Source: Circulation - February 14, 2019 Category: Cardiology Authors: Yu Q, Tai YY, Tang Y, Zhao J, Negi V, Culley MK, Pilli J, Sun W, Brugger K, Mayr J, Saggar R, Saggar R, Wallace WD, Ross DJ, Waxman AB, Wendell SG, Mullett SJ, Sembrat J, Rojas M, Khan OF, Dahlman JE, Sugahara M, Kagiyama N, Satoh T, Zhang M, Feng N, Gorc Tags: Circulation Source Type: research

Elevated expression of GNAS promotes breast cancer cell proliferation and migration via the PI3K/AKT/Snail1/E-cadherin axis
ConclusionThe data suggested that GNAS promoted breast cancer cell proliferation and migration (EMT) through the PI3K/AKT/Snail1/E-cadherin signaling pathway. These findings also indicate that GNAS can serve as a potential prognostic indicator and novel therapeutic target in breast cancer.
Source: Clinical and Translational Oncology - February 14, 2019 Category: Cancer & Oncology Source Type: research

Design, mechanism, delivery and therapeutics of canonical and Dicer-substrate siRNA
Publication date: Available online 13 February 2019Source: Asian Journal of Pharmaceutical SciencesAuthor(s): Maria Abdul Ghafoor Raja, Haliza Katas, Muhammad Wahab AmjadAbstractUpon the discovery of RNA interference (RNAi), canonical small interfering RNA (siRNA) has been recognized to trigger sequence-specific gene silencing. Despite the benefits of siRNAs as potential new drugs, there are obstacles still to be overcome, including off-target effects and immune stimulation. More recently, Dicer substrate siRNA (DsiRNA) has been introduced as an alternative to siRNA. Similarly, it also is proving to be potent and target-sp...
Source: Asian Journal of Pharmaceutical Sciences - February 13, 2019 Category: Drugs & Pharmacology Source Type: research

AKR1D1 regulates glucocorticoid availability and glucocorticoid receptor activation in human hepatoma cells
Publication date: Available online 12 February 2019Source: The Journal of Steroid Biochemistry and Molecular BiologyAuthor(s): Nikolaos Nikolaou, Laura L Gathercole, Lucy Kirkwood, James E Dunford, Beverly A. Hughes, Lorna C. Gilligan, Udo Oppermann, Trevor M. Penning, Wiebke Arlt, Leanne Hodson, Jeremy W. TomlinsonAbstractSteroid hormones, including glucocorticoids and androgens, have potent actions to regulate many cellular processes within the liver. The steroid A-ring reductase, 5β-reductase (AKR1D1), is predominantly expressed in the liver, where it inactivates steroid hormones and, in addition, plays a crucial role ...
Source: The Journal of Steroid Biochemistry and Molecular Biology - February 13, 2019 Category: Biochemistry Source Type: research

ASAP Self-Assembly of siRNA/PEG- < italic toggle="yes" > b < /italic > -Catiomer at Integer Molar Ratio into 100 nm-Sized Vesicular Polyion Complexes (siRNAsomes) for RNAi and Codelivery of Cargo Macromolecules
Journal of the American Chemical SocietyDOI: 10.1021/jacs.8b13641
Source: Journal of the American Chemical Society - February 13, 2019 Category: Chemistry Authors: Beob Soo Kim, Sayan Chuanoi, Tomoya Suma, Yasutaka Anraku, Kotaro Hayashi, Mitsuru Naito, Hyun Jin Kim, Ick Chan Kwon, Kanjiro Miyata, Akihiro Kishimura, Kazunori Kataoka Source Type: research

Inhibition of Bruton ’s Tyrosine Kinase Modulates Microglial Phagocytosis: Therapeutic Implications for Alzheimer’s Disease
AbstractBruton ’s tyrosine kinase (BTK), a critical component of B cell receptor signaling, has recently been implicated in regulation of the peripheral innate immune response. However, the role of BTK in microglia, the resident innate immune cells of the central nervous system, and its involvement in the pathob iology of neurodegenerative disease has not been explored. Here we found that BTK is a key regulator of microglial phagocytosis. Using potent BTK inhibitors and small interfering RNA (siRNA) against BTK, we observed that blockade of BTK activity decreased activation of phospholipase gamma 2, a recen tly identifie...
Source: Journal of NeuroImmune Pharmacology - February 13, 2019 Category: Drugs & Pharmacology Source Type: research

Expression of PDK1 in malignant pheochromocytoma as a new promising potential therapeutic target
ConclusionWe have demonstrated for the first time that PDK1 is overexpressed in human malignant PCC and plays an important role in the malignant biological behaviors of PC12 cell. Specifically, we have revealed that knockdown of PDK1 could attenuate activation of the Akt signaling. These data suggest that PDK1 could be a new promising potential therapeutic target in human cancer treatment for malignant PCC.
Source: Clinical and Translational Oncology - February 13, 2019 Category: Cancer & Oncology Source Type: research

Periostin plays role in force-induced stem cell potential by periodontal ligament stem cells.
This study suggests a proper magnitude of compressive force could be one important factor involved in the modulation of the pluripotency of PDLSCs through the action of periostin. The precise mechanism by which periostin regulates stemness requires further detailed investigation. PMID: 30761669 [PubMed - as supplied by publisher]
Source: Cell Biology International - February 13, 2019 Category: Cytology Authors: Panchamanon P, Pavasant P, Leethanakul C Tags: Cell Biol Int Source Type: research

The VGVAPG Peptide Regulates the Production of Nitric Oxide Synthases and Reactive Oxygen Species in Mouse Astrocyte Cells In Vitro.
Abstract The products of elastin degradation, namely elastin-derived peptides (EDPs), are detectable in the cerebrospinal fluid of healthy individuals and in patients after ischemic stroke, and their number increases with age. Depending on their concentrations, both nitric oxide (NO) and reactive oxygen species (ROS) take part either in myocardial ischemia reperfusion injury or in neurovascular protection after ischemic stroke. The aim of our study was to determine the impact of VGVAPG peptide on ROS and NO production and expression of endothelial nitric oxide synthase (eNos), inducible nitric oxide synthase (iNos...
Source: Neurochemical Research - February 13, 2019 Category: Neuroscience Authors: Szychowski KA, Gmiński J Tags: Neurochem Res Source Type: research

Viruses, Vol. 11, Pages 152: Interferon Regulatory Factor 3-Mediated Signaling Limits Middle-East Respiratory Syndrome (MERS) Coronavirus Propagation in Cells from an Insectivorous Bat
ram Misra Insectivorous bats are speculated to be ancestral hosts of Middle-East respiratory syndrome (MERS) coronavirus (CoV). MERS-CoV causes disease in humans with thirty-five percent fatality, and has evolved proteins that counteract human antiviral responses. Since bats experimentally infected with MERS-CoV do not develop signs of disease, we tested the hypothesis that MERS-CoV would replicate less efficiently in bat cells than in human cells because of its inability to subvert antiviral responses in bat cells. We infected human and bat (Eptesicus fuscus) cells with MERS-CoV and observed that the virus grew to hig...
Source: Viruses - February 13, 2019 Category: Virology Authors: Arinjay Banerjee Darryl Falzarano Noreen Rapin Jocelyne Lew Vikram Misra Tags: Article Source Type: research

Lysophosphatidic acid receptor 1 inhibitor, AM095, attenuates diabetic nephropathy in mice by downregulation of TLR4/NF-κB signaling and NADPH oxidase
In conclusion, AM095 is effective in preventing the pathogenesis of DN by inhibiting TLR4/NF-κB and the NADPH oxidase system, consequently inhibiting the inflammatory signaling cascade in renal tissue of diabetic mice, suggesting that LPAR1 antagonism might provide a potential therapeutic target for DN.
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - February 12, 2019 Category: Molecular Biology Source Type: research

Endoplasmic reticulum stress-dependent autophagy inhibits glycated high-density lipoprotein-induced macrophage apoptosis by inhibiting CHOP pathway.
This study was designed to explore the inductive effect of glycated high-density lipoprotein (gly-HDL) on endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP)-mediated macrophage apoptosis and its relationship with autophagy. Our results showed that gly-HDL caused macrophage apoptosis with concomitant activation of ER stress pathway, including nuclear translocation of activating transcription factor 6, phosphorylation of protein kinase-like ER kinase (PERK) and eukaryotic translation initiation factor 2α, and CHOP up-regulation, which were inhibited by 4-phenylbutyric acid (PBA, an ER stress inhibitor) and th...
Source: J Cell Mol Med - February 12, 2019 Category: Molecular Biology Authors: Tian H, Li Y, Kang P, Wang Z, Yue F, Jiao P, Yang N, Qin S, Yao S Tags: J Cell Mol Med Source Type: research

Activation of T Lymphocytes as a Novel Mechanism in Beta1-Adrenergic Receptor Autoantibody-Induced Cardiac Remodeling
ConclusionsCollectively, we demonstrate that β1-AAmAb-induced cardiac remodeling via mediating T lymphocyte disorder and releasing a variety of IL-6.
Source: Cardiovascular Drugs and Therapy - February 12, 2019 Category: Cardiology Source Type: research

p53-Mediated activities in NS-5 neural stem cells: effects of ethanol.
CONCLUSIONS: Thus, it appears that ethanol and TGFβ1 affect proliferation, DNA repair, and survival of NSCs via p53-mediated activities. This article is protected by copyright. All rights reserved. PMID: 30748015 [PubMed - as supplied by publisher]
Source: Alcoholism, Clinical and Experimental Research - February 12, 2019 Category: Addiction Authors: Miller MW Tags: Alcohol Clin Exp Res Source Type: research

Protective effects of ethyl gallate on H 2 O 2 -induced mitochondrial dysfunction in PC12 cells
AbstractOxidative stress has been suggested to play an important role in neuronal injury. Ethyl gallate (EG) is the ethyl ester of gallic acid which has been acknowledged as an antioxidant. We previously demonstrated that EG effectively inhibited H2O2-induced cytotoxicity and decreased the ROS levels in PC12 cells, while the relevant mechanisms of action of this compound remain largely uncharacterized. The present study was carried out in an attempt to clarify the underlying mechanisms of EG against H2O2-induced neurotoxicity in PC12 cells. EG pretreatment attenuated H2O2-induced mitochondrial dysfunction as indicated by t...
Source: Metabolic Brain Disease - February 12, 2019 Category: Neurology Source Type: research

Curcumin Alleviates β Amyloid-Induced Neurotoxicity in HT22 Cells via Upregulating SOD2
In this study, the HT22 neuronal cells were exposed to Aβ to imitate neuronal injury in Alzheimer’s disease (AD). After 24-h treatment, 10 μM Aβ decreased cell viability and mitochondrial functions, including mitochondrial complex activities and mitochondrial membrane potential (MMP), and also downregulated anti-oxidants SOD2, glutathione (GSH), and catalase (CAT) levels (P <  0.05), meanwhile, increased lactic dehydrogenase (LDH) release, apoptosis level, intracellular reactive oxygen species (ROS) and mitochondrial superoxide accumulation (P <  0.05). And, co-administration of 1 μM curcumin signific...
Source: Journal of Molecular Neuroscience - February 12, 2019 Category: Neuroscience Source Type: research

Glypican-3 gene silencing for ovarian cancer using siRNA-PLGA hybrid micelles in a murine peritoneal dissemination model
Publication date: Available online 10 February 2019Source: Journal of Pharmacological SciencesAuthor(s): Mai Hazekawa, Takuya Nishinakagawa, Tomoyo Kawakubo-Yasukochi, Manabu NakashimaAbstractSmall interfering RNA (siRNA) has received much attention and for possible therapeutic applications to treat incurable chronic and genetic diseases, including cancer. However, the development of safe and efficient carriers for siRNA delivery still remains formidable hurdles for in vivo. The purpose of this study is to prepare siRNA–PLGA hybrid micelles to deliver the siRNA into the ovarian cancer cells and to evaluate of gene silenc...
Source: Journal of Pharmacological Sciences - February 11, 2019 Category: Drugs & Pharmacology Source Type: research

Comparative Study of the Effects of Ferrochelatase ‐siRNA Transfection Mediated by Ultrasound Microbubbles and Polyethyleneimine in Combination with Low‐dose ALA to Enhance PpIX Accumulation in Human Endometrial Cancer Xenograft Nude Mice Models
Red fluorescence caused by the accumulation of PpIX in endometrial cancer xenografts in nude mice after high ‐dose ALA injection could be detected easily byin  vivo animal imaging system, but low ‐dose ALA (1.0 mg kg−1) was injected into xenografts, there was no red fluorescence of tumor. However, knockdown of FECH in nude mice was performed by transfection with FECH ‐siRNA mediated by PEI and ultrasound microbubbles alone or in combination, then 1.0 mg kg−1 ALA was injected, apparent red fluorescence of the xenografts was observed, and the fluorescence intensity was PEI+ ultrasound microbubbles  >  PEI...
Source: Photochemistry and Photobiology - February 11, 2019 Category: Science Authors: Xian Zhang, Longfei Chen, Lvfen Gao, Xuesong Gao, Nan Li, Yuwei Song, Xinke Huang, Shaoqiang Lin, Xiaoyu Wang Tags: Research Article Source Type: research

Nuclear accumulation of UBC9 contributes to SUMOylation of lamin A/C and nucleophagy in response to DNA damage.
CONCLUSIONS: Our findings suggest that nuclear DNA leakage activates nucleophagy through UBC9-mediated SUMOylation of lamin A/C, leading to degradation of nuclear components including lamin A/C and leaked nuclear DNA. PMID: 30744690 [PubMed - in process]
Source: Clinical Breast Cancer - February 11, 2019 Category: Cancer & Oncology Authors: Li Y, Jiang X, Zhang Y, Gao Z, Liu Y, Hu J, Hu X, Li L, Shi J, Gao N Tags: J Exp Clin Cancer Res Source Type: research

The circular RNome of primary breast cancer RESEARCH
Circular RNAs (circRNAs) are a class of RNAs that is under increasing scrutiny, although their functional roles are debated. We analyzed RNA-seq data of 348 primary breast cancers and developed a method to identify circRNAs that does not rely on unmapped reads or known splice junctions. We identified 95,843 circRNAs, of which 20,441 were found recurrently. Of the circRNAs that match exon boundaries of the same gene, 668 showed a poor or even negative (R < 0.2) correlation with the expression level of the linear gene. In silico analysis showed only a minority (8.5%) of circRNAs could be explained by known splicing events...
Source: Genome Research - February 11, 2019 Category: Genetics & Stem Cells Authors: Smid, M., Wilting, S. M., Uhr, K., Rodriguez-Gonzalez, F. G., de Weerd, V., Prager-Van der Smissen, W. J. C., van der Vlugt-Daane, M., van Galen, A., Nik-Zainal, S., Butler, A., Martin, S., Davies, H. R., Staaf, J., van de Vijver, M. J., Richardson, A. L. Tags: RESEARCH Source Type: research

TGF- β1 Decreases β2-Agonist-Induced Relaxation in Human Airway Smooth Muscle.
TGF-β1 Decreases β2-Agonist-Induced Relaxation in Human Airway Smooth Muscle. Am J Respir Cell Mol Biol. 2019 Feb 11;: Authors: Ojiaku CA, Chung E, Parikh V, Williams JK, Schwab A, Fuentes AL, Corpuz ML, Lui V, Paek S, Bexiga NM, Narayan S, Nunez FJ, Ahn K, Ostrom RS, An SS, Panettieri RA Abstract Helper T effector cytokines implicated in asthma modulate the contractility of human airway smooth muscle (HASM) cells. We have reported recently that a profibrotic cytokine, transforming growth factor beta 1 (TGF-β1), induces HASM cell shortening and airway hyper-responsiveness (AHR). Here we assessed wh...
Source: American Journal of Respiratory Cell and Molecular Biology - February 11, 2019 Category: Molecular Biology Authors: Ojiaku CA, Chung E, Parikh V, Williams JK, Schwab A, Fuentes AL, Corpuz ML, Lui V, Paek S, Bexiga NM, Narayan S, Nunez FJ, Ahn K, Ostrom RS, An SS, Panettieri RA Tags: Am J Respir Cell Mol Biol Source Type: research

NOTCH3 overexpression and post-transcriptional regulation by miR-150 were associated with EGFR-TKI resistance in lung adenocarcinoma.
Authors: Zhang Y, Chen B, Wang Y, Zhao Q, Wu W, Zhang P, Miao L, Sun S Abstract Acquired resistance remains a key challenge in epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) therapy in lung adenocarcinoma (LUAD). Recent studies have shown that Notch signaling is associated with drug resistance. However, its role and possible mechanisms in EGFR-TKI resistance are not yet clear. In our study, we found that among 4 members of NOTCH1-4, only NOTCH3 was up-regulated in LUAD tissues and TKI-resistant cell line (HCC827GR6). Knockdown of NOTCH3 by siRNA significantly inhibited proliferative abilit...
Source: Oncology Research - February 10, 2019 Category: Cancer & Oncology Tags: Oncol Res Source Type: research

Cancers, Vol. 11, Pages 202: SYK Inhibition Potentiates the Effect of Chemotherapeutic Drugs on Neuroblastoma Cells in Vitro
In this study, we observed elevated SYK gene expression in neuroblastoma compared to neural crest and benign neurofibroma. While SYK protein was detected in the majority of examined neuroblastoma tissues it was less frequently observed in neuroblastoma cell lines. Depletion of SYK by siRNA and the use of small molecule SYK inhibitors significantly reduced the cell viability of neuroblastoma cell lines expressing SYK protein. Moreover, SYK inhibition decreased ERK1/2 and Akt phosphorylation. The SYK inhibitor BAY 613606 enhanced the effect of different chemotherapeutic drugs. Transient expression of a constitutive active SY...
Source: Cancers - February 10, 2019 Category: Cancer & Oncology Authors: Conny T ümmler Gianina Dumitriu Malin Wickstr öm Peter Coopman Andrey Valkov Per Kogner John Inge Johnsen Ugo Moens Baldur Sveinbj örnsson Tags: Article Source Type: research

Nr5a2 promotes cancer stem cell properties and tumorigenesis in nonsmall cell lung cancer by regulating Nanog
In the present study, we have provided convincing evidence in vitro and in vivo demonstrating thatNr5a2 can induce lung cancer stem cells (CSC) properties and promote tumorigenesis and progression through transcriptional up ‐regulation of Nanog. AbstractLung cancer has the highest mortality rate due to late diagnosis and high incidence of metastasis. Cancer stem cells (CSCs) are a subgroup of cancer cells with self ‐renewal capability similar to that of normal stem cells (NSCs). While CSCs may play an important role in cancer progression, mechanisms underlying CSC self‐renewal and the relationship between self‐rene...
Source: Cancer Medicine - February 10, 2019 Category: Cancer & Oncology Authors: Ting Ye, Jingyuan Li, Zhiwei Sun, Yongli Liu, Liangsheng Kong, Shixia Zhou, Junlin Tang, Jianyu Wang, H. Rosie Xing Tags: ORIGINAL RESEARCH Source Type: research

Nox1/Ref-1-Mediated Activation of CREB Promotes Gremlin1-Driven Endothelial Cell Proliferation & Migration
Publication date: Available online 8 February 2019Source: Redox BiologyAuthor(s): Daniel S. de Jesus, Evan DeVallance, Yao Li, Micol Falabella, Danielle Guimaraes, Sruti Shiva, Brett Kaufman, Mark T. Gladwin, Patrick J. PaganoAbstractPulmonary arterial hypertension (PAH) is a complex degenerative disorder marked by aberrant vascular remodeling associated with hyperproliferation and migration of endothelial cells (ECs). Previous reports implicated bone morphogenetic protein antagonist Gremlin 1 in this process; however, little is known of the molecular mechanisms involved. The current study was designed to test whether redo...
Source: Redox Biology - February 9, 2019 Category: Biology Source Type: research

Protective Effects of Broussonetia kazinoki Siebold Fruit Extract against Palmitate-Induced Lipotoxicity in Mesangial Cells.
In conclusion, BKFE induced the expression of antioxidant enzymes via activation of Nrf2 and protected against PA-induced lipotoxicity in mesangial cells. PMID: 30728845 [PubMed]
Source: Evidence-based Complementary and Alternative Medicine - February 9, 2019 Category: Complementary Medicine Tags: Evid Based Complement Alternat Med Source Type: research

Fli-1 transcription factor regulates the expression of caspase-1 in lung pericytes
Publication date: April 2019Source: Molecular Immunology, Volume 108Author(s): Pengfei Li, Andrew J. Goodwin, James A. Cook, Perry V. Halushka, Xian K. Zhang, Hongkuan FanAbstractOur previous data demonstrated that Friend leukemia virus integration 1 (Fli-1), an ETS transcription factor, governs pericyte loss and vascular dysfunction in cecal ligation and puncture-induced murine sepsis by regulating essential pyroptosis markers including caspase-1. However, whether Fli-1 regulates caspase-1 expression levels in vitro and how Fli-1 regulates caspase-1 remain unknown. Our present work further demonstrated that overexpressed ...
Source: Molecular Immunology - February 9, 2019 Category: Allergy & Immunology Source Type: research

HIPK1 Interference Attenuates Inflammation and Oxidative Stress of Acute Lung Injury via Autophagy.
CONCLUSIONS</strong> Decreased HIPK1 in ALI showed protective effects in attenuating inflammation and oxidative stress and enhancing autophagy, indicating HIPK1 as a possible target in ALI management. PMID: 30734722 [PubMed - in process]
Source: Medical Science Monitor - February 9, 2019 Category: Research Tags: Med Sci Monit Source Type: research

Translocator protein 18 kDa ligand alleviates neointimal hyperplasia in the diabetic rat artery injury model via activating PKG
This study suggests that TSPO inhibition suppresses the proliferation and migration of VSMCs induced by hyperglycemia, consequently, preventing atherosclerosis and restenosis after angioplasty in diabetic conditions. TSPO may be a potential therapeutic target to reduce arterial remodeling induced by angioplasty in diabetes.
Source: Life Sciences - February 9, 2019 Category: Biology Source Type: research

Piperlongumine-induced nuclear translocation of the FOXO3A transcription factor triggers BIM-mediated apoptosis in cancer cells.
We report here that an association of FOXO3A with the pro-apoptotic protein BIM (also known as BCL2-like 11, BCL2L11) has a direct and specific function in PL-induced cancer cell death. Using HeLa cells stably expressing a FOXO3A-GFP fusion protein and several other cancer cell lines, we found that PL treatment induces FOXO3A dephosphorylation and nuclear translocation and promotes its binding to the BIM gene promoter, resulting in the up-regulation of BIM in the cancer cell lines. Accordingly, PL inhibited cell viability and caused intrinsic apoptosis in a FOXO3A-dependent manner. Of note, siRNA-mediated FOXO3A knockdown ...
Source: Biochemical Pharmacology - February 9, 2019 Category: Drugs & Pharmacology Authors: Liu Z, Shi Z, Lin J, Zhao S, Hao M, Xu J, Li Y, Zhao Q, Tao L, Diao A Tags: Biochem Pharmacol Source Type: research

Co-targeting RNA Polymerases IV and V Promotes Efficient De Novo DNA Methylation in Arabidopsis
Publication date: Available online 7 February 2019Source: CellAuthor(s): Javier Gallego-Bartolomé, Wanlu Liu, Peggy Hsuanyu Kuo, Suhua Feng, Basudev Ghoshal, Jason Gardiner, Jenny Miao-Chi Zhao, Soo Young Park, Joanne Chory, Steven E. JacobsenSummaryThe RNA-directed DNA methylation (RdDM) pathway in plants controls gene expression via cytosine DNA methylation. The ability to manipulate RdDM would shed light on the mechanisms and applications of DNA methylation to control gene expression. Here, we identified diverse RdDM proteins that are capable of targeting methylation and silencing in Arabidopsis when tethered to an art...
Source: Cell - February 8, 2019 Category: Cytology Source Type: research

Genistein suppresses psoriasis-related inflammation through a STAT3-NF- κB-dependent mechanism in keratinocytes.
In this study, we investigated the effects of genistein on imiquimod (IMQ)-induced psoriasis-like skin lesions in vivo and explored the mechanisms underlying those effects in vitro. It was found that genistein can significantly improve IMQ-induced pathological scores of cutaneous skin lesions in mice, reduce epidermal thickness, and inhibit the expression of inflammatory factors,including interleukin (IL)-1β, IL-6, tumour necrosis factor-alpha (TNF-α), chemokine ligand 2 (CCL2), IL-17 and IL-23. In vitro studies, genistein inhibited the proliferation of human keratinocyte HaCaT cells and inhibited the expression of inf...
Source: International Immunopharmacology - February 8, 2019 Category: Allergy & Immunology Authors: Wang A, Wei J, Lu C, Chen H, Zhong X, Lu Y, Li L, Huang H, Dai Z, Han L Tags: Int Immunopharmacol Source Type: research

Tissue- and sex-specific small RNAomes reveal sex differences in response to the environment
This study provides important sex- and tissue-specific expression data of miRNA, piRNA and siRNA as well as mechanistic insights into sex-differences of gene regulation in response to environmental cues.
Source: PLoS Genetics - February 8, 2019 Category: Genetics & Stem Cells Authors: Alexandra Bezler Source Type: research

Baicalin induced colon cancer cells apoptosis through miR-217/DKK1-mediated inhibition of Wnt signaling pathway.
Abstract To analyze the anti-tumor mechanism of Baicalin in human colon cancer. The MTT assay and colony formation assay demonstrated that Baicalin treatment inhibits the proliferation of DLD1 and HCT-116 cells. The apoptosis rates were induced upon Baicalin treatment and which was determined by FACS. The qPCR and western blot analysis showed that Baicalin promotes expression of DKK1 (Dickkopf), an important antagonist of Wnt signaling pathway, thereby reduces the expression of its downstream protein β-catenin and c-Myc. Reduction of DKK1 expression by siRNA attenuates β-catenin and c-Myc expression. microRNA-21...
Source: Molecular Biology Reports - February 8, 2019 Category: Molecular Biology Authors: Jia Y, Chen L, Guo S, Li Y Tags: Mol Biol Rep Source Type: research

CircRNA hsa-circ-0014359 promotes glioma progression by regulating miR-153/PI3K signaling.
Abstract RNA back splicing produces circRNA, a new type of non-coding RNA. Studies have indicated that circRNAs play important roles in malignant tumors of the central nervous system. Here, we aimed to evaluate the expression of the circRNA, hsa-circ-0014359 (circ-0014359) in human glioma cell lines to assess its function in glioma progression and prognosis. The expression of circ-0014359 was increased in T98G and SHG44 cancer cell lines and glioma tissues from patients, when compared with control cells and tissue. SiRNA-mediated silencing of circ-0014359 potently inhibited cell viability, migration, invasion, and...
Source: Biochemical and Biophysical Research communications - February 8, 2019 Category: Biochemistry Authors: Shi F, Shi Z, Zhao Y, Tian J Tags: Biochem Biophys Res Commun Source Type: research

The arginine methyltransferase PRMT5 and PRMT1 distinctly regulate the degradation of anti-apoptotic protein CFLARL in human lung cancer cells.
CONCLUSIONS: PRMT5 and PRMT1 mediate the distinct effects on CFLARL degradation by regulating the binding of E3 ligase ITCH in NSCLC cells. This study identifies a cell death mechanism that is fine-tuned by PRMT1/5 that modulate CFLARL degradation in human NSCLC cells. PMID: 30736843 [PubMed - in process]
Source: Clinical Lung Cancer - February 8, 2019 Category: Cancer & Oncology Authors: Li M, An W, Xu L, Lin Y, Su L, Liu X Tags: J Exp Clin Cancer Res Source Type: research

Mucin 1 downregulation impairs the anti-necroptotic effects of glucocorticoids in human bronchial epithelial cells
Publication date: Available online 7 February 2019Source: Life SciencesAuthor(s): Huojun Zhang, Qian Liu, Luxia Kong, Shuyun XuAbstractAimsTo investigate whether mucin 1 (MUC1) downregulation reduced the sensitivity of tumor necrosis factor-alpha (TNF-α)-induced bronchial epithelial cells to glucocorticoid-mediated necroptosis and explore the underlying mechanisms.Main methodsThe human lung bronchial epithelial cell line (16HBE) was transfected with small interfering RNA (siRNA) against MUC1 and then stimulated by TNF-α, where some cells were pretreated with dexamethasone. Flow cytometry was performed to analyze necropto...
Source: Life Sciences - February 7, 2019 Category: Biology Source Type: research

The role of the fat mass and obesity-associated protein in the proliferation of pancreatic cancer cells.
Authors: Tang X, Liu S, Chen D, Zhao Z, Zhou J Abstract Fat mass and obesity-associated (FTO) protein has been identified as a critical demethylase in regulating cellular mRNA stability by removing N6-methyladenosine (m6A) residues in mRNA. Even though the role of FTO in body energy metabolism has been well established, its role in cancer cell homeostasis remains unclear. In the present study, by using RNA interference, it was indicated that FTO is required for pancreatic cancer cell proliferation. Knockdown of FTO resulted in compromised proliferation of pancreatic cancer cells. Furthermore, DNA synthesis was comp...
Source: Oncology Letters - February 7, 2019 Category: Cancer & Oncology Tags: Oncol Lett Source Type: research

Cellular and radiobiological effects of carbonic anhydrase IX in human breast cancer cells.
In conclusion, combination of CAIX inhibition and irradiation is a promising treatment strategy against breast cancer with hypoxia‑induced CAIX expression. PMID: 30720123 [PubMed - as supplied by publisher]
Source: Oncology Reports - February 7, 2019 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

Optimization of chitosan nanoparticles as an anti-HIV siRNA delivery vehicle.
Abstract Chitosan has emerged as a promising polysaccharide for gene/siRNA delivery. However, additional works will be required to modify chitosan nanoparticles. In the present study, chitosan nanoparticles were well modified to introduce anti-HIV siRNA into two mammalian cell lines, macrophage RAW 264.7 and HEK293. We first generated two stable cell lines expressing HIV-1 Tat, and then designed and generated an efficient anti-tat siRNA. The nanoparticles were prepared by using different concentrations of chitosan, polyethylenimine (PEI) and carboxymethyl dextran (CMD) in various formulations and then their physic...
Source: International Journal of Biological Macromolecules - February 6, 2019 Category: Biochemistry Authors: Mobarakeh VI, Modarressi MH, Rahimi P, Bolhassani A, Arefian E, Atyabi F, Vahabpour R Tags: Int J Biol Macromol Source Type: research

In vivo evaluation and Alzheimer's disease treatment outcome of siRNA loaded dual targeting drug delivery system.
Abstract To deliver drugs to treat Alzheimer's disease (AD), nanoparticles should firstly penetrate through blood brain barrier, and then target neurons. Recently, we developed an Apo A-I and NL4 dual modified nanoparticle (ANNP) to deliver beta-amyloid converting enzyme 1 (BACE1) siRNA. Although promising in vitro results were obtained, the in vivo performance was not clear. Therefore, in this study, we further evaluated the in vivo neuroprotective effect and toxicity of the ANNP/siRNA. The ANNP/siRNA was 80.6 nm with good stability when incubated with serum. The ANNP/siRNA could target both bEnd.3 and PC12 cells...
Source: Current Pharmaceutical Biotechnology - February 4, 2019 Category: Biotechnology Authors: Zhang C, Shen L, Gu Z, Liu X, Lin H Tags: Curr Pharm Biotechnol Source Type: research

Engineering multifunctional bioactive citric acid-based nanovectors for intrinsical targeted tumor imaging and specific siRNA gene delivery in vitro/in vivo.
Abstract Targeted tumor imaging and efficient specific gene delivery in vivo has been one of the main challenges in gene-based cancer diagnosis and therapy. Herein, we engineered a citric acid-based polymer with intrinsical photoluminescence and gene loading capacity to achieve targeted delivery of siRNA and tumor imaging in vitro and in vivo. The multifunctional platform was formed from the self-assembling of poly (citric acid)-polymine conjugated with folic acid and rhodamine B (PPFR). PPFR showed stable photoluminescent ability and could effectively bind and protect the siRNA against RNase degradation. PPFR als...
Source: Biomaterials - February 2, 2019 Category: Materials Science Authors: Wang M, Guo Y, Xue Y, Niu W, Chen M, Ma PX, Lei B Tags: Biomaterials Source Type: research

Ocular Instillation of Vitamin A-Coupled Liposomes Containing HSP47 siRNA Ameliorates Dry Eye Syndrome in Chronic Graft-Versus-Host Disease
Chronic graft-versus-host disease (GVHD) is characterized by multiorgan fibrosis and affects the quality of life of transplant survivors. Ocular manifestations are found in 40-60% of GVHD patients, and the most common symptom is dry eye syndrome associated with lacrimal gland fibrosis. We previously demonstrated heat shock protein 47 (HSP47), a collagen specific molecular chaperone, plays a critical role in excessive collagen synthesis in chronic GVHD, and systemic administration of vitamin A-coupled liposomes carrying HSP47 siRNA (VA-lip HSP47) ameliorates skin and salivary gland fibrosis in chronic GVHD (Yamakawa, et al, Blood 2018).
Source: Biology of Blood and Marrow Transplantation - January 31, 2019 Category: Hematology Authors: Hiroyuki Ohigashi, Daigo Hashimoto, Shuichiro Takahashi, Tomohiro Yamakawa, Eiko Hayase, Takanori Teshima Tags: 229 Source Type: research

GSE102057 Synthetic lethal siRNA screen for TN-IBC cell line SUM149PT using kinome library with EPA treatment
Contributors : Angie M Torres-Adorno ; Yuan Qi ; Naoto T UenoSeries Type : OtherOrganism : Homo sapiensSynthetic lethal siRNA screen using a kinome library containing 939 druggable genes in the TN-IBC cell line SUM149PT, in combination with EPA treatment.
Source: GEO: Gene Expression Omnibus - January 31, 2019 Category: Genetics & Stem Cells Tags: Other Homo sapiens Source Type: research

Silencing the target rhoptry neck protein (RON) gene responsible for the invasion of Toxoplasma gondii with siRNA transfection.
Authors: Yürük M, Aksoy T, Sivcan E, Nergiz H Abstract Toxoplasma gondii is a coccidian protozoan that causes toxoplasmosis is a common disease in Turkey as well as all over the world. It causes various clinical symptoms depending on the immune system status, age, or location of the disease. There is an organelle called the apical complex at the anterior end of the parasite. Rhoptry Neck Proteins (RONs), a component of this organelle, play a critical role in the formation of "moving junction" and parasitophorous vacuoles during host cell invasion. On the other hand, interfering RNA (iRNA) treatment options develo...
Source: Mikrobiyoloji Bulteni - January 27, 2019 Category: Microbiology Tags: Mikrobiyol Bul Source Type: research

siRNA against TSG101 reduces proliferation and induces G0/G1 arrest in renal cell carcinoma - involvement of c-myc, cyclin E1, and CDK2.
Conclusions: TSG101 promotes proliferation of RCC cells. This positive effect on tumor growth involves activation of c-myc and cyclin E1/CDK2 and their effect on cell cycle distribution. PMID: 30675171 [PubMed - in process]
Source: Cellular and Molecular Biology Letters - January 26, 2019 Category: Biochemistry Authors: Xu C, Zheng J Tags: Cell Mol Biol Lett Source Type: research

Artificial cationic peptides that increase nuclease resistance of siRNA without disturbing RNAi activity.
Authors: Maeda Y, Iwata Hara R, Nishina K, Yoshida-Tanaka K, Sakamoto T, Yokota T, Wada T Abstract Properties of cationic peptides bearing amino or guanidino groups with various side chain lengths that bind to double stranded RNAs (dsRNAs) were investigated. Peptides with shorter side chain lengths effectively bound to dsRNAs (12mers) increasing their thermal stability. NMR measurements suggested that the cationic peptide binds to the inner side of the major groove of dsRNA. These peptides also increased the thermal stability of siRNA and effectively protected from RNase A digestion. On the other hand, both peptide...
Source: Nucleosides, Nucleotides and Nucleic Acids - January 22, 2019 Category: Biochemistry Tags: Nucleosides Nucleotides Nucleic Acids Source Type: research