FASEB bioAdvancesPub Date : 2026-05-27eCollection Date: 2026-06-01DOI: 10.1096/fba.2025-00290
Ting Zhang, Jialong Qian, Li Zhu, Zhihua Zhou, Xin Wang, Yan Liang, Luyu Wang, Chunsheng Zhang, Ren Bu, Hong Liu, Changjin Xu, Gang Li
{"title":"Lanthanum Chloride in Vascular Calcification: Effects on Nano-Hydroxyapatite and PPARγ/Wnt/β-Catenin.","authors":"Ting Zhang, Jialong Qian, Li Zhu, Zhihua Zhou, Xin Wang, Yan Liang, Luyu Wang, Chunsheng Zhang, Ren Bu, Hong Liu, Changjin Xu, Gang Li","doi":"10.1096/fba.2025-00290","DOIUrl":"10.1096/fba.2025-00290","url":null,"abstract":"<p><p>This study investigated the effects of lanthanum chloride on vascular calcification associated with chronic kidney disease (CKD) and the mechanisms involved in changes in nano-hydroxyapatite. Vascular calcification was induced in CKD rats using a high-phosphorus diet and adenine. Human vascular smooth muscle cells (hVSMCs) were calcified in vitro using sodium β-glycerophosphate (β-GP) and saturated nano-hydroxyapatite. The effects of lanthanum chloride were evaluated using various analytical methods, including serum biochemistry, EVG, Vonkossa staining, Alizarin Red staining, Ca<sup>2+</sup> detection, Western blotting, and transmission electron microscopy. The results showed that lanthanum chloride effectively inhibited calcium deposition and osteogenic differentiation, a finding confirmed in both in vivo and in vitro experiments. Scanning electron microscopy (SEM) analysis of the calcified crystals revealed altered crystal morphology and a decreased calcium-to-phosphorus ratio after treatment. X-ray diffraction confirmed that these crystals were hydroxyapatite. Proteomic analysis indicated that the effects of lanthanum chloride were associated with apoptosis and the PPARγ/Wnt/β-catenin signaling pathway. Lanthanum chloride inhibits apoptosis in human vascular smooth muscle cells (hVSMCs), while PPARγ inhibitors can reverse this effect. In summary, lanthanum chloride may significantly reduce vascular calcification in patients with CKD by altering the morphology of hydroxyapatite and activating PPARγ to inhibit apoptosis.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 6","pages":"e70118"},"PeriodicalIF":2.4,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13238516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197966","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}
FASEB bioAdvancesPub Date : 2026-05-21eCollection Date: 2026-05-01DOI: 10.1096/fba.2025-00120
Katelyn Rygel, Kasey Gillespie, Kristy Welshhans
{"title":"Conditional Knockout of Paxillin in Mouse Cortical Pyramidal Neurons Does Not Impair Axon Outgrowth or Corpus Callosum Size.","authors":"Katelyn Rygel, Kasey Gillespie, Kristy Welshhans","doi":"10.1096/fba.2025-00120","DOIUrl":"10.1096/fba.2025-00120","url":null,"abstract":"<p><p>Axon growth is an essential cellular process during neural development, and its dysregulation contributes to numerous neurodevelopmental disorders. During axon growth, extracellular signals direct neurons to extend projections that connect with their synaptic targets. Paxillin is a key member of adhesion sites that control motility by linking the intracellular actin cytoskeleton to the extracellular matrix. Paxillin also binds to the cytoskeletal protein, tubulin. However, little is known about the role of adhesion proteins in neurons. Here, we use conditional paxillin knockout mice to investigate how the loss of paxillin in pyramidal cortical neurons affects developing neuron morphology. Surprisingly, loss of paxillin in pyramidal cortical neurons caused no change in axon length or soma area between control (<i>Pxn</i> <sup><i>F/F</i></sup> ) and conditional paxillin knockout (<i>Pxn</i> <sup><i>F/F; Emx1-Cre</i></sup> ) mice at basal conditions. Following brain-derived neurotrophic factor stimulation, the loss of paxillin resulted in no change in soma area or axonal β-tubulin levels, but did result in a significant increase in axon length, as compared to control. Finally, the corpus callosum size was not significantly different between <i>Pxn</i> <sup><i>F/F</i></sup> and <i>Pxn</i> <sup><i>F/F; Emx1-Cre</i></sup> animals. In summary, these data suggest that paxillin is not required for axonal growth during neural development.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 5","pages":"e70120"},"PeriodicalIF":2.4,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240227/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197960","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}
FASEB bioAdvancesPub Date : 2026-05-21eCollection Date: 2026-05-01DOI: 10.1096/fba.2026-00055
David M Cauvi, Dennis Hawisher, Ikenna Aniegbuna, Julia Derunes, Antonio De Maio
{"title":"Altered Expression of Dual-Specificity Phosphatases in Macrophages Exposed to Lipid Nanoparticles.","authors":"David M Cauvi, Dennis Hawisher, Ikenna Aniegbuna, Julia Derunes, Antonio De Maio","doi":"10.1096/fba.2026-00055","DOIUrl":"10.1096/fba.2026-00055","url":null,"abstract":"<p><p>Acute inflammation is rapidly elicited in response to pathogens, toxins, and other cellular components that interact with immune cells through surface receptors, activating signaling cascades that lead to the expression of molecules aimed at neutralizing the pathogen and stimulating other cells to begin the healing process. However, a robust inflammatory response can be detrimental if it is prolonged. Therefore, the inflammatory response must be tightly regulated to prevent secondary harmful effects. In this regard, cells contain molecular switches that turn the inflammatory process on and off. The rapid response to infection and injury is mediated by constitutive cellular proteins that are activated by posttranslational modifications, of which phosphorylation is the most common. Consequently, compensatory mechanisms often involve the removal of phosphate groups by phosphatases. A family of phosphatases known as dual-specificity phosphatases (DUSPs), which dephosphorylate both tyrosine and serine/threonine residues, has emerged as a critical mechanism for controlling inflammation. To date, more than 40 DUSPs have been identified in the human genome. Despite their shared catalytic specificity, they appear to participate in diverse cellular processes and are expressed in response to various stimuli. In the present study, we detected a distinctive pattern of DUSP expression in response to exogenous lipid nanoparticles and toxins. These observations suggest that the transcriptional regulation of several DUSPs may be coordinated. They also raise the possibility that DUSPs may play redundant roles to ensure the proper resolution of the inflammatory response.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 5","pages":"e70117"},"PeriodicalIF":2.4,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13240192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148197939","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}
FASEB bioAdvancesPub Date : 2026-05-18eCollection Date: 2026-05-01DOI: 10.1096/fba.2025-00294
Shiyin Chen, Jiawei Mao, Lin Xu, Linbei Lu, Yajuan Hao
{"title":"Interplay of RNA m<sup>6</sup>A/m<sup>1</sup>A/m<sup>5</sup>C/m<sup>7</sup>G/ψ Regulators Predicting the Prognosis of Pancreatic Cancer.","authors":"Shiyin Chen, Jiawei Mao, Lin Xu, Linbei Lu, Yajuan Hao","doi":"10.1096/fba.2025-00294","DOIUrl":"10.1096/fba.2025-00294","url":null,"abstract":"<p><p>N<sup>6</sup>-methyladenosine (m<sup>6</sup>A), N<sup>1</sup>-methyladenosine (m<sup>1</sup>A), 5-methylcytosine (m<sup>5</sup>C), 7-methylguanosine (m<sup>7</sup>G), and pseudouridine (ψ) have been identified as the most prevalent epitranscriptomic modifications on eukaryotic RNAs. It is not yet clear about the comprehensive analysis of RNA m<sup>6</sup>A/m<sup>1</sup>A/m<sup>5</sup>C/m<sup>7</sup>G/ψ in pancreatic cancer, one of the most aggressive malignancies all over the whole world. We have identified that most of the RNA m<sup>6</sup>A/m<sup>1</sup>A/m<sup>5</sup>C/m<sup>7</sup>G/ψ regulators are highly expressed in pancreatic cancer. Copy number variations (CNVs) or the methylation level of some genes are associated with their mRNA expression and affect the overall survival of patients. The expression of most of the regulators is positively related to the immune cell infiltration of the tumor microenvironment (TME). Furthermore, the regulators or TME-infiltrated cells are associated with tumor heterogeneity or tumor stemness. According to the similarity of TME-infiltrating cells, we classify patients into two different clusters, and we find that patients in cluster 1 (C1) are at high risk, have worse prognoses, and are more sensitive to drug treatment than cluster 2 (C2). Three machine learning algorithms, least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random forest (RF), show that some regulators have a strong correlation with survival. Our study has revealed the potential roles of regulators in pancreatic cancer, which may provide new insights into the field of pancreatic cancer research.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"8 ","pages":"e70121"},"PeriodicalIF":2.4,"publicationDate":"2026-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13182732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147971249","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}