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In the present study, the effect of different ratios of GelMA concentration has been exhibited for wound dressing implementation by the electrospinning method using a new polymer combination of Gelatin methacrylate (GelMA)/Polycaprolactone (PCL)/Chitosan (CS). The nanofiber composites were fabricated due to their biocompatible, biodegradable, improved mechanical strength, low degradation rate, and hydrophilic nature to develop cell-mimicking, cell adhesion, proliferation, and differentiation. Different concentrations of GelMA were added to the PCL/CS solution as 5, 10, and 20 wt%, respectively, in the formic acid/acetic acid (7:3) solution. A photoinitiator was added to the solution for photo-crosslinking of GelMA. The influence of different solution concentrations (5, 10, and 20 wt%) on the structure’s nanofiber production and fiber morphology was examined. SEM micrographs revealed that varied GelMA concentrations resulted in suitable and stable nanofiber composites. The average diameter of nanofiber composites grows as the GelMA concentration rises. FTIR, DSC, tensile test, degradation, and swelling test were evaluated. The results demonstrated that high mechanical strength, hydrophilic properties, and a slow degradation rate were observed with the presence and increment of GelMA concentration within the nanofiber composites. The antibacterial potential of GelMA/PCL/CS nanofiber composites was evaluated against P. aeruginosa and S. aureus using a disc diffusion assay. In vitro cell culture research was conducted by seeding NIH 3T3 fibroblast cells on nanofiber composites, proving these cells’ high cell proliferation rate, viability, and adhesion. 10 wt% GelMA-based nanofiber composites were found to have great potential for wound dressing applications.

Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and the third leading cause of cancer-related deaths worldwide. A substantial body of literature supports the crucial role of vitamin D (VD) in the etiology, progression, prognosis, and treatment of cancer. Recent clinical studies have found an inverse correlation between CRC incidence and serum VD levels. However, the low water solubility of VD and its anticarcinogenic activity at supraphysiological plasma levels, which causes hypercalcemia, required carrier systems. Carbon-based nanomaterials are excellent eco-friendly candidates, with exceptional chemical resistance, efficient mechanical properties, and negligible weight. Furthermore, composite aerogels manufactured from these nanomaterials have gained interest due to their extensive surface areas and porous structures, which make them suitable for delivering drugs. Our research aimed to study the development of composite aerogels loaded with VD by utilizing carbon nanofibers (CNFs) in an aerogel matrix provided to colon cancer cells. For this purpose, Aero1 as a drug delivery system was first prepared and characterized using XRD, FTIR, and SEM methods. Biochemical methods were employed to evaluate the antiproliferative, apoptotic, and anti-migratory effects on colon cancer cells. FTIR and XRD measurements confirmed the production of aerogels. SEM analysis revealed that aerogels have a non-uniform surface. The findings showed that aerogels can effectively deliver VD to the colon cancer cells, while also inhibiting cancer cell proliferation and migration. This research suggests that the Aero1 drug delivery system could be a valuable tool in the fight against colon cancer and other health issues.

In the present study, the various 28 hybrid molecules containing hydrazone and sulfonate moiety were synthesized and characterized by FTIR, 1H-NMR, 13C-NMR spectroscopy and LC-MS spectrometry, besides elemental analysis. The compounds were evaluated for their antiproliferative effects against six cancer cell lines, namely A549 (non-small cell lung cancer), MCF-7 (breast cancer), HT-29 (colorectal adenocarcinoma cancer), PC-3 (androgen-independent prostate adenocarcinoma), Hep3B (hepatocellular carcinoma cancer), and HeLa (epitheloid cervix carcinoma cancer). Among all the target compounds, compounds 4g and 4h exhibited more promising effects on MCF-7 cell lines (IC50=17.8 mM and 21.2 mM, respectively) with high selectivity. Further mechanistic studies proposed that compounds 4g and 4h induced apoptosis is mediated through the intrinsic apoptotic pathway with changes in mitochondrial membrane potential by finally activating caspase-9 and caspase-3. The results have been encouraging enough to merit further investigation.

The goal of this study was to design and fabricate a 3D-printed wound dressing using chitosan as a bioink, with the ability to release the antibiotic drug amoxicillin (AMX) in response to mild electrical stimulation. This was achieved through the incorporation of bismuth ferrite (BFO) nanoparticles, which have both magnetic and ferroelectric properties. The chitosan-based scaffolds containing various concentrations of BFO were analyzed using Fourier transform infrared spectroscopy, and the release of AMX from the scaffolds was evaluated in vitro under electrical stimulation. The results demonstrated that the scaffolds had a suitable structure for drug loading and release, and the release of AMX was successfully controlled by the applied electrical stimulus. The maximum tensile strength (4.97 ± 0.34 MPa) was observed at the ratio of 6% CHT/0.025% BFO scaffolds and the scaffold with 6% CHT/0.075% BFO had the maximum cell viability of (~130%) at 168 h incubation time. This study highlights the potential of BFO to deliver therapeutic drugs from a 3D-printed chitosan scaffold in a controlled manner.

The present study is on the production of graphene-based materials via modification of graphene oxide (GO) using a simple, easy to handle and green method. Natural substances cinnamaldehyde (CA) an...

BACKGROUND/AIMS: This study was aimed to investigate the protective effects of swimming on nonalcoholic fatty liver disease associated with high-fat-diet-induced obesity using microscopic and biochemical parameters. MATERIALS AND METHODS: Sprague–Dawley male rats were fed either standard chow (STD group; 6% fat) or a high-fat diet (HFD group; 45% fat) for 18 weeks. The animals were divided into 4 groups: STD, STD+exercise (EXC), HFD, and HFD+EXC. The exercise groups were given swimming training for 5 days of week, 1 hour per day, during the last 6 weeks of the experiment. At the end of the experiment, the liver samples were evaluated morphologically and ultrastructurally, and malondialdehyde (MDA) and glutathione (GSH) levels were evaluated in the liver samples. RESULTS: Normal morphology of the liver parenchyma with hepatocytes and sinusoids was observed in the STD and STD+EXC groups. Steatosis, lipid accumulation, ballooned hepatocytes, decrease of glycogen deposits, and fibrosis in the periportal area were observed in the HFD group. Liver MDA level was increased and GSH level was decreased in the HFD group. Exercise ameliorated these morphologic and oxidative changes in the HFD-induced liver damage. CONCLUSION: On the basis of morphologic and biochemical analysis, we could conclude that swimming ameliorated obesity-induced liver damage by regulating lipid accumulation and oxidative damage.

A series of new 1,3,4-oxadizole derivatives containing thioether group, has been synthesized to investigate their mPGES-1 inhibitory activities. The synthesized compounds were also evaluated for their anticancer and COX-1/2 inhibitory activities. All compounds were checked for their purity using TLC and HPLC analyses. The melting points, elemental analysis, FT-IR, H-1-/C-13-NMR and LR-MS data were utilized for structural characterization. The most potent derivative was 2-[5-{[2-methyl-5-(propan-2-yl)phenoxy]methyl}-1,3,4-oxadiazol-2-yl)sulphanyl]-1-(phenyl)ethan-1-one 3a, which showed inhibitory activity against mPGES-1 with an IC50 of 4.95 mu M. Docking studies with mPGES-1 and COX-1/2 enzymes revealed their affinity and potential binding mechanism for the tested compounds. Marmara University

Background: The aerial parts of Dipsacus laciniatus are traditionally used in the treatment of colds as cold tea; decoction prepared from its roots and aerial parts are used for the treatment of diabetes and cancer, respectively. The extraction procedures and solvents are important steps in the processing of bioactive constituents from the plant materials. Objective: The aim of this study was to evaluate in vitro antioxidant, antimicrobial, anticholinesterase and cytotoxic activities for the first time in plant’s different extracts. Methods: The antioxidant activities of extracts were examined using FRAP and CUPRAC methods, including total phenolic and flavonoids contents. In addition, the antimicrobial, anticholinesterase and cytotoxic activities of extracts were investigated using microdilution, Ellman and MTT methods, respectively. Results: In the present study, methanol extract showed stronger iron (III) ion reduction (FRAP) and copper (II) ion reducing antioxidant capacity (CUPRAC) than other extracts and also contained higher total phenolic and flavonoid compounds. It was also found that there was a linear relationship between antioxidant activity and phenolic compounds in this study. It was demonstrated that the chloroform and methanol extracts showed moderate antimicrobial activity against S. epidermidis and C. albicans strains. The chloroform extract had a strong and selective cytotoxic activity for the MCF-7 and HT-29 cell lines, while the methanol extract showed low cytotoxic activity on the same cell lines. In addition, according to the obtained data, chloroform extract showed a toxic effect on normal cell line (NIH/3T3), but other extracts showed no toxic effect. Conclusion: Since methanol extract has no toxic effect on normal cell line and has strong antioxidant, anticholinesterase and antimicrobial activity, it is thought that this extract may be useful as an antioxidant, anticholinesterase and antimicrobial agents in the future.

Background:Hydrazide-hydrazones constitute an important class of compounds for new drug development. In this study, a series of 39 new acylhydrazones (3-41), derived from (2S)-3-methyl- 2-[[(4-methylphenyl)sulfonyl]amino]butanoic acid hydrazide were synthesized with further aim to achieve biologically active acylhydrazones carrying an amino acid side chain.Methods:Compounds 3-41 were synthesized by microwave-assisted method. All synthesized compounds have been tested for their anti-HIV activity compound 21 was subjected to a new set of 2DNMR analysis for the characterization of the isomers in solution and determination of its 3D structure.Results:The IC50 values for compounds 2-40 were found between >125-10.90 µg/ml against HIV- 1(IIIB) and HIV-2(ROD) strains in MT-4 cells. Compounds 3, 6, 10, 12, 23, 24, 27, 32, and 37 with CC50 values between 10.90-14.50 µg/ml were selected to evaluate for their antileukemia activity. IC50 values for these mentioned compounds were found as >100μM on human chronic myelogenous leukemia, K562 cell line.Conclusion:Some compounds with IC50 values between 10.90-14.50 μg/ml will be of benefit in the development of novel leads.

We investigated the protective effects of swimming exercise on high-fat diet-induced heart and aorta damage by evaluating oxidative stress and the endothelial nitric oxide (NO) system. Sprague Dawley rats were fed either standard chow (STD, 6% fat) or high-fat diet (HFD; 45% fat) for 18 weeks, with half of the animals trained by daily swimming sessions (EXC; 1 h per day for 5 days/week) for the last 6 weeks of the experimental period and half kept sedentary (SED). Heart and aorta tissues were prepared for routine light and electron microscopy evaluation. Endothelial NOS (eNOS) and inducible NOS (iNOS) distribution in the tissue samples were examined by immunohistochemistry. Biochemical examinations, including blood serum lipid profiles, malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), and tissue NO levels were measured. Deteriorated heart and aorta morphology, increased MDA levels and iNOS-immunoreactivity (iNOS-ir), as well as decreased GSH, NO, SOD, and eNOS-ir parameters were observed in the HFD + SED group. These morphological and biochemical parameters were ameliorated in the HFD + EXC group. Our study revealed that obesity-induced iNOS activation and increased oxidative stress in cardiac and aorta tissues. Exercise protected the obesity-induced cardiac and aortic tissue damage by modulating oxidant/antioxidant balance via involvement of the NO system.

We evaluated the effects of Rubus tereticaulis in healing process by determining the total carbonyl content, collagen synthesis, and total protein level on rat wounded tissues. Wounds were performed in the back of 54 Wistar rats, using a biopsy punch instrument with 0.6 mm in diameter. Rats were randomly divided into three groups: (i) un-treatment wounds group served as “controls”, (ii) Madecassol® used as “positive control” group, and (iii) the application of topical cream of R. tereticaulis served as “treatment” group of wound healing. The animals were killed at the end of experiment under anesthesia with ketamine, and tissue samples were collected for the evaluation at three times intervals (3rd, 7th, and 14th day). The wounded areas were analyzed for total carbonyl content, collagen, and total protein levels by HPLC, ELISA, and spectrophotometric methods, respectively. Total carbonyl content in the treatment group was significantly lower in comparison with control group on 3rd day (2.839 ± 0.438 vs. 3.216 ± 0.216 nmol carbonyl/mol protein; p

This study aims to determine the potential protective effects of ferulic acid against cisplatin-induced nephrotoxicity and to compare its effect with curcumin, a well-known protective agent against cisplatin- induced toxicity in rats. Administration of cisplatin resulted in high BUN (Blood Urea Nitrogen), creatinine, MDA (Malondialdehyde), MPO (Myeloperoxidase), TOS (Total Oxidative Status), PtNT (Protein Nitrotyrosine) levels ( p 0.05 ). Histological observations showed abnormal morphology of kidney; in addition with appearance of TUNEL positive cells indicating apoptosis in cisplatin administered group. HO-1 (Heme Oxygenase-1) levels measured by RT-PCR (Real Time Polymerase Chain Reaction), and TAS (Total Antioxidative Status) revealed antioxidant depletion due to cisplatin toxicity in animals ( p 0.05 ). All parameters showed improvement in groups treated with ferulic acid ( p 0.05 ). Ferulic acid treatment was found significant in preventing oxidative stress, increasing antioxidative status and regaining histological parameters to normal, indicating nephroprotective and antioxidant effects of this phenolic compound.

The objective of this study was to establish reference intervals for growth arrest-specific 6 (GAS6), a vitamin K-dependent protein, in human adult plasma according to the Guideline of Clinical and Laboratory Standards Institute (CLSI) C28-A3. Blood samples were collected from 308 healthy volunteers aged 18-72 (157 female, 151 male). A non-parametric approach was used to calculate the reference interval. The plasma GAS6 reference interval was determined, with 90% confidence interval: the lower limit (2.5 percentile) was 2.5 (1.9-3.1) μg/L and the upper limit (97.5 percentile) = 18.8 (18.0-22.3) μg/L. Harris-Boyd's test did not suggest partitioning by age or gender: medians for males [7.8 (5.8-10.7) μg/L] and females [9.9 (7.1-13.5) μg/L]. Three age-subgroups were tested: 18-29 years (n = 168); 30-44 years (n = 73); 45-72 years (n = 67). The intra- and inter-assay variations were 12.6% (mean, 5.2 ± 0.7 μg/L) and 14.0% (mean, 9.2 ± 1.3 μg/L), respectively. The mean recovery was 104%. This study reports plasma GAS6 reference intervals established first according to the guideline of CLSI C28-A3.

BACKGROUND: The aim of this study was to evaluate the possible protective effects of dapagliflozin in an experimental sepsis model in rats. METHODS: Saline (1 mL/kg, p.o.) or dapagliflozin (10 mg/kg, p.o.) was administered to Sprague-Dawley rats for 5 days prior to the surgical procedures. Under anesthesia, sepsis was induced by cecal ligation puncture, while sham control groups underwent laparotomy only. Blood urea nitrogen, creatinine, and glucose levels were measured in serum samples and the levels of malondialdehyde (MDA), glutathione (GSH), myeloperoxidase (MPO), tumor necrosis factor alpha, interleukin 1 beta, caspase 8, and caspase 9 were determined in tissue samples (kidney, liver, and lung). Histological evaluation was also performed. RESULTS: The administration of dapagliflozin in a sepsis model reduced oxidative stress (MDA), increased antioxidant levels (GSH), and reduced inflammation (MPO) in the kidney (p

The synthesis and biomedical applications of nano/micromotors have attracted great attention. In this work, preparation and characterization of catalytic gold/poly(3,4-ethylenedioxythiophene)/platinum (Au/PEDOT/Pt) micromotors were reported to present their contribution for cancer biomarker miRNA-21 detection. Potential use of these motors for possible cancer treatment was also illustrated after their biocompability had shown. At first, anti-miRNA probe immobilized Au/PEDOT/Pt micromotors (probe DNA/Au/PEDOT/Pt/MMs) were used for the sensitive and selective recognition of synthetic miRNA-21 target sequence to present the proof-of-concept. Then intracellular studies were carried out using four types of cancer cells (human breast cancer cell line, MCF-7, human colorectal adenocarcinoma cell line, HT-29, human lung carcinoma cell line, A-549 and human osteosarcoma cell line, SJSA-1). These studies illustrated the high selectivity of probe DNA/Au/PEDOT/Pt micromotors for MCF-7 and SJSA-1 cells. Later, antiproliferative and cytotoxic effects of the micromotors and their potential use for breast cancer treatment were investigated.

Background and Objective: The current study aimed to evaluate cardiovascular risk factors, haematological and biochemical parameters, and serum endocan concentrations in lichen planus (LP) patients. Methods: This study was conducted with 86 cases, including 43 LP patients and 43 healthy controls. Cardiovascular risk factors, haematological and biochemical parameters, and endocan levels were evaluated. Results: The serum endocan concentrations of LP patients were not significantly different from those of the healthy controls (p > 0.05). There were no significant differences in the serum endocan levels according to classification by cardiovascular risk factors and smoking history (p > 0.05). In the LP group, white blood cell count, platelet distribution width and monocyte count/high-density lipoprotein cholesterol ratios were significantly higher when compared to the healthy controls (p < 0.05). The LP group had a lower mean platelet volume than the healthy controls (p < 0.05). Conclusions: Serum endocan levels did not change significantly in patients with LP, and there were significant differences in haematological and biochemical parameters.

Objectives: Some novel 1-(2-methyl-5-nitro-1H-imidazol-1-yl)-3-(substituted phenoxy)propan-2-ol derivatives (3a-g) were designed and synthesized. Materials and Methods: Compounds 3a-g were obtained by refluxing ornidazole (1) with the corresponding phenolic compounds (2a-g) in the presence of anhydrous K2 CO3 in acetonitrile. Results: Following the structure elucidation, the in vitro antimicrobial activity and cytotoxic effects of compounds 3a-g on K562 leukemia and NIH/3T3 mouse embryonic fibroblast cells were measured. As a part of this study, the compliance of the compounds with the drug-likeness properties was evaluated. The physico-chemical parameters (log P, TPSA, nrotb, number of hydrogen bond donors and acceptors, logS) were calculated using the software OSIRIS. Conclusion: All the synthesized compounds except 3a showed significant activity (MIC=4-16 µg mL-1) against the bacterial strain Bacillus subtilis as compared to the standard drug, whereas antileukemic activities were rather limited. Furthermore, all the compounds were nontoxic and the selectivity index outcome indicated that the antileukemic and antimicrobial effects of the compounds were selective with good estimated oral bioavailability and drug-likeness scores. © Turk J Pharm Sci, Published by Galenos Publishing House.

Sahin, Sadik/0000-0002-7107-9719 WOS: 000367014300006 PubMed: 26647795 PURPOSE: To investigate the effects of remifentanil as an antioxidant and analyze the histopathologic, biochemical changes in experimental ischemia-reperfusion (I/R) exposed rat uteri. METHODS: Wistar albino rats were assigned to three groups (n = 7). 2h period of ischemia was followed by 1h of reperfusion in the I/R and the I/R-remifentanil groups. After ischemia, no drug was administered in the sham and I/R groups. In the I/R-remifentanil group, remifentanil infusion (2 mu g/kg/min) was started in the ischemia period, and continued until the end of reperfusion. After the ischemic and reperfusion period, the ischemic uterine horns were removed surgically for biochemical and histopathologic examination. Tissue damage scores (endometrial epithelial glandular leukocytosis, degeneration, and endometrial stromal changes) were examined. Malondialdehyde levels and catalase, superoxide dismutase enzyme activities in tissue were measured. RESULTS: We found significantly lower epithelial leukocytosis and cell degeneration in the I/R-remifentanil group (p

Tolmetin hydrazide and a novel series of tolmetin hydrazide-hydrazones 4a-l were synthesized in this study. The structures of the new compounds were determined by spectral (FT-IR, (1)H NMR) methods. N'-[(2,6-Dichlorophenyl)methylidene]-2-[1-methyl-5-(4-methylbenzoyl)-1H-pyrrol-2-yl]acetohydrazide (4g) was evaluated in vitro using the MTT colorimetric method against the colon cancer cell lines HCT-116 (ATCC, CCL-247) and HT-29 (ATCC, HTB-38) to determine growth inhibition and cell viability at different doses. Compound 4g exhibited anti-cancer activity with an IC50 value of 76 μM against colon cancer line HT-29 (ATCC, HTB-38) and did not display cytotoxicity toward control NIH3T3 mouse embryonic fibroblast cells compared to tolmetin. In addition, this compound was evaluated for caspase-3, caspase-8, caspase-9, and annexin-V activation in the apoptotic pathway, which plays a key role in the treatment of cancer. We demonstrated that the anti-cancer activity of this compound was due to the activation of caspase-8 and caspase-9 involved in the apoptotic pathway. In addition, in this study, we investigated the catalytical effect of COX on the HT-29 cancer line, the apoptotic mechanism, and the moleculer binding of tolmetin and compound 4g on the COX enzyme active site.

Growth arrest-specific 6 (Gas6) is a newly discovered vitamin K-dependent protein, which is a ligand for TAM receptors [Tyro3 (Sky), Axl, and Mer] from the tyrosine kinase family. Gas6 knockout mice were resistant to venous and arterial thrombosis. There are contradictory reports on the presence of Gas6 and its receptors in mouse platelets. The objective of this study was to investigate whether Gas6 and its receptors were present in mouse platelets or not.Specific pathogen-free BALB/c male and female mice of 8-10 weeks old and 25-30 g in weight were anesthetized under light ether anesthesia and blood samples were taken from their hearts. RNAs were isolated from isolated platelets, and then mRNAs encoding Gas6 and TAM receptors were detected by reverse transcription-polymerase chain reaction (RT-PCR). Protein concentrations of Gas6 and TAM receptors in platelets were measured by ELISA, but not those of Mer, because of the absence of any commercial ELISA kit for mouse specimens.RT-PCR results indicated the presence of mRNAs encoding Gas6 and Mer in mouse platelets. However, although RT-PCR reactions were performed at various temperatures and cycles, we could not detect the presence of mRNAs encoding Axl and Tyro3 (Sky). Receptor protein levels of Axl and Tyro3 were below the detection limits of the ELISA method.We found the presence of mRNAs encoding Gas6 and the receptor Mer in mouse platelets, but not Axl and Tyro3. Gas6, Axl, and Tyro3 protein levels were below the detection limits of the ELISA. The presence of mRNA is not obvious evidence of protein expression in platelets that have no nucleus or DNA. Further studies are required to clarify the presence of Gas6/TAM receptors in platelets using real-time PCR and more sensitive immunological methods, and future studies on mechanisms will indicate whether the Gas6/TAM pathway is a strategy for treatment of disorders.Amaç: Gas6 proteini (growth arrest specific 6), K vitaminine bağımlı protein ailesinin yeni bir üyesi olup reseptör tirozin kinazlardan TAM reseptörlerinin [Tyro3 (Sky), Axl ve Mer] bir ligandıdır. Gas6 geni susturulmuş farelerin, venöz tromboembolizme daha dirençli oldukları görülmüştür. Fare trombositlerinde Gas6 proteininin var olup olmadığı konusunda birbiriyle çelişkili yayınlar bulunmaktadır. Biz bu araştırmada, fare trombositlerinde Gas6 proteini ve reseptörlerinin varlığını hem mRNA hem de protein seviyesinde araştırmayı amaçladık. Gereç ve Yöntemler: Spesifik patojen içermeyen 8-10 haftalık, 25-30 gr ağırlığındaki Balb-C ırkı dişi/erkek fareler hafif eter anestezisi altında bayıltıp, kalpten kan örnekleri alındı. Önce trombositlerden mRNA’lar elde edildi. Daha sonra ters transkripsiyon-polimeraz zincir reaksiyonu (RT-PCR) yöntemiyle Gas6 ve TAM reseptörlerinin herbirini kodlayan mRNA’lar araştırıldı. Trombositlerdeki Gas6 ve TAM reseptör proteinleri ELISA yöntemiyle ölçüldü. Ancak farede Mer protein seviyesini ölçen bir ELISA kiti henüz üretilmediği için Mer seviyesi ölçülemedi. Bulgular: RT-PCR sonuçları fare trombositlerinde Gas6 ve Mer’i kodlayan mRNA’ların var olduğunu gösterdi. Çeşitli sıcaklık ve döngülerde RT-PCR deneyleri yapıldığı halde, Axl ve Tyro3’e (Sky) ait mRNA varlığı saptanamadı. Gas6, Axl ve Tyro3 (Sky) protein seviyeleri ELISA yöntemlerinin en düşük ölçüm sınırlarının altındaydı. Sonuç: Biz fare trombositlerinde, Gas6 ve onun reseptörlerinden sadece Mer’i kodlayan mRNA’ların var olduğunu bulduk ama Axl ve Tyro3’ü kodlayan mRNA’ların varlığını saptayamadık. Protein olarak Gas6, Axl ve Tyro3 seviyeri, ELISA yöntemlerinin ölçüm limitlerinin altındaydı. Trombositlerde mRNA’ların var olması, protein sentezinin burada yapıldığının kesin bir kanıtı değildir. Çünkü trombositlerde DNA yoktur. Trombositlerde Gas6/TAM reseptörlerinin varlığını daha iyi aydınlatmak için Gerçek Zamanlı-PCR ve yüksek duyarlılığa sahip immunolojik yöntemlerle yapılacak ileri araştırmalara ihtiyaç vardır. Bu moleküllerin fizyolojik mekanizması aydınlatıldığında hastalıkların tedavisinde yeni bir strateji olabilir.

53rd Congress of the European-Societies-of-Toxicology (EUROTOX) -- SEP 10-13, 2017 -- Bratislava, Slovakia WOS: 000425486700342 Formaldehyde (F) is a genotoxic substance that causes detrimental effects on the upper respiratory system. St. John’s wort (SJW) is a medicinal plant has antioxidative and anti-inflammatory properties. The present study is aimed to investigate the possible protective effect of SJW on F-induced lung toxicity via determination of malondialdehyde (MDA), glutathione (GSH), interleukin-6 (IL-6) and TNF-alpha levels and DNA damage in rats. European Society of Toxicology

WOS: 000318810800005, PubMed ID: 23609809, Etodolac hydrazide and a novel series of etodolac hydrazide-hydrazones 315 and etodolac 4-thiazolidinones 1626 were synthesized in this study. The structures of the new compounds were determined by spectral (FT-IR, 1H NMR, 13C NMR, HREI-MS) methods. Some selected compounds were determined at one dose toward the full panel of 60 human cancer cell lines by the National Cancer Institute (NCI, Bethesda, USA). 2-(1,8-Diethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-yl)acetic acid[(4-chlorophenyl)methylene]hydrazide 9 demonstrated the most marked effect on the prostate cancer cell line PC-3, with 58.24% growth inhibition at 105M (10 mu M). Using the MTT colorimetric method, compound 9 was evaluated in vitro against the prostate cell line PC-3 and the rat fibroblast cell line L-929, for cell viability and growth inhibition at different doses. Compound 9 exhibited anticancer activity with an IC50 value of 54 mu M (22.842 mu g/mL) against the PC-3 cells and did not display any cytotoxicity toward the L-929 rat fibroblasts, compared to etodolac. In addition, this compound was evaluated for caspase-3 and Bcl-2 activation in the apoptosis pathway, which plays a key role in the treatment of cancer., Scientific and Technical Research Council of Turkey (TUBITAK) [SBAG-HYD-339 (108S257)], This research was supported by The Scientific and Technical Research Council of Turkey (TUBITAK), Research Fund Project Number: SBAG-HYD-339 (108S257). The authors are grateful to Dr. Jurgen Gross from the Institute of Organic Chemistry, University of Heidelberg, for his generous help on obtaining HR-EI/FAB mass spectra of the synthesized compounds. We thank the Division of Cancer Research, National Cancer Institute, Bethesda, MD, USA, for the anticancer activity screening. Etodolac was supplied by Bilim Pharmaceutical Industry Inc.

WOS: 000316611700079, PubMed ID: 23519201, A series of novel N-(3-substituted aryl/alkyl-4-oxo-1,3-thiazolidin-2-ylidene)-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamides 2a-e were synthesized by the addition of ethyl alpha-bromoacetate and anhydrous sodium acetate in dry ethanol to N-(substituted aryl/alkylcarbamothioyl)-4-[5-(4-methylphenyl)-3-(trifluoro-methyl)- 1H-pyrazol-1-yl] benzene sulfonamides 1a-e, which were synthesized by the reaction of alkyl/aryl isothiocyanates with celecoxib. The structures of the isolated products were determined by spectral methods and their anti-inflammatory, analgesic, antioxidant, anticancer and anti-HCV NS5B RNA-dependent RNA polymerase (RdRp) activities evaluated. The compounds were also tested for gastric toxicity and selected compound 1a was screened for its anticancer activity against 60 human tumor cell lines. These investigations revealed that compound 1a exhibited anti-inflammatory and analgesic activities and further did not cause tissue damage in liver, kidney, colon and brain compared to untreated controls or celecoxib. Compounds 1c and 1d displayed modest inhibition of HCV NS5B RdRp activity. In conclusion, N-(ethylcarbamothioyl)-4-[5-(4-methylphenyl)- 3-(trifluoromethyl)-1H-pyrazol-1-yl] benzenesulfonamide (1a) may have the potential to be developed into a therapeutic agent., Research Fund of Marmara University [SAG-A-310510-0175]; National Institute of Health [CA153147], We wish to thank the National Cancer Institute for in vitro pharmacological screening. This work was generously supported by the Research Fund of Marmara University, project number: SAG-A-310510-0175 to S. G. K. HCV NS5B inhibition studies were supported by the National Institute of Health Research Grant CA153147 to N.K.-B. The authors are grateful to Jurgen Gross from the Institute of Organic Chemistry, University of Heidelberg, for his generous help on obtaining HR-EI mass spectra of the synthesized compounds.

Objective: Thrombocytopenia remains a serious problem in patients treated with highdose chemotherapy and bone marrow transplantation. In recent years, infusion of ex vivo expanded megakaryocytes (Mk) progenitors into patients has been proposed as a strategy for shortening the time of platelet engraftment. The development of in vitro culture methods to obtain sufficient numbers of Mks from haematopoietic stem cells (HSC) is an important target in basic and clinical research projects. The aim of this study was to develop a two-step ex vivo expansion culture system of Mk progenitors from peripheral blood stem cells (PBSC). Methods: PBSC were harvested from three healthy adult donors. CD34+ cells were isolated and cultured in serum free media supplemented with thrombopoietin (TPO) (50 ng/ml), Interleukin 3 (IL-3) (20 ng/ml) and Interleukin 6 (IL-6) (20 ng/ml) for 12 days followed by an incubation with IL-6 (20 ng/ml) and TPO (50 ng/ml) for another 9 days. The differentiation of Mks was monitored by flow cytometry (% of CD34+/41+ cells). The morphology of the cells was studied by light, electron and fluorescence microscopy. Results: Morphological analysis of cells generated after 7 days of culture showed typical aspects of developing Mks. The percentage of CD41+ cells was higher than 70 on day 21. Conclusion: The results obtained in this study demonstrated that this two-step culture system is an effective method to obtain high rates of megakaryocytes. It is obvious that this promising method needs further development for clinical applications.

Objective: The aim of this study is to determine relationship of cytochrome P-450 2C19 (CYP2C19) enzymes polymorphism, side effects, and medication adherence in patients who have been diagnosed with major depression and have utilized selective serotonin reuptake inhibitors. Methods: Fifty-three major depression patients (mean of age: 33.25 +/- 11.29 years old; male/female: 7/46) were included in this study. Polymorphisms were determined from genomic DNA by using the 'Real-Time Polymerase Chain Reaction' method. Side effects and medication adherence levels were assessed by using the 'Toronto Side Effects Scale' and the four items medication adherence scale (Morisky, Green and Levine), respectively. Results: The most common side effects that patients reported were drowsiness/daytime somnolence (54.7%), malaise or fatigue (43.4%), sweating (43.4%), nausea (41.5%) and dry mouth (41.5%). Only nine (17%) patients were found to be highly adherent to their medication. When evaluating the CYP2C19 polymorphisms of patients, 37.7%, 24.5% and 20.8% of the patients were classified as intermediate, extensive and ultra-rapid metabolizers, respectively. Allele frequencies of CYP2C19*17 and CYP2C19* 2 was calculated as 24.5% and 27.4%, respectively. Although there were some differences in side effect scores and medication adherences among the polymorphism groups, these relationships were not found to be statistically significant. Conclusion: This study shows that patients who utilized antidepressants frequently experienced side effects and had low medication adherence. Another interesting finding is the high rate of ultrarapid metabolizers of CYP2C19.

In this study, a series of thiosemicarbazide derivatives 12-14, 1,2,4-triazol-3-thione derivatives 15-17 and compounds bearing 2-(4H-1,2,4-triazole-3-ylthio)acetamide structure 18-32 have been synthesized starting from phenolic compounds such as 2-naphthol, paracetamol and thymol. Structures and purity of the target compounds were confirmed by the use of their chromatographic and spectral data besides microanalysis. All of the synthesized new compounds 12-32 were evaluated for their anti-HIV activity. Among these compounds, three representatives 18, 19 and 25 were selected and evaluated by the National Cancer Institute (NCI) against the full panel of 60 human cancer cell lines derived from nine different cancer types. Antiproliferative effects of the selected compounds were demonstrated in human tumor cell lines K-562, A549 and PC-3. These compounds inhibited cell growth assessed by MTT assay. Compound 18, 19 and 25 exhibited anti-cancer activity with IC50 values of 5.96 μM (PC-3 cells), 7.90 μM (A549/ATCC cells) and 7.71 μM (K-562 cells), respectively. After the cell viability assay, caspase activation and Bcl-2 activity of the selected compounds were measured and the loss of mitochondrial membrane potential (MMP) was detected. Compounds 18, 19 and 25 showed a significant increase in caspase-3 activity in a dose-dependent manner. This was not observed for caspase-8 activity with compound 18 and 25, while compound 19 was significantly elevated only at the dose of 50 μM. In addition, all three compounds significantly decreased the mitochondrial membrane potential and expression of Bcl-2.

Background There is substantial evidence to suggest that oxidative stress plays a significant role in the development of acute brain injury after subarachnoid hemorrhage (SAH). Objective To investigate the putative neuroprotective effect of nesfatin-1, a novel peptide with anorexigenic properties, in a rat model of SAH. Methods Male Wistar albino rats were randomly divided into control, saline-treated SAH, and nesfatin-1 (10 μg/kg IP)-treated SAH groups. To induce SAH, rats were injected with 0.3 mL blood into their cisterna magna. Forty-eight hours after SAH induction, neurological examination scores were recorded and the rats were decapitated. Brain tissue samples were taken for the determination of blood-brain barrier (BBB) permeability, brain water content, and oxidative stress markers and for histological analysis. Results The neurological examination scores were increased on the second day of SAH induction. SAH resulted in impaired blood-brain barrier and edema, along with increased levels of brain tumor necrosis factor-α, interleukin-1β, interleukin-6, lipid peroxidation, protein carbonylation, and myeloperoxidase activity with concomitant decreases in antioxidant enzymes. Conversely, in the nesfatin-1-treated SAH group, SAH-induced neurological impairment and oxidative brain injury were ameliorated by nesfatin treatment. Furthermore, SAH-induced morphological changes in the basilar arteries were improved by nesfatin-1 treatment, whereas caspase-3 activity and SAH-induced elevations in the plasma levels of proinflammatory cytokines were also depressed by nesfatin-1 treatment. Conclusion These findings suggest that nesfatin-1, which appears to have antiapoptotic and anti-inflammatory properties, exerts neuroprotection in SAH-induced injury in rats by inhibiting neutrophil infiltration and subsequent release of inflammatory mediators.

In this study, for the first time, the morphology of the dorsal and ventral skin of Triturus karelinii using light microscopy through histochemical methods was described. The skin exhibited basic morphological characteristics of the other urodeles: the epidermis composed of keratinized stratified epithelium with numerous conical protrusions and the dermis subdivided into spongy and compact layers. In the spongious dermis, three distinct types of glands were observed, namely serous, mucous and mixed glands. These glands were alveolar and occurred in both males and females. The morphologies of all three skin glands differed from anurans and other urodeles, having peculiar characteristics. Serous glands exhibited three different appearances. An unusual finding in mucous glands was the different appearance of their granules, showing diverse density after staining with PAS and AB. The histochemical analysis clearly demonstrated the presence of neutral, acid and sulfated mucins in the adenocytes of mucous glands. Mixed glands formed by mucous and serous glands exhibited the same morphological traits of both types of glands. Light microscopic observations revealed that the dorsal and ventral skin showed structural similarities with some minor differences, possibly resulting from their functions.

The field of reproductive biology has undergone significant developments in the last decade. The notion that there is a fixed reserve pool of oocytes before birth was established by Zuckerman in 1951. However, in 2004, an article published in nature challenged this central dogma of mammalian reproductive biology. Tilly's group reported the existence of ovarian germline stem cells (GSCs) in postnatal ovaries of mice and suggested that the bone marrow could be an extragonadal source of ovarian GSCs. These findings were strongly criticized; however, several independent groups have since successfully isolated and characterized ovarian GSCs in postnatal mice. The ovarian GSCs are located in the ovarian surface epithelium and express markers of undifferentiated GSCs. When transplanted into mouse ovaries, mouse ovarian GSCs could differentiate and produce embryos and offspring. Similarly, in a recent study, ovarian GSCs were found to be present in the ovaries of women of reproductive age. Conversely, there is increasing evidence that stem cells responsible for maintaining a healthy state in normal tissue may be a source of some cancers, including ovarian cancer. Cancer stem cells (CSCs) have been found in many tissues, including ovaries. Some researchers have suggested that ovarian cancer may be a result of the transformation and dysfunction of ovarian GSCs with self-renewal properties. Drug resistant and metastasis-generating CSCs are responsible for many important problems affecting ovarian cancer patients. Therefore, the identification of CSCs will provide opportunities for the development of new therapeutic strategies for treatments for infertility and ovarian cancer. In this article, we summarize the current understanding of ovarian GSCs in adult mammals, and we also discuss whether there is a relationship between GSCs and CSCs.

Preeclampsia (PE) is a hypertensive disease of pregnancy complicating 2-8% of all pregnancies. The exact pathophysiology still remains unknown. Growth arrest-specific 6 (Gas6) is a member of the vitamin K-dependent protein family and it has been suggested as a novel atherothrombotic risk factor with anti-angiogenic and pro-atherogenic properties. The goal of the our study was to investigate the relationships between the c.834 + 7GA polymorphism of GAS6, plasma Gas6 levels and PE.A total of 150 women, including 82 preeclamptic pregnant women and 68 normotensive pregnant (NP) women, were recruited in the current study. Blood samples were taken from all participants. Plasma Gas6 levels measured by an enzyme-linked immunosorbent assay. GAS6 polymorphism was determined using a PCR-RFLP method.The plasma Gas6 levels of preeclamptic patients were significantly lower than those of NP women (8.65 ± 3.70 ng/ml and 10.89 ± 4.23 ng/ml respectively, p0.001). The GG genotype was the most prevalent, and the risk of PE was 3.5-fold higher in pregnant women with GG genotype compared to woman with AA genotype (p0.01). The A allele was less frequent in preeclamptic patients than in control subjects (OR = 2.118, 95% CI = 1.330-3.371, p0.001).Our results suggest that GAS6 c.834 + 7GA polymorphism may have a pivotal role in the pathogenesis of PE suggesting that the A allele has a protective role for PE.

A novel series of new tolmetin hydrazide derivatives, N -Alkyl/Arylsubstitued- 2-{[1-methyl-5-(4-methylbenzoyl)-1 H -pyrol-2-yl]acetyl}hydrazinecarbothioamides [ 4a-j ] have been synthesized in this study. The structures of the new compounds were determined by spectral (FT-IR, 1 H-NMR, 13 C-NMR and 2D-NMR) methods and their purity were proven by elemental analysis and TLC. Tolmetin [1] and N -(4-fluorophenyl) -2-{[1-methyl-5-(4-methylbenzoyl)-1 H- pyrol-2-yl]acetyl}hydrazinecarbothioamide [SGK-524; 4d] were evaluated for in vitro using the MTT colorimetric method for anticancer activity. Androjen-independed human prostate cancer cell line PC-3 (ATCC, CRL-1435) , human colon cancer cell lines HCT-116 (ATCC, CCL-247) and HT-29 (ATCC, HTB-38) were used in this study. Compound 4d exhibited anticancer activity against PC-3 whereas Tolmetin showed minor activity comparing to compound 4d .

Preeclampsia is a hypertensive disease of pregnancy complicating 5-8% of all pregnancies. A growing body of evidence demonstrated that inflammation in microvasculature plays a major role in the pathogenesis of preeclampsia. Although circulating platelets are in rested state, when they are exposed to soluble mediators or microparticles in the inflamed vasculature as in preeclampsia, platelets are activated by engagement of the mediators on surface receptors. Upon activation, platelets degranulate some soluble and adhesion molecules. When soluble mediators released into the local microenvironment, they modulate the interactions between platelets, leukocytes and endothelial cells. Adhesion molecules expressed on the surface may initiate adherence between platelets, leukocytes and endothelial cells. Platelet-leukocyte aggregates promote the recruitment of neutrophils into the inflamed microvasculature. In addition to this, adherent platelets on endothelial cells induce production of inflammatory cytokines thus lead to amplification of inflammatory response. In this review, we mention platelet dysfunction in preeclamptic pregnancies and inflammatory role of platelets in the pathogenesis of preeclampsia., Preeklampsi tüm gebeliklerin %5-8’ ini komplike eden gebeliğin hipertansif hastalığıdır. Preeklampsi patogenezinde kılcal damar yatağındaki inflamasyon önemli rol oynar. Preeklampside olduğu gibi dolaşımda serbest halde bulunan mikropartiküllerle trombositlerin karşılaşması sonucunda trombositler aktive olurlar. Aktive olan trombositler dolaşıma serbest moleküller salarlar ve hücre yüzeylerindeki adhezyon moleküllerinin artmasına neden olurlar. Serbest moleküller trombosit, lökosit ve endotel hücreleri arasındaki etkileşimleri düzenlerler. Adhezyon molekülleri de trombosit, lökosit ve endotel hücrelerinin birbirlerine bağlanmasına aracılık ederler. Oluşan trombosit-lökosit agregatları nötrofillerin inflamasyonun olduğu damarsal yapılara göçünün artmasına neden olur. Ayrıca, endotel hücrelerine bağlanan trombositler sitokinlerin yapımına ve inflamatuvar yanıtın artmasına neden olur. Bu derlemede, preeklamptik gebelerde trombosit fonksiyon bozuklukları ve trombositlerin preeklampsi patogenezindeki inflamatuvar rolünden bahsedeceğiz.

53rd Congress of the European-Societies-of-Toxicology (EUROTOX) -- SEP 10-13, 2017 -- Bratislava, Slovakia WOS: 000425486700346 … European Society of Toxicology

Bu calisma kapsaminda 2-amino-4-substitue piridin bilesiklerinden hareketle sentezlenen tiyoure turevleri [1- 4], 2-imino-1,3-tiyazolidin-4-on halkalarinin [5, 6] sentez baslangic maddelerini olusturmaktadir. 4-Tiyazolidinon halka kapamasi ve sentezi icin iki farkli yontem optimize edilmistir. Sentezlenen bilesiklerin yapilari elementel analiz, IR, 1H-NMR, 13C-NMR ve kutle spektrumu ile kanitlanmis, safliklari ise ITK ile kontrol edilmistir. Elde edilen bilesikler antiviral ve antikanser etkinlikleri acisindan degerlendirilmistir. Murine norovirus, Yellow fever, Enterovirus ve Chikungunya suslarina karsi antiviral etkileri incelenen bilesiklerin 0,3 μM’dan yuksek EC50 degerine sahip olduklari tespit edilmistir. Sitotoksisiteleri NIH3T3 hucre hatti uzerinde incelenen bilesiklerin antikanser etkileri PC-3, A549, HeLa, HT-29, MCF-7, SJSA1 ve K562 hucre hatlarina karsi incelenmis %61’in uzerinde proliferasyon degerine sahip olduklari gozlemlenmistir.

Bu calismanin amaci, Tanacetum argenteum subsp. argenteum bitkisinin toprak ustu kisimlarindan elde edilen n-hekzan, kloroform, metanol ve sulu metanol ekstrelerinin antimikrobiyal ve antiproliferatif aktivitelerini arastirmaktir. Ekstrelerin antiproliferatif aktivitesi dort farkli insan kanser hucre hatlarina (A549: Akciger adenokarsinoma, Hela; Serviks adenokarsinoma, HT-29: Kolon adenokarsinoma, MCF-7; Meme adenokarsinoma) karsi MTT yontemiyle test edilmistir. Ekstrelerin antimikrobiyal aktivitesi ise Staphylococcus aureus ATCC 29213, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 25922, Enterococcus faecalis ATCC 29212, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 27853, Proteus mirabilis ATCC 14153, ve Candida albicans ATCC 10231 suslarina karsi mikro-broth dilusyon yontemiyle arastirilmistir. Kloroform ekstresi 30 μg/ mL konsantrasyonda HT-29 and MCF-7 hucre hatlarinin gelisimini sirasiyla % 89 ve % 73 oraninda durdururken, n-hekzan ekstresi ise ayni konsantrasyonda bu hucre hatlarinin gelisimini sirasiyla % 75 ve % 74 oraninda inhibe etmistir. Ayni zamanda kloroform ekstresi A-549 and HeLa hucre hatlarinin gelisimi sirasiyla % 75 ve % 62 oraninda durdurarak onemli bir antiproliferatif aktivite gostermistir. Kloroform ekstresi, Staphylococcus aureus and S. epidermidis’e karsi 625 μg/ mL’lik MIK degerleriyle orta derecede antibakteriyel aktivite gostermistir. Metanol ve sulu methanol ekstreleri ise 1250 μg/mL’lik MIK degerleriyle Staphylococcus epidermidis ve Candida albicans suslarina karsi zayif antimikrobiyal aktivite gostermistir. Bu sonuclar, n-hekzan ve kloroform ekstresinin bu calismada kullanilan insan kanser hucre dizilerine karsi onemli bir antikanser aktiviteye sahip olduklarini gosterdi.

To find out whether there is a correlation between the extent of platelet activation and inflammation and the severity of preeclampsia (PE) in the third trimester of pregnancy.Forty-one women with PE (n = 23 severe, n = 18 mild) and 80 normotensive pregnant (NP) women were included in the study. Their blood samples were obtained and interleukin (IL)-8 and IL-10 levels measured by an enzyme-linked immunosorbent assay. Basal CD61 and CD62P expressions on CD41-positive platelets were analyzed with the use of flow-cytometry. Platelet aggregation was induced by adenosine diphosphate and determined by aggregometry.CD62P expression was increased in severely preeclamptic women, and the platelet aggregation was decreased in both mildly and severely preeclamptic women in comparison with NP women. However, CD61 expression was similar among the groups. An enhanced inflammatory response was seen in severely preeclamptic women demonstrated by increased levels of IL-8 and decreased levels of IL-10. However, the intensity of platelet activation did not correlate directly with the change in plasma levels of IL-8 and IL-10 in preeclamptic women.Platelets may have a role in the inflammatory response in PE. However, the severity of inflammation is found to be independent from the intensity of platelet activation in preeclamptic women. This seems to be related to mechanisms causing alterations of cytokine levels such as IL-8 and IL-10, rather than platelet activation.

A series of polyurethane film were prepared from poly(ethylene glycol) with different molecular weight (PEG 1500, 3000, and 8000) and castor oil by one-shot bulk polymerization method. Hexamethylene diisocyanate and 1,4-buthane diol were used as diisocyanate and chain extender, respectively. In order to characterize the samples, their density, swelling ratio, water contact angle, surface free energy, gel content, thermal, and viscoelastic properties were determined. The effect of the soft segment length (SSL) and hard segment content (HSC) of all polyurethane films on their shape memory behavior such as shape fixity (Rf) and shape recovery (Rr) rates were investigated by bending test. Direct contact and MTT tests were used for assessment of cell adhesion and proliferation. The relatively high Rf and Rr values were obtained for the samples programmed at high temperature difference. Rf increased with decreasing HSC. On the other hand, Rr tended to decrease with increasing SSL. After evaluating experimental data by a nonlinear equation, it was found that HSC is more effective parameter on shape memory property than SSL. The gel content, swelling ratio, and water contact angle of the samples were dependent on both SSL and HSC in their structures. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40590.

Aims: New biomarkers are required to detect diabetic nephropathy earlier in persons with type 2 diabetes mellitus. Recent experimental studies indicate that growth arrest-specific protein 6 (Gas6) may have a role in pathogenesis of complications associated with diabetes. The objective of the current study is to examine whether plasma Gas6 concentrations are associated with albuminuria in persons with type 2 diabetes mellitus. Methods: About 32 patients with diabetes which have micro or macroalbuminuria, 37 patients with diabetes and normoalbuminuria, and 30 healthy volunteers were recruited. Plasma Gas6 levels were measured by ELISA. Hemoglobin A(1c) (HbA(1c)), serum C reactive protein, fibrinogen and 24-h urine samples for microalbuminuria were analyzed by Primus PDQ, Beckman Coulter Immage 800, STA Compact and Roche Cobas Integra 800 analyzer, respectively. Statistical analysis was performed using SPSS (Statistical Package for Social Sciences) for Windows 11.5. Results: There was a noteworthy difference among the three groups for Gas6 according to the Kruskal-Wallis test (p