Immunohistochemical neuroinflammatory markers in the hippocampus of PTZ-kindled rats under conditions of rapamycin and axitinib treatment

The aim of the study is to determine the level of HIF-1α, TNF-α, and NF-kB in the hippocampus of kindled rats treated with rapamycin and axitinib. Materials and methods. Kindling was produced in 29 rats by administration of three-week pentylenetetrazole (PTZ, 35.0 mg/kg, i.p.). Treatment with rapamycin (0.5 mg/kg, i.p.) and axitinib (2.5 mg/kg, i.p.) was performed for ten days in fully kindled rats. The avidin-biotin-peroxidase method was used for hippocampal slice staining. For negative control, staining was performed using only secondary antibodies. Results. The HIF-1α expression increased in kindled rats raised by 1.77 times compared to the control (p<0.001). Axitinib treatment resulted in of HIF-1α level of 16.7 % (p<0.05) compared with kindled animals, while combined treatment with rapamycin and axitinib reduced HIF-1α by 33.8 % (p<0.01). In kindled rats, TNF-α expression was 3.74 times greater than in control (p<0.001). Rapamycin treatment reduced TNF-α by 31.0 % (p<0.01). Axitinib treatment caused a reduction of TNF-α by 21.1 % (p<0.05). Combined treatment with rapamycin and axitinib reduced TNF-α by 48.0 % (p<0.001) but still exceeded the TNF-α in control by 1.95 times (p<0.01). NF-kB level in kindled rats exceeded the control by three times (p0.05), while axitinib – by 26.5 % (p<0.05) compared with kindled rats. Combined treatment with rapamycin and axitinib resulted in NF-kB reduction by 56.7 % compared with kindled rats (p<0.001). Conclusions. PTZ-kindling resulted in an increase in the immunoreactivity of HIF-1α, TNF-α, and NF-kB in the hippocampus. Combined treatment with rapamycin and axitinib engendered prevention of generalized seizures and normalized the level of HIF-1α and NF-kB with a significant reduction of TNF-α. Effects of treatment favours of synergy action of rapamycin and axitini

The cardiotoxic effects of acute and chronic grayanotoxin-III in rats

The purpose of this study is to histologically and immunohistochemically determine the changes created by grayanotoxin-III (GTX-III), which is a sodium channel neurotoxin, on heart tissues in different dosages. Rats were randomly divided into 10 groups to determine the acute and chronic effects of GTX-III. While the rats in groups 1 and 6 were control rats, the rats in groups 2-5 (1, 2, 4, and 8 mu g/kg bw GTX-III) received a single dose of intraperitoneal GTX-III, and the rats in groups 7-10 received GTX-III every day for 3 weeks. As a result of the trial, in the heart tissues, histopathological changes were determined by hematoxylin-eosin staining, interleukin-1 (IL-1 beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and brain natriuretic peptide (BNP) were determined by the avidin-biotin peroxidase method, and apoptosis was examined by immunohistochemistry (IHC) analysis and the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining method. In the immunohistochemistry sense, while the BNP level in the AGTX-III groups did not vary significantly, an increase in dosage significantly increased the IL-6, IL-1 beta, and TNF-alpha levels in comparison to the control groups. In their comparison to the control groups, the BNP levels increase and the IL-6 and IL-1 beta levels decreased in the CGTX-III groups. TUNEL analysis revealed that apoptosis increased in both the acute and chronic groups

Histological, immunohistochemical and biochemical effects of bee bread on stomach tissue of obese rats

Obesity is a major health problem threatening humanity in medical, social and psychological dimensions. In this study, we aimed to determine the histological, immunohistochemical and biochemical effects of bee bread, added to diets of obese rats in different doses, on leptin and ghrelin expression. In the study, 40 female Sprague-Dawley (200-250 g) rats were randomly divided into 5 equal groups and then assigned to control and obesity groups. The obesity group consisted of four subgroups: high-fat diet group, 100 and 200 mg/kg/bw groups, and metformin group. Histopathological evaluation revealed structural deterioration and necrotic areas in the epithelium and glands of the obese rats' stomach tissue, while in their serum and gastric tissues, the MDA level was significantly higher than in the other groups. There was a negative correlation between leptin and ghrelin levels. Apoptotic cells increased with obesity, but the application of beebread was similarly effective as metformin administration in reducing this increase (Tab. 5, Fig. 4, Ref. 51). Text in PDF www.elis.s

A heritable profile of six miRNAs in autistic patients and mouse models.

Autism spectrum disorder (ASD) is a group of developmental pathologies that impair social communication and cause repetitive behaviors. The suggested roles of noncoding RNAs in pathology led us to perform a comparative analysis of the microRNAs expressed in the serum of human ASD patients. The analysis of a cohort of 45 children with ASD revealed that six microRNAs (miR-19a-3p, miR-361-5p, miR-3613-3p, miR-150-5p, miR-126-3p, and miR-499a-5p) were expressed at low to very low levels compared to those in healthy controls. A similar but less pronounced decrease was registered in the clinically unaffected parents of the sick children and in their siblings but never in any genetically unrelated control. Results consistent with these observations were obtained in the blood, hypothalamus and sperm of two of the established mouse models of ASD: valproic acid-treated animals and Cc2d1a(+/-) heterozygotes. In both instances, the same characteristic miRNA profile was evidenced in the affected individuals and inherited together with disease symptoms in the progeny of crosses with healthy animals. The consistent association of these genetic regulatory changes with the disease provides a starting point for evaluating the changes in the activity of the target genes and, thus, the underlying mechanism(s). From the applied societal and medical perspectives, once properly confirmed in large cohorts, these observations provide tools for the very early identification of affected children and progenitors