IUBMB Life最新文献_第10页

Characterization of Mitoribosomal Small Subunit unit genes related immune and pharmacogenomic landscapes in renal cell carcinoma 肾细胞癌中与免疫和药物基因组学相关的 Mitoribosomal 小亚基单位基因的特征。

IF 3.7 3区生物学

IUBMB Life Pub Date : 2024-03-29 DOI: 10.1002/iub.2818

Zhihao Wei, Chenchen Liu, Jiaqian Liang, Xuan Zhou, Kaming Xue, Keshan Wang, Xiaoping Zhang

{"title":"Characterization of Mitoribosomal Small Subunit unit genes related immune and pharmacogenomic landscapes in renal cell carcinoma","authors":"Zhihao Wei, Chenchen Liu, Jiaqian Liang, Xuan Zhou, Kaming Xue, Keshan Wang, Xiaoping Zhang","doi":"10.1002/iub.2818","DOIUrl":"10.1002/iub.2818","url":null,"abstract":"Mitoribosomes are essential for the production of biological energy. The Human Mitoribosomal Small Subunit unit (MRPS) family, responsible for encoding mitochondrial ribosomal small subunits, is actively engaged in protein synthesis within the mitochondria. Intriguingly, MRPS family genes appear to play a role in cancer. A multistep process was employed to establish a risk model associated with MRPS genes, aiming to delineate the immune and pharmacogenomic landscapes in clear cell renal cell carcinoma (ccRCC). MRPScores were computed for individual patients to assess their responsiveness to various treatment modalities and their susceptibility to different therapeutic targets and drugs. While MRPS family genes have been implicated in various cancers as oncogenes, our findings reveal a contrasting tumor suppressor role for MRPS genes in ccRCC. Utilizing an MRPS-related risk model, we observed its excellent prognostic capability in predicting survival outcomes for ccRCC patients. Remarkably, the subgroup with high MRPS-related scores (MRPScore) displayed poorer prognosis but exhibited a more robust response to immunotherapy. Through in silico screening of 2183 drug targets and 1646 compounds, we identified two targets (RRM2 and OPRD1) and eight agents (AZ960, carmustine, lasalocid, SGI-1776, AZD8055_1059, BPD.00008900_1998, MK.8776_2046, and XAV939_1268) with potential therapeutic implications for high-MRPScore patients. Our study represents the pioneering effort in proposing that molecular classification, diagnosis, and treatment strategies can be formulated based on MRPScores. Indeed, a high MRPScore profile appears to elevate the risk of tumor progression and mortality, potentially through its influence on immune regulation. This suggests that the MRPS-related risk model holds promise as a prognostic predictor and may offer novel insights into personalized therapeutic strategies.","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 9","pages":"647-665"},"PeriodicalIF":3.7,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Mitochondrial respiratory supercomplexes of the yeast Saccharomyces cerevisiae 酵母菌线粒体呼吸超级复合物。

IF 3.7 3区生物学

IUBMB Life Pub Date : 2024-03-26 DOI: 10.1002/iub.2817

Mazzen H. Eldeeb, Lizeth J. Camacho Lopez, Flavia Fontanesi

{"title":"Mitochondrial respiratory supercomplexes of the yeast Saccharomyces cerevisiae","authors":"Mazzen H. Eldeeb, Lizeth J. Camacho Lopez, Flavia Fontanesi","doi":"10.1002/iub.2817","DOIUrl":"10.1002/iub.2817","url":null,"abstract":"The functional and structural relationship among the individual components of the mitochondrial respiratory chain constitutes a central aspect of our understanding of aerobic catabolism. This interplay has been a subject of intense debate for over 50 years. It is well established that individual respiratory enzymes associate into higher-order structures known as respiratory supercomplexes, which represent the evolutionarily conserved organizing principle of the mitochondrial respiratory chain. In the yeast Saccharomyces cerevisiae, supercomplexes are formed by a complex III homodimer flanked by one or two complex IV monomers, and their high-resolution structures have been recently elucidated. Despite the wealth of structural information, several proposed supercomplex functions remain speculative and our understanding of their physiological relevance is still limited. Recent advances in the field were made possible by the construction of yeast strains where the association of complex III and IV into supercomplexes is impeded, leading to diminished respiratory capacity and compromised cellular competitive fitness. Here, we discuss the experimental evidence and hypotheses relative to the functional roles of yeast respiratory supercomplexes. Moreover, we review the current models of yeast complex III and IV assembly in the context of supercomplex formation and highlight the data scattered throughout the literature suggesting the existence of cross talk between their biogenetic processes.","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 8","pages":"485-504"},"PeriodicalIF":3.7,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iub.2817","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140287472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Autophagy inhibition potentiates energy restriction-induced cell death in hepatocellular carcinoma cells 抑制自噬可增强能量限制诱导的肝癌细胞死亡。

IF 3.7 3区生物学

IUBMB Life Pub Date : 2024-03-18 DOI: 10.1002/iub.2816

Sara M. Elgendy, Dana M. Zaher, Nadin H. Sarg, Nour N. Abu Jayab, Dima W. Alhamad, Taleb H. Al-Tel, Hany A. Omar

{"title":"Autophagy inhibition potentiates energy restriction-induced cell death in hepatocellular carcinoma cells","authors":"Sara M. Elgendy, Dana M. Zaher, Nadin H. Sarg, Nour N. Abu Jayab, Dima W. Alhamad, Taleb H. Al-Tel, Hany A. Omar","doi":"10.1002/iub.2816","DOIUrl":"10.1002/iub.2816","url":null,"abstract":"Hepatocellular carcinoma (HCC) significantly contributes to cancer-related mortality due to the limited response of HCC to current anticancer therapies, thereby necessitating more effective treatment approaches. Energy restriction mimetic agents (ERMAs) have emerged as potential therapies in targeting the Warburg effect, a unique metabolic process in cancer cells. However, ERMAs exhibit limited efficacy when used as monotherapy. Additionally, ERMAs have been found to induce autophagy in cancer cells. The role of autophagy in cancer survival remains a subject of debate. Thus, it is crucial to ascertain whether ERMA-induced autophagy is a mechanism for cell survival or cell death in HCC. Our study aims to investigate the effect of autophagy inhibition on the survival of HCC cells treated with ERMAs while also examining the potential of combining an autophagy inhibitor such as spautin-1 with ERMAs to enhance HCC cell death. Our results suggest a cytoprotective role for ERMA-induced autophagy in HCC cells, as combining the autophagy inhibitor spautin-1 with ERMAs effectively suppressed ERMA-induced autophagy and synergistically enhanced their antitumor activity. The treatment combination promoted HCC death through apoptosis, cell cycle arrest, and inhibition of AKT and ERK activation, which are known to play a key role in cellular proliferation. Collectively, our findings highlight a potential strategy to combat HCC by combining energy restriction with autophagy inhibition.","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 8","pages":"577-588"},"PeriodicalIF":3.7,"publicationDate":"2024-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140143487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Retraction: miR-212/132 downregulates SMAD2 expression to suppress the G1/S phase transition of the cell cycle and the epithelial to mesenchymal transition in cervical cancer cells 撤稿：miR-212/132 下调 SMAD2 的表达，从而抑制宫颈癌细胞的细胞周期 G1/S 期转变和上皮细胞向间质细胞的转变。

IF 4.6 3区生物学

IUBMB Life Pub Date : 2024-03-14 DOI: 10.1002/iub.2815

{"title":"Retraction: miR-212/132 downregulates SMAD2 expression to suppress the G1/S phase transition of the cell cycle and the epithelial to mesenchymal transition in cervical cancer cells","authors":"","doi":"10.1002/iub.2815","DOIUrl":"10.1002/iub.2815","url":null,"abstract":"Retraction: ‘ miR-212/132 downregulates SMAD2 expression to suppress the G1/S phase transition of the cell cycle and the epithelial to mesenchymal transition in cervical cancer cells’ by Jian-Li Zhao, Le Zhang, Xu Guo, Jing-Hua Wang, Wen Zhou, Min Liu, Xin Li and Hua Tang, IUBMB Life 2015, 67, 380–394\u0000 : The above article, published online on 15 May 2015 on Wiley Online Library (https://doi.org/10.1002/iub.1381) has been retracted by agreement between the journal's Editor in Chief, Dr. Efstathios S. Gonos, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. Several flaws and inconsistencies were found, including image manipulation in Figures 3C, 4C, 5B, 6B, 7C, 7D, 8B, 8C and 8D, and the editors consider the conclusions of this article to be invalid. The authors were contacted regarding the findings and the proposed retraction, but we did not receive a response.","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 6","pages":"363"},"PeriodicalIF":4.6,"publicationDate":"2024-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iub.2815","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140131463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Particulate matters 2.5 induce tumor progression in lung cancer by increasing the activity of hnRNPA2B1 resulting in retarding mRNA decay of oxidative phosphorylation 颗粒物 2.5 通过增加 hnRNPA2B1 的活性，从而延缓氧化磷酸化的 mRNA 衰减，诱导肺癌的肿瘤进展。

IF 3.7 3区生物学

IUBMB Life Pub Date : 2024-03-07 DOI: 10.1002/iub.2813

Wen Bian, Haifeng Yu, Xiaofei Zhang, Yuxuan Wang, Bin Ni

{"title":"Particulate matters 2.5 induce tumor progression in lung cancer by increasing the activity of hnRNPA2B1 resulting in retarding mRNA decay of oxidative phosphorylation","authors":"Wen Bian, Haifeng Yu, Xiaofei Zhang, Yuxuan Wang, Bin Ni","doi":"10.1002/iub.2813","DOIUrl":"10.1002/iub.2813","url":null,"abstract":"Particulate matter 2.5 (PM2.5) has been implicated in lung injury and various cancers, yet its precise mechanistic role remains elusive. To elucidate the key signaling pathways underpinning PM2.5-induced lung cancer progression, we embarked on a study examining the impact of PM2.5 both in vitro and in vivo. Lung cancer cell lines, A549 and H157, were employed for the in vitro investigations. Overexpression or knockdown techniques targeting the hnRNPA2B1 protein were implemented. Lung cancer cells were treated with a medium containing PM2.5 and subsequently prepared for in vitro evaluations. Cell growth, invasion, and migration were gauged using transwell and CCK-8 assays. Apoptosis was ascertained through flow cytometry and western blotting of pertinent proteins. Seahorse analyses probed the influence of PM2.5 on lung cancer energy metabolism. The RNA stability assay was employed to discern the impact of PM2.5 on the stability of oxidative phosphorylation-related genes in lung cancer. Our findings revealed that PM2.5 augmented cell proliferation, migration, and invasion rates. Similarly, a diminished apoptosis rate was observed in PM2.5-treated cells. Elevated expression of hnRNPA2B1 was detected in lung cancer cells exposed to PM2.5. Moreover, in cells treated with PM2.5, hnRNPA2B1 knockdown markedly curtailed cell proliferation by inducing G1–S cell cycle arrest and bolstered lung cancer cell apoptosis in vitro; it also curbed xenograft tumor growth. Mechanistically, our data suggest that PM2.5 undermines the stability of mRNA transcripts associated with oxidative phosphorylation (OXPHOS) and augments the formation of processing bodies (P-bodies), leading to an upsurge in OXPHOS levels. In conclusion, PM2.5 appears to drive lung cancer progression and migration by modulating the energy metabolism of lung cancer in a hnRNPA2B1-dependent manner.","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 8","pages":"563-576"},"PeriodicalIF":3.7,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Nano-therapeutics: The upcoming nanomedicine to treat cancer 纳米疗法：即将问世的治疗癌症的纳米药物。

IF 3.7 3区生物学

IUBMB Life Pub Date : 2024-03-05 DOI: 10.1002/iub.2814

Hamda Khan, Uzma Shahab, Ahmed Alshammari, Amjad R. Alyahyawi, Rihab Akasha, Talal Alharazi, Rizwan Ahmad, Afreen Khanam, Safia Habib, Kirtanjot Kaur, Saheem Ahmad, Moinuddin

{"title":"Nano-therapeutics: The upcoming nanomedicine to treat cancer","authors":"Hamda Khan, Uzma Shahab, Ahmed Alshammari, Amjad R. Alyahyawi, Rihab Akasha, Talal Alharazi, Rizwan Ahmad, Afreen Khanam, Safia Habib, Kirtanjot Kaur, Saheem Ahmad,  Moinuddin","doi":"10.1002/iub.2814","DOIUrl":"10.1002/iub.2814","url":null,"abstract":"Nanotechnology is considered a successful approach for cancer diagnosis and treatment. Preferentially, cancer cell recognition and drug targeting via nano-delivery system include the penetration of anticancer agents into the cell membrane to damage the cancer cell by protein modification, DNA oxidation, or mitochondrial dysfunction. The past research on nano-delivery systems and their target has proven the beneficial achievement in a malignant tumor. Modern perceptions using inventive nanomaterials for cancer management have been offered by a multifunctional platform based on various nano-carriers with the probability of imaging and cancer therapy simultaneously. Emerging nano-delivery systems in cancer therapy still lack knowledge of the biological functions behind the interaction between nanoparticles and cancer cells. Since the potential of engineered nanoparticles addresses the various challenges, limiting the success of cancer therapy subsequently, it is a must to review the molecular targeting of a nano-delivery system to enhance the therapeutic efficacy of cancer. This review focuses on using a nano-delivery system, an imaging system, and encapsulated nanoparticles for cancer therapy.","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 8","pages":"468-484"},"PeriodicalIF":3.7,"publicationDate":"2024-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140028040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Evolution and variation in amide aminoacyl-tRNA synthesis 酰胺氨基酰-tRNA合成的进化和变异。

IF 3.7 3区生物学

IUBMB Life Pub Date : 2024-02-23 DOI: 10.1002/iub.2811

Alexander M. Lewis, Trevor Fallon, Georgia A. Dittemore, Kelly Sheppard

{"title":"Evolution and variation in amide aminoacyl-tRNA synthesis","authors":"Alexander M. Lewis, Trevor Fallon, Georgia A. Dittemore, Kelly Sheppard","doi":"10.1002/iub.2811","DOIUrl":"10.1002/iub.2811","url":null,"abstract":"The amide proteogenic amino acids, asparagine and glutamine, are two of the twenty amino acids used in translation by all known life. The aminoacyl-tRNA synthetases for asparagine and glutamine, asparaginyl-tRNA synthetase and glutaminyl tRNA synthetase, evolved after the split in the last universal common ancestor of modern organisms. Before that split, life used two-step indirect pathways to synthesize asparagine and glutamine on their cognate tRNAs to form the aminoacyl-tRNA used in translation. These two-step pathways were retained throughout much of the bacterial and archaeal domains of life and eukaryotic organelles. The indirect routes use non-discriminating aminoacyl-tRNA synthetases (non-discriminating aspartyl-tRNA synthetase and non-discriminating glutamyl-tRNA synthetase) to misaminoacylate the tRNA. The misaminoacylated tRNA formed is then transamidated into the amide aminoacyl-tRNA used in protein synthesis by tRNA-dependent amidotransferases (GatCAB and GatDE). The enzymes and tRNAs involved assemble into complexes known as transamidosomes to help maintain translational fidelity. These pathways have evolved to meet the varied cellular needs across a diverse set of organisms, leading to significant variation. In certain bacteria, the indirect pathways may provide a means to adapt to cellular stress by reducing the fidelity of protein synthesis. The retention of these indirect pathways versus acquisition of asparaginyl-tRNA synthetase and glutaminyl tRNA synthetase in lineages likely involves a complex interplay of the competing uses of glutamine and asparagine beyond translation, energetic costs, co-evolution between enzymes and tRNA, and involvement in stress response that await further investigation.","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 8","pages":"505-522"},"PeriodicalIF":3.7,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/iub.2811","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

The complex relationship between late-onset caloric restriction and synaptic plasticity in aged Wistar rats 晚期热量限制与老龄 Wistar 大鼠突触可塑性之间的复杂关系

IF 3.7 3区生物学

IUBMB Life Pub Date : 2024-02-23 DOI: 10.1002/iub.2812

Milica Prvulovic, Srdjan Sokanovic, Valentina Simeunovic, Andjela Vukojevic, Milena Jovic, Smilja Todorovic, Aleksandra Mladenovic

{"title":"The complex relationship between late-onset caloric restriction and synaptic plasticity in aged Wistar rats","authors":"Milica Prvulovic, Srdjan Sokanovic, Valentina Simeunovic, Andjela Vukojevic, Milena Jovic, Smilja Todorovic, Aleksandra Mladenovic","doi":"10.1002/iub.2812","DOIUrl":"10.1002/iub.2812","url":null,"abstract":"Age-related reduction in spine density, synaptic marker expression, and synaptic efficiency are frequently reported. These changes provide the cellular and molecular basis for the cognitive decline characteristic for old age. Nevertheless, there are several approaches that have the potential to ameliorate these processes and improve cognition, caloric restriction being one of the most promising and widely studied. While lifelong caloric restriction is known for its numerous beneficial effects, including improved cognitive abilities and increased expression of proteins essential for synaptic structure and function, the effects of late-onset and/or short-term CR on synaptic plasticity have yet to be investigated. We have previously documented that the effects of CR are strongly dependent on whether CR is initiated in young or old subjects. With this in mind, we conducted a long-term study in aging Wistar rats to examine changes in the expression of several key synaptic markers under the regimen of CR started at different time points in life. We found a significant increase in the expression of both presynaptic and postsynaptic markers. However, taking into account previously reported changes in the behavior detected in these animals, we consider that this increase cannot represent beneficial effect of CR.","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 8","pages":"548-562"},"PeriodicalIF":3.7,"publicationDate":"2024-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139931231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Exosomes derived from Baicalin-pretreated bone mesenchymal stem cells improve Th17/Treg imbalance after hepatic ischemia–reperfusion via FGF21 and the JAK2/STAT3 pathway 经Baicalin预处理的骨间充质干细胞产生的外泌体可通过FGF21和JAK2/STAT3途径改善肝缺血再灌注后Th17/Treg的失衡。

IF 3.7 3区生物学

IUBMB Life Pub Date : 2024-02-21 DOI: 10.1002/iub.2810

Baoyan Zhang, Linfeng Su, Zhichao Chen, Min Wu, Jianfeng Wei, Yonghua Lin

{"title":"Exosomes derived from Baicalin-pretreated bone mesenchymal stem cells improve Th17/Treg imbalance after hepatic ischemia–reperfusion via FGF21 and the JAK2/STAT3 pathway","authors":"Baoyan Zhang, Linfeng Su, Zhichao Chen, Min Wu, Jianfeng Wei, Yonghua Lin","doi":"10.1002/iub.2810","DOIUrl":"10.1002/iub.2810","url":null,"abstract":"Baicalin is an active compound extracted from Scutellaria baicalensis with antioxidant and anti-inflammatory properties. Bone mesenchymal stem cells (BMSCs)-derived exosomes have shown promise for the treatment of hepatic ischemia–reperfusion (I/R) injury. This study aims to investigate the role of Baicalin-pretreated BMSCs-derived exosomes in hepatic I/R injury and its mechanisms. BMSCs were pretreated with or without Baicalin, and their exosomes (Ba-Exo and Exo) were collected and characterized. These exosomes were administered to mice via tail vein injection. Treatment with Exo and Ba-Exo significantly suppressed the elevation of ALT and AST induced by hepatic injury. Additionally, both Exo and Ba-Exo treatments resulted in a reduction in the liver weight-to-body weight ratio. RT-PCR results revealed a significant downregulation of pro-inflammatory cytokines with Exo and Ba-Exo treatment. Both Exo and Ba-Exo treatment improved the Th17/Treg cell imbalance induced by I/R and reduced hepatic injury. Additionally, exosomes were cocultured with normal liver cells, and the expression of fibroblast growth factor 21 (FGF21) in liver cells was elevated through Ba-Exo treatment. After treatment, the JAK2/STAT3 pathway was inhibited, and FOXO1 expression was upregulated. Finally, recombinant FGF21 was injected into mouse tail veins to assess its effects. Recombinant FGF21 injection further inhibited the JAK2/STAT3 pathway, increased FOXO1 expression, and improved the Th17/Treg cell imbalance. In conclusion, this study confirms the protective effects of Exo and Ba-Exo against hepatic I/R injury. Ba-Exo mitigates hepatic I/R injury, achieved through inducing FGF21 expression in liver cells, inhibiting the JAK2/STAT3 pathway, and activating FOXO1 expression. Therefore, baicalin pretreatment emerges as a promising strategy to enhance the therapeutic capability of BMSCs-derived exosomes for hepatic I/R.","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 8","pages":"534-547"},"PeriodicalIF":3.7,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139912649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Alternative splicing generates a novel ferroportin isoform with a shorter C-terminal and an intact iron- and hepcidin-binding property 交替剪接产生了一种新型铁皮质素异构体，其 C 端较短，但具有完整的铁和肝素结合特性。

IF 3.7 3区生物学

IUBMB Life Pub Date : 2024-02-13 DOI: 10.1002/iub.2809

Pallavi Juneja, Naira Rashid, Faizan Abul Qais, Supriya Tanwar, Insha Sultan, Faizan Ahmad, Sayeed ur Rehman

{"title":"Alternative splicing generates a novel ferroportin isoform with a shorter C-terminal and an intact iron- and hepcidin-binding property","authors":"Pallavi Juneja, Naira Rashid, Faizan Abul Qais, Supriya Tanwar, Insha Sultan, Faizan Ahmad, Sayeed ur Rehman","doi":"10.1002/iub.2809","DOIUrl":"10.1002/iub.2809","url":null,"abstract":"Ferroportin (FPN) is a transmembrane protein and is the only known iron exporter that helps in maintaining iron homeostasis in vertebrates. To maintain stable iron equilibrium in the body, ferroportin works in conjunction with a peptide called hepcidin. In this study, we have identified an alternatively spliced novel isoform of the human SLC40A1 gene, which encodes for the FPN protein and is found to be expressed in different tissues. The novel transcript has an alternate last exon and encodes 31-amino acid long peptide sequence that replaces 104 amino acids at C-terminal in the novel transcript. Molecular modelling and molecular dynamics (MD) simulation studies revealed key structural features of the novel isoform (FPN-N). FPN-N was predicted to have 12 transmembrane domains similar to the reported isoform (FPN), despite being much smaller in size. FPN-N was found to interact with hepcidin, a key regulator of ferroportin activity. Also, the iron-binding sites were retained in the novel isoform as revealed by the MD simulation of FPN-N in bilipid membrane. The novel isoform identified in this study may play important role in iron homeostasis. However, further studies are required to characterize the FPN-N isoform and decipher its role inside the cell.","PeriodicalId":14728,"journal":{"name":"IUBMB Life","volume":"76 8","pages":"523-533"},"PeriodicalIF":3.7,"publicationDate":"2024-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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