The serious drawbacks of the conventional treatment of pancreatic ductal adenocarcinoma (PDAC) such as nonspecific toxicity and high resistance to chemo and radiation therapy, have prompted the development and application of countless small interfering RNA (siRNA)‐based therapeutics. Recent advances in drug delivery systems hold great promise for improving siRNA‐based therapeutics and developing a new class of drugs, known as nano‐siRNA drugs. However, many fundamental questions, regarding toxicity, immunostimulation, and poor knowledge of nano‐bio interactions, need to be addressed before clinical translation. In this review, we provide recent achievements in the design and development of various nonviral delivery vehicles for pancreatic cancer therapy. More importantly, codelivery of conventional anticancer drugs with siRNA as a new revolutionary pancreatic cancer combinational therapy is completely discussed.
The serious drawbacks of conventional pancreatic ductal adenocarcinoma (PDAC) therapy like nonspecific toxicity and high resistance to chemo and radiation therapy, prompted the development and application of countless siRNA-based therapeutics. Significant technological success has been achieved in this area; however, the major challenges to siRNA-based therapeutics becoming a new paradigm in the pancreatic cancer therapy stem from enzymatic digestion, off-target effects, difficulty to enter cells, induction of innate immune responses, and renal clearance. Recent advances in drug delivery systems hold great promise for improving siRNA-based therapeutics and developing a new class of drugs, nano-siRNA drugs. However, a number of fundamental questions, regarding toxicity, immunostimulation, and poor knowledge of nano-bio interactions, need to be addressed before clinical translation. In this review, we provide recent achievements in designing and development of various non-viral delivery vehicles for pancreatic cancer therapy. More importantly, co-delivery of conventional anticancer drugs with siRNA as a new revolutionary pancreatic cancer combinational therapy is completely discussed.
Protein complexes are involved in many vital biological processes. Therefore, researchers need these protein complexes for biochemical and biophysical studies. Several methods exist for expressing multi-subunit proteins in eukaryotic cells, such as 2A sequences, IRES, or intein. Nevertheless, each of these elements has several disadvantages that limit their usage. In this article, we suggest a new system for expressing multi-subunit proteins, which have several advantages over existing methods meanwhile it, lacks most of their disadvantages. Leishmania is a unicellular eukaryote and member of the Trypanosomatidae family. In the expression system of Leishmania, pre-long RNAs that contain several protein sequences transcribe. Then these long RNAs separate into mature mRNAs in the process named trans splicing. For producing multi-subunit protein, Leishmania transformed with a vector containing the sequences of all subunits. Therefore, those subunits translate and form the complex under eukaryotic cell conditions. The sequence of each protein must separate by the spatial sequence needed for trans splicing. Based on a Leishmania expression pattern, not only is it possible to produce the complexes with the correct structures and post-translational modifications, but also it is possible to overcome previous method problems.
Engineered probiotics (EPs) are a group of probiotics whose proteome is manipulated by biotechnological techniques. EPs have attracted a lot of attention in recent researches for preventing and treating chronic diseases. The current study has been conducted to provide an overview regarding the EPs application in the treatment of chronic disease by a comprehensive systematic review of the published articles up to January 2022. To retrieve the related publications, three databases (PubMed/MEDLINE, Web of Sciences, and Scopus) were searched systematically. Finally, all human (n = 2) and
Background: Leishmania is a eukaryotic protozoan parasite belonging to the Trypanosomatidae family. The Iranian Lizard Leishmania (I.L.L.), which is non-pathogenic to mammals, shows great promise to be used as an expression system for recombinant protein production. Unlike other Leishmania strains, the ideal culture medium for I.L.L. has not been established, although it is commonly cultured in the RPMI1640 medium.
Methods: We investigated the growth rate of the wild and recombinant I.L.L. in BHI, RPMI1640, LB, and M199 media with and without FBS, hemin, or lyophilized rabbit serum. Subsequently, the expression rate of the recombinant protein in these media was compared.
Results: The growth rate of I.L.L. in RPMI1640 medium and LB broth was similar and supplementation with 10% FBS did not affect the growth rate. The amount of protein expression in the LB medium was higher than in the other three media.
Conclusion: The LB broth is an appropriate medium for I.L.L. culture and recombinant protein production.
Objectives: Juvenile idiopathic arthritis (JIA) is a childhood autoimmune rheumatoid disease. Past studies have confirmed that JIA is a complex disease, which means that genes and environmental factors affect the aetiology of the disease. In this study, we analysed the expression of interleukin 32, forkhead box P3 (FOXP3), methyl-CpG binding domain protein 1 (MBD1), and methyl-CpG-binding protein 2 (MECP2) in peripheral blood mononuclear cells of children with JIA in comparison with the expression of those in healthy children. Interleukin 32 is an inflammatory factor, FOXP3 is a transcription factor, and MBD1 and MECP2 are binding proteins that bind to the methylated deoxyribonucleic acid (DNA). Material and methods: We collected blood from JIA patients who had been diagnosed and classified into clinical subtypes by a rheumatologist from the division of paediatric rheumatology. Healthy children, whose clinical and preclinical analysis confirmed they had no disease and just came to the hospital for a check-up or minor surgical procedures were considered as a control group. Age and gender were matched in patients and the control group. Total ribonucleic acid was extracted from blood, and cDNA was synthesized. Eventually, the transcript levels were analysed by quantitative polymerase chain reaction, and statistical analysis was carried out. Results: Statistical analysis of gene expressions in young females affected by JIA demonstrated that MECP2 and FOXP3 were increased significantly (p-value = 0.002 and 0.05, respectively). Interleukin 32 gene expression was also increased (p-value = 0.14), whereas MBD1 gene expression was decreased (p-value = 0.06); however, these changes in the expression of all 4 genes were not significant in young males. Conclusions: Different expression levels of the mentioned genes between affected young females and males result from hormones in both gender and also methotrexate (MTX) drug. Also, the reason affected young females are more prone to JIA than males can be the lower level of FOXP3 expression in healthy females than healthy males.
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