Bulletin of Experimental Biology and Medicine最新文献

We propose a model of combination treatment of Lewis lung carcinoma (LLC) in C57BL/6 mice that includes tumor resection and chemotherapy. A single injection of 5×106 LLC cells into the right lateral subcostal region caused the growth of the primary tumor and its metastasis to the lung. For reducing metastasis and mortality after resection, the primary tumor should be removed with subcutaneous fat on day 8 after inoculation. Antitumor and antimetastatic effects and reduced mortality were achieved by intraperitoneal injection of carboplatin (63.3 mg/kg) and paclitaxel (13.3 mg/kg); chemotherapy was administered twice. The combination of the two approaches increased the survival: the antitumor and antimetastatic effects were observed in 60% of mice with LLC relative to resection alone or treatment with cytostatics alone. However, chemoresistance was formed in 40% of mice, the values of the tumor growth inhibition index and the metastasis inhibition index decreased. This was accompanied by the appearance of cancer stem cells in the circulation with the potential for the formation of spheroids in vitro. The presented model (combination of tumor resection and chemotherapy) can be used in the development of new approaches to improve treatment efficiency in patients with lung cancer.

We studied the influence of the α₁-adrenergic receptor agonist methoxamine on the frequency of spontaneous activity and the parameters of electrical activity of the atrial myocardium from 21-day-old rats with normal sinus (preserved sinus node) or paced rhythm. Stimulation with methoxamine increased the frequency of spontaneous activity. Under the conditions of preserved sinus rhythm, the α₁-adrenergic agonist decreased the duration of the repolarization phase of the action potential, whereas at paced rhythm, this parameter increased.

We studied the expression levels of microRNAs (miR-21, miR-27a, miR-221, and miR-429) in the thymus of female Wistar rats after surgical treatment of breast cancer (BC) and after photodynamic therapy for BC followed by tumor resection. In the group without treatment, the levels of pro-oncogenic miR-21, miR-27a, and miR-221 in the thymus were reduced in comparison with those in the group of intact control. After surgical treatment of BC, the levels of miR-21 and miR-27a in the thymus increased in comparison with those in BC without treatment. Surgical removal of the tumor followed by photodynamic therapy led to an even greater increase in the levels of miR-21 and miR-27a in the thymus in comparison with those in the group of surgical treatment alone. Expression of the tumor-suppressive miR-429 in the thymus significantly exceeds the levels in the BC without treatment and BC+surgery groups.

The number of microglia cells and astrocytes in layer V of the cerebral cortex was estimated on day 7 after damage caused by a unilateral focal traumatic brain injury of the left hemisphere sensorimotor cortex. Quantitative assessment was performed by counting immunocytochemically stained microglia cells (Iba1 marker) and activated astrocytes (GFAP) at different distances from the lesion site. Activation of microglial and astroglial cells was observed not only in the marginal zone of the lesion of the left hemisphere, but also in the intact hemisphere. The data obtained indicate the dissemination of inflammation in focal traumatic brain injury.

The optimal balance of the intestinal microbiota is considered to be an essential part of the human body that affects many metabolic processes. However, the exact role of the gut microbiota in metabolism is still not fully understood. To investigate the metabolic role of gut microbiota, the content of short-chain fatty acids and tryptophan metabolites was studied in mice with sodium dextran sulfate-induced colitis. It was found that the production of short-chain fatty acids increased on experimental day 14, but by experimental day 60, they completely disappeared. At the same time, indoles of bacterial origin increased on experimental day 60.

Cerebral palsy (CP) is the most common neuromuscular disorder in children with no effective therapeutic methods. To examine CP, a large variety of methods and animal models was developed, the most popular are the hypoxic-ischemic (HI) injury and/or LPS injection in mice. In the presented work, HI and LPS were applied on the postnatal day 9 to humanized immunodeficiency mouse pups, thereupon 3 behavioral tests were performed in 8 weeks later. Both HI and LPS caused significant behavioral deficits assessed in the Rotarod test. In gait dynamics and open-field tests, HI and LPS caused significant behavioral deficits reported by some parameters, and the effect of HI was more severe. Additionally, HI and LPS produced the different effects on gait dynamics of the fore and hind paws. Thus, both HI and LPS induced the behavioral disorders in mice, but HI was more suitable for the development of humanized immunodeficiency mouse model of CP.

Endogenous multiple modified LDL (mLDL) and the renin-angiotensin system play a significant role in the development of atherosclerosis. It has been found that by behavioral and hemodynamic parameters the physiological activity of angiotensin II (Ang II) in combination with mLDL is considerably modified due to weakening of its diuretic effect and the inversion of hypertensive and tachyarrhythmic effects. Atherosclerosis is a long-term pathological process, so a single administration of artificially synthesized Ang I-mLDL complexes can be considered a model of the first contact of the body with pathogenic factors. We believe that angiotensin complexes with mLDL participate in adaptive and compensatory mechanisms at the initial stages of atherosclerosis and later contribute to its progression.

We studied the effect of urinary urea concentration on the hemolysin production and cytotoxicity of the uropathogenic Morganella morganii strain MM 190. The highest hemolytic activity of M. morganii cultivated in urine with low urea concentration (23 and 82 mmol/liter) was observed between 3rd and 4th hours of post-inoculation, while in urine with standard urea level (117 mmol/liter), the activity was observed at 5th hour of post-inoculation. Our findings indicate a correlation between this activity and the expression of the hlyA gene. Bacterial culture fluid containing hemolysin caused the death of up to 40% of urothelial cells; cytotoxicity was more pronounced against OKP-GS kidney carcinoma cells compared to T-24 bladder carcinoma cells. Hence, in urine with higher urea concentrations, hemolytic activity of bacteria was observed at later stages of growth, and this culture fluid exhibited higher cytotoxicity.

A method of intraoperative modeling of liver cirrhosis in an experiment has been developed. Mature male Wistar rats underwent typical liver resection (~70% of the initial volume). After resection, intrahepatic injection of 1 ml ademetionine was performed (controls received 0.9% NaCl in the same volume). On days 1, 5, 7, and 14 after surgery, the blood and tissue samples were taken, then the animals were euthanized. Laboratory tests revealed significant deviations in the indicators of cytolysis, cholestasis, and liver cell insufficiency syndromes in the experimental group. Morphological study showed a decrease in the number of mitoses, the development of fibrotic, cirrhotic, and inflammatory changes in the liver. After intrahepatic administration of ademetionine, significant liver dysfunction was observed that did not recover by day 14 after resection, pronounced shifts in laboratory parameters, as well as the development of fibrous, cirrhotic, and inflammatory liver changes.

FoxP3⁺ T-regulatory (Treg) lymphocytes and cytokine production by cells from the stromal vascular fraction (SVF) of epicardial (EAT) and thymus (TAT) adipose tissue of 42 patients with chronic coronary heart disease (CHD) were studied. In the SVF of TAT in patients with Gensini Score (GS)≥74 (the most severe atherosclerosis), the production of IL-1β, TNF, IL-4, and IFNγ was higher, while FoxP3 translocation into the nucleus was lower than in patients with GS<74. The GS index directly correlated with the production of IL-4, IL-1β, and TNF by cells of the SVF of TAT, and inversely - with the production of TNF, IL-17, and IL-10 by cells of the SVF of EAT. The proportion of CD25^hiFoxP3⁺Treg with FoxP3 nuclear translocation in TAT inversely correlated with IFNγ production in TAT and directly correlated with IL-4 production in EAT. The results obtained suggest that the severity of coronary atherosclerosis is interrelated with the ability of SVF cells of EAT and TAT to produce cytokines and the properties of FoxP3⁺Treg lymphocytes.