Coronavirus Disease 2019: A Brief Review of the Clinical Manifestations and Pathogenesis to the Novel Management Approaches and Treatments

The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19) in China, which spread to the rest of the world, led the World Health Organization to classify it as a global pandemic. COVID-19 belongs to the Bettacoronavirus genus of the Coronaviridae family, and it mainly spreads through the respiratory tract. Studies have now confirmed a human-to-human transmission as the primary pathway of spread. COVID-19 patients with a history of diseases such as respiratory system diseases, immune deficiency, diabetes, cardiovascular disease, and cancer are prone to adverse events (admission to the intensive care unit requiring invasive ventilation or even death). The current focus has been on the development of novel therapeutics, including antivirals, monoclonal antibodies, and vaccines. However, although there is undoubtedly an urgent need to identify effective treatment options against infection with COVID-19, it is equally important to clarify management protocols for the other significant diseases from which these patients may suffer, including cancer. This review summarizes the current evidence regarding the epidemiology, pathogenesis, and management of patients with COVID-19. It also aims to provide the reader with insights into COVID-19 in pregnant patients and those with cancer, outlining necessary precautions relevant to cancer patients. Finally, we provide the available evidence on the latest potent antiviral drugs and vaccines of COVID-19 and the ongoing drug trials

A scoping review on the potentiality of PD-L1-inhibiting microRNAs in treating colorectal cancer: Toward single-cell sequencing-guided biocompatible-based delivery

Tumoral programmed cell death ligand 1 (PD-L1) has been implicated in the immune evasion and development of colorectal cancer. Although monoclonal immune checkpoint inhibitors can exclusively improve the prognosis of patients with microsatellite instability-high (MSI-H) and tumor mutational burden-high (TMB-H) colorectal cancer, specific tumor-suppressive microRNAs (miRs) can regulate multiple oncogenic pathways and inhibit the de novo expression of oncoproteins, like PD-L1, both in microsatellite stable (MSS) and MSI-H colorectal cancer cells. This scoping review aimed to discuss the currently available evidence regarding the therapeutic potentiality of PD-L1-inhibiting miRs for colorectal cancer. For this purpose, the Web of Science, Scopus, and PubMed databases were systematically searched to obtain peer-reviewed studies published before 17 March 2021. We have found that miR-191-5p, miR-382-3p, miR-148a-3p, miR-93-5p, miR-200a-3p, miR-200c-3p, miR-138-5p, miR-140-3p, and miR-15b-5p can inhibit tumoral PD-L1 in colorectal cancer cells. Besides inhibiting PD-L1, miR-140-3p, miR-382-3p, miR-148a-3p, miR-93-5p, miR-200a-3p, miR-200c-3p, miR-138-5p, and miR-15b-5p can substantially reduce tumor migration, inhibit tumor development, stimulate anti-tumoral immune responses, decrease tumor viability, and enhance the chemosensitivity of colorectal cancer cells regardless of the microsatellite state. Concerning the specific, effective, and safe delivery of these miRs, the single-cell sequencing-guided biocompatible-based delivery of these miRs can increase the specificity of miR delivery, decrease the toxicity of traditional nanoparticles, transform the immunosuppressive tumor microenvironment into the proinflammatory one, suppress tumor development, decrease tumor migration, and enhance the chemosensitivity of tumoral cells regardless of the microsatellite state

The expression pattern of Immune checkpoints after chemo/radiotherapy in the tumor microenvironment

As a disease with the highest disease-associated burden worldwide, cancer has been the main subject of a considerable proportion of medical research in recent years, intending to find more effective therapeutic approaches with fewer side effects. Combining conventional methods with newer biologically based treatments such as immunotherapy can be a promising approach to treating different tumors. The concept of “cancer immunoediting” that occurs in the field of the tumor microenvironment (TME) is the aspect of cancer therapy that has not been at the center of attention. One group of the role players of the so-called immunoediting process are the immune checkpoint molecules that exert either co-stimulatory or co-inhibitory effects in the anti-tumor immunity of the host. It involves alterations in a wide variety of immunologic pathways. Recent studies have proven that conventional cancer therapies, such as chemotherapy, radiotherapy, or a combination of them, i.e., chemoradiotherapy, alter the “immune compartment” of the TME. The mentioned changes encompass a wide range of variations, including the changes in the density and immunologic type of the tumor-infiltrating lymphocytes (TILs) and the alterations in the expression patterns of the different immune checkpoints. These rearrangements can have either anti-tumor immunity empowering or immune attenuating sequels. Thus, recognizing the consequences of various chemo(radio)therapeutic regimens in the TME seems to be of great significance in the evolution of therapeutic approaches. Therefore, the present review intends to summarize how chemo(radio)therapy affects the TME and specifically some of the most important, well-known immune checkpoints’ expressions according to the recent studies in this field

Sucrose gradient analysis and electron micrographs of purified VLPs.

<p>Pellets derived from 293T cells transfected with prME or Ed395 were subjected to a 5 to 20% (wt/wt) sucrose gradient ultracentrifugation; each of the 10 fractions was subjected to Western blot analysis using a dengue-immune serum. (B) Gradient-purified particles from fractions 4 and 10 were subjected to immunogold labeling using anti-E mAb (1H10-6-7), stained with 2% PTA and photographed at the same magnification. White bar: 100 nm. (C) The size of particles (diameter) of fractions 4 and 10 derived from prME and fraction 10 derived from Ed395 were determined by measuring more than 130 particles from electron micrographs. The particles size (diameter) is shown in nm.</p

Resistance mechanisms to immune checkpoints blockade by monoclonal antibody drugs in cancer immunotherapy: Focus on myeloma

Baradaran, Behzad/0000-0002-8642-6795; Hajiasgharzadeh, Khalil/0000-0003-4593-4803; baghbanzadeh, amir/0000-0002-1261-3213WOS: 000543385400001PubMed: 32592235Multiple myeloma (MM) is a clonal B-cell malignancy characterized by the accumulation of neoplastic proliferation of a plasma cell in the bone marrow that produces a monoclonal immunoglobulin. the immune checkpoint inhibitors against programmed death-1/programmed death-1 ligand and cytotoxic T-lymphocyte antigen 4 axis have demonstrated appropriate anticancer activity in several solid tumors and liquid cancers, and are rapidly transforming the practice of medical oncology. However, in a high percentage of patients, the efficacy of immune checkpoints blockade remains limited due to innate or primary resistance. Moreover, the malignancies progress in many patients due to acquired or secondary resistance, even after the clinical response to immune checkpoints' blockade. the evidence shows that multiple tumor-intrinsic and tumor-extrinsic factors and alterations in signaling pathways are involved in primary and secondary resistance to immune checkpoints blockade. Improved identification of intrinsic and extrinsic factors and mechanisms of resistance or response to immune checkpoints blockade may not only provide novel prognostic or predictive biomarkers but also guide the optimal combination/sequencing of immune checkpoint blockade therapy in the clinic. Here, we review the underlying biology and role of immune checkpoints blockade in patients with MM. Furthermore, we review the host and tumor-related factor effects on immune checkpoints blockade in MM immunotherapy.Tabriz University of Medical SciencesTabriz University of Medical Science

The impact of microRNAs on myeloid-derived suppressor cells in cancer

Inflammation promotes cancer development. To a large extent, this can be attributed to the recruitment of myeloid-derived suppressor cells (MDSCs) to tumors. These cells are known for establishing an immunosuppressive tumor microenvironment by suppressing T cell activities. However, MDSCs also promote metastasis and angiogenesis. Critically, as small non-coding RNAs that regulate gene expression, microRNAs (miRNAs) control MDSC activities. In this review, we discuss how miRNA networks regulate key MDSC signaling pathways, how they shape MDSC development, differentiation and activation, and how this impacts tumor development. By targeting the expression of miRNAs in MDSCs, we can alter their main signaling pathways. In turn, this can compromise their ability to promote multiple hallmarks of cancer. Therefore, this may represent a new powerful strategy for cancer immunotherapy.</p

MiR-144: A New Possible Therapeutic Target and Diagnostic/Prognostic Tool in Cancers

MicroRNAs (miRNAs) are small and non-coding RNAs that display aberrant expression in the tissue and plasma of cancer patients when tested in comparison to healthy individuals. In past decades, research data proposed that miRNAs could be diagnostic and prognostic biomarkers in cancer patients. It has been confirmed that miRNAs can act either as oncogenes by silencing tumor inhibitors or as tumor suppressors by targeting oncoproteins. MiR-144s are located in the chromosomal region 17q11.2, which is subject to significant damage in many types of cancers. In this review, we assess the involvement of miR-144s in several cancer types by illustrating the possible target genes that are related to each cancer, and we also briefly describe the clinical applications of miR-144s as a diagnostic and prognostic tool in cancers

The Positive and Negative Immunoregulatory Role of B7 Family: Promising Novel Targets in Gastric Cancer Treatment

Gastric cancer (GC), with a heterogeneous nature, is the third leading cause of death worldwide. Over the past few decades, stable reductions in the incidence of GC have been observed. However, due to the poor response to common treatments and late diagnosis, this cancer is still considered one of the lethal cancers. Emerging methods such as immunotherapy with immune checkpoint inhibitors (ICIs) have transformed the landscape of treatment for GC patients. There are presently eleven known members of the B7 family as immune checkpoint molecules: B7-1 (CD80), B7-2 (CD86), B7-H1 (PD-L1, CD274), B7-DC (PDCD1LG2, PD-L2, CD273), B7-H2 (B7RP1, ICOS-L, CD275), B7-H3 (CD276), B7-H4 (B7x, B7S1, Vtcn1), B7-H5 (VISTA, Gi24, DD1α, Dies1 SISP1), B7-H6 (NCR3LG1), B7-H7 (HHLA2), and Ig-like domain-containing receptor 2 (ILDR2). Interaction of the B7 family of immune-regulatory ligands with the corresponding receptors resulted in the induction and inhibition of T cell responses by sending co-stimulatory and co-inhibitory signals, respectively. Manipulation of the signals provided by the B7 family has significant potential in the management of GC

The emerging role of noncoding RNAs in systemic lupus erythematosus: new insights into the master regulators of disease pathogenesis

: Auto-immune diseases are a form of chronic disorders in which the immune system destroys the body's cells due to a loss of tolerance to self-antigens. Systemic lupus erythematosus (SLE), identified by the production of autoantibodies in different body parts, is one of the most well-known examples of these diseases. Although the etiology of SLE is unclear, the disease's progression may be affected by genetic and environmental factors. As studies in twins provide adequate evidence for genetic involvement in the SLE, other phenomena such as metallization, histone modifications, and alterations in the expression of noncoding RNAs (ncRNAs) also indicate the involvement of epigenetic factors in this disease. Among all the epigenetic alterations, ncRNAs appear to have the most crucial contribution to the pathogenesis of SLE. The ncRNAs' length and size are divided into three main classes: micro RNAs, long noncoding RNAs (LncRNA), and circular RNAs (circRNAs). Accumulating evidence suggests that dysregulations in these ncRNAs contributed to the pathogenesis of SLE. Hence, clarifying the function of these groups of ncRNAs in the pathophysiology of SLE provides a deeper understanding of the disease. It also opens up new opportunities to develop targeted therapies for this disease

The Regulatory Cross-Talk between microRNAs and Novel Members of the B7 Family in Human Diseases: A Scoping Review

The members of the B7 family, as immune checkpoint molecules, can substantially regulate immune responses. Since microRNAs (miRs) can regulate gene expression post-transcriptionally, we conducted a scoping review to summarize and discuss the regulatory cross-talk between miRs and new B7 family immune checkpoint molecules, i.e., B7-H3, B7-H4, B7-H5, butyrophilin like 2 (BTNL2), B7-H6, B7-H7, and immunoglobulin like domain containing receptor 2 (ILDR2). The current study was performed using a six-stage methodology structure and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. PubMed, Embase, Scopus, Cochrane, ProQuest, and Google Scholar were systematically searched to obtain the relevant records to 5 November 2020. Two authors independently reviewed the obtained records and extracted the desired data. After quantitative and qualitative analyses, we used bioinformatics approaches to extend our knowledge about the regulatory cross-talk between miRs and the abovementioned B7 family members. Twenty-seven articles were identified that fulfilled the inclusion criteria. Studies with different designs reported gene–miR regulatory axes in various cancer and non-cancer diseases. The regulatory cross-talk between the aforementioned B7 family molecules and miRs might provide valuable insights into the pathogenesis of various human diseases