Ornidazole Inhibits the Angiogenesis and Migration Abilities of Non-small Cell Lung.

BACKGROUND: Around the world, non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths among all cancers. Despite advancements in new therapeutic approaches over the past few decades, the five-year survival rate still remains disappointing. The lack of effective anti-angiogenic and anti-migration drugs is the biggest obstacle to the treatment of metastatic lung cancer. Therefore, there is a need to develop new and effective therapeutic compounds targeting anti-angiogenic and anti-migration pathways for the treatment of lung cancer. Ornidazole is a nitroimidazole agent widely used in the treatment of parasitic infections such as trichomonas vaginalis, amebiasis and giardiasis. This study aimed to investigate the anti-proliferative, anti-angiogenic and anti-mitotic activities of the anti-parasitic drug Ornidazole in two human lung cancer cell lines (A549, H1299). METHODS: We determined the effects of Ornidazole, on cell viability, apoptosis, migration, angiogenesis and metastatic ability against NSCLC in lung cancer cell lines. Its action on the mRNA and protein expression levels of VEGFA, VEGFR2, NRP1, Casp9, Casp3, Bax, Bcl-2, PIK3CA, AKT, MTOR, PTEN and FOX3A was assessed. Furthermore, in this study the effects on cell migration, cell viability and proliferation was evaluated through wound healing, MTT and Crystal violet assays. RESULTS: This study demonstrated that Ornidazole effectively reduces cell viability and migration ability, inhibits angiogenesis and metastatic abilities in NSCLC cells. CONCLUSIONS: In conclusion, these results may shed light on the treatment of NSCLC, and we suggest the anti-parasitic drug Ornidazole as a new agent with potential anti-angiogenic and anti-mitotic activity by interfering with the molecular pathways that trigger tumor angiogenesis and migration.

Relationship between uric acid to albumin ratio and saphenous vein graft disease in patients with coronary artery bypass graft.

OBJECTIVE: Saphenous vein graft disease (SVGD) remains a challenging issue for patients with coronary artery bypass grafting (CABG). It is associated with poor outcomes and atherosclerosis is the major cause of SVGD. Uric acid to albumin ratio (UAR) is a new marker which associated with cardiovascular mortality. We aim to evaluate the relationship between the SVGD and UAR. METHODS: We retrospectively enrolled 237 patients who underwent elective coronary angiography (CAG) for stable angina or positive stress test results >1 year after CABG. The patients were divided into two groups; SVGD (+) patients and SVGD (-) patients. The SVGD was defined as presence of at least 50% stenosis in at least 1 SVG. RESULTS: UAR were significantly higher in the SVGD (+) group (P < 0.001). Similarly, Hs-CRP, white blood cell count, and neutrophil count were significantly higher in SVGD (+) group (P = 0.03, P = 0.027 P = 0.01, respectively). In multivariate logistic regression analysis, time interval after CABG [OR = 1.161, 95% confidence interval (CI) 1.078-1.250; P < 0.001] and UAR (OR = 2.691, 95% CI 1.121-6.459; P < 0.001) were found to be independent predictors of SVGD. CONCLUSION: Our results suggested that UAR could be a simple and available marker to predict SVGD in patients with CABG who underwent elective percutaneous coronary intervention.

Left atrial function index and left atrial electromechanical functions in anxiety disorders.

BACKGROUND: There is a close linkage between anxiety disorders (ADs), and development of cardiovascular disease (CVD) and atrial fibrillation (AF). We aimed to investigate left atrial function index (LAFI) and its components, LA mechanical functions and atrial conduction times in AD patients and age- and gender-matched control group patients for the first time in the literature. METHODS: A total of 48 AD patients and 33 healthy subjects were enrolled to the study prospectively. Echocardiographic parameters including two-dimensional conventional echocardiography, diastolic functions, LA mechanical functions, LAFI, atrial conduction times and atrial electromechanical delay (AEMD) were calculated. RESULTS: The velocity-time integral of the LV outflow tract (LVOT-VTI), LAFI and LA conduit volume were significantly lower in AD patients. Atrial electromechanical coupling as established from lateral mitral annulus (PA lateral) was significantly higher in AD group than control group. Inter-AEMD and left intra-AEMD were also higher in AD group compared to control group. Age, gender, body surface area (BSA), conduit volume, LVOT-VTI and LAFI were significant factors associated with AD in univariate analysis. However, only BSA and LVOT-VTI (Odds ratio [OR]: 0.79, 95 CI%: 0.66-0.95, p = 0.013) were independently associated with AD in multivariate analysis. Age, gender, conduit volume and LAFI (OR: 0.25, 95 CI%: 0.03-2.12, p = 0.204) were not found to be independent associates of AD. CONCLUSION: LAFI is impaired in patients suffering from AD compared to their age- and gender-matched counterparts but this impairment originates from lower levels of LVOT-VTI calculations in AD patients. Thus, LVOT-VTI, but not LAFI, is independently associated with AD.

The Association Between Atherogenic Index of Plasma and No-Reflow Phenomenon in Acute Coronary Syndrome.

BACKGROUND: The atherogenic index of plasma (AIP) is a biomarker of plasma atherogenicity. Elevated AIP is linked with adverse cardiac events. We sought to examine the association of admission AIP and no-reflow phenomenon (NRP) in acute coronary syndrome (ACS) patient population treated with percutaneous coronary intervention (PCI). METHODS: Eight hundred eight-four ACS patients were included to statistical tests retrospectively and classified according to the occurrence of NRP: NRP (-) (n = 662) and NRP (+) (n = 186). AIP levels were calculated through the formula log10 (triglyceride-to-high-density lipoprotein cholesterol ratio). RESULTS: AIP levels were higher in NRP (+) patients compared to NRP (-) group patients. The receiver operating characteristic (ROC) curve analysis for AIP to predict NRP yielded an area under the ROC curve value 0.643 [95% confidence interval (CI): 0.596-0.690, P <.001]. AIP was associated with NRP in univariate logistic regression analysis [Odds Ratio (OR): 2.46; P =.001; CI: 1.44 (lower limit)-4.21 (upper limit)]. However, AIP did not emerge as a significant prognostic factor of NRP in multiple logistic regression analysis [OR: 2.11; P =.422; CI: 0.34 (lower limit)-13.11 (upper limit)]. On the other hand, peak troponin T (log10) was an independent prognostic factor for NRP [OR: 0.13; P <.001; CI: 0.10 (lower limit)-0.37 (upper limit)] occurrence. CONCLUSION: The AIP level on admission is not a statistically significant prognostic factor of NRP. However, peak troponin T (log10) is an independent prognostic parameter of NRP.

In Silico Integrated Analysis of Genomic, Transcriptomic, and Proteomic Data Reveals QTL-Specific Genes for Bacterial Canker Resistance in Tomato (Solanum lycopersicum L.).

Bacterial canker of tomato, caused by Clavibacter michiganensis subsp. michiganensis (Cmm), is a devasting disease that leads to significant yield losses. Although QTLs originating from three wild species (Solanum arcanum, S. habrochaites, and S. pimpinellifolium) were identified, none of the QTLs was annotated for candidate gene identification. In the present study, a QTL-based physical map was constructed to reveal the meta-QTLs for Cmm resistance. As a result, seven major QTLs were mapped. Functional annotation of QTLs revealed 48 candidate genes. Additionally, experimentally validated Cmm resistance-related genes based on transcriptomic and proteomic studies were mapped in the genome and 25 genes were found to be located in the QTL regions. The present study is the first report to construct a physical map for Cmm resistance QTLs and identify QTL-specific candidate genes. The candidate genes identified in the present study are valuable targets for fine mapping and developing markers for marker-assisted selection in tomatoes for Cmm resistance breeding.

Mapping QTLs for Super-Earliness and Agro-Morphological Traits in RILs Population Derived from Interspecific Crosses between Pisum sativum × P. fulvum.

Earliness in crop plants has a vital role in prevention of heat-induced drought stress and in combating global warming, which is predicted to exacerbate in the near future. Furthermore, earliness may expand production into northern areas or higher altitudes, having relatively shorter growing season and may also expand arable lands to meet global food demands. The primary objective of the present study was to investigate quantitative trait loci (QTLs) for super-earliness and important agro-morphological traits in a recombinant inbred line (RIL) population derived from an interspecific cross. A population of 114 RILs developed through single-seed descent from an interspecific cross involving Pisum sativum L. and P. fulvum Sibth. et Sm. was evaluated to identify QTLs for super-earliness and important agro-morphological traits. A genetic map was constructed with 44 SSRs markers representing seven chromosomes with a total length of 262.6 cM. Of the 14 QTLs identified, two were for super-earliness on LG2, one for plant height on LG3, six for number of pods per plant on LG2, LG4, LG5 and LG6, one for number of seeds per pod on LG6, one for pod length on LG4 and three for harvest index on LG3, LG5, and LG6. AA205 and AA372-1 flanking markers for super-earliness QTLs were suggested for marker-assisted selection (MAS) in pea breeding programs due to high heritability of the trait. This is the first study to map QTLs originating from P. sativum and P. fulvum recently identified species with super-earliness character and the markers (AA205 and AA372-1) linked to QTLs were valuable molecular tools for pea breeding.

Assessment of Tp-e interval, Tp-e/QT, and Tp-e/QTc ratios in patients with acromegaly.

BACKGROUND: Cardiovascular complications, including ventricular arrhythmias associated with abnormalities of ventricular repolarization, are the leading cause of morbidity and mortality in patients with acromegaly. Herein, we aimed to investigate ventricular repolarization using Tp-e interval, Tp-e interval/QT, and Tp-e interval/QTc ratios in acromegalic patients compared to healthy subjects. METHODS: A total of 29 patients (aged 51.9 ± 11.2, 65.5% women) with acromegaly and 30 control subjects (aged 47.3 ± 14.4, 63.3% women) were enrolled in the study. Tp-e and QT interval, corrected QT (QTc), Tp-e/QT, and Tp-e/QTc ratios were calculated from the 12-lead electrocardiogram. RESULTS: Tp-e interval (89.28 ± 12.16 vs. 75.97 ± 9.92 ms; p < 0.001), Tp-e/QT ratio (0.237 ± 0.045 vs. 0.212 ± 0.029; p = 0.019), and Tp-e/ QTc ratio (0.218 ± 0.031 vs. 0.195 ± 0.026; p = 0.003) were significantly higher in patients with acromegaly compared to control group. A positive correlation was determined between left atrial volume index (LAVI) and Tp-e interval (r = 0.272, p = 0.039). DISCUSSION: The current study is the first to have shown significantly increased Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio were increased in acromegalic patients. These results may be important for screening malignant arrhythmic events in acromegaly.

Total Synthesis of Cryptoconcatone D via Construction of 1,3-Diol Units Using Chiral Horner-Wittig Reagents.

The modular synthesis of 1,3-polyols using a chiral phosphine oxide building block is reported. This versatile building block works in a repetitive way for the stereocontrolled synthesis of a tetraol key intermediate, which serves for the first total synthesis of the potentially anti-inflammatory natural product cryptoconcatone D. A new route toward the chiral building block is also presented: Starting from 2-deoxy-d-ribose, the optimized sequence now makes the use of the building block more attractive to practicing chemists again.

Machine learning algorithms revealed distorted retinal vascular branching in individuals with bipolar disorder.

BACKGROUND: Converging evidence designate vascular vulnerability in bipolar disorder. The predisposition progresses into distortion in time, thus detection of the vascular susceptibility may help reducing morbidity and mortality. It was aimed to assess retinal fundus vasculature in cardiovascular risk-free patients with bipolar disorder. METHODS: Total of 68 individuals (38 patients with bipolar disorder, 30 healthy controls) were enrolled. In order to avoid from degenerative processes, participants were between 18 and 45 years of age, vascular risk factors were eliminated. Microscopic retinal fundus images were processed with machine learning algorithms (multilayer perceptron and support vector machine) and artificial neural network approaches. RESULTS: In comparison to the healthy control group, the bipolar disorder group had lower number of breaking points (P < 0.001), lower number of curved vessel segments (P < 0.001). Total length of smooth vessels was longer (P = 0.040), and total length of curved vessel segments was significantly shorter (P < 0.001) than the control group. Vascular endothelial growth factor levels and gender were the confounders. There were significant correlations between vascular measures and serum lipid levels. LIMITATIONS: Sample size was small and patients were on various medications. CONCLUSIONS: These results indicate distortion in retinal vascular branching in bipolar disorder. Disrupted branching may reflect disturbed prosperity of retinal vascular plexus in patients with bipolar disorder. Alterations in the retinal vessels might be indicators of disruption in cerebral vascular system efficiency and thus neurovascular unit dysfunction in bipolar disorder.

Inhibition of cytochrome P450 monooxygenase-catalyzed oxylipin formation by flavonoids: Evaluation of structure-activity relationship towards CYP4F2-selective inhibitors.

Epoxy- and hydroxy-fatty acids are physiologically active lipid mediators which are formed from arachidonic acid and other fatty acids by cytochrome P450 monooxygenase (CYP) catalytic activity. In this study, we investigated the structure-activity relationship of the inhibition of fatty acid-oxidizing CYP by flavonoids. A sum of 65 naturally occurring as well as new flavonoids were synthesized and tested in a multi-enzyme assay. Substituents at C2' and C7-position of the flavone structure caused epoxygenase blockade, while electronegative substituents at C4'-position led to ω-hydroxylase-selective inhibition. We identified 4'-trifluoromethylflavone as a potent and selective compound, inhibiting 20-HETE formation with an IC50 of 2.8 µM (1.3 µM-6.1 µM) in human liver microsomes. This inhibition is achieved by selective inhibition of CYP4F2 [IC50: 0.76 µM (0.42 µM-1.4 µM)], while the other human ω-hydroxylating CYP, CYP4A11, is not affected. The compound is also active in microsomes from rat and mouse liver [IC50: 1.4 µM (0.77 µM-2.7 µM) and 0.71 µM (0.24 µM-2.2 µM), respectively]. Moreover, it exhibits moderate permeability properties in PAMPA and CaCo-2 transwell systems (papp: 4.6 ±â€¯0.6 × 10-6 cm/s and 4.1 ±â€¯0.4 × 10-6 cm/s, respectively) and is stable to metabolic conversion in vitro. With this inhibitor, we provide a novel tool to selectively investigate the CYP4F2-catalyzed 20-HETE formation and its role in physiology.

Investigation of antibacterial, antifungal, antibiofilm, antioxidant and anticancer properties of methanol extracts of Salvia marashica Ilçim, Celep & Dogan and Salvia caespitosa Montbret & Aucher ex Benth plants with medicinal importance.

In this study, Antimicrobial, Antifungal and Antibiofilm activity tests on 16 bacteria and 2 fungi of Salvia marashica Ilçim, Celep & Dogan and Salvia caespitosa Montbret & Aucher ex Benth species were performed by Agar Well Diffusion and Microdilution methods. Salvia species showed sensitivity with a zone diameter of 12-16 mm. Concentrations of 0.5 mg/ml to 16 mg/ml by the dilution method were used to determine the Minimum inhibited concentration (MIC) and Minimum bactericidal concentration (MBK). The MIC values of the plants are mostly 0.5 mg/ml - 4 mg/ml and MBC values are between 0.5 mg/ml - 8 mg/ml. Antifungal activity findings are remarkable on the species and it has been observed to have very high effects especially on Candida parapsilosis. When the antioxidant research findings are examined; It was observed that Salvia marashica and Salvia caespitosa plants have approximately 75% antioxidant activity at 1 mg/ml, and findings mostly directly proportional between concentrations and antioxidant activity capacity were recorded. MCF-7 and HUVEC cell lines were used to investigate anticancer activity properties. In line with the findings, while the IC50 value of Salvia marashica on the MCF-7 Cell line was 0.125 mg/ml, it was 1.65 mg/ml in the HUVEC cell line, while the IC50 value of Salvia caespitosa on the MCF-7 Cell line was 0.115 mg/ml in the HUVEC Cell line. It was found to be 9.87 mg/ml. It has been proven that both Salvia species have a cytotoxic effect on the MCF-7 Cell line.

VR-Caps: A Virtual Environment for Capsule Endoscopy.

Current capsule endoscopes and next-generation robotic capsules for diagnosis and treatment of gastrointestinal diseases are complex cyber-physical platforms that must orchestrate complex software and hardware functions. The desired tasks for these systems include visual localization, depth estimation, 3D mapping, disease detection and segmentation, automated navigation, active control, path realization and optional therapeutic modules such as targeted drug delivery and biopsy sampling. Data-driven algorithms promise to enable many advanced functionalities for capsule endoscopes, but real-world data is challenging to obtain. Physically-realistic simulations providing synthetic data have emerged as a solution to the development of data-driven algorithms. In this work, we present a comprehensive simulation platform for capsule endoscopy operations and introduce VR-Caps, a virtual active capsule environment that simulates a range of normal and abnormal tissue conditions (e.g., inflated, dry, wet etc.) and varied organ types, capsule endoscope designs (e.g., mono, stereo, dual and 360∘ camera), and the type, number, strength, and placement of internal and external magnetic sources that enable active locomotion. VR-Caps makes it possible to both independently or jointly develop, optimize, and test medical imaging and analysis software for the current and next-generation endoscopic capsule systems. To validate this approach, we train state-of-the-art deep neural networks to accomplish various medical image analysis tasks using simulated data from VR-Caps and evaluate the performance of these models on real medical data. Results demonstrate the usefulness and effectiveness of the proposed virtual platform in developing algorithms that quantify fractional coverage, camera trajectory, 3D map reconstruction, and disease classification. All of the code, pre-trained weights and created 3D organ models of the virtual environment with detailed instructions how to setup and use the environment are made publicly available at https://github.com/CapsuleEndoscope/VirtualCapsuleEndoscopy and a video demonstration can be seen in the supplementary videos (Video-I).

De novo assembly and characterization of the first draft genome of quince (Cydonia oblonga Mill.).

Quince (Cydonia oblonga Mill.) is the sole member of the genus Cydonia in the Rosacea family and closely related to the major pome fruits, apple (Malus domestica Borkh.) and pear (Pyrus communis L.). In the present work, whole genome shotgun paired-end sequencing was employed in order to assemble the first draft genome of quince. A genome assembly that spans 488.4 Mb of sequence corresponding to 71.2% of the estimated genome size (686 Mb) was produced in the study. Gene predictions via ab initio and homology-based sequence annotation strategies resulted in the identification of 25,428 and 30,684 unique putative protein coding genes, respectively. 97.4 and 95.6% of putative homologs of Arabidopsis and rice transcription factors were identified in the ab initio predicted genic sequences. Different machine learning algorithms were tested for classifying pre-miRNA (precursor microRNA) coding sequences, identifying Support Vector Machine (SVM) as the best performing classifier. SVM classification predicted 600 putative pre-miRNA coding loci. Repetitive DNA content of the assembly was also characterized. The first draft assembly of the quince genome produced in this work would constitute a foundation for functional genomic research in quince toward dissecting the genetic basis of important traits and performing genomics-assisted breeding.

Mitral annular calcification and its severity predict high risk for cardio-embolic stroke in elderly patients with first diagnosed atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia worldwide and a large proportion of patients with AF are older than 75 years of age. Mitral annular calcification (MAC), which is usually observed in advanced age, is associated with increased risk of AF and cardio-embolic stroke in the general population. OBJECTIVES: This study was performed to assess whether presence of MAC and its severity predict cardio-embolic stroke in elderly patients with first diagnosed AF. METHODS: In this cross-sectional study, 72 elderly patients suffering from acute cardio-embolic stroke with first diagnosed AF and 79 elderly control group patients with first diagnosed AF and without stroke were investigated. A parasternal short-axis view at the level of the mitral annulus was used for MAC measurements. The severity of MAC was measured from the anterior to posterior edge at its greatest width. RESULTS: MAC thicknesses were significantly higher in the stroke group. ROC curve analysis showed that a cut point of 2.5 mm for the value of MAC thickness exhibited 68.1% sensitivity and 77.2% specificity for detecting cardio-embolic stroke in elderly patients with AF. In multivariate logistic regression analysis, MAC thickness (OR = 1.173, 95% CI 1.083-1.270; p < 0.001) was found to be independent predictor of cardio-embolic stroke in elderly patients with AF. CONCLUSION: MAC thickness may provide useful information for the relevant risk evaluation of elderly patients with AF. Pre-stroke MAC presence and its severity appear to have better clinical value for predicting cardio-embolic stroke in elderly patients with AF, independent from traditional risk factors for stroke.

Inflammatory Conditions in Acute Coronary Syndrome Patients Treated with Percutaneous Coronary Intervention of Saphenous Vein Graft.

The study aimed to evaluate the inflammatory blood parameters in acute coronary syndrome (ACS) patients with a history of coronary artery bypass graft (CABG) and treated with percutaneous coronary intervention (PCI) of saphenous vein graft (SVG). A total of 347 patients who underwent urgent SVG PCI with the diagnosis of ACS were included in the study. After the application of exclusion criteria, 79 patients were allocated into two groups, namely, successful PCI ( n = 59) and unsuccessful PCI ( n = 20), and included in the statistical analysis. Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) levels were significantly higher in patients with unsuccessful SVG PCI. In the logistic regression analysis, PLR, C-reactive protein, and diabetes mellitus emerged as independent factors associated with unsuccessful SVG PCI. The area under the curve for PLR was 0.70 (95% confidence interval: 0.55-0.85, p = 0.006). The cut-off value of PLR (128.99) was associated with 70.0% sensitivity and 69.5% specificity. Elevated inflammatory status is associated with unsuccessful PCI of SVG in ACS patients. Increased PLR levels on admission is an independent predictor of this situation. This cheap and simple marker can help us to predict unsuccessful SVG PCI in ACS patients.