Avicenna Journal of Medical Biotechnology
Volume:13 Issue: 1, Jan-Mar 2021

The application of non-viral systems for delivering genes to cells is becoming a very interesting issue, especially in the treatment of neoplasms such as Breast Cancer (BC). Polymer-based non-viral systems are safe and feasible gene carriers to be used in targeted cancer therapy. SALL4 gene encodes a transcription factor and is overexpressed in some cancers.

In this study, carboxyalkylated-PEI25 (25 kDa) was used to deliver plasmids expressing SALL4-siRNA into MCF-7 cells. DLS and AFM were applied to determine the size of nanoparticles. The MTT method was used to assess cytotoxicity, and the efficiency of transfection was confirmed both qualitatively and quantitatively. Finally, the effect of silencing SALL4 was investigated on the migration of MCF7 cells using the scratch test.

The results showed that transferring the SALL4-siRNA using PEI25G10C50 reduced the expression of the corresponding transcription factor by 14 folds which attenuated the migration of MCF-7 cells by 58%.

In conclusion, PEI25G10C50 can serve as an effective gene delivery system for treating BC by targeting SALL-4.

Metallic nanoparticles are useful materials to be applied in biomedical research. In this study, the possible apoptotic and anti-metastatic activity of Zinc Oxide Nanoparticles (ZnONPs) was assessed in breast cancer cells.

First, in vitro cell viability was investigated by MTT assay in two human breast cancer cells (MCF-7 and T47D) and normal Human Embryonic Kidney (HEK293) cells at 37°C overnight. Apoptosis induced by ZnONPs was evaluated by annexin V/PI staining, cell cycle analysis and caspase assay in cancerous cells. Moreover, quantitative real-time PCR was employed for the detection of two metastasis suppressor genes (KAI-1 and NM23) expression in cancerous cells.

Data demonstrated that ZnONPs exert a dose-dependent inhibitory effect on the viability of T47D and MCF-7 cells, while no cytotoxic effect was observed on normal HEK293 cells. The mRNA expression levels of KAI-1 and non-metastatic protein (NM23) genes were up-regulated in ZnONP-exposed cancerous cells. ZnONPs were also found to enhance the apoptosis properties of cells by annexin V/PI staining, and caspase assay in cancerous cells. Furthermore, ZnONPs can increase sub-G1 population as compared to negative control.

Our findings showed that ZnONPs induce apoptotic activity and can modulate metastasis by up-regulating of KAI-1 and NM23 gene expression in two breast cancer (MCF-7 and T47D) cells.

The prevalence of Coronary Artery Disease (CAD) in developing countries is on the rise, owing to rapidly changing lifestyle. Therefore, it is imperative that the underlying genetic and molecular mechanisms be understood to develop specific treatment strategies. Comprehensive disease network and Gene Ontology (GO) studies aid in prioritizing potential candidate genes for CAD and also give insights into gene function by establishing gene and disease pathway relationships.

In the present study, CAD-associated genes were collated from different data sources and protein-protein interaction network was constructed using STRING. Highly interconnected network clusters were inferred and GO analysis was performed.

Interrelation between genes and pathways were analyzed on ClueGO and 38 candidates were identified from 1475 CAD-associated genes, which were significantly enriched in CAD-related pathways such as metabolism and regulation of lipid molecules, platelet activation, macrophage derived foam cell differentiation, and blood coagulation and fibrin clot formation.

Integrated network and ontology analysis enables biomarker prioritization for common complex diseases such as CAD. Experimental validation and future studies on the prioritized genes may reveal valuable insights into CAD development mechanism and targeted treatment strategies.

Tau is a disordered Microtubule Associated Protein (MAP) which prefers to bind and stabilize microtubules. Phosphorylation of tau in particular enhances tautubulin interaction which otherwise detaches from tubulin during hyperphosphorylation. The reason behind their destabilization, detachment and the role of β subunit (from microtubule) and the projection domain (Tau) in microtubule stability remains elusive till date. Thus, a complete 3D structural investigation of tau protein is much needed to address these queries as the existing crystal structures are in fragments and quite limited.

In this study, the modelled human tau protein was subjected to phosphorylation and hyperphosphorylation which were later considered for docking with microtubules (βα subunits-inter dimer) and vinblastine.

Phosphorylated tau protein interacts with both α- and β subunits. But stronger bonding was with α- compared to β subunits. Regarding β subunit, proline rich loop and projection domain actively participated in tau binding. Interestingly, hyperphosphorylation of tau increases MAP domain flexibility which ultimately results in tau detachment, the main reason behind tangle formation in Alzheimer’s disease.

This study being the first of its kind emphasizes the role of projection domain and proline rich region of β-subunit in stabilizing the tau-tubulin interaction and also the effect of hyperphosphorylation in protein-protein and protein-drug binding.

The purpose of this study was to systematically review the prevalence of class 1 integrons, antibiotic resistance pattern in Pseudomonas aeruginosa (P. aeruginosa) isolated from clinical samples other than burn samples.

The Web of Science, PubMed, Scopus, and Science Direct databases were searched using keywords based on the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. The cross-sectional studies published from 1st January 2000 until 1st January 2019 were included which addressed the prevalence of class 1 integrons and antibiotic-resistance in P. aeruginosa isolated from clinical samples other than burn samples. Meta-analysis was conducted using Comprehensive Meta-Analysis (CMA) software. The random-effects model, Cochran’s Q and I2 tests were applied for statistical analyses.

Eight articles met the eligibility standards for including in the present metaanalysis. The combined prevalence of class 1 integrons in P. aeruginosa isolated from clinical samples other than burn samples was reported by 40% (95% CI:26.1-55.8%). The pooled prevalence of Multi-Drug Resistant (MDR) P. aeruginosa isolates was 70.1%. The highest prevalence of combined antibiotic resistance was related to carbenicillin with a resistance rate of 79.9%. In general, 6 (75%) out of the 8 included studies showed the correlation between the presence of class 1 integrons and antibiotic resistance.

Regarding the correlation between the presence of integrons and the high antibiotic resistance reported by studies included in the present review, there is the need for preventive measures to prevent the spread of resistance by integrons and transferring to other micro-organisms.

Silver nanoparticles (AgNP) are commonly used metallic nanoparticles in health care systems. Colon cancer incidence is increasing worldwide. In this study, AgNP was synthesized using β-sitosterol and its cytotoxic potential was evaluated in human colon cancer (HT-29) cells.

Characterization of AgNP was analyzed by TEM and spectrophotometry analysis. HT-29 cells were treated with different concentrations (2, 4, 6, 8 and 10 ng/ ml) of AgNPs and cytotoxicity was evaluated by MTT assay. The apoptosis was analyzed by the flow cytometry. The expression of p53 protein was analyzed by western blotting.

β-sitosterol mediated AgNP are spherical in shape and induced concentration-dependent cytotoxicity in HT-29 cells. AgNP caused apoptosis related morphological changes as evidenced by annexin positive staining. AgNP treatments also induced the p53 expression in HT-29 cells.

Our present result suggests that β-sitosterol mediated AgNP induce apoptosis in colon cancer cells and this finding may pave the way for further experimental analysis in vivo.

The present study aimed to investigate the antifungal activity of Nanoparticles (NPs) against amphotericin B-resistant Candida glabrata (C. glabrata) strains.

Twelve resistant (C. glabrata) strains were isolated from archived clinical isolates. Antifungal activity was conducted according to Clinical and Laboratory Standards Institute’s (CLSI) guidelines, document M27-A3/S4. The Scanning Electron Microscope (SEM) was used to observe the morphological changes of strains exposed to each nanoparticle.

Minimum Inhibitory Concentration (MIC) of nanoparticles of all strains was in the concentration range of 0.125 to 0.5 µg/Ml. The synthesized Ag-NPs showed superior antifungal activity against (C. glabrata) compared to Se-NPs and Au-NPs. The scanning electron microscope images revealed the difference in the fungal morphology between the untreated and treated fungi with nanoparticles.

The Ag-NPs, followed by Se-NPs synthesized, revealed significant antifungal activity against resistance regardless of their antifungal-resistant mechanisms.