👤 Kejian Lin

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Also published as: Ai-Hsuan Lin, Aifu Lin, Ailong Lin, Aiping Lin, Aizhen Lin, Alexander Lin, Alexander P Lin, Ann Lin, Bei Lin, Bencheng Lin, Bi-Yun Lin, Biaoyang Lin, Bichun Lin, Bihua Lin, Bin Lin, Binbin Lin, Bing-Biao Lin, Bing-Jin Lin, Bing-Xue Lin, Bing-Yao Lin, Bingbing Lin, Bingqi Lin, Bo Lin, Bo-Wen Lin, Bode Lin, Bonnie Lin, Boxu Lin, Brian Leei Lin, Brian Lin, Bridget M Lin, C H Lin, C T Lin, C Y Lin, Cai-Xia Lin, Caiyu Lin, Chang Lin, Chang-Ching A Lin, Changchun Lin, Changpo Lin, Chao Lin, Chao-Chieh Lin, Chao-Feng Lin, Chao-Hsiung Lin, Chaohui Lin, Charles P Lin, Chen Lin, Chen-Yong Lin, Cheng Lin, Cheng-Chieh Lin, Cheng-Li Lin, Cheng-Yen Lin, Chengping Lin, Chengqi Lin, Chengyuan Lin, Chenquan Lin, Chi-Hung Lin, Chi-Shiuan Lin, Chi-Ying Lin, Chia-Chin Lin, Chia-Hao Lin, Chia-Ho Lin, Chia-Hsin Lin, Chia-Hung Lin, Chia-Liang Lin, Chia-Yu Lin, Chiao-Huang Lin, Chiao-Mei Lin, Chien-Ju Lin, Chien-Wei Lin, Chien-Yu Lin, Chih-Chun Lin, Chih-Hsun Lin, Chih-Ming Lin, Chih-Pei Lin, Chih-Yu Lin, Chii-Mei Lin, Chin-Hsien Lin, Chin-Sheng Lin, Chin-Yu Lin, Ching-Hung Lin, Ching-Yih Lin, Ching-Yu Lin, Chingju Lin, Cho-Hao Lin, Chuan Lin, Chuan-Chao Lin, Chun Lin, Chun-Lin Lin, Chun-Mao Lin, Chung-Hsien Lin, Chung-Ming Lin, Chunhua Lin, Chunming Lin, Chyuan-Sheng Lin, Cindy Lin, Cong Lin, Cuei-Jyuan Lin, Cui-Jun Lin, Cuilan Lin, Dafeng Lin, Daiqiong Lin, Dan Lin, Dan-Yu Lin, Daniel W Lin, Danyu Lin, Dao-Chao Lin, De-Chen Lin, Ding Lin, Dong Lin, Dong-Tsamn Lin, Dongmei Lin, Dongru Lin, Dongxin Lin, Dongzi Lin, Douglas I Lin, Eugene Lin, F Lin, Fan Lin, Fan-Li Lin, Fang Lin, Fangrui Lin, Fangyu Lin, Fangzhao Lin, Fei Lin, Fen Lin, Feng Lin, Feng-Chang Lin, Feng-Ming Lin, Feng-Yen Lin, Foxiang Lin, Fu Sheng Lin, Fujun Lin, Gang Lin, Ge Lin, Grace Lin, Guan-Bo Lin, Guang-Yao Lin, Guangzheng Lin, Gufa Lin, Guihu Lin, Guimei Lin, Guo-Wang Lin, Guofu Lin, Guoqiang Lin, Guowen Lin, H G Lin, H R Lin, Hai Lin, Haibiao Lin, Haimiao Lin, Haipeng Lin, Haitong Lin, Haiyan Lin, Han Lin, Han-Huei Lin, Hang Lin, Hang-Yan Lin, Hanyu Lin, Hao Lin, Hao-Yu Lin, Haochang Lin, Haocheng Lin, Haodong Lin, Haoyi Lin, Haoyu Lin, He Lin, Heng Lin, Heng-Huei Lin, Henghui Lin, Hening Lin, Hong Lin, Hongcheng Lin, Hongchun Lin, Honghuang Lin, Hongkun Lin, Hongsheng Lin, Hongyan Lin, Hsiao-Yun Lin, Hsien-Chih Lin, Hsin-Ti Lin, Hsing-Pei Lin, Hsiu-Chu Lin, Hua Lin, Huanhuan Lin, Hui Lin, Hui-Hsuan Lin, Hui-Ju Lin, Hui-Kuan Lin, Hui-Ping Lin, Hui-Ru Lin, Hui-Yan Lin, Hui-Yi Lin, Huijuan Lin, Huilan Lin, Huimei Lin, Huisheng Lin, Hung-Chih Lin, Hung-Ju Lin, Hung-Jung Lin, I-Ching Lin, I-Jung Lin, I-Ling Lin, Jake Lin, James A Lin, Jamie S Lin, Jane-Ming Lin, Jeng-Feng Lin, Jia Lin, Jia-Bin Lin, Jia-Feng Lin, Jia-Li Lin, Jia-Qi Lin, Jiabin Lin, Jiacheng Lin, Jiaheng Lin, Jiahui Lin, Jiajing Lin, Jiali Lin, Jiamao Lin, Jiamei Lin, Jian-Yu Lin, JianMin Lin, Jiandie D Lin, Jiandie Lin, Jianfei Lin, Jiang Lin, Jianhao Lin, Jianhua Lin, Jianhui Lin, Jianjian Lin, Jiantao Lin, Jianwei Lin, Jianyin Lin, Jiaqi Lin, Jiaqian Lin, Jiaquan Lin, Jiarui Lin, Jiatong Lin, Jiayang Lin, Jiayi Lin, Jiayuh Lin, Jie Lin, Jie Ming Lin, Jieye Lin, Jieying Lin, Jijin Lin, Jim Jr-Min Lin, Jin Lin, Jin'e Lin, Jin-Ru Lin, Jinchuan Lin, Jing Lin, Jing-Ping Lin, Jing-Ying Lin, Jing-Yu Lin, Jinghan Lin, Jingmei Lin, Jingyu Lin, Jingyuan Lin, Jinlong Lin, Jinxiu Lin, Jinzhong Lin, Jiu Lin, Jiuann-Huey Ivy Lin, Jiunn-Lee Lin, Jiyan Lin, Jo-Yu Lin, Joanne Lin, Johnson Lin, Jue Lin, Juin-Han Lin, Jun-Ming Lin, Junjian Lin, Junnan Lin, Junyi Lin, Kai Lin, Kai-Hsin Lin, Kai-Min Lin, Kai-Yan Lin, Kai-Yen Lin, Kang Lin, Kashuai Lin, Katia Lin, Ke Lin, Ke-Shin Lin, Keng-Hung Lin, Kim Y Lin, Kimberly Y Lin, Kongying Lin, Kuan-Hung Lin, Kuang Lin, L Lin, L Y Lin, Lanyan Lin, Le-Hang Lin, Lei Lin, Leilei Lin, Lezhen Lin, Li An Lin, Li Lin, Li-An Lin, Li-Ching Lin, Li-E Lin, Li-Fen Lin, Li-Ling Lin, Li-Rong Lin, Li-Song Lin, Lian-Yu Lin, Liang-Chun Lin, Liang-Tzung Lin, Lihao Lin, Lijin Lin, Liling Lin, Limei Lin, Lin Lin, Ling Lin, Ling-Li Lin, Liping Lin, Lisong Lin, Liwen Lin, Lizhong Lin, Lizhu Lin, Long Lin, Long-Yau Lin, Lu Lin, Luping Lin, M Lin, Manjie Lin, Mao-Shin Lin, Mao-Tsun Lin, Mary Grace Lin, Mei-Chi Lin, Meifang Lin, Meizhen Lin, Meng-Fei Lin, Meng-Wei Lin, Mengsha Lin, Mengxin Lin, Mengyao Lin, Miao Lin, Miao-Chong Joy Lin, Min Lin, Min-Huan Lin, Min-Jie Lin, Min-Rou Lin, Ming-Der Lin, Ming-Hong Lin, Ming-Huei Lin, Ming-Tai Lin, Ming-Wei Lin, Mingkuan Lin, Mingmei Lin, Mingqun Lin, Mingrui Lin, Mingxing Lin, Mingying Lin, Monica Lin, Nan Lin, Nancy U Lin, Nianwei Lin, Ning Lin, Ning-Ning Lin, Ningning Lin, Pei Lin, Pei-Chin Lin, Pei-Lin Lin, Pei-Yi Lin, Peijia Lin, Peng Lin, Peng-Chan Lin, Pengfei Lin, Penghui Lin, Ping Lin, Pingping Lin, Po-Han Lin, Qi Lin, Qian Lin, Qianmeng Lin, Qiannan Lin, Qiao Lin, Qiao-Hong Lin, Qiaoxuan Lin, Qichang Lin, Qin Lin, Qing Lin, Qinghua Lin, Qingling Lin, Qingqing Lin, Qingxiang Lin, Qinlu Lin, Qiong Lin, Qiongfen Lin, Qitai Lin, Qiuling Lin, Qu Lin, Quan-Zhen Lin, R-I Lin, Raozhou Lin, Renjing Lin, Richard Z Lin, Rong Lin, Ronghai Lin, Rongjie Lin, Ru Lin, Rui Lin, Ruifan Lin, Ruilang Lin, Ruiyi Lin, Rutao Lin, S C Lin, S K Lin, S L Lin, S Lin, S Y Lin, S-J Lin, Sen Lin, Sen-Qing Lin, Sha Lin, Shan Lin, Shanyi Lin, Shanyun Lin, Shaowei Lin, Sharon Lin, Sheldon S Lin, Sheng Lin, Sheng-Cai Lin, Sheng-Che Lin, Sheng-Jia Lin, Sheng-Wei Lin, Sheng-Xiang Lin, Shengjie Lin, Shi Lin, Shiaw-Yih Lin, Shibo Lin, Shih-Cherng Lin, Shih-Chieh Lin, Shih-Fan Lin, Shih-Wei Lin, Shih-Yi Lin, Shihui Lin, Shijie Lin, Shin-Yu Lin, Shing-Jong Lin, Shinian Lin, Shinn-Zong Lin, Shinne-Ren Lin, Shiow J Lin, Shiow Lin, Shiping Lin, Shiru Lin, Shiya Lin, Shiyu Lin, Shu Lin, Shu-Chun Lin, Shu-Hui Lin, Shu-Rung Lin, Shu-Wha Lin, Shuai Lin, Shuaijun Lin, Shuan-Pei Lin, Shuhai Lin, Shujuan Lin, Shun-Guo Lin, Shuo Lin, Shuqian Lin, Shyr-Yi Lin, Si-Xian Lin, Simin Lin, Simon Lin, Siong-Chi Lin, Sisi Lin, Siying Lin, Song-Shu Lin, Songyi Lin, Sophia Lin, Spencer Lin, Su-Fang Lin, Sue-Jane Lin, Sufen Lin, Suyang Lin, Suzhen Lin, Ta-Hsien Lin, Tai-Chi Lin, Tao Lin, Tianfeng Lin, Tianxin Lin, Tien-Huang Lin, Tim Lin, Ting Lin, Ting-Hsu Lin, Ting-ting Lin, Tingsheng Lin, Tingting Lin, Tse-I Lin, Tsu-Kung Lin, Tsung-Hsien Lin, Tsung-Shih Lin, Tung-Yi Lin, Tzu-Chien Lin, Vicky Lin, Wan-Wan Lin, Wan-Yu Lin, Wan-Yun Lin, Wanhui Lin, Wanjun Lin, Wei Lin, Wei-De Lin, Wei-Ling Lin, Wei-Ting Lin, Wei-Tso Lin, Wei-Wen Lin, Wei-Xiong Lin, Wei-Yin Lin, Wei-Yu Lin, WeiHao Lin, Weichun Lin, Weiji Lin, Weilong Lin, Weimin Lin, Weiqiang Lin, Wen-Jun Lin, Wen-Jye Lin, Wenjian Lin, Wenming Lin, Wenxin Lin, X J Lin, X Lin, Xi Lin, Xian-Bin Lin, Xian-Zi Lin, Xianchai Lin, Xiandong Lin, Xiang-Quan Lin, Xiangquan Lin, Xiangwu Lin, Xiangyang Lin, Xianke Lin, Xianmei Lin, Xianzhi Lin, Xianzi Lin, Xiao Lin, Xiao-Chun Lin, Xiao-long Lin, Xiaodi Lin, Xiaohan Lin, Xiaohong Lin, Xiaohui Lin, Xiaojing Lin, Xiaoling Lin, Xiaolong Lin, Xiaomin Lin, Xiaoqing Lin, Xiaowei Lin, Xiaoyan Lin, Xiaoyang Lin, Xiaoyi Lin, Xiaoyu Lin, Xiaozeng Lin, Xihong Lin, Xin Lin, Xin-Mei Lin, Xin-Xiu Lin, Xinchun Lin, Xinda Lin, Xing Lin, Xingguang Lin, Xinhua Lin, Xinrong Lin, Xinshi Lin, Xinxin Lin, Xinyao Lin, Xiu-Ru Lin, Xixiao Lin, Xu Lin, Xue Lin, Xue-Jing Lin, Xuefei Lin, Xuehua Lin, Xuejing Lin, Xuelian Lin, Xuemei Lin, Xuewan Lin, Xuyao Lin, Xuyong Lin, Y C Lin, Y Lin, Y M Lin, Ya-Hui Lin, Ya-Lin Lin, Ya-Qiu Lin, Ya-Tin Lin, Yan Lin, Yan-Ling Lin, Yancheng Lin, Yang Lin, Yang-Hsiang Lin, Yani Lin, Yanjun Lin, Yanke Lin, Yanni Lin, Yanqin Lin, Yanxia Lin, Yanzhu Lin, Yao Lin, Yao-Ping Lin, Yaohui Lin, Yaqiu Lin, Ye Lin, Yen-Chun Lin, Yen-Feng Lin, Yen-Hong Lin, Yen-Kuang Lin, Yen-Lin Lin, Yen-Shu Lin, Yen-Yi Lin, Yi Lin, Yi-An Lin, Yi-Chen Lin, Yi-Haou Lin, Yi-Hsiung Lin, Yi-Hsuan Lin, Yi-Hui Lin, Yi-Jang Lin, Yi-Ling Lin, Yi-Nan Lin, Yi-Tzu Lin, Yi-Wen Lin, Yichuan Lin, Yifei Lin, Yifeng Lin, Yihui Lin, Yilong Lin, Yina Lin, Ying Lin, 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articles

Proteomic biomarkers of Kleine-Levin syndrome.

Julien Hédou, Katie L Cederberg, Aditya Ambati +13 more · 2022 · Sleep · Oxford University Press · added 2026-04-24
Kleine-Levin syndrome (KLS) is characterized by relapsing-remitting episodes of hypersomnia, cognitive impairment, and behavioral disturbances. We quantified cerebrospinal fluid (CSF) and serum protei Show more
Kleine-Levin syndrome (KLS) is characterized by relapsing-remitting episodes of hypersomnia, cognitive impairment, and behavioral disturbances. We quantified cerebrospinal fluid (CSF) and serum proteins in KLS cases and controls. SomaScan was used to profile 1133 CSF proteins in 30 KLS cases and 134 controls, while 1109 serum proteins were profiled in serum from 26 cases and 65 controls. CSF and serum proteins were both measured in seven cases. Univariate and multivariate analyses were used to find differentially expressed proteins (DEPs). Pathway and tissue enrichment analyses (TEAs) were performed on DEPs. Univariate analyses found 28 and 141 proteins differentially expressed in CSF and serum, respectively (false discovery rate <0.1%). Upregulated CSF proteins included IL-34, IL-27, TGF-b, IGF-1, and osteonectin, while DKK4 and vWF were downregulated. Pathway analyses revealed microglial alterations and disrupted blood-brain barrier permeability. Serum profiles show upregulation of Src-family kinases (SFKs), proteins implicated in cellular growth, motility, and activation. TEA analysis of up- and downregulated proteins revealed changes in brain proteins (p < 6 × 10-5), notably from the pons, medulla, and midbrain. A multivariate machine-learning classifier performed robustly, achieving a receiver operating curve area under the curve of 0.90 (95% confidence interval [CI] = 0.78-1.0, p = 0.0006) in CSF and 1.0 (95% CI = 1.0-1.0, p = 0.0002) in serum in validation cohorts, with some commonality across tissues, as the model trained on serum sample also discriminated CSF samples of controls versus KLS cases. Our study identifies proteomic KLS biomarkers with diagnostic potential and provides insight into biological mechanisms that will guide future research in KLS. Show less
no PDF DOI: 10.1093/sleep/zsac097
IL27

IL-27 Induces CCL5 Production by T Lymphocytes, Which Contributes to Antitumor Activity.

Aiyan Hu, Jianmin Zhu, Chunxi Zeng +10 more · 2022 · Journal of immunology (Baltimore, Md. : 1950) · added 2026-04-24
IL-27 is a pleiotropic cytokine that exhibits stimulatory/regulatory functions on multiple lineages of immune cells including T lymphocytes. In this study, we demonstrate that IL-27 directly induces C Show more
IL-27 is a pleiotropic cytokine that exhibits stimulatory/regulatory functions on multiple lineages of immune cells including T lymphocytes. In this study, we demonstrate that IL-27 directly induces CCL5 production by T lymphocytes, particularly CD8 Show less
📄 PDF DOI: 10.4049/jimmunol.2100885
IL27

MiR-138-5p Targets MACF1 to Aggravate Aging-related Bone Loss.

Zhihao Chen, Ying Huai, Gaoyang Chen +18 more · 2022 · International journal of biological sciences · added 2026-04-24
Senile osteoporosis is one of the major health problems in an aging society. Decreased bone formation due to osteoblast dysfunction may be one of the causes of aging-related bone loss. With increasing Show more
Senile osteoporosis is one of the major health problems in an aging society. Decreased bone formation due to osteoblast dysfunction may be one of the causes of aging-related bone loss. With increasing evidence suggesting that multiple microRNAs (miRNAs) play important roles in osteoblast function, the relationship between miRNAs and senile osteoporosis has become a popular research topic. Previously, we confirmed that mechanoresponsive miR-138-5p negatively regulated bone anabolic action. In this study, the miR-138-5p level was found to be negatively correlated with BMD and osteogenic markers in bone specimens of senile osteoporotic patients by bioinformatic analysis and experimental verification. Furthermore, high miR-138-5p levels aggravated the decrease of aged osteoblast differentiation Show less
📄 PDF DOI: 10.7150/ijbs.71411
MACF1

Genetic Factors Associated with Prostate Cancer Conversion from Active Surveillance to Treatment.

Yu Jiang, Travis J Meyers, Adaeze A Emeka +94 more · 2022 · HGG advances · Elsevier · added 2026-04-24
Yu Jiang, Travis J Meyers, Adaeze A Emeka, Lauren Folgosa Cooley, Phillip R Cooper, Nicola Lancki, Irene Helenowski, Linda Kachuri, Daniel W Lin, Janet L Stanford, Lisa F Newcomb, Suzanne Kolb, Antonio Finelli, Neil E Fleshner, Maria Komisarenko, James A Eastham, Behfar Ehdaie, Nicole Benfante, Christopher J Logothetis, Justin R Gregg, Cherie A Perez, Sergio Garza, Jeri Kim, Leonard S Marks, Merdie Delfin, Danielle Barsa, Danny Vesprini, Laurence H Klotz, Andrew Loblaw, Alexandre Mamedov, S Larry Goldenberg, Celestia S Higano, Maria Spillane, Eugenia Wu, H Ballentine Carter, Christian P Pavlovich, Mufaddal Mamawala, Tricia Landis, Peter R Carroll, June M Chan, Matthew R Cooperberg, Janet E Cowan, Todd M Morgan, Javed Siddiqui, Rabia Martin, Eric A Klein, Karen Brittain, Paige Gotwald, Daniel A Barocas, Jeremiah R Dallmer, Jennifer B Gordetsky, Pam Steele, Shilajit D Kundu, Jazmine Stockdale, Monique J Roobol, Lionne D F Venderbos, Martin G Sanda, Rebecca Arnold, Dattatraya Patil, Christopher P Evans, Marc A Dall'Era, Anjali Vij, Anthony J Costello, Ken Chow, Niall M Corcoran, Soroush Rais-Bahrami, Courtney Phares, Douglas S Scherr, Thomas Flynn, R Jeffrey Karnes, Michael Koch, Courtney Rose Dhondt, Joel B Nelson, Dawn McBride, Michael S Cookson, Kelly L Stratton, Stephen Farriester, Erin Hemken, Walter M Stadler, Tuula Pera, Deimante Banionyte, Fernando J Bianco, Isabel H Lopez, Stacy Loeb, Samir S Taneja, Nataliya Byrne, Christopher L Amling, Ann Martinez, Luc Boileau, Franklin D Gaylis, Jacqueline Petkewicz, Nicholas Kirwen, Brian T Helfand, Jianfeng Xu, Denise M Scholtens, William J Catalona, John S Witte Show less
Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for prosta Show more
Men diagnosed with low-risk prostate cancer (PC) are increasingly electing active surveillance (AS) as their initial management strategy. While this may reduce the side effects of treatment for prostate cancer, many men on AS eventually convert to active treatment. PC is one of the most heritable cancers, and genetic factors that predispose to aggressive tumors may help distinguish men who are more likely to discontinue AS. To investigate this, we undertook a multi-institutional genome-wide association study (GWAS) of 5,222 PC patients and 1,139 other patients from replication cohorts, all of whom initially elected AS and were followed over time for the potential outcome of conversion from AS to active treatment. In the GWAS we detected 18 variants associated with conversion, 15 of which were not previously associated with PC risk. With a transcriptome-wide association study (TWAS), we found two genes associated with conversion ( Show less
📄 PDF DOI: 10.1016/j.xhgg.2021.100070
MAST3

MYBPC3 deficiency in cardiac fibroblasts drives their activation and contributes to fibrosis.

Xiaodong Zou, Hongsheng Ouyang, Feng Lin +5 more · 2022 · Cell death & disease · Nature · added 2026-04-24
Genetic mutations in the MYBPC3 gene encoding cardiac myosin binding protein C (cMyBP-C) are the most common cause of hypertrophic cardiomyopathy (HCM). Myocardial fibrosis (MF) plays a critical role Show more
Genetic mutations in the MYBPC3 gene encoding cardiac myosin binding protein C (cMyBP-C) are the most common cause of hypertrophic cardiomyopathy (HCM). Myocardial fibrosis (MF) plays a critical role in the development of HCM. However, the mechanism for mutant MYBPC3-induced MF is not well defined. In this study, we developed a R495Q mutant pig model using cytosine base editing and observed an early-onset MF in these mutant pigs shortly after birth. Unexpectedly, we found that the "cardiac-specific" MYBPC3 gene was actually expressed in cardiac fibroblasts from different species as well as NIH3T3 fibroblasts at the transcription and protein levels. CRISPR-mediated disruption of Mybpc3 in NIH3T3 fibroblasts activated nuclear factor κB (NF-κB) signaling pathway, which increased the expression of transforming growth factor beta (TGF-β1) and other pro-inflammatory genes. The upregulation of TGF-β1 promoted the expression of hypoxia-inducible factor-1 subunit α (HIF-1α) and its downstream targets involved in glycolysis such as GLUT1, PFK, and LDHA. Consequently, the enhanced aerobic glycolysis with higher rate of ATP biosynthesis accelerated the activation of cardiac fibroblasts, contributing to the development of HCM. This work reveals an intrinsic role of MYBPC3 in maintaining cardiac fibroblast homeostasis and disruption of MYBPC3 in these cells contributes to the disease pathogenesis of HCM. Show less
📄 PDF DOI: 10.1038/s41419-022-05403-6
MYBPC3

MicroRNA expression profiles in familial hypertrophic cardiomyopathy with myosin-binding protein C3 (MYBPC3) gene mutations.

Li-Rong Lin, Xue-Qun Hu, Li-Hong Lu +5 more · 2022 · BMC cardiovascular disorders · BioMed Central · added 2026-04-24
Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant inherited disease caused by mutations in genes encoding cardiac sarcomere proteins. MicroRNAs (miRNAs) play an important role in th Show more
Familial hypertrophic cardiomyopathy (FHCM) is an autosomal dominant inherited disease caused by mutations in genes encoding cardiac sarcomere proteins. MicroRNAs (miRNAs) play an important role in the pathogenesis of FHCM. In the present study, we aimed to determine the miRNA profile in FHCM patients with myosin-binding protein C3 (MYBPC3) gene mutations. We recruited three FHCM patients and age- and sex-matched controls. The three probands all had hypertrophic obstructive cardiomyopathy with severe myocardial hypertrophy, and two of the three had a history of sudden cardiac death, representing a "malignant" phenotype. We then compared the miRNA expression profiles of three FHCM patients carrying MYBPC3 gene mutations with those of the normal control group using miRNA sequencing technology. Differentially expressed miRNAs were verified using real-time polymerase chain reaction (qPCR). Target genes and signaling pathways of the identified differentially expressed miRNAs were predicted using bioinformatics analysis. A total of 33 significantly differentially expressed miRNAs were detected in the peripheral blood of the three probands, of which 28 were upregulated, including miR-208b-3p, and 5 were downregulated. Real-time PCR confirmed the upregulated expression of miR-208b-3p in FHCM patients (P < 0.05). Bioinformatics analysis showed that miR-208b-3p was mainly enriched in 79 target genes including UBE2V2, MED13, YBX1, CNKSR2, GATA4, andSOX5/6, et al. Gene ontology (GO) analysis of target genes showed that miR-208b was mainly involved in the processes of negative regulation of transcription from RNA polymerase II promoter, and regulation of transcription, DNA templated. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the target genes regulated by miR-208b-3p were mainly involved in the Wnt signaling pathway. These findings suggest that FHCM patients with MYBPC3 gene mutations have a specific miRNA expression profile, and that miR-208b-3p is significantly upregulated in cardiac hypertrophy. Our results also indicate that miRNA-208b-3p activates the Wnt signaling pathway through its target gene to promote cardiac hypertrophy. Show less
📄 PDF DOI: 10.1186/s12872-022-02714-6
MYBPC3

Identification of Crucial Genes and Key Functions in Type 2 Diabetic Hearts by Bioinformatic Analysis.

Xin Huang, Kai-Jie Zhang, Jun-Jie Jiang +3 more · 2022 · Frontiers in endocrinology · Frontiers · added 2026-04-24
Type 2 diabetes (T2D) patients with SARS-CoV-2 infection hospitalized develop an acute cardiovascular syndrome. It is urgent to elucidate underlying mechanisms associated with the acute cardiac injury Show more
Type 2 diabetes (T2D) patients with SARS-CoV-2 infection hospitalized develop an acute cardiovascular syndrome. It is urgent to elucidate underlying mechanisms associated with the acute cardiac injury in T2D hearts. We performed bioinformatic analysis on the expression profiles of public datasets to identify the pathogenic and prognostic genes in T2D hearts. Cardiac RNA-sequencing datasets from Show less
📄 PDF DOI: 10.3389/fendo.2022.801260
MYBPC3

Inhibiting cardiac myeloperoxidase alleviates the relaxation defect in hypertrophic cardiomyocytes.

Chrishan J A Ramachandra, Myu Mai Ja Kp, Jasper Chua +15 more · 2022 · Cardiovascular research · Oxford University Press · added 2026-04-24
Hypertrophic cardiomyopathy (HCM) is characterized by cardiomyocyte hypertrophy and disarray, and myocardial stiffness due to interstitial fibrosis, which result in impaired left ventricular filling a Show more
Hypertrophic cardiomyopathy (HCM) is characterized by cardiomyocyte hypertrophy and disarray, and myocardial stiffness due to interstitial fibrosis, which result in impaired left ventricular filling and diastolic dysfunction. The latter manifests as exercise intolerance, angina, and dyspnoea. There is currently no specific treatment for improving diastolic function in HCM. Here, we investigated whether myeloperoxidase (MPO) is expressed in cardiomyocytes and provides a novel therapeutic target for alleviating diastolic dysfunction in HCM. Human cardiomyocytes derived from control-induced pluripotent stem cells (iPSC-CMs) were shown to express MPO, with MPO levels being increased in iPSC-CMs generated from two HCM patients harbouring sarcomeric mutations in the MYBPC3 and MYH7 genes. The presence of cardiomyocyte MPO was associated with higher chlorination and peroxidation activity, increased levels of 3-chlorotyrosine-modified cardiac myosin binding protein-C (MYBPC3), attenuated phosphorylation of MYBPC3 at Ser-282, perturbed calcium signalling, and impaired cardiomyocyte relaxation. Interestingly, treatment with the MPO inhibitor, AZD5904, reduced 3-chlorotyrosine-modified MYBPC3 levels, restored MYBPC3 phosphorylation, and alleviated the calcium signalling and relaxation defects. Finally, we found that MPO protein was expressed in healthy adult murine and human cardiomyocytes, and MPO levels were increased in diseased hearts with left ventricular hypertrophy. This study demonstrates that MPO inhibition alleviates the relaxation defect in hypertrophic iPSC-CMs through MYBPC3 phosphorylation. These findings highlight cardiomyocyte MPO as a novel therapeutic target for improving myocardial relaxation associated with HCM, a treatment strategy which can be readily investigated in the clinical setting, given that MPO inhibitors are already available for clinical testing. Show less
no PDF DOI: 10.1093/cvr/cvab077
MYBPC3

Snail-regulated exosomal microRNA-21 suppresses NLRP3 inflammasome activity to enhance cisplatin resistance.

Han-Ying Cheng, Chia-Hsin Hsieh, Po-Han Lin +5 more · 2022 · Journal for immunotherapy of cancer · added 2026-04-24
Compared with the precise targeting of drug-resistant mutant cancer cells, strategies for eliminating non-genetic adaptation-mediated resistance are limited. The pros and cons of the existence of infl Show more
Compared with the precise targeting of drug-resistant mutant cancer cells, strategies for eliminating non-genetic adaptation-mediated resistance are limited. The pros and cons of the existence of inflammasomes in cancer have been reported. Nevertheless, the dynamic response of inflammasomes to therapies should be addressed. Tumor-derived exosomes were purified by differential ultracentrifugation and validated by nanoparticle tracking analysis and transmission electron microscopy. A proximity ligation assay and interleukin-1β (IL-1β) level were used for detecting activation of NLRP3 inflammasomes. RNA sequencing was used to analyze the exosomal RNAs. We demonstrated that in cancer cells undergoing Snail-induced epithelial-mesenchymal transition (EMT), tumor cells suppress NLRP3 inflammasome activities of tumor-associated macrophages (TAMs) in response to chemotherapy through the delivery of exosomal miR-21. Mechanistically, miR-21 represses This finding reveals the mechanism of EMT-mediated resistance beyond cancer stemness through modulation of post-treatment inflammasome activity. It also highlights the dynamic remodeling of the TME throughout metastatic evolution. Show less
no PDF DOI: 10.1136/jitc-2022-004832
SNAI1

GMI, Ganoderma microsporum protein, suppresses cell mobility and increases temozolomide sensitivity through induction of Slug degradation in glioblastoma multiforme cells.

Ai-Jung Tseng, Tsung-Hsi Tu, Wei-Jyun Hua +7 more · 2022 · International journal of biological macromolecules · Elsevier · added 2026-04-24
Glioblastoma multiforme (GBM), which is a malignant primary brain tumor, is the cancer that spreads most aggressively into the adjacent brain tissue. Patients with metastatic GBM have a poor chance of Show more
Glioblastoma multiforme (GBM), which is a malignant primary brain tumor, is the cancer that spreads most aggressively into the adjacent brain tissue. Patients with metastatic GBM have a poor chance of survival. In this study, we examined the anti-GBM mobility effect of small protein, called GMI, which is cloned and purified from Ganoderma microsporum. Proteomic profiles showed that GMI-mediated proteins were involved in cell motility and cell growth functions. Specifically, we demonstrated that GMI significantly suppressed cell migration and invasion of GBM cells. GMI combined with temozolomide (TMZ), which is a traditional chemotherapeutic agent for GBM treatment, synergistically inhibited motility in GBM cells. Mechanistically, we demonstrated that GMI induced proteasome-dependent degradation of Slug, which is a critical transcription factor, is frequently linked to metastasis and drug resistance in GBM. Knockdown of Slug reduced cell viability and colony formation of GBM cells but enhanced TMZ-suppressed cell migration and viability. The results of this study show that targeting Slug degradation is involved in GMI-suppressed mobility of GBM cells. Moreover, GMI may be a potential supplementary agent for the suppression of GBM. Show less
no PDF DOI: 10.1016/j.ijbiomac.2022.08.024
SNAI1

IKBKE phosphorylates and stabilizes Snail to promote breast cancer invasion and metastasis.

Wei Xie, Qiwei Jiang, Xueji Wu +9 more · 2022 · Cell death and differentiation · Nature · added 2026-04-24
IKBKE, a non-canonical inflammatory kinase, is frequently amplified or activated, and plays predominantly oncogenic roles in human cancers, especially in breast cancer. However, the potential function Show more
IKBKE, a non-canonical inflammatory kinase, is frequently amplified or activated, and plays predominantly oncogenic roles in human cancers, especially in breast cancer. However, the potential function and underlying mechanism of IKBKE contributing to breast cancer metastasis remain largely elusive. Here, we report that depletion of Ikbke markedly decreases polyoma virus middle T antigen (PyVMT)-induced mouse mammary tumorigenesis and subsequent lung metastasis. Biologically, ectopic expression of IKBKE accelerates, whereas depletion of IKBKE attenuates breast cancer invasiveness and migration in vitro and tumor metastasis in vivo. Mechanistically, IKBKE tightly controls the stability of transcriptional factor Snail in different layers, in particular by directly phosphorylating Snail, which markedly blocks the E3 ligase β-TRCP1-mediated Snail degradation, resulting in breast cancer epithelial-mesenchymal transition (EMT) and metastasis. These findings together reveal a novel oncogenic function of IKBKE in promoting breast cancer metastasis by governing Snail abundance, and highlight the potential of targeting IKBKE for metastatic breast cancer therapies. Show less
no PDF DOI: 10.1038/s41418-022-00940-1
SNAI1

Cellular junction and mesenchymal factors delineate an endometriosis-specific response of endometrial stromal cells to the mesothelium.

Li-Ling Lin, Simran Makwana, Meizhen Chen +6 more · 2022 · Molecular and cellular endocrinology · Elsevier · added 2026-04-24
Endometriosis is a debilitating gynecologic disorder that affects ∼10% of women of reproductive age. Endometriosis is characterized by growth of endometriosis lesions within the abdominal cavity, gene Show more
Endometriosis is a debilitating gynecologic disorder that affects ∼10% of women of reproductive age. Endometriosis is characterized by growth of endometriosis lesions within the abdominal cavity, generally thought to arise from retrograde menstruation of shed endometrial tissue. While the pathophysiology underlying peritoneal endometriosis lesion formation is still unclear, the interaction between invading endometrial tissue and the peritoneal mesothelial lining is an essential step in lesion formation. In this study, we assessed proteomic differences between eutopic endometrial stromal cells (ESCs) from women with and without endometriosis in response to peritoneal mesothelial cell (PMC) exposure, using single-cell cytometry by time-of-flight (CyTOF). Co-cultured primary eutopic ESCs from women with and without endometriosis with an established PMC line were subjected to immunostaining with a panel of Maxpar CyTOF metal-conjugated antibodies (n = 28) targeting cell junction and mesenchymal markers, which are involved in cell-cell adhesions and epithelial-mesenchymal transition. Exposure of the ESCs to PMCs resulted in a drastic shift in cellular expression profiles in ESCs derived from endometriosis, whereas little effect by PMCs was observed in ESCs from non-endometriosis subjects. The transcription factor SNAI1 was consistently repressed by PMC interactions. ESCs from endometriosis patients are unique in that they respond to PMCs by undergoing changes in adhesive properties and mesenchymal characteristics that would facilitate lesion formation. Show less
no PDF DOI: 10.1016/j.mce.2021.111481
SNAI1

Lysosomal protein transmembrane 5 promotes lung-specific metastasis by regulating BMPR1A lysosomal degradation.

Bo Jiang, Xiaozhi Zhao, Wei Chen +13 more · 2022 · Nature communications · Nature · added 2026-04-24
Organotropism during cancer metastasis occurs frequently but the underlying mechanism remains poorly understood. Here, we show that lysosomal protein transmembrane 5 (LAPTM5) promotes lung-specific me Show more
Organotropism during cancer metastasis occurs frequently but the underlying mechanism remains poorly understood. Here, we show that lysosomal protein transmembrane 5 (LAPTM5) promotes lung-specific metastasis in renal cancer. LAPTM5 sustains self-renewal and cancer stem cell-like traits of renal cancer cells by blocking the function of lung-derived bone morphogenetic proteins (BMPs). Mechanistic investigations showed that LAPTM5 recruits WWP2, which binds to the BMP receptor BMPR1A and mediates its lysosomal sorting, ubiquitination and ultimate degradation. BMPR1A expression was restored by the lysosomal inhibitor chloroquine. LAPTM5 expression could also serve as an independent predictor of lung metastasis in renal cancer. Lastly, elevation of LAPTM5 expression in lung metastases is a common phenomenon in multiple cancer types. Our results reveal a molecular mechanism underlying lung-specific metastasis and identify LAPTM5 as a potential therapeutic target for cancers with lung metastasis. Show less
no PDF DOI: 10.1038/s41467-022-31783-6
WWP2

Sequencing of 640,000 exomes identifies

Parsa Akbari, Ankit Gilani, Olukayode Sosina +59 more · 2021 · Science (New York, N.Y.) · Science · added 2026-04-24
Large-scale human exome sequencing can identify rare protein-coding variants with a large impact on complex traits such as body adiposity. We sequenced the exomes of 645,626 individuals from the Unite Show more
Large-scale human exome sequencing can identify rare protein-coding variants with a large impact on complex traits such as body adiposity. We sequenced the exomes of 645,626 individuals from the United Kingdom, the United States, and Mexico and estimated associations of rare coding variants with body mass index (BMI). We identified 16 genes with an exome-wide significant association with BMI, including those encoding five brain-expressed G protein-coupled receptors ( Show less
📄 PDF DOI: 10.1126/science.abf8683
GIPR

GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice.

Ricardo J Samms, Michael E Christe, Kyla Al Collins +25 more · 2021 · The Journal of clinical investigation · added 2026-04-24
Tirzepatide (LY3298176), a dual GIP and GLP-1 receptor (GLP-1R) agonist, delivered superior glycemic control and weight loss compared with GLP-1R agonism in patients with type 2 diabetes. However, the Show more
Tirzepatide (LY3298176), a dual GIP and GLP-1 receptor (GLP-1R) agonist, delivered superior glycemic control and weight loss compared with GLP-1R agonism in patients with type 2 diabetes. However, the mechanism by which tirzepatide improves efficacy and how GIP receptor (GIPR) agonism contributes is not fully understood. Here, we show that tirzepatide is an effective insulin sensitizer, improving insulin sensitivity in obese mice to a greater extent than GLP-1R agonism. To determine whether GIPR agonism contributes, we compared the effect of tirzepatide in obese WT and Glp-1r-null mice. In the absence of GLP-1R-induced weight loss, tirzepatide improved insulin sensitivity by enhancing glucose disposal in white adipose tissue (WAT). In support of this, a long-acting GIPR agonist (LAGIPRA) was found to enhance insulin sensitivity by augmenting glucose disposal in WAT. Interestingly, the effect of tirzepatide and LAGIPRA on insulin sensitivity was associated with reduced branched-chain amino acids (BCAAs) and ketoacids in the circulation. Insulin sensitization was associated with upregulation of genes associated with the catabolism of glucose, lipid, and BCAAs in brown adipose tissue. Together, our studies show that tirzepatide improved insulin sensitivity in a weight-dependent and -independent manner. These results highlight how GIPR agonism contributes to the therapeutic profile of dual-receptor agonism, offering mechanistic insights into the clinical efficacy of tirzepatide. Show less
no PDF DOI: 10.1172/JCI146353
GIPR

GIP-GIPR promotes neurite outgrowth of cortical neurons in Akt dependent manner.

Long Teng, Tuchen Guan, Beibei Guo +6 more · 2021 · Biochemical and biophysical research communications · Elsevier · added 2026-04-24
The intrinsic capacity of axonal growth is varied among the neurons form different tissues or different developmental stages. In this study, we established an in vitro model to compare the axonal grow Show more
The intrinsic capacity of axonal growth is varied among the neurons form different tissues or different developmental stages. In this study, we established an in vitro model to compare the axonal growth of neurons from embryonic 18 days, post-natal 1 day and post-natal 3 days rat. The E18 neurons showed powerful ability of neuritogenensis and axon outgrowth and the ability decreased rapidly along with development. The transcriptome profile of these neurons revealed a set of genes positively correlated with the capacity of neurite outgrowth. Glucose-dependent insulinotropic polypeptide receptor (GIPR) is identified as a gene to promote neurite outgrowth, which was approved by siRNA knock down assay in E18 neuron. Glucose-dependent insulinotropic polypeptide (GIP), a ligand of GIPR secreted from enteroendocrine K cells, is well-known for its role in nutrient sensing and intake. To verify the effect of GIP-GIPR signal on neurite outgrowth, we administrated GIP to stimulate the E18 neurons, the results showed that GIP significantly improved extension of axon. We further revealed that GIP increased Rac1/Cdc42 phosphorylation in Akt dependent manner. In summary, our study established an in vitro model to screen the genes involved in neurite outgrowth, and we provided mechanical insight on the GIP-GIPR axis to promote axonal outgrowth. Show less
no PDF DOI: 10.1016/j.bbrc.2020.11.120
GIPR

Mouse Spexin: (II) Functional Role as a Satiety Factor inhibiting Food Intake by Regulatory Actions Within the Hypothalamus.

Matthew K H Wong, Yuan Chen, Mulan He +3 more · 2021 · Frontiers in endocrinology · Frontiers · added 2026-04-24
Spexin (SPX) is a pleiotropic peptide with highly conserved protein sequence from fish to mammals and its biological actions are mediated by GalR2/GalR3 receptors expressed in target tissues. Recently Show more
Spexin (SPX) is a pleiotropic peptide with highly conserved protein sequence from fish to mammals and its biological actions are mediated by GalR2/GalR3 receptors expressed in target tissues. Recently, SPX has been confirmed to be a novel satiety factor in fish species but whether the peptide has a similar function in mammals is still unclear. Using the mouse as a model, the functional role of SPX in feeding control and the mechanisms involved were investigated. After food intake, serum SPX in mice could be up-regulated with elevations of transcript expression and tissue content of SPX in the glandular stomach but not in other tissues examined. As revealed by immunohistochemical staining, food intake also intensified SPX signals in the major cell types forming the gastric glands (including the foveolar cells, parietal cells, and chief cells) within the gastric mucosa of glandular stomach. Furthermore, IP injection of SPX was effective in reducing food intake with parallel attenuation in transcript expression of NPY, AgRP, NPY type 5 receptor (NPY5R), and ghrelin receptor (GHSR) in the hypothalamus, and these inhibitory effects could be blocked by GalR3 but not GalR2 antagonism. In agreement with the central actions of SPX, similar inhibition on feeding and hypothalamic expression of NPY, AgRP, NPY5R, and GHSR could also be noted with ICV injection of SPX. In the same study, in contrast to the drop in NPY5R and GHSR, SPX treatment could induce parallel rises of transcript expression of leptin receptor (LepR) and melanocortin 4 receptor (MC4R) in the hypothalamus. These findings, as a whole, suggest that the role of SPX as a satiety factor is well conserved in the mouse. Apparently, food intake can induce SPX production in glandular stomach and contribute to the postprandial rise of SPX in circulation. Through GalR3 activation, this SPX signal can act within the hypothalamus to trigger feedback inhibition on feeding by differential modulation of feeding regulators (NPY and AgRP) and their receptors (NPY5R, GHSR, LepR, and MC4R) involved in the feeding circuitry within the CNS. Show less
📄 PDF DOI: 10.3389/fendo.2021.681647
MC4R

Deletion of the Feeding-Induced Hepatokine TSK Ameliorates the Melanocortin Obesity Syndrome.

Qiuyu Wang, Peng Zhang, Isin Cakir +3 more · 2021 · Diabetes · added 2026-04-24
Work in recent decades has established that metabolic hormones released by endocrine cells and diverse other cell types serve to regulate nutrient intake and energy homeostasis. Tsukushi (TSK) is a le Show more
Work in recent decades has established that metabolic hormones released by endocrine cells and diverse other cell types serve to regulate nutrient intake and energy homeostasis. Tsukushi (TSK) is a leucine-rich repeat-containing protein secreted primarily by the liver that exerts an inhibitory effect on brown fat sympathetic innervation and thermogenesis. Despite this, physiological regulation of TSK and the mechanisms underlying its effects on energy balance remain poorly understood. Here we show that hepatic expression and plasma concentrations of TSK are induced by feeding and regulated by melanocortin-4 receptor (MC4R) signaling. We generated TSK and MC4R-double-knockout mice to elucidate the nature of cross talk between TSK and the central regulatory circuit of energy balance. Remarkably, TSK inactivation restores energy balance, ameliorates hyperphagia, and improves metabolic health in MC4R-deficient mice. TSK ablation enhances thermogenic gene expression in brown fat, dampens obesity-association inflammation in the liver and adipose tissue, and protects MC4R-null mice from diet-induced nonalcoholic steatohepatitis. At the cellular level, TSK deficiency augments feeding-induced c-Fos expression in the paraventricular nucleus of the hypothalamus. These results illustrate physiological cross talk between TSK and the central regulatory circuit in maintaining energy balance and metabolic homeostasis. Show less
no PDF DOI: 10.2337/db21-0161
MC4R

Activation of the Melanocortin-4 receptor signaling by α-MSH stimulates nerve-dependent mouse digit regeneration.

Hanqian Xu, Hailin Zhang, Yanqing Fang +4 more · 2021 · Cell regeneration (London, England) · BioMed Central · added 2026-04-24
Expression of Mc4r in peripheral organs indicates it has broader roles in organ homeostasis and regeneration. However, the expression and function of Mc4r in the mouse limb and digit has not been full Show more
Expression of Mc4r in peripheral organs indicates it has broader roles in organ homeostasis and regeneration. However, the expression and function of Mc4r in the mouse limb and digit has not been fully investigated. Our previous work showed that Mc4r-/- mice fail to regenerate the digit, but whether activation of MC4R signaling could rescue digit regeneration, or stimulate proximal digit regeneration is not clear. We analyzed the expression dynamics of Mc4r in the embryonic and postnatal mouse limb and digit using the Mc4r-gfp mice. We found that Mc4r-GFP is mainly expressed in the limb nerves, and in the limb muscles that are undergoing secondary myogenesis. Expression of Mc4r-GFP in the adult mouse digit is restricted to the nail matrix. We also examined the effect of α-MSH on mouse digit regeneration. We found that administration of α-MSH in the Mc4r+/- mice rescue the delayed regeneration of distal digit tip. α-MSH could rescue distal digit regeneration in denervated hindlimbs. In addition, α-MSH could stimulate regeneration of the proximally amputated digit, which is non-regenerative. Mc4r expression in the mouse limb and digit is closely related to nerve tissues, and α-MSH/MC4R signaling has a neurotrophic role in mouse digit tip regeneration. Show less
📄 PDF DOI: 10.1186/s13619-021-00081-9
MC4R

Identification and characterization of two novel melanocortin-3 receptor mutations in Chinese obese individuals.

Wei Wang, Yue-Jun Lin, Zhao-Xia Chen +1 more · 2021 · Biochimica et biophysica acta. Molecular basis of disease · Elsevier · added 2026-04-24
The melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R), known as neural melanocortin receptors, have been implicated to be critical components of the hypothalamic leptin-melanocortin pa Show more
The melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R), known as neural melanocortin receptors, have been implicated to be critical components of the hypothalamic leptin-melanocortin pathway and related to obesity pathogenesis. In contrast to extensive evidence from physiologic, biological, genetic studies demonstrating that MC4R is a critical regulator in obesity, whether MC3R mutation causes obesity is still controversial. In the present study, we screened for coding variants in the MC3R gene of 176 obese individuals (mean BMI 34.84 ± 0.19 kg/m Show less
no PDF DOI: 10.1016/j.bbadis.2021.166107
MC4R

Pharmacological evaluation of MRAP proteins on Xenopus neural melanocortin signaling.

Xiaolu Tai, Song Xue, Cong Zhang +5 more · 2021 · Journal of cellular physiology · Wiley · added 2026-04-24
Melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R), two neural G protein-coupled receptors are known to be functionally critical for energy balance in vertebrates. As allosteric regulat Show more
Melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R), two neural G protein-coupled receptors are known to be functionally critical for energy balance in vertebrates. As allosteric regulators of melanocortin receptors, melanocortin accessory proteins (MRAPs) are also involved in energy homeostasis. The interaction of MRAPs and melanocortin signaling was previously shown in mammals and zebrafish, but nothing had been reported in amphibians. As the basal class of tetrapods, amphibians occupy a phylogenetic transition between teleosts and terrestrial animals. Here we examined the evolutionary conservation of MC3R, MC4R, and MRAPs between diploid Xenopus tropicalis (xt-) and other chordates and investigated the pharmacological regulatory properties of MRAPs on the neural MC3R and MC4R signaling. Our results showed that xtMRAP and xtMRAP2 both exerted robust potentiation effect on agonist (α-MSH and adrenocorticotropin [ACTH]) induced activation and modulated the basal activity and cell surface translocation of xtMC3R and xtMC4R. In addition, the presence of two accessory proteins could convert xtMC3R and xtMC4R into ACTH-preferred receptors. These findings suggest that the presence of MRAPs exhibits fine control over the pharmacological activities of the neuronal MC3R and MC4R signaling in the Xenopus tropicalis, which is physiologically relevant with the complicated transition of feeding behaviors during their life history. Show less
no PDF DOI: 10.1002/jcp.30306
MC4R

Pharmacological modulation of dual melanocortin-4 receptor signaling by melanocortin receptor accessory proteins in the Xenopus laevis.

Lei Li, Ying Xu, Jihong Zheng +5 more · 2021 · Journal of cellular physiology · Wiley · added 2026-04-24
Physiological modulation of melanocortin-4 receptor (MC4R) signaling by MRAP2 proteins plays an indispensable role in appetite control and energy homeostasis in the central nervous system. Great inter Show more
Physiological modulation of melanocortin-4 receptor (MC4R) signaling by MRAP2 proteins plays an indispensable role in appetite control and energy homeostasis in the central nervous system. Great interspecies differences of the interaction and regulation of melanocortin receptors by MRAP protein family have been reported in several diploid vertebrates but never been investigated in the tetrapod amphibian Xenopus laevis. Here, we performed phylogenetic and synteny-based analyses to explore the evolutionary aspects of dual copies of X. laevis MC4R (xlMC4R) and MRAP2 (xlMRAP2) proteins. Our data showed that xlMRAPs directly interacted with xlMC4Rs on the cell surface as a functional antiparallel dimeric topology and pharmacological studies suggested a homology specific regulatory pattern of the melanocortin system in X. laevis. Show less
no PDF DOI: 10.1002/jcp.30280
MC4R

Excess Folic Acid Supplementation before and during Pregnancy and Lactation Alters Behaviors and Brain Gene Expression in Female Mouse Offspring.

Xingyue Yang, Wenyan Sun, Qian Wu +9 more · 2021 · Nutrients · MDPI · added 2026-04-24
Use of folic acid (FA) during early pregnancy protects against birth defects. However, excess FA has shown gender-specific neurodevelopmental toxicity. Previously, we fed the mice with 2.5 times the r Show more
Use of folic acid (FA) during early pregnancy protects against birth defects. However, excess FA has shown gender-specific neurodevelopmental toxicity. Previously, we fed the mice with 2.5 times the recommended amount of FA one week prior to mating and during the pregnancy and lactation periods, and detected the activated expression of Show less
📄 PDF DOI: 10.3390/nu14010066
ANGPTL4

PPARβ/δ Agonist Alleviates Diabetic Osteoporosis

Miao Chen, Weimin Lin, Rui Ye +2 more · 2021 · Frontiers in cell and developmental biology · Frontiers · added 2026-04-24
Diabetic osteoporosis is a common complication in diabetic patients, leading to increased fracture risk and impaired bone healing. As a member of the peroxisome proliferator-activated receptor (PPAR) Show more
Diabetic osteoporosis is a common complication in diabetic patients, leading to increased fracture risk and impaired bone healing. As a member of the peroxisome proliferator-activated receptor (PPAR) family, PPARβ/δ agonist is suggested as a therapeutic target for the treatment of metabolic syndrome, and has been reported to positively regulate bone turnover by improving osteogenesis. However, its regulatory role in diabetic osteoporosis has not been reported yet. Here, we explored the therapeutic effects and potential mechanisms of PPARβ/δ agonist to the osteoporotic phenotypes of diabetic mice. Our results indicated that the osteoporotic phenotypes could be significantly ameliorated in diabetic mice by the administration of PPARβ/δ agonists. Show less
📄 PDF DOI: 10.3389/fcell.2021.753194
ANGPTL4

Recombinant angiopoietin-like protein 4 attenuates intestinal barrier structure and function injury after ischemia/reperfusion.

Zi-Yi Wang, Jian-Yu Lin, Yang-Rong Feng +8 more · 2021 · World journal of gastroenterology · added 2026-04-24
Intestinal barrier breakdown, a frequent complication of intestinal ischemia-reperfusion (I/R) including dysfunction and the structure changes of the intestine, is characterized by a loss of tight jun Show more
Intestinal barrier breakdown, a frequent complication of intestinal ischemia-reperfusion (I/R) including dysfunction and the structure changes of the intestine, is characterized by a loss of tight junction and enhanced permeability of the intestinal barrier and increased mortality. To develop effective and novel therapeutics is important for the improvement of outcome of patients with intestinal barrier deterioration. Recombinant human angiopoietin-like protein 4 (rhANGPTL4) is reported to protect the blood-brain barrier when administered exogenously, and endogenous ANGPTL4 deficiency deteriorates radiation-induced intestinal injury. To identify whether rhANGPTL4 may protect intestinal barrier breakdown induced by I/R. Intestinal I/R injury was elicited through clamping the superior mesenteric artery for 60 min followed by 240 min reperfusion. Intestinal epithelial (Caco-2) cells and human umbilical vein endothelial cells were challenged by hypoxia/ reoxygenation to mimic I/R Indicators including fluorescein isothiocyanate-conjugated dextran (4 kilodaltons; FD-4) clearance, ratio of phosphorylated myosin light chain/total myosin light chain, myosin light chain kinase and loss of zonula occludens-1, claudin-2 and VE-cadherin were significantly increased after intestinal I/R or cell hypoxia/reoxygenation. rhANGPTL4 treatment significantly reversed these indicators, which were associated with inhibiting the inflammatory and oxidative cascade, excessive activation of cellular autophagy and apoptosis and improvement of survival rate. Similar results were observed rhANGPTL4 can function as a protective agent against intestinal injury induced by intestinal I/R and improve survival Show less
📄 PDF DOI: 10.3748/wjg.v27.i32.5404
ANGPTL4

Gut Microbiota of Chinese Obese Children and Adolescents With and Without Insulin Resistance.

Xin Yuan, Ruimin Chen, Ying Zhang +3 more · 2021 · Frontiers in endocrinology · Frontiers · added 2026-04-24
The intestinal flora of gut microbiota in obese Chinese children and adolescents with and without insulin resistance (IR) was analyzed, as well as associations between the gut microbiota and two serum Show more
The intestinal flora of gut microbiota in obese Chinese children and adolescents with and without insulin resistance (IR) was analyzed, as well as associations between the gut microbiota and two serum cytokines related to glucose metabolism, adropin and angiopoietin-like 4 (ANGPTL4). Clinical data, fecal bacterial composition, glucose-related hormones, and serum adipokines (adropin and ANGPTL4) were analyzed in 65 Chinese children with exogenous obesity. The composition of the gut microbiota was determined by 16S rRNA-based metagenomics and IR was calculated using the homeostasis model assessment (HOMA). The 65 obese subjects were divided into two groups: insulin sensitive (IS) (n=40, 57.5% males) or IR (n=25, 60% males). Principal coordinates analysis revealed that the gut microbiota samples from the IS group clustered together and separated partly from the IR group (p=0.008). By Mann-Whitney In obese children, the gut microbiome in IR subjects was significantly discordant from the IS subjects, and the abundance of some metabolism-related bacteria correlated with the serum concentrations of adropin and ANGPTL4. These observations infer that the gut microbiota may be involved in the regulation of glucose metabolism in obesity. Show less
📄 PDF DOI: 10.3389/fendo.2021.636272
ANGPTL4

Plasma asprosin, CCDC80 and ANGPTL4 levels are associated with metabolic and cardiovascular risk in patients with inflammatory bowel disease.

Hao-Hua Wang, Wan-Ying Luo, Min Lin +3 more · 2021 · Physiological research · added 2026-04-24
Asprosin, coiled-coil domain-containing 80(CCDC80) and angiopoietin-like4(ANGPTL4) are newly discovered adipocytokine that affects glucose tolerance, insulin resistance and cardiovascular diseases. Th Show more
Asprosin, coiled-coil domain-containing 80(CCDC80) and angiopoietin-like4(ANGPTL4) are newly discovered adipocytokine that affects glucose tolerance, insulin resistance and cardiovascular diseases. The goal of this study was to investigate if a relationship exists among asprosin, CCDC80 and ANGPTL4 and inflammatory bowel disease (IBD). Fifty subjects with newly diagnosed IBD and fifty healthy individuals were enrolled. Patients were treated with standard therapies for 3 months. Plasma asprosin, CCDC80 and ANGPTL4 levels were measured with enzyme-linked immunosorbent assay. High resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia (flow-mediated dilation, FMD) and after sublingual glyceryltrinitrate.Compare with healthy individuals, plasma CCDC80,erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels and homeostasis modelassessment of insulin resistance (HOMA-IR) were significantly higher (p < 0.05, respectively), whereas plasma asprosin,ANGPTL4 levels and FMD were significantly lower inboth UC and CD patients(p <0.05). Plasma CCDC80 levels were significantly higher in patients with CD (p<0.05), while plasma asprosin and ANGPTL4 levels were lower (p<0.05) as compared with those in patients with UC. Standard therapies increased plasma asprosin, ANGPTL4 levels and FMD in both UC and CD (p<0.05),UC and CD patientswhile decreased plasma CCDC80, ESR, CRP levels and HOMA-IR (p<0.05). The changes in HOMA-IR and FMD were correlated with the changes in plasma asprosin, CCDC80 and ANGPTL4 levels over the study period (p<0.05). Plasma asprosin, CCDC80 and ANGPTL4 levels may be applied as a significant marker for early stage of insulin resistance and atherosclerosis in IBD, especially of CD. Show less
no PDF DOI: 10.33549/physiolres.934547
ANGPTL4

Depression Augments Plasma APOA4 without Changes of Plasma Lipids and Glucose in Female Adolescents Carrying G Allele of APOA4 rs5104.

Qi Wei Guo, Yan Jun Si, Yi Lin Shen +4 more · 2021 · Journal of molecular neuroscience : MN · Springer · added 2026-04-24
The association of apolipoprotein AIV (APOA4) with depression or plasma levels of lipids and glucose has been inconsistently reported. However, interplays between APOA4 and depression on the levels ha Show more
The association of apolipoprotein AIV (APOA4) with depression or plasma levels of lipids and glucose has been inconsistently reported. However, interplays between APOA4 and depression on the levels have not been explored yet. The present study aimed to investigate plasma levels of APOA4, lipids, and glucose in adolescents with different genotypes of APOA4 rs5104 and with or without depression. Depressive symptoms were assessed in 631 adolescents by Beck Depression Inventory (BDI). A total score of 14 was defined as the cutoff point for depression. Plasma levels of triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), glucose, and insulin were measured by routine methods, and APOA4 by enzyme-linked immunosorbent assays. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism analyses and verified by DNA sequencing. Female adolescents had higher prevalence of depression than male subjects only in G allele carriers (p = 0.015), but not in AA homozygotes. Risk factors of depression and predictors of depression severity were different between G allele carriers and AA homozygotes. Lower levels of glucose (p = 0.003) were observed in male G allele carriers than those in male AA homozygotes and increased TG levels (p = 0.008) in female G allele carriers when compared with those in female AA homozygotes. When both APOA4 rs5104 and depression were taken into account, subjects with depression had higher levels of plasma APOA4 than adolescents without depression only in female G allele carriers (p = 0.043), but no significant changes of plasma lipids and glucose. Depression augments plasma APOA4 levels without changes of plasma lipids and glucose in female adolescents carrying G allele of APOA4 rs5104. These results may provide a novel explanation for the inconsistent relationship between depression, APOA4, and plasma levels of lipids and glucose in the literature. Show less
📄 PDF DOI: 10.1007/s12031-020-01766-7
APOA4

High prevalence of APOA1/C3/A4/A5 alterations in luminal breast cancers among young women in East Asia.

Ching-Hung Lin, Ruby Yun-Ju Huang, Tzu-Pin Lu +9 more · 2021 · NPJ breast cancer · Nature · added 2026-04-24
In East Asia, the breast cancer incidence rate among women aged <50 years has rapidly increased. Emerging tumors are distinctly characterized by a high prevalence of estrogen receptor (ER)-positive/hu Show more
In East Asia, the breast cancer incidence rate among women aged <50 years has rapidly increased. Emerging tumors are distinctly characterized by a high prevalence of estrogen receptor (ER)-positive/human epidermal growth factor receptor (HER2)-negative cancer. In the present study, we identified unique genetic alterations in these emerging tumors. We analyzed gene copy number variations (CNVs) in breast tumors from 120 Taiwanese patients, and obtained public datasets of CNV and gene expression (GE). The data regarding CNV and GE were separately compared between East Asian and Western patients, and the overlapping genes identified in the comparisons were explored to identify the gene-gene interaction networks. In the age <50 years/ER + /HER2- subgroup, tumors of East Asian patients exhibited a higher frequency of copy number loss in APOA1/C3/A4/A5, a lipid-metabolizing gene cluster (33 vs. 10%, P < .001) and lower APOA1/C3/A4/A5 expressions than tumors of Western patients. These copy number loss related- and GE-related results were validated in another Taiwanese cohort and in two GE datasets, respectively. The copy number loss was significantly associated with poor survival among Western patients, but not among East Asian patients. Lower APOA1, APOC3, and APOA5 expressions were associated with higher ESTIMATE immune scores, indicating an abundance of tumor-infiltrating immune cells. In conclusion, APOA1/C3/A4/A5 copy number loss was more prevalent in luminal breast tumors among East Asian women aged <50 years, and its immunomodulatory effect on the tumor microenvironment possibly plays various roles in the tumor biology of East Asian patients. Show less
📄 PDF DOI: 10.1038/s41523-021-00299-5
APOA5

Quantitative Proteomics Analysis of Differentially Expressed Proteins in Serum of Former Uranium Miners by Isobaric Tags for the Relative and Absolute Quantitation.

Xuhong Dang, Haipeng Lin, Yayi Yuan +8 more · 2021 · Dose-response : a publication of International Hormesis Society · SAGE Publications · added 2026-04-24
The carcinogenicity of radon has been convincingly documented through epidemiological studies of underground miners. However, there is a lack of early warning indicators for radon radiation damage. In Show more
The carcinogenicity of radon has been convincingly documented through epidemiological studies of underground miners. However, there is a lack of early warning indicators for radon radiation damage. In this study, mixed serum samples of 3 groups were collected from 27 underground uranium miners and seven aboveground miners according to the radiation exposure dose. The differentially expressed proteins in the serum were identified using the isobaric tags for the relative and absolute quantitation (iTRAQ)-based method. Some differentially expressed proteins were validated by enzyme-linked immunosorbent assay (ELISA) in 84 underground and 32 aboveground miners. A total of 25 co-differentially expressed proteins in 2 underground miner groups were screened, of which 9 were downregulated and 13 were upregulated. Biological process analysis of these proteins using Metascape showed that 5 GO terms were enriched, such as negative regulation of very-low-density lipoprotein particle clearance, endocytosis, and regulated exocytosis. The results of the ELISA for the expression levels of GCN1, CIP2A, and IGHV1-24 in the serum of 116 miners' serum showed that the levels of GCN1 and CIP2A were consistent with the iTRAQ results. In conclusion, APOC1, APOC2, APOC3, ORM1, ORM2, ANTXR1, GCN1, and CIP2A may be potential early markers of radon radiation damage. Show less
📄 PDF DOI: 10.1177/15593258211056190
APOC3