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Aim: This study aimed to measure the effects of Scilla autumnalis extracts which might act as potential plant based chemotherapeutic, on U87 glioblastoma cell line. Material and Method: Cytotoxicity assays were performed by determining the cell viability of the samples with MTT (3 – (4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide). Gene expression levels of glucose transporter 1 (GLUT1), Glucose transporter 3 (GLUT3), Glucose transporter 4 (GLUT4), Hexokinase 1 (HK1) and Hexokinase 2 (HK2), multidrug resistance1 (MDR1), Cytochrome P450 Family 2 Subfamily E Member 1 (CYP2E1) and Pregnane X receptor (PXR) was analyzed in glioblastoma cells using quantitative real-time RT-PCR. Results: According to the analysis, we observed a 10% increase in the expression of Glut1, however, we did not observe a difference in Glut3 expression. For Glut4, root ethanol extract decreased its expression by 13% but shoot extracts elevated the expression levels by only 5–6%. We determined the low expression levels of HK1 and HK2 in glioblastoma compared to the control group. S.autumnalis root extract led to a slight increase in MDR1 expression. We found that the expression level of CYP2E1 was 20% lower in glioblastoma cells treated with Scilla autumnalis root and shoots extracts compared to the control group. We determined downregulation in PXR expression. Conclusion: This study may contribute significantly to the understanding of the cytotoxic effect of Scilla autumnalis. This approach may allow the possibility of Scilla autumnalis plant extract as a candidate drug for the treatment of glioblastoma.

Nanoemulsions are an isotropical mixture of oil, surfactant, and water with droplet diameter approximately in the range of 10-100 nm. They are being exponentially used for drug delivery systems for the influential administration of therapeutical agents because of their potential advantages over other approaches. Nanoemulsions can be used to design delivery systems that have increased drug loading, enhanced drug solubility, increased bioavailability, controlled drug release, and enhanced protection against chemical or enzymatic degradation. Moreover, nanoemulsions have better thermodynamical stability to flocculation, sedimentation, and creaming than conventional emulsions. Their small droplet dimensions and large droplet surface area positively influence drug transport and delivery, along with allowing targeting to specific sites. This chapter focuses on recent applications of nanoemulsions in the area of drug delivery.

The study was aimed to evaluate the inhibitory activity towards angiotensin converting enzyme I (ACE-I), antioxidant capacity and phenolics of Alchemilla vulgaris (lady’s mantle) naturally grows in Turkey. Aqueous extracts of lady’s mantle were used for enzyme inhibition assay on angiotensin converting enzyme I purified from sheep lungs. Trolox equivalent antioxidant capacity (TEAC) and DPPH assays were also used for monitoring of antioxidant profile of methanolic and aqueous extracts. Total phenolics of the extracts from lady’s mantle were also analyzed. Our research results indicated that lady’s mantle could have important anti-hypertensive effects due to their potent inhibitory activity towards angiotensin converting enzyme I.

Aims: Nondiabetic patients were studied to determine whether modest elevations in plasma mannose may be associated with a greater incidence of coronary artery disease (CAD). Materials and Methods: Plasma insulin, mannose, glucose, hexokinase 1-2, GLUT1-GLUT4 levels, and serum mannose phosphate isomerase enzyme levels were evaluated with respect to subsequent CAD using records from 120 nondiabetic CAD patients and 120 healthy volunteers. CAD was identified from myocardial infarction and new diagnoses of angina. Results: Of 120 nondiabetic CAD patients studied, their plasma GLUT4 and HK1 levels were significantly lower than those of the control group. In addition, a significant increase in plasma mannose levels was found in the patient group compared to the control group. Conclusion: Our findings showed that elevated baseline mannose levels in plasma are associated with an increased risk of CAD over time. © Copyright 2020, Mary Ann Liebert, Inc., publishers 2020.

Background/Aim: Endoplasmic reticulum (ER) stress plays a critical role in the development of cardiac hypertrophy and heart failure. Heart failure is a crucial health problem that affects 23 million people worldwide, causes approximately 2.4 million people to be hospitalized every year in the USA, and leads to the death of more than 300,000 people. In this study, we aimed to investigate the clinical significance of ER stress markers and the predictive value of acute decompensated heart failure in patients with low ejection fraction heart failure (ADHF). Patients and Methods: This is a prospective case control study. The data included laboratory parameters pertaining to patients with ADHF in the emergency service and lipid parameters obtained during their admission to the hospital. In addition, the same parameters obtained from the control group patients with chronic heart failure (CHF) during their routine polyclinic control were recorded in the data set. Admission time to the hospital and length of hospital stay were included in the data. The levels of glucose regulated protein (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and C/EBP homologous protein (CHOP) in peripheral blood serum obtained from the patients and the control group were measured using the ELISA method. Results: Serum GRP78 concentration was lower in the HF group (p=0.003) compared to the control. The median value of serum PERK concentration in the HF group was higher than that of the control group (573 pg/ml, IQR=477.5-650 vs. 495.5 pg/ml, IQR=294-648, respectively) (p=0.001). However, there were no statistically significant differences in GRP78 and PERK serum concentrations between ADHF and CHF subgroups. Receiver operating characteristic (ROC) curve analysis showed greater area under the curve (AUC) for the serum GRP78 levels of the healthy individuals (AUC=0.748, 95% CI=0.681-0.814, p=0.0003). The serum GRP78 level was found to be 80% sensitive and 70% specific at 147.5 pg/ml (p=0.0003) for distinguishing healthy individuals from HF patients. In the ADHF subgroup, there was a moderate correlation between hospitalization time and serum CHOP concentrations (Spearman rho=0.586 and p=0.001). Conclusion: High GRP78 serum concentration may protect the patient from ER stress. In addition, the serum PERK level is high in patients with HF, whereas it is insufficient in predicting acute decompensation. CHOP may be useful in predicting the length of hospital stay in patients with ADHF. © 2019 International Institute of Anticancer Research. All rights reserved.

Dipeptidyl peptidase-IV (DPP-IV) is one of the mammalian serine proteases participated in the pathogenesis of diseases and DPP-IV inhibitors are now widely used as antidiabetic drugs. A new water soluble ternary copper (II) complex,-[Cu(py-phen) (phe) (H2O)]NO3·H2O-(py-phen:pyrazino[2,3f][1,10]phenanthroline, phe:phenylalanine), has been synthesized and characterized by CHN analysis, ESI-MS, FTIR and single-crystal X-ray diffraction techniques. Fluorescence spectroscopy was researched to study the interaction between the complex and bovine serum albumin (BSA) and dipeptidyl peptidase-IV (DPP-IV). Chromophore of BSA and DPP-IV enzyme is changed upon addition of the complex. Additionally, the complex was shown to have promising inhibitory activities against DPP-IV with lower IC50 value. This study may provide new insights into the development of effective agents against diabetes. © 2018 Elsevier B.V.

Amaç: Dipeptidil peptidaz IV(DPP IV); çeşitli proseslerin regülasyonunda özellikle plazma glukoz dengesinin sağlanmasında önemli rol oynayan inkretin peptid hormonlarının [glukagon benzeri peptid-1 (GLP-1) ve glukoz-bağımlı insülinotropik polipeptid (GIP)] yıkımından sorumlu bir serin amino (ekzo) peptidazdır. Bu enzimin inhibisyonunun gerçekleştirilmesi ile diyabetin kontrol altına alınması, son yıllarda benimsenen stratejilerin başında gelmektedir. Bu çalışmanın amacı, antidiyabetik özelliğe sahip 16 bitkinin DPP IV inhibisyon etkinliğinin farklı koşullarda hazırlanan sulu ekstraklarında protein değerleri esas alınarak belirlenmesidir.Metod: DPP IV inhibisyonu, oda sıcaklığı ve 60°C'de hazırlanan bitki sulu ekstraktlarının spesifik inhibitör aktivitelerinin ölçülmesi ile değerlendirildi.Bulgular: Test edilen bitkilerden V. vinifera L., A. dracunculus L., P. laurocerasus L., R. caesius L. ve O. europea L.'nın sulu ekstraktlarında DPP IV inhibitor aktivitesinin IC50 değerleri 0.04-0.09 mg protein/ml olarak gözlendi. Yapılan kinetik analizler ile A. dracunculus ekstraktının inhibitor potansiyelinin diğer ekstraktlara göre daha güçlü olduğu belirlendi. Sonuç: Bu çalışma ile seçilmiş olan antidiyabetik tıbbi gıdaların sulu ekstraktlarında DPP IV inhibitor aktivitesinin taranması ve ön karakterizasyonu için ilk rapor oluş- turulmuştur. Bu çalışma tip 2 diyabet tedavisinde kullanılabilecek bitkiler için DPP IV inhibitörleri taranmasına yönelik yeni bir bakış açısı sağlayacaktır., Objective: Dipeptidyl peptidase IV (DPP IV) is a serine amino (exo) peptidase which regulates various processes most notably plasma glucose homeostasis by cleaving incretin peptide hormones as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulin releasing polypeptide (GIP). Realization of the inhibition of this enzyme in controlling diabetes is one of the strategies adopted in recent years. the present study was designed to investigate the DPP IV inhibitory effects of sixteen plant having antidiabetic property in aqueous extracts in correlation with their protein content.Methods: in vitro DPP IV inhibition was evaluated by the specific inhibitory activity of plant aqueous extracts prepared without and with heat (60°C) treatment.Results: Among the tested plants Vitis vinifera L., Artemisia dracunculus L., Prunus laurocerasus L., Rubus caesius L. and Olea europaea L. extracts showed DPP IV inhibitory activity with respect to IC50 values of 0.04-0.09 mg protein/ml. Kinetic analysis indicated that the inhibitor potency of A. dracunculus extract was stronger than the other extracts.Conclusion: the present study is the first report on screening and preliminary characterization of DPP IV inhibitory activity in aqueous extracts of selected antidiabetic medicinal food. This study could provide a new insight into DPP IV inhibitors from plants that could be useful for treatment of Type 2 diabetes.

New active sites can be introduced into naturally occurring enzymes by the chemical modification of specific amino acid residues in concert with genetic techniques. Chemical strategies have had a significant impact in the field of enzyme design such as modifying the selectivity and catalytic activity which is very different from those of the corresponding native enzymes. Thus, chemical modification has been exploited for the incorporation of active site binding analogs onto protein templates and for atom replacement in order to generate new functionality such as the conversion of a hydrolase into a peroxidase. The introduction of a coordination complex into a substrate binding pocket of trypsin could probably also be extended to various enzymes of significant therapeutic and biotechnological importance. The aim of this study is the conversion of trypsin into a copper enzyme: tyrosinase by chemical modification. Tyrosinase is a biocatalyst (EC.1.14.18.1) containing two atoms of copper per active site with monooxygenase activity. The active site of trypsin (EC 3.4.21.4), a serine protease was chemically modified by copper (Cu(+2)) introduced p-aminobenzamidine (pABA- Cu(+2): guanidine containing schiff base metal chelate) which exhibits affinity for the carboxylate group in the active site as trypsin-like inhibitor. Trypsin and the resultant semisynthetic enzyme preparation was analysed by means of its trypsin and catechol oxidase/tyrosinase activity. After chemical modification, trypsin-pABA-Cu(+2) preparation lost 63% of its trypsin activity and gained tyrosinase/catechol oxidase activity. The kinetic properties (K(cat), K(m), K(cat)/K(m)), optimum pH and temperature of the trypsin-pABA-Cu(+2) complex was also investigated.

WOS: 000269322600008, PubMed ID: 19454542, Background: Type 2 diabetes is a complex disease that still requires a great deal of work to be carried out to understand the pathophysiology. Recently, researchers have focused on studying the organs and tissues known to be involved in the development of the type 2 phenotype using a proteomic approach. Little work has been reported on plasma of type 2 diabetics in whom the clinical status has been well characterized. In this study, changes in plasma proteins of type 2 diabetics were investigated by proteomic analysis in well-characterized individuals with type 2 diabetes (early and late stage) and control groups (with or without a family history of diabetes). Methods: Samples were analysed by two-dimensional gel electrophoresis and significantly differentiated proteins were identified by nano-LC-ESI-MS. Results: A total of 12 protein signatures that were differentially displayed with high significance compared with controls were selected. Four of the differentially displayed proteins were identified as haptoglobin alpha2, haptoglobin Hp2(fragment) and transthyretin and Chain A (formerly prealbumin), and all were up-regulated. Thiol-specific antioxidant protein, Chain A, tertiary structures of three amyloidogenic transthretin variants and haptoglobin-related protein precursor were all down-regulated in controls with a family history of diabetes, early and late diabetic patients in comparison with the control. Conclusion: A proteomic-based approach was used to discover and identify the differentially expressed proteins in various states of type 2 diabetes.