Novel Mutation in FRDA Gene among Iranian Patients with Friedreich's Ataxia

Introduction: Friedrich Ataxia’s diagnosis is typically based on clinical symptoms and extended GAA repeats. However, in some rare cases the disease is caused as a result of the mutation in the exons of the FRDA (Friedreich's ataxia) gene. The current study aimed to examine point mutations in exon 1 of the FRDA gene with the goal of finding a better way for diagnosing people suspected of this disease. Materials and Methods: In this study, 30 suspected patients of Friedrich Ataxia underwent PCR molecular test. Subsequently, sequencing and long PCR were utilized to assess exon 1 in five patients with extended repeats. Results: In total, 25 participants who had extended repeats were diagnosed with Friedrich Ataxia. In one out of the five patients, the nucleotide change from G to T was observed in the nucleotide number 815324. Conclusion: Since the change had a heterozygous nature, it did not cause any deficiency in Frataxin protein. Given that family marriages are prevalent in Iran, there is a possibility of homozygosity with this mutation or other mutations. It is thus recommended that gene sequencing should be performed for individuals with suspected Friedrich Ataxia

Niosomal Formulation for Co-Administration of Hydrophobic Anticancer Drugs into MCF-7 Cancer Cells

Introduction: Designing and developing drug delivery systems has received tremendous attention during the last decade. The treatment of cancer cells is a complicated process due to the existence of different biological pathways. Therefore, the co-delivery of different drugs could have a synergic effect on the treatment process.Materials and Methods: In this study, different types of span (20, 60, 80) and cholesterol were utilized to formulate tamoxifen/curcumin co-loaded niosomes as a drug carrier system for breast cancer chemotherapy. Niosome characterization was performed through a set of instrument analysis techniques including scanning electron microscopy (SEM) and dynamic light scattering. Release behavior was studied by dialysis method at (pH = 5, 7.4). The stability was monitored during two months storage at two temperatures (4 and 25 °C). Cytotoxicity activity of the best niosomal formulation were assessed on MCF-7 cells, using MTT assay.Results: The optimal niosomal formulation with span 80 and lipid-to-drug molar ratio of 20 was selected, with maximum encapsulation of both drugs and minimum size. Drug release behavior at physiological pH (7.4) (with significant drug release under acidic conditions (pH = 5) and storage stability of up to 2 weeks with little change in drug efficacy and measurement makes it a proper candidate for breast cancer treatment.Conclusion: Finally, the results of this study showed the importance of creating highly biocompatible formulations, allowing the simultaneous transfer of two drugs with controlled release to cancer cells which could improve the chemotherapy process with the synergistic effect of the two drugs

Anti-regulatory T cell vaccines in immunotherapy: focusing on FoxP3 as target

Anti- tumor vaccination elicits imperfect immune responses against tumor cells; that is related to the presence of suppressive obstacles in the tumor microenvironment. The main members of suppressive milieu of tumor are heteroogenous groups of immune cells in which regulatory T cell is a substantial component. Tregs express different immunomodulatory molecules such as FoxP3. Transcription factor, FoxP3, is a specific intracellular marker of Treg and crucial for Treg development. Therefore it is an attractive target for cancer treatment. This article reviews some recent anti-Treg vaccine focusing on FoxP3 to ameliorate anti-tumor immune responses. Among them, fusion vaccine of FoxP3-Fc(IgG) recombinant DNA vaccine and its accordant protein vaccine represents effective results

The therapeutic effect of conditioned medium of human amniotic membrane stem cells on heart failure in rats

Background. The conditioned medium of stem cells plays an important role in the treatment of various diseases such as heart damage, but its molecular mechanisms are unknown. Therefore, this study aimed to investigate one of the mechanisms of the effect of this substance in the treatment of male rats with heart failure. Methods. A total of 20 male rats were divided into four groups, control, heart failure, heart failure receiving culture medium, and medium condition groups. Heart failure was induced in all groups except the comtrol group with isoproterenol, then, culture medium and conditioned medium were injected into the related animals 28 days after HF induction. Afterward, the expressions of caspase 3 and 9 factors were examined. Results. Changes in the expressions of caspase 3, caspase 9, and GAPDH genes in the four groups were evaluated real-time PCR. Furthermore, the average expressions of caspase 3 and 9 in four groups were compared using ELISA. All data revealed that the induction of heart failure increased the expression of apoptotic factors compared to the control group, and that the treatment with a conditioned medium caused a significant decrease in apoptotic factors compared to the heart failure group (P≤0.05). Conclusion. It was concluded that the conditioned medium of human amniotic membrane mesenchymal stem cells was able to improve heart failure by targeting the apoptosis pathway. Practical Implications. The findings of this study highlighted the importance of this compound as a suitable candidate for treating heart failure in the future

Efficient targeting of HIF-1α mediated by YC-1 and PX-12 encapsulated niosomes: potential application in colon cancer therapy

Abstract A number of molecular biofactors have been documented in pathogenesis and poor prognosis of colorectal cancer (CRC). Among them, the Hypoxia-Inducible Factor (HIF-1a) is frequently reported to become over-expressed, and its targeting could restrict and control a variety of essential hallmarks of CRC. Niosomes are innovative drug delivery vehicles with the encapsulating capacity for co-loading both hydrophilic and hydrophobic drugs at the same time. Also, they can enhance the local accumulation while minimizing the dose and side effects of drugs. YC-1 and PX-12 are two inhibitors of HIF-1a. The purpose of this work was to synthesize dual-loaded YC-1 and PX-12 niosomes to efficiently target HIF-1α in CRC, HT-29 cells. The niosomes were prepared by the thin-film hydration method, then the niosomal formulation of YC-1 and PX-12 (NIO/PX-YC) was developed and optimized by the central composition method (CCD) using the Box-Behnken design in terms of size, polydispersity index (PDI), entrapment efficiency (EE). Also, they are characterized by DLS, FESEM, and TEM microscopy, as well as FTIR spectroscopy. Additionally, entrapment efficiency, in vitro drug release kinetics, and stability were assessed. Cytotoxicity, apoptosis, and cell cycle studies were performed after the treatment of HT-29 cells with NIO/PX-YC. The expression of HIF-1αat both mRNA and protein levels were studied after NIO/PX-YC treatment. The prepared NIO/PX-YC showed a mean particle size of 185 nm with a zeta potential of about-7.10 mv and a spherical morphology. Also, PX-12 and YC-1 represented the entrapment efficiency of about %78 and %91, respectively, with a sustainable and controllable release. The greater effect of NIO/PX-YC than the free state of PX-YC on the cell survival rate, cell apoptosis, and HIF-1α gene/protein expression were detected (p < 0.05). In conclusion, dual loading of niosomes with YC-1 and PX-12 enhanced the effect of drugs on HIF-1α inhibition, thus boosting their anticancer effects. Graphical Abstrac