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FUT8-mediated aberrant N-glycosylation of SEMA7A promotes head and neck squamous cell carcinoma progression

International Journal of Oral Science 2024年第2期16卷 333-348页

作者： Zhonglong Liu Xiaoyan Meng Yuxin Zhang Jingjing Sun Xiao Tang Zhiyuan Zhang Liu Liu Yue He Department of Oral Maxillofacial&Head and Neck Oncology Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral DiseaseShanghaiChina Department of Oral Surgery Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineCollege of StomatologyShanghai Jiao Tong UniversityNational Center for StomatologyNational Clinical Research Center for Oral DiseasesShanghaiChina Department of Oral Pathology Shanghai Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineNational Clinical Research Center for Oral Disease ShanghaiShanghaiChina

SEMA7A belongs to the Semaphorin family and is involved in the oncogenesis and tumor *** glycosylation has been intricately linked with immune escape and tumor ***7A is a highly glycosylated protein with five glycosylated *** underlying mechanisms of SEMA7A glycosylation and its contribution to immunosuppression and tumorigenesis are ***,we identify overexpression and aberrant N-glycosylation of SEMA7A in head and neck squamous cell carcinoma,and elucidate fucosyltransferase FUT8 catalyzes aberrant core fucosylation in SEMA7A at N-linked oligosaccharides(Asn 105,157,258,330,and 602)via a direct protein‒protein interaction.A glycosylated statue of SEMA7A is necessary for its intra-cellular trafficking from the cytoplasm to the *** EGF triggers SEMA7A N-glycosylation through increasing the binding affinity of SEMA7A toward FUT8,whereas TGF-β1 promotes abnormal glycosylation of SEMA7A via induction of epithelial–mesenchymal *** N-glycosylation of SEMA7A leads to the differentiation of CD8^(+)T cells along a trajectory toward an exhausted state,thus shaping an immunosuppressive microenvironment and being resistant immunogenic cell *** of SEMA7A significantly improves the clinical outcome of EGFR-targeted and anti-PD-L1-based ***,we also define RBM4,a splice regulator,as a downstream effector of glycosylated SEMA7A and a pivotal mediator of PD-L1 alternative *** findings suggest that targeting FUT8-SEMA7A axis might be a promising strategy for improving antitumor responses in head and neck squamous cell carcinoma patients.

关键词： aberrant squamous SEMA

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The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair

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Bone Research 2024年第2期12卷 289-301页

作者： Heeseog Kang Amy L.Strong Yuxiao Sun Lei Guo Conan Juan Alec C.Bancroft Ji Hae Choi Chase A.Pagani Aysel A.Fernandes Michael Woodard Juhoon Lee Sowmya Ramesh Aaron W.James David Hudson Kevin N.Dalby Lin Xu Robert J.Tower Benjamin Levi Center for Organogenesis Regeneration and TraumaDepartment of SurgeryUniversity of Texas SouthwesternDallasTX 75390USA Section of Plastic Surgery Department of SurgeryUniversity of MichiganAnn ArborMI 48109USA Quantitative Biomedical Research Center Peter O’Donnell Jr.School of Public HealthUniversity of Texas SouthwesternDallasTX 75390USA Department of Orthopedics and Sports Medicine University of WashingtonSeattleWA 98195USA Division of Chemical Biology and Medicinal Chemistry College of PharmacyUniversity of Texas at AustinAustinTX 78712USA Department of Pathology Johns Hopkins UniversityBaltimoreMD 21218USA

While hypoxic signaling has been shown to play a role in many cellular processes,its role in metabolism-linked extracellular matrix(ECM)organization and downstream processes of cell fate after musculoskeletal injury remains to be ***(HO)is a debilitating condition where abnormal bone formation occurs within extra-skeletal *** andhypoxia-inducible factor 1α(HIF-1α)activation have been shown to promote ***,the underlying molecular mechanisms bywhich the HIF-1αpathway in mesenchymal progenitor cells(MPCs)contributes to pathologic bone formation remain to ***,we used a proven mouse injury-induced HO model to investigate the role of HIF-1αon aberrant cell ***-cell RNA sequencing(scRNA-seq)and spatial transcriptomics analyses of the HO site,we found that collagen ECM organizationis the most highly up-regulated biological process in *** mesenchymal cell-specific deletion of Hif1α(Hoxa11-CreER^(T2);Hif1a^(fl/fl))significantly mitigated HO in ***-seq analysis of these Hoxa11-CreER^(T2);Hif1a^(fl/fl)mice identified the PLOD2/LOXpathway for collagen cross-linking as downstream of the HIF-1αregulation of ***,our scRNA-seq data and mechanisticstudies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α*** a translational aspect,a pan-LOX inhibitor significantly decreased HO.A newly screened compound revealed that the inhibition of PLOD2 activity in MPCssignificantly decreased osteogenic differentiation and glycolytic *** suggests that the HIF-1α/PLOD2/LOX axis linked tometabolism regulates HO-forming MPC *** results suggest that the HIF-1α/PLOD2/LOX pathway represents a promisingstrategy to mitigate HO formation.

关键词： metabolism skeletal aberrant

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Neuron-to-vessel signaling is a required feature of aberrant stem cell commitment after soft tissue trauma

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Bone Research 2022年第3期10卷 615-626页

作者： Qizhi Qin Mario Gomez-Salazar Masnsen Cherief Chase A.Pagani Seungyong Lee Charles Hwang Robert J.Tower Sharon Onggo Yuxiao Sun Abhinav Piplani Zhao Li Sowmya Ramesh Thomas L.Clemens Benjamin Levi Aaron W.James Department of Pathology Johns Hopkins UniversityBaltimoreMD 21205USA Center for Organogenesis and Trauma Department of SurgeryUniversity of TexasSouthwesternTXUSA Department of Plastic Surgery HarvardCambridgeMA 02138USA Department of Orthopaedics Johns Hopkins UniversityBaltimoreMD 21205USA Baltimore Veterans Administration Medical Center BaltimoreMD 21201USA

The functional interdependence of nerves and blood vessels is a well-established concept during tissue morphogenesis, yet the role of neurovascular coupling in proper and aberrant tissue repair is an emerging field of interest. Here, we sought to define the regulatory relationship of peripheral nerves on vasculature in a severe extremity trauma model in mice, which results in aberrant cell fate and heterotopic ossification(HO). First, a high spatial degree of neurovascular congruency was observed to exist within extremity injury associated heterotopic ossification. Vascular and perivascular cells demonstrate characteristic responses to injury,as assessed by single cell RNA sequencing. This vascular response to injury was blunted in neurectomized mice, including a decrease in endothelial proliferation and type H vessel formation, and a downregulation of key transcriptional networks associated with angiogenesis. Independent mechanisms to chemically or genetically inhibit axonal ingrowth led to similar deficits in HO site angiogenesis, a reduction in type H vessels, and heterotopic bone formation. Finally, a combination of single cell transcriptomic approaches within the dorsal root ganglia identified key neural-derived angiogenic paracrine factors that may mediate neuron-to-vascular signaling in HO. These data provide further understanding of nerve-to-vessel crosstalk in traumatized soft tissues, which may reflect a key determinant of mesenchymal progenitor cell fate after injury.

关键词： aberrant trauma nerves

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Inhibition of aberrant Hif1αactivation delays intervertebral disc degeneration in adult mice

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Bone Research 2022年第1期10卷 65-80页

作者： Zuqiang Wang Hangang Chen Qiaoyan Tan Junlan Huang Siru Zhou Fengtao Luo Dali Zhang Jing Yang Can Li Bo Chen Xianding Sun Liang Kuang Wanling Jiang Zhenhong Ni Quan Wang Shuai Chen Xiaolan Du Di Chen Chuxia Deng Liangjun Yin Lin Chen Yangli Xie Center of Bone Metabolism and Repair Department of Wound Repair and Rehabilitation MedicineState Key Laboratory of TraumaBurns and Combined InjuryTrauma CenterResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqingChina Senior Department of Orthopedics the Fourth Medical Center of PLA General HospitalBeijingChina Department of Orthopedic Surgery The Second Affiliated HospitalChongqing Medical UniversityChongqingChina Research Center for Human Tissues and Organs Degeneration Shenzhen Institutes of Advanced TechnologyChinese Academy of SciencesShenzhenChina Faculty of Health Sciences University of MacaoMacao SARChina

The intervertebral disc(IVD) is the largest avascular tissue. Hypoxia-inducible factors(HIFs) play essential roles in regulating cellular adaptation in the IVD under physiological conditions. Disc degeneration disease(DDD) is one of the leading causes of disability, and current therapies are ineffective. This study sought to explore the role of HIFs in DDD pathogenesis in mice. The findings of this study showed that among HIF family members, Hif1α was significantly upregulated in cartilaginous endplate(EP) and annulus fibrosus(AF) tissues from human DDD patients and two mouse models of DDD compared with controls. Conditional deletion of the E3 ubiquitin ligase Vhl in EP and AF tissues of adult mice resulted in upregulated Hif1α expression and age-dependent IVD degeneration. aberrant Hif1α activation enhanced glycolytic metabolism and suppressed mitochondrial function. On the other hand, genetic ablation of the Hif1α gene delayed DDD pathogenesis in Vhl-deficient mice. Administration of 2-methoxyestradiol(2ME2), a selective Hif1α inhibitor, attenuated experimental IVD degeneration in mice. The findings of this study show that aberrant Hif1α activation in EP and AF tissues induces pathological changes in DDD, implying that inhibition of aberrant Hif1α activity is a potential therapeutic strategy for DDD.

关键词： Hif1α degeneration aberrant

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Identification of two aberrant transcripts derived from a hybridoma with amplification of functional immunoglobulin variable genes

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Cellular & Molecular Immunology 2010年第5期7卷 349-354页

作者： Guipeng Ding Ximin Chen Jin Zhu Brian Cao Department of Pathology Nanjing Medical UniversityNanjingChina Huadong Medical Institute of Biotechniques NanjingChina Laboratory of Antibody Technology Van Andel Research InstituteGrand RapidsMIUSA

Murine monoclonal antibodies(mAbs)are widely used but have limitations if administered in *** use of chimeric or humanized mAbs can reduce *** first step in producing such mAbs is to clone murine variable genes from a hybridoma,but it is possible to amplify both functional and aberrant variable genes,as they coexist in the *** the development of a murine–human chimeric antibody,we have cloned from a hybridoma the functional heavy chain variable region(VH)and light chain variable region(VL)genes of a mAb that blocks the binding of anthrax lethal factor to protective *** this study,we report the detection of two aberrant transcripts from a hybridoma produced using myeloma cell line OUR-1,the development of a method to distinguish between the functional and abundant aberrant VL transcripts,and the origins of these aberrant *** aberrant VL gene is derived from OUR-1 cells,while the aberrant VH gene might derive from antibody repertoires in B cells or from gene rearrangement in the hybridoma *** aberrant VH and VL genes in this study may facilitate discrimination between the functional and aberrant variable genes from hybridoma cells.

关键词： aberrant gene rearrangement non-functional immunoglobulin OUR-1 variable gen

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Bilateral common carotid artery common trunk with aberrant right subclavian artery combined with right subclavian steal syndrome: A case report

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World Journal of Clinical Cases 2019年第21期7卷 3639-3648页

作者： Yuan-Yuan Sun Guo-Ming Zhang You-Bin Zhang Xin Du Mao-Long Su Department of Ultrasound Xiamen Cardiovascular Hospital Xiamen UniversityXiamen 361000Fujian ProvinceChina Department of Cardiology Xiamen Cardiovascular Hospital Xiamen UniversityXiamen 361000Fujian ProvinceChina Department of Radiology Zhongshan Hospital Xiamen UniversityXiamen 361000Fujian ProvinceChina

BACKGROUND We report a rare case of numbness in the right hand,finally diagnosed as bilateral common carotid artery common trunk with aberrant right subclavian artery combined with right subclavian steal syndrome and explain the cause of these *** SUMMARY The patient was a 65-year-old *** complained of dizziness,numbness and weakness of the right hand for 6 *** was diagnosed with bilateral common carotid artery common trunk with aberrant right subclavian artery combined with right subclavian steal syndrome by ultrasound,enhanced computed tomography,computed tomography angiography and other *** the surgical risks,the patient refused the aberrant right subclavian artery stent implantation and was *** hypothesize that these two kinds of deformity and right subclavian steal syndrome may not occur by accident and result from multiple *** Bilateral common carotid artery common trunk with aberrant right subclavian artery combined with right subclavian steal syndrome is *** case reminds interventional radiologists of the possibility of these abnormalities before surgery.

关键词： Bilateral common carotid artery common trunk aberrant right subclavianartery Right subclavian steal syndrome Case report

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Correction of RNA aberrant splice increases foreign gene expression in transgenic mice

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Chinese Science Bulletin 1999年第3期44卷 221-225页

作者： Yifan Lu Chai Tian Jixian Deng Peitang Huang Acad Mil Med Sci Inst Biotechnique Beijing 100071 Peoples R China Chinese Acad Med Sci Cardiovasc Inst Beijing 100037 Peoples R China Chinese Acad Med Sci Fuwai Hosp Beijing 100037 Peoples R China

Transgenic mice with mammary gland secreting human granulocyte colony stimulating factor (G-CSF) were produced using mice whey acid protein gene promoter. It was found that there was very low expression level in mammary gland. Human G-CSF cDNA was obtained by RT-PCR from transgenic mice mammary gland. Sequence analysis showed that this G-CSF gene deleted the 4th exon, and compared with human G-CSF genomic DNA, there were donor and acceptor splice sites in the deletion fragment. It was considered that the 3rd and 4th introns also delete in G-CSF fragment. The transgenic construct was corrected by deleting the 3rd and 4th introns to construct the minigene, which was used to produce transgenic mice by microinjection. Northern blot showed that G-CSF expression using the new construct increased 5.4 times as that before in transgenic mice. The results suggested that it was possible that RNA aberrant splice result in low expression in transgenic mice.

关键词： transgenic RNA aberrant splice expression.

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Total endovascular repair of aberrant right subclavian artery using caster branched stent-graft

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Journal of Geriatric Cardiology 2018年第12期15卷 751-754页

作者： Guo-Yi SUN Wei GUO Xiao-Ping LIU Xin JIA Jiang XIONG Hong-Peng ZHANG Xiao-Hui MA Feng CHEN Sen-Hao JIA Jie LIU Yang-Yang GE Department of Vascular and Endovascular Surgery Chinese PLA General HospitalBeijingChina Department of ICU PLA Rocket Force Characteristic Medical CenterBeijingChina

A 57-year-old man has 20-year history of hypertension presented with intermittent chronic pain in the chest area and shoulder blades over the last three *** tomographic angiography(CTA)on admission revealed a chronic type B aortic dissection(TBAD)with an aberrant right subclavian artery(ARSA)crossed behind the trachea and bovine aortic arch(Figure IB).

关键词： aberrant right subclavian artery Aortic dissection Branch stent-graft Thoracic endovascular aortic repair

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SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics to induce robust virus propagation

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2702-2715页

作者： Hye Jin Shin Wooseong Lee Keun Bon Ku Gun Young Yoon Hyun-Woo Moon Chonsaeng Kim Mi-Hwa Kim Yoon-Sun Yi Sangmi Jun Bum-Tae Kim Jong-Won Oh Aleem Siddiqui Seong-Jun Kim Department of Convergent Research of Emerging Virus Infection Korea Research Institute of Chemical TechnologyDaejeon 34114Republic of Korea Gyeongnam Biohealth Research Center Gyeongnam Branch InstituteKorea Institute of ToxicologyJinju 52834Republic of Korea Center for Research Equipment Korea Basic Science InstituteCheongjuChungcheongbuk-do 28119Republic of Korea Department of Biotechnology Yonsei UniversitySeoul 03722Republic of Korea Division of Infectious Diseases School of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA Present address:Department of Microbiology Chungnam National University School of MedicineDaejeon 35015Republic of Korea

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a‘highly transmissible respiratory pathogen,leading to severe multiorgan ***,knowledge regarding SARS-CoV-2-induced cellular alterations is *** this study,we report that SARSCoV-2 aberrantly elevates mitochondrial bioenergetics and activates the EGFR-mediated cell survival signal cascade during the early stage of viral ***-CoV-2 causes an increase in mitochondrial transmembrane potential via the SARS-CoV-2 RNAnucleocapsid cluster,thereby abnormally promoting mitochondrial elongation and the OXPHOS process,followed by enhancing ATP ***,SARS-CoV-2 activates the EGFR signal cascade and subsequently induces mitochondrial EGFR trafficking,contributing to abnormal OXPHOS process and viral *** EGFR inhibitors remarkably reduce SARS-CoV-2 propagation,among which vandetanib exhibits the highest antiviral *** of SARS-CoV-2-infected cells with vandetanib decreases SARS-CoV-2-induced EGFR trafficking to the mitochondria and restores SARS-CoV-2-induced aberrant elevation in OXPHOS process and ATP generation,thereby resulting in the reduction of SARS-CoV-2 ***,oral administration of vandetanib to SARS-CoV-2-infected hACE2 transgenic mice reduces SARS-CoV-2 propagation in lung tissue and mitigates SARS-CoV-2-induced lung *** also exhibits potent antiviral activity against various SARS-CoV-2 variants of concern,including alpha,beta,delta and omicron,in in vitro cell culture *** together,our findings provide novel insight into SARS-CoV-2-induced alterations in mitochondrial dynamics and EGFR trafficking during the early stage of viral infection and their roles in robust SARS-CoV-2 propagation,suggesting that EGFR is an attractive host target for combating COVID-19.

关键词： alterations aberrant thereby

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aberrant Adrenocortical Tissue Associated with Resected Lipoma of Spermatic Cord in an Adult

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Open Journal of Urology 2014年第12期4卷 151-154页

作者： Motoi Takeuchi Koichi Okuya Ryu-Ichi Kato Noriomi Miyao Yasuhiro Konishi Department of Urology Muroran City General Hospital Muroran Japan Department of Gastroenterological Surgery Muroran City General Hospital Muroran Japan Department of Pathology Muroran City General Hospital Muroran Japan

aberrant adrenocortical tissue in spermatic cord is rare in adult population. We report an unusual case of a 52-year-old male patient with an aberrant adrenocortical tissue which is incidentally resected within lipoma of spermatic cord and identified on microscopic examination. Although he was diagnosed with right inguinal hernia, there was no significant hernia orifice intraoperatively. When the 2nd operation by anterior open approach was undergone, there was a fat-like tissue adhered to the spermatic cord. It was removed and the histopathological finding first revealed aberrant adrenocortical tissue in the resected lipoma of spermatic cord (Figure 1). This abnormal tissue is usually found incidentally during inguinal operation. In general, most of the aberrant adrenal tissue becomes atrophic by adult life. Moreover, it is not clinically significant and also not associated with endocrine abnormalities.

关键词： aberrant Adrenocortical Tissue Inguinal Hernia Spermatic Cord Lipoma Adult

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