Predictive Performance of Physiologically Based Pharmacokinetic Models for the Effect of Food on Oral Drug Absorption: Current Status.

A comprehensive search in literature and published US Food and Drug Administration reviews was conducted to assess whether physiologically based pharmacokinetic (PBPK) modeling could be prospectively used to predict clinical food effect on oral drug absorption. Among the 48 resulted food effect predictions, ∼50% were predicted within 1.25-fold of observed, and 75% within 2-fold.

Evaluation of Model-Based Prediction of Pharmacokinetics in the Renal Impairment Population.

Dose recommendations for specific populations are not always provided and, when available, typically rely on empirical derivation from a small fraction of the general population. In this study, a prediction/confirmation framework was applied to 2 model-based methods, physiologically based pharmacokinetics (PBPK) and a static model, to evaluate their ability to predict clearance in mild, moderate, and severe renal impairment populations and to inform dosing recommendations in these populations. Simulated renal impairment/healthy subject AUC ratios (AUCRs) from PBPK and static models were compared with observed AUCRs from dedicated clinical studies in renal impairment subjects for 7 drugs eliminated primarily by renal clearance.

Interleukin 17A as a good predictor of the severity of Mycoplasma pneumoniae pneumonia in children.

Early distinction between severe Mycoplasma pneumoniae pneumonia (MPP) and mild MPP is still difficult. The aim of this study was to analyze cytokines in bronchoalveolar lavage fluid (BALF) and explore predicting factors of severe MPP in children. Retrospective analysis was performed on 150 children with MPP or bronchial foreign body (FB) admitted in our hospital.

Endothelial insulin receptors differentially control insulin signaling kinetics in peripheral tissues and brain of mice.

Insulin receptors (IRs) on endothelial cells may have a role in the regulation of transport of circulating insulin to its target tissues; however, how this impacts on insulin action in vivo is unclear. Using mice with endothelial-specific inactivation of the IR gene (EndoIRKO), we find that in response to systemic insulin stimulation, loss of endothelial IRs caused delayed onset of insulin signaling in skeletal muscle, brown fat, hypothalamus, hippocampus, and prefrontal cortex but not in liver or olfactory bulb. At the level of the brain, the delay of insulin signaling was associated with decreased levels of hypothalamic proopiomelanocortin, leading to increased food intake and obesity accompanied with hyperinsulinemia and hyperleptinemia.

Model-based meta-analysis of progression-free survival in non-Hodgkin lymphoma patients.

Background: Non-Hodgkin lymphoma (NHL) is a group of lymphoproliferative malignancies with varying treatment responses and progression-free survival (PFS) times. The objective of this study was to quantify the effect of treatment and patient-population characteristics on PFS in patients with NHL.

Methods: A database was developed from 513 NHL clinical trials reported from 1993 to 2015.

Relationship between response rates and median progression-free survival in non-Hodgkin's lymphoma: A meta-analysis of published clinical trials.

Demonstration of clinical effectiveness of a non-Hodgkin's lymphoma (NHL) treatment generally involves determination of progression-free survival (PFS). However, the long evaluation time of PFS limits its utility to make timely decisions in drug development. Therefore, the objective of this analysis was to determine the relationship between response rates and median PFS in NHL.

Sustained NFκB inhibition improves insulin sensitivity but is detrimental to muscle health.

Older adults universally suffer from sarcopenia and approximately 60-70% are diabetic or prediabetic. Nonetheless, the mechanisms underlying these aging-related metabolic disorders are unknown. NFκB has been implicated in the pathogenesis of several aging-related pathologies including sarcopenia and type 2 diabetes and has been proposed as a target against them.

Circumvent the uncertainty in the applications of transcriptional signatures to tumor tissues sampled from different tumor sites.

The expression measurements of thousands of genes are correlated with the proportions of tumor epithelial cell (PTEC) in clinical samples. Thus, for a tumor diagnostic or prognostic signature based on a summarization of expression levels of the signature genes, the risk score for a patient may dependent on the tumor tissues sampled from different tumor sites with diverse PTEC for the same patient. Here, we proposed that the within-samples relative expression orderings (REOs) based gene pairs signatures should be insensitive to PTEC variations.

Advances in the research of celery, an important Apiaceae vegetable crop.

Celery (Apium graveolens L.), one of the most important vegetables in Apiaceae family, is cultivated worldwide and utilized in food and cosmetic industries because it is an excellent source of vitamins, phenolic compounds, volatile oils and other nutrients. Celery extracts possess various medicinal properties, such as antibacterial, anti-inflammatory and lowering blood glucose and serum lipid levels.

Effect of Antipyretic Therapy on Mortality in Critically Ill Patients with Sepsis Receiving Mechanical Ventilation Treatment.

. The study aimed to investigate the effectiveness of antipyretic therapy on mortality in critically ill patients with sepsis requiring mechanical ventilation. .

Transcriptome analysis of bronchoalveolar lavage fluid from children with severe Mycoplasma pneumoniae pneumonia reveals novel gene expression and immunodeficiency.

Background: A growing number of severe Mycoplasma pneumoniae pneumonia (MPP) cases have been reported recently. However, the pathogenesis of severe MPP is not clear. In the current study, transcriptome sequencing was used to identify gene expression and alternative splicing profiles to provide insights into the pathogenesis of severe MPP.

A simple way to detect disease-associated cellular molecular alterations from mixed-cell blood samples.

Blood is a promising surrogate for solid tissue to investigate disease-associated molecular biomarkers. However, proportion changes of the constituent cells in the often-used peripheral whole blood (PWB) or peripheral blood mononuclear cell (PBMC) samples may influence the detection of cell-specific alterations under disease states. We propose a simple method, Ref-REO, to detect molecular alterations in leukocytes using the mixed-cell blood samples.

Adipocyte Dynamics and Reversible Metabolic Syndrome in Mice with an Inducible Adipocyte-Specific Deletion of the Insulin Receptor.

Insulin and IGF1 signaling are important for adipose tissue development and function; however, their role in mature adipocytes is unclear. Mice with a tamoxifen-inducible knockout of insulin and/or IGF1 receptors (IR/IGF1R) demonstrate a rapid loss of white and brown fat due to increased lipolysis and adipocyte apoptosis. This results in insulin resistance, glucose intolerance, hepatosteatosis, islet hyperplasia with hyperinsulinemia, and cold intolerance.

AP2/ERF Transcription Factors Involved in Response to Tomato Yellow Leaf Curly Virus in Tomato.

Tomato yellow leaf curly virus (TYLCV), transmitted by the whitefly (), causes leaf curling and yellowing, plant dwarfism, and growth inhibition in tomato ( L.). The APETALA2 (AP2) and ethylene response factor (ERF) transcription factor (TF) family, the largest plant-specific TF family, was identified to function in plant development and pathogen defense.

Arg156 in the AP2-Domain Exhibits the Highest Binding Activity among the 20 Individuals to the GCC Box in BnaERF-B3-hy15, a Mutant ERF Transcription Factor from .

To develop mutants of the ERF factor with more binding activities to the GCC box, we performed directed evolution by using DNA shuffling and screened mutants through yeast one-hybrid assay. Here, a series of mutants were obtained and used to reveal key amino acids that induce changes in the DNA binding activity of the BnaERF-B3 protein. With the BnaERF-B3-hy15 as the template, we produced 12 mutants which host individual mutation of potential key residues.

Suitable Reference Genes for Accurate Gene Expression Analysis in Parsley () for Abiotic Stresses and Hormone Stimuli.

Parsley, one of the most important vegetables in the Apiaceae family, is widely used in the food, medicinal, and cosmetic industries. Recent studies on parsley mainly focus on its chemical composition, and further research involving the analysis of the plant's gene functions and expressions is required. qPCR is a powerful method for detecting very low quantities of target transcript levels and is widely used to study gene expression.

Members of WRKY Group III transcription factors are important in TYLCV defense signaling pathway in tomato (Solanum lycopersicum).

Background: Transmitted by the whitefly Bemisia tabaci, tomato yellow leaf curly virus (TYLCV) has posed serious threats to plant growth and development. Plant innate immune systems against various threats involve WRKY Group III transcription factors (TFs). This group participates as a major component of biological processes in plants.

Differential expression analysis for individual cancer samples based on robust within-sample relative gene expression orderings across multiple profiling platforms.

The highly stable within-sample relative expression orderings (REOs) of gene pairs in a particular type of human normal tissue are widely reversed in the cancer condition. Based on this finding, we have recently proposed an algorithm named RankComp to detect differentially expressed genes (DEGs) for individual disease samples measured by a particular platform. In this paper, with 461 normal lung tissue samples separately measured by four commonly used platforms, we demonstrated that tens of millions of gene pairs with significantly stable REOs in normal lung tissue can be consistently detected in samples measured by different platforms.

Expression profiles of genes involved in jasmonic acid biosynthesis and signaling during growth and development of carrot.

Jasmonates (JAs) are recognized as essential regulators in response to environmental stimuli and plant development. Carrot is an Apiaceae vegetable with great value and undergoes significant size changes over the course of plant growth. However, JA accumulation and its potential roles in carrot growth remain unclear.

The Contagion of Interstate Violence: Reminders of Historical Interstate (but Not Intrastate) Violence Increase Support for Future Violence Against Unrelated Third-Party States.

Five experiments investigated the war contagion phenomenon in the context of international relations, hypothesizing that reminders of past inter- (but not intra-) state war will increase support for future, unrelated interstate violence. After being reminded of the Korean War as an interstate rather than intrastate conflict, South Koreans showed stronger support for violent responses to new, unrelated interstate tensions (Study 1). Replicating this war contagion effect among Americans, we demonstrated that it was mediated by heightened perceived threat from, and negative images of, a fictitious country unrelated to the past war (Study 2), and moderated by national glorification (Study 3).

Psychological Disorders and Psychosocial Resources of Patients with Newly Diagnosed Bladder and Kidney Cancer: A Cross-Sectional Study.

Purpose: Psychological disorders have been proven to be associated with poor physiological, psychological and immune outcomes in cancer patients. However, despite of many challenges of the changed self-image/body image and the altered sexual/urinary function, relatively little is known about psychological disorders of patients with newly diagnosed bladder and kidney cancer. We aimed to investigate the prevalence of depression, anxiety, post-traumatic stress disorder (PTSD) and the associated psychosocial factors among bladder/kidney cancer patients.

Effects of social support, hope and resilience on quality of life among Chinese bladder cancer patients: a cross-sectional study.

Background: Improvement of quality of life has been one of goals in health care for people living with bladder cancer. Meanwhile, positive psycho-social variables in oncology field have increasingly received attention. However, the assessment of quality of life of bladder cancer patients and the integrative effects of positive psycho-social variables has limited reporting.

The Associations of Psychological Stress with Depressive and Anxiety Symptoms among Chinese Bladder and Renal Cancer Patients: The Mediating Role of Resilience.

Background: The prevalence of depressive and anxiety symptoms and their associated factors in bladder and renal cancer patients are not well evaluated in China. Given the growing attention to positive psychological constructs in the field of oncology, it is necessary to explore the effects of these constructs on depressive and anxiety symptoms. This study aims to explore the associations of psychological stress with depressive and anxiety symptoms among Chinese bladder and renal cancer patients and the mediating role of resilience in these relationships.

Identifying Reproducible Molecular Biomarkers for Gastric Cancer Metastasis with the Aid of Recurrence Information.

To precisely diagnose metastasis state is important for tailoring treatments for gastric cancer patients. However, the routinely employed radiological and pathologic tests for tumour metastasis have considerable high false negative rates, which may retard the identification of reproducible metastasis-related molecular biomarkers for gastric cancer. In this research, using three datasets, we firstly shwed that differentially expressed genes (DEGs) between metastatic tissue samples and non-metastatic tissue samples could hardly be reproducibly detected with a proper statistical control when the metastatic and non-metastatic samples were defined by TNM stage alone.

Validation and Comparison of Reference Genes for qPCR Normalization of Celery (Apium graveolens) at Different Development Stages.

A suitable reference gene is an important prerequisite for guarantying accurate and reliable results in qPCR analysis. Celery is one of the representative vegetable in Apiaceae and is widely cultivated and consumed in the world. However, no reports have been previously published concerning reference genes in celery.