Metallothionein Alleviates Glutathione Depletion-Induced Oxidative Cardiomyopathy through CISD1-Dependent Regulation of Ferroptosis in Murine Hearts
This study was designed to discern the effect of heavy scavenger metallothionein on glutathione (GSH) deprivation-evoked cardiac anomalies and mechanisms involved with an emphasis on ferroptosis. WT and cardiac metallothionein transgenic mice received GSH synthase inhibitor buthionine sulfoximine (BSO, 30 mM in drinking water) for 14 days prior to assessment of myocardial morphology and function. BSO evoked cardiac remodeling and contractile anomalies including cardiac hypertrophy, interstitial fibrosis, enlarged left ventricular chambers, deranged ejection fraction, fraction shortening, cardiomyocyte contractile capacity,...
Source: Am J Pathol - February 28, 2024 Category: Pathology Authors: Feng-Juan Li Shouzhi Fu Hua Ye Yi-Han Hu Jianxin Chen Jamie R Privratsky Wei Yu Feng Dong Russel J Reiter Maolong Dong Jun Guo Jun Ren Source Type: research

Serine Supports Epithelial and Immune Cell Function in Colitis
Am J Pathol. 2024 Feb 26:S0002-9440(24)00071-3. doi: 10.1016/j.ajpath.2024.01.021. Online ahead of print.ABSTRACTInflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that are largely driven by immune cell activity, while mucosal healing is critical for remission. Serine is a non-essential amino acid that supports epithelial and immune cell metabolism and proliferation, however, whether these roles impact IBD pathogenesis is not well understood. Here, we show that serine synthesis increases selectively in the epithelial cells of colons from patients with IBD and murine models of...
Source: Am J Pathol - February 28, 2024 Category: Pathology Authors: Ji Dong K Bai Suchandrima Saha Michael Wood Bo Chen Jinyu Li Lukas E Dow David C Montrose Source Type: research

Ferroptosis contributes to microvascular dysfunction in diabetic retinopathy
Am J Pathol. 2024 Feb 26:S0002-9440(24)00069-5. doi: 10.1016/j.ajpath.2024.01.019. Online ahead of print.ABSTRACTFerroptosis is a new form of cell death characterized by iron-dependent lipid peroxidation. Whether ferroptosis is involved in retinal microvascular dysfunction under diabetic condition is not known. The expression of ferroptosis related genes in patients with proliferative diabetic retinopathy (PDR) and in diabetic mice was determined with RT-qPCR. Reactive oxygen species (ROS), iron content, lipid peroxidation products, and ferroptosis-associated proteins in the cultured human retinal microvascular endothelial...
Source: Am J Pathol - February 28, 2024 Category: Pathology Authors: Qun Liu Chao-Qun Liu Wan-Zhao Yi Pei-Wen Ouyang Bo-Fan Yang Qi Liu Jing-Min Liu Ya-Ni Wu Ai-Rong Liang Yu-Hong Cui Jing Meng Xiu-Yun Li Hong-Wei Pan Source Type: research

The role of microRNA and long non-coding RNA in cholestatic liver diseases
Am J Pathol. 2024 Feb 26:S0002-9440(24)00075-0. doi: 10.1016/j.ajpath.2024.02.006. Online ahead of print.ABSTRACTCholestatic liver diseases encompass a range of organic damages, metabolic disorders, and dysfunctions within the hepatobiliary system, arising from various pathogenic causes. These factors contribute to disruptions in bile production, secretion, and excretion. Cholestatic liver diseases can be classified into intrahepatic and extrahepatic cholestasis according to the location of occurrence. The etiology of cholestatic liver diseases are complex, which include drugs, poisons, viruses, parasites, bacteria, autoim...
Source: Am J Pathol - February 28, 2024 Category: Pathology Authors: Yudian Zhang Ying Liu Wen Huo Longfei He Bowen Li Hui Wang Fanyin Meng Chenggang Duan Bingru Zhou Jinbo Wu Rong Chen Juan Xing Ying Wan Source Type: research

The Unrecognized Role of Ninjurin 2 in Inflammation, Metabolism and Pyroptosis
Am J Pathol. 2024 Feb 26:S0002-9440(24)00067-1. doi: 10.1016/j.ajpath.2024.02.002. Online ahead of print.NO ABSTRACTPMID:38417699 | DOI:10.1016/j.ajpath.2024.02.002 (Source: Am J Pathol)
Source: Am J Pathol - February 28, 2024 Category: Pathology Authors: Juan Liu Wenwei Hu Zhaohui Feng Source Type: research

The Role of Hyaluronan/RHAMM Interactions in the Modulation of Macrophage Polarization and Cartilage Repair
This study shows an increased expression of RHAMM in pro-inflammatory macrophages. Interfering with HA/RHAMM interactions using a 15mer RHAMM-mimetic, HA binding peptide (P15-1) together with high molecular weight (HMW)HA reduced the expression and release of inflammatory markers and increased the expression of anti-inflammatory markers in pro-inflammatory macrophages. Interfering with HA/RHAMM interactions in vivo during the regeneration of a full thickness cartilage defect after microfracture surgery in rabbits using three intra-articular injections of P15-1 together with HMWHA reduced the number of pro-inflammatory macr...
Source: Am J Pathol - February 25, 2024 Category: Pathology Authors: Emilia Bianchini Yun Jin Ashley Sin You Jin Lee Charles Lin Utkarsh Anil Cassie Hamill Mary K Cowman Thorsten Kirsch Source Type: research

Rat Model of Type 2 Diabetes Mellitus Recapitulates Human Disease in the Anterior Segment of the Eye
This study evaluates changes in the anterior segment, including crystalline lens health, corneal endothelial cell density, aqueous humor metabolites and ciliary body vasculature, in a rat model of type 2 diabetes mellitus (T2DM) compared with human eyes. Sprague-Dawley male rats were fed a high fat diet (HFD, 45% fat) or normal diet, and HFD rats were injected intraperitoneally with streptozotocin (STZ) to create a model of T2DM. Microscopic analysis was performed to determine cataract formation and corneal endothelial cell density. Metabolomics of rat aqueous humor was performed to determine diabetes-related aqueous alter...
Source: Am J Pathol - February 25, 2024 Category: Pathology Authors: Cheryl L Wang Jessica M Skeie Chantal Allamargot Andrew S Goldstein Darryl Y Nishimura James M Huffman Benjamin T Aldrich Gregory A Schmidt Leandro B C Teixeira Markus H Kuehn Mark Yorek Mark A Greiner Source Type: research

Role of Platelet Activating Factor (PAF) as a Mediator of Inflammatory Diseases and Preterm Delivery
Am J Pathol. 2024 Feb 23:S0002-9440(24)00068-3. doi: 10.1016/j.ajpath.2024.01.018. Online ahead of print.ABSTRACTNearly 70% of preterm deliveries occur spontaneously, and the clinical pathways involved include preterm labor (PTL) and preterm premature rupture of membranes (pPROM). Prediction of preterm delivery is considered crucial due to the significant effects of preterm birth on health and the economy at both the personal and community levels. Although similar inflammatory processes occur in both term and preterm delivery, the premature activation of these processes or exaggerated inflammatory response triggered by inf...
Source: Am J Pathol - February 25, 2024 Category: Pathology Authors: Hanan Hamimi Wahid Fatin Najihah Anahar Nurul Husna Isahak Juwairiyah Mohd Zoharodzi Siti Nur Lina Mohammad Khoiri Nurul Hayati Mohamad Zainal Norhidayah Kamarudin Hamizah Ismail Mohammed Imad Al-Deen Mustafa Mahmud Source Type: research

DNA hypomethylation mediated transcription dysregulation participates in pathogenesis of polycystic ovary syndrome
Am J Pathol. 2024 Feb 23:S0002-9440(24)00072-5. doi: 10.1016/j.ajpath.2024.02.003. Online ahead of print.ABSTRACTPolycystic ovary syndrome is a highly heterogenous and genetically complex endocrine disorder. Although the etiology remains mostly elusive, growing evidences suggested abnormal changes of DNA methylation correlate well with systemic and tissue-specific dysfunctions in polycystic ovary syndrome. Dehydroepiandrosterone-induced polycystic ovary syndrome-like mouse model was generated, which has similar metabolic and reproductive phenotype as human polycystic ovary syndrome patients, and used to experimentally vali...
Source: Am J Pathol - February 25, 2024 Category: Pathology Authors: Pengbo Cao Haoran Li Peijun Wang Xinna Zhang Yuxuan Guo Keyu Zhao Jiaojiao Guo Xihe Li Buhe Nashun Source Type: research

The Role of Hyaluronan/RHAMM Interactions in the Modulation of Macrophage Polarization and Cartilage Repair
This study shows an increased expression of RHAMM in pro-inflammatory macrophages. Interfering with HA/RHAMM interactions using a 15mer RHAMM-mimetic, HA binding peptide (P15-1) together with high molecular weight (HMW)HA reduced the expression and release of inflammatory markers and increased the expression of anti-inflammatory markers in pro-inflammatory macrophages. Interfering with HA/RHAMM interactions in vivo during the regeneration of a full thickness cartilage defect after microfracture surgery in rabbits using three intra-articular injections of P15-1 together with HMWHA reduced the number of pro-inflammatory macr...
Source: Am J Pathol - February 25, 2024 Category: Pathology Authors: Emilia Bianchini Yun Jin Ashley Sin You Jin Lee Charles Lin Utkarsh Anil Cassie Hamill Mary K Cowman Thorsten Kirsch Source Type: research

Rat Model of Type 2 Diabetes Mellitus Recapitulates Human Disease in the Anterior Segment of the Eye
This study evaluates changes in the anterior segment, including crystalline lens health, corneal endothelial cell density, aqueous humor metabolites and ciliary body vasculature, in a rat model of type 2 diabetes mellitus (T2DM) compared with human eyes. Sprague-Dawley male rats were fed a high fat diet (HFD, 45% fat) or normal diet, and HFD rats were injected intraperitoneally with streptozotocin (STZ) to create a model of T2DM. Microscopic analysis was performed to determine cataract formation and corneal endothelial cell density. Metabolomics of rat aqueous humor was performed to determine diabetes-related aqueous alter...
Source: Am J Pathol - February 25, 2024 Category: Pathology Authors: Cheryl L Wang Jessica M Skeie Chantal Allamargot Andrew S Goldstein Darryl Y Nishimura James M Huffman Benjamin T Aldrich Gregory A Schmidt Leandro B C Teixeira Markus H Kuehn Mark Yorek Mark A Greiner Source Type: research

Role of Platelet Activating Factor (PAF) as a Mediator of Inflammatory Diseases and Preterm Delivery
Am J Pathol. 2024 Feb 23:S0002-9440(24)00068-3. doi: 10.1016/j.ajpath.2024.01.018. Online ahead of print.ABSTRACTNearly 70% of preterm deliveries occur spontaneously, and the clinical pathways involved include preterm labor (PTL) and preterm premature rupture of membranes (pPROM). Prediction of preterm delivery is considered crucial due to the significant effects of preterm birth on health and the economy at both the personal and community levels. Although similar inflammatory processes occur in both term and preterm delivery, the premature activation of these processes or exaggerated inflammatory response triggered by inf...
Source: Am J Pathol - February 25, 2024 Category: Pathology Authors: Hanan Hamimi Wahid Fatin Najihah Anahar Nurul Husna Isahak Juwairiyah Mohd Zoharodzi Siti Nur Lina Mohammad Khoiri Nurul Hayati Mohamad Zainal Norhidayah Kamarudin Hamizah Ismail Mohammed Imad Al-Deen Mustafa Mahmud Source Type: research

DNA hypomethylation mediated transcription dysregulation participates in pathogenesis of polycystic ovary syndrome
Am J Pathol. 2024 Feb 23:S0002-9440(24)00072-5. doi: 10.1016/j.ajpath.2024.02.003. Online ahead of print.ABSTRACTPolycystic ovary syndrome is a highly heterogenous and genetically complex endocrine disorder. Although the etiology remains mostly elusive, growing evidences suggested abnormal changes of DNA methylation correlate well with systemic and tissue-specific dysfunctions in polycystic ovary syndrome. Dehydroepiandrosterone-induced polycystic ovary syndrome-like mouse model was generated, which has similar metabolic and reproductive phenotype as human polycystic ovary syndrome patients, and used to experimentally vali...
Source: Am J Pathol - February 25, 2024 Category: Pathology Authors: Pengbo Cao Haoran Li Peijun Wang Xinna Zhang Yuxuan Guo Keyu Zhao Jiaojiao Guo Xihe Li Buhe Nashun Source Type: research

The Role of Hyaluronan/RHAMM Interactions in the Modulation of Macrophage Polarization and Cartilage Repair
This study shows an increased expression of RHAMM in pro-inflammatory macrophages. Interfering with HA/RHAMM interactions using a 15mer RHAMM-mimetic, HA binding peptide (P15-1) together with high molecular weight (HMW)HA reduced the expression and release of inflammatory markers and increased the expression of anti-inflammatory markers in pro-inflammatory macrophages. Interfering with HA/RHAMM interactions in vivo during the regeneration of a full thickness cartilage defect after microfracture surgery in rabbits using three intra-articular injections of P15-1 together with HMWHA reduced the number of pro-inflammatory macr...
Source: Am J Pathol - February 25, 2024 Category: Pathology Authors: Emilia Bianchini Yun Jin Ashley Sin You Jin Lee Charles Lin Utkarsh Anil Cassie Hamill Mary K Cowman Thorsten Kirsch Source Type: research

Rat Model of Type 2 Diabetes Mellitus Recapitulates Human Disease in the Anterior Segment of the Eye
This study evaluates changes in the anterior segment, including crystalline lens health, corneal endothelial cell density, aqueous humor metabolites and ciliary body vasculature, in a rat model of type 2 diabetes mellitus (T2DM) compared with human eyes. Sprague-Dawley male rats were fed a high fat diet (HFD, 45% fat) or normal diet, and HFD rats were injected intraperitoneally with streptozotocin (STZ) to create a model of T2DM. Microscopic analysis was performed to determine cataract formation and corneal endothelial cell density. Metabolomics of rat aqueous humor was performed to determine diabetes-related aqueous alter...
Source: Am J Pathol - February 25, 2024 Category: Pathology Authors: Cheryl L Wang Jessica M Skeie Chantal Allamargot Andrew S Goldstein Darryl Y Nishimura James M Huffman Benjamin T Aldrich Gregory A Schmidt Leandro B C Teixeira Markus H Kuehn Mark Yorek Mark A Greiner Source Type: research