Leptin, the first discovered adipokine, has been connected to various physiological and pathophysiological processes, including cancerogenesis. Increasing evidence confirms its influence on prostate cancer cells. However, studies on the effects of leptin on the proliferation and apoptosis of the androgen-sensitive LNCaP line of prostate cancer cells brought conflicting results. Therefore, we performed studies on the effects of high LEP concentration (1 × 10−6 M) on gene expression profile, change of selected signaling pathways, proliferation and apoptosis of LNCaP cells. RTCA (real-time cell analyzer) revealed inhibitory effect of LEP on cell proliferation, but lower LEP concentrations (10−8 and 10−10 M) did not affect cell division. Moreover, flow cytometry with a specific antibody for Cleaved PARP-1, an apoptosis marker, confirmed the activation of apoptosis in leptin-exposed LNCaP line of prostate cancer cells. Within 24 h LEP (10−6 M) increases expression of 297 genes and decreases expression of 119 genes. Differentially expressed genes (DEGs) were subjected to functional annotation and clusterization using the DAVID bioinformatics tools. Most ontological groups are associated with proliferation and apoptosis (seven groups), immune response (six) and extracellular matrix (two). These results were confirmed by the Gene Set Enrichment Analysis (GSEA). The leptin’s effect on apoptosis stimulation was also confirmed using Pathview library. These results were also confirmed by qPCR method. The results of Western Blot analysis (exposure to LEP 10 min, 1, 2, 4 and 24 h) suggest (after 24 h) decrease of p38 MAPK, p44-42 mitogen-activated protein kinase and Bcl-2 phosphorylated at threonine 56. Moreover, exposure of LNCaP cells to LEP significantly stimulates the secretion of matrix metallopeptidase 7 (MMP7). Obtained results suggest activation of apoptotic processes in LNCaP cells cultured at high LEP concentration. At the same time, this activation is accompanied by inhibition of proliferation of the tested cells.
Annotation: Diabetes mellitus is considered not only a serious chronic disease, but also as an important medical and social problem that is becoming increasingly important. Disease management programs are needed to empower patients and help them develop the necessary skills for selfmanagement of their condition. Objective: To evaluate the effectiveness of the Type 2 Diabetes Management Program at the primary health care level. Methods: Study design is a prospective study, case-control. The study of the intervention group included 114 adults with type 2 diabetes participating in the Disease Management Program and the control group-60 adults with type 2 diabetes not participating in the Disease Management Program. All the investigated persons live in the service area of the municipal polyclinic No. 4 of Aktobe city (Aktobe region, Western region of Kazakhstan). A traditional care which included regular follow-ups every 3 months was provided in the control group. The selection of patients in the control group was carried out by random sampling. Both groups were randomized by age, gender, and duration of illness. The main result evaluated glycated hemoglobin levels, blood pressure, body mass index, and low density lipoprotein levels after 9 months. Results: According to the data obtained after 9 months of the study the analysis showed a decrease in the average level of glycated hemoglobin in the intervention group (7.8 ± 1.5%) compared with the control group (8.6 ± 1.8%) (p <0.05). And also in the intervention group (134.6 ± 12.5 and 83.3 ± 6.5) compared with the control group (125.7 ± 10.4 and 80.7 ± 6.2), systolic and diastolic blood pressure is shown below. There were no statistically significant differences between the groups according to body mass index and low-density lipoprotein. Findings: This Diabetes Management Program allows you to control such indicators as glycated hemoglobin and blood pressure in a positive direction. While both body mass index and low density lipoproteins remained at the same level due to the short observation time.
There is no consensus exercise programme to reduce body weight and improve body composition simultaneously preventing bone loss or stimulating osteogenesis. This pilot study compared the effect of endurance and endurance-strength training on body composition and bone metabolism in centrally obese women. Recruited subjects were randomly assigned to three-month endurance (n = 22) or endurance-strength training (n = 22). Body composition, bone mineral density (BMD) and content (BMC) were assessed before and after the intervention and markers of bone formation and resorption were measured. Both training significantly decreased fat mass; however, endurance-strength training had a more favourable effect on lean mass for the gynoid area (p = 0.0211) and legs (p = 0.0381). Endurance training significantly decreased total body BMC and BMD (p = 0.0440 and p = 0.0300), whereas endurance-strength training only reduced BMD (p = 0.0063). Changes in densitometric parameters did not differ between the groups but endurance training increased osteocalcin levels (p = 0.04845), while endurance-strength training increased tartrate-resistant acid phosphatase 5b concentrations (p = 0.00145). In conclusion, both training programmes were effective in the reduction of fat mass simultaneously negatively affecting bone health. However, endurance-strength training seemed to be more effective in increasing lean mass. The study protocol was registered in the ClinicalTrials.gov database under the number NCT03444207, date of registration: 23 February 2018 (retrospective registration).
Purpose To compare the new spectral-domain optical coherence tomography (SD-OCT) algorithm for measuring circumpapillary retinal nerve fiber layer (RNFL) thickness centered on Bruch's membrane opening (BMO), RNFLBMO1, with the conventional circumpapillary RNFL thickness measurement centered on the optic disc (RNFLDİ), and assess the BMO-minimum rim width (BMO-MRW) in nonglaucomatous eyes with large discs. Methods This prospective, cross-sectional, observational study included a total of 91 eyes of 91 patients having nonglaucomatous eyes with large discs (Group 1) and 50 eyes of 50 healthy subjects (Group 2). The optic nerve head (ONH) parameters obtained by confocal scanning laser ophthalmoscopy (CSLO), peripapillary RNFL thickness, BMO area, and BMO-MRW were imaged with SD-OCT. Results The mean disc size was 3.06 ± 0.42 mm2 (range, 2.61–4.68) in Group 1 and 1.95 ± 0.23 mm2 (range, 1.6–2.43) in Group 2 (p=0.0001). The mean BMO area was 2.9 ± 0.58 mm2 (range, 1.26–4.62) in Group 1 and 2.05 ± 0.31 mm2 (range, 1.51–2.82) in Group 2 (p=0.0001). The difference between RNFLDİ and RNFLBMO1 measurements in Group 1 was stronger than in Group 2 because it was significant in all sectors in large discs. The mean global BMO-MRW thickness was significantly thinner in large discs; it was 252.95 ± 42.16 µ (range, 170–420) in Group 1 and 326.06 ± 73.39 µ (range, 210–440) in Group 2 (p=0.0001). There was a positive correlation between BMO-MRW thickness measurements and RNFL thickness parameters, both with RNFLDİ and RNFLBMO1, in global and all optic nerve sectors except temporal quadrants with r = 0.257–0.431 (p ≤ 0.001–0.01) in Group 1. But in control group, Group 2, there was a weak correlation or no correlation between BMO-MRW thickness measurements and RNFL thickness parameters with r = −0.256–0.328 (p=0.797–0.02). Conclusion The new circumpapillary RNFL scanning algorithm centered on BMO is better to assess the RNFL thickness and BMO-MRW in large discs for the early diagnosis of glaucoma.
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