Systemic lupus erythematosus (SLE) is a systemic autoimmune rheumatic disease of unknown etiology, characterized by hyperproduction of non-organ-specific autoantibodies to various components of the cell nucleus and the development of immune-inflammatory damage to internal organs. Currently, SLE is considered as a prototype of a systemic human autoimmune pathology, the central mechanism of immunopathogenesis of which is a violation of immunological tolerance to self-antigens, due to a complex interaction of genetic, epigenetic, environmental factors. The publication discusses the history of the study of SLE, the contribution of Russian scientists (V.A. Nasonova and others) to the study of th is problem, current trends in clinical and scientific research related to the improvement of diagnostic criteria and pharmacotherapy of this disease.

Сердечно-сосудистые осложнения при системной красной волчанке: механизмы ускоренного развития атеросклероза, диагностика, возможности коррекции

Rheumatoid arthritis (RA) is a multifactorial incurable immune-inflammatory disease. Progression leads to joint deformation, cartilage and bone tissue destruction, and subsequent disability. The primary goal of RA pharmacotherapy is to achieve disease remission. For this purpose, several classes of drugs are used: basic anti-inflammatory drugs (DMARDs), which are a large group of synthetic and biological drugs that are combined according to their ability to influence the pathogenetic mechanisms of RA; glucocorticoids, which are recommended for use in combination with DMARDs; and non-steroidal anti-inflammatory drugs, which are used to relieve acute and chronic pain. The treatment of RA is a long-term process, and the drugs used for this condition are not always safe and not always effective, which leads to discontinuation of treatment in 20–50 % of patients. Therefore, there is a need to develop new pharmacological targets that can increase drug effectiveness and reduce drug toxicity. One promising therapeutic target is proteinase-activated receptors (PARs), particularly PAR2, whose activation contributes to the occurrence of inflammation, fibrosis, and proliferation of connective tissue. Experiments have demonstrated that inhibition of PAR2 activity prevents the development of RA pathogenesis and positively modifies the course of the disease. The search for drugs that inhibit PAR2 was carried out in the following directions: indirect blockade of PAR2 activity; creation of monoclonal antibodies; search for PAR2 inhibitors among peptide compounds; synthesis of low-molecular-weight inhibitory substances.

The aim of the study was to reveal the relationship between the activity of inflammation, the infectious component, platelet function and dyslipidemia, in the development of subclinical atherosclerosis in patients with systemic lupus erythematosus (SLE).Material and methods. Fifty women with SLE at the age of 52.0 [48.0–58.0] years and disease duration – 11.5 [6.0– 22.0] years were examined. The control group consisted of 21 healthy women. The concentration of high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), IgG antibodies to Chlamydia pneumonia (at IgG CP), the level of Toll-like receptor (TLR2), platelet factor 4 (PF4) and antibodies to oxidized high-density lipoproteins (at oxLDL) were determined by enzyme immunoassay. Platelet aggregation indices, lipid spectrum, intima-media thickness (IMT) of common carotid arteries were investigated.Results. A significant increase in IMT of the common carotid artery (1.00 [0.80–1.10] and 0.80 [0.70–0.90] mm, respectively; p<0.01) and TKIM of the carotid bifurcation (1.10 [1.00–1.20] and 0.80 [0.70–1.10] mm, respectively; p<0.01), increased hsCRP concentration (3.67 [2.17–5.92] and 0.74 [0.30–1.26] mg/L, respectively; p<0.01), IL-6 (1.72 [1.39–2.68] and 0.60 [0.22–0.75] pg/mL, respectively; p<0.01). Significant platelet activation was noted in SLE: significant increase in TF4 concentration (21.5 [19.80–23.28] and 18.30 [13.88–20.46] ng/mL, respectively; p<0.01), marked dyslipidemia, increased concentration of oxLDL (3.16 [1.45–4.60] and 1.39 [1.26–2.04] kp, respectively; p<0.01). At IgG CP concentration and TLR2 values in patients with SLE did not differ from controls.Conclusion. In addition to traditional risk factors for the development of cardiovascular disease, the association between SLE and subclinical atherosclerotic lesions of the vascular wall can be explained by additional risk factors – inflammation and autoimmune processes. The role of the infectious component is for further study.

Diaphorase (NQO1, NAD(P)H:quinone oxidoreductase 1) is an important biomarker of the presence and progression of cancer and also plays a key role in the activation of prodrugs used in targeted chemotherapy of tumors. This work aimed to compare data from long-term studies of the role of diaphorase in the intracellular activation of prodrugs used in targeted chemotherapy of oncologic diseases. The review includes data from relevant publications describing the biochemical functions of diaphorase, its role in oncology, and possibilities for increasing the effectiveness of antitumor therapy through induction of this enzyme. Articles published from 2000 to 2025 and indexed in the databases PubMed, ScienceDirect, and eLIBRARY.RU were analyzed. The study used methods of internet analysis, content analysis, and historical and descriptive-analytical approaches. Diaphorase accelerates the two-electron reduction of quinones to hydroquinones, preventing the formation of free radicals whereas simultaneously providing bioreductive activation of a number of cytotoxic drugs. Overexpression of diaphorase in malignant cells makes it possible to use this enzyme as a biocatalytic mechanism for selective delivery and activation of prodrugs, thereby increasing therapeutic effectiveness. The review examines modern enzyme–prodrug strategies, including ADEPT (Antibody-Directed Enzyme Prodrug Therapy), GDEPT (Gene-Directed Enzyme Prodrug Therapy), and PMT (Prodrug Monotherapy), as well as prospects for induction of diaphorase by compounds of the 1,2-dithiole-3-thione class and phytochemical agents. The relationship between NQO1 activity, mitochondrial dysfunction of tumor cells, and initiation of apoptosis is emphasized. Overall, diaphorase is considered a promising molecular target for the development of new bioreductive and mitochondria-targeted antitumor drugs.