Pirogov Russian National Research Medical University (formerly known as Russian State Medical University or RSMU) is a medical higher education institution in Moscow, Russia founded in 1906. It is fully accredited and recognized by Russia's Ministry of Education and Science and is under the authority of the Ministry of Health and Social Development. Named after Russian surgeon and pedagogue N.I. Pirogov (1810-1888).[citation needed].I.I.[citation needed].
Aging is characterized by progressive loss of physiological resilience accompanied by increased susceptibility to chronic diseases. Among the interconnected hallmarks of aging, cellular senescence has emerged as a central driver of systemic inflammation through the senescence-associated secretory phenotype (SASP). Senescent cells accumulate across multiple tissues with advancing age and secrete complex mixtures of cytokines, growth factors, and proteases that reshape tissue microenvironments and propagate inflammatory signaling locally and systemically. Increasing evidence indicates that SASP composition is highly heterogeneous and depends on cell lineage, metabolic state, and the nature of the senescence-inducing stressor. Recent discoveries further demonstrate that inflammatory signaling in senescent cells is sustained by multiple nucleic acid–sensing pathways, including both cGAS–STING–dependent DNA sensing and mitochondrial RNA–mediated activation of RIG-I–like receptors. Concurrently, senescent cells deploy immune-evasion mechanisms that limit clearance by cytotoxic lymphocytes and natural killer cells, facilitating their persistence within aging tissues. Accumulation of senescent cells therefore represents a critical mechanistic link between molecular damage and the systemic inflammatory state known as inflammaging. This review synthesizes current understanding of tissue-specific SASP programs across immune, vascular, metabolic, hepatic, and neural systems. Particular emphasis is placed on mechanisms that amplify local senescence into organism-wide inflammation, including endocrine signaling, extracellular vesicle trafficking, and sex-dependent modulation of senescence pathways.
OBJECTIVE:To evaluate the efficacy and safety of mesenchymal stem cell (MSC)-based therapies in improving endometrial thickness and reproductive outcomes in women with refractory thin endometrium or Asherman's syndrome. METHODS:Following PRISMA 2020 guidelines, a systematic search of PubMed, Cochrane Library, Embase, Scopus, ClinicalTrials.gov, and Google Scholar through June 2025 was performed. Eighteen clinical studies involving 323 patients were included. MSCs derived from umbilical cord, bone marrow, adipose tissue, endometrium, or menstrual blood were administered via intrauterine infusion, transmyometrial injection, or scaffold-assisted delivery. The primary outcome was change in endometrial thickness; secondary outcomes included clinical pregnancy rate, live birth rate, and miscarriage rate. RESULTS:Meta-analysis demonstrated a significant increase in endometrial thickness following MSC therapy compared to baseline or control (mean difference = 2.35 mm; 95 % CI, 1.97-2.74; p < 0.00001). Subgroup analysis showed the largest gains in endometrial- and adipose-derived MSC groups. Randomized controlled trials confirmed higher clinical pregnancy (OR = 2.72; p = 0.002) and live birth rates (OR = 2.27; p = 0.01), with a reduced miscarriage rate (OR = 0.24; p = 0.004). No serious adverse events were reported. CONCLUSION:While MSC therapy appears to be safe, its efficacy must be confirmed by large-scale randomized trials before it can be presented to the public or recommended as an effective approach for endometrial regeneration.
Epilepsy is one of the most common neurological diseases, so that women account for about 50% of patients. The effect of antiepileptic drugs on women's reproductive function is an important and relevant area of medical research. It is now known that many antiepileptic drugs can have significant effects on the reproductive system, affecting both hormone levels and fertility. These effects require careful consideration while choosing therapy for women of reproductive age, especially for those who plan pregnancy or face conception problems. Despite the proven effectiveness for the currently used drugs and their variability, one third of patients achieve no permanent remission of epilepsy. Knowing the pathogenesis underlying development of this disease, in real life, drugs should be used not so much to stop seizures but rather to prevent their emergence. This article examines the mechanisms of action for antiepileptic drugs, their potential impact on reproductive function, and issues related to the management of side effects in clinical practice as well as the individual selection of the most effective and safe therapy.
This review offers an in-depth analysis of mitochondrial DNA (mtDNA) mutations in colorectal cancer stem cells (CSCs), emphasizing their significant impact on tumor dynamics and potential therapeutic strategies. CSCs are a special subpopulation due to their unique capabilities for self-renewal, differentiation, and resistance to conventional therapies. Given that CSCs significantly differ from other tumor cell subpopulations, particularly in their metabolic properties, and considering that colorectal cancer is a malignancy characterized by mitochondrial dysfunction, this review aims to put together existing data on the differences in the mitochondrial genome of CSCs compared to other colorectal tumor cell subpopulations. Additionally, the review seeks to explore the potential roles of these differences and to identify new ideas for therapeutic strategies. Key topics include the identification and properties of CSCs in colorectal cancer, the distinctive features of the mitochondrial genome, and the functional consequences of mtDNA mutations. The review hypothesizes that CSCs rely on well-functioning mitochondria for crucial aspects like energy production; yet, mtDNA mutations can lead to mitochondrial dysfunction, altering CSC characteristics and influencing cancer progression. The article discusses emerging therapeutic approaches targeting mitochondrial function in colorectal CSCs and highlights the need for advanced research, including the development of preclinical models and exploration of targeted therapies, to improve the understanding and treatment of colorectal cancer.
The aim of this narrative review is to evaluate the methods of intrauterine adhesions (IUAs) formation in animal models for future enhancement in anti-adhesion therapy research.Studies (published until October 2025) were identified by searching PubMed, The Cochrane Library and Google scholar databases. Of 464 screened records, 10 studies met the inclusion criteria and were analyzed. Such methods as curettage, excision, chemical and electrothermal injury of endometrium were examined in order to choose the most effective one in intrauterine formation process. We aimed to evaluate which experimental models most closely replicate clinically relevant scenarios in humans, such as post-inflammatory adhesions and adhesions developing after intrauterine interventions. Mechanical injury models, such as endometrial scraping or partial resection, closely replicate adhesions following obstetric and gynecological procedures. Chemical models alone or combined with mechanical trauma, enhance necrosis and fibrosis, resulting in more severe adhesions and making them suitable for studying advanced IUAs and uterine remodeling. Models with dual mechanical–infectious approaches particularly relevant for post-infectious IUAs.Using animal models in research on IUAs provides objective data by ensuring consistent conditions across study groups. This includes controlled housing and uniform animal characteristics such as identical genetic backgrounds, co-morbidities, immune factors, and predisposition to adhesion formation.
