COVID-19 is a global catastrophic event that causes severe acute respiratory syndrome. The mechanism of the disease remains unclear, and hypoxia is one of the main complications. There is no currently approved protocol for treatment. The microbial threat as induced by COVID-19 causes the activation of macrophages to produce a huge amount of inflammatory molecules and nitric oxide (NO). Activation of macrophages population into a pro-inflammatory phenotype induces a self-reinforcing cycle. Oxidative stress and NO contribute to this cycle, establishing a cascade inflammatory state that can kill the patient. Interrupting this vicious cycle by a simple remedy may save critical patients’ lives. Nitrite, nitrate (the metabolites of NO), methemoglobin, and prooxidant-antioxidant-balance levels were measured in 25 ICU COVID-19 patients and 25 healthy individuals. As the last therapeutic option, five patients were administered methylene blue-vitamin C–N-acetyl Cysteine (MCN). Nitrite, nitrate, methemoglobin, and oxidative stress were significantly increased in patients in comparison to healthy individuals. Four of the five patients responded well to treatment. In conclusion, NO, methemoglobin and oxidative stress may play a central role in the pathogenesis of critical COVID-19 disease. MCN treatment seems to increase the survival rate of these patients. Considering the vicious cycle of macrophage activation leading to deadly NO, oxidative stress, and cytokine cascade syndrome; the therapeutic effect of MCN seems to be reasonable. Accordingly, a wider clinical trial has been designed. It should be noted that the protocol is using the low-cost drugs which the FDA approved for other diseases. Trial registration number NCT04370288.

Background:Thalassemia is a common hemoglobin disorder in Iran and one of the major public health problems. Although blood transfusions are lifesavers for thalassemia patients, they may be associated with some complications especially erythrocyte alloimmunization. The purpose of this study was to investigate the prevalence of red blood cell alloantibodies and to determine types of these antibodies among multiple-transfused thalassemic patients.Materials and Methods:A total of 313 thalassemia patients in the northeast of Iran, who received regular blood transfusion, were included in this study. Screening of antibodies was performed on fresh serum of all patients and then antibodies were identified in patients’ serum that had positive antibody screening test using a panel of recognized blood group antigens.Results:We identified 12 alloantibodies in 9 patients (2.87%) that all were against Rhesus (Rh) blood group antigens (D, C, E). Three patients developed 2 antibodies, and others had one antibody. The most common alloantibodies were Anti-D (88.88%) and followed by Anti-C and Anti-E. Higher frequency of alloimmunization was observed in female, Rh negative and splenectomized patients.Conclusion:This study showed that evaluation of the packed cells for Rh (C, E) from the start of transfusion can be helpful in decreasing the rate of alloantibody synthesis.

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ObjectiveThis study sought to evaluate platelet volume indices (mean platelet volume [MPV], platelet distribution width [PDW], and platelet large cell ratio [P-LCR]) in varicocele patients, and compare it with platelet volume parameters in healthy controls.MethodsThis cross-sectional study involved 2 groups: group 1 included 51 varicocele subjects and group 2 consisted of 50 healthy control subjects of similar ages. Peripheral venous blood samples were collected with ethylenediaminetetraacetic acid-K2 anticoagulant between 8:30 AM and 10 AM following an overnight fast. Platelet volume parameters (MPV, PDW, and P-LCR) were measured in both groups within 2 hours of sampling.ResultsThe mean PDW, MPV, and P-LCR were 13.9±2.5%, 10.1±1.3 fL, and 27.3±7.8% in varicocele patients, respectively, and were 12.6±2.4%, 9.3±1.1 fL, and 21.9±6.4% in the control group, respectively. The mean PDW, MPV, and P-LCR were significantly higher in the varicocele group than the control group.ConclusionThe results of the present study suggest that vascular components may play an important role in the pathophysiology of varicocele; therefore, there is a great need for prospective studies to confirm this relationship.

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Background Exosome administration is a novel medical approach that promises excellent immunomodulatory properties without the conventional side effects of current antitumor necrosis factor drugs and stem cells. This study aimed to assess the safety and efficacy of using mesenchymal stem cell (MSC) exosomes to treat refractory fistulas in patients with inflammatory bowel disease. Methods MSCs were derived from the umbilical cords and their exosomes were isolated. Five patients with refractory perianal Crohn’s disease fistulas with a median age of 35 years (range 31–47 years) were enrolled in the study. Exosome injections were administered in the operating room to patients with refractory fistula (fistulas that are irresponsive to anti-tumor necrosis factor-α administration within 6 months). Six months later, a physical examination, face-to-face interviews, and magnetic resonance imaging were employed to evaluate the therapy responses of patients. Results The outcomes within 6 months after initiation of therapy showed that four patients had responded to therapy. Three patients who received exosome injections exhibited complete healing, while one reported no improvement and active discharge from the fistula site. In addition, five patients (100%) reported neither systemic nor local adverse effects. Conclusions Injection of exosomes extracted from MSCs demonstrates safety and a satisfactory therapeutic effect, as evidenced in this and other studies, and may play a significant role in the future treatment of gastrointestinal fistulas.

Thrombin initiates proinflammatory signaling responses through activation of protease-activated receptors (PARs) in in vitro and in vivo systems. Proinflammatory signaling function of thrombin increases secretion of proinflammatory cytokines and chemokines, triggers vascular permeability, promotes leukocyte migration, and induces adhesion molecule expression. Thrombin as a potent signaling molecule is strongly implicated in a number of proinflammatory disorders including severe sepsis, cancer, cardiovascular disease, and of special interest in this review neurodegenerative disorders. This review summarizes the role of thrombin in the pathogenesis of central nervous system (CNS) inflammatory diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), promoting greater understanding and clinical management of these diseases. J. Cell. Physiol. 232: 482-485, 2017. © 2016 Wiley Periodicals, Inc.

Thrombin-induced activation of protease-activated receptors (PARs) represents a link between inflammation and cancer. Proinflammatory signaling functions of thrombin are associated with several inflammatory diseases including neurodegenerative, cardiovascular, and of special interest in this review cancer. Thrombin-induced inflammatory responses up-regulates expression of cytokines, adhesion molecules, angiogenic factors, and matrix-degrading proteases that facilitate tumor cells proliferation, angiogenesis, invasion, and metastasis. This review summarizes the current knowledge about the mechanisms of thrombin-mediated proinflammatory responses in cancer pathology for a better understanding and hence a better management of this disease.