Advanced biologyPub Date : 2025-01-30DOI: 10.1002/adbi.202400626
Sharda Yadav, Sanjaya Kc, Mark A T Blaskovich, Cu-Tai Lu, Alfred K Lam, Nam-Trung Nguyen
{"title":"RhoA and Rac1 as Mechanotransduction Mediators in Colorectal Cancer.","authors":"Sharda Yadav, Sanjaya Kc, Mark A T Blaskovich, Cu-Tai Lu, Alfred K Lam, Nam-Trung Nguyen","doi":"10.1002/adbi.202400626","DOIUrl":"https://doi.org/10.1002/adbi.202400626","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a leading cause of cancer-related deaths, creating an urgent need for innovative diagnostic solutions. Mechanobiology, a cutting-edge field that investigates how physical forces influence cell behavior, is now revealing new insights into cancer progression. This research focuses on two crucial players: RhoA and Rac1, small yet powerful proteins that regulate the structure and movement of cancer cells. RhoA controls cell adhesion and migration, while Rac1 drives cell movement and invasion. As CRC tumors grow and reshape the colon's mechanical environment, these pathways become disrupted, accelerating cancer progression. Examining the level of RhoA and Rac1 in CRC clinical samples under mechanical strain reveals their potential as diagnostic markers. Tracking the activity of these proteins can unlock valuable insights into cancer cell dissemination, offering new avenues for understanding and diagnosing CRC. This approach holds promise for earlier detection and better outcomes by offering key insights for more effective diagnostic strategies.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400626"},"PeriodicalIF":3.2,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062978","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 : 2025-01-22DOI: 10.1002/adbi.202400713
Arturo Bevilacqua, Cristiano Giuliani, Giovanna Di Emidio, Samuel H Myers, Vittorio Unfer, Carla Tatone
{"title":"Murine Models and Human Cell Line Models to Study Altered Dynamics of Ovarian Follicles in Polycystic Ovary Syndrome.","authors":"Arturo Bevilacqua, Cristiano Giuliani, Giovanna Di Emidio, Samuel H Myers, Vittorio Unfer, Carla Tatone","doi":"10.1002/adbi.202400713","DOIUrl":"https://doi.org/10.1002/adbi.202400713","url":null,"abstract":"<p><p>Polycystic ovary syndrome is one of the most common endocrine disorders in women of reproductive age, characterized by functional and structural alterations of the female reproductive organs. Due to the unknown underlying molecular mechanisms, in vivo murine models and in vitro human cellular models are developed to study the syndrome. These models are used to analyze various aspects of the pathology by replicating the conditions of the syndrome. Even though the complexity of polycystic ovary syndrome and the challenge of reproducing all its features leave several questions unanswered, studies conducted to date have elucidated some of the alterations in ovarian follicle molecular and cellular mechanisms involved in the syndrome, and do not require the employment of complex and invasive techniques on human patients. This review examines ovarian functions and their alterations in polycystic ovary syndrome, explores preclinical in vivo and in vitro models, and highlights emerging research and medical perspectives. It targets researchers, healthcare professionals, and academics, including endocrinologists, cell biologists, and reproductive medicine specialists, studying the molecular and cellular mechanisms of the syndrome.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400713"},"PeriodicalIF":3.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998384","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 : 2025-01-22DOI: 10.1002/adbi.202400752
Farhan Anjum, Kush Kaushik, Abdul Salam, Chayan Kanti Nandi
{"title":"Chromatin Marks H3K4me3 and H3K9me3 in Triple-Negative Breast Cancer Cell Lines.","authors":"Farhan Anjum, Kush Kaushik, Abdul Salam, Chayan Kanti Nandi","doi":"10.1002/adbi.202400752","DOIUrl":"https://doi.org/10.1002/adbi.202400752","url":null,"abstract":"<p><p>Triple-negative breast cancer (TNBC) is the most lethal and aggressive breast cancer among all the breast cancer subtypes. Despite several attempts, to date, there is an extensive lack of therapeutic intervention. Hence, there is a dire need for an effective biomarker to timely diagnose TNBC. Here, utilizing super-resolution microscopy, the remodeling structural aspects of euchromatin and heterochromatin in TNBC are studied and the results are compared with non-cancerous and non-TNBC cell lines. The nanoscopic visualization reveals a distinct difference in chromatin remodeling in TNBC in comparison to the other two cell lines. While the euchromatin density is found to increase, the heterochromatin is found to decrease. A complete switching of the heterochromatin-euchromatin ratio is observed in TNBC cells thus proposing that chromatin remodeling and chromatin morphological changes can be pursued as one of the targets for diagnostic purposes. Increased expression of structure specific recognition protein-1(SSRP-1) protein supports the increased rate of chromatin remodeling in breast cancer cell lines. The results may lead to developing a new strategy for diagnosing TNBC patients.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400752"},"PeriodicalIF":3.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998261","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 : 2025-01-22DOI: 10.1002/adbi.202400549
Qin Jiang, Xiang Lin, Mimi Zhai, Yi Gong, Yamin Li, Sushun Liu
{"title":"The Role of ROS and Its Sources in Tumorigenesis: Friend or Foe?","authors":"Qin Jiang, Xiang Lin, Mimi Zhai, Yi Gong, Yamin Li, Sushun Liu","doi":"10.1002/adbi.202400549","DOIUrl":"https://doi.org/10.1002/adbi.202400549","url":null,"abstract":"<p><p>Ponicidin has demonstrated effectiveness against HCC by promoting mitochondria apoptosis and generating ROS through the stabilization of the Keap1-PGAM5 complex. However, ROS can exhibit both tumor-promoting and tumor-suppressing activities in cancers, and exhibit different effects depending on its source-mtROS vs non-mtROS. Additionally, since ROS from different sources possesses distinct functions, mitochondria-targeted antioxidants, and non-targeted antioxidants may have entirely different effects on cancer progression. To address this complexity, novel measurement techniques such as MitoSOX, MitoPY1, and siDMA are used to specifically assess mtROS, providing deeper insights into mitochondrial function during treatment. Therefore, distinguishing the sources of ROS and separately detecting and targeting mtROS and non-mtROS can further clarify the anti-tumor mechanisms of ponicidin and provide a foundation for subsequent research.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400549"},"PeriodicalIF":3.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998387","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 : 2025-01-18DOI: 10.1002/adbi.202400539
Mousumi Akter, Hossein Moghimianavval, Gary D Luker, Allen P Liu
{"title":"Light-Triggered Protease-Mediated Release of Actin-Bound Cargo from Synthetic Cells.","authors":"Mousumi Akter, Hossein Moghimianavval, Gary D Luker, Allen P Liu","doi":"10.1002/adbi.202400539","DOIUrl":"10.1002/adbi.202400539","url":null,"abstract":"<p><p>Synthetic cells offer a versatile platform for addressing biomedical and environmental challenges, due to their modular design and capability to mimic cellular processes such as biosensing, intercellular communication, and metabolism. Constructing synthetic cells capable of stimuli-responsive secretion is vital for applications in targeted drug delivery and biosensor development. Previous attempts at engineering secretion for synthetic cells have been confined to non-specific cargo release via membrane pores, limiting the spatiotemporal precision and specificity necessary for selective secretion. Here, a protein-based platform termed TEV Protease-mediated Releasable Actin-binding Protein (TRAP) is designed and constructed for selective, rapid, and triggerable secretion in synthetic cells. TRAP is designed to bind tightly to reconstituted actin networks and is proteolytically released from bound actin, followed by secretion via cell-penetrating peptide membrane translocation. TRAP's efficacy in facilitating light-activated secretion of both fluorescent and luminescent proteins is demonstrated. By equipping synthetic cells with a controlled secretion mechanism, TRAP paves the way for the development of stimuli-responsive biomaterials, versatile synthetic cell-based biosensing systems, and therapeutic applications through the integration of synthetic cells with living cells for targeted delivery of protein therapeutics.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400539"},"PeriodicalIF":3.2,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998262","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 : 2025-01-11DOI: 10.1002/adbi.202400408
S Sergio, B Spedicato, G Corallo, A Inguscio, M Greco, D Musarò, D Vergara, A F Muro, G De Sabbata, L R Soria, N Brunetti Pierri, M Maffia
{"title":"β-Catenin/c-Myc Axis Modulates Autophagy Response to Different Ammonia Concentrations.","authors":"S Sergio, B Spedicato, G Corallo, A Inguscio, M Greco, D Musarò, D Vergara, A F Muro, G De Sabbata, L R Soria, N Brunetti Pierri, M Maffia","doi":"10.1002/adbi.202400408","DOIUrl":"https://doi.org/10.1002/adbi.202400408","url":null,"abstract":"<p><p>Ammonia a by-product of nitrogen containing molecules is detoxified by liver into non-toxic urea and glutamine. Impaired ammonia detoxification leads to hyperammonemia. Ammonia has a dual role on autophagy, it acts as inducer at low concentrations and as inhibitor at high concentrations. However, little is known about the mechanisms responsible for this switch. Wnt/β-catenin signalling is emerging for its role in the regulation of ammonia metabolizing enzymes and autophagosome synthesis through c-Myc. Here, using Huh7 cell line, we show a modulation in c-Myc expression under different ammonia concentrations. An increase in c-Myc expression and in its transcriptional regulator β-catenin was detected at low concentrations of ammonia, when autophagy is active, whereas these modifications were lost under high ammonia concentrations. These observations were also recapitulated in the livers of spf-ash mice, a model of constitutive hyperammonaemia due to deficiency in ornithine transcarbamylase enzyme. Moreover, c-Myc-mediated activation of autophagy plays a cytoprotective role in cells under ammonia stress conditions as confirmed through the pharmacological inhibition of c-Myc in Huh7 cells treated with low ammonia concentrations. In conclusion, the unravelled role of c-Myc in modulating ammonia induced autophagy opens new landscapes for the development of novel strategies for the treatment of hyperammonemia.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400408"},"PeriodicalIF":3.2,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969172","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 : 2025-01-06DOI: 10.1002/adbi.202400538
Joaquin Montilla-Rojo, Thomas F Eleveld, Marnix van Soest, Sanne Hillenius, Dennis M Timmerman, Ad J M Gillis, Bernard A J Roelen, Christine L Mummery, Leendert H J Looijenga, Daniela C F Salvatori
{"title":"Depletion of TP53 in Human Pluripotent Stem Cells Triggers Malignant-Like Behavior.","authors":"Joaquin Montilla-Rojo, Thomas F Eleveld, Marnix van Soest, Sanne Hillenius, Dennis M Timmerman, Ad J M Gillis, Bernard A J Roelen, Christine L Mummery, Leendert H J Looijenga, Daniela C F Salvatori","doi":"10.1002/adbi.202400538","DOIUrl":"https://doi.org/10.1002/adbi.202400538","url":null,"abstract":"<p><p>Human pluripotent stem cells (hPSCs) tend to acquire genetic aberrations upon culture in vitro. Common aberrations are mutations in the tumor suppressor TP53, suspected to confer a growth-advantage to the mutant cells. However, their full impact in the development of malignant features and safety of hPSCs for downstream applications is yet to be elucidated. Here, TP53 is knocked out in hPSCs using CRISPR-Cas9 and compared them with isogenic wild-type hPSCs and human germ cell tumor lines as models of malignancy. While no major changes in proliferation, pluripotency, and transcriptomic profiles are found, mutant lines display aberrations in some of the main chromosomal hotspots for genetic abnormalities in hPSCs. Additionally, enhanced clonogenic and anchorage-free growth, alongside resistance to chemotherapeutic compounds is observed. The results indicate that common TP53-depleting mutations in hPSCs, although potentially overlooked by standard analyses, can impact their behavior and safety in a clinical setting.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400538"},"PeriodicalIF":3.2,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930376","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":"Advanced 2D Nanomaterials for Phototheranostics of Breast Cancer: A Paradigm Shift.","authors":"Arpana Parihar, Kritika Gaur, Paromita Sarbadhikary","doi":"10.1002/adbi.202400441","DOIUrl":"10.1002/adbi.202400441","url":null,"abstract":"<p><p>Breast cancer is the leading cause of women's deaths and associated comorbidities. The advanced and targeted strategies against breast cancer have gained considerable attention due to their potential enhanced therapeutic efficacy over conventional therapies. In this context, phototherapies like photodynamic therapy (PDT) and photothermal therapy (PTT) have shown promise as an effective and alternative strategy due to reduced side effects, noninvasiveness, and spatiotemporal specificity. With the advent of nanotechnology, several types of nanomaterials that have shown excellent prospects in increasing the efficacy of photo therapies have been exploited in cancer treatment. In recent years, 2D nanomaterials have stood out promising because of their unique ultrathin planar structure, chemical, physical, tunable characteristics, and corresponding remarkable physiochemical/biological properties. In this review, the potential and the current status of several types of 2D nanomaterials such as graphene-based nanomaterials, Mxenes, Black phosphorous, and Transition Metal Dichalcogenides for photo/thermo and combination-based imaging and therapy of breast cancer have been discussed. The current challenges and prospects in terms of translational potential in future clinical oncology are highlighted.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400441"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142611996","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 : 2025-01-01Epub Date: 2024-11-05DOI: 10.1002/adbi.202400470
Esmée Dekker, Javier Triñanes, Amadeo Muñoz Garcia, Natascha de Graaf, Eelco de Koning, Françoise Carlotti
{"title":"Enhanced BMP Signaling Alters Human β-Cell Identity and Function.","authors":"Esmée Dekker, Javier Triñanes, Amadeo Muñoz Garcia, Natascha de Graaf, Eelco de Koning, Françoise Carlotti","doi":"10.1002/adbi.202400470","DOIUrl":"10.1002/adbi.202400470","url":null,"abstract":"<p><p>Inflammation contributes to the pathophysiology of diabetes. Identifying signaling pathways involved in pancreatic β-cell failure and identity loss can give insight into novel potential treatment strategies to prevent the loss of functional β-cell mass in diabetes. It is reported earlier that the immunosuppressive drug tacrolimus has a detrimental effect on human β-cell identity and function by activating bone morphogenetic protein (BMP) signaling. Here it is hypothesized that enhanced BMP signaling plays a role in inflammation-induced β-cell failure. Single-cell transcriptomics analyses of primary human islets reveal that IL-1β+IFNγ and IFNα treatment activated BMP signaling in β-cells. These findings are validated by qPCR. Furthermore, enhanced BMP signaling with recombinant BMP2 or 4 triggers a reduced expression of key β-cell maturity genes, associated with increased ER stress, and impaired β-cell function. Altogether, these results indicate that inflammation-activated BMP signaling is detrimental to pancreatic β-cells and that BMP-signaling can be a target to preserve β-cell identity and function in a pro-inflammatory environment.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400470"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11760635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581926","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":"IL-12p70 Induces Neuroprotection via the PI3K-AKT-BCL2 Axis to Mediate the Therapeutic Effect of Electroacupuncture on Postoperative Cognitive Dysfunction.","authors":"Tingting Huang, Jie Hong, Jia Ling, Lin Zhu, Wei Zhao, Xinlu Zhang, Xinze Yan, Chen Hu, Ruijie Zhang, Chen Gao, Shengzhao Zhang, Chen Chen, Runhuai Yang, Weiwei Wu, Chunhui Wang, Qian Gao","doi":"10.1002/adbi.202400172","DOIUrl":"10.1002/adbi.202400172","url":null,"abstract":"<p><p>Postoperative cognitive dysfunction (POCD), a postsurgical decline in cognitive function, primarily affects older adults and worsens their prognosis. Although elevated interleukin-12p70 (IL-12p70) is closely correlated with slower cognitive decline in older adults, its role in POCD remains unclear. Here, IL-12p70 is identified as a significant mediator of therapeutic effect of electroacupuncture (EA) on POCD. EA at acupoints ST36, GV20, and GV24 significantly enhanced cognitive behaviors of POCD mice. IL-12p70, downregulated in POCD mice but rescued by EA treatment, is the cytokine closely associated with EA's therapeutic effect. Clinically, IL-12p70 is downregulated in older adults' serum post-surgery. Furthermore, IL-12p70 exerts a potent neuroprotective effect in both neuronal cell lines and primary hippocampal neurons. The PI3K-AKT-BCL2 axis enriched by in silico analysis is validated as the signaling mechanism underlying IL-12p70-induced neuroprotection. In vivo, beneficial effects of EA treatment on the activation of PI3K-AKT-BCL2 axis and POCD are reproduced by IL-12p70 administration but attenuated by IL-12p70 knockdown. The findings reveal a novel mechanism underlying the therapeutic effect of EA on POCD, demonstrating that IL-12p70 exerts a neuroprotective effect by activating PI3K-AKT-BCL2 axis in hippocampal neurons. The newly-discovered function and mechanism of IL-12p70 highlight its potential in treating cognitive disorders.</p>","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e2400172"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142542999","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}