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Search results for: Scrambled siRNA

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#33540053   2021/02/02 To Up

Silencing Epidermal Growth Factor Receptor in Hypothlamic Paraventricular Nucleus Reduces Extracellular Signal-related Kinase 1 and 2 Signaling and Sympathetic Excitation in Heart Failure Rats.

Activation of extracellular signal-related kinases 1 and 2 (ERK1/2) signaling in cardiovascular regulatory regions of the brain contributes to sympathetic excitation in myocardial infarction (MI)-induced heart failure (HF) by increasing brain renin-angiotensin system (RAS) activity, neuroinflammation, and endoplasmic reticulum (ER) stress. The mechanisms eliciting brain ERK1/2 signaling in HF are still poorly understood. We tested the involvement of the epidermal growth factor receptor (EGFR) which, upon activation, stimulates ERK1/2 activity. Adult male Sprague-Dawley rats received bilateral microinjections of a lentiviral vector encoding a small interfering RNA (siRNA) for EGFR, or a scrambled siRNA, into the hypothalamic paraventricular nucleus (PVN), a recognized source of sympathetic overactivity in HF. One week later, coronary artery ligation was performed to induce HF. Four weeks later, the EGFR siRNA-treated HF rats, compared with scrambled the siRNA-treated HF rats, had lower mRNA and protein levels of EGFR, lower levels of phosphorylated (p-) EGFR and p-ERK1/2 and lower mRNA levels of the inflammatory mediators TNF-α, IL-1β and cyclooxygenase-2, the RAS components angiotensin-converting enzyme and angiotensin II type 1a receptor and the ER stress markers BIP and ATF4 in the PVN. They also had lower plasma and urinary norepinephrine levels and improved peripheral manifestations of HF. Additional studies revealed that p-EGFR was increased in the PVN of HF rats, compared with sham-operated control rats. These results suggest that activation of EGFR in the PVN triggers ERK1/2 signaling, along with ER stress, neuroinflammation and RAS activity, in MI-induced HF. Brain EGFR may be a novel target for therapeutic intervention in MI-induced HF.
Yang Yu, Shun-Guang Wei, Robert M Weiss, Robert B Felder

2497 related Products with: Silencing Epidermal Growth Factor Receptor in Hypothlamic Paraventricular Nucleus Reduces Extracellular Signal-related Kinase 1 and 2 Signaling and Sympathetic Excitation in Heart Failure Rats.

2 Pieces/Box10ug20ug200ul10ug10ug100.00 ug100ug100ug Lyophilized100ug100ul100ug Lyophilized

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#33467640   2021/01/15 To Up

Modulation of p75 on Mesenchymal Stem Cells Increases Their Vascular Protection in Retinal Ischemia-Reperfusion Mouse Model.

Mesenchymal stem cells (MSCs) are a promising therapy to improve vascular repair, yet their role in ischemic retinopathy is not fully understood. The aim of this study is to investigate the impact of modulating the neurotrophin receptor; p75 on the vascular protection of MSCs in an acute model of retinal ischemia/reperfusion (I/R). Wild type (WT) and p75 mice were subjected to I/R injury by increasing intra-ocular pressure to 120 mmHg for 45 min, followed by perfusion. Murine GFP-labeled MSCs (100,000 cells/eye) were injected intravitreally 2 days post-I/R and vascular homing was assessed 1 week later. Acellular capillaries were counted using trypsin digest 10-days post-I/R. In vitro, MSC-p75 was modulated either genetically using siRNA or pharmacologically using the p75 modulator; LM11A-31, and conditioned media were co-cultured with human retinal endothelial cells (HREs) to examine the angiogenic response. Finally, visual function in mice undergoing retinal I/R and receiving LM11A-31 was assessed by visual-clue water-maze test. I/R significantly increased the number of acellular capillaries (3.2-Fold) in WT retinas, which was partially ameliorated in p75 retinas. GFP-MSCs were successfully incorporated and engrafted into retinal vasculature 1 week post injection and normalized the number of acellular capillaries in p75 retinas, yet ischemic WT retinas maintained a 2-Fold increase. Silencing p75 on GFP-MSCs coincided with a higher number of cells homing to the ischemic WT retinal vasculature and normalized the number of acellular capillaries when compared to ischemic WT retinas receiving scrambled-GFP-MSCs. In vitro, silencing p75-MSCs enhanced their secretome, as evidenced by significant increases in SDF-1, VEGF and NGF release in MSCs conditioned medium; improved paracrine angiogenic response in HREs, where HREs showed enhanced migration (1.4-Fold) and tube formation (2-Fold) compared to controls. In parallel, modulating MSCs-p75 using LM11A-31 resulted in a similar improvement in MSCs secretome and the enhanced paracrine angiogenic potential of HREs. Further, intervention with LM11A-31 significantly mitigated the decline in visual acuity post retinal I/R injury. In conclusion, p75 modulation can potentiate the therapeutic potential of MSCs to harness vascular repair in ischemic retinopathy diseases.
Sally L Elshaer, Hang-Soo Park, Laura Pearson, William D Hill, Frank M Longo, Azza B El-Remessy

1196 related Products with: Modulation of p75 on Mesenchymal Stem Cells Increases Their Vascular Protection in Retinal Ischemia-Reperfusion Mouse Model.

1 mg2 ml10 ug5 x 10A5 cells/vial1 x 10^6 cells/vial1 mg100ug Lyophilized100 μg1 mL100ug Lyophilized1 vial

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#33429003   2021/01/09 To Up

LncRNA ZFAS1 inhibits triple-negative breast cancer by targeting STAT3.

Triple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer with fewer treatment options than other types of invasive breast cancer due to the loss of the estrogen, progesterone receptors and low levels of the HER2 protein, resulting in a poor prognosis for these patients. Here, we found that the expression of the lncRNA, ZFAS1, was significantly downregulated (∼3.0-fold) in blood samples of TNBC patients (n=40) compared to matched healthy controls (n=40). Functionally, silencing of ZFAS1 promoted cell proliferation and colonization of human MDA-MB-231 TNBC cells by inhibiting the expression levels of the cyclin-dependent kinase (CDK) inhibitors p21 (CDKN1A) and p27 (CDKN1B) compared to the scrambled siRNA control cells. Further, we found that downregulation of ZFAS1 led to decreased protein levels of the epithelial markers, E-cadherin, Claudin-1, and Zo-1, with increased protein levels of the mesenchymal markers, Slug and ZEB1. In addition, by utilizing the bioinformatic tools such as RAID v2.0 (RNA Interactome Database Version 2.0), AnnoLnc (Annotate human lncRNA database), and GEPIA (Gene Expression Profiling Interactive Analysis), we identified a strong negative correlation between ZFAS1 and signal transducer and activator of transcription 3 (STAT3) gene expression (R = -0.11, p-value = 0.0002). Further, we observed that decreased ZFAS1 expression significantly (p < 0.05) increased STAT3 and phosphorylated STAT3 (at Ser727 residue) protein levels in TNBC cells. The composite data indicate that ZFAS1 may function as a tumor-suppressor lncRNA with potential as a diagnostic/prognostic marker and may offer a new target for the treatment of TNBC patients.
Uttam Sharma, Tushar Singh Barwal, Akanksha Khandelwal, Akshay Malhotra, Manjit Kaur Rana, Amrit Pal Singh Rana, Evgeny N Imyanitov, Karen M Vasquez, Aklank Jain

1324 related Products with: LncRNA ZFAS1 inhibits triple-negative breast cancer by targeting STAT3.

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#33270996   2020/12/03 To Up

Dec2 attenuates autophagy in inflamed periodontal tissues.

Transcriptional regulation of autophagy depends on the transcription factors coordinated inflammatory feedback mechanism. Here, we provide a comprehensive functional characterization of periodontal ligament fibroblasts (PDLFs) treated with Porphyromonas gingivalis lipopolysaccharide (LPS), aiming to reveal previously unappreciated biological changes and to investigate how a transcription factor differentiated embryonic chondrocytes 2 (Dec2)-deficient environment influences the function of autophagy in nflamed human PDLFs.
Shunichi Oka, Xiaoyan Li, Fuyuki Sato, Fengzhu Zhang, Nitesh Tewari, Chongchong Chen, Liangjun Zhong, Makoto Makishima, Yi Liu, Ujjal K Bhawal

1903 related Products with: Dec2 attenuates autophagy in inflamed periodontal tissues.



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#33245410   2020/11/27 To Up

NOD2 induces VCAM-1 and ET-1 gene expression via NF-κB in human umbilical vein endothelial cells with muramyl dipeptide stimulation.

Endothelial dysfunction is involved in various aspects of vascular biology and different stages of cardiovascular diseases (CVDs). Nucleotide-binding oligomerization domain-containing protein (NOD) 2, a pivotal innate immune receptor for muramyl dipeptide (MDP), has been reported to be a central regulator in CVDs. Previously, we reported that NOD2 played a leading role in MDP-triggered oxidative stress in endothelial cells (ECs). However, whether NOD2 participates in the regulatory mechanism of vascular cell adhesion molecule‑1 (VCAM-1) and endothelin‑1 (ET-1) expression was not elucidated.
Ling-Jun Kong, Ya-Nan Wang, Zi Wang, Qian-Zhou Lv

1375 related Products with: NOD2 induces VCAM-1 and ET-1 gene expression via NF-κB in human umbilical vein endothelial cells with muramyl dipeptide stimulation.

1.00 flask1.00 flask1.00 flask1.00 flask1.00 flask96 wells (1 kit)1x10e7 cells100ug Lyophilized 100ul100uL100ug Lyophilized10ug

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#33227912   2020/11/19 To Up

High-Glucose-Induced Rab20 Upregulation Disrupts Gap Junction Intercellular Communication and Promotes Apoptosis in Retinal Endothelial and Müller Cells: Implications for Diabetic Retinopathy.

To investigate whether high glucose (HG) alters Rab20 expression and compromises gap junction intercellular communication (GJIC) and cell survival, retinal cells were studied for altered intracellular trafficking of connexin 43 (Cx43). Retinal endothelial cells (RRECs) and retinal Müller cells (rMCs) were grown in normal (N; 5 mM glucose) or HG (30 mM glucose) medium for seven days. In parallel, cells grown in HG medium were transfected with either Rab20 siRNA or scrambled siRNA as a control. Rab20 and Cx43 expression and their localization and distribution were assessed using Western Blot and immunostaining, respectively. Changes in GJIC activity were assessed using scrape load dye transfer, and apoptosis was identified using differential dye staining assay. In RRECs or rMCs grown in HG medium, Rab20 expression was significantly increased concomitant with a decreased number of Cx43 plaques. Importantly, a significant increase in the number of Cx43 plaques and GJIC activity was observed in cells transfected with Rab20 siRNA. Additionally, Rab20 downregulation inhibited HG-induced apoptosis in RRECs and rMCs. Results indicate HG-mediated Rab20 upregulation decreases Cx43 localization at the cell surface, resulting in compromised GJIC activity. Reducing Rab20 expression could be a useful strategy in preventing HG-induced vascular and Müller cell death associated with diabetic retinopathy.
Dongjoon Kim, Casey Stottrup Lewis, Vijay P Sarthy, Sayon Roy

2403 related Products with: High-Glucose-Induced Rab20 Upregulation Disrupts Gap Junction Intercellular Communication and Promotes Apoptosis in Retinal Endothelial and Müller Cells: Implications for Diabetic Retinopathy.

1.00 flask1.00 flask1.00 flask1.00 flask1.00 flask1.00 flask1.00 flask96 assays500 MG100ug0.1 mg

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#33135714   // To Up

Nanobody-displaying porous silicon nanoparticles for the co-delivery of siRNA and doxorubicin.

Targeted delivery of chemotherapeutics to cancer cells has the potential to yield high drug concentrations in cancer cells while minimizing any unwanted side effects. However, the development of multidrug resistance in cancer cells may impede the accumulation of chemotherapy drugs within these, decreasing its therapeutic efficacy. Downregulation of multidrug resistance-related proteins such as MRP1 with small interfering RNA (siRNA) is a promising approach in the reversal of drug resistance. The co-delivery of doxorubicin (Dox) and siRNA against MRP1 (siMRP1) by using nanoparticles comprised of biocompatible porous silicon (pSi) presents itself as a novel opportunity to utilize the biomaterial's high loading capacity and large accessible surface area. Additionally, to increase the selectivity and retention of the delivery vehicle at the tumor site, nanobodies were incorporated onto the nanoparticle surface via a polyethylene glycol (PEG) linker directed towards either the epidermal growth factor receptor (EGFR) or the prostate specific membrane antigen (PSMA). The nanobody-displaying pSi nanoparticles (pSiNPs) demonstrated effective gene silencing, inhibiting MRP1 expression by 74 ± 6% and 74 ± 4% when incubated with EGFR-pSiNPs and PSMA-pSiNPs, respectively, in prostate cancer cells. The downregulation of MRP1 led to a further increase in cytotoxicity when both siRNA and Dox were delivered in conjunction in both cancer cell monocultures and spheroids when compared to free Dox or Dox and a scrambled sequence of siRNA. Altogether, nanobody-displaying pSiNPs are an effective carrier for the dual delivery of both siRNA and Dox for cancer treatment.
Terence Tieu, Marcin Wojnilowicz, Pie Huda, Kristofer J Thurecht, Helmut Thissen, Nicolas H Voelcker, Anna Cifuentes-Rius

1004 related Products with: Nanobody-displaying porous silicon nanoparticles for the co-delivery of siRNA and doxorubicin.

2.50 nmol 1 G 100 G 2x5L4x500ng25 mg250ul500IU 5 G10.1 mg100 ug

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#33100215   2020/10/25 To Up

Knockdown of long non-coding RNA SOX2OT downregulates SOX2 to improve hippocampal neurogenesis and cognitive function in a mouse model of sepsis-associated encephalopathy.

Aberrant hippocampal neurogenesis is an important pathological feature of sepsis-associated encephalopathy. In the current study, we examined the potential role of the long noncoding RNA (lncRNA) sex-determining region Y-box 2 (SOX2) overlapping transcript (SOX2OT), a known regulator of adult neurogenesis in sepsis-induced deficits in hippocampal neurogenesis and cognitive function.
Jialin Yin, Yanan Shen, Yanna Si, Yuan Zhang, Jiayue Du, Xiajuan Hu, Mengmeng Cai, Hongguang Bao, Yan Xing

1455 related Products with: Knockdown of long non-coding RNA SOX2OT downregulates SOX2 to improve hippocampal neurogenesis and cognitive function in a mouse model of sepsis-associated encephalopathy.

1 mg100ug Lyophilized100 μg100 μg0.2 mL100.00 ug100 μg100 ul16-22 Sample Kit100.00 ug1 mg0.2 mg

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