Recent Advance on Drug Therapy Related to Myocardial Ischemia Reperfusion Injury

Myocardial ischemia reperfusion injury (MIRI) means complete or partial artery obstruction of coronary artery, and ischemic myocardium will be recirculating in a period of time. Although the ischemic myocardium can be restored to normal perfusion, its tissue damage will instead be progressive. An aggravated pathological process. MIRI is a complex entity where many inflammatory mediators play different roles, both to enhance myocardial infarction-derived damage and to heal injury. Therefore, the research and development of drugs for the prevention and treatment of this period has also become the focus. This article first studied pathophysiology of MIRI, and reviewed the research progress of MIRI-related drugs. Research results show that: MIRI is inevitable for myocardial ischemia, with the possible to double damage via the ischemic condition. Therefore, it is a serious complication and one of the most popular diseases in the world. It has always been difficult to find an effective treatment for this disease, because it is difficult to explore the inflammation behind its pathophysiology.

Gut Microbiome and Organ Fibrosis

Fibrosis is a pathological process associated with most chronic inflammatory diseases. It is defined by an excessive deposition of extracellular matrix proteins and can affect nearly every tissue and organ system in the body. Fibroproliferative diseases, such as intestinal fibrosis, liver cirrhosis, progressive kidney disease and cardiovascular disease, often lead to severe organ damage and are a leading cause of morbidity and mortality worldwide, for which there are currently no effective therapies available. In the past decade, a growing body of evidence has highlighted the gut microbiome as a major player in the regulation of the innate and adaptive immune system, with severe implications in the pathogenesis of multiple immune-mediated disorders. Gut microbiota dysbiosis has been associated with the development and progression of fibrotic processes in various organs and is predicted to be a potential therapeutic target for fibrosis management. In this review we summarize the state of the art concerning the crosstalk between intestinal microbiota and organ fibrosis, address the relevance of diet in different fibrotic diseases and discuss gut microbiome-targeted therapeutic approaches that are current being explored.

Role of Lactate in Inflammatory Processes: Friend or Foe

During an inflammatory process, shift in the cellular metabolism associated with an increase in extracellular acidification are well-known features. This pH drop in the inflamed tissue is largely attributed to the presence of lactate by an increase in glycolysis. In recent years, evidence has accumulated describing the role of lactate in inflammatory processes; however, there are differences as to whether lactate can currently be considered a pro- or anti-inflammatory mediator. Herein, we review these recent advances on the pleiotropic effects of lactate on the inflammatory process. Taken together, the evidence suggests that lactate could exert differential effects depending on the metabolic status, cell type in which the effects of lactate are studied, and the pathological process analyzed. Additionally, various targets, including post-translational modifications, G-protein coupled receptor and transcription factor activation such as NF-κB and HIF-1, allow lactate to modulate signaling pathways that control the expression of cytokines, chemokines, adhesion molecules, and several enzymes associated with immune response and metabolism. Altogether, this would explain its varied effects on inflammatory processes beyond its well-known role as a waste product of metabolism.

Gypenosides Attenuate Pulmonary Fibrosis by Inhibiting the AKT/mTOR/c-Myc Pathway

Gypenosides (Gyps), the major active constituents isolated from Gynostemma pentaphyllum, possess anti-inflammatory and antioxidant activities. Previous studies have demonstrated that Gyps displayed potent ameliorative effects on liver fibrosis and renal fibrosis. In this study, we found that Gyps significantly reduced the mortality of bleomycin-induced pulmonary fibrosis mice (40% mortality rate of mice in the model group versus 0% in the treatment group). Masson staining showed that Gyps could reduce the content of collagen in the lung tissue of pulmonary fibrosis mice Masson staining and immunohistochemistry demonstrated that the expression of the collagen gene α-SMA and fibrosis gene Col1 markedly decreased after Gyps treatment. The active mitosis of fibroblasts is one of the key processes in the pathogenesis of fibrotic diseases. RNA-seq showed that Gyps significantly inhibited mitosis and induced the G2/M phase cell cycle arrest. The mTOR/c-Myc axis plays an important role in the pathological process of pulmonary fibrosis. RNA-seq also demonstrated that Gyps inhibited the mTOR and c-Myc signaling in pulmonary fibrosis mice, which was further validated by Western blot and immunohistochemistry. AKT functions as an upstream molecule that regulates mTOR. Our western blot data showed that Gyps could suppress the activation of AKT. In conclusion, Gyps exerted anti-pulmonary fibrosis activity by inhibiting the AKT/mTOR/c-Myc pathway.

LOCAL HYPOXIA AND IMMUNODEFICIENCY. EFFECT OF OBESITY ON REDUCING THE EFFECTIVENESS OF TREATMENT FOR BACTERIAL VAGINOSIS

Проведен анализ результатов обследования 143 больных бактериальным вагинозом с учетом наличия у них алиментарного ожирения. Все женщины, принимавшие участие в нашем исследовании, дали письменное информированное согласие на участие в нем. Исследование проводили до начала лечения бактериального вагиноза. В зависимости от наличия алиментарного ожирения больных разделили на 2 группы. В I группу вошли 97 с нормальным весом телом, без признаков алиментарного ожирения. Во II группе у 46 больных отмечалось увеличение массы тела, соответствующее алиментарному ожирению II степени. Критериями для анализа являлись результатами бактериоскопического исследования мазков из влагалища, окрашенных по Грамму и выявления в них количественных показателей «ключевых клеток» и показатели оксиметрии, определение интегративного коэффициента Кслиз%, отражающий содержание кислорода в слизистой оболочке, по отношению к показателям, зарегистрированным на II пальце кисти, позволяющего прогнозировать результативность лечения. Таким образом, на фоне алиментарного ожирения еще до начала лечения интенсивность патологического процесса при бактериальном вагинозе была более выражена, чем без него. При этом локальные гипоксия и иммунодефицит свидетельствовали о риске снижения эффективности лечения The analysis of the results of examination of 143 patients with bacterial vaginosis, taking into account the presence of alimentary obesity, was carried out. All women who took part in our study gave written informed consent to participate in it. The study was carried out before starting treatment for bacterial vaginosis. Depending on the presence of alimentary obesity, the patients were divided into 2 groups. Group I included 97 people with normal body weight, without signs of alimentary obesity. In group II, 46 patients showed an increase in body weight corresponding to alimentary obesity of the II degree. The criteria for the analysis were the results of bacterioscopic examination of vaginal smears stained according to Gram and the identification of quantitative indicators of "key cells" in them and oximetry indicators, determination of the integrative coefficient Cmucous membrane% , reflecting the oxygen content in the mucous membrane, in relation to the indicators recorded on the second finger of the hand, which allows predicting the effectiveness of treatment. Thus, amid alimentary obesity, even before the start of treatment, the intensity of the pathological process with bacterial vaginosis was more pronounced than without it. At the same time, local hypoxia and immunodeficiency indicated the risk of a decrease in the effectiveness of treatment.

Precision resection of pulmonary tuberculoma using Nd:YAG-laser

The objective of the study: a comparative study of immediate and long-term results of pulmonary tuberculoma precision resection with Nd:YAG-laser with a wavelength of 1,318 nm and atypical resection with suturing devices.Subjects and Methods. Two groups of 58 patients each were compared. The groups were comparable in terms of gender, age, the nature of the concomitant pathology and the main pathological process. In Group I, patients were operated on using precision 1,318-nm Nd:YAG-laser resection, and in Group II, the sublobar resection with suturing devices were used.Results. The mean duration of hospital stay in Groups I and II was 19.10 ± 6.02 and 19.20 ± 6.02 days respectively (p > 0.05), the duration of surgery made 65 [55; 75] and 55 [45; 60] minutes (p > 0.05), the mean volume of surgical blood loss was 50 [33; 70] and 70 [50; 165] ml (p > 0.05), and the mean duration of pleural cavity drainage after surgery was 4 [3; 5] and 4 [3; 6] days (p > 0.05). Statistically significant differences were noted in the mean volume of the resected part of the lung: 14.0 ± 7.4 mm3 in Group I versus 95.0 ± 9.7 mm3 in Group II (p ≤ 0.05). The complete clinical and radiological cure was achieved in 70% of patients in Group I and 82% in Group II. According to MSCT data, in 91.6% of cases, a thin linear scar is formed in the area of precision intervention.Conclusion: The surgical methods are comparable in terms of immediate and long-term results but precision laser resection minimizes the removal of intact tissue during the removal of tuberculomas.

Activation of Transcription Factor EB Alleviates Tubular Epithelial Cell Injury via Restoring Lysosomal Homeostasis in Diabetic Nephropathy

Disruption of lysosomal homeostasis contributes to the tubulopathy of diabetic nephropathy; however, its underlying mechanisms remain unclear. Herein, we report that decreased activity of transcription factor EB (TFEB) is responsible for the disturbed lysosome biogenesis and clearance in this pathological process. This was confirmed by the findings that insufficient lysosomal replenishment and damaged lysosomal clearance coincided with TFEB inactivation, which was mediated by mTOR hyperactivation in the renal tubular epithelial cells (TECs) of diabetic nephropathy. Furthermore, either TFEB overexpression or pharmacological activation of TFEB enhanced lysosomal clearance via promoting lysosomal biogenesis and protected TECs by reducing apoptosis in vitro. In addition, pharmacological activation of TFEB attenuated renal tubule injury, apoptosis, and inflammation in db/db mice. In conclusion, diabetes-induced mTOR activation represses TFEB function, thereby perturbing lysosomal homeostasis through impairing lysosomal biogenesis and clearance in TECs. Moreover, TFEB activation protects TECs from diabetic injuries via restoring lysosomal homeostasis.

Laser Reconstruction of Spinal Discs Experiments and Clinic

Degenerative disease of the intervertebral discs (DDD) is currently a serious problem facing the world community. The surgical methods and conservative therapy used today, unfortunately, do not stop the pathological process, but serve as a palliative method that temporarily relieves pain and improves the patient’s quality of life. Therefore, at present, there is an active search for new methods of treating DDD. Among new techniques of treatment, biological methods, and minimally invasive surgery, including the use of laser radiation, which, depending on the laser parameters, can cause ablative or modifying effects on the disc tissue, have acquired considerable interest. Here, we analyze a new approach to solving the DDD problem: laser tissue modification. This review of publications is focused on the studies of the physicochemical foundations and clinical applications of a new method of laser reconstruction of intervertebral discs. Thermomechanical action of laser radiation modifies tissue and leads to its regeneration as well as to a long-term restoration of disc functions, elimination of pain and the return of patients to normal life.

Assessment of the degree of lameness in cows

Relevance. The structure of the hoof of cows is a complex biological mechanism consisting of the hoof joint, hoof bone, finger pad, sole, hoof wall, etc. According to V.A. Lukyanovsky (1982), hooves are an additional heart of the animal, since when the hoof hits the ground, the blood actively rises, which allows to create auxiliary pressure in the blood vessels, facilitating the work of the heart muscle. When this system is violated, pathologies of the cardiovascular system often develop. The appearance of foci of the pathological process in different parts of the hoof will not only disrupt the work of the heart, but also cause discomfort, pain, and most importantly — lameness, which will be the driving force in a significant decrease in the productivity of cattle.Methods. Scientists identify three main signs of developing lameness in an animal. The first is the position of the back when walking, normally the back should be smooth and straight, while with the onset of lameness, the animal will carefully rearrange the limb, thereby straining the dorsal muscles, after which a bend in the back will be observed. The second sign is a short step, since with pain syndrome, the animal tries to minimize the load on the diseased limb. The third sign will be the obvious protection of the diseased limb, as a result of which the animal will completely cease to rely on the limb, both when walking and when standing.Results. A systematic approach will allow us to present a mathematical model of a healthy animal and of lame one. Thus, the following pattern can be identified: In order to receive nutrients together with the feed, the cow must reach the feeder, therefore, depending on the degree of lameness, there is a decrease in the consumption of dry matter, up to 15%. Based on this, it can be calculated that with a lack of nutrients and energy, there will be a decrease in milk yield of up to 36%. Which, according to P.I. Nikanorov and I.M. Kasyanov, will lead to a loss of up to 300 kg of milk for the entire lactation period. It was found that in the presence of overgrown and deformed hooves, the daily milk yield of cows is reduced by 5–12%, and with the appearance of cracks in the fragments of the horny capsule — by 19–20%. Also, the birth of a calf is required to obtain milk, and the presence of lameness will negatively affect the production of reproductive hormones, lead to the appearance of “quiet” hunting, which in turn will indirectly lead to a loss of milk productivity.

miR-190a-5p Partially Represses the Abnormal Electrical Activity of SCN3B in Cardiac Arrhythmias by Downregulation of IL-2

Cardiac arrhythmias (CAs) are generally caused by disruption of the cardiac conduction system; interleukin-2 (IL-2) is a key player in the pathological process of CAs. This study aimed to investigate the molecular mechanism underlying the regulation of IL-2 and the sodium channel current of sodium voltage-gated channel beta subunit 3 (SCN3B) by miR-190a-5p in the progression of CAs. ELISA results suggested the concentration of peripheral blood serum IL-2 in patients with atrial fibrillation (AF) to be increased compared to that in normal controls; fluorescence in situ hybridization indicated that the expression of IL-2 in the cardiac tissues of patients with AF to be upregulated and that miR-190a-5p to be downregulated. Luciferase reporter assay, quantitative real-time-PCR, and whole-cell patch-clamp experiments confirmed the downregulation of IL-2 by miR-190a-5p and influence of the latter on the sodium current of SCN3B. Overall, miR-190a-5p suppressed the increase in SCN3B sodium current caused by endogenous IL-2, whereas miR-190a-5p inhibitor significantly reversed this effect. IL-2 was demonstrated to be directly regulated by miR-190a-5p. We, therefore, concluded that the miR-190a-5p/IL-2/SCN3B pathway could be involved in the pathogenesis of CAs and miR-190a-5p might acts as a potential protective factor in pathogenesis of CAs.