Jale Yuzugulen - Academia.edu (original) (raw)

Papers by Jale Yuzugulen

European Journal of Pharmacology

Frontiers in Immunology

The tumour vasculature is well-established to display irregular structure and hierarchy that is c... more The tumour vasculature is well-established to display irregular structure and hierarchy that is conducive to promoting tumour growth and metastasis while maintaining immunosuppression. As tumours grow, their metabolic rate increases while their distance from blood vessels furthers, generating a hypoxic and acidic tumour microenvironment. Consequently, cancer cells upregulate the expression of pro-angiogenic factors which propagate aberrant blood vessel formation. This generates atypical vascular features that reduce chemotherapy, radiotherapy, and immunotherapy efficacy. Therefore, the development of therapies aiming to restore the vasculature to a functional state remains a necessary research target. Many anti-angiogenic therapies aim to target this such as bevacizumab or sunitinib but have shown variable efficacy in solid tumours due to intrinsic or acquired resistance. Therefore, novel therapeutic strategies such as combination therapies and nanotechnology-mediated therapies may ...

Metabolic Syndrome and Related Disorders, 2022

Background: This is the study to assess alterations on adiponectin, leptin, and metabolic syndrom... more Background: This is the study to assess alterations on adiponectin, leptin, and metabolic syndrome components in women and men bipolar disorder (BD) patients with normal weight and obesity who received valproic acid (VPA) and lithium (Li). Methods: Thirty-six women and 51 men were included. Commercial kits were used to determine all parameters. Metabolic syndrome components were determined according to the NCEP ATP III criteria. Results: Patients who received Li and VPA significantly differ in waist circumference (WC) and triglyceride (TG) levels (in women and men). Normal weight patients received both drugs, significant differences were considered in high-density lipoprotein-cholesterol (HDL-C), WC, and TG levels compared to healthy controls, but there were significant differences in TG, leptin, and adiponectin levels in obese patients who received VPA. There were significant negative and positive correlation between leptin and adiponectin and WC and TG in women and men BD patients treated with VPA and Li. There were significant positive correlation between leptin and adiponectin and WC and TG and significant negative correlation with HDL-C in normal weight BD patients treated with VPA and Li, respectively, while there was only a significant positive correlation between leptin and adiponectin, and TG in obese BD patients treated with VPA. Conclusions: It looks like that patients treated with both drugs for our suggested time may increase leptin and adiponectin levels. Correlation differences between leptin and adiponectin, and metabolic syndrome components may be important parameters in women, men, normal weight, and obese BD patients. Monitoring of body composition and adipokines may benefit in medical care of these patients.

Pharmaceutical Sciences, 2020

Background: Cholestatic liver disease primarily affects hepatic tissue. Cholestasis could also in... more Background: Cholestatic liver disease primarily affects hepatic tissue. Cholestasis could also influence the function of other organs rather than the liver. Cholestasis-induced kidney injury is a severe clinical complication known as "cholemic nephropathy" (CN). Bile duct ligation (BDL) is a trustworthy experimental model for inducing CN. Although the precise mechanism of renal injury in cholestasis is not fully recognized, several studies revealed the role of oxidative stress in CN. There is no promising pharmacological intervention against CN. Carnosine (CAR) is a peptide extensively investigated for its pharmacological effects. Radical scavenging and antioxidative stress are major features of CAR. The current study aimed to evaluate the role of CAR supplementation on the CN. Methods: CAR was administered (250 and 500 mg/kg, i.p) to BDL rats for 14 consecutive days. Urine and serum markers of renal injury, biomarkers of oxidative stress in the kidney tissue, and renal hi...

Molecular Genetics and Metabolism Reports, 2016

Journal of the American Heart Association, Jan 23, 2015

Endothelin 1 (ET-1) contributes to chronic kidney disease (CKD) development and progression, and ... more Endothelin 1 (ET-1) contributes to chronic kidney disease (CKD) development and progression, and endothelin receptor antagonists are being investigated as a novel therapy for CKD. The proET-1 peptides, endothelin-like domain peptide (ELDP) and C-terminal pro-ET-1 (CT-proET-1), are both potential biomarkers of CKD and response to therapy with endothelin antagonists. We assessed plasma and urine ELDP and plasma CT-proET-1 in CKD patients with minimal comorbidity. Next, in a randomized double-blind crossover study of 27 subjects with proteinuric CKD, we examined the effects of 6 weeks of treatment with placebo, sitaxentan (endothelin A antagonist), and nifedipine on these peptides alongside the primary end points of proteinuria, blood pressure, and arterial stiffness. Plasma ELDP and CT-proET-1 increased with CKD stage (both P<0.0001), correlating inversely with estimated glomerular filtration rate (both P<0.0001). Following intervention, placebo and nifedipine did not affect pla...

Life Sciences, 2013

sections. Micro-CT data showed a decrease of bone volume/tissue volume (BV/TV, 10.9 ± 0.4%) in TE... more sections. Micro-CT data showed a decrease of bone volume/tissue volume (BV/TV, 10.9 ± 0.4%) in TET-1 mice primary spongiosa when compared to the age-and gender-matched littermates (12.8 ± 0.5%, p b 0.05). In contrast, there was no significant difference in the density of subchondral trabecular bone (secondary spongiosa) between TET-1 mice (23.5 ± 3.6%) and their littermates (25.7 ± 1.4%, p N 0.05).It was revealed histologically that articular chondrocytes underwent hypertrophic changes together with thickening of calcified cartilage in TET-1 mice as compared to their littermates. In summary, TET-1 mice present OAlike changes and overexpression of ET-1 contributes to hypertrophic changes of articular chondrocytes.

Scientific Reports, Jul 10, 2017

Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac and renal diseases, and in the pro... more Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac and renal diseases, and in the progression of tumour growth in cancer, but current diagnosis and treatment remain inadequate. Peptides derived from the 212 amino acid precursor preproendothelin-1 (ppET-1) may have utility as biomarkers, or cause biological effects that are unaffected by endothelin receptor antagonists. Here, we used specific immunoassays and LC-MS/MS to identify NT-proET-1 (ppET-1 [18-50]), Endothelin-Like Domain Peptide (ELDP, ppET-1 [93-166]) and CT-proET-1 (ppET-1 [169-212]) in conditioned media from cultured endothelial cells. Synthesis of these peptides correlated with ET-1, and plasma ELDP and CT-proET-1 were elevated in patients with chronic heart failure. Clearance rates of NT-proET-1, ELDP and CT-proET-1 were determined after i.v. injection in anaesthetised rats. CT-proET-1 had the slowest systemic clearance, hence providing a biological basis for it being a better biomarker of ET-1 synthesis. ELDP contains the evolutionary conserved endothelin-like domain sequence, which potentially confers biological activity. On isolated arteries ELDP lacked direct vasoconstrictor effects. However, it enhanced ET-1 vasoconstriction and prolonged the increase in blood pressure in anaesthetised rats. ELDP may therefore contribute to disease pathogenesis by augmenting ET-1 responses. The 21-amino acid vasoconstrictor peptide endothelin-1 (ET-1) was first described almost 30 years ago 1. Subsequent research has strongly linked increased expression of ET-1 to pathological processes underlying cardiovascular, renal and lung diseases 2-6 , where it not only acts as a vasoconstrictor but also causes inflammation, vascular remodelling and fibrosis 7-13. ET-1 peptides also play a role in cancer cell proliferation and tumour growth 14. Current use of endothelin receptor antagonists (ERA) is mainly restricted to treatment of pulmonary hypertension 5, 6. Other disease areas, particularly those involving fibrosis or tumour growth, are largely resistant to ERA treatment 14. However, observations that over expression of the EDN1 gene leads to a lethal heart failure that is not prevented by ERA indicate that there are undiscovered aspects of endothelin biology that require further investigation 7. There are three endothelin isoforms-ET-1, ET-2 and ET-3-generated from three separate genes 15. ET-1 is the main isoform expressed in the cardiovascular system. Human ET-1 is derived from a 212 amino acid precursor-preproET-1 (ppET-1) 16, 17. All three isoforms are 21 amino acids long and contain four Cys residues that form two intra-chain disulphide bridges at Cys 1-Cys 15 and Cys 3-Cys 111, 15. This unusual structure is an evolutionary conserved characteristic of this family of peptides 18, 19 .

Proendothelin-1 Derived Peptides Identifies a Co-secreted Modulator of ET-1 Vasoconstriction, and... more Proendothelin-1 Derived Peptides Identifies a Co-secreted Modulator of ET-1 Vasoconstriction, and Provides Insights for Biomarker Measurements.

Cirrhosis-associated muscle mass loss or sarcopenia is a common complication (17-30% prevalence) ... more Cirrhosis-associated muscle mass loss or sarcopenia is a common complication (17-30% prevalence) in cirrhotic patients. However, the pathogenesis of this complication is poorly understood. Therefore, finding the mechanisms of sarcopenia could lead to the development of therapeutic strategies against this complication. In the current study, rats underwent bile duct ligation (BDL) surgery, and their skeletal muscle (gastrocnemius; GS) was isolated and assessed 28 and 56 days after BDL operation. Significant increase in biomarkers of oxidative stress, including reactive oxygen species (ROS) formation, lipid peroxidation, and increased oxidized glutathione (GSSG) levels were detected in the muscle of cirrhotic animals. Skeletal muscle tissue antioxidant capacity and reduced glutathione (GSH) were also significantly decreased in BDL rats. Moreover, deterioration of several mitochondrial indices, including mitochondrial depolarization, increased mitochondrial permeabilization, depleted AT...

Bulletin of Pharmaceutical Sciences. Assiut, 2021

Gastric cancer is one of the main cancer-related death causes in the world threatening almost 12 ... more Gastric cancer is one of the main cancer-related death causes in the world threatening almost 12 million human lives by 2020. Achillea millefolium L. (yarrow) with domestic Iranian name of Bumadaran, has been as a curative plant for several medical conditions for a long time. Its antimicrobial and wound healing effects have been reported and in this study, we aimed to survey the in-vitro cytotoxic and anti-cancer effects of this plant. After taxonomically identification of Achillea millefolium L., its hydroalcoholic extract was extracted and the AGS gastric cancer and L-929 normal fibroblastic cell-lines with treated by the different concentrations of extract in 3 time periods (24, 48, and 72 hrs). MTT assay was performed for the evaluation of cytotoxic effects. The 24 hrs treatment did not affect cell survival, notably, while the concentrations of 64 and 16 μg/ml were determined as IC50 concentrations at 48 and 72 hrs incubation times respectively. The 72 hrs incubation time with 1...

metrioid endometrial adenocarcinoma (EC), the molecular and cellular mechanisms of this anti-tumo... more metrioid endometrial adenocarcinoma (EC), the molecular and cellular mechanisms of this anti-tumorigenic response remain unclear. Therefore, we investigated whether gamma ray irradiation induces changes in the number of FoxP3 T-regulatory lymphocytes (Tregs), CD56 natural killer cells (NK), and the expression of progesterone receptor membrane component 1 (PGRMC1) in the tumor microenvironment (TME). Materials and Methods: According to the inclusion criteria, 127 cases were selected and grouped into irradiation-treated (Rad) and control (underwent surgery) groups and analyzed using immunohistochemistry. Predictive prognostic values were analyzed using Mann-Whitney U test, ROC analysis, relative risk, log-rank, Spearman rank tests and multivariate Cox’s regression. Results: We observed significant differences (p < 0.001) between the radiation-treated patients and the control groups in FoxP3 Tregs numbers, CD56 NK cells and PGRMC1 expression. Gamma ray induced a 3.71and 3.39-fold in...

Dietary consumption to various nuts, berries, and particularly pomegranate is an important source... more Dietary consumption to various nuts, berries, and particularly pomegranate is an important source of ellagitannins. These molecules are particularly subject to gastrointestinal metabolism producing urolithins as their metabolites. Urolithins (i.e., hydroxylated benzo[c]chromen-6-one analogues) have a greater absorption than the ellagitannins thus; greater bioavailability is of great significance. Therefore, the biological activities obtained through the use of ellagitannin rich foods are mainly attributed tourolithins. These compounds possess a good peripheral distribution. In addition, some of their further metabolitescan penetrate to the central nervous system which, is of a topic of interest for CNS related pathologies. This review has aimed to introduce the structure and metabolism related formation of different urolithins concomitant to their biological activities discovered so far in the literature.

Behavioural Brain Research

Orexins or hypocretins are excitatory neuropeptides predominantly produced by neuronal clusters i... more Orexins or hypocretins are excitatory neuropeptides predominantly produced by neuronal clusters in the lateral hypothalamus. The orexinergic system's involvement in pain modulation makes it a candidate for pain control alternative to the opioid system. Moreover, orexin-1 and orexin -2 receptors (OX1r and OX2r, respectively) play a role in responsiveness to stressful stimuli. Some evidence indicates that the Cornu Ammonis 1 (CA1) region of the hippocampus potentially participates in the modulation of both pain and stress. In quest of better understanding the interaction between orexin receptors and stress-induced analgesia (SIA), The present study examined the involvement of OX1r and OX2r within the CA1 in response to acute pain after exposure to forced swim stress (FSS) for a 6-min period. Adult male Wistar rats received different doses of OX1r antagonist (SB334867; 1, 3, 10, and 30 nmol), OX2r antagonist (TCS OX2 29; 3, 10, 30 and 100 nmol), or vehicle (0.5µl DMSO) through an implanted cannula. After that, animals individually experienced acute pain by performing the tail-flick test. Results indicated that FSS produces antinociceptive responses in the tail-flick test. Blockade of both orexin receptors within the CA1 region attenuated the analgesic effect of FSS. The antinociceptive effect of swim stress was prevented by lower doses of SB334867 than TCS OX2 29. These findings show that the orexinergic system might be partially involved in the SIA via the OX1 and OX2 receptors in the hippocampal CA1 region.