Rapid LC-MS/MS Evaluation of Collagen and Elastin Crosslinks in Human and Mouse Lung Tissue with a Novel Bioanalytical Surrogate Matrix Approach.

Alterations to post-translational crosslinking modifications in the extracellular matrix (ECM) are known to drive the pathogenesis of fibrotic diseases, including idiopathic pulmonary fibrosis (IPF). Thus, the methodology for measuring crosslinking dynamics is valuable for understanding disease progression. The existing crosslinking analysis sample preparation and liquid chromatography tandem mass spectrometry (LC-MS/MS) methods are typically labor-intensive and time-consuming which limits throughput.

Modulating lung fibroblast activation via senolysis of senescent human alveolar epithelial cells.

Idiopathic pulmonary fibrosis (IPF) is an age-related disease with poor prognosis and limited therapeutic options. Activation of lung fibroblasts and differentiation to myofibroblasts are the principal effectors of disease pathology, but damage and senescence of alveolar epithelial cells, specifically type II (ATII) cells, has recently been identified as a potential trigger event for the progressive disease cycle. Targeting ATII senescence and the senescence-associated secretory phenotype (SASP) is an attractive therapeutic strategy; however, translatable primary human cell models that enable mechanistic studies and drug development are lacking.

Smoking, nicotine and pregnancy 2 (SNAP2) trial: protocol for a randomised controlled trial of an intervention to improve adherence to nicotine replacement therapy during pregnancy.

Introduction: Smoking during pregnancy is harmful to unborn babies, infants and women. Nicotine replacement therapy (NRT) is offered as the usual stop-smoking support in the UK. However, this is often used in insufficient doses, intermittently or for too short a time to be effective.

An anti-TNF-glucocorticoid receptor modulator antibody-drug conjugate is efficacious against immune-mediated inflammatory diseases.

Glucocorticoids (GCs) are efficacious drugs used for treating many inflammatory diseases, but the dose and duration of administration are limited because of severe side effects. We therefore sought to identify an approach to selectively target GCs to inflamed tissue. Previous work identified that anti-tumor necrosis factor (TNF) antibodies that bind to transmembrane TNF undergo internalization; therefore, an anti-TNF antibody-drug conjugate (ADC) would be mechanistically similar, where lysosomal catabolism could release a GC receptor modulator (GRM) payload to dampen immune cell activity.

IL11-mediated stromal cell activation may not be the master regulator of pro-fibrotic signaling downstream of TGFβ.

Fibrotic diseases, such as idiopathic pulmonary fibrosis (IPF) and systemic scleroderma (SSc), are commonly associated with high morbidity and mortality, thereby representing a significant unmet medical need. Interleukin 11 (IL11)-mediated cell activation has been identified as a central mechanism for promoting fibrosis downstream of TGFβ. IL11 signaling has recently been reported to promote fibroblast-to-myofibroblast transition, thus leading to various pro-fibrotic phenotypic changes.

Development of "Baby, Me, & NRT": A Behavioral Intervention to Improve the Effectiveness of Nicotine Replacement Therapy in Pregnancy.

Background: The effectiveness of Nicotine Replacement Therapy (NRT) for smoking cessation in pregnancy is limited by inconsistent and incorrect use. This paper describes the development process for "Baby, Me, & NRT", a novel pregnancy-specific intervention aimed at enhancing adherence to NRT.

Methods: An integrated approach to intervention development was used, combining evidence, theory, stakeholders' feedback, and tailoring principles.

Comparison of a Daily Smartphone App and Retrospective Questionnaire Measures of Adherence to Nicotine Replacement Therapy Among Pregnant Women: Observational Study.

Background: Few studies have investigated how to best measure adherence to smoking cessation medications, but continuous usage measures are recommended.

Objective: In this first study of its kind, we compared methods for measuring adherence to nicotine replacement therapy (NRT) among pregnant women, investigating the completeness and validity of data collected from daily assessments using a smartphone app versus data collected from retrospective questionnaires.

Methods: Women aged ≥16 years who were daily smokers and <25 weeks pregnant were offered smoking-cessation counseling and encouraged to use NRT.

Development and Content Validation of a Questionnaire for Measuring Beliefs About Using Nicotine Replacement Therapy for Smoking Cessation in Pregnancy.

Introduction: Improving adherence to nicotine replacement therapy (NRT) in pregnancy may result in higher smoking cessation rates. Informed by the Necessities and Concerns Framework, we developed an intervention targeting pregnancy NRT adherence. To evaluate this, we derived the NRT in pregnancy necessities and concerns questionnaire (NiP-NCQ), which measures perceived need for NRT and concerns about potential consequences.

Developing a taxonomy to describe offspring outcomes in studies involving pregnant mammals' exposure to non-tobacco nicotine: A systematic scoping review.

Introduction: Many countries recommend Nicotine Replacement Therapy (NRT) for smoking cessation in pregnancy. Preclinical studies of nicotine exposure to pregnant mammals could indicate how nicotine may adversely affect the developing fetus. As a first step towards summarising this literature, we undertook a systematic scoping review to determine the number and nature of offspring outcomes studied.

Epiregulin is a dendritic cell-derived EGFR ligand that maintains skin and lung fibrosis.

Immune cells are fundamental regulators of extracellular matrix (ECM) production by fibroblasts and have important roles in determining extent of fibrosis in response to inflammation. Although much is known about fibroblast signaling in fibrosis, the molecular signals between immune cells and fibroblasts that drive its persistence are poorly understood. We therefore analyzed skin and lung samples of patients with diffuse cutaneous systemic sclerosis, an autoimmune disease that causes debilitating fibrosis of the skin and internal organs.

Epithelial dysfunction is prevented by IL-22 treatment in a Citrobacter rodentium-induced colitis model that shares similarities with inflammatory bowel disease.

Inflammatory bowel disease (IBD) is characterized by a dysregulated intestinal epithelial barrier leading to breach of barrier immunity. Here we identified similar protein expression changes between IBD and Citrobacter rodentium-infected FVB mice with respect to dysregulation of solute transporters as well as components critical for intestinal barrier integrity. We attribute the disease associated changes in the model to the emergence of undifferentiated intermediate intestinal epithelial cells.

Anti-microRNA-21 Therapy on Top of ACE Inhibition Delays Renal Failure in Alport Syndrome Mouse Models.

Alport mice serve as an animal model for renal fibrosis. MicroRNA-21 (miR-21) expression has been shown to be increased in the kidneys of Alport syndrome patients. Here, we investigated the nephroprotective effects of Lademirsen anti-miR-21 therapy.

Quantitative in vivo micro-computed tomography for monitoring disease activity and treatment response in a collagen-induced arthritis mouse model.

A painful, chronic condition, Rheumatoid Arthritis, is marked by bone erosion and soft tissue swelling at the joint. As treatments are investigated in pre-clinical models, characterizing disease progression is integral to assessing treatment efficacy. Here, in vivo and ex vivo micro-computed tomography (µCT) are used in parallel with traditional caliper score measurement to quantify physiological changes in the tarsal region in a murine, collagen-induced arthritis model.

Smoking Cessation Support for Pregnant Women Provided by English Stop Smoking Services and National Health Service Trusts: A Survey.

Reducing smoking rates in pregnancy continues to be a public health priority. Given a recent UK government policy change resulting in The National Health Service (NHS) making a significant new contribution to cessation support in pregnancy in England, in addition to that of Local Authorities (LA), an up-to-date assessment of national support offered to pregnant women is needed. LA Stop Smoking Service (SSS) managers and representatives from maternity services in NHS Trusts were invited to participate in an online survey in autumn 2020.

Barriers and Facilitators to Staying Smoke-Free after Having a Baby, a Qualitative Study: Women's Views on Support Needed to Prevent Returning to Smoking Postpartum.

Background: Postpartum return to smoking (PPRS) is a common and important public health problem. Interventions to prevent PPRS have not been shown to be effective. We aimed to qualitatively explore the barriers and facilitators to staying smoke-free after having a baby, and women's views on the support needed to avoid PPRS to inform future intervention development.

Comparison of saliva cotinine and exhaled carbon monoxide concentrations when smoking and after being offered dual nicotine replacement therapy in pregnancy.

Background And Aims: Although English Stop Smoking Services routinely offer dual nicotine replacement therapy (NRT) to help pregnant women to quit smoking, little is known about how nicotine and tobacco smoke exposures following this compare with that from smoking. We compared, in pregnant women when smoking and after being offered dual NRT, saliva cotinine and exhaled carbon monoxide (CO) concentrations and numbers of daily cigarettes smoked.

Design And Setting: Secondary analysis of data from three sequential, observational, mixed-methods cohort studies conducted as part of the Nicotine Replacement Effectiveness and Delivery in Pregnancy programme.

Smoking and vaping patterns during pregnancy and the postpartum: A longitudinal UK cohort survey.

Introduction: There is limited information about longitudinal patterns of vaping during pregnancy and the postpartum. We describe the prevalence, frequency, and reasons for vaping throughout pregnancy and postpartum. We also describe temporal patterns in pregnant women's vaping.

Agreement and Disparities between Women and Stop-Smoking Specialists about How to Promote Adherence to Nicotine Replacement Therapy in Pregnancy.

Evidence for the effectiveness of nicotine replacement therapy (NRT) for smoking-cessation in pregnancy is weak. This has been attributed to insufficient dosing and low adherence. This study investigated the acceptability of key messages and delivery modes for a behavioral intervention to increase NRT adherence in pregnancy.

Optimized Culture Conditions for Improved Growth and Functional Differentiation of Mouse and Human Colon Organoids.

Background & Aims: Diligent side-by-side comparisons of how different methodologies affect growth efficiency and quality of intestinal colonoids have not been performed leaving a gap in our current knowledge. Here, we summarize our efforts to optimize culture conditions for improved growth and functional differentiation of mouse and human colon organoids.

Methods: Mouse and human colon organoids were grown in four different media.

Mechanisms and regulation of IL-22-mediated intestinal epithelial homeostasis and repair.

Aims: Ulcerative colitis and Crohn's disease, collectively known as inflammatory bowel disease (IBD), are chronic inflammatory disorders of the intestine for which key elements in disease initiation and perpetuation are defects in epithelial barrier integrity. Achieving mucosal healing is essential to ameliorate disease outcome and so new therapies leading to epithelial homeostasis and repair are under investigation. This study was designed to determine the mechanisms by which IL-22 regulates intestinal epithelial cell function.

Understanding pregnant women's adherence-related beliefs about Nicotine Replacement Therapy for smoking cessation: A qualitative study.

Introduction: Reducing smoking during pregnancy is a public health priority. Nicotine replacement therapy (NRT) is offered routinely to pregnant women who smoke in the United Kingdom. However, evidence of treatment efficacy in this population is weak, most likely due to poor adherence.