Objectives Insufficient production and/or increased decomposition of the potent endogenous vasodilator nitric oxide plays an important role in development and progression of arterial hypertension and its complications. One of the most effective means of stimulating endogenous nitric oxide synthesis is controlled adaptation to hypoxia. This study examined the effect of a 20-day, intermittent, normobaric intermittent hypoxia conditioning (IHC) program on blood pressure (BP) and nitric oxide production in patients with stage 1 arterial hypertension. Methods The IHC sessions consisted of four to 10 cycles of alternating 3-min hypoxia (10% FIO₂) and 3-min room air breathing. BP was monitored for 24 h before and after IHC, and nitric oxide synthesis was evaluated by 24-h urinary excretion of the stable nitric oxide metabolites nitrate and nitrite. Results IHC increased nitric oxide synthesis and decreased BP in hypertensive patients to values similar to those of normotensive individuals. Significant inverse correlations were found between nitric oxide production and disease duration, SBP, and DBP. Moreover, IHC enhancement of nitric oxide synthesis was especially robust in patients with arterial hypertension of more than 5 years duration. The reduction in BP persisted for at least 3 months in 28 of 33 hypertensive patients. Conclusion IHC exerted a robust, persistent therapeutic effect and can be considered as an alternative, nonpharmacological treatment for patients with stage 1 arterial hypertension. The antihypertensive action of IHC is associated with normalization of nitric oxide production.

M1 macrophages target tumor cells. However, many tumors produce anti-inflammatory cytokines, which reprogram the anti-tumor M1 macrophages into the pro-tumor M2 macrophages. We have hypothesized that the problem of pro-tumor macrophage reprogramming could be solved by using a special M3 switch phenotype. The M3 macrophages, in contrast to the M1 macrophages, should respond to anti-inflammatory cytokines by increasing production of pro-inflammatory cytokines to retain its anti-tumor properties. Objectives of the study were to form an M3 switch phenotype in vitro and to evaluate the effect of M3 macrophages on growth of Ehrlich ascites carcinoma (EAC) in vitro and in vivo. Tumor growth was initiated by an intraperitoneal injection of EAC cells into C57BL/6J mice. 1) The M3 switch phenotype can be programed by activation of M1-reprogramming pathways with simultaneous inhibition of the M2 phenotype transcription factors, STAT3, STAT6, and/or SMAD3. 2) M3 macrophages exerted an anti-tumor effect both in vitro and in vivo, which was superior to anti-tumor effects of cisplatin or M1 macrophages. 3) The anti-tumor effect of M3 macrophages was due to their anti-proliferative effect. Development of new biotechnologies for restriction of tumor growth using in vitro reprogrammed M3 macrophages is very promising.

Life expectancy and age-related diseases burden increased significantly over the past few decades. Age-related conditions are commonly discussed in a very limited paradigm of depleted cellular proliferation and maturation with exponential accumulation of senescent cells. However, most recent evidence showed that the majority of age-associated ailments, i.e., diabetes mellitus, cardiovascular diseases and neurodegeneration. These diseases are closely associated with tissue nonspecific inflammation triggered and controlled by mesenchymal stromal cell secretion. Mesenchymal stromal cells (MSCs) are known as the most common type of cells for therapeutic approaches in clinical practice. Side effects and complications of MSC-based treatments increased interest in the MSCs secretome as an alternative concept for validation tests in regenerative medicine. The most recent data also proposed it as an ideal tool for cell-free regenerative therapy and tissue engineering. However, senescent MSCs secretome was shown to hold the role of ‘key-driver’ in inflammaging. We aimed to review the immunomodulatory effects of the MSCs-secretome during cell senescence and provide eventual insight into the interpretation of its beneficial biological actions in inflammaging-associated diseases.

Aim: The present paper aims to systematize data concerning the prevalence and risk of dental erosion (DE) in adult patients with gastroesophageal reflux disease (GERD) compared to controls. Materials and methods: Core electronic databases, i.e., MEDLINE/PubMed, EMBASE, Cochrane, Google Scholar, and the Russian Science Citation Index (RSCI), were searched for studies assessing the prevalence and risk of DE in adult GERD patients with publication dates ranging from 1 January 1985 to 20 January 2022. Publications with detailed descriptive statistics (the total sample size of patients with GERD, the total sample size of controls (if available), the number of patients with DE in the sample of GERD patients, the number of patients with DE in the controls (if available)) were selected for the final analysis. Results: The final analysis included 28 studies involving 4379 people (2309 GERD patients and 2070 control subjects). The pooled prevalence of DE was 51.524% (95 CI: 39.742–63.221) in GERD patients and 21.351% (95 CI: 9.234–36.807) in controls. An association was found between the presence of DE and GERD using the random-effects model (OR 5.000, 95% CI: 2.995–8.345; I² = 79.78%) compared with controls. When analyzing studies that only used validated instrumental methods for diagnosing GERD, alongside validated DE criteria (studies that did not specify the methodologies used were excluded), a significant association between the presence of DE and GERD was revealed (OR 5.586, 95% CI: 2.311–13.503; I² = 85.14%). Conclusion: The meta-analysis demonstrated that DE is quite often associated with GERD and is observed in about half of patients with this extremely common disease of the upper gastrointestinal tract.

BACKGROUND:The majority of tumors trigger macrophage reprogramming from an anti-tumor M1 phenotype towards a pro-tumor M2 phenotype. The M2 phenotype promotes tumor growth. We hypothesized that increasing the number of M1 macrophages in a tumor would...

Aim. To perform a meta-analysis of the data on Rebamipide efficacy and safety as a part of Helicobacter pylori eradication therapy in Russian patients. Materials and methods. A search for original studies was conducted in the electronic database of the Russian Science Citation Index (RSCI) on the Scientific Electronic Library (SEL Elibrary.ru). Google (Google.com) was used for the "grey" search. All Russian controlled studies comparing the efficacy and/or safety of Rebamipide as a part of the regimen of H. pylori eradication therapy were included in the final analysis. Results. In 6 included controlled trials with a cumulative population (considering double comparisons between multiple groups) of 531 patients (273 in Rebamipide groups and 258 in groups without Rebamipide), the pooled eradication effectiveness was 90.376% (95% confidence interval CI 86.31193.560) in patients receiving Rebamipide and 81.681% (95% CI 76.49986.141) in patients receiving eradication regimens without Rebamipide. The meta-analysis showed that the Rebamipide addition to eradication regimens significantly improved efficacy (odds ratio 2.162, 95% CI 1.2683.685; p=0.005). No significant heterogeneity was found between study results (p=0.863; I2=0.00%); therefore, a fixed effects model was used in the resulting analysis. In addition, the meta-analysis of included studies showed a reduction of adverse events (odds ratio 0.569, 95% CI 0.3330.970) in the groups receiving Rebamipide; p=0.038). This effect of Rebamipide deserves special attention and requires additional study, as the result was at the border of statistical significance in the subanalysis of three studies with a large margin of risk reduction in one of them (with the largest sample of patients). Conclusion. The present meta-analysis demonstrated that the Rebamipide addition to H. pylori eradication regimens significantly improves the treatment effectiveness in the Russian patient population.