Cell Biology International最新文献

{"title":"Targeting mTOR and Its Associated Signaling to Induce Cell Death in Breast Cancer Stem Cells.","authors":"Kirti S Prabhu, Zahwa Mariyam, Syed A Rahman, Shilpa Kuttikrishnan, Fareed Ahmad, Ummu Habeeba, Abdul Q Khan, Afsheen Raza, Said Dermime, Salahddin A Gehani, Kulsoom Junejo, Shahab Uddin","doi":"10.1002/cbin.70071","DOIUrl":"10.1002/cbin.70071","url":null,"abstract":"<p><p>Breast cancer (BC) is a frequently diagnosed neoplasm in women and the second major cause of cancer-related deaths. Many BC patients develop metastasis and advanced tumors, increasing morbidity and mortality. There is substantial evidence that tumor relapses in BC patients are driven by a unique population of cells called cancer stem cells (CSCs). Breast CSCs confer stemness to BC and survive through the maintenance of several mechanisms, among which is the involvement of the mTOR signaling pathway. mTOR and its associated AKT signaling play a crucial role in regulating CSCsin various human cancers, including breast cancer. This study investigated the role of targeting mTOR/AKT signaling in the modulation of cell death in 2D and 3D breast cancer models. Torin-2, a dual mTOR inhibitor, effectively suppressed cell proliferation by inducing mitochondrial apoptosis. The inhibition of mTOR led to a decrease in AKT activity and downregulation of key translational machinery components, including 4EBP1, eIF4E, and p70S6K. Torin-2 treatment activated autophagy signaling in both 2D and 3D cell models. The induction of autophagy was evidenced by an increase in the autophagy protein LC3II/I in response to Torin-2 treatment. In addition, Torin-2 treatment of spheroids derived from breast cancer cells suppressed the expression of stem cell marker ALDH. Altogether, the dual inhibition of mTORC1 and mTORC2 by Torin-2 resulted in a more profound antitumor activity. This broader and more potent inhibition of the mTOR pathway contributes to effectiveness in suppressing 2D and 3D breast cancer cell growth and survival.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882305","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":"The Cytotoxic and Immune-Regulatory Roles of CD8⁺T Cell-Derived Exosomes in Cancer: A Systematic Review.","authors":"Manouchehr Fadaee, Niloufar Orooji, Masoud Lahouty, Danial Mahrooghi, Morteza Abdi, Golnaz Mobayen, Fatemeh Alizadeh, Atefe Alimoradi, Tohid Kazemi","doi":"10.1002/cbin.70069","DOIUrl":"https://doi.org/10.1002/cbin.70069","url":null,"abstract":"<p><p>The second most significant contributor to the global mortality rate resulting from non-communicable diseases is cancer. Cancer cells are recognized for their interactions with adjacent noncancerous cells, such as immune and stromal cells, within the tumor microenvironment, which play a crucial role in influencing tumor progression, metastasis, and resistance. T cell activation is a pivotal process that facilitates the immune system's ability to combat malignancies, characterized by a multi-step signaling cascade leading to T cell proliferation and differentiation. During this activation phase, T cells release a variety of extracellular vesicles, particularly exosomes, which serve as critical regulators of intercellular communication within the tumor microenvironment. These vesicles contain bioactive molecules such as proteins, microRNAs, and immunomodulatory factors that influence tumor growth, immune evasion, and therapeutic responses. CD8⁺T cell-derived exosomes (CD8⁺T-Exos) have been shown to inhibit tumor metastasis by carrying microRNAs that downregulate tumor-promoting genes while also enhancing immune responses by activating CD8⁺T lymphocytes. By elucidating the diverse functions of CD8⁺T-Exos, this review highlights their potential as both biomarkers and therapeutic agents in cancer treatment.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815900","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":"Spleen Tyrosine Kinase Exacerbates Anti-Citrullinated Protein/Peptide Antibody-Mediated Osteoclast Bone Resorption via Promotion of Vav3 Phosphorylation.","authors":"Tongxin Wang, Li Zhu, Ying Pan, Bomiao Ju, Xiuyuan Feng, Lingfei Mo, Lan He, Yining Sun","doi":"10.1002/cbin.70068","DOIUrl":"https://doi.org/10.1002/cbin.70068","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by abnormal bone resorption. Anti-citrullinated protein/peptide antibodies (ACPAs), detected in most RA patients, can stimulate osteoclasts differentiation by targeting osteoclast precursors, thereby enhancing bone resorption. However, the underlying mechanism of ACPAs-induced osteoclast activation on bone resorption in RA remains unknown. In this study, ACPA-positive (ACPA⁺) IgG promoted the maturation of osteoclasts. Phalloidin and wheat germ agglutinin (WGA) staining demonstrated that the ACPA⁺ IgG group exhibited significantly higher mean fluorescence intensity, cell volume, and wheat agglutinin coloring in osteoclasts compared to the ACPA-negative (ACPA^-) IgG group. Additionally, ACPA⁺ IgG stimulation significantly upregulated the p-SYK/SYK ratio in osteoclasts. SYK knockdown had no effect on osteoblast differentiation, but significantly decreased the area of bone lacunae, and attenuated osteoclasts bone resorption. Furthermore, SYK knockdown significantly decreased Vav3 phosphorylation, and colocalization of SYK and Vav3 was observed in osteoclasts. Notably, SYK and Vav3 enrichment at the leading edge of the osteoclasts was abrogated in the SYK-shRNA group. The number of actin rings was also significantly lower in the SYK-shRNA group compared to the SYK-shRNA-NC group. In conclusion, ACPA⁺ IgG induction not only promoted osteoclastogenesis but also increased SYK phosphorylation and bone resorption. SYK exacerbated osteoclast bone resorption by promoting Vav3 phosphorylation. These findings provide valuable insights for identifying novel therapeutic targets in RA.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144815899","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":"Organoids and Organoids-on-Chip in Traditional Chinese Medicine Research: Applications, Advantages, and Future Prospects","authors":"Tao Li,&nbsp;Yifan Yang,&nbsp;Fengrui Yang,&nbsp;Yuan Li,&nbsp;Haifa Qiao,&nbsp;Yongmei Yan,&nbsp;Xia Ding","doi":"10.1002/cbin.70067","DOIUrl":"10.1002/cbin.70067","url":null,"abstract":"<div>\u0000 \u0000 <p>Modernizing traditional Chinese medicine (TCM) requires preserving its foundational principles while integrating contemporary innovations and clarifying therapeutic methods. Organoids and organoids-on-chip technologies offer advanced models of human organs, and serve as an excellent platform for investigating TCM theories and complex herbal formulas. To systematically summarize recent progress in using organoids and organoids-on-chip in TCM research, and critically assess their technical advantages and future potential, relevant articles and information were sourced from scientific databases such as PubMed, SpringerLink, Web of Science, ScienceDirect, and VIP. The application of organoids and organoids-on-chip technologies in TCM research encompasses theory interpretation, efficacy evaluation, mechanism elucidation, toxicity assessment, active ingredient screening, and formula optimization. These applications offer significant advantages, such as unveiling holistic effects, deciphering mechanistic bases through dynamic visualization approaches, and demonstrating personalized therapeutic benefits. Enhancing physiological relevance, automation, and intelligent applications are future development directions. Organoids and organoids-on-chip represent transformative tools for the modernization of TCM. Future advancements in vascularization, neural network development, and the integration of artificial intelligence are anticipated to address existing limitations, thereby enhancing physiological relevance and clinical translation. These advancements are expected to promote global acceptance and innovation in TCM.</p>\u0000 </div>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"49 10","pages":"1233-1244"},"PeriodicalIF":3.1,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144793570","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":"Modeling Lipopolysaccharide-Elicited Inflammation Using 3D Mouse Gastric Organoids.","authors":"Aoqing Xu, Xiyu Wang, Zhifan Ye, Tao Li, Fengrui Yang, McKay Mullen, Xia Ding, Xing Liu, Zhikai Wang","doi":"10.1002/cbin.70066","DOIUrl":"https://doi.org/10.1002/cbin.70066","url":null,"abstract":"<p><p>Colonization of Helicobacter pylori (H. pylori) in stomach often causes gastritis, an inflammation of the stomach lining that is closely associated with serious conditions like ulcers and gastric cancer. Of the toxicity mechanisms, microbial lipopolysaccharide (LPS) binding to TLR4 receptor on the glandular cells activates the NF-κB pathway, inducing pro-inflammatory cytokine release and immune cell infiltration, which results in the tissue damage. However, whether LPS has any direct damaging effect on gastric epithelial cells has been in debate. By using mouse gastric organoids that were grown from the isolated glands and maintained the cellular compositions, we demonstrate various effects of variable LPS concentrations on the glandular epithelial cells, including mild promotion of cell proliferation at the low concentration and induced loss of cell polarity and altered gene expressions at the high concentration. These findings provide insights into how LPS directly affects the stomach lining.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144783616","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":"Anti-Biofouling Coatings Based on Ultra-Slippery Surfaces.","authors":"Alexander B Tesler, Wolfgang H Goldmann","doi":"10.1002/cbin.70065","DOIUrl":"https://doi.org/10.1002/cbin.70065","url":null,"abstract":"<p><p>Traditional treatment of biofouling with toxic paints or antibiotics has significant limitations and challenges, including negative impacts on surrounding ecosystems and the emergence of resistant microbial strains. Antibiotics often prove ineffective in penetrating the dense and protective structure of biofilms, rendering traditional antimicrobial approaches less effective and leading to chronic infections. Toxic paints, while initially effective in reducing microbial colonization, contribute to long-term environmental contamination and harm non-target organisms. In contrast, novel technologies such as aerophilic surfaces, a special type of superhydrophobic surface, and liquid-infused slippery surfaces offer promising alternatives to conventional biofilm management technologies. While aerophilic surfaces create a physical barrier that inhibits biofilm formation by reducing the direct contact of aqueous media with solid surfaces, liquid-infused slippery surfaces enhance the anti-biofouling effect by maintaining a protective lubricating layer that prevents organisms from settling. These nontoxic technologies not only provide a more sustainable and effective means of combating biofilms but also minimize the environmental impact associated with conventional treatments. By leveraging the unique properties of advanced materials, we can increase the durability and effectiveness of surfaces, leading to improved outcomes in various fields, including medical devices and marine applications.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144944621","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":"Lactate Prevents Glucose Deprivation-Induced Parthanatos in Gastric Cancer Cells Through Alleviating Intracellular Reactive Oxygen Species.","authors":"Dun Niu, Yiniu Xia, Xingyu Qin, Ming Zhang, Sichun Pan, Xuemiao Yuan, Guotao Tang, Wenbin Ai, Yuxuan Liang, Zhongli Li, Zhizhong Xie","doi":"10.1002/cbin.70064","DOIUrl":"https://doi.org/10.1002/cbin.70064","url":null,"abstract":"<p><p>Most evidence obtained to date suggests a pivotal role for lactate in the control of tumor growth and metastasis. However, the precise mechanism by which lactate decreases tumor cell death remains incompletely defined. Here, we report that parthanatos, a kind of poly (ADP-ribose) polymerase-1 (PARP1) dependent but caspase-independent programmed cell death, does occur in two gastric cancer cell lines (MKN28 and MGC803) under glucose-deprived conditions. Lactate prevented the glucose deprivation-induced parthanatos in an acid-independent manner. In addition, glucose deprivation increased intracellular reactive oxygen species (ROS) generation, whereas lactate reduces ROS levels by promoting NADPH generation. AG120, a selective inhibitor of isocitrate dehydrogenase 1 (IDH1) that catalyzes cytosolic NADPH generation, effectively eliminated the effect of lactate on NADPH generation and reversed the protective effect of lactate on glucose deprivation-induced parthanatos. Similar effects were also observed when lactate dehydrogenase B (LDHB) was knocked down. Our findings reveal that lactate prevents glucose deprivation-induced parthanatos in gastric cancer cells by alleviating intracellular oxidative stress, reflecting a new mechanism by which lactate facilitates the adaptation of tumor cells to the nutrient-deficient tumor microenvironment and promotes tumor development.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144759279","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":"Fibroblast-Derived Extracellular Vesicles Ameliorate the Skin Injury Microenvironment to Promote Wound Healing.","authors":"Minjie Liu, Ganqin Ye, Ruiyang Li, Tenghui Gao, Caiwei Zhuang, Shiyun Huang, Sheng Wang, Jinhua Hu, Andy Peng Xiang, Mei Hua Jiang","doi":"10.1002/cbin.70063","DOIUrl":"https://doi.org/10.1002/cbin.70063","url":null,"abstract":"<p><p>Fibroblasts are pivotal cellular components in cutaneous wound healing and are regarded as promising therapeutic candidates. However, their functional heterogeneity within tissue microenvironments significantly limits their clinical application. In contrast, whether fibroblast-derived extracellular vesicles (EVs) can overcome fibroblast heterogeneity while retaining the bioactivity and regenerative potential of homeostatic fibroblasts remains unclear. In this study, we systematically analyzed and compared the therapeutic potential and functional advantages of human dermal fibroblast-derived EVs (hDF-EVs) in promoting cutaneous wound healing. Our findings highlight the translational potential of fibroblast-derived EVs as a novel strategy to improve clinical outcomes for skin injuries. hDF-EVs were internalized by fibroblasts and keratinocytes at the wound margins, thereby attenuating early inflammatory responses and accelerating tissue repair following dermal excisional injuries. hDF-EVs significantly enhanced the proliferation and migration of both fibroblasts and keratinocytes in a coculture system. Transcriptomic analysis revealed that hDF-EVs upregulated genes involved in cell proliferation and cytokine regulation. Integrated miRNA profiling revealed a subset of hDF-EVs-enriched miRNAs that mechanistically orchestrate fibroblast activation through coordinated MAPK, Wnt, and Ras signaling axis engagement, consequently reprogramming inflammatory mediator secretion dynamics in wound microenvironments. Furthermore, cytokine array analysis demonstrated that hDF-EVs enhanced the expression of various cytokines, including Amphiregulin, GCSF, IL-7, and IL-2, while activating Ras, Rap1, PI3K-Akt, and MAPK signaling pathways during the early stage of wound healing. Collectively, hDF-EVs promote wound healing by modulating early growth factor dynamics and enhancing fibroblast-keratinocyte crosstalk, presenting a novel cell-free strategy for skin regeneration.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728316","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":"TFAP2C Affects PI3K/AKT/mTOR Pathway-Mediated EMT for Glioblastoma Development Through Transcriptional Regulation.","authors":"Shilin Li, Kebo Liu, Xiaoyang Li, Hao Zi, Kaiyuan Jiang","doi":"10.1002/cbin.70062","DOIUrl":"https://doi.org/10.1002/cbin.70062","url":null,"abstract":"<p><p>Transcription factor AP-2 gamma (TFAP2C) plays a pro-cancer role in various malignancies. Yet, the action of TFAP2C in glioblastoma (GBM) is unknown. This study aimed to investigate the effects of TFAP2C in GBM and the potential mechanism. TFAP2C knockdown in GBM cell lines was employed to examine its impact on cell proliferation, migration, and invasion (PMI), as well as epithelial-mesenchymal transition (EMT) development, and its association with the PI3K/AKT/mTOR (PAM) pathway by co-overexpressing PI3K or SC79 treatment (AKT agonist). The binding of TFAP2C and the PI3K promoter was predicted and validated. Finally, the above effects and mechanisms were verified in in vivo animal experiments. TFAP2C expression was strikingly heightened in human GBM cell lines and showed a negative correlation with patient survival. TFAP2C silencing inhibited GBM cell PMI, N-cadherin and Vimentin expression, and the PAM pathway, and activated E-cadherin and ZO-1 expression. Overexpression of PI3K or SC79 treatment reversed the above changes, suggesting that TFAP2C promotes GBM cell PMI and EMT via the PAM pathway. Mechanistically, TFAP2C binds to the promoter of PI3K and regulates PI3K transcription. Finally, the in vitro results were further validated in animal experiments. In conclusion, TFAP2C promotes PI3K transcription through direct binding to the promoter of PI3K and activates the PAM pathway to promote GBM proliferation and EMT, providing a potential therapeutic target for GBM.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144641950","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":"Exploring Hippo YAP/TAZ Signaling: A Novel Avenue for Cardiovascular Disorders","authors":"Arwa Mithaiwala,&nbsp;Angel Godad","doi":"10.1002/cbin.70052","DOIUrl":"10.1002/cbin.70052","url":null,"abstract":"<p>Significant attention has been paid to the Hippo signaling pathway and its effectors Yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) in cellular proliferation, survival, tissue homeostasis during development as well as cancer. While initially investigated in the context of oncogenesis, recent studies have just indicated its importance to cardiovascular diseases (CVD) like cardiac myocardial infarction (MI), cardiac hypertrophy, and heart failure (HF). This review focuses on therapeutic targets, regulatory mechanisms and signaling crosstalk between Hippo YAP/TAZ pathway with other traditional pathways like PI3K/AKT, TGF-β, WNT/β-catenin in CVD. Thus, although targeted YAP/TAZ activation in the myocardium may enhance regeneration/differentiation, its dysregulation promotes maladaptive cardiac remodeling characterized by hypertrophy and fibrosis. A better appreciation of the nuanced control on YAP/TAZ in different cardiovascular indications may point to an opportunity for precision therapeutics. In this review, we have discussed strategies to target specific components of the Hippo pathway as potential therapeutic approaches with implications for fibrosis reduction by LATS1/2 inhibition or cardiomyocyte survival promotion via MST1/2 suppression. The role of noncoding RNAs in YAP/TAZ activity modulation is further illustrated and provides us with possible therapeutic avenues that can be explored for noninvasive treatments.</p>","PeriodicalId":9806,"journal":{"name":"Cell Biology International","volume":"49 9","pages":"1079-1101"},"PeriodicalIF":3.1,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625472","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}