Jian Ma, Haitao Li, Qianqian Gao, Weixing Zhang, Changhong Zhu, Jian Chen, Yang Ling, Xin Shao, Ziyan Li
Background : The Wnt/ β -catenin signaling pathway plays crucial roles in tumor budding and the epithelial–mesenchymal transition (EMT). Myeloid ecotropic viral insertion site 3 (MEIS3)—a direct target of Wnt/ β -catenin—promotes vagal neural crest cell migration into the gut tissue during development; however, its role in cancer progression remains unclear. In this study, the role of MEIS3 in colorectal cancer (CRC) progression was investigated. Methods : We analyzed the association between MEIS3 protein expression and the clinical stages of CRC patients, and the effect on tumor cell migration and invasion by wound healing and transwell assays. Finally, we analyzed the association between MEIS3 expression and the disease-free survival (DFS) and overall survival of CRC patients through Kaplan–Meier analysis. Results : We found that MEIS3 expression was strongly associated with CRC progression and could be employed to assess DFS in postoperative patients. MEIS3-positive cells were mainly distributed in the growth front and tumor–stroma interface of the CRC tissues, which contain abundant EMT-active and tumor budding cells dominating cancer metastasis. Moreover, MEIS3 promoted CRC cell migration and invasion by regulating effectors including laminin subunit beta 1, matrix metalloprotein 2, and vimentin. MEIS3 protein expression increased with CRC progression according to the clinical stage, which could be used as a biomarker to stratify CRC patients. The 5-year DFS of MEIS3-high patients was poorer than that of MEIS3-low patients (40.6% vs . 61.7%; p < 0.0001). Moreover, the 5-year DFS of stage II patients with MEIS3-high expression (53.4%) was comparable to that of stage III patients with MEIS3-low expression (49.5%), while the 5-year DFS of MEIS3-high patients in stage III (30.9%) was comparable to that of stage IV patients (29.6%). Conclusions : This study showed that MEIS3 can promote cancer cell metastasis and thus may be a promising biomarker for higher rates of recurrence in postoperative patients with stage II/III CRC.
{"title":"High MEIS3 Expression Indicates a Poor Prognosis for Patients with Stage II/III Colorectal Cancer","authors":"Jian Ma, Haitao Li, Qianqian Gao, Weixing Zhang, Changhong Zhu, Jian Chen, Yang Ling, Xin Shao, Ziyan Li","doi":"10.31083/j.fbl2812338","DOIUrl":"https://doi.org/10.31083/j.fbl2812338","url":null,"abstract":"Background : The Wnt/ β -catenin signaling pathway plays crucial roles in tumor budding and the epithelial–mesenchymal transition (EMT). Myeloid ecotropic viral insertion site 3 (MEIS3)—a direct target of Wnt/ β -catenin—promotes vagal neural crest cell migration into the gut tissue during development; however, its role in cancer progression remains unclear. In this study, the role of MEIS3 in colorectal cancer (CRC) progression was investigated. Methods : We analyzed the association between MEIS3 protein expression and the clinical stages of CRC patients, and the effect on tumor cell migration and invasion by wound healing and transwell assays. Finally, we analyzed the association between MEIS3 expression and the disease-free survival (DFS) and overall survival of CRC patients through Kaplan–Meier analysis. Results : We found that MEIS3 expression was strongly associated with CRC progression and could be employed to assess DFS in postoperative patients. MEIS3-positive cells were mainly distributed in the growth front and tumor–stroma interface of the CRC tissues, which contain abundant EMT-active and tumor budding cells dominating cancer metastasis. Moreover, MEIS3 promoted CRC cell migration and invasion by regulating effectors including laminin subunit beta 1, matrix metalloprotein 2, and vimentin. MEIS3 protein expression increased with CRC progression according to the clinical stage, which could be used as a biomarker to stratify CRC patients. The 5-year DFS of MEIS3-high patients was poorer than that of MEIS3-low patients (40.6% vs . 61.7%; p < 0.0001). Moreover, the 5-year DFS of stage II patients with MEIS3-high expression (53.4%) was comparable to that of stage III patients with MEIS3-low expression (49.5%), while the 5-year DFS of MEIS3-high patients in stage III (30.9%) was comparable to that of stage IV patients (29.6%). Conclusions : This study showed that MEIS3 can promote cancer cell metastasis and thus may be a promising biomarker for higher rates of recurrence in postoperative patients with stage II/III CRC.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"177 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138997238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background : Rheumatoid arthritis (RA) is a chronic inflammatory disease with a high rate of disability accompanied by various complications. The pathogenesis of RA is complex with multiple targets and links. This study aims to investigate pharmacological effects and mechanism of Rhodojaponin III in RA. Methods : The bovine type II collagen-induced arthritis (CIA) rat model and tumor necrosis factor-alpha (TNF-α ) induced human umbilical vein endothelial cells (HUVECs) model were constructed. Different concentrations of Rhodojaponin III were utilized for intervention. The progression of CIA was assessed by the arthritis index (AI). Pathological changes in knee joints and synovium were observed. The expressions of angiogenesis-related cytokines were detected. The proliferation, migration, invasion
背景：类风湿性关节炎（RA）是一种慢性炎症性疾病，致残率高，并伴有各种并发症。类风湿关节炎的发病机制复杂，具有多靶点、多环节的特点。本研究旨在探讨红豆皂苷 III 对类风湿关节炎的药理作用和机制。方法：构建牛 II 型胶原诱导的关节炎（CIA）大鼠模型和肿瘤坏死因子-α（TNF-α）诱导的人脐静脉内皮细胞（HUVECs）模型。利用不同浓度的红豆皂苷 III 进行干预。用关节炎指数（AI）评估 CIA 的进展。观察膝关节和滑膜的病理变化。检测了血管生成相关细胞因子的表达。研究还发现了与血管生成相关的细胞因子的表达。
{"title":"A Study on the Pharmacological Effects and Mechanism of Rhodojaponin III in Rheumatoid Arthritis","authors":"Xiaorong Liu, Shuofu Li, Yin Xu, Wenya Mei, Ribao Zhou","doi":"10.31083/j.fbl2812337","DOIUrl":"https://doi.org/10.31083/j.fbl2812337","url":null,"abstract":"Background : Rheumatoid arthritis (RA) is a chronic inflammatory disease with a high rate of disability accompanied by various complications. The pathogenesis of RA is complex with multiple targets and links. This study aims to investigate pharmacological effects and mechanism of Rhodojaponin III in RA. Methods : The bovine type II collagen-induced arthritis (CIA) rat model and tumor necrosis factor-alpha (TNF-α ) induced human umbilical vein endothelial cells (HUVECs) model were constructed. Different concentrations of Rhodojaponin III were utilized for intervention. The progression of CIA was assessed by the arthritis index (AI). Pathological changes in knee joints and synovium were observed. The expressions of angiogenesis-related cytokines were detected. The proliferation, migration, invasion","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"26 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2023-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139000754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Melina Steichert, Willi Cawello, M. Bajčetić, J. Breur, M. Dalinghaus, Christoph Male, Saskia N. de Wildt, Stephanie Läer, on behalf of the LENA Consortium
Background : Plasma renin activity (PRA) has gained relevance as prognostic marker in adults with heart failure. The use of PRA as a clinically meaningful parameter in children and children with heart failure requires a thorough knowledge of the factors that influence PRA to correctly assess PRA levels. We aim to evaluate the influence of age, heart failure and angiotensin-converting enzyme inhibitor (ACEi) on PRA levels in children. Methods : We conducted a systematic literature search to identify studies on PRA levels in healthy children and in children with heart failure. In addition, we analysed PRA data measured before (n = 35, aged 25 days–2.1 years), 4 hours after (n = 34) and within the first 8 days of enalapril treatment (n = 29) in children with heart failure from the European project Labeling of Enalapril from Neonates up to Adolescents (LENA). Results : Age has a profound effect on PRA levels in healthy children, as PRA levels in the literature are up to about 7 times higher in neonates than in older children. Children with heart failure younger than 6 months showed 3–4 times higher PRA levels than healthy peers in both the literature and the LENA studies. In the LENA studies, the ACEi enalapril significantly increased median predose PRA by a factor of 4.5 in children with heart failure after 4.7 ± 1.6 days of treatment (n = 29, p < 0.01). Prior to treatment with enalapril, LENA subjects with symptomatic heart failure (Ross score ≥ 3) had a significantly higher PRA than LENA subjects with asymptomatic heart failure of comparable age (Ross score ≤ 2, p < 0.05). Conclusions : Age, heart failure and ACEi treatment have a notable influence on PRA and must be considered when assessing PRA as a clinically meaningful parameter.
背景：血浆肾素活性（PRA）已成为成人心力衰竭患者的预后指标。在儿童和心衰患儿中使用 PRA 作为有临床意义的参数，需要全面了解影响 PRA 的因素，以正确评估 PRA 水平。我们旨在评估年龄、心衰和血管紧张素转换酶抑制剂（ACEi）对儿童 PRA 水平的影响。方法：我们进行了系统性文献检索，以确定有关健康儿童和心衰儿童 PRA 水平的研究。此外，我们还分析了欧洲 "从新生儿到青少年的依那普利标签项目"（LENA）中心力衰竭儿童在依那普利治疗前（35 人，年龄为 25 天-2.1 岁）、治疗后 4 小时（34 人）和最初 8 天内（29 人）的 PRA 数据。结果：年龄对健康儿童的 PRA 水平有深远影响，因为文献中新生儿的 PRA 水平最高约为年龄较大儿童的 7 倍。在文献和 LENA 研究中，6 个月以下心衰患儿的 PRA 水平比健康儿童高 3-4 倍。在 LENA 研究中，ACEi 依那普利可显著提高心衰患儿用药前 PRA 的中位数，治疗 4.7 ± 1.6 天后提高 4.5 倍（n = 29，p < 0.01）。在使用依那普利治疗前，有症状心衰的 LENA 受试者（Ross 评分≥ 3）的 PRA 明显高于年龄相当的无症状心衰 LENA 受试者（Ross 评分≤ 2，P＜0.05）。结论 ：年龄、心力衰竭和 ACEi 治疗对 PRA 有显著影响，在评估 PRA 作为临床意义的参数时必须加以考虑。
{"title":"Influence of Age, Heart Failure and ACE Inhibitor Treatment on Plasma Renin Activity in Children: Insights from a Systematic Review and the European LENA Project","authors":"Melina Steichert, Willi Cawello, M. Bajčetić, J. Breur, M. Dalinghaus, Christoph Male, Saskia N. de Wildt, Stephanie Läer, on behalf of the LENA Consortium","doi":"10.31083/j.fbl2812335","DOIUrl":"https://doi.org/10.31083/j.fbl2812335","url":null,"abstract":"Background : Plasma renin activity (PRA) has gained relevance as prognostic marker in adults with heart failure. The use of PRA as a clinically meaningful parameter in children and children with heart failure requires a thorough knowledge of the factors that influence PRA to correctly assess PRA levels. We aim to evaluate the influence of age, heart failure and angiotensin-converting enzyme inhibitor (ACEi) on PRA levels in children. Methods : We conducted a systematic literature search to identify studies on PRA levels in healthy children and in children with heart failure. In addition, we analysed PRA data measured before (n = 35, aged 25 days–2.1 years), 4 hours after (n = 34) and within the first 8 days of enalapril treatment (n = 29) in children with heart failure from the European project Labeling of Enalapril from Neonates up to Adolescents (LENA). Results : Age has a profound effect on PRA levels in healthy children, as PRA levels in the literature are up to about 7 times higher in neonates than in older children. Children with heart failure younger than 6 months showed 3–4 times higher PRA levels than healthy peers in both the literature and the LENA studies. In the LENA studies, the ACEi enalapril significantly increased median predose PRA by a factor of 4.5 in children with heart failure after 4.7 ± 1.6 days of treatment (n = 29, p < 0.01). Prior to treatment with enalapril, LENA subjects with symptomatic heart failure (Ross score ≥ 3) had a significantly higher PRA than LENA subjects with asymptomatic heart failure of comparable age (Ross score ≤ 2, p < 0.05). Conclusions : Age, heart failure and ACEi treatment have a notable influence on PRA and must be considered when assessing PRA as a clinically meaningful parameter.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"5 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139007709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dandan Li, M. Ou, Guandong Dai, Peng Zhu, Qi Luo, Jieping Chen, Zahir Shah, Igor M. Samokhvalov, Lianghong Yin, Guoping Sun, D. Tang, Yong Dai
Background : Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by recurring bone fractures. Some OI patients have other clinical manifestations such as growth retardation, dental abnormalities, blue sclera, and hearing loss. The relationship between the phenotype and genotype of OI is indistinct, and there is no cure for OI. Therefore, an appropriate disease model is urgently needed to understand the pathophysiology of OI. Induced pluripotent stem cells (iPSCs) are capable of developing into three germ layers and have the same genetic background as the donor cells they were derived from; thus, they are an appropriate disease model. Methods : Blood samples collected from the proband and her affected children and one unaffected child were used for genotyping by whole genome sequencing. A patient-specific iPSC line and a healthy donor iPSC line were generated by reprogramming peripheral blood mononuclear cells with episomal plasmids containing seven transcription factors, namely, OCT4 , SOX2 , NANOG , LIN28 , cMYC , KLF4 , and SV40LT . Results : The proband and her two affected children were homozygous for a mutation in collagen type I alpha 1 exon 10, c.725G > T, predicting a p.G242V substitution. A patient-specific iPSC line and a healthy donor iPSC line were generated and characterized in terms of their human embryonic stem cell-like morphology, expression of pluripotency markers, and the ability to differentiate into cells of three germ layers. Conclusions : Here, we report the phenotyping and iPSC disease modeling of an OI family. The detailed phenotyping of the OI family and establishment of iPSCs from an OI patient and healthy family member will provide a powerful tool to evaluate the pathophysiology of OI and develop targeted therapies
背景：成骨不全症（OI）是一种罕见的遗传性疾病，以反复骨折为特征。一些 OI 患者还有其他临床表现，如生长迟缓、牙齿异常、蓝色巩膜和听力损失。骨质疏松症的表型与基因型之间的关系并不明确，而且骨质疏松症无法治愈。因此，迫切需要一种合适的疾病模型来了解 OI 的病理生理学。诱导多能干细胞（iPSCs）能够发育成三个生殖层，并且与供体细胞具有相同的遗传背景，因此是一种合适的疾病模型。方法：通过全基因组测序对采集自疑似患者及其受影响子女和一名未受影响子女的血液样本进行基因分型。通过用含有七种转录因子（即 OCT4、SOX2、NANOG、LIN28、cMYC、KLF4 和 SV40LT）的外显子质粒对外周血单核细胞进行重编程，产生了患者特异性 iPSC 株和健康供体 iPSC 株。结果：原告和她的两个患儿均为 I 型胶原蛋白α1 第 10 号外显子 c.725G > T 基因突变的同源基因，预测为 p.G242V 取代。我们生成了一个患者特异性 iPSC 株系和一个健康供体 iPSC 株系，并对其类似人类胚胎干细胞的形态、多能性标记的表达以及分化为三个生殖层细胞的能力进行了鉴定。结论：在此，我们报告了一个 OI 家族的表型和 iPSC 疾病模型。对 OI 家族的详细表型分析以及从 OI 患者和健康家族成员建立 iPSC 将为评估 OI 的病理生理学和开发靶向疗法提供强有力的工具。
{"title":"Genotypic Characterization of a Chinese Family with Osteogenesis Imperfecta and Generation of Disease-Specific Induced Pluripotent Stem Cells","authors":"Dandan Li, M. Ou, Guandong Dai, Peng Zhu, Qi Luo, Jieping Chen, Zahir Shah, Igor M. Samokhvalov, Lianghong Yin, Guoping Sun, D. Tang, Yong Dai","doi":"10.31083/j.fbl2812336","DOIUrl":"https://doi.org/10.31083/j.fbl2812336","url":null,"abstract":"Background : Osteogenesis imperfecta (OI) is a rare genetic disorder characterized by recurring bone fractures. Some OI patients have other clinical manifestations such as growth retardation, dental abnormalities, blue sclera, and hearing loss. The relationship between the phenotype and genotype of OI is indistinct, and there is no cure for OI. Therefore, an appropriate disease model is urgently needed to understand the pathophysiology of OI. Induced pluripotent stem cells (iPSCs) are capable of developing into three germ layers and have the same genetic background as the donor cells they were derived from; thus, they are an appropriate disease model. Methods : Blood samples collected from the proband and her affected children and one unaffected child were used for genotyping by whole genome sequencing. A patient-specific iPSC line and a healthy donor iPSC line were generated by reprogramming peripheral blood mononuclear cells with episomal plasmids containing seven transcription factors, namely, OCT4 , SOX2 , NANOG , LIN28 , cMYC , KLF4 , and SV40LT . Results : The proband and her two affected children were homozygous for a mutation in collagen type I alpha 1 exon 10, c.725G > T, predicting a p.G242V substitution. A patient-specific iPSC line and a healthy donor iPSC line were generated and characterized in terms of their human embryonic stem cell-like morphology, expression of pluripotency markers, and the ability to differentiate into cells of three germ layers. Conclusions : Here, we report the phenotyping and iPSC disease modeling of an OI family. The detailed phenotyping of the OI family and establishment of iPSCs from an OI patient and healthy family member will provide a powerful tool to evaluate the pathophysiology of OI and develop targeted therapies","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"27 3","pages":""},"PeriodicalIF":3.1,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139007788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background : Pyroptosis plays a crucial role in anti-tumor immunity and in formation of the immune microenvironment. However, whether pyroptosis is involved in the progression of clear cell renal cell carcinoma (ccRCC) is still unclear. Personalized treatment of ccRCC requires detailed molecular classification to inform a specific therapy. Methods : Molecular subtyping of ccRCC was performed based on consensus clustering of pyroptosis-related genes. The characteristics of these molecular subtypes were explored at the genome, transcriptome and protein levels. Single-cell RNA sequencing and CIBERSORT analysis were used to analyse the immune microenvironment of ccRCC, while Lasso regression was used to develop a prediction model based on hub genes. Expression of the pyroptosis-related gene GSDMB was also investigated at the tissue and cellular levels. Results : Two molecular subtypes were identified based on the clustering of pyroptosis-related genes. Cluster 1 was associated with activation of classical oncogenic pathways, especially the angiogenesis pathway. Cluster 2 was associated with activation of immune-related pathways and high levels of immunosuppressive cells, exhausted CD8 + T cells, and tumor-associated fibroblast infiltration. Clusters 1 and 2 were thus defined as the angiogenic and inflamed subtypes, respectively. The two subtypes were predictive of the response of ccRCC to anti-angiogenic therapy and immunotherapy, with Cluster 1 patients benefiting from anti-angiogenic therapy and Cluster 2 patients showing better response to anti-PD1 inhibitor therapy. Furthermore, a 9-gene expression signature ( HJURP , NUF2 , KIF15 , MELK , TPX2 , PLK1 , CDCA3 , CTLA4 , FOXP3 ) was identified that could predict outcome and response to immune checkpoint blockade therapy in test cohorts. Finally, GSDMB was found to be involved in the development of renal clear cell carcinoma. Conclusions : These results on pyroptosis-related genes in ccRCC provide a theoretical basis for understanding molecular heterogeneity and for the development of individualized treatment strategies.
{"title":"Pyroptosis-Related Subtypes Predict the Response of Clear Cell Renal Cell Carcinoma to Targeted Therapy","authors":"Jinpeng Ma, Zhijian Kang, Guang Yang, Xinyue Wang, Minggui Si, Yuting Wang, Guangbin Li, Shiyu Bai, Fanshu Zeng, Min Li, Ziqi Wang, Lu Wang, Wanhai Xu","doi":"10.31083/j.fbl2812334","DOIUrl":"https://doi.org/10.31083/j.fbl2812334","url":null,"abstract":"Background : Pyroptosis plays a crucial role in anti-tumor immunity and in formation of the immune microenvironment. However, whether pyroptosis is involved in the progression of clear cell renal cell carcinoma (ccRCC) is still unclear. Personalized treatment of ccRCC requires detailed molecular classification to inform a specific therapy. Methods : Molecular subtyping of ccRCC was performed based on consensus clustering of pyroptosis-related genes. The characteristics of these molecular subtypes were explored at the genome, transcriptome and protein levels. Single-cell RNA sequencing and CIBERSORT analysis were used to analyse the immune microenvironment of ccRCC, while Lasso regression was used to develop a prediction model based on hub genes. Expression of the pyroptosis-related gene GSDMB was also investigated at the tissue and cellular levels. Results : Two molecular subtypes were identified based on the clustering of pyroptosis-related genes. Cluster 1 was associated with activation of classical oncogenic pathways, especially the angiogenesis pathway. Cluster 2 was associated with activation of immune-related pathways and high levels of immunosuppressive cells, exhausted CD8 + T cells, and tumor-associated fibroblast infiltration. Clusters 1 and 2 were thus defined as the angiogenic and inflamed subtypes, respectively. The two subtypes were predictive of the response of ccRCC to anti-angiogenic therapy and immunotherapy, with Cluster 1 patients benefiting from anti-angiogenic therapy and Cluster 2 patients showing better response to anti-PD1 inhibitor therapy. Furthermore, a 9-gene expression signature ( HJURP , NUF2 , KIF15 , MELK , TPX2 , PLK1 , CDCA3 , CTLA4 , FOXP3 ) was identified that could predict outcome and response to immune checkpoint blockade therapy in test cohorts. Finally, GSDMB was found to be involved in the development of renal clear cell carcinoma. Conclusions : These results on pyroptosis-related genes in ccRCC provide a theoretical basis for understanding molecular heterogeneity and for the development of individualized treatment strategies.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"216 ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139011079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background : Prostate cancer (PCa) is a prevalent form of malignant tumors affecting the prostate gland and is frequently diagnosed in males in Western countries. Identifying diagnostic and prognostic biomarkers is not only important for screening drug targets but also for understanding their pathways and reducing the cost of experimental verification of PCa. The objective of this study was to identify and validate promising diagnostic and prognostic biomarkers for PCa. Methods : This study implemented a machine learning technique to evaluate the diagnostic and prognostic biomarkers of PCa using protein-protein interaction (PPI) networks. In addition, multi-database validation and literature review were performed to verify the diagnostic biomarkers. To optimize the prognosis of our results, univariate Cox regression analysis was utilized to screen survival-related genes. This study employed stepwise multivariate Cox regression analysis to develop a prognostic risk model. Finally, receiver operating characteristic analysis confirmed that these predictive biomarkers demonstrated a substantial level of sensitivity and specificity when predicting the prognostic survival of patients. Results : The hub genes were UBE2C (Ubiquitin Conjugating Enzyme E2 C), CCNB1 (Cyclin B1), TOP2A (DNA Topoisomerase II Alpha), TPX2 (TPX2 Microtubule Nucleation Factor), CENPM (Centromere Protein M), F5 (Coagulation Factor V), APOE (Apolipoprotein E), NPY (Neuropeptide Y), and TRIM36 (Tripartite Motif Containing 36). All of these hub genes were validated by multiple databases. By validation in these databases, these 10 hub genes were significantly involved in significant pathways. The risk model was constructed by a four-gene-based prognostic factor that included TOP2A , UBE2C , MYL9 , and FLNA . Conclusions : The machine learning algorithm combined with PPI networks identified hub genes that can serve as diagnostic and prognostic biomarkers for PCa. This risk model will enable patients with PCa to be more accurately diagnosed and predict new drugs in clinical trials.
{"title":"A Machine Learning Method for Predicting Biomarkers Associated with Prostate Cancer","authors":"Yanqiu Tong, Zhongle Tan, Pu Wang, Xi Gao","doi":"10.31083/j.fbl2812333","DOIUrl":"https://doi.org/10.31083/j.fbl2812333","url":null,"abstract":"Background : Prostate cancer (PCa) is a prevalent form of malignant tumors affecting the prostate gland and is frequently diagnosed in males in Western countries. Identifying diagnostic and prognostic biomarkers is not only important for screening drug targets but also for understanding their pathways and reducing the cost of experimental verification of PCa. The objective of this study was to identify and validate promising diagnostic and prognostic biomarkers for PCa. Methods : This study implemented a machine learning technique to evaluate the diagnostic and prognostic biomarkers of PCa using protein-protein interaction (PPI) networks. In addition, multi-database validation and literature review were performed to verify the diagnostic biomarkers. To optimize the prognosis of our results, univariate Cox regression analysis was utilized to screen survival-related genes. This study employed stepwise multivariate Cox regression analysis to develop a prognostic risk model. Finally, receiver operating characteristic analysis confirmed that these predictive biomarkers demonstrated a substantial level of sensitivity and specificity when predicting the prognostic survival of patients. Results : The hub genes were UBE2C (Ubiquitin Conjugating Enzyme E2 C), CCNB1 (Cyclin B1), TOP2A (DNA Topoisomerase II Alpha), TPX2 (TPX2 Microtubule Nucleation Factor), CENPM (Centromere Protein M), F5 (Coagulation Factor V), APOE (Apolipoprotein E), NPY (Neuropeptide Y), and TRIM36 (Tripartite Motif Containing 36). All of these hub genes were validated by multiple databases. By validation in these databases, these 10 hub genes were significantly involved in significant pathways. The risk model was constructed by a four-gene-based prognostic factor that included TOP2A , UBE2C , MYL9 , and FLNA . Conclusions : The machine learning algorithm combined with PPI networks identified hub genes that can serve as diagnostic and prognostic biomarkers for PCa. This risk model will enable patients with PCa to be more accurately diagnosed and predict new drugs in clinical trials.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"61 10","pages":""},"PeriodicalIF":3.1,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138595545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Minmin Li, Ning Song, Dongyuan Sun, Yang Yu, Wentian Zheng, Xinyue Zhang, Jicheng Ying, Rongqi Sun, Mengqi Xu, Tao Guo, Yingying Jiang
{"title":"Transcriptome Mapping of the Internal N7-Methylguanosine Methylome in Messenger RNAs in Human Oral Squamous Cell Carcinoma","authors":"Minmin Li, Ning Song, Dongyuan Sun, Yang Yu, Wentian Zheng, Xinyue Zhang, Jicheng Ying, Rongqi Sun, Mengqi Xu, Tao Guo, Yingying Jiang","doi":"10.31083/j.fbl2812330","DOIUrl":"https://doi.org/10.31083/j.fbl2812330","url":null,"abstract":"","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"60 11","pages":""},"PeriodicalIF":3.1,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138596362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nonalcoholic fatty liver disease (NAFLD) constitutes a commonly diagnosed liver pathology with perturbed lipid metabolism, which is mainly caused by excessive accumulation of fat in hepatocytes by various pathogenic factors. Currently, there are no effective drug treatments for NAFLD. Ferroptosis represents a novel form of programmed cell death depending on iron, which is driven by large cellular amounts of reactive oxygen species (ROS) and lipid peroxides. Ferroptosis plays critical regulatory roles in the pathogenesis of NAFLD, and overaccumulation of Fe 2+ contributes to lipid peroxidation, which subsequently aggravates NAFLD. Therefore, ferroptosis suppression might constitute an important target for NAFLD treatment. This article reviews the discovery, production pathways, and defense mechanisms of ferroptosis, and explores its association with NAFLD. This may provide new reference targets and strategies for the development of NAFLD drugs from the perspective of ferroptosis.
{"title":"Lipid Peroxidation in Ferroptosis and Association with Nonalcoholic Fatty Liver Disease","authors":"Shengnan Zhao, Yan Guo, Xunzhe Yin","doi":"10.31083/j.fbl2812332","DOIUrl":"https://doi.org/10.31083/j.fbl2812332","url":null,"abstract":"Nonalcoholic fatty liver disease (NAFLD) constitutes a commonly diagnosed liver pathology with perturbed lipid metabolism, which is mainly caused by excessive accumulation of fat in hepatocytes by various pathogenic factors. Currently, there are no effective drug treatments for NAFLD. Ferroptosis represents a novel form of programmed cell death depending on iron, which is driven by large cellular amounts of reactive oxygen species (ROS) and lipid peroxides. Ferroptosis plays critical regulatory roles in the pathogenesis of NAFLD, and overaccumulation of Fe 2+ contributes to lipid peroxidation, which subsequently aggravates NAFLD. Therefore, ferroptosis suppression might constitute an important target for NAFLD treatment. This article reviews the discovery, production pathways, and defense mechanisms of ferroptosis, and explores its association with NAFLD. This may provide new reference targets and strategies for the development of NAFLD drugs from the perspective of ferroptosis.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"15 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138594293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bailey Kennedy, Sonia Mirza, Tania Mandiangu, Rosi Bissinger, Theresa E. Stotesbury, Holly Jones-Taggart, Julia Green-Johnson, Syed M. Qadri
Background : Interspecies variations in mammalian red blood cells (RBCs) are observed in circulating RBC lifespan, cell size, fluidity, aggregation, water permeability, metabolism, lipid composition, and the overall proteome. Bovine RBC cell membrane is deficient in phosphatidylcholine and exhibits anomalies in the arrangement of phosphatidylethanolamine within the lipid bilayer. However, like human RBCs, virtually all the aminophospholipid phosphatidylserine (PS) is found within the cytoplasmic side of the cell membrane of intact circulating bovine RBCs. During apoptotic cell death of human and murine RBCs, PS translocates to the outer leaflet of the cell membrane via Ca 2+ -dependent and -independent signaling mechanisms. However, little is known about this process in bovine RBCs. Methods : Using cytofluorometry analyses, we characterized and compared the cell death responses in bovine and human RBCs in vitro exposed to various pathophysiologic cell stressors. Results : Ionic stress, by ionophore treatment, and oxidative stress enhanced cytoplasmic Ca 2+ levels and cell membrane PS expression in both bovine and human RBCs. Fever-grade hyperthermia and energy starvation promoted Ca 2+ influx and elevated reactive oxygen species levels in both human and bovine RBCs. However, bovine RBCs displayed minimal increases in PS expression elicited by hyperthermia, energy starvation, and extracellular hypertonicity as compared to human RBCs. In response to decreased extracellular osmolality, bovine RBCs exhibited significantly enhanced fragility as compared to human RBCs. Conclusions : Bovine RBCs display differential cell death patterns as compared to human RBCs, only partly explained by increased Ca 2+ influx and oxidative stress. Premature removal of circulating RBCs could potentially contribute to the pathogenesis of anemia in cattle caused by a wide range of factors such as systemic diseases, parasitic infections, and nutritional deficiencies.
{"title":"Examination of Bovine Red Blood Cell Death in Vitro in Response to Pathophysiologic Proapoptotic Stimuli","authors":"Bailey Kennedy, Sonia Mirza, Tania Mandiangu, Rosi Bissinger, Theresa E. Stotesbury, Holly Jones-Taggart, Julia Green-Johnson, Syed M. Qadri","doi":"10.31083/j.fbl2812331","DOIUrl":"https://doi.org/10.31083/j.fbl2812331","url":null,"abstract":"Background : Interspecies variations in mammalian red blood cells (RBCs) are observed in circulating RBC lifespan, cell size, fluidity, aggregation, water permeability, metabolism, lipid composition, and the overall proteome. Bovine RBC cell membrane is deficient in phosphatidylcholine and exhibits anomalies in the arrangement of phosphatidylethanolamine within the lipid bilayer. However, like human RBCs, virtually all the aminophospholipid phosphatidylserine (PS) is found within the cytoplasmic side of the cell membrane of intact circulating bovine RBCs. During apoptotic cell death of human and murine RBCs, PS translocates to the outer leaflet of the cell membrane via Ca 2+ -dependent and -independent signaling mechanisms. However, little is known about this process in bovine RBCs. Methods : Using cytofluorometry analyses, we characterized and compared the cell death responses in bovine and human RBCs in vitro exposed to various pathophysiologic cell stressors. Results : Ionic stress, by ionophore treatment, and oxidative stress enhanced cytoplasmic Ca 2+ levels and cell membrane PS expression in both bovine and human RBCs. Fever-grade hyperthermia and energy starvation promoted Ca 2+ influx and elevated reactive oxygen species levels in both human and bovine RBCs. However, bovine RBCs displayed minimal increases in PS expression elicited by hyperthermia, energy starvation, and extracellular hypertonicity as compared to human RBCs. In response to decreased extracellular osmolality, bovine RBCs exhibited significantly enhanced fragility as compared to human RBCs. Conclusions : Bovine RBCs display differential cell death patterns as compared to human RBCs, only partly explained by increased Ca 2+ influx and oxidative stress. Premature removal of circulating RBCs could potentially contribute to the pathogenesis of anemia in cattle caused by a wide range of factors such as systemic diseases, parasitic infections, and nutritional deficiencies.","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"67 1","pages":""},"PeriodicalIF":3.1,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138594695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Community Structure and Diversity of Rhizosphere Soil and Endophytic Bacteria during the Period of Growth of Moso Bamboo Shoots","authors":"Zong-sheng Yuan, Fang Liu, Zhi-hao Zeng, Hui Pan","doi":"10.31083/j.fbl2812329","DOIUrl":"https://doi.org/10.31083/j.fbl2812329","url":null,"abstract":"","PeriodicalId":50430,"journal":{"name":"Frontiers in Bioscience-Landmark","volume":"84 24","pages":""},"PeriodicalIF":3.1,"publicationDate":"2023-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138600116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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