Query: siRNA

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Total 16013 results found since Jan 2013.

CYP3A suppression during diet-induced nonalcoholic fatty liver disease is independent of PXR regulation
Publication date: Available online 24 May 2019Source: Chemico-Biological InteractionsAuthor(s): Hang Zeng, Yiming Lin, Jiande Gong, Sisi Lin, Jianguo Gao, Chunxiao Li, Zemin Feng, Hong Zhang, Jie Zhang, Youming Li, Chaohui YuAbstractCytochrome P450 3A (CYP3A) activity is inhibited, and its expression is suppressed during many diseases, including nonalcoholic fatty liver disease (NAFLD). However, the mechanism is controversial. Here, we report that PXR may not take part in the downregulation of CYP3A during NAFLD. Hepatic CYP3A11 (major subtype of mouse CYP3A) mRNA and protein expression was significantly decreased in both ...
Source: Chemico Biological Interactions - May 25, 2019 Category: Biochemistry Source Type: research

Mutation-Targeted siRNA Therapy for Connexin 26-Associated Keratitis-Ichthyosis-Deafness Syndrome
ConclusionTo that end, a KID syndrome cell line (KID-KC) was established from primary keratinocytes of a KID syndrome patient with heterozygous p.D50N mutation, which displayed impaired gap junction intercellular communication and hyperactive hemichannels, confirmed by dye transfer, patch clamp and neurobiotin uptake assays. In KID-KCs, treatment with AS-siRNA led to robust inhibition of the mutant GJB2 allele without altering expression of the wildtype allele. This resulted in correction of both gap junction intercellular communication and hemichannel activity. Furthermore, AS-siRNA treatment caused only low-level off-tar...
Source: Cytotherapy - May 24, 2019 Category: Cytology Source Type: research

Exosomes loaded with PTEN siRNA leads to functional recovery after complete transection of the spinal cord by specifically targeting the damaged area
ConclusionMSC-exo were extracted from Human bone marrow mesenchymal stem cells. All rats had complete transection of the spinal cord. MSC-exo were loaded with co-incubation together with siRNA for PTEN conjugated to cholesterol. The MSC-exo were given by intranasal administration 1-4 hours post-SCI.
Source: Cytotherapy - May 24, 2019 Category: Cytology Source Type: research

KLF5 silence attenuates proliferation and epithelial-mesenchymal transition induction in Hep-2 cells through NF- κB signaling pathway.
CONCLUSIONS: These results revealed that silencing KLF5 expression reduced the proliferation, migration and invasion and EMT abilities by inhibiting the NF-κB pathway in Hep-2 cells. Our results suggest that KLF5 may be a potential therapeutic target in laryngeal carcinoma. PMID: 31115014 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - May 24, 2019 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Linc00261 suppresses growth and metastasis of non-small cell lung cancer via repressing epithelial-mesenchymal transition.
CONCLUSIONS: We demonstrated that linc00261 was lowly expressed in NSCLC tissues and cells. It inhibited cell proliferation and metastasis by downregulating Snail expression via EMT. This might provide a novel sight for the biological treatment for NSCLC. PMID: 31115010 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - May 24, 2019 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

Long non-coding RNA 00152 promotes cell proliferation in cervical cancer via regulating miR-216b-5p/HOXA1 axis.
CONCLUSIONS: Our findings revealed a novel molecular mechanism underlying LINC00152 modulating CC progression through the miR-216b-5p/HOXA1 pathway, suggesting that LINC00152 might potentially act as an effective diagnostic marker and therapeutic target for cervical cancer. PMID: 31114990 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - May 24, 2019 Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research

The complement receptor C5aR2 promotes protein kinase R expression and contributes to NLRP3 inflammasome activation and HMGB1 release from macrophages Signal Transduction
In conclusion, these findings reveal that C5aR2 contributes to NLRP3 inflammasome activation and HMGB1 release from macrophages.
Source: Journal of Biological Chemistry - May 24, 2019 Category: Chemistry Authors: Songlin Yu, Dan Wang, Lingmin Huang, Yening Zhang, Ruiheng Luo, Dickson Adah, Yiting Tang, Kai Zhao, Ben Lu Tags: Immunology Source Type: research

Direct Inhibition of IRF-Dependent Transcriptional Regulatory Mechanisms Associated With Disease
Interferon regulatory factors (IRFs) are a family of homologous proteins that regulate the transcription of interferons (IFNs) and interferon-induced gene expression. As such they are important modulating proteins in the Toll-like receptor (TLR) and interferon signaling pathways, which are vital elements of the innate immune system. IRFs have a multi-domain structure, with the N-terminal part acting as a DNA binding domain (DBD) that recognizes a DNA-binding motif similar to the IFN-stimulated response element (ISRE). The C-terminal part contains the IRF-association domain (IAD), with which they can self-associate, bind to...
Source: Frontiers in Immunology - May 24, 2019 Category: Allergy & Immunology Source Type: research

Inhibition of angiotensin II-induced cerebrovascular smooth muscle cell proliferation by LRRC8A downregulation through suppressing PI3K/AKT activation
This study aims to investigate the effect of leucine-rich repeat-containing 8A (LRRC8A), an essential component of volume-sensitive chloride channels, on cerebrovascular smooth muscle cell proliferation. The data showed that LRRC8A expression was increased in mouse brain artery during angiotensin II (AngII)-induced cerebrovascular remodeling. Similarly, AngII also increased the expression of LRRC8A in human brain vascular smooth muscle cells (HBVSMCs). Knockdown of LRRC8A by siRNA significantly inhibited AngII-induced the proliferation, migration, and invasion in HBVSMCs. The inhibition of HBVSMCs proliferation by LRRC8A d...
Source: Human Cell - May 24, 2019 Category: Cytology Source Type: research

Mechanism of interactions between endoplasmic reticulum stress and autophagy in hypoxia/reoxygenation ‑induced injury of H9c2 cardiomyocytes.
Mechanism of interactions between endoplasmic reticulum stress and autophagy in hypoxia/reoxygenation‑induced injury of H9c2 cardiomyocytes. Mol Med Rep. 2019 May 09;: Authors: Guan G, Yang L, Huang W, Zhang J, Zhang P, Yu H, Liu S, Gu X Abstract Endoplasmic reticulum (ER) stress and autophagy are involved in myocardial ischemia‑reperfusion (I/R) injury; however, their roles in this type of injury remain unclear. The present study investigated the roles of ER stress and autophagy, and their underlying mechanisms, in H9c2 cells during hypoxia/reoxygenation (H/R) injury. Cell viability was detected b...
Source: Molecular Medicine Reports - May 23, 2019 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

Delivery of siRNA using folate receptor-targeted pH-sensitive polymeric nanoparticles for rheumatoid arthritis therapy
Publication date: Available online 22 May 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Xiangshi Sun, Shiyan Dong, Xiangyu Li, Kongtong Yu, Fengying Sun, Robert J. Lee, Youxin Li, Lesheng TengAbstractSystemic delivery of siRNA to target tissues is difficult to achieve owing to its limited cellular uptake and poor serum stability. Herein, polymeric nanoparticles were developed for systemic administration of siRNA to inflamed tissues. The polymeric nanoparticles were composed of PK3 as a pH-sensitive polymer, folate-polyethyleneglycol-poly(lactide-co-glycolide) as a targeting ligand, and a DOTAP/si...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - May 23, 2019 Category: Nanotechnology Source Type: research

Sphingosine kinase 2 is a negative regulator of inflammatory macrophage activation
In conclusion, SPHK2 is an anti-inflammatory protein in human macrophages that is inversely coupled to inflammatory cytokine production. This needs consideration when targeting SPHK2 with specific inhibitors.
Source: Biochimica et Biophysica Acta (BBA) Molecular and Cell Biology of Lipids - May 23, 2019 Category: Lipidology Source Type: research

GSE131667 CD248 knockdown in in vitro differentiated adipocytes exposed to hypoxia
Contributors : Paul Petrus ; Mikael Ryd énSeries Type : Expression profiling by arrayOrganism : Homo sapiensHuman adipose tissue derived stem cells were differentiated to adipocytes in vitro. At the end of differentiation, cells were treated with siRNA targeting CD248 followed by exposure to 1% oxygen levels.Microarray analysis were performed to identify differentially regulated genes.
Source: GEO: Gene Expression Omnibus - May 23, 2019 Category: Genetics & Stem Cells Tags: Expression profiling by array Homo sapiens Source Type: research

RasGRP1 is a target for VEGF to induce angiogenesis and involved in the endothelial ‐protective effects of metformin under high glucose in HUVECs
AbstractImpaired angiogenesis in endothelial cells is a hallmark of diabetes vascular complications. Ras guanine ‐releasing protein 1 (RasGRP1) is a guanine nucleotide exchange factor for Ras, and its role in endothelial angiogenesis has not been investigated. Given the importance of Ras in vascular endothelial growth factor (VEGF)‐induced angiogenesis, we hypothesized that RasGRP1 may be a critical pathwa y downstream of VEGF and involved in endothelial angiogenesis. Furthermore, we investigate whether RasGRP1‐dependent VEGF signaling was downregulated under high glucose conditions mimicking diabetes and required fo...
Source: IUBMB Life - May 23, 2019 Category: Research Authors: Jing Xu, Miao Liu, Muqiao Yu, Jiayi Shen, Jiecan Zhou, Jinglei Hu, Yong Zhou, Wei Zhang Tags: Research Communication Source Type: research

P120-catenin regulates pulmonary fibrosis and TGF-β induced lung fibroblast differentiation
In this study, we investigated the expression and role of P120 in pulmonary fibrosis and transforming growth factor beta (TGF-β) mediated lung fibroblast-to-myofibroblast differentiation (fibroblast differentiation). Our data indicated that P120 expression increased in lung fibrotic foci and primary lung fibroblasts isolated from bleomycin- (BLM) challenged mice, compared to controls. In vitro, TGF-β induced P120 expression in human lung fibroblasts, and siRNA-mediated SMAD3 depletion inhibited TGF-β stimulated P120 expression. Blocking nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway throu...
Source: Life Sciences - May 22, 2019 Category: Biology Source Type: research

Histone deacetylase 6 inhibitor tubastatin A attenuates angiotensin II-induced hypertension by preventing cystathionine γ-lyase protein degradation
Publication date: Available online 21 May 2019Source: Pharmacological ResearchAuthor(s): Zhexi Chi, Hye-Eun Byeon, Eunjeong Seo, Quynh-Anh T. Nguyen, Wonbeom Lee, Yunyong Jeong, Juyong Choi, Deepesh Pandey, Dan E. Berkowitz, Jae Hyung Kim, Sang Yoon LeeAbstractCystathionine γ-lyase (CSEγ) is a hydrogen sulfide (H2S)-producing enzyme. Endothelial H2S production can mediate vasodilatory effects, contributing to the alleviation of hypertension (high blood pressure). Recent studies have suggested a role of histone deacetylase 6 (HDAC6) in hypertension, although its underlying mechanisms are poorly understood. Here, we addres...
Source: Pharmacological Research - May 22, 2019 Category: Drugs & Pharmacology Source Type: research

Design and evaluation of ionizable peptide amphiphiles for siRNA delivery
Publication date: Available online 22 May 2019Source: International Journal of PharmaceuticsAuthor(s): Patrick Neuberg, Alain Wagner, Jean-Serge Remy, Antoine KichlerAbstractSmall interfering RNAs (siRNAs) can down-regulate the expression of a target mRNA molecule in a sequence-specific manner, making them an attractive new class of drugs with broad potential for the treatment of diverse human diseases. Here, we report the synthesis of a series of cationic amphiphiles which were obtained by the coupling of amino acids and dipeptides onto a lipidic double chain. The new amphiphiles presenting a peptidic motif on a short hyd...
Source: International Journal of Pharmaceutics - May 22, 2019 Category: Drugs & Pharmacology Source Type: research

L1-ORF1p and Ago2 are involved in a siRNA-mediated regulation for promoter activity of L1-5'UTR.
CONCLUSIONS: L1-5'UTR harbors both sense and antisense promoter activity and a dsRNA-mediated regulation is responsible for L1-5'UTR regulation. Agos proteins and L1-ORF1p were engaged in this process. PMID: 31112282 [PubMed - as supplied by publisher]
Source: Folia Histochemica et Cytobiologica - May 22, 2019 Category: Cytology Tags: Folia Histochem Cytobiol Source Type: research

P-cadherin mutations are associated with high basal Wnt activity and stemness in canine mammary tumor cell lines.
Conclusion: It is concluded that expression of mutated CDH3 is associated with activation of cSRC, stabilization of ß-catenin and a rounded morphology related to a stemness/EMT phenotype. A decreased Wnt activity can be found also by cSRC inhibition, but CDH3 silencing has an additional effect on morphology indicating reversal of EMT. PMID: 31105876 [PubMed]
Source: Oncotarget - May 22, 2019 Category: Cancer & Oncology Tags: Oncotarget Source Type: research

Inhibition of SGK1 confers vulnerability to redox dysregulation in cervical cancer
Publication date: Available online 20 May 2019Source: Redox BiologyAuthor(s): Min Wang, Yijue Xue, Lanlin Shen, Pan Qin, Xiaolin Sang, Zhiwei Tao, Jingyan Yi, Jia Wang, Pixu Liu, Hailing ChengAbstractCervical cancer has poor prognosis and patients are often diagnosed at advanced stages of the disease with limited treatment options. There is thus an urgent need for the discovery of new therapeutic strategies in cervical cancer. The activation of SGK1 has been linked to the development of various cancer types but little is known about the role of SGK1 in cervical cancer and its potential as a therapeutic target. Here we repo...
Source: Redox Biology - May 22, 2019 Category: Biology Source Type: research

A novel circular RNA hsa_circ_0008035 contributes to gastric cancer tumorigenesis through targeting the miR-375/YBX1 axis.
This study aims to uncover the mechanism by which circRNAs regulate gastric cancer tumorigenesis. Among the microarray data, we screened dysregulated circRNAs and identified an up-regulated circRNA, hsa_circ_0008035. Functionally, the hsa_circ_0008035 silencing by the siRNA transfection inhibited the proliferation and invasion of gastric cancer cells. Mechanically, hsa_circ_0008035 acted as a sponge for the miR-375 and absorbed its expression, and miR-375 was found to target YBX1 3'-UTR, constructing a hsa_circ_0008035/miR-375/YBX1 axis. Taken together, these findings are evidence that circRNA hsa_circ_0008035 promotes gas...
Source: American Journal of Translational Research - May 22, 2019 Category: Research Tags: Am J Transl Res Source Type: research

HSC-specific knockdown of GGPPS alleviated CCl4-induced chronic liver fibrosis through mediating RhoA/Rock pathway.
Authors: Lai SS, Fu X, Cheng Q, Yu ZH, Jiang EZ, Zhao DD, Yu DC, Qiu YD, Gao X, Ju HX, Wang W, Jiang Q, Zhu MS, Li CJ, Xue B Abstract Hepatic stellate cells (HSCs) play a critical role in the pathogenesis and reversal of liver fibrosis. Targeting HSCs is of great significance in the treatment of hepatic fibrosis, and has attracted wide attention of scholars. Here we demonstrated that expression of geranylgeranyldiphosphate synthase (GGPPS) predominantly increased in HSCs in murine fibrotic liver. HSC-specific knockdown of GGPPS using vitamin A-coupled liposome carrying siRNA-ggpps decreased activation of HSCs and a...
Source: American Journal of Translational Research - May 22, 2019 Category: Research Tags: Am J Transl Res Source Type: research

Combination of cetuximab with met inhibitor in control of cetuximab-resistant oral squamous cell carcinoma.
Conclusions: This study demonstrates that Met/HGF expression results in OSCC resistance to cetuximab and tumor recurrence after cetuximab therapy; thus, inhibition of Met/HGF activity could restore OSCC sensitivity to cetuximab. PMID: 31105843 [PubMed]
Source: American Journal of Translational Research - May 22, 2019 Category: Research Tags: Am J Transl Res Source Type: research

MicroRNA-186-5p represses neuroblastoma cell growth via downregulation of Eg5.
In this study, we analyzed the expression level and role of miRNA-186-5p and Eg5 in neuroblastoma and neuroblastoma cell lines SHSY-5Y, Kelly, NBL-S and SK-N-AS. Results of Real-time PCR and immunohistochemistry showed that the expression level of Eg5 in tumor tissues was higher than that in tumor adjacent tissues, while miRNA-186-5p expression level in tumor tissues was lower than that in tumor adjacent tissues. miRNA-186-5p mimics or Eg5 siRNA was transfected into SHSY-5Y and Kelly cells, CCK-8 and soft agar clone formation tests' results showed that the cell proliferation was inhibited. Flow cytometry analysis of cell a...
Source: American Journal of Translational Research - May 22, 2019 Category: Research Tags: Am J Transl Res Source Type: research

Graphene Quantum Dots: Synthesis, Characterization, Cell Viability, Genotoxicity for Biomedical Applications
We report the synthesis and applications of a novel N-doped graphene quantum dots (GQDs) using hydrothermal reaction between citric acid and p-aminophenol. The synthesized N-doped GQDs have been characterized physico-chemically and evaluated its antioxidant, antimicrobial, DNA binding and cleavage activities. siRNA loading studies were performed and their effects on cells were evaluated. Obtained results indicate that monodisperse solution of N-doped GQDs has been obtained with particles size ca. ∼10.9±1.3 nm. UV-Vis spectroscopy studies of the interactions between the N-doped GQDs and calf thymus DNA (CT-DNA) showed th...
Source: Saudi Pharmaceutical Journal - May 22, 2019 Category: Drugs & Pharmacology Source Type: research

Emodin Rescues Intrahepatic Cholestasis via Stimulating FXR/BSEP Pathway in Promoting the Canalicular Export of Accumulated Bile
Conclusions: Emodin has a protective effect and a rescue activity on cholestasis via stimulating FXR/BSEP pathways in promoting the canalicular export of accumulated bile.
Source: Frontiers in Pharmacology - May 22, 2019 Category: Drugs & Pharmacology Source Type: research

Inhibition of TRIB3 Protects Against Neurotoxic Injury Induced by Kainic Acid in Rats
Epilepsy refers to a group of neurological disorders of varying etiology characterized by recurrent seizures, resulting in brain dysfunction. Endoplasmic reticulum (ER) stress is highly activated in the process of epilepsy-related brain injury. However, the mechanisms by which ER stress triggers neuronal apoptosis remain to be fully elucidated. Tribbles pseudokinase 3 (TRIB3) is a pseudokinase that affects a number of cellular functions, and its expression is increased during ER stress. Here, we sought to clarify the role of TRIB3 in neuronal apoptosis mediated by ER stress. In the kainic acid (KA) (10 mg/kg)-induced rat s...
Source: Frontiers in Pharmacology - May 22, 2019 Category: Drugs & Pharmacology Source Type: research

TNF- α/calreticulin dual signaling induced NLRP3 inflammasome activation associated with HuR nucleocytoplasmic shuttling in rheumatoid arthritis
ConclusionsTNF- α/CRT dual signaling induced NLRP3 inflammasome activation, which could be suppressed by HuR knockdown presumably due to the block of HuR translocating from nucleus to cytoplasma.
Source: Inflammation Research - May 22, 2019 Category: Research Source Type: research

Zinc deficiency up-regulates ET-1 mediated secretion and endothelial cell migration through nuclear HIF-1 translocation.
CONCLUSION: Altogether, the results suggest that zinc deficiency up-regulates ET-1 signaling through HIF-1 activation and stimulates endothelial cell migration suggesting an important role of zinc in the vascular consequences of IH and OSA mediated by the HIF-1-ET- signaling. PMID: 31116583 [PubMed - as supplied by publisher]
Source: Am J Physiol Cell Ph... - May 22, 2019 Category: Cytology Authors: Morand J, Briancon-Marjollet A, Lemarié E, Gonthier B, Arnaud J, Korichneva I, Godin-Ribuot D Tags: Am J Physiol Cell Physiol Source Type: research

OGR1 mediates the inhibitory effects of acidic environment on proliferation and angiogenesis of endothelial progenitor cells.
This study attempted to whether OGR1 mediates the effects of acid on proliferation, migration, and angiogenesis in EPCs. FITC-UEA-I and Dil-Ac-LDL double-staining methods were used to identify EPCs. Expression of OGR1 was analyzed by RT-PCR and western blot after incubation in media ranging in pH, cell counting kit-8 and cell cycle analysis were used to analyze proliferation and cell cycle distribution. Scratch test, transwell migration assay, and tube formation experiments were performed to analyze migration and vascularization of EPCs after silencing OGR1 with siRNA. The result show EPCs were positive for FITC-UEA-I and ...
Source: Cell Biology International - May 22, 2019 Category: Cytology Authors: Ding S, Xu J, Zhang Q, Chen F, Zhang J, Gui K, Xiong M, Li B, Ruan Z, Zhao M Tags: Cell Biol Int Source Type: research

Cinnamon and its Metabolite Protect the Nigrostriatum in a Mouse Model of Parkinson ’s Disease Via Astrocytic GDNF
This study underlines the importance of sodium benzoate (NaB), a metabolite of commonly-used spice cinnamon, a food-additive and an FDA-approved drug against hyperammonemia, in stimulating GDNF in primary mouse and human astrocytes. Presence of cAMP response element (CRE) in theGdnf gene promoter, recruitment of CREB to theGdnf promoter by NaB and abrogation of NaB-mediated GDNF expression by siRNA knockdown of CREB suggest that NaB induces the transcription ofGdnf via CREB. Finally, oral administration of NaB and cinnamon itself increased the level of GDNF in vivo in the substantia nigra pars compacta (SNpc) of normal as ...
Source: Journal of NeuroImmune Pharmacology - May 22, 2019 Category: Drugs & Pharmacology Source Type: research

GSE131503 Small extracellular vesicles are key regulators of non-cell autonomous intercellular communication in senescence via the interferon protein, IFITM3
Contributor : Robert LoweSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensSenescence is a cellular phenotype present in health and disease, characterized by a stable cell cycle arrest and an inflammatory response, denominated senescence-associated secretory phenotype (SASP). The SASP is important in influencing the behaviour of neighbouring cells and altering the microenvironment; yet, this role has been mainly attributed to soluble factors. Here, we show that both the soluble factors in addition to small extracellular vesicles (sEV) are capable of transmitting paracrine senescence to ...
Source: GEO: Gene Expression Omnibus - May 21, 2019 Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research

GSE125507 CRISPR-Cas9 screening of KSHV-transformed cells identifies XPO1 as a vulnerable target of cancer cells by inducing p62 SQSTM1-mediated p53 activation in PML bodies
Contributors : Marion Gruffaz ; Hongfeng Yuan ; Hui Liu ; Sangsu Bae ; Jin-Soo Kim ; Chun Lu ; Yufei Huang ; Shou-Jiang GaoSeries Type : OtherOrganism : Rattus norvegicusMislocalization of oncogenes and tumor suppressors resulting from aberrant nuclear export promotes uncontrolled cell proliferation and growth transformation of cancer cells. We performed a genome-wide CRISPR-Cas9 screening in matched primary and KSHV-transformed cells, and identified genes that were pro-growth and growth-suppressive of both types of cells, of which exportin XPO1 was a critical factor for the survival of transformed cells. Using XPO1 inhibi...
Source: GEO: Gene Expression Omnibus - May 21, 2019 Category: Genetics & Stem Cells Tags: Other Rattus norvegicus Source Type: research

Increased Expression of lncRNA UCA1 and HULC Is Required for Pro-inflammatory Response During LPS Induced Sepsis in Endothelial Cells
Systemic uncontrolled inflammatory response, also termed as sepsis, is responsible for many mortalities. Bacterial endotoxin, lipopolysaccharide (LPS), is a major cause of sepsis in endothelial cells. Even though a lot of research has been done to define underlying mechanisms of LPS induced sepsis, the role of long noncoding RNAs (lncRNAs), a group of>200 kb RNAs in sepsis is not well-defined. Expression of pro-inflammatory mediators IL6, ICAM1, and VCAM1 (which encodes interleukin-6, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1, respectively) were determined following LPS treatment of human der...
Source: Frontiers in Physiology - May 21, 2019 Category: Physiology Source Type: research

Cancers, Vol. 11, Pages 701: Transglutaminase-2 Mediates the Biomechanical Properties of the Colorectal Cancer Tissue Microenvironment that Contribute to Disease Progression
In conclusion, this study demonstrates a role for TG2 in the stromal response to invading tumour, leading to tissue stiffening and poor outcome in patients.
Source: Cancers - May 21, 2019 Category: Cancer & Oncology Authors: Robin Delaine-Smith Nicola Wright Chris Hanley Rebecca Hanwell Rahul Bhome Marc Bullock Cole Drifka Kevin Eliceiri Gareth Thomas Martin Knight Alex Mirnezami Nicholas Peake Tags: Article Source Type: research

Peroxisome Proliferator-Activated Receptor γ Agonist Rosiglitazone Protects Blood–Brain Barrier Integrity Following Diffuse Axonal Injury by Decreasing the Levels of Inflammatory Mediators Through a Caveolin-1-Dependent Pathway
In conclusion, we provide evidence that PPAR γ plays an important role in a series of processes associated with DAI, and that the PPARγ agonist RSG can protect BBB integrity by decreasing the levels of inflammatory mediators through a caveolin-1-dependent pathway.
Source: Inflammation - May 20, 2019 Category: Allergy & Immunology Source Type: research

Cyclic RNA Molecule circ_0007766 Promotes the Proliferation of Lung Adenocarcinoma Cells by Up-regulating the Expression of Cyclin D1/CyclinE1/CDK4
Conclusion In vitro functional studies have shown that circ_0007766 may promote the proliferation and migration of lung adenocarcinoma cells. Further molecular mechanism studies have found that circ_0007766 can up-regulate the expression of Cyclin D1/Cyclin E1/CDK4, which are the key proteins of cell cycle, and thus promote the malignant proliferation of lung adenocarcinoma. From the perspective of circRNA, this study will provide new clues for the pathogenesis, development and prognosis of lung adenocarcinoma, and provide new target for clinical treatment. 
 DOI: 10.3779/j.issn.1009-3419.2019.05.03
Source: Chinese Journal of Lung Cancer - May 20, 2019 Category: Cancer & Oncology Source Type: research

A Bcr-Abl Inhibitor GNF-2 Attenuates Inflammatory Activation of Glia and Chronic Pain
GNF-2 is an allosteric inhibitor of Bcr-Abl. It was developed as a new class of anti-cancer drug to treat resistant chronic myelogenous leukemia. Recent studies suggest that c-Abl inhibition would provide a neuroprotective effect in animal models of Parkinson’s disease as well as in clinical trials. However, the role of c-Abl and effects of GNF-2 in glia-mediated neuroinflammation or pain hypersensitivity has not been investigated. Thus, in the present study, we tested the hypothesis that c-Abl inhibition by GNF-2 may attenuate the inflammatory activation of glia and the ensuing pain behaviors in animal models. Our resul...
Source: Frontiers in Pharmacology - May 20, 2019 Category: Drugs & Pharmacology Source Type: research

Pyruvate responsiveness based on α-oxohydrazone formation for intracellular siRNA release from polyion complex (PIC)-based carriers.
This study provides the rationale for a smart design of pyruvate-responsive materials in the cell, based on α-oxohydrazone formation. PMID: 31091092 [PubMed - as supplied by publisher]
Source: Biomacromolecules - May 15, 2019 Category: Biochemistry Authors: Takemoto H, Wang CL, Nomoto T, Matsui M, Tomoda K, Nishiyama N Tags: Biomacromolecules Source Type: research

Strategies, design, and chemistry in siRNA delivery systems.
Abstract Emerging therapeutics that utilize RNA interference (RNAi) have the potential to treat broad classes of diseases due to their ability to reversibly silence target genes. In August 2018, the FDA approved the first siRNA therapeutic, called ONPATTRO™ (Patisiran), for the treatment of transthyretin-mediated amyloidosis. This was an important milestone for the field of siRNA delivery that opens the door for additional siRNA drugs. Currently, >20 small interfering RNA (siRNA)-based therapies are in clinical trials for a wide variety of diseases including cancers, genetic disorders, and viral infections. T...
Source: Advanced Drug Delivery Reviews - May 15, 2019 Category: Drugs & Pharmacology Authors: Dong Y, Siegwart DJ, Anderson DG Tags: Adv Drug Deliv Rev Source Type: research

i-Fect Scores Again
This study is the first to demonstrate that the stabilization of HIF1A expression underpins the development of bortezomib-induced neuropathic pain. Crucially, these findings reveal that the initiation and maintenance of bortezomib-induced neuropathic pain are regulated by distinct mechanisms.
Source: Neuromics - May 13, 2019 Category: Neuroscience Tags: chemotherapy i-Fect RNAi siRNA siRNA delivery in-vivo Source Type: news

Silencing AXL by covalent siRNA-gelatin-antibody nanoconjugate inactivates mTOR/EMT pathway and stimulates p53 for TKI sensitization in NSCLC
Publication date: Available online 12 May 2019Source: Nanomedicine: Nanotechnology, Biology and MedicineAuthor(s): Dhananjay Suresh, Ajit Zambre, Soumavo Mukherjee, Shreya Ghoshdastidar, Yuexu Jiang, Trupti Joshi, Anandhi Upendran, Raghuraman KannanAbstractNon-small cell lung cancer (NSCLC) is the leading cause of cancer mortality with the 5-year survival rate remains a dismal 16% for the past 40 years. Drug resistance is a major obstacle to achieving long-term patient survival. Identifying and validating molecular biomarkers responsible for resistance and thereby adopting multi-directional therapy is necessary to imp...
Source: Nanomedicine: Nanotechnology, Biology and Medicine - May 12, 2019 Category: Nanotechnology Source Type: research

Biodistribution/Biostability Assessment of siRNA after Intravenous and Intratracheal Administration to Mice, Based on Comprehensive Analysis of In Vivo/Ex Vivo/Polyacrylamide Gel Electrophoresis Fluorescence Imaging
Publication date: Available online 10 May 2019Source: International Journal of PharmaceuticsAuthor(s): Tomoyuki Okuda, Yoko Toyoda, Takashi Murakami, Hirokazu OkamotoAbstractWe performed in vivo/ex vivo/polyacrylamide gel electrophoresis (PAGE) fluorescence imaging of near-infrared fluorescence (NIRF)-labeled siRNA (Cy5.5-siGL3) in mice to investigate the validity of each fluorescence imaging result as the biodistribution/biostability assessment of siRNA. Statistically significant correlations could be obtained between the in vivo and ex vivo fluorescence intensities of Cy5.5 in the relevant regions/tissues, except the lun...
Source: International Journal of Pharmaceutics - May 11, 2019 Category: Drugs & Pharmacology Source Type: research

Knockdown siRNA Targeting the Mitochondrial Sodium-Calcium Exchanger-1 Inhibits the Protective Effects of Two Cannabinoids Against Acute Paclitaxel Toxicity
AbstractTreatment with cannabidiol (CBD) or KLS-13019 (novel CBD analog), has previously been shown to prevent paclitaxel-induced mechanical allodynia in a mouse model of chemotherapy-induced peripheral neuropathy (CIPN). The mechanism of action for CBD- and KLS-13019-mediated protection now has been explored with dissociated dorsal root ganglion (DRG) cultures using small interfering RNA (siRNA) to the mitochondrial Na+ Ca2+ exchanger-1 (mNCX-1). Treatment with this siRNA produced a 50 –55% decrease in the immunoreactive (IR) area for mNCX-1 in neuronal cell bodies and a 72–80% decrease in neuritic IR area as determin...
Source: Journal of Molecular Neuroscience - May 10, 2019 Category: Neuroscience Source Type: research

Effect of thermal and shear stresses in the spray drying process on the stability of siRNA dry powders
In conclusion, stable siRNA based particles for inhalation purposes could be produced using the spray drying technology.Graphical abstract
Source: International Journal of Pharmaceutics - May 9, 2019 Category: Drugs & Pharmacology Source Type: research

i-Fect in Action
This study is the first to demonstrate that the stabilization of HIF1A expression underpins the development of bortezomib-induced neuropathic pain. Crucially, these findings reveal that the initiation and maintenance of bortezomib-induced neuropathic pain are regulated by distinct mechanisms.Looking to up your odds for high percentage siRNA Transfection? Try i-Fect.
Source: siRNA and DsiRNA Transfection Efficiency - May 9, 2019 Category: Neuroscience Tags: Chemotherapy i-Fect in vivo RNAi neuropathic pain siRNA delivery in-vivo Source Type: news

i-Fect used to Study Angiogenesis in Brain Injury
This study revealed that LDHA, which is a known damage marker, promotes CNS-specific angiogenesis. LDHA-mediated angiogenesis depends on vimentin on the surface of vascular endothelial cells. The work described here proposes a novel mechanism by which neurodegeneration drives angiogenesis in the CNS.A mixture of ouri-FectTM and LDHA siRNA, in this study, were directly injected into mice cortexes: Hsiaoyun Lin, Rieko Muramatsu, Noriko Maedera, Hiroto Tsunematsu, Machika Hamaguchi, Yoshihisa Koyama, Mariko Kuroda, Kenji Ono, Makoto Sawada, Toshihide Yamashita.Extracellular Lactate Dehydrogenase A Release ...
Source: siRNA and DsiRNA Transfection Efficiency - May 9, 2019 Category: Neuroscience Tags: Angiogenesis iFect TBI traumatic brain injury Source Type: news

Resveratrol and siRNA in combination reduces Hsp27 expression and induces caspase-3 activity in human glioblastoma cells.
This study is the first report showing that resveratrol reduces Hsp27 levels, and siRNA-mediated Hsp27 silencing enhances the therapeutic effects of resveratrol in glioma cells. Our results suggest that resveratrol administration in combination with Hsp27 silencing has a potential to be used as a candidate for GBM treatment. PMID: 31073903 [PubMed - as supplied by publisher]
Source: Cell Stress and Chaperones - May 9, 2019 Category: Cytology Authors: Önay Uçar E, Şengelen A Tags: Cell Stress Chaperones Source Type: research

Development of simple isocratic HPLC methods for siRNA quantitation in lipid-based nanoparticles
Publication date: 5 August 2019Source: Journal of Pharmaceutical and Biomedical Analysis, Volume 172Author(s): Zongyun Huang, William P. FishAbstractThis paper describes the development of simple and user-friendly HPLC methods that can quantitate the amount of small interfering RNA (siRNA) in lipid-based nanoparticle (LNP) formulations. The methods have been used as alternative chromatographic approaches to the size exclusion chromatography in order to perform “fit for purpose” analysis such as determining the amount of released siRNA from LNP formulations as a part of in-vitro release testing. Two HPLC conditions were...
Source: Journal of Pharmaceutical and Biomedical Analysis - May 8, 2019 Category: Drugs & Pharmacology Source Type: research

Let-7 miRNA and CDK4 siRNA co-encapsulated in Herceptin-conjugated liposome for breast cancer stem cells
In conclusion, an efficient liposomal delivery system for the combination of miRNA and siRNA to target the BCSCs was developed and could be used as an efficacious therapeutic modality for breast cancer.Graphical AbstractHerceptin-conjugated cationic liposome can enhance the cellular uptake of let-7 miRNA and CDK4 siRNA toward the HER-2 expressing breast cancer stem cells.
Source: Asian Journal of Pharmaceutical Sciences - May 8, 2019 Category: Drugs & Pharmacology Source Type: research