This Month in AJP
Am J Pathol. 2024 Apr 8:S0002-9440(24)00126-3. doi: 10.1016/j.ajpath.2024.04.001. Online ahead of print.NO ABSTRACTPMID:38599460 | DOI:10.1016/j.ajpath.2024.04.001 (Source: Am J Pathol)
Source: Am J Pathol - April 10, 2024 Category: Pathology Source Type: research

Differentiation of type 17 MAIT cells in circulation contributes to the severity of sepsis
This study identified a higher proportion of circulating MAIT17 with expression of IL-17A and RORγt in sepsis patients. The proportion of MAIT17 was correlated with the severity of sepsis. Single-cell RNA sequencing (scRNA-seq) analysis revealed an enhanced expression of lactate dehydrogenase A (LDHA) in MAIT17 in sepsis patients. Cell-culture experiments demonstrated that Phosphoinositide 3-kinase (PI3K)-LDHA signaling was required for RORγt expression in MAIT17. Finally, the elevated levels of plasma IL-18 promoted the differentiation of circulating MAIT17 in sepsis. In summary, this study reveals a new role of circula...
Source: Am J Pathol - April 10, 2024 Category: Pathology Authors: Xinying Li Sicheng Fu Hao Cheng Min Ma Zijian Song Jun Li Shuang Wu Chong Zhang Xiaoxia Wang Maoyu Tang Xuexue Pu Qiang Ji Jinquan Liang Zhibin Zhao Heinrich K örner Bin Li Min Shao Hua Wang Source Type: research

This Month in AJP
Am J Pathol. 2024 Apr 8:S0002-9440(24)00126-3. doi: 10.1016/j.ajpath.2024.04.001. Online ahead of print.NO ABSTRACTPMID:38599460 | DOI:10.1016/j.ajpath.2024.04.001 (Source: Am J Pathol)
Source: Am J Pathol - April 10, 2024 Category: Pathology Source Type: research

Differentiation of type 17 MAIT cells in circulation contributes to the severity of sepsis
This study identified a higher proportion of circulating MAIT17 with expression of IL-17A and RORγt in sepsis patients. The proportion of MAIT17 was correlated with the severity of sepsis. Single-cell RNA sequencing (scRNA-seq) analysis revealed an enhanced expression of lactate dehydrogenase A (LDHA) in MAIT17 in sepsis patients. Cell-culture experiments demonstrated that Phosphoinositide 3-kinase (PI3K)-LDHA signaling was required for RORγt expression in MAIT17. Finally, the elevated levels of plasma IL-18 promoted the differentiation of circulating MAIT17 in sepsis. In summary, this study reveals a new role of circula...
Source: Am J Pathol - April 10, 2024 Category: Pathology Authors: Xinying Li Sicheng Fu Hao Cheng Min Ma Zijian Song Jun Li Shuang Wu Chong Zhang Xiaoxia Wang Maoyu Tang Xuexue Pu Qiang Ji Jinquan Liang Zhibin Zhao Heinrich K örner Bin Li Min Shao Hua Wang Source Type: research

This Month in AJP
Am J Pathol. 2024 Apr 8:S0002-9440(24)00126-3. doi: 10.1016/j.ajpath.2024.04.001. Online ahead of print.NO ABSTRACTPMID:38599460 | DOI:10.1016/j.ajpath.2024.04.001 (Source: Am J Pathol)
Source: Am J Pathol - April 10, 2024 Category: Pathology Source Type: research

Differentiation of type 17 MAIT cells in circulation contributes to the severity of sepsis
This study identified a higher proportion of circulating MAIT17 with expression of IL-17A and RORγt in sepsis patients. The proportion of MAIT17 was correlated with the severity of sepsis. Single-cell RNA sequencing (scRNA-seq) analysis revealed an enhanced expression of lactate dehydrogenase A (LDHA) in MAIT17 in sepsis patients. Cell-culture experiments demonstrated that Phosphoinositide 3-kinase (PI3K)-LDHA signaling was required for RORγt expression in MAIT17. Finally, the elevated levels of plasma IL-18 promoted the differentiation of circulating MAIT17 in sepsis. In summary, this study reveals a new role of circula...
Source: Am J Pathol - April 10, 2024 Category: Pathology Authors: Xinying Li Sicheng Fu Hao Cheng Min Ma Zijian Song Jun Li Shuang Wu Chong Zhang Xiaoxia Wang Maoyu Tang Xuexue Pu Qiang Ji Jinquan Liang Zhibin Zhao Heinrich K örner Bin Li Min Shao Hua Wang Source Type: research

TFE3/PI3K/Akt/mTOR axis in renal cell carcinoma affects tumor microenvironment
Am J Pathol. 2024 Apr 6:S0002-9440(24)00122-6. doi: 10.1016/j.ajpath.2024.02.022. Online ahead of print.ABSTRACTThe role of the PI3K/Akt pathway in renal cell carcinoma (RCC) progression, metastasis, and resistance to therapies has not been thoroughly investigated. Transcription factor E3 (TFE3) expression is related to poorer prognosis and tumor microenvironment in patients with RCC. We aimed to determine the relationship between TFE3 and the PI3K/Akt pathway. TFE3 downregulation was achieved by transient transfection of small interfering RNA (siRNA) and short hairpin RNA (shRNA) in UOK146 cells. TFE3 overexpression was i...
Source: Am J Pathol - April 8, 2024 Category: Pathology Authors: Chung Su Hwang Yun Kyung Kang Ji Yun Kim So Hyun Shin Joon Young Park Ji Sun Song So Young Kim Se Jin Jung Jung Hee Lee Ju-Young Na Dong Hoon Shin Jee Yeon Kim Sung Woo Park Hyun Jung Lee Source Type: research

Role of HNF4alpha-cMyc Interaction in CDE-diet Induced Liver Injury and Regeneration
This study investigated the role of HNF4α-cMyc interaction in regulating liver injury and regeneration using the choline-deficient and ethionine-supplemented (CDE) diet model. WT, hepatocyte-specific HNF4α-KO, cMyc-KO, and HNF4α-cMyc double knockout (DKO) mice were fed a CDE diet for one week to induce subacute liver injury. To study regeneration, CDE diet was followed by normal chow diet for one week. WT mice showed significant liver injury and decreased HNF4α mRNA and protein expression after one week of a CDE diet. HNF4α deletion resulted in significantly higher injury with increased inflammation, fibrosis, prolife...
Source: Am J Pathol - April 8, 2024 Category: Pathology Authors: Manasi Kotulkar Julia Barbee Diego Paine-Cabrera Dakota Robarts Maura O'Neil Udayan Apte Source Type: research

Graph perceiver network for lung tumor and bronchial premalignant lesion stratification from histopathology
Am J Pathol. 2024 Apr 6:S0002-9440(24)00124-X. doi: 10.1016/j.ajpath.2024.03.009. Online ahead of print.ABSTRACTBronchial premalignant lesions (PMLs) precede the development of invasive lung squamous carcinoma (LUSC), posing a significant challenge in distinguishing those likely to advance to LUSC from those that might regress without intervention. In this context, we present a novel computational approach, the Graph Perceiver Network (GRAPE-Net), leveraging hematoxylin and eosin (H&E) stained whole slide images (WSIs) to stratify endobronchial biopsies of PMLs across a spectrum from normal to tumor lung tissues. GRAPE...
Source: Am J Pathol - April 8, 2024 Category: Pathology Authors: Rushin H Gindra Yi Zheng Emily J Green Mary E Reid Sarah A Mazzilli Daniel T Merrick Eric J Burks Vijaya B Kolachalama Jennifer E Beane Source Type: research

TFE3/PI3K/Akt/mTOR axis in renal cell carcinoma affects tumor microenvironment
Am J Pathol. 2024 Apr 6:S0002-9440(24)00122-6. doi: 10.1016/j.ajpath.2024.02.022. Online ahead of print.ABSTRACTThe role of the PI3K/Akt pathway in renal cell carcinoma (RCC) progression, metastasis, and resistance to therapies has not been thoroughly investigated. Transcription factor E3 (TFE3) expression is related to poorer prognosis and tumor microenvironment in patients with RCC. We aimed to determine the relationship between TFE3 and the PI3K/Akt pathway. TFE3 downregulation was achieved by transient transfection of small interfering RNA (siRNA) and short hairpin RNA (shRNA) in UOK146 cells. TFE3 overexpression was i...
Source: Am J Pathol - April 8, 2024 Category: Pathology Authors: Chung Su Hwang Yun Kyung Kang Ji Yun Kim So Hyun Shin Joon Young Park Ji Sun Song So Young Kim Se Jin Jung Jung Hee Lee Ju-Young Na Dong Hoon Shin Jee Yeon Kim Sung Woo Park Hyun Jung Lee Source Type: research

Role of HNF4alpha-cMyc Interaction in CDE-diet Induced Liver Injury and Regeneration
This study investigated the role of HNF4α-cMyc interaction in regulating liver injury and regeneration using the choline-deficient and ethionine-supplemented (CDE) diet model. WT, hepatocyte-specific HNF4α-KO, cMyc-KO, and HNF4α-cMyc double knockout (DKO) mice were fed a CDE diet for one week to induce subacute liver injury. To study regeneration, CDE diet was followed by normal chow diet for one week. WT mice showed significant liver injury and decreased HNF4α mRNA and protein expression after one week of a CDE diet. HNF4α deletion resulted in significantly higher injury with increased inflammation, fibrosis, prolife...
Source: Am J Pathol - April 8, 2024 Category: Pathology Authors: Manasi Kotulkar Julia Barbee Diego Paine-Cabrera Dakota Robarts Maura O'Neil Udayan Apte Source Type: research

Graph perceiver network for lung tumor and bronchial premalignant lesion stratification from histopathology
Am J Pathol. 2024 Apr 6:S0002-9440(24)00124-X. doi: 10.1016/j.ajpath.2024.03.009. Online ahead of print.ABSTRACTBronchial premalignant lesions (PMLs) precede the development of invasive lung squamous carcinoma (LUSC), posing a significant challenge in distinguishing those likely to advance to LUSC from those that might regress without intervention. In this context, we present a novel computational approach, the Graph Perceiver Network (GRAPE-Net), leveraging hematoxylin and eosin (H&E) stained whole slide images (WSIs) to stratify endobronchial biopsies of PMLs across a spectrum from normal to tumor lung tissues. GRAPE...
Source: Am J Pathol - April 8, 2024 Category: Pathology Authors: Rushin H Gindra Yi Zheng Emily J Green Mary E Reid Sarah A Mazzilli Daniel T Merrick Eric J Burks Vijaya B Kolachalama Jennifer E Beane Source Type: research

Poorly Differentiated Hepatocellular Carcinoma Cells Avoid Apoptosis by Interacting with T Cells via CD40-CD40L Linkage
We examined CD40 levels in HCC patient tissues and various HCC cell lines, studying their interaction with CD4+T cells. RNA sequencing analysis was performed to explore the mechanisms of CD40 induction. Poorly differentiated HCC tumour tissues exhibited high membrane-bound CD40 (mCD40) expression, in contrast to non-tumour areas. Poorly differentiated HCC cell lines showed high expression of mCD40 with low CD40 promoter methylation which were opposite of well-differentiated ones. Solely modulating CD40 expression in HCC cells exerted no direct consequences on cell growth or appearance. Interestingly, HLFs co-cultured with ...
Source: Am J Pathol - March 28, 2024 Category: Pathology Authors: Hanh Vinh Ngo Thuy Thi Thanh Le Hieu Ngoc Vu Hai Hoang Hiroko Ikenaga Misako Sato-Matsubara Sawako Uchida-Kobayashi Hayato Urushima Khanh Van Nguyen Ha Thi Nguyen Hiroji Shinkawa Shoji Kubo Naoko Ohtani Masaru Enomoto Akihiro Tamori Norifumi Kawada Source Type: research

TGF- β1 Drives Integrin-Dependent Pericyte Migration and Microvascular Destabilization in Fibrotic Disease
Am J Pathol. 2024 Mar 26:S0002-9440(24)00118-4. doi: 10.1016/j.ajpath.2024.02.021. Online ahead of print.ABSTRACTInteractions between endothelial cells (ECs) and mural pericytes (PCs) are critical to maintaining the stability and function of the microvascular wall. Abnormal interactions between these two cell types are a hallmark of progressive fibrotic diseases such as systemic sclerosis (also known as scleroderma). However, the role that PCs play in signaling microvascular dysfunction remains underexplored. It is hypothesized that integrin-matrix interactions contribute to PC migration from the vascular wall and conversi...
Source: Am J Pathol - March 28, 2024 Category: Pathology Authors: Amanda S Pellowe Michelle J Wu Tae-Yun Kang Tracy D Chung Adrian Ledesma-Mendoza Erica Herzog Andre Levchenko Ian Odell John Varga Anjelica L Gonzalez Source Type: research

Enhanced Optic Nerve Expansion and Altered Ultrastructure of Elastic Fibers Induced by Lysyl Oxidase Inhibition in a Mouse Model of Marfan Syndrome
Am J Pathol. 2024 Mar 26:S0002-9440(24)00115-9. doi: 10.1016/j.ajpath.2024.03.002. Online ahead of print.ABSTRACTTwo major constituents of exfoliation material, fibrillin-1 and lysyl oxidase-like 1 (encoded by FBN1 and LOXL1), are implicated in exfoliation glaucoma, yet their individual contributions to ocular phenotype are minor. To test the hypothesis that a combination of FBN1 mutation and LOXL1 deficiency exacerbates ocular phenotypes, the pan-LOX inhibitor β-aminopropionitrile (BAPN) was used to treat adult wild-type (WT) and Fbn1C1041G/+ mice for 8 weeks and their eyes were examined. Although intraocular pressure di...
Source: Am J Pathol - March 28, 2024 Category: Pathology Authors: Hang-Jing Wu Evan Krystofiak John Kuchtey Rachel W Kuchtey Source Type: research