Pub Date : 2026-01-22DOI: 10.1016/j.jare.2026.01.043
Feipeng Cui, Mengfan Wang, Linxi Tang, Yudiyang Ma, Jianing Wang, Lei Zheng, Meiqi Xing, Junqing Xie, Lin Han, Yaohua Tian
{"title":"Residential greenness, air pollution, and epilepsy: Insight in genetic susceptibility and life expectancy","authors":"Feipeng Cui, Mengfan Wang, Linxi Tang, Yudiyang Ma, Jianing Wang, Lei Zheng, Meiqi Xing, Junqing Xie, Lin Han, Yaohua Tian","doi":"10.1016/j.jare.2026.01.043","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.043","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"117 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-21DOI: 10.1016/j.jare.2026.01.030
Yimei Zheng, Boyu Chen, Xuanxiang Huang, Chao Ai, Hui Teng, Lei Chen
{"title":"Boosting luteolin bioavailability via P-glycoprotein efflux inhibition: a self-microemulsifying drug delivery systems","authors":"Yimei Zheng, Boyu Chen, Xuanxiang Huang, Chao Ai, Hui Teng, Lei Chen","doi":"10.1016/j.jare.2026.01.030","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.030","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"62 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-20DOI: 10.1016/j.jare.2026.01.051
Marta Chierichetti, Roberta Andreotti, Barbara Tedesco, Veronica Ferrari, Laura Cornaggia, Paola Pramaggiore, Marta Cozzi, Ali Mohamed, Rocio Magdalena, Margherita Piccolella, Giulia Boarolo, Valeria Crippa, Paola Rusmini, Mariarita Galbiati, Carlo Rinaldi, Eric N. Anderson, Udai Bhan Pandey, Maria Pennuto, Riccardo Cristofani, Angelo Poletti
Introduction
Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disease caused by a CAG-repeat expansion in the androgen receptor (AR) gene,translated into an elongated polyglutamine (polyQ) tract in the protein. Androgens trigger ARpolyQ toxicity, thus most potential therapeutic approaches involve androgen reduction or AR negative modulation, with severe endocrine side effects.
Objective
A start codon (I-AUGs) controls AR translation, while a second one, (II-AUG) downstream to I-AUG and the CAG repeat, drives translation of the shorter AR isoform (AR-A) lacking the polyQ tract, but preserves all relevant AR functional domains. Here, we studied AR-A behaviour and its effect on ARpolyQ toxicity in SBMA.
Methods
We took advantage of both cellular and Drosophila melanogaster SBMA models to asses AR-A behaviour and effect on ARpolyQ aggregation and functions.
Results
Comparative expression analyses of AR isoforms revealed that AR-A is predominantly located in the mouse brainstem and spinal cord of the central nervous system, but not in muscle. AR-A retains partial androgenic activity, but does not aggregate. Since ARpolyQ and AR-A can heterodimerize, we tested the effect of AR-A on ARpolyQ behaviour, showing that AR-A has a pro-solubilizing effect on ARpolyQ aggregates and that the heterodimers retain the transcriptional activity. Finally, we tested the effect of AR-A in a fly model of SBMA. Flies expressing AR-A alone showed no signs of external eye degeneration, in contrast to those expressing expanded ARpolyQ. Notably, co-expression of AR-A with ARpolyQ significantly reduced ARpolyQ aggregation and eye degeneration, supporting our hypothesis that AR-A enhances ARpolyQ solubility and mitigates its toxicity in vivo.
Conclusions
Altogether, our results demonstrate that an increased expression of AR-A may have a role in protecting against ARpolyQ aggregation and toxicity. These findings suggest that AR-A could represent a promising avenue for developing an alternative therapeutic strategy that warrants further investigation.
{"title":"The alternative androgen receptor isoform a mitigates toxicity of polyglutamine-elongated mutant androgen receptor in spinal and bulbar muscular atrophy","authors":"Marta Chierichetti, Roberta Andreotti, Barbara Tedesco, Veronica Ferrari, Laura Cornaggia, Paola Pramaggiore, Marta Cozzi, Ali Mohamed, Rocio Magdalena, Margherita Piccolella, Giulia Boarolo, Valeria Crippa, Paola Rusmini, Mariarita Galbiati, Carlo Rinaldi, Eric N. Anderson, Udai Bhan Pandey, Maria Pennuto, Riccardo Cristofani, Angelo Poletti","doi":"10.1016/j.jare.2026.01.051","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.051","url":null,"abstract":"<h3>Introduction</h3>Spinal and bulbar muscular atrophy (SBMA) is an X-linked neuromuscular disease caused by a CAG-repeat expansion in the androgen receptor (AR) gene,translated into an elongated polyglutamine (polyQ) tract in the protein. Androgens trigger ARpolyQ toxicity, thus most potential therapeutic approaches involve androgen reduction or AR negative modulation, with severe endocrine side effects.<h3>Objective</h3>A start codon (I-AUGs) controls AR translation, while a second one, (II-AUG) downstream to I-AUG and the CAG repeat, drives translation of the shorter AR isoform (AR-A) lacking the polyQ tract, but preserves all relevant AR functional domains. Here, we studied AR-A behaviour and its effect on ARpolyQ toxicity in SBMA.<h3>Methods</h3>We took advantage of both cellular and Drosophila melanogaster SBMA models to asses AR-A behaviour and effect on ARpolyQ aggregation and functions.<h3>Results</h3>Comparative expression analyses of AR isoforms revealed that AR-A is predominantly located in the mouse brainstem and spinal cord of the central nervous system, but not in muscle. AR-A retains partial androgenic activity, but does not aggregate. Since ARpolyQ and AR-A can heterodimerize, we tested the effect of AR-A on ARpolyQ behaviour, showing that AR-A has a pro-solubilizing effect on ARpolyQ aggregates and that the heterodimers retain the transcriptional activity. Finally, we tested the effect of AR-A in a fly model of SBMA. Flies expressing AR-A alone showed no signs of external eye degeneration, in contrast to those expressing expanded ARpolyQ. Notably, co-expression of AR-A with ARpolyQ significantly reduced ARpolyQ aggregation and eye degeneration, supporting our hypothesis that AR-A enhances ARpolyQ solubility and mitigates its toxicity <em>in vivo</em>.<h3>Conclusions</h3>Altogether, our results demonstrate that an increased expression of AR-A may have a role in protecting against ARpolyQ aggregation and toxicity. These findings suggest that AR-A could represent a promising avenue for developing an alternative therapeutic strategy that warrants further investigation.","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"383 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-20DOI: 10.1016/j.jare.2026.01.052
Aleksandra Wilk, Natalia Wilkosz, Marzena Rugiel, Marta Saluga, Kamil Kawon, Tetiana Stepanenko, Katarzyna Bulat, Aleksandra Wajda, Michał Szuwarzynski, Anna Zajaczkowska, Anna Morgunowicz, Grzegorz Chodaczek, Víctor Navarro-Esteve, David Perez-Guaita, Joanna Chwiej, Katarzyna M. Marzec
{"title":"Next-generation diabetes diagnostics: spectrochemical staging of red blood cells using vibrational spectroscopy","authors":"Aleksandra Wilk, Natalia Wilkosz, Marzena Rugiel, Marta Saluga, Kamil Kawon, Tetiana Stepanenko, Katarzyna Bulat, Aleksandra Wajda, Michał Szuwarzynski, Anna Zajaczkowska, Anna Morgunowicz, Grzegorz Chodaczek, Víctor Navarro-Esteve, David Perez-Guaita, Joanna Chwiej, Katarzyna M. Marzec","doi":"10.1016/j.jare.2026.01.052","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.052","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"54 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-19DOI: 10.1016/j.jare.2026.01.050
Junaid Iqbal, Hui-Xuan Wu, Yan-Xuan Wu, Hong-Li Jiang, Long Li, Xuan-Yu Zhou, Yan-Hong Bu, Hou-De Zhou
{"title":"MetsObesity: a novel classification system for predicting 15-year cardiovascular risk in the UK Biobank population","authors":"Junaid Iqbal, Hui-Xuan Wu, Yan-Xuan Wu, Hong-Li Jiang, Long Li, Xuan-Yu Zhou, Yan-Hong Bu, Hou-De Zhou","doi":"10.1016/j.jare.2026.01.050","DOIUrl":"https://doi.org/10.1016/j.jare.2026.01.050","url":null,"abstract":"","PeriodicalId":14952,"journal":{"name":"Journal of Advanced Research","volume":"21 1","pages":""},"PeriodicalIF":10.7,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146001283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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