β-Blockade Prevents Post-Ischemic Myocardial Decompensation Via βAR-Dependent Protective Sphingosine-1 Phosphate Signaling.

Background: Although β-blockers increase survival in patients with heart failure (HF), the mechanisms behind this protection are not fully understood, and not all patients with HF respond favorably to them. We recently showed that, in cardiomyocytes, a reciprocal down-regulation occurs between β-adrenergic receptors (ARs) and the cardioprotective sphingosine-1-phosphate (S1P) receptor- (S1PR).

Objectives: The authors hypothesized that, in addition to salutary actions due to direct βAR-blockade, agents such as metoprolol (Meto) may improve post-myocardial infarction (MI) structural and functional outcomes via restored S1PR signaling, and sought to determine mechanisms accounting for this effect.

Interleukin-10 Inhibits Bone Marrow Fibroblast Progenitor Cell-Mediated Cardiac Fibrosis in Pressure-Overloaded Myocardium.

Background: Activated fibroblasts (myofibroblasts) play a critical role in cardiac fibrosis; however, their origin in the diseased heart remains unclear, warranting further investigation. Recent studies suggest the contribution of bone marrow fibroblast progenitor cells (BM-FPCs) in pressure overload-induced cardiac fibrosis. We have previously shown that interleukin-10 (IL10) suppresses pressure overload-induced cardiac fibrosis; however, the role of IL10 in inhibition of BM-FPC-mediated cardiac fibrosis is not known.

microRNA in Cardiovascular Aging and Age-Related Cardiovascular Diseases.

Over the last decades, life expectancy has significantly increased although several chronic diseases persist in the population, with aging as the leading risk factor. Despite improvements in diagnosis and treatment, many elderlies suffer from cardiovascular problems that are much more frequent in an older, more fragile organism. In the long term, age-related cardiovascular diseases (CVDs) contribute to the decline of quality of life and ability to perform normal activities of daily living.

Relationship between microRNA-146a expression and plasma renalase levels in hemodialyzed patients.

Background: microRNA (miRNA) belongs to the non-coding RNAs family responsible for the regulation of gene expression. Renalase is a protein composed of 342 amino acids, secreted by the kidneys and possibly plays an important role in the regulation of sympathetic tone and blood pressure. The aim of the present study was to investigate plasma renalase concentration, and explore the relationship between miRNA-146a-5p expression and plasma renalase levels in hemodialyzed patients.

Thoracic and respirable aerosol fractions of spray products containing non-volatile compounds.

A versatile and simple mass balance method for the measurement of the release fraction of thoracic and respirable particles of non-volatile compounds of spray products is presented. The release fractions are defined as the ratio between the mass of suspended non-volatile particulate matter in the thoracic and respirable particle size range and the total mass of non-volatile material released with the spray action. For its determination, a spray bolus of short duration and of defined mass is sprayed into a well stirred control chamber.

Therapeutic inhibition of miR-375 attenuates post-myocardial infarction inflammatory response and left ventricular dysfunction via PDK-1-AKT signalling axis.

Aims: Increased miR-375 levels has been implicated in rodent models of myocardial infarction (MI) and with patients with heart failure. However, no prior study had established a therapeutic role of miR-375 in ischemic myocardium. Therefore, we assessed whether inhibition of MI-induced miR-375 by LNA anti-miR-375 can improve recovery after acute MI.

Noncanonical Roles of G Protein-coupled Receptor Kinases in Cardiovascular Signaling.

G protein-coupled receptor kinases (GRKs) are classically known for their role in regulating the activity of the largest known class of membrane receptors, which influence diverse biological processes in every cell type in the human body. As researchers have tried to uncover how this family of kinases, containing only 7 members, achieves selective and coordinated control of receptors, they have uncovered a growing number of noncanonical activities for these kinases. These activities include phosphorylation of nonreceptor targets and kinase-independent molecular interactions.

Structure-Based Design of Highly Selective and Potent G Protein-Coupled Receptor Kinase 2 Inhibitors Based on Paroxetine.

In heart failure, the β-adrenergic receptors (βARs) become desensitized and uncoupled from heterotrimeric G proteins. This process is initiated by G protein-coupled receptor kinases (GRKs), some of which are upregulated in the failing heart, making them desirable therapeutic targets. The selective serotonin reuptake inhibitor, paroxetine, was previously identified as a GRK2 inhibitor.

Trends on Analytical Characterization of Polysorbates and Their Degradation Products in Biopharmaceutical Formulations.

Among many other applications, polysorbates (PSs) are used as the most common surfactants in biopharmaceutical products in particular to protect proteins against interfacial stress. Structural heterogeneity, presence of degradants and other impurities, and tendency for degradation are interrelated features found in commercial PSs with a direct impact on their functional properties in biopharmaceutical products. These pose a challenge for the analytical characterization of PSs at different stages of product development.

Specificity and reproducibility of nasal biomarkers in patients with allergic rhinitis after allergen challenge chamber exposure.

Background: Allergic rhinitis is an inflammatory disease that causes cellular influx and mediator release in the nose. These inflammatory changes might be used as nasal biomarkers to assess the efficacy of novel anti-allergic treatments.

Objective: To assess the specificity and reproducibility of nasal biomarkers in patients with allergic rhinitis after grass pollen exposure in an allergen challenge chamber.

The prognostic role of sex, race, and human papillomavirus in oropharyngeal and nonoropharyngeal head and neck squamous cell cancer.

Background: Human papillomavirus (HPV) is a well-established prognostic marker for oropharyngeal squamous cell cancer (OPSCC). Because of the limited numbers of women and nonwhites in studies to date, sex and racial/ethnic differences in prognosis have not been well explored. In this study, survival differences were explored by the tumor HPV status among 1) patients with OPSCCs by sex and race and 2) patients with nonoropharyngeal (non-OP) head and neck squamous cell cancers (HNSCCs).

Application of Chromatographic and Spectroscopic Methods towards the Quality Assessment of Ginger (Zingiber officinale) Rhizomes from Ecological Plantations.

The usefulness of ginger in the food industry and pharmacotherapy is strictly related to its content of various components. The study elucidates the chemical composition of rhizomes cultivated on ecological plantations on Shikoku Island (Japan). GC-MS analysis of terpene content, LC-MS determination of phenolic content, and the determination of 12 elements using AAS spectrometry were performed to give more detailed insight into the samples.

Targeting β3-Adrenergic Receptors in the Heart: Selective Agonism and β-Blockade.

Cardiac diseases, such as heart failure, remain leading causes of morbidity and mortality worldwide, with myocardial infarction as the most common etiology. HF is characterized by β-adrenergic receptor (βAR) dysregulation that is primarily due to the upregulation of G protein-coupled receptor kinases that leads to overdesensitization of β1 and β2ARs, and this clinically manifests as a loss of inotropic reserve. Interestingly, the "minor" βAR isoform, the β3AR, found in the heart, lacks G protein-coupled receptor kinases recognition sites, and is not subject to desensitization, and as a consequence of this, in human failing myocardium, the levels of this receptor remain unchanged or are even increased.

Integrative computational analysis of transcriptional and epigenetic alterations implicates DTX1 as a putative tumor suppressor gene in HNSCC.

Over a half million new cases of Head and Neck Squamous Cell Carcinoma (HNSCC) are diagnosed annually worldwide, however, 5 year overall survival is only 50% for HNSCC patients. Recently, high throughput technologies have accelerated the genome-wide characterization of HNSCC. However, comprehensive pipelines with statistical algorithms that account for HNSCC biology and perform independent confirmatory and functional validation of candidates are needed to identify the most biologically relevant genes.

Mitochondrial fusion dynamics is robust in the heart and depends on calcium oscillations and contractile activity.

Mitochondrial fusion is thought to be important for supporting cardiac contractility, but is hardly detectable in cultured cardiomyocytes and is difficult to directly evaluate in the heart. We overcame this obstacle through in vivo adenoviral transduction with matrix-targeted photoactivatable GFP and confocal microscopy. Imaging in whole rat hearts indicated mitochondrial network formation and fusion activity in ventricular cardiomyocytes.

GRK2 as negative modulator of NO bioavailability: Implications for cardiovascular disease.

Nitric oxide (NO), initially identified as endothelium-derived relaxing factor (EDRF), is a gaso-transmitter with important regulatory roles in the cardiovascular, nervous and immune systems. In the former, this diatomic molecule and free radical gas controls vascular tone and cardiac mechanics, among others. In the cardiovascular system, it is now understood that β-adrenergic receptor (βAR) activation is a key modulator of NO generation.

Functional characterisation and cell specificity of BvSUT1, the transporter that loads sucrose into the phloem of sugar beet (Beta vulgaris L.) source leaves.

Sugar beet (Beta vulgaris L.) is one of the most important sugar-producing plants worldwide and provides about one third of the sugar consumed by humans. Here we report on molecular characterisation of the BvSUT1 gene and on the functional characterisation of the encoded transporter.

Evaluation of proposed staging systems for human papillomavirus-related oropharyngeal squamous cell carcinoma.

Background: Patients with human papillomavirus (HPV)-related oropharyngeal cancer (OPC) have improved survival when compared with those with HPV-negative OPC. Unfortunately, the American Joint Committee on Cancer seventh edition (AJCC-7ed) staging system does not account for the prognostic advantage observed with HPV-positive OPC. The purpose of the current study was to validate and compare 2 recently proposed staging systems for HPV-positive OPC.

β2-Adrenergic receptor-dependent chemokine receptor 2 expression regulates leukocyte recruitment to the heart following acute injury.

Following cardiac injury, early immune cell responses are essential for initiating cardiac remodeling and tissue repair. We previously demonstrated the importance of β2-adrenergic receptors (β2ARs) in the regulation of immune cell localization following acute cardiac injury, with deficient leukocyte infiltration into the damaged heart. The purpose of this study was to investigate the mechanism by which immune cell-expressed β2ARs regulate leukocyte recruitment to the heart following acute cardiac injury.

Head and neck surgical subspecialty training in Africa: Sustainable models to improve cancer care in developing countries.

Background: Cancer poses a health crisis in the developing world where surgery is the mainstay of treatment for head and neck cancers. However, a shortage of surgeons with appropriate skills exists. How do we train head and neck surgeons in developing countries and avoid a brain drain? The ideal model provides appropriate affordable training leading to establishment of head and neck cancer centers that teach and train others.

Cardiac Fibroblast GRK2 Deletion Enhances Contractility and Remodeling Following Ischemia/Reperfusion Injury.

Rationale: G protein-coupled receptor kinase 2 (GRK2) is an important molecule upregulated after myocardial injury and during heart failure. Myocyte-specific GRK2 loss before and after myocardial ischemic injury improves cardiac function and remodeling. The cardiac fibroblast plays an important role in the repair and remodeling events after cardiac ischemia; the importance of GRK2 in these events has not been investigated.

Assessing HER2 testing quality in breast cancer: variables that influence HER2 positivity rate from a large, multicenter, observational study in Germany.

Despite >10 years of routine human epidermal growth factor receptor 2 (HER2) testing in breast cancer, testing quality is still an issue. Guidelines recommend assessing HER2 positivity rates as a quality indicator; however, the extent to which patient- or tumor-related factors influence HER2 positivity is still unknown. The present study analyzed these influences to identify pathology centers with HER2 positivity rates unexplained by patient- or tumor-related factors.

Vasopressin type 1A receptor deletion enhances cardiac contractility, β-adrenergic receptor sensitivity and acute cardiac injury-induced dysfunction.

Vasopressin type 1A receptor (V1AR) expression is elevated in chronic human heart failure (HF) and contributes to cardiac dysfunction in animal models, in part via reduced β-adrenergic receptor (βAR) responsiveness. Although cardiac V1AR overexpression and V1AR stimulation are each sufficient to decrease βAR activity, it is unknown whether V1AR inhibition conversely augments βAR responsiveness. Further, although V1AR has been shown to contribute to chronic progression of HF, its impact on cardiac function following acute ischaemic injury has not been reported.