Frontiers in Molecular Biosciences最新文献

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Identification and validation of reference genes for quantitative gene expression analysis under 409 and 415 nm antimicrobial blue light treatment. 409和415 nm抗菌蓝光处理下基因定量表达分析内参基因的鉴定和验证。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2025-01-06 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1467726
Beata Kruszewska-Naczk, Mariusz Grinholc, Aleksandra Rapacka-Zdonczyk
{"title":"Identification and validation of reference genes for quantitative gene expression analysis under 409 and 415 nm antimicrobial blue light treatment.","authors":"Beata Kruszewska-Naczk, Mariusz Grinholc, Aleksandra Rapacka-Zdonczyk","doi":"10.3389/fmolb.2024.1467726","DOIUrl":"10.3389/fmolb.2024.1467726","url":null,"abstract":"<p><strong>Introduction: </strong>Reverse transcription quantitative real-time polymerase chain reaction Q7 (RT‒qPCR) is a commonly used tool for gene expression quantification. Because the qPCR method depends on several variables that can influence the analysis process, stably expressed genes should be selected for relative gene expression studies. To date, there is insufficient information on the selection of appropriate reference genes for antimicrobial photodynamic inactivation (aPDI) and antimicrobial blue light (aBL) treatment. Therefore, the purpose of the present study was to determine the most stable reference gene under treatment with aBL under sublethal conditions and to evaluate differences in the expression of the selected gene after aBL treatment in comparison to the nontreated control.</p><p><strong>Methods: </strong>Selection of stable reference genes was performed using 4 programs: BestKeeper, geNorm, NormFinder and RefFinder under 409 and 415 nm aBL treatment.</p><p><strong>Results: </strong>The results revealed that the gene encoding the integration host factor β subunit (ihfB) in <i>Escherichia coli</i> was the most stably expressed gene after both 409 and 415 nm aBL treatment. Three programs, RefFinder, geNorm, and NormFinder, indicated that this gene had the most stable expression in comparison to the other reference gene candidates. The next best candidates were cysG, uidA, and gyrA. NormFinder revealed ihfB as the single gene and cysG - gyrA as the combination of reference genes with the best stability.</p><p><strong>Discussion: </strong>Universal reference genes are characterized by stable expression that remains consistent across various stress conditions. Consequently, it is essential to evaluate reference genes for each specific stress factor under investigation. In the case of aBL at different wavelengths, we identified genes that maintain stable expression following irradiation.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1467726"},"PeriodicalIF":3.9,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11743365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003115","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}
引用次数: 0
ProAD - A database of rotary ion-translocating ATPases in prokaryotic genomes. ProAD -一个原核生物基因组中旋转离子易位atp酶的数据库。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2025-01-03 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1471556
A V Litvin, A S Lapashina, A P Ermidis, M S Gelfand, B A Feniouk
{"title":"ProAD - A database of rotary ion-translocating ATPases in prokaryotic genomes.","authors":"A V Litvin, A S Lapashina, A P Ermidis, M S Gelfand, B A Feniouk","doi":"10.3389/fmolb.2024.1471556","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1471556","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1471556"},"PeriodicalIF":3.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003055","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}
引用次数: 0
Unveiling and validating biomarkers related to the IL-10 family in chronic sinusitis with nasal polyps: insights from transcriptomics and single-cell RNA sequencing analysis. 揭示和验证慢性鼻窦炎伴鼻息肉中与IL-10家族相关的生物标志物:来自转录组学和单细胞RNA测序分析的见解
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2025-01-03 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1513951
Xinghong Liu, Yi Peng, Ling Guo, Weilan Xiong, Weijiang Liao, Jiangang Fan
{"title":"Unveiling and validating biomarkers related to the IL-10 family in chronic sinusitis with nasal polyps: insights from transcriptomics and single-cell RNA sequencing analysis.","authors":"Xinghong Liu, Yi Peng, Ling Guo, Weilan Xiong, Weijiang Liao, Jiangang Fan","doi":"10.3389/fmolb.2024.1513951","DOIUrl":"10.3389/fmolb.2024.1513951","url":null,"abstract":"<p><strong>Introduction: </strong>Extensive efforts have been made to explore members of the IL-10 family as potential therapeutic strategies for various diseases; however, their biological role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains underexplored.</p><p><strong>Methods: </strong>Gene expression datasets GSE136825, GSE179265, and GSE196169 were retrieved from the Gene Expression Omnibus (GEO) for analysis. Candidate genes were identified by intersecting differentially expressed genes (DEGs) between the CRSwNP and control groups (DEGsall) with those between the high- and low-score groups within the CRSwNP cohort (DEGsNP). Biomarker selection was performed using the Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine Recursive Feature Elimination (SVM-RFE), and the Boruta algorithm. Further refinement of biomarkers was carried out using receiver operating characteristic (ROC) analysis, with genes demonstrating an area under the curve (AUC) greater than 0.7 being considered significant. Genes exhibiting consistent expression trends and significant differences across both GSE136825 and GSE179265 were selected as potential biomarkers. Cell-type annotation was performed on GSE196169, and the expression profiles of the biomarkers across various cell types were analyzed. A competing endogenous RNA (ceRNA) network and a biomarker-drug interaction network were also established. Additionally, the mRNALocater database was utilized to determine the cellular localization of the identified biomarkers.</p><p><strong>Results: </strong>The intersection of 1817 DEGsall and 24 DEGsNP yielded 15 candidate genes. Further filtering through LASSO, SVM-RFE, and Boruta led to the identification of seven candidate biomarkers: PRB3, KRT16, MUC6, SPAG4, FGFBP1, NR4A1, and GSTA2. Six of these genes demonstrated strong diagnostic performance in GSE179265, while four biomarkers, showing both significant differences and consistent expression trends, were validated in both GSE179265 and GSE136825. Single-cell sequencing analysis of GSE196169 revealed seven distinct cell types, including endothelial cells, with the biomarkers predominantly expressed in epithelial cells. The ceRNA network comprised nine nodes and eleven edges, with only FGFBP1 exhibiting a complete lncRNA-miRNA-mRNA interaction.</p><p><strong>Discussion: </strong>This study identifies several novel biomarkers and their associated drugs for CRSwNP therapy, as well as potential therapeutic targets, such as spiperone and arnenous acid, identified through molecular docking. Ultimately, this work underscores the identification of four IL-10 family-related biomarkers, providing a theoretical foundation for future clinical research in CRSwNP.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1513951"},"PeriodicalIF":3.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738911/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003172","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}
引用次数: 0
Editorial: Revolutionizing life sciences: the nobel leap in artificial intelligence-driven biomodeling. 社论:生命科学革命:人工智能驱动的生物建模领域的诺贝尔飞跃。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2025-01-03 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1540823
Valentina Tozzini, Cecilia Giulivi
{"title":"Editorial: Revolutionizing life sciences: the nobel leap in artificial intelligence-driven biomodeling.","authors":"Valentina Tozzini, Cecilia Giulivi","doi":"10.3389/fmolb.2024.1540823","DOIUrl":"10.3389/fmolb.2024.1540823","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1540823"},"PeriodicalIF":3.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738921/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003024","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}
引用次数: 0
LncRNA HOXA10-AS as a novel biomarker and therapeutic target in human cancers. LncRNA HOXA10-AS作为人类癌症的新生物标志物和治疗靶点。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2025-01-03 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1520498
Xin Hu, Yong Wang, Sijia Zhang, Xiaosi Gu, Xiaoyu Zhang, Lianlian Li
{"title":"LncRNA HOXA10-AS as a novel biomarker and therapeutic target in human cancers.","authors":"Xin Hu, Yong Wang, Sijia Zhang, Xiaosi Gu, Xiaoyu Zhang, Lianlian Li","doi":"10.3389/fmolb.2024.1520498","DOIUrl":"10.3389/fmolb.2024.1520498","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are crucial regulatory molecules that participate in numerous cellular development processes, and they have gathered much interest recently. HOXA10 antisense RNA (HOXA10-AS, also known as HOXA-AS4) is a novel lncRNA that was identified to be dysregulated in some prevalent malignancies. In this review, the clinical significance of HOXA10-AS for the prognosis of various cancers is analyzed. In addition, the major advances in our understanding of the cellular biological functions and mechanisms of HOXA10-AS in different human cancers are summarized. These cancers include esophageal carcinoma (ESCA), gastric cancer (GC), glioma, laryngeal squamous cell carcinoma (LSCC), acute myeloid leukemia (AML), lung adenocarcinoma (LUAD), nasopharyngeal carcinoma (NPC), oral squamous cell carcinoma (OSCC), and pancreatic cancer. We also note that the aberrant expression of HOXA10-AS promotes malignant progression through various underlying mechanisms. In conclusion, HOXA10-AS is expected to serve as an ideal clinical biomarker and an effective cancer therapy target.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1520498"},"PeriodicalIF":3.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11738949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143003146","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}
引用次数: 0
Disparate molecular mechanisms in cardiac ryanodine receptor channelopathies. 心脏瑞诺定受体通道病变的不同分子机制。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-12-24 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1505698
Yadan Zhang, Monika Seidel, Camille Rabesahala de Meritens, Astrid Beckmann, Syeda Ahmed, Melanie Hurtz, F Anthony Lai, Esther Zorio, Dimitris Parthimos, Spyros Zissimopoulos
{"title":"Disparate molecular mechanisms in cardiac ryanodine receptor channelopathies.","authors":"Yadan Zhang, Monika Seidel, Camille Rabesahala de Meritens, Astrid Beckmann, Syeda Ahmed, Melanie Hurtz, F Anthony Lai, Esther Zorio, Dimitris Parthimos, Spyros Zissimopoulos","doi":"10.3389/fmolb.2024.1505698","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1505698","url":null,"abstract":"<p><strong>Aims: </strong>Mutations in the cardiac ryanodine receptor (RyR2) are associated with catecholaminergic polymorphic ventricular tachycardia (CPVT). This study investigates the underlying molecular mechanisms for CPVT mutations within the RyR2 N-terminus domain (NTD).</p><p><strong>Methods and results: </strong>We consulted the high-resolution RyR2 structure in both open and closed configuration to identify mutations G357S/R407I and A77T, which lie within the NTD intra- and inter-subunit interface with the Core Solenoid (CSol), respectively. Their structural and functional roles were compared to R169L, a mutation that lies within the NTD-NTD inter-subunit interface. Using chemical cross-linking and co-immunoprecipitation assays, we show that R169L disrupts NTD tetramerization, while it does not alter the NTD-CSol interaction. Single cell Ca<sup>2+</sup> imaging revealed that R169L increases the number of spontaneous Ca<sup>2+</sup> transients and the proportion of oscillating cells, while reducing the Ca<sup>2+</sup> store content. G357S and R407I do not affect NTD tetramerization, but they also do not alter the NTD-CSol interaction. Functionally, RyR2<sup>G357S</sup>-expressing cells have Ca<sup>2+</sup> handling properties similar to RyR2<sup>WT</sup>. A77T enhances the NTD-CSol interaction, while it does not affect NTD tetramerization. Like R169L, A77T also increases the number of spontaneous Ca<sup>2+</sup> transients and the proportion of oscillating cells, and it reduces the Ca<sup>2+</sup> store content. However, unlike R169L that displays Ca<sup>2+</sup> transients of normal amplitude and shorter duration, Ca<sup>2+</sup> transients for A77T are of smaller amplitude and normal duration.</p><p><strong>Conclusion: </strong>The NTD-CSol inter-subunit interface variant, A77T, produces a hyperactive channel by altering a different structure-function parameter to other CPVT mutations within the RyR2 NTD. Reduced NTD-NTD inter-subunit interaction and reinforced NTD inter-subunit interaction with CSol are distinct molecular mechanisms for gain-of-function RyR2 arrhythmogenic mutations.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1505698"},"PeriodicalIF":3.9,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947339","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}
引用次数: 0
Effects of Vaccinium-derived antioxidants on human health: the past, present and future. 疫苗衍生抗氧化剂对人体健康的影响:过去、现在和未来。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-12-20 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1520661
Amrita Ghosh, Samir C Debnath, Abir U Igamberdiev
{"title":"Effects of <i>Vaccinium</i>-derived antioxidants on human health: the past, present and future.","authors":"Amrita Ghosh, Samir C Debnath, Abir U Igamberdiev","doi":"10.3389/fmolb.2024.1520661","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1520661","url":null,"abstract":"<p><p>Dietary intake of <i>Vaccinium</i> berries has demonstrated significant potential in preventing many risk factors associated with metabolic syndromes in the human population. In recent years, a multitude of research has shown the role of antioxidants derived from <i>Vaccinium</i> berries on chronic diseases such as cardiovascular disorders, diabetes, obesity, and cancer. Several studies have also investigated the effect of <i>Vaccinium</i> berry consumption on their ability to modulate the risk factors associated with oxidative stress, vascular function, inflammation, and lipid metabolism. Regarding cancer, studies showed that the consumption of berries reduces inflammation, inhibits angiogenesis, protects against DNA damage within the cell, and controls apoptosis and proliferation rates in malignant tumours. However, which components are responsible for the health benefits is still unclear. Reports show that whole berry consumption usually confers positive effects on human health, and the health-promoting potentials are likely due to the presence of polyphenols with antioxidant activities. Among these polyphenols, various <i>Vaccinium</i> berry species have been reported to contain anthocyanins and flavonoids. These two polyphenolic compounds are known to have higher antioxidant activity and are beneficial for human health. There are now several studies and human clinical trials documenting the beneficial effects of <i>Vaccinium</i> berries, and these findings suggest that they may be promising for preventing and treating neurodegenerative diseases. This review focuses primarily on dietary <i>Vaccinium</i> berries consumption effects on human health and their potential role as therapeutic agents.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1520661"},"PeriodicalIF":3.9,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931156","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}
引用次数: 0
Corrigendum: A sulfuryl group transfer strategy to selectively prepare sulfated steroids and isotopically labelled derivatives. 勘误:硫酰基转移策略选择性制备硫酸类固醇和同位素标记衍生物。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-12-19 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1504226
Jaber A Alshehri, Daniel M Gill, Alan M Jones
{"title":"Corrigendum: A sulfuryl group transfer strategy to selectively prepare sulfated steroids and isotopically labelled derivatives.","authors":"Jaber A Alshehri, Daniel M Gill, Alan M Jones","doi":"10.3389/fmolb.2024.1504226","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1504226","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/fmolb.2021.776900.].</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1504226"},"PeriodicalIF":3.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11693584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921406","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}
引用次数: 0
Development of 6-amido-4-aminoisoindolyn-1,3-diones as p70S6K1 inhibitors and potential breast cancer therapeutics. 6-氨基-4-氨基异吲哚林1,3-二酮作为p70S6K1抑制剂和潜在的乳腺癌治疗药物的研究进展。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-12-19 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1481912
Adrian Thornton, Rajesh Komati, Hogyoung Kim, Jamiah Myers, Kymmia Petty, Rion Sam, Elijah Johnson-Henderson, Keshunna Reese, Linh Tran, Vaniyambadi Sridhar, Christopher Williams, Jayalakshmi Sridhar
{"title":"Development of 6-amido-4-aminoisoindolyn-1,3-diones as p70S6K1 inhibitors and potential breast cancer therapeutics.","authors":"Adrian Thornton, Rajesh Komati, Hogyoung Kim, Jamiah Myers, Kymmia Petty, Rion Sam, Elijah Johnson-Henderson, Keshunna Reese, Linh Tran, Vaniyambadi Sridhar, Christopher Williams, Jayalakshmi Sridhar","doi":"10.3389/fmolb.2024.1481912","DOIUrl":"10.3389/fmolb.2024.1481912","url":null,"abstract":"<p><strong>Introduction: </strong>Many breast cancer therapeutics target the PI3K/AKT/mTOR oncogenic pathway. Development of resistance to the therapeutics targeting this pathway is a frequent occurrence. Therapeutics targeting p70S6K1, a downstream member of this pathway, have recently gained importance due to its critical role in all types of breast cancer and its status as a prognostic marker. We have developed a new class of p70S6K1 inhibitors that show growth inhibition of MCF7 breast cancer cells.</p><p><strong>Methods: </strong>A series of 6-amido-4-aminoisoindolyn-1,3-dione compounds was developed against p70S6K1 using docking, computational modeling tools, and synthesis of the designed compounds. The p70S6K1 inhibition potency of the compounds was investigated in an initial high-throughput screening followed by IC<sub>50</sub> determination for the most active ones. The best compounds were subjected to proliferation assays on MCF7 breast cancer cells. The targeting of p70S6K1 by the compounds was confirmed by studying the phosphorylation status of downstream protein rpS6.</p><p><strong>Results: </strong>In this study, we have identified a new class of compounds as p70S6K1 inhibitors that function as growth inhibitors of MCF7 breast cancer cells. The structural features imparting p70S6K1 inhibition potency to the compounds have been mapped. Our studies indicate that substitutions on the phenacetyl group residing in the cleft A of the protein do not contribute to the inhibition potency. Three compounds (<b>5b, 5d</b>, and <b>5f</b>) have been identified to have sub-micromolar inhibition potency for p70S6K1. These compounds also exhibited growth inhibition of MCF7 cells by 40%-60% in the presence of estradiol.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1481912"},"PeriodicalIF":3.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142920633","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}
引用次数: 0
Circulating biomarkers associated with pediatric sickle cell disease. 与儿童镰状细胞病相关的循环生物标志物
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-12-19 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1481441
Cecilia Elorm Lekpor, Felix Abekah Botchway, Adel Driss, Alaijah Bashi, Afua D Abrahams, Kwadwo Asamoah Kusi, Godfred Futagbi, Ernest Alema-Mensah, William Agbozo, Wesley Solomon, Adriana Harbuzariu, Andrew A Adjei, Jonathan K Stiles
{"title":"Circulating biomarkers associated with pediatric sickle cell disease.","authors":"Cecilia Elorm Lekpor, Felix Abekah Botchway, Adel Driss, Alaijah Bashi, Afua D Abrahams, Kwadwo Asamoah Kusi, Godfred Futagbi, Ernest Alema-Mensah, William Agbozo, Wesley Solomon, Adriana Harbuzariu, Andrew A Adjei, Jonathan K Stiles","doi":"10.3389/fmolb.2024.1481441","DOIUrl":"10.3389/fmolb.2024.1481441","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Sickle cell disease (SCD) is a genetic blood disorder caused by a mutation in the HBB gene, which encodes the beta-globin subunit of hemoglobin. This mutation leads to the production of abnormal hemoglobin S (HbS), causing red blood cells to deform into a sickle shape. These deformed cells can block blood flow, leading to complications like chronic hemolysis, anemia, severe pain episodes, and organ damage. SCD genotypes include HbSS, HbSC (HbC is an abnormal variant of hemoglobin), and HbS/β-thalassemia. Sickle cell trait (SCT), HbAS, represents the carrier state, while other hemoglobin variants include HbCC, HbAC, and the normal HbAA. Over 7.5 million people worldwide live with SCD, with a high mortality rate in sub-Saharan Africa, including Ghana. Despite its prevalence, SCD is underdiagnosed and poorly managed, especially in children. Characterized by intravascular hemolysis, SCD leads to oxidative stress, endothelial activation, and systemic inflammation. Identifying circulating blood biomarkers indicative of organ damage and systemic processes is vital for understanding SCD and improving patient management. However, research on biomarkers in pediatric SCD is limited and few have been identified and validated. This study explores specific circulating biomarkers in pediatric SCD in Ghana (West Africa), hypothesizing that inflammatory and neuronal injury markers in children with SCD could predict disease outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Clinical data were collected from 377 children aged 3-8 years with various Hb genotypes, including SCD and SCT, at Korle-Bu Teaching Hospital in Accra, Ghana (2021-2022). A total of 80 age- and sex-matched subjects were identified. A cross-sectional study utilized a multiplexed immunoassay procedure to evaluate serum biomarkers, including cytokines, chemokines, vascular injury markers, systemic inflammation markers, cell-free heme scavengers, brain-derived neurotrophic factor (BDNF), and angiogenic factors.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Elevated levels of BDNF, Ang-2, CXCL10, CCL11, TNF-α, IL-6, IL-10, IL12p40, ICAM-1, VCAM-1, Tie-2, and VEGFA were observed in HbSS subjects, correlating with hemoglobin level, leukocyte, and erythrocyte counts. Heme scavengers like HO-1, hemopexin, and haptoglobin also correlated with these parameters. ROC and AUC analyses demonstrated the potential of these biomarkers in predicting SCD outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;These findings suggest that there are significant differences between biomarker expression among the different genotypes examined. We conclude that a predictive algorithm based on these biomarkers could be developed and validated through longitudinal assessment of within-genotype differences and correlation of the data with disease severity or outcomes. With such a tool one can enhance SCD management and improve patient outcomes. This approach may pave the way for personalized interventions and better clinica","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1481441"},"PeriodicalIF":3.9,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11694143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921398","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}
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