Biomolecules最新文献_第10页

The Role of Cancer Organoids in Ferroptosis, Pyroptosis, and Necroptosis: Functions and Clinical Implications. 肿瘤类器官在铁下垂、焦下垂和坏死下垂中的作用：功能和临床意义。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-05-02 DOI: 10.3390/biom15050659

Dingci Lu, Bingqian Xia, Tianquan Feng, Gui Qi, Zhaowu Ma

{"title":"The Role of Cancer Organoids in Ferroptosis, Pyroptosis, and Necroptosis: Functions and Clinical Implications.","authors":"Dingci Lu, Bingqian Xia, Tianquan Feng, Gui Qi, Zhaowu Ma","doi":"10.3390/biom15050659","DOIUrl":"https://doi.org/10.3390/biom15050659","url":null,"abstract":"The enduring prevalence of cancer worldwide constitutes a significant public health challenge, thereby emphasizing the imperative for the development of therapeutic models capable of accounting for the heterogeneity inherent in tumors. In this context, cancer organoids have emerged as powerful tools for studying tumor biology, providing valuable insights into the complex interactions within the tumor microenvironment. Concurrently, research is increasingly focused on non-apoptotic forms of regulated cell death (RCD)-including ferroptosis, pyroptosis, and necroptosis-which exert pivotal influences on cancer development and progression. Cancer organoids not only recapitulate the genetic and phenotypic heterogeneity of the original tumors but also enable more precise investigations into the roles of non-apoptotic RCDs within oncology. This review explores the utility of cancer organoids in delineating the molecular mechanisms underlying RCDs and their implications for cancer biology and treatment responses. By synthesizing recent research findings, it highlights the essential role of organoid models in uncovering the intricate details of non-apoptotic RCDs. Furthermore, it emphasizes promising directions for future research that aim to deepen our understanding of these pathways and their therapeutic potential. The integration of organoid models into investigations of ferroptosis, pyroptosis, and necroptosis provides novel insights into oncogenic mechanisms and facilitates the development of targeted therapeutic strategies. By bridging cancer organoids with human pathophysiology, this approach not only provides a transformative framework for dissecting oncogenic pathways but also enables the design of precision therapeutics that selectively target the molecular machinery underlying non-apoptotic RCDs.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interaction Between PHF8 and a Segment of KDM2A, Which Is Controlled by the Phosphorylation Status at a Specific Serine in an Intrinsically Disordered Region of KDM2A, Regulates rRNA Transcription and Cell Proliferation in a Breast Cancer Cell Line. 在乳腺癌细胞系中，PHF8与KDM2A片段的相互作用调节rRNA转录和细胞增殖，这一相互作用受KDM2A内在紊乱区域特定丝氨酸磷酸化状态的控制。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-05-02 DOI: 10.3390/biom15050661

Kengo Okamoto, Yutaro Mihara, Sachiko Ogasawara, Takashi Murakami, Sinya Ohmori, Tetsuya Mori, Toshiyuki Umata, Yuki Kawasaki, Kazuya Hirano, Hirohisa Yano, Makoto Tsuneoka

{"title":"Interaction Between PHF8 and a Segment of KDM2A, Which Is Controlled by the Phosphorylation Status at a Specific Serine in an Intrinsically Disordered Region of KDM2A, Regulates rRNA Transcription and Cell Proliferation in a Breast Cancer Cell Line.","authors":"Kengo Okamoto, Yutaro Mihara, Sachiko Ogasawara, Takashi Murakami, Sinya Ohmori, Tetsuya Mori, Toshiyuki Umata, Yuki Kawasaki, Kazuya Hirano, Hirohisa Yano, Makoto Tsuneoka","doi":"10.3390/biom15050661","DOIUrl":"https://doi.org/10.3390/biom15050661","url":null,"abstract":"Mild starvation due to low concentrations of an inhibitor of glycolysis, 2-deoxy-D-glucose, activates AMP-activated protein kinase (AMPK) and lysine-specific demethylase 2A (KDM2A) to reduce rRNA transcription and cell proliferation in breast cancer cells. However, the mechanisms of how AMPK regulates KDM2A are unknown. Here, we found that PHD finger protein 8 (PHF8) interacted with KDM2A and contributed to the reduction in rRNA transcription and cell proliferation by 2-deoxy-D-glucose in a breast cancer cell line, MCF-7. We analyzed how KDM2A bound PHF8 in detail and found that PHF8 interacted with KDM2A via two regions of KDM2A. One of the regions contained an intrinsically disordered region (IDR). IDRs can show rapidly switchable protein-protein interactions. Deletion of the PHF8-binding region activated KDM2A to reduce rRNA transcription, and 2-deoxy-D-glucose reduced the interaction between PHF8 and the KDM2A fragment containing the PHF8-binding region. A 2-deoxy-D-glucose or AMPK activator dephosphorylated KDM2A at Ser731, which is located on the N-terminal side of the PHF8-binding region. Replacement of Ser731 by Ala decreased binding of PHF8 to the KDM2A fragment that contains the PHF8-binding region and Ser731 and reduced rRNA transcription and cell proliferation. These results suggest that the mode of interaction between KDM2A and PHF8 is regulated via dephosphorylation of KDM2A through AMPK to control rRNA transcription, and control of the phosphorylation state of Ser731 would be a novel target for breast cancer therapy.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Residue-Specific Structural and Dynamical Coupling of Protein and Hydration Water Revealed by Molecular Dynamics Simulations. 分子动力学模拟揭示了蛋白质和水合水的残基特异性结构和动力学耦合。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-05-02 DOI: 10.3390/biom15050660

Shuai Wang, Jun Gao, Xiakun Chu

{"title":"Residue-Specific Structural and Dynamical Coupling of Protein and Hydration Water Revealed by Molecular Dynamics Simulations.","authors":"Shuai Wang, Jun Gao, Xiakun Chu","doi":"10.3390/biom15050660","DOIUrl":"https://doi.org/10.3390/biom15050660","url":null,"abstract":"Proteins and their surrounding hydration water engage in a dynamic interplay that is critical for maintaining structural stability and functional integrity. However, the intricate coupling between protein dynamics and the structural order of hydration water remains poorly understood. Here, we employ all-atom molecular dynamics simulations to investigate this relationship across four representative proteins. Our results reveal that protein residues with greater flexibility or solvent exposure are surrounded by more disordered hydration water, akin to bulk water, whereas rigid and buried non-polar residues are associated with structurally ordered hydration shells. Due to their strong hydrogen bonding and electrostatic interactions, charged residues exhibit the most disordered hydration water, while non-polar residues are associated with the structurally most ordered hydration water. We further uncovered a positive correlation between the relaxation dynamics of protein residues and their hydration water: slower (faster) protein relaxation is coupled with slower (faster) relaxation of the structural order of hydration water. Notably, this coupling weakens with increasing residue flexibility or solvent exposure, with non-polar residues displaying the strongest coupling, and charged residues the weakest. To further uncover their coupling mechanism, we elucidate residue-specific coupled fluctuations between protein residues and hydration water by generating scatter plots. These findings provide a comprehensive understanding of the mechanisms underlying protein-water interactions, offering valuable insights into the role of hydration water in protein stability, dynamics, and function.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enzymatic Glycosylation of Ganoderma Terpenoid via Bacterial Glycosyltransferases and Glycoside Hydrolases. 细菌糖基转移酶和糖苷水解酶对灵芝萜类酶的糖基化作用。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-05-01 DOI: 10.3390/biom15050655

Te-Sheng Chang, Jiumn-Yih Wu, Hsiou-Yu Ding, Tzi-Yuan Wang

{"title":"Enzymatic Glycosylation of Ganoderma Terpenoid via Bacterial Glycosyltransferases and Glycoside Hydrolases.","authors":"Te-Sheng Chang, Jiumn-Yih Wu, Hsiou-Yu Ding, Tzi-Yuan Wang","doi":"10.3390/biom15050655","DOIUrl":"https://doi.org/10.3390/biom15050655","url":null,"abstract":"Glycosylation is a critical enzymatic modification that involves the attachment of sugar moieties to target compounds, considerably influencing their physicochemical and biological characteristics. This review explored the role of two primary enzyme classes-glycosyltransferases (GTs) and glycoside hydrolases (GHs, glycosidases)-in catalyzing the glycosylation of natural products, with a specific focus on Ganoderma triterpenoids. While GTs typically use activated sugar donors, such as uridine diphosphate glucose, certain GHs can leverage more economical sugar sources, such as sucrose and starch, through transglycosylation. This paper also reviewed strategies for producing novel terpenoid glycosides, particularly recently isolated bacterial GTs and GHs capable of glycosylating terpenoids and flavonoids. It summarized the newly synthesized glycosides' structures and biotransformation mechanisms, enhanced aqueous solubility, and potential applications. The regioselectivity and substrate specificity of GTs and GHs in catalyzing O-glycosylation (glucosylation) at distinct hydroxyl and carboxyl groups were compared. Furthermore, a special case in which the novel glycosylation reactions were mediated by GHs, including the formation of unique glycoside anomers, was included. The advantages and specific capabilities of GT/GH enzymes were evaluated for their potential in biotechnological applications and future research directions. Novel fungal triterpenoid glycosides produced through various glycosidases and sugars is expected to expand their potential applications in the future.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drosophila as a Genetic Model System to Study Organismal Energy Metabolism. 果蝇作为研究机体能量代谢的遗传模型系统。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-05-01 DOI: 10.3390/biom15050652

Arely V Diaz, Izel Tekin, Tânia Reis

引用次数: 0

The Anticonvulsant Effects of Different Cannabis Extracts in a Zebrafish Model of Epilepsy. 不同大麻提取物对斑马鱼癫痫模型的抗惊厥作用。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-05-01 DOI: 10.3390/biom15050654

Karen Jackson, Maytal Shabat-Simon, Jonathan Bar-On, Rafi Steckler, Soliman Khatib, Snait Tamir, Paula Adriana Pitashny

{"title":"The Anticonvulsant Effects of Different Cannabis Extracts in a Zebrafish Model of Epilepsy.","authors":"Karen Jackson, Maytal Shabat-Simon, Jonathan Bar-On, Rafi Steckler, Soliman Khatib, Snait Tamir, Paula Adriana Pitashny","doi":"10.3390/biom15050654","DOIUrl":"https://doi.org/10.3390/biom15050654","url":null,"abstract":"Epilepsy is a widespread neurological disorder that remains a critical global public health challenge. While numerous antiepileptic drugs (AEDs) are available, many patients either fail to achieve adequate seizure control or experience significant side effects. One promising alternative is pure cannabidiol (CBD), but using a whole cannabis extract may be equally effective and preferred for some patients. In the current study, we employed the pentylenetetrazole (PTZ)-induced hyperactivity model in zebrafish to compare the effects of CBD with various cannabis extracts. We evaluated three cannabis strains, each subjected to three different extraction methods, and benchmarked the results against the commercially available AED valproic acid (VPA). Our findings revealed that 5.7 µg/mL of CBD and 10 µg/mL of different extracts significantly reduced movement compared to PTZ and VPA. In addition, effective extracts produced effects similar to pure CBD despite containing much lower molecule levels. These results reinforced and expanded previous evidence supporting the clinical potential of both CBD and whole cannabis extracts for seizure control while suggesting a possible entourage effect. Further research is necessary to determine which patients may benefit more from pure CBD versus those who might prefer whole cannabis extracts.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Transformative Role of Nanotechnology in the Management of Diabetes Mellitus: Insights from Current Research. 纳米技术在糖尿病管理中的变革作用：来自当前研究的见解。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-05-01 DOI: 10.3390/biom15050653

Natalia G Vallianou, Maria Dalamaga, Argyro Pavlou, Eleni Rebelos, Nikolaos Nektarios Karamanolis, Eleftheria Papachristoforou, Evangelos Mavrothalassitis, Ioanna Eleftheriadou, Nikolaos Tentolouris, Dimitris Kounatidis

{"title":"The Transformative Role of Nanotechnology in the Management of Diabetes Mellitus: Insights from Current Research.","authors":"Natalia G Vallianou, Maria Dalamaga, Argyro Pavlou, Eleni Rebelos, Nikolaos Nektarios Karamanolis, Eleftheria Papachristoforou, Evangelos Mavrothalassitis, Ioanna Eleftheriadou, Nikolaos Tentolouris, Dimitris Kounatidis","doi":"10.3390/biom15050653","DOIUrl":"https://doi.org/10.3390/biom15050653","url":null,"abstract":"Nanotechnology refers to the science that modulates molecules to the nanoscale dimension. Nanomedicine, i.e., the utilization of nanotechnology for diagnosing and treating several disorders, is a subject of ongoing research. The concept behind nanomedicine in diabetes mellitus (DM) treatment stems from the need to ameliorate absorption and distribution of antidiabetic therapies in order to overcome barriers, namely the pH throughout the gastrointestinal tract, the gut microbiota, the temperature/heat and the difficulties in the incorporation of drugs into the cells. Thus, the scope of nanomedicine is particularly challenging and demanding, considering the fact that the human body is a perpetually changing entity in order to achieve homeostasis. In this review, we will delve into various nanoparticles that are being studied in terms of antidiabetic treatment, their pros and cons and the expanding knowledge in this field. Despite the fact that nanomedicine seems to be very promising, there are still many gaps in our understanding of how the human body addresses its utilization. Moreover, its high costs, along with an as-yet unclear safety profile, remain a significant barrier to widespread adoption. In this review, we will describe both phytochemicals and chemical compounds that nanomedicine seeks to exploit in order to pave the way for a more efficacious and comprehensive management of diabetes mellitus.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tannic Acid and Ethacridine Lactate Attenuate Markers of Stress-Induced Intestinal Barrier Dysfunctions in Murine Small Intestinal Organoids. 单宁酸和乳酸乙沙啶可减弱应激诱导的小鼠小肠类器官肠屏障功能障碍标志物。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-04-30 DOI: 10.3390/biom15050650

Louisa Filipe Rosa, Steffen Gonda, Nadine Roese, Stephan C Bischoff

{"title":"Tannic Acid and Ethacridine Lactate Attenuate Markers of Stress-Induced Intestinal Barrier Dysfunctions in Murine Small Intestinal Organoids.","authors":"Louisa Filipe Rosa, Steffen Gonda, Nadine Roese, Stephan C Bischoff","doi":"10.3390/biom15050650","DOIUrl":"https://doi.org/10.3390/biom15050650","url":null,"abstract":"(1) Background: Tannacomp® is a drug consisting of tannin albuminate, a complex of tannic acid (TA) and ethacridine lactate (Eta) used for treating acute and traveler's diarrhea. TA is thought to modulate gastrointestinal barrier function, but the underlying mechanisms and whether Eta has similar effects remains unclear. (2) Methods: to investigate the effects of TA and Eta on the intestinal barrier, stress responses were induced in murine intestinal organoids by lipopolysaccharide (LPS) exposure or withdrawal of growth factors from cell culture medium (GFRed). Further, organoids were exposed to either TA (0.01 mg/mL) or Eta (0.002 mg/mL) and markers of inflammatory response and gut barrier function were assessed. (3) Results: TA and Eta reduced several inflammatory markers such as interleukin 6, interleukin 1β, tumor necrosis factor α, and myeloid differentiation primary response 88 in stressed organoids. In addition, TA and Eta attenuated LPS- and GFRed-mediated gut barrier dysfunctions, with normalization of tight junction, adherent junction and mucin gene expression and reduction of Nod2- and matrix metalloproteinase 7-dependent activation of antimicrobial peptides. (4) Conclusions: our data show that TA and Eta modulate markers of inflammation and the intestinal barrier and suggest novel mechanisms of action of this drug that could broaden its treatment indications.","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 5","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Time-Dependent Kinetic Complexities in Enzyme Assays: A Review. 酶分析中随时间变化的动力学复杂性：综述。

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-04-30 DOI: 10.3390/biom15050641

Juan Luis Rendón, Juan Pablo Pardo

引用次数: 0

Immunotherapy in Advanced Cutaneous Melanoma: From the Optimal Treatment Duration to the Impact on Survival in Case of Early Discontinuation Due to Immune-Related Adverse Events. 晚期皮肤黑色素瘤的免疫治疗：从最佳治疗时间到由于免疫相关不良事件而早期停药对生存的影响

IF 4.8 2区生物学

Biomolecules Pub Date : 2025-04-30 DOI: 10.3390/biom15050651

Giacomo Triggiano, Gaetano Pezzicoli, Marco Tucci

引用次数: 0