Myxoma Virus Combination Therapy Enhances Lenalidomide and Bortezomib Treatments for Multiple Myeloma.

This study aimed to explore the effectiveness and safety of Myxoma virus (MYXV) in MM cell lines and primary myeloma cells obtained from patients with multiple myeloma. Myeloma cells were isolated from MM patients and cultured. MYXV, lenalidomide, and bortezomib were used in MM cells. The cytotoxicity assay was investigated using WST-1. Apoptosis was assessed through flow cytometry with Annexin V/PI staining and caspase-9 concentrations using ELISA. To explore MYXV entry into MM cells, monoclonal antibodies were used. Moreover, to explore the mechanisms of MYXV entry into MM cells, we examined the level of GFP-labeled MYXV within the cells after blocking with monoclonal antibodies targeting BCMA, CD20, CD28, CD33, CD38, CD56, CD86, CD117, CD138, CD200, and CD307 in MM cells. The study demonstrated the effects of treating Myxoma virus with lenalidomide and bortezomib. The treatment resulted in reduced cell viability and increased caspase-9 expression. Only low-dose CD86 blockade showed a significant difference in MYXV entry into MM cells. The virus caused an increase in the rate of apoptosis in the cells, regardless of whether it was administered alone or in combination with drugs. The groups with the presence of the virus showed higher rates of early apoptosis. The Virus, Virus + Bortezomib, and Virus + Lenalidomide groups had significantly higher rates of early apoptosis (p < 0.001). However, the measurements of late apoptosis and necrosis showed variability. The addition of MYXV resulted in a statistically significant increase in early apoptosis in both newly diagnosed and refractory MM patients. Our results highlight that patient-based therapy should also be considered for the effective management of MM.

Patients with severe coronavirus disease 2019 have high frequency of factor 5 Leiden and prothrombin gene mutations.

We investigated the frequency of factor 5 Leiden (FVL) and prothrombin gene (PTG) mutations in patients with severe coronavirus disease 2019 (COVID-19). Our primary aim is to reveal whether these mutations are associated with severity of disease and mortality. A total of 249 patients were included in this cross-sectional study. Severe COVID-19 cases (with oxygen saturation of less than 90 mmHg and who received ventilation support invasively or noninvasively) were included. FVL and PTG mutations were identified by real time- PCR technique. Frequency of mutations for FVL was 11.7%, whereas for PTG was 3.5%. The frequency of FVL and PTG's mutations in our patient group was found to be significantly higher than the normal population ( P  < 0.0001, 0.004, respectively). There was no difference in the frequency of mutations of FVL and PTG between the patients ventilated - invasively and noninvasively. There was also no difference in D-dimer, ferritin, fibrinogen, ex status, and entubational status between the groups of FVL and PTG mutated and wild-type. To the best of our knowledge, it is the first time that we have examined the frequencies of FVL and PGM's mutations in severe COVID-19 disease on such a large scale. The frequencies of both mutations in severe COVID-19 patients were higher than in the healthy population. We believe that studies prospectively designed, including asymptomatic and mild COVID-19 patients, will provide more comprehensive information on the subject.

The role of oxidants and reactive nitrogen species in irritable bowel syndrome: a potential etiological explanation.

BACKGROUND: The aim of this study was to evaluate the plasma concentrations of malondialdehyde (MDA) and nitric oxide (NO) and the plasma activities of oxidant and antioxidant enzymes in patients with IBS. MATERIAL/METHODS: A total of 36 patients with IBS were included in the study. Thirty-five healthy subjects were selected to form the control group. Superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), xanthine oxidase (XO), adenosine deaminase (AD) activities, and malondialdehyde (MDA) and nitric oxide (NO) concentrations were studied in the serum samples of all patients and controls. RESULTS: Plasma XO and AD activities, and MDA and NO concentrations were significantly higher in IBS patients than in controls. The SOD, CAT, and GSH-Px activities in the serum of patients with IBS were significantly lower than that of controls. CONCLUSIONS: These results suggest that lipid peroxidation and alterations in the oxidant-antioxidant enzymatic system may play a role in the pathogenesis of IBS. Increased lipid peroxidation in IBS may be related to an increase in NO level and XO activity and a decrease in antioxidant enzymes activities. In addition, increased AD activity may have a role in immunological changes of IBS patients.