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Respiratory Research Nov 2023Idiopathic pulmonary fibrosis (IPF) is a heterogeneous disease that is pathologically characterized by areas of normal-appearing lung parenchyma, active fibrosis...
BACKGROUND
Idiopathic pulmonary fibrosis (IPF) is a heterogeneous disease that is pathologically characterized by areas of normal-appearing lung parenchyma, active fibrosis (transition zones including fibroblastic foci) and dense fibrosis. Defining transcriptional differences between these pathologically heterogeneous regions of the IPF lung is critical to understanding the distribution and extent of fibrotic lung disease and identifying potential therapeutic targets. Application of a spatial transcriptomics platform would provide more detailed spatial resolution of transcriptional signals compared to previous single cell or bulk RNA-Seq studies.
METHODS
We performed spatial transcriptomics using GeoMx Nanostring Digital Spatial Profiling on formalin-fixed paraffin-embedded (FFPE) tissue from 32 IPF and 12 control subjects and identified 231 regions of interest (ROIs). We compared normal-appearing lung parenchyma and airways between IPF and controls with histologically normal lung tissue, as well as histologically distinct regions within IPF (normal-appearing lung parenchyma, transition zones containing fibroblastic foci, areas of dense fibrosis, and honeycomb epithelium metaplasia).
RESULTS
We identified 254 differentially expressed genes (DEGs) between IPF and controls in histologically normal-appearing regions of lung parenchyma; pathway analysis identified disease processes such as EIF2 signaling (important for cap-dependent mRNA translation), epithelial adherens junction signaling, HIF1α signaling, and integrin signaling. Within IPF, we identified 173 DEGs between transition and normal-appearing lung parenchyma and 198 DEGs between dense fibrosis and normal lung parenchyma; pathways dysregulated in both transition and dense fibrotic areas include EIF2 signaling pathway activation (upstream of endoplasmic reticulum (ER) stress proteins ATF4 and CHOP) and wound healing signaling pathway deactivation. Through cell deconvolution of transcriptome data and immunofluorescence staining, we confirmed loss of alveolar parenchymal signals (AGER, SFTPB, SFTPC), gain of secretory cell markers (SCGB3A2, MUC5B) as well as dysregulation of the upstream regulator ATF4, in histologically normal-appearing tissue in IPF.
CONCLUSIONS
Our findings demonstrate that histologically normal-appearing regions from the IPF lung are transcriptionally distinct when compared to similar lung tissue from controls with histologically normal lung tissue, and that transition zones and areas of dense fibrosis within the IPF lung demonstrate activation of ER stress and deactivation of wound healing pathways.
Topics: Humans; Eukaryotic Initiation Factor-2; Idiopathic Pulmonary Fibrosis; Lung; Transcriptome; Fibrosis
PubMed: 37978501
DOI: 10.1186/s12931-023-02572-6 -
Cardiovascular Diagnosis and Therapy Jun 2018Congenital pulmonary vascular anomalies are typically found in infancy or early childhood however, some may remain silent and present in adult patients. Anomalies may be... (Review)
Review
Congenital pulmonary vascular anomalies are typically found in infancy or early childhood however, some may remain silent and present in adult patients. Anomalies may be separated into anatomic categories based on involvement of the pulmonary arteries, pulmonary veins or both with or without involvement of the lung parenchyma. Association with congenital heart disease and other syndromes is very common. Computed tomography (CT) and magnetic resonance imaging (MRI) are both invaluable at assessment of these anomalies allowing for both diagnosis and detailed treatment planning. This article will focus primarily on the use of CT, as the high resolution evaluation of the lung parenchyma is also important in many of these conditions. In young patients especially, rapid heart rate and concerns of radiation exposure are important considerations when performing CT. This article will discuss scan techniques as well as clinical diagnostic considerations and basic endovascular treatment of congenital pulmonary vascular anomalies.
PubMed: 30057871
DOI: 10.21037/cdt.2018.01.02 -
Biology Aug 2023The central nervous system (CNS) plays a crucial role in regulating bodily functions by sensing and integrating environmental cues and maintaining proper physiological... (Review)
Review
The central nervous system (CNS) plays a crucial role in regulating bodily functions by sensing and integrating environmental cues and maintaining proper physiological conditions. Recent research has revealed that CNS functions are closely coordinated with the immune system. As even minor disturbances of the immune system in the CNS can lead to various dysfunctions, diseases, or even death, it is highly specialized and segregated from that in peripheral regions. Microglia in the parenchyma and macrophages at the interface between the CNS and peripheral regions are essential immune cells in the CNS that monitor environmental changes. Recent omics analyses have revealed that these cells exhibit highly heterogeneous populations. In this review, we summarize the functions and diversity of microglia in the brain parenchyma and those of macrophages in the border regions, such as the meninges, perivascular spaces, and choroid plexus.
PubMed: 37626977
DOI: 10.3390/biology12081091 -
Fluids and Barriers of the CNS Feb 2022The glymphatic hypothesis proposes a mechanism for extravascular transport into and out of the brain of hydrophilic solutes unable to cross the blood-brain barrier. It... (Review)
Review
The glymphatic hypothesis proposes a mechanism for extravascular transport into and out of the brain of hydrophilic solutes unable to cross the blood-brain barrier. It suggests that there is a circulation of fluid carrying solutes inwards via periarterial routes, through the interstitium and outwards via perivenous routes. This review critically analyses the evidence surrounding the mechanisms involved in each of these stages. There is good evidence that both influx and efflux of solutes occur along periarterial routes but no evidence that the principal route of outflow is perivenous. Furthermore, periarterial inflow of fluid is unlikely to be adequate to provide the outflow that would be needed to account for solute efflux. A tenet of the hypothesis is that flow sweeps solutes through the parenchyma. However, the velocity of any possible circulatory flow within the interstitium is too small compared to diffusion to provide effective solute movement. By comparison the earlier classical hypothesis describing extravascular transport proposed fluid entry into the parenchyma across the blood-brain barrier, solute movements within the parenchyma by diffusion, and solute efflux partly by diffusion near brain surfaces and partly carried by flow along "preferred routes" including perivascular spaces, white matter tracts and subependymal spaces. It did not suggest fluid entry via periarterial routes. Evidence is still incomplete concerning the routes and fate of solutes leaving the brain. A large proportion of the solutes eliminated from the parenchyma go to lymph nodes before reaching blood but the proportions delivered directly to lymph or indirectly via CSF which then enters lymph are as yet unclear. In addition, still not understood is why and how the absence of AQP4 which is normally highly expressed on glial endfeet lining periarterial and perivenous routes reduces rates of solute elimination from the parenchyma and of solute delivery to it from remote sites of injection. Neither the glymphatic hypothesis nor the earlier classical hypothesis adequately explain how solutes and fluid move into, through and out of the brain parenchyma. Features of a more complete description are discussed. All aspects of extravascular transport require further study.
Topics: Animals; Biological Transport; Glymphatic System; Humans
PubMed: 35115036
DOI: 10.1186/s12987-021-00282-z -
Chirurgia (Bucharest, Romania : 1990) 2017Laparoscopic adrenalectomy became the gold standard for adrenal disease, from incidentaloma to cancer. Partial adrenalectomy is difficult to accept due to its technical...
Laparoscopic adrenalectomy became the gold standard for adrenal disease, from incidentaloma to cancer. Partial adrenalectomy is difficult to accept due to its technical difficulties as well as hemorrhagic risk and a consensus has not been reached. On the other hand, in selected cases of benign adrenal tumors, adrenalectomy may be futile, partial resections being perfectly justified and with lower hemorrhagic risks. For functioning tumors smaller than 3 cm with an anterior or lateral location, partial adrenalectomy may be indicated. The key points reside in adenoma identification, preservation of the remaining glandular parenchyma and its blood supply with dissection in the space between the adenoma and the normal parenchyma. Laparoscopic partial adrenalectomy is feasible and effective for the treatment of benign tumors. Although partial resections have clear-cut advantages over conventional adrenalectomy especially for bilateral tumors, it remains a difficult intervention.
Topics: Adrenal Gland Diseases; Adrenal Gland Neoplasms; Adrenalectomy; Feasibility Studies; Humans; Laparoscopy; Treatment Outcome
PubMed: 28266298
DOI: 10.21614/chirurgia.112.1.77 -
Frontiers in Cellular Neuroscience 2024Innate lymphoid cells (ILCs) are largely tissue-resident cells that participate in the maintenance of tissue homeostasis and react early to inflammatory events. Mature... (Review)
Review
Innate lymphoid cells (ILCs) are largely tissue-resident cells that participate in the maintenance of tissue homeostasis and react early to inflammatory events. Mature ILCs are divided into three major groups based on the transcription factors required for their development and function. Under physiological conditions, ILCs are present within the choroid plexus and meninges while the CNS parenchyma is almost devoid of these cells. However, pathological conditions such as autoimmune neuroinflammation and viral infections of the CNS result in the infiltration of ILCs into parenchyma. In this article, we provide an overview of the involvement and function of the ILCs within the CNS during physiological conditions and in infections, autoimmune diseases, neurodegeneration, and injury.
PubMed: 38450285
DOI: 10.3389/fncel.2024.1364485 -
Plants (Basel, Switzerland) Jun 2021Woody plants are characterised by a highly complex vascular system, wherein the secondary xylem (wood) is responsible for the axial transport of water and various... (Review)
Review
Woody plants are characterised by a highly complex vascular system, wherein the secondary xylem (wood) is responsible for the axial transport of water and various substances. Previous studies have focused on the dead conductive elements in this heterogeneous tissue. However, the living xylem parenchyma cells, which constitute a significant functional fraction of the wood tissue, have been strongly neglected in studies on tree biology. Although there has recently been increased research interest in xylem parenchyma cells, the mechanisms that operate in these cells are poorly understood. Therefore, the present review focuses on selected roles of xylem parenchyma and its relevance in wood functioning. In addition, to elucidate the importance of xylem parenchyma, we have compiled evidence supporting the hypothesis on the significance of parenchyma cells in tree functioning and identified the key unaddressed questions in the field.
PubMed: 34205276
DOI: 10.3390/plants10061247 -
Polymers Feb 2022In this paper, we introduced a bamboo longitudinal flattening technology and analyzed the effects of the softening-flattening process on the physical and mechanical...
In this paper, we introduced a bamboo longitudinal flattening technology and analyzed the effects of the softening-flattening process on the physical and mechanical properties of moso bamboo. This is a newer bamboo processing technology that can enhance the utilization and reduce pollution compared with traditional bamboo-based products. Results showed that the parenchyma cells distorted and compacted due to the flattening process. The hemicellulose and cellulose content decreased, while the content of lignin presented an increasing tendency. As expected, the dimensional stability of moso bamboo enhanced due to the decrement of hemicellulose. The softening-flattening process positively contributed to the micro-mechanical properties of treated bamboo specimens. For example, the hardness and modulus of elasticity of the untreated bamboo sample increased from 0.58 and 15.7 GPa to 0.8 and 17.5 GPa, respectively. In addition, the changes in cellulose crystallinity and mechanical properties were also investigated in this paper. The cellulose crystallinity increased from 37.5% to 43.2%, significantly. However, the modulus of rupture of the flattened bamboo board decreased from 9000 to 7500 MPa due to the grooves made by the flattening roller. The MOE of flattening bamboo board showed the same decreasing tendency.
PubMed: 35215729
DOI: 10.3390/polym14040816