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.

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.

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.

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.

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.

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.

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.

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, molecular docking and ADMET study of ionic liquid as anticancer inhibitors of DNA and COX-2, TOPII enzymes.

A new ionic liquid was synthesized by the reaction of caprolactam with salicylic acid (CL-SA) and characterized by analysis of spectroscopic and DSC data. The optimized geometry and the electrostatic potential map of CL-SA were calculated with DFT method using the wb97xd/6-31++G(d,p) level of theory. Molecular docking study of the CL-SA was carried out to clarify the probable binding modes between the title compound and DNA and COX-2 and TOPII enzymes. In silico ADMET study was also performed for predicting pharmacokinetic and toxicity profile of the synthesized ionic liquid which expressed good oral drug-like behavior and non-toxic nature. It was revealed that the compound has a potential to become a lead molecule in drug discovery process.Communicated by Ramaswamy H. Sarma.

Role of aortic stiffness and inflammation in the etiology of young-onset hypertension

Background/aim: Young-onset hypertension is a form of condition diagnosed in patients aged below 40. Cytokines such as interleukin (IL)-6 and also MCP-1 may play a role in the development of arterial hypertension. Aortic stiffness can be detected by measuring pulse wave velocity (PWV). We aimed to explore the relationship between inflammation and aortic stiffness and investigate their roles in the etiology of young-onset hypertension. Materials and methods: We enrolled 16 patients diagnosed with young-onset hypertension and 16 volunteers without hypertension. The plasma levels of MCP-1 and IL-6 were determined using an enzyme-linked immunosorbent assay and quantitative enzyme-linked immunoassay, respectively. Carotid-femoral PWV was measured using an arteriograph device. Results: Compared with those in normotensive controls, the plasma levels of IL-6 and MCP-1 and the PWV values were significantly higher in patients with young-onset hypertension (P < 0.001). PWV values were also positively correlated with the levels of MCP-1 and IL-6. However, no statistically significant difference was noted in intima-media thickness between the two groups (P = 0.224). Conclusion: In this study, increased PWVs and the levels of inflammation markers were associated with aortic stiffness and inflammation in patients with young-onset hypertension, suggesting they have a role in the etiology of hypertension.

The Effect of Boric Acid and Borax on Oxidative Stress, Inflammation, ER Stress and Apoptosis in Cisplatin Toxication and Nephrotoxicity Developing as a Result of Toxication.

The development of treatment protocols that can reduce side effects in chemotherapy applications is extremely important in terms of cancer treatment. In this context, it was aimed to investigate the effects of boric acid and borax on cisplatin toxicity (nephrotoxicity) in rats. In the experimental phase, eight groups were formed from rats. Boric acid and borax were given to the treatment groups with three different doses using gavage. On the fifth day of the study, cisplatin (10 mg/kg) was administered to all rats except the control group. At the end of the study, oxidative stress-related (GSH, MDA, PCO, GPx, 8-OHdG), inflammation-related (TNF-α, IL-1ß, IL-18, MCP-1, ICAM, TGF-ß), apoptosis-related (p53, caspase 1, 3, 8, 12, bcl-2, bcl-xL, NFkB), and ER stress-related (GRP78, ATF-6, PERK) basic parameters were analyzed in serum, erythrocyte, and kidney tissues. Kidney tissues were also examined by histopathological and immunohistochemical methods. Borax and boric acid at different doses decreased inflammation and oxidative stress caused by cisplatin toxicity and increased ER stress. As a result of the treatments applied to experimental animals, it was determined that boric acid and borax reduced apoptotic damage in kidney tissue, but the decrease was statistically significant only in 200 mg/kg boric acid-administered group. In the study, low anti-apoptotic effects of borate doses with the anti-inflammatory and antioxidant effect may be due to increased ER stress at the relevant doses. Further studies on the effects of boron compounds on ER stress and apoptotic mechanisms may clarify this issue. Thus, possible side effects or if there are new usage areas of borone compounds which have many usage areas in clinics can be detected.

Structural analysis, spectroscopic characterization and molecular docking studies of the cyclic heptapeptide.

The theoretically possible stable conformer of the cyclic heptapeptide, that has significant anti-metastatic activity, was examined by conformational analysis followed by DFT calculations. Experimental infrared and Raman spectroscopy, together with theoretical DFT (6-31G (d,p) basis set)-based quantum chemical calculations, have been used to understand the structural and spectral characteristics of cyclo(Gly-Arg-Gly-Asp-Ser-Pro-Ala) {cyclo(GRGDSPA)}. A complete analysis of the vibrational spectrum has been reported on the basis of potential energy distribution (PED%) data of the vibrational modes. Finally, the calculation results were applied to simulate infrared and Raman spectra of the title compound. The simulated spectra satisfactorily coincide with the experimental spectra. In addition, molecular electrostatic potential and frontier molecular orbital analysis were investigated using theoretical calculations. The stability of the molecule, arising from hyperconjugative interaction and charge delocalization, has been analyzed using natural bond orbital analysis and a high E(2) value reveals the presence of strong interaction between donors and acceptors. Molecular docking studies with fibronectin were performed on cyclo(GRGDSPA) in order to understand its inhibitory nature. The results indicate that the docked ligand {cyclo(GRGDSPA)} forms a stable complex with human fibronectin and gives a binding affinity value of -7.7 kcal/mol, which points out that cyclo(GRGDSPA) might exhibit inhibitory activity against the attachment of melanoma cells to human fibronectin.

Efficacy of neuromuscular electrical stimulation in patients with COPD followed in intensive care unit.

INTRODUCTION: Serious problems on muscle strength and functional status can be seen in bedridden-patients with chronic obstructive pulmonary diseases (COPD) receiving mechanical ventilation. We aimed to investigate the impact of active extremity mobilization and neuromuscular electrical stimulation (NMES) on weaning processes, discharge from hospital and inflammatory mediators in COPD patients receiving mechanical ventilation. METHODS: Thirty conscious COPD patients (F/M:15/15) hospitalized in the intensive care unit (ICU) with diagnosis of respiratory failure were enrolled to this study. Patients were randomized into three groups, including 10 patients for each. Active extremity-exercise training and NMES were applied to Group-1, only NMES was applied to Group-2 and active extremity exercise training was applied to Group-3. Muscle strengths, mobilization duration and weaning situation were evaluated. Serum cytokine levels were evaluated. RESULTS: Lower extremity muscle-strength was significantly improved in Group-1 (from 3.00 to 5.00, P = 0.014) and 2 (from 4.00 to 5.00, P = 0.046). Upper extremity muscle strength was also significantly improved in all three groups (from 4.00 to 5.00 for all groups, P = 0.038, P = 0.046 and P = 0.034, respectively). Duration of mobilization and discharge from the ICU were similar among groups. There was a significant decrease in serum interleukin (IL)-6 level in Group-1 and in serum IL-8 level in Group-1 and Group-2 after rehabilitation. CONCLUSION: This study indicates that pulmonary rehabilitation can prevent loss of muscle strength in ICU. Nevertheless, we consider that further studies with larger populations are needed to examine the impact of NMES and/or active and passive muscle training in bedridden ICU patients who are mechanically ventilated.

Antioxidant, Antiapoptotic and Inflammatory Effects of Interleukin-18 Binding Protein on Kidney Damage Induced by Hepatic Ischemia Reperfusion.

OBJECTIVE: Acute kidney injury (AKI) is a serious condition that can be induced by liver transplantation, major hepatic resection or prolonged portal vein occlusion. The AKI can increase the frequency of postoperative complications. In the current study, we aimed to investigate whether interleukin-18 binding protein (IL-18BP) pretreatment has a protective effect against possible kidney injury-mediated liver ischemia-reperfusion (IR) achieved by Pringle maneuver in an experimental rat model. MATERIALS AND METHODS: A total of 21 Wistar albino rats were included in this study. Animals were equally and randomly separated into 3 groups as follows: Sham (n = 7), IR group (n = 7) and IR + IL-18BP group (n = 7). Serum aspartate transaminase, alanine aminotransaminase and lactate dehydrogenase enzyme activities and serum urea and creatinine levels were determined. Tumor necrosis factor-α, IL-6, IL-1ß, interferon gamma, total oxidant status, total antioxidant status and oxidative stress index were measured in kidney tissue homogenate samples. Histopathological examination and immunohistochemical Caspase-3 staining were applied to examine the general morphologic structure and apoptosis. RESULTS: Renal total oxidant status; oxidative stress index; IL-18 levels; serum aspartate transaminase, alanine aminotransaminase and lactate dehydrogenase activities and creatinine levels were significantly lower in IR + IL-18BP group, when compared with the IR group. Beside this, total antioxidant status levels were remarkably higher in IR + IL-18BP group, when compared with the IR group. The caspase-3 expression degree in IR group was remarkably higher than other groups. CONCLUSIONS: It has been demonstrated that IL-18BP pretreatment may have inflammatory, antioxidant and antiapoptotic effects against AKI induced by hepatic IR.

Comparison of the Anti-inflammatory Effects of Proanthocyanidin, Quercetin, and Damnacanthal on Benzo(a)pyrene Exposed A549 Alveolar Cell Line.

Phytochemical compounds are emerging as a new group of anti-inflammatory, antioxidant, and anti-cancer agents that help minimize toxicity in patients with pulmonary diseases. The goal of this study was to investigate the potential curative effects of Quercetin (QC), Damnacanthal (DAM), and Proanthocyanidine (PA) on inflammatory mediators and oxidative stress parameters and to examine the viability of the A549 cell line treated with benzo(a)pyrene (BaP) in vitro. The A549 cell line was treated with BaP, a BaP/QC combination, a BaP/DAM combination, and BaP/PA combination. Inflammatory markers, oxidative stress parameters, mRNA expression levels of apoptotic and antiapoptotic proteins, and cell viability were assessed, and the results were compared. There were higher levels of lactate dehydrogenase after BaP treatment of A549 cell lines. Interferon-γ level significantly decreased in the QC, DAM, and PA-treated group (P < 0.001). IL-1ß and TNF-α levels significantly decreased after PA and QC treatments (P < 0.001). Some of the oxidative stress markers (NO, MDA, TOS) and OSI decreased, while antioxidant (GSH) levels increased after treatment with QC, DAM, and PA. The QC and DAM treatments profoundly upregulated apoptotic gene expression and downregulated antiapoptotic gene expression. Viability of QC, DAM, and PA-treated cells was found to be significantly higher in comparison to the control and BaP-treated groups (p < 0.001). Our results revealed that A549 cell lines treated with BaP-stimulated necrosis produced higher level of inflammatory cytokines and oxidative stress parameters. Treatments with PA, QC, and DAM reduced inflammatory response induced by BaP exposure.

Assessment of inflammatory biomarkers and oxidative stress in pulmonary thromboembolism: follow-up results.

Instability in circulation, hypoperfusion, hypoxia, and ischemia in pulmonary thromboembolism (PTE) may occur as a result of failure in pulmonary circulation. All these conditions cause inflammation and oxidative stress. We aimed to investigate inflammatory markers, asymmetric dimethylarginine (ADMA) levels, and the oxidant-antioxidant balance in patients with PTE. This study was conducted as a prospective case-control study. Thirty-eight patients with PTE enrolled to the study. Age- and gender-matched 38 healthy subjects without risk factors for pulmonary embolism were selected as control group. Venous blood samples were obtained from the PTE patients during the initial diagnosis and at the first month of treatment and from the control subjects. Interleukine-6 (IL-6), tumor necrosis factor alpha (TNF-α), total antioxidant status (TAS), total oxidant status (TOS), and ADMA levels were measured for all the samples. The results of patients and healthy subjects were compared. The mean age of the control group was 51.81 ± 15.18 years, and the mean age of the patients was 52.90 ± 18.22 years (p = 0.770). Deep venous thrombosis was present in 68 % of the patients. While we found significant differences between the patient and control groups in terms of IL-6, TAS, TNF-α, ADMA and oxidative stress index (OSI) values (p = 0.001, p = 0.011, p = 0.038, p = 0.028, and p = 0.024, respectively), the TOS value was not different between the groups (p = 0.080). The ADMA, TNF-α, TAS, TOS, and OSI values of the patients during the initial diagnosis and at the first month of treatment were not different (p > 0.05). The results of this study indicate an increased inflammation, endothelial damage, and oxidative stress in PTE. No difference at the first month of therapy suggests ongoing processes. We consider that these markers may be useful in the diagnosis and follow up of PTE.

Anticancer effects of thymoquinone, caffeic acid phenethyl ester and resveratrol on A549 non-small cell lung cancer cells exposed to benzo(a)pyrene.

BACKGROUND: Phytochemical compounds are emerging as a new generation of anticancer agents with limited toxicity in cancer patients. The purpose of this study was to investigate the potential effcts of thymoquinone, caffeic acid phenylester (CAPE) and resveratrol on inflammatory markers, oxidative stress parameters, mRNA expression levels of proteins and survival of lung cancer cells in Vitro. MATERIALS AND METHODS: The A549 cell line was treated with benzo(a)pyrene, benzo(a)pyrene plus caffeic acid phenylester (CAPE), benzo(a)pyrene plus resveratrol (RES), and benzo(a)pyrene plus thymoquinone (TQ). Inflammatory markers, oxidative stress parameters, mRNA expression levels of apoptotic and anti-apoptotic proteins and cell viability were assessed and results were compared among study groups. RESULTS: TQ treatment up-regulated Bax and down-regulated Bcl2 proteins and increased the Bax/Bcl2 ratio. CAPE and TQ also up-regulated Bax expression. RES and TQ down-regulated the expression of Bcl-2. All three agents decreased the expression of cyclin D and increased the expression of p21. However, the most significant up-regulation of p21 expression was observed in TQ treated cells. CAPE, RES and TQ up-regulated TRAIL receptor 1 and 2 expression. RES and TQ down-regulated the expression of NF-kappa B and IKK1. Viability of CAPE, RES and TQ treated cells was found to be significantly decreased when compared with the control group (p=0.004). CONCLUSIONS: Our results revealed up-regulation of the key upstream signaling factors, which ultimately cause increase in their regulatory p53 levels affecting the induction of G2/M cell cycle arrest and apoptosis. Overall these results provide mechanistic insights for understanding the molecular basis and utility of the anti-tumor activity of TQ, RES and CAPE.

Increased levels of mean platelet volume: a possible relationship with idiopathic sudden hearing loss.

Mean platelet volume (MPV) is one of the platelet function indices which reflects the platelet production rate and functions. While vascular occlusion, acute or chronic syndromes and vasculitis are increasing the MPV levels, infections, autoimmune diseases, and inflammatory situations reduce it. The indicator for idiopathic sudden sensorineural hearing loss (ISHL) etiology remains a matter of debate because it is associated with many different disorders. We evaluated MPV levels in ISHL patients. Forty patients with ISHL and 40 healthy, age and sex matched subjects were enrolled to the study. Audiometer and laboratory results were recorded. Comparative multivariate analyses between indicator factors and hearing outcomes were conducted. MPV and platelet distribution width is significantly higher in ISHL. Platelet count is lower in the ISHL than control group (p < 0.001), (p < 0.001), (p = 0.003), respectively. Our findings indicate that, ISHL appears to be characterized by ischaemic or thrombotic events. Considering the increased MPV levels; MPV may be used to evaluate ISHL as an hepler indicator.