To increase the efficiency of interpretation of mast cell's contribution to the state of a specific tissue microenvironment, it is necessary to detail the molecular composition of their secretome and analyze the pathways of degranulation. Developed method of combining immunomorphological and histochemical staining protocols contributes to the most objective detection of the integral level of tryptase expression in the intraorgan population of the skin mast cells. Novel technique for tryptase detection expands the possibilities of morphological analysis, provides researchers with additional data on the structure of the mast cell population and helps visualize the processing and cytological features and structural targets of tryptase during the development of adaptive and pathological reactions. Objective determination of the tryptase profile for organ-specific mast cell populations is in great demand in clinical practice for the interpretation of pathological processes, including inflammation and oncogenesis.
Hydrogen has been shown to exhibit selective antioxidant properties against hydroxyl radicals, and exerts antioxidant and anti-inflammatory effects. The monocrotaline-induced model of pulmonary hypertension is suitable for studying substances with antioxidant activity because oxidative stress is induced by monocrotaline. On day 1, male Wistar rats were subcutaneously injected with a water–alcohol solution of monocrotaline or a control with an only water–alcohol solution. One group of monocrotaline-injected animals was placed in a plastic box that was constantly ventilated with atmospheric air containing 4% of molecular hydrogen, and the two groups of rats, injected with monocrotaline or vehicle, were placed in boxes ventilated with atmospheric air. After 21 days, hemodynamic parameters were measured under urethane narcosis. The results showed that, although hydrogen inhalation had no effect on the main markers of pulmonary hypertension induced by monocrotaline injection, there was a reduction in systemic blood pressure due to its systolic component, and a decrease in TGF-β expression, as well as a reduction in tryptase-containing mast cells.
Smooth muscle tissue (SMT) is one of the main structural components of visceral organs, acting as a key factor in the development of adaptive and pathological conditions. Despite the crucial part of SMT in the gastrointestinal tract activity, the mechanisms of its gravisensitivity are still insufficiently studied. The study evaluated the content of smooth muscle actin (α-SMA) in the membranes of the gastric fundus and jejunum in C57BL/6N mice (30-day space flight), in Mongolian gerbils Meriones unguiculatus (12-day orbital flight) and after anti-orthostatic suspension according to E.R. Morey-Holton. A morphometric analysis of α-SMA in the muscularis externa of the stomach and jejunum of mice and Mongolian gerbils from space flight groups revealed a decreased area of the immunopositive regions, a fact indicating a weakening of the SMT functional activity. Gravisensitivity of the contractile structures of the digestive system may be due to changes in the myofilament structural components of the smooth myocytes or myofibroblast actin. A simulated antiorthostatic suspension revealed no significant changes in the content of the α-SMA expression level, a fact supporting an alteration in the functional properties of the muscularis externa of the digestive hollow organs under weightless environment. The data obtained contribute to the novel mechanisms of the SMT contractile apparatus remodeling during orbital flights and can be used to improve preventive measures in space biomedicine.
Previously we suggested a new pharmaceutical derived from coordination complex of Co3+ with polyacrylic acid (PAA) exhibiting hemostatic and microbicidal activity, namely Hestatin. Differences in the physiological activity of Hestatin synthesized from PAA 10 kDa (Hestatin 10) and 200 kDa (Hestatin 200) were shown. We tested the acute toxicity of Hestatin and its effect on the healing rate of sterile wounds in rats. Free 10 kDa PAA, emulsion wax, emulsion wax carrying resveratrol, and dexpanthenol were tested for comparison. Hestatin 10 exhibited no acute toxicity when administered intragastrically at dosages of 5 g per kg. Hestatin 10 surpassed all tested drugs in its wound healing ability. Histological analysis of skin sections of rats in the area of healing defects showed an increased rate of synthesis of reticular fibers compared to the placebo. In the early stages of wound healing (inflammatory phase), Hestatin 10 stimulated taxis of mast cells (MCs) to the wound bottom but not to the wound perimeter. At the final stage of wound healing (remodeling phase), Hestatin 10 promoted MC evacuation from the skin defect area. This effect is the opposite of the well-known wound-healing agents (dexpanthenol and resveratrol), which enhance MC infiltration into the defect area in the remodeling phase.
Both apoptotic and inflammatory caspases play a significant role in developing and maintaining an organism’s homeostasis. Recently, various studies have described various cross-interactions among various caspases. For instance, interleukin-1β activation is initiated by caspase-1 and caspase-8. Programmed cell death is launched not exclusively by internal and external factors to serve as a foundation for physiological development and realization of cellular and organism functions. The caspases involved in this process provide a complicated function related to cell homeostasis regulation. Caspases also participate in adaptation processes associated with changing environmental conditions, including microgravity. Phenotypical analysis of knockdown laboratory animals can reveal the physiological functions of caspases, giving preference to mice. For instance, this approach allows us to determine the role of caspases in the pathogenesis of different pathologic conditions, such as malignancies and autoimmune and infectious diseases. Caspases are considered by a wide spectrum of authors as therapeutic targets. In general, the topic of caspases and their functions is very broad. In this review, we only discuss some aspects of the impact of caspases on various types of cell death.
20 June 2024 in Russian Journal of Evidence-Based Gastroenterology
Objective. This study aimed to investigate the morphology of the healing process dynamics in simulated bleeding stomach defects (BSD) during endoscopic treatment with alginate polymer polysaccharide hemostatic hydrogel (APPHH). Material and methods. The study involved 12 large laboratory animals (dogs). The experimental model of BSD, developed by E.F. Cherednikov et al., was utilized. Endoscopic hemostasis in experimental BSD was performed by pneumatic flow insufflation of powdered APPHH onto the bleeding defect (Patent RU №2762120). Control BSD were left untreated. Evaluation criteria included hemostasis time and assessment of macroscopic and microscopic features of BSD healing. Results. The hemostasis time with APPHH in endoscopic treatment of experimental BSD was 6.0 (4.0—8.0) seconds. Spontaneous hemostasis in control BSD occurred at 26.5 (25.3—32.0) seconds. Assessment of BSD healing processes revealed faster and more favorable regeneration in experimental BSD compared to control BSD, evidenced by macroscopic changes and morphological confirmation of mucosal changes at the BSD edges. Pathomorphological examination of gastrobiopsies showed no damage to stomach tissue by APPHH. Conclusion. Experimental studies demonstrate that APPHH reduces simulated bleeding cessation time, improves BSD healing quality, and does not damage gastric mucosa. This suggests potential clinical application in treating ulcerative gastrointestinal bleeding.