The FASEB Journal最新文献

Characterization of Novel Splicing Mutations and a Recurrent Deletion in COLQ Congenital Myasthenic Syndrome COLQ先天性肌无力综合征中新的剪接突变和复发性缺失的特征

IF 4.4 2区生物学

The FASEB Journal Pub Date : 2025-07-24 DOI: 10.1096/fj.202501466R

Yue Liu, Zhiguang Li, Yan Shi, Yongpei Xu, Zhiqiang Wang, Ning Wang, Kang Yang

{"title":"Characterization of Novel Splicing Mutations and a Recurrent Deletion in COLQ Congenital Myasthenic Syndrome","authors":"Yue Liu, Zhiguang Li, Yan Shi, Yongpei Xu, Zhiqiang Wang, Ning Wang, Kang Yang","doi":"10.1096/fj.202501466R","DOIUrl":"https://doi.org/10.1096/fj.202501466R","url":null,"abstract":"<div>\u0000 \u0000 Congenital myasthenic syndromes (CMS) represent a heterogeneous group of inherited disorders resulting from mutations in genes that encode proteins essential for neuromuscular transmission. Among these, mutations in the collagen-like tail subunit of asymmetric acetylcholinesterase (COLQ) define a distinct subtype of CMS, necessitating specialized diagnostic and therapeutic strategies to improve patient outcomes. Herein, we analyzed five COLQ-CMS patients, focusing on their clinical features, electrophysiologic findings, genetic characteristics, and therapeutic responses. All five patients exhibited limb-girdle weakness, and two experienced acute respiratory insufficiency. The age of symptom onset ranged from 2 to 33 years, with an average diagnostic delay of 14 years. All patients exhibited a decremental response to repetitive nerve stimulation and myopathic features on electromyography. Using whole exome sequencing (WES), complemented by PCR-based screening and reverse transcription-PCR (RT-PCR) to clarify deletion and splicing mutations, five variants of the COLQ gene were identified. These included two novel splicing mutations, c.393 + 3A>G and c.814_814 + 2dup, which caused aberrant splicing and premature truncation. Additionally, we found the deletion of exon 14–15 of the COLQ gene in three patients. All patients received salbutamol, leading to significant alleviation of primary symptoms during treatment. In conclusion, our findings offer critical insights into the clinical diagnosis and management of COLQ-CMS and highlight the importance of recognizing clinical heterogeneity, diagnostic delays, and early genetic diagnosis, which may ultimately assist clinicians in accurately identifying and effectively treating such conditions.\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688034","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

Acetate Administration Ameliorates Streptozotocin-Induced Hyperglycemia and Adipose Tissue Loss 醋酸盐管理改善链脲佐菌素引起的高血糖和脂肪组织损失

IF 4.4 2区生物学

The FASEB Journal Pub Date : 2025-07-24 DOI: 10.1096/fj.202500776R

Chi Zhang, Zhihong Wang, Ling Luo, Xiangpeng Liu, Zhihao Jia, Yong Zhang

{"title":"Acetate Administration Ameliorates Streptozotocin-Induced Hyperglycemia and Adipose Tissue Loss","authors":"Chi Zhang, Zhihong Wang, Ling Luo, Xiangpeng Liu, Zhihao Jia, Yong Zhang","doi":"10.1096/fj.202500776R","DOIUrl":"https://doi.org/10.1096/fj.202500776R","url":null,"abstract":"Short-chain fatty acids (SCFAs) are products of gut microbiota through fermentation of soluble fibers. Recent studies have highlighted the beneficial roles of SCFAs in various physiological and pathological conditions, including diabetes. In this study, we applied streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) to investigate the potential role of SCFAs in the pathogenesis of T1DM. We found a significant increase in the abundance of SCFA metabolism-related bacteria in mice surviving after 5 month post-STZ injection (mpi), coupled with improved hyperglycemia. While the expression levels of SCFA receptors, including Ffar2 and Ffar3, were significantly upregulated in the intestine of mice at 5 mpi. Consequently, we employed acetate and propionate gavage, which are two of the most dominant SCFAs in the gut and serum, to explore the physiological roles and molecular mechanisms of SCFAs in the progression of T1DM. We found that mice gavaged with acetate had reduced fasting blood glucose levels and less body weight loss. Body composition analysis indicated that acetate administration prevents STZ-induced white adipose tissue (WAT) loss. At the molecular level, acetate treatment increased the genes involved in fatty acid biosynthesis and decreased the protein levels related to lipid catabolism in WAT. In addition, the structure and diversity of gut microbiota were also recovered after acetate treatment in STZ-induced T1D mice. Taken together, our results indicate that acetate is beneficial for T1DM mice by ameliorating STZ-induced hyperglycemia and adipose loss.","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202500776R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687987","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

Kinesin KIF16B Participates in G2/M Transition and Microtubule Dynamics via Aurora A-PLK1 in Oocyte Meiosis Kinesin KIF16B通过Aurora A-PLK1参与卵母细胞减数分裂中G2/M转变和微管动力学

IF 4.4 2区生物学

The FASEB Journal Pub Date : 2025-07-24 DOI: 10.1096/fj.202501664R

Meng-Xiang Li, Kun-Huan Zhang, Yuan-Jing Zou, Ping-Shuang Lu, Shao-Chen Sun, Yue Wang

{"title":"Kinesin KIF16B Participates in G2/M Transition and Microtubule Dynamics via Aurora A-PLK1 in Oocyte Meiosis","authors":"Meng-Xiang Li, Kun-Huan Zhang, Yuan-Jing Zou, Ping-Shuang Lu, Shao-Chen Sun, Yue Wang","doi":"10.1096/fj.202501664R","DOIUrl":"https://doi.org/10.1096/fj.202501664R","url":null,"abstract":"<div>\u0000 \u0000 KIF16B is a member of the kinesin-3 family of motor proteins, which facilitates processes such as vesicle transport, microtubule dynamics, and organelle function during mitosis. In this study, we explored the role of KIF16B in meiosis. Our findings indicate that KIF16B is involved in the meiotic G2–M transition and spindle assembly in oocytes. KIF16B was consistently expressed throughout the meiotic cell cycle of mouse oocytes. After the occurrence of germinal vesicle breakdown, KIF16B became concentrated on microtubules. The exhaustion of KIF16B induced the impairment of meiotic cell cycle progression, which was due to the inactivation of CDK1 and the reduction in the level of cyclin B1, consequently resulting in the failure of germinal vesicle breakdown. Furthermore, aberrant spindle phenotypes and disordered chromosome alignment were observed in KIF16B-depleted oocytes, along with improper kinetochore–microtubule attachments. These abnormal K–MT attachments resulted in the persistent activation of BubR1/Bub3 at the kinetochores. Moreover, KIF16B knockdown destabilized α-tubulin by affecting the activity of histone deacetylase 6 (HDAC6). Further analysis revealed that KIF16B participated in the Ran GTPase-dependent activation of TPX2, which in turn regulated the phosphorylation levels of Aurora A–polo-like kinase 1 (PLK1), driving the proper assembly of the spindle. In conclusion, our data indicated that KIF16B is crucial for meiosis resumption and spindle assembly in mouse oocytes.\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144687988","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

Phagocytosed Photoreceptor Outer Segment Particles Within the Retinal Pigment Epithelium Show Diurnal Rhythmicity and Variation Between Cone Subtypes in Larval Zebrafish 斑马鱼幼鱼视网膜色素上皮内的吞噬光感受器外段颗粒显示出昼夜节律性和锥体亚型之间的差异

IF 4.4 2区生物学

The FASEB Journal Pub Date : 2025-07-24 DOI: 10.1096/fj.202500211R

Jenni Partinen, Noora Emilia Nevala, Sanni Erämies, Teemu Olavi Ihalainen, Soile Nymark

{"title":"Phagocytosed Photoreceptor Outer Segment Particles Within the Retinal Pigment Epithelium Show Diurnal Rhythmicity and Variation Between Cone Subtypes in Larval Zebrafish","authors":"Jenni Partinen, Noora Emilia Nevala, Sanni Erämies, Teemu Olavi Ihalainen, Soile Nymark","doi":"10.1096/fj.202500211R","DOIUrl":"https://doi.org/10.1096/fj.202500211R","url":null,"abstract":"Phagocytosis of retinal rod and cone outer segment (OS) tips by the retinal pigment epithelium (RPE) occurs daily to prevent the accumulation of harmful compounds in the photoreceptors. Rhythmic bursts seen as increased numbers of phagocytosed OS particles in the RPE are known to appear once or twice a day depending on the animal species. Yet, the variation of this rhythmicity between the distinct photoreceptor types is not well understood. We used zebrafish to compare the phagosome numbers and their daily rhythms between the different cone subtypes. We immunolabeled the different cone opsins from the histological sections of the eyes of zebrafish larvae that were collected at seven different time points throughout a 24 h circadian cycle. Internalized OS particles were then quantified using confocal microscopy and image analysis. Interestingly, the results revealed the presence of OS particles of all cone subtypes in the RPE throughout the day in larval zebrafish. However, we observed a significant increase in the phagosome numbers from UV and blue cones at two time points, whereas the number of green cone OS particles was more constant, probably reflecting their more immature developmental stage. We also investigated whether the rhythmicity is regulated by external light by keeping the larvae in constant darkness before sample preparation. We found that the complete darkness condition diminished the phagosome numbers of all cone subtypes and abolished the daytime peaks in the UV and blue cones, indicating that the rhythmicity is strongly affected by the external light in the larval zebrafish. Our findings provide new understanding on the rhythmicity of cone OS phagocytosis and its regulation.","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202500211R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688033","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

TNF-α Promotes Synovial Inflammation and Cartilage Bone Destruction in Rheumatoid Arthritis via NF-κB/YY1/miR-103a-3p Axis TNF-α通过NF-κB/YY1/miR-103a-3p轴促进类风湿关节炎滑膜炎症和软骨骨破坏

IF 4.4 2区生物学

The FASEB Journal Pub Date : 2025-07-23 DOI: 10.1096/fj.202501452R

Yue Yuan, Nan Mu, Yan Li, Jintao Gu, Chu Chu, Xiaobo Yu, Jiefang Kang, Tao Li, Yaping Yan, Hai Zhang, Yan Liu, Hua Xu, Changli Wang, Dawei Zhang, Qiang Sun, Wei Zhang, Zhaohui Zheng, Guodong Feng, Xiaochang Xue

{"title":"TNF-α Promotes Synovial Inflammation and Cartilage Bone Destruction in Rheumatoid Arthritis via NF-κB/YY1/miR-103a-3p Axis","authors":"Yue Yuan, Nan Mu, Yan Li, Jintao Gu, Chu Chu, Xiaobo Yu, Jiefang Kang, Tao Li, Yaping Yan, Hai Zhang, Yan Liu, Hua Xu, Changli Wang, Dawei Zhang, Qiang Sun, Wei Zhang, Zhaohui Zheng, Guodong Feng, Xiaochang Xue","doi":"10.1096/fj.202501452R","DOIUrl":"https://doi.org/10.1096/fj.202501452R","url":null,"abstract":"<div>\u0000 \u0000 Tumor necrosis factor alpha (TNF-α) plays important roles in inflammation and bone destruction in rheumatoid arthritis (RA), but the detailed mechanism is still not fully elucidated. Here, we found that the levels of microRNA (miR)-103a-3p were decreased markedly in the inflamed synovial tissues of patients with RA compared with osteoarthritis (OA) or healthy control subjects. Further studies uncovered that miR-103a-3p was significantly downregulated by TNF-α/IL-1β in RA fibroblast-like synoviocytes (FLSs) through an NF-κB–dependent manner via the de novo produced transcription factor Yin Yang 1 (YY1). In addition, downregulation of miR-103a-3p in FLSs promoted NF-κB signaling pathway activation, inflammatory cytokines secretion, and bone marrow-derived monocytes (BMMs) cells differentiation into osteoclasts, whereas ectopic expression of miR-103a-3p had the opposite effects. Notably, miR-103a-3p was downregulated thousands of times in the sera of RA patients and CIA mice, while the blockade of TNF-α with infliximab greatly recovered its levels in RA patients in sustained remission. Consistently, rescue of miR-103a-3p expression by an agomiR potently ameliorated inflammatory responses and bone erosion in CIA mice. Mechanistically, mitogen-activated protein kinase kinase kinase 7 (MAP3K7) and Dickkopf-related protein 1 (DKK1) were identified as the direct targets of miR-103a-3p, by which it exerts the effects on synovial inflammation and cartilage bone destruction. Taken together, miR-103a-3p mediates TNF-triggered synovial inflammation and joint bone destruction via targeting MAP3K7 and DKK1; it thus serves as a candidate target for RA treatment.\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681329","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

EDIL3 Deficiency Attenuates Liver Fibrosis Through Inhibiting Hepatic Stellate Cells Activation via the Integrin αvβ3-ERK1/2-RUNX2 Axis in MASH Mice EDIL3缺乏通过整合素αvβ3-ERK1/2-RUNX2轴抑制肝星状细胞活化，从而减轻MASH小鼠肝纤维化

IF 4.4 2区生物学

The FASEB Journal Pub Date : 2025-07-23 DOI: 10.1096/fj.202403088R

Cheng Wei, Dongwei Lu, Jianfang Liu, Juan-Juan Qin, Menglong Wang, Fang Lei

{"title":"EDIL3 Deficiency Attenuates Liver Fibrosis Through Inhibiting Hepatic Stellate Cells Activation via the Integrin αvβ3-ERK1/2-RUNX2 Axis in MASH Mice","authors":"Cheng Wei, Dongwei Lu, Jianfang Liu, Juan-Juan Qin, Menglong Wang, Fang Lei","doi":"10.1096/fj.202403088R","DOIUrl":"https://doi.org/10.1096/fj.202403088R","url":null,"abstract":"<div>\u0000 \u0000 Metabolic Dysfunction-Associated Steatohepatitis (MASH) emerges as an advanced stage of Metabolic Dysfunction-Associated Steatotic Liver Disease, marked by significant liver damage characterized by fat accumulation, inflammation, hepatocyte injury, and progressive fibrosis. Epidermal Growth Factor-like repeat and Discoidin I-like domain-containing protein 3 (EDIL3), a protein containing epidermal growth factor-like repeats and discoidin I-like domains, interacts with membrane integrins to modulate inflammation, fibrosis, and vascular remodeling. However, the potential role of EDIL3 in the progression of liver fibrosis in MASH remains unclear. Our study unveiled a significant correlation between plasma EDIL3 levels and liver fibrosis severity in a UK Biobank population. In choline-deficient, L-amino acid-defined high-fat diet-induced MASH mouse models, EDIL3 liver expression was markedly upregulated, whereas EDIL3 deficiency mitigated liver damage, lipid accumulation, and fibrosis. Transcriptomic analysis indicated that EDIL3 deficiency substantially impacts extracellular matrix-related processes and inhibits Hepatic Stellate Cells (HSCs) activation in MASH. Mechanistically, EDIL3 binds to integrin αvβ3, activating HSCs via the ERK1/2-RUNX2 pathway. In summary, our findings demonstrate that EDIL3 regulates HSC activation through the integrin αvβ3-ERK1/2-RUNX2 axis, influencing liver fibrosis in MASH, thus offering a potential therapeutic avenue for MASH and fibrotic liver diseases.\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681330","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

Sirt1-Mediated Transcriptional Inhibition of Nr4a3 Alleviates Severe Acute Pancreatitis-Associated Acute Lung Injury sirt1介导的Nr4a3转录抑制减轻严重急性胰腺炎相关急性肺损伤

IF 4.4 2区生物学

The FASEB Journal Pub Date : 2025-07-23 DOI: 10.1096/fj.202501210R

Xiaolin Dou, Zhongcheng Zhu, Qizhen Chen, Yebin Lu

{"title":"Sirt1-Mediated Transcriptional Inhibition of Nr4a3 Alleviates Severe Acute Pancreatitis-Associated Acute Lung Injury","authors":"Xiaolin Dou, Zhongcheng Zhu, Qizhen Chen, Yebin Lu","doi":"10.1096/fj.202501210R","DOIUrl":"https://doi.org/10.1096/fj.202501210R","url":null,"abstract":"<div>\u0000 \u0000 Acute lung injury (ALI) is closely associated with high mortality in severe acute pancreatitis (SAP). Nr4a3 is a nuclear receptor with proinflammatory effects. The role of Nr4a3 in SAP-associated ALI is unclear. Caerulein (CRE)-induced AP mice represented significant pancreatic and lung pathological injury, with high Nr4a3 expression in lung tissues. Nr4a3 expression in lung tissues of AP mice inhibited CD31 expression, suggesting lung microvascular injury. In vitro and in vivo experiments were performed to investigate the effect of Nr4a3 inhibition in mitigating SAP-associated ALI. Nr4a3 downregulation reduced permeability, increased trans-endothelial electrical resistance (TEER) and VE-cadherin expression in TNF-α-induced human pulmonary microvascular endothelial cells (hPMVECs), suggesting recovered endothelial barrier function. Nr4a3 knockdown attenuated lung injury in AP mice, as reflected by restored lung edema and endothelial barrier function. Reduced inflammatory cell counts and mediators indicated that Nr4a3 knockdown mitigated lung inflammation in AP mice. The up-regulation of Nr4a3 in TNF-α-induced hPMVECs was further elevated after Sirt1 (a deacetylase) inhibition. Mechanistically, Sirt1 deficiency increased the enrichment of CREB at the Nr4a3 promoter through acetylating H3K27, thereby promoting Nr4a3 expression. Rescue experiments in vivo demonstrated that Nr4a3 knockdown attenuated lung injury aggravated by Sirt1 inhibition. These results suggested that Sirt1 might prevent CREB enrichment by inhibiting histone acetylation in the Nr4a3 promoter, thereby suppressing Nr4a3 expression and ultimately attenuating ALI.\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681401","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

A Novel Exopolysaccharide, Highly Prevalent in Marine Spongiibacter, Triggers Pyroptosis to Exhibit Potent Anticancer Effects 一种新型的外多糖，在海洋海绵状菌中高度流行，引发热亡，显示出有效的抗癌作用

IF 4.4 2区生物学

The FASEB Journal Pub Date : 2025-07-23 DOI: 10.1096/fj.202500412R

Ge Liu, Yeqi Shan, Chaomin Sun

{"title":"A Novel Exopolysaccharide, Highly Prevalent in Marine Spongiibacter, Triggers Pyroptosis to Exhibit Potent Anticancer Effects","authors":"Ge Liu, Yeqi Shan, Chaomin Sun","doi":"10.1096/fj.202500412R","DOIUrl":"https://doi.org/10.1096/fj.202500412R","url":null,"abstract":"<div>\u0000 \u0000 Pyroptosis is an inflammatory programmed cell death. In recent years, the potential of pyroptosis in tumor treatment has received widespread attention and has become a promising anti-tumor therapeutic strategy. EPS3.9 is a novel deep-sea bacterial exopolysaccharide that we obtained and has potent anti-tumor activity. EPS3.9 consisted of mannose and glucose with a molar ratio of 1:0.42. The average molecular weight of EPS3.9 was 17.1 kDa. EPS3.9 can induce lytic cell death in tumor cells. Mechanism analysis has revealed that it can directly target 5 membrane phospholipids and exert tumor cytotoxic activity through triggering NLRP3 inflammasome-mediated pyroptosis in the human monocytic leukemia THP-1 cells. EPS3.9 also has significant anti-tumor effects in Huh7.5 tumor-bearing mice and can activate anti-tumor immune responses. Besides, this active exopolysaccharide is ubiquitous among the genus Spongiibacter. This study provides an important theoretical basis for EPS3.9 as a new type of marine carbohydrate anti-tumor drug candidate and also provides scientific evidence for the feasibility and potential of tumor treatment by triggering pyroptosis.\u0000 </div>","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681208","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

Engineering Nanoparticles and Bioscaffolds for Targeted microRNA Delivery in Cardiovascular Regeneration—A Comprehensive Review 工程纳米颗粒和生物支架在心血管再生中靶向递送microRNA的综合综述

IF 4.4 2区生物学

The FASEB Journal Pub Date : 2025-07-23 DOI: 10.1096/fj.202501226RR

Jekhan Andimadam Madana Saravanan, Azam Ali, Rajesh Katare

{"title":"Engineering Nanoparticles and Bioscaffolds for Targeted microRNA Delivery in Cardiovascular Regeneration—A Comprehensive Review","authors":"Jekhan Andimadam Madana Saravanan, Azam Ali, Rajesh Katare","doi":"10.1096/fj.202501226RR","DOIUrl":"https://doi.org/10.1096/fj.202501226RR","url":null,"abstract":"Cardiovascular diseases, particularly myocardial infarction (MI), remain a leading cause of mortality worldwide, primarily due to the extensive loss of cardiomyocytes and the heart's limited regenerative capacity. MI, caused by obstructed blood flow, results in cardiac muscle damage, scar tissue formation, and ultimately, heart failure. While heart transplantation is the definitive treatment, its application is limited by donor shortages and the risk of immune rejection. This underscores the urgent need for regenerative strategies. MicroRNAs (miRNAs) play a crucial role in regulating myocardial healing post-ischemia, with specific miRNAs such as miR-92a, miR-126, and miR-145 shown to promote angiogenesis. However, the therapeutic application of miRNAs is hindered by delivery challenges at both extracellular and intracellular levels. This review explores the potential of nanoparticles (NPs) and engineered bioscaffolds to address these obstacles. We first examine the role of miRNAs in post-MI cardiovascular remodeling, followed by an overview of current challenges in miRNA-based therapy delivery. We then discuss the use of NPs and electrospun nanofibrous scaffolds in this context. Finally, we review existing cardiac bioscaffolds, their limitations, and future directions for developing optimized nanofibrous scaffolds for effective cardiac regeneration.","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202501226RR","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681207","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

Characterization of the Nicotinamide Adenine Dinucleotide Biosynthesis Pathway and Regulatory Mechanisms in Streptococcus mutans 变异链球菌烟酰胺腺嘌呤二核苷酸生物合成途径及其调控机制的研究

IF 4.4 2区生物学

The FASEB Journal Pub Date : 2025-07-22 DOI: 10.1096/fj.202500944R

Haojie Yu, Dandan Shao, Yuheng Zhao, Shuojie Lv, Ruoxi Tao, Yu Sang, Jie Ren, Paul R Cooper, Qingjing Wang

{"title":"Characterization of the Nicotinamide Adenine Dinucleotide Biosynthesis Pathway and Regulatory Mechanisms in Streptococcus mutans","authors":"Haojie Yu, Dandan Shao, Yuheng Zhao, Shuojie Lv, Ruoxi Tao, Yu Sang, Jie Ren, Paul R Cooper, Qingjing Wang","doi":"10.1096/fj.202500944R","DOIUrl":"https://doi.org/10.1096/fj.202500944R","url":null,"abstract":"NAD+ and its derivatives, which act as redox coenzymes, are crucial for cellular metabolism and energy production. Nevertheless, the processes by which Streptococcus mutans, a bacterium known for causing dental caries, synthesizes NAD+ are not well elucidated. Through a genome-wide screen, we identified the nicotinic acid salvage pathway and the evolutionarily incomplete PnuC–NadR pathway involved in NAD+ biosynthesis in S. mutans UA159. The nicotinic acid pathway is regulated by SmNiaR, a nicotinic acid-responsive transcription regulator featuring an N-terminal DNA-binding winged helix-turn-helix-like domain and a C-terminal 3-histidine domain. Notably, a single-site amino acid substitution at site K97 in SmNiaR can reverse its DNA-binding ability, an effect mediated by acetylation at this site, which impacts the intracellular production of NAD+ and NADH. Additionally, the deletion of niaR in S. mutans UA159 impaired bacterial proliferation, reduced acid production, and altered biofilm formation, resulting in attenuated virulence in the rat caries model. Conclusively, the regulation of NAD+ homeostasis via SmNiaR contributes significantly to the cariogenic virulence of S. mutans.","PeriodicalId":50455,"journal":{"name":"The FASEB Journal","volume":"39 14","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fj.202500944R","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144672631","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