Update on immune-based therapy strategies targeting cancer stem cells.

Accumulating data reveals that tumors possess a specialized subset of cancer cells named cancer stem cells (CSCs), responsible for metastasis and recurrence of malignancies, with various properties such as self-renewal, heterogenicity, and capacity for drug resistance. Some signaling pathways or processes like Notch, epithelial to mesenchymal transition (EMT), Hedgehog (Hh), and Wnt, as well as CSCs' surface markers such as CD44, CD123, CD133, and epithelial cell adhesion molecule (EpCAM) have pivotal roles in acquiring CSCs properties. Therefore, targeting CSC-related signaling pathways and surface markers might effectively eradicate tumors and pave the way for cancer survival. Since current treatments such as chemotherapy and radiation therapy cannot eradicate all of the CSCs and tumor relapse may happen following temporary recovery, improving novel and more efficient therapeutic options to combine with current treatments is required. Immunotherapy strategies are the new therapeutic modalities with promising results in targeting CSCs. Here, we review the targeting of CSCs by immunotherapy strategies such as dendritic cell (DC) vaccines, chimeric antigen receptors (CAR)-engineered immune cells, natural killer-cell (NK-cell) therapy, monoclonal antibodies (mAbs), checkpoint inhibitors, and the use of oncolytic viruses (OVs) in pre-clinical and clinical studies. This review will mainly focus on blood malignancies but also describe solid cancers.

Novel Gene-Correction-Based Therapeutic Modalities for Monogenic Liver Disorders.

The majority of monogenic liver diseases are autosomal recessive disorders, with few being sex-related or co-dominant. Although orthotopic liver transplantation (LT) is currently the sole therapeutic option for end-stage patients, such an invasive surgical approach is severely restricted by the lack of donors and post-transplant complications, mainly associated with life-long immunosuppressive regimens. Therefore, the last decade has witnessed efforts for innovative cellular or gene-based therapeutic strategies. Gene therapy is a promising approach for treatment of many hereditary disorders, such as monogenic inborn errors. The liver is an organ characterized by unique features, making it an attractive target for in vivo and ex vivo gene transfer. The current genetic approaches for hereditary liver diseases are mediated by viral or non-viral vectors, with promising results generated by gene-editing tools, such as CRISPR-Cas9 technology. Despite massive progress in experimental gene-correction technologies, limitations in validated approaches for monogenic liver disorders have encouraged researchers to refine promising gene therapy protocols. Herein, we highlighted the most common monogenetic liver disorders, followed by proposed genetic engineering approaches, offered as promising therapeutic modalities.

The nano-based theranostics for respiratory complications of COVID-19.

High morbidity and mortality caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made coronavirus disease 2019 (COVID-19) the leading challenge for health experts all over the world. Currently, there is no specific treatment for COVID-19; however, thanks to worldwide intense attempts, novel vaccines such as mRNA-1273 (Moderna TX, Inc.) and BNT162b2 (Biontech/Pfizer) were developed very fast and FDA approved them for emergency use. Nanomedicine-based drug delivery can be an advanced therapeutic strategy to deal with clinical complications of COVID-19. Given the fact that SARS-CoV-2 typically affects the respiratory tract, application of inhalable nanoparticles (NPs) for targeted drug delivery to the alveolar space appears to be an effective and promising therapeutic strategy. Loading the medicinal components into NPs enhances the stability, bioavailability, solubility and sustained release of them. This approach can circumvent major challenges in efficient drug delivery such as solubility and any adverse impact of medicinal components due to off-targeted delivery and resulting systemic complications. Inhalable NPs could be delivered through nasal sprays, inhalers, and nebulizers. NPs also could interfere in virus attachment to host cells and prevent infection. Moreover, nanomedicine-based technologies can facilitate accurate and rapid detection of virus compared to the conventional methods. In this review, the nano-based theranostics modalities for the management of respiratory complications of COVID-19 were discussed.

Evaluation of expression of common genes in the intestine and peripheral blood mononuclear cells (PBMC) associated with celiac disease.

AIM: this study was conducted to investigate expression of the genes associated with CD in the target tissue in order to estimate contribution of each single gene to development of immune response. Then, the same set of genes was evaluated in peripheral blood mononuclear cells (PBMCs). BACKGROUND: Celiac disease (CD) is a chronic systemic autoimmune disease of the small intestine occurring in genetically-susceptible individuals. There are several genes related to immune response. METHODS: For this purpose, the genes related to CD were extracted from public databases (documents of proteomics and microarray-based techniques) and were organized in a protein-protein interaction network using the search tool for retrieval of interacting genes/proteins (STRING) database as a plugin of Cytoscape software version 3.6.0. The main genes were introduced and enriched via ClueGO to find the related biochemical pathways. The network was analyzed, and the most important genes were introduced based on central indices. RESULTS: Among 20 CD genes as hub and bottleneck nodes, there were 7 genes with common expression in blood and intestinal tissue (C-X-C motif chemokine 11(CXCL11), granzyme B (GZMB), interleukin 15(IL-15), interleukin 17(IL-17A), interleukin 23(IL-23A), t-box transcription factor 21(TBX21), and tumor necrosis factor alpha-induced protein 3(TNFAIP3)). CONCLUSION: The enriched biological process related to the central nodes of celiac network indicated that most of hub-bottleneck genes are the well-known ones involved in different types of autoimmune and inflammatory diseases.