A comprehensive review on novel targeted therapy methods and nanotechnology-based gene delivery systems in melanoma.

Melanoma, a malignant form of skin cancer, has been swiftly increasing in recent years. Although there have been significant advancements in clinical treatment underlying a well-understanding of melanoma-susceptible genes and the molecular basis of melanoma pathogenesis, the permanency of response to therapy is frequently constrained by the emergence of acquired resistance and systemic toxicity. Conventional therapies, including surgical resection, chemotherapy, radiotherapy, and immunotherapy, have already been used to treat melanoma and are dependent on the cancer stage. Nevertheless, ineffective side effects and the heterogeneity of tumors pose major obstacles to the therapeutic treatment of malignant melanoma through such strategies. In light of this, advanced therapies including nucleic acid therapies (ncRNA, aptamers), suicide gene therapies, and gene therapy using tumor suppressor genes, have lately gained immense attention in the field of cancer treatment. Furthermore, nanomedicine and targeted therapy based on gene editing tools have been applied to the treatment of melanoma as potential cancer treatment approaches nowadays. Indeed, nanovectors enable delivery of the therapeutic agents into the tumor sites by passive or active targeting, improving therapeutic efficiency and minimizing adverse effects. Accordingly, in this review, we summarized the recent findings related to novel targeted therapy methods as well as nanotechnology-based gene systems in melanoma. We also discussed current issues along with potential directions for future research, paving the way for the next-generation of melanoma treatments.Sección Deptal. de Bioquímica y Biología Molecular (Biológicas)Fac. de Ciencias BiológicasTRUEEuropean UnionNextGeneration (EU/PRTR)Ministerio de Ciencia e Innovación (MICINN)/Agencia Estatal de Investigación (AEI)Ministerio de UniversidadesUniversidad Complutense de Madrid (UCM)pu

Expression of OX40 Gene and its Serum Levels in Neuromyelitis Optica Patients

Neuromyelitis optica (NMO), also known as Devic’s disease, is an autoimmune disorder of the central nervous system (CNS) in which immune system cells and antibodies primarily attack the optic nerves and the spinal cord. OX40 (CD134) is a tumor necrosis factor (TNF)-receptor family member expressed primarily on activated CD4+ and CD8+ T-cells. In an autoimmune disease, OX40 is typically up-regulated at sites of inflammation, and increases in the number of peripheral CD4+ T-cells expressing OX40. OX40 and its ligand OX40L are key TNF members that augment T-cell expansion, cytokine production, and promote T-cell survival. The aim of this study was to evaluate and compare of OX40 gene expression and its serum levels in patients with NMO and healthy controls. Twenty sex-/age-matched healthy controls (HC) (median age = 32 years, 15 females/5 males) were engaged for the present study. Expression of OX40 at the transcript level and serum protein levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assays, respectively. The results indicated OX40 expression in patients was significantly lower than in healthy controls (p = 0.001). However, the serum level of OX40 was not significantly different between groups (p = 0.37). In addition, the results indicated that CD134 expression was not age-related (p = 0.041). Overall, this study suggests to us that OX40 levels are not a suitable marker for diagnosis or treatment of NMO

Association of Clinical Features with Spike Glycoprotein Mutations in Iranian COVID-19 Patients

Background: Mutations in spike glycoprotein, a critical protein of SARS-CoV-2, could directly impact pathogenicity and virulence. The D614G mutation, a non-synonymous mutation at position 614 of the spike glycoprotein, is a predominant variant circulating worldwide. This study investigated the occurrence of mutations in the crucial zone of the spike gene and the association of clinical symptoms with spike mutations in isolated viruses from Iranian patients infected with SARS-CoV-2 during the second and third waves of the COVID-19 epidemic in Isfahan, the third-largest city in Iran. Methods: The extracted RNA from 60 nasopharyngeal samples of COVID-19 patients were subjected to cDNA synthesis and RT-PCR (in three overlapping fragments). Each patient’s reverse transcriptase polymerase chain reaction (RT-PCR) products were assembled and sequenced. Information and clinical features of all sixty patients were collected, summarized, and analyzed using the GENMOD procedure of SAS 9.4. Results: Analysis of 60 assembled sequences identified nine nonsynonymous mutations. The D614G mutation has the highest frequency among the amino acid changes. In our study, in 31 patients (51.66%), D614G mutation was determined. For all the studied symptoms, no significant relationship was observed with the incidence of D614G mutation. Conclusions: D614G, a common mutation among several of the variants of SARS-CoV-2, had the highest frequency among the studied sequences and its frequency increased significantly in the samples of the third wave compared to the samples of the second wave of the disease

Gene Editing-Based Technologies for <i>Beta-hemoglobinopathies</i> Treatment

Beta (β)-thalassemia is a group of human inherited abnormalities caused by various molecular defects, which involves a decrease or cessation in the balanced synthesis of the β-globin chains in hemoglobin structure. Traditional treatment for β-thalassemia major is allogeneic bone marrow transplantation (BMT) from a completely matched donor. The limited number of human leukocyte antigen (HLA)-matched donors, long-term use of immunosuppressive regimen and higher risk of immunological complications have limited the application of this therapeutic approach. Furthermore, despite improvements in transfusion practices and chelation treatment, many lingering challenges have encouraged researchers to develop newer therapeutic strategies such as nanomedicine and gene editing. One of the most powerful arms of genetic manipulation is gene editing tools, including transcription activator-like effector nucleases, zinc-finger nucleases, and clustered regularly interspaced short palindromic repeat–Cas-associated nucleases. These tools have concentrated on γ- or β-globin addition, regulating the transcription factors involved in expression of endogenous γ-globin such as KLF1, silencing of γ-globin inhibitors including BCL11A, SOX6, and LRF/ZBTB7A, and gene repair strategies. In this review article, we present a systematic overview of the appliances of gene editing tools for β-thalassemia treatment and paving the way for patients’ therapy