128 results match your criteria: "Rutgers Institute for Translational Medicine and Science[Affiliation]"

Introduction: The New Jersey Kids Study (NJKS) is a transdisciplinary statewide initiative to understand influences on child health, development, and disease. We conducted a mixed-methods study of project planning teams to investigate team effectiveness and relationships between team dynamics and quality of deliverables.

Methods: Ten theme-based working groups (WGs) (e.

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N-cadherin antagonism is bronchoprotective in severe asthma models.

Sci Adv

November 2024

Lung and Vascular Inflammation Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Severe asthma induces substantial mortality and chronic disability due to intractable airway obstruction, which may become resistant to currently available therapies including corticosteroids and β-adrenergic agonist bronchodilators. A key effector of these changes is exaggerated airway smooth muscle (ASM) cell contraction to spasmogens. No drugs in clinical use effectively prevent ASM hyperresponsiveness in asthma across all severities.

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Background: Coronavirus disease 2019 (COVID-19) pneumonia requires considerable healthcare resources.

Research Objective: Examine if a single dose of infliximab or abatacept, in addition to remdesivir and steroids, decreased resource utilization among participants hospitalized with COVID-19 pneumonia.

Study Design And Methods: Accelerating COVID-19 Therapeutic Interventions and Vaccines Immunomodulator (ACTIV-1 IM) master protocol was a randomized, placebo-controlled trial examining the potential benefit in time to recovery and mortality of immunomodulators infliximab, abatacept, and cenicriviroc.

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The urgent need for effective treatments for acute and chronic lung diseases underscores the significance of developing innovative preclinical human research tools. The 2023 ATS Workshop on Precision Cut Lung Slices (PCLS) brought together 35 experts to discuss and address the role of human tissue-derived PCLS as a unique tool for target and drug discovery and validation in pulmonary medicine. With increasing interest and usage, along with advancements in methods and technology, there is a growing need for consensus on PCLS methodology and readouts.

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Leucine-rich repeat containing 8A (LRRC8A) is an obligatory constituent of the volume-regulated anion channel (VRAC) that is fundamental to a wide range of biological processes, including regulating cell size, proliferation, and migration. Here we explored the physiological role for VRAC in excitation-contraction (E-C) coupling and shortening of human airway smooth muscle (HASM). In HASM cells, pharmacological inhibition of VRAC with DCPIB (0.

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Bronchomotor tone imbalance evokes airway hyperresponsiveness.

Expert Rev Respir Med

November 2024

Rutgers Institute for Translational Medicine and Science, Child Health Institute of New Jersey, Rutgers, The State University of New Jersey, New Brunswick, NJ, USA.

Introduction: Obstructive airway diseases asthma and COPD represent a significant healthcare burden. Airway hyperresponsiveness (AHR), a salient feature of these two diseases, remains the main therapeutic target. Airway smooth muscle (ASM) cell is pivotal for bronchomotor tone and development of AHR in airway diseases.

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Correction to: G signaling in asthma.

Respir Res

October 2024

Department of Biochemistry and Molecular Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.

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Age and Hair Cortisol Levels as Predictors of SARS-CoV-2 Infection.

Int J Environ Res Public Health

September 2024

Environmental and Occupational Health Sciences Institute, Rutgers School of Public Health, Piscataway, NJ 08854, USA.

Chronic psychosocial stress is known to adversely impact immune function. During the SARS-CoV-2 pandemic, occupational stress among workers in healthcare was at an unprecedented level due to risks of infection and work demands. We performed a nested case-control study to investigate the associations between chronic stress and the risks of contracting SARS-CoV-2.

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G signaling in asthma.

Respir Res

August 2024

Department of Biochemistry and Molecular Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.

Shortening of airway smooth muscle and bronchoconstriction are pathognomonic for asthma. Airway shortening occurs through calcium-dependent activation of myosin light chain kinase, and RhoA-dependent calcium sensitization, which inhibits myosin light chain phosphatase. The mechanism through which pro-contractile stimuli activate calcium sensitization is poorly understood.

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Article Synopsis
  • - Precision Cut Lung Slices (PCLS) are an advanced ex vivo technique used to study lung diseases like fibrosis and injury, offering a more realistic model than traditional methods.
  • - This method involves carefully slicing lung tissue to preserve its structure and function, making it a valuable resource for research on airway diseases.
  • - PCLS create a controlled environment that helps researchers analyze complex interactions in lung tissue, leading to better insights into lung health and disease mechanisms.
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This summary describes the results of a clinical study called MANDALA that was published in the in 2022. In the MANDALA study, researchers looked at a new asthma rescue inhaler that contains both and in a single inhaler (known as , AIRSUPRA™). This summary describes the results for people aged 18 yearsand older who took part in the study.

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Asthma is a heterogeneous inflammatory disease of the airways, affecting many children, adolescents, and adults worldwide. Up to 10% of people with asthma have severe disease, associated with a higher risk of hospitalizations, greater healthcare costs, and poorer outcomes. Patients with severe asthma generally require high-dose inhaled corticosteroids and additional controller medications to achieve disease control; however, many patients remain uncontrolled despite this intensive treatment.

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Editorial for special issue-human precision cut lung slices: an Ex vivo platform for therapeutic target discovery and drug testing in lung disease.

Respir Res

March 2024

Rutgers Institute for Translational Medicine and Science, Rutgers University, 89 French Street, Room 4268, New Brunswick, NJ, 08901, USA.

Publications utilizing precision cut lung slices (PCLS) steadily increased from the 1970's, with a significant increase in 2010, to tripling by 2023. PCLS have been used to study a vast array of pulmonary diseases and exposures to pathogens and toxicants to understand pathogenesis of disease but also to examine basic cellular mechanisms that underly lung biology. This Special Issue will highlight new, exciting, and novel research using PCLS, while acknowledging the substantial fund of knowledge that has been gained using this platform.

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Prevention of asthma exacerbations and reduction of systemic corticosteroid burden remain unmet needs in asthma. US asthma guidelines recommend concomitant short-acting β-agonist (SABA) and inhaled corticosteroid (ICS) as an alternative reliever at step 2. The Food and Drug Administration approved a pressurized metered-dose inhaler containing albuterol and budesonide for as-needed treatment or prevention of bronchoconstriction and for reducing exacerbation risk in patients with asthma aged ≥18 years.

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Introduction: Triple therapy (fluticasone furoate/umeclidinium/vilanterol; FF/UMEC/VI) has been shown to improve symptoms and reduce exacerbations in patients with chronic obstructive pulmonary disease (COPD) and a history of exacerbations. This real-world study compared exacerbation rates and healthcare resource utilization (HCRU) before and after initiation of FF/UMEC/VI in patients with COPD previously treated with inhaled corticosteroid (ICS)/long-acting β-agonist (LABA).

Methods: This retrospective cohort study included commercial and Medicare Advantage with Part D administrative claims data from September 01, 2016, to March 31, 2020, of patients diagnosed with COPD.

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Patients with severe uncontrolled asthma (SUA) overwhelmingly contribute to the economic burden of asthma and may require biologic therapy. However, the impact of the CoronaVirus Disease of 2019 (COVID-19) on asthma costs and biologic use has yet to be evaluated. The objective was to test the hypothesis that SUA costs and biologic use decreased during the pandemic.

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Prorelaxant E-type Prostanoid Receptors Functionally Partition to Different Procontractile Receptors in Airway Smooth Muscle.

Am J Respir Cell Mol Biol

November 2023

Center for Translational Medicine, Jane and Leonard Korman Lung Institute, Division of Pulmonary, Allergy & Critical Care Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania.

Article Synopsis
  • Prostaglandin E2 (PGE2) affects airway muscle cells through four specific EP receptor subtypes (EP1-EP4), particularly focusing on the EP2 and EP4 receptors.
  • Researchers found that the EP4 receptor (agonist ONO-329) was more effective than the EP2 receptor (agonist ONO-259) in relaxing airway muscle contractions induced by methacholine, but both were similar in responses to histamine.
  • The study revealed that the different effects of these agonists aren’t due to overall changes in protein signaling, but instead relate to the regulation of specific proteins that control muscle contraction and the structure of the actin cytoskeleton, suggesting intricate signaling pathways involving multiple receptors.
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Identification of a β-arrestin-biased negative allosteric modulator for the β-adrenergic receptor.

Proc Natl Acad Sci U S A

August 2023

Department of Biochemistry and Molecular Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107.

Article Synopsis
  • Catecholamine-stimulated β-adrenergic receptor (βAR) signaling controls various physiological functions and impacts airway disease treatments, primarily through a well-known pathway involving G-adenylyl cyclase, cAMP, and PKA.
  • Regulation of βAR signaling is influenced by GRKs and β-arrestins, which can lead to desensitization and alternative signaling that counteracts the primary pathway, presenting a challenge for maximizing βAR therapy effectiveness.
  • A small molecule screen identified DFPQ, which selectively inhibits β-arrestin recruitment to βAR without disrupting its coupling to G proteins, offering a potential therapeutic advantage by preventing receptor desensitization and maintaining the efficacy of β
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Article Synopsis
  • Metastasis is rare at the cellular level, with only about 1 in 1.5 billion cancer cells capable of successfully completing the metastatic process.
  • Cells exhibiting a Polyaneuploid Cancer Cell (PACC) phenotype, characterized by enlargement and increased genomic content, have shown increased movement and adaptability in response to stress, which may enhance their metastasis competence.
  • Various techniques demonstrate that PACC cells possess hyper-elastic properties and express vimentin, suggesting they are better equipped for successful invasion and migration, warranting further investigation.
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Article Synopsis
  • - A study was conducted to test dexpramipexole, a new oral drug aimed at reducing eosinophils in patients with eosinophilic asthma, to see if it is safe and effective.
  • - In a trial involving 103 participants, those taking dexpramipexole (especially the 150 mg and 75 mg doses) showed significant reductions in eosinophil levels compared to the placebo group and maintained a good safety profile.
  • - The results indicate that dexpramipexole effectively lowers eosinophils, but more extensive studies are needed to evaluate its overall impact on asthma outcomes.
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Background: Severe eosinophilic asthma (SEA) is characterised by elevated blood/sputum eosinophil counts and airway inflammation, which can lead to mucus plug-mediated airway obstruction, increased exacerbation frequency, declines in lung function, and death. Benralizumab targets the alpha-subunit of the interleukin-5 receptor found on eosinophils, leading to rapid and near complete eosinophil depletion. This is expected to result in reduced eosinophilic inflammation, reduced mucus plugging and improved airway patency and airflow distribution.

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Article Synopsis
  • Rhinoviruses are a major trigger for asthma exacerbations, causing airway hyperresponsiveness and reducing the effectiveness of asthma treatments in children and adults.
  • Using models like human precision-cut lung slices and airway epithelial cells, the study found that RV-C15 significantly reduces the effectiveness of bronchodilators like formoterol.
  • The research suggests that RV-C15 impacts cellular pathways regulating airway relaxation, and it notes that the loss of bronchodilation occurs even with inactivated virus, indicating virus replication is not necessary for this effect.
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Article Synopsis
  • The phase 3 MANDALA trial showed that the combination inhaler of albuterol and budesonide significantly reduced severe asthma exacerbations compared to using albuterol alone in patients already on inhaled corticosteroids.
  • The DENALI study aimed to determine if both components of the inhaler contribute to its overall effectiveness in asthma treatment.
  • Results indicated that both albuterol-budesonide combinations improved lung function more than either component alone, while the safety profile was comparable to that of the individual drugs.
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