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1.
IUBMB Life ; 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38662920

ABSTRACT

The aim of this study was to develop an alternative treatment method for neurodegenerative diseases with dopaminergic neuron loss such as Parkinson's disease by differentiating cells obtained from human olfactory mucosa-derived neural stem cells (hOM-NSCs) with neurotrophic agents in vitro. hOM-NSCs were isolated and subjected to immunophenotypic and MTT analyses. These hOM-NSCs were then cultured in a 3D environment to form neurospheres. The neurospheres were subjected to immunophenotypic analysis and neuronal differentiation assays. Furthermore, hOM-NSCs were differentiated into dopaminergic neuron-like cells in vitro. After differentiation, the dopaminergic neuron-like cells were subjected to immunophenotypic (TH, MAP2) and genotypic (DAT, PITX3, NURR1, TH) characterization. Flow cytometric analysis showed that NSCs were positive for cell surface markers (CD56, CD133). Immunofluorescence analysis showed that NSCs were positive for markers with neuronal and glial cell characteristics (SOX2, NESTIN, TUBB3, GFAP and NG2). Immunofluorescence analysis after differentiation of hOM-NSCs into dopaminergic neuron-like cells in vitro showed that they were positive for a protein specific for dopaminergic neurons (TH). qRT-PCR analysis showed that the expression of dopaminergic neuron-specific genes (DAT, TH, PITX3, NURR1) was significantly increased. It was concluded that hOM-NSCs may be a source of neural stem cells that can be used for cell replacement therapies in neurodegenerative diseases such as Parkinson's disease, are resistant to cell culture, can differentiate into neuronal and glial lineage, are easy to obtain and are cost effective.

2.
Article in English | MEDLINE | ID: mdl-38536434

ABSTRACT

Targeting lung cancer stem cells (LC-SCs) for metastasis may be an effective strategy against lung cancer. This study is the first on epithelial-mesenchymal transition (EMT) properties of boric acid (BA) in LC-SCs. LC-SCs were isolated using the magnetic cell sorting (MACS) method. Tumor-sphere formation and flow cytometry confirmed CSC phenotype. The cytotoxic effect of BA was measured by MTT analysis, and the effect of BA on EMT was examined by migration analysis. The expression levels of ZEB1, SNAIL1, ITGA5, CDH1, ITGB1, VIM, COL1A1, and LAMA5 genes were analyzed by RT-qPCR. E-cadherin, Collagen-1, MMP-3, and Vimentin expressions were analyzed immunohistochemically. Boric acid slightly reduced the migration of cancer cells. Increased expression of transcription factor SNAIL (p < 0.001), but not ZEB1, was observed in LC-SCs. mRNA expression levels of ITGB1 (p < 0.01), ITGA5 (p < 0.001), COL1A1 (p < 0.001), and LAMA5 (p < 0.001) increased; CDH1 and VIM decreased in LC-SCs. Moreover, while E-cadherin (p < 0.001) and Collagen-1 (p < 0.01) immunoreactivities significantly increased, MMP-3 (p < 0.001) and Vimentin (p < 0.01) immunoreactivities decreased in BA-treated LC-SCs. To conclude, the current study provided insights into the efficacy and effects of BA against LC-SCs regarding proliferation, EMT, and cell death for future studies.

3.
Curr Mol Med ; 2023 Oct 19.
Article in English | MEDLINE | ID: mdl-37859306

ABSTRACT

BACKGROUND: Cartilage injuries are currently the most prevalent joint disease. Previous studies have emphasized the use of stem cells as the effective treatment for regenerating cartilage damage. OBJECTIVE: In this study, considering the difficulties of the cellular therapy method, it was hypothesized that human synovial fluid-derived mesenchymal stem cell (hSFMSC) exosomes as a SC source could be used to treat these injuries as a safer and cell-free therapeutic alternative procedure due to its direct relevance to cartilage regeneration. Moreover, this study aimed to determine the miRNA and target genes required for the formation of SC treatment combined with gene therapy in order to reveal the mechanism of cartilage regeneration and increase its effectiveness. METHODS: MSCs were characterized by flow cytometry, and immunocytochemical and differentiation analyses were done. To characterize functionally isolated exosomes, in vitro uptake analysis was performed. RT-qPCR was used to examine in terms of the advantages of cellular and cell-free therapy, mature human chondroblasts derived by differentiation from hSF-MSCs and human chondrocyte profiles were compared in order to demonstrate the above profile of hSF-MSCs and exosomes isolated from them, and the effectiveness of SC therapy in repairing cartilage damage. RESULTS: According to our findings, the expression level of hsa-miR-155-5p was found to be considerably higher in chondrocytes differentiated from human synovial fluid MSCs than in mature human chondrocytes. These findings were also supported by the TGF-signalling pathway and chondrogenesis marker genes. CONCLUSION: It was concluded that hSF-MSCs and exosomes can be used in the treatment of cartilage damage, and hsa-miR-155-5p can be used as a target miRNA in a new gene therapy approach because it increases the therapeutic effect on cartilage damage.

4.
Macromol Biosci ; 23(12): e2300204, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37532233

ABSTRACT

Permanent injury to corneal limbal stem cells after ocular surface chemical and thermal injuries is a major cause of corneal blindness. In this study, a PRP-laden GelMA hydrogel contact lens is manufactured which is aimed to support the limbal niche after ocular surface insults thereby preventing limbal stem cell failure. GelMA with varying platelet-rich plasma (PRP) concentrations (5%, 10%, and 20%) is photopolymerized using a visible light crosslinking system followed by characterizations of mechanical properties, growth factor release, enzymatic degradation, and in vitro cytotoxicity. The addition of 10% PRP into 10% GelMA hydrogel precursor solution results in the highest tensile and compressive modulus (38 and 110 kPa, respectively) and burst pressure (251±37.66 mmHg). Degradation time varies according to the concentration of the collagenase enzyme tested (0, 2.5, 5, and 40 µg/mL) and is most prolonged with 20% PRP. EGF and TGF-ß release profiles suggest an initial burst release followed by sustained release, most consistent in the 10% PRP sample. Although cell viability decreases on day 1, rapid recovery is observed and is approximately 120% after day 21. PRP-laden GelMA in the form of a contact lens may be a promising biomaterial-based treatment approach for the maintenance of limbal epithelial stem cells after ocular surface insults.


Subject(s)
Contact Lenses , Platelet-Rich Plasma , Hydrogels/chemistry , Cornea , Intercellular Signaling Peptides and Proteins , Platelet-Rich Plasma/chemistry , Platelet-Rich Plasma/metabolism
5.
Gene ; 865: 147337, 2023 May 20.
Article in English | MEDLINE | ID: mdl-36878417

ABSTRACT

This study aimed to investigate the differences between the exosomal microRNA-127-5p expression profiles of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) and human synovial fluid-derived mesenchymal stem cells (hSF-MSCs) during chondrogenesis in terms of regenerative treatment of cartilage. Synovial fluid-derived mesenchymal stem cells, adipose tissue-derived mesenchymal stem cells, and human fetal chondroblast cells (hfCCs) were directed to chondrogenic differentiation. Alcian Blue and Safranin O stainings were performed to detect chondrogenic differentiation histochemically. Exosomes derived from chondrogenic differentiated cells and their exosomes were isolated and characterized. microRNA-127-5p expressions were measured by Quantitative reverse transcription PCR (qRT-PCR). Significantly higher levels of microRNA-127-5p expression in differentiated hAT-MSCs exosomes, similar to human fetal chondroblast cells, which are the control group in the chondrogenic differentiation process, were observed. hAT-MSCs are better sources of microRNA-127-5p than hSF-MSCs for stimulating chondrogenesis or in the regenerative therapy of cartilage-related pathologies. hAT-MSCs exosomes are rich sources of microRNA-127-5p and can be an essential candidate for cartilage regeneration treatments.


Subject(s)
Exosomes , Mesenchymal Stem Cells , MicroRNAs , Humans , Synovial Fluid/metabolism , Exosomes/genetics , Exosomes/metabolism , Chondrogenesis/genetics , Cell Differentiation , MicroRNAs/genetics , MicroRNAs/metabolism , Mesenchymal Stem Cells/metabolism , Cells, Cultured
6.
Med Oncol ; 39(12): 191, 2022 Sep 07.
Article in English | MEDLINE | ID: mdl-36071274

ABSTRACT

Klotho is an anti-aging, anti-inflammator, and anti-oxidative protein and has been shown to important role in tumorigenesis, proliferation, survival, autophagy, and resistance to tumor suppressor effects in several types of human cancers. In this study, we aimed to investigate possible anti-tümör and apoptotic effects of exogen klotho in human colorectal adenocarcinoma cells (HT-29) and healthy colon cells (CCD 841 CoN). The WST-8 test was used to determine the half-maximum inhibitory concentration (IC50) of the klotho protein. AO-PI fluorescent staining techniques and Annexin V-PI flow cytometry was utilized to observe and detect the apoptosis of cancer cells induced by klotho. Our results demonstrated that klotho had a cytotoxic effect against colorectal adenocarcinoma cells in a dose-dependent manner. Our Annexin V-PI flow cytometric and AO-PI fluorescent analyses showed that klotho induced quantitative and morphological changes that indicate apoptotic induction in the human colorectal adenocarcinoma. This study results proved for the first time that klotho may be an effective potential therapeutic agent that may be used in adjuvant therapy in human colorectal adenocarcinoma it does not affect selectively healthy colon cells and but leading cancer cells to apoptosis.


Subject(s)
Adenocarcinoma , Colorectal Neoplasms , Klotho Proteins , Adenocarcinoma/drug therapy , Annexin A5/pharmacology , Cell Survival , Colorectal Neoplasms/pathology , HT29 Cells , Humans
7.
Drug Chem Toxicol ; 45(6): 2727-2738, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34628987

ABSTRACT

We investigated the presence of myocardial apoptosis on isoproterenol (ISO)-induced myocardial injury (MI) after long-term high dose alcohol consumption and examined the antiapoptotic role of calpain inhibitor 1. Male Wistar Albino rats (n = 108) were divided into six groups: Control, alcohol (ethanol was given during 30 days for chronic alcohol consumption), MI (150 mg/kg ISO injection at last two days of alcohol consumption), alcohol + MI, alcohol + MI + calpain inhibitor 1 (10 mg/kg inhibitor was injected at 15 min before ISO injections) and Dimethyl Sulfoxide (DMSO) groups. Biochemical, histological, and morphometric methods determined apoptosis levels in the heart tissue of rats. Cytochrome c, caspase 3, and calpain levels were significantly high in alcohol, MI, and alcohol + MI groups. In contrast, mitochondrial cardiolipin content was found to be low in alcohol, MI, and alcohol + MI groups. These parameters were close to the control group in the therapy group. Histological and morphometric data have supported biochemical results. As a result of our biochemical data, myocardial apoptosis was seen in the alcohol, MI, and especially alcohol after MI groups. Calpain inhibitor 1 reduced apoptotic cell death and prevented myocardial tissue injury in these groups. The efficiency of calpain inhibitor was very marked in MI after long-term high dose alcohol consumption.


Subject(s)
Alcoholism , Myocardial Infarction , Animals , Male , Rats , Alcohol Drinking , Alcoholism/metabolism , Alcoholism/pathology , Apoptosis , Calpain/metabolism , Calpain/pharmacology , Cardiolipins/metabolism , Cardiolipins/pharmacology , Cardiolipins/therapeutic use , Caspase 3/metabolism , Cytochromes c/metabolism , Dimethyl Sulfoxide/metabolism , Dimethyl Sulfoxide/pharmacology , Dimethyl Sulfoxide/therapeutic use , Ethanol/toxicity , Isoproterenol/toxicity , Myocardial Infarction/drug therapy , Myocardial Infarction/pathology , Myocardial Infarction/prevention & control , Myocardium/metabolism , Rats, Wistar
8.
Med Oncol ; 38(12): 146, 2021 Oct 23.
Article in English | MEDLINE | ID: mdl-34687379

ABSTRACT

Human Klotho gene has many known functions such as anti-aging and anti-tumor, and decreased expression of this gene causes malignant formations in most types of cancer, including colon cancer. Interacting with TRAIL death receptors (DR4 and DR5) induces an apoptotic effect in cancer treatments by reducing the proliferation of cancer cells. The present study aimed to investigate downstream effect of overexpression of Klotho gene, which is known to have an antitumor effect on resistant human colon cancer cells, by examining its action on TRAIL death and decoy (DcR1 and DcR2) receptors for the first time. For this purpose, upregulation of human Klotho gene was achieved with CRISPR/Cas9-mediated system in resistant human colon cancer Caco-2 cells. To determine the effect of upregulation of Klotho gene on cancer cells evaluations with flow cytometry, WST-8, qRT-PCR, ELISA, and immunohistochemical analysis were performed. Then, Klotho gene was knocked out and its apoptotic effect was tested to find out whether it is due to overexpression of Klotho gene or not. Our results indicate that overexpression of Klotho gene in Caco-2 cells via CRISPR/Cas9-sensitized TRAIL death receptor DR4 suppresses the proliferation of cells by leading to apoptosis. Thus, this study conducted on apoptosis-resistant colon cancer cells may bring new insights about the role of Klotho gene in colon cancer.


Subject(s)
CRISPR-Cas Systems/physiology , Colonic Neoplasms/pathology , Gene Expression Regulation, Neoplastic , Klotho Proteins/genetics , Receptors, TNF-Related Apoptosis-Inducing Ligand/physiology , Apoptosis , Caco-2 Cells , Colonic Neoplasms/genetics , Humans , Signal Transduction/physiology
9.
Rev Port Cardiol (Engl Ed) ; 39(12): 687-693, 2020 Dec.
Article in English, Portuguese | MEDLINE | ID: mdl-33190967

ABSTRACT

INTRODUCTION AND OBJECTIVES: D-dimers are a determinant of hypercoagulable state and have been found to be related to acute coronary syndromes. We aimed to establish the association between increased D-dimer levels and coronary artery disease (CAD) severity using SYNTAX Score (SS) II in patients with ST elevation myocardial infarction (STEMI) who underwent primary percutaneous coronary intervention (PCI). METHODS: This retrospective study included 300 consecutive patients (81.7% males, mean age 55±12 years) with STEMI who underwent a primary PCI. Patients were divided into two groups according to their median SSII [SSII<25 as a low group (n=151) and SSII≥25 as a high group (n=149)]. Blood samples for D-dimers and the other biochemical parameters were obtained from each patient at admission. RESULTS: When compared with the low SSII group, frequency of female gender, no-reflow phenomenon, D-dimer levels, thrombus score, creatine kinase MB and troponin were significantly higher, whereas left ventricular ejection fraction (LVEF) and glomerular filtration rate (GFR) were lower in the high SSII group (p<0.05, for all). D-dimer levels, thrombus score, LVEF, GFR and no-reflow phenomenon were independent predictors of CAD severity (p<0.05, for all). Receiver operating characteristic curve analysis showed that the D-dimer cut-off value for predicting the severity of CAD was 0.26 µg/ml (69.8% sensitivity and 65.6% specificity, p<0.001). CONCLUSION: Increased D-dimer levels are associated with the severity of CAD based on Syntax Score II, in patients with STEMI who successfully underwent revascularization with a primary PCI.


Subject(s)
Coronary Artery Disease , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , Adult , Aged , Female , Fibrin Fibrinogen Degradation Products , Humans , Male , Middle Aged , Retrospective Studies , ST Elevation Myocardial Infarction/surgery , Severity of Illness Index , Stroke Volume , Ventricular Function, Left
10.
J Gynecol Obstet Hum Reprod ; 49(9): 101835, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32585394

ABSTRACT

The aim of the present study was to investigate the expression patterns of prokineticins (PROK) and prokineticin receptors (PROKR) in the endometrium of women with recurrent implantation failure (RIF). Fifteen (15) women with RIF and 15 fertile controls were enrolled in this study. Endometrial samples were taken from study participants with an endometrial biopsy cannula during the implantation window. Real time polymerase chain reaction and immunohistochemistry were used to determine PROK/PROKR mRNA expression and protein localization, respectively. PROK1 mRNA levels were 6.09 times higher compared to endometrial samples obtained from women with RIF than in samples obtained from fertile controls, whereas PROKR1 mRNA levels were 2.46 times lower in endometrial samples obtained from women with RIF than in samples from fertile controls. In addition, decreased PROKR1 was supported by immunohistochemistry analysis at protein level. There was no statistically significant difference between women with RIF and fertile controls regarding PROK2 and PROKR2 levels. Altered expression of the PROK1/PROKR1 system could be one of the numerous abnormalities in the endometrium of women with RIF.


Subject(s)
Embryo Implantation/physiology , Endometrium/metabolism , Fertilization in Vitro , Gastrointestinal Hormones/genetics , Gene Expression/physiology , Receptors, G-Protein-Coupled/genetics , Vascular Endothelial Growth Factor, Endocrine-Gland-Derived/genetics , Adult , Endometrium/chemistry , Female , Gastrointestinal Hormones/analysis , Gastrointestinal Hormones/physiology , Humans , Infertility, Female/genetics , Infertility, Female/therapy , Pregnancy , RNA, Messenger/analysis , Receptors, G-Protein-Coupled/analysis , Receptors, G-Protein-Coupled/physiology , Treatment Failure , Vascular Endothelial Growth Factor, Endocrine-Gland-Derived/analysis , Vascular Endothelial Growth Factor, Endocrine-Gland-Derived/physiology
11.
Immunobiology ; 224(4): 585-594, 2019 07.
Article in English | MEDLINE | ID: mdl-31072631

ABSTRACT

Mesenchymal stem cells (MSCs) are strong immunomodulatory cells investigated in numerous clinical studies on fatal pathologies, such as graft versus host disease and autoimmune diseases; e.g., systemic lupus erythematosus, Crohn's disease, and ulcerative colitis. Macrophages are one of the critical cells linking the innate and adaptive immune system, and it has been shown that MSCs can differentiate between pro-inflammatory M1 phenotype and anti-inflammatory M2 phenotype of macrophages. However, it has not yet been fully clarified whether these differentiated macrophages are functional. In this study, we compared the immunomodulatory effects on the CD4 T cells of M1, M2a and M2c macrophages with the macrophages that directly and indirectly cultured with MSCs. We analyzed the changes in CD14, CD64, CD80, CD163 and CD200R expression to evaluate macrophage phenotypes, and the changes in CD4, IFN-g, IL-4, IL-17a and FoxP3 expression to evaluate T helper subsets using the FACS method. The changes in IL-1b, IL-4, IL-10, IL-12p70, IL-17a and IFN-g in the media supernatants were analyzed using the Luminex method. We also performed WST-1 and Caspase-3 ELISA analyses to observe the proliferation and apoptosis status of the T cells. MSCs were found to differentiate macrophages into a distinctive phenotype, which was close to the M2c phenotype, but was not considered as an M2c cell due to the low expression of CD163, a characteristic marker for M2c. While MEM-D, MEM-ID and MSCs showed similar inhibitory effects on the Th2 and Th17 cells, the most significant increase in Treg cell frequencies was seen in MEM-D cells. Macrophages can alter their phenotypes and functions according to the stimuli from the environment. The fact that macrophages educated with MSCs suppressed the production of all the cytokines we evaluated even after the removal of MSCs suggests that these cells may be differentiated by MSCs into a suppressive macrophage subgroup. However, the Treg cell activation caused by direct interactions between MSCs and macrophage cells may be the most prominent observation of this study compared to previous work. As a result, according to our data, the interactions between MSCs and macrophages may lead to differentiation of macrophage cells into an immunosuppressive phenotype, and these macrophages may suppress the T lymphocyte subgroups at least as effectively as MSCs. However, our data obtained from in vitro experiments should be supported by future in vivo studies.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Immunomodulation , Macrophages/immunology , Mesenchymal Stem Cells/immunology , Adipose Tissue/cytology , Apoptosis , Biomarkers , CD4-Positive T-Lymphocytes/metabolism , Cell Proliferation , Cells, Cultured , Immunophenotyping , Macrophages/metabolism , Mesenchymal Stem Cells/metabolism
12.
Kidney Blood Press Res ; 43(3): 807-819, 2018.
Article in English | MEDLINE | ID: mdl-29843153

ABSTRACT

BACKGROUND/AIMS: Hypertension is the leading cause of death worldwide. Chronic high blood pressure induces inflammation. Tumor necrosis factor (TNF)-α plays a major role in inflammation and also depresses the synthesis of erythropoietin, which exerts protective effects on tissue; however, the mechanism is still unclear. We investigated the protective effect of erythropoietin against tissue damage caused by hypertension in the kidney and whether this effect was suppressed by TNF-α. METHODS: First, we detected the optimum chronic dose for darbepoetin-α (Depo), which is a long-acting erythropoietin analog for rats. We separated 60 female adult rats into 6 groups: control, Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), L-NAME+Depo, L-NAME+Remicade (an anti-TNF-α antibody), L-NAME+Depo+Remicade, Depo, and control. After 1 month of treatment, we measured cardiovascular parameters, took blood samples, sacrificed the rats, and removed kidneys for analyses. RESULTS: The apoptotic index and the plasma and kidney mRNA levels of TNF-α increased in the L-NAME group and decreased in all other treatment groups. Macrophage accumulation increased in the L-NAME and L-NAME+Remicade groups, while it decreased in the Depo group. The mRNA abundance of TNF receptor 1 (TNFR1) decreased slightly in the Depo group and TNFR2 increased significantly in the same group. CONCLUSION: Erythropoietin protects kidney tissue against hypertension by preventing the apoptotic effects of TNF-α by blocking macrophage accumulation, decreasing TNF-α levels, and switching the TNF-α receptors from the apoptotic receptor TNFR1 to the proliferative receptor TNFR2.


Subject(s)
Erythropoietin/pharmacology , Hypertension/drug therapy , Kidney/drug effects , Tumor Necrosis Factor-alpha/pharmacology , Animals , Darbepoetin alfa/pharmacology , Erythropoietin/therapeutic use , Female , Hypertension/chemically induced , Kidney/pathology , Kidney/physiopathology , NG-Nitroarginine Methyl Ester/adverse effects , Protective Agents/pharmacology , Rats , Receptors, Tumor Necrosis Factor, Type I/metabolism , Receptors, Tumor Necrosis Factor, Type II/metabolism
13.
Childs Nerv Syst ; 33(3): 407-417, 2017 Mar.
Article in English | MEDLINE | ID: mdl-28062893

ABSTRACT

PURPOSE: Alcohol consumption in pregnancy may cause fetal alcohol syndrome (FAS) in the infant. This study aims to investigate prenatal alcohol exposure related neuroapoptosis on the cerebral cortex tissues of newborn rats and possible neuroprotective effects of betaine, folic acid, and combined therapy. METHODS: Pregnant rats were divided into five experimental groups: control, ethanol, ethanol + betaine, ethanol + folic acid, and ethanol + betaine + folic acid combined therapy groups. We measured cytochrome c release, caspase-3, calpain and cathepsin B and L. enzyme activities. In order to observe apoptotic cells in the early stages, TUNEL method was chosen together with histologic methods such as assessing the diameters of the apoptotic cells, their distribution in unit volume and volume proportion of cortical intact neuron nuclei. RESULTS: Calpain, caspase-3 activities, and cytochrome c levels were significantly increased in alcohol group while cathepsin B and L. activities were also found to be elevated albeit not statistically significant. These increases were significantly reversed by folic acid and betaine + folic acid treatments. While ethanol increased the number of apoptotic cells, this increase was prevented in ethanol + betaine and ethanol + betaine + folic acid groups. Morphometric examination showed that the mean diameter of apoptotic cells was increased with ethanol administration while this increase was reduced by betaine and betaine + folic acid treatments. CONCLUSION: We observed that ethanol is capable of triggering apoptotic cell death in the newborn rat brains. Furthermore, folic acid, betaine, and combined therapy of these supplements may reduce neuroapoptosis related to prenatal alcohol consumption, and might be effective on preventing fetal alcohol syndrome in infants.


Subject(s)
Apoptosis/drug effects , Betaine/therapeutic use , Cerebral Cortex/pathology , Ethanol/toxicity , Folic Acid/therapeutic use , Neuroprotective Agents/therapeutic use , Prenatal Exposure Delayed Effects , Animals , Animals, Newborn , Apoptosis/physiology , Blood Alcohol Content , Calpain/metabolism , Caspase 3/metabolism , Cathepsin B/metabolism , Cathepsin L/metabolism , Central Nervous System Depressants/toxicity , Cytochromes c/metabolism , Disease Models, Animal , Female , Pregnancy , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/drug therapy , Prenatal Exposure Delayed Effects/pathology , Rats , Rats, Sprague-Dawley
14.
Kardiol Pol ; 75(2): 174-180, 2017.
Article in English | MEDLINE | ID: mdl-27391914

ABSTRACT

BACKGROUND: Increasing evidence suggests a relationship between vitamin D (VD) insufficiency and cardiovascular disease. AIM: We aimed to investigate the association between serum 25-hydroxyvitamin D (25-OH VD) with coronary tortuosity (CT) in patients with normal or near-normal (< 40% stenosis) coronary arteries. METHODS: The present study was cross-sectional and observational. We enrolled 356 consecutive patients who had undergone coronary angiography for suspected ischaemic heart disease and were found to have normal or near-normal coronary arteries. Patients were categorised as VD insufficient (< 30 ng/mL) or VD sufficient (≥ 30 ng/dL). CT was defined as the presence of ≥ three bends (defined as ≥ 45° change in vessel direction) along the main trunk of at least one coronary artery, present both in systole and in diastole. RESULTS: The study populations were divided into two groups according to the presence of CT: patients with CT (n = 103, 29%) and patients without CT (NCT; n = 253, 71%). CT is more frequently seen in elderly women and is positively correlated with hypertension. The incidence of VD insufficiency was significantly higher in the CT group (n = 46, 45%) than in the NCT group (n = 90, 36%; p = 0.005). In further multivariate logistic regression analyses, adjustment for major clinical parameters affecting CT showed statistically significant correlations between 25-OH VD and CT (odds ratio = 0.77, 95% confidence interval 0.66-0.98, p = 0.006). CONCLUSIONS: Vitamin D insufficiency was independently associated with coronary tortuosity.


Subject(s)
Coronary Artery Disease/complications , Vitamin D Deficiency/complications , Adult , Aged , Coronary Angiography , Coronary Artery Disease/blood , Coronary Artery Disease/diagnosis , Cross-Sectional Studies , Female , Humans , Hypertension , Logistic Models , Male , Middle Aged , Vitamin D/analogs & derivatives , Vitamin D/blood
15.
Ulus Travma Acil Cerrahi Derg ; 22(5): 423-431, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27849317

ABSTRACT

BACKGROUND: The aim of this study was to investigate the effect of natural antioxidants resveratrol and quercetin on oxidative stress and secondary cell damage in rats with acute spinal cord injury. METHODS: In this experimental study, 42 male Sprague-Dawley rats were used. Spinal cord injury was performed with clip compression method at level of T4-5. The study was conducted using 6 groups: control, trauma, trauma and solvent, trauma and resveratrol, trauma and quercetin, and trauma with combined resveratrol and quercetin. All rats were euthanized 48 hours after the procedure. Effects of resveratrol and quercetin on serum and tissue total antioxidant capacity and paraoxanase activity level were examined. RESULTS: Compared to trauma group, there was a significant increase in total antioxidant capacity and paraoxanase activity level in resveratrol, quercetin, and combined treatment groups. There was no significant difference between resveratrol and quercetin groups with regard to total antioxidant capacity and paraoxanase activity level. Total antioxidant capacity and paraoxanase activity level were significantly higher in solvent group than trauma group. In histopathological evaluation, there was a decrease in polymorphonuclear leukocyte infiltration in solvent, resveratrol, quercetin, and combined treatment groups. CONCLUSION: Biochemical and histological staining results of present study showed that resveratrol and quercetin may be effective in preventing secondary damage in spinal cord injury.


Subject(s)
Antioxidants/therapeutic use , Quercetin/therapeutic use , Spinal Cord Injuries/prevention & control , Stilbenes/therapeutic use , Animals , Antioxidants/administration & dosage , Disease Models, Animal , Inflammation , Male , Oxidative Stress , Quercetin/administration & dosage , Rats , Rats, Sprague-Dawley , Resveratrol , Spinal Cord Injuries/pathology , Stilbenes/administration & dosage
16.
Turk Neurosurg ; 26(6): 878-889, 2016.
Article in English | MEDLINE | ID: mdl-27509453

ABSTRACT

AIM: To determine whether the serum level of glial fibrillary acidic protein (GFAP), an important indicator of neuron damage, correlates with the extent of tissue damage in the rat with induced head trauma and to obtain data in order to avoid unnecessary cranial computed tomography analyses. MATERIAL AND METHODS: Three-month-old male Sprague-Dawley rats were used. Rats were divided into 5 groups. The experimental head trauma model was examined in five groups (n=8) as follows: The control group had no intervention; Group 1: Head trauma was induced by dropping a 25 mg ball from a height of 20 cm; Group 2: Head trauma was induced by dropping a 50 mg ball from a height of 20 cm; Group 3: Head trauma was induced by dropping a 50 mg ball from a height of 80 cm; Group 4: Head trauma was induced by dropping a 100 mg ball from a height of 80 cm. Thus, according to the Newton's Law, respectively 0.05, 0.1, 0.2 and 0.4 N trauma was created. Serum GFAP levels were analyzed and the damage to cerebral tissues was evaluated in all groups. RESULTS: We determined that number of apoptotic cells and particularly the number of GFAP (+) protoplasmic astrocytes at the perilesional region of the cortex increased in association with the increased serum GFAP level as long as the severity of the trauma increased. CONCLUSION: Serum GFAP concentration can be used as a marker of the severity of head trauma and traumatic brain injury. However, more animal studies are required to reflect this result in clinical practice.


Subject(s)
Craniocerebral Trauma/blood , Craniocerebral Trauma/pathology , Glial Fibrillary Acidic Protein/blood , Neurons/pathology , Animals , Apoptosis , Astrocytes/pathology , Biomarkers/blood , Cerebral Cortex/pathology , Craniocerebral Trauma/diagnosis , Craniocerebral Trauma/diagnostic imaging , Disease Models, Animal , Male , Rats
17.
Kardiol Pol ; 74(9): 954-60, 2016.
Article in English | MEDLINE | ID: mdl-27112941

ABSTRACT

BACKGROUND: CHADS2 and CHA2DS2-VASc scores are widely used in clinical practice and include similar risk factors for the development of coronary artery disease (CAD). It is known that the factors comprising the newly defined CHA2DS2-VASc-HSF score promote atherosclerosis and are associated with severity of CAD. AIM: To investigate the association of the CHA2DS2-VASc-HSF score with the severity of CAD as assessed by SYNTAX score (SxS) in patients with ST segment elevation myocardial infarction (STEMI). METHODS: A total of 454 consecutive patients with STEMI (males 79%, mean age 57.3 ± 12.9 years), who underwent primary percutaneous coronary intervention were included in our study. The patients were divided into three groups according to the SxS tertiles: low SxS group (SxS < 14; 151 patients), intermediate SxS group (SxS 14-20; 152 patients), and high SxS group (SxS ≥ 21; 151 patients). RESULTS: The CHADS2, CHA2DS2-VASc, and CHA2DS2VASc-HSF scores were found to be significantly different among the SxS groups (p < 0.001, p < 0.001, and p < 0.001). After multivariate analysis, the CHA2DS2-VASc-HSF score was associated with high SxS (odds ratio [OR] 1.258, 95% confidence interval [CI] 1.026-1.544; p = 0.028) together with age (OR 1.032, 95% CI 1.013-1.050; p = 0.001) and ejection fraction (OR 0.927, 95% CI 0.901-0.955; p < 0.001). CONCLUSIONS: A newly diagnosed CHA2DS2-VASc-HSF score predicts the severity of atherosclerosis in patients with STEMI.


Subject(s)
ST Elevation Myocardial Infarction/diagnosis , Severity of Illness Index , Adult , Aged , Female , Humans , Male , Middle Aged , Percutaneous Coronary Intervention , Prognosis , Retrospective Studies , ST Elevation Myocardial Infarction/surgery
18.
Turk Kardiyol Dern Ars ; 44(2): 130-6, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27111311

ABSTRACT

OBJECTIVE: Thyroid disease is a common endocrine disease with important effects on the cardiovascular system. As an adaptive response to myocardial ischemia, coronary collateral circulation (CCC) plays an important role in obstructive coronary artery disease (CAD). The association between serum thyroid hormone levels and development of CCC was investigated in the present study. METHODS: In total, 430 consecutive patients who underwent coronary angiography procedure and had documented total occlusion in at least 1 major coronary artery were investigated retrospectively. Degree of CCC was classified according to Cohen-Rentrop method. Serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were assessed by the chemiluminescence immunoassay technique. RESULTS: In spite of diabetes mellitus (p=0.019), smoking (p<0.001), and TSH (p<0.001), FT3 (p<0.001), FT4 (p=0.015), and subclinical hypothyroidism (SCH) (p<0.001) ratios were significantly different between groups. In regression analysis, SCH (p=0.024), DM (p=0.021), smoking (p<0.001), and heart failure (p=0.029) were independent predictors of poor CCC development in multivariate model 1. When regression analyses were performed based on multivariate model 2, TSH (p<0.001), FT3 (p<0.001), heart failure (p=0.022), smoking (p<0.001), and hyperlipidemia (HPL) (p=0.046) were independent predictors of poor CCC development. CONCLUSION: In addition to traditional risk factors, SCH, higher serum TSH, and lower FT3 levels were associated with development of poor CCC in patients with obstructive CA.


Subject(s)
Collateral Circulation/physiology , Coronary Artery Disease/epidemiology , Hypothyroidism/epidemiology , Thyroid Hormones/blood , Coronary Artery Disease/blood , Coronary Artery Disease/complications , Humans , Hypothyroidism/blood , Hypothyroidism/complications , Multivariate Analysis , Retrospective Studies
19.
Blood Coagul Fibrinolysis ; 27(5): 490-3, 2016 Jul.
Article in English | MEDLINE | ID: mdl-24686100

ABSTRACT

Stroke is the leading cause of disability worldwide. It is known that atrial fibrillation and left atrial enlargement contribute ischemic stroke, and mean platelet volume (MPV) increases in patients with ischemic stroke and atrial fibrillation. We aimed to determine whether higher MPV is associated with ischemic stroke in patients with sinus rhythm. We evaluated 74 patients in sinus rhythm and with ischemic stroke (Group 1) and 90 age-matched and sex-matched healthy individuals as control group (Group 2). After physical and echocardiographic examination, 24-48 h Holter monitoring and complete blood counts were studied. There were no statistically significant differences in age, sex rates, and comorbidities between groups. Left atrial diameter was higher in Group 1 than Group 2 (P = 0.001), but both were in normal range. MPV was significantly higher in Group 1 (P < 0.001) and was an independent determinant [odds ratio (OR): 1.840; P < 0.001; 95% confidence interval (CI) 1.330-2.545] of ischemic stroke with left atrial (OR: 1.138; P = 0.006; 95% CI 1.037-1.248). In conclusion, higher MPV is associated with acute ischemic stroke in patients with sinus rhythm and without heart failure or left atrial enlargement. MPV and left atrial diameter are independent predictors of ischemic stroke in this patient population.


Subject(s)
Arrhythmia, Sinus/diagnosis , Atrial Fibrillation/diagnosis , Blood Platelets/pathology , Cardiomegaly/diagnosis , Stroke/diagnosis , Aged , Arrhythmia, Sinus/blood , Arrhythmia, Sinus/complications , Atrial Fibrillation/blood , Atrial Fibrillation/complications , Biomarkers/blood , Cardiomegaly/blood , Cardiomegaly/complications , Case-Control Studies , Female , Heart Atria/metabolism , Heart Atria/pathology , Humans , Male , Mean Platelet Volume , Middle Aged , Stroke/blood , Stroke/complications
20.
Balkan Med J ; 32(3): 260-5, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26185713

ABSTRACT

BACKGROUND: The scar tissue formed by episiotomy during vaginal delivery, and the related pain, is very frequent. The change in the normal anatomy can cause cosmetic and physiologic problems. It can affect and cause deterioration in sexual functions. Therefore, making the right diagnosis and applying the right surgical procedures are very important. AIMS: Our aim was to examine the effect of the perineoplasty operation on the sexual dysfunctions that present due to vaginal delivery. STUDY DESIGN: Self-controlled study. METHODS: Forty patients, who attended our clinic between April 2012 and May 2013, and who were between the ages of 20 and 50 years, were included in the study. The patients had complaints of scar tissue in the perineum and various sexual dysfunctions after vaginal delivery, and they were suitable for perineoplasty. The Female Sexual Function Index (FSFI) questionnaire was applied to the patients before and 6 months after the operation, and the results were compared. RESULTS: After the perineoplasty operation, there was a statistically significant improvement in the patients in the domains of sexual desire, arousal, lubrication, orgasm, and sexual satisfaction (p<0.005). However, there was no significant improvement in the feeling of pain during sexual intercourse (p=0.184). The mean±SD total FSFI score increased significantly after the operation (p<0.005). CONCLUSION: The sexual dysfunctions that develop due to perineal damage during vaginal delivery can benefit significantly from the perineoplasty operation if the indications are correct. However, vaginal perineoplasty did not provide an improvement in dyspareunia.

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