Frontiers in Molecular Biosciences最新文献

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Integrating network analysis with differential expression to uncover therapeutic and prognostic biomarkers in esophageal squamous cell carcinoma. 将网络分析与差异表达相结合,发现食管鳞状细胞癌的治疗和预后生物标志物。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-08-21 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1425422
Sana Khurshid, Shahabuddin Usmani, Raiyan Ali, Saira Hamid, Tariq Masoodi, Hana Q Sadida, Ikhlak Ahmed, Mohd Shahnawaz Khan, Inara Abeer, Ibrahim Altedlawi Albalawi, Ruqaiah I Bedaiwi, Rashid Mir, Ammira S Al-Shabeeb Akil, Ajaz A Bhat, Muzafar A Macha
{"title":"Integrating network analysis with differential expression to uncover therapeutic and prognostic biomarkers in esophageal squamous cell carcinoma.","authors":"Sana Khurshid, Shahabuddin Usmani, Raiyan Ali, Saira Hamid, Tariq Masoodi, Hana Q Sadida, Ikhlak Ahmed, Mohd Shahnawaz Khan, Inara Abeer, Ibrahim Altedlawi Albalawi, Ruqaiah I Bedaiwi, Rashid Mir, Ammira S Al-Shabeeb Akil, Ajaz A Bhat, Muzafar A Macha","doi":"10.3389/fmolb.2024.1425422","DOIUrl":"10.3389/fmolb.2024.1425422","url":null,"abstract":"<p><p><b>Introduction:</b> Esophageal squamous cell carcinoma (ESCC) accounts for over 90% of all esophageal tumors. However, the molecular mechanism underlying ESCC development and prognosis remains unclear, and there are still no effective molecular biomarkers for diagnosing or predicting the clinical outcome of patients with ESCC. Here, we used bioinformatics analysis to identify potential biomarkers and therapeutic targets for ESCC. <b>Methodology:</b> Differentially expressed genes (DEGs) between ESCC and normal esophageal tissue samples were obtained by comprehensively analyzing publicly available RNA-seq datasets from the TCGA and GTEX. Gene Ontology (GO) annotation and Reactome pathway analysis identified the biological roles of the DEGs. Moreover, the Cytoscape 3.10.1 platform and subsidiary tools such as CytoHubba were used to visualize the DEGs' protein-protein interaction (PPI) network and identify hub genes, Furthermore our results are validated by using Single-cell RNA analysis. Results: Identification of 2524 genes exhibiting altered expression enriched in pathways including keratinization, epidermal cell differentiation, G alpha(s) signaling events, and biological process of cell proliferation and division, extracellular matrix (ECM) disassembly, and muscle function. Moreover, upregulation of hallmarks E2F targets, G2M checkpoints, and TNF signaling. CytoHubba revealed 20 hub genes that had a valuable influence on the progression of ESCC in these patients. Among these, the high expression levels of four genes, CDK1 MAD2L1, PLK1, and TOP2A, were associated with critical dependence for cell survival in ESCC cell lines, as indicated by CRISPR dependency scores, gene expression data, and cell line metadata. We also identify the molecules targeting these essential hub genes, among which GSK461364 is a promising inhibitor of PLK1, BMS265246, and Valrubicin inhibitors of CDK1 and TOP2A, respectively. Moreover, we identified that elevated expression of MMP9 is associated with worse overall survival in ESCC patients, which may serve as potential prognostic biomarker or therapeutic target for ESCC. The single-cell RNA analysis showed MMP9 is highly expressed in myeloid, fibroblast, and epithelial cells, but low in T cells, endothelial cells, and B cells. This suggests MMP9's role in tumor progression and matrix remodeling, highlighting its potential as a prognostic marker and therapeutic target. <b>Discussion:</b> Our study identified key hub genes in ESCC, assessing their potential as therapeutic targets and biomarkers through detailed expression and dependency analyses. Notably, MMP9 emerged as a significant prognostic marker with high expression correlating with poor survival, underscoring its potential for targeted therapy. These findings enhance our understanding of ESCC pathogenesis and highlight promising avenues for treatment.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1425422"},"PeriodicalIF":3.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132362","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
Predictive value analysis of the interaction network of Tks4 scaffold protein in colon cancer. Tks4 支架蛋白相互作用网络对结肠癌的预测价值分析
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-08-21 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1414805
Álmos Tilajka, Anita Kurilla, Loretta László, Anna Lovrics, Julianna Novák, Tamás Takács, László Buday, Virag Vas
{"title":"Predictive value analysis of the interaction network of Tks4 scaffold protein in colon cancer.","authors":"Álmos Tilajka, Anita Kurilla, Loretta László, Anna Lovrics, Julianna Novák, Tamás Takács, László Buday, Virag Vas","doi":"10.3389/fmolb.2024.1414805","DOIUrl":"10.3389/fmolb.2024.1414805","url":null,"abstract":"<p><strong>Background: </strong>Colorectal carcinoma (CRC) has emerged as one of the most widespread cancers and was the third leading cause of cancer-related mortality in 2020. The role of the podosomal protein Tks4 in tumor formation and progression is well established, including its involvement in gastric carcinoma and hepatocellular carcinoma; however, exploration of Tks4 and its associated EMT-regulating interactome in the context of colon cancer remains largely unexplored.</p><p><strong>Methods: </strong>We conducted a comprehensive bioinformatic analysis to investigate the mRNA and protein expression levels of Tks4 and its associated partner molecules (CD2AP, GRB2, WASL, SRC, CTTN, and CAPZA1) across different tumor types. We quantified the expression levels of Tks4 and its partner molecules using qPCR, utilizing a TissueScan colon cancer array. We then validated the usefulness of Tks4 and its associated molecules as biomarkers via careful statistical analyses, including Pearson's correlation analysis, principal component analysis (PCA), multiple logistic regression, confusion matrix analysis, and ROC analysis.</p><p><strong>Results: </strong>Our findings indicate that the co-expression patterns of the seven examined biomarker candidates better differentiate between tumor and normal samples compared with the expression levels of the individual genes. Moreover, variable importance analysis of these seven genes revealed four core genes that yield consistent results similar to the seven genes. Thus, these four core genes from the Tks4 interactome hold promise as potential combined biomarkers for colon adenocarcinoma diagnosis and prognosis.</p><p><strong>Conclusion: </strong>Our proposed biomarker set from the Tks4 interactome shows promising sensitivity and specificity, aiding in colon cancer prevention and diagnosis.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1414805"},"PeriodicalIF":3.9,"publicationDate":"2024-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11371697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132363","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: Immune infiltration and immunotherapy in cancer studies. 社论:癌症研究中的免疫渗透和免疫疗法。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-08-20 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1459242
Udayan Bhattacharya, Pooja Chauhan, Manish Goyal
{"title":"Editorial: Immune infiltration and immunotherapy in cancer studies.","authors":"Udayan Bhattacharya, Pooja Chauhan, Manish Goyal","doi":"10.3389/fmolb.2024.1459242","DOIUrl":"10.3389/fmolb.2024.1459242","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1459242"},"PeriodicalIF":3.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11369506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125300","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
PBMC-engrafted humanized mice models for evaluating immune-related and anticancer drug delivery systems. 用于评估免疫相关给药系统和抗癌给药系统的 PBMC 接种人源化小鼠模型。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-08-20 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1447315
Yoshie Kametani, Ryoji Ito, Yoshiyuki Manabe, Jerzy K Kulski, Toshiro Seki, Hitoshi Ishimoto, Takashi Shiina
{"title":"PBMC-engrafted humanized mice models for evaluating immune-related and anticancer drug delivery systems.","authors":"Yoshie Kametani, Ryoji Ito, Yoshiyuki Manabe, Jerzy K Kulski, Toshiro Seki, Hitoshi Ishimoto, Takashi Shiina","doi":"10.3389/fmolb.2024.1447315","DOIUrl":"10.3389/fmolb.2024.1447315","url":null,"abstract":"<p><p>Immune-related drug delivery systems (DDSs) in humanized mouse models are at the forefront of cancer research and serve as bridges between preclinical studies and clinical applications. These systems offer unique platforms for exploring new therapies and understanding their interactions with human cells and the immune system. Here, we focus on a DDS and a peripheral blood mononuclear cell (PBMC)-engrafted humanized mouse model that we recently developed, and consider some of the key components, challenges, and applications to advance these systems towards better cancer treatment on the basis of a better understanding of the immune response. Our DDS is unique and has a dual function, an anticancer effect and a capacity to fine-tune the immune reaction. The PBL-NOG-hIL-4-Tg mouse system is superior to other available humanized mouse systems for the development of such multifunctional DDSs because it supports the rapid reconstruction of an individual donor's immunity and avoids the onset of graft-versus-host disease.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1447315"},"PeriodicalIF":3.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125301","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
The biochemistry of melanogenesis: an insight into the function and mechanism of melanogenesis-related proteins. 黑色素生成的生物化学:对黑色素生成相关蛋白的功能和机制的深入了解。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-08-20 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1440187
Feifei Wang, Wenjing Ma, Dongjie Fan, Jing Hu, Xiaohong An, Zuding Wang
{"title":"The biochemistry of melanogenesis: an insight into the function and mechanism of melanogenesis-related proteins.","authors":"Feifei Wang, Wenjing Ma, Dongjie Fan, Jing Hu, Xiaohong An, Zuding Wang","doi":"10.3389/fmolb.2024.1440187","DOIUrl":"10.3389/fmolb.2024.1440187","url":null,"abstract":"<p><p>Melanin is an amino acid derivative produced by melanocyte through a series of enzymatic reactions using tyrosinase as substrate. Human skin and hair color is also closely related to melanin, so understanding the mechanisms and proteins that produce melanin is very important. There are many proteins involved in the process of melanin expression, For example, proteins involved in melanin formation such as p53, HNF-1α (Hepatocyte nuclear factor 1α), SOX10 (Sry-related HMg-Box gene 10) and pax3 (paired box gene 3), MC1R(Melanocortin 1 Receptor), MITF (Microphthalmia-associated transcription factor), TYR (tyrosinase), TYRP1 (tyrosinase-related protein-1), TYRP2 (tyrosinase-related protein-2), and can be regulated by changing their content to control the production rate of melanin. Others, such as OA1 (ocular albinism type 1), Par-2 (protease-activated receptor 2) and Mlph (Melanophilin), have been found to control the transfer rate of melanosomes from melanocytes to keratinocytes, and regulate the amount of human epidermal melanin to control the depth of human skin color. In addition to the above proteins, there are other protein families also involved in the process of melanin expression, such as BLOC, Rab and Rho. This article reviews the origin of melanocytes, the related proteins affecting melanin and the basic causes of related gene mutations. In addition, we also summarized the active ingredients of 5 popular whitening cosmetics and their mechanisms of action.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1440187"},"PeriodicalIF":3.9,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11368874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125302","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: Enzyme targeting for the development of novel antimicrobials. 社论:酶靶向开发新型抗菌药物。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-08-19 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1472318
Elena G Salina, Chunhua Qiao, Laurent R Chiarelli
{"title":"Editorial: Enzyme targeting for the development of novel antimicrobials.","authors":"Elena G Salina, Chunhua Qiao, Laurent R Chiarelli","doi":"10.3389/fmolb.2024.1472318","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1472318","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1472318"},"PeriodicalIF":3.9,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11366822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119382","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
A comprehensive pan-cancer analysis revealing the role of ITPRIPL1 as a prognostic and immunological biomarker. 一项全面的泛癌症分析揭示了 ITPRIPL1 作为预后和免疫生物标志物的作用。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-08-15 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1452290
Wenyuan Duan, Wen Tian, Zhongyi Li, Yunsong Liu, Linping Xu
{"title":"A comprehensive pan-cancer analysis revealing the role of ITPRIPL1 as a prognostic and immunological biomarker.","authors":"Wenyuan Duan, Wen Tian, Zhongyi Li, Yunsong Liu, Linping Xu","doi":"10.3389/fmolb.2024.1452290","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1452290","url":null,"abstract":"<p><p>Inositol 1,4,5-Trisphosphate Receptor-Interacting Protein-Like 1 (ITPRIPL1), a single-pass type I membrane protein located in the membrane, functions as an inhibitory ligand of CD3ε. Recent studies have shown that its expression suppresses T cells activation and promote tumor immune evasion. Despite increasing evidence suggesting that ITPRIPL1 plays a significant role in tumor growth, no systematic pan-cancer analysis of ITPRIPL1 has been conducted to date. This study utilized datasets curated from The Cancer Genome Atlas, Genotype Tissue-Expression, and Human Protein Atlas to investigate the relationship between ITPRIPL1 expression and clinical outcomes, immune infiltration, and drug sensitivity across 33 cancer types. We employed multiple methods to assess its prognostic value in pan-cancer, such as univariate Cox regression, survival analysis, and ROC curve analysis and explored the relationship between ITPRIPL1 and tumor mutation burden (TMB), tumor microsatellite instability (MSI), CNV, DNA methylation, immune-related genes, immune cell infiltration, and drug sensitivity to reveal its immunological role. The mRNA expression levels of the ITPRIPL1 gene vary significantly across multiple types of cancer and significantly reduced in breast cancer. Conversely, high ITPRIPL1 expression was associated with a better prognosis in BRCA. Furthermore, the expression of ITPRIPL1 highly correlates with the presence of tumor-infiltrating immune cells and immune checkpoint genes across various types of cancers. Additionally, ITPRIPL1 expression was associated with TMB in 6 cancer types and with MSI in 13 cancer types. High expression of ITPRIPL1 serves as a protective factor in certain cancer types, correlating with longer overall survival in BRCA. Our study further confirms that ITPRIPL1 participates in regulating immune infiltration and affecting the prognosis of patients in pan-cancer. These findings underscore the promising potential of ITPRIPL1 as a therapeutic target for human cancer.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1452290"},"PeriodicalIF":3.9,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11357910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106116","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
Enhanced enrichment of extracellular vesicles for laboratory and clinical research from drop-sized blood samples. 从液滴大小的血液样本中富集细胞外囊泡,用于实验室和临床研究。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-08-15 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1365783
Alexa Guerrero-Alba, Sandhya Bansal, Aryan N Sankpal, Geetanjali Mitra, Mohammad Rahman, Ranjithkumar Ravichandran, Christin Poulson, Timothy P Fleming, Michael A Smith, Ross M Bremner, T Mohanakumar, Narendra V Sankpal
{"title":"Enhanced enrichment of extracellular vesicles for laboratory and clinical research from drop-sized blood samples.","authors":"Alexa Guerrero-Alba, Sandhya Bansal, Aryan N Sankpal, Geetanjali Mitra, Mohammad Rahman, Ranjithkumar Ravichandran, Christin Poulson, Timothy P Fleming, Michael A Smith, Ross M Bremner, T Mohanakumar, Narendra V Sankpal","doi":"10.3389/fmolb.2024.1365783","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1365783","url":null,"abstract":"<p><p>In the realm of biomedical advancement, extracellular vesicles (EVs) are revolutionizing our capacity to diagnose, monitor, and predict disease progression. However, the comprehensive exploration and clinical application of EVs face significant limitations due to the current isolation techniques. The size exclusion chromatography, commercial precipitation reagents, and ultracentrifugation are frequently employed, necessitating skilled operators and entailing challenges related to consistency, reproducibility, quality, and yields. Notably, the formidable challenge of extracellular vesicle isolation persists when dealing with clinical samples of limited availability. This study addresses these challenges by aiming to devise a rapid, user-friendly, and high-recovery EVs isolation technique tailored for blood samples. The NTI-EXO precipitation method demonstrated a 5-fold increase in the recovery of serum EVs compared to current methodologies. Importantly, we illustrate that a mere two drops of blood (∼100 µL) suffice for the recovery of enriched EVs. The integrity and quality of these isolated EVs were rigorously assessed for the size, purity, and contaminants. This method was validated through the successful isolation of EVs from organ transplant recipients to detect disease-specific exosomal markers, including LKB1, SARS-CoV-2 spike protein, and PD-L1. In conclusion, NTI-EXO method can be used for small clinical samples, thereby advancing discoveries in the EV-centric domain and propelling the frontiers of biomedical research and clinical applications.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1365783"},"PeriodicalIF":3.9,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11358096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142117043","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
Application of clinical blood metabogram for diagnosis of early-stage Parkinson's disease: a pilot study. 应用临床血液代谢图诊断早期帕金森病:一项试点研究。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-08-14 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1407974
Petr G Lokhov, Oxana P Trifonova, Elena E Balashova, Dmitry L Maslov, Michael V Ugrumov, Alexander I Archakov
{"title":"Application of clinical blood metabogram for diagnosis of early-stage Parkinson's disease: a pilot study.","authors":"Petr G Lokhov, Oxana P Trifonova, Elena E Balashova, Dmitry L Maslov, Michael V Ugrumov, Alexander I Archakov","doi":"10.3389/fmolb.2024.1407974","DOIUrl":"https://doi.org/10.3389/fmolb.2024.1407974","url":null,"abstract":"<p><p>In terms of time, cost, and reproducibility of clinical laboratory tests, a mass spectrometric clinical blood metabogram (CBM) enables the investigation of the blood metabolome. Metabogram's components provide clinically relevant information by describing related groups of blood metabolites connected to humoral regulation, the metabolism of lipids, carbohydrates and amines, lipid intake into the organism, and liver function. For further development of the CBM approach, the ability of CBM to detect metabolic changes in the blood in the early stages of Parkinson's disease (PD) was studied in this work. In a case-control study (n = 56), CBM enabled the detection of the signature in blood metabolites related to 1-2.5 clinical stages of PD, according to the modified Hoehn and Yahr scale, which is formed by alterations in eicosanoids, phospholipids and, presumably, in the butadione metabolism. The CBM component-based diagnostic accuracy reached 77%, with a specificity of 71% and sensitivity of 82%. The research results extend the range of disorders for which CBM is applicable and offer new opportunities for revealing PD-specific metabolic alterations and diagnosing early-stage PD.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1407974"},"PeriodicalIF":3.9,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11350164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142106117","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
qPCR detection of Mycobacterium leprae DNA in urine samples of leprosy patients using the Rlep gene target. 使用 Rlep 基因靶标对麻风病人尿液样本中的麻风分枝杆菌 DNA 进行 qPCR 检测。
IF 3.9 3区 生物学
Frontiers in Molecular Biosciences Pub Date : 2024-08-13 eCollection Date: 2024-01-01 DOI: 10.3389/fmolb.2024.1435679
D Diana, M C Harish
{"title":"qPCR detection of <i>Mycobacterium leprae</i> DNA in urine samples of leprosy patients using the <i>Rlep</i> gene target.","authors":"D Diana, M C Harish","doi":"10.3389/fmolb.2024.1435679","DOIUrl":"10.3389/fmolb.2024.1435679","url":null,"abstract":"<p><strong>Background: </strong>Leprosy, a chronic infectious disease caused by <i>Mycobacterium leprae</i>, continues to pose a public health challenge in many parts of the world. Early and accurate diagnosis is crucial for effective treatment and prevention of disabilities associated with the disease. Molecular techniques such as PCR have demonstrated great potential as a diagnostic tool for directly detecting <i>M. leprae</i> DNA in different clinical samples, providing better sensitivity and specificity than conventional diagnostic techniques. The objective of this study was to measure the amount of <i>M. leprae</i> DNA in leprosy patients' urine samples using the <i>Rlep</i> gene target through qPCR.</p><p><strong>Methods: </strong>Different clinical samples such as smear, blood, and urine samples were collected from leprosy patients and healthy individuals. Leprosy patients were classified by the Ridley-Jopling classification. The Ziehl-Neelsen staining method was used for the slit skin smear (SSS) samples, and the bacteriological index (BI) was calculated for leprosy patients. DNA extraction and qPCR were performed for all three types of clinical samples using the <i>Rlep</i> gene target.</p><p><strong>Results: </strong>The <i>Mycobacterial leprae</i> DNA was successfully detected and quantified in all clinical samples across all types of leprosy among all the study groups using the <i>Rlep</i> gene (129 bp) target. The <i>Rlep</i> gene target was able to detect the presence of <i>M. leprae</i> DNA in 100% of urine, 96.1% of blood, and 92.2% of SSS samples of leprosy patients. Urine samples showed significant differences (p < 0.001) between the control and the different clinical forms and between borderline tuberculoid (BT) and pure neuritic leprosy (PNL) cases. There are significant differences in cycle threshold (Ct) values between control cases and clinical categories (p < 0.001), as well as specific differences within clinical categories (p < 0.001), reflecting the variability in bacterial load and detection sensitivity across different sample types and clinical manifestations of leprosy.</p><p><strong>Conclusion: </strong>Overall, this study's findings suggest that the qPCR technique can be used to detect <i>M. leprae</i> DNA in urine samples of leprosy patients using the <i>Rlep</i> gene target. It can also be used for diagnosing the disease and monitoring the effectiveness of anti-leprosy drugs, including multi-drug therapy (MDT), across various leprosy disease groups.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"11 ","pages":"1435679"},"PeriodicalIF":3.9,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11347395/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079900","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
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