Cellular localization of FOXO3 determines its role in cataractogenesis
The transcription factor FOXO3 is a core regulator of cellular homeostasis, stress response, and longevity. The cellular localization of FOXO3 is closely related to its function. Here, we explored the role of FOXO3 in cataract formation. FOXO3 showed nuclear translocation in lens epithelial cells arranged in a single layer on lens capsule tissues from both human cataract and N-methyl-N-nitrosourea (MNU)-induced rat cataract, also in MNU-injured human lens epithelial cell lines (HLECs). FOXO3 knockdown inhibited the MNU-induced increase in expression of genes related to cell cycle arrest (GADD45 α and CCNG2) and apoptosis ...
Source: American Journal of Pathology - July 27, 2023 Category: Pathology Authors: Xiaoqi Li, Yingxin Qu, Qinghua Yang, Runpu Li, Yumei Diao, Junyi Wang, Lingling Wu, Chuyue Zhang, Shaoyuan Cui, Limin Qin, Deyi Zhuo, Huiyi Wang, Liqiang Wang, Yifei Huang Tags: Regular Article Source Type: research
The Role of Gut Microbiota in Glaucoma Progression and Other Retinal Diseases
As a rapidly growing field, microbiota research offers novel approaches to promoting ocular health and treating major retinal diseases, such as glaucoma. Gut microbiota changes throughout life; however, certain patterns of population changes have been increasingly associated with specific diseases. It has been well established that disrupted microbiome contributes to central nervous system diseases, including Alzheimer disease, Parkinson disease, multiple sclerosis, and glioma, suggesting that it could play a prominent role in neurodegenerative diseases. (Source: American Journal of Pathology)
Source: American Journal of Pathology - July 23, 2023 Category: Pathology Authors: Julie Chen, Dong Feng Chen, Kin-Sang Cho Tags: Mini-Review Source Type: research
The Role Gut Microbiota in Glaucoma Progression and Other Retinal Diseases
As a rapidly growing field, microbiota research offers novel approaches to promoting ocular health and treating major retinal diseases, such as glaucoma. Gut microbiota change throughout life; however certain patterns of population changes have been increasingly associated with specific diseases. It has been well established that disrupted microbiome contributes to central nervous system (CNS) diseases, including Alzheimer ’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS), and glioma, suggesting that they could play a prominent role in neurodegenerative diseases. (Source: American Journal of Pathology)
Source: American Journal of Pathology - July 23, 2023 Category: Pathology Authors: Julie Chen, Dong Feng Chen, Kin-Sang Cho Tags: Mini-Review Source Type: research
Current advances of Mitochondrial dysfunction and cardiovascular disease and promising therapeutic strategies
Mitochondria are “cellular power stations” and essential organelles for maintaining cellular homeostasis. Dysfunctional mitochondria have emerged as a key factor in the occurrence and development of cardiovascular disease. This review focuses on the advances in the relationship between mitochondrial dysfunction and cardiovascular diseases such as atherosclerosis, heart failure, myocardial ischemia reperfusion injury, and pulmonary arterial hypertension. Moreover, the clinical value and challenges of mitochondria-targeted strategies, including mitochondria-targeted antioxidants, mitochondrial quality contro l modulators...
Source: American Journal of Pathology - July 20, 2023 Category: Pathology Authors: Dexiang Xia, Yue Liu, Peng Wu, Dangheng Wei Tags: Review Source Type: research
This Month in AJP
Organoids may help elucidate the mechanisms underlying progression of primary sclerosing cholangitis (PSC). Using primary liver cell lines derived from normal and PSC patients, Zhang et al (Am J Pathol, AJPA-D-22-00549) developed scaffold-free multi-cellular 3D cholangiocyte organoids (3D-CHO). Primary cholangiocytes, liver endothelial cells (LECs), and hepatic stellate cells (HSCs) were isolated from human liver samples from healthy donors and PSC patients to form 3D-CHOs, which were kept viable for up to 1 month. (Source: American Journal of Pathology)
Source: American Journal of Pathology - July 10, 2023 Category: Pathology Tags: This Month in AJP Source Type: research
Anti-Inflammatory and Pro-resolving Actions of the N-Terminal Peptides Ac2-26, Ac2-12, and Ac9-25 of Annexin A1 on Conjunctival Goblet Cell Function
Annexin A1 (AnxA1) is the main mediator of the anti-inflammatory actions of glucocorticoids. AnxA1 functions as a pro-resolving mediator in cultured rat conjunctival goblet cells to ensure tissue homeostasis through stimulation of intracellular [Ca2+] ([Ca2+]i) and mucin secretion. AnxA1 has several N-terminal peptides with anti-inflammatory properties of their own, including Ac2-26, Ac2-12, and Ac9-25. The increase in [Ca2+]i caused by AnxA1 and its N-terminal peptides in goblet cells was measured to determine which formyl peptide receptors the compounds use and the action of the peptides on histamine stimulation. (Sour...
Source: American Journal of Pathology - July 7, 2023 Category: Pathology Authors: Anne V. Lyngstadaas, Markus V. Olsen, Jeffrey Bair, Menglu Yang, Robin R. Hodges, Tor P. Utheim, Charles N. Serhan, Darlene A. Dartt Tags: Regular article Source Type: research
Anti-Inflammatory and Pro-resolving Actions of the N-Terminal Peptides Ac2-26, Ac2-12 and Ac9-25 of Annexin A1 on Conjunctival Goblet Cell Function
Annexin A1 (AnxA1) is the main mediator of the anti-inflammatory actions of glucocorticoids. AnxA1 functions as a pro-resolving mediator in cultured rat conjunctival goblet cells to ensure tissue homeostasis through stimulation of intracellular [Ca2+] ([Ca2+]i) and mucin secretion. AnxA1 has several N-terminal peptides with anti-inflammatory properties of their own, including Ac2-26, Ac2-12 and Ac9-25. The increase in [Ca2+]i caused by AnxA1 and its N-terminal peptides in goblet cells was measured to determine which formyl peptide receptors (FPRs) the compounds use and the action of the peptides on histamine stimulation. (...
Source: American Journal of Pathology - July 7, 2023 Category: Pathology Authors: Anne V. Lyngstadaas, Markus V. Olsen, Jeffrey Bair, Menglu Yang, Robin R. Hodges, Tor P. Utheim, Charles N. Serhan, Darlene A. Dartt Tags: Regular Article Source Type: research
The Expression of Parthanatos Markers and miR-7a-5p Mimic Protects Photoreceptors from Parthanatos by Repressing α-Synuclein in Retinal Detachment
Retinal detachment (RD) refers to the separation between the neuroepithelium and the pigment epithelium layer. It is an important disease leading to irreversible vision damage worldwide, in which photoreceptor cell death plays a major role. α-Synuclein (α-syn) is reportedly involved in numerous mechanisms of neurodegenerative diseases, but the association with photoreceptor damage in RD has not been studied. In this research, elevated transcription levels of α-syn and parthanatos proteins were discovered in the vitreous of patients with RD. (Source: American Journal of Pathology)
Source: American Journal of Pathology - July 6, 2023 Category: Pathology Authors: Xueyan Gao, Lisong Wang, Xing Lu, Yuanye Yan, Yue Guo, Jing Wang, Li Lu, Kai Dong Tags: Regular article Source Type: research
The Role of Gut Microbiome-Derived Short-Chain Fatty Acid Butyrate in Hepatobiliary Diseases
The multiple beneficial effects of the short-chain fatty acid butyrate on human health, produced from fermentable carbohydrates by gut microbiota in the colon, are well known. At the intestinal level, butyrate regulates metabolism, helps in the transepithelial transport of fluids, inhibits inflammation, and induces the epithelial defense barrier. The liver receives a large amount of short-chain fatty acids along with the blood that travels from the gut via the portal vein. In many recent studies, butyrate has been reported to help prevent nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, inflammation, cancer,...
Source: American Journal of Pathology - July 6, 2023 Category: Pathology Authors: Kishor Pant, Senthil K. Venugopal, Maria J. Lorenzo Pisarello, Sergio A. Gradilone Tags: Review Source Type: research
Stress and Liver Fibrogenesis
Stress response pathways are crucial for cells to adapt to physiological and pathologic conditions. Increased transcription and translation in response to stimuli place a strain on the cell, necessitating increased amino acid supply, protein production and folding, and disposal of misfolded proteins. Stress response pathways, such as the unfolded protein response (UPR) and the integrated stress response (ISR), allow cells to adapt to stress and restore homeostasis; however, their role and regulation in pathologic conditions, such as hepatic fibrogenesis, are unclear. (Source: American Journal of Pathology)
Source: American Journal of Pathology - July 6, 2023 Category: Pathology Authors: Zachary Hanquier, Jagannath Misra, Reese Baxter, Jessica L. Maiers Tags: Review Source Type: research
The expression of parthanatos markers and miR-7 mimic protects photoreceptors from parthanatos by repressing α-synuclein in retinal detachment
Retinal detachment refers to the separation between the neuroepithelium and the pigment epithelium layer. It is an important disease leading to irreversible vision damage worldwide, in which photoreceptor cell death plays a major role. Alpha-synuclein ( α-syn) is reportedly involved in numerous mechanisms of neurodegenerative diseases, but the association with photoreceptor damage in retinal detachment has not been studied. In this research, elevated transcription levels of α-syn and parthanatos proteins were discovered in the vitreous of patient s with retinal detachment. (Source: American Journal of Pathology)
Source: American Journal of Pathology - July 6, 2023 Category: Pathology Authors: Xueyan Gao, Lisong Wang, Xing Lu, Yuanye Yan, Yue Guo, Jing Wang, Li Lu, Kai Dong Tags: Regular Article Source Type: research
Stress and Liver Fibrogenesis: Understanding the role and regulation of stress response pathways in Hepatic Stellate Cells
Stress response pathways are crucial for cells to adapt to physiological and pathological conditions. Increased transcription and translation in response to stimuli places a strain on the cell, necessitating increased amino acid supply, protein production and folding, and disposal of misfolded proteins. Stress response pathways such as the Unfolded Protein Response (UPR) and the Integrated Stress Response (ISR) allow cells to adapt to stress and restore homeostasis; however, their role and regulation in pathological conditions such as hepatic fibrogenesis are unclear. (Source: American Journal of Pathology)
Source: American Journal of Pathology - July 6, 2023 Category: Pathology Authors: Zachary Hanquier, Jagannath Misra, Reese Baxter, Jessica L. Maiers Tags: Review Source Type: research
The Role of Gut Microbiome-Derived Short Chain Fatty Acid Butyrate in Hepatobiliary Diseases
The multiple beneficial effects of the short-chain fatty acid (SCFA) butyrate on human health, produced from fermentable carbohydrates by gut microbiota in the colon, are well known. At the intestinal level, butyrate regulates metabolism, helps in the transepithelial transport of fluids, inhibits inflammation, and induces the epithelial defense barrier. The liver receives a large amount of SCFAs along with the blood that travels from the gut via the portal vein. In many recent studies, butyrate has been reported to help prevent NAFLD, NASH, inflammation, cancer, and liver injuries. (Source: American Journal of Pathology)
Source: American Journal of Pathology - July 6, 2023 Category: Pathology Authors: Kishor Pant, Senthil K. Venugopal, Maria J. Lorenzo Pisarello, Sergio A. Gradilone Tags: Review Source Type: research
Sex-Dependent Differences in Cholestasis
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are cholestatic liver diseases that have significant clinical impact with debilitating symptoms and mortality. PBC is predominantly seen in perimenopausal and postmenopausal women; men who are diagnosed with PBC have worse clinical outcomes and all-cause mortality. In contrast, 60% to 70% of patients with PSC are men; the data indicate that female sex may be an independent factor against PSC-related complications. These findings suggest a sex-dependent biological basis for these differences. (Source: American Journal of Pathology)
Source: American Journal of Pathology - July 5, 2023 Category: Pathology Authors: AbdiGhani Ismail, Lindsey Kennedy, Heather Francis Tags: Review Source Type: research
Aberrations in energetic metabolism and stress-related pathways contribute to pathophysiology in the Neb cKO mouse model of nemaline myopathy
Nemaline myopathy (NM) is a genetically and clinically heterogeneous disease that is diagnosed based on the presence of nemaline rods on skeletal muscle biopsy. While NM has typically been classified by causative genes, disease severity or prognosis cannot be predicted well. The common pathological endpoint of nemaline rods (despite diverse genetic causes) and an unexplained range of muscle weakness suggests that shared secondary processes contributed to the pathogenesis of NM. We speculated that these processes could be identified through a proteome wide interrogation utilizing a mouse model of severe NM in combination wi...
Source: American Journal of Pathology - July 5, 2023 Category: Pathology Authors: Rebecca A. Slick, Jennifer A. Tinklenberg, Jessica Sutton, Liwen Zhang, Hui Meng, Margaret Beatka, Mark Vanden Avond, Mariah J. Prom, Emily Ott, Federica Montanaro, James Heisner, Rafael Toro, Henk Granzier, Aron M. Geurts, David Stowe, R. Blake Hill, Mic Tags: Regular Article Source Type: research
