Diminazene aceturate (DIZE), an angiotensin-converting enzyme 2 (ACE2) activator, exerts anti-inflammatory and antifibrotic effects in a variety of human chronic diseases. However, the role of DIZE in kidney fibrosis and the underlying mechanism remain unclear. Therefore, we investigated the effects of DIZE on the progression of renal fibrosis after unilateral ureteral obstruction (UUO), a well-established model of chronic kidney disease. Methods: C57BL/6 female or male mice were subjected to right UUO. Mice received 15 mg/kg DIZE or vehicle (saline) daily. On the 7th day after UUO, kidneys were collected for analysis of renal fibrosis (α-smooth muscle actin, phosphorylated SMAD3, transforming growth factor (TGF)-β, Masson’s trichrome, and Sirius red staining), inflammation (macrophage infiltration, proinflammatory cytokines/ chemokines), apoptosisecrotic cell death (TUNEL and periodic acid-Schiff staining), and ACE2 activity and messenger RNA (mRNA) expression. Results: Treatment with DIZE exacerbated renal fibrosis by upregulating the profibrotic TGF-β/SMAD3 pathway, proinflammatory cytokine/chemokines (interleukin [IL]-1β, monocyte chemoattractant protein-1, IL-6, and macrophage inflammatory protein-2) levels, M2 macrophage accumulation (CD206, IL-4, IL-10, and CX3CL1), and apoptoticecrotic cell death in the obstructed kidneys of female mice but not male mice. However, DIZE treatment had no effect on ACE2 activity or mRNA expression. Conclusion: DIZE exacerbates UUO-induced renal fibrosis by aggravating tubular damage, apoptosis, and inflammation through independent of angiotensin (1–7), angiotensin II levels, and ACE2 expression/activity, rather than protecting against renal fibrosis after UUO. DIZE also has powerful effects on recruiting macrophages, including the M2-polarized subtype, in female UUO mice.

Purpose: Smoking is a risk factor for the development of asthma and worsens the long-term prognosis of asthma. This study investigated the effect of cigarette smoke extract (CSE) on innate immune cells such as innate lymphoid cells (ILCs) and macrophages in a murine model of induced asthma. Methods: Six-week-old female BALB/C mice were exposed to ovalbumin (OVA) via an intranasal route with or without CSE for 8 weeks to establish a chronic murine asthma model. Airway hyperresponsiveness (AHR), airway inflammatory cells from bronchoalveolar lavage fluid, and the population of CD4 + T cells, ILCs, and macrophages in the lungs were studied to evaluate the effect of chronic CSE exposure on asthma. Results: Mice intranasally exposed to CSE along with OVA treatment (CSE/OVA) had significantly enhanced AHR, eosinophilic inflammation, increased IL-13 and IL-17 producing CD4 + T cells compared to mice intranasally exposed to OVA only. On the contrary, the frequency of Foxp3 + in CD4 + T cells was reduced in the CSE/OVA group. CSE enhanced the dendritic cell (DC) population, especially MHCII + DC with antigen-presenting capacity. Among ILCs, the CSE/OVA group showed a significant increase of IL-13-producing type 2 ILCs, but not interferon-γ+ ILC1s and IL-17 + ILC3s. . Among macrophages, alveolar macrophage and Ym-1 and FIZZ1 positive M2 macrophage populations were significantly induced by CSE exposure alone and when combined with OVA treatment. Conclusion In this study, we showed that long-term exposure to cigarette smoke contributes to the inception and aggravation of asthmatic inflammation by enhancing DCs, ILC2, and M2 alveolar macrophage populations in the mouse model.

No abstract available.
Biopsy, Fine-Needle* ; Thyroid Neoplasms*

No abstract available.
Lymphoma* ; Neoplasms, Plasma Cell*

No abstract available.

No abstract available.

Background: Digital pathology (DP) using whole slide imaging is a recently emerging game changer technology that can fundamentally change the way of working in pathology. The Digital Pathology Study Group (DPSG) of the Korean Society of Pathologists (KSP) published a consensus report on the recommendations for pathologic practice using DP. Accordingly, the need for the development and implementation of a quality assurance program (QAP) for DP has been raised. Methods: To provide a standard baseline reference for internal and external QAP for DP, the members of the Committee of Quality Assurance of the KSP developed a checklist for the Redbook and a QAP trial for DP based on the prior DPSG consensus report. Four leading institutes participated in the QAP trial in the first year, and we gathered feedback from these institutes afterwards. Results: The newly developed checklists of QAP for DP contain 39 items (216 score): eight items for quality control of DP systems; three for DP personnel; nine for hardware and software requirements for DP systems; 15 for validation, operation, and management of DP systems; and four for data security and personal information protection. Most participants in the QAP trial replied that continuous education on unfamiliar terminology and more practical experience is demanding. Conclusions The QAP for DP is essential for the safe implementation of DP in pathologic practice. Each laboratory should prepare an institutional QAP according to this checklist, and consecutive revision of the checklist with feedback from the QAP trial for DP needs to follow.

A 41-year-old female presented with complaint of left hip and buttock pain. Magnetic resonance imaging (MRI) showed multi-focal bone marrow signal intensity changes in left iliac bone, sacrum and femur with an area of necrosis. The primary radiological differential diagnosis was multi-focal tuberculous osteomyelitis. Subsequent pelvic bone biopsy and bone marrow biopsy confirmed the diagnosis of B-cell precursor acute lymphoblastic leukemia with extensive necrosis, which is infrequent in leukemia. When musculoskeletal symptoms precede peripheral blood abnormalities and MRI scanning reveals multi-focal necrotic lesions rather than diffuse signal change, it can be difficult to identify and/or advance leukemia as differential diagnosis.

Background: Immunohistochemistry (IHC) has played an essential role in the diagnosis of hematolymphoid neoplasms. However, IHC interpretations can be challenging in daily practice, and exponentially expanding volumes of IHC data are making the task increasingly difficult. We therefore developed a machine-learning expert-supporting system for diagnosing lymphoid neoplasms. Methods: A probabilistic decision-tree algorithm based on the Bayesian theorem was used to develop mobile application software for iOS and Android platforms. We tested the software with real data from 602 training and 392 validation cases of lymphoid neoplasms and compared the precision hit rates between the training and validation datasets. Results: IHC expression data for 150 lymphoid neoplasms and 584 antibodies was gathered. The precision hit rates of 94.7% in the training data and 95.7% in the validation data for lymphomas were not statistically significant. Results in most B-cell lymphomas were excellent, and generally equivalent performance was seen in T-cell lymphomas. The primary reasons for lack of precision were atypical IHC profiles for certain cases (e.g., CD15-negative Hodgkin lymphoma), a lack of disease-specific markers, and overlapping IHC profiles of similar diseases. Conclusions Application of the machine-learning algorithm to diagnosis precision produced acceptable hit rates in training and validation datasets. Because of the lack of origin- or disease- specific markers in differential diagnosis, contextual information such as clinical and histological features should be taken into account to make proper use of this system in the pathologic decision-making process.

Purpose: Asthma is a chronic airway inflammatory disorder and is associated with macrophages. Statin, a well-known lipid-lowering agent, has recently been noted for its anti-inflammatory effect on macrophage. This study was designed to evaluate the antiasthmatic effect of atorvastatin via modulation of macrophage activation by using an animal model of allergic asthma. Methods: Atorvastatin 40 mg/kg was given by gavage once a day for 3 days before challenge of ovalbumin (OVA); airway hyperresponsiveness (AHR), airway inflammatory cells, and cytokines were evaluated in the murine asthma model. The direct effect of atorvastatin on the activation of macrophages In vitro was determined using the alveolar macrophage cell line CRL-2456. Results: Administration of atorvastatin reduced the numbers of total inflammatory cells, macrophages, and eosinophils as well as lung histology enhanced in the murine asthma model. AHR measured by enhanced pause was significantly reduced after atorvastatin administration in the murine asthma model (P< 0.05). Atorvastatin administration resulted in the reduction in serum OVA-specific IgE levels and the increase in serum OVA-specific IgG2a levels (P< 0.05). The mRNA levels of Ccr3, Il-17, and Muc5ac enhanced by OVA challenge were decreased by treatment with atorvastatin (P< 0.05). Along with these improvement in allergic inflammatory changes, the population of CD11c-CD206+ macrophages as well as the expression of Ym-1 and Relm-α in the lungs were reduced with atorvastatin (P< 0.05). In vitro test with CRL-2456 showed that atorvastatin reduced the expression of Cd206, Arg-1, and Fgf-2 induced by IL-4 stimulation (P< 0.05). Conclusion This study highlighted the antiasthmatic effect of atorvastatin on the suppression of M2 macrophage activation in allergic asthma.