VRAC Complex Modulates Mechano-Electrical Signal Responses in Human Airway Smooth Muscle Shortening.

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.

Starving a Cell Promotes Airway Smooth Muscle Relaxation: Inhibition of Glycolysis Attenuates Excitation-Contraction Coupling.

Bronchomotor tone modulated by airway smooth muscle shortening represents a key mechanism that increases airway resistance in asthma. Altered glucose metabolism in inflammatory and airway structural cells is associated with asthma. Although these observations suggest a causal link between glucose metabolism and airway hyperresponsiveness, the mechanisms are unclear.

TGF-β: The missing link in obesity-associated airway diseases?

Obesity is emerging as a global public health epidemic. The co-morbidities associated with obesity significantly contribute to reduced quality of life, mortality, and global healthcare burden. Compared to other asthma comorbidities, obesity prominently engenders susceptibility to inflammatory airway diseases such as asthma and chronic obstructive pulmonary disease (COPD), contributes to greater disease severity and evokes insensitivity to current therapies.

The Role of HMGB1, a Nuclear Damage-Associated Molecular Pattern Molecule, in the Pathogenesis of Lung Diseases.

High-mobility group protein box 1 (HMGB1), a ubiquitous nuclear protein, regulates chromatin structure and modulates the expression of many genes involved in the pathogenesis of lung cancer and many other lung diseases, including those that regulate cell cycle control, cell death, and DNA replication and repair. Extracellular HMGB1, whether passively released or actively secreted, is a danger signal that elicits proinflammatory responses, impairs macrophage phagocytosis and efferocytosis, and alters vascular remodeling. This can result in excessive pulmonary inflammation and compromised host defense against lung infections, causing a deleterious feedback cycle.

Intrauterine cleaning after placental delivery at cesarean section: a randomized controlled trial.

Objective: The objective of this study is to evaluate whether omission of intrauterine cleaning increases intraoperative and postoperative complications among women who deliver via cesarean section.

Methods: We randomized 206 women undergoing primary elective cesarean deliveries to intrauterine cleaning or omission of cleaning. Postpartum endomyometritis rates across groups were the primary outcome.

A hypothesis-directed approach to the targeted development of a multiplexed proteomic biomarker assay for cancer.

In recent years, hundreds of candidate protein biomarkers have been identified using discovery-based proteomics. Despite the large number of candidate biomarkers, few proteins advance to clinical validation. We propose a hypothesis-driven approach to identify candidate biomarkers, previously characterized in the literature, with the highest probability of clinical applicability.