A case report of rhino‑facial mucormycosis in a non‑diabetic patient with COVID‑19: a systematic review of literature and current update

Background: COVID-19 disease may be associated with a wide range of bacterial and fungal infections. We report a patient with COVID-19 infection who developed rhino-facial mucormycosis during treatment with corticosteroids. Case presentation: A 59-year-old non-diabetic male patient was admitted with a diagnosis of COVID-19 based on positive RT-PCR and CT of the lungs. Due to sever lung involvement, he was treated with methylprednisolone. The patient was re-admitted to hospital, due to nasal obstruction and left side facial and orbital swelling, several days after discharge. In sinus endoscopic surgery, debridement was performed and the specimens were sent to pathology and mycology laboratories. A nasal biopsy showed wide hyphae without septa. The sequenced PCR product revealed Rhizopus oryzae. Despite all medical and surgical treatment, the patient died. In addition, the characteristics of patients with COVID-19-associated mucormycosis were reviewed in 44 available literatures. In most studies, diabetes mellitus was the most common predisposing factor for mucormycosis. Conclusion: Our report highlights the need for assessing the presence of mucormycosis in patients with COVID-19 and also it shows that physicians should consider the potential for secondary invasive fungal infections in COVID 19case

Molecular identification and evaluation of the ability to produce phospholipase and proteinase by aspergillus environmental isolates obtained from hospital

Background: One of the causes of nosocomial infections is the dispersion of Aspergillus spores in the environment. The secretion of hydrolytic enzymes is considered as a virulence factor in Aspergillus species. The aim of this study was to identify environmental Aspergillus isolates via sequencing the beta-tubulin gene and evaluating the ability to produce phospholipase and proteinase in vitro. Methods: 93 Aspergillus colonies were collected from the emergency, surgical wards, intensive care unit, and operation theatres of two teaching hospitals in Qazvin Province, Iran. The β-tubulin gene region was amplified using polymerase chain reaction (PCR) method, and 40 isolates were sequenced. Evaluation of proteinase and phospholipase production was performed using yeast carbon base (YCB) with bovine serum albumin and egg yolk agar medium, respectively. Findings: Based on β-tubulin sequence, Aspergillus (A.) flavus (30%), A. tuberculosis (25%), A. fumigatus (20%), A. niger (10%), A. sydowii (7.5%), A. terreus (5%), and A. nidulans (2.5%) were identified. Evaluation of extracellular enzymes showed that 82.5% of the isolates had proteinase ability with a mean proteinase of 0.73 ± 0.13, and 52.5% of the studied Aspergillus isolates had phospholipase activity with a mean of 0.81 ± 0.17. Conclusion: Our study showed that environmental strains have high proteinase production. Therefore, it seems necessary to better understand the association of virulence factors with aspergillosis infection in future studies. Keywords: Aspergillus; Tubulin; Peptide hydrolases; Phospholipas

Arginase 1 (Arg1) as an Up-Regulated Gene in COVID-19 Patients: A Promising Marker in COVID-19 Immunopathy

Background: The coronavirus disease 2019 (COVID-19) outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic. It is well-established that SARS-CoV-2 infection can lead to dysregulated immune responses. Arginase-1 (Arg1), which has a pivotal role in immune cells, can be expressed in most of the myeloid cells, e.g., neutrophils and macrophages. Arg1 has been associated with the suppression of antiviral immune responses. Methods: Whole blood was taken from 21 COVID-19 patients and 21 healthy individuals, and after RNA extraction and complementary DNA (cDNA) synthesis, gene expression of Arg1 was measured by real-time PCR. Results: The qPCR results showed that the expression of Arg1 was significantly increased in COVID-19 patients compared to healthy individuals (p < 0.01). The relative expression analysis demonstrated there were approximately 2.3 times increased Arg1 expression in the whole blood of COVID-19 patients. Furthermore, the receiver operating characteristic (ROC) analysis showed a considerable diagnostic value for Arg1 expression in COVID-19 (p = 0.0002 and AUC = 0.8401). Conclusion: Arg1 might be a promising marker in the pathogenesis of the disease, and it could be a valuable diagnostic tool

The Role of Hemoglobin Subunit Delta in the Immunopathy of Multiple Sclerosis: Mitochondria Matters

Although the exact pathophysiology of MS has not been identified, mitochondrial stress can be one of the culprits in MS development. Herein, we have applied microarray analysis, single-cell sequencing analysis, and ex vivo study to elucidate the role of mitochondrial stress in PBMCs of MS patients

Novel insights into the treatment of SARS-CoV-2 infection : An overview of current clinical trials

The emergence of the global pandemic caused by the novel SARS-CoV-2 virus has motivated scientists to find a definitive treatment or a vaccine against it in the shortest possible time. Current efforts towards this goal remain fruitless without a full understanding of the behavior of the virus and its adaptor proteins. This review provides an overview of the biological properties, functional mechanisms, and molecular components of SARS-CoV-2, along with investigational therapeutic and preventive approaches for this virus. Since the proteolytic cleavage of the S protein is critical for virus penetration into cells, a set of drugs, such as chloroquine, hydroxychloroquine, camostat mesylate have been tested in clinical trials to suppress this event. In addition to angiotensin-converting enzyme 2, the role of CD147 in the viral entrance has also been proposed. Mepolizumab has shown to be effective in blocking the virus's cellular entrance. Antiviral drugs, such as remdesivir, ritonavir, oseltamivir, darunavir, lopinavir, zanamivir, peramivir, and oseltamivir, have also been tested as treatments for COVID-19. Regarding preventive vaccines, the whole virus, vectors, nucleic acids, and structural subunits have been suggested for vaccine development. Mesenchymal stem cells and natural killer cells could also be used against SARS-CoV-2. All the above-mentioned strategies, as well as the role of nanomedicine for the diagnosis and treatment of SARS-CoV-2 infection, have been discussed in this review. (C) 2020 Elsevier B.V. All rights reserved.Peer reviewe

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 Systematic Review on the Therapeutic Potentiality of PD-L1-Inhibiting MicroRNAs for Triple-Negative Breast Cancer: Toward Single-Cell Sequencing-Guided Biomimetic Delivery

The programmed death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD-1) is a well-established inhibitory immune checkpoint axis in triple-negative breast cancer (TNBC). Growing evidence indicates that tumoral PD-L1 can lead to TNBC development. Although conventional immune checkpoint inhibitors have improved TNBC patients’ prognosis, their effect is mainly focused on improving anti-tumoral immune responses without substantially regulating oncogenic signaling pathways in tumoral cells. Moreover, the conventional immune checkpoint inhibitors cannot impede the de novo expression of oncoproteins, like PD-L1, in tumoral cells. Accumulating evidence has indicated that the restoration of specific microRNAs (miRs) can downregulate tumoral PD-L1 and inhibit TNBC development. Since miRs can target multiple mRNAs, miR-based gene therapy can be an appealing approach to inhibit the de novo expression of oncoproteins, like PD-L1, restore anti-tumoral immune responses, and regulate various intracellular singling pathways in TNBC. Therefore, we conducted the current systematic review based on the preferred reporting items for systematic reviews and meta-analyses (PRISMA) to provide a comprehensive and unbiased synthesis of currently available evidence regarding the effect of PD-L1-inhibiting miRs restoration on TNBC development and tumor microenvironment. For this purpose, we systematically searched the Cochrane Library, Embase, Scopus, PubMed, ProQuest, Web of Science, Ovid, and IranDoc databases to obtain the relevant peer-reviewed studies published before 25 May 2021. Based on the current evidence, the restoration of miR-424-5p, miR-138-5p, miR-570-3p, miR-200c-3p, miR-383-5p, miR-34a-5p, miR-3609, miR-195-5p, and miR-497-5p can inhibit tumoral PD-L1 expression, transform immunosuppressive tumor microenvironment into the pro-inflammatory tumor microenvironment, inhibit tumor proliferation, suppress tumor migration, enhance chemosensitivity of tumoral cells, stimulate tumor apoptosis, arrest cell cycle, repress the clonogenicity of tumoral cells, and regulate various oncogenic signaling pathways in TNBC cells. Concerning the biocompatibility of biomimetic carriers and the valuable insights provided by the single-cell sequencing technologies, single-cell sequencing-guided biomimetic delivery of these PD-L1-inhibiting miRs can decrease the toxicity of traditional approaches, increase the specificity of miR-delivery, enhance the efficacy of miR delivery, and provide the affected patients with personalized cancer therapy

Evaluation of Biofilm Formation, Hydrolytic Eenzymes and Antifungal Susceptibility of Planktonic Cells of Candida Albicans Species Isolated from Different Clinical Samples

Background: Candida species are common organisms in human and animal mucosa that cause a wide range of Candida infections in immunocompromised patients. This study investigated the ability to produce proteinase, phospholipase and hemolysin as well as biofilm formation in different clinical isolates of Candida albicans. Methods: In this study, ninety-four C. albicans were identified using phenotypic tests and amplification of the hyphal wall protein (HWP1) gene, and the proteinase, phospholipase and hemolysin production in specific mediums, as well as the ability to biofilm formation using the crystal violet method were evaluated. Then, the antifungal susceptibility of planktonic cells was tested on the basis of the CLSI- M27-A3/S protocol. Findings: In this study, the proteinase, phospholipase and hemolysin activities of C.albicans isolated from different body sites were 82%, 75.5%, and 68%, respectively. Additionally, 74.5% of the isolates had the ability to biofilm formation. Among the isolates being studied, the strains isolated from the oral cavity showed the highest activity of proteinase, hemolysin and biofilm formation, and the strains isolated from vaginal secretions showed the highest level of phospholipase activity. The susceptibility pattern of C. albicans species to antifungals showed that all isolates were sensitive to AMB and VRC, and resistance to FLC and ITC was reported as 5.4% and 2.2%, respectively. Conclusion: The results show the importance of molecular epidemiology studies and understanding the role of hydrolytic enzymes and biofilm production in C. albicans strains. Keywords: Candida albicans; Antifungal agents; Disease susceptibility; Virulence; Biofilm

Human papillomavirus E5 protein, the undercover culprit of tumorigenesis

Abstract Human papillomavirus (HPV) is the most common viral infection of the reproductive tract worldwide. It has been well documented that the HPV oncoproteins E6 and E7 play important roles in cancer progression and maintenance. However, the high risk HPV E5 protein is also demonstrated to affect some cellular pathway and signaling in human cell lines. In this letter we argue for the need of further investigation and suggest that the HPV E5 protein should be acknowledged as an oncoprotein of HPV

Viral infection and atherosclerosis

AbstractSeveral risk factors have been described for the pathogenesis of atherosclerosis. Infectious diseases are suggested to be acausative factor, and some viruses have been studied for their relation with atherosclerotic diseases. Studies report two hypotheses,direct and indirect effects, for the role of viral infections in atherogenesis. Viruses are able to initiate atherosclerosis by twodifferent pathways. They can exert their direct effects on atherogenesis by infecting vascular cells and then inducing inflammationin the endotheliumand smooth muscle cells. Alternatively, they can also apply indirect effects by infecting non-vascular cellsand inducing systemic inflammation. In this review, we consider the available data about the effects and correlations of DNA andRNA viruses on atherosclerosis.Keywords Viral infection . Atherosclerosis . Inflammatio