Cells最新文献

{"title":"Correction: Kobayashi et al. Pathogenesis of Graves' Disease Determined Using Single-Cell Sequencing with Thyroid Autoantigen Peptide Stimulation in B Cells. <i>Cells</i> 2025, <i>14</i>, 1102.","authors":"Genki Kobayashi, Takuro Okamura, Yoshitaka Hashimoto, Kimiko Sakai, Madoka Sumi, Dan Imai, Nobuko Kitagawa, Masahide Hamaguchi, Takahiro Tsujikawa, Shigeru Hirano, Michiaki Fukui","doi":"10.3390/cells15090751","DOIUrl":"10.3390/cells15090751","url":null,"abstract":"<p><p>Takahiro Tsujikawa and Shigeru Hirano were not included as authors in the original publication [...].</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 9","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13130824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763628","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}

{"title":"Metformin Alleviates Cadmium-Induced Autophagic Flux Impairment-Dependent Apoptosis by Activating AMPK in Neuronal Cells.","authors":"Wen Wu, Xiaoling Chen, Tong Ji, Qianyun Yu, Long Hou, Zhihan Zhou, Baoming Gong, Ming Xu, Wei Gao, Shile Huang, Long Chen","doi":"10.3390/cells15080739","DOIUrl":"https://doi.org/10.3390/cells15080739","url":null,"abstract":"<p><p>Cadmium (Cd), a common environmental and occupational toxicant, is an important risk factor for neurodegenerative diseases. Metformin has been found to have neuroprotective effect, in addition to antidiabetic function. Our recent studies have identified that metformin ameliorates Cd neurotoxicity via blocking ROS-dependent PP5/AMPK-JNK signaling pathway. Here we further show that metformin protected PC12 cells and primary neurons from Cd-poisoning by mitigating Cd-induced increases in ATG5/LC3-II/p62 levels and autophagosomes. Knockdown of ATG5 dramatically potentiated the inhibitory effects of metformin on Cd-induced LC3-II, cleavage of caspase-3, accumulation of autophagosomes and apoptosis in PC12 cells. Addition of chloroquine (CQ) strengthened the basic and Cd-elevated ATG5/LC3-II/p62 levels, autophagosome accumulation and cell apoptosis, whereas metformin powerfully blocked the events, implying a metformin-promoted autophagic flux-dependent mechanism involved. Further research revealed that metformin prevented Cd-induced autophagic flux impairment and cell apoptosis, which was attributed to restraining Cd inactivation of AMPK. This is supported by the findings that activation of AMPK with AICAR or ectopic expression of constitutively active AMPKα (AMPKα-ca) reinforced the inhibitory effects of metformin on Cd-evoked ATG5/LC3-II/p62/autophagosomes and apoptosis in PC12 cells and/or primary neurons. Taken together, the results indicate that metformin protects neuronal cells from Cd-induced autophagic flux impairment-dependent apoptosis by activating AMPK. Our studies highlight that metformin has a great potential for prevention of Cd toxicity related to neurodegenerative diseases.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762660","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}

{"title":"Combined CDK4/6 Inhibition and Radiation: Effects on Cellular Senescence, Cell Cycle Regulation, and Cell Death in Mammary Carcinoma Cells.","authors":"Lisa Quarz, Luitpold V Distel, Stefanie Corradini, Laura S Hildebrand","doi":"10.3390/cells15080734","DOIUrl":"https://doi.org/10.3390/cells15080734","url":null,"abstract":"<p><p>CDK4/6 inhibitors such as palbociclib, ribociclib and abemaciclib are commonly used in the clinical treatment of HR-positive, HER2-negative metastatic or locally advanced breast cancer. Patients with metastatic disease often receive palliative radiotherapy for symptom control of bone metastases and/or local lesions, typically administered in close temporal proximity to CDK4/6 inhibitor therapy, although treatment with the inhibitors may be temporarily paused during the radiotherapy period in some cases. In this study, we investigated the extent to which senescence is induced by CDK4/6 inhibitors, ionizing radiation, and the combination of the two, compared to other types of cell fate. Eight breast cancer cell lines with different molecular subtypes and two healthy cell lines (fibroblasts and keratinocytes) were treated with CDK inhibition using palbociclib, ribociclib or abemaciclib and with or without a single dose of 2 Gy ionizing radiation. Cellular senescence, cell death in form of apoptosis and necrosis, and the cell cycle were analyzed using flow cytometry. We focused mainly on understanding how CDK inhibition can trigger cellular senescence. Our data showed that in many cell lines -but not all-the use of CDK inhibitors induced senescence much more strongly than cell death. Except for one cell line, significantly more cell lines died necrotically than apoptotically. Neither apoptosis nor necrosis was responsible for a major cell fate after CDK inhibition. Combination therapy with irradiation did not show a clear additive effect. In cell lines, senescence is clearly triggered by CDK4/6 inhibitors and even more so when in combination with ionizing radiation, which, when transferred to patients, could lead to less damage caused by cell loss, such as necrotic areas. However, it could also lead to more senescence-specific side effects, such as inflammation-induced tumors and fibrosis.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763641","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}

{"title":"Correction: Kim et al. The Suppression of Ubiquitin C-Terminal Hydrolase L1 Promotes the Transdifferentiation of Auditory Supporting Cells into Hair Cells by Regulating the mTOR Pathway. <i>Cells</i> 2024, <i>13</i>, 737.","authors":"Yeon Ju Kim, In Hye Jeong, Jung Ho Ha, Young Sun Kim, Siung Sung, Jeong Hun Jang, Yun-Hoon Choung","doi":"10.3390/cells15080732","DOIUrl":"https://doi.org/10.3390/cells15080732","url":null,"abstract":"<p><p>In the original publication [...].</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763564","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}

{"title":"A Tiered Approach to Human Synapse Proteomics: Optimized LC-MS/MS Analysis of Whole-Tissue Lysate and Synaptosome Preparations from Frozen Post-Mortem Brain Samples.","authors":"Femke C Roig-Kuhn, Remco V Klaassen, Frank T W Koopmans, Tiara S Z Koolman, August B Smit, Sabine Spijker","doi":"10.3390/cells15080736","DOIUrl":"https://doi.org/10.3390/cells15080736","url":null,"abstract":"<p><p>Recent advancements in neuroproteomics have enabled detailed analysis of protein expression in the human brain, yet resolving synaptic dysfunction-a central feature of many neurological and psychiatric disorders-requires careful methodological consideration. Leveraging the high sensitivity of modern liquid chromatography-tandem mass spectrometry (LC-MS/MS), we evaluated the utility of whole-tissue lysates versus enriched synaptosome preparations for detecting synaptic protein signatures. First, we optimized and standardized a sample preparation protocol for frozen human gray matter (GM) by refining the suspension trapping (sTRAP) digestion method using thin human tissue sections. We accomplished low technical variation by minimizing sample handling and achieved a highly reproducible sample preparation workflow by rigorously applying standardization and randomization across dissection, processing, and LC-MS/MS runs. Second, comparative LC-MS/MS analysis showed that while whole-tissue lysates provide a high-throughput survey of the synaptic proteome, synaptosome isolation is required to investigate synapse-specific proteins to detect alterations at the terminal that are obscured in the soma. Because these methods offer distinct but synergistic levels of information, we recommend a tiered neuroproteomics strategy. This approach utilizes whole-tissue lysates for broad disease-associated screening and consistent quantification in large cohorts, followed by targeted synaptosome proteomics to provide a unique window of insight into synaptic composition and stability. This integrated workflow respects the biological necessity of spatial resolution while maintaining the reproducibility required for robust human brain proteomics. Furthermore, initial tissue-level analysis provides the necessary context to correctly interpret synaptosome data in cases of global synapse loss or gain.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763682","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}

{"title":"Spatial Protein Expression Analysis in Lungs Using Capillary-Based Immunoassay After Laser-Assisted Microdissection.","authors":"Stefan Hadzic, Marija Gredic, Vanessa Nebel, Norbert Weissmann, Cheng-Yu Wu","doi":"10.3390/cells15080737","DOIUrl":"https://doi.org/10.3390/cells15080737","url":null,"abstract":"<p><p>Unravelling the cellular and molecular mechanisms underlying lung injury and repair requires precise spatial context. Profiling cell-to-cell transcriptional variability and spatial orientation has become increasingly sophisticated, but validating results at the protein level still remains challenging, particularly for low-expressed proteins or small-scale samples. Here, we present a workflow established by our group for spatial protein analysis in the lung by combining two commercially available platforms: (1) laser-assisted microdissection (LMD) with (2) a capillary electrophoretic-based immunoassay (CEI). Using this workflow, we demonstrate a simple, accessible, and sensitive method for spatially capturing regions of interest to investigate small-scale samples or low-expressed proteins. This workflow provides an additional option for orthogonal validation for researchers using omics-based approaches. Furthermore, we validated transcriptome analysis results at the protein level by applying this workflow to a pre-clinical model of cigarette smoke (CS)-induced lung injury. In line with the previous findings, the results showed a significant downregulation of the endothelial cell marker in LMD-enriched alveolar regions, suggesting spatial capillary rarefaction, and activation of the mitogen-activated protein kinase (MAPK) signalling pathway in pulmonary vasculature of CS-exposed mice. Our approach overcomes traditional challenges and provides new opportunities for understanding complex disease pathomechanisms and identifying potential therapeutic targets.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763665","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}

{"title":"Neuroglial-Breast Cancer Crosstalk Shapes the Brain Metastatic Niche.","authors":"Sabine Hombach-Klonisch, Eric Hall, Reem Amin, Emily Fedora, Jerry Vriend, Marshall Pitz, Thomas Klonisch","doi":"10.3390/cells15080735","DOIUrl":"https://doi.org/10.3390/cells15080735","url":null,"abstract":"<p><p>Breast cancer brain metastasis (BCBM) affects up to 30% of patients with metastatic disease and carries a median survival of only 4-18 months. Emerging evidence reveals that BCBM cells are not passive survivors, but active participants that hijack core neurotransmitter networks, GABA (gamma-aminobutyric acid) and glutamate, to fuel their growth. BCBM, particularly triple-negative breast cancer (TNBC), frequently switch to a GABAergic mode utilizing brain-derived GABA as an oncometabolite. In parallel, BCBM cells can also form direct synapses with neurons, tapping into excitatory input through glutamatergic receptors to drive tumor cell proliferation and survival. Concurrently, reprogrammed astrocytes establish gap junctions, secrete growth factors, and provide metabolic support. Together, tumor cells, neurons, and astrocytes form a pathological partnership locked in feedback loops sustaining metastatic progression. This review focuses on the unique mechanisms employed by distinct breast cancer subtypes and maps the metastatic progression from pre-metastatic to mature brain metastatic niche formation of BCBM. We highlight opportunities to repurpose neurological drugs to disrupt these communication axes.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114959/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763364","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}

{"title":"Correction: Jung et al. miR-409-3p Regulates IFNG and p16 Signaling in the Human Blood of Aging-Related Hearing Loss. <i>Cells</i> 2024, 13, 1595.","authors":"Junseo Jung, Jeongmin Lee, Hyunsook Kang, Kyeongjin Park, Young Sun Kim, Jungho Ha, Seongjun So, Siung Sung, Jeong Hyeon Yun, Jeong Hun Jang, Seong Jun Choi, Yun-Hoon Choung","doi":"10.3390/cells15080738","DOIUrl":"https://doi.org/10.3390/cells15080738","url":null,"abstract":"<p><p>In the original publication [...].</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763632","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}

{"title":"Sphingolipid Expression During Corneal Wound Healing in a Sphingosine Kinase 1 Knockout Model.","authors":"Sandip K Basu, Steve Mabry, Peter Nsiah, Sarah E Nicholas, Nataliya Lenchik, Mark Altawil, Chi-Yang Chiu, Daniel J Stephenson, Charles E Chalfant, Dimitrios Karamichos, Nawajes Mandal","doi":"10.3390/cells15080733","DOIUrl":"https://doi.org/10.3390/cells15080733","url":null,"abstract":"<p><p>Corneal scarring is a result of unregulated fibrotic processes in wound healing, which causes visual impairment. Bioactive sphingolipids (SPLs) are known to modulate physiological processes that are central to wound healing. Of these bioactive SPLs, sphingosine-1-phosphate (S1P) is perhaps the most studied. Previous research has shown that knocking out sphingosine kinase 1 (Sphk1), which produces S1P, alters SPL species metabolism and improves wound healing in mice corneas. However, it is unknown how SphK1 knockout (<i>SphK1^-/-</i>) affects SPL metabolism during stages of corneal wound healing. Following an alkali burn procedure on wild-type (WT) and <i>SphK1^-/-</i> mice, corneal lipidomic profiles in unburned corneas at 1, 7, 14, and 28 days post-injury (DPI) were measured. Significant differences in SPL species between genotypes, both in uninjured mouse corneas and during distinct stages of corneal burn healing, were observed. WT mice expressed burn healing stage-dependent modulation of SPL species, with decreased expression of most SPL species observed at 1 and 14 DPI. Interestingly, this wild-type SPL modulation was absent in most measured SPL species in the <i>SphK1^-/-</i> corneas. These findings provide evidence for a previously unknown modulatory role of SphK1 and S1P on the expression of SPLs during corneal wound healing.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13115462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763698","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}

{"title":"Effects of Age on Intervertebral Disc Tissue Morphology and Gene Expression in the ADAM8-Inactivation Mouse.","authors":"Lutian Yao, Huan Wang, Zuozhen Tian, Frances S Shofer, Ling Qin, Yejia Zhang","doi":"10.3390/cells15080730","DOIUrl":"https://doi.org/10.3390/cells15080730","url":null,"abstract":"<p><p><b>Purpose</b>: To determine which age of mice should be used to compare the effects of ADAM8 mutation on intervertebral disc (IVD) responses to injury. <b>Methods</b>: IVDs of ADAM8 mutant (<i>Adam8^EQ</i>) and wild type (WT) mice, aged 3, 10 and 18 months were injured. IVD tissues were harvested 1 week post injury for histological and molecular studies. <b>Results</b>: Histological scores increased with aging in intact IVDs, and there were no differences between <i>Adam8^EQ</i> and WT mice (n = 11-28; <i>p</i> > 0.05). Safranin O-staining was less intense in 10-month than in 3-month-old mice, in both intact and injured IVDs (n = 3-15; <i>p</i> < 0.05). <i>Cxcl1</i>, <i>Il6</i>, and <i>Adam8</i> gene expression levels were higher in the injured tail IVDs of 3-month-old <i>Adam8^EQ</i> than WT mice (n = 18-30; <i>p</i> < 0.05); the injury-related differences diminished with increasing age. <b>Conclusions</b>: No histological differences were found between <i>Adam8^EQ</i> and WT mouse IVDs at 3, 10 or 18 months of age, in the intact or injured discs. The differences in inflammatory marker gene expression were detectable at age 3 months, but were less evident when the injury occurred at age 10 or 18 months. Therefore, to identify differences in injury responses between WT and <i>Adam8^EQ</i> mouse IVDs, 3-month-old mice are superior to older mice.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"15 8","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13114854/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147763565","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}