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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 Local ADSC Delivery Methods Accelerate Healing of Large Unburned Full-Thickness Skin Defects by Promoting an Optimal Wound Microenvironment(Mdpi, 2026) Gurunluoglu, Semra; Satilmis, Basri; Gul, Mehmet; Dundar, Muhammed; Gurunluoglu, Kubilay; Karaaslan, Ezgi; Koc, AhmetBackground: This study introduces an experimental model of a large, full-thickness skin defect and evaluates how adipose-derived stem cells characterized by high self-renewal and differentiation capacity affect both wound healing and the wound microenvironment when delivered using two different local application methods. Materials and Methods: In this preclinical study, we established an excisional full-thickness skin defect model involving approximately 30% of the total body surface area (TBSA). Five experimental groups were formed, each containing equal numbers of male and female rats: (1) subdermal ADSC injection (ADSC-I) (n = 8), (2) application of an acellular dermal matrix (ADM) seeded with ADSCs (n = 8) (ADSC-ADM), (3) ADM alone (n = 8), (4) subdermal saline injection (n = 8) (SS-I), and (5) an untreated skin-defect sham group (n = 8). Wound healing and wound microenvironment parameters were assessed at regular intervals using macroscopic and microscopic evaluations, as well as various quantitative measurements. The study was terminated when complete wound closure was achieved in all animals of at least one experimental group. Results: The most favorable healing outcomes were observed in the two ADSC-treated groups. More favorable microenvironmental conditions in the stem cell groups were detected from day 14 onward. Complete closure of the dermal defects occurred by day 32 in the ADSC-I group, whereas none of the other groups achieved full wound closure within the study period. Conclusions: Local application of adipose-derived stem cells may accelerate wound healing by favorably modulating the wound microenvironment.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 Prospective Analysis of Perioperative Stress Response in Living Donor Liver Transplantation for Hepatitis B-Related Liver Disease(Mdpi, 2025) Tuncer, Adem; Akbulut, Sami; Sahin, Tevfik Tolga; Satilmis, Basri; Ogut, Zeki; Dalda, Yasin; Yilmaz, SezaiBackground: Liver transplantation is a life-saving procedure for patients with end-stage liver disease, yet the immunological consequences of surgical trauma in these patients are not fully understood. The liver plays a central role in immune regulation, and its dysfunction in HBV-related chronic liver disease may alter the systemic stress response to surgery. Aim: This study aims to evaluate the stress response to surgical trauma of patients undergoing living donor liver transplantation (LDLT) for HBV-related chronic liver disease in comparison to living liver donors (LLDs). Methods: This prospective study included 20 LDLT recipients with HBV infection and 20 LLDs who underwent living donor hepatectomy between August 2020 and February 2021. Specific biochemical markers (IL-1, IL-4, IL-6, IL-22, IFN-gamma, TNF-alpha, TGF-beta, GM-CSF, GLDH, and GalactB) were measured at designated intervals: preoperative day 0 (Preop), immediately after incision (Incision), post-hepatectomy (Hepatectomy), postoperative day 0 (POD0), POD1, and POD3 using enzyme-linked immunosorbent assay (ELISA). Routine hematological and biochemical parameters (WBC, HGB, PLT, RDW, MPV, PDW, AST, ALT, ALP, GGT, albumin, total bilirubin, plateletcrit, phosphorus, fibrinogen, and INR) were measured regularly at five predetermined times: Preop, POD0, POD1, POD2, and POD3. Results: Prior to LDLT, LDLT recipients had significantly lower levels of pro-inflammatory cytokines (IL-1, IL-6, TNF-alpha, IFN-gamma) compared to LLDs (p < 0.05). However, following liver implantation, these cytokine levels increased significantly at POD0, POD1, and POD3 (p < 0.001). Specifically, IL-1 levels elevated from 0 in the preop period to 21.5 (97.5) in POD3, and IL-6 elevated from 0 in the preop period to 28.3 at POD3 (p = 0.056). Similarly, TNF-alpha and IFN-gamma levels exhibited significant upward trends (p < 0.05). In contrast, cytokine levels in LLDs remained stable throughout the perioperative period, revealing no statistically significant variations (p > 0.05). Routine hematological and biochemical parameters demonstrated significant postoperative fluctuations in LDLT recipients, reflecting the metabolic and immune restoration process. Conclusions: These findings indicate that patients with HBV-related chronic liver disease exhibit a diminished stress response to trauma due to underlying immune dysregulation caused by chronic hepatic dysfunction. However, after LDLT, the stress response gradually normalizes, suggesting that liver transplantation not only restores hepatic function but also reestablishes immune homeostasis, potentially reducing infection risks and improving postoperative recovery. These findings emphasize the crucial role of the liver in regulating the body's stress response to trauma and highlight the immunological benefits of LDLT in restoring immune homeostasis.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.Öğe The impact of subdermal adipose derived stem cell injections and early excision on systemic oxidative stress and wound healing in rats with severe scald burns(Elsevier Sci Ltd, 2024) Gurunluoglu, Kubilay; Satilmis, Basri; Gul, Mehmet; Dundar, Muhammed; Gokturk, Nurcan; Akbulut, Sami; Koc, AhmetAim: This study aims to develop an experimental treatment model effective against oxidative stress in the acute period of severe burns and to analyze the mechanisms of healing large wound defects. Methods: Five rats, including 2 females and 3 males, were used as donors to obtain adipose- derived stem cells (ADSC) from the inguinal fat pad. The stem cells were labeled with green fluorescent protein. The study included four groups of 17 rats, each with grade 3 scalding burns on 30 % of their body surface, and a control group of 10 rats with an equal number of males and females. After early excision, 106 6 ADSC-derived stem cells were administered subdermally to the burned wound and autografted to the stem cell group (n = 17). The early excision group (n = 17) received early excision and autograft, with 2 ml of normal saline injected subdermally into the burn wound edge. The PLM group (n = 17) was treated with a polylactic membrane (PLM) dressing after the burn. No treatment was given to the burn group (n = 17). Ten rats from all groups were sacrificed on the 4th day post-burn for oxidative stress evaluation. The control group (n = 10) was sacrificed on day 4. Blood and tissue samples were collected post-sacrifice. Oxidative stress and inflammation in the blood, as well as cell damage in the skin, liver, kidneys, and lungs, were investigated histopathologically and biochemically on the 4th day post-burn. On the 70th day after burn, wound healing was examined macroscopically and histopathologically. Results: On the 4th day, oxidative stress results showed that the levels of Total Oxidative Capacity (TOC) in the blood were lowest in the stem cell (7.4 [6-8.8]), control (6.7 [5.9-7.6]), and early excision (7.5 [6.6-8.5]) groups, with no significant difference between them. The burn group (14.7 [12.5-16.9]) had the highest TOC levels. The PLM group (9.7 [8.6-10.7]) had lower TOC levels than the burn group but higher levels than the other groups. Histopathological examination on the 4th day revealed low liver caspase-3 immunoreactivity in the stem cell and early excision groups among the burn groups. Caspase3 immunoreactivity levels were as follows: stem cell group (20 [10-30]), early excision group (25 [15-50]), PLM group (70 [50-100]), control group (0), and burn group (80 [60-120]). Other oxidative stress and end-organ damage outcomes were consistent with these results. All rats in the stem cell group had burn wounds that healed completely by the 70th day. Examination of the skin and its appendages from the stem cell group with an immunofluorescence microscope demonstrated green coloration, indicating incorporation of stem cells. Conclusion: Stem cells may have the potential to form new skin and its appendages, providing better healing for large skin defects. Early excision treatment, by removing local necrotic tissues after extensive and deep burns, can prevent end-organ damage due to systemic oxidative stress and inflammation. We also believe that when these two treatments are used together, they can achieve the best results. (c) 2024 Elsevier Ltd and ISBI. All rights are reserved, including those for text and data mining, AI training, and similar technologies.Öğe The role of neopterin in cross-talk between tumor and tumor microenvironment in hepatocellular carcinoma(De Gruyter Poland Sp Z O O, 2024) Satilmis, Basri; Cicek, Egemen; Karakas, Serdar; Kutluturk, Koray; Otan, Emrah; Yilmaz, Sezai; Sahin, Tevfik TolgaNeopterin is a marker of activated immune response, but its role in hepatocarcinogenesis is unknown. The present study aims to evaluate the effects of neopterin on prooncogenic/proinflammatory, apoptotic pathways, and other molecular mechanisms in HCC. We used SNU449, Huh-7, SK-Hep-1, and HepG2 cell lines. A cell viability assay was performed with different concentrations of neopterin. RT-PCR, Western blotting, transwell migration, scratch assay, and reactive oxygen species (ROS) production assays were performed at inhibition concentration 50 of neopterin, which was 40 mu M for SNU449 and 80 mu M for other cell lines. There were significant changes in mTOR, STAT3, PI3K, and interleukin-6 gene expressions, which were also supported by the protein expressions. Neopterin did not affect apoptosis in SNU449, while apoptosis increased by all doses of neopterin in SK-Hep-1 and HepG2. ROS production was increased in all cell lines in response to neopterin. Cell migration was reduced in SK-Hep1 and HepG2 but did not change in SNU449 and Huh-7. Our study showed that neopterin is not just a byproduct. The results suggest that neopterin may be a paracrine factor that modulates pro-inflammatory and pro-oncogenic pathways responsible for the biological behavior of HCC in a chronic inflammatory tumor microenvironment.











