Gasdermin B (GSDMB) on chromosome 17q21 demonstrates a strong genetic linkage to asthma, but its function in asthma is unknown. Here we identified that GSDMB is highly expressed in lung bronchial epithelium in human asthma. Overexpression of GSDMB in primary human bronchial epithelium increased expression of genes important to both airway remodeling [TGF-β1, 5-lipoxygenase (5-LO)] and airwayhyperresponsiveness (AHR) (5-LO). Interestingly, hGSDMBZp3-Cre mice expressing increased levels of the human GSDMB transgene showed a significant spontaneous increase in AHR and a significant spontaneous increase in airway remodeling, with increased smooth muscle mass and increased fibrosis in the absence of airway inflammation. In addition, hGSDMB Zp3-Cre mice showed increases in the same remodeling and AHR mediators (TGF-β1, 5-LO) observed in vitro in GSDMBoverexpressing epithelial cells. GSDMB induces TGF-β1 expression via induction of 5-LO, because knockdown of 5-LO in epithelial cells overexpressing GSDMB inhibited TGF-β1 expression. These studies demonstrate that GSDMB, a gene highly linked to asthma but whose function in asthma is previously unknown, regulates AHR and airway remodeling without airway inflammation through a previously unrecognized pathway in which GSDMB induces 5-LO to induce TGF-β1 in bronchial epithelium.GSDMB | asthma | airway-hyperresponsiveness | remodeling | inflammation

Idiopathic pulmonary fibrosis (IPF) is a fatal disorder resulting from the progressive remodeling of lungs, with no known effective treatment. Although transforming growth factor (TGF)-b has a wellestablished role in lung fibrosis, clinical experience with neutralizing antibodies to TGF-b has been disappointing, and strategies to directly suppress TGF-b1 secretion are needed. In this study we used a combination of in silico, in vitro, and in vivo approaches to identify microRNAs involved in TGF-b1 regulation and to validate the role of miR-326 in pulmonary fibrosis.We show that hsa-miR-326 regulates TGF-b1 expression and that hsa-miR-326 levels are inversely correlated to TGF-b1 protein levels in multiple human cell lines. The increase in TGF-b1 expression during the progression of bleomycin-induced lung fibrosis in mice was associated with loss of mmu-miR-326. Restoration of mmu-miR-326 levels by intranasal delivery of miR-326 mimics was sufficient to inhibit TGF-b1 expression and attenuate the fibrotic response. Moreover, human IPF lung specimens had markedly diminished miR-326 expression as compared with nonfibrotic lungs. Additional targets of miR-326 controlling TGF-b signaling and fibrosis-related pathways were identified, and miR-326 was found to down-regulate profibrotic genes, such as Ets1, Smad3, and matrix metalloproteinase 9, whereas it up-regulates antifibrotic genes, such as Smad7. Our results suggest for the first time that miR-326 plays a key role in regulating TGF-b1 expression and other profibrotic genes and could be useful in developing better therapeutic strategies for alleviating lung fibrosis.

An epidemiological profile of vitiligo in Calcutta is presented. Prevalence data were gathered from 15,685 individuals drawn from the general population; pedigree data were collected through 293 vitiligo patients. The overall prevalence of vitiligo is about 5 per 1,000 individuals. There are no significant sex or age differences in prevalence rates. About a 4.5-fold increase in prevalence is observed among close biological relatives of affected individuals. There is, however, no clearcut correspondence between relative risks and kinship coefficients. There are no significant differences in the frequencies of various types of vitiligo between probands with and without positive family history. The overall mean and modal ages of onset are about 22 years and 15 years, respectively. The mean ages among males (24.8 years) and females (19.3 years) are significantly different.

Imaging is playing an increasingly important role in the detection of prostate cancer (PCa). This review summarizes the key imaging modalities—multiparametric ultrasound (US), multiparametric magnetic resonance imaging (MRI), MRI–US fusion imaging, and positron emission tomography (PET) imaging—used in the diagnosis and localization of PCa. Emphasis is laid on the biological and functional characteristics of tumors that rationalize the use of a specific imaging technique. Changes to anatomical architecture of tissue can be detected by anatomical grayscale US and T2-weighted MRI. Tumors are known to progress through angiogenesis—a fact exploited by Doppler and contrast-enhanced US and dynamic contrast-enhanced MRI. The increased cellular density of tumors is targeted by elastography and diffusion-weighted MRI. PET imaging employs several different radionuclides to target the metabolic and cellular activities during tumor growth. Results from studies using these various imaging techniques are discussed and compared.

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