Cells最新文献_第8页

The TIP60-CD44 Axis Modulates Colorectal Cancer Stemness. TIP60-CD44轴调控结直肠癌干性

IF 5.1 2区生物学

Cells Pub Date : 2025-05-09 DOI: 10.3390/cells14100686

Asad Mohammad, Sudhakar Jha

{"title":"The TIP60-CD44 Axis Modulates Colorectal Cancer Stemness.","authors":"Asad Mohammad, Sudhakar Jha","doi":"10.3390/cells14100686","DOIUrl":"10.3390/cells14100686","url":null,"abstract":"HIV-1 Tat-interactive protein of 60 kDa (TIP60) is a lysine acetyltransferase protein that can acetylate histone and non-histone proteins. This study highlights TIP60's role in regulating colorectal cancer (CRC) stemness. The depletion of TIP60 resulted in a marked decrease in cellular proliferation, highlighting TIP60's involvement in the progression of CRC. Additionally, the loss of TIP60 impacted colony formation, transitioning from densely packed structures to dispersed spindle networks along with the loss of E-cadherin, indicating its role in the epithelial-mesenchymal transition (EMT). Three-dimensional culture models suggest that TIP60 is vital for spheroid formation, highlighting its importance in maintaining cancer stem cell properties in CRC. TIP60-depleted cells showed increased invasion in a 3D basement membrane extract (BME) invasion matrix, demonstrating its essential role in cellular invasiveness. Mechanistically, the reduction of TIP60 resulted in a decrease in CD44 expression, a critical marker for cancer stem cells (CSCs). Notably, CD44 overexpression restored the efficiency of spheroid formation and cell proliferation while reversing the EMT phenotype. Developing the TIP60-CD44 axis as a therapeutic target to treat CRC stemness and metastasis will help decrease the burden due to the deadly disease.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12110716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149334","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

Epithelial Dysfunction in Congenital Diaphragmatic Hernia: Mechanisms, Models and Emerging Therapies. 先天性膈疝的上皮功能障碍：机制、模型和新兴疗法。

IF 5.1 2区生物学

Cells Pub Date : 2025-05-09 DOI: 10.3390/cells14100687

Ophelia Aubert, Olivia M Dinwoodie, Richard Wagner, Xingbin Ai

{"title":"Epithelial Dysfunction in Congenital Diaphragmatic Hernia: Mechanisms, Models and Emerging Therapies.","authors":"Ophelia Aubert, Olivia M Dinwoodie, Richard Wagner, Xingbin Ai","doi":"10.3390/cells14100687","DOIUrl":"10.3390/cells14100687","url":null,"abstract":"Congenital diaphragmatic hernia (CDH) is a complex disorder whereby improper formation of the diaphragm allows herniation of the internal organs into the thoracic cavity, resulting in pulmonary hypoplasia among other complications. Although epithelial dysfunction is central to CDH pathology, relatively little attention has been paid to the underlying mechanisms orchestrating epithelial malfunction. Proinflammatory signaling downstream of impaired mechanotransduction due to in utero lung compression has been elucidated to drive epithelial cell phenotypes. This has been illustrated by a reduction in nuclear YAP and the upregulation of NF-kB in CDH models. In this review, we draw from recent findings using emerging technologies to examine epithelial cell mechanisms in CDH and discuss the role of compression as a central and, crucially, sufficient driver of CDH phenotypes. In recognition of the limitations of using genetic knockout models to recapitulate such a heterogenic and etiologically complicated disease, we discuss alternative models such as the established nitrofen rat model, air-liquid interface (ALI) cultures, organoids and ex vivo lung explants. Throughout, we acknowledge the importance of involving mechanical compression in the modeling of CDH in order to faithfully recapitulate the disease. Finally, we explore novel therapeutic strategies from stem cell and regenerative therapies to precision medicine and the importance of defining CDH endotypes in order to guide treatments.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149292","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

Intracellular Inclusions Induced by Patient-Derived and Amplified α-Synuclein Aggregates Are Morphologically Indistinguishable. 由患者来源的和扩增的α-突触核蛋白聚集体诱导的细胞内包涵体在形态学上难以区分。

IF 5.1 2区生物学

Cells Pub Date : 2025-05-09 DOI: 10.3390/cells14100684

Rabab Al-Lahham, Mark E Corkins, Mohd Ishtikhar, Prakruti Rabadia, Santiago Ramirez, Victor Banerjee, Mohammad Shahnawaz

{"title":"Intracellular Inclusions Induced by Patient-Derived and Amplified α-Synuclein Aggregates Are Morphologically Indistinguishable.","authors":"Rabab Al-Lahham, Mark E Corkins, Mohd Ishtikhar, Prakruti Rabadia, Santiago Ramirez, Victor Banerjee, Mohammad Shahnawaz","doi":"10.3390/cells14100684","DOIUrl":"10.3390/cells14100684","url":null,"abstract":"Lewy Body Disease (LBD) and Multiple System Atrophy (MSA) are synucleinopathies with distinct prognoses and neuropathologies, however, with overlapping clinical symptoms. Different disease characteristics are proposed to be determined by distinct conformations of alpha-synuclein (α-Syn) aggregates, which can self-propagate and spread between cells via a prion-like mechanism. The goal of this study is to investigate whether α-syn aggregates amplified from brain and CSF samples of LBD and MSA patients using the Seed Amplification Assay (SAA) maintain α-Syn seeding properties similar to those of α-syn aggregates derived from patients' brains. To address this, SAA-amplified and un-amplified α-Syn aggregates from LBD and MSA patients' brains, as well as SAA-amplified α-Syn aggregates from LBD and MSA patients' CSF samples, were used to treat synuclein biosensor cells, and induced intracellular α-Syn inclusions were analyzed by confocal microscopy. Our data indicate that induced α-Syn aggregates from LBD and MSA patients' brains have similar seeding properties and morphological characteristics in the α-Syn biosensor cells as those amplified from LBD and MSA patients' brains, as well as those amplified from LBD and MSA patients' CSF samples. In this study, we demonstrated that, regardless of the source of aggregates, the seeds from LBD and MSA produce cellular accumulation of α-Syn with distinct morphologies, confirming the presence of different conformational strains of α-Syn in LBD and MSA and allowing us to differentiate synucleinopathies based on the morphology of aggregates and seeding properties.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12110328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149351","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

Reversible Modulation of Motile Cilia by a Benzo[e][1,2,4]triazinone: A Potential Non-Hormonal Approach to Male Contraception. 苯并三嗪酮对纤毛运动的可逆调节[e][1,2,4]：一种潜在的非激素男性避孕方法。

IF 5.1 2区生物学

Cells Pub Date : 2025-05-09 DOI: 10.3390/cells14100688

Maria Chatzifrangkeskou, Alexandra Perdiou, Revekka Kreouzou, Georgia A Zissimou, Dragos F Flesariu, Panayiotis A Koutentis, Paris A Skourides

{"title":"Reversible Modulation of Motile Cilia by a Benzo[e][1,2,4]triazinone: A Potential Non-Hormonal Approach to Male Contraception.","authors":"Maria Chatzifrangkeskou, Alexandra Perdiou, Revekka Kreouzou, Georgia A Zissimou, Dragos F Flesariu, Panayiotis A Koutentis, Paris A Skourides","doi":"10.3390/cells14100688","DOIUrl":"10.3390/cells14100688","url":null,"abstract":"Motile cilia play essential roles in various physiological processes including fluid flow generation and sperm motility. In this study, we identified 1,3-diphenyl-6-(4-phenylpiperazin-1-yl)benzo[e][1,2,4]triazin-7(1H)-one as a potent and reversible modulator of ciliary function using the Xenopus laevis model. This benzotriazinone derivative inhibits ciliary-driven fluid flow by inducing cilia detachment without causing toxicity in developing embryos. Unlike traditional deciliation agents that rely on calcium signaling, this compound induces cilia loss through a shear stress-driven mechanism at the transition zone, without disrupting tissue morphology or the apical actin network. Importantly, it also induces flagellar loss and impairs sperm motility at picomolar concentrations. Our findings highlight the potential of this 6-(4-phenylpiperazin-1-yl)-substituted benzotriazinone as a non-hormonal male contraceptive and underscore a novel mechanism of cilia modulation that may have broader implications for the treatment of cilia-related disorders.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12110593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149509","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

Naringenin Targets PI3K p85alpha to Suppress PI3K/AKT Signaling Pathway and Ameliorate Disordered MMP-9 Secretion in Cigarette Smoke Extract-Induced Alveolar Macrophages In Vitro. 柚皮素靶向PI3K p85alpha抑制PI3K/AKT信号通路并改善香烟烟雾提取物诱导的肺泡巨噬细胞MMP-9分泌紊乱

IF 5.1 2区生物学

Cells Pub Date : 2025-05-08 DOI: 10.3390/cells14100678

Weiyang Fan, Ziyan Xu, Mengli Zhong, Xiao Wu, Pan Chen, Zhen Chen, Weiwei Su, Hao Wu, Peibo Li

{"title":"Naringenin Targets PI3K p85alpha to Suppress PI3K/AKT Signaling Pathway and Ameliorate Disordered MMP-9 Secretion in Cigarette Smoke Extract-Induced Alveolar Macrophages In Vitro.","authors":"Weiyang Fan, Ziyan Xu, Mengli Zhong, Xiao Wu, Pan Chen, Zhen Chen, Weiwei Su, Hao Wu, Peibo Li","doi":"10.3390/cells14100678","DOIUrl":"10.3390/cells14100678","url":null,"abstract":"Background: Naringenin has demonstrated potential therapeutic effects against cigarette smoke-induced lung injury; however, its underlying mechanisms of regulating matrix metalloproteinase-9 (MMP-9) in alveolar macrophages remain unclear.Methods: The regulatory mechanisms of naringenin in cigarette smoke extract (CSE)-induced alveolar macrophages were investigated using proteomics, and then, naringenin's targets were further validated by Western blot, molecular docking, molecular dynamics (MD) simulations, cellular thermal shift assay (CETSA), and enzyme activity assay.Results: The proteomics revealed that the PI3K/AKT signaling pathway might play a crucial role in naringenin's inhibition of MMP-9. Western blot analysis confirmed that naringenin significantly inhibited CSE-upregulated PI3K/AKT signaling pathway and reduced MMP-9 expression in MH-S cells. Notably, the PI3K activator 740Y-P reversed naringenin's effects on MMP-9. Additionally, molecular docking, MD simulations, and CETSA identified PI3K p85alpha as the potential binding site for naringenin, and naringenin markedly inhibited CSE-induced PI3K activity. In in vitro experiments, naringenin inhibiting MMP-9 secretion in alveolar macrophages contributed to alleviating elastin and E-cadherin damage in alveolar epithelial cells. Furthermore, naringenin effectively suppressed CSE-induced MMP-9 secretion in primary mouse alveolar macrophages and human THP-1-differentiated macrophages.Conclusions: Our findings revealed that naringenin, a potential candidate for treating smoking-induced lung injury, directly targeted PI3K p85alpha, inhibiting PI3K activity and MMP-9 expression in CSE-induced alveolar macrophages via suppressing the PI3K/AKT signaling pathway.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149476","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

Effects of Cisplatin on the Radiation Response and DNA Damage Markers in Peripheral Blood Lymphocytes Ex Vivo. 顺铂对体外放射线反应及外周血淋巴细胞DNA损伤标志物的影响。

IF 5.1 2区生物学

Cells Pub Date : 2025-05-08 DOI: 10.3390/cells14100682

Sebastian Zahnreich, Aisha Bhatti, Barea Ahmad, Sophia Drabke, Justus Kaufmann, Heinz Schmidberger

{"title":"Effects of Cisplatin on the Radiation Response and DNA Damage Markers in Peripheral Blood Lymphocytes Ex Vivo.","authors":"Sebastian Zahnreich, Aisha Bhatti, Barea Ahmad, Sophia Drabke, Justus Kaufmann, Heinz Schmidberger","doi":"10.3390/cells14100682","DOIUrl":"10.3390/cells14100682","url":null,"abstract":"Platinum-based radiochemotherapy is associated with hematologic side effects, impacting patient outcomes. However, the clinical mechanisms of cisplatin and its interaction with ionizing radiation (IR), including in biodosimetry for radiotherapy, have not yet been fully clarified. For this purpose, healthy donors' peripheral blood lymphocytes (PBLs) were pretreated with cisplatin in a pulse (1-4 h) or continuous (24 h) regimen followed by X-rays. DNA damage was assessed as DNA double-strand breaks using repair foci of γH2AX and 53BP1 after 0.5 h and 24 h in G1 PBLs and a proliferation-based cytokinesis-block micronucleus assay. Additionally, cell death and proliferation activity were measured. Unlike a 1 h pulse, a 24 h cisplatin pretreatment caused a concentration-dependent increase in cisplatin-induced foci while decreasing IR-induced foci, especially 24 h after irradiation. This was accompanied by increased apoptosis, with cisplatin and IR having additive effects. Both genotoxins alone caused a dose-dependent increase in micronuclei, while cisplatin significantly reduced binuclear cells, especially after the 24 h treatment, leading to lower micronuclei frequencies post-irradiation. Our results show that prolonged cisplatin exposure, even at low concentrations, impacts the vitality and division activity of PBLs, with significantly stronger effects post-irradiation. This has major implications and must be considered for the detection of DNA damage-associated biomarkers in PBLs used in clinical prediction or biodosimetry during radiotherapy.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149152","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

Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses. ALS-FTD蛋白聚集的分子机制：聚焦于TDP-43和细胞保护反应。

IF 5.1 2区生物学

Cells Pub Date : 2025-05-08 DOI: 10.3390/cells14100680

Enza Maria Verde, Valentina Secco, Andrea Ghezzi, Jessica Mandrioli, Serena Carra

{"title":"Molecular Mechanisms of Protein Aggregation in ALS-FTD: Focus on TDP-43 and Cellular Protective Responses.","authors":"Enza Maria Verde, Valentina Secco, Andrea Ghezzi, Jessica Mandrioli, Serena Carra","doi":"10.3390/cells14100680","DOIUrl":"10.3390/cells14100680","url":null,"abstract":"Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD) are two neurodegenerative disorders that share common genes and pathomechanisms and are referred to as the ALS-FTD spectrum. A hallmark of ALS-FTD pathology is the abnormal aggregation of proteins, including Cu/Zn superoxide dismutase (SOD1), transactive response DNA-binding protein 43 (TDP-43), fused in sarcoma/translocated in liposarcoma (FUS/TLS), and dipeptide repeat proteins resulting from C9orf72 hexanucleotide expansions. Genetic mutations linked to ALS-FTD disrupt protein stability, phase separation, and interaction networks, promoting misfolding and insolubility. This review explores the molecular mechanisms underlying protein aggregation in ALS-FTD, with a particular focus on TDP-43, as it represents the main aggregated species inside pathological inclusions and can also aggregate in its wild-type form. Moreover, this review describes the protective mechanisms activated by the cells to prevent protein aggregation, including molecular chaperones and post-translational modifications (PTMs). Understanding these regulatory pathways could offer new insights into targeted interventions aimed at mitigating cell toxicity and restoring cellular function.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149455","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

Identification of Prognostic Biomarkers of Ovarian High-Grade Serous Carcinoma: A Preliminary Study Using Spatial Transcriptome Analysis and Multispectral Imaging. 鉴定卵巢高级别浆液性癌的预后生物标志物：利用空间转录组分析和多光谱成像的初步研究。

IF 5.1 2区生物学

Cells Pub Date : 2025-05-08 DOI: 10.3390/cells14100681

Haeyoun Kang, Je-Gun Joung, Hyun Park, Min Chul Choi, Doohyun Koh, Ju-Yeon Jeong, Jimin Lee, Sook-Young Kim, Daun Jung, Sohyun Hwang, Hee Jung An

{"title":"Identification of Prognostic Biomarkers of Ovarian High-Grade Serous Carcinoma: A Preliminary Study Using Spatial Transcriptome Analysis and Multispectral Imaging.","authors":"Haeyoun Kang, Je-Gun Joung, Hyun Park, Min Chul Choi, Doohyun Koh, Ju-Yeon Jeong, Jimin Lee, Sook-Young Kim, Daun Jung, Sohyun Hwang, Hee Jung An","doi":"10.3390/cells14100681","DOIUrl":"10.3390/cells14100681","url":null,"abstract":"Ovarian cancer is a lethal malignancy, with most patients initially responding to chemotherapy but frequently experiencing recurrence. Previous studies primarily examined tumor characteristics using limited genetic markers or bulk RNA sequencing. Here, we used spatial transcriptomics via the GeoMx® platform, alongside multispectral immune cell immunofluorescence (IF), to identify biomarkers associated with disease progression following first-line treatment of high-grade serous carcinoma (HGSC). We identified several spatial biomarkers linked to non-recurrence, including elevated NKG7 expression in CD45+ immune cell regions (p = 0.0011) and higher TFPI2 and PIGR expression in tumor areas (p = 2.09 × 10-6), both associated with improved progression-free survival. Multispectral IF revealed significantly higher regulatory T cell (Treg) to CD8+ T cell ratios in the tumor nests and stroma of recurrent patients (p = 0.016, 0.048). Tregs were also found closer to cancer cells or macrophages than CD8+ T cells in recurrent tumors (p = 0.048), correlating with poor survival. Integrated analysis showed that immune cell density and immune pathway scores in the recurrent group positively correlated with cancer pathway scores, except for NF-κB. This comprehensive analysis revealed clues to interactions between different immune cells and identified biomarkers that may be useful for predicting recurrence of HGSC.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12110039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149335","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

Impact of Drp1 Loss on Organelle Interaction, Metabolism, and Inflammation in Mouse Liver. Drp1缺失对小鼠肝脏细胞器相互作用、代谢和炎症的影响。

IF 5.1 2区生物学

Cells Pub Date : 2025-05-08 DOI: 10.3390/cells14100679

Lixiang Wang, Seiji Nomura, Nao Hasuzawa, Sadaki Yokota, Ayako Nagayama, Kenji Ashida, Junjiro Rikitake, Yoshinori Moriyama, Masatoshi Nomura, Ken Yamamoto

{"title":"Impact of Drp1 Loss on Organelle Interaction, Metabolism, and Inflammation in Mouse Liver.","authors":"Lixiang Wang, Seiji Nomura, Nao Hasuzawa, Sadaki Yokota, Ayako Nagayama, Kenji Ashida, Junjiro Rikitake, Yoshinori Moriyama, Masatoshi Nomura, Ken Yamamoto","doi":"10.3390/cells14100679","DOIUrl":"10.3390/cells14100679","url":null,"abstract":"Dynamin-related protein 1 (Drp1) is a crucial player in mitochondrial fission and liver function. The interactions between mitochondria, endoplasmic reticulum (ER), and lipid droplets (LDs) are fundamental for lipid metabolism. This study utilized liver-specific Drp1 knockout (Drp1LiKO) mice to investigate the effects of Drp1 deficiency on organelle interactions, metabolism, and inflammation. Our analysis revealed disrupted interactions between mitochondria and LDs, as well as altered interactions among ER, mitochondria, and LDs in Drp1LiKO mice. Through mass spectrometry and microarray analysis, we identified changes in lipid profiles and perturbed expression of lipid metabolism genes in the livers of Drp1LiKO mice. Further in vitro experiments using primary hepatocytes from Drp1LiKO mice confirmed disturbances in lipid metabolism and increased inflammation. These findings highlight the critical involvement of Drp1 in regulating organelle interactions for efficient lipid metabolism and overall liver health. Targeting Drp1-mediated organelle interactions may offer potential for developing therapies for liver diseases associated with disrupted lipid metabolism.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 10","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12109831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144149318","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

Experimental and Mathematical Model of Platelet Hemostasis Kinetics. 血小板止血动力学的实验与数学模型。

IF 5.1 2区生物学

Cells Pub Date : 2025-05-07 DOI: 10.3390/cells14090677

Bogdan Gerda, Anastasiya Volkova, Irina Dobrylko, Aleksandra Yu Andreyeva, Thomas Dandekar, Mikhail A Panteleev, Stepan Gambaryan, Igor Mindukshev

{"title":"Experimental and Mathematical Model of Platelet Hemostasis Kinetics.","authors":"Bogdan Gerda, Anastasiya Volkova, Irina Dobrylko, Aleksandra Yu Andreyeva, Thomas Dandekar, Mikhail A Panteleev, Stepan Gambaryan, Igor Mindukshev","doi":"10.3390/cells14090677","DOIUrl":"10.3390/cells14090677","url":null,"abstract":"Upon activation, platelets undergo rapid phenotypic transitions to maintain hemostasis, yet the kinetics governing these transitions remain poorly quantified. We present an integrated experimental and mathematical model describing platelet transitions between resting, activated, aggregating, inhibited, and exhausted phenotypes, determined by experiment rate constants for these reactions. Theoretical simulations of platelet transitions accurately describe the independently determined experimental read-out. Platelet aggregation under the conditions used directly correlates with the activation of αIIbβ3 integrins, demonstrating that the parameters of platelet aggregation achieved by the laser diffraction technique can be used for the evaluation of the rapid activation and deactivation kinetics of αIIbβ3 integrins. We demonstrate that platelet desensitization occurs at multiple activation stages, with distinct kinetic profiles for shape change and integrin deactivation. We also show that even 5 s of receptor-mediated PKA activation (iloprost) is sufficient for a complete inhibition of ADP-induced platelet aggregation. However, when iloprost was added after platelet stimulation by ADP, platelet activation was not fully inhibited, and after 180 s, aggregation became irreversible. The presented data help to understand the mechanisms of platelet transition between different phenotypes. The model effectively characterizes key physiological phenotypes and can serve as a modular framework for integration into more comprehensive models.","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 9","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12071887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974214","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