Viral Vectors, Exosomes, and Vexosomes: Potential armamentarium for delivering CRISPR/Cas to cancer cells.

The underlying cause of cancer is genetic disruption, so gene editing technologies, particularly CRISPR/Cas systems can be used to go against cancer. The field of gene therapy has undergone many transitions over its 40-year history. Despite its many successes, it has also suffered many failures in the battle against malignancies, causing really adverse effects instead of therapeutic outcomes. At the tip of this double-edged sword are viral and non-viral-based vectors, which have profoundly transformed the way scientists and clinicians develop therapeutic platforms. Viruses such as lentivirus, adenovirus, and adeno-associated viruses are the most common viral vectors used for delivering the CRISPR/Cas system into human cells. In addition, among non-viral vectors, exosomes, especially tumor-derived exosomes (TDEs), have proven to be quite effective at delivering this gene editing tool. The combined use of viral vectors and exosomes, called vexosomes, seems to be a solution to overcoming the obstacles of both delivery systems.

Comparison of oncolytic virotherapy and nanotherapy as two new miRNA delivery approaches in lung cancer.

Lung cancer is known as the second leading cause of cancer death. Finding ways to detect early-stage lung cancer can remarkably increase the survival rate. Biomarkers such as microRNAs can be helpful in cancer diagnosis, predicting its prognosis, and patients' chances of survival. Numerous studies have confirmed the correlation between microRNA expression and the likelihood of patients surviving after treatment. Consequently, it is necessary to study the expression profile of microRNAs during and after treatment. Oncolytic virotherapy and nanotherapy are two neoteric methods that use various vectors to deliver microRNAs into cancer cells. Although these treatments have not yet entered into the clinical trials, much progress has been made in this area. Analyzing the expression profile of microRNAs after applying nanotherapy and oncolytic virotherapy can evaluate the effectiveness of these methods. This review refers to the studies conducted about these two approaches. The advantages and disadvantages of these methods in delivery and affecting microRNA expression patterns are discussed below.

Should all patients with hypertension be worried about developing severe coronavirus disease 2019 (COVID-19)?

BACKGROUND: Hypertension, the most common comorbidity among coronavirus disease 2019 (COVID-19) patients, is accompanied by worse clinical outcomes, but there is lack of evidence about prognostic factors among COVID-19 patients with hypertension. We have come up with some prognostic factors to predict the severity of COVID-19 among hypertensive patients. In addition, epidemiologic, clinical and laboratory differences among COVID-19 patients with and without underlying hypertension were evaluated. METHODS: Medical profiles of 598 COVID-19 cases were analyzed. Patients were divided into two comparative groups according to their positive or negative history of hypertension. Then, epidemiologic, clinical, laboratory and radiological features and also clinical outcomes were compared. RESULTS: 176 (29.4%) patients had underlying hypertension. Diabetes was significantly higher in hypertensive group [72 (40.9%) vs 76 (18%)] (P-value: 0.001). Cardiovascular and renal disorders were significantly higher in hypertensive patients. (P-value: 0.001 and 0.013 respectively). In COVID-19 patients with hypertension, severe/critical types were significantly higher. [42(23.8%) vs. 41(9.7%)], (P-value: 0.012). In the logistic regression model, Body mass index > 25 (ORAdj: 1.8, 95% CI: 1.2 to 2.42; P-value: 0.027), age over 60 (ORAdj: 1.26, 95% CI: 1.08 to 1.42; P-value: 0.021), increased hospitalization period (ORAdj: 2.1, 95% CI: 1.24 to 2.97; P-value: 0.013), type 2 diabetes (ORAdj: 2.22, 95% CI: 1.15 to 3.31; P-value: 0.001) and chronic kidney disease (ORAdj: 1.83, 95% CI: 1.19 to 2.21; P-value: 0.013) were related with progression of COVID-19. CONCLUSION: Hypertensive patients with Age > 60-year-old, BMI > 25 Kg/m2, CVD, diabetes and chronic kidney disease are associated with poor outcomes in those with COVID-19 infection.

Changes in Th17 cells frequency and function after ozone therapy used to treat multiple sclerosis patients.

BACKGROUND: Multiple sclerosis (MS) is a neurodegenerative autoimmune disease with chronic inflammation. In the course of the disease, the increased levels of Th17 cell, and its relevant inflammatory factors, may cause disease inflammation and progression. Ozone therapy with anti-oxidant and anti-inflammatory functions is known as a beneficial therapeutic approach. The current non-controlled study aimed to evaluate the therapeutic implications of ozone autohemotherapy on Th17 responses in MS patients. METHODS: 20 MS patients as the experimental group received ozone therapy (100 ml of O2/O3 compound (25 ugs/ml concentration) with 100 ml of autologous blood) twice per week for 6 months. The frequency of Th17 cells, gene expression of the relevant factors (RORÉ£t, IL-17, IL-23, miR-141, miR-155, and miR-200), as well as the secretion levels of IL-17 and IL-23 cytokines, were compared between the patient and control groups, as well as the group of patients before and after ozone therapy using the flow cytometry, Real-time PCR, and ELISA techniques, respectively. RESULTS: Findings indicated the significant decrease in the frequency of Th17 cells (P = 0.0002), the expression levels of RORÉ£t and IL-17 (P = 0.0001 and P = 0.0004, respectively), as well as miR-141 and miR-155 (P<0.0001 and P<0.0001, respectively) in post-treatment condition with Ozone compared to pre-treatment condition. Also, the significant reduction in the secretion level of IL-17 (P = 0.043) was detected in treated patients. DISCUSSION: Since increased levels and responses of Th17 cells may have critical roles in MS pathogenesis and inflammation, our findings revealed that ozone autohemotherapy could lower the Th17 responses in peripheral blood of MS patients and can be a beneficial approach in MS treatment.

Decreased expression of miR-20a and miR-92a in the serum from sulfur mustard-exposed patients during the chronic phase of resulting illness.

CONTEXT: Sulfur mustard (SM), with extensive nucleophilic and alkylating properties, was employed during the Iran-Iraq war by Iraqi forces. The most critical complications attributed to SM are related to dangerous pulmonary disorders collectively known as "mustard lung". The symptoms gradually emerge over a long period, becoming chronic, and are dependent on time and the amount of exposed SM. Because of the unknown and complex nature of the disease, no differential diagnostic method or absolute treatment strategy has been formally developed. OBJECTIVE: The aim of our study was to determine the expression pattern of the microRNAs (miRNAs) miR-92a and miR-20a in the serum of patients with mustard lung along with that of normal individuals. miRNAs have been shown to possess stable persistence in biofluids like plasma and serum and are considered non-aggressive biomarkers helpful for diagnosis and treatment of many diseases. MATERIALS AND METHODS: A highly sensitive approach called stem-loop real-time quantitative polymerase chain reaction was employed to study the expression of miRNAs. RESULTS: The expression of miR-92a and miR-20a was significantly down-regulated in the serum of patients with mustard lung compared to the control group. DISCUSSION: Down-regulation of miR-92a and miR-20a may be due to chronic epigenetic alterations after SM exposure, which finally leads to changes in vital cellular processes such as differentiation, proliferation and so forth. CONCLUSION: Our findings may provide a differential diagnostic method that is effective for diagnosing lung diseases caused by SM exposure. Additionally, these miRNAs may be regarded as probable targets for treatment of lung injuries.

Evaluation of miR-9 and miR-143 expression in urine specimens of sulfur mustard exposed patients.

Sulfur mustard (SM) or mustard gas is a chemical alkylating agent that causes blisters in the skin (blister gas), burns the eyes and causes lung injury. Some major cellular pathways are involved in the damage caused by mustard gas such as NF-κb signaling, TGF-ß signaling, WNT pathway, inflammation, DNA repair and apoptosis. MicroRNAs are non-coding small RNAs (19-25 nucleotides) that are involved in the regulation of gene expression and are found in two forms, extracellular and intracellular. Changes in the levels of extracellular microRNAs are directly associated with many diseases, it is thus common to study the level of extracellular microRNAs as a biomarker to determine the pathophysiologic status. In this study, 32 mustard gas injured patients and 32healthy subjects participated. Comparative evaluation of miR-9 and miR-143 expression in urine samples was performed by Real Time PCR and Graph Pad software. The Mann Whitney t-test analysis of data showed that the expression level of miR-143 and miR-9 had a significant decrease in sulfur mustard individuals with the respective p-value of 0.0480 and 0.0272 compared to normal samples, with an imbalance of several above mentioned pathways. It seems that reducing the expression level of these genes has a very important role in the pathogenicity of mustard gas injured patients.