Frontiers in Cell and Developmental Biology最新文献

The differentiation state of small intestinal organoid models influences prediction of drug-induced toxicity.

IF 4.6 2区生物学

Frontiers in Cell and Developmental Biology Pub Date : 2025-01-23 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1508820

Jessica A Klein, Julia D Heidmann, Tomomi Kiyota, Aaron Fullerton, Kimberly A Homan, Julia Y Co

{"title":"The differentiation state of small intestinal organoid models influences prediction of drug-induced toxicity.","authors":"Jessica A Klein, Julia D Heidmann, Tomomi Kiyota, Aaron Fullerton, Kimberly A Homan, Julia Y Co","doi":"10.3389/fcell.2025.1508820","DOIUrl":"10.3389/fcell.2025.1508820","url":null,"abstract":"Drug-induced intestinal toxicity (GIT) is a frequent dose-limiting adverse event that can impact patient compliance and treatment outcomes. In vivo, there are proliferative and differentiated cell types critical to maintaining intestinal homeostasis. Traditional in vitro models using transformed cell lines do not capture this cellular complexity, and often fail to predict intestinal toxicity. Primary tissue-derived intestinal organoids, on the other hand, are a scalable Complex in vitro Model (CIVM) that recapitulates major intestinal cell lineages and function. Intestinal organoid toxicity assays have been shown to correlate with clinical incidence of drug-induced diarrhea, however existing studies do not consider how differentiation state of the organoids impacts assay readouts and predictivity. We employed distinct proliferative and differentiated organoid models of the small intestine to assess whether differentiation state alone can alter toxicity responses to small molecule compounds in cell viability assays. In doing so, we identified several examples of small molecules which elicit differential toxicity in proliferative and differentiated organoid models. This proof of concept highlights the need to consider which cell types are present in CIVMs, their differentiation state, and how this alters interpretation of toxicity assays.","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1508820"},"PeriodicalIF":4.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364240","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

The Batten disease gene Cln3 is required for the activation of intestinal stem cell during regeneration via JAK/STAT signaling in Drosophila.

IF 4.6 2区生物学

Frontiers in Cell and Developmental Biology Pub Date : 2025-01-23 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1508714

Zihua Yu, Jinhua Yan, Zhiming Liu, Haiyan Wang, Guanzheng Luo, Haiyang Chen

{"title":"The Batten disease gene Cln3 is required for the activation of intestinal stem cell during regeneration via JAK/STAT signaling in Drosophila.","authors":"Zihua Yu, Jinhua Yan, Zhiming Liu, Haiyan Wang, Guanzheng Luo, Haiyang Chen","doi":"10.3389/fcell.2025.1508714","DOIUrl":"10.3389/fcell.2025.1508714","url":null,"abstract":"CLN3 mutation causes Juvenile neuronal ceroid lipofuscinosis (JNCL, also known as Batten disease), an early onset neurodegenerative disorder. Patients who suffer from Batten disease often die at an early age. However, the mechanisms underlying how CLN3 loss develops Batten disease remain largely unclear. Here, using Drosophila midgut system, we demonstrate that Drosophila Cln3 has no effect on midgut homeostasis maintaince, including cellular component, intestinal stem cells (ISCs) proliferation and differentiation, but is necessary for ISC activation upon tissue damage. Cell type-specific Gal4 screening reveals that the failure of ISC activation during regeneration caused by Cln3 loss is ISC-autonomous. Through genetic analyses, we elucidate that JAK/STAT signaling in ISCs is not activated with Cln3 depletion upon tissue damage, and functions downstream of Cln3. Our study provides a potential mechanism underlying the development of CLN3-mediated Batten disease at cellular level.","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1508714"},"PeriodicalIF":4.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364223","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

Dual role of pyroptosis in liver diseases: mechanisms, implications, and therapeutic perspectives.

IF 4.6 2区生物学

Frontiers in Cell and Developmental Biology Pub Date : 2025-01-23 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1522206

Siyuan Yang, Yunyi Zou, Chunhua Zhong, Zuoqiong Zhou, Xiyang Peng, Changfa Tang

{"title":"Dual role of pyroptosis in liver diseases: mechanisms, implications, and therapeutic perspectives.","authors":"Siyuan Yang, Yunyi Zou, Chunhua Zhong, Zuoqiong Zhou, Xiyang Peng, Changfa Tang","doi":"10.3389/fcell.2025.1522206","DOIUrl":"10.3389/fcell.2025.1522206","url":null,"abstract":"Pyroptosis, a form of programmed cell death induced by inflammasome with a mechanism distinct from that of apoptosis, occurs via one of the three pathway types: classical, non-classical, and granzyme A/B-dependent pyroptosis pathways. Pyroptosis is implicated in various diseases, notably exhibiting a dual role in liver diseases. It facilitates the clearance of damaged hepatocytes, preventing secondary injury, and triggers immune responses to eliminate pathogens and damaged cells. Conversely, excessive pyroptosis intensifies inflammatory responses, exacerbates hepatocyte damage and promotes the activation and proliferation of hepatic stellate cells, accelerating liver fibrosis. Furthermore, by sustaining an inflammatory state, impacts the survival and proliferation of cancer cells. This review comprehensively summarizes the dual role of pyroptosis in liver diseases and its therapeutic strategies, offering new theoretical foundations and practical guidance for preventing and treating of liver diseases.","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1522206"},"PeriodicalIF":4.6,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11798966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364218","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

Role of spindle assembly checkpoint proteins in gametogenesis and embryogenesis.

IF 4.6 2区生物学

Frontiers in Cell and Developmental Biology Pub Date : 2025-01-22 eCollection Date: 2024-01-01 DOI: 10.3389/fcell.2024.1491394

Renju Pun, Brian J North

引用次数: 0

Hydroxyurea mitigates diabetic kidney disease through mTOR-S6K signaling pathway in STZ-induced diabetic mice.

IF 4.6 2区生物学

Frontiers in Cell and Developmental Biology Pub Date : 2025-01-22 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1529901

Wanying Cheng, Cenzhu Wang, Meican Ma, Yu Zhou

{"title":"Hydroxyurea mitigates diabetic kidney disease through mTOR-S6K signaling pathway in STZ-induced diabetic mice.","authors":"Wanying Cheng, Cenzhu Wang, Meican Ma, Yu Zhou","doi":"10.3389/fcell.2025.1529901","DOIUrl":"10.3389/fcell.2025.1529901","url":null,"abstract":"Background: Diabetic kidney disease (DKD) is the leading risk factor for end-stage renal disease (ESRD). Hydroxyurea (HU), a sickle cell disease (SCD) drug approved by FDA, shows protective effect in nephropathy. This study aims to understand whether the application of HU could be effective to treat DKD.Methods: The streptozotocin (STZ)-induced diabetic mice, and high glucose (HG)-treated human renal mesangial cells (HRMCs) were used to investigate the effect of HU on DKD. Serum creatinine and blood urea nitrogen levels reflecting renal function were evaluated. Histology was used to evaluate pathological changes. Indicators of inflammation and apoptosis were detected. Lastly, the mTOR-S6K pathway was explored by detecting the protein expression of S6K and phosphorylated S6K.Results: In STZ-induced diabetic mice, administration of HU (20 mg/kg) in drinking water for 16 weeks resulted in significant reductions in creatinine and urea nitrogen levels, alongside mitigating histopathological damage. Additionally, HU effectively suppressed the inflammatory response and apoptosis within the kidneys. HRMC cells were cultivated in HG conditions, and HU effectively attenuated the HG-induced inflammation and apoptosis. Moreover, HU treatment significantly inhibited the mTOR signaling pathway in both in both in vivo and in vitro experiments.Conclusion: This study unveils a new role of HU in alleviating diabetic kidney disease by modulating inflammation and apoptosis through the mTOR-S6K pathway. However, since HU did not significantly affect blood glucose levels, its therapeutic potential may be best realized when used in combination with standard antidiabetic therapies. Such a combination approach could simultaneously address hyperglycemia and renal dysfunction, offering a more comprehensive management strategy for DKD.","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1529901"},"PeriodicalIF":4.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794838/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254742","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

Multitasking muscle: engineering iPSC-derived myogenic progenitors to do more.

IF 4.6 2区生物学

Frontiers in Cell and Developmental Biology Pub Date : 2025-01-22 eCollection Date: 2024-01-01 DOI: 10.3389/fcell.2024.1526635

Mark Stephen Hamer, Fabio M V Rossi

引用次数: 0

Recent advances in plant kinetochore research.

IF 4.6 2区生物学

Frontiers in Cell and Developmental Biology Pub Date : 2025-01-22 eCollection Date: 2024-01-01 DOI: 10.3389/fcell.2024.1510019

Elena Kozgunova

引用次数: 0

Salivary miRNAs and cytokines associated with diagnosis and prognosis of oral squamous cell carcinoma.

IF 4.6 2区生物学

Frontiers in Cell and Developmental Biology Pub Date : 2025-01-22 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1531016

Yuxiao Qin, Xiaodan Dong, Bo Li

引用次数: 0

IVF cycle safety when a positive passive air sampling occurs under laminar flow hood in absence of a detectable contamination in the embryo culture.

IF 4.6 2区生物学

Frontiers in Cell and Developmental Biology Pub Date : 2025-01-22 eCollection Date: 2024-01-01 DOI: 10.3389/fcell.2024.1474242

Claudia Omes, Roberto Bassani, Patrizia Cambieri, Fausto Baldanti, Rossella Elena Nappi

{"title":"IVF cycle safety when a positive passive air sampling occurs under laminar flow hood in absence of a detectable contamination in the embryo culture.","authors":"Claudia Omes, Roberto Bassani, Patrizia Cambieri, Fausto Baldanti, Rossella Elena Nappi","doi":"10.3389/fcell.2024.1474242","DOIUrl":"10.3389/fcell.2024.1474242","url":null,"abstract":"Microbiological contamination in the embryo culture media might affect embryo early development and clinical outcomes during IVF procedures. Infections in the genital tract represent the most common causes of culture contamination, but also environmental air quality might have a detrimental effect on reproductive outcomes of infertile couples undergoing IVF procedures. Monitoring microbiological contamination in an embryology laboratory is mandatory and daily tests are performed under laminar vertical flow hood. In this study, we investigated the IVF outcome of procedures carried out during 5 years of laboratory activity when a positive passive air sampling occurs under laminar flow hood in the absence of clear contamination in the embryo culture. We performed 570 air samplings, and we isolated at least 1 CFU of microorganisms in the TSA settle plate in 13 cases (2.28%). No infections were suspected in the culture media given the absence of detectable microorganisms under the microscope or a turbidity/color change of culture media visible to the naked eye (0% contamination rate). There were no statistically significant differences in biochemical pregnancy, live birth rate, and abortion between the \"contaminated\" Group P and the \"negative\" Group N. Surprisingly, we found a better outcome in terms of clinical pregnancy rate in Group P as compared to Group N, a finding likely due to the accidental lower age of Group P (p = 0.0133). Data showed that, in the absence of a detectable contamination in the embryo culture media, IVF cycles are safe when an air positive sample occurs in Grade A environment.","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"12 ","pages":"1474242"},"PeriodicalIF":4.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11799669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364199","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

Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer.

IF 4.6 2区生物学

Frontiers in Cell and Developmental Biology Pub Date : 2025-01-22 eCollection Date: 2025-01-01 DOI: 10.3389/fcell.2025.1525345

Dequan Liu, Lei Liu, Xiangyu Che, Guangzhen Wu

{"title":"Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer.","authors":"Dequan Liu, Lei Liu, Xiangyu Che, Guangzhen Wu","doi":"10.3389/fcell.2025.1525345","DOIUrl":"10.3389/fcell.2025.1525345","url":null,"abstract":"Oncogenes are typically overexpressed in tumor tissues and often linked to poor prognosis. However, recent advancements in bioinformatics have revealed that many highly expressed genes in tumors are associated with better patient outcomes. These genes, which act as tumor suppressors, are referred to as \"paradoxical genes.\" Analyzing The Cancer Genome Atlas (TCGA) confirmed the widespread presence of paradoxical genes, and KEGG analysis revealed their role in regulating tumor metabolism. Mechanistically, discrepancies between gene and protein expression-affected by pre- and post-transcriptional modifications-may drive this phenomenon. Mechanisms like upstream open reading frames and alternative splicing contribute to these inconsistencies. Many paradoxical genes modulate the tumor immune microenvironment, exerting tumor-suppressive effects. Further analysis shows that the stage- and tumor-specific expression of these genes, along with their environmental sensitivity, influence their dual roles in various signaling pathways. These findings highlight the importance of paradoxical genes in resisting tumor progression and maintaining cellular homeostasis, offering new avenues for targeted cancer therapy.","PeriodicalId":12448,"journal":{"name":"Frontiers in Cell and Developmental Biology","volume":"13 ","pages":"1525345"},"PeriodicalIF":4.6,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11794808/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254641","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