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  • Article |

    Using approaches involving chimeric mice and macrophage-adipocyte cocultures, the authors demonstrate that PFKFB3 disruption only in hematopoietic cells exacerbates the severity of diet-induced adipose tissue inflammation and systemic insulin resistance. Mechanistically, macrophage factors generated in response to PFKFB3 disruption act to enhance adipocyte proinflammatory responses and impair adipocyte insulin signaling.

    • Bilian Zhu
    • , Xin Guo
    • , Hang Xu
    • , Boxiong Jiang
    • , Honggui Li
    • , Yina Wang
    • , Qiongli Yin
    • , Tianhao Zhou
    • , James J. Cai
    • , Shannon Glaser
    • , Fanyin Meng
    • , Heather Francis
    • , Gianfranco Alpini
    •  & Chaodong Wu
  • Article |

    Recent studies highlight a prominent role of human lung pericytes in lung diseases. However, human lung pericytes usually stop growth within ten passages. This study successfully established an immortalized human lung pericyte cell line, which exhibited sustained proliferation, retained pericyte characteristics and function, is a promising tool for in vitro pericyte studies.

    • Pengfei Li
    • , Yan Wu
    • , Andrew J. Goodwin
    • , Perry V. Halushka
    • , Carole L. Wilson
    • , Lynn M. Schnapp
    •  & Hongkuan Fan
  • Article |

    In this study, the authors reveal that the hypoxic microenvironment stimulates glioma to generate miR-1246- and miR-10b-5p-rich exosomes, which are delivered to normoxic glioma cells to promote their migration and invasion by targeting FRK and TFAP2A respectively. Treatment targeting the exosomes and microRNAs may impair the motility of gliomas, providing a novel direction for the development of antitumor therapy.

    • Mingyu Qian
    • , Zihang Chen
    • , Xiaofan Guo
    • , Shaobo Wang
    • , Zongpu Zhang
    • , Wei Qiu
    • , Yanhua Qi
    • , Shouji Zhang
    • , Jianye Xu
    • , Rongrong Zhao
    • , Hao Xue
    •  & Gang Li
  • Article |

    The abnormal differentiation of Th17 cells is a vital promoter of immune thrombocytopenia (ITP) progression. In this study, the authors found that miR-199a-5p is downregulated during ITP. Supplementation of extracellular vesicles (EVs) derived from miR-199a-5p-modified ADSCs markedly repress Th17 differentiation by transferring miR-199a-5p to CD4+T cells, thus ameliorating experimental ITP.

    • Jianqin Li
    • , Yanlin Xia
    • , Xiaoru Fan
    • , Xiaofang Wu
    • , Feiyun Yang
    • , Shaoyan Hu
    •  & Zhaoyue Wang
  • Article |

    This study confirms that the expression of GTSE1 in prostate cancer is significantly increased and negatively correlated with patient prognosis. Furthermore, GTSE1 promotes prostate cancer cell proliferation via the SP1/FOXM1 signaling pathway, which facilitates tumorigenesis and progression. These results suggest that GTSE1 has potential value as a prognostic marker and therapeutic target in prostate cancer.

    • Wenjie Lai
    • , Weian Zhu
    • , Xiaojuan Li
    • , Yuefu Han
    • , Yu Wang
    • , Qu Leng
    • , Mingzhao Li
    •  & Xingqiao Wen
  • Article |

    This study reveals that upregulation of lncRNA small nucleolar RNA host gene 5 (SNHG5), mediated by Yin Yang 1 (YY1), activates connective tissue growth factor (CTGF)/vascular endothelial growth factor (VEGFA) axis via targeting miR-26b to regulate angiogenesis of acute myelogenous leukemia (AML), providing new insights into mechanisms of AML.

    • Zhen-Jiang Li
    • , Jing Cheng
    • , Yuan Song
    • , Hui-Hui Li
    •  & Ji-Fu Zheng
  • Article |

    This paper reports the optimisation of digital pathology approaches for evaluating drug responses in patient-derived explants at endpoint. The authors compare three image analysis software platforms and find that all three generate comparable data to that of a histomorphometrist. They also demonstrate the power of multi-immunofluorescence staining for monitoring multiple biomarkers simultaneously compared to virtual double staining of sequential sections by immunohistochemistry.

    • Gareth J. Miles
    • , Ian Powley
    • , Seid Mohammed
    • , Lynne Howells
    • , J Howard. Pringle
    • , Tim Hammonds
    • , Marion MacFarlane
    •  & Catrin Pritchard
  • Article
    | Open Access

    The authors show that plasminogen activator inhibitor-1 (PAI-1) derived from cancer-associated fibroblasts promotes the invasion of esophageal squamous cell carcinoma (ESCC) cells and the migration of macrophages via lipoprotein receptor-related protein 1 (LRP1). High expression of PAI-1 and/or LRP1 is associated with poor prognosis in patients with ESCC, and the PAI-1/LRP1 axis could be a target of anticancer therapy.

    • Hiroki Sakamoto
    • , Yu-ichiro Koma
    • , Nobuhide Higashino
    • , Takayuki Kodama
    • , Kohei Tanigawa
    • , Masaki Shimizu
    • , Masataka Fujikawa
    • , Mari Nishio
    • , Manabu Shigeoka
    • , Yoshihiro Kakeji
    •  & Hiroshi Yokozaki
  • Article |

    The correlation between SMAD4 mutations and clinico-molecular features in a Chinese non-small cell lung cancer (NSCLC) cohort was studied using next-generation sequencing. Integrated bioinformatics analyses based on public databases were conducted to further investigate the prognostic value of SMAD4. Results showed that SMAD4 alteration was associated with poor survival and resistance to platinum-based chemotherapy, suggesting that SMAD4 alteration might be a predictive marker in NSCLC.

    • Yue Wang
    • , Qianqian Xue
    • , Qiang Zheng
    • , Yan Jin
    • , Xuxia Shen
    • , Mu Yang
    • , Xiaoyan Zhou
    •  & Yuan Li
  • Article
    | Open Access

    Vascular endothelial growth factor secreted by placenta-derived mesenchymal stem cells (PD-MSCs) promotes follicular development and ovarian function after ovariectomy through vascular remodeling. These results provide fundamental data for understanding the therapeutic mechanisms of stem cell therapy based on placenta-derived mesenchymal stem cells PD-MSCs and provide a theoretical foundation for their application for obstetrical and gynecological diseases, including infertility and menopause.

    • Jinki Cho
    • , Tae-Hee Kim
    • , Jin Seok
    • , Ji Hye Jun
    • , Hyeri Park
    • , Minyeoung Kweon
    • , Ja-Yun Lim
    •  & Gi Jin Kim
  • Article |

    Chronic stress can change hepatic lipid accumulation via elevation of hepatic β-muricholic acid levels in nonalcoholic steatohepatitis mice, disrupting bile acid homeostasis by induction of hepatic Cyp7a1 expression. This study describes a new role βMCA in the liver, indicating its potential usefulness for nonalcohol fatty liver disease therapy.

    • Sayuri Takada
    • , Tsutomu Matsubara
    • , Hideki Fujii
    • , Misako Sato-Matsubara
    • , Atsuko Daikoku
    • , Naoshi Odagiri
    • , Yuga Amano-Teranishi
    • , Norifumi Kawada
    •  & Kazuo Ikeda
  • Article |

    This study demonstrates that ATF-3 plays a suppressive function in melanoma tumor progression via a significant decrease in expression in metastatic melanoma and correlation with tumor virulence. ATF-3 overexpression significantly inhibits cell growth, migration, and invasion in vitro, and abrogates tumor growth in a human melanoma xenograft mouse model in vivo.

    • Tingjian Zu
    • , Diana Wang
    • , Shuyun Xu
    • , Catherine A. A. Lee
    • , Ellen Zhen
    • , Charles H. Yoon
    • , Phammela Abarzua
    • , Shuangshuang Wang
    • , Natasha Y. Frank
    • , Xunwei Wu
    • , Christine G. Lian
    •  & George F. Murphy
  • Article |

    This study shows that exercise increases adropin levels and inhibits NLRP3 inflammasome activation in mice with diet-induced nonalcoholic steatohepatitis (NASH). Furthermore, adropin suppresses palmitic acid-induced NLRP3 inflammasome activation in hepatocytes and Kupffer cells. These results indicate that exercise may inhibit NLRP3 inflammasome activation via adropin induction, resulting in NASH improvement.

    • Wenqi Yang
    • , Ling Liu
    • , Yuan Wei
    • , Chunlu Fang
    • , Shujing Liu
    • , Fu Zhou
    • , Yaping Li
    • , Ge Zhao
    • , Ziyi Guo
    • , Yuan Luo
    •  & Liangming Li
  • Article |

    Nitric oxide (NO) plays an important role in tumor biology, including the generation and maintenance of cancer stem cells (CSCs) subpopulations. Here the authors show that the inhibition of NO production in estrogen-positive breast cancer not only impact the CSC subpopulation but also enhance the efficacy of hormonal therapy with tamoxifen.

    • Laura M. López-Sánchez
    • , Rafael Mena
    • , Silvia Guil-Luna
    • , Ana Mantrana
    • , Jon Peñarando
    • , Marta Toledano-Fonseca
    • , Francisco Conde
    • , Juan R. De la Haba-Rodríguez
    • , Enrique Aranda
    •  & Antonio Rodríguez-Ariza
  • Article |

    Abnormal expression of myocardial infarction-related transcription factor 2 (Mirt2) is associated with myocardial infarction, cardiomyocyte apoptosis and oxidative stress in rats with acute myocardial infarction (AMI). These effects involve the miR-764/PDK1/AKT axis. Therefore, the current findings provide a theoretical basis for the diagnosis and treatment of clinical myocardial infarction by monitoring changes in Mirt2 levels.

    • Fen Zhu
    • , Qing Li
    • , Jun Li
    • , Benlei Li
    •  & Dongsheng Li
  • Article
    | Open Access

    An increase in podocyte apoptosis is positively correlated with the cytoplasmic distribution of YAP in focal segmental glomerulosclerosis (FSGS). YAP inhibition by verteporfin induces nuclear exclusion of YAP, thus increasing the podocyte apoptosis and accelerating disease progression. Therefore, this study suggests that YAP activation and nuclear distribution in podocytes is an endogenous anti-apoptotic mechanism during the progression of FSGS.

    • Qiyuan Zhuang
    • , Fang Li
    • , Jun Liu
    • , Hongyu Wang
    • , Yuchen Tian
    • , Zhigang Zhang
    • , Feng Wang
    • , Zhonghua Zhao
    • , Jianchun Chen
    •  & Huijuan Wu
  • Article
    | Open Access

    Injury-induced transforming growth factor β1 increases sphingosine 1-phosphate (S1P) generation by upregulating in sphingosine kinase 1 activity. The high levels of S1P formation stimulate the S1PR3-linked signaling pathway, which in turn increases vascular endothelial growth factor-A expression levels and angiogenesis in mouse corneas.

    • Shingo Yasuda
    • , Takayoshi Sumioka
    • , Hiroki Iwanishi
    • , Yuka Okada
    • , Masayasu Miyajima
    • , Kana Ichikawa
    • , Peter S. Reinach
    •  & Shizuya Saika
  • Article |

    SECISBP2 overexpression is an independent negative prognostic predictor in diffuse large B-cell lymphoma. Additionally, SECISBP2 positively correlates with selenoprotein expression. In vitro, SECISBP2 knockout increases intracellular reactive oxygen species accumulation via the downregulation of selenoproteins, inhibiting cell growth and promoting cell death after doxorubicin treatment. Therefore, SECISBP2 is a potential therapeutic target for malignant lymphoma.

    • Towako Taguchi
    • , Morito Kurata
    • , Iichiroh Onishi
    • , Yuko Kinowaki
    • , Yunosuke Sato
    • , Sayuri Shiono
    • , Sachiko Ishibashi
    • , Masumi Ikeda
    • , Masahide Yamamoto
    • , Masanobu Kitagawa
    •  & Kouhei Yamamoto
  • Article |

    The authors show that genomes of female infertility patients harbor mutations within miRNA genes and 3’ UTR miRNA binding sites that are likely to affect maternal transcript clearance. Such disruption may not be compatible with zygotic genome activation and could cause a failure in embryonic development, implantation or cause early miscarriage, resulting in an infertility diagnosis.

    • Katarzyna M. Tyc
    • , Anthony Wong
    • , Richard T. Scott Jr
    • , Xin Tao
    • , Karen Schindler
    •  & Jinchuan Xing
  • Article |

    The authors report the feasibility of generating, expanding, and enumerating viable patient-derived intraductal papillary mucinous neoplasm (IPMN) tumor and normal pancreatic organoids from fresh and cryopreserved resected tissue. Organoids were characterized histologically and genomically and recapitulated the morphological and mutational profiles of resected IPMNs, suggesting promise of organoids for translational efforts.

    • Francisca Beato
    • , Dayana Reverón
    • , Kaleena B. Dezsi
    • , Antonio Ortiz
    • , Joseph O. Johnson
    • , Dung-Tsa Chen
    • , Karla Ali
    • , Sean J. Yoder
    • , Daniel Jeong
    • , Mokenge Malafa
    • , Pamela Hodul
    • , Kun Jiang
    • , Barbara A. Centeno
    • , Mahmoud A. Abdalah
    • , Jodi A. Balasi
    • , Alexandra F. Tassielli
    • , Bhaswati Sarcar
    • , Jamie K. Teer
    • , Gina M. DeNicola
    • , Jennifer B. Permuth
    •  & Jason B. Fleming
  • Article |

    In this study, the authors provide evidence that ectopic expression of oncogenic mutant Kras in pancreatic ducts generates early and late (PanIN) and pancreatic ductal adenocarcinoma (PDAC) . They characterized this Ras rheostat model which reveals elevated Kras mutation frequency and loss of PTEN are important drivers of PanIN and invasive ductal derived PDAC.

    • Kanchan Singh
    • , Melissa Pruski
    • , Rachael Bland
    • , Mamoun Younes
    • , Sushovan Guha
    • , Nirav Thosani
    • , Anirban Maitra
    • , Brooks D. Cash
    • , Florencia McAllister
    • , Craig D. Logsdon
    • , Jeffrey T. Chang
    •  & Jennifer M. Bailey-Lundberg
  • Article |

    In this study, effect of Osr1 deficiency in promoting non-alcoholic fatty liver disease progression was examined. The authors demonstrate that Osr1 regulates hepatic inflammation and cell survival through multiple signaling pathways and DNA methylation modification.

    • Yi Zhou
    • , Zhimin Liu
    • , Ernest C. Lynch
    • , Leya He
    • , Henghui Cheng
    • , Lin Liu
    • , Zhen Li
    • , Jiangyuan Li
    • , Lauren Lawless
    • , Ke K. Zhang
    •  & Linglin Xie
  • Article |

    The authors investigated the clinicopathologic significance of microRNA-130b expression and analyzed its cancer-specific functions using a cancer cell line. High microRNA-130b expression was associated with adverse clinicopathologic parameters and poor patient outcomes. In vitro, downregulation of microRNA-130b caused a decrease in cell proliferation, migration, and invasion. Hence, miR-130b is a potential therapeutic target for lung cancer.

    • Yeseul Kim
    • , Hyunsung Kim
    • , Seongsik Bang
    • , Seungyun Jee
    •  & Kiseok Jang
  • Article |

    C-X-C chemokine receptor type 5 (CXCR5) regulates retinal pigment epithelium (RPE) homeostasis through PI3K/AKT signaling and by suppression of FOXO1 activation. CXCR5-deficency leads to decreased RPE differentiation, compromised barrier function, and increase in epithelial-mesenchymal transition markers (αSMA, N-cadherin, and vimentin) in CXCR5-deficient RPE cells in vitro and in CXCR5−/− mice.

    • Anton Lennikov
    • , Anthony Mukwaya
    • , Madhu Sudhana Saddala
    •  & Hu Huang
  • Article |

    The authors present an assessment of the utility of “third-generation” nanopore sequencing for the confirmation and characterization of mobile element insertions. and discuss how implementation of long-read nanopore sequencing can offer benefits over existing molecular approaches.

    • Christopher M. Watson
    • , Laura A. Crinnion
    • , Helen Lindsay
    • , Rowena Mitchell
    • , Nick Camm
    • , Rachel Robinson
    • , Caroline Joyce
    • , George A. Tanteles
    • , Domhnall J. O’ Halloran
    • , Sergio D. J. Pena
    • , Ian M. Carr
    •  & David T. Bonthron
  • Article
    | Open Access

    Epithelial-to-mesenchymal transition of epithelium and airway epithelial cell proliferation disorder are key events in idiopathic pulmonary fibrosis (IPF) pathogenesis. In the present study, the miR-184/TP63 axis modulates the TGF-β1-induced fibrotic alterations in epithelial cell lines and bleomycin-induced pulmonary fibrosis in mice, confirming that miR-184/TP63 axis is involved in IPF progression.

    • Jianmin Li
    • , Chanyuan Pan
    • , Chao Tang
    • , Wenwen Tan
    • , Weiwei Zhang
    •  & Jing Guan
  • Article
    | Open Access

    Ascorbate can act as an oxidant to induce tumor cell death at a pharmacological dose. Here the authors show that this response is associated with increases in GPCR Gi/o activity. This effect promotes rises in intracellular Ca2+ influx through transient receptor potential channel activity in retinoblastoma cells.

    • Jakub Oronowicz
    • , Jacqueline Reinhard
    • , Peter Sol Reinach
    • , Szymon Ludwiczak
    • , Huan Luo
    • , Marah Hussain Omar Ba Salem
    • , Miriam Monika Kraemer
    • , Heike Biebermann
    • , Vinodh Kakkassery
    •  & Stefan Mergler
  • Article |

    Cardiovascular diseases are the leading cause of death worldwide. Myocardial ischaemia/reperfusion (I/R) injury is a major risk for cardiovascular disease. Herein, the authors demonstrate that circPAN3 ameliorates myocardial I/R injury by absorbing miR-421 to regulate Pink1-mediated autophagy, which may provide potential therapeutic targets in I/R injury.

    • Cheng-Long Zhang
    • , Tian-Yi Long
    • , Si-Si Bi
    • , Sayed-Ali Sheikh
    •  & Fei Li
  • Article
    | Open Access

    This study demonstrates that NFAT5 promotes oral squamous cell carcinoma progression in the hyperosmotic environment through increased expression of DPAGT1, an essential enzyme for protein glycosylation, and altered EGFR subcellular localization from the cytoplasm to the plasma membrane in tumor cells.

    • Shohei Yoshimoto
    • , Hiromitsu Morita
    • , Miho Matsuda
    • , Yoshinori Katakura
    • , Masato Hirata
    •  & Shuichi Hashimoto
  • Article |

    The authors describe a sarcoma with a novel fusion between NUTM1 and MXI1, a member of the MAD gene family. Transcriptome analysis and in vitro studies showed that MXI1-NUTM1 partially phenocopied MYC, providing evidence that MAD family members, normally repressors of MYC activity, can be converted into MYC-like mimics by fusion to NUTM1.

    • Christopher R. McEvoy
    • , Holly Holliday
    • , Niko Thio
    • , Catherine Mitchell
    • , David Y. Choong
    • , Bhargavi Yellapu
    • , Hui San Leong
    • , Huiling Xu
    • , Stephen Lade
    • , Judy Browning
    • , Elena A. Takano
    • , David J. Byrne
    • , Anthony J. Gill
    • , Cuong P. Duong
    • , Jason Li
    • , Andrew P. Fellowes
    • , Stephen B. Fox
    • , Alexander Swarbrick
    •  & Owen W. J. Prall
  • Article |

    This study describes how miR-221-3p in endothelial cells reduces angiogenesis by inhibiting hypoxia-inducible factor-1α. Because antagonism of miR-221-3p significantly improves the cardiac function of mice with heart failure it may be a new and effective molecular target for progressing and treatment of heart failure.

    • Yuying Li
    • , Chenghui Yan
    • , Jiahui Fan
    • , Zhiwei Hou
    •  & Yaling Han
  • Article |

    In this paper, the authors describe the development and validation of a novel image signature-based radiomics model. A total of 655 glioma patients were enrolled to build this model which is shown to be an effective tool to achieve multilayer preoperative diagnosis and prognostic stratification of gliomas.

    • Huigao Luo
    • , Qiyuan Zhuang
    • , Yuanyuan Wang
    • , Aibaidula Abudumijiti
    • , Kuangyu Shi
    • , Axel Rominger
    • , Hong Chen
    • , Zhong Yang
    • , Vanessa Tran
    • , Guoqing Wu
    • , Zeju Li
    • , Zhen Fan
    • , Zengxin Qi
    • , Yuxiao Guo
    • , Jinhua Yu
    •  & Zhifeng Shi
  • Article |

    Both ASIC1a and VEGF are highly expressed in rheumatoid arthritis synovial tissue and are associated with vascular disease. Interfering with ASIC1a in vitro using silencing, blocking, and overexpression interferes with the release of VEGF under acid stimulation. Blocking ASIC1a in the articular cavity of rats with adjuvant arthritis not only reduces the expression of VEGF in the synovium, but also reduces the proliferation and lesions of blood vessels and interferes with the development of the disease.

    • Xuewen Qian
    • , Yihao Zhang
    • , Jingjing Tao
    • , Ruowen Niu
    • , Sujing Song
    • , Cong Wang
    • , Xiaoqing Peng
    •  & Feihu Chen
  • Article |

    SOX2 is expressed frequently in small cell lung cancer (SCLC). ASCL1 is a potent driver of SOX2 expression and regulates INSM1 expression in the major subtype, SCLC-A (ASCL1). However, SOX2 also regulates distinct genes in the hippo pathway in the minor subtype SCLC-Y (YAP1). These results show that ASCL1-SOX2 axis is a potential therapeutic target in SCLC.

    • Yuki Tenjin
    • , Kumi Matsuura
    • , Shinji Kudoh
    • , Shingo Usuki
    • , Tatsuya Yamada
    • , Akira Matsuo
    • , Younosuke Sato
    • , Haruki Saito
    • , Kosuke Fujino
    • , Joeji Wakimoto
    • , Takaya Ichimura
    • , Hirotsugu Kohrogi
    • , Takuro Sakagami
    • , Hitoshi Niwa
    •  & Takaaki Ito
  • Article |

    Computational modeling has emerged as a promising and cost-effective alternative method for screening potentially endocrine active compounds. This study applies classic machine learning algorithms and deep learning approaches to a panel of over 7500 compounds tested against 18 Toxicity Forecaster assays related to nuclear estrogen receptor (ERα and ERβ) activity.

    • Heather L. Ciallella
    • , Daniel P. Russo
    • , Lauren M. Aleksunes
    • , Fabian A. Grimm
    •  & Hao Zhu
  • 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
  • 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
  • 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