journal
https://read.qxmd.com/read/37717941/resolvin-d2-gpr18-enhances-bone-marrow-function-and-limits-steatosis-and-hepatic-collagen-accumulation-in-aging
#1
JOURNAL ARTICLE
Hannah Fitzgerald, Jesse L Bonin, Sayeed Khan, Maya Eid, Sudeshna Sadhu, Allison Rahtes, Masharh Lipscomb, Nirupam Biswas, Christa Decker, Melisande Nabage, Ramon Bossardi Ramos, Giesse Albeche Duarte, Michael Marinello, Anne Chen, Hasan Basri Aydin, Hebe Agustina Mena, Kurrim Gilliard, Matthew Spite, C Michael DiPersio, Alejandro Adam, Katherine C MacNamara, Gabrielle Fredman
Aging is associated with non-resolving inflammation and tissue dysfunction. Resolvin D2 (RvD2) is a pro-resolving ligand that acts through the G-protein coupled receptor (GPCR) called GPR18. Unbiased RNA sequencing revealed increased Gpr18 expression in macrophages from old mice, and in livers from elderly humans, which was associated with increased steatosis and fibrosis in middle-aged (MA) and old mice. MA mice that lack GPR18 on myeloid cells had exacerbated steatosis and hepatic fibrosis, which was associated with a decline in Mac2+ macrophages...
September 15, 2023: American Journal of Pathology
https://read.qxmd.com/read/37717940/estrogen-related-receptor-agonism-reverses-mitochondrial-dysfunction-and-inflammation-in-the-aging-kidney
#2
JOURNAL ARTICLE
Xiaoxin X Wang, Komuraiah Myakala, Andrew E Libby, Ewa Krawczyk, Julia Panov, Bryce A Jones, Kanchan Bhasin, Nataliia Shults, Yue Qi, Kristopher W Krausz, Patricia M Zerfas, Shogo Takahashi, Parnaz Daneshpajouhnejad, Avi Titievsky, Elizaveta Taranenko, Cyrielle Billon, Arindam Chatterjee, John K Walker, Chris Albanese, Jeffrey B Kopp, Avi Z Rosenberg, Frank J Gonzalez, Udayan Guha, Leonid Brodsky, Thomas P Burris, Moshe Levi
A gradual decline in renal function occurs even in healthy aging individuals. In addition to aging, per se, concurrent metabolic syndrome and hypertension, which are common in the aging population, can induce mitochondrial dysfunction and inflammation, which collectively contribute to age-related kidney dysfunction and disease. This study examined the role of the nuclear hormone receptors, the estrogen-related receptors (ERRs), in regulation of age-related mitochondrial dysfunction and inflammation. The ERRs were decreased in both aging human and mouse kidneys and were preserved in aging mice with lifelong caloric restriction (CR)...
September 15, 2023: American Journal of Pathology
https://read.qxmd.com/read/37704096/this-month-in-ajp
#3
JOURNAL ARTICLE
(no author information available yet)
No abstract text is available yet for this article.
September 11, 2023: American Journal of Pathology
https://read.qxmd.com/read/37689386/depletion-of-bone-marrow-hematopoietic-cells-in-ebola-virus-infected-rhesus-macaques-a-possible-cause-of-hematologic-abnormalities-in-ebola-virus-disease
#4
JOURNAL ARTICLE
David X Liu, Bapi Pahar, Donna L Perry, Huanbin Xu, Timothy K Cooper, Louis M Huzella, Randy J Hart, Amanda M W Hischak, John Bernbaum, Marisa St Claire, Russell Byrum, Richard S Bennett, Travis Warren, Michael R Holbrook, Lisa E Hensley, Ian Crozier, Connie S Schmaljohn
The pathophysiology of long-recognized hematological abnormalities in Ebola virus disease (EVD) is unknown. From limited human sampling (of peripheral blood), it has been postulated that emergency hematopoiesis plays a role in severe EVD, but the systematic characterization of the bone marrow (BM) has not occurred in human disease or in nonhuman primate models. In a lethal rhesus macaque (RhM) model of EVD, sternal BMs from eighteen RhMs were characterized after intramuscular exposure to Ebola virus (EBOV) Kikwit as compared to uninfected controls (n=3)...
September 7, 2023: American Journal of Pathology
https://read.qxmd.com/read/37689385/the-role-of-endoplasmic-reticulum-in-lipotoxicity-during-masld-pathogenesis
#5
REVIEW
Nanditha Venkatesan, Luke C Doskey, Harmeet Malhi
Perturbations in lipid and protein homeostasis induce endoplasmic reticulum (ER) stress in metabolic-dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD). Lipotoxic and proteotoxic stress can activate the unfolded protein response (UPR) transducers: Inositol Requiring Enzyme1α, PKR-like ER Kinase and Activating Transcription Factor 6α. Collectively, these pathways induce expression of genes that encode functions to resolve the protein folding defect and ER stress by increasing the protein folding capacity of the ER and degradation of misfolded proteins...
September 7, 2023: American Journal of Pathology
https://read.qxmd.com/read/37689384/elucidating-the-morphogenic-and-signaling-roles-of-defined-growth-factors-controlling-human-endothelial-cell-lumen-formation-versus-sprouting-behavior
#6
JOURNAL ARTICLE
Prisca K Lin, Gretchen M Koller, George E Davis
We have previously shown that five growth factors (Factors) [i.e. insulin, fibroblast growth factor-2 (FGF-2), stem cell factor (SCF), interleukin-3 (IL-3), and stromal-derived factor-1 alpha (SDF-1α)] in combination are necessary for human ECs to undergo tube morphogenesis, a process requiring both lumen formation and sprouting behavior. Here, we investigate why they are required by subdividing the Factors into 4 separate groups: Insulin only, Insulin + FGF-2, no FGF-2 (all Factors but without FGF-2), and all Factors...
September 7, 2023: American Journal of Pathology
https://read.qxmd.com/read/37689383/defective-uterine-spiral-artery-remodelling-and-placental-senescence-in-a-pregnant-rat-model-of-polycystic-ovary-syndrome
#7
JOURNAL ARTICLE
Min Hu, Yuehui Zhang, Xu Zhang, XiuYing Zhang, Xinyue Huang, Yaxing Lu, Yijia Li, Mats Brännström, Amanda Nancy Sferruzzi-Perri, Linus R Shao, Håkan Billig
Pregnancy-related problems have been linked to impairments in maternal uterine spiral artery (SpA) remodelling. The mechanisms underlying this association are still unclear, as are whether hyperandrogenism and insulin resistance - the two common manifestations of polycystic ovary syndrome (PCOS) - affect uterine SpA remodelling. This study verified previous work in which exposure to 5-dihydrotestosterone (DHT) and insulin (INS) in rats during pregnancy resulted in hyperandrogenism, insulin intolerance, and higher foetal mortality...
September 7, 2023: American Journal of Pathology
https://read.qxmd.com/read/37683929/elucidating-the-role-of-the-microbiome-in-ocular-diseases
#8
EDITORIAL
Wendy Luo, Dimitra Skondra
No abstract text is available yet for this article.
September 6, 2023: American Journal of Pathology
https://read.qxmd.com/read/37673331/adolescence-and-the-microbiome-implications-for-healthy-growth-and-maturation
#9
REVIEW
Matthew D Carson, Caroline Westwater, Chad M Novince
The gut microbiota was initially thought to develop into a stable, adult-like profile during early postnatal life. The formation of the gut microbiota during early life has been shown to contribute to healthy growth and has lifelong implications for host health. Adolescence, the developmental period between childhood and adulthood, is a critical window for healthy growth and maturation. The composition of the gut microbiota in adolescents is distinct from that of children and adults, which supports the premise that the gut microbiota continues to develop during adolescence toward an adult-like profile...
September 4, 2023: American Journal of Pathology
https://read.qxmd.com/read/37673330/renal-fibrosis-is-alleviated-through-targeted-inhibition-of-interleukin-11-induced-renal-tubular-epithelial-to-mesenchymal-transition
#10
JOURNAL ARTICLE
Yaqin Li, Congwei Luo, Yiqun Zeng, Zerong Zheng, Danping Tao, Qiao Liu, Yiyu Hong, Shuo Wang, Haibo Long, Zhaozhong Xu
Renal fibrosis is a pathological process that leads to irreversible renal failure without effective treatment. Epithelial-to-mesenchymal transition (EMT) plays a key role in the pathogenesis of renal fibrosis. Herein, we found that tubular aberrant expression of Interleukin (IL)-11 is critically involved in renal fibrosis. IL-11 and its receptor IL-11Rα1 were significantly induced in unilateral ureteral obstruction (UUO) kidneys and were mainly expressed by renal tubular epithelial cells (RTECs), co-localised with transforming growth factor (TGF)-β1...
September 4, 2023: American Journal of Pathology
https://read.qxmd.com/read/37673329/the-sympathetic-nervous-system-promotes-hepatic-lymphangiogenesis-which-is-protective-against-liver-fibrosis
#11
JOURNAL ARTICLE
Masatake Tanaka, Jain Jeong, Courtney Thomas, Xuchen Zhang, Pengpeng Zhang, Junji Saruwatari, Reiichiro Kondo, Matthew McConnell, Teruo Utsumi, Yasuko Iwakiri
The liver is the largest lymph-producing organ. In cirrhotic patients, lymph production significantly increases concomitant with lymphangiogenesis. The aim of this study was to determine the mechanism of lymphangiogenesis in liver and its implication in liver fibrosis. Liver biopsies from portal hypertensive patients with portal-sinusoidal vascular disease(PSVD)(n=22) and liver cirrhosis(n=5) were evaluated for hepatic lymphatic vessels(LVs) comparing with controls(n=9, n=6, respectively). For mechanistic studies, rats with partial portal vein ligation(PPVL) and bile duct ligation(BDL) were used...
September 4, 2023: American Journal of Pathology
https://read.qxmd.com/read/37673328/sortilin-driven-cancer-secretome-enhances-tumorigenic-properties-of-hepatocellular-carcinoma-via-de-novo-lipogenesis
#12
JOURNAL ARTICLE
Kristy Kwan-Shuen Chan, Kwan-Yung Au, Long-Hin Suen, Bernice Leung, Cheuk-Yan Wong, Wei-Qiang Leow, Tony Kiat-Hon Lim, Irene Oi-Lin Ng, Clive Yik-Sham Chung, Regina Cheuk-Lam Lo
A growing body of evidence suggests de novo lipogenesis (DNL) as a key metabolic pathway adopted by cancers to fuel tumorigenic processes. While increased DNL has also been reported in hepatocellular carcinoma (HCC), understanding on molecular mechanisms driving DNL remains limited. In the present study, we investigated the functional role of sortilin, a member of the vacuolar protein sorting 10 protein (Vps10p) receptor family, in HCC. Sortilin was overexpressed in HCC and associated with poorer survival outcome...
September 4, 2023: American Journal of Pathology
https://read.qxmd.com/read/37673327/domain-and-histopathology-adaptations-based-classification-for-malignancy-grading-system
#13
JOURNAL ARTICLE
Vicky Mudeng, Mifta Nur Farid, Gelan Ayana, Se-Woon Choe
Through accurate proliferation rate quantification, an appropriate treatment for breast cancer may be devised. Pathologists use breast tissue biopsy glass slides stained with hematoxylin and eosin to obtain grading information. However, this manual evaluation may lead to high costs and ineffectiveness because diagnosis depends on the facility and the pathologists' insights and experiences. A convolutional neural network is considered feasible as a computer-based observer to improve clinicians' capacity in grading breast cancer...
September 4, 2023: American Journal of Pathology
https://read.qxmd.com/read/37673326/granulocyte-colony-stimulating-factor-is-a-determinant-of-severe-bronchopulmonary-dysplasia-and-coincident-retinopathy
#14
JOURNAL ARTICLE
Lakshanie C Wickramasinghe, Evelyn Tsantikos, Alida Kindt, April L Raftery, Timothy A Gottschalk, Jessica G Borger, Atul Malhotra, Gary P Anderson, Peter van Wijngaarden, Anne Hilgendorff, Margaret L Hibbs
Bronchopulmonary dysplasia (BPD, also called chronic lung disease of immaturity) afflicts approximately one-third of all extremely premature infants causing lifelong lung damage. There is no effective treatment other than supportive care. Retinopathy of prematurity (ROP), which irreversibly impairs vision, is common in BPD, suggesting related pathogenesis, but specific mechanisms of BPD and ROP are obscure. A neonatal mouse hyperoxic model of coincident BPD and retinopathy was used to screen for candidate mediators, which revealed that granulocyte colony-stimulating factor (G-CSF/CSF3) was significantly upregulated in mouse lung lavage fluid and plasma at postnatal day 14 in response to hyperoxia...
September 4, 2023: American Journal of Pathology
https://read.qxmd.com/read/37676196/tryptophan-metabolites-target-transmembrane-and-ig-domain-containing-1-signaling-to-augment-renal-tubular-injury
#15
JOURNAL ARTICLE
Mostafa Belghasem, Wenqing Yin, Saran Lotfollahzadeh, Xiaosheng Yang, Rosana D Meyer, Marc A Napoleon, Isaac E Sellinger, Aniket Vazirani, Elena Metrikova, Asha Jose, Anna Zhebrun, Stephen A Whelan, Norman Lee, Nader Rahimi, Vipul C Chitalia
Chronic kidney disease (CKD) is characterized by the accumulation of uremic toxins and renal tubular damage. Tryptophan-derived uremic toxins [indoxyl sulfate (IS) and kynurenine (Kyn)] are well-characterized tubulotoxins. Emerging evidence suggests that transmembrane and Ig domain-containing 1 (TMIGD1) protects tubular cells and promotes survival. However, the direct molecular mechanism(s) underlying how these two opposing pathways crosstalk remains unknown. We posited that IS and Kyn mediate tubular toxicity through TMIGD1 and the loss of TMIGD1 augments tubular injury...
August 30, 2023: American Journal of Pathology
https://read.qxmd.com/read/37634709/limbal-stem-cell-dysfunction-induced-by-severe-dry-eye-via-activation-of-the-p38-mapk-signaling-pathway
#16
JOURNAL ARTICLE
Sijie Lin, Minqing Cai, Lingyu Zhang, Yi Mao, Han Wu, Xiaodong Liu, Yixuan Li, Minghui Liang, Xinxuan Cheng, Fei Yu, Hui He, Rongrong Zong, Huping Wu, Zuguo Liu, Shangkun Ou, Wei Li
Severe dry eye (SDE) can cause grievous damage of the ocular surface and result in vision impairment and even blindness. To investigate the fate of limbal stem cells in SDE and the underlying mechanism, we established an SDE rat model by removing the extra orbital and infraorbital lacrimal glands and maintained it in a low-humidity environment. One month after the operation, aqueous tear secretion dramatically reduced, blood vessels invaded into the central cornea, and inflammatory cells infiltrated into the limbal stroma...
August 25, 2023: American Journal of Pathology
https://read.qxmd.com/read/37572947/the-continuing-saga-of-timp2-emerging-roles-in-tissue-homeostasis-and-cancer-progression
#17
REVIEW
William G Stetler-Stevenson
Tissue inhibitors of metalloproteinases (TIMPs) are a conserved family of proteins that were originally identified as cytokine-like erythroid growth factors. Subsequently, TIMPs were characterized as endogenous inhibitors of Matrixin proteinases. These proteinases are the primary mediators of extracellular matrix turnover in pathologic conditions such as cancer invasion and metastasis. Thus, TIMPs were immediately recognized as important regulators of tissue homeostasis. However, TIMPs also demonstrate unique biological activities that are independent of metalloproteinase regulation...
August 10, 2023: American Journal of Pathology
https://read.qxmd.com/read/37544502/standardized-classification-of-lung-adenocarcinoma-subtypes-and-improvement-of-grading-assessment-through-deep-learning
#18
JOURNAL ARTICLE
Kris Lami, Noriaki Ota, Shinsuke Yamaoka, Andrey Bychkov, Keitaro Matsumoto, Wataru Uegami, Jijgee Munkhdelger, Kurumi Seki, Odsuren Sukhbaatar, Richard Attanoos, Sabina Berezowska, Luka Brcic, Alberto Cavazza, John C English, Alexandre Todorovic Fabro, Kaori Ishida, Yukio Kashima, Yuka Kitamura, Brandon T Larsen, Alberto M Marchevsky, Takuro Miyazaki, Shimpei Morimoto, Mutsumi Ozasa, Anja C Roden, Frank Schneider, Maxwell L Smith, Kazuhiro Tabata, Angela M Takano, Tomonori Tanaka, Tomoshi Tsuchiya, Takeshi Nagayasu, Hidenori Sakanashi, Junya Fukuoka
The histopathologic distinction of lung adenocarcinoma (LADC) subtypes is subject to high interobserver variability, which can compromise the optimal assessment of patient prognosis. Therefore, this study developed convolutional neural networks capable of distinguishing LADC subtypes and predicting disease-specific survival, according to the recently established LADC tumor grades. Consensus LADC histopathologic images were obtained from 17 expert pulmonary pathologists and one pathologist in training. Two deep learning models (AI-1 and AI-2) were trained to predict eight different LADC classes...
August 5, 2023: American Journal of Pathology
https://read.qxmd.com/read/37544504/the-cellular-molecular-and-pathological-consequences-of-stress-on-the-liver
#19
EDITORIAL
Jessica L Maiers, Sanjukta Chakraborty
No abstract text is available yet for this article.
August 4, 2023: American Journal of Pathology
https://read.qxmd.com/read/37544503/urothelium-specific-expression-of-mutationally-activated-pik3ca-initiates-early-lesions-of-non-invasive-bladder-cancer
#20
JOURNAL ARTICLE
Lauren Shuman, Jonathan Pham, Thomas Wildermuth, Xue-Ru Wu, Vonn Walter, Joshua I Warrick, David J DeGraff
Despite the fact that ∼70% of bladder cancers are non-invasive and have high recurrence rates, early stage disease is understudied. The relative lack of models to validate the contribution of molecular drivers of bladder tumorigenesis is a significant issue. While mutations in PIK3CA are frequent in human bladder cancer, an in vivo model for understanding their contribution to bladder tumorigenesis is unavailable. Therefore, a Upk2-Cre/Pik3caH1047R mouse model expressing one or two R26-Pik3caH1047R alleles in a urothelium-specific manner was created...
August 4, 2023: American Journal of Pathology
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