Intrathoracic non-tuberculous mycobacteriosis with endobronchial lesion in a child aged 11 with HIV infection diagnosed by bronchoscopic biopsy, EBUS-TBNA and confocal laser endomicroscopy.

The diagnosis of intrathoracic non-tuberculous mycobacteriosis (NTM) is challenging. We report a case of a pediatric pulmonary NTM with endobronchial lesion and lymphadenitis in a child with HIV infection diagnosed by bronchoscopic biopsy, EBUS-TBNA and probe-based confocal laser endomicroscopy (pCLE). The pCLE showed a large number of highly fluorescent cells and zones of density and disorganized elastin fibers at alveolar areas.

Probe-based confocal laser endomicroscopy in the diagnosis of diffuse cystic lung disease in Sjögren's syndrome.

Sjögren's syndrome is a systemic autoimmune disease characterized by lymphocytic infiltration of various organs with a wide frequency of pulmonary involvement. Diffuse cystic lung disease in Sjögren's syndrome is a rare condition and requires differential diagnosis with other cystic pathologies such as lymphangioleyomiomatosis or Langerhans cell histiocytosis. Probe-based confocal laser endomicroscopy (pCLE) is a method of in vivo investigation of airways and lung tissue at a microscopic level during bronchoscopy.

COVID-19 and : New Atherogenic Factor? A Case Report and Autopsy Findings.

Patients with COVID-19 demonstrate higher rates of cardiovascular complications, including thromboses and thromboembolism. One may suppose that the action of SARS-CoV-2 transforms stable atherosclerotic plaques into unstable status. Cardiovascular complications in COVID-19 may be caused by progressive viral alteration of the blood vessels, including .

Ectonucleoside triphosphate diphosphohydrolase-1 (CD39) impacts TGF-β1 responses: insights into cardiac fibrosis and function following myocardial infarction.

Extracellular purine nucleotides and nucleosides released from activated or injured cells influence multiple aspects of cardiac physiology and pathophysiology. Ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1; CD39) hydrolyzes released nucleotides and thereby regulates the magnitude and duration of purinergic signaling. However, the impact of CD39 activity on post-myocardial infarction (MI) remodeling is incompletely understood.

Integrated Cells and Collagen Fibers Spatial Image Analysis.

Modern technologies designed for tissue structure visualization like brightfield microscopy, fluorescent microscopy, mass cytometry imaging (MCI) and mass spectrometry imaging (MSI) provide large amounts of quantitative and spatial information about cells and tissue structures like vessels, bronchioles etc. Many published reports have demonstrated that the structural features of cells and extracellular matrix (ECM) and their interactions strongly predict disease development and progression. Computational image analysis methods in combination with spatial analysis and machine learning can reveal novel structural patterns in normal and diseased tissue.

HLA-DR cancer cells expression correlates with T cell infiltration and is enriched in lung adenocarcinoma with indolent behavior.

Lung adenocarcinoma (ADC) is a heterogeneous group of tumors associated with different survival rates, even when detected at an early stage. Here, we aim to investigate whether CyTOF identifies cellular and molecular predictors of tumor behavior. We developed and validated a CyTOF panel of 34 antibodies in four ADC cell lines and PBMC.

Adenosine/TGFβ axis in regulation of mammary fibroblast functions.

Cancer associated fibroblasts (CAF) play a key role in cancer progression and metastasis. Diminished TGFβ response on CAF correlates with poor outcome and recurrence in cancer patients. Mechanisms behind lost TGFβ signaling on CAF are poorly understood, but, utilizing MMTV-PyMT mouse model, we have previously demonstrated that in tumor microenvironment myeloid cells, producing adenosine, contribute to downregulated TGFβ signaling on CAFs.

[Morphological characteristics of pulmonary tuberculosis concurrent with lung cancer].

Unlabelled: The pathogenetic relationship between pulmonary tuberculosis and lung cancer in their concurrence is now still the subject of discussion.

Objective: To study the pathogenetic relationship between pulmonary tuberculosis and lung cancer.

Material And Methods: The investigators examined surgical material from 51 patients (41 men) aged 41-73 years (mean age, 63.

Integration of the ImageJ Ecosystem in the KNIME Analytics Platform.

Open-source software tools are often used for analysis of scientific image data due to their flexibility and transparency in dealing with rapidly evolving imaging technologies. The complex nature of image analysis problems frequently requires many tools to be used in conjunction, including image processing and analysis, data processing, machine learning and deep learning, statistical analysis of the results, visualization, correlation to heterogeneous but related data, and more. However, the development, and therefore application, of these computational tools is impeded by a lack of integration across platforms.

Myeloid Cell-Derived TGFβ Signaling Regulates ECM Deposition in Mammary Carcinoma via Adenosine-Dependent Mechanisms.

TGFβ plays a crucial role in the tumor microenvironment by regulating cell-cell and cell-stroma interactions. We previously demonstrated that TGFβ signaling on myeloid cells regulates expression of CD73, a key enzyme for production of adenosine, a protumorigenic metabolite implicated in regulation of tumor cell behaviors, immune response, and angiogenesis. Here, using an MMTV-PyMT mouse mammary tumor model, we discovered that deletion of TGFβ signaling on myeloid cells (PyMT/TGFβRII) affects extracellular matrix (ECM) formation in tumor tissue, specifically increasing collagen and decreasing fibronectin deposition.

Beyond the H&E: Advanced Technologies for in situ Tissue Biomarker Imaging.

For decades, histopathology with routine hematoxylin and eosin staining has been and remains the gold standard for reaching a morphologic diagnosis in tissue samples from humans and veterinary species. However, within the past decade, there has been exponential growth in advanced techniques for in situ tissue biomarker imaging that bridge the divide between anatomic and molecular pathology. It is now possible to simultaneously observe localization and expression magnitude of multiple protein, nucleic acid, and molecular targets in tissue sections and apply machine learning to synthesize vast, image-derived datasets.

Emerin Deregulation Links Nuclear Shape Instability to Metastatic Potential.

Abnormalities in nuclear shape are a well-known feature of cancer, but their contribution to malignant progression remains poorly understood. Here, we show that depletion of the cytoskeletal regulator, Diaphanous-related formin 3 (DIAPH3), or the nuclear membrane-associated proteins, lamin A/C, in prostate and breast cancer cells, induces nuclear shape instability, with a corresponding gain in malignant properties, including secretion of extracellular vesicles that contain genomic material. This transformation is characterized by a reduction and/or mislocalization of the inner nuclear membrane protein, emerin.

[On the histo- and morphogenesis of sclerosing pneumocytoma and its diagnostic criteria].

The paper presents the data available in the literature on the pathogenesis, clinical and morphological, histological and immunohistochemical features of pulmonary sclerosing pneumocytoma (SP). The paper gives the detailed histological and immunohistochemical characteristics of 6 SP cases. The need for the differential diagnosis of SP is determined by the features and complexity of their histo- and morphogenesis within a single tumor and a complex diagnostic study.

Ablation Is Associated With Increased Nitro-Oxidative Stress During Ischemia-Reperfusion Injury: Implications for Human Ischemic Cardiomyopathy.

Background: Despite increased secondary cardiovascular events in patients with ischemic cardiomyopathy (ICM), the expression of innate cardiac protective molecules in the hearts of patients with ICM is incompletely characterized. Therefore, we used a nonbiased RNAseq approach to determine whether differences in cardiac protective molecules occur with ICM.

Methods And Results: RNAseq analysis of human control and ICM left ventricular samples demonstrated a significant decrease in expression with ICM.

Correction: Deletion of Fibroblast Growth Factor Receptor 2 from the Peri-Wolffian Duct Stroma Leads to Ureteric Induction Abnormalities and Vesicoureteral Reflux.

[This corrects the article DOI: 10.1371/journal.pone.

Impact of cardiac-specific expression of CD39 on myocardial infarct size in mice.

Aims: Prior work suggests that ischemic preconditioning increases the level of CD39 in the heart and contributes to cardiac protection. Therefore, we examined if targeted cardiac expression of CD39 protects against myocardial injury.

Main Methods: Mice with cardiac-specific expression of human CD39 (αMHC/hCD39-Tg) were generated, characterized and subjected to left coronary artery ischemia-reperfusion injury and infarct size at 24h following injury quantified.

Role of the CD39/CD73 Purinergic Pathway in Modulating Arterial Thrombosis in Mice.

Objective: Circulating blood cells and endothelial cells express ectonucleoside triphosphate diphosphohydrolase-1 (CD39) and ecto-5'-nucleotidase (CD73). CD39 hydrolyzes extracellular ATP or ADP to AMP. CD73 hydrolyzes AMP to adenosine.

Extracellular nucleotide regulation and signaling in cardiac fibrosis.

Following myocardial infarction, purinergic nucleotides and nucleosides are released via non-specific and specific mechanisms in response to cellular activation, stress, or injury. These extracellular nucleotides are potent mediators of physiologic and pathologic responses, contributing to the inflammatory and fibrotic milieu within the injured myocardium. Via autocrine or paracrine signaling, cell-specific effects occur through differentially expressed purinergic receptors of the P2X, P2Y, and P1 families.

Delayed treatment with PTBA analogs reduces postinjury renal fibrosis after kidney injury.

No therapies have been shown to accelerate recovery or prevent fibrosis after acute kidney injury (AKI). In part, this is because most therapeutic candidates have to be given at the time of injury and the diagnosis of AKI is usually made too late for drugs to be efficacious. Strategies to enhance post-AKI repair represent an attractive approach to address this.

A PTBA small molecule enhances recovery and reduces postinjury fibrosis after aristolochic acid-induced kidney injury.

Phenylthiobutanoic acids (PTBAs) are a new class of histone deacetylase (HDAC) inhibitors that accelerate recovery and reduce postinjury fibrosis after ischemia-reperfusion-induced acute kidney injury. However, unlike the more common scenario in which patients present with protracted and less clearly defined onset of renal injury, this model of acute kidney injury gives rise to a clearly defined injury that begins to resolve over a short period of time. In these studies, we show for the first time that treatment with the PTBA analog methyl-4-(phenylthio)butanoate (M4PTB) accelerates recovery and reduces postinjury fibrosis in a progressive model of acute kidney injury and renal fibrosis that occurs after aristolochic acid injection in mice.

Histone deacetylase inhibitor enhances recovery after AKI.

At present, there are no effective therapies to ameliorate injury, accelerate recovery, or prevent postinjury fibrosis after AKI. Here, we sought to identify candidate compounds that accelerate recovery after AKI by screening for small molecules that increase proliferation of renal progenitor cells in zebrafish embryos. One compound identified from this screen was the histone deacetylase inhibitor methyl-4-(phenylthio)butanoate, which we subsequently administered to zebrafish larvae and mice 24-48 hours after inducing AKI.

Deletion of fibroblast growth factor receptor 2 from the peri-wolffian duct stroma leads to ureteric induction abnormalities and vesicoureteral reflux.

Purpose: Pax3cre-mediated deletion of fibroblast growth factor receptor 2 (Fgfr2) broadly in renal and urinary tract mesenchyme led to ureteric bud (UB) induction defects and vesicoureteral reflux (VUR), although the mechanisms were unclear. Here, we investigated whether Fgfr2 acts specifically in peri-Wolffian duct stroma (ST) to regulate UB induction and development of VUR and the mechanisms of Fgfr2 activity.

Methods: We conditionally deleted Fgfr2 in ST (Fgfr2(ST-/-)) using Tbx18cre mice.

Organ-specific defects in insulin-like growth factor and insulin receptor signaling in late gestational asymmetric intrauterine growth restriction in Cited1 mutant mice.

Late gestational placental insufficiency resulting in asymmetric intrauterine organ growth restriction (IUGR) is associated with an increased incidence of diabetes, cardiovascular and renal disease in adults. The molecular mechanisms mediating these defects are poorly understood. To explore this, we investigated the mechanisms leading to IUGR in Cited1 knockout mice, a genetic model of late gestational placental insufficiency.

Bmp2 and Bmp4 exert opposing effects in hypoxic pulmonary hypertension.

The bone morphogenetic protein (BMP) type 2 receptor ligand, Bmp2, is upregulated in the peripheral pulmonary vasculature during hypoxia-induced pulmonary hypertension (PH). This contrasts with the expression of Bmp4, which is expressed in respiratory epithelia throughout the lung. Unlike heterozygous null Bmp4 mice (Bmp4(LacZ/+)), which are protected from the development of hypoxic PH, mice that are heterozygous null for Bmp2 (Bmp2(+/-)) develop more severe hypoxic PH than their wild-type littermates.