Biochimica et biophysica acta. Molecular basis of disease最新文献_第10页

KIAA1199/CEMIP knockdown attenuates cardiac remodeling post myocardial infarction by activating TSP4 pathway in mice KIAA1199/CEMIP 基因敲除可通过激活小鼠 TSP4 通路减轻心肌梗死后的心脏重塑。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-08-20 DOI: 10.1016/j.bbadis.2024.167473

{"title":"KIAA1199/CEMIP knockdown attenuates cardiac remodeling post myocardial infarction by activating TSP4 pathway in mice","authors":"","doi":"10.1016/j.bbadis.2024.167473","DOIUrl":"10.1016/j.bbadis.2024.167473","url":null,"abstract":"<div><h3>Background</h3><p>Excessive activation of cardiac fibroblasts (CFs) significantly contributes to adverse cardiac remodeling post-myocardial infarction (MI). CEMIP, initially recognized as an enzyme involved in hyaluronic acid (HA) degradation, has also been implicated in the activation of pulmonary fibroblasts. Nevertheless, the role and mechanism of CEMIP in adverse cardiac remodeling following MI remain largely unexplored.</p></div><div><h3>Materials and methods</h3><p>RNA sequencing (RNA-seq) was performed on cardiac tissue harvested from the infarct/peri-infarct region of mice 28 days post-MI. RNA-seq was conducted on primary cardiac fibroblasts (CFs) transfected with adenovirus overexpressing CEMIP. Adeno-associated virus serotype 9 (AAV9) was engineered for in vivo CEMIP knockdown to elucidate its impact on cardiac remodeling. Immunoprecipitation coupled with mass spectrometry (IP-MS) and co-immunoprecipitation (co-IP) were employed to elucidate the mechanism by which CEMIP affected cardiac remodeling.</p></div><div><h3>Key findings</h3><p>RNA-seq of fibrotic heart tissue at day 28 post-MI revealed a significant upregulation of CEMIP. In vitro, CEMIP facilitated the activation of cardiac fibroblasts. In vivo, knockdown of CEMIP markedly reduced cardiac fibrosis and improved cardiac function post-MI. IP-MS and co-immunoprecipitation (co-IP) confirmed that CEMIP interacted with TSP4 through the G8 domain. Further experiments confirmed that CEMIP promoted TSP4 degradation in lysosomes in an ACTN4-dependent manner, thereby activating the FAK signaling pathway.</p></div><div><h3>Significance</h3><p>Our findings suggest that CEMIP significantly contributes to cardiac remodeling post-MI, which might be a novel approach for treating cardiac fibrosis following MI.</p></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142037995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to paper entitled “Seronegative patients with primary Sjogren's syndrome and non-pSS sicca test positive for anti-SSA/Ro52 and -Ro60 in saliva” [Published in: BBA – Mol. Basis Dis. Volume 1870, Issue 5, June 2024, 167168] 题为 "血清阴性的原发性 Sjogren's 综合征和非 SSS sicca 患者唾液中抗 SSA/Ro52 和 -Ro60 检测呈阳性 "的论文更正[发表于：BBA - Mol. Basis Dis. 第 1870 卷第 5 期，2024 年 6 月，167168]。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-08-20 DOI: 10.1016/j.bbadis.2024.167474

引用次数: 0

Necroptosis in alveolar epithelial cells drives lung inflammation and injury caused by SARS-CoV-2 infection 肺泡上皮细胞的坏死推动了 SARS-CoV-2 感染引起的肺部炎症和损伤。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-08-20 DOI: 10.1016/j.bbadis.2024.167472

引用次数: 0

Sec13 promotes glycolysis by inhibiting Ubqln1 mediated Pgm1 ubiquitination in ALI 在 ALI 中，Sec13 通过抑制 Ubqln1 介导的 Pgm1 泛素化促进糖酵解。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-08-17 DOI: 10.1016/j.bbadis.2024.167475

{"title":"Sec13 promotes glycolysis by inhibiting Ubqln1 mediated Pgm1 ubiquitination in ALI","authors":"","doi":"10.1016/j.bbadis.2024.167475","DOIUrl":"10.1016/j.bbadis.2024.167475","url":null,"abstract":"<div><p>Acute lung injury (ALI) is a severe lung damage characterized by acute hypoxemia, increased pulmonary vascular permeability, and inflammatory reactions. Despite current treatments, mortality from ALI remains high. This study found that Sec13 is highly expressed in ALI and regulates it by glycolysis and epithelial-mesenchymal transition (EMT). In an ALI mouse model and cell model, Sec13 expression increased, accompanied by enhanced glycolysis, EMT, and inflammation. Sec13 knockdown suppressed these effects, alleviating ALI. Sec13 forms a protein complex with Pgm1, an enzyme regulating glucose-6-phosphate (G6P) production, and Ubqln1, an ubiquitin ligase. Sec13 inhibits Ubqln1-mediated Pgm1 ubiquitination, thereby stabilizing Pgm1. In ALI, Pgm1 binding to Sec13 increased but binding to Ubqln1 decreased. Sec13 knockdown decreased lactate, G6P, EMT markers, and inflammatory cytokines. Pgm1 knockdown produced similar effects. Ubqln1 overexpression suppressed inflammation but decreased Pgm1 expression. In conclusion, Sec13 plays a key role in ALI by inhibiting Ubqln1-mediated Pgm1 ubiquitination, affecting glycolysis and EMT. Sec13 and Pgm1 may be new targets for treating ALI.</p></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanism of multifunctional adaptor protein SHARPIN regulating myocardial fibrosis and how SNP mutation affect the prognosis of myocardial infarction 多功能适配蛋白SHARPIN调控心肌纤维化的机制及SNP突变对心肌梗死预后的影响

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-08-17 DOI: 10.1016/j.bbadis.2024.167467

{"title":"Mechanism of multifunctional adaptor protein SHARPIN regulating myocardial fibrosis and how SNP mutation affect the prognosis of myocardial infarction","authors":"","doi":"10.1016/j.bbadis.2024.167467","DOIUrl":"10.1016/j.bbadis.2024.167467","url":null,"abstract":"<div><p>Myocardial fibrosis (MF) is characterized by the excessive deposition of extracellular matrix within the heart, often following a cardiovascular insult. SHARPIN, a protein implicated in fibrosis, has emerged as a potential therapeutic target. This study aimed to elucidate the molecular mechanisms of SHARPIN in MF and to investigate the influence of its single nucleotide polymorphism (SNP), rs117299156, on myocardial infarction (MI) patients. A mouse model of Angiotensin II (AngII)-induced MF was established in SHARPIN heterozygous (SHARPIN+/−) and wild-type mice. Adult mouse cardiac fibroblasts (CFs) were isolated and subjected to adenovirus-encapsulated SHARPIN short hairpin RNA (shRNA) infection. Transcriptomic analysis was performed on CFs from SHARPIN+/− and wild-type (WT) mice, complemented by single-cell sequencing data from human cardiac tissues. Additionally, the association between the rs117299156 mutation and cardiovascular events in MI patients was assessed. Our findings indicate that SHARPIN is predominantly expressed in CFs and is upregulated in fibrotic myocardium. Partial knockdown of SHARPIN in murine hearts mitigated AngII-induced cardiac dysfunction and MF. Furthermore, reduced SHARPIN expression in CFs attenuated TGF-β1-induced collagen synthesis, cell proliferation, and myofibroblast transformation. Notably, MI patients carrying the rs117299156_C allele exhibited a reduced incidence of stroke events compared to those without the mutation.</p></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0925443924004605/pdfft?md5=277aebcb87aa9f01c75b9402edf76a35&pid=1-s2.0-S0925443924004605-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Accumulation of damaged mitochondria in aging astrocytes due to mitophagy dysfunction: Implications for susceptibility to mitochondrial stress 有丝分裂吞噬功能障碍导致衰老星形胶质细胞中受损线粒体的积累：对线粒体压力易感性的影响

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-08-15 DOI: 10.1016/j.bbadis.2024.167470

{"title":"Accumulation of damaged mitochondria in aging astrocytes due to mitophagy dysfunction: Implications for susceptibility to mitochondrial stress","authors":"","doi":"10.1016/j.bbadis.2024.167470","DOIUrl":"10.1016/j.bbadis.2024.167470","url":null,"abstract":"<div><p>Aging disrupts brain function, leading to cognitive decline and neurodegenerative diseases. Senescent astrocytes, a hallmark of aging, contribute to this process through unknown mechanisms. This study investigates how senescence impacts astrocytic mitochondrial dynamics, which are critical for brain health. Our research, conducted using aged mouse brains, represents the first evidence of morphologically damaged mitochondria in astrocytes, along with functional alterations in mitochondrial respiration. <em>In vitro</em> experiments revealed that senescent astrocytes exhibit an increase in mitochondrial fragmentation and impaired mitophagy. Concurrently, there was an upregulation of mitochondrial biogenesis, indicating a compensatory response to mitochondrial damage. Importantly, these senescent astrocytes were more susceptible to mitochondrial stress, a vulnerability reversed by rapamycin treatment. These findings suggest a potential link between senescence, impaired mitochondrial quality control, and increased susceptibility to mitochondrial stress in astrocytes. Overall, our study highlights the importance of addressing mitochondrial dysfunction and senescence-related changes in astrocytes as a promising approach for developing therapies to counter age-related neurodegeneration and improve brain health.</p></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impaired IL-27 signaling aggravates macrophage senescence and sensitizes premature ovarian insufficiency induction by high-fat diet IL-27信号受损会加剧巨噬细胞衰老，并使高脂饮食诱发的卵巢早衰变得敏感。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-08-15 DOI: 10.1016/j.bbadis.2024.167469

{"title":"Impaired IL-27 signaling aggravates macrophage senescence and sensitizes premature ovarian insufficiency induction by high-fat diet","authors":"","doi":"10.1016/j.bbadis.2024.167469","DOIUrl":"10.1016/j.bbadis.2024.167469","url":null,"abstract":"<div><p>Premature ovarian insufficiency (POI) critically affects female reproductive health, with obesity being a significant and recognized risk factor. Interleukin-27 (IL-27), known for its role in immune modulation and inflammation, has garnered attention in metabolic syndrome research. Nonetheless, the role of these immunometabolic factors on the initiation of POI remains to be unraveled. Our investigation delves into the influence of impaired IL-27 signaling on POI induction, particularly under the challenge of a high-fat diet (HFD). We analyzed patients' serum profiles and established a correlation of increased serum triglycerides with decreased IL-27 levels in POI cases. Experiments on C57BL/6 mice lacking the IL-27 receptor alpha (<em>Il27ra</em><sup>−/−</sup>) revealed that when subjected to HFD, these mice developed hallmark POI symptoms. This includes escalated lipid deposition in both liver and ovarian tissues, increased ovarian macrophages cellular aging, and diminished follicle count, all pointing to compromised ovarian function. These findings unveil a novel pathway wherein impaired IL-27 signaling potentiates the onset of POI in the presence of HFD. Understanding the intricate interplay between IL-27, metabolic alterations, and immune dysregulation sheds light on potential therapeutic avenues for managing POI, offering hope for improved reproductive health outcomes.</p></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oleanonic acid ameliorates mutant Aβ precursor protein-induced oxidative stress, autophagy deficits, ferroptosis, mitochondrial damage, and ER stress in vitro 齐墩果酸可改善突变体 Aβ 前体蛋白诱导的体外氧化应激、自噬缺陷、铁变态反应、线粒体损伤和 ER 应激。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-08-10 DOI: 10.1016/j.bbadis.2024.167459

{"title":"Oleanonic acid ameliorates mutant Aβ precursor protein-induced oxidative stress, autophagy deficits, ferroptosis, mitochondrial damage, and ER stress in vitro","authors":"","doi":"10.1016/j.bbadis.2024.167459","DOIUrl":"10.1016/j.bbadis.2024.167459","url":null,"abstract":"<div><p>Accumulation in the brain of amyloid-β (Aβ), derived from cleavage of Aβ precursor protein (APP), is a hallmark of Alzheimer's disease (AD). Oleanonic acid (OA), a phytochemical from several plants, has proven anti-inflammatory effects, but its role in AD remains unknown. Here we found that OA reduced APP expression and inhibited oxidative stress <em>via</em> Nrf2/HO-1 signaling in SH-SY5Y neuroblastoma cells stably overexpressing APP. OA suppressed phosphorylated mTOR but increased autophagy markers ATG5 and LC3-II. Moreover, OA rescued ferroptosis-related factors GPX4, NCOA, and COX2 and ER stress markers GRP78, CHOP, and three main induction pathways of ER stress including IRE1/XBP1s, PERK/EIF2α, and ATF6. OA alleviated mitochondrial damage through MFN1, MFN2, OPA1, FIS1, and DRP1. Furthermore, OA upregulated GDF11 expression and downregulated phosphorylation of ErbB4 and TrkB without affecting BDNF levels. Thus, OA might protect neurons from APP-induced neurotoxicity by inhibiting oxidative stress, autophagy deficits, ferroptosis, mitochondrial damage, and ER stress in AD, providing a new promising therapeutic strategy in patients with AD.</p></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multiple myeloma exosomal miRNAs suppress cGAS-STING antiviral immunity 多发性骨髓瘤外泌体miRNA抑制cGAS-STING抗病毒免疫力

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-08-10 DOI: 10.1016/j.bbadis.2024.167457

{"title":"Multiple myeloma exosomal miRNAs suppress cGAS-STING antiviral immunity","authors":"","doi":"10.1016/j.bbadis.2024.167457","DOIUrl":"10.1016/j.bbadis.2024.167457","url":null,"abstract":"<div><p>DNA virus infection is a significant cause of morbidity and mortality in patients with multiple myeloma (MM). Monocyte dysfunction in MM patients plays a central role in infectious complications, but the precise molecular mechanism underlying the reduced resistance of monocytes to viruses in MM patients remains to be elucidated. Here, we found that MM cells were able to transfer microRNAs (miRNAs) to host monocytes/macrophages via MM cell-derived exosomes, resulting in the inhibition of innate antiviral immune responses. The screening of miRNAs enriched in exosomes derived from the bone marrow (BM) of MM patients revealed five miRNAs that negatively regulate the cGAS-STING antiviral immune response. Notably, silencing these miRNAs with antagomiRs in MM-bearing C57BL/KaLwRijHsd mice markedly reduced viral replication. These findings identify a novel mechanism whereby MM cells possess the capacity to inhibit the innate immune response of the host, thereby rendering patients susceptible to viral infection. Consequently, targeting the aberrant expression patterns of characteristic miRNAs in MM patients is a promising avenue for therapeutic intervention. Considering the miRNA score and relevant clinical factors, we formulated a practical and efficient model for the optimal assessment of susceptibility to DNA viral infection in patients with MM.</p></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Additional statin treatment enhances the efficacy of HER2 blockade and improves prognosis in Rac1-high/HER2-positive breast cancer 额外的他汀类药物治疗可增强 HER2 阻断剂的疗效，并改善 Rac1 高/HER2 阳性乳腺癌患者的预后。

IF 4.2 2区生物学

Biochimica et biophysica acta. Molecular basis of disease Pub Date : 2024-08-10 DOI: 10.1016/j.bbadis.2024.167458

{"title":"Additional statin treatment enhances the efficacy of HER2 blockade and improves prognosis in Rac1-high/HER2-positive breast cancer","authors":"","doi":"10.1016/j.bbadis.2024.167458","DOIUrl":"10.1016/j.bbadis.2024.167458","url":null,"abstract":"<div><p>The prognosis of HER2-positive breast cancer (BC) has improved with the development of anti-HER2 therapies; however, the problem remains that there are still cases where anti-HER2 therapies do not respond well. We found that the expression of <em>SREBF2</em>, a master transcriptional factor in the mevalonate pathway, was correlated with <em>ERBB2</em> (HER2) expression and a poor prognosis in HER2-positive BC. The target gene expressions of <em>SREBF2</em> were associated with higher expression of <em>ERBB2</em> in HER2-positive BC cells. Statins, anti-hypercholesterolemia drugs that inhibit the mevalonate pathway, enhanced the efficacy of HER2-targeting agents with inducing apoptosis in a geranylgeranylation-dependent manner. Mechanistically, statins specifically inhibited membrane localization of Rac1, a target protein of geranylgeranylation, and suppressed the activation of HER2 downstreams AKT and ERK pathways. Consistently, retrospective analysis showed a longer recurrence-free survival in Rac1-high/HER2-positive BC patients treated with HER2-targeting agents with statins than without statins. Our findings thus suggest that Rac1 expression could be used as a biomarker to stratify HER2-positive BC patients that could benefit from dual blockade, <em>i.e.</em>, targeting HER2 with inhibition of geranylgeranylation of Rac1 using statins, thereby opening avenues for precision medicine in a new subset of Rac1-high/HER2-positive BC.</p></div>","PeriodicalId":8821,"journal":{"name":"Biochimica et biophysica acta. Molecular basis of disease","volume":null,"pages":null},"PeriodicalIF":4.2,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0925443924004514/pdfft?md5=177137c817c1317eca3765fd8e2aa7d3&pid=1-s2.0-S0925443924004514-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0