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Fatal neuroinvasion of SARS-CoV-2 in K18-hACE2 mice is partially dependent on hACE2 expression bioRxiv. Pathol. Pub Date : 2021-01-13 Mariano Carossino; Paige Montanaro; Aoife O'Connell; Devin Kenney; Hans Gertje; Kyle Grosz; Susanna Kurnick; Markus Bosmann; Mohsan Saeed; Udeni Balasuriya; Florian Douam; Nicholas Crossland
Animal models recapitulating the distinctive features of severe COVID-19 are critical to enhance our understanding of SARS-CoV-2 pathogenesis. Transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) under the cytokeratin 18 promoter (K18-hACE2) represent a lethal model of SARS-CoV-2 infection. However, the cause(s) and mechanisms of lethality in this mouse model remain unclear. Here
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Ineffectual AEC1 Differentiation from KRT8hi Transitional Cells without Fibrosis Associated with Fatal Acute Respiratory Failure in COVID-19 ARDS bioRxiv. Pathol. Pub Date : 2021-01-13 Christopher Ting; Mohit Aspal; Neil Vaishampayan; Steven K. Huang; Fa Wang; Carol Farver; Rachel Lynne Zemans
COVID-19 ARDS is associated with prolonged ventilator dependence and high mortality, but the underlying mechanisms are unknown. Critical to the pathogenesis of ARDS is injury to the alveolar epithelial cell (AEC) barrier; clinical recovery requires epithelial regeneration. We previously identified a KRT8hi transitional state that regenerating AEC2s adopt during differentiation into AEC1s, the persistence
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Utilisation of semiconductor sequencing for the detection of predictive biomarkers in glioblastoma bioRxiv. Pathol. Pub Date : 2021-01-11 Gareth Williams; Robert Thatcher; Keeda-Marie Hardisty; Marco Loddo
The standard treatment for glioblastoma involves a combination of surgery, radiation and chemotherapy but have limited impact on survival. The exponential increase in targeted agents directed at pivotal oncogenic pathways now provide new therapeutic opportunities for this tumour type. However, lack of comprehensive precision oncology testing at diagnosis means such therapeutic opportunities are potentially
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IRGM/Irgm1 Aggravates Progression of Atherosclerosis by Inducing Macrophage Apoptosis bioRxiv. Pathol. Pub Date : 2021-01-08 Shaohong Fang; Song Sun; Hengxuan Cai; Xinran Hao; Xiaoyi Zou; Xin Wan; Jiangtian Tian; Zhaoying Li; Shanjie Wang; Zhongze He; Wei Huang; Chenchen Liang; Zhenming Zhang; Liming Yang; Jinwei Tian; Bo Yu; Bo Sun
Acute coronary syndrome (ACS) caused by plaque rupture (PR) is the chief culprit behind cardiovascular death, yet its exact mechanism remains unclear. Immunity-related GTPase (IRGM/Irgm1) has been widely studied in several inflammatory diseases, but the role of IRGM/Irgm1 in atherosclerosis is poorly characterized. Here, we shed light on the mechanism by which IRGM/Irgm1 contributes to plaque vulnerability
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The peripheral T cell population is associated with pneumonia severity in cynomolgus monkeys experimentally infected with severe acute respiratory syndrome coronavirus 2 bioRxiv. Pathol. Pub Date : 2021-01-07 Noriyo Nagata; Naoko Iwata-Yoshikawa; Kaori Sano; Akira Ainai; Nozomi Shiwa; Masayuki Shirakura; Noriko Kishida; Tomoko Arita; Yasushi Suzuki; Toshihiko Harada; Yasuhiro Kawai; Yasushi Ami; Shun Iida; Harutaka Katano; Seiichiro Fujisaki; Tsuyoshi Sekizuka; Hiroyuki Shimizu; Tadaki Suzuki; Hideki Hasegawa
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global pandemic that began in December 2019. Lymphopenia is a common feature in severe cases of COVID-19; however, the role of T cell responses during infection is unclear. Here, we inoculated six cynomolgus monkeys, divided into two groups according to the CD3+ T cell population in
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Protection against reinfection with D614- or G614-SARS-CoV-2 isolates in hamsters bioRxiv. Pathol. Pub Date : 2021-01-07 Marco Brustolin; Jordi Rodon; Maria Luisa Rodriguez de la Concepcion; Carlos Avila-Nieto; Guillermo Cantero; Monica Perez; Te Nigeer; Marc Noguera-Julian; Victor Guallar; Alfonso Valencia; Nuria Roca; Nuria Izquierdo-Useros; Julia Blanco; Bonaventura Clotet; Albert Bensaid; Jorge Carrillo; Julia Vergara-Alert; Joaquim Segales
Reinfections with SARS-CoV-2 have already been documented in humans, although its real incidence is currently unknown. Besides having great impact on public health, this phenomenon raises the question if immunity generated by a single infection is sufficient to provide sterilizing/protective immunity to a subsequent SARS-CoV-2 re-exposure. The Golden Syrian hamster is a manageable animal model to explore
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Pixelwise H-score: a novel digital image analysis based-metric to quantify membrane biomarker expression from immunohistochemistry images bioRxiv. Pathol. Pub Date : 2021-01-06 Sripad Ram; Pamela Vizcarra; Pamela Whalen; Shibing Deng; Amy Jackson-Fisher; Steven Pirie-Shepherd; Xiaoling Xia; Eric Powell
Immunohistochemistry (IHC) assays play a central role in evaluating biomarker expression in tissue sections for diagnostic and research applications. Manual scoring of IHC images, which is the current standard of practice, is known to have several shortcomings in terms of reproducibility and scalability to large scale studies. Here, by using a digital image analysis-based approach, we introduce a new
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Compensatory hepatic adaptation accompanies permanent absence of intrahepatic biliary network due to YAP1 loss in liver progenitors bioRxiv. Pathol. Pub Date : 2021-01-04 Laura M Molina; Junjie Zhu; Qin Li; Tirthadipa Pradhan-Sundd; Khaled Sayed; Nathaniel Jenkins; Ravi Vats; Sungjin Ko; Shikai Hu; Minakshi Poddar; Sucha Singh; Junyan Tao; Prithu Sundd; Aatur Singhi; Simon C Watkins; Xiaochao Ma; Panayiotis V Benos; Andrew Feranchak; Kari Nejak-Bowen; Alan Watson; Aaron Bell; Satdarshan P Monga
YAP1 regulates cell plasticity during liver injury, regeneration and cancer, but its role in liver development is unknown. YAP1 activity was detected in biliary cells and in cells at the hepato-biliary bifurcation in single-cell RNA-sequencing analysis of developing livers. Hepatoblast deletion of Yap1 led to no impairment in Notch-driven SOX9+ ductal plate formation, but prevented the formation of
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CRP immunodeposition and proteomic analysis in abdominal aortic aneurysm bioRxiv. Pathol. Pub Date : 2020-12-30 Eun Na Kim; Jiyoung Yu; Joon Seo Lim; Hwangkyo Jeong; Chong Jai Kim; Jae-Sung Choi; So Ra Kim; Hee-Sung Ahn; Kyunggon Kim; Se Jin Oh
Objective: The molecular mechanisms of the degeneration of the aortic wall in abdominal aortic aneurysm (AAA) are poorly understood. The monomeric form of C-reactive protein (mCRP) is deposited in damaged cardiovascular organs and aggravates the prognosis; however, it is unknown whether mCRP is deposited in the degenerated aorta of abdominal aortic aneurysm (AAA). We investigated whether mCRP is deposited
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C1q/CTRP1 exerts neuroprotective effects in TBI rats by regulating inflammation and autophagy bioRxiv. Pathol. Pub Date : 2020-12-29 Ming Pei; Chaoqun Wang; Zhengdong Li; Jianhua Zhang; Ping Huang; Jiawen Wang; Jiang Huang; Donghua Zou; Yijiu Chen
Objective: C1q/CTRP1 is a newly discovered adiponectin protein, which is highly expressed in adipose and heart tissues. Recent studies have revealed that C1q/CTRP1 can regulate metabolism and inhibit inflammation. CTRP1 is also expressed in brain tissues and vascular cells of human and rat, and research on cerebral hemorrhage and cerebral ischemia-reperfusion injury demonstrates that the CTRP family
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Increased ketohexokinase-A governs fructose-induced podocyte hypertrophy by IL-6/STAT3 signaling activation bioRxiv. Pathol. Pub Date : 2020-12-29 Jie Zhou; Dong-Mei Zhang; Jie Yang; Hong Ding; Tu-Shuai Li; Zhi-Hong Liu; Li Chen; Rui-Qing Jiao; Ling-Dong Kong
Glomerular hypertrophy is crucial for podocyte damage and proteinuria. Our previous study showed that fructose induced podocyte injury. However, the molecular mechanism underlying podocyte hypertrophy under fructose is unclear. We observed that fructose significantly initiated the hypertrophy in rat glomeruli and cultured differentiated human podocytes (HPCs). Consistently, it induced inflammatory
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Evaluation of exosome-encapsulated miR-23a/b in the diagnosis of human coronary heart diseases bioRxiv. Pathol. Pub Date : 2020-12-28 Changzhi Xu; Hui Xiao; Yanhua Yi; Donglin Zhu; Xiaojing Yue; Yun Xi
Objective: Coronary heart disease (CHD) is currently one of the major causes of death with high morbidity. Due to the increasing heterogeneity and complexity in the CHDs progression, biomarkers for specific diagnosis and monitoring of disease progression need to be developed. The study was aimed to investigate the roles of serum exosomal miR-23a and miR-23b in diagnosis of CHDs. Methods: 16 healthy
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The root of the transmissible cancer: first description of a widespread Mytilus trossulus-derived cancer lineage in M. trossulus bioRxiv. Pathol. Pub Date : 2020-12-26 Maria Skazina; Nelly Odintsova; Maria Maiorova; Angelina Ivanova; Risto Vainola; Petr Strelkov
Two lineages of bivalve transmissible neoplasia (BTN), BTN1 and BTN2, are known in blue mussels Mytilus. Both lineages derive from the Pacific mussel M. trossulus and are identified primarily by the unique genotypes of the nuclear gene EF1α. BTN1 is found in populations of M. trossulus from the Northeast Pacific, while BTN2 has been detected in populations of other Mytilus species worldwide but not
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Pulmonary stromal expansion and intra-alveolar coagulation are primary causes of Covid-19 death bioRxiv. Pathol. Pub Date : 2020-12-26 Laszlo Szekely; Bela Bozoky; Matyas Bendek; Masih Ostad; Pablo Lavignasse; Lars Haag; Jieyu Wu; Xu Jing; Soham Gupta; Elisa Saccon; Anders Sonnerborg; Yihai Cao; Mikael Bjornstedt; Attila Szakos
Most Covid-19 victims are old and die from unrelated causes. Here we present twelve complete autopsies, including two rapid autopsies of young patients where the cause of death was Covid-19 ARDS. The main virus induced pathology was in the lung parenchyma and not in the airways. Most coagulation events occurred in the intra-alveolar and not in the intra-vascular space and the few thrombi were mainly
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Authentication of In Situ Measurements for Thoracic Aortic Aneurysms in Mice bioRxiv. Pathol. Pub Date : 2020-12-24 Satoko Ohno-Urabe; Masayoshi Kukida; Michael K Franklin; Hong S. Lu; Alan Daugherty; Hisashi Sawada
Aortic diameter is a standard parameter for defining disease severity of thoracic aortic aneurysms. In mouse studies, aortic diameters can be measured directly in situ, but this approach has the potential confounder of underestimation due to the absence of physiological arterial pressure. In the present study, we developed an in situ approach for authentic aortic measurements. Thoracic aortic aneurysms
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Cell-type apoptosis in lung during SARS-CoV-2 infection bioRxiv. Pathol. Pub Date : 2020-12-24 Yakun Liu; Tania M. Garron; Qing Chang; Zhengchen Su; Changcheng Zhou; Eric C. Gong; Junying Zheng; Whitney Yin; Thomas Ksiazek; Trevor Brasel; Yang Jin; Paul Boor; Jason Edward Comer; Bin Gong
The SARS-CoV-2 pandemic has inspired renewed interest in understanding the fundamental pathology of acute respiratory distress syndrome (ARDS) following infection because fatal COVID-19 cases are commonly linked to respiratory failure due to ARDS. The pathologic alteration known as diffuse alveolar damage in endothelial and epithelial cells is a critical feature of acute lung injury in ARDS. However
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New look at RSV infection : tissue clearing and 3D imaging of the entire mouse lung at cellular resolution. bioRxiv. Pathol. Pub Date : 2020-12-23 Maxence Fretaud; Delphyne Descamps; Daphne Laubreton; Marie-Anne Rameix-Welti; Jean Francois Eleouet; Thibaut Larcher; Marie Galloux; Christelle langevin
Background: Respiratory Syncytial Virus (RSV) is the major cause of severe acute respiratory tract illness in young children worldwide and a main pathogen for the elderly and immune-compromised people. In the absence of vaccines or effective treatments, a better characterization of the pathogenesis of RSV infection is required. To date, the pathophysiology of the disease and its diagnosis mostly relied
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15-PGDH as a Negative Regulator of Age-Related Organ Fitness bioRxiv. Pathol. Pub Date : 2020-12-22 Won Jin Ho; Julianne N.P. Smith; Young Soo Park; Matthew Hadiono; Kelsey F. Christo; Alvin Jogasuria; Yongyou Zhang; Alyssia V. Broncano; Lakshmi Kasturi; Dawn M. Dawson; Stanton L. Gerson; Sanford D. Markowitz; Amar B. Desai
Emerging evidence implicates the eicosanoid molecule prostaglandin E2 (PGE2) in conferring a regenerative phenotype to multiple organ systems following tissue injury. As aging is in part characterized by loss of tissue stem cell regenerative capacity, we tested the hypothesis that the prostaglandin-degrading enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) contributes to the diminished organ
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PKA drives paracrine crisis and WNT4-dependent testis tumor in Carney complex bioRxiv. Pathol. Pub Date : 2020-12-22 Cyril Djari; Isabelle Sahut-Barnola; Amandine Septier; Ingrid Plotton; Nathanaelle Montanier; Damien Dufour; Adrien Levasseur; James Wilmouth; Jean-Christophe Pointud; Fabio Faucz; Crystal Kamilaris; Antoine-Guy Lopez; Florian Guillou; Amanda Swain; Seppo J Vainio; Igor Tauveron; Pierre Val; Herve Lefebvre; Constantine Stratakis; Antoine Martinez; A.Marie Lefrancois-Martinez
Large Cell Calcifying Sertoli Cell Tumors (LCCSCTs) are among the most frequent lesions occurring in Carney complex (CNC) male patients. Although they constitute a key diagnostic criterion for this rare multiple neoplasia syndrome resulting from inactivating mutations of the tumor suppressor PRKAR1A leading to unrepressed PKA activity, the LCCSCT pathogenesis and origin remain elusive. Mouse models
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Repurposing Nintedanib for Pathological Cardiac Remodeling and Dysfunction bioRxiv. Pathol. Pub Date : 2020-12-22 Prachi Umbarkar; Anand P. Singh; Sultan Tousif; Qinkun Zhang; Palaniappan Sethu; Hind Lal
Background: Heart Failure (HF) is the leading cause of death worldwide. Myocardial fibrosis, one of the clinical manifestations implicated in almost every form of heart disease, contributes significantly to HF development. However, there is no approved drug specifically designed to target cardiac fibrosis. Nintedanib (NTB) is an FDA approved tyrosine kinase inhibitor for idiopathic pulmonary fibrosis
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Africanized honeybees in Colombia exhibit high prevalence but low level of infestation of Varroa mites and low prevalence of pathogenic viruses bioRxiv. Pathol. Pub Date : 2020-12-21 Victor Manuel Tibata; Andres Sanchez; Evan Young-Palmer; Howard Junca; Victor Manuel Solarte; Shayne Madella; Fernando Ariza; Judith Figueroa; Miguel Corona
The global spread of the ectoparasitic mite Varroa destructor has promoted the spread and virulence of highly infectious honey bee viruses. This phenomenon is considered the leading cause for the increased number of colony losses experienced by the mite-susceptible European honey bee populations in the Northern Hemisphere. Most of the honey bee populations in Central and South America are Africanized
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Immunological and pathological outcomes of SARS-CoV-2 challenge after formalin-inactivated vaccine immunisation of ferrets and rhesus macaques bioRxiv. Pathol. Pub Date : 2020-12-21 Kevin R Bewley; Karen E R Gooch; Kelly M Thomas; Stephanie R Longet; Nathan Wiblin; Laura Hunter; Kin Chan; Phillip Brown; Rebecca A Russell; Catherine Ho; Gillian Slack; Holly E Humphries; Leonie Alden; Lauren Allen; Marilyn Aram; Natalie Baker; Emily Brunt; Rebecca Cobb; Susan Fotheringham; Debbie Harris; Chelsea Kennard; Stephanie Leung; Kathryn A Ryan; Howard Tolley; Nadina Wand; Andrew White;
There is an urgent requirement for safe and effective vaccines to prevent novel coronavirus disease (COVID-19) caused by SARS-CoV-2. A concern for the development of new viral vaccines is the potential to induce vaccine-enhanced disease (VED). This was reported in several preclinical studies with both SARS-CoV-1 and MERS vaccines but has not been reported with SARS-CoV-2 vaccines. We have used ferret
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Gastrointestinal ulceration in calves presented to a central Iowa veterinary referral facility: An underappreciated morbidity? bioRxiv. Pathol. Pub Date : 2020-12-18 Allison P Mosichuk; Joseph Smith; Dane Tatarniuk; Amanda Kreuder
The objective of this retrospective investigation is to identify the incidence of gastrointestinal ulceration as a co-morbidity in calves presenting to a referral veterinary hospital. Approximately 24% of calves presented to the hospital that died or were euthanized had evidence of gastrointestinal ulceration. Previous administration of an NSAID was significantly associated with the presence of ulcers
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Proteomic identification of the UDP-GlcNAc : PI α1-6 GlcNAc-transferase subunits of the glycosylphosphatidylinositol biosynthetic pathway of . bioRxiv. Pathol. Pub Date : 2020-12-16 Zhe Ji; Michele Tinti; Michael A J Ferguson
The first step of glycosylphosphatidylinositol (GPI) anchor biosynthesis in all eukaryotes is the addition of N-acetylglucosamine (GlcNAc) to phosphatidylinositol (PI) which is catalysed by a UDP-GlcNAc : PI α1-6 GlcNAc-transferase. This enzyme has been shown to be a complex of at least seven subunits in mammalian cells and a similar complex of homologous subunits has been postulated in yeast. Homologs
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Global gene-expression analysis reveals the molecular processes underlying ClC-5 loss-of-function in novel Dent Disease 1 cellular models bioRxiv. Pathol. Pub Date : 2020-12-16 Monica Duran; Carla Burballa; Gerard Cantero-Recasens; Cristian Butnaru; Vivek Malhotra; Gema Ariceta; Eduard Sarro; Anna Meseguer
Dent disease 1 (DD1) is a rare X-linked renal proximal tubulopathy characterized by low molecular weight proteinuria (LMWP) and variable degree of hypercalciuria, nephrocalcinosis and/or nephrolithiasis with progression to chronic kidney disease (CKD). Although loss-of-function mutations in the gene CLCN5 encoding the electrogenic Cl-/H+ antiporter ClC-5, which impair endocytic uptake in proximal tubule
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Plasma glutathione status as indicator of pre-analytical centrifugation delay bioRxiv. Pathol. Pub Date : 2020-12-16 Tomin Tamara; Natalie Bordag; Elmar Zuegner; Abdullah Al-Baghdadi; Maximilian Schinagl; Ruth Birner-Gruenberger; Matthias Schittmayer
Prolonged incubation of blood prior to plasma preparation can significantly influence the quality of the resulting data. Different markers for this pre-clinical variability have been proposed over the years but with limited success. In this study we explored the usefulness of glutathione (GSH) status, namely ratio of reduced to oxidized glutathione (GSH/GSSG), as potential marker of plasma preparation
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Human liver microbiota modeling strategy at the early onset of fibrosis bioRxiv. Pathol. Pub Date : 2020-12-12 Remy Burcelin; Camille Champion; Radu M. Neagoe; Maria Effernberger; Daniela T Sala; Florence Servant; Jeffrey E Christensen; Maria Arnoriaga-Rodríguez; Jacques Amar; Benjamin Lelouvier; Fabrice Gamboa; Herbert Tilg; Massimo Federici; José Manuel Fernández-Real; Jean-Michel Loubes
To understand the pathophysiological impact of liver microbiota on the early stages of fibrosis we identified the corresponding microbiota sequences and overcome the impact of different group size and patient origins with adapted statistical approaches. Liver samples with low liver fibrosis scores (F0, F1, F2) were collected from Romania(n=36), Austria(n=10), Italy(n=19), and Spain(n=17). The 16SrDNA
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Osteoprotegerin expression in liver is induced by IL-13 through TGF-β bioRxiv. Pathol. Pub Date : 2020-12-12 Adhyatmika Adhyatmika; Kurnia SS Putri; Emilia Gore; Keri Mangnus; Catharina Reker-Smit; Detlef Schuppan; Leonie Beljaars; Peter Olinga; Barbro N Melgert
Backgrounds: Osteoprotegerin (OPG) is a profibrotic mediator produced by myofibroblasts under influence of transforming growth factor β (TGFβ). Its expression in experimental models of liver fibrosis correlates well with disease severity and treatment responses. The regulation of OPG in liver tissue is largely unknown and we therefore set out to elucidate which growth factors/interleukins associated
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Analysis of the area and the number of pulmonary alveoli through the normal aging process in CD1 mouse bioRxiv. Pathol. Pub Date : 2020-12-11 Marta Ortega-Martínez; Esthefania Gutiérrez-Arenas; Vanessa Gutiérrez-Dávila; Alberto Niderhauser-García; Ricardo M Cerda-Flores; Gilberto Jaramillo-Rangel
During the aging process, the lung exhibits structural changes accompanied by a decline in its function. The related information currently available is still scarce and contradictory. In addition, changes in some pulmonary parameters through aging process are species- and strain- dependent. The aim of this study was the assessment of the area and the number of pulmonary alveoli through the normal aging
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Testing for the resistance of newly generated hybrid cacao germplasm in the gene pool of Cocoa Research Institute of Nigeria (CRIN) against Phytophthora megakarya pathogen causing black pod disease of cocoa. bioRxiv. Pathol. Pub Date : 2020-12-07 Abdul-Akeem Abiodun Tijani; HENRY Azuka Otuonye; Mariam Oluleke Otusanya; Abideen Olaitan Olaiya; Omotayo Olalekan Adenuga; Clement Gboyega Afolabi
Black pod disease caused by P. Palmivora and P. megakarya is an important disease affecting cacao in West Africa which produces 70% of the world output. Resistance to the pathogen is therefore, an important factor to be considered when breeding for high yielding and earliness in fruiting. Resistance to the pathogen using Leaf Disc Test (LDT) was conducted at the Plant Pathology Laboratory, Ibadan,
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Spike Protein of SARS-CoV-2 Activates Macrophages and Contributes to Induction of Acute Lung Inflammations in Mice bioRxiv. Pathol. Pub Date : 2020-12-07 Xiaoling Cao; Yan Tian; Vi Nguyen; Yuping Zhang; Chao Gao; Rong Yin; Wayne Carver; Daping Fan; Helmut Albrecht; Taixing Cui; Wenbin Tan
Background: Coronavirus disease 2019 (COVID-19) patients exhibit multiple organ malfunctions with a primary manifestation of acute and diffuse lung injuries. The Spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial to mediate viral entry into host cells; however, whether it can be cellularly pathogenic and contribute to pulmonary hyper-inflammations in COVID-19 is
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Loss of phosphatidylserine flippase β-subunit Tmem30a in podocytes leads to albuminuria and glomerulosclerosis bioRxiv. Pathol. Pub Date : 2020-12-05 Xianjun Zhu; Wenjing Liu; Lei Peng; Wanli Tian; Yi Li; Ping Zhang; Kuanxiang Sun; Yeming Yang; Xiao Li; Guisen Li
Phosphatidylserine (PS) is asymmetrically concentrated in the cytoplasmic leaflet of eukaryotic cell plasma membranes. This asymmetry is regulated by a group of P4 ATPases (named PS flippases) and its β-subunit TMEM30A. The disruption of PS flippase leads to severe human diseases. Tmem30a is essential in the mouse retina, cerebellum and liver. However, the role of Tmem30a in the kidney, where it is
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Effect of belt electrode-skeletal muscle electrical stimulation on immobilization-induced muscle fibrosis bioRxiv. Pathol. Pub Date : 2020-12-05 Yuichiro Honda; Natsumi Tanaka; Yasuhiro Kajiwara; Yasutaka Kondo; Hideki Kataoka; Junya Sakamoto; Ryuji Akimoto; Atsushi Nawata; Minoru Okita
Purpose: Macrophage accumulation in response to decreasing myonuclei may be the major mechanism underlying immobilization-induced muscle fibrosis in muscle contracture, an intervention strategy suppressing these lesions is necessary. Therefore, this research investigated the effect of belt electrode-skeletal muscle electrical stimulation (B-SES), a new electrical stimulation device, to the macrophage
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SARS-CoV-2 Spike Protein Impairs Endothelial Function via Downregulation of ACE2 bioRxiv. Pathol. Pub Date : 2020-12-04 Yuyang Lei; Jiao Zhang; Cara R. Schiavon; Ming He; Lili Chen; Hui Shen; Yichi Zhang; Qian Yin; Yoshitake Cho; Leonardo Andrade; Gerry S. Shadel; Mark Hepokoski; Ting Lei; Hongliang Wang; Jin Zhang; Jason X.-J. Yuan; Atul Malhotra; Uri Manor; Shengpeng Wang; Zu-Yi Yuan; John Y-J. Shyy
Coronavirus disease 2019 (COVID-19) includes the cardiovascular complications in addition to respiratory disease. SARS-CoV-2 infection impairs endothelial function and induces vascular inflammation, leading to endotheliitis. SARS-CoV-2 infection relies on the binding of Spike glycoprotein (S protein) to angiotensin converting enzyme 2 (ACE2) in the host cells. We show here that S protein alone can
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Molecular characterization of the coat protein gene revealed considerable diversity of viral species complex in Garlic (Allium sativum L.) bioRxiv. Pathol. Pub Date : 2020-12-03 Abel Debebe Mitiku; Dawit Tesfaye Degefu; Adane Abrham; Desta Fekadu Mejan; Pauline Asami; Solomon Maina; Timothy Holton
Garlic is one of the most crucial Allium vegetables used as seasoning of foods. It has a lot of benefits from the medicinal and nutritional point of view; however, its production is highly constrained by both biotic and abiotic challenges. Among these, viral infections are the most prevalent factors affecting crop productivity around the globe. This experiment was conducted on eleven selected garlic
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Osteoprotegerin is elevated in pulmonary fibrosis and associates with IPF progression bioRxiv. Pathol. Pub Date : 2020-12-03 Habibie Habibie; Kurnia Putri; Carian E Boorsma; David Brass; Peter Heukels; Marlies Wijsenbeek-Lourens; Mirjam Kool; Maarten van der Berge; Theo Borghuis; Corry Anke Brandsma; Tji Gan; Peter Olinga; Wim Timens; Nicolas Kahn; Michael Kreuter; Janette Burgess; Barbro N Melgert
Osteoprotegerin (OPG), a decoy receptor for receptor activator of NF-kB ligand (RANKL), is used as a biomarker for assessing severity of liver fibrosis. However, its expression and role in pulmonary fibrosis are unknown. We hypothesized that OPG also has a role in pulmonary fibrosis. Human and mouse control and fibrotic lung tissue were used to examine OPG expression, and mouse precision-cut lung slices
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Lack of evidence of ACE2 expression and replicative infection by SARS-CoV-2 in human endothelial cells bioRxiv. Pathol. Pub Date : 2020-12-02 Ian McCracken; Gaye Saginc; Liqun He; Alik Huseynov; Alison Daniels; Sarah Fletcher; Claire Peghaire; Viktoria Kalna; Maarja Andaloussi Mae; Lars Muhl; Nicky M. Craig; Samantha J. Griffiths; Jurgen G. Haas; Christine Tait Burkard; Urban Lendahl; Graeme M. Birdsey; Christer Betsholtz; Michela Noseda; Andrew Baker; Anna M Randi
A striking feature of severe COVID-19 is thrombosis in large as well as small vessels of multiple organs. This has led to the assumption that SARS-CoV-2 virus directly infects and damages the vascular endothelium. However, endothelial expression of ACE2, the cellular receptor for SARS-CoV-2, has not been convincingly demonstrated. Interrogating human bulk and single-cell transcriptomic data, we found
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Inhibition of lysyl oxidase-like 2 ameliorates folic acid-induced renal tubulointerstitial fibrosis bioRxiv. Pathol. Pub Date : 2020-12-01 Sung-Eun Choi; Nara Jeon; Hoon Young Choi; Hyeon Joo Jeong; Beom Jin Lim
Tubulointerstitial fibrosis is characterized by accumulation of the extracellular matrix in the interstitium. Lysyl oxidase-like 2 (LOXL2), a member of the lysyl oxidase family, is known for promoting cancer metastasis, invasion, and stromal fibrosis in various organs. Our previous study demonstrated expression of LOXL2 in kidney podocytes and tubular epithelial cells, and the association between elevated
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Optimising passive surveillance of a neglected tropical disease in the era of elimination: A modelling study bioRxiv. Pathol. Pub Date : 2020-12-01 Joshua Longbottom; Charles Wamboga; Paul R. Bessell; Steve J. Torr; Michelle Stanton
Background: Surveillance is an essential component of global programs to eliminate infectious diseases and avert epidemics of (re-)emerging diseases. As the numbers of cases decline, costs of treatment and control diminish but those for surveillance remain high even after the "last" case. Reducing surveillance may risk missing persistent or (re-)emerging foci of disease. Here, we use a simulation-based
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Furfural residues as soil amendments for long-term seed corn production: effects on community composition and diversity of rhizosphere microbiota bioRxiv. Pathol. Pub Date : 2020-11-27 Yunchen Zhao; Guangquan Chen; Yuru Chen; Xuelin Song; Zhanwen Xiao; Zhijiang Wang; Wenjiang Fu
Furfural residues's influence on maize rhizosphere microbiota subjected to long-term monocropping is poorly understood. In this study, high-throughput sequencing was employed to investigate the rhizosphere microbiota composition and its variation under long-term field monocropping for maize seed production. The results showed that unplanted, chemical fertilizer (only) treated soil, and furfural residue
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The effect of ischaemic postconditioning on mucosal integrity and function in equine jejunal ischaemia bioRxiv. Pathol. Pub Date : 2020-11-26 Nicole Verhaar; Gerhard Breves; Marion Hewicker-Trautwein; Christiane Pfarrer; Karl Rohn; Marion Burmester; Nadine Schnepel; Stephan Neudeck; Lara Twele; Sabine Kaestner
Background: Ischaemic postconditioning (IPoC) has been shown to ameliorate ischaemia reperfusion injury in different species and tissues. Objectives: To assess the feasibility of IPoC in equine small intestinal ischaemia and to assess its effect on histomorphology, electrophysiology and paracellular permeability. Study design: randomized controlled terminal in vivo experiment Methods: Experimental
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Fat Tissue Regulates the Pathogenesis and Severity of Cardiomyopathy in Murine Chagas Disease bioRxiv. Pathol. Pub Date : 2020-11-26 Jyothi F Nagajyothi; Kezia Lizardo; Janeesh P Ayyappan; Neelam Oswal; Louis M Weiss; Philipp E Scherer
Chronic Chagas cardiomyopathy (CCC) caused by a parasite Trypanosoma cruzi is a life-threatening disease in Latin America, for which there is no effective drug or vaccine. The pathogenesis of CCC is complex and multifactorial. Previously, we demonstrated T. cruzi infected mice lose a significant amount of fat tissue which correlates with progression of CCC. Based on this an investigation was undertaken
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RpoS Contributes to Successful Opportunistic Colonization by Human Enteric Pathogens during Plant Disease bioRxiv. Pathol. Pub Date : 2020-11-25 Amelia Helen Lovelace; Sangwook Lee; Diana M Downs; Ziad Soufi; Pedro Bota; Gail M. Preston; Brian H Kvitko
With an increase in foodborne illnesses associated with the consumption of fresh produce, it is important to understand the interactions between human bacterial enteric pathogens and plants. It was previously established that diseased plants can create a permissive environment for opportunistic endophytic colonization of enteric pathogens. However, the factors that contribute to the colonization of
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Improve Concentration Of Frequency And Time (ConceFT) By Novel Complex Spherical Designs bioRxiv. Pathol. Pub Date : 2020-11-23 Matt Sourisseau; Yuguang Wang; Robert S. Womersley; Hau-tieng Wu; Wei-Hsuan Yu
Concentration of frequency and time (ConceFT) is a generalized multitaper algorithm introduced to analyze complicated non-stationary time series. To avoid the randomness in the original ConceFT algorithm, we apply the novel complex spherical design technique to standardize ConceFT, which we coin CQU-ConceFT. The proposed CQU-ConceFT is applied to visualize the spindle structure in the electroencephalogram
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Large-scale transcriptomics to dissect two years of the life of a fungal phytopathogen interacting with its host plant bioRxiv. Pathol. Pub Date : 2020-11-23 Elise J Gay; Jessica L Soyer; Nicolas Lapalu; Juliette Linglin; Isabelle Fudal; Corinne Da Silva; Patrick Wincker; Jean-Marc Aury; Corinne Cruaud; Anne Levrel; Jocelyne Lemoine; Regine Delourme; Thierry Rouxel; Marie-Helene Balesdent
The fungus Leptosphaeria maculans has an exceptionally long and complex relationship with its host plant, Brassica napus, during which it switches between different lifestyles, including asymptomatic, biotrophic, necrotrophic, and saprotrophic stages. The fungus is also exemplary of two-speed genome organisms in which gene-rich and repeat-rich regions alternate. Except for a few stages of plant infection
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Eip74EF is a dominant modifier for ALS-FTD linked mutant VCP phenotypes in Drosophila, but not miR-34 bioRxiv. Pathol. Pub Date : 2020-11-22 Madeleine R Chalmers; JiHye Kim; Nam Chul Kim
In 2012 Liu et al. reported that miR-34 is an age-related miRNA regulating age-associated events and long-term brain integrity in Drosophila. They demonstrated that modulating miR-34 and its downstream target Eip74EF showed beneficial effects on age-related diseases using a Drosophila model of SCA3trQ78. These results imply that miR-34 could be a general genetic modifier and therapeutic candidate for
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Human hepatocyte PNPLA3 148M exacerbates rapid non-alcoholic steatohepatitis development in chimeric mice bioRxiv. Pathol. Pub Date : 2020-11-20 Mohammad Kabbani; Eleftherios Michailidis; Sandra Steensels; Clifton G. Fulmer; Joseph M Luna; Jérémie Le Pen; Matteo Tardelli; Brandon Razooky; Inna Ricardo-Lax; Chenhui Zou; Briana Zeck; Ansgar F. Stenzel; Corrine Quirk; Lander Foquet; Alison W. Ashbrook; William M. Schneider; Serkan Belkaya; Gadi Lalazar; Yupu Liang; Meredith Pittman; Lindsey Devisscher; Hiroshi Suemizu; Neil D. Theise; Luis Chiriboga;
Advanced non-alcoholic fatty liver disease (NAFLD) is a rapidly emerging global health problem associated with pre-disposing genetic polymorphisms, most strikingly an isoleucine to methionine substitution in patatin-like phospholipase domain-containing protein 3 (PNPLA3-I148M). Here, we study how human hepatocytes with PNPLA3 148I and 148M variants engrafted in the livers of chimeric mice respond to
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Effects of Endogenous Angiotensin II on Abdominal Aortic Aneurysms and Atherosclerosis in Angiotensin II-infused Mice bioRxiv. Pathol. Pub Date : 2020-11-20 Masayoshi Kukida; Hisashi Sawada; Satoko Ohno-Urabe; Deborah A. Howatt; Jessica J. Moorleghen; Marko Poglitsch; Alan Daugherty; Hong S. Lu
Angiotensin II (Angll), a major effector of the renin-angiotensin system, exerts critical roles in regulating vascular function. AngII infusion induces abdominal aortic aneurysms (AAAs) and exacerbates atherosclerosis in hypercholesterolemic mice. We determined the effects of AngII infusion on endogenous AngII regulation and AngII-mediated AAAs and atherosclerosis. AngII infusion increased renal, but
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Multiscale three-dimensional pathology findings of COVID-19 diseased lung using high-resolution cleared tissue microscopy bioRxiv. Pathol. Pub Date : 2020-11-20 Guang Li; Sharon E Fox; Brian Summa; Bihe Hu; Carola Wenk; Aibek Akmatbekov; Jack L Harbert; Richard S. Vander Heide; J. Quincy Brown
The study of pulmonary samples from individuals who have died as a direct result of COVID-19 infection is vital to our understanding of the pathogenesis of this disease. Histopathologic studies of lung tissue from autopsy of patients with COVID-19 specific mortality are only just emerging. All existing reports have relied on traditional 2-dimensional slide-based histological methods for specimen preparation
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Cannabidiol Attenuates Pulmonary Arterial Hypertension by Normalizing the Mitochondrial Function in Vascular Smooth Muscle Cells bioRxiv. Pathol. Pub Date : 2020-11-19 Xiaohui Lu; Jingyuan Zhang; Huijiao Liu; Wenqiang Ma; Xin Tan; Shubin Wang; Yu Leo; Fazheng Ren; Xiru Li; Xiangdong Li
Pulmonary artery hypertension (PAH) is a chronic disease associated with enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs) and dysfunctional mitochondria, which was with limited therapeutic options. It has been proved that cannabidiol (CBD) had antioxidant effects in many cardiovascular diseases, whereas the efficacy of CBD in PAH is unknown. To defined the effect of CBD in PAH
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Maternal RND3/RhoE deficiency impairs placental mitochondrial function in preeclampsia by modulating PPARγ-UCP2 cascade bioRxiv. Pathol. Pub Date : 2020-11-12 Liping Huang; Yanlin Ma; Lu Chen; Jiang Chang; Mei Zhong; Zhijian Wang; Ying Sun; Xia Chen; Fei Sun; Lu Xiao; Jianing Chen; Yinjun Lai; Chuming Yan; Xiaojing Yue
Preeclampsia (PE) is a life-threatening disease of the pregnant women, and has a profound influence on fetal development. Mitochondrial-mediated placental oxidative stress plays key role in the etiology of PE. However, the underlying mechanism remains to be revealed. Here, we identify Rnd3, a small Rho GTPase, participating in the regulation of placental mitochondrial reactive oxygen species (ROS)
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Study on the efficacy of Cynodon dactylon against Infectious Myonecrosis Virus (IMNV) in Penaeus vannamei bioRxiv. Pathol. Pub Date : 2020-11-09 Rajeev Kumar Jha; Soy Daniel Wisoyo; Kristina Kristina; Sarayut Srisombat
Infectious myonecrosis virus (IMNV) is one of the most pathogenic viruses causing severe mortality in Penaeus vannamei in many countries. Several strategies have been implemented to inhibit the presence of IMNV disease. The present study was carried out to examine the antiviral activity of Cynodon dactylon ethanolic extract on IMNV disease in shrimp by in vivo testing. The C. dactylon plant extract
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Mice with Induced Pulmonary Comorbidities Display Severe Lung Inflammation and Mortality following Exposure to SARS-CoV-2 bioRxiv. Pathol. Pub Date : 2020-11-09 Reut Falach; Liat Bar-On; Shlomi Lazar; Tamar Kadar; Ohad Mazor; Moshe Aftalion; David Gur; Ohad Shifman; Ofir Israeli; Inbar Cohen-Gihon; Galia Zaide; Hila Gutman; Yentl Evgy; Yaron Vagima; Efi Makdasi; Dana Stein; Ronit Rosenfeld; Ron Alcalay; Eran Zahavy; Haim Levy; Itai Glinert; Amir Ben-Shmuel; Tomer Israely; Sharon Melamed; Boaz Politi; Hagit Achdout; Shmuel Yitzhaki; Chanoch Kronman; Tamar Sabo
Severe manifestations of COVID-19 are mostly restricted to people with comorbidities. Here we report that induced mild pulmonary morbidities render SARS-CoV-2-refractive CD-1 mice to be susceptible to this virus. Specifically, SARS-CoV-2 infection after application of low-doses of the acute-lung-injury stimulants bleomycin or ricin caused a severe disease in CD-1 mice, manifested by sustained body
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Flagellin from Pseudomonas aeruginosa modulates SARS-CoV-2 infectivity in CF airway epithelial cells by increasing TMPRSS2 expression bioRxiv. Pathol. Pub Date : 2020-11-06 Manon Ruffin; Jeanne Bigot; Claire Calmel; Julia Mercier; Andrés Pizzorno; Manuel Rosa-Calatrava; Harriet Corvol; Viviane Balloy; Olivier Terrier; Loïc Guillot
The major challenge of the COVID-19 health crisis is to identify the factors of susceptibility to SARS-Cov2 in order to adapt the recommendations to the populations and to reduce the risk of getting COVID-19 to the most vulnerable people especially those having chronic respiratory diseases including cystic fibrosis (CF). Airway epithelial cells (AEC) are playing a critical role in the immune response
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Ivermectin reduces coronavirus infection in vivo: a mouse experimental model bioRxiv. Pathol. Pub Date : 2020-11-02 Ana Paula Arevalo; Romina Pagotto; Jorge Porfido; Hellen Daghero; Mercedes Segovia; Kanji Yamasaki; Belen Varela; Marcelo Hill; Jose Manuel Verdes; Maite Duhalde Vega; Mariela Bollati-Fogolin; Martina Crispo
SARS-CoV2 is a single strand RNA virus member of the type 2 coronavirus family, responsible for causing COVID-19 disease in humans. The objective of this study was to test the ivermectin drug in a murine model of coronavirus infection using a type 2 family RNA coronavirus similar to SARS-CoV2, the mouse hepatitis virus (MHV). BALB/cJ female mice were infected with 6,000 PFU of MHV-A59 (Group Infected;
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Spectral Signatures of L-DOPA-Induced Dyskinesia Depend on L-DOPA Dose and are Suppressed by Ketamine bioRxiv. Pathol. Pub Date : 2020-10-19 Tony Ye; Mitchell J. Bartlett; Scott J. Sherman; Torsten Falk; Stephen L. Cowen
L-DOPA-induced dyskinesias (LID) are debilitating motor symptoms of dopamine-replacement therapy for Parkinson’s disease (PD) that emerge after years of L-DOPA treatment. While there is an abundance of research into the cellular and synaptic origins of LID, less is known about how LID impacts systems-level circuits and neural synchrony, how synchrony is affected by the dose and duration of L-DOPA exposure
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Linking Enzyme Upregulation to Autophagic Failure: A Potential Biomarker for GM1 Gangliosidosis bioRxiv. Pathol. Pub Date : 2020-10-28 Sarah Smith; Jessica Larsen
With an increasing aging population, neurodegenerative diseases are having an increased impact on society. Typically, these diseases are diagnosed significantly past symptom onset, decreasing the possibility of effective treatment. A non-invasive biomarker and specific target are needed to diagnose and treat the disease before late-stage symptoms. GM1 Gangliosidosis is a lysosomal storage disease where
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Resveratrol reduces COMPopathy in mice through activation of autophagy bioRxiv. Pathol. Pub Date : 2020-10-27 Jacqueline T Hecht; Francoise Coustry; Alka Veerisetty; Mohammad G Hossain; Karen Posey
Misfolding mutations in cartilage oligomeric matrix protein (COMP) cause it to be retained within in ER of chondrocytes, stimulating a multitude of damaging cellular responses including ER stress, inflammation and oxidative stress which ultimately culminates in the death of growth plate chondrocytes and pseudoachondroplasia (PSACH). Previously, we demonstrated that an antioxidant, resveratrol, substantially
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Allantoin induces pruritus by activating MrgprD in chronic kidney disease bioRxiv. Pathol. Pub Date : 2020-10-26 Zongxiang Tang; yan yang; yuling sun; donglang guan; dan chen; dijun wang; tongtong liu; meixiao sheng; jing tao; jun shi; chan zhu; Guang Yu; Xinzhong Dong