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Öğe Adipose-derived stem cells in the treatment of hepatobiliary diseases and sepsis(Baishideng Publishing Group Inc, 2022) Satilmis, Basri; Cicek, Gizem Selen; Cicek, Egemen; Akbulut, Sami; Sahin, Tevfik Tolga; Yilmaz, SezaiDetermination of the mesenchymal stem cells is one of the greatest and most exciting achievements that tissue engineering and regenerative medicine have achieved. Adipose-derived mesenchymal stem cells (AD-MSC) are easily isolated and cultured for a long time before losing their stem cell characteristics, which are self-renewal and pluripotency. AD-MSC are mesenchymal stem cells that have pluripotent lineage characteristics. They are easily accessible, and the fraction of stem cells in the adipose tissue lysates is highest among all other sources of mesenchymal stem cells. It is also HLA-DR negative and can be transplanted allogenically without the need for immunosuppression. These advantages have popularized its use in many fields including plastic reconstructive surgery. However, in the field of hepatology and liver transplantation, the progress is slower. AD-MSC have the potential to modulate inflammation, ameliorate ischemia-reperfusion injury, and support liver and biliary tract regeneration. These are very important for the treatment of various hepatobiliary diseases. Furthermore, the anti-inflammatory potential of these cells has paramount importance in the treatment of sepsis. We need alternative therapeutic approaches to treat end-stage liver failure. AD-MSC can provide a means of therapy to bridge to definitive therapeutic alternatives such as liver transplantation. Here we propose to review theoretic applications of AD-MSC in the treatment of hepatobiliary diseases and sepsis.Öğe Antioxidant activity and luteolin content of Marchantia polymorpha L(Tubitak Scientific & Technological Research Council Turkey, 2012) Gokbulut, Alper; Satilmis, Basri; Batcioglu, Kadir; Cetin, Barbaros; Sarer, EnginAntioxidant activity of the methanol and ethyl acetate extracts of Marchantia polymorpha L., which grows naturally in Turkey, was tested by DPPH and ABTS methods. According to the applied methods, both extracts exhibited moderate activity. Some phenolic compounds that could be responsible for the activity were investigated by RP-HPLC, qualitatively and quantitatively, in the methanolic extract of liverwort. While caffeic acid, chlorogenic acid, rutin, myricetin, quercetin, and kaempferol were not found in the extract, luteolin as the liable antioxidant agent was determined as 0.0052 +/- 0.0002% among the investigated compounds.Öğe Antioxidant and Antimicrobial Activities, and Phenolic Compounds of Selected Inula species from Turkey(Sage Publications Inc, 2013) Gokbulut, Alper; Ozhan, Onural; Satilmis, Basri; Batcioglu, Kadir; Gunal, Selami; Sarer, EnginThree Inula species, I. viscosa, I. helenium ssp. turcoracemosa and I. montbretiana, collected from different locations of Anatolia were investigated for their antioxidant and antimicrobial potential, and their total phenolic content and phenolic composition. Antioxidant activities of various extracts of the plant parts were measured using DPPH radical scavenging and ABTS assays. Antimicrobial potential of methanol extracts of the plant parts was determined by the agar dilution method against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, Candida albicans and Candida tropicalis. All the extracts were more active against Gram-positive bacteria and yeasts than Gram-negative bacteria. The extracts exhibited antioxidant and antimicrobial activities in different concentrations. Total phenolic concentration of the extracts was estimated with Folin-Ciocalteu reagent using gallic acid as standard. The total phenolic content varied widely in different parts of the three tested Inula species, ranging from 21.1 +/- 0.8 to 190.9 +/- 6.1 mg GAE/g extract. Phenolic components, such as chlorogenic acid, caffeic acid, rutin, myricetin, quercetin, luteolin and kaempferol were quantified by HPLC-DAD in the methanol extracts of the Inula species. It was obvious that the antioxidant and antimicrobial properties of the plants were due to the phenolics.Öğe Assessment of Liver Regeneration in Patients Who Have Undergone Living Donor Hepatectomy for Living Donor Liver Transplantation(Mdpi, 2023) Satilmis, Basri; Akbulut, Sami; Sahin, Tevfik Tolga; Dalda, Yasin; Tuncer, Adem; Kucukakcali, Zeynep; Ogut, ZekiBackground: Inflammation and the associated immune pathways are among the most important factors in liver regeneration after living donor hepatectomy. Various biomarkers, especially liver function tests, are used to show liver regeneration. The aim of this study was to evaluate the course of liver regeneration following donor hepatectomy (LDH) by routine and regeneration-related biomarkers. Method: Data from 63 living liver donors (LLDs) who underwent LDH in Inonu University Liver Transplant Institute were prospectively analyzed. Serum samples were obtained on the preoperative day and postoperative days (POD) 1, 3, 5, 10, and 21. Regenerative markers including alfa-fetoprotein (AFP), des carboxy prothrombin (DCP), ornithine decarboxylase (ODC), retinol-binding protein 4 (RBP4), and angiotensin-converting enzyme isotype II (ACEII) and liver function tests including alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transferase (GGT), alkaline phosphatase (ALP) and total bilirubin levels were all analyzed. Results: The median age of the LLDs was 29.7 years and 28 LLDs were female. Eight LLDs developed postoperative complications requiring relaparotomy. The routine laboratory parameters including AST (<0.001), ALT (<0.001), ALP (<0.001), and total bilirubin (<0.001) showed a significant increase over time until postoperative day (POD) 3. For the regeneration-related parameters, except for the RBP4, all parameters including ACEII (p = 0.006), AFP (p = 0.002), DCP (p = 0.007), and ODC (p = 0.002) showed a significant increase in POD3. The regeneration parameters showed a different pattern of change. In right-lobe liver grafts, ACEII (p = 0.002), AFP (p = 0.035), and ODC (p = 0.001) showed a significant increase over time. DCP (p = 0.129) and RBP4 (p = 0.335) showed no significant changes in right-lobe liver grafts. Conclusions: Regenerative markers are increased in a sustained fashion following LDH. This is more prominent following right-lobe grafts which are indicative of progenitor-associated liver regeneration.Öğe Comparison of stereochemical structures of cholesterol from different sources by HPLC(Marmara Univ, Fac Pharmacy, 2012) Satilmis, Basri; Guldur, Tayfun; Karakurt, Arzu; Buyuktuncel, Ebru; Ertan, MevlutIt is known that only one stereoisomeric form, nat-cholesterol, naturally occurs. Nat-cholesterol and its enantiomer, ent-cholesterol, sometimes show enantiospecific interactions with biological molecules. If cholesterol is naturally found only one form, then the question of why does cholesterol show an enantiomeric selectivity? arises. For this purpose, stereoisomer analysis of cholesterol obtained from porcine liver and wool wax were carried out with three different high performance liquid chromatography (HPLC) systems including reversed-phase, reversed-phase with different cyclodextrins as a mobile phase modifier, and chiral. Results from HPLC analysis of both cholesterol samples by permethylated gamma-cyclodextrin and amylose tris-(3,5-dimethylphenylcarbamate) chiral columns showed that there was no stereoisomer of cholesterol present. However reversed-phase HPLC analysis of cholesterol samples from porcine liver carried out with various cyclodextrins as mobile phase modifiers presented a peak which was not observed in the analysis of cholesterol samples from wool wax. On the other hand, different storage conditions of cholesterol samples and addition of cyclodextrins as mobile phase modifiers produced almost identical alterations in chromatograms of fresh samples by reversed-phase HPLC. This could be attributed to catalytic properties of cyclodextrins. Cyclodextrins may not be suitable as a mobile phase modifier in the stereoisomer analysis of cholesterol with high performance liquid chromatography.Öğe Development of Some Antiplatelet Salts as Drug Active Ingredients and Investigation Biological Activities(Springer, 2023) Uslu, Harun; Satilmis, Basri; Uyumlu, Ayse Burcin; Saglik, Begum Nurpelin; Levent, Serkan; Ozkay, Yusuf; Genc, Metin FikretIn this study, prasugrel and prasugrel salts: prasugrel + trans-1,2-cyclohexanedicarboxylic acid (1a), prasugrel + maleic acid (2a), prasugrel + citric acid (3a), prasugrel + oxalic acid (4a), and prasugrel + trometamol (5a) were synthesized and investigated for their biological activities.Ex vivo antiplatelet and in vitro cytotoxic activities were experimentally researched. Antiproliferative activity was not observed for prasugrel and prasugrel salts, and it was also determined that there was no cytotoxic effect. Ex vivo experiments were carried out on diabetic and nondiabetic rats. When the study results were examined, 2a and 3a were seen to be effective prasugrel salts for antiplatelet activity.Öğe The Effect of Pringle Maneuver Applied during Living Donor Hepatectomy on the Ischemia-Reperfusion Injury Observed in the Donors and Recipients(Mdpi, 2024) Dalda, Yasin; Akbulut, Sami; Sahin, Tevfik Tolga; Tuncer, Adem; Ogut, Zeki; Satilmis, Basri; Dalda, OzlemBackground and Objectives: The aim of this study is to evaluate the clinical and laboratory changes of ischemia and reperfusion injury in the remnant livers of donors with and without Pringle maneuver. Furthermore, we evaluated the recipients who have been transplanted with liver grafts from these donors. Methods and Materials: A total of 108 patients (54 living liver donors and 54 liver recipients) who underwent donor hepatectomy and recipients who living donor liver transplantation, were included in this randomized double-blind study between February 2021 and June 2021. The donors were divided into two groups: Pringle maneuver applied (n = 27) and Pringle maneuver not applied (n = 27). Similarly, recipients with implanted liver obtained from these donors were divided into two groups as the Pringle maneuver was performed (n = 27) and not performed (n = 27). Blood samples from donors and recipients were obtained on pre-operative, post-operative 0 h day (day of surgery), post-operative 1st day, post-operative 2nd day, post-operative 3rd day, post-operative 4th day, post-operative 5th day, and liver tissue was taken from the graft during the back table procedures. Liver function tests and complete blood count, coagulation tests, IL-1, IL-2, IL-6, TNF-alpha, and beta-galactosidase measurements, and histopathological findings were examined. Results: There was no statistically significant difference in the parameters of biochemical analyses for ischemia-reperfusion injury at all periods in the donors with and without the Pringle maneuver. Similarly, there was no statistically significant difference between in the recipients in who received liver grafts harvested with and without the Pringle maneuver. There was no statistically significant difference between the two recipient groups in terms of perioperative bleeding and early bile duct complications (p = 0.685). In the histopathological examinations, hepatocyte damage was significantly higher in the Pringle maneuver group (p = 0.001). Conclusions: Although the histological scoring of hepatocyte damage was found to be higher in the Pringle maneuver group, the Pringle maneuver did not augment ischemia-reperfusion injury in donors and recipients that was evaluated by clinical and laboratory analyses.Öğe Effects of reciprocal interactions between various dietary fats and circadian phases on postprandial hyperlipidemia in rats(Taylor & Francis Ltd, 2018) Satilmis, Basri; Kayhan, Basak; Guldur, TayfunExpression levels of various intestinal proteins involved in postprandial lipoprotein assembly as well as plasma triglyceride concentration exhibit daily oscillations indicating circadian control. The length of the carbon chain and degree and position of unsaturation of fatty acids influence triglyceride secretion by the enterocytes. To this end, effects of reciprocal interactions of various single fats/oil (olive oil, fish oil or butter) gavaging either in active or passive phase were investigated in rats. Fat/oil gavaged in the active phase of circadian rhythm resulted in higher postprandial serum triglyceride levels compared to that in the passive phase. Moreover, olive oil led to higher MTP activity and apo B-48 gene expression, while fish oil gavaging caused more prominent apo B-48 and MTP gene expression when they were given in the passive phase. The present results indicate that circadian time at which fat or oil gavaged once might exert influence on postprandial lipoprotein synthesis/assembly.Öğe Hepatic Arginase - Nitric oxide imbalance: Impact of carcinogenesis and therapeutic effect of sodium channel blockage in an in vivo rat model(Walter De Gruyter Gmbh, 2016) Batcioglu, Kadir; Yildirim, Battal; Satilmis, Basri; Uyumlu, Ayse Burcin; Genc, Metin Fikret; Bentli, Recep; Djamgoz, Mustafa B. A.Objective: Nitric oxide synthase and arginase are frequently antagonistic and interactive, although both use L-arginine as common substrate. Their balance is of potential functional importance. How the balance changes in cancer is unknown. Increasing evidence suggests that progression of carcinomas involves functional voltage-gated sodium channel (VGSC) activity. Methods: The present study extended this study to liver and aimed to determine whether (i) DMBA carcinogenesis would affect the activities of arginase and NOS and (ii) treatment with Na-channel blocker RS100642 would ameliorate the impact of the carcinogen on the arginase-NOS balance. Results: DMBA application significantly increased arginase activity and, correspondingly, the level of L-ornithine by 25-33%. In contrast, NOS activity decreased by 11%. Importantly, RS100642 treatment completely suppressed the effect on arginase. Conclusion: It is concluded (i) that DMBA carcinogenesis changes the hepatic arginase-NOS balance, increasing the overall dominance of arginase and (ii) that VGSC inhibition has a protective effect on liver.Öğe Hepatocellular Carcinoma Tumor Microenvironment and Its Implications in Terms of Anti-tumor Immunity: Future Perspectives for New Therapeutics(Springer, 2021) Satilmis, Basri; Sahin, Tevfik Tolga; Cicek, Egemen; Akbulut, Sami; Yilmaz, SezaiPurpose Hepatocellular cancer is an insidious tumor that is often diagnosed in a later stage of life. The tumor microenvironment is the key to tumorigenesis and progression. Many cellular and non-cellular components orchestrate the intricate process of hepatocarcinogenesis. The most important feature of hepatocellular cancer is the immune evasion process. The present review aims to summarize the key components of the tumor microenvironment in the immune evasion process. Methods Google Scholar and PubMed databases have been searched for the mesh terms Hepatocellular carcinoma or Liver Cancer and microenvironment. The articles were reviewed and the components of the tumor microenvironment were summarized. Results The tumor microenvironment is composed of tumor cells and non-tumoral stromal and immune cells. HCC tumor microenvironment supports aggressive tumor behavior, provides immune evasion, and is an obstacle for current immunotherapeutic strategies. The components of the tumor microenvironment are intratumoral macrophages (tumor-associated macrophages (TAM)), bone marrow-derived suppressor cells, tumor-associated neutrophils (TAN), fibroblasts in the tumor microenvironment, and the activated hepatic stellate cells. Conclusion There are intricate mechanisms that drive hepatocarcinogenesis. The tumor microenvironment is at the center of all the complex and diverse mechanisms. Effective and multistep immunotherapies should be developed to target different components of the tumor microenvironment.Öğe Investigation of a weak magnetic field effect on the in vitro catalytic activity of adenosine deaminase and xanthine oxidase(General Physiol And Biophysics, 2011) Batcioglu, Kadir; Dogan, Metin; Uyumlu, Ayse B.; Satilmis, Basri; Bayri, Nevzat; Atalay, Selcuk; Demirtas, HakanThe effect of a weak magnetic field (MF) on adenosine deaminase (ADA) and xanthine oxidase (XOD) activities have been investigated. A 50 Hz uniform MF was generated, and the magnitude of the field was kept constant at 5.8 mT. The changes in ADA activity over time were significantly different in and out of the MF; MF caused a steeper decline in ADA activity compared to the situation when no MF is present. In addition, MF caused a significant increase in XOD activity. There were no significant time-related changes for either enzyme in the absence of the MF. We suggest that a weak MF affects enzymatic systems.Öğe Neuroprotective effects of the new Na channel blocker rs100642 in global ischemic brain injury(Termedia Publishing House Ltd, 2019) Kamisli, Suat; Basaran, Cenk; Batcioglu, Kadir; Oztanir, Mustafa Namik; Gul, Mehmet; Satilmis, Basri; Uyumlu, Ayse BurcinIntroduction: RS100642, a mexiletine analogue, is a novel sodium channel blocker with neuroprotective and antioxidant activities. The protectivity of RS100642, which has been shown against focal cerebral ischemia, was investigated in global cerebral ischemia in this study. Material and methods: Global cerebral ischemia was induced for five minutes in adult male Wistar Albino rats via the 4-vessel occlusion method. Intravenous administration of 1 mg/kg RS100642 following reperfusion for 30 min (RS100642 group) was compared with a sham treatment group (ischemia group) and nonischemized group (control) histologically based on morphology and caspase-3 immunohistochemistry, and biochemically based both on measurement of oxidative stress including malondialdehyde (MDA) levels, superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) activities and on assessment of apoptosis including caspase-3 and -8 activities and tumor necrosis factor alpha (TNF-alpha) levels at the end of 6 h. Results: While the RS100642 group had significantly lower MDA levels and higher SOD activities than the sham treatment group (p < 0.05), GPx and CAT activities of the RS100642 and sham treatment groups were similar (p > 0.05) and significantly lower than those of the controls (p < 0.05). Necrosis and caspase-3 activity and immunoreactivity in the RS100642 group were significantly lower than those in the sham treatment group (p < 0.05), while there was no significant difference between groups regarding caspase-8 and TNF-alpha (p > 0.05). Conclusions: Na+ channel blockade by RS100642 has remarkable neuroprotective effects following global brain ischemia/reperfusion damage. Further research is required to determine the optimum dose and time of administration.Öğe Oxidative Stress in the in vivo DMBA Rat Model of Breast Cancer: Suppression by a Voltage-gated Sodium Channel Inhibitor (RS100642)(Wiley, 2012) Batcioglu, Kadir; Uyumlu, A. Burcin; Satilmis, Basri; Yildirim, Battal; Yucel, Neslihan; Demirtas, Hakan; Onkal, RustemBreast cancer (BCa) was induced in vivo in female rats with 7,12-dimethylbenz(a)anthracene (DMBA). Two main questions were addressed. Firstly, would the carcinogenesis be accompanied by oxidative stress as signalled by superoxide dismutase, glutathione peroxidase, malondialdehyde and total nitrate? Secondly, would treating the rats additionally with a blocker of voltage-gated sodium channel (VGSC) activity, shown previously to promote BCa progression, affect the oxidative responses? The DMBA-induced increases in the antioxidant systems were completely blocked by the VGSC inhibitor RS100642, which also significantly prolonged the lifespan. We conclude that VGSC inhibition in vivo can significantly protect against oxidative stress and improve survival from tumour burden.Öğe Phenethyl isothiocyanate protects against cyclophosphamide-induced nephrotoxicity via nuclear factor E2-related factor 2 pathway in rats(Sage Publications Ltd, 2023) Uyumlu, Ayse Burcin; Satilmis, Basri; Atici, Bugrahan; Taslidere, AsliPhenethyl isothiocyanate (PEITC), a secondary metabolite in Cruciferous plants, exerts chemopreventive and antioxidant effects. However, its therapeutic potential in cyclophosphamide (CP)-induced nephrotoxicity is not clear. So, we focused to research on the effect of PEITC against renal toxicity caused by CP and its relationship to the Nrf2 signaling mechanism. Thirty female Wistar albino rats were allocated to three groups: control (n = 10), CP (n = 10), and PEITC-pretreated group (150 mu mol/kg b.w. orally; n = 10). The antioxidant enzyme activities and levels of malondialdehyde (MDA), sirtuin 1 (SIRT1), glutathione-S-transferase (GST), nuclear factor E2-related factor 2 (Nrf2), nuclear factor kappa B (NF-kappa B), serum urea, and creatinine (Cr) were measured. In the CP group, serum urea and Cr, MDA, and NF-kappa B levels have risen, and the activities of antioxidant enzymes and SIRT1, Nrf2, and GST levels have reduced significantly (P < 0.05). PEITC diminished levels of Cr, urea, MDA, and NF-kappa B while it enhanced antioxidant enzyme activities and GST, Nrf2, and SIRT1 levels significantly (P < 0.05). Pretreatment with PEITC ameliorated kidney tissue injury. The renal protective effect of the PEITC was supported by the histological analysis of the kidney. PEITC prevented CP-induced nephrotoxicity by decreasing oxidative damage through Nrf2 and SIRT1 activation and NF-kappa B inhibition. Therefore, we have suggested that PEITC may be a useful agent for protection against CP-induced renal injury.Öğe Synthesis of PEITC-loaded gold nanoparticles and evaluation of the hepatoprotective effect on CCl4-induced damage through Nrf2 pathway(Walter De Gruyter Gmbh, 2023) Uyumlu, Ayse Burcin; Yilmaz, Hatice Caglar; Satilmis, Basri; Erdemoglu, SemaObjectives: The purpose of the study was to prepare an effective and new drug delivery system for enhancing the stability of Phenethyl isothiocyanate (PEITC), and its hepatoprotective effect in the carbon tetrachloride (CCl4)-induced damage in hepatocellular carcinoma G2 (HepG2) cell line via nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway.Methods: Gold nanoparticles were synthesized and then characterized by XRD, SEM, SEM-EDX analysis, hydrodynamic diameter and zeta potential measurements. 1.0024 mM PEITC, a naturally occurring isothiocyanate, an active ingredient was loaded onto the characterized AuNPs. The cytotoxicity test of PEITC-AuNP and effects on ALT, AST, Nrf2 levels and total antioxidant capacity (TAC) of CCI4-induced HepG2 cells were investigated.Results: PEITC-AuNPs and PEITC decreased ALT and AST levels (p < 0.05). This reduction was greater with PEITC-AuNPs. PEITC-AuNPs increased Nrf2 level but it was nonsignificantly (p > 0.05). PEITC didn't increase the Nrf2 level in CCI4-induced HepG2 cells. TAC of both PEITC-AuNPs and PEITC administration increased significantly compared with CCl4 group (p < 0.05). But PEITC-AuNPs enhanced the TAC level higher than PEITC significantly (p < 0.05).Conclusions: PEITC-AuNPs were more effective than PEITC which resulted in more hepatoprotective and antioxidant effects via Nrf2 activation against CCl4-induced liver injury in HepG2 cells.
