Modelling the impact of nucleolin expression level on the activity of F3 peptide-targeted pH-sensitive pegylated liposomes containing doxorubicin

Background: Doxorubicin (DOX) is the most common drugs used in cancer therapy, including Hepatocellular Carcinoma (HCC). Drug resistance, is one of chemotherapy’s significant problems. Emerging studies have shown that microRNAs (miRNAs) could participate in regulating this mechanism. Nevertheless, the impact of miRNAs on HCC chemoresistance is still enigmatic. Objective: Investigating the role of miR-520c-3p in enhancement of anti-tumor effect of DOX against HepG2 cells. Methods: Expression profile for liver related miRNAs (384 miRNAs) has been analyzed on HepG2 cells treated with DOX using qRT-PCR. miR-520c-3p, the most deregulated miRNA, was selected for combination treatment with DOX. Expression level for LEF1, CDK2, CDH1, VIM, Mcl-1 and TP53 was evaluated in miR-520c-3p transfected cells. Cell viability, colony formation, wound healing as well as apoptosis assays have been demonstrated. Furthermore, Mcl-1 protein level was measured using western blot technique. Results: The present data indicated that miR-520c-3p overexpression could render HepG2 cells chemo-sensitive to DOX through enhancing its suppressive effects on proliferation, migration, and induction of apoptosis. The suppressive effect of miR-520c-3p involved altering the expression levels of some key regulators of cell cycle, proliferation, migration and apoptosis including LEF1, CDK2, CDH1, VIM, Mcl-1 and TP53. Interestingly, Mcl-1 was found to be one of the potential targets of miR-520c-3p, and its protein expression level was down-regulated upon miR-520c-3p overexpression. Conclusion: Our data referred to the tumor suppressor function of miR-520c-3p that could modulate chemosensitivity of HepG2 cells toward DOX treatment, providing a promising therapeutic strategy in HCC.

Download Full-text

The impact of gene-body H3K36me3 patterns on gene expression level changes in chronic myelogenous leukemia

Gene ◽

10.1016/j.gene.2021.145862 ◽

2021 ◽

pp. 145862

Author(s):

Lu-Qiang Zhang ◽

Jun-Jie Liu ◽

Li Liu ◽

Guo-Liang Fan ◽

Yan-Nan Li ◽

...

Keyword(s):

Gene Expression ◽

Chronic Myelogenous Leukemia ◽

Myelogenous Leukemia ◽

Gene Expression Level ◽

Expression Level ◽

Gene Body ◽

The Impact

Download Full-text

The Impact of HER2/neu Expression Level on Response to the E75 Vaccine: From U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02

Clinical Cancer Research ◽

10.1158/1078-0432.ccr-08-1126 ◽

2009 ◽

Vol 15 (8) ◽

pp. 2895-2904 ◽

Cited By ~ 73

Author(s):

Linda C. Benavides ◽

Jeremy D. Gates ◽

Mark G. Carmichael ◽

Ritesh Patel ◽

Jarrod P. Holmes ◽

...

Keyword(s):

Clinical Trials ◽

Expression Level ◽

The Impact

Download Full-text

Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases

Cells ◽

10.3390/cells9112346 ◽

2020 ◽

Vol 9 (11) ◽

pp. 2346

Author(s):

Aline Yammine ◽

Amira Zarrouk ◽

Thomas Nury ◽

Anne Vejux ◽

Norbert Latruffe ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Expression Level ◽

Cholesterol Oxidation ◽

Mrna Levels ◽

Antioxidant Genes ◽

Dietary Polyphenols ◽

N2a Cells ◽

Age Related ◽

The Impact

The Mediterranean diet is associated with health benefits due to bioactive compounds such as polyphenols. The biological activities of three polyphenols (quercetin (QCT), resveratrol (RSV), apigenin (API)) were evaluated in mouse neuronal N2a cells in the presence of 7-ketocholesterol (7KC), a major cholesterol oxidation product increased in patients with age-related diseases, including neurodegenerative disorders. In N2a cells, 7KC (50 µM; 48 h) induces cytotoxic effects characterized by an induction of cell death. When associated with RSV, QCT and API (3.125; 6.25 µM), 7KC-induced toxicity was reduced. The ability of QCT, RSV and API to prevent 7KC-induced oxidative stress was characterized by a decrease in reactive oxygen species (ROS) production in whole cells and at the mitochondrial level; by an attenuation of the increase in the level and activity of catalase; by attenuating the decrease in the expression, level and activity of glutathione peroxidase 1 (GPx1); by normalizing the expression, level and activity of superoxide dismutases 1 and 2 (SOD1, SOD2); and by reducing the decrease in the expression of nuclear erythroid 2-like factor 2 (Nrf2) which regulates antioxidant genes. QCT, RSV and API also prevented mitochondrial dysfunction in 7KC-treated cells by counteracting the loss of mitochondrial membrane potential (ΨΔm) and attenuating the decreased gene expression and/or protein level of AMP-activated protein kinase α (AMPKα), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) implicated in mitochondrial biogenesis. At the peroxisomal level, QCT, RSV and API prevented the impact of 7KC by counteracting the decrease in ATP binding cassette subfamily D member (ABCD)3 (a peroxisomal mass marker) at the protein and mRNA levels, as well as the decreased expresssion of genes associated with peroxisomal biogenesis (Pex13, Pex14) and peroxisomal β-oxidation (Abcd1, Acox1, Mfp2, Thiolase A). The 7KC-induced decrease in ABCD1 and multifunctional enzyme type 2 (MFP2), two proteins involved in peroxisomal β-oxidation, was also attenuated by RSV, QCT and API. 7KC-induced cell death, which has characteristics of apoptosis (cells with fragmented and/or condensed nuclei; cleaved caspase-3; Poly(ADP-ribose) polymerase (PARP) fragmentation) and autophagy (cells with monodansyl cadaverine positive vacuoles; activation of microtubule associated protein 1 light chain 3–I (LC3-I) to LC3-II, was also strongly attenuated by RSV, QCT and API. Thus, in N2a cells, 7KC induces a mode of cell death by oxiapoptophagy, including criteria of OXIdative stress, APOPTOsis and autoPHAGY, associated with mitochondrial and peroxisomal dysfunction, which is counteracted by RSV, QCT, and API reinforcing the interest for these polyphenols in prevention of diseases associated with increased 7KC levels.

Download Full-text

Distinct Expression and Methylation Patterns for Genes with Different Fates following a Single Whole-Genome Duplication in Flowering Plants

Molecular Biology and Evolution ◽

10.1093/molbev/msaa105 ◽

2020 ◽

Vol 37 (8) ◽

pp. 2394-2413 ◽

Cited By ~ 3

Author(s):

Tao Shi ◽

Razgar Seyed Rahmani ◽

Paul F Gugger ◽

Muhua Wang ◽

Hui Li ◽

...

Keyword(s):

Protein Interactions ◽

Flowering Plants ◽

Expression Level ◽

Small Scale ◽

Whole Genome ◽

Functional Constraints ◽

Expression Divergence ◽

Protein Protein Interactions ◽

Methylation Patterns ◽

The Impact

Abstract For most sequenced flowering plants, multiple whole-genome duplications (WGDs) are found. Duplicated genes following WGD often have different fates that can quickly disappear again, be retained for long(er) periods, or subsequently undergo small-scale duplications. However, how different expression, epigenetic regulation, and functional constraints are associated with these different gene fates following a WGD still requires further investigation due to successive WGDs in angiosperms complicating the gene trajectories. In this study, we investigate lotus (Nelumbo nucifera), an angiosperm with a single WGD during the K–pg boundary. Based on improved intraspecific-synteny identification by a chromosome-level assembly, transcriptome, and bisulfite sequencing, we explore not only the fundamental distinctions in genomic features, expression, and methylation patterns of genes with different fates after a WGD but also the factors that shape post-WGD expression divergence and expression bias between duplicates. We found that after a WGD genes that returned to single copies show the highest levels and breadth of expression, gene body methylation, and intron numbers, whereas the long-retained duplicates exhibit the highest degrees of protein–protein interactions and protein lengths and the lowest methylation in gene flanking regions. For those long-retained duplicate pairs, the degree of expression divergence correlates with their sequence divergence, degree in protein–protein interactions, and expression level, whereas their biases in expression level reflecting subgenome dominance are associated with the bias of subgenome fractionation. Overall, our study on the paleopolyploid nature of lotus highlights the impact of different functional constraints on gene fate and duplicate divergence following a single WGD in plant.

Download Full-text

Delivery of docetaxel using pH-sensitive liposomes based on D-α-tocopheryl poly(2-ethyl-2-oxazoline) succinate: Comparison with PEGylated liposomes

Asian Journal of Pharmaceutical Sciences ◽

10.1016/j.ajps.2018.07.005 ◽

2019 ◽

Vol 14 (4) ◽

pp. 391-404 ◽

Cited By ~ 5

Author(s):

Shu Han ◽

Ruiyang Sun ◽

Hong Su ◽

Jing Lv ◽

Huan Xu ◽

...

Keyword(s):

Ph Sensitive ◽

Pegylated Liposomes

Download Full-text

QbD Based Media Development for the Production of Fab Fragments in E. coli

Bioengineering ◽

10.3390/bioengineering6020029 ◽

2019 ◽

Vol 6 (2) ◽

pp. 29 ◽

Cited By ~ 3

Author(s):

Deepak Kumar ◽

Jyoti Batra ◽

Claire Komives ◽

Anurag Rathore

Keyword(s):

Product Quality ◽

Process Parameters ◽

Basal Medium ◽

Fractional Factorial ◽

Age Related Macular Degeneration ◽

Expression Level ◽

Maximum Effect ◽

Manufacturing Cost ◽

Fab Fragment ◽

The Impact

Ranibizumab is a biotherapeutic Fab fragment used for the treatment of age-related macular degeneration and macular oedema. It is currently expressed in the gram-negative bacterium, Escherichia coli. However, low expression levels result in a high manufacturing cost. The protein expression can be increased by manipulating nutritional requirements (carbon source, nitrogen source, buffering agent), process parameters (pH, inducer concentration, agitation, temperature), and the genetic make-up of the producing strain. Further, understanding the impact of these factors on product quality is a requirement as per the principles of Quality by Design (QbD). In this paper, we examine the effect of various media components and process parameters on the expression level and quality of the biotherapeutic. First, risk analysis was performed to shortlist different media components based on the literature. Next, experiments were performed to screen these components. Eight components were identified for further investigation and were examined for their effect and interactions using a Fractional Factorial experimental design. Sucrose, biotin, and pantothenate were found to have the maximum effect during Fab production. Furthermore, cyanocobalamin glutathione and biotin-glutathione were the most significant interactions observed. Product identification was performed with Liquid Chromatography–Mass Spectrometry (LC-MS), the expression level was quantified using Bio-layer Interferometry, Reverse Phase-HPLC, and SDS-PAGE, and product quality were measured by RP-HPLC. Overall, a five-fold enhancement of the target protein titer was obtained (from 5 mg/L to 25 mg/L) using the screened medium components vis-a-vis the basal medium, thereby demonstrating the efficacy of the systematic approach purported by QbD.

Download Full-text