Androgen receptor interacting proteins in prostate cancer development and therapy resistance
Endocrine therapy for prostate cancer is based on the use of drugs that diminish androgen concentration and androgen receptor (AR) signaling inhibitors and is limited by the functional consequences of AR point mutations and increased expression of constitutively active receptors. Many coactivators (> 280) interact with different AR regions. Most studies have determined the expression of coactivators and their effects in the presence of increasing concentrations of androgen or the anti-androgen enzalutamide. (Source: American Journal of Pathology)
Source: American Journal of Pathology - December 15, 2023 Category: Pathology Authors: Zoran Culig, Martin Puhr Tags: Review Source Type: research
Vitamin D receptor activation reduces hepatic inflammation via enhancing macrophage autophagy in cholestatic mice
Macrophage autophagy dysfunction aggravates liver injury by activating inflammasomes, which can cleave pro-IL-1 β to its active, secreted form. Here, to determine whether the vitamin D (VD)/ VD receptor (VDR) axis could upregulate macrophage autophagy function to inhibit the activation of inflammasome-dependent IL-1β during cholestasis. Paricalcitol (PAL, VDR agonist) was intraperitoneally injected into bil e duct ligated (BDL) mice for 5 days. Research found that upregulation of VDR expression by PAL reduced liver injury by reducing the oxidative stress (OS)-induced inflammatory reaction in macrophages. (Source: America...
Source: American Journal of Pathology - December 15, 2023 Category: Pathology Authors: Tianfu Wen, Jing Xie, Liman Ma, Zhiqing Hao, Weiwei Zhang, Tingyao Wu, Lihua Li Tags: Regular Article Source Type: research
Clonal origin and lineage ambiguity in mixed neuroendocrine carcinoma of the uterine cervix
In this study, a panel of organoid lines from patients with SCNEC/cervix was established and focused on one line, which retained a mixed tumor phenotype, both in vitro and in vivo. Histologically, both organoids and xenograft tumors showed distinct differentiation into either SCNEC or adenocarcinoma in some regions and ambiguous differentiation in others. (Source: American Journal of Pathology)
Source: American Journal of Pathology - December 14, 2023 Category: Pathology Authors: Masamune Masuda, Keita Iida, Sadahiro Iwabuchi, Mie Tanaka, Satoshi Kubota, Hiroyuki Uematsu, Kunishige Onuma, Yoji Kukita, Kikuya Kato, Shoji Kamiura, Aya Nakajima, Roberto Coppo, Mizuki Kanda, Kiyoshi Yoshino, Yutaka Ueda, Eiichi Morii, Tadashi Kimura, Tags: Regular Article Source Type: research
IL-22 Binding Protein Controls IL-22 –Driven Bleomycin-Induced Lung Injury
The high mortality rates of acute lung injury and acute respiratory distress syndrome challenge the field to identify biomarkers and factors that can be exploited for therapeutic approaches. IL-22 is a cytokine that has antibacterial and reparative properties in the lung. However, it also can exacerbate inflammation and requires tight control by the extracellular inhibitory protein known as IL-22 binding protein (IL-22BP) (Il22ra2). Here, the necessity of IL-22BP in controlling and preventing acute lung injury is shown using IL-22BP knockout mice (Il22ra2 −/−) in the bleomycin model of acute lung injury/acute respirato...
Source: American Journal of Pathology - December 13, 2023 Category: Pathology Authors: Zhe Zhang, Mazvita B. Chakawa, Joshua A. Frydman, Michaela J. Allen, Michelle Galeas Pena, MaryJane Jones, Derek Pocias Tags: Regular article Source Type: research
Suppression of Overactive Insulin-Like Growth Factor 1 Attenuates Trauma-Induced Heterotopic Ossification in Mice
In this study, using an Achilles tendon puncture-induced HO model, we revealed that overactive insulin-like growth factor 1 (IGF-1) was involved in the progression of HO in mice. (Source: American Journal of Pathology)
Source: American Journal of Pathology - December 13, 2023 Category: Pathology Authors: Dong Mao, Kai Wang, Hong Jiang, Jingyi Mi, Xiaoyun Pan, Gang Zhao, Yongjun Rui Tags: Regular article Source Type: research
IL-22 binding protein controls IL-22 driven bleomycin-induced lung injury
The high mortality rates of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) challenge the field to identify biomarkers and factors that can be exploited for therapeutic approaches. IL-22 is a cytokine that has antibacterial and reparative properties in the lung. However, it can also exacerbate inflammation and requires tight control by the extracellular inhibitory protein known as IL-22 binding protein (IL-22BP) (Il22ra2). Here we demonstrate the necessity of IL-22BP in controlling and preventing acute lung injury using IL-22BP knockout mice (Il22ra2-/-) in the bleomycin model of ALI/ARDS. (Source: A...
Source: American Journal of Pathology - December 13, 2023 Category: Pathology Authors: Zhe Zhang, Mazvita B. Chakawa, Joshua A. Frydman, Michaela J. Allen, Michelle Galeas Pena, MaryJane Jones, Derek Pociask Tags: Regular Article Source Type: research
Suppression of overactive IGF-1 attenuates trauma-induced heterotopic ossification in mice
In this study, using an Achilles tendon puncture-induced HO model, we revealed that overactive insulin-like growth factor 1 (IGF-1) was involved in the progression of HO in mice. (Source: American Journal of Pathology)
Source: American Journal of Pathology - December 13, 2023 Category: Pathology Authors: Dong Mao, Kai Wang, Hong Jiang, Jingyi Mi, Xiaoyun Pan, Gang Zhao, Yongjun Rui Tags: Regular Article Source Type: research
Vision Transformers for Breast Cancer Human Epidermal Growth Factor Receptor 2 Expression Staging without Immunohistochemical Staining
This article argues for the effectiveness of customized vision transformers in staging HER2 expression in breast cancer using only hematoxylin and eosin –stained images. This work introduces a spatial transformer network for weakly localizing critical image features before using a vision transformer-based deep learning architecture. (Source: American Journal of Pathology)
Source: American Journal of Pathology - December 12, 2023 Category: Pathology Authors: Gelan Ayana, Eonjin Lee, Se-woon Choe Tags: Regular article Source Type: research
A complex interplay between Notch effectors and β-catenin signaling in morular differentiation of endometrial carcinoma cells
Notch signaling contributes to tissue development and homeostasis, but little is known about its roles in morular differentiation of endometrial carcinoma (Em Ca) cells. The current study focused on crosstalk between Notch and β-catenin signaling in Em Ca with morules. Promoters of hairy and enhancer of split 1 (Hes1) and mastermind-like 2 (MAML2) were activated by Notch intracellular domain 1 (NICD1) but not β-catenin; we also observed a positive feedback loop between Hes1 and MAML2. Immunoreactivities for nuclear β-c atenin, Hes1, and MAML2, as well as the interaction between β-catenin and Hes1 or MAML2, were signifi...
Source: American Journal of Pathology - December 12, 2023 Category: Pathology Authors: Ako Yokoi, Akari Murayama, Miki Hashimura, Yasuko Oguri, Yohei Harada, Naomi Fukagawa, Misato Hayashi, Mototsugu Ono, Kensuke Ohhigata, Makoto Saegusa Tags: Regular Article Source Type: research
Vision transformers for breast cancer human epidermal growth factor receptor 2 (HER2) expression staging without immunohistochemical (IHC) staining
This article argues for the effectiveness of customized vision transformers in staging HER2 expression in breast cancer using only H&E-stained images. This work introduces a spatial transformer network (STN) for weakly localizing critical image features before utilizing a vision transformer-based deep learning architecture. (Source: American Journal of Pathology)
Source: American Journal of Pathology - December 12, 2023 Category: Pathology Authors: Gelan Ayana, Eonjin Lee, Se-woon Choe Tags: Regular Article Source Type: research
This Month in AJP
microRNA 29 (miR-29) has been implicated in skin repair. Using human skin samples, cultured cells, and a cutaneous wound healing mouse model, Robinson and Thiagarajan et al (Am J Pathol, AJPA-D-23-00323) studied the effect of inhibiting miR-29 on epidermal regeneration. Inhibition of miR-29 promoted angiogenesis both in vivo and in vitro and increased maturation of provisional granulation tissue in vivo. miR-29 target mRNA laminin C2 may facilitate these processes. Inhibition of miR-29 or up-regulation of laminin C2 may improve skin repair. (Source: American Journal of Pathology)
Source: American Journal of Pathology - December 9, 2023 Category: Pathology Tags: This Month in AJP Source Type: research
Vascular Endothelial Growth Factor-C Treatment Enhances Cerebrospinal Fluid Outflow during Toxoplasma gondii Brain Infection but Does Not Improve Cerebral Edema
Cerebral edema frequently develops in the setting of brain infection and can contribute to elevated intracranial pressure, a medical emergency. Currently, it is incompletely understood how excess fluid is cleared from the brain. Previous studies have shown that interstitial fluid is transported out of the brain along perivascular channels that collect into the cerebrospinal fluid (CSF) –filled subarachnoid space. CSF is then removed from the central nervous system through venous and lymphatic routes. (Source: American Journal of Pathology)
Source: American Journal of Pathology - December 6, 2023 Category: Pathology Authors: Michael A. Kovacs, Isaac W. Babcock, Ana Royo Marco, Lydia A. Sibley, Abigail G. Kelly, Tajie H. Harris Tags: Regular article Source Type: research
VEGF-C treatment enhances cerebrospinal fluid outflow during Toxoplasma gondii brain infection but does not improve cerebral edema
Cerebral edema frequently develops in the setting of brain infection and can contribute to elevated intracranial pressure, a medical emergency. Currently, it is incompletely understood how excess fluid is cleared from the brain. Previous studies have shown that interstitial fluid is transported out of the brain along perivascular channels that collect into the cerebrospinal fluid (CSF)-filled subarachnoid space. CSF is then removed from the central nervous system through venous and lymphatic routes. (Source: American Journal of Pathology)
Source: American Journal of Pathology - December 6, 2023 Category: Pathology Authors: Michael A. Kovacs, Isaac W. Babcock, Ana Royo Marco, Lydia A. Sibley, Abigail G. Kelly, Tajie H. Harris Tags: Regular Article Source Type: research
Understanding One Half of the Sex Difference Equation
Diabetes is a prevalent disease, primarily characterized by high blood sugar (hyperglycemia). Significantly higher rates of myocardial dysfunction have been noted in individuals with diabetes, even in those without coronary artery disease or high blood pressure (hypertension). Numerous molecular mechanisms have been identified through which diabetes contributes to the pathology of diabetic cardiomyopathy, which presents as cardiac hypertrophy and fibrosis. At the cellular level, oxidative stress and inflammation in cardiomyocytes are triggered by hyperglycemia. (Source: American Journal of Pathology)
Source: American Journal of Pathology - December 5, 2023 Category: Pathology Authors: Mika'il Visanji, Daniel E. Venegas-Pino, Geoff H. Werstuck Tags: Review Source Type: research
Understanding One Half of the Sex Difference Equation: The Modulatory Effects of Testosterone on Diabetic Cardiomyopathy
Diabetes is a prevalent disease, primarily characterized by high blood sugar (hyperglycemia). Significantly higher rates of myocardial dysfunction have been noted in individuals with diabetes, even in those without coronary artery disease or high blood pressure (hypertension). Numerous molecular mechanisms have been identified, through which diabetes contributes to the pathology of diabetic cardiomyopathy, which presents as cardiac hypertrophy and fibrosis. At the cellular level, oxidative stress and inflammation in cardiomyocytes are triggered by hyperglycemia. (Source: American Journal of Pathology)
Source: American Journal of Pathology - December 5, 2023 Category: Pathology Authors: Mika ’il Visanji, Daniel E. Venegas-Pino, Geoff H. Werstuck Tags: Review Source Type: research
