GPX3 Variant Genotype Affects the Risk of Developing Severe Forms of COVID-19

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(22), С. 16151 - 16151

Опубликована: Ноя. 10, 2023

In SARS-CoV-2 infection, excessive activation of the immune system intensively increases reactive oxygen species levels, causing harmful hyperinflammatory and oxidative state cumulative effects which may contribute to COVID-19 severity. Therefore, we assumed that antioxidant genetic profile, independently complemented with laboratory markers, modulates The study included 265 patients. Polymorphism GSTM1, GSTT1, Nrf2 rs6721961, GSTM3 rs1332018, GPX3 rs8177412, GSTP1 rs1695, GSTO1 rs4925, GSTO2 rs156697, SOD2 rs4880 GPX1 rs1050450 genes was determined appropriate PCR-based methods. Inflammation (interleukin-6, CRP, fibrinogen, ferritin) organ damage (urea, creatinine, transaminases LDH) complete blood count coagulation status (d-dimer, fibrinogen) were measured. We found significant association for progression patients lymphocytes below 1.0 × 109/L (OR = 2.97, p 0.002). Increased IL-6 CRP also associated disease 8.52, 0.001, OR 10.97, < respectively), as well elevated plasma AST LDH 2.25, 0.021, 4.76, respectively). Of all examined polymorphisms, risk developing severe forms rs8177412 variant genotype 2.42, 0.032). This finding could be particular importance in future, complementing other diagnostic tools prediction course.

Язык: Английский

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The effect of DNA repair gene variants on COVID-19 disease: susceptibility, severity, and clinical course

Nucleosides Nucleotides & Nucleic Acids, Год журнала: 2023, Номер 42(8), С. 571 - 585

Опубликована: Янв. 28, 2023

Oxidative stress (OS), which leads to DNA damage, plays a role in the pathogenesis of Coronavirus disease 2019 (COVID-19). We aimed evaluate repair gene variants [X-ray cross complementing 4 (XRCC4) rs28360071, rs6869366, and X-ray cross-complementary 1 (XRCC1) rs25487] susceptibility COVID-19 Turkish population. also evaluated its effect on clinical course disease. A total 300 subjects, including 200 patients 100 healthy controls, were included this study. These genotyped using polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymorphism (RFLP) methods. The divided into three groups: those with mild or severe infection; who died lived at 28-day follow-up; required inpatient treatment intensive care. There 87 women (43.5%) 113 men (56.5%) patient group. Hypertension was most common comorbidity (26%). In group, XRCC4 rs6869366 G/G genotype G allele frequency increased compared while G/T T/T frequencies found be higher controls patients. For XRCC1 rs25487, A/A A/G genotypes significantly associated All hospitalized care unit had genotype. study, we for first time impact susceptibility. Results suggested that rs25487 suspectibility course.

Язык: Английский

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Efficacies of S-nitrosoglutathione (GSNO) and GSNO reductase inhibitor in SARS-CoV-2 spike protein induced acute lung disease in mice

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Дек. 8, 2023

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially surfaced in late 2019, often triggers pulmonary complications, encompassing various disease mechanisms such as intense lung inflammation, vascular dysfunction, and embolism. Currently, however, there’s no drug addressing all these simultaneously. This study explored the multi-targeting potential of S-nitrosoglutathione (GSNO) N6022, an inhibitor GSNO reductase (GSNOR) on markers inflammatory, vascular, thrombotic diseases related to COVID-19-induced disease. For this, was induced C57BL/6 mice through intranasal administration recombinant SARS-CoV-2 spike protein S1 domain (SP-S1). exhibited fever, body weight loss, increased blood levels expression proinflammatory cytokines (e.g., TNF-α IL-6) well inflammation mediated by ICAM-1 VCAM-1 infiltration immune cells neutrophils, monocytes, activated cytotoxic helper T cells). Further, hyperpermeability (lung Evans blue extravasation) leading edema development elevated coagulation factors fibrinogen, thrombin, platelets, von Willebrand factor) fibrin deposition. Similar patients with COVID-19, male showed more than female mice, along higher GSNOR lungs. Optimization treatment exogenous or inhibition N6022 (or knockout) protects against SP-S1-induced both genders. These findings provide evidence for efficacies inhibitors multi-mechanistic nature SP-associated acute-lung

Язык: Английский

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Inflammation Related to Association of Low Uric Acid and Progression to Severe Disease in Patients Hospitalized for Non-Severe Coronavirus Disease 2019

Biomedicines, Год журнала: 2023, Номер 11(3), С. 854 - 854

Опубликована: Март 10, 2023

Uric acid has antioxidant properties. To examine whether a low uric level is associated with severe coronavirus disease 2019 (COVID-19) progression via inflammation, alveolar damage, and/or coagulation abnormality, retrospective observational study of 488 patients non-severe COVID-19 and serum ≤7 mg/dL at admission was conducted. Serum C-reactive protein (CRP), Krebs von den Lungen 6 (KL-6), plasma D-dimer levels were also measured as markers respectively. Median values for acid, CRP, KL-6, 4.4 mg/dL, 3.33 252.0 U/mL, 0.8 µg/mL, Among the total cohort, 95 (19.5%) progressed to median (interquartile range) time 7 (4-14) days. Multivariable Cox proportional hazards regression analysis showed that higher rate progression. However, inversely CRP level, association between significantly different without inclusion. In contrast, no such found KL-6 or level. Low may contribute increased inflammation in subjects hyperuricemia.

Язык: Английский

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PARAMETERS OF FREE RADICAL OXIDATION IN THE BLOOD OF PATIENTS WITH NON-SMALL CELL LUNG CANCER AND COVID-19 IN ANAMNESIS

Ulyanovsk Medico-biological Journal, Год журнала: 2023, Номер 4, С. 73 - 87

Опубликована: Дек. 21, 2023

The role of redox processes imbalance in the onset malignant transformation and neoplasia progression is well known. It has been suggested that COVID-19 a metabolic disease. Reactive oxygen species (ROS) glutathione-dependent antioxidant system contribute much to its development. Moreover, there an opinion it necessary precisely identify free radical oxidation products status blood patients. purpose study evaluate intensity lipid peroxidation parameters cells lung cancer patients with anamnesis. Materials methods. We studied lymphocytes neutrophils non-small cell (NSCLC) stages I-IIIA (T1-3NХM0). main group included 30 NSCLC (15 men 15 women) who had suffered severe moderate COVID-19. control consisted women asymptomatic or mild SARS-CoV-2. Conventional spectrophotometric methods were used levels malondialdehyde (MDA), diene conjugates (DC) reduced glutathione (RG), activity superoxide dismutase (SOD) peroxidase (GP). Statistical analysis data was performed using Statistica 10.0. Results: In both sexes COVID-19, MDA almost two times as high those A higher DC level anamnesis observed only lymphocytes, – neutrophils. Women groups characterized by MDA, DC, lymphocyte SOD compared men. Increased RG group. decrease neutrophils, accompanied increased level. Conclusion. anamnesis, CRP activation observed. Its severity correlates past severity.

Язык: Английский

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