Daidzein nanosuspension in combination with cisplatin to enhance therapeutic efficacy against A549 non-small lung cancer cells: an in vitro evaluation.

Lung cancer is the most common cause of cancer-related mortality, chemo-resistance, and toxicity limit treatment. The focus is on innovative combined phytotherapy to improve treatment outcomes. Our aim was to investigate the potential effects of daidzein nanosuspension (DZ-NS) and its combination with cisplatin (CIS) on A549 non-small lung cancer cells. Cytotoxicity was investigated using MTT and Chou-Talalay methods. Oxidative, apoptotic, and inflammatory markers were analyzed by ELISA and qRT-PCR. The IC50 value for DZ-NS was 25.23 µM for 24 h and was lower than pure DZ (IC50 = 835 µM for pure DZ). DZ-NS (at IC50x2 and IC50 values) showed synergistic cytotoxicity with CIS. The cells treated with DZ-NS had low TOS and OSI levels. However, DZ-NS failed to regulate Cas3 and TGF-ß1 activation in A549 cells. MMP-9 gene expression was significantly suppressed in DZ-NS-treated cells, especially in combination therapy. DZ represents a potential combination option for the treatment of lung cancer, and its poor toxicokinetic properties limit its clinical use. To overcome these limitations, the effects of the nanosuspension formulation were tested. DZ-NS showed a cytotoxic effect on A549 cells and optimized the therapeutic effect of CIS. This in vitro synergistic effect was mediated by suppression of MMP-9 and not by oxidative stress or Cas3-activated apoptosis. This study provides the basis for an in vivo and clinical trial of DZ-NS with concurrent chemotherapy.

Protective effect of valproic acid on ischemia-reperfusion induced spinal cord injury in a rat model.

PURPOSE: This study aims to determine the anti-inflammatory, antioxidant, and anti-apoptotic effects of valproic acid (VPA) on rat spinal cord tissue in ischemia-reperfusion (IR) injury model created by abdominal aorta occlusion. MATERIALS AND METHODS: Sprague Dawley rat (male sex) weighing 190-260 g divided into four experimental groups: control only underwent laparotomy, sham group, pre-IR injury (200 mg/kg dose), and post-IR injury (300 mg/kg) VPA. We measured serum levels of TNF-α, IL-6, IL-1ß, IL-18, Total Oxidant Status (TOS) and Total Antioxidant Status (TAS), and serum Oxidative Stress Index (OSI) ratio, and tissue expression of Bax and Bcl2, Caspase3, and Bax/Bcl2 ratio. RESULTS: Serum IL-18 was higher in the sham than the control group(P = 0.001), and there were declines in the pre-IR treatment (P = 0.002) and the post-IR treatment when compared to sham (P = 0.001). Despite these reductions, IL-18 expression levels in both the pre- and post-IR treatment groups were higher than in the control group (P = 0.001 & P = 0.003). The favorable effects of pre-IR VPA administration on immunohistochemical biomarkers were superior to post-IR VPA administration. CONCLUSIONS: Comparative analyses between prophylactic VPA administration and post-IR interventions revealed congruence in their anti-inflammatory and anti-apoptotic ramifications. VPA can reduce spinal cord IR injury in an aortic occlusion model of rats.

Shedding light into the biological activity of aminopterin, via molecular structural, docking, and molecular dynamics analyses.

In this study, the structural and anticancer properties of aminopterin, as well as its antiviral characteristics, were elucidated. The preferred conformations of the title molecule were investigated with semiempirical AM1 method, and the obtained the lowest energy conformer was then optimized by using density functional (DFT/B3LYP) method with 6-311++G(d,p) as basis set. The vibrational frequencies of the optimized structure were calculated by the same level of theory and were compared with the experimental values. The vibrational assignments were performed based on the computed potential energy distribution (PED) of the vibrational modes. The molecular electrostatic potential (MEP) and frontier molecular orbitals (HOMO, LUMO) analyses were carried out for the optimized structure and the chemical reactivity has been scrutinized. To enlighten the biological activity of aminopterin as anticancer and anti-COVID-19 agents, aminopterin was docked into DNA, αIIBß3 and α5ß1integrins, human dihydrofolate reductase, main protease (Mpro) of SARS-CoV-2 and SARS-CoV-2/ACE2 complex receptor. The binding mechanisms of aminopterin with the receptors were clarified. The molecular docking results revealed the strong interaction of the aminopterin with DNA (-8.2 kcal/mol), αIIBß3 and α5ß1 integrins (-9.0 and -10.8 kcal/mol, respectively), human dihydrofolate reductase (-9.7 kcal/mol), Mpro of SARS-CoV-2 (-6.7 kcal/mol), and SARS-CoV-2/ACE2 complex receptor (-8.1 kcal/mol). Moreover, after molecular docking calculations, top-scoring ligand-receptor complexes of the aminopterin with SARS-CoV-2 enzymes (6M03 and 6M0J) were subjected to 50 ns all-atom MD simulations to investigate the ligand-receptor interactions in more detail, and to determine the binding free energies accurately. The predicted results indicate that the aminopterin may significantly inhibit SARS-CoV-2 infection. Thus, in this study, as both anticancer and anti-COVID-19 agents, the versatility of the biological activity of aminopterin was shown.Communicated by Ramaswamy H. Sarma.

Production of fungal chitosan and fabrication of fungal chitosan/polycaprolactone electrospun nanofibers for tissue engineering.

The present study investigated that chitosan production of Rhizopus oryzae NRRL 1526 and Aspergillus niger ATCC 16404. Fungal chitosans were characterized by scanning electron microscopy (SEM)-energy dispersive X-ray analysis, Fourier transform infrared spectroscopy (FTIR), differential scanning calorimeter and deacetylation degrees of fungal chitosans were determined. The percentage yield of Ro-chitosan and An-chitosan were determined as 18.6% and 12.5%, respectively. According to percentage of chitosan yield and the results of the characterization studies, chitosan that obtained from Rhizopus oryzae NRRL 1526 was selected for subsequent studies. Cytotoxicity of chitosan obtained from Rhizopus oryzae NRRL 1526 was determined by MTT assay on human dermal fibroblast cell line. Acording to results of the cytotoxicity test fungal chitosan was nontoxic on cells. The high cell viability was observed 375 µg/mL concentration at 24th, 48th h periods and at the 187.5 µg/ml 72nd h periods on cells. The fungal chitosan obtained from Rhizopus oryzae NRRL 1526 was used to fabrication of electrospun nanofibers. Fungal chitosan based polymer solutions were prepared by adding different substances and different electrostatic spinning parameters were used to obtain most suitable nanofiber structure. Characterization studies of nanofibers were carried out by SEM, FTIR and X-ray diffraction. The most suitable nanofiber structure was determined as F4 formula. The nanofiber structure was evaluated to be thin, bead-free, uniform, flexible and easily remove from surface and taking the shape of the area. After the characterization analysis of fungal chitosan it was determined that the chitosan, which obtained from Rhizopus oryzae NRRL 1526 is actually chitosan polymer and this polymer is usable for pharmaceutical areas and biotechnological applications. The electrospun nanofiber that blends fungal chitosan and PCL polymers were fabricated successfully and that it can be used as fabrication wound dressing models. RESEARCH HIGHLIGHTS: Extraction of chitosan from Rhizopus oryzae NRRL 1526 and Aspergillus niger ATCC 16404 and characterization scanning electron microscopy-energy dispersive X-ray analysis, Fourier transform infrared spectroscopy, differential scanning calorimeter. Fabrication and characterization of the fungal chitosan/PCL electrospun nanofibers.

Molecular docking of the pentapeptide derived from rice bran protein as anticancer agent inhibiting both receptor and non-receptor tyrosine kinases.

The cationic pentapeptide Glu-Gln-Arg-Pro-Arg (EQRPR) belongs to the family of anti-cancer peptides with significant anti-cancer activity. However, the mechanism by which the peptide performs this activity is unknown. In this study, we explored the pharmaceutical profile of Glu-Gln-Arg-Pro-Arg pentapeptide and revealed its anticancer properties by in silico docking studies. Moreover, the effect of EQRPR behavior of the DPPC membrane was investigated by means of Langmuir monolayer technique and the results were discussed in terms of mutual interactions. To evaluate the binding mechanisms, the pentapeptide and its various D-amino acid substituted analogs were docked to both epidermal growth factor receptor (EGFR) tyrosine kinase and proto-oncogene tyrosine-protein kinase, Fyn. Simultaneous binding of the pentapeptides to both EGFR and Fyn proteins, which are receptor- and non-receptor-kinases, respectively, suggest that these peptides can be an effective agent for cancer treatment. Moreover, to show the potential of the investigated pentapeptides to overcome the generated mutation-related drug resistance to EGFR targeted therapies, molecular docking investigations of EQRPR and all its D-analogs were performed against the prospective targets: Wild type EGFRWT and mutant EGFRT790M. Erlotinib and TAK-285 were used as reference molecules. The strong interaction of the peptide with EGFRWT (from -9.24 to -9.75 kcal/mol) and the secondary mutant EGFRT790M (from -9.28 to -9.64 kcal/mol) observed in most cancer recurrence cases indicates its good potential to overcome drug resistance in cancer therapy. In addition, the pharmacological properties of the investigated pentapeptides were revealed by in silico ADME (Absorption, Distribution, Metabolism, Excretion) and toxicity analysis.Communicated by Ramaswamy H. Sarma.

Structural and vibrational investigations and molecular docking studies of a vinca alkoloid, vinorelbine.

Vinorelbine, a vinca alkaloid, is an antimitotic drug that inhibits polymerisation process of tubulins to microtubules, and is widely used in cancer chemotherapy. Due to the importance of the structure-activity relationship, in this work the conformational preferences of the vinorelbine molecule were surched by PM3 method. The obtained lowest energy conformer was then optimized at DFT/B3LYP/6-31G(d,p) level of theory and the structural characteristics were determined. Frontier orbital (HOMO, LUMO) and molecular electrostatic potential (MEP) analyses were performed for the optimized structure. The experimental FT-IR, Raman and UV-VIS spectral data of vinorelbine along with the theoretical DFT/B3LYP/6-31G(d,p) calculations were investigated in detail. The vibrational wavenumbers were assigned based on the calculated potential energy distribution (PED) of the vibrational modes. To shed light into the anticancer property of vinorelbine as microtubule destabilizer, the most favourable binding mode and the interaction details between vinorelbine and tubulin were revealed by molecular docking studies of vinorelbine into the α,ß-tubulin (PDB IDs: 4O2B; 1SA0; 7CNN) and binding free energies were calculated by the combination of Molecular Mechanics/Generalized Born Surface Area (MMGBSA) and Molecular Mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) methods {MM/PB(GB)SA}. The calculated vinorelbine-7CNN binding free energy, using by MM/PB(GB)SA approach, was found to be the best (-50.39 kcal/mol), and followed by vinorelbine-4O2B (-28.5 kcal/mol) and vinorelbine-1SA0 (-17.59 kcal/mol) systems. Moreover, the interaction of vinorelbine with the cytochrome P450 enzymes (CYP), which are known to help in the metabolism of many drugs in the body, was investigated by docking studies against CYP2D6 and CYP3A4 targets.Communicated by Ramaswamy H. Sarma.

Multi-criteria evaluation of medical waste management process under intuitionistic fuzzy environment: A case study on hospitals in Turkey.

Waste management has come to the fore in the whole world with the increasing impact of the Covid-19 pandemic along with concerns about human health, environmental threats, and socio-economic factors, etc. Medical waste is one of the waste types that need special management processes including particularly collection, storage, separation, and disposal. Healthcare activities create a great amount of medical waste deriving from the hospitals. This study aims to determine the hospital that carries out medical waste management in the most effective way in Erzurum, Turkey. To handle intense uncertainty in the evaluation process, the case is analyzed by Intuitionistic Fuzzy Multi-Criteria Decision-Making (IFMCDM) methods. The present study contributes to the literature by focusing on a real case problem under IF environment in a Group Decision-Making (GDM) framework. Additionally, based on the literature review and expert judgments, the evaluation criteria relevant to the case are defined in this paper. To this end, a four-phased integrated methodology that involves Intuitionistic Fuzzy Weighted Averaging (IFWA), IF Analytical Hierarchy Process (IFAHP), IF Technique for Order Preference by Similarity to Ideal Solution (IFTOPSIS) and One-Dimensional Sensitivity Analysis, is conducted. Firstly, IFWA is aimed to express the significance levels of decision makers (DMs) based on their knowledge, qualifications and experiences. Secondly, IFAHP is used to calculate the importance weights of the decision criteria and IFTOPSIS is preferred to rank the available hospitals. Then, sensitivity analysis is employed to display robustness. According to the results, the most important criteria are Qualified personnel, Health institution infrastructure, and Control of waste, respectively and the most efficient hospital is determined.

The relationship of biochemical factors related to calcium metabolism with temporomandibular disorders.

OBJECTIVE: The aim of this study is to investigate the relationship between calcium metabolism-related biochemical factors (alkaline phosphatase, vitamin D, parathyroid hormone (PTH), calcium, phosphorus and magnesium), and temporomandibular joint (TMJ) disk displacement with reduction (DDWR). MATERIALS AND METHODS: This prospective observational study included patients with temporomandibular disorders (TMDs) (n = 50) and healthy controls (n = 50) of similar age and sex. The diagnosis of TMJ DDWR was made using the diagnostic criteria for temporomandibular joint disorders (DC/TMD). Both groups were compared in terms of serum alkaline phosphatase, 25 (OH) vitamin D, PTH, calcium, magnesium, and phosphorus levels. P<0.005 was accepted as a significant difference. RESULTS: There was no significant difference between the groups in terms of age, gender, and body mass index (BMI). Calcium levels of patients with TMD were statistically significantly lower than control patients (p<0.05). While there was no significant difference between the two groups in terms of mean VIT D, the number of people with severe Vit D deficiency (<10 ng) in the TMD group was significantly higher than in the control group (p<0.05). There was no statistically significant difference between the groups in terms of serum alkaline phosphatase, magnesium, phosphorus and PTH levels. CONCLUSION: The differences in serum calcium and vitamin D levels seen in the study indicate that biochemical factors related to calcium metabolism may be associated with TMJ DDWR. These results suggest that calcium and vitamin D deficiency should be evaluated and corrected in patients with TMD.

Effects of three endotracheal tube cuff pressure control measures on microaspiration of gastric content: Study protocol for randomised controlled trial.

AIM: To analyse the effect of endotracheal tube cuff pressure control measures on the microaspiration of the stomach contents by measuring at the level of pepsin in deep tracheal aspiration. DESIGN: A single-blind, randomised controlled trial. METHODS: This trial protocol was reported using the SPIRIT checklist. Endotracheal tube cuff pressure control will be provided with pilot balloon finger palpation, intermittent and continuous. The pepsin level will be measured during deep tracheal secretions in order to assess the effect of different endotracheal tube cuff pressure control measures on the microaspiration of the stomach contents. The samples will be examined within the first 4 h, between the 5th and 24th hours, and between the 25th and 48th hours after intubation. The level of pepsin will be considered positive according to the cut-off value. In addition, the effect of different endotracheal tube cuff pressure controls on the incidence of ventilator-associated pneumonia will be examined. In study group 1, study group 2 and the control group, the number of patients is planned to be 56. TRIAL REGISTRATION: ClinicalTrials.gov Identifier, Number NCT04061083. Registered in 2019. DISCUSSION: The findings will show the effect of different endotracheal tube cuff pressure control methods on microaspiration of stomach content and the possible changes in pepsin level in deep tracheal aspirates. CONCLUSION: This study will shed light on future studies regarding pepsin level as a biomarker in treatment and follow-up patients receiving mechanical ventilator support using an ETT and emphasise the importance of multidisciplinary studies. RELEVANCE TO CLINICAL PRACTICE: As a result of the findings to be obtained from this study, the effect of endotracheal tube cuff pressure control on gastric content microaspiration and ventilator-associated pneumonia will be determined and the most appropriate endotracheal tube cuff pressure control method will be identified to prevent it. Nurses' awareness of endotracheal tube cuff pressure measurement methods will be increased. The frequency and methods of endotracheal tube cuff pressure control will provide strong evidence that can be included in the ventilator-associated pneumonia prevention care bundle.

The role of effective factors on suicidal tendency of women in Turkey.

Background/Aim: This study aims to identify the variables that influence the suicidal tendency of women who are married, have had a relationship or are currently in a relationship in Turkey. Methods: This study uses cross-sectional data from the 2014 Hacettepe University Institute of Population Studies National Research on Domestic Violence Against Women in Turkey. Data from 6,458 women between the ages of 15 and 49 were analyzed in this dataset. Binary logistic regression was used to determine the factors influencing women's suicidal tendencies. Results: Based on the analysis's findings, age, education level, health status, number of children, the sector in which the spouse/partner works, the drinking status of the spouse/partner, the situation where the spouse/partner fights with another man in a way that involves physical violence, the cheating status of the spouse/partner, the controlling behaviour of the spouse/partner, exposure to various types of violence by both the spouse/partner and someone other than the partner, and the household income level variables were found to be associated with the suicidal tendency of women. Conclusion: Prioritizing women who are, in particular, between the ages of 15 and 24, live in the south of Turkey, have a high school education, are in poor health, are childless, have low household incomes, live with an unemployed spouse or partner, and are exposed to various forms of violence from their partner or other sources can be achieved more effective results in reducing and preventing women's suicidal behaviors.

Epicardial Fat Tissue Thickness and Omentin in Patients with Atrial Fibrillation

Abstract Background: Although electrical and structural remodeling has been recognized to be important in the pathophysiology of atrial fibrillation, the mechanisms underlying remodeling process are unknown. There has been increasing interest in the involvement of inflammatory molecules and adipokines released from the epicardial fat tissue in the pathophysiology of atrial fibrillation. Objectives: In our study, we aimed to investigate the relationship of atrial fibrillation with increased epicardial adipose tissue, inflammatory molecules released from this tissue and omentin. Methods: Thirty-six patients who were followed up with a diagnosis of permanent AF at the cardiology outpatient clinic 33 individuals without atrial fibrillation (controls) were included in the study. Epicardial adipose tissue thickness of patients was measured by echocardiography. Serum omentin, IL 6, IL 1 beta, TNF alpha and CRP levels were measured. Man-Whitney U test was performed for comparisons and significance was established at 5% (p<0.05). Results: Epicardial adipose tissue thickness was significantly greater in the patient group (6mm [4-5.5]) than controls (4mm [3-5.5]) (p <0.001). No significant difference was found in the concentrations of omentin or inflammatory molecules between the groups. Conclusion: No relationship was found between atrial fibrillation and serum levels or omentin or inflammatory markers. A relationship between epicardial adipose tissue thickness measured by echocardiography and atrial fibrillation was determined.

The Relationships Between Chocolate Consumption and Endothelial Dysfunction in Patients with Heart Failure.

OBJECTIVE: Dietary recommendations, in addition to medications, have recently become important in the treatment of heart failure. Our study aimed to show the positive effects of both milk chocolate and dark chocolate on heart failure through endothelial functions. METHODS: Twenty patients with heart failure and reduced ejection fraction were included in the study. In this randomized, crossover study, some of the patients consumed milk chocolate and some consumed dark chocolate. We recorded the patients' 6-minute walking tests, flow- mediated dilatation values, plasma catechin, epicatechin, and N-terminal pro-brain natri- uretic peptide values before and after chocolate consumption. After 2 weeks, their chocolate consumption was changed. The same parameters were measured again. RESULTS: A significant decrease was observed in N-terminal pro-brain natriuretic peptide values after consumption of both milk chocolate (356 ± 54.2 and 310 ± 72.1 pg/mL; P = .007) and dark chocolate (341 ± 57 and 301 ± 60.1 pg/mL;P=.028). Flow-mediated dilation values increased after dark chocolate consumption (8.9 ± 3% and 14 ± 4.5%; P = .019). CONCLUSION: Chocolate consumption acutely decreases N-terminal pro-brain natriuretic pep- tide values in heart failure. Dark chocolate consumption also seems to improve endothelial functions by increasing flow-mediated dilation values.

Lupeol inhibits pesticides induced hepatotoxicity via reducing oxidative stress and inflammatory markers in rats.

The present study was aimed at investigating the toxicity of various pesticides on rat liver. It also aimed to show whether this toxicity could be avoided using lupeol. Adult male Wistars albino rats were randomly divided into nine groups. Control groups were given saline, corn oil, and lupeol; pesticide groups were given malathion, chlorpyrifos, and tebuconazole; in the other three treatments, same doses of pesticides and lupeol were given to the rats for ten days. Histopathological examination showed severe degenerative changes in the pesticide groups. Serum AChE activities, liver GSH, total antioxidant capacity levels, AChE, CAT, SOD, GPx, GR, Na+/K+-ATPase, ARE, and PON were decreased, while serum TNF-α, liver LPO, HP, NO, AOPP, total oxidant status, ROS, and oxidative stress index levels as well as AST, ALT, ALP, GST, arginase and xanthine oxidase activities were increased in the pesticides administered groups. It was observed that the PCNA levels determined by the immunohistochemical method increased in the pesticide groups. Also, the results Raman spectroscopy suggest that the technique may be used to understand/have an insight into pesticide toxicity mechanisms. The administration of lupeol demonstrated a hepatoprotective effect against pesticide-induced toxicity.

Structural and spectral analysis of anticancer active cyclo(Ala-His) dipeptide.

The theoretically possible most stable conformation of the cyclic dipeptide, which has a significant anticancer activity, was examined by conformational analysis method and then by DFT calculations. With DFT calculations, cyclo(Ala-His) dipeptide was found to be more stable in boat form than in planar conformation. Moreover, conformations of the dimeric forms of the title molecule were investigated. The dimeric forms of the cyclo(Ala-His) dipeptide were created by combining two identical cyclo(Ala-His) monomers, in lowest energy configuration and as a result three energetically possible dimeric structures were obtained. The solid phase FTIR and Raman spectra of cyclo(Ala-His) have been recorded. The spectra were interpreted with the aid of quantum chemical calculations based on density functional theory, using B3LYP and wb97xd methods with 6-311++G(d,p) basis set, in order to elucidate structural and spectral properties of the investigated molecule. Experimental vibrational spectra are found to be in accord with the simulated vibrational spectra. The assignment of the vibrational modes was performed depending on the calculated potential energy distribution (PED). In slico molecular docking of cyclo(Ala-His) was also carried out with DNA. The drug likeness and ADMET properties were analyzed for the prediction of pharmacokinetic profiles. The results revealed that the compound has the potential to be the leading molecule in the drug discovery process.

Evaluation of anti-cancer and anti-covid-19 properties of cationic pentapeptide Glu-Gln-Arg-Pro-Arg, from rice bran protein and its d-isomer analogs through molecular docking simulations.

Bioactive peptides derived from food proteins are becoming increasingly popular due to the growing awareness of their health-promoting properties. The structure and mechanism of anti-cancer action of pentapeptide Glu-Gln-Arg-Pro-Arg (EQRPR) derived from a rice bran protein are not known. Theoretical and experimental methods were employed to fill this gap. The conformation analysis of the EQRPR pentapeptide was performed first and the obtained lowest energy conformer was optimized. The experimental structural data obtained by FTIR and CD spectroscopies agree well with the theoretical results. d-isomer introduced one-by-one to each position and all D-isomers of the peptide were also examined for its possible anti-proteolytic and activity enhancement properties. The molecular docking revealed avid binding of the pentapeptide to the integrins α5ß1 and αIIbß3, with Kd values of 90 nM and 180 nM, respectively. Moreover, the EQRPR and its D-isomers showed strong binding affinities to apo- and holo-forms of Mpro, spike glycoprotein, ACE2, and dACE2. The predicted results indicate that the pentapeptide may significantly inhibit SARS-CoV-2 infection. Thus, the peptide has the potential to be the leading molecule in the drug discovery process as having multifunctional with diverse biological activities.

The Effect of Nasal Steroid and Antihistamine Use on Total Oxidative Stress and Antioxidant Status in the Treatment of Allergic Rhinitis.

INTRODUCTION: The purpose of this study is to determine the post-treatment levels of total oxidant status (TOS) and total antioxidant status (TAS), that are increased due to pathophysiology, and to compare those with pre-treatment levels in allergic rhinitis patients.Material-Methods: Among 84 patients clinically diagnosed with allergic rhinitis, 31 patients were started only on nasal steroid treatment (mometasone furoate), and 53 patients were started on nasal steroid and oral antihistamine treatment (mometasone furoate + rupatadine fumarate 10 mg). Blood samples were taken from the patients at the first examination and at post-treatment month 1.TAS and TOS were measured from the blood samples. RESULTS: While no significant change was determined in mean TAS levels with treatment, a statistically significant decrease was determined in TOS values in post-treatment period (P < .01). There was no significant change in TAS and TOS values of patients only using nasal steroids, while a significant decrease was determined in post-treatment TOS values of patients using both nasal steroids and oral antihistamines (P < .001). It was determined that TOS values of women were significantly lower compared to men, and it was also reduced in seasonal allergic rhinitis compared to perennial allergic rhinitis (P < .05 for both). CONCLUSION: In allergic rhinitis patients, concomitant use of nasal steroids and antihistamines significantly decreases total oxidative stress. It may be stated that the addition of antihistamines to allergic rhinitis treatment positively affects treatment.

Synthesis, molecular modelling, FT-IR, Raman and NMR characterization, molecular docking and ADMET study of new nickel(II) complex with an N4-tetradentate thiosemicarbazone.

A new nickel(II) complex was synthesized by using S-propyl-thiosemicarbazide and 2-amino-3,5-dibromobenzaldehyde. The complex, obtained by the template effect of nickel ions, was structurally analysed by experimental and theoretical vibrational spectroscopy, NMR and density functional theory (DFT) calculations. By using DFT/B3LYP method with 6-311++G(d, p) basis set, the most stable molecular structure of the title molecule was calculated. The fundamental vibrational wavenumbers, IR and Raman intensities for the optimized structure of the molecule under investigation were determined and compared with the experimental vibrational spectra. The vibrational assignment was achieved using the calculated potential energy distributions of the vibrational modes. Moreover, the molecular electrostatic potential (MEP), the highest occupied molecular orbital (HOMO) and the lowest occupied molecular orbital (LUMO) energies were calculated, Molecular docking of the molecule was carried out against DNA in order to identify the potential inhibitory action of the title compound. The findings suggested that the aforementioned compound has a strong binding affinity to interact with DNA residues DT8, DC9, DG12, DG16, DA17, and DA18 through the intermolecular hydrogen bonds. Also the performed in silico ADMET analysis was the prediction of the synthesized molecule's pharmacokinetic and toxicity profile expressing good oral drug like actions and non-toxic nature. The complex has been shown to have the possibility to become a model molecule for drug development processes.Communicated by Ramaswamy H. Sarma.

Synthesis, antimicrobial activity, molecular docking and ADMET study of a caprolactam-glycine cluster.

Density functional theory calculations were performed with DFT method using both b3lyp/6-311++G(d,p) and wb97xd/6-311++G(d,p) levels of theory to predict the molecular geometry, to evaluate the molecular electrostatic potential and frontier molecular orbitals of synthesized a new compound: caprolactam-glysine cluster (CL-Gly). Molecular docking study of the CL-Gly was carried out to clarify the interaction and the probable binding modes, between the title compound and DNA. The antibacterial activities of CL-Gly cluster against Gram-positive and Gram-negative bacteria was determined. In silico ADMET study was also performed for predicting pharmacokinetic and toxicity profile of the synthesized cluster which expressed good drug-like behavior and non-toxic nature. It was revealed that the compound has importance in drug discovery process.Communicated by Ramaswamy H. Sarma.

Anti-inflammatory and anti-apoptotic effect of nesfatin-1 on liver ischemia-reperfusion injury.

INTRODUCTION: Severe local and systemic tissue injury develop during reperfusion, which is a period during which arterial blood flow and tissue oxygenation are re-established. In this study, we aimed to investigate the anti-inflammatory, antioxidant and protective effects of nesfatin in IR damage developing in liver. MATERIAL AND METHODS: Twenty-four male Wistar-Albino rats were divided to three groups which contained eight rats in all groups. The rats were subjected to 30 minutes of hepatic pedicule occlusion followed by 2h of reperfusion to induce I/R damage. Nesfatin1 (10 µg/ kg) was administered, 30 min prior to ischemia and immediately before the reperfusion period. RESULTS: The findings showed that while the blood levels of AST, ALT and LDH were markedly elevated in the I/R group, they returned to normal levels upon treatment in the Nesfatin group. While IL-1 α, IL-1ß, IL-6, TNF-α and IFN- γ levels in blood and tissue were lower after therapy in the Nesfatin group compared to the I/R group, statistically significant decreases were only noted in IL-1ß, IL-6, TNF-α and IFN- γ levels. TAS levels increased in the treatment group, while upon nesfatin treatment statistically significant decreases were noted in TOS and OSI levels. Histopathological investigations also showed statistically significant decreases in Bax and Caspase-3 staining intensity and the number of stained cells in the Nesfatin group. CONCLUSION: The nesfatin has antioxidant activity and anti-inflammatory effect on improvement of liver functions and histopathological findings in liver ischemia and reperfusion injury. KEY WORDS: Anti-inflammatory, Anti apoptotic Liver ischemia-reperfusion injury, Nesfatin-1.

Synthesis, FT-IR and NMR characterization, antimicrobial activity, cytotoxicity and DNA docking analysis of a new anthraquinone derivate compound.

A new anthraquinone [1-(2-Aminoethyl)piperazinyl-9,10-dioxo-anthraquinone] derivative was synthesized and characterized by density functional theory (DFT) calculations, experimental and theoretical vibrational spectroscopy and NMR techniques. The most stable molecular structure of the title molecule was determined by DFT B3LYP method with 6-31++G(d,p) and 6-311++G(d,p) basis sets. The fundamental vibrational wavenumbers, IR and Raman intensities for the optimized structure of the investigated molecule were calculated and compared with the experimental vibrational spectra. The vibrational assignment of the molecule was done using the potential energy distribution analysis. The molecular electrostatic potential (MEP), highest occupied molecular orbital (HOMO) and lowest occupied molecular orbital (LUMO) were also calculated. The antibacterial activities of the new anthraquinone derivative against Gram-positive and Gram-negative bacteria were determined, and it was shown that the highest effectiveness was against Staphylococcus aureus and S. epidermidis while no activity was against Gram-negative bacteria. Moreover, the antimycotic activity of the title compound was examined and the cytotoxicity of anthraquinone derivate was determined. In order to find the possible inhibitory activity of the title compound, molecular docking of the molecule was carried out against DNA. The results indicated that the mentioned compound has a good binding affinity to interact with the DC3, DG4, DA5, DC21 and DC23 residues of DNA via the intermolecular hydrogen bonds. [Formula: see text] Communicated by Ramaswamy H. Sarma.