The present study investigated a joint contribution of matrix metalloproteinases (MMPs) genes to ischemic stroke (IS) development and analyzed interactions between MMP genes and genome‐wide associated loci for IS. A total of 1288 unrelated Russians (600 IS patients and 688 healthy individuals) from Central Russia were recruited for the study. Genotyping of seven single nucleotide polymorphisms (SNPs) of MMP genes (rs1799750, rs243865, rs3025058, rs11225395, rs17576, rs486055, and rs2276109) and eight genome‐wide associated loci for IS were done using Taq‐Man–based assays and MALDI‐TOF mass spectrometry iPLEX platform, respectively. Allele − 799T at rs11225395 of the MMP8 gene was significantly associated with a decreased risk of IS after adjustment for sex and age (OR = 0.82; 95%CI, 0.70‐0.96; P = 0.016). The model‐based multifactor dimensionality reduction method has revealed 21 two‐order, 124 three‐order, and 474 four‐order gene‐gene (G×G) interactions models meaningfully (Pperm < 0.05) associated with the IS risk. The bioinformatic analysis enabled establishing the studied MMP gene polymorphisms possess a clear regulatory potential and may be targeted by gene regulatory networks driving molecular and cellular pathways related to the pathogenesis of IS. In conclusion, the present study was the first to identify an association between polymorphism rs11225395 of the MMP8 gene and IS risk. The study findings also indicate that MMPs deserve special attention as a potential class of genes influencing the multistep mechanisms of cerebrovascular disease including atherosclerosis in cerebral arteries, acute cerebral artery occlusion as well as the ischemic injury of the brain and its recovery.
Purpose of the study. The investigation is aimed to provide a systematic comparison of different contrasting methods for in vivo micro-CT diagnostic of orthotopic colorectal cancer models extracted by ortotopic implantation into the caecum of immunocompromised mice BALB/c Nude lines.Materials and methods. BALB/c Nude (N = 25) female mice were implanted by transplanted human colorectal cancer strain into the cecum. 20 days after the implantation mice were administered with iodine-based contrast agent Optiray by means of different administration method (intravenously, per os, intraperitoneally, per rectum) and micro-CT scans have been registered via Quantum GX2 tomograph. Measurement of tumor nodes was performed both by means of estimation from micro-CT images via RadiAnt DICOM Viewer software and by means of explicit measurements using calipers upon laparotomy and posthumously. At the last stage of the study, the animals were euthanized by cervical dislocation. The tumors were excised, measured with a caliper and placed in 10 % formalin for the standard histological analysis according to the standard methods.Results. The average volumes of tumor xenografts in animals with intravenous, oral, and intraperitoneal contrast administration measured at micro-CT were 53.7 ± 5.2 mm3, 52.7 ± 6.4 mm3 and 63.6 ± 5.6 mm3 respectively; measured at laparotomy – 43.0 ± 5.5 mm3, 44.5 ± 5.4 mm3 and 58.5 ± 5.5 mm3 respectively; measured post-mortem – 55.2 ± 6.6 mm3, 53.2 ± 8.8 mm3 and 65.9 ± 3.8 mm3 respectively. The average volumes of tumor xenografts isolated post-mortem in these groups were comparable with the values shown at micro-CT, but larger than the volumes measured at laparotomy.Conclusion. The results obtained demonstrated that intravenous, peroral and intraperitoneal administration techniques provide the best visualization of laboratory rodents pathological tissue upon in vivo micro-CT diagnostics and thus are preferred.
Purpose of the study. Evaluation of the antioxidant status and DNA damage in tissues of subcutaneous xenografts of non-small cell lung cancer and in peritumoral tissues created using the A549 and H1299 cell cultures.Materials and methods. The study included 35 intact male Balb/c Nude immunodeficient mice. Cell lines A549 and H1299 were used as transplantable tumor biomaterial. A CDX model was created in accordance with the protocol for supratentorial injections (Ozawa T., James C. D., 2010) adapted for this experiment. Growth rates were controlled and intracranial xenografts were visualized using a high-resolution micro-CT system. The activity of catalase and superoxide dismutase was determined with non-denaturing electrophoresis in 8 % and 12 % polyacrylamide gel. The concentrations of sulfhydryl groups were determined according to Ellman. The DNA damage in lymphocytes was determined by the comet assay.Results. The experiment resulted in the creation of models of brain tumors characterized by intracranial growth pattern in 100 %. The activity of catalase in the studied lysates of intracranial xenografts, peritumoral tissue and healthy tissues of tumor-bearing animals in all experimental groups increased statistically significantly relative to the healthy tissue of intact animals, and the greatest differences from the control were recorded in the group of animals with implanted H1299 culture at a concentration of 1 × 106 . Superoxide dismutase activity in the studied lysates of intracranial xenografts and peritumoral tissues statistically significantly increased compared to the control sample in all experimental groups. The highest increase in the SOD activity was observed in the tissues of intracranial xenografts with the highest tumor load, which amounted to 28.8 % and 32.9 % of the changes relative to the control sample. A statistically significant increase in the concentration of SH-groups relative to the control sample in tumor tissue lysates was revealed in all experimental groups, and the highest concentration (36.2 ± 0.47) was observed in the group of experimental animals with the highest tumor load. Percentage change in tail moment (DNA damage indicator) in groups O1, O2, O3 and O4 increased statistically significantly compared to the control sample by 55.8 %, 111.8 %, 97.3 % and 170 %, respectively.Conclusions. The observed increase in the activity of the antioxidant defense system, accumulation of oxidative modifications of proteins, and an increase in DNA double-strand breaks in the tissues of intracranial xenografts of non-small cell lung cancer in vivo suggest that the created models reflect processes similar to those in tumors of human non-small cell lung cancer.
the tumor growth index. By the end of the experiment, subcutaneous xenograft volumes and the tumor growth indices in the groups receiving temozolomide or bortezomib monotherapy, as well as in the temozolomide+bortezomib group, were statistically significantly lower than the corresponding values in the control group. The highest ITG% value was registered in the temozolomide+bortezomib group (85.38%); the values in groups with temozolomide and bortezomib monotherapy were 57.32% and 63.11%, respectively. Studies of the antitumor efficacy of the bortezomib and temozolomide combination in human subcutaneous PDX-glioblastomas demonstrate a synergistic effect of these drugs.
The present article is dedicated to the current practices of providing the internally displaced persons with social housing and living premises from Funds for temporary living. The author comes to the conclusion that despite the implementation of the decentralization of power reform in Ukraine, within which the local self-government system gained more financial opportunities, the problem of extremely low housing provision for citizens in need of better living conditions continues to be one of the most pressing economic and social problems in Ukraine. It is emphasized that the issue of housing for internally displaced persons remains one of the most important for them. The article provides an in-depth analysis of the «transformation» of the Law of Ukraine "On Housing Fund for Social Purpose" taking into account contemporary socio-economic changes in the state and society. It is substantiated that the state policy should be aimed at modernization of the state housing policy by combining the efforts of the state and private capital, which will allow to build not only social housing and, for example, to lease it with further redemption, but also affordable. It is argued that currently the Law of Ukraine “On Housing Fund for Social Purpose” does not actually work and is declarative in nature, and therefore it does not fulfill its basic purpose - to ensure the constitutional right of socially vulnerable part of the population of Ukraine to receive social housing. If the abovementioned Law is not changed it will not solve the housing problems of internally displaced persons. In order to account the social housing in Ukraine, it is proposed to recognize the necessity of carrying out its inventory. The article reflects the key aspects of the practical implementation of internally displaced persons’ right to housing from the Temporary Housing Funds exclusively for internally displaced persons. The need to increase the awareness of internally displaced persons about existing housing programs and their ability to participate in these programs, including the possibility of obtaining housing from Temporary Housing Funds exclusively for internally displaced persons, was emphasized.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.