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Efficient Incorporation of DOPA into Proteins Free from Competition with Endogenous Translation Termination Machinery.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-06 DOI: 10.3390/biom15030382
Youhui Yang, Yingchen Wang, Zhaoguan Wang, Hao Qi
{"title":"Efficient Incorporation of DOPA into Proteins Free from Competition with Endogenous Translation Termination Machinery.","authors":"Youhui Yang, Yingchen Wang, Zhaoguan Wang, Hao Qi","doi":"10.3390/biom15030382","DOIUrl":"10.3390/biom15030382","url":null,"abstract":"<p><p>3,4-Dihydroxy-L-phenylalanine (DOPA) is a promising noncanonical amino acid (ncAA) that introduces novel catechol chemical features into proteins, expanding their functional potential. However, the most common approach to incorporating ncAAs into proteins relies on stop codon suppression, which is often limited by the competition of endogenous translational termination machinery. Here, we employed a special in vitro protein expression system that facilitates the efficiency of DOPA incorporation into proteins by removing essential Class I peptide release factors through targeted degradation. In the absence of both RF1 and RF2, we successfully demonstrated DOPA incorporation at all three stop codons (TAG, TAA, and TGA). By optimizing the concentration of engineered DOPA-specific aminoacyl-tRNA synthetase (DOPARS), DOPA, and DNA template, we achieved a synthesis yield of 2.24 µg of sfGFP with 100% DOPA incorporation in a 20 μL reaction system. DOPARS exhibited a dissociation constant (<i>Kd</i>) of 11.7 μM for DOPA but showed no detectable binding to its native counterpart, tyrosine. Additionally, DOPA was successfully incorporated into a reverse transcriptase, which interfered with its activity. This system demonstrates a fast and efficient approach for precise DOPA incorporation into proteins, paving the way for advanced protein engineering applications.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728209","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 Association Among Bipolar Disorder, Mitochondrial Dysfunction, and Reactive Oxygen Species.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-06 DOI: 10.3390/biom15030383
Yuki Kageyama, Shohei Okura, Ayaka Sukigara, Ayaka Matsunaga, Kunio Maekubo, Takafumi Oue, Koki Ishihara, Yasuhiko Deguchi, Koki Inoue
{"title":"The Association Among Bipolar Disorder, Mitochondrial Dysfunction, and Reactive Oxygen Species.","authors":"Yuki Kageyama, Shohei Okura, Ayaka Sukigara, Ayaka Matsunaga, Kunio Maekubo, Takafumi Oue, Koki Ishihara, Yasuhiko Deguchi, Koki Inoue","doi":"10.3390/biom15030383","DOIUrl":"10.3390/biom15030383","url":null,"abstract":"<p><p>Mitochondria, often known as the cell's powerhouses, are primarily responsible for generating energy through aerobic oxidative phosphorylation. However, their functions extend far beyond just energy production. Mitochondria play crucial roles in maintaining calcium balance, regulating apoptosis (programmed cell death), supporting cellular signaling, influencing cell metabolism, and synthesizing reactive oxygen species (ROS). Recent research has highlighted a strong link between bipolar disorder (BD) and mitochondrial dysfunction. Mitochondrial dysfunction contributes to oxidative stress, particularly through the generation of ROS, which are implicated in the pathophysiology of BD. Oxidative stress arises when there is an imbalance between the production of ROS and the cell's ability to neutralize them. In neurons, excessive ROS can damage various cellular components, including proteins in neuronal membranes and intracellular enzymes. Such damage may interfere with neurotransmitter reuptake and the function of critical enzymes, potentially affecting brain regions involved in mood regulation and emotional control, which are key aspects of BD. In this review, we will explore how various types of mitochondrial dysfunction contribute to the production of ROS. These include disruptions in energy metabolism, impaired ROS management, and defects in mitochondrial quality control mechanisms such as mitophagy (the process by which damaged mitochondria are selectively degraded). We will also examine how abnormalities in calcium signaling, which is crucial for synaptic plasticity, can lead to mitochondrial dysfunction. Additionally, we will discuss the specific mitochondrial dysfunctions observed in BD, highlighting how these defects may contribute to the disorder's pathophysiology. Finally, we will identify potential therapeutic targets to improve mitochondrial function, which could pave the way for new treatments to manage or mitigate symptoms of BD.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940798/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728029","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
Current and Emerging Assays for Measuring Human T-Cell Responses Against Beta-Cell Antigens in Type 1 Diabetes.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-06 DOI: 10.3390/biom15030384
Ting-Chen Lin, Matthew Lacorcia, Stuart I Mannering
{"title":"Current and Emerging Assays for Measuring Human T-Cell Responses Against Beta-Cell Antigens in Type 1 Diabetes.","authors":"Ting-Chen Lin, Matthew Lacorcia, Stuart I Mannering","doi":"10.3390/biom15030384","DOIUrl":"10.3390/biom15030384","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is an autoimmune disease caused by T-cell mediated destruction of the pancreatic insulin-producing beta cells. Currently, the development of autoantibodies is the only measure of beta-cell autoimmunity used in the clinic. Despite T-cells' well-accepted role in the autoimmune pathogenesis of human T1D, autoimmune T-cell responses against beta cells remain very difficult to measure. An assay capable of measuring beta-cell antigen-specific T-cell responses has been a long-sought goal. Such an assay would facilitate the direct monitoring of T1D-associated T-cell responses facilitating, earlier diagnosis and rapid evaluation of candidate immune therapies in clinical trials. In addition, a simple and robust assay for beta-cell antigen-specific T-cell responses would be a powerful tool for dissecting the autoimmune pathogenesis of human T1D. Here, we review the challenges associated with measuring beta-cell antigen-specific T-cell responses, the current assays which are used to achieve this and, finally, we discuss BASTA, a promising emerging assay for measuring human beta-cell antigen-specific CD4<sup>+</sup> T-cell responses.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728080","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
Metabolomic Profiling and In Vitro Evaluation of Cytotoxic, Genotoxic, and Antigenotoxic Effects of Staphylea pinnata L. Extract from Italian Flora.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-06 DOI: 10.3390/biom15030385
Ghanya Al-Naqeb, Fabio Pietrolucci, Mauro Commisso, Aliki Kalmpourtzidou, Amanda Oldani, Sara Boussetta, Beatrice Maccarini, Rachele De Giuseppe, Hellas Cena
{"title":"Metabolomic Profiling and In Vitro Evaluation of Cytotoxic, Genotoxic, and Antigenotoxic Effects of <i>Staphylea pinnata</i> L. Extract from Italian Flora.","authors":"Ghanya Al-Naqeb, Fabio Pietrolucci, Mauro Commisso, Aliki Kalmpourtzidou, Amanda Oldani, Sara Boussetta, Beatrice Maccarini, Rachele De Giuseppe, Hellas Cena","doi":"10.3390/biom15030385","DOIUrl":"10.3390/biom15030385","url":null,"abstract":"<p><p><i>Staphylea pinnata</i> L., (<i>S. pinnata</i>), has long been recognized in Europe as both a wild food source and a traditional medicinal. This study aimed to characterize the metabolomic profile of the leaf extract of <i>S. pinnata</i> and assess its cytotoxic, genotoxic, and antigenotoxic effects in vitro for the first time. The methanolic extract of the leaves was analyzed using Ultra-Performance Liquid Chromatography-High-Resolution Mass Spectrometry (UPLC-HRMS). To evaluate its cytotoxic, genotoxic, and antigenotoxic properties, the cytokinesis block micronucleus assay was performed on Chinese hamster ovarian K1 cells. The analysis revealed a wide variety of metabolites in the extract, with B-type procyanidins and prodelphinidins being the most abundant. The genotoxicity of the extract varied depending on its concentration; at the lowest concentration (75 μg/mL), it showed no genotoxic effects and exhibited antigenotoxic properties by reducing the frequency of micronuclei induced by mitomycin C. However, at the highest concentration (300 μg/mL), the extract demonstrated genotoxic effects. In conclusion, the <i>S. pinnata</i> extract displayed both genotoxic and antigenotoxic properties, which may be attributed to its phytochemical composition. These findings highlight the complex nature of the plant's bioactive compounds, suggesting potential therapeutic applications with careful consideration of dosage. Additional research is necessary to understand the mechanisms underlying these properties.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727802","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
Neurocellular Stress Response to Mojave Type A Rattlesnake Venom: Study of Molecular Mechanisms Using Human iPSC-Derived Neural Stem Cell Model.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-06 DOI: 10.3390/biom15030381
Satish Kumar, Miriam Aceves, Jose Granados, Lorena Guerra, Felicia Juarez, Earl Novilla, Ana C Leandro, Marcelo Leandro, Juan Peralta, Sarah Williams-Blangero, Elda E Sanchez, Jacob A Galan, John Blangero, Joanne E Curran
{"title":"Neurocellular Stress Response to Mojave Type A Rattlesnake Venom: Study of Molecular Mechanisms Using Human iPSC-Derived Neural Stem Cell Model.","authors":"Satish Kumar, Miriam Aceves, Jose Granados, Lorena Guerra, Felicia Juarez, Earl Novilla, Ana C Leandro, Marcelo Leandro, Juan Peralta, Sarah Williams-Blangero, Elda E Sanchez, Jacob A Galan, John Blangero, Joanne E Curran","doi":"10.3390/biom15030381","DOIUrl":"10.3390/biom15030381","url":null,"abstract":"<p><p>The Mojave rattlesnake venom shows significant geographical variability. The venom of Type A animals primarily contains β-neurotoxin referred to as Mojave Toxin (MTX), which makes bites from this snake particularly feared. We performed a genome-wide transcriptomic analysis of the neurocellular response to Mojave Type A rattlesnake venom using induced pluripotent stem cell-derived neural stem cells to unveil the molecular mechanisms underlying the damage caused by this snake's envenomation. Our results suggest that snake venom metalloproteases, although having a limited repertoire in Type A venom, facilitate venom spread by digesting the tissue's extracellular matrix. The MTX, which is composed of heterodimers of basic and acidic phospholipase-A2, co-opts the host arachidonic acid and Ca<sup>2+</sup> second messenger mechanisms and triggers multiple signaling cascades, such as the activation of MAPKs and NF-κB-regulated proinflammatory genes; the neurotransmitter overload in excitatory synapses leading to a presynaptic blockade of nerve signals; and the upregulation of unfolded protein response (UPR) due to the depletion of Ca<sup>2+</sup> from the endoplasmic reticulum. The upregulated UPR and the oxidative stress caused by reactive oxygen species generated in cytochromeP4501A1-mediated hydroxylation of arachidonic acid contribute to mitochondrial toxicity. The activation of UPR, mitochondrial toxicity, and oxidative stress synergistically contributed to apoptotic and ferroptotic cell death.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728264","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
Deep Thought on the HIV Cured Cases: Where Have We Been and What Lies Ahead?
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-05 DOI: 10.3390/biom15030378
Qing Xiao, Sanxiu He, Chaoyu Wang, Yixing Zhou, Chensi Zeng, Jun Liu, Tingting Liu, Tingting Li, Xi Quan, Linyue Wang, Liuyue Zhai, Yi Liu, Jun Li, Xiaomei Zhang, Yao Liu
{"title":"Deep Thought on the HIV Cured Cases: Where Have We Been and What Lies Ahead?","authors":"Qing Xiao, Sanxiu He, Chaoyu Wang, Yixing Zhou, Chensi Zeng, Jun Liu, Tingting Liu, Tingting Li, Xi Quan, Linyue Wang, Liuyue Zhai, Yi Liu, Jun Li, Xiaomei Zhang, Yao Liu","doi":"10.3390/biom15030378","DOIUrl":"10.3390/biom15030378","url":null,"abstract":"<p><p>Antiretroviral therapy (ART) can effectively suppress the replication of human immunodeficiency virus (HIV), but it cannot completely eradicate the virus. The persistent existence of the HIV reservoir is a major obstacle in the quest for a cure. To date, there have been a total of seven cured cases of HIV worldwide. These patients all cleared HIV while undergoing allogeneic stem cell transplantation (allo-HSCT) for hematological malignancies. However, in these cases, the specific mechanism by which allo-HSCT leads to the eradication of HIV remains unclear, so it is necessary to conduct an in-depth analysis. Due to the difficulty in obtaining donors and the risks associated with transplantation, this treatment method is not applicable to all HIV patients. There is still a need to explore new treatment strategies. In recent years, emerging therapies such as neutralizing antibody immunotherapy, chimeric antigen receptor T cell (CAR-T) therapy, gene editing, and antiviral therapies targeting the reservoir have attracted wide attention due to their ability to effectively inhibit HIV replication. This article first elaborates on the nature of the HIV reservoir, then deeply explores the treatment modalities and potential success factors of HIV cured cases, and finally discusses the current novel treatment methods, hoping to provide comprehensive and feasible strategies for achieving the cure of HIV.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728251","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
Cardiovascular-Endocrine-Metabolic Medicine: Proposing a New Clinical Sub-Specialty Amid the Cardiometabolic Pandemic.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-05 DOI: 10.3390/biom15030373
Nikolaos Theodorakis, Maria Nikolaou, Andrew Krentz
{"title":"Cardiovascular-Endocrine-Metabolic Medicine: Proposing a New Clinical Sub-Specialty Amid the Cardiometabolic Pandemic.","authors":"Nikolaos Theodorakis, Maria Nikolaou, Andrew Krentz","doi":"10.3390/biom15030373","DOIUrl":"10.3390/biom15030373","url":null,"abstract":"<p><p>Cardiovascular-Renal-Hepatic-Metabolic diseases are on the rise worldwide, creating major challenges for patient care and clinical research. Although these conditions share common mechanisms and often respond to similar treatments-such as lifestyle changes and newer cardiometabolic drugs (e.g., SGLT2 inhibitors, GLP-1 receptor agonists)-clinical management remains divided among multiple specialties. Recently proposed curricula in Cardiometabolic Medicine and Preventive Cardiology reflect an effort to address this fragmentation. In addition, recent studies reveal that hormonal deficiencies may increase cardiovascular risk and worsen heart failure, with emerging data showing that correcting these imbalances can improve exercise capacity and possibly reduce major cardiac events. To overcome gaps in care, we propose a new sub-specialty: Cardiovascular-Endocrine-Metabolic Medicine. This approach unifies three main pillars: (1) Lifestyle medicine, emphasizing nutrition, physical activity, and smoking cessation; (2) the Integrated Medical Management of obesity, diabetes, hypertension, dyslipidemia, heart failure with preserved ejection fraction, early-stage kidney disease, metabolic-associated liver disease, and related conditions; and (3) hormonal therapies, focused on optimizing sex hormones and other endocrine pathways to benefit cardiometabolic health. By bridging cardiology, endocrinology, and metabolic medicine, this sub-specialty offers a more seamless framework for patient care, speeds up the adoption of new treatments, and sets the stage for innovative research-all critical steps in addressing the escalating cardiometabolic pandemic.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727408","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
PRAG1 Condensation Drives Cell Contraction Under Stress.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-05 DOI: 10.3390/biom15030379
Peiwu Ye, Peiran Jiang, Luyu Ye, Min Liu, Qiuyuan Fang, Peilin Yu, Jianhong Luo, Huanxing Su, Wei Yang
{"title":"PRAG1 Condensation Drives Cell Contraction Under Stress.","authors":"Peiwu Ye, Peiran Jiang, Luyu Ye, Min Liu, Qiuyuan Fang, Peilin Yu, Jianhong Luo, Huanxing Su, Wei Yang","doi":"10.3390/biom15030379","DOIUrl":"10.3390/biom15030379","url":null,"abstract":"<p><p>Peak1-related, kinase-activating pseudokinase 1 (PRAG1), a member of the pseudopodium-enriched atypical kinase (PEAK) family of pseudokinases, has been reported to play a role in regulating cell morphology. However, the molecular mechanism for this function remains elusive. In this study, we demonstrate that PRAG1 forms dynamic condensates in cells mediated by its αN and αJ helices. Importantly, we found that PRAG1 condensates functioned in mediating cell contraction, while condensate-formation-deficient PRAG1 mutants lost this function. Remarkably, the formation of spherical PRAG1 condensates appears to be a common phenomenon in diverse stress models, as well as in dopaminergic (DA) neurons derived from a Parkinson's disease patient. Our findings reveal a novel mechanism through which PRAG1 drives cell contraction and suggest a potential link between aberrant PRAG1 phase separation and stress-induced cell contraction. PRAG1 condensation drives cell contraction under stress.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11939857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728277","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
Interplay Between Traditional and Scientific Knowledge: Phytoconstituents and Their Roles in Lung and Colorectal Cancer Signaling Pathways.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-05 DOI: 10.3390/biom15030380
Ilma Imtiaz, Janet Schloss, Andrea Bugarcic
{"title":"Interplay Between Traditional and Scientific Knowledge: Phytoconstituents and Their Roles in Lung and Colorectal Cancer Signaling Pathways.","authors":"Ilma Imtiaz, Janet Schloss, Andrea Bugarcic","doi":"10.3390/biom15030380","DOIUrl":"10.3390/biom15030380","url":null,"abstract":"<p><p>Natural plant products have been used for cancer treatment since ancient times and continue to play a vital role in modern anticancer drug development. However, only a small fraction of identified medicinal plants has been thoroughly investigated, particularly for their effects on cellular pathways in lung and colorectal cancers, two under-researched cancers with poor prognostic outcomes (lung cancers). This review focuses on the lung and colorectal cancer signaling pathways modulated by bioactive compounds from eleven traditional medicinal plants: <i>Curcuma longa</i>, <i>Astragalus membranaceus</i>, <i>Glycyrrhiza glabra</i>, <i>Althaea officinalis</i>, <i>Echinacea purpurea</i>, <i>Sanguinaria canadensis</i>, <i>Codonopsis pilosula</i>, <i>Hydrastis canadensis</i>, <i>Lobelia inflata</i>, <i>Scutellaria baicalensis</i>, and <i>Zingiber officinale</i>. These plants were selected based on their documented use in traditional medicine and modern clinical practice. Selection criteria involved cross-referencing herbs identified in a scoping review of traditional cancer treatments and findings from an international survey on herbal medicine currently used for lung and colorectal cancer management by our research group and the availability of existing literature on their anticancer properties. The review identifies several isolated phytoconstituents from these plants that exhibit anticancer properties by modulating key signaling pathways such as PI3K/Akt/mTOR, RAS/RAF/MAPK, Wnt/β-catenin, and TGF-β in vitro. Notable constituents include sanguinarine, berberine, hydrastine, lobeline, curcumin, gingerol, shogaol, caffeic acid, echinacoside, cichoric acid, glycyrrhizin, 18-β-glycyrrhetinic acid, astragaloside IV, lobetyolin, licochalcone A, baicalein, baicalin, wogonin, and glycyrol. Curcumin and baicalin show preclinical effectiveness but face bioavailability challenges, which may be overcome by combining them with piperine or using oral extracts to enhance gut microbiome conversion, integrating traditional knowledge with modern strategies for improved outcomes. Furthermore, herbal extracts from <i>Echinacea</i>, <i>Glycyrrhiza</i>, and <i>Codonopsis,</i> identified in traditional knowledge, are currently in clinical trials. Notably, curcumin and baicalin also modulate miRNA pathways, highlighting a promising intersection of modern science and traditional medicine. Thus, the development of anticancer therapeutics continues to benefit from the synergy of traditional knowledge, scientific innovation, and technological advancements.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728262","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 Human Thyroid-Derived CI-huThyrEC Cell Line Expresses the Thyrotropin (TSH) Receptor and Thyroglobulin but Lacks Other Essential Characteristics of Thyroid Follicular Cells.
IF 4.8 2区 生物学
Biomolecules Pub Date : 2025-03-05 DOI: 10.3390/biom15030375
Mathias Halbout, Peter A Kopp
{"title":"The Human Thyroid-Derived CI-huThyrEC Cell Line Expresses the Thyrotropin (TSH) Receptor and Thyroglobulin but Lacks Other Essential Characteristics of Thyroid Follicular Cells.","authors":"Mathias Halbout, Peter A Kopp","doi":"10.3390/biom15030375","DOIUrl":"10.3390/biom15030375","url":null,"abstract":"<p><p><b><i>Background:</i></b> Thyroid hormone synthesis requires the normal function of thyroid follicular cells and adequate nutritional intake of iodine. For in vitro studies on thyroid cell pathophysiology, the immortalized FRTL5 rat thyroid cell line and a derivative thereof, the PCCL3 cell line, are widely used. However, a permanent human thyroid cell line is currently lacking. A recent report described a cell line obtained from human thyroid cells designated as Cl-huThyrEC. <b><i>Methods</i></b>: Four clones of Cl-huThyrEC cells were obtained and cultured in the presence of thyroid stimulating hormone (TSH). The expression of key genes defining the thyroid follicular cell phenotype was determined by reverse-transcription PCR (RT-PCR) in FRTL5, PCCL3, and Cl-huThyrEC cells. The latter were cultured as monolayers and as organoids in Matrigel. Iodide uptake was measured and compared among the cell lines. <b><i>Results:</i></b> Gene expression analysis reveals that Cl-huThyrEC cells express the thyroid-restricted transcription factors (<i>PAX8</i>, <i>NKX2.1</i>, <i>FOXE1</i>), the TSH receptor (<i>TSHR</i>), and thyroglobulin (<i>TG</i>), but they do not express the sodium-iodide symporter (<i>NIS</i>), thyroid peroxidase (<i>TPO</i>), and pendrin (<i>SLC26A4</i>). In functional studies, Cl-huThyrEC cells are unable to concentrate iodide. <b><i>Conclusions:</i></b> Despite the expression of certain key genes that are limited or restricted to thyroid follicular cells, Cl-huThyrEC cells lack some of the essential characteristics of thyroid follicular cells, in particular, <i>NIS</i>. Hence, their utility as a model system for thyroid follicular cells is limited.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"15 3","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728326","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
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