Effect of a Peptide Construct on Differentiated Macrophage MMP-2 and MMP-9 Levels of Varicose Patients

2020 ◽  
Vol 25 (40) ◽  
pp. 4303-4309
Author(s):  
Golnaz Esfandiari ◽  
Azim S. Biranvand ◽  
Adeleh Poursaleh ◽  
Naser Kakavandi ◽  
Fahimeh Fattahi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Varicose Veins ◽  
Docking Studies ◽  
Activity Levels ◽  
Matrix Remodeling ◽  
The Matrix ◽  
Enzyme Functions ◽  
Catalytic Functions ◽  
Gene Expression Levels ◽  
Expression And Activity

Background: The Matrix Metalloproteinase (MMPs) secreted from macrophages can affect the extracellular matrix remodeling process and improve varicose veins. Aim: The aim of this study was to investigate the MMP-2 and MMP-9 gene expression and activity levels in the differentiated macrophages M2 of subjects with varicose veins, and to evaluate a peptide construct on their catalytic functions. Methods: The macrophages were differentiated from the monocytes using M-CSF. The MMP-2 and MMP-9 gene expression and activity levels were measured by RT-qPCR and Zymography techniques, respectively. A peptide construct (ESLCG) was predicted with bioinformatics tools, and was prepared for the study of enzyme functions as compared to Batimastat. Furthermore, the docking studies were obtained for the evaluation of interactions between peptide construct, Batimastat and enzyme 3D structures. Results: The results showed significant increases in MMP2 and MMP9 gene expression levels (P <0.001 and P <0.004, respectively) and gelatinolytic activities (P <0.001 and P <0.0001, respectively) in the macrophages. In agreement with the inhibitory effects of Batimastat, the peptide construct inhibited the MMP-2 and MMP-9 gelatinolytic activities up to 6.8 and 6.5 folds in the concentration of 150 µM. The docking analyses showed that the Lys187, Arg98, Leu49, Gly189, Leu190, Met97, Tyr53 and Phe57 residues of MMP-2 and the Leu187, His190, Glu402, His401, His405 and His411 residues of MMP-9 are interacted with the atoms of Batimastat and ESLCG peptide. Conclusion: The ESLCG peptide may be applied as an inhibitor of MMP-2 and MMP-9 enzymes in the subjects with varicose veins.

scholarly journals The Gene Expression of MMP-2 and TIMP-1 in Non-pathological Paratumoral and Autopsy Lung Tissues

2021 ◽  
Vol 4 (1) ◽  
pp. 61-65
Author(s):  
Elahe Esmaeili ◽  
◽  
Sara Ghaffarpour ◽  
Alireza Sadeghipour ◽  
Tooba Ghazanfari ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Tissue ◽  
Matrix Metalloproteinase 2 ◽  
Control Group ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Formalin Fixed ◽  
Gene Expression Levels

Background: Finding a sample of healthy tissue is a critical challenge in research studies. Non-pathological Tissue adjacent to the tumor (NAT) specimens is usually used as the control in several studies. However, little is known about the similarity of NAT to healthy tissues. Here, we compared the expression of Matrix Metalloproteinase 2 (MMP-2) and its inhibitor, Tissue Inhibitors of MMP (TIMP)-1 as extracellular matrix remodeling factors in NAT and autopsy lung tissue. Materials and Methods: RNA of 7 NAT and 6 Formalin-Fixed Paraffin-Embedded (FFPE) lung autopsies from healthy people as the control group was extracted, and cDNA was synthesized. The gene expression levels of MMP-2 and TIMP-1 were evaluated by real-time PCR. Results: There were no significant differences in the expression of MMP-2, TIMP-1, or their ratio between the two groups. Conclusion: The results showed that NAT could be used as healthy controls in lung tissue studies for MMP-2 and TIMP-1.

Effects of selenium, zinc, insulin and metallothionein on cadmium-induced oxidative stress and metallothionein gene expression levels in diabetic rats

2020 ◽  
Vol 31 (2) ◽  
Author(s):  
Huseyin Gungor ◽  
Haki Kara
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Diabetic Rats ◽  
Control Group ◽  
Activity Levels ◽  
Sod Activity ◽  
Expression Levels ◽  
Group 6 ◽  
Group 5 ◽  
Gene Expression Levels

AbstractBackgroundThe aim of this study was to investigate the effects of selenium, zinc, insulin, and metallothionein on oxidative damage and metallothionein (MT) gene expression levels in streptozotocin (STZ)-induced type 1 diabetic rats exposed to Cd.MethodsRats were categorized under eight groups (control, STZ, Cd, STZ + Cd, Group 5, Group 6, Group 7, and STZ + Cd + MT [n:8/group]) were used. After diabetes was induced by STZ (55 mg/kg, i.p.), Cd was administered (1 mg/kg CdCl, orally) for 4 weeks. In cadmium-treated groups selenium (Na2SeO3 1.5 mg/kg, i.p.), zinc (ZnSO4 10 mg/kg via oral gavage), insulin (insulin glargine, 2U/day, s.c.), and MT (1mg/kg, every other 10 days, s.c.) were administered. MT gene expression levels, MDA levels, GPx, SOD, and CAT activity levels were determined in liver and kidney tissues.ResultsMT gene expression and MDA levels increased (p < 0.05) while GPx and SOD activity levels decreased (p < 0.05) in STZ, Cd, and STZ + Cd groups. In Group 5, Group 6, Group 7, and Group 8 groups MT gene expression and MDA levels were decreased while GPx and SOD activity levels were increased (p < 0.05). CAT activity significantly increased (p < 0.05) in STZ + Cd group while there were no significance in other groups (p > 0.05). Compared to the control, Group 5, Group 6, Group 7, and Group 8 groups provided no difference for alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and creatinine levels (p > 0.05).ConclusionsOur results suggest that Se, insulin, Zn and MT may have protective effects against hepatotoxicity and nephrotoxicity caused by Cd exposure in diabetic rats by reducing oxidative stress and MT gene expression levels.

scholarly journals The Effect of Strontium-Substituted Hydroxyapatite Nanofibrous Matrix on Osteoblast Proliferation and Differentiation

Membranes ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 624
Author(s):  
Shiao-Wen Tsai ◽  
Yu-Wei Hsu ◽  
Whei-Lin Pan ◽  
Fu-Yin Hsu
Keyword(s):  
Gene Expression ◽  
Bone Graft ◽  
Adipogenic Differentiation ◽  
Expression Levels ◽  
Cell Carrier ◽  
Proliferation And Differentiation ◽  
The Matrix ◽  
Biological Similarity ◽  
Good Biocompatibility ◽  
Gene Expression Levels

Natural bone tissue consists primarily of bioapatite and collagen. Synthetic hydroxyapatite (HA) possesses good biocompatibility, bioactivity, and osteoconductivity due to its chemical and biological similarity to bioapatite. Hence, HA has been widely used as a bone graft, cell carrier and drug/gene delivery carrier. Moreover, strontium-substituted hydroxyapatite (SrHA) can enhance osteogenic differentiation and inhibit adipogenic differentiation of mesenchymal stem cells. Hence, SrHA has the potential to be used as a bone graft for bone regeneration. It is widely accepted that cell adhesion and most cellular activities are sensitive to the topography and molecular composition of the matrix. Electrospun polymer or polymer-bioceramic composite nanofibers have been demonstrated to enhance osteoblast differentiation. However, to date, no studies have investigated the effect of nanofibrous bioceramic matrices on osteoblasts. In this study, hydroxyapatite nanofiber (HANF) and strontium-substituted hydroxyapatite nanofiber (SrHANF) matrices were fabricated by electrospinning. The effect of the HANF components on MG63 osteoblast-like cells was evaluated by cell morphology, proliferation, alkaline phosphatase activity (ALP) and gene expression levels of RUNX2, COLI, OCN and BSP. The results showed that MG63 osteoblast-like cells exhibited higher ALP and gene expression levels of RUNX2, COLI, BSP and OCN on the SrHANF matrix than the HANF matrix. Hence, SrHANFs could enhance the differentiation of MG63 osteoblast-like cells.

scholarly journals Dysregulations of MicroRNA and Gene Expression in Chronic Venous Disease

2020 ◽  
Vol 9 (5) ◽  
pp. 1251 ◽  
Author(s):  
Daniel P. Zalewski ◽  
Karol P. Ruszel ◽  
Andrzej Stępniewski ◽  
Dariusz Gałkowski ◽  
Jacek Bogucki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mononuclear Cells ◽  
Varicose Veins ◽  
Expression Profiles ◽  
Lower Limbs ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Operating Characteristics ◽  
Potential Biomarker ◽  
Pathologic Features

Chronic venous disease (CVD) is a vascular disease of lower limbs with high prevalence worldwide. Pathologic features include varicose veins, venous valves dysfunction and skin ulceration resulting from dysfunction of cell proliferation, apoptosis and angiogenesis. These processes are partly regulated by microRNA (miRNA)-dependent modulation of gene expression, pointing to miRNA as a potentially important target in diagnosis and therapy of CVD progression. The aim of the study was to analyze alterations of miRNA and gene expression in CVD, as well as to identify miRNA-mediated changes in gene expression and their potential link to CVD development. Using next generation sequencing, miRNA and gene expression profiles in peripheral blood mononuclear cells of subjects with CVD in relation to healthy controls were studied. Thirty-one miRNAs and 62 genes were recognized as potential biomarkers of CVD using DESeq2, Uninformative Variable Elimination by Partial Least Squares (UVE-PLS) and ROC (Receiver Operating Characteristics) methods. Regulatory interactions between potential biomarker miRNAs and genes were projected. Functional analysis of microRNA-regulated genes revealed terms closely related to cardiovascular diseases and risk factors. The study shed new light on miRNA-dependent regulatory mechanisms involved in the pathology of CVD. MicroRNAs and genes proposed as CVD biomarkers may be used to develop new diagnostic and therapeutic methods.

scholarly journals Alternative splicing during mammalian organ development

2021 ◽  
Author(s):  
Pavel V. Mazin ◽  
Philipp Khaitovich ◽  
Margarida Cardoso-Moreira ◽  
Henrik Kaessmann
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Regulatory Networks ◽  
Organ Development ◽  
Functional Diversification ◽  
Mammalian Genomes ◽  
Species Comparisons ◽  
Time Specific ◽  
The Brain ◽  
Gene Expression Levels

AbstractAlternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during development show the strongest signals of conserved and regulated AS. Newly emerged cassette exons are typically incorporated late in testis development, but those retained during evolution are predominantly brain specific. Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart. In these regulatory networks, AS affords substantial functional diversification of genes through the generation of tissue- and time-specific isoforms from broadly expressed genes.

scholarly journals A Sparse and Low-Rank Regression Model for Identifying the Relationships Between DNA Methylation and Gene Expression Levels in Gastric Cancer and the Prediction of Prognosis

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 854
Author(s):  
Yishu Wang ◽  
Lingyun Xu ◽  
Dongmei Ai
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Dna Methylation ◽  
Regression Model ◽  
The Cancer Genome Atlas ◽  
Low Rank ◽  
Expression Levels ◽  
Rank Regression ◽  
Prediction Of Prognosis ◽  
Gene Expression Levels

DNA methylation is an important regulator of gene expression that can influence tumor heterogeneity and shows weak and varying expression levels among different genes. Gastric cancer (GC) is a highly heterogeneous cancer of the digestive system with a high mortality rate worldwide. The heterogeneous subtypes of GC lead to different prognoses. In this study, we explored the relationships between DNA methylation and gene expression levels by introducing a sparse low-rank regression model based on a GC dataset with 375 tumor samples and 32 normal samples from The Cancer Genome Atlas database. Differences in the DNA methylation levels and sites were found to be associated with differences in the expressed genes related to GC development. Overall, 29 methylation-driven genes were found to be related to the GC subtypes, and in the prognostic model, we explored five prognoses related to the methylation sites. Finally, based on a low-rank matrix, seven subgroups were identified with different methylation statuses. These specific classifications based on DNA methylation levels may help to account for heterogeneity and aid in personalized treatments.

scholarly journals Testicular Melatonin and Its Pathway in Roe Deer Bucks (Capreolus capreolus) during Pre- and Post-Rut Periods: Correlation with Testicular Involution

Animals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1874
Author(s):  
Alberto Elmi ◽  
Nadia Govoni ◽  
Augusta Zannoni ◽  
Martina Bertocchi ◽  
Chiara Bernardini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Correlation Analysis ◽  
Roe Deer ◽  
Capreolus Capreolus ◽  
Reproductive Activity ◽  
Melatonin Receptors ◽  
Local Synthesis ◽  
Testicular Weight ◽  
And Function ◽  
Gene Expression Levels

Roe deer are seasonal breeders with a complete yearly testicular cycle. The peak in reproductive activity is recorded during summer, the rutting period, with the highest levels of androgens and testicular weight. Melatonin plays a pivotal role in seasonal breeders by stimulating the hypothalamus–pituitary–gonads axis and acting locally; in different species, its synthesis within testes has been reported. The aim of this study was to evaluate the physiological melatonin pattern within roe deer testes by comparing data obtained from animals sampled during pre- and post-rut periods. Melatonin was quantified in testicular parenchyma, along with the genetic expression of enzymes involved in its local synthesis (AANAT and ASMT) and function (UCP1). Melatonin receptors, MT1-2, were quantified both at protein and gene expression levels. Finally, to assess changes in reproductive hormonal profiles, testicular dehydroepiandrosterone (DHEA) was quantified and used for a correlation analysis. Melatonin and AANAT were detected in all samples, without significant differences between pre- and post-rut periods. Despite DHEA levels confirming testicular involution during the post-rut period, no correlations appeared between such involution and melatonin pathways. This study represents the first report regarding melatonin synthesis in roe deer testes, opening the way for future prospective studies in the physiology of this species.

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