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Introduction: Coronavirus infectious disease 2019 (COVID-19) is a viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pathogenassociated molecular patterns (PAMPs) can be detected by host pattern-recognition receptors (PRRs) expressed in inherent immune cells. The polymorphisms in PRRs leads to different recognizing and immune responses against viral infections. Methods: Single-nucleotide polymorphisms of PRRs, minor allele frequency (MAF), and their geographical distribution were obtained from the Ensembl genome database. Interaction between the common polymorphic forms of PRRs (including TLR3, TLR7, RIG-1, and MDA-5) and SARS-CoV-2 virus genome (dsRNA) were predicted using the hybrid protein-RNA docking algorithm HDOCK server. Also, the global distribution of common SNPs and their MAFs were statistically analyzed using SPSS, ver.16. Results: The wild-type TLR3 and TLR3 SNP rs73873710 had the same docking energy score (-330.48 kcal/mol), and had lower docking energy scores compared to the other two SNPs, rs3775290 and rs3775291 (-301.42 and-295.81 kcal/mol, respectively). TLR7 SNP rs179008 had a higher docking energy score (-423.03 kcal/mol), comparing to the wild-type TLR7 (-445.46 kcal/mol). Also, there was a statistically significant direct relationship between MAF of TLR3 SNP rs3775290 and rs3775291 with SARS-CoV-2 prevalence (P=0.021 and P=0.023, respectively) and prevalence/population ratio of COVID-19 (P=0.026 and P<0.001, respectably). Conclusion: Wild-type TLR3 and TLR3 SNP rs73873710 can recognize the SARS-CoV-2 dsRNA genome through a better performance compared to TLR3 SNP rs3775290 and TLR3 SNP rs3775291. Therefore, our in-silico study established that PRRs SNPs are associated with antiviral responses against SARS-CoV-2.

In the last 2 decades, a wide variety of studies have been conducted on epigenetics and its role in various cancers. A major mechanism of epigenetic regulation is DNA methylation, including aberrant DNA methylation variations such as hypermethylation and hypomethylation in the promoters of critical genes, which are commonly detected in tumors and mark the early stages of cancer development. Therefore, epigenetic therapy has been of special importance in the last decade for cancer treatment. In epigenetic therapy, all efforts are made to modulate gene expression to the normal status. Importantly, recent studies have shown that epigenetic therapy is focusing on the new gene editing technology, CRISPR-Cas9. This tool was found to be able to effectively modulate gene expression and alter almost any sequence in the genome of cells, resulting in events such as a change in acetylation, methylation, or histone modifications. Of note, the CRISPR-Cas9 system can be used for the treatment of cancers caused by epigenetic alterations. The CRISPR-Cas9 system has greater advantages than other available methods, including potent activity, easy design and high velocity as well as the ability to target any DNA or RNA site. In this review, we described epigenetic modulators, which can be used in the CRISPR-Cas9 system, as well as their functions in gene expression alterations that lead to cancer initiation and progression. In addition, we surveyed various species of CRISPR-dead Cas9 (dCas9) systems, a mutant version of Cas9 with no endonuclease activity. Such systems are applicable in epigenetic therapy for gene expression modulation through chemical group editing on nucleosomes and chromatin remodeling, which finally return the cell to the normal status and prevent cancer progression.

The immune system is essential in recognizing and eliminating tumor cells. The unique characteristics of the tumor microenvironment (TME), such as heterogeneity, reduced blood flow, hypoxia, and acidity, can reduce the efficacy of cell-mediated immunity. The primary goal of cancer immunotherapy is to modify the immune cells or the TME to enable the immune system to eliminate malignancies successfully. Nanobodies, known as single-domain antibodies, are light chain-free antibody fragments produced from Camelidae antibodies. The unique properties of nanobodies, including high stability, reduced immunogenicity, enhanced infiltration into the TME of solid tumors and facile genetic engineering have led to their promising application in cell-mediated immunotherapy. They can promote the cancer therapy either directly by bridging between tumor cells and immune cells and by targeting cancer cells using immune cell-bound nanobodies or indirectly by blocking the inhibitory ligands/receptors. The T-cell activation can be engaged through anti-CD3 and anti-4-1BB nanobodies in the bispecific (bispecific T-cell engagers (BiTEs)) and trispecific (trispecific T-cell engager (TriTEs)) manners. Also, nanobodies can be used as natural killer (NK) cell engagers (BiKEs, TriKEs, and TetraKEs) to create an immune synapse between the tumor and NK cells. Nanobodies can redirect immune cells to attack tumor cells through a chimeric antigen receptor (CAR) incorporating a nanobody against the target antigen. Various cancer antigens have been targeted by nanobody-based CAR-T and CAR-NK cells for treating both hematological and solid malignancies. They can also cause the continuation of immune surveillance against tumor cells by stopping inappropriate inhibition of immune checkpoints. Other roles of nanobodies in cell-mediated cancer immunotherapy include reprogramming macrophages to reduce metastasis and angiogenesis, as well as preventing the severe side effects occurring in cell-mediated immunotherapy. Here, we highlight the critical functions of various immune cells, including T cells, NK cells, and macrophages in the TME, and discuss newly developed immunotherapy methods based on the targeted manipulation of immune cells and TME with nanobodies.

Leukemia is an uncontrollable growth of hematopoietic cells due to a mutation in DNA followed by cellular dysregulation and one or more chromosomal disorder that generally leads to a clonal abnormality. Theoretical and technical inability in early screening and distinguishing cancer, tumor tolerance to common treatment methods, repeated relapses of cancer after remission phase, heterogeneous chromosomal abnormality, and the side effects of current chemotherapies are some of challenges that we face with leukemia and other malignancies. Induced pluripotent stem cells (iPSC) opened a promising window to a wide range of diseases, including leukemia. Overcoming the barriers in leukemia is possible with iPSC technology. Induced hematopoietic stem cell transplantation (and gene therapy), induced cytotoxic T-lymphocytes and reprogrammed NK cells that strengthen the immune system, miRNAs, modeling approaches, and supportive cares are some aspects of the novel treatment based on iPSC technology.

Erythropoietin (EPO) is an important hormone responsible for the stimulation of hematopoiesis which is impaired in a variety of diseases, such as chronic kidney disease, cancer chemotherapy, and the use of some anti-HIV drugs. Difficulties in the purification of endogenous EPO due to problems such as technical limitations, heterogeneity of target cells, inadequate amount and immunogenicity of the resultant product, had limited the entry of endogenous EPO in the clinical applications. The integration of medical biotechnology and hematology has introduced novel procedures for the production of human recombinant erythropoietin (rHuEPO), and other erythropoiesis-stimulating agents (ESAs). To investigate and produce rHuEPO, the first step is to recognize the molecular biology and functional pathways, structure, metabolism, and basic physiology of EPO. In this review, all clinical indications, side effects, challenges and notable points regarding EPO, rHuEPO, and other ESAs have also been addressed along with its molecular characterization, such as the modifications needed to optimize their rHuEPO biosynthesis.

Introduction: Integronsare are mobile genetic elements which play an essential role in the distribution of antibiotic-resistant genes among bacteria. This study aimed to investigate the Class I integron in Klebsiella pneumoniae clinical isolates and its association with multiple drug resistance (MDR). Methods: We obtained 30 K. pneumoniae isolates from patients admitted to the ICU at Shahid Beheshti Hospital in Babol City, Mazandaran province, Iran. Different classes of antimicrobials were used to determine the resistance pattern. A polymerase chain reaction (PCR) was performed to detect the int1 gene of the class I integrons. We also investigated the suitability of the two pairs of primers for the detection of the intl gene. Results: Antibiotic susceptibility testing revealed 90% resistance to ceftizoxime, cefotaxime, and cefepime, 88.6% to cefazolin, gentamicin, ticarcillin, and ceftriaxone, 83.3% to imipenem, 60% to ciprofloxacin, 56.6% to ofloxacin, and 36.6% to amikacin. The PCRs with two pairs of primers, one designed previously and the other in this study, detected int1 in 36.6% and 60% of samples, respectively. Conclusion: The int1 gene was of high prevalence (60%) in K. pneumoniae isolates. This factor could play a significant role in the spread of MDR strains. Also, failure to adhere to essential points in the design of the primer can lead to the production of primers with low specificity and efficiency, which reduces the proper identification of antibiotic resistance genes.