Query: siRNA

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Interactions of thymic stromal lymphopoietin with TLR2 and TLR4 regulate anti-fungal innate immunity in Aspergillus fumigatus-induced corneal infection.
Abstract Thymic stromal lymphopoietin (TSLP) is an interleukin 7 (IL-7)-like four helix bundle cytokine that plays diverse roles in the regulation of immune responses. In fungal infection, pattern recognition receptors (PRRs), including the cell surface Toll-like receptors (TLRs) and cytoplasmic NOD-like receptors, recognize pathogen-associated molecular patterns to initiate downstream signal cascades to active immune responses. Our previous studies reported that, in vitro human cornea epithelium cells represented a novel target of TSLP and that TSLP/TSLPR/STAT5 signaling played an important role in the response t...
Source: Experimental Eye Research - March 7, 2019 Category: Opthalmology Authors: Dai C, Wu J, Chen C, Wu X Tags: Exp Eye Res Source Type: research

Identification of rigosertib for the treatment of recessive dystrophic epidermolysis bullosa-associated squamous cell carcinoma.
CONCLUSIONS: These data support a "first in RDEB" phase II clinical trial of rigosertib to assess tumor targeting in patients with late stage, metastatic and/ or unresectable SCC. PMID: 30846478 [PubMed - as supplied by publisher]
Source: Clinical Cancer Research - March 7, 2019 Category: Cancer & Oncology Authors: Atanasova VS, Pourreyron C, Farshchian M, Lawler ME, Brown CA, Watt S, Wright S, Warkala M, Guttmann-Gruber C, Pinon-Hofbauer J, Fuentes I, Prisco M, Rashidghamat E, Has C, Salas-Alanis JC, Palisson F, Hovnanian A, McGrath JA, Mellerio J, Bauer JW, South Tags: Clin Cancer Res Source Type: research

Regulation of Proliferation and Epithelial-to-Mesenchymal Transition (EMT) of Gastric Cancer by ZEB1 via Modulating Wnt5a and Related Mechanisms.
CONCLUSIONS ZEB1 expression is increased in GC tumor tissues and is associated with pathological features. The downregulation of ZEB1 can facilitate cell apoptosis via mediating Wnt5a, further suppressing GC cell proliferation and migration, and reducing EMT occurrence. PMID: 30829316 [PubMed - in process]
Source: Medical Science Monitor - March 6, 2019 Category: Research Tags: Med Sci Monit Source Type: research

SOCS3 ablation enhances DC-derived Th17 immune response against Candida albicans by activating IL-6/STAT3 in vitro
In this study, a si-RNA method is used to repress expression of the cytokine signaling-3 suppressor (SOCS3) in murine bone marrow-DCs, and then the maturation of DCs and the subsequent T-cell response after exposure to C. albicans are monitored in vitro.Key findingsAlong with a higher expression of the DC maturation markers CD40, CD86 and MHC-II, IL-6/STAT3 is markedly upregulated in the SOCS3 siRNA-treated DCs after exposure to C. albicans as compared with control DCs. In response to DCs maturation, CD4+ T cells have an increased expression of Th17 cell markers –– including the retinoic acid-related orphan nuclear hor...
Source: Life Sciences - March 6, 2019 Category: Biology Source Type: research

β-Hydroxybutyrate, a ketone body, reduces the cytotoxic effect of cisplatin via activation of HDAC5 in human renal cortical epithelial cells
In this study, we used human renal cortical epithelial (HRCE) cells. The anti-apoptotic effect of βOHB was evaluated using flow cytometry analysis. The expression of apoptosis-related proteins and HDACs was evaluated by western immunoblot.Key findingsThe results showed that βOHB significantly reduced cisplatin-induced apoptosis in HRCE cells. Furthermore, βOHB significantly reduced cisplatin-induced cleavage of caspase-3, acetylation of histone H3, and phosphorylation of AMP-activated kinase. This anti-apoptotic effect of βOHB was markedly attenuated by an inhibitor of HDAC4/5, and βOHB-mediated suppression of cleavag...
Source: Life Sciences - March 6, 2019 Category: Biology Source Type: research

EZH2 promotes gastric cancer cells proliferation by repressing p21 expression
In this study, immunohistochemical analysis was conducted to investigate the EZH2 expression in gastric cancer. We found that EZH2 levels were increased in gastric cancer tissues compared with adjacent normal tissues. Moreover, patients with high levels of EZH2 expression had a relatively poor prognosis. Furthermore, knockdown of EZH2 expression by siRNA could impair cell proliferation and invasion both in vitro and vivo. Finally, we found that EZH2 influences gastric cancer cells proliferation partly through regulating p21 expression. Our findings present that EZH2 over-expression can be identified as a poor prognostic bi...
Source: Pathology Research and Practice - March 6, 2019 Category: Pathology Source Type: research

The mechanism of miR-192 in regulating high glucose-induced MCP-1 expression in rat glomerular mesangial cells.
CONCLUSIONS: MiR-192 expression was upregulated to increase the expression of inflammatory factor MCP-1 by inhibiting the expression of Zeb1, which was mediated by breaking the regulatory loop of Zeb1 and miR-200b/c in rat mesangial cells cultured in high glucose. PMID: 30827272 [PubMed - as supplied by publisher]
Source: Endocrine, Metabolic and Immune Disorders Drug Targets - March 6, 2019 Category: Drugs & Pharmacology Tags: Endocr Metab Immune Disord Drug Targets Source Type: research

Cyclic Dinucleotides Inhibit Osteoclast Differentiation Through STING ‐Mediated Interferon‐β Signaling
In this study, we investigated the effect of CDNs on the differentiation and function of osteoclasts and osteoblasts. When bone marrow‐derived macrophages (BMMs) were differentiated into osteoclasts with macrophage colony‐stimulating factor (M‐CSF) and receptor activator of NF‐κB ligand (RANKL) in the presence of CDNs, the differentiation was inhibited by CDNs in a dose‐d ependent manner. In contrast, CDNs did not influence the differentiation of committed osteoclasts or osteoblast precursors. STING signaling pathway appeared to be critical for CDNs‐mediated inhibition of osteoclast differentiation since CDNs ...
Source: Journal of Bone and Mineral Research - March 6, 2019 Category: Orthopaedics Authors: Yeongkag Kwon, Ok ‐Jin Park, Jiseon Kim, Jae‐Ho Cho, Cheol‐Heui Yun, Seung Hyun Han Tags: Original Article Source Type: research

Activation of HO-1 protects placental cells function in oxidative stress via regulating ZO-1/occludin.
Abstract We previously confirmed that Nuclear factor erythroid 2-related factor-2 (Nrf2) and heme oxygenase (HO-1) play synergistic roles in the pathogenesis of preeclampsia. To further explore the function of HO-1 in the pathogenesis of preeclampsia, we established oxidative stress models respectively with human first-trimester trophoblast/simian virus (HTR8/SVneo) and human umbilical vein endothelial cells (HUVECs) and then assessed the effect of HO-1 on the two cell lines in oxidative stress conditions. The cell oxidative stress models were incubated with Hemin (an inducer of HO-1), then, the HTR8/SVneo cells w...
Source: Biochemical and Biophysical Research communications - March 6, 2019 Category: Biochemistry Authors: Li J, Zhou J, Tian B, Chu Y, Zhang N, Hu X, Wan X, Ye Y Tags: Biochem Biophys Res Commun Source Type: research

Modeling Pancreatic Cancer Dynamics with Immunotherapy.
This study concludes that mono-immunotherapy is unlikely to control the pancreatic cancer and combined immunotherapies between anti-TGF-[Formula: see text] and adoptive transfers of immune cells can prolong patient survival. We show through numerical explorations that how these two types of immunotherapies are scheduled is important to survival. Applying TGF-[Formula: see text] inhibition first followed by adoptive immune cell transfers can yield better survival outcomes. PMID: 30843136 [PubMed - as supplied by publisher]
Source: Bulletin of Mathematical Biology - March 6, 2019 Category: Bioinformatics Authors: Hu X, Ke G, Jang SR Tags: Bull Math Biol Source Type: research

Characterisation of deubiquitylating enzymes in the cellular response to high-LET ionising radiation and complex DNA damage
Complex DNA damage (CDD) formation, which increases with increasing linear energy transfer (LET), is a major contributor to the therapeutic effect of radiotherapy. However little is known of the enzymes and mechanisms that control the cellular response to CDD and co-ordinate its repair. Using siRNA screening of deubiquitylating enzymes, we identify major roles for USP6 and ultimately PARP-1 protein in regulating CDD repair and in promoting cell survival in response to high-LET radiation.
Source: International Journal of Radiation Oncology * Biology * Physics - March 6, 2019 Category: Radiology Authors: Rachel J. Carter, Catherine M. Nickson, James M. Thompson, Andrzej Kacperek, Mark A. Hill, Jason L. Parsons Tags: Biology Contribution Source Type: research

Camptothecin induces c-Myc- and Sp1-mediated hTERT expression in LNCaP cells: Involvement of reactive oxygen species and PI3K/Akt.
Abstract Camptothecin (CPT), a quinoline alkaloid isolated from Camptotheca acuminate, targets topoisomerase I, which is continuously expressed in cancer cells. However, the molecular mechanisms responsible for CPT-induced telomerase inhibition remain unclear. Unexpectedly, we found that CPT upregulates hTERT expression and concomitantly increases telomerase activity. However, transfection of hTERT-targeting siRNA had no effect on CPT-induced G2/M phase arrest, suggesting that CPT-induced telomerase activation was not related to G2/M phase arrest. CPT simultaneously increased Nrf2 expression and the level of intra...
Source: Food and Chemical Toxicology - March 6, 2019 Category: Food Science Authors: Dilshara MG, Jayasooriya RGPT, Choi YH, Kim GY Tags: Food Chem Toxicol Source Type: research

Metformin reduced NLRP3 inflammasome activity in Ox-LDL stimulated macrophages through adenosine monophosphate activated protein kinase and protein phosphatase 2A.
Abstract Metformin has been suggested to have cardiovascular protective effects. Previous researches showed that metformin activates Adenosine Monophosphate Activated Protein Kinase (AMPK) and Protein Phosphatase 2A (PP2A). This research aimed to elucidate whether and how metformin affects NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activity in oxidized low-density lipoprotein (ox-LDL) stimulated macrophages. Macrophages were treated with ox-LDL and metformin in a continuous manner, and NLRP3 inflammasome activation was evaluated by detecting IL-1β and caspase-1 p10 release by ELISA and western blot...
Source: European Journal of Pharmacology - March 6, 2019 Category: Drugs & Pharmacology Authors: Zhang L, Lu L, Zhong X, Yue Y, Hong Y, Li Y, Li Y Tags: Eur J Pharmacol Source Type: research

lnc TINCR induced by NOD1 mediates inflammatory response in 3T3-L1 adipocytes.
CONCLUSIONS: lnc TINCR is a positive regulator of inflammation-induced insulin resistance presumably via activation of NOD1 signaling pathways. PMID: 30851423 [PubMed - as supplied by publisher]
Source: Gene - March 6, 2019 Category: Genetics & Stem Cells Authors: Fang YX, Zou Y, Wang GT, Huang SH, Zhou YJ, Zhou YJ Tags: Gene Source Type: research

Chronic administration of nano-sized PAMAM dendrimers in vivo inhibits EGFR-ERK1/2-ROCK signaling pathway and attenuate diabetes-induced vascular remodeling and dysfunction
This study showed chronic in vivo administration of PAMAM dendrimers in an animal model of diabetes inhibited EGFR-ERK1/2-ROCK signaling and improved diabetes-induced vascular remodeling and dysfunction in a dose, generation (G6 > G5) and surface chemistry-dependent manner (cationic> anionic> neutral). Thus, naked PAMAM dendrimers have the propensity to modulate key (e.g. EGFR) cell signaling cascades with associated pharmacological consequences in vivo that are dependent on their physicochemical properties. PAMAMs, alone or in combination with vasculoprotective agents, might therefore have a beneficial role in t...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - March 5, 2019 Category: Nanotechnology Source Type: research

GSE127828 Dynamic imbalance between cancer cell subpopulations induced by Transforming Growth Factor Beta (TGF- β) is associated with a DNA methylome switch methylation
Contributor : Hector Hernandez-VargasSeries Type : Methylation profiling by genome tiling arrayOrganism : Homo sapiensDistinct subpopulations of neoplastic cells within tumors, including hepatocellular carcinoma (HCC), display pronounced ability to initiate new tumors and induce metastasis. Recent evidence suggests that signals from transforming growth factor beta (TGF- β) may increase the survival of these so called tumor initiating cells leading to poor HCC prognosis. However, how TGF-β establishes and modifies the key features of these cell subpopulations is not fully understood. In the present report we describe the ...
Source: GEO: Gene Expression Omnibus - March 5, 2019 Category: Genetics & Stem Cells Tags: Methylation profiling by genome tiling array Homo sapiens Source Type: research

GSE127763 Dynamic imbalance between cancer cell subpopulations induced by Transforming Growth Factor Beta (TGF- β) is associated with a DNA methylome switch expression array
Contributor : Hector Hernandez-VargasSeries Type : Expression profiling by arrayOrganism : Homo sapiensDistinct subpopulations of neoplastic cells within tumors, including hepatocellular carcinoma (HCC), display pronounced ability to initiate new tumors and induce metastasis. Recent evidence suggests that signals from transforming growth factor beta (TGF- β) may increase the survival of these so called tumor initiating cells leading to poor HCC prognosis. However, how TGF-β establishes and modifies the key features of these cell subpopulations is not fully understood. In the present report we describe the differential DN...
Source: GEO: Gene Expression Omnibus - March 5, 2019 Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research

GSE114235 Exosome release is regulated by mTORC1 via a Rab27A-dependent mechanism
Contributors : Wenchong Zou ; Xiaochun BaiSeries Type : Non-coding RNA profiling by high throughput sequencingOrganism : Homo sapiensExosomes are small membrane-bound vesicles released into extracellular spaces by many types of cells. These nanovesicles carry proteins, mRNA and miRNA and are involved in cell waste management and intercellular communication. In the present study we show that exosome release, which leads to net loss of cellular membrane and protein content, is negatively regulated by mechanistic target of rapamycin complex 1 (mTORC1). We find that in cells and animal models exosome release is inhibited by su...
Source: GEO: Gene Expression Omnibus - March 5, 2019 Category: Genetics & Stem Cells Tags: Non-coding RNA profiling by high throughput sequencing Homo sapiens Source Type: research

Upregulated expression of MNX1-AS1 long noncoding RNA predicts poor prognosis in gastric cancer.
In this study, we investigated the clinicopathological significance and biological function of MNX1-AS1 in gastric cancer (GC). The expression of MNX1-AS1 was analyzed by qRT-PCR in 96 GC and adjacent non-tumor tissues in relation to clinicopathological features and overall survival (OS) of patients, and in five human GC cell lines compared to a normal gastric epithelial cell line. Loss-of-function experiments using small interfering RNA (siRNA) targeting MNX1-AS1 (si-MNX1-AS1) were carried out in AGS and MGC-803 GC cell lines. Cell proliferation (CCK-8 assay), migration (Transwell) and invasion (Transwell Matrigel), and p...
Source: Bosnian Journal of Basic Medical Sciences - March 5, 2019 Category: General Medicine Tags: Bosn J Basic Med Sci Source Type: research

PCV2 replication promoted by oxidative stress is dependent on the regulation of autophagy on apoptosis
AbstractPorcine circovirus type 2 (PCV2) is an economically important swine pathogen but some extra trigger factors are required for the development of PCV2-associated diseases. By evaluating cap protein expression, viral DNA copies and the number of infected cells, the present study further confirmed that oxidative stress can promote PCV2 replication. The results showed that oxidative stress induced autophagy in PCV2-infected PK15 cells. Blocking autophagy with inhibitor 3-methyladenine or ATG5-specific siRNA significantly inhibited oxidative stress-promoted PCV2 replication. Importantly, autophagy inhibition significantl...
Source: Veterinary Research - March 5, 2019 Category: Veterinary Research Source Type: research

MicroRNA-183 inhibition exerts suppressive effects on diabetic retinopathy by inactivating BTG1-mediated PI3K/Akt/VEGF signaling pathway.
In this study, we demonstrated that miR-183 silencing inhibiting cell growth and tube formation in vascular endothelial cells of DR rats via the PI3K/Akt/VEGF signaling pathway by upregulating BTG1. PMID: 30835506 [PubMed - as supplied by publisher]
Source: Am J Physiol Endocri... - March 5, 2019 Category: Endocrinology Authors: Zhang ZZ, Qin XH, Zhang J Tags: Am J Physiol Endocrinol Metab Source Type: research

Non-invasive Use of Positron Emission Tomography to Monitor Diethyl maleate and Radiation-Induced Changes in System x C − Activity in Breast Cancer
Conclusion[18F]FASu is a specific system xC− PET radiotracer and as such it can be used to monitor system xC− activity due to OS. As such, [18F]FASu has the potential to be used in therapy response monitoring by PET. Further optimization is required forin vivo application.
Source: Molecular Imaging and Biology - March 5, 2019 Category: Molecular Biology Source Type: research

LINE1 Derepression in Aged Wild-Type and SIRT6-Deficient Mice Drives Inflammation.
Abstract Mice deficient for SIRT6 exhibit a severely shortened lifespan, growth retardation, and highly elevated LINE1 (L1) activity. Here we report that SIRT6-deficient cells and tissues accumulate abundant cytoplasmic L1 cDNA, which triggers strong type I interferon response via activation of cGAS. Remarkably, nucleoside reverse-transcriptase inhibitors (NRTIs), which inhibit L1 retrotransposition, significantly improved health and lifespan of SIRT6 knockout mice and completely rescued type I interferon response. In tissue culture, inhibition of L1 with siRNA or NRTIs abrogated type I interferon response, in add...
Source: Cell Metabolism - March 5, 2019 Category: Cytology Authors: Simon M, Van Meter M, Ablaeva J, Ke Z, Gonzalez RS, Taguchi T, De Cecco M, Leonova KI, Kogan V, Helfand SL, Neretti N, Roichman A, Cohen HY, Meer MV, Gladyshev VN, Antoch MP, Gudkov AV, Sedivy JM, Seluanov A, Gorbunova V Tags: Cell Metab Source Type: research

The Long Non-Coding RNA CPR Regulates Cardiomyocyte Proliferation and Cardiac Repair.
CONCLUSIONS: Together, our findings identified that CPR is a suppressor of cardiomyocyte proliferation, and it indicates that lncRNA(s) take parts in the regulation of cardiomyocyte proliferation and cardiac repair. Our study provides an lncRNA-based therapeutic strategy for effective cardiac repair and regeneration. PMID: 30832495 [PubMed - as supplied by publisher]
Source: Circulation - March 5, 2019 Category: Cardiology Authors: Ponnusamy M, Liu F, Zhang YH, Li RB, Zhai M, Liu F, Zhou LY, Liu CY, Yan KW, Dong YH, Wang M, Qian LL, Shan C, Xu S, Wang Q, Zhang YH, Li PF, Zhang J, Wang K Tags: Circulation Source Type: research

MAP kinase and autophagy pathways cooperate to maintain RAS mutant cancer cell survival Medical Sciences
Oncogenic mutations in the small GTPase KRAS are frequently found in human cancers, and, currently, there are no effective targeted therapies for these tumors. Using a combinatorial siRNA approach, we analyzed a panel of KRAS mutant colorectal and pancreatic cancer cell lines for their dependency on 28 gene nodes that...
Source: Proceedings of the National Academy of Sciences - March 5, 2019 Category: Science Authors: Chih-Shia Lee, Liam C. Lee, Tina L. Yuan, Sirisha Chakka, Christof Fellmann, Scott W. Lowe, Natasha J. Caplen, Frank McCormick, Ji Luo Tags: PNAS Plus Source Type: research

MicroRNA ‑92a promotes cell proliferation, migration and survival by directly targeting the tumor suppressor gene NF2 in colorectal and lung cancer cells.
MicroRNA‑92a promotes cell proliferation, migration and survival by directly targeting the tumor suppressor gene NF2 in colorectal and lung cancer cells. Oncol Rep. 2019 Feb 19;: Authors: Alcantara KMM, Garcia RL Abstract Inactivation of the tumor suppressor protein Merlin leads to the development of benign nervous system tumors in neurofibromatosis type2 (NF2). Documented causes of Merlin inactivation include deleterious mutations in the encoding neurofibromin2 gene (NF2) and aberrant Merlin phosphorylation leading to proteasomal degradation. Rare somatic NF2 mutations have also been detected in com...
Source: Oncology Reports - March 4, 2019 Category: Cancer & Oncology Tags: Oncol Rep Source Type: research

circRNA ‑CER mediates malignant progression of breast cancer through targeting the miR‑136/MMP13 axis.
circRNA‑CER mediates malignant progression of breast cancer through targeting the miR‑136/MMP13 axis. Mol Med Rep. 2019 Feb 18;: Authors: Qu Y, Dou P, Hu M, Xu J, Xia W, Sun H Abstract Chondrocyte extracellular matrix‑related circular RNAs (circRNA‑CER) have been demonstrated to be involved in various diseases. However, its role in the development of human breast cancer is not clearly understood. The aims of the present study were to assess circRNA‑CER expression in paired cancer tissue and adjacent non‑tumor tissue from 24 patients with breast cancer, and to explore the roles and mechani...
Source: Molecular Medicine Reports - March 4, 2019 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

A thermosensitive gel based on w1/o/w2 multiple microemulsions for the vaginal delivery of small nucleic acid.
Authors: Wang J, Wang Y, Wang Z, Wang F, He J, Yang X, Xie W, Liu Y, Zhang Y Abstract The present study aims at designing a thermosensitive gel prepared from w1/o/w2 multiple microemulsions (MMEs) for the vaginal delivery of siRNA. The w1/o/w2 MMEs were prepared by two-step emulsifications: the first step was to prepare primary emulsions (w1/o) by low energy emulsification (LEE); the second step was to obtain stable w1/o/w2 MMEs by self-emulsifying. An extensive formulation optimization process was undertaken. The final w1/o/w2 MMEs could be formed in ddH2O, phosphate buffer solution (PBS, pH 7.4) and 1640 culture ...
Source: Drug Delivery - March 4, 2019 Category: Drugs & Pharmacology Tags: Drug Deliv Source Type: research

A new Th-17 cytokine in hidradenitis suppurativa: antimicrobial and pro-inflammatory role of IL-26.
CONCLUSIONS: Our findings suggest that infection susceptibility in HS might be related to IL-26. Despite the role of bacteria remains controversial in HS, this paper supports that there is a defect of antimicrobial response in these patients. This article is protected by copyright. All rights reserved. PMID: 30829398 [PubMed - as supplied by publisher]
Source: The British Journal of Dermatology - March 4, 2019 Category: Dermatology Authors: Scala E, Di Caprio R, Cacciapuoti S, Caiazzo G, Fusco A, Tortorella E, Fabbrocini G, Balato A Tags: Br J Dermatol Source Type: research

miR-194 Inhibits Liver Cancer Stem Cell Expansion by Regulating RAC1 pathway.
Abstract Liver cancer stem cells (CSCs) contribute to tumorigenesis, progression, drug resistance and recurrence of hepatocellular carcinoma (HCC). However, the underlying mechanism for the propagation of liver CSCs remains unclear. Herein, we observed low expression of miR-194 in chemoresistant HCC cells. A remarkable decrease of miR-194 was detected in EpCAM or CD133-positive liver CSCs and CSC-enriched hepatoma spheres. Interference miR-194 facilitated liver CSCs expansion by enhancing the self-renewal of liver CSCs. While up-regulating miR-194 inhibited liver CSCs expansion by suppressing the self-renewal of l...
Source: Experimental Cell Research - March 4, 2019 Category: Cytology Authors: Ran RZ, Chen J, Cui LJ, Lin XL, Fan MM, Cong ZZ, Zhang H, Tan WF, Zhang QG, Zhang YJ Tags: Exp Cell Res Source Type: research

LncRNA MRAK048635_P1 is critical for vascular smooth muscle cell function and phenotypic switching in essential hypertension.
In conclusion, our findings reveal that decreased MRAK048635_P1 is probably an important factor for vascular remodeling by affecting VSMC cell function and phenotypic switching in essential hypertension. PMID: 30833363 [PubMed - as supplied by publisher]
Source: Bioscience Reports - March 4, 2019 Category: Biomedical Science Authors: Fang G, Qi J, Huang L, Zhao X Tags: Biosci Rep Source Type: research

VEGF antagonism attenuates cerebral ischemia/reperfusion-induced injury via inhibiting endoplasmic reticulum stress-mediated apoptosis.
Abstract Endoplasmic reticulum (ER) stress-mediated apoptosis pathway is considered to play a vital role in mediating stroke and other cerebrovascular diseases. Previous studies have showed that vascular endothelial growth factor (VEGF) antagonism reduced cerebral ischemic/reperfusion (CI/R) damage, but whether attenuation of ER stress-induced apoptosis is contributing to its mechanisms remains elusive. Our study aimed to investigate the protective effect of VEGF antagonism on CI/R-induced injury. First, oxygen-glucose deprivation and re-oxygenation (OGD/R) BEND3 cell model was constructed to estimate siRNA-VEGF o...
Source: Biological and Pharmaceutical Bulletin - March 2, 2019 Category: Drugs & Pharmacology Authors: Feng SQ, Zong SY, Liu JX, Chen Y, Xu R, Yin X, Zhao R, Li Y, Luo TT Tags: Biol Pharm Bull Source Type: research

Effect of telmisartan on expression of metadherin in the kidney of mice with unilateral ureter obstruction.
CONCLUSIONS: Telmisartan can suppress the production of extracellular matrix proteins and the expression of metadhein to attenuate UUO-induced renal fibrosis in mice. PMID: 30890502 [PubMed - in process]
Source: Journal of Southern Medical University - March 2, 2019 Category: Universities & Medical Training Authors: Peng F, Li H, Yin B, Wang Y, Chen Y, Xu Z, Luo C, Long H Tags: Nan Fang Yi Ke Da Xue Xue Bao Source Type: research

Effect of modification of MTDH gene expression on colorectal cancer aggressiveness.
CONCLUSIONS: MTDH has an important role in promoting CRC aggravation. Also, inhibition of MTDH expression may attenuate the carcinogenic behavior of CRC cells. Furthermore, MTDH-associated NF-κB p65 signaling pathways may be involved in mediating the biological behavior of CRC. PMID: 30836117 [PubMed - as supplied by publisher]
Source: Gene - March 2, 2019 Category: Genetics & Stem Cells Authors: El-Ashmawy NE, El-Zamarany EA, Khedr EG, Abo-Saif MA Tags: Gene Source Type: research

eIF4E is a critical regulator of human papillomavirus (HPV)-immortalized cervical epithelial (H8) cell growth induced by nicotine.
Abstract Tobacco smoke is known as a cofactor in the development of cervical precancer and cancer caused by human papillomavirus (HPV). The main component in cigarette smoke, nicotine, can be concentrated more strongly in cervical mucus than in blood and it has been implicated as a cocarcinogen that promotes a serial of cancers development through multiple prosurvival pathways. Although the mechanisms of nicotine-induced cell proliferation have been well studied in some epithelial cells, the molecular mechanism of its action in cervical epithelial cells is still unclear. The aims of this study were to investigate ...
Source: Toxicology - March 2, 2019 Category: Toxicology Authors: Chen L, Wang H Tags: Toxicology Source Type: research

Major yolk protein and HSC70 are essential for the activation of the TLR pathway via interacting with MyD88 in Apostichopus japonicus.
Abstract The Toll cascade plays important functions in innate immunity against infectious pathogens in animals. Toll cascade as an ancient immune defender were conserved among different species. The activation of the TLR pathway between different species often involves different interacting proteins. The core members of this pathway have been well established in a wide range of organisms, including the marine invertebrate sea cucumber. However, these proteins do not function as single isolated entities but are engaged in a dynamic physical network with other proteins in the biomolecular context of a cell. To fill ...
Source: Archives of Biochemistry and Biophysics - March 2, 2019 Category: Biochemistry Authors: Lv Z, Li C, Guo M, Shao Y, Zhang W, Zhao X Tags: Arch Biochem Biophys Source Type: research

SNHG6 is upregulated in primary breast cancers and promotes cell cycle progression in breast cancer-derived cell lines
ConclusionsOur results indicate that lncRNA SNHG6 is involved in breast cancer development and may be considered as a potential biomarker for the diagnosis, prognosis and treatment of breast cancer.
Source: Cellular Oncology - March 2, 2019 Category: Cancer & Oncology Source Type: research

EPHA4 regulates vascular smooth muscle cell contractility and is a sex-specific hypertension risk gene in individuals with type 2 diabetes
Conclusion: EPHA4 appears to be a sex-specific hypertension risk gene in type 2 diabetic patients. Forward EPHA4 signalling reduces VSMC contractility, and estrogen is a modifier of this effect. The effect of EPHA4 on VSMCs contractility explains the association of EPHA4 gene with hypertension risks in female patients.
Source: Journal of Hypertension - March 1, 2019 Category: Cardiology Tags: ORIGINAL PAPERS: Heart and vessels Source Type: research

Cationic lipoplexes for treatment of cancer stem cell-derived murine lung tumors.
This study outlines the fabrication of a lipoplex of SOX2 small interfering RNA (CL-siSOX2) for targeted treatment of SOX2-enriched, CSC-derived orthotopic and xenograft lung tumors in CB-17 SCID mice. CL-siSOX2 induced tumor contraction in Cisplatin-naïve and Cisplatin-treated groups by 85% and 94% respectively. Reduction in tumor weight and volume following treatment with CL-siSOX2 was associated with reduced protein expression of SOX2 and markers of tumor initiation, inflammation, invasion and metastasis in mice tumor xenografts. And histological staining of lung tumor sections showed reduction in SOX2 expression was a...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - March 1, 2019 Category: Nanotechnology Source Type: research

Effect of mGluR7 on proliferation of human embryonic neural stem cells
This study is to investigate the effect of metabotropic glutamate receptor 7 (mGluR7) on the proliferation of human embryonic neural stem cells (NSCs) and its molecular mechanism. Human embryonic NSCs were isolated. The pCMV2-GV146-GFP-mGluR7 plasmid was transfected to over-express mGluR7 while mGluR7 siRNA was transfected to knockdown mGluR7. MTT assay was used to analyze cell proliferation. Flow cytometry was used to detect cell cycle and apoptosis. Protein and mRNA levels were analyzed by Western blot and RT-qPCR, respectively. The viability of human NSCs and the diameter of neurospheres after 24 hours, 48 hours, ...
Source: Medicine - March 1, 2019 Category: Internal Medicine Tags: Research Article: Observational Study Source Type: research

A small-molecule ligand of valosin-containing protein/p97 inhibits cancer cell-accelerated fibroblast migration Cell Biology
In this study, we screened ∼16,000 compounds from the RIKEN Natural Products Depository chemical library for inhibitors of enhanced NIH3T3 cell migration in the presence of MCF7. We identified NPD8733 as an inhibitor of cancer cell–enhanced fibroblast migration. This inhibition was observed not only in a wound-healing co-culture assay but also in a Transwell migration assay. Using NPD8733 and a structurally similar but inactive derivative, NPD8126, on immobilized beads, we found that NPD8733, but not NPD8126, specifically binds to valosin-containing protein (VCP)/p97, a member of the ATPase-associated with diverse cell...
Source: Journal of Biological Chemistry - March 1, 2019 Category: Chemistry Authors: Kruthi Suvarna, Kaori Honda, Makoto Muroi, Yasumitsu Kondoh, Hiroyuki Osada, Nobumoto Watanabe Tags: Molecular Bases of Disease 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 - March 1, 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

Down-regulated TMED10 in Alzheimer disease induces autophagy via ATG4B activation.
Abstract Several studies have shown that dysfunction of macroautophagy/autophagy is associated with many human diseases, including neurodegenerative disease and cancer. To explore the molecular mechanisms of autophagy, we performed a cell-based functional screening with SH-SY5Y cells stably expressing GFP-LC3, using an siRNA library and identified TMED10 (transmembrane p24 trafficking protein 10), previously known as the γ-secretase-modulating protein, as a novel regulator of autophagy. Further investigations revealed that depletion of TMED10 induced the activation of autophagy. Interestingly, protein-protein int...
Source: Autophagy - March 1, 2019 Category: Cytology Authors: Shin JH, Park SJ, Jo DS, Park NY, Kim JB, Bae JE, Jo YK, Hwang JJ, Lee JA, Jo DG, Kim JC, Jung YK, Koh JY, Cho DH Tags: Autophagy Source Type: research

Inhibition of miR-23a attenuates doxorubicin-induced mitochondria-dependent cardiomyocyte apoptosis by targeting the PGC-1 α/Drp1 pathway.
CONCLUSIONS AND IMPLICATIONS: Increased miR-23a promoted mitochondrial injury in the Dox-induced cellular model. Inhibition of miR-23a attenuated cardiomyocyte damage by directly targeting PGC-1α/p-Drp1, thereby inhibiting mitochondria-dependent apoptosis. These findings may provide a new potential target for the treatment of Dox-induced cardiotoxicity. PMID: 30831132 [PubMed - as supplied by publisher]
Source: Toxicology and Applied Pharmacology - March 1, 2019 Category: Toxicology Authors: Du J, Hang P, Pan Y, Feng B, Zheng Y, Chen T, Zhao L, Du Z Tags: Toxicol Appl Pharmacol Source Type: research

Complement C3a promotes proliferation, migration and stemness in cutaneous squamous cell carcinoma.
CONCLUSIONS: C3a enhanced cell proliferation, migration and stemness in cSCC, and this activity was correlated with activation of the Wnt and β-catenin pathway. PMID: 30825266 [PubMed - as supplied by publisher]
Source: J Cell Mol Med - March 1, 2019 Category: Molecular Biology Authors: Fan Z, Qin J, Wang D, Geng S Tags: J Cell Mol Med Source Type: research

TXNIP-mediated nuclear factor- κB signaling pathway and intracellular shifting of TXNIP in uric acid-induced NLRP3 inflammasome.
CONCLUSION: This study showed that activation of MSU-induced NLRP3 inflammasome requires TXNIP-mediated NF-κB signaling pathway and intracellular TXNIP shifting. PMID: 30833078 [PubMed - as supplied by publisher]
Source: Biochemical and Biophysical Research communications - March 1, 2019 Category: Biochemistry Authors: Kim SK, Choe JY, Park KY Tags: Biochem Biophys Res Commun Source Type: research

Arginine vasopressin attenuates the effects of TNF- α in aortic endothelial cells by inducing ectodomain shedding of TNF receptor 1.
Arginine vasopressin attenuates the effects of TNF-α in aortic endothelial cells by inducing ectodomain shedding of TNF receptor 1. Biochem Biophys Res Commun. 2019 Mar 01;: Authors: Yang WS, Moon SY, Han NJ, Lee MJ, Park SK Abstract In septic shock, arginine vasopressin (AVP) is commonly used as a vasopressor to restore blood pressure. Exogenous AVP may have anti-inflammatory effects as well. We investigated whether AVP modulates the effects of tumor necrosis factor-α (TNF-α) in human aortic endothelial cells (HAECs). TNF-α stimulated intercellular adhesion molecule-1 expression, while AVP pretre...
Source: Biochemical and Biophysical Research communications - March 1, 2019 Category: Biochemistry Authors: Yang WS, Moon SY, Han NJ, Lee MJ, Park SK Tags: Biochem Biophys Res Commun Source Type: research

LIM kinase 1 acts as a profibrotic mediator in permanent atrial fibrillation patients with valvular heart disease.
Abstract Atrial fibrillation (AF) is the most frequently diagnosed cardiac arrhythmia worldwide. Patients with permanent atrial fibrillation are at an increased risk of developing valvular heart disease. Atrial fibrosis occurs in this pathophysiological setting. LIM kinase 1 (LIMK1) is a serine/threonine kinase that regulates microtubule stability and actin polymerization in fibroblasts. LIMK1 has been implicated in the pathogenesis of atrial fibrillation. Clinical data and biopsies of the right atrial appendage were collected from 50 patients with valvular heart disease who underwent heart valve replacement surge...
Source: Journal of Biosciences - March 1, 2019 Category: Biomedical Science Authors: Chen Q, Gimple RC, Li G, Chen J, Wu H, Li R, Xie J, Xu B Tags: J Biosci Source Type: research

Activation of EMT in colorectal cancer by MTDH/NF- κB p65 pathway.
This study tries to investigate the effect of MTDH gene up-regulation on the activation of EMT in colorectal cancer (CRC) cells and identify the role of NF-κB p65. The CaCO2 cells were divided into three groups: one control group of cultured CaCO2 cells (C1), and two groups of CaCO2 cells co-transfected using human MTDH expression plasmid with either siRNA targeting human NF-κB p65 or its negative control (C2 and C3 respectively). The gene modification was confirmed by qPCR and the effect of gene modification on CRC aggravation was studied. MTDH up-regulation significantly promoted CRC cell proliferation, activated anaer...
Source: Molecular and Cellular Biochemistry - March 1, 2019 Category: Biochemistry Authors: El-Ashmawy NE, El-Zamarany EA, Khedr EG, Abo-Saif MA Tags: Mol Cell Biochem Source Type: research