Articles

  • Article |

    The two Na+ and water pore-forming claudins, claudin-2 and claudin-15, are reciprocally regulated during human development. This study shows that expression of these claudins is altered in celiac disease, graft-versus-host disease, and common variable immunodeficiency, but that the specific claudin affected differed between children and adults, suggesting distinct contributions to diarrheal pathophysiology.

    • M. Lora D. M. Ong
    • , Sunil Yeruva
    • , Anne Sailer
    • , Steven P. Nilsen
    •  & Jerrold R. Turner
  • Article |

    Most of the cancer-associated genes mutated only in high-grade gastrointestinal stromal tumors (GISTs) are mainly involved in cell cycle control. High-grade GISTs had more MYC copy number gains than matched low-grade tumors. The authors show that alterations in cell cycle regulation-associated genes, may promote primary progression from low-grade GISTs to high-grade tumors by regulating tumor cell proliferation.

    • Peifeng Li
    • , Mingyang Li
    • , Kaijing Wang
    • , Yixiong Liu
    • , Yingmei Wang
    • , Danhui Zhao
    • , Jia Chai
    • , Jing Ma
    • , Xia Li
    • , Jie Wei
    • , Linni Fan
    • , Feng Zhang
    • , Jing Ye
    • , Qingguo Yan
    • , Shuangping Guo
    •  & Zhe Wang
  • Article |

    The authors provide an in-depth explanation of how HO-1 activation, through PI3K/Akt pathway, protects the lung from oxidative injury in the setting of sepsis by regulating mitochondrial quality control. This study presents a rationale for developing HO-1 therapy to prevent sepsis-related lung injury.

    • Jia Shi
    • , Jianbo Yu
    • , Yuan Zhang
    • , Lili Wu
    • , Shuan Dong
    • , Lina Wu
    • , Lingzhi Wu
    • , Shihan Du
    • , Yanfang Zhang
    •  & Daqing Ma
  • Article
    | Open Access

    While the transcription factor TBX3 is widely studied in tumorigenesis, the functionality of the two isoforms (TBX3iso1 and TBX3iso2) which differ in their DNA-binding domain is not well understood. By utilizing a nude mouse xenograft model, the authors identified differential tumorigenic potential between TBX3 isoforms, with TBX3iso1 (but not TBX3iso2) promoting invasive carcinoma in vivo through induction of angiogenesis. This process is moderated by downstream mediators osteopontin (OPN) and hyaluronan synthase 2 (HAS2).

    • Milica Krstic
    • , Haider M. Hassan
    • , Bart Kolendowski
    • , M. Nicole Hague
    • , Pieter. H. Anborgh
    • , Carl O. Postenka
    • , Joseph Torchia
    • , Ann F. Chambers
    •  & Alan B. Tuck
  • Article
    | Open Access

    The endocannabinoid (EC) system has been implicated in the pathogenesis nonalcoholic fatty liver diseases (NAFLD). Here the authors demonstrate that endocannabinoid receptor 1 (CB1) receptor knockout in vivo and pharmacologic antagonization of CB1 in cell culture decreases expression of lipid droplet binding protein perilipin 2, which might be an essential step in lipid breakdown. Thus, pharmacologic modulation of the CB1-perilipin 2 axis might represent a novel therapeutic approach for the treatment of steatosis.

    • Karuna Irungbam
    • , Yuri Churin
    • , Tomomitsu Matono
    • , Jakob Weglage
    • , Matthias Ocker
    • , Dieter Glebe
    • , Martin Hardt
    • , Alica Koeppel
    • , Martin Roderfeld
    •  & Elke Roeb
  • Article |

    This study suggests a potential mechanism wherein microRNA-21-5p (miR-21-5p) inhibition downregulates autophagy, migration ability, and LC3B expression via PTEN/AKT signaling in electron beam (EB)-irradiated keloid fibroblasts, effectively preventing local invasion and recurrence. Therefore, miR-21-5p could be a new therapeutic target, to replace EB irradiation, and control keloid relapse.

    • Li Yan
    • , Lian-Zhao Wang
    • , Ran Xiao
    • , Rui Cao
    • , Bo Pan
    • , Xiao-Yan Lv
    • , Hu Jiao
    • , Qiang Zhuang
    • , Xue-Jian Sun
    •  & Yuan-Bo Liu
  • Article |

    Bone marrow mesenchymal stem cells (BMSC) or BMSC-derived exosome transplantation improves rat ovarian function after chemotherapy-induced ovarian failure. Furthermore, transfer of miR-144-5p using BMSC-derived exosomes decreases granulosa cell (GCs) apoptosis via the PTEN pathway. Thus, a cell-free therapeutic strategy may be possible for ovarian failure.

    • Meiling Yang
    • , Li Lin
    • , Chunli Sha
    • , Taoqiong Li
    • , Dan Zhao
    • , Hong Wei
    • , Qi Chen
    • , Yueqin Liu
    • , Xiaofang Chen
    • , Wenlin Xu
    • , Yuefeng Li
    •  & Xiaolan Zhu
  • Article |

    This study reveals that adhesion molecule ICAM-1 is markedly upregulated in the aorta after angiotensin II infusion. Blockage of soluble ICAM-1 prevents Ang II-induced arterial hypertension and vascular remodeling by reducing macrophage adhesion, suggesting that targeting ICAM-1 may represent a new therapeutic target for hypertension.

    • Ping-Ping Lang
    • , Jie Bai
    • , Yun-Long Zhang
    • , Xiao-Lei Yang
    • , Yun-Long Xia
    • , Qiu-Yue Lin
    •  & Hui-Hua Li
  • Article |

    The role of the prostaglandin E1 receptor EP1 in hypertensive kidney disease remains controversial. EP1 mediates thick ascending limb chloride transport response to prostaglandin E2 and inhibits vasopressin-mediated water transport in the inner medullary collecting duct (IMCD). Though the IMCD transport is unaltered by hypertension, its responsiveness to vasopressin is reduced in diabetes. Moreover, EP1 is protective against glomerular and endothelial injury in hypertensive kidney disease, unlike its harmful role in diabetic kidney disease. This highlights the importance of carefully examining disease state (diabetes vs hypertension) when characterizing underlying disease processes.

    • Rania Nasrallah
    • , Joseph Zimpelmann
    • , Susan J. Robertson
    • , Jamie Ghossein
    • , Jean-Francois Thibodeau
    • , C. R. J. Kennedy
    • , Alex Gutsol
    • , Fengxia Xiao
    • , Dylan Burger
    • , Kevin D. Burns
    •  & Richard L. Hébert
  • Article |

    The authors investigated global analysis coupled shotgun proteomics and in silico metabolic pathway analyses in malignant lymphoma and normal lymphocytes. Trifunctional protein subunit alfa (HADHA) was detected as a lymphoma-specific protein and a prognostic predictor. In vitro, downregulation of HADHA inhibited cell growth and increase susceptibility of cell death stimuli. Therefore, HADHA may be a potential therapeutic target in refractory malignant lymphoma cases.

    • Kouhei Yamamoto
    • , Shinya Abe
    • , Ayaka Honda
    • , Jun Hashimoto
    • , Yuuki Aizawa
    • , Sachiko Ishibashi
    • , Taro Takemura
    • , Nobutaka Hanagata
    • , Masahide Yamamoto
    • , Osamu Miura
    • , Morito Kurata
    •  & Masanobu Kitagawa
  • Article |

    In this study, the authors show that RIP1/RIP3/MLKL-mediated necroptosis is activated in a mouse model of Parkinson’s disease. Blockade of necroptosis through pharmacological intervention by Nec-1 or deletion of RIP3/MLKL gene increased dopamine levels and the number of dopaminergic neurons in mice. Moreover, necroptosis enhanced the expression of pro-inflammatory genes, which may have initiated neuroinflammation and in turn aggravated dopaminergic neuron necroptosis.

    • Qing-Song Lin
    • , Ping Chen
    • , Wei-Xiong Wang
    • , Chen-Chao Lin
    • , Yao Zhou
    • , Liang-Hong Yu
    • , Yuan-Xiang Lin
    • , Yan-Fang Xu
    •  & De-Zhi Kang
  • Article |

    Vitamin D and its analogues demonstrated in this study antifibrotic effects in a murine fibrosis model compared to calcitriol. In this study, the hypocalcemic vitamin D analog paricalcitol was superior in respect to side effects and efficacy, indication that such analogs could be considered for the treatment of liver fibrosis.

    • Florian P. Reiter
    • , Liangtao Ye
    • , Florian Bösch
    • , Ralf Wimmer
    • , Renate Artmann
    • , Andreas Ziesch
    • , Veronika Kanitz
    • , Doris Mayr
    • , Christian J. Steib
    • , Michael Trauner
    • , Ivonne Regel
    • , Alexander L. Gerbes
    • , Julia Mayerle
    • , Simon Hohenester
    • , Enrico N. de Toni
    •  & Gerald Denk
  • Article |

    This study shows that scavenger receptor type I knockout mice (Scarb1-/-) have high adrenocorticotropic hormone (ACTH) levels but are osteopenic. Bone differentiation of Scarb1-/- mesenchymal stem cells at normal ACTH concentrations is reduced. However, 0–10 nM ACTH increases, but 100–1000 nM ACTH reduces wild-type osteoblast differentiation. Therefore, ACTH and the high-density lipoprotein receptor Scarb1 play independent roles in osteoblast differentiation.

    • Irina L. Tourkova
    • , Steven F. Dobrowolski
    • , Cassandra Secunda
    • , Mone Zaidi
    • , Ioanna Papadimitriou-Olivgeri
    • , Dionysios J. Papachristiou
    •  & Harry C. Blair
  • Article |

    Acute kidney injury and endothelial hyperpermeability are main features observed during severe sepsis with low survival rate. Transient receptor potential melastatin 7 (TRPM7) calcium channel inhibition protects against endotoxemia-induced kidney injury potentially by means of endothelial hyperpermeability decreasing. Remarkably, TRPM7 inhibition improves survival in endotoxemic animals.

    • Sebastian Gatica
    • , Vicente Villegas
    • , Alejandro Vallejos
    • , Pedro Olivares
    • , Víctor Aballai
    • , Felipe Lagos-Meza
    • , Cesar Echeverria
    • , Claudio Cabello-Verrugio
    • , Diego Varela
    •  & Felipe Simon
  • Article |

    CRISPR/dCas9 blocks TGF-β2-induced mouse double minute 2 (MDM2) expression by targeting its second promoter, without affecting the basal expression. Epithelial to mesenchymal transition is blocked by MDM2 suppression in retinal pigment epithelial cells. In this way, CRIPSR/dCas9 is a promising novel therapy for proliferative vitreoretinopathy without interfering basal gene function.

    • Bing Liu
    • , Jingyuan Song
    • , Haote Han
    • , Zhengping Hu
    • , Na Chen
    • , Jing Cui
    • , Joanne Aiko Matsubara
    • , Jingxiang Zhong
    •  & Hetian Lei
  • Article |

    The Niemann–Pick C1-like intracellular cholesterol transporter gene and a number of genes in the cholesterol synthesis pathway are transcriptionally regulated by SREBP-2. The liganded Ah receptor increases proteolytic turnover of transcriptionally active SREBP2. Thus, Ah receptor ligands are capable of attenuating cholesterol uptake into Caco-2 cells.

    • Gulsum E. Muku
    • , Ann Kusnadi
    • , Guray Kuzu
    • , Rachel Tanos
    • , Iain A. Murray
    • , Krishne Gowda
    • , Shantu Amin
    •  & Gary H. Perdew
  • Article |

    Allergic asthma is one of the most common immune-mediated disorders. The authors investigated the possibility that TPRV4 cation channels facilitate the development of allergic asthma and subsequent pulmonary fibrosis in the lung. Their data suggest that TPRV4 is dispensable in the initiation and development of airway asthma and subsequent fibrosis.

    • Senthilkumar Palaniyandi
    • , Arunraj M. Rajendrakumar
    • , Sivakumar Periasamy
    • , Rishov Goswami
    • , Wenbin Tuo
    • , Xiaoping Zhu
    •  & Shaik O. Rahaman
  • Article |

    This study investigates lipid droplet (LD) trafficking and LD velocity (LDV) in cancer. LD density correlated with prostate tumor grade and high grade tumors had significantly higher LDV when compared to low grade tumors. Acidifying conditions drove up velocities and LDV was normalized with blockade of H+ proton pump, V-ATPase.

    • Francesca Nardi
    • , Philip Fitchev
    • , Kyrsten M. Brooks
    • , Omar E. Franco
    • , Kevin Cheng
    • , Simon W. Hayward
    • , Michael A. Welte
    •  & Susan E. Crawford
  • Article |

    This study was performed to evaluate role of RORα in mouse testicular structure. Lack of RORα expression induces apoptosis, reduces germ cells differentiation, and may cause infertility. RORα is one of the essential proteins regulating testicular structure. RORα-deficient mice may be a suitable model for studying mutation-induced of human infertility.

    • Ramy K. A. Sayed
    • , Doaa M. Mokhtar
    • , Marisol Fernández-Ortiz
    • , Germaine Escames
    •  & Darío Acuña-Castroviejo
  • Article |

    • Sandra Martinez-Morilla
    • , John McGuire
    • , Patricia Gaule
    • , Lauren Moore
    • , Balazs Acs
    • , Delphine Cougot
    • , Allen M. Gown
    • , Hadi Yaziji
    • , Wei-Lien Wang
    • , Richard W. Cartun
    • , Jason L. Hornick
    • , Lynette M. Sholl
    • , Jingxin Qiu
    • , Mari Mino-Kenudson
    • , Eunhee S. Yi
    • , Mary Beth Beasley
    • , Daniel T. Merrick
    • , Abiy B. Ambaye
    • , Zhong J. Zhang
    • , Jill Walker
    •  & David L. Rimm
  • Article |

    Obesity causes complications in the treatment of asthma. This manuscript explores the role of Notch pathway in animal models. The authors found that the inhibition of the Notch pathway by a γ-secretase inhibitor suppresses Th17-associated airway hyperresponsiveness in obese asthmatic mice. This finding may provide a novel insight into asthma treatment in the clinic.

    • Zeyu Zeng
    • , Lei Wang
    • , Weihui Ma
    • , Rongying Zheng
    • , Hong Zhang
    • , Xinxin Zeng
    • , Hui Zhang
    •  & Weixi Zhang
  • Article |

    The severe immunodeficiency of NOD.Cg-PrkdcscidIl2rgtm1Wjl (NSG) mice, a widely used strain for generating patient-derived xenografts from primary tumors, impairs drug metabolism and reduces tolerability towards common cytostatic drugs. Consequently, dose finding and tolerance tests are strongly recommended prior to perform large-scale cancer precision medicine approaches.

    • Claudia Maletzki
    • , Stephanie Bock
    • , Philipp Fruh
    • , Karolis Macius
    • , Anika Witt
    • , Friedrich Prall
    •  & Michael Linnebacher
  • Article |

    The authors show that Muc5ac−/− mice develop spontaneous gastric antro-pyloric hyperplasia and adenomas. Interestingly, Muc5ac−/− mice have suppression of gastric corpus mucous metaplasia and key proinflammatory cytokines (Tnfα and Il-17a) in a setting of enhanced Helicobacter pylori colonization, thus implying a complex role for Muc5ac in gastric homeostasis.

    • Sureshkumar Muthupalani
    • , Zhongming Ge
    • , Joanna Joy
    • , Yan Feng
    • , Carrie Dobey
    • , Hye-Youn Cho
    • , Robert Langenbach
    • , Timothy C. Wang
    • , Susan J. Hagen
    •  & James G. Fox
  • Article |

    This study shows how telomerase reverse transcriptase (TERT) assists growth differentiation factor 11 (GDF11) to rejuvenate senescent endothelial progenitor cells via the Smad2/3 and eNOS pathways. Therapeutically, it may be possible to exploit TERT mediated-GDF11 signaling to activate senescent stem cells in the myocardial ischemic microenvironment.

    • Lan Zhao
    • , Shaoheng Zhang
    • , Jin Cui
    • , Weiguang Huang
    • , Jiahong Wang
    • , Feng Su
    • , Nannan Chen
    •  & Qunlin Gong
  • Article |

    The authors established and characterized a novel gastroesophageal junction (GEJ) cancer cell line derived from the malignant pleural effusion of a treated GEJ cancer patient. This cell line represents a valuable addition to the limited number of bona fide GEJ cancer cell lines for both basic and translational research.

    • Wei Zhang
    • , Taylor A. Williams
    • , Ankur S. Bhagwath
    • , Jared S. Hiermann
    • , Craig D. Peacock
    • , D. Neil Watkins
    • , Peiguo Ding
    • , Jason Y. Park
    • , Elizabeth A. Montgomery
    • , Arlene A. Forastiere
    • , Chunfa Jie
    • , Brandi L. Cantarel
    • , Thai H. Pham
    •  & David H. Wang
  • Article |

    Transcription factor STAT3 constitutively activated in cancer promotes tumor progression. The authors detected activated STAT3 in human metastatic melanoma cells and identified new STAT3 targets. STAT3 regulates a discrete set of genes in melanoma cells and its knockdown impairs cell migration and invasion via regulation of its transcriptional target SERPINA3.

    • Dorota W. Kulesza
    • , Kavita Ramji
    • , Marta Maleszewska
    • , Jakub Mieczkowski
    • , Michal Dabrowski
    • , Salem Chouaib
    •  & Bozena Kaminska
  • Article
    | Open Access

    TGF-β plays a key role in fibrosis. β-catenin is common transcription factor in major TGF-β profibrotic signaling pathways and binds competitively to either TCF or Foxo transcription factors. In human kidney biopsies, the authors found that β-catenin/Foxo interaction was negatively correlated, while that of β-catenin/TCF was positively correlated with kidney fibrosis. They further identified β-catenin/Foxo-dependent protection against TGF-β-induced profibrotic changes in tubular cells and kidney fibrosis.

    • Padmashree Rao
    • , Min Pang
    • , Xi Qiao
    • , Hong Yu
    • , Hailong Wang
    • , Ying Yang
    • , Xiaojun Ren
    • , Min Hu
    • , Titi Chen
    • , Qi Cao
    • , Yiping Wang
    • , Matloob Khushi
    • , Geoff Zhang
    • , Yuan Min Wang
    • , Chow Heok P’ng
    • , Brian Nankivell
    • , Vincent W. Lee
    • , Stephen I. Alexander
    • , Guoping Zheng
    •  & David C. Harris
  • Article |

    The calcium signal is a regulator of the acquisition of a more mesenchymal phenotype. Our work in MDA-MB-468 breast cancer cells identifies a complex relationship between factor-specific induction of the epithelial–mesenchymal marker vimentin and the differential involvement of the canonical store-operated calcium channel ORAI1 and the calcium channel component TRPC1.

    • Teneale A. Stewart
    • , Iman Azimi
    • , Daneth Marcial
    • , Amelia A. Peters
    • , Silke B. Chalmers
    • , Kunsala T. D. S Yapa
    • , Erik W. Thompson
    • , Sarah J. Roberts-Thomson
    •  & Gregory R. Monteith
  • Article |

    Wnt11 is more strongly expressed in small cell lung cancer (SCLC) than in non-SCLC. Ascl1 promotes Wnt11 expression by altering H3K27Ac levels at the enhancer region of the WNT11 gene. Ascl1-induces Wnt11 regulates neuroendocrine differentiation, cell proliferation, and E-cadherin expression in SCLC. The Ascl1-Wnt11 axis has potential as a therapeutic target and supports the clinical utility of Wnt11 as a biological marker in SCLC.

    • Yuki Tenjin
    • , Shinji Kudoh
    • , Sho Kubota
    • , Tatsuya Yamada
    • , Akira Matsuo
    • , Younosuke Sato
    • , Takaya Ichimura
    • , Hirotsugu Kohrogi
    • , Goro Sashida
    • , Takuro Sakagami
    •  & Takaaki Ito
  • Article |

    Mitotic density is part of breast cancer grading yet is hampered by interobserver variability. The authors developed a deep learning algorithm which automatically locates the mitotic hotspot in breast tumors. Counting mitoses within this predefined hotspot considerably improved interobserver agreement. Mitotic counts assessed by the algorithm were comparable to the observers’ results.

    • Maschenka C. A. Balkenhol
    • , David Tellez
    • , Willem Vreuls
    • , Pieter C. Clahsen
    • , Hans Pinckaers
    • , Francesco Ciompi
    • , Peter Bult
    •  & Jeroen A. W. M. van der Laak
  • Article |

    ********The authors engineered and constructed a circRNA containing both miR-21 and miR-93 binding sites, then deployed it against esophageal carcinoma. This novel multi-miR circular sponge significantly inhibits endogenous miR-21 and miR-93 activities, suppresses cellular proliferation, migration and tumor growth. These findings suggest an entirely new area of research based on developing synthetic circular RNA sponges as tools for miR-directed molecular therapy.

    • Zhe Wang
    • , Ke Ma
    • , Yulan Cheng
    • , John M. Abraham
    • , Xi Liu
    • , Xiquan Ke
    • , Zhirong Wang
    •  & Stephen J. Meltzer
  • Article |

    The authors present a rare case of intracranial solitary fibrous tumors/hemangiopericytomas (SFT/HPC) with intraspinal metastasis. A DSTYK mutation (Met296Ile) was identified as a potential driver of intraspinal metastasis. This DSTYK mutation promotes cell migration and invasion of SFT/HPC cells via activation of ERK1/2/MMP2/9 signaling, which may provide new biological insights for SFT/HPC study.

    • Guodong Tang
    • , Yufei Yang
    • , Li Shang
    • , Fu Jun
    •  & Qing Liu
  • Article |

    In this work, the authors propose a new framework based on deep-learning to comprehensively assess the microvascular condition of the glioma patients by automated analysis of the H&E stained whole slide images. They show that microvascularity has a tight relationship with the diagnosis of glioma and can be used as an important prognostic indicator.

    • Xieli Li
    • , Qisheng Tang
    • , Jinhua Yu
    • , Yuanyuan Wang
    •  & Zhifeng Shi
  • Article |

    The authors report a previously unappreciated miR-26a-mediated regulatory model in which miR-26a promotes invasion/metastasis by inhibiting the phosphatase PTEN and inhibits cell proliferation by repressing the methyltransferase EZH2 in hepatocellular carcinoma. Although therapeutic miR-26a delivery significantly suppresses tumorigenesis in mice, further studies are warranted before it is a relevant as a target for HCC therapy.

    • Wen-Tao Zhao
    • , Xiao-Lin Lin
    • , Yu Liu
    • , Liu-Xin Han
    • , Jing Li
    • , Tao-Yan Lin
    • , Jun-Wen Shi
    • , Sheng-Chun Wang
    • , Mei Lian
    • , Heng-Wei Chen
    • , Yan Sun
    • , Kang Xu
    • , Jun-Shuang Jia
    • , Rong-cheng Luo
    •  & Dong Xiao
  • Article |

    The biologic features of diffuse large B-cell lymphoma (DLBCL) with PD-L1 expression remains unknown. This study demonstrates that DLBCL with PD-L1 expression features an activated B-cell receptor signal pathway, and that inhibiting BCR and blocking PD-L1 expression may synergize to target DLBCL.

    • Wei-Ge Wang
    • , Xiang-Nan Jiang
    • , Dong Sheng
    • , Chen-Bo Sun
    • , Jimmy Lee
    • , Xiao-Yan Zhou
    •  & Xiao-Qiu Li
  • Article
    | Open Access

    This paper examines whether the nuclear E3 ubiquitin ligase MDM2 and/or the cyclin-dependent kinase CDK4 produce well-differentiated liposarcoma (WDLPS)/dedifferentiated liposarcoma (DDLPS) using transformed human bone marrow stem cells through in vitro and in vivo functional experiments. The authors found that co-overexpression of MDM2 and CDK4 causes high-grade sarcoma with a dedifferentiated liposarcoma-like morphology.

    • Yu Jin Kim
    • , Mingi Kim
    • , Hyung Kyu Park
    • , Dan Bi Yu
    • , Kyungsoo Jung
    • , Kyoung Song
    •  & Yoon-La Choi
  • Article |

    Trp53 null and R270H mutations had comparable effects on tumor phenotypes in a genetically engineered mouse model of colorectal cancer (CRC). The mouse tumors with Trp53 null or R270H mutations as well as human CRCs with null or codon R273 missense mutations had similar gene expression profiles. These findings raise questions about a general role for gain-of-function effects for mutant p53 proteins in CRC.

    • Jinyu Tang
    • , Ying Feng
    • , Rork Kuick
    • , Megan Green
    • , Maranne Green
    • , Naoya Sakamoto
    • , Yuki Kurosu
    • , Jeffry Lin
    • , Kathleen R. Cho
    •  & Eric R. Fearon
  • Article |

    The authors employed a monoclonal antibody, 297-11A, to determine preferential display of sialyl 6′-sulfo N-acetyllactosamine-capped O-glycans on high endothelial venules (HEVs) in human peripheral lymph nodes. These glycans were also displayed on HEV-like vessels in tumor-infiltrating lymphocyte aggregates in various cancers. Thus, 297-11A-positive sulfated glycans likely function in physiologic and pathologic lymphocyte trafficking.

    • Manami Tsutsumiuchi
    • , Hitomi Hoshino
    • , Akiya Kogami
    • , Toshiki Tsutsumiuchi
    • , Osamu Yokoyama
    • , Tomoya O. Akama
    •  & Motohiro Kobayashi
  • Article |

    RXRα phosphorylation-deficient mutant mice with the mutation Thr 167 to Ala exhibit altered regulation of metabolic pathway gene expression in white adipose tissue. This result, combined with data on muscle and liver gene expression, suggest that the RXRα Thr 167 phosphorylation signal coordinates these three organs for regulation of energy metabolism and maintenance of glucose homeostasis.

    • Tatsuya Sueyoshi
    • , Tsutomu Sakuma
    • , Sawako Shindo
    • , Muluneh Fashe
    • , Tomohiko Kanayama
    • , Manas Ray
    • , Rick Moore
    •  & Masahiko Negishi
  • Article |

    High-mobility group box 1 (HMGB1) is actively secreted from inflammatory cells and acts via a non-cell autonomous mechanism to mediating cell proliferation and migration. The authors sought to determine the role of HMGB1 in modulation of dopaminergic neurons. Their results suggest that an increase of HMGB1, released from astrocytes, upregulates TH expression in a Parkinsonian mouse model, thereby maintaining dopaminergic neuronal functions.

    • Soo Jeong Kim
    • , Min Jeong Ryu
    • , Jeongsu Han
    • , Yunseon Jang
    • , Min Joung Lee
    • , Xianshu Ju
    • , Ilhwan Ryu
    • , Yu Lim Lee
    • , Eungseok Oh
    • , Woosuk Chung
    • , Jun Young Heo
    •  & Gi Ryang Kweon
  • Article |

    In this paper, the authors show that miR-135b-5p has prognostic value for ductal carcinoma in situ with microinvasion (DCIS-Mi). The inhibition of miR-135b-5p promotes cell proliferation, epithelial–mesenchymal transition, migration and invasion by targeting (SDCBP). The MiR-135b-5p/SDCBP axis is a crucial determinant of breast cancer metastasis at a very early stage.

    • Tianjie Pu
    • , Mengjia Shen
    • , Shi Li
    • , Libo Yang
    • , Hongwei Gao
    • , Lin Xiao
    • , Xiaorong Zhong
    • , Hong Zheng
    • , Yueping Liu
    • , Feng Ye
    •  & Hong Bu
  • Article |

    Lack of expression of Tgf-β1 in the embryonic lung mesenchyme led to severe lung hypoplasia, increase of cell apoptosis and reduced lung branching morphogenesis. In the mutant lung, FGF10 signaling pathway was inhibited and the vascular system was underdeveloped. This genetic mouse model will be helpful to identify the key pathogenic mechanisms underlying lung hypoplasia in humans.

    • Niki Noe
    • , Ashley Shim
    • , Katelyn Millette
    • , Yongfeng Luo
    • , Mohamad Azhar
    • , Wei Shi
    • , David Warburton
    •  & Gianluca Turcatel
  • Article |

    Both toll-like receptors and nucleotide-binding oligomerization domain (NOD)-like receptors induce an inflammatory response at risk of causing tissue damage. However, the cross-regulation between interleukin-1 (IL-1) receptors and NOD2 is not completely understood. The authors show that IL-1α/β increase NOD2-induced inflammatory response by enhancing muramyl dipeptide-induced activation of MAPK signaling pathways via ERK, JNK, and P38.

    • Sushan Li
    • , Ping Deng
    • , Manzhi Wang
    • , Xueting Liu
    • , Manli Jiang
    • , Binyuan Jiang
    • , Li Yang
    •  & Jinyue Hu