Spermidine suppresses oral carcinogenesis through autophagy induction, DNA damage repair and oxidative stress reduction
In this study, we investigated the role of autophagy in oral carcinogenesis using the model of oral squamous cell carcinoma (OSCC) induced by carcinogen 4-nitroquinoline 1-oxide (4NQO), mimicking molecular and histopathological aspects of human OSCC. The induction of autophagy by spermidine (SPD) treatment reduced the severity of lesions and the incidence of OSCC in mice exposed to 4NQO. On the other hand, autophagy inhibition by chloroquine treatment had no protection. Using the comet assay, we identified that SPD reduced 4NQO-induced DNA damage, likely related to the activation of DNA repair and decreasing reactive oxyge...
Source: Am J Pathol - September 23, 2023 Category: Pathology Authors: Fernanda Borchers Coeli-Lacchini Gabriel da Silva Monica Belentani Jovelina Samara Ferreira Alves Tatiane Resende Ushida Glauce Trevisan Lunardelli Cristiana Bernadelli Garcia Tarc ília Aparecida Silva Norberto Peporine Lopes Andr éia Machado Leopoldino Source Type: research

Ablation of dual specificity phosphatase 6 protects against non-alcoholic fatty liver disease via CYP4A and MAPK
In this study, we used a high-fat diet (HFD)-induced murine non-alcoholic fatty liver disease (NAFLD) model to investigate the role of DUSP6 in this disease. Wild-type (WT) and Dusp6-haploinsufficient (HI) mice developed severe obesity and liver pathology consistent with NAFLD when exposed to HFD. In contrast, Dusp6-knockout (KO) mice completely eliminated these phenotypes. Furthermore, primary hepatocytes isolated from WT mice exposed to palmitic and oleic acids exhibited abundant intracellular lipid accumulation, while hepatocytes from Dusp6-KO mice showed minimal lipid accumulation. Transcriptome analysis revealed signi...
Source: Am J Pathol - September 23, 2023 Category: Pathology Authors: Can Jiang Yuriko Saiki Shuto Hirota Kosei Iwata Xinyue Wang Yutaka Ito Keigo Murakami Takehiro Imura Jun Inoue Atsushi Masamune Akiyoshi Hirayama Masafumi Goto Toru Furukawa Source Type: research

Tumor mutation burden-related histopathological features for predicting overall survival in gliomas using graph deep learning
This study aimed to identify the TMB-related histopathological features from hematoxylin and eosin slides and explore their prognostic value in gliomas. We detected the TMB-related features using a graph convolutional neural network from whole slide image (WSI) of patients from The Cancer Genome Atlas dataset (619 patients), and evaluated the correlation between features and TMB in an external validation set (237 patients). Then we used TMB-related features for predicting overall survival (OS) of patients to investigate whether these features have potential for prognostic prediction. Moreover, biological pathways underlyin...
Source: Am J Pathol - September 23, 2023 Category: Pathology Authors: Caixia Sun Tao Luo Zhenyu Liu Jia Ge Lizhi Shao Xiangyu Liu Bao Li Song Zhang Qi Qiu Wei Wei Shuo Wang Xiu-Wu Bian Jie Tian Source Type: research

Toxoplasma gondii induces pyroptosis in human placental trophoblast and amniotic cells by inducing ROS production and activation of cathepsin B and NLRP1/NLRP3/NLRC4/AIM2 inflammasome
Am J Pathol. 2023 Sep 21:S0002-9440(23)00362-0. doi: 10.1016/j.ajpath.2023.08.016. Online ahead of print.ABSTRACTToxoplasma gondii infection in pregnant women may cause fetal anomaly; however, the underlying mechanisms remain unclear. Here, we investigated whether T. gondii induces pyroptosis in human placental cells and the underlying mechanisms. Human placental trophoblast (BeWo and HTR-8/SVneo) and amniotic (WISH) cells were infected with T. gondii, and then ROS production, cathepsin B (CatB) release, inflammasome activation, and pyroptosis induction were evaluated. Moreover, the molecular mechanisms of these effects we...
Source: Am J Pathol - September 23, 2023 Category: Pathology Authors: Juan-Hua Quan Fei Fei Gao Tian-Zhong Ma Wei Ye Xiang Gao Ming-Zhu Deng Lan-Lan Yin In-Wook Choi Jae-Min Yuk Guang-Ho Cha Young-Ha Lee Jia-Qi Chu Source Type: research

Increasing energetic demands on photoreceptors in diabetes corrects retinal lipid dysmetabolism and reduces subsequent microvascular damage
Am J Pathol. 2023 Sep 21:S0002-9440(23)00360-7. doi: 10.1016/j.ajpath.2023.09.004. Online ahead of print.ABSTRACTMechanisms responsible for the pathogenesis of diabetic retinal disease remain incompletely understood, but likely involve multiple cellular targets, including photoreceptors. Evidence suggests that dysregulated de novo lipogenesis in photoreceptors is a critical early target of diabetes. Following on this observation, the present study aimed to determine whether two interventions shown to improve diabetic retinopathy in mice - pharmacologic visual cycle inhibition and prolonged dark adaptation - reduce photorec...
Source: Am J Pathol - September 23, 2023 Category: Pathology Authors: Sheng Zhang Xiaochao Wei Megan Bowers Sebastian Jessberger Marcin Golczak Clay F Semenkovich Rithwick Rajagopal Source Type: research

Spermidine suppresses oral carcinogenesis through autophagy induction, DNA damage repair and oxidative stress reduction
In this study, we investigated the role of autophagy in oral carcinogenesis using the model of oral squamous cell carcinoma (OSCC) induced by carcinogen 4-nitroquinoline 1-oxide (4NQO), mimicking molecular and histopathological aspects of human OSCC. The induction of autophagy by spermidine (SPD) treatment reduced the severity of lesions and the incidence of OSCC in mice exposed to 4NQO. On the other hand, autophagy inhibition by chloroquine treatment had no protection. Using the comet assay, we identified that SPD reduced 4NQO-induced DNA damage, likely related to the activation of DNA repair and decreasing reactive oxyge...
Source: Am J Pathol - September 23, 2023 Category: Pathology Authors: Fernanda Borchers Coeli-Lacchini Gabriel da Silva Monica Belentani Jovelina Samara Ferreira Alves Tatiane Resende Ushida Glauce Trevisan Lunardelli Cristiana Bernadelli Garcia Tarc ília Aparecida Silva Norberto Peporine Lopes Andr éia Machado Leopoldino Source Type: research

Ablation of dual specificity phosphatase 6 protects against non-alcoholic fatty liver disease via CYP4A and MAPK
In this study, we used a high-fat diet (HFD)-induced murine non-alcoholic fatty liver disease (NAFLD) model to investigate the role of DUSP6 in this disease. Wild-type (WT) and Dusp6-haploinsufficient (HI) mice developed severe obesity and liver pathology consistent with NAFLD when exposed to HFD. In contrast, Dusp6-knockout (KO) mice completely eliminated these phenotypes. Furthermore, primary hepatocytes isolated from WT mice exposed to palmitic and oleic acids exhibited abundant intracellular lipid accumulation, while hepatocytes from Dusp6-KO mice showed minimal lipid accumulation. Transcriptome analysis revealed signi...
Source: Am J Pathol - September 23, 2023 Category: Pathology Authors: Can Jiang Yuriko Saiki Shuto Hirota Kosei Iwata Xinyue Wang Yutaka Ito Keigo Murakami Takehiro Imura Jun Inoue Atsushi Masamune Akiyoshi Hirayama Masafumi Goto Toru Furukawa Source Type: research

Tumor mutation burden-related histopathological features for predicting overall survival in gliomas using graph deep learning
This study aimed to identify the TMB-related histopathological features from hematoxylin and eosin slides and explore their prognostic value in gliomas. We detected the TMB-related features using a graph convolutional neural network from whole slide image (WSI) of patients from The Cancer Genome Atlas dataset (619 patients), and evaluated the correlation between features and TMB in an external validation set (237 patients). Then we used TMB-related features for predicting overall survival (OS) of patients to investigate whether these features have potential for prognostic prediction. Moreover, biological pathways underlyin...
Source: Am J Pathol - September 23, 2023 Category: Pathology Authors: Caixia Sun Tao Luo Zhenyu Liu Jia Ge Lizhi Shao Xiangyu Liu Bao Li Song Zhang Qi Qiu Wei Wei Shuo Wang Xiu-Wu Bian Jie Tian Source Type: research

Toxoplasma gondii induces pyroptosis in human placental trophoblast and amniotic cells by inducing ROS production and activation of cathepsin B and NLRP1/NLRP3/NLRC4/AIM2 inflammasome
Am J Pathol. 2023 Sep 21:S0002-9440(23)00362-0. doi: 10.1016/j.ajpath.2023.08.016. Online ahead of print.ABSTRACTToxoplasma gondii infection in pregnant women may cause fetal anomaly; however, the underlying mechanisms remain unclear. Here, we investigated whether T. gondii induces pyroptosis in human placental cells and the underlying mechanisms. Human placental trophoblast (BeWo and HTR-8/SVneo) and amniotic (WISH) cells were infected with T. gondii, and then ROS production, cathepsin B (CatB) release, inflammasome activation, and pyroptosis induction were evaluated. Moreover, the molecular mechanisms of these effects we...
Source: Am J Pathol - September 23, 2023 Category: Pathology Authors: Juan-Hua Quan Fei Fei Gao Tian-Zhong Ma Wei Ye Xiang Gao Ming-Zhu Deng Lan-Lan Yin In-Wook Choi Jae-Min Yuk Guang-Ho Cha Young-Ha Lee Jia-Qi Chu Source Type: research

Increasing energetic demands on photoreceptors in diabetes corrects retinal lipid dysmetabolism and reduces subsequent microvascular damage
Am J Pathol. 2023 Sep 21:S0002-9440(23)00360-7. doi: 10.1016/j.ajpath.2023.09.004. Online ahead of print.ABSTRACTMechanisms responsible for the pathogenesis of diabetic retinal disease remain incompletely understood, but likely involve multiple cellular targets, including photoreceptors. Evidence suggests that dysregulated de novo lipogenesis in photoreceptors is a critical early target of diabetes. Following on this observation, the present study aimed to determine whether two interventions shown to improve diabetic retinopathy in mice - pharmacologic visual cycle inhibition and prolonged dark adaptation - reduce photorec...
Source: Am J Pathol - September 23, 2023 Category: Pathology Authors: Sheng Zhang Xiaochao Wei Megan Bowers Sebastian Jessberger Marcin Golczak Clay F Semenkovich Rithwick Rajagopal Source Type: research

Spermidine suppresses oral carcinogenesis through autophagy induction, DNA damage repair and oxidative stress reduction
In this study, we investigated the role of autophagy in oral carcinogenesis using the model of oral squamous cell carcinoma (OSCC) induced by carcinogen 4-nitroquinoline 1-oxide (4NQO), mimicking molecular and histopathological aspects of human OSCC. The induction of autophagy by spermidine (SPD) treatment reduced the severity of lesions and the incidence of OSCC in mice exposed to 4NQO. On the other hand, autophagy inhibition by chloroquine treatment had no protection. Using the comet assay, we identified that SPD reduced 4NQO-induced DNA damage, likely related to the activation of DNA repair and decreasing reactive oxyge...
Source: Am J Pathol - September 23, 2023 Category: Pathology Authors: Fernanda Borchers Coeli-Lacchini Gabriel da Silva Monica Belentani Jovelina Samara Ferreira Alves Tatiane Resende Ushida Glauce Trevisan Lunardelli Cristiana Bernadelli Garcia Tarc ília Aparecida Silva Norberto Peporine Lopes Andr éia Machado Leopoldino Source Type: research

Ablation of dual specificity phosphatase 6 protects against non-alcoholic fatty liver disease via CYP4A and MAPK
In this study, we used a high-fat diet (HFD)-induced murine non-alcoholic fatty liver disease (NAFLD) model to investigate the role of DUSP6 in this disease. Wild-type (WT) and Dusp6-haploinsufficient (HI) mice developed severe obesity and liver pathology consistent with NAFLD when exposed to HFD. In contrast, Dusp6-knockout (KO) mice completely eliminated these phenotypes. Furthermore, primary hepatocytes isolated from WT mice exposed to palmitic and oleic acids exhibited abundant intracellular lipid accumulation, while hepatocytes from Dusp6-KO mice showed minimal lipid accumulation. Transcriptome analysis revealed signi...
Source: Am J Pathol - September 23, 2023 Category: Pathology Authors: Can Jiang Yuriko Saiki Shuto Hirota Kosei Iwata Xinyue Wang Yutaka Ito Keigo Murakami Takehiro Imura Jun Inoue Atsushi Masamune Akiyoshi Hirayama Masafumi Goto Toru Furukawa Source Type: research

Tumor mutation burden-related histopathological features for predicting overall survival in gliomas using graph deep learning
This study aimed to identify the TMB-related histopathological features from hematoxylin and eosin slides and explore their prognostic value in gliomas. We detected the TMB-related features using a graph convolutional neural network from whole slide image (WSI) of patients from The Cancer Genome Atlas dataset (619 patients), and evaluated the correlation between features and TMB in an external validation set (237 patients). Then we used TMB-related features for predicting overall survival (OS) of patients to investigate whether these features have potential for prognostic prediction. Moreover, biological pathways underlyin...
Source: Am J Pathol - September 23, 2023 Category: Pathology Authors: Caixia Sun Tao Luo Zhenyu Liu Jia Ge Lizhi Shao Xiangyu Liu Bao Li Song Zhang Qi Qiu Wei Wei Shuo Wang Xiu-Wu Bian Jie Tian Source Type: research

Toxoplasma gondii induces pyroptosis in human placental trophoblast and amniotic cells by inducing ROS production and activation of cathepsin B and NLRP1/NLRP3/NLRC4/AIM2 inflammasome
Am J Pathol. 2023 Sep 21:S0002-9440(23)00362-0. doi: 10.1016/j.ajpath.2023.08.016. Online ahead of print.ABSTRACTToxoplasma gondii infection in pregnant women may cause fetal anomaly; however, the underlying mechanisms remain unclear. Here, we investigated whether T. gondii induces pyroptosis in human placental cells and the underlying mechanisms. Human placental trophoblast (BeWo and HTR-8/SVneo) and amniotic (WISH) cells were infected with T. gondii, and then ROS production, cathepsin B (CatB) release, inflammasome activation, and pyroptosis induction were evaluated. Moreover, the molecular mechanisms of these effects we...
Source: Am J Pathol - September 23, 2023 Category: Pathology Authors: Juan-Hua Quan Fei Fei Gao Tian-Zhong Ma Wei Ye Xiang Gao Ming-Zhu Deng Lan-Lan Yin In-Wook Choi Jae-Min Yuk Guang-Ho Cha Young-Ha Lee Jia-Qi Chu Source Type: research

Increasing energetic demands on photoreceptors in diabetes corrects retinal lipid dysmetabolism and reduces subsequent microvascular damage
Am J Pathol. 2023 Sep 21:S0002-9440(23)00360-7. doi: 10.1016/j.ajpath.2023.09.004. Online ahead of print.ABSTRACTMechanisms responsible for the pathogenesis of diabetic retinal disease remain incompletely understood, but likely involve multiple cellular targets, including photoreceptors. Evidence suggests that dysregulated de novo lipogenesis in photoreceptors is a critical early target of diabetes. Following on this observation, the present study aimed to determine whether two interventions shown to improve diabetic retinopathy in mice - pharmacologic visual cycle inhibition and prolonged dark adaptation - reduce photorec...
Source: Am J Pathol - September 23, 2023 Category: Pathology Authors: Sheng Zhang Xiaochao Wei Megan Bowers Sebastian Jessberger Marcin Golczak Clay F Semenkovich Rithwick Rajagopal Source Type: research