{"title":"PAK4 is Required for Meiotic Resumption, Spindle Assembly, and Cortical Migration in Mouse Oocytes During Meiotic Maturation","authors":"Ke Song, Dandan Chen, Jingyu Li, Jiaqi Zhang, Ying Tian, Xiangning Xu, Bicheng Wang, Ziqi Huang, Shuo Lou, Jingyi Kang, Ningning Zhang, Xiaokui Yang, Wei Ma","doi":"10.1002/adbi.202400307","DOIUrl":"10.1002/adbi.202400307","url":null,"abstract":"<p>Oocyte meiotic errors can cause infertility, miscarriage, and birth defects. Here the role and the underlying mechanism of p21 activated kinase 4 (PAK4) in mouse oocyte meiosis is evaluated. It is found that PAK4 expression and its phosphorylation are detected in high level at germinal vesicle (GV) stage, and gradually decreased after meiotic resumption in oocytes. PAK4 has direct physical interaction with both mitogen-activated protein kinases 1/2 (MEK1/2) and Paxillin, they are colocalized on the spindle structure during metaphases I and II. Phospho-PAK4 is distributed beneath the cytoplasmic membrane and on the chromosomes, and colocalized with the microtubule organizing center (MTOC) proteins, Pericentrin and γ-tubulin, as well as phosphor-MEK1/2 and phosphor-Paxillin on spindle poles. PAK4 inhibition by chemical inhibitor LCH-7749944, specific Pak4 morpholino oligo or the dominant negative mutant Pak4<sup>K350, 351 M</sup> influence the meiotic resumption, spindle assembly and its cortical migration, and associated with the downregulation in the dephosphorylation of cyclin dependent kinase 1 (CDK1) and the levels of Cyclin B1, MEK1/2, Paxillin, g-tubulin, acetylated a-tubulin, Arp3, and Cofilin phosphorylation in oocytes. In sum, PAK4 functions to sustain the rational levels of Cyclin B1, MEK1/2, Paxillin, y-tubulin, acetylated a-tubulin, Arp3, and phosphor-Cofilin in mouse oocytes, thereby promotes the meiotic resumption, spindle assembly, and migration during meiotic maturation.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455621","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}
Advanced biologyPub Date : 2024-10-16DOI: 10.1002/adbi.202400308
Sharon Saarinen, Ramsha Khan, Marta Patrian, Juan Pablo Fuenzalida-Werner, Rubén D Costa, Petr Zimcik, Veronika Novakova, Tero-Petri Ruoko, Nikolai V Tkachenko, Eduardo Anaya-Plaza, Mauri A Kostiainen
{"title":"Elucidating the Supramolecular Interaction of Positively Supercharged Fluorescent Protein with Anionic Phthalocyanines.","authors":"Sharon Saarinen, Ramsha Khan, Marta Patrian, Juan Pablo Fuenzalida-Werner, Rubén D Costa, Petr Zimcik, Veronika Novakova, Tero-Petri Ruoko, Nikolai V Tkachenko, Eduardo Anaya-Plaza, Mauri A Kostiainen","doi":"10.1002/adbi.202400308","DOIUrl":"https://doi.org/10.1002/adbi.202400308","url":null,"abstract":"<p><p>Developing bioinspired materials to convert sunlight into electricity efficiently is paramount for sustainable energy production. Fluorescent proteins are promising candidates as photoactive materials due to their high fluorescence quantum yield and absorption extinction coefficients in aqueous media. However, developing artificial bioinspired photosynthetic systems requires a detailed understanding of molecular interactions and energy transfer mechanisms in the required operating conditions. Here, the supramolecular self-assembly and photophysical properties of fluorescent proteins complexed with organic dyes are investigated in aqueous media. Supercharged mGreenLantern protein, mutated to have a charge of +22, is complexed together with anionic zinc phthalocyanines having 4 or 16 carboxylate groups. The structural characterization reveals a strong electrostatic interaction between the moieties, accompanied by partial conformational distortion of the protein structure, yet without compromising the mGreenLantern chromophore integrity as suggested by the lack of emission features related to the neutral form of the chromophore. The self-assembled biohybrid shows a total quenching of protein fluorescence, in favor of an energy transfer process from the protein to the phthalocyanine, as demonstrated by fluorescence lifetime and ultrafast transient absorption measurements. These results provide insight into the rich photophysics of fluorescent protein-dye complexes, anticipating their applicability as water-based photoactive materials.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400308"},"PeriodicalIF":3.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455619","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}
Advanced biologyPub Date : 2024-10-16DOI: 10.1002/adbi.202400235
Xin Zhang, Suchan Liao, Lingling Huang, Jinhua Wang
{"title":"Prospective Intervention Strategies Between Skeletal Muscle Health and Mitochondrial Changes During Aging","authors":"Xin Zhang, Suchan Liao, Lingling Huang, Jinhua Wang","doi":"10.1002/adbi.202400235","DOIUrl":"10.1002/adbi.202400235","url":null,"abstract":"<p>Sarcopenia is a geriatric condition characterized by a decrease in skeletal muscle mass and function, significantly impacting both quality of life and overall health. Mitochondria are the main sites of energy production within the cell, and also produce reactive oxygen species (ROS), which maintain mitochondrial homeostasis-mitophagy (clearing damaged mitochondria); mitochondrial dynamics, which involve fusion and fission to regulate mitochondrial morphology; mitochondrial biogenesis, which ensures the functionality and homeostasis of mitochondria. Sarcopenia is linked to mitochondrial dysfunction, suggesting that muscle mitochondrial function therapy should be investigated. Extrinsic therapies are extensively examined to identify new treatments for muscular illnesses including sarcopenia. Changes in muscle physiology and lifestyle interventions, such as pharmacological treatments and exercise, can modulate mitochondrial activity in older adults. This PubMed review encompasses the most significant mitophagy and sarcopenia research from the past five years. Animal models, cellular models, and human samples are well covered. The review will inform the development of novel mitochondria-targeted therapies aimed at combating age-related muscle atrophy.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455622","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}
Advanced biologyPub Date : 2024-10-16DOI: 10.1002/adbi.202400386
Irfan Qasam, Shah Nawaz, Hema Kumari, Narendra Chauhan, Yedukondalu Nalli, Govind Yadav
{"title":"Evaluation of Anti-Inflammatory and Immunosuppressant Potential of Isotelekin in Lipopolysaccharide (LPS) Stimulated Macrophage (RAW 264.7) and Sheep Red Blood Cells (SRBC) Sensitized Murine Models","authors":"Irfan Qasam, Shah Nawaz, Hema Kumari, Narendra Chauhan, Yedukondalu Nalli, Govind Yadav","doi":"10.1002/adbi.202400386","DOIUrl":"10.1002/adbi.202400386","url":null,"abstract":"<p>The present study explored the natural compound Isotelekin isolated from <i>Inula racemose</i> against anti-inflammatory and immunomodulatory potential in LPS-induced RAW264.7 cell lines and immune-elevated SRBC-sensitized animal models. Isotelekin in in vitro studies, inhibited the production of Th-1 cytokines Interleukin-6 (IL-6), Tumour necrosis factor (TNF-α), and Interferon-gamma (INF-γ), and increased Th-2 cytokines Interleukin-10 (IL-10). Whereas it inhibited the nitrites and reactive oxygen species (ROS) production by mitigating the effect of LPS significantly. In vivo immunomodulatory activity in Delayed-type hypersensitivity (DTH) and Hemagglutinating antibody (HA), Isotelekin suppressed the cellular as well as humoral immunity in immune-affected and SRBC-sensitized mice. Isotelekin decreased the phagocytic responses against carbon particles and plaque-forming mainly IgG (Immunoglobulin G) production. Additionally, Isotelekin showed immunosuppressive potential through the evaluation of splenocytes, allograft acceptance, and haematological parameters. Molecular studies, including western blot analysis and immunocytochemistry, revealed that Isotelekin reduced the expression of iNOS (Inducible nitric oxide synthase), COX-2 (Cyclo-Oxygenase 2), and p-IkBα (Phospho I-kappa-B-alpha), and significantly inhibited the nuclear translocation of NF-κB/p65. Based on these results, Isotelekin at 10 µ<span>m</span> in in vitro and at 30 mg kg<sup>−1</sup> in in vivo demonstrated strong anti-inflammatory and immunosuppressive therapeutic potential.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455620","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}
{"title":"Chemical Proteomics Approaches for Screening Small Molecule Inhibitors Covalently Binding to SARS-Cov-2","authors":"Liuhai Zheng, Qian Zhang, Piao Luo, Fei Shi, Ying Zhang, Xiaoxue He, Yehai An, Guangqing Cheng, Xiaoyan Pan, Zhijie Li, Boping Zhou, Jigang Wang","doi":"10.1002/adbi.202300612","DOIUrl":"10.1002/adbi.202300612","url":null,"abstract":"<p>Although various strategies have been used to prevent and treat SARS-CoV-2, the spread and evolution of SARS-CoV-2 is still progressing rapidly. The emerging variants Omicron and its sublineage have a greater ability to spread and escape nearly all current monoclonal antibodies treatments, highlighting an urgent need to develop therapeutics targeting current and emerging Omicron variants or recombinants with breadth and potency. Here, some small molecule drugs are rapidly identified that could covalently binding to receptor binding domain (RBD) protein of Omicron through the combined application of artificial intelligence (AI) and activity-based protein profiling (ABPP) technology. The surface plasmon resonance (SPR) and pseudo-virus neutralization experiments further reveal that an FDA-approved drug gallic acid has robust neutralization potency against Omicron pseudo-virus with the IC<sub>50</sub> values of 23.56 × 10<sup>−6</sup> <span>m</span>. Taken together, a platform combining AI intelligence, biochemical, SPR, molecular docking, and pseudo-virus-based screening for rapid identification and evaluation of potential anti-SARS-CoV-2 small molecule drugs is established and the effectiveness of the platform is validated.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"8 11","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455617","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}
{"title":"Electroacupuncture Slows Experimental Myopia Progression by Improving Retinal Mitochondrial Function: A Study Based on Single-Cell RNA Sequencing","authors":"Jiawen Hao, Yunxiao Xie, Huixia Wei, Zhaohui Yang, Ruixue Zhang, Zhongyu Ma, Miao Zhang, Xiaoshi Du, Xuewei Yin, Jinpeng Liu, Bo Bao, Hongsheng Bi, Dadong Guo","doi":"10.1002/adbi.202400269","DOIUrl":"10.1002/adbi.202400269","url":null,"abstract":"<p>This study aimed to establish a complete atlas of retinal cells in lens-induced myopia (LIM) and electroacupuncture (EA) intervention by single-cell RNA sequencing (scRNA-seq) and to explore the potential mechanism of EA in improving experimental myopia progression in guinea pigs. scRNA-seq is used to assess changes in individual cellular gene levels in the retina of LIM- and EA-treated guinea pigs. In addition, the role of EA in slowing myopia progression by improving retinal mitochondrial function is further investigated. scRNA-seq identified ten cell clusters in the retina of LIM and EA guinea pigs and mitochondrial respiratory chain-related genes in Cones and Muller-glia cells—Cytochrome oxidase subunit III (COX3), NADH dehydrogenase subunit 4 (ND4), and NADH dehydrogenase subunit 2 (ND2) are closely related to lens-induced myopia. A comprehensive atlas in the retina of LIM and EA guinea pigs at a single-cell level is established, and the positive role of EA in improving retinal mitochondrial function to slow the experimental myopia progression in guinea pigs is revealed.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"8 12","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455618","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}
Advanced biologyPub Date : 2024-10-13DOI: 10.1002/adbi.202470101
Jessica L. Funnell, Jasper Fougere, Diana Zahn, Silvio Dutz, Ryan J. Gilbert
{"title":"Delivery of TGFβ3 from Magnetically Responsive Coaxial Fibers Reduces Spinal Cord Astrocyte Reactivity In Vitro (Adv. Biology 10/2024)","authors":"Jessica L. Funnell, Jasper Fougere, Diana Zahn, Silvio Dutz, Ryan J. Gilbert","doi":"10.1002/adbi.202470101","DOIUrl":"https://doi.org/10.1002/adbi.202470101","url":null,"abstract":"<p><b>Drug Delivery</b></p><p>Spinal cord injury (SCI) is a devastating condition that severely impacts patient quality of life, and there are no available treatments that restore lost function. Biomaterials can provide local, sustained release of therapeutics, but drug-releasing biomaterials do not address variability in injury severity. To tune delivery to a unique injury, Ryan J. Gilbert and co-workers developed a fibrous scaffold that can be stimulated with a magnetic field to alter the release rate of a growth factor. The authors found that sustained release of the growth factor resulted in a greater reduction of spinal cord astrocyte reactivity compared to bolus delivery in vitro. The astrocytes treated with the drug-releasing scaffold supported sensory neuron growth in coculture, shown in the flourescence image. Article number 2300531 provides a foundation for developing biomaterials capable of tunable growth factor release in response to externally applied magnetic fields for SCI treatment.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"8 10","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202470101","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142439046","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}
{"title":"Idiopathic Pulmonary Fibrosis Caused by Damaged Mitochondria and Imbalanced Protein Homeostasis in Alveolar Epithelial Type II Cell","authors":"Zhaoxiong Dong, Xiaolong Wang, Peiwen Wang, Mingjian Bai, Tianyu Wang, Yanhui Chu, Yan Qin","doi":"10.1002/adbi.202400297","DOIUrl":"10.1002/adbi.202400297","url":null,"abstract":"<p>Alveolar epithelial Type II (ATII) cells are closely associated with early events of Idiopathic pulmonary fibrosis (IPF). Proteostasis dysfunction, endoplasmic reticulum (ER) stress, and mitochondrial dysfunction are known causes of decreased proliferation of alveolar epithelial cells and the secretion of pro-fibrotic mediators. Here, a large body of evidence is systematized and a cascade relationship between protein homeostasis, endoplasmic reticulum stress, mitochondrial dysfunction, and fibrotropic cytokines is proposed, providing a theoretical basis for ATII cells dysfunction as a possible pathophysiological initiating event for idiopathic pulmonary fibrosis.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/adbi.202400297","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399093","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}
Advanced biologyPub Date : 2024-10-08DOI: 10.1002/adbi.202400383
Zhuo Pei, Jing Fan, Maolin Tang, Yuhong Li
{"title":"Ferroptosis: A New Strategy for the Treatment of Fibrotic Diseases","authors":"Zhuo Pei, Jing Fan, Maolin Tang, Yuhong Li","doi":"10.1002/adbi.202400383","DOIUrl":"10.1002/adbi.202400383","url":null,"abstract":"<p>Ferroptosis is a new type of cell death characterized by iron dependence and the excessive accumulation of lipid reactive oxygen species (lipid ROS) that has gradually become better characterized. There is sufficient evidence indicating that ferroptosis is associated with a variety of human life activities and diseases, such as tumor suppression, ischemic organ injury, and degenerative disorders. Notably, ferroptosis is also involved in the initiation and development of fibrosis in various organs, including liver fibrosis, pulmonary fibrosis, renal fibrosis, and cardiac fibrosis, which is usually irreversible and refractory. Although a large number of patients with fibrosis urgently need to be treated, the current treatment options are still limited and unsatisfactory. Organ fibrosis involves a series of complex and orderly processes, such as parenchymal cell damage, recruitment of inflammatory cells and activation of fibroblasts, which ultimately leads to the accumulation of extracellular matrix (ECM) and the formation of fibrosis. An increasing number of studies have confirmed the close association between these pathological processes and ferroptosis. This review summarizes the role and function of ferroptosis in fibrosis and proposes several potential therapeutic strategies and pathways based on ferroptosis.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":"9 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387155","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}