Proteomic Biomarkers of Survival in Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) causes progressive lung scarring and high mortality. Reliable and accurate prognostic biomarkers are urgently needed. To identify and validate circulating protein biomarkers of IPF survival.

Regulation of epithelial transitional states in murine and human pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive scarring disease arising from impaired regeneration of the alveolar epithelium after injury. During regeneration, type 2 alveolar epithelial cells (AEC2s) assume a transitional state that upregulates multiple keratins and ultimately differentiate into AEC1s. In IPF, transitional AECs accumulate with ineffectual AEC1 differentiation.

Fatal COVID-19 and Non-COVID-19 Acute Respiratory Distress Syndrome Is Associated with Incomplete Alveolar Type 1 Epithelial Cell Differentiation from the Transitional State without Fibrosis.

Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 and other etiologies results from injury to the alveolar epithelial cell (AEC) barrier resulting in noncardiogenic pulmonary edema, which causes acute respiratory failure; recovery requires epithelial regeneration. During physiological regeneration in mice, type 2 AECs (AEC2s) proliferate, exit the cell cycle, transiently assume a transitional state, then differentiate into type 1 AECs (AEC1s); in humans, persistence of the transitional state is associated with pulmonary fibrosis. It is unknown whether transitional cells emerge and differentiate into AEC1s without fibrosis in human ARDS and why transitional cells differentiate into AEC1s during physiological regeneration but persist in fibrosis.

Fatal COVID-19 and non-COVID-19 Acute Respiratory Distress Syndrome is Associated with Incomplete Alveolar Type 1 Epithelial Cell Differentiation from the Transitional State Without Fibrosis.

ARDS due to COVID-19 and other etiologies results from injury to the alveolar epithelial cell (AEC) barrier resulting in noncardiogenic pulmonary edema, which causes acute respiratory failure; clinical recovery requires epithelial regeneration. During physiologic regeneration in mice, AEC2s proliferate, exit the cell cycle, and transiently assume a transitional state before differentiating into AEC1s; persistence of the transitional state is associated with pulmonary fibrosis in humans. It is unknown whether transitional cells emerge and differentiate into AEC1s without fibrosis in human ARDS and why transitional cells differentiate into AEC1s during physiologic regeneration but persist in fibrosis.

Association of Regulatory Genetic Variants for Protein Kinase Cα with Mortality and Drug Efficacy in Patients with Heart Failure.

Purpose: Protein kinase C alpha (gene: PRKCA) is a key regulator of cardiac contractility. Two genetic variants have recently been discovered to regulate PRKCA expression in failing human heart tissue (rs9909004 [T → C] and rs9303504 [C → G]). The association of those variants with clinical outcomes in patients with heart failure (HF), and their interaction with HF drug efficacy, is unknown.

Serine protease inhibitor 6 plays a critical role in protecting murine granzyme B-producing regulatory T cells.

Regulatory T cells (Tregs) play a pivotal role in the maintenance of immune tolerance and hold great promise as cell therapy for a variety of immune-mediated diseases. However, the cellular mechanisms that regulate Treg maintenance and homeostasis have yet to be fully explored. Although Tregs express granzyme-B (GrB) to suppress effector T cells via direct killing, the mechanisms by which they protect themselves from GrB-mediated self-inflicted damage are unknown.

Impairment of immune systems in diabetes.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease that involves the progressive destruction of the insulin-producing beta cells in the islets of langerhans. It is a complex process that results from the loss of tolerance to insulin and other beta-cell-specific antigens. Various genetic and environmental factors have been studied so far, but precise causation has yet to be established.

Belatacept: a new era of immunosuppression?

Full T-cell activation in alloimmunity requires the engagement of several costimulatory molecules. CTLA-4-Ig and its commercially available fusion proteins, belatacept and abatacept, are used to block CD80/86 and promote T-cell tolerance. Belatacept, a higher binding affinity molecule, is currently approved for clinical use in renal transplantation.

The novel role of SERPINB9 in cytotoxic protection of human mesenchymal stem cells.

Clinical trials using allogeneic mesenchymal stem cells (MSCs) are ongoing for the purpose of providing therapeutic benefit for a variety of human disorders. Pertinent to their clinical use are the accessibility to sufficient quantities of these cells allowing for repetitive administration, as well as a better understanding of the specific mechanisms by which allogeneic MSCs evade host immune responses that in turn influence their life span following administration. In this report, we sought to characterize and compare human peripheral blood MSCs (hPB-MSCs) with bone marrow-derived MSCs.

Chaotic resonance: two-state model with chaos-induced escape over potential barrier.

We consider the resonant effects of chaotic fluctuations on a strongly damped particle in a bistable potential driven by weak sinusoidal perturbation. We derive analytical expressions of chaos-induced transition rate between the neighboring potential wells based on the inhomogeneous Smoluchowski equation. Our first-order analysis reveals that the transition rate has the form of the Kramers escape rate except for a perturbed prefactor.

Chaos-induced escape over a potential barrier.

We investigate the statistical parity of a class of chaos-generated noises on the escape of strongly damped particles out of a potential well. We show that statistical asymmetry in the chaotic fluctuations can lead to a skewed Maxwell-Boltzmann distribution in the well. Depending on the direction of skew, the Kramers escape rate is enhanced or suppressed accordingly.

Analysis on the origin of directed current from a class of microscopic chaotic fluctuations.

We show that the Perron-Frobenius equation of microscopic chaos based on double symmetric maps leads to an inhomogeneous Smoluchowski equation with a source term. Our perturbative analysis reveals that the source term gives rise to a directed current for a strongly damped particle in a spatially periodic potential. In addition, our result proves that in the zeroth-order limit, the position distribution of the particle obeys the Smoluchowski equation even though the fluctuating force is deterministic.