FEBS Open Bio最新文献_第4页

Regorafenib as a potential drug for severe COVID-19: inhibition of inflammasome activation in mice 瑞非尼作为治疗严重COVID-19的潜在药物：抑制小鼠炎症小体激活

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2025-02-03 DOI: 10.1002/2211-5463.70002

Ju Hwan Jeong, Sun-Ok Kim, Seong Cheol Min, Eung-Gook Kim, Min-Suk Song, Eun-Young Shin

引用次数: 0

Pharmacological effects of osimertinib on a chicken chorioallantoic membrane xenograft model with the EGFR exon-19-deleted advanced NSCLC mutation. 奥西替尼对EGFR外显子19缺失晚期NSCLC突变鸡绒毛膜尿囊膜异种移植模型的药理作用

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2025-01-30 DOI: 10.1002/2211-5463.13970

David Barthélémy, Arnaud Vigneron, Xavier Rousset, Jérome Guitton, Emmanuel Grolleau, Margaux Raffin, Julie Balandier, Gaëlle Lescuyer, Mathilde Bardou, Florence Geiguer, Sébastien Couraud, Claire Bardel, Jean Viallet, Nazim Benzerdjeb, Léa Payen

{"title":"Pharmacological effects of osimertinib on a chicken chorioallantoic membrane xenograft model with the EGFR exon-19-deleted advanced NSCLC mutation.","authors":"David Barthélémy, Arnaud Vigneron, Xavier Rousset, Jérome Guitton, Emmanuel Grolleau, Margaux Raffin, Julie Balandier, Gaëlle Lescuyer, Mathilde Bardou, Florence Geiguer, Sébastien Couraud, Claire Bardel, Jean Viallet, Nazim Benzerdjeb, Léa Payen","doi":"10.1002/2211-5463.13970","DOIUrl":"https://doi.org/10.1002/2211-5463.13970","url":null,"abstract":"Non-small cell lung cancer (NSCLC) affects 10-50% of patients with epidermal growth factor receptor (EGFR) mutations. Osimertinib is a third-generation EGFR tyrosine kinase inhibitor (TKI) that radically changes the outcome of patients with tumors bearing EGFR sensitizing or EGFR T790M resistance mutations. However, resistance usually occurs, and new therapeutic combinations need to be explored. The chorioallantoic membrane (CAM) xenograft model is ideal for studying aggressive tumor growth and the responses to complex therapeutic combinations due to its vascularization and complex microenvironment. This study aims to demonstrate the relevance of analyzing a complex therapeutic response to osimertinib treatment, especially through advanced transcriptomic analysis with the CAM model, which has been limited thus far. We engrafted HCC827 cells (EGFR p.E746_A750del) into the CAM model and treated them with various osimertinib doses for 7 days. The study involved supervised multivariate discrimination and ontology analysis of human transcriptional data. We found that CDX tumor growth inversely correlated with osimertinib dosage, with a notable 35% tumor weight reduction at 10 μm. Transcriptomic analysis revealed that osimertinib reduces EGFR pathway activity and its effectors, and dampens chemotaxis, immune recruitment and angiogenesis, indicating that effectiveness extends beyond cellular mechanisms to the tissue level. This was supported by a 15% reduction in blood vessels around the xenograft in osimertinib-treated cases. This study is the first to demonstrate that ontological analysis of transcriptomic data in the CAM model aligns with clinical observations, highlighting the relevance of this methodology for understanding and ameliorating the efficacy of targeted therapy in NSCLC.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Tryptophan-sensing receptor GPR142 expression levels are directly regulated by proinflammatory cytokines in ghrelin-producing cells. 色氨酸感知受体GPR142的表达水平直接受促炎细胞因子在生长素产生细胞中的调节。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2025-01-30 DOI: 10.1002/2211-5463.13973

Yoko Ueda, Hiroshi Iwakura, Takuya Ensho, Mika Bando-Shimizu, Asako Doi, Norihiko Matsutani, Shuhei Morita, Hidefumi Inaba, Hiroyuki Ariyasu, Naoki Fukuda, Keiji Hayata, Toshiyasu Ojima, Masahiro Nishi, Taka-Aki Matsuoka, Hiroki Yamaue, Takashi Akamizu

{"title":"Tryptophan-sensing receptor GPR142 expression levels are directly regulated by proinflammatory cytokines in ghrelin-producing cells.","authors":"Yoko Ueda, Hiroshi Iwakura, Takuya Ensho, Mika Bando-Shimizu, Asako Doi, Norihiko Matsutani, Shuhei Morita, Hidefumi Inaba, Hiroyuki Ariyasu, Naoki Fukuda, Keiji Hayata, Toshiyasu Ojima, Masahiro Nishi, Taka-Aki Matsuoka, Hiroki Yamaue, Takashi Akamizu","doi":"10.1002/2211-5463.13973","DOIUrl":"https://doi.org/10.1002/2211-5463.13973","url":null,"abstract":"GPR142 is a tryptophan-sensing receptor that has been implicated in the regulation of inflammation. In this study, we investigated the relationships between inflammatory cytokine and GPR142 expression by using cellular, animal models, and human stomach samples. We found that addition of TNF-α, IL-6, and IL-1β into the culture of ghrelin-producing cell line, MGN3-1 cells, increased GPR142 mRNA expression levels. Lipopolysaccharide (LPS) injection to mice significantly increased GPR142 expression in the stomach, confirming the results observed in the cellular model. GPR142 mRNA expression levels in the stomach samples of morbidly obese patients were positively correlated with TNF-α, IL-6, and IL-1β mRNA levels. Taken together our results suggest that GPR142 expression is under the direct control of proinflammatory cytokines and support further investigation of GPR142 potential roles in inflammation.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Real-world genomic landscape of colon and rectal cancer 结肠癌和直肠癌的真实基因组图谱。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2025-01-26 DOI: 10.1002/2211-5463.13957

Markus Schulze, XiaoZhe Wang, Jawad Hamad, Julia C. F. Quintanilha, Lincoln W. Pasquina, Julia F. Hopkins, Juergen Scheuenpflug, Zheng Feng

引用次数: 0

Young, female and scientist: exploring barriers, challenges and opportunities 青年、女性和科学家：探索障碍、挑战和机遇。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2025-01-24 DOI: 10.1002/2211-5463.13972

Nohelly Derosiers, Eline Bernaerts, Jessica L. Braun, Victoria Pozo Garcia, Radosveta Gencheva, Ana Paredes Garcia, Ioannis Tsagakis

引用次数: 0

An open chat between Prof Asifa Akhtar and Klaudia Jaczynska Asifa Akhtar教授和Klaudia Jaczynska之间的公开聊天。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2025-01-24 DOI: 10.1002/2211-5463.13971

Asifa Akhtar, Klaudia Jaczynska, Ioannis Tsagakis

引用次数: 0

Comparative activity of dimethyl fumarate derivative IDMF in three models relevant to multiple sclerosis and psoriasis. 富马酸二甲酯衍生物IDMF在多发性硬化症和牛皮癣相关的三种模型中的比较活性。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2025-01-17 DOI: 10.1002/2211-5463.13969

Yulin He, Guiyi Gong, Geovani Quijas, Simon Ming-Yuen Lee, Ratan K Chaudhuri, Krzysztof Bojanowski

引用次数: 0

FAM136A depletion induces mitochondrial stress and reduces mitochondrial membrane potential and ATP production. FAM136A缺失诱导线粒体应激，降低线粒体膜电位和ATP的产生。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2025-01-16 DOI: 10.1002/2211-5463.13967

Yushi Otsuka, Masato Yano

{"title":"FAM136A depletion induces mitochondrial stress and reduces mitochondrial membrane potential and ATP production.","authors":"Yushi Otsuka, Masato Yano","doi":"10.1002/2211-5463.13967","DOIUrl":"https://doi.org/10.1002/2211-5463.13967","url":null,"abstract":"FAM136A deficiency has been associated with Ménière's disease. However, the underlying mechanism of action of this protein remains unclear. We hypothesized that FAM136A functions in maintaining mitochondria, even in HepG2 cells. To better characterize FAM136A function, we analyzed the cellular response caused by its depletion. FAM136A depletion induced reactive oxygen species (ROS) and reduced both mitochondrial membrane potential and ATP production. However, cleaved caspase-9 levels did not increase significantly. We next investigated why the depletion of FAM136A reduced the mitochondrial membrane potential and ATP production but did not lead to apoptosis. Depletion of FAM136A induced the mitochondrial unfolded protein response (UPRmt) and the expression levels of gluconeogenic phosphoenolpyruvate carboxykinases (PCK1 and PCK2) and ketogenic 3-hydroxy-3-methylglutaryl-CoA synthases (HMGCS1 and HMGCS2) were upregulated. Furthermore, depletion of FAM136A reduced accumulation of holocytochrome c synthase (HCCS), a FAM136A interacting enzyme that combines heme to apocytochrome c to produce holocytochrome c. Notably, the amount of heme in cytochrome c did not change significantly with FAM136A depletion, although the amount of total cytochrome c protein increased significantly. This observation suggests that greater amounts of cytochrome c remain unbound to heme in FAM136A-depleted cells.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Expression and purification of E140 protein antigen fragments of Plasmodium vivax and Plasmodium berghei for serological assays. 间日疟原虫和伯氏疟原虫E140蛋白抗原片段的表达和纯化及血清学检测。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2025-01-15 DOI: 10.1002/2211-5463.13939

Rodolfo Ferreira Marques, Edit Ábrahám, Hiromi Muramatsu, Daniel Youssef Bargieri, Norbert Pardi, Zoltán Lipinszki

{"title":"Expression and purification of E140 protein antigen fragments of Plasmodium vivax and Plasmodium berghei for serological assays.","authors":"Rodolfo Ferreira Marques, Edit Ábrahám, Hiromi Muramatsu, Daniel Youssef Bargieri, Norbert Pardi, Zoltán Lipinszki","doi":"10.1002/2211-5463.13939","DOIUrl":"https://doi.org/10.1002/2211-5463.13939","url":null,"abstract":"Malaria, a life-threatening disease caused by Plasmodium parasites, continues to pose a significant global health threat, with nearly 250 million infections and over 600 000 deaths reported annually by the WHO. Fighting malaria is particularly challenging partly due to the complex life cycle of the parasite. However, technological breakthroughs such as the development of the nucleoside-modified mRNA lipid nanoparticle (mRNA-LNP) vaccine platform, along with the discovery of novel conserved Plasmodium antigens such as the E140 protein, present new opportunities in malaria prevention. Importantly, production of recombinant proteins for malaria vaccine evaluation by serological assays often represents an additional hurdle because many Plasmodium proteins are complex and often contain transmembrane domains that make production and purification particularly difficult. This research protocol provides a step-by-step guide for the production and purification of P. berghei and P. vivax E140 protein fragments that can be used to test humoral immune responses against this novel malaria vaccine target. We demonstrate that the purified proteins can be successfully used in enzyme-linked immunosorbent assay (ELISA) to evaluate antigen-specific binding antibody responses in sera obtained from E140 mRNA-LNP-vaccinated mice. Therefore, these proteins can contribute to the development and evaluation of E140-based malaria vaccines.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Evaluation of synaptotagmin-1 action models by all-atom molecular dynamics simulations. 全原子分子动力学模拟评价synaptotagmin-1作用模型。

IF 2.8 4区生物学

FEBS Open Bio Pub Date : 2025-01-15 DOI: 10.1002/2211-5463.13966

Josep Rizo, Klaudia Jaczynska, Christian Rosenmund

{"title":"Evaluation of synaptotagmin-1 action models by all-atom molecular dynamics simulations.","authors":"Josep Rizo, Klaudia Jaczynska, Christian Rosenmund","doi":"10.1002/2211-5463.13966","DOIUrl":"https://doi.org/10.1002/2211-5463.13966","url":null,"abstract":"Neurotransmitter release is triggered in microseconds by the two C2 domains of the Ca2+ sensor synaptotagmin-1 and by SNARE complexes, which form four-helix bundles that bridge the vesicle and plasma membranes. The synaptotagmin-1 C2B domain binds to the SNARE complex via a 'primary interface', but the mechanism that couples Ca2+-sensing to membrane fusion is unknown. Widespread models postulate that the synaptotagmin-1 Ca2+-binding loops accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers or helping bridge the membranes, but these models do not seem compatible with SNARE binding through the primary interface, which orients the Ca2+-binding loops away from the fusion site. To test these models, we performed molecular dynamics simulations of SNARE complexes bridging a vesicle and a flat bilayer, including the synaptotagmin-1 C2 domains in various configurations. Our data do not support the notion that insertion of the synaptotagmin-1 Ca2+-binding loops causes substantial membrane curvature or major perturbations of the lipid bilayers that could facilitate membrane fusion. We observed membrane bridging by the synaptotagmin-1 C2 domains, but such bridging or the presence of the C2 domains near the site of fusion hindered the action of the SNAREs in bringing the membranes together. These results argue against models predicting that synaptotagmin-1 triggers neurotransmitter release by inducing membrane curvature, perturbing bilayers or bridging membranes. Instead, our data support the hypothesis that binding via the primary interface keeps the synaptotagmin-1 C2 domains away from the site of fusion, orienting them such that they trigger release through a remote action.","PeriodicalId":12187,"journal":{"name":"FEBS Open Bio","volume":" ","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002703","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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