FASEB bioAdvances最新文献_第5页

Retrotransposons in Bone and Joint Diseases. 骨关节疾病中的反转录转座子。

IF 2.4

FASEB bioAdvances Pub Date : 2026-05-18 eCollection Date: 2026-05-01 DOI: 10.1096/fba.2026-00044

Ye Liu, H Josh Jang, Tao Yang

{"title":"Retrotransposons in Bone and Joint Diseases.","authors":"Ye Liu, H Josh Jang, Tao Yang","doi":"10.1096/fba.2026-00044","DOIUrl":"10.1096/fba.2026-00044","url":null,"abstract":"Retrotransposons, including non-LTR elements such as LINEs and viral-derived endogenous retroviruses (ERVs), have long been dismissed as \"junk DNA\" and thought to be biochemically inert. However, emerging evidence suggests that the erosion of epigenetic control during aging and pathological states can lead to the awakening of these dormant genetic elements. Although the role of ERVs in cancer and neurodegeneration is increasingly recognized, their impact on musculoskeletal health has received little attention. This perspective review synthesizes recent and previous findings linking retrotransposon reactivation (particularly ERVs) to osteoarthritis (OA), rheumatoid arthritis (RA), and potentially osteoporosis. We discuss the epigenetic mechanisms that typically silence ERVs in musculoskeletal tissues, how these mechanisms fail in disease, and how the resulting reactivation leads to viral and molecular mimicry. These processes trigger both innate and adaptive immune responses, as well as cellular senescence. Finally, we highlight the therapeutic potential of targeting retrotransposon dysregulation, including its encoded proteins and nucleic acid-sensing pathways to treat chronic bone and joint disorders.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 ","pages":"e70115"},"PeriodicalIF":2.4,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13181433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enhancing the Therapeutic Profile of Dapagliflozin: Chitosan Nanoparticle Encapsulation for Intestinal Applications. 提高达格列净的治疗效果：肠用壳聚糖纳米颗粒包封。

IF 2.4

FASEB bioAdvances Pub Date : 2026-05-14 eCollection Date: 2026-05-01 DOI: 10.1096/fba.2026-00050

Agni Klonari, Antrea-Maria Athinodorou, Eirini Papanikolaou, Anastasia Skonta, Myrto G Bellou, Lampros Lakkas, Konstantinos I Tsamis, Georgios S Markopoulos, Haralambos Stamatis, Petros Bozidis, Dimitrios Peschos, Yannis V Simos

{"title":"Enhancing the Therapeutic Profile of Dapagliflozin: Chitosan Nanoparticle Encapsulation for Intestinal Applications.","authors":"Agni Klonari, Antrea-Maria Athinodorou, Eirini Papanikolaou, Anastasia Skonta, Myrto G Bellou, Lampros Lakkas, Konstantinos I Tsamis, Georgios S Markopoulos, Haralambos Stamatis, Petros Bozidis, Dimitrios Peschos, Yannis V Simos","doi":"10.1096/fba.2026-00050","DOIUrl":"10.1096/fba.2026-00050","url":null,"abstract":"Dapagliflozin is a sodium-glucose cotransporter-2 (SGLT-2) inhibitor primarily used to treat type 2 diabetes by lowering blood glucose levels. In addition to its antidiabetic action, it has demonstrated cardioprotective and renoprotective effects, along with antioxidant, anti-inflammatory, and anticancer activities. Encapsulation of dapagliflozin in nanocarriers represents an innovative strategy to improve existing therapies and develop targeted treatments. Such formulations can enhance solubility and stability, improve epithelial permeability and bioavailability, and reduce potential side effects. This study investigates the cellular and molecular effects of dapagliflozin encapsulated in chitosan nanoparticles, focusing on colon (Caco-2) cells. The findings showed that free dapagliflozin significantly reduced cell viability, whereas the encapsulated form preserved high cell viability. In addition, the encapsulated drug effectively reduced reactive oxygen species levels, maintaining its antioxidant activity. Free dapagliflozin did not increase the expression of Nrf2, NFκB, or HO-1 signaling pathways. In contrast, encapsulation in chitosan nanoparticles resulted in increased expression of all three pathways, indicating potential regulatory involvement in these signaling mechanisms.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 ","pages":"e70116"},"PeriodicalIF":2.4,"publicationDate":"2026-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13173360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 2

FASEB bioAdvances Pub Date : 2026-05-14

引用次数: 0

Synaptic Inhibition in the Accessory Olfactory Bulb Regulates Pheromone Location Learning and Memory. 副嗅球突触抑制调节信息素位置学习和记忆。

IF 2.4

FASEB bioAdvances Pub Date : 2026-05-13 eCollection Date: 2026-05-01 DOI: 10.1096/fba.2025-00332

Shruti D Marathe, Sanyukta Pandey, Devesh Rawat, Susobhan Das, Nixon M Abraham

{"title":"Synaptic Inhibition in the Accessory Olfactory Bulb Regulates Pheromone Location Learning and Memory.","authors":"Shruti D Marathe, Sanyukta Pandey, Devesh Rawat, Susobhan Das, Nixon M Abraham","doi":"10.1096/fba.2025-00332","DOIUrl":"10.1096/fba.2025-00332","url":null,"abstract":"Pheromone signaling is pivotal in driving the social and reproductive behaviors of rodents. Learning and memorizing the pheromone locations involve olfactory subsystems. To study the neural basis of this behavior, we trained female heterozygous knockouts of GluA2 (AMPAR subunit) and NR1 (NMDAR subunit), targeting GAD65 interneuron population, in a pheromone location learning assay. We observed impaired memory of pheromone locations on early and late recall periods, pointing towards the possible role of ionotropic glutamate receptors (iGluRs) and thereby the synaptic inhibition in pheromone location learning. Correlated changes were observed in the expression levels of activity-regulated cytoskeletal (Arc) protein, which is critical for memory consolidation, in the associated brain areas. Further, to probe the involvement of the main and accessory olfactory bulbs (MOB and AOB) in pheromone location learning, we knocked out GluA2 and NR1 from MOB and/or AOB neuronal circuits by stereotaxic injection of Cre-dependent AAV5 viral particles. Perturbing the inhibitory circuits of MOB and AOB or AOB-alone resulted in pheromone location memory deficits. These results confirm the role of iGluRs and the synaptic inhibition exerted by the interneuron network of AOB in regulating learning and memory of pheromone locations.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 ","pages":"e70110"},"PeriodicalIF":2.4,"publicationDate":"2026-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13172612/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147962738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 2

FASEB bioAdvances Pub Date : 2026-05-13

引用次数: 0

APOE4 Drives Sex- and Diet-Dependent Effects on AD-Like Pathology, Cognition, and Mitochondrial Function. APOE4驱动ad样病理、认知和线粒体功能的性别和饮食依赖效应。

IF 2.4

FASEB bioAdvances Pub Date : 2026-05-06 eCollection Date: 2026-05-01 DOI: 10.1096/fba.2026-00121

Chelsea N Johnson, Colton R Lysaker, Xin Cao, Vivien Csikos, Frederick Boakye, Paul J Kueck, Edziu Franczak, Paige C Geiger, Jill K Morris, John P Thyfault, Heather M Wilkins

{"title":"APOE4 Drives Sex- and Diet-Dependent Effects on AD-Like Pathology, Cognition, and Mitochondrial Function.","authors":"Chelsea N Johnson, Colton R Lysaker, Xin Cao, Vivien Csikos, Frederick Boakye, Paul J Kueck, Edziu Franczak, Paige C Geiger, Jill K Morris, John P Thyfault, Heather M Wilkins","doi":"10.1096/fba.2026-00121","DOIUrl":"10.1096/fba.2026-00121","url":null,"abstract":"Apolipoprotein E4 (APOE4) is the strongest genetic risk factor for Alzheimer's disease (AD), yet it's unclear how this allele promotes disease. While factors like diet and sex may modify AD susceptibility in APOE4 carriers, the interaction between these factors is poorly understood. Here, we sought to determine if APOE4, sex, and diet interact to influence AD related outcomes in mice. Male and female APOE3 and APOE4 targeted replacement (TR) mice were fed a low-fat diet or high-fat diet from 4 to 8 months old. Serum neurodegenerative disease biomarkers, brain amyloid beta (Aβ), APOE, and tau, learning and memory, hippocampal mitochondrial function and proteomics data were collected. Serum GFAP and NfL were unaffected by APOE4, while HFD was associated with greater serum NfL and GFAP. Whole brain Aβ was significantly altered by sex, diet, and genotype. There was a main effect of genotype on levels of brain APOE with levels being lower in APOE4 mice. APOE4 TR mice also exhibited impaired learning before diet. Proteomic analysis revealed that APOE4 exerts diet- and sex-dependent effects on mitochondrial pathways. This included downregulation of pyruvate metabolism in HFD males and oxidative phosphorylation in HFD females. Basal respiration was lower in APOE4 versus APOE3 TR females. We provide novel evidence that APOE4 may drive early sex- and diet-dependent reductions in pathways that support brain mitochondrial energy metabolism.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 ","pages":"e70113"},"PeriodicalIF":2.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13146351/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 2

FASEB bioAdvances Pub Date : 2026-05-06

引用次数: 0

IF 2

FASEB bioAdvances Pub Date : 2026-05-02

引用次数: 0

MicroRNA 15a and 16 Regulate Proteostasis in Non-Small Cell Lung Cancer. MicroRNA 15a和16在非小细胞肺癌中调节蛋白平衡。

IF 2.4

FASEB bioAdvances Pub Date : 2026-05-02 eCollection Date: 2026-05-01 DOI: 10.1096/fba.2026-00075

Patrick J Ryan, Bethany C Guerra, Peter Nghiem, Steven E Riechman, Mariana Janini Gomes, James D Fluckey

引用次数: 0

Network Analysis Identifies Microsomal Glutathione S-Transferase as a Potential Regulator of Oxidative Stress and Proteasome Dysfunction in Human Osteoarthritic Menisci. 网络分析确定微粒体谷胱甘肽s -转移酶是人类骨关节炎半月板氧化应激和蛋白酶体功能障碍的潜在调节因子。

IF 2.4

FASEB bioAdvances Pub Date : 2026-04-27 eCollection Date: 2026-05-01 DOI: 10.1096/fba.2025-00302

Xinjie Wu, Amina Hamzatova, Cecilia Aulin, Wei Sun, Andre Struglics, David A Hart, Paul W Ackermann, Aisha S Ahmed

{"title":"Network Analysis Identifies Microsomal Glutathione S-Transferase as a Potential Regulator of Oxidative Stress and Proteasome Dysfunction in Human Osteoarthritic Menisci.","authors":"Xinjie Wu, Amina Hamzatova, Cecilia Aulin, Wei Sun, Andre Struglics, David A Hart, Paul W Ackermann, Aisha S Ahmed","doi":"10.1096/fba.2025-00302","DOIUrl":"10.1096/fba.2025-00302","url":null,"abstract":"Osteoarthritis (OA)-related meniscal degeneration involves complex interactions between oxidative stress and proteasomal dysfunction. However, the molecular drivers of regional meniscal vulnerability remain poorly defined. This study integrated multiple transcriptomic datasets from OA and control menisci to identify functional networks and hub genes by using weighted gene co-expression network analysis. Human meniscal tissues from medial and lateral compartments were harvested during total knee arthroplasty and subjected to western blot analysis. In vitro assays on the basis of human chondrocytes were exposed to lipopolysaccharide or the proteasome inhibitor MG132 (carbobenzoxy-l-leucyl-l-leucyl-l-leucinal) to evaluate the stimulus-specific regulation of identified network and hub genes. Weighted gene co-expression network analysis revealed microsomal glutathione S-transferase (MGST1) as the hub gene within a module enriched for ubiquitination and proteasome activity. Experimental validation in human meniscal tissues demonstrated pronounced upregulation of MGST1, ubiquitin-conjugating enzyme E2 N (UBE2N), and proteasome activator complex subunit alpha (PSMA) in mechanically overloaded medial compartments compared to lateral regions. In vitro studies demonstrated stimulus-specific modulation: lipopolysaccharide-induced inflammatory stress upregulated MGST1, whereas proteasome inhibition via MG132 led to its downregulation. These findings highlight a dynamic interplay between redox adaptation and proteostasis, where chronic mechanical stress drives MGST1-mediated antioxidant responses and compensatory ubiquitination. Together, these results suggest that joint tissues dynamically adapt to mechanical and inflammatory challenges by modulating oxidative stress defenses and protein quality control mechanisms, processes central to OA pathophysiology.","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 ","pages":"e70101"},"PeriodicalIF":2.4,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13111912/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147766601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0