Functional Polymorphisms Regulate FOXO1 Transcript Expression and Contribute to the Risk and Symptom Severity of HDM-Induced Allergic Rhinitis.

Introduction: FOXO1 plays an important role in regulating immune processes that contribute to allergic inflammation; however, genetic variants influencing FOXO1 expression in AR pathogenesis remains unclear. This study aimed to investigate the functional effect of FOXO1 single nucleotide polymorphisms (SNPs) on AR development by performing genetic association and functional analysis studies.

Methods: This study belongs to a part of an ongoing Singapore/Malaysia cross-sectional genetics and epidemiological study (SMCSGES).

Isthmin-1 attenuates allergic Asthma by stimulating adiponectin expression and alveolar macrophage efferocytosis in mice.

Background: Allergic asthma is a common respiratory disease that significantly impacts human health. Through in silico analysis of human lung RNASeq, we found that asthmatic lungs display lower levels of Isthmin-1 (ISM1) expression than healthy lungs. ISM1 is an endogenous anti-inflammatory protein that is highly expressed in mouse lungs and bronchial epithelial cells, playing a crucial role in maintaining lung homeostasis.

ISM1 suppresses LPS-induced acute lung injury and post-injury lung fibrosis in mice.

Background: Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) are clinical syndromes characterized by acute lung inflammation, pulmonary edema and hypoxemia, with up to 50% mortality rate without effective pharmacological therapy. Following the acute inflammation, repair and remodeling occurs which in some cases resulting in lung fibrosis. The pathophysiology of ALI/ARDS remains incompletely understood.

ISM1 protects lung homeostasis via cell-surface GRP78-mediated alveolar macrophage apoptosis.

Alveolar macrophages (AMs) are critical for lung immune defense and homeostasis. They are orchestrators of chronic obstructive pulmonary disease (COPD), with their number significantly increased and functions altered in COPD. However, it is unclear how AM number and function are controlled in a healthy lung and if changes in AMs without environmental assault are sufficient to trigger lung inflammation and COPD.

Changing epidemiology of hand, foot, and mouth disease in Hong Kong, 2001-2009.

We report the surveillance findings of hand, foot, and mouth disease (HFMD) collected from a general practitioner-based sentinel surveillance system and outbreaks reported by institutions and a laboratory-based enterovirus surveillance system in Hong Kong from 2001 to 2009. A seasonal peak was detected in the warmer months (May-July), along with a smaller winter peak (October-December) from 2006 onwards. The number of older children (>5 years) infected increased from 25.

Aldose reductase deficiency prevents diabetes-induced blood-retinal barrier breakdown, apoptosis, and glial reactivation in the retina of db/db mice.

In 15-month-old db/db mice, signs of diabetic retinopathy, including blood-retinal barrier breakdown, loss of pericytes, neuro-retinal apoptosis, glial reactivation, and proliferation of blood vessels, were evident. These changes in the diabetic retina were associated with increased expression of aldose reductase (AR). To further understand the role of AR in the pathogenesis of diabetic retinopathy, we generated db/db mice with an AR null mutation (AR-/- db/db).

Directed evolution of high-affinity antibody mimics using mRNA display.

We constructed a library of >10(12) unique, covalently coupled mRNA-protein molecules by randomizing three exposed loops of an immunoglobulin-like protein, the tenth fibronectin type III domain (10Fn3). The antibody mimics that bound TNF-alpha were isolated from the library using mRNA display. Ten rounds of selection produced 10Fn3 variants that bound TNF-alpha with dissociation constants (K(d)) between 1 and 24 nM.