Cilomilast Modulates Rhinovirus-Induced Airway Epithelial ICAM-1 Expression and IL-6, CXCL8 and CCL5 Production.

Cilomilast, a phosphodiesterase-4 (PDE4) selective inhibitor, has anti-inflammatory effects in vitro and in vivo and reduces COPD exacerbations. We tested the hypothesis that cilomilast inhibits virus-induced airway epithelial intercellular adhesion molecule-1 (ICAM-1) expression and inflammatory cytokine/chemoattractants, IL-6, CXCL8, and CCL5 production in vitro. BEAS-2B bronchial epithelial cells were incubated with 0.

Altered immunophenotypic expression in the peripheral bladder cancer immune landscape.

Treatments targeting the immune system only benefit a subset of patients with bladder cancer (BC). Biomarkers predictive of BC progression and response to specific therapeutic interventions are required. We evaluated whether peripheral blood immune subsets and expression of clinically relevant immune checkpoint markers are associated with clinicopathologic features of BC.

GelMA, Click-Chemistry Gelatin and Bioprinted Polyethylene Glycol-Based Hydrogels as 3D Ex Vivo Drug Testing Platforms for Patient-Derived Breast Cancer Organoids.

3D organoid model technologies have led to the development of innovative tools for cancer precision medicine. Yet, the gold standard culture system (Matrigel®) lacks the ability for extensive biophysical manipulation needed to model various cancer microenvironments and has inherent batch-to-batch variability. Tunable hydrogel matrices provide enhanced capability for drug testing in breast cancer (BCa), by better mimicking key physicochemical characteristics of this disease’s extracellular matrix.

Modelling the tumor immune microenvironment for precision immunotherapy.

The complexity of the cellular and acellular players within the tumor microenvironment (TME) allows for significant variation in TME constitution and role in anticancer treatment response. Spatial alterations in populations of tumor cells and adjacent non-malignant cells, including endothelial cells, fibroblasts and tissue-infiltrating immune cells, often have a major role in determining disease progression and treatment response in cancer. Many current standard systemic antineoplastic treatments target the cancer cells and could be further refined to directly target commonly dysregulated cell populations of the TME.

Culture of Bladder Cancer Organoids as Precision Medicine Tools.

Current in vitro therapeutic testing platforms lack relevance to tumor pathophysiology, typically employing cancer cell lines established as two-dimensional (2D) cultures on tissue culture plastic. There is a critical need for more representative models of tumor complexity that can accurately predict therapeutic response and sensitivity. The development of three-dimensional (3D) ex vivo culture of patient-derived organoids (PDOs), derived from fresh tumor tissues, aims to address these shortcomings.

Patient-Derived Explants as a Precision Medicine Patient-Proximal Testing Platform Informing Cancer Management.

Precision medicine approaches that inform clinical management of individuals with cancer are progressively advancing. Patient-derived explants (PDEs) provide a patient-proximal platform that can be used to assess sensitivity to standard of care (SOC) therapies and novel agents. PDEs have several advantages as a patient-proximal model compared to current preclinical models, as they maintain the phenotype and microenvironment of the individual tumor.

The long non-coding RNA GHSROS reprograms prostate cancer cell lines toward a more aggressive phenotype.

It is now appreciated that long non-coding RNAs (lncRNAs) are important players in orchestrating cancer progression. In this study we characterized , a human lncRNA gene on the opposite DNA strand (antisense) to the ghrelin receptor gene, in prostate cancer. The lncRNA was upregulated by prostate tumors from different clinical datasets.

The mitochondrial genome of the black-tailed dusky antechinus ().

In this study, we report the mitochondrial genome of the black-tailed antechinus (), a recently-discovered, endangered carnivorous marsupial inhabiting a caldera that straddles the border of Australia's mid-east coast. The circular genome is 17,334 bp in length and has an AT content of 63.3%.

Characterisation of the Expression of Neurotensin and Its Receptors in Human Colorectal Cancer and Its Clinical Implications.

: Colorectal Cancer (CRC) accounts for 9% of cancer deaths globally. Hormonal pathways play important roles in some cancers. This study investigated the association of CRC expression of neurotensin (NTS), NTS receptors 1 and 3 (NTSR1 and NTSR3) and clinical outcomes.

Bronchial mucosal inflammation and illness severity in response to experimental rhinovirus infection in COPD.

Background: Respiratory viral infection causes chronic obstructive pulmonary disease (COPD) exacerbations. We previously reported increased bronchial mucosa eosinophil and neutrophil inflammation in patients with COPD experiencing naturally occurring exacerbations. But it is unclear whether virus per se induces bronchial mucosal inflammation, nor whether this relates to exacerbation severity.

The long non-coding RNA GHSROS facilitates breast cancer cell migration and orthotopic xenograft tumour growth.

Recent evidence suggests that numerous long non‑coding RNAs (lncRNAs) are dysregulated in cancer, and have critical roles in tumour development and progression. The present study investigated the ghrelin receptor antisense lncRNA growth hormone secretagogue receptor opposite strand (GHSROS) in breast cancer. Reverse transcription‑quantitative polymerase chain reaction revealed that GHSROS expression was significantly upregulated in breast tumour tissues compared with normal breast tissue.

The mitochondrial genome of the black-tailed dasyure ().

In this study, we report the mitochondrial genome of the black-tailed dasyure () of New Guinea. The circular genome is 17,736 bp in length and has an AT content of 60.5%.

No effect of unacylated ghrelin administration on subcutaneous PC3 xenograft growth or metabolic parameters in a Rag1-/- mouse model of metabolic dysfunction.

Ghrelin is a peptide hormone which, when acylated, regulates appetite, energy balance and a range of other biological processes. Ghrelin predominately circulates in its unacylated form (unacylated ghrelin; UAG). UAG has a number of functions independent of acylated ghrelin, including modulation of metabolic parameters and cancer progression.

Limited short-term effects on human prostate cancer xenograft growth and epidermal growth factor receptor gene expression by the ghrelin receptor antagonist [D-Lys]-GHRP-6.

Purpose: The ghrelin axis regulates many physiological functions (including appetite, metabolism, and energy balance) and plays a role in disease processes. As ghrelin stimulates prostate cancer proliferation, the ghrelin receptor antagonist [D-Lys]-GHRP-6 is a potential treatment for castrate-resistant prostate cancer and for preventing the metabolic consequences of androgen-targeted therapies. We therefore explored the effect of [D-Lys]-GHRP-6 on PC3 prostate cancer xenograft growth.

Bronchial mucosal IFN-α/β and pattern recognition receptor expression in patients with experimental rhinovirus-induced asthma exacerbations.

Background: The innate immune system senses viral infection through pattern recognition receptors (PRRs), leading to type I interferon production. The role of type I interferon and PPRs in rhinovirus-induced asthma exacerbations in vivo are uncertain.

Objectives: We sought to compare bronchial mucosal type I interferon and PRR expression at baseline and after rhinovirus infection in atopic asthmatic patients and control subjects.

Resource Use and Real-World Outcomes for Ranibizumab Treat and Extend for Neovascular Age-Related Macular Degeneration in the UK: Interim Results from TERRA.

Introduction: Ranibizumab is an inhibitor of vascular endothelial growth factor-A (anti-VEGF) approved for the treatment of neovascular age-related macular degeneration (nAMD). The treat and extend (T&E) regimen can potentially reduce the burden of clinic visits compared with a pro re nata (PRN) regimen. Retrospective, interim analyses of clinical effectiveness, treatment and resource use patterns were conducted using real-world data in England and Wales from the TERRA study.

Whole-Genome Sequence of the Metastatic PC3 and LNCaP Human Prostate Cancer Cell Lines.

The bone metastasis-derived PC3 and the lymph node metastasis-derived LNCaP prostate cancer cell lines are widely studied, having been described in thousands of publications over the last four decades. Here, we report short-read whole-genome sequencing (WGS) and assembly of PC3 (ATCC CRL-1435) and LNCaP (clone FGC; ATCC CRL-1740) at ∼70 × coverage. A known homozygous mutation in and homozygous loss of were robustly identified in the PC3 cell line, whereas the LNCaP cell line exhibited a larger number of putative inactivating somatic point and indel mutations (and in particular a loss of stop codon events).

Barriers to higher education: commonalities and contrasts in the experiences of Hindu and Muslim young women in urban Bengaluru.

Gender inequalities in educational attainment have attracted considerable attention and this article aims to contribute to our understanding of young women's access to higher education. The article is based on our in-depth interviews with 26 Hindu and Muslim young women attending colleges in urban Bengaluru (formerly Bangalore), south India, and explores the barriers they confronted in fulfilling their aspirations. We highlight the similarities amongst the young women, as well as the distinctive experiences of the Hindu and Muslim interviewees.

Insights from engraftable immunodeficient mouse models of hyperinsulinaemia.

Hyperinsulinaemia, obesity and dyslipidaemia are independent and collective risk factors for many cancers. Here, the long-term effects of a 23% Western high-fat diet (HFD) in two immunodeficient mouse strains (NOD/SCID and Rag1 ) suitable for engraftment with human-derived tissue xenografts, and the effect of diet-induced hyperinsulinaemia on human prostate cancer cell line xenograft growth, were investigated. Rag1 and NOD/SCID HFD-fed mice demonstrated diet-induced impairments in glucose tolerance at 16 and 23 weeks post weaning.

MUC13 overexpression in renal cell carcinoma plays a central role in tumor progression and drug resistance.

Metastatic renal cell carcinoma is a largely incurable disease, and existing treatments targeting angiogenesis and tyrosine kinase receptors are only partially effective. Here we reveal that MUC13, a cell surface mucin glycoprotein, is aberrantly expressed by most renal cell carcinomas, with increasing expression positively correlating with tumor grade. Importantly, we demonstrated that high MUC13 expression was a statistically significant independent predictor of poor survival in two independent cohorts, particularly in stage 1 cancers.

Contextualizing Women's Agency in Marital Negotiations: Muslim and Hindu Women in Karnataka, India.

We use 36 in-depth interviews, with 18 Muslim and 18 Hindu women in Karnataka, India, to explore the relationships between women's educational attainments and women's exercise of agency in spousal selection and the timing of marriage. We have outlined three kinds of agency, namely, convinced, resistance, and complicit, and the contexts in which they were deployed by our participants during their marriage negotiations. Our examination of the role of education across this spectrum of agential capacities during marriage negotiations suggests that the linkages between education and agency are not straightforward.

Effects of a community-based salt reduction program in a regional Australian population.

Background: Salt reduction is a public health priority but there are few studies testing the efficacy of plausible salt reduction programs.

Methods: A multi-faceted, community-based salt reduction program using the Communication for Behavioral Impact framework was implemented in Lithgow, Australia. Single 24-h urine samples were obtained from 419 individuals at baseline (2011) and from 572 at follow-up (2014).

Erosion Remineralization Efficacy of Gel-to-Foam Fluoride Toothpastes in situ: A Randomized Clinical Trial.

This single-center, randomized, placebo-controlled, four-treatment, four-period crossover study compared the enamel remineralization effects of low- and medium-abrasivity gel-to-foam toothpastes and a reference toothpaste (all 1,450 ppm fluoride as NaF) versus placebo toothpaste (0 ppm fluoride) using a short-term in situ erosion model. Subjects (n = 56) wearing a palatal appliance holding acid-softened bovine enamel specimens brushed their teeth with the test toothpastes. Thereafter, the specimens were removed for analysis of percent surface microhardness recovery (%SMHR) and percent relative erosion resistance (%RER) at 2, 4, and 8 h.

Multi-species sequence comparison reveals conservation of ghrelin gene-derived splice variants encoding a truncated ghrelin peptide.

The peptide hormone ghrelin is a potent orexigen produced predominantly in the stomach. It has a number of other biological actions, including roles in appetite stimulation, energy balance, the stimulation of growth hormone release and the regulation of cell proliferation. Recently, several ghrelin gene splice variants have been described.