Latest Research

  • Article |

    Polarization-second harmonic microscopy was utilized to investigate whether collagen ultrastructure in thyroid due to four carcinoma types and Graves’ disease could be differentiated in human histopathology samples. Three parameters were extracted, revealing that the degree of linear polarization and χ(2)zzz/χ(2)zxx were effective in differentiating some diseases, while the parameter χ(2)xyz/χ(2)zxx was less effective.

    • Danielle Tokarz
    • , Richard Cisek
    • , Ariana Joseph
    • , Sylvia L. Asa
    • , Brian C. Wilson
    •  & Virginijus Barzda
  • Article |

    This study demonstrates that small clusters (sCLs) of tumor cells with high expression of LGR5 continuously form in the invasive front in a colorectal cancer xenograft model. This structure is characterized by stress response and partial/hybrid epithelial-mesenchymal transition. These sCLs are an important contributor to tumor growth and the expansion of cancer stem cells.

    • Masaki Yamazaki
    • , Atsuhiko Kato
    • , Eiji Oki
    • , Yoko Zaitsu
    • , Chie Kato
    • , Kiyotaka Nakano
    • , Miho Nakamura
    • , Takuya Sakomura
    • , Shigeto Kawai
    • , Etsuko Fujii
    • , Noriaki Sawada
    • , Takeshi Watanabe
    • , Hiroshi Saeki
    •  & Masami Suzuki
  • Article |

    Overexpression of pigment epithelium-derived factor (PEDF) in placenta-derived mesenchymal stem cells (PD-MSCs) improved the mitochondrial activities, and induced regeneration of oxidative stress-damaged RPE through regulating oxidative status and mitochondrial biogenesis. Therefore, genetic modification of PD-MSCs with PEDF might be a new cell therapy for treatment of retinal degenerative diseases.

    • Jae Yeon Kim
    • , Sohae Park
    • , So Hyun Park
    • , Dongsook Lee
    • , Gyu Hyun Kim
    • , Jung Eun Noh
    • , Kea Joo Lee
    •  & Gi Jin Kim
  • Article |

    Combination of antihypertensive drugs with NSAID analgesics may cause a syndrome called triple whammy (TW) acute kidney injury (AKI), most often in the elderly. A rat model reveals that the TW-AKI is a prerenal form of AKI, only occurring in previously dehydrated rats, a condition particularly rife among the aged.

    • Laura Prieto-García
    • , Laura Vicente-Vicente
    • , Víctor Blanco-Gozalo
    • , Omar Hidalgo-Thomas
    • , María C. García-Macías
    • , Armin Kurtz
    • , Anita T. Layton
    • , Ana B. Sanz
    • , Ana I. Morales
    • , Carlos Martínez-Salgado
    • , Miguel Pericacho
    • , Sandra M. Sancho-Martínez
    •  & Francisco J. López-Hernández
  • Article |

    In this study, the authors assess the early pathogenesis of cystic fibrosis (CF) pig gallbladder disease. The CF pig gallbladder epithelium lacks cAMP-stimulated anion and fluid transport. CF pig gallbladders also demonstrate increased luminal mucins MUC5AC and MUC5B accumulation without significant changes in the epithelial expression of gel-forming mucins compared to non-CF pigs.

    • Keyan Zarei
    • , Mallory R. Stroik
    • , Nick D. Gansemer
    • , Andrew L. Thurman
    • , Lynda S. Ostedgaard
    • , Sarah E. Ernst
    • , Ian M. Thornell
    • , Linda S. Powers
    • , Alejandro A. Pezzulo
    • , David K. Meyerholz
    •  & David A. Stoltz
  • Article |

    The authors investigated the role of extracellular cold-inducible RNA-binding protein (eCIRP) in acute pancreatitis (AP) and found that eCIRP acts as a potent regulator of neutrophil extracellular traps (NETs) formation in AP. They observed that eCIRP itself is one of the NETs associated proteins. Furthermore, they demonstrate that C23 (a potent eCIRP inhibitor) reduces NETs formation and inflammation in AP.

    • Johan Linders
    • , Raed Madhi
    • , Milladur Rahman
    • , Matthias Mörgelin
    • , Sara Regner
    • , Max Brenner
    • , Ping Wang
    •  & Henrik Thorlacius
  • Article |

    To investigate genetic homozygosity in pediatric teratomas, this study analyses 13 sacrococcygeal, 12 ovarian, and 3 testicular teratomas in children by short tandem repeat (STR) genotyping. While genetic homozygosity is frequent in adult ovarian teratomas, no evidence of genetic homozygosity is seen in patients younger than 4 years, arguing pediatric teratomas arise at an earlier stage of germ cell development.

    • Olivia L. Snir
    • , Maura DeJoseph
    • , Xinyu Wu
    • , Douglas Rottmann
    • , Serena Wong
    • , Natalia Buza
    •  & Pei Hui
  • Article |

    The authors show that exposure of neonatal mice to the toxin biliatresone creates an animal model of biliary atresia. Such mice develop clinical signs of biliary obstruction, inflammatory cell infiltration and liver fibrosis.

    • Yifan Yang
    • , Junfeng Wang
    • , Yong Zhan
    • , Gong Chen
    • , Zhen Shen
    • , Shan Zheng
    •  & Rui Dong
  • Article |

    HNRNPA2B1 regulates the splicing of MST1R and promotes the expression of a cancer-specific isoform, RON∆165, in head and neck cancer cells. RON∆165 activates the Akt/PKB pathway and leads to increased expression of epithelial to mesenchymal transition regulators such as TWIST2, E-cadherin, vimentin, and ZEB1 and promotes the invasive behavior of head and neck cancer.

    • Amit Gupta
    • , Sandhya Yadav
    • , Archana PT
    • , Jharna Mishra
    • , Atul Samaiya
    • , Rajendra Kumar Panday
    •  & Sanjeev Shukla
  • Technical Report |

    Accurate quantification of steatosis in liver biopsies is a key step in the treatment of patients with fatty liver diseases. To assist pathologists for such analysis tasks, we develop a novel deep learning-based framework to segment overlapped steatosis droplets in whole slide liver biopsy images. Quantitative measurements of steatosis at both pixel and object-level present strong correlation with clinical data, suggesting its potential for clinical decision support.

    • Mousumi Roy
    • , Fusheng Wang
    • , Hoang Vo
    • , Dejun Teng
    • , George Teodoro
    • , Alton B. Farris
    • , Eduardo Castillo-Leon
    • , Miriam B. Vos
    •  & Jun Kong
  • Technical Report |

    Detailed protocols for immunohistochemical and in situ hybridization assays for the detection of SARS-CoV-2 are provide so they can be readily implemented in pathology laboratories and medical examiner offices for diagnostic and research purposes. These assays were found to represent a sensitive and specific method for detecting the virus in tissue samples.

    • Alejandro Best Rocha
    • , Edana Stroberg
    • , Lisa M. Barton
    • , Eric J. Duval
    • , Sanjay Mukhopadhyay
    • , Nicole Yarid
    • , Tiffany Caza
    • , Jon D. Wilson
    • , Daniel J. Kenan
    • , Michael Kuperman
    • , Shree G. Sharma
    •  & Christopher P. Larsen
  • Article |

    PCP4/PEP19 knockdown in neuroblastoma cells induce neurite outgrowth, upregulation of NeuroD1 and downregulation of Ascl1 expression, suggesting that PCP4/PEP19 can suppress neurite outgrowth and neuronal differentiation through the regulation of NeuroD1 and Ascl1. Immunohistochemistry shows nuclear localization of PCP4/PEP19 in neuroblastoma cells. PCP4/PEP19 may therefore be an intranuclear negative regulator of neuronal differentiation.

    • Ikumi Kitazono
    • , Taiji Hamada
    • , Takuya Yoshimura
    • , Mari Kirishima
    • , Seiya Yokoyama
    • , Toshiaki Akahane
    •  & Akihide Tanimoto
  • Article |

    The therapeutic effects of CP-25 on experimental Sjögren’s syndrome has been shown to be associated with the inhibition of the JAK1-STAT1/2-CXCL13 signaling pathway in HSGEC, which impedes the migration of B cells into the salivary gland. The study provides an experimental foundation for CP-25 as a potential drug in the treatment of human autoimmune disorder, Sjögren’s syndrome.

    • Huaxun Wu
    • , Xiaoyun Chen
    • , Fang Gu
    • , Pengying Zhang
    • , Shixia Xu
    • , Qi Liu
    • , Qiaolin Zhang
    • , Xinming Wang
    • , Chun Wang
    • , Heinrich Körner
    •  & Wei Wei
  • Technical Report |

    Liquid biopsy is a novel promising, but technically challenging tool in oncology. We compared various circulating DNA extraction and sequencing systems used within four Swiss laboratories. Results were highly congruent, with perfect sensitivity down to 1% mutation frequency. We also determined several key factors to validate when implementing such tests.

    • Thibaud Koessler
    • , Viola Paradiso
    • , Salvatore Piscuoglio
    • , Ronny Nienhold
    • , Liza Ho
    • , Yann Christinat
    • , Luigi M. Terracciano
    • , Gieri Cathomas
    • , Andreas Wicki
    • , Thomas A. McKee
    •  & Thierry Nouspikel
  • Article
    | Open Access

    The authors demonstrate that cholestasis impairs hepatic lipid storage via AMP-activated protein kinase (AMPK) and CREB signaling in hepatitis B virus surface protein transgenic mice. The pharmacological modulation of AMPK and CREB signaling might be a promising therapeutic concept for the treatment of fatty liver diseases.

    • Karuna Irungbam
    • , Martin Roderfeld
    • , Hannah Glimm
    • , Felix Hempel
    • , Franziska Schneider
    • , Laura Hehr
    • , Dieter Glebe
    • , Yuri Churin
    • , Gertrud Morlock
    • , Imanuel Yüce
    •  & Elke Roeb
  • Article |

    MiR-126-5p expression decreases abdominal aorta dilation in mice with Ang II-induced abdominal aortic aneurysm (AAA), and its agomirs limit experimental AAA formation. MiR-126-5p inhibits Ang II- and PDGF-BB-induced dedifferentiation of aortic smooth muscle cells (AoSMCs) in vitro. MiR-126-5p promotes contractile switching of AoSMCs exposed to Ang II by targeting VEPH1.

    • Xiaofeng Shi
    • , Wei Ma
    • , Yongquan Pan
    • , Yongqi Li
    • , Han Wang
    • , Shuang Pan
    • , Yu Tian
    • , Caiming Xu
    •  & Lei Li
  • Article |

    This study reports novel pro-tumorigenic functions for CD38 in cancer associated fibroblasts (CAFs). In vivo, CAF CD38 promotes melanoma expansion. Mechanistically, CD38 enhances CAF migration towards cancer cells as well as tumor cell migration and invasion. Further, CD38 enables de novo endothelial tube formation by upregulating angiogenic transcripts and pro-angiogenic secreted factors.

    • Bar Ben Baruch
    • , Einav Mantsur
    • , Janusz Franco-Barraza
    • , Eran Blacher
    • , Edna Cukierman
    •  & Reuven Stein
  • Technical Report |

    An orally infected hamster model of Coxsackievirus A16 (CV-A16) hand-foot-and-mouth disease (HFMD) and encephalomyelitis demonstrating central nervous system and squamous epithelial infection, reminiscent of complicated human CV-A16 HFMD is described. This novel and consistent animal model should be useful to investigate viral pathogenesis, model person-to-person transmission, and to test antivirals and vaccines.

    • Yuan Teng Hooi
    • , Kien Chai Ong
    • , Soon Hao Tan
    • , David Perera
    •  & Kum Thong Wong
  • Article
    | Open Access

    Proteomic profiling may contribute to the analysis and classification of cancer. The authors applied the digital western blot technique DigiWest with a panel of 102 proteins and phosphoproteins in combination with a machine learning algorithm to classify the tissue origin of five common cancer types in fresh frozen and formalin-fixed paraffin-embedded tissue. DigiWest profiling represents a valuable method for cancer classification, yielding conclusive and decisive data, thus making this approach attractive for routine clinical applications.

    • Teresa Bockmayr
    • , Gerrit Erdmann
    • , Denise Treue
    • , Philipp Jurmeister
    • , Julia Schneider
    • , Anja Arndt
    • , Daniel Heim
    • , Michael Bockmayr
    • , Christoph Sachse
    •  & Frederick Klauschen
  • Article |

    The authors demonstrate that mechanical strain enhances proliferation and migration of breast cancer (BCa) cells. Oscillatory strain (OS)-exposed triple negative breast cancer cells produced more exosomes with immunomodulatory potential. Preconditioning BCa cells with OS before transplantation in vivo increased tumor growth, infiltration of immunesuppressive myeloid-lineage cells, and enhanced exosome-mediated cellular cross-talk.

    • Yong Wang
    • , Kayla F. Goliwas
    • , Paige E. Severino
    • , Kenneth P. Hough
    • , Derek Van Vessem
    • , Hong Wang
    • , Sultan Tousif
    • , Roy P. Koomullil
    • , Andra R. Frost
    • , Selvarangan Ponnazhagan
    • , Joel L. Berry
    •  & Jessy S. Deshane
  • Article |

    Fibronectin 1 (FN-1) promotes differentiation and mineralization of osteoblasts by activating the WNT/β-catenin pathway. Integrin β1 (ITGB1) acts as an indispensable signaling molecule for the interplay between FN-1 and β-catenin. Treatment with FN-1 and ITGB1 is a potential therapeutic strategy for improvement of bone formation in osteoporosis.

    • Chengliang Yang
    • , Chong Wang
    • , Jing Zhou
    • , Qingyang Liang
    • , Feng He
    • , Feng Li
    • , Ye Li
    • , Jinzhong Chen
    • , Fan Zhang
    • , Chao Han
    • , Jia Liu
    • , Kai Li
    •  & Yujin Tang
  • Article |

    This study reveals that miR-185-5p alleviates endoplasmic reticulum (ER) stress, prevents epithelial dedifferentiation and subsequently improves renal fibrosis by downregulating activating transcription factor 6 (ATF6). The miR-185-5p/ATF6 pathway is proposed as a novel regulatory mechanism for renal fibrosis and may provide a therapeutic strategy for renal fibrosis associated with ER stress.

    • Quan Yuan
    • , Tianhua Xu
    • , Ying Chen
    • , Wei Qu
    • , Dan Sun
    • , Xiaodan Liu
    •  & Li Sun
  • Technical Report |

    The authors developed an in vivo model to assess patterns of peritoneal dissemination of colorectal cancer cell lines that recapitulates the high heterogeneity observed between patients. Great variation in the extent of peritoneal outgrowth, localization and clonal dynamics between cell lines was observed and a putative association with KRAS pathway activation was identified.

    • Vivian P. Bastiaenen
    • , Charlotte E. L. Klaver
    • , Maartje C. S. van der Heijden
    • , Lisanne E. Nijman
    • , Maria C. Lecca
    • , Pieter J. Tanis
    • , Kristiaan J. Lenos
    •  & Louis Vermeulen
  • Article |

    This study examined the contribution of ACE2 in diabetes onset and the role of ACE2 in the progression of diabetic nephropathy in NOD mouse. ACE2 loss leads to an impaired glucose and insulin homeostasis, RAS activation, increase in oxidative stress, and RIPK1 within the pancreas. In the kidney, ACE2 deletion induced podocyte loss, RAS modulation, and renal fibrosis activation in an early phase of diabetes.

    • Heleia Roca-Ho
    • , Vanesa Palau
    • , Javier Gimeno
    • , Julio Pascual
    • , María José Soler
    •  & Marta Riera
  • Article
    | Open Access

    RNA of sufficient quality and quantity can be extracted from formalin-fixed paraffin-embedded (FFPE) samples to obtain comprehensive transcriptome profiling using the 3′ massive analysis of c-DNA ends (MACE) RNA-sequencing technology. Thus, MACE provides an opportunity for utilizing FFPE samples stored in histological archives.

    • Stefaniya Boneva
    • , Anja Schlecht
    • , Daniel Böhringer
    • , Hans Mittelviefhaus
    • , Thomas Reinhard
    • , Hansjürgen Agostini
    • , Claudia Auw-Haedrich
    • , Günther Schlunck
    • , Julian Wolf
    •  & Clemens Lange
  • Article |

    This study provides insight into the function of Sox13 in hepatocellular carcinoma (HCC). Sox13 serves as a key regulator of HCC cell migration, invasion, and epithelial-to-mesenchymal transition by transactivating Twist1. Sox13 forms heterodimers with Sox5 to enhance Twist1 transcriptional activity. In addition, overexpression of Sox13 indicates poor prognosis for HCC patients. These findings implicate Sox13 as a potential therapeutic target for HCC.

    • Min Feng
    • , Fei Fang
    • , Ting Fang
    • , Hui Jiao
    • , Song You
    • , Xiaomin Wang
    •  & Wenxiu Zhao
  • Article |

    This study reveals that inhibition of miR-181a-5p protects immature rats from epilepsy, including hippocampal insults, neuronal apoptosis, astrocyte and microglia activation, neuroinflammation, and oxidative stress. This protection is achieved through the SIRT1 pathway, which may be a novel therapeutic target for epilepsy.

    • Huimin Kong
    • , Huaili Wang
    • , Zhihong Zhuo
    • , Zhenbiao Li
    • , Peichao Tian
    • , Jing Wu
    • , Jian Liu
    • , Zheng Chen
    • , Jiyao Zhang
    •  & Qiang Luo
  • Article |

    Medulloblastoma (MB) cells form three-dimensional tumoroids in vitro that can be passaged and preserved. MB cells in tumoroids retain the tumorigenic potential and hedgehog signaling, which relies on stromal astrocytes and astrocyte-derived extracellular matrix. These findings provide a valuable cell model for the basic and preclinical studies of MB.

    • Yan Cheng
    • , Janusz Franco-Barraza
    • , Yuan Wang
    • , Chaonan Zheng
    • , Li Zhang
    • , Yanghui Qu
    • , Yaqiu Long
    • , Edna Cukierman
    •  & Zeng-jie Yang
  • Article
    | Open Access

    The authors. show that CCL3 derived from both tumor-associated macrophages and esophageal squamous cell carcinoma (ESCC) cells promotes cell migration and invasion of ESCC cells via binding CCR5. High expression of CCL3 and/or CCR5 associates with poor prognosis in ESCC patients. CCL3–CCR5 axis could be a specific target of anti-cancer therapy.

    • Takayuki Kodama
    • , Yu-ichiro Koma
    • , Noriaki Arai
    • , Aya Kido
    • , Naoki Urakawa
    • , Mari Nishio
    • , Manabu Shigeoka
    •  & Hiroshi Yokozaki
  • Article |

    The authors developed a novel simplified assay for glioblastoma transcriptional classification on formalin-fixed-paraffin-embedded tissue samples. On such dataset, immunohistochemical profiles, based on expression of a restricted panel of gene classifiers, were integrated by machine learning approach to generate a glioblastoma transcriptional signature based on protein quantification that allowed to efficiently assign transcriptional subgroups to an extended cohort. Correlations with both histopathological features and clinical outcome have been also performed.

    • Francesca Orzan
    • , Francesca Pagani
    • , Manuela Cominelli
    • , Luca Triggiani
    • , Stefano Calza
    • , Francesca De Bacco
    • , Daniela Medicina
    • , Piera Balzarini
    • , Pier Paolo Panciani
    • , Roberto Liserre
    • , Michela Buglione
    • , Marco Maria Fontanella
    • , Enzo Medico
    • , Rossella Galli
    • , Claudio Isella
    • , Carla Boccaccio
    •  & Pietro Luigi Poliani
  • Article |

    Intestinal farnesoid X receptor (FXR) deficiency in mice leads to more severe liver injury and inflammation with ethanol treatment, which is associated with increased intestinal leakage. These results suggest that intestinal FXR may be critical in maintaining gut integrity and the epithelial barrier to protect the liver from ethanol-induced injury.

    • Mingxing Huang
    • , Bo Kong
    • , Min Zhang
    • , Daniel Rizzolo
    • , Laura E. Armstrong
    • , Justin D. Schumacher
    • , Monica D. Chow
    • , Yi-Horng Lee
    • , Laurie B. Joseph
    • , Mary Stofan
    • , Lanjing Zhang
    •  & Grace L. Guo
  • Article
    | Open Access

    Wolfram syndrome is a prototype of endoplasmic reticulum (ER) stress disorder characterized by diabetes, visual impairment, and neurodegeneration. Currently, there is no treatment that can halt or reverse the disease progression. Here, the authors show that mesencephalic astrocyte-derived neurotrophic factor-based regenerative gene therapy is an emerging therapeutic strategy for Wolfram syndrome and other ER stress-related disorders.

    • Jana Mahadevan
    • , Shuntaro Morikawa
    • , Takuya Yagi
    • , Damien Abreu
    • , Simin Lu
    • , Kohsuke Kanekura
    • , Cris M. Brown
    •  & Fumihiko Urano
  • Article |

    Thrombospondin-1 (TSP1) is a matrix protein that binds it high affinity receptor CD47. Both TSP1 and CD47 are upregulated in the kidney in response to injury and this promotes the development of fibrosis by inducing transforming growth factor-β and other fibrogenic factors. The authors were able to block or eliminate CD47-based signal transduction to reduce renal fibrosis.

    • Sohel M. Julovi
    • , Barkha Sanganeria
    • , Nikita Minhas
    • , Kedar Ghimire
    • , Brian Nankivell
    •  & Natasha M. Rogers
  • Article |

    The authors developed nervous-system-specific Nrbf2 knockout mice and found that they exhibited profound learning and memory deficits. RNAseq analyses have identified altered expression of genes related to protein folding and quality control. Aberrant aggregates of some of these key proteins are evident in the hippocampus.

    • Xiaosen Ouyang
    • , Israr Ahmad
    • , Michelle S. Johnson
    • , Matthew Redmann
    • , Jason Craver
    • , Willayat Y. Wani
    • , Gloria A. Benavides
    • , Balu Chacko
    • , Peng Li
    • , Martin Young
    • , Anil G. Jegga
    • , Victor Darley-Usmar
    •  & Jianhua Zhang
  • Article |

    This study reports laboratory data and disease outcome of 54 severe- and critical-type COVID-19 hospitalized adult patients in Wuhan, China. Decreased peripheral blood lymphocyte count, prolonged PT, increased secondary fibrinolytic activity, and significantly increased inflammatory factors sIL-2R and IL-6 correlated with the severity of the disease.

    • Yanlei Li
    • , Yanbing Hu
    • , Jinyan Yu
    •  & Tiangang Ma
  • Article |

    Adeno-associated virus type 2 encoding the prolactin fragment vasoinhibin (AAV2 vasoinhibin) reduces joint inflammation and bone loss in antigen-induced arthritis in mice by inhibiting pannus angiogenesis and vasopermeability via the blockage of VEGF-induced eNOS activation. These findings suggest the potential benefit of vasoinhibin gene therapy in arthritis.

    • Georgina Ortiz
    • , Maria G. Ledesma-Colunga
    • , Zhijian Wu
    • , Jose F. García-Rodrigo
    • , Norma Adan
    • , Gonzalo Martínez de la Escalera
    •  & Carmen Clapp
  • Technical Report |

    This study on myxoid liposarcoma, based on mass spectrometry imaging of N-glycans, has revealed that increases in high-mannose-type as well as tri- and tetra-antennary complex-type N-glycans are associated with morphological progression of the disease. The increased abundance of tri-antennary complex-type glycans was also associated with a poor disease-specific survival for the patients.

    • Bram Heijs
    • , Stephanie Holst-Bernal
    • , Marieke A. de Graaff
    • , Inge H. Briaire-de Bruijn
    • , Mar Rodriguez-Girondo
    • , Michiel A. J. van de Sande
    • , Manfred Wuhrer
    • , Liam A. McDonnell
    •  & Judith V. M. G. Bovée
  • Technical Report
    | Open Access

    Brightfield multiplex immunohistochemistry (IHC) is improved by replacing broadly absorbing chromogens with narrowband covalently deposited chromogens, and sequentially illuminating with light channels matched to chromogen absorbance bands, synchronized with monochromatic image acquisition. Light emitting diodes provide a path to rapid multispectral imaging. Spectral unmixing provided accurate representations of biomarkers that faithfully reproduced 3,3′-diaminobenzidine IHC.

    • Larry E. Morrison
    • , Mark R. Lefever
    • , Lauren J. Behman
    • , Torsten Leibold
    • , Esteban A. Roberts
    • , Uwe B. Horchner
    •  & Daniel R. Bauer
  • Article |

    Traditional RNA sequencing data may fail to detect the exact cellular changes in tumor cells. With comprehensively single-cell and traditional RNA-seq data, these authors detected and compared differentially expressed genes in lung adenocarcinoma. These results may improve our understanding of cellular and molecular differences between cancerous and non-malignant tissue and provide tumor markers as well as potential therapeutic targets.

    • Zhencong Chen
    • , Mengnan Zhao
    • , Ming Li
    • , Qihai Sui
    • , Yunyi Bian
    • , Jiaqi Liang
    • , Zhengyang Hu
    • , Yuansheng Zheng
    • , Tao Lu
    • , Yiwei Huang
    • , Cheng Zhan
    • , Wei Jiang
    • , Qun Wang
    •  & Lijie Tan
  • Article
    | Open Access

    Increased levels of histone H2B (H2B), a damage-associated protein, are found in the vitreous of patients with acute primary angle closure. Elevated H2B causes severe inflammation and subsequent retinal ganglion cell death through toll-like receptor 4 (TLR4) signaling. These results provide new insight for the mechanism of retinal ganglia degeneration.

    • Yasunari Munemasa
  • Article |

    Matricellular protein SPOCK1 expression positively correlates with liver fibrosis and hepatic stellate cell activation. SPOCK1 is upregulated by PDGF-BB via the PI3K/Akt/FoxM1 signaling pathway and induces pro-fibrogenic responses. Additionally, it promotes stellate cell pro-fibrogenic responses through the integrin α5β1/PI3K/Akt signaling pathway. SPOCK1 is therefore a promising therapeutic target for liver fibrosis.

    • Zhipeng Du
    • , Zhuoying Lin
    • , Zhihui Wang
    • , Danfei Liu
    • , Dean Tian
    •  & Limin Xia
  • Article |

    Digital spatial profiling is a new high-plex technology with potential to multiplex hundreds of proteins on a single slide. Here the authors validate the digital aspect of the technology on a control tissue microarray with known amounts of PD-L1 expression to show it has quantitative capacity comparable to quantitative immunofluorescence.

    • Swati Gupta
    • , Jon Zugazagoitia
    • , Sandra Martinez-Morilla
    • , Kit Fuhrman
    •  & David L. Rimm
  • Article |

    Synovial mesenchymal stem cells (MSCs) are an attractive cell source for transplantation in the meniscus of the knee because of their high chondrogenic potential. This study describes the morphological features of synovial MSC adhesion to the meniscus and provides ways to increase the number of adherent MSCs so that clinical outcomes can be improved.

    • So Suzuki
    • , Mitsuru Mizuno
    • , Yuriko Sakamaki
    • , Ayako Mimata
    • , Kentaro Endo
    • , Yuji Kohno
    • , Nobutake Ozeki
    • , Koji Otabe
    • , Hisako Katano
    • , Kunikazu Tsuji
    • , Hideyuki Koga
    •  & Ichiro Sekiya
  • Article |

    The authors observed an increase of talin-vinculin spatial proximities in the livers of spotted fever Rickettsia australis or Ebola virus-infected mice when compared to mock mice. Furthermore, using EPAC1 knockout mice, they found that deletion of EPAC1 suppresses the formation of spatial proximal complex of talin-vinculin in rickettsial infections.

    • Yakun Liu
    • , Jie Xiao
    • , Ben Zhang
    • , Thomas R. Shelite
    • , Zhengchen Su
    • , Qing Chang
    • , Barbara Judy
    • , Xiang Li
    • , Aleksandra Drelich
    • , Jiani Bei
    • , Yixuan Zhou
    • , Junying Zheng
    • , Yang Jin
    • , Shannan L. Rossi
    • , Shao-Jun Tang
    • , Maki Wakamiya
    • , Tais Saito
    • , Thomas Ksiazek
    • , Bhupendra Kaphalia
    •  & Bin Gong
  • Article |

    The interaction of genetic and epigenetic mechanisms is one of the underlying causes of phenotypic variability in diseases like type 2 diabetes. The authors identified the methylation-dependent CpG-SNP in the MTHFD1 gene as a regulator of allele-specific gene expression in peripheral blood mononuclear cells, which may perturb one-carbon metabolism in diabetes.

    • Manik Vohra
    • , Prabha Adhikari
    • , Sydney C.D’. Souza
    • , Shivashankar K. Nagri
    • , Shashikiran Umakanth
    • , Kapaettu Satyamoorthy
    •  & Padmalatha S. Rai
  • Article |

    SiO2-mediated epithelial–mesenchymal transition via the nuclear transcription factor Ets-like protein-1 (ELK-1) due to oxidative stress and the downstream signaling of ZC3H4 expression. These findings suggest that the nuclear transcription factor ELK-1 may be useful as a novel target for the treatment of pulmonary fibrosis.

    • Rong Jiang
    • , Qianqian Gao
    • , Mingxia Chen
    •  & Tingting Yu
  • Article |

    The ability to characterize the cellular composition and spatial organization of the tumor microenvironment has been limited by the techniques available to image the necessary number of biomarkers for broad phenotyping at a subcellular resolution. This study demonstrates the capabilities of Multiplexed Ion Beam Imaging (MIBI) for cell phenotype identification and their spatial relationships across multiple tumor types.

    • Jason Ptacek
    • , Darren Locke
    • , Rachel Finck
    • , Mary-Ellen Cvijic
    • , Zhuyin Li
    • , Jay G. Tarolli
    • , Murat Aksoy
    • , Yari Sigal
    • , Yi Zhang
    • , Matt Newgren
    •  & Jessica Finn