Biolmpacts
Volume:14 Issue: 1, Jan 2024

Epidermal growth factor receptor (EGFR) is a cell surface protein that plays a vital role in regulating cell growth and division. However, certain tumors, such as colorectal cancer (CRC), can exhibit an overexpression of EGFR, resulting in uncontrolled cell growth and tumor progression. To address this issue, therapies targeting and inhibiting EGFR activity have been developed to suppress cancer growth. Nevertheless, resistance to these therapies poses a significant obstacle in cancer treatment. Recent research has focused on comprehending the underlying mechanisms contributing to anti-EGFR resistance and identifying new targets to overcome this striking challenge. Long noncoding RNAs (lncRNAs) are a class of RNA molecules that do not encode proteins but play pivotal roles in gene regulation and cellular processes. Emerging evidence suggests that lncRNAs may participate in modulating resistance to anti-EGFR therapies in CRC. Consequently, combining lncRNA targeting with the existing treatment modalities could potentially yield improved clinical outcomes. Illuminating the involvement of lncRNAs in anti-EGFR resistance mechanisms of cancer cells can provide valuable insights into the development of novel anti-EGFR therapies in several solid tumors.

Patient-derived induced pluripotent stem cells (iPSCs) have been widely used as disease models to test new therapeutic strategies. Moreover, the regenerative potential of stem cells can be improved with the use of biologically active compounds. Our study was designed to explore the effect of honokiol, a small polyphenol molecule extracted from Magnolia officinalis, on the survival and culture time of iPSCderived neurons from a sporadic Alzheimer’s disease (AD) patient. This study aimed to generate iPSCs from peripheral blood mononuclear cells (PBMCs) of an AD patient using episomal plasmids with a nucleofector system and differentiate them into neurons. These iPSCderived neurons were used to investigate the effect of honokiol extracted from M. officinalis on their survival and long-term cultures.

IPSCs were generated from PBMCs of an AD patient by introducing Oct-3/4, Sox2, Klf4, L-Myc, and Lin28 using Nucleofector™ Technology. Differentiation of neurons derived from iPSCs was carried out using inducers and recognized by biomarkers. The viability of iPSC-derived neurons with the addition of honokiol extracted from the bark of M. officinalis was determined by the MTT analytical kit.

IPSCs were generated by reprogramming AD patient-derived PBMCs and subsequently converted into neurons. The survival and growth of iPSC-derived neurons were significantly enhanced by adding honokiol in the experiment conditions.

AD iPSC-derived neurons had a high viability rate when cultured in the presence of honokiol. These results have shown that AD iPSC-derived neurons can be an excellent model for screening neurotrophic agents and improving the conditions for long-term cultures of human iPSC-derived neurons. Honokiol proves to be a potential candidate for cellular therapeutics against neurodegenerative disorders.

Urinary tract infection (UTI) is one of the most common infections, usually caused by uropathogenic Escherichia coli (UPEC). However, antibiotics are a usual treatment for UTIs; because of increasing antibiotic-resistant strains, vaccination can be beneficial in controlling UTIs. Using immunoinformatics techniques is an effective and rapid way for vaccine development.

Three conserved protective antigens (FdeC, Hma, and UpaB) were selected to develop a novel multiepitope vaccine consisting of subunit B of cholera toxin (CTB) as a mucosal build-in adjuvant to enhance the immune responses. Epitopes-predicted B and T cells and suitable linkers were used to separate them and effectively increase the vaccine's immunogenicity. The vaccine protein's primary, secondary, and tertiary structures were evaluated, and the best 3D model was selected. Since CTB is the TLR2 ligand, molecular docking was made between the vaccine protein and TLR2. Molecular dynamic (MD) simulation was employed to evaluate the stability of the vaccine protein- TLR2 complex. The vaccine construct was subjected to in silico cloning.

The designed vaccine protein has multiple properties in the analysis. The HADDOCK outcomes show an excellent interaction between vaccine protein and TLR2. The MD results confirm the stability of the vaccine protein- TLR2 complex during the simulation. In silico cloning verified the expression efficiency of our vaccine protein.

The results of this study suggest that our designed vaccine protein could be

Ex vivo blood production is an urgent need of most countries, and creating production protocols can save the lives of many patients. Despite the recent advances in blood production in ex vivo conditions, its high-scale production is not yet possible, and requires further studies. Therefore, by transfecting fibroblast cells with miR-16, and miR-451 genes, as well as applying low frequency electromagnetic fields (ELF-EMF) treatment, we tried to increase the differentiation of these cells into CD71+ and CD235a+ erythroid like progenitors.

After preparation, and cultivation of human dermal transgenic fibroblast cells, they were transfected by Plenti3-hsa-miR451, Plenti3-hsa-miR16 and Plenti3-backbone inserted into E. coli Stbl4 genome. Then, transgenic fibroblast cells were treated with 10mT ELF-EMF every day for 20 minutes for 7 days. Using a flow cytometer, the expressions of CD71, and CD235a were studied in these cells, and the expressions of genes involved in hematopoiesis were studied using the RT-PCR technique.

The results indicated an increase in the differentiation of fibroblast cells treated with 10mT ELF-EMF to erythroid like progenitors. Furthermore, the percentage of CD71+ and CD235a+ cells was the highest in irradiated cells encoding miR-16 and miR-451, which indicates their differentiation into erythroid like progenitors. Also, in the transgenic cells treated with ELF-EMF, an increase in the expressions of α-chain, β-chain, γ-chain and GATA1 genes was observed, which indicates the potential of these cells for hematopoiesis. However, there was no significant difference in the expression of CD34 and CD38 genes in these cell lines.

Both ELF-EMF and upregulations of miR-16 and miR-451 lead to improved differentiation of fibroblast cells into erythroid like progenitors.

Biomaterials currently utilized for the regeneration of myocardial tissue seem to associate with certain restrictions, including deficiency of electrical conductivity and sufficient mechanical strength. These two factors play an important role in cardiac tissue engineering and regeneration. The contractile property of cardiomyocytes depends on directed signal transmission over the electroconductive systems that happen inside the innate myocardium. Because of their distinctive electrical behavior, electroactive materials such as graphene might be used for the regeneration of cardiac tissue.

In this review, we aim to provide deep insight into the applications of graphene and graphene derivative-based hybrid polymeric scaffolds in cardiomyogenic differentiation and cardiac tissue regeneration.

Synthetic biodegradable polymers are considered as a platform because their degradation can be controlled over time and easily functionalized. Therefore, graphene-polymeric hybrid scaffolds with anisotropic electrical behavior can be utilized to produce organizational and efficient constructs for macroscopic cardiac tissue engineering. In cardiac tissue regeneration, natural polymer based-scaffolds such as chitosan, gelatin, and cellulose can provide a permissive setting significantly supporting the differentiation and growth of the human induced pluripotent stem cells -derived cardiomyocytes, in large part due to their negligible immunogenicity and suitable biodegradability.

Cardiac tissue regeneration characteristically utilizes an extracellular matrix (scaffold), cells, and growth factors that enhance cell adhesion, growth, and cardiogenic differentiation. From the various evaluated electroactive polymeric scaffolds for cardiac tissue regeneration in the past decade, graphene and its derivatives-based materials can be utilized efficiently for cardiac tissue engineering.

Imaging a non-small cell lung cancer (NSCLC) using radiolabeled tyrosine kinase inhibitors (TKIs) has attracted attention due to their unique interaction with the target epidermal growth factor receptor (EGFR). Olmutinib (OTB) is one of the third-generation EGFR TKIs, which selectively inhibit EGFR L858R/T790M mutation. In this study, we aim to estimate the interaction of the iodinated OTB (I-OTB)-receptor complex by molecular docking. Furthermore, we will synthesize the I-OTB and evaluate its activity toward EGFR L858R/T790M by in vitro cytotoxicity assay.

A molecular docking simulation was carried out using an AutoDock Vina program package to estimate the interaction of the ligand-receptor complex. The I-OTB, N-{3-iodo-5-[(2- {[4-(4-methylpiperazin-1-yl)phenyl]aminothieno{3,2-d}pyrimidin-4-yl)oxy]phenyl} acrylamide, was synthesized by introducing an iodine atom in the phenyl group in the 3-aryloxyanilide structure. The half inhibitory concentration (IC50) was determined by employing a 2-(2-methoxy- 4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H tetrazolium monosodium salt (WST- 8) assay to evaluate the activity of I-OTB.

The docking study exhibited that I-OTB could take an interaction similar to that of the parent compound. We successfully synthesized I-OTB and confirmed its structure by instrumental analysis. The binding energy of OTB and I-OTB in complex with EGFR T790M are -8.7 and -7.9 kcal/mol, respectively. The cytotoxicity assay showed that I-OTB also has an affinity towards the EGFR L858R/T790M mutation with the IC50 10.49 ± 5.64 𝜇M compared to the EGFR wild type with the IC50 over than 10 𝜇M.

The cytotoxicity effect of I-OTB was comparable to that of OTB. This result indicates that the iodine substituent in OTB did not alter the parent compound selectivity toward double mutations EGFR L858R/T790M. Therefore, I-OTB is prominent for radioiodination, and [123/124I] I-OTB may be a promising candidate for EGFR L858R/T790M mutation imaging.

Peptide-based research has attained new avenues in the antibiotics and cancer drug resistance era. The basis of peptide design research lies in playing with or altering physicochemical parameters. Here in this work, we have done exploratory data analysis (EDA) of physicochemical parameters of antimicrobial peptides (AMPs) and anticancer peptides (ACPs), two promising therapeutics for microbial and cancer drug resistance to deduce patterns and trends.

Briefly, we have captured the natural AMPs and ACPs data from the APD3 database. After cleaning the data manually and by CD-HIT web server, further data analysis has been done using Python-based packages, modlAMP and Pandas. We have extracted the descriptive statistics of 10 physicochemical parameters of AMPs and ACPs to build a comprehensive dataset containing all major parameters. The global analysis of datasets has been done using modlAMP to find the initial patterns in global data. The subsets of AMPs and ACPs were curated based on the length of the peptides and were analyzed by Pandas package to deduce the graphical profile of AMPs and ACPs.

EDA of AMPs and ACPs shows selectivity in the length and amino acid compositions. The distribution of physicochemical parameters in defined quartile ranges was observed in the descriptive statistical and graphical analysis. The preferred length range of AMPs and ACPs was found to be 21-30 amino acids, whereas few outliers in each parameter were evident after EDA analysis.

The derived patterns from natural AMPs and ACPs can be used for the rational design of novel peptides. The statistical and graphical data distribution findings will help in combining the different parameters for potent design of novel AMPs and ACPs.

Breast cancer is the most common cancer in women worldwide, and the triple-negative subtype is the most invasive, with limited therapeutic options. Since miRNAs are involved in many cellular processes, they harbor great value for cancer treatment. Therefore, in this study, we have investigated the anti-proliferative and anti-invasive roles of miR342 in 4T1 triple-negative cells in vitro and also studied the effect of this miRNA on tumor progression and the expression of its target genes in vivo.

4T1 cells were transduced with conditioned media of miR342-transfected Hek-LentiX cells. MTT and clonogenic assays were used to assess the viability and colony-forming ability of 4T1 cells. Apoptosis and invasion rates were respectively evaluated by annexin/7-AAD and wound healing assays. At last, in vivo tumor progression was evaluated using H&E staining, real-time PCR, and immunohistochemistry.

The viability of transduced-4T1 cells reduced significantly 48 hours after cell seeding and colony forming ability of these cells reduced to 50% of the control group. Also, miR342 imposed apoptotic and anti-invasive influence on these cells in vitro. A 30-day follow-up of the breast tumor in the mice model certified significant growth suppression along with reduced mitotic index and tumor grade in the treatment group. Moreover, decreased expression of Bcl2l1, Mcl1, and ID4, as miR342 target genes, was observed, accompanied by reduced expression of VEGF and Bcl2/Bax ratio at the protein level.

To conclude, our data support the idea that miR342 might be a potential therapeutic target for the treatment of triple-negative breast cancer (TNBC).