Loss of cell junctional components and matrix alterations drive cell desquamation and fibrotic changes in Idiopathic Pulmonary Fibrosis.

Unlabelled: The distal bronchioles in Idiopathic Pulmonary Fibrosis (IPF) exhibit histopathological abnormalities such as bronchiolization, peribronchiolar fibrosis and honeycomb cysts that contribute to the overall architectural remodeling of lung tissue seen in the disease. Here we describe an additional histopathologic finding of epithelial desquamation in patients with IPF, wherein epithelial cells detach from the basement membrane of the distal bronchioles. To understand the mechanism driving this pathology, we performed spatial transcriptomics of the epithelial cells and spatial proteomics of the basement membrane of the distal bronchioles from IPF patients and patients with no prior history of lung disease.

Dedifferentiated early postnatal lung myofibroblasts redifferentiate in adult disease.

Alveolarization ensures sufficient lung surface area for gas exchange, and during bulk alveolarization in mice (postnatal day [P] 4.5-14.5), alpha-smooth muscle actin (SMA) myofibroblasts accumulate, secrete elastin, and lay down alveolar septum.

The age of bone marrow dictates the clonality of smooth muscle-derived cells in atherosclerotic plaques.

Aging is the predominant risk factor for atherosclerosis, the leading cause of death. Rare smooth muscle cell (SMC) progenitors clonally expand giving rise to up to ~70% of atherosclerotic plaque cells; however, the effect of age on SMC clonality is not known. Our results indicate that aged bone marrow (BM)-derived cells non-cell autonomously induce SMC polyclonality and worsen atherosclerosis.

Drug infused AlO-bioactive glass coatings toward the cure of orthopedic infection.

A unique implant coated substrate with dual-drug-eluting system exhibiting antibacterial, anti-inflammatory, and bone regenerative capacity has been fabricated using spray pyrolysis deposition (SPD) method. Bioglass (BG) and BG-alumina (BG-Al) composites coatings with different concentrations of Al incorporated on BG network over the Cp-Ti substrate were fabricated using SPD technique. Phase purity of BG and BG-Al composites were analyzed by XRD in which NaCaSiO and β-NaCa(PO)SiO) and Na(AlSiO) phases were formed.

Distinct roles of KLF4 in mesenchymal cell subtypes during lung fibrogenesis.

During lung fibrosis, the epithelium induces signaling to underlying mesenchyme to generate excess myofibroblasts and extracellular matrix; herein, we focus on signaling in the mesenchyme. Our studies indicate that platelet-derived growth factor receptor (PDGFR)-β cells are the predominant source of myofibroblasts and Kruppel-like factor (KLF) 4 is upregulated in PDGFR-β cells, inducing TGFβ pathway signaling and fibrosis. In fibrotic lung patches, KLF4 is down-regulated, suggesting KLF4 levels decrease as PDGFR-β cells transition into myofibroblasts.

Impact of copper on in-vitro biomineralization, drug release efficacy and antimicrobial properties of bioactive glasses.

This study highlights the incorporation of copper in the bioactive glasses (BAG) network that greatly influences the morphological, structural and biological properties. By increasing the copper incorporation in BAG, increment in cell volume was obtained from XRD patterns, and concomitantly, dominant phosphate bands and latent silica bands were observed by FT-IR and Raman spectroscopic results. The Cu addition also affected particle appearance to vary from spherical to cluster-like cubes in 1.

The novel gene apnoia regulates Drosophila tracheal tube size.

Background: Distinct tube size is critical for the function of human tubular organs such as the lung, vascular system, and kidney. Aberrant tube sizes can lead to devastating human illnesses, including polycystic kidney disease. The Drosophila trachea provides a premier genetic system to investigate the fundamental mechanisms that regulate tube size.

regulates apical luminal matrix to control tube size in trachea.

The embryonic tracheal network is an excellent model to study tube size. The chitin-based apical luminal matrix and cell polarity are well known to regulate tube size in trachea. Defects in luminal matrix and cell polarity lead to tube overexpansion.

NCK-dependent pericyte migration promotes pathological neovascularization in ischemic retinopathy.

Pericytes are mural cells that surround capillaries and control angiogenesis and capillary barrier function. During sprouting angiogenesis, endothelial cell-derived platelet-derived growth factor-B (PDGF-B) regulates pericyte proliferation and migration via the platelet-derived growth factor receptor-β (PDGFRβ). PDGF-B overexpression has been associated with proliferative retinopathy, but the underlying mechanisms remain poorly understood.

Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells.

Smooth muscle cells (SMCs) play a key role in atherogenesis. However, mechanisms regulating expansion and fate of pre-existing SMCs in atherosclerotic plaques remain poorly defined. Here we show that multiple SMC progenitors mix to form the aorta during development.

Vascular Cells in Blood Vessel Wall Development and Disease.

The vessel wall is composed of distinct cellular layers, yet communication among individual cells within and between layers results in a dynamic and versatile structure. The morphogenesis of the normal vascular wall involves a highly regulated process of cell proliferation, migration, and differentiation. The use of modern developmental biological and genetic approaches has markedly enriched our understanding of the molecular and cellular mechanisms underlying these developmental events.

The novel Smad protein Expansion regulates the receptor tyrosine kinase pathway to control Drosophila tracheal tube size.

Tubes with distinct shapes and sizes are critical for the proper function of many tubular organs. Here we describe a unique phenotype caused by the loss of a novel, evolutionarily-conserved, Drosophila Smad-like protein, Expansion. In expansion mutants, unicellular and intracellular tracheal branches develop bubble-like cysts with enlarged apical membranes.

Gene expression profiling of Drosophila tracheal fusion cells.

The Drosophila trachea is a premier genetic system to investigate the fundamental mechanisms of tubular organ formation. Tracheal fusion cells lead the branch fusion process to form an interconnected tubular network. Therefore, fusion cells in the Drosophila trachea will be an excellent model to study branch fusion in mammalian tubular organs, such as kidneys and blood vessels.

A comparison of midline and tracheal gene regulation during Drosophila development.

Within the Drosophila embryo, two related bHLH-PAS proteins, Single-minded and Trachealess, control development of the central nervous system midline and the trachea, respectively. These two proteins are bHLH-PAS transcription factors and independently form heterodimers with another bHLH-PAS protein, Tango. During early embryogenesis, expression of Single-minded is restricted to the midline and Trachealess to the trachea and salivary glands, whereas Tango is ubiquitously expressed.

Novel mechanisms of tube-size regulation revealed by the Drosophila trachea.

The size of various tubes within tubular organs such as the lung, vascular system and kidney must be finely tuned for the optimal delivery of gases, nutrients, waste and cells within the entire organism. Aberrant tube sizes lead to devastating human illnesses, such as polycystic kidney disease, fibrocystic breast disease, pancreatic cystic neoplasm and thyroid nodules. However, the underlying mechanisms that are responsible for tube-size regulation have yet to be fully understood.

Evaluation of dose coverage to target volume and normal tissue sparing in the adjuvant radiotherapy of gastric cancers: 3D-CRT compared with dynamic IMRT.

Purpose: To assess the potential advantage of intensity-modulated radiotherapy (IMRT) over 3D-conformal radiotherapy (3D-CRT) planning in postoperative adjuvant radiotherapy for patients with gastric carcinoma.

Methods And Materials: In a retrospective study, for plan comparison, dose distribution was recalculated in 15 patients treated with 3D-CRT on the contoured structures of same CT images using an IMRT technique. 3D-conformal plans with three fields and four-fields were compared with seven-field dynamic IMRT plans.

RNAi interference by dsRNA injection into Drosophila embryos.

Genetic screening is one of the most powerful methods available for gaining insights into complex biological process (1). Over the years many improvements and tools for genetic manipulation have become available in Drosophila (2). Soon after the initial discovery by Frie and Mello (3) that double stranded RNA can be used to knockdown the activity of individual genes in Caenorhabditis elegans, RNA interference (RNAi) was shown to provide a powerful reverse genetic approach to analyze gene functions in Drosophila organ development (4, 5).

Primary gastrointestinal lymphoma: 30-year experience at the Cancer Institute, Madras, India.

A retrospective study was conducted of 49 patients with primary gastrointestinal lymphoma to analyze clinicopathological features, prognostic factors, and results of treatment. Intestinal lymphomas (63%) were more common than gastric lymphomas (29%). Endoscopic biopsy was diagnostic in 64% of gastric lymphomas, while 97% of intestinal lymphomas required laparotomy for diagnosis.