Xiangyu Li, Kai Zhao, Yun Lu, Jianming Wang, Wei Yao
{"title":"Genetic Analysis of Platelet-Related Genes in Hepatocellular Carcinoma Reveals a Novel Prognostic Signature and Determines PRKCD as the Potential Molecular Bridge.","authors":"Xiangyu Li, Kai Zhao, Yun Lu, Jianming Wang, Wei Yao","doi":"10.1186/s12575-022-00185-9","DOIUrl":"10.1186/s12575-022-00185-9","url":null,"abstract":"<p><strong>Background: </strong>Hepatocellular carcinoma (HCC) belongs to a representative lethality gastrointestinal malignancy, and comprehensive management of HCC remains intractable at present on account of its invasive biological feature that is easy to relapse and early metastasis. The intimate connection between platelets and tumor progression has been widely reported, and platelet-related indicators are also used in the clinical practice of carcinoma. This work is designed to investigate the significance of platelet-related genes in the prognostic prediction of patients with HCC and their potential role in the cross-talk between HCC cells and platelets in the tumor microenvironment.</p><p><strong>Methods: </strong>By integrating the RNA-seq data and clinicopathological information of HCC patients, we extracted prognosis-associated platelet-related genes based on the univariate cox analysis and further established a relevant prognostic signature via the lasso cox regression analysis, and two independent HCC cohorts were used as external validation. Multiple bioinformatics methods were utilized to explore the underlying functional discrepancy between different risk groups classified by the risk model. And in vitro proliferation, invasion, and migration assays were conducted to investigate the effect of platelet stimulation on HCC cells' viability and motility, and flow cytometric analysis was exerted to demonstrate the influence of HCC cells on platelet activation.</p><p><strong>Results: </strong>A novel platelet-related risk model was developed and patients both in the training and testing cohorts were divided into distinct risk subgroups according to the median risk score. It was observed that the high-risk status was closely associated with poor prognosis and worse clinicopathological parameters. Meanwhile, an obvious discrepancy in the constitution of the immune microenvironment also indicated that distinct immune status might be a potential determinant affecting prognosis as well as immunotherapy reactiveness. Moreover, in vitro experiments demonstrated that PRKCD could act as a molecular bridge between tumor cells and platelets, which could either participate in regulating tumor malignant phenotype or mediating platelet activation.</p><p><strong>Conclusions: </strong>In brief, this work reveals a novel platelet-related risk signature for prognostic evaluation of HCC patients and confirms that PRKCD is a key messenger in HCC cell-platelet interaction and plays a crucial role in mediating platelet-induced tumor progression.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"24 1","pages":"22"},"PeriodicalIF":3.7,"publicationDate":"2022-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9719151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10333145","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}
{"title":"Circadian gene CSNK1D promoted the progression of hepatocellular carcinoma by activating Wnt/β-catenin pathway via stabilizing Dishevelled Segment Polarity Protein 3.","authors":"Mengqi Zhu, Jianping Zhang, Saiyan Bian, Xue Zhang, Yiping Shen, Zhiyu Ni, Shiyu Xu, Chun Cheng, Wenjie Zheng","doi":"10.1186/s12575-022-00183-x","DOIUrl":"https://doi.org/10.1186/s12575-022-00183-x","url":null,"abstract":"<p><strong>Purpose: </strong>A variety of studies have connected circadian rhythm to the initiation and progression of hepatocellular carcinoma (HCC). The purpose of this study was to figure out about the circadian genes' profile characteristics, prognostic significance, and targeted values in HCC.</p><p><strong>Methods: </strong>The expression profiles and prognostic significance of circadian genes in the cancer genome atlas liver hepatocellular carcinoma (TCGA-LIHC) database were investigated using bioinformatics analysis. The expression features of Casein Kinase 1 Delta (CSNK1D), a robust signature gene, was further detected by immunohistochemistry, western blotting and Real-time quantitative PCR (RT-qPCR) in a local HCC cohort. The effect of CSNK1D on corresponding phenotypes of HCC cells was evaluated using Cell Counting Kit-8 (CCK8), flowcytometry, clone assay, Transwell assay, and xenograft assay. In addition, the underlying mechanisms of CSNK1D in the Wnt/β-catenin signaling were validated by multiple molecular experiments.</p><p><strong>Results: </strong>Abnormal expression of the Circadian genome was associated with the malignant clinicopathological characteristics of HCC patients. A 10 circadian gene-based signature with substantial prognostic significance was developed using Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. Of them, CSNK1D, significantly elevated in a local HCC cohort, was chosen for further investigation. Silencing or overexpression of CSNK1D significantly reduced or increased proliferation, invasion, sorafenib resistance, xenograft development, and epithelial-mesenchymal transformation (EMT) of HCC cells, respectively. Mechanically, CSNK1D exacerbated the aggressiveness of HCC cells by activating Wnt/β-catenin signaling through interacting with Dishevelled Segment Polarity Protein 3 (DVL3).</p><p><strong>Conclusions: </strong>The Circadian gene CSNK1D was found to contribute to HCC progression by boosting the Wnt/β-catenin pathway, hinting that it could be a prospective therapeutic target for HCC.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"24 1","pages":"21"},"PeriodicalIF":6.4,"publicationDate":"2022-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9717411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10321211","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}
{"title":"The untargeted urine volatilome for biomedical applications: methodology and volatilome database.","authors":"Maria Llambrich, Jesús Brezmes, Raquel Cumeras","doi":"10.1186/s12575-022-00184-w","DOIUrl":"10.1186/s12575-022-00184-w","url":null,"abstract":"<p><p>Chemically diverse in compounds, urine can give us an insight into metabolic breakdown products from foods, drinks, drugs, environmental contaminants, endogenous waste metabolites, and bacterial by-products. Hundreds of them are volatile compounds; however, their composition has never been provided in detail, nor has the methodology used for urine volatilome untargeted analysis. Here, we summarize key elements for the untargeted analysis of urine volatilome from a comprehensive compilation of literature, including the latest reports published. Current achievements and limitations on each process step are discussed and compared. 34 studies were found retrieving all information from the urine treatment to the final results obtained. In this report, we provide the first specific urine volatilome database, consisting of 841 compounds from 80 different chemical classes.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"24 1","pages":"20"},"PeriodicalIF":6.4,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9714113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10321195","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}
Bashar Haruna Gulumbe, Usman Abubakar Haruna, Joseph Almazan, Ibrahim Haruna Ibrahim, Abdullahi Adamu Faggo, Abbas Yusuf Bazata
{"title":"Combating the menace of antimicrobial resistance in Africa: a review on stewardship, surveillance and diagnostic strategies.","authors":"Bashar Haruna Gulumbe, Usman Abubakar Haruna, Joseph Almazan, Ibrahim Haruna Ibrahim, Abdullahi Adamu Faggo, Abbas Yusuf Bazata","doi":"10.1186/s12575-022-00182-y","DOIUrl":"10.1186/s12575-022-00182-y","url":null,"abstract":"<p><p>The emergence of antibiotic-resistant pathogens has threatened not only our ability to deal with common infectious diseases but also the management of life-threatening complications. Antimicrobial resistance (AMR) remains a significant threat in both industrialized and developing countries alike. In Africa, though, poor clinical care, indiscriminate antibiotic use, lack of robust AMR surveillance programs, lack of proper regulations and the burden of communicable diseases are factors aggravating the problem of AMR. In order to effectively address the challenge of AMR, antimicrobial stewardship programs, solid AMR surveillance systems to monitor the trend of resistance, as well as robust, affordable and rapid diagnostic tools which generate data that informs decision-making, have been demonstrated to be effective. However, we have identified a significant knowledge gap in the area of the application of fast and affordable diagnostic tools, surveillance, and stewardship programs in Africa. Therefore, we set out to provide up-to-date information in these areas. We discussed available hospital-based stewardship initiatives in addition to the role of governmental and non-governmental organizations. Finally, we have reviewed the application of various phenotypic and molecular AMR detection tools in both research and routine laboratory settings in Africa, deployment challenges and the efficiency of these methods.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"24 1","pages":"19"},"PeriodicalIF":3.7,"publicationDate":"2022-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9685880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10384510","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}
Hyueyun Kim, Ji Ha Choi, C. Moon, J. Kang, M. Woo, Minsuk Kim
{"title":"Shrimp miR-965 transfers tumoricidal mitochondria","authors":"Hyueyun Kim, Ji Ha Choi, C. Moon, J. Kang, M. Woo, Minsuk Kim","doi":"10.1186/s12575-022-00178-8","DOIUrl":"https://doi.org/10.1186/s12575-022-00178-8","url":null,"abstract":"","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2022-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42149571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Establishment and Fractionation of Metastatic Axillary Lymph Node Cell Suspension for Determination of Protein Expression Levels of Nuclear cFOS and Cytosolic TGFβ1 from Breast Cancer Patients","authors":"Ivanović, Vesna, Dedović-Tanić, Nasta, Milovanović, Zorka, Stojiljković, Bratislav, Demajo, Miroslav, Mandušić, Vesna","doi":"10.1186/s12575-022-00167-x","DOIUrl":"https://doi.org/10.1186/s12575-022-00167-x","url":null,"abstract":"Metastatic Axillary Lymph Node (mALN) status is currently the most important prognostic factor in the management of primary breast cancer (BC). Thus, development of specimens which enable identification of new mALN markers, involved in the progression of the disease, are of considerable interest. The specific aim of this work was to describe the method of establishment of Metastatic Axillary Nodal Cell Suspension and its fractionation, termed Fractionated Nodal Cell Suspension (FNCS), into nuclear and cytosolic extracts to enable determination of protein expression levels of nuclear cFOS and cytosolic Transforming Growth Factor β1 (TGFβ1) in BC patients. To standardize the procedure, HeLa cells were successfully fractionated into nuclear/cytosolic extracts with confirmed presence of nuclear cFOS and cytosolic TGFβ1 proteins. Subsequently, the ALN Cell Suspension specimens were obtained and further fractionated from a pilot sample of six ALN tissue pairs, mALN versus autologous normal ALN (nALN), dissected from invasive BC patients. The mALN/nALN results revealed overexpression of both nuclear cFOS and cytosolic TGFβ1 protein levels. However, only the TGFβ1 data exhibited statistically significant overexpression, which was proportional to the respective values of mALN diameter of tumor deposits. Detailed protocol for establishment and fractionation of mALN cell suspension specimens, termed FNCS, into nuclear and cytosolic extracts is here described for the first time. This approach might be a convenient ex vivo model for simultaneous analysis of protein, RNA and DNA biomarkers from nuclear/cytosolic extracts of the same mALN tissue sample. It might have potential to enable, in the age of genomics and personalized medicine, an identification of novel mALN biomarkers and thus improve the screening, diagnosis and prognosis of invasive BC.","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"28 7","pages":""},"PeriodicalIF":6.4,"publicationDate":"2022-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138496084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
N. Bargahi, S. Ghasemali, Samaneh Jahandar-Lashaki, Atefeh Nazari
{"title":"Recent advances for cancer detection and treatment by microfluidic technology, review and update","authors":"N. Bargahi, S. Ghasemali, Samaneh Jahandar-Lashaki, Atefeh Nazari","doi":"10.1186/s12575-022-00166-y","DOIUrl":"https://doi.org/10.1186/s12575-022-00166-y","url":null,"abstract":"","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2022-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44827946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Circ-ABCB10 knockdown inhibits the malignant progression of cervical cancer through microRNA-128-3p/ZEB1 axis.","authors":"Wei Feng, Ruixia Guo, Dongya Zhang, Ruitao Zhang","doi":"10.1186/s12575-021-00154-8","DOIUrl":"https://doi.org/10.1186/s12575-021-00154-8","url":null,"abstract":"<p><strong>Aims: </strong>We focused on the detailed functions of circ-ABCB10 in cervical cancer (CC) development and its mechanisms.</p><p><strong>Background: </strong>The increasing findings have proposed the central roles of circular RNAs (circRNAs) in the tumorigenesis of various human cancers. Circ-ABCB10 displays promising oncogenic effect in several tumors.</p><p><strong>Methods: </strong>Circ-ABCB10 and miR-128-3p production levels in CC tissues and cells were tested through RT-qPCR. The association of circ-ABCB10 expression with clinicopathologic parameters of CC patients was statistically analyzed. Cell proliferation, invasion, apoptosis, and epithelial-mesenchymal transition (EMT) were evaluated by MTT, transwell invasion assays, flow cytometry analyses, and western blot examination of EMT markers. The binding activity between miR-128-3p and circ-ABCB10 or zinc finger E-box binding homeobox 1 (ZEB1) was explored through pull-down assay or luciferase reporter assay. The influence of circ-ABCB10 on CC tumorigenesis was evaluated by in vivo xenograft experiments.</p><p><strong>Results: </strong>The elevated circ-ABCB10 expression was determined in CC tissues and cells. Moreover, higher production level of circ-ABCB10 was close related to lymph-node metastasis, Federation of Gynecology and Obstetrics (FIGO) stage, and tumor size in CC patients. Loss of circ-ABCB10 weakened cell proliferative and invasive abilities, inhibited EMT, and induced apoptosis in CC. Loss of circ-ABCB10 inhibited ZEB1 expression by serving as a sponge of miR-128-3p in CC cells. Circ-ABCB10 sponged miR-128-3p to enhance cell proliferation, invasion, EMT and inhibit apoptosis in CC cells. Xenograft tumor assays confirmed that circ-ABCB10 knockdown inhibited CC tumor growth.</p><p><strong>Conclusion: </strong>Our study suggests that circ-ABCB10 depletion inhibits proliferation, invasion and EMT and promotes apoptosis of cervical cancer cells through miR-128-3p/ZEB1 axis and represses CC tumor growth.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"23 1","pages":"17"},"PeriodicalIF":6.4,"publicationDate":"2021-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9942262","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}
{"title":"Mutational Analysis of Ocriplasmin to Reduce Proteolytic and Autolytic Activity in Pichia pastoris.","authors":"Roghayyeh Baghban, Safar Farajnia, Younes Ghasemi, Reyhaneh Hoseinpoor, Azam Safary, Mojtaba Mortazavi, Nosratollah Zarghami","doi":"10.1186/s12575-020-00138-0","DOIUrl":"10.1186/s12575-020-00138-0","url":null,"abstract":"<p><strong>Background: </strong>Ocriplasmin (Jetrea) is using for the treatment of symptomatic vitreomacular adhesion. This enzyme undergoes rapid inactivation and limited activity duration as a result of its autolytic nature after injection within the eye. Moreover, the proteolytic activity can cause photoreceptor damage, which may result in visual impairment in more serious cases.</p><p><strong>Results: </strong>The present research aimed to reduce the disadvantages of ocriplasmin using site-directed mutagenesis. To reduce the autolytic activity of ocriplasmin in the first variant, lysine 156 changed to glutamic acid and, in the second variant for the proteolytic activity reduction, alanine 59 mutated to threonine. The third variant contained both mutations. Expression of wild type and three mutant variants of ocriplasmin constructs were done in the Pichia pastoris expression system. The mutant variants were analyzed in silico and in vitro and compared to the wild type. The kinetic parameters of ocriplasmin variants showed both variants with K156E substitution were more resistant to autolytic degradation than wild-type. These variants also exhibited reduced K<sub>cat</sub> and V<sub>max</sub> values. An increase in their Km values, leading to a decreased catalytic efficiency (the K<sub>cat</sub>/K<sub>m</sub> ratio) of autolytic and mixed variants. Moreover, in the variant with A59T mutation, K<sub>cat</sub> and V<sub>max</sub> values have reduced compared to wild type. The mix variants showed the most increase in Km value (almost 2-fold) as well as reduced enzymatic affinity to the substrate. Thus, the results indicated that combined mutations at the ocriplasmin sequence were more effective compared with single mutations.</p><p><strong>Conclusions: </strong>The results indicated such variants represent valuable tools for the investigation of therapeutic strategies aiming at the non-surgical resolution of vitreomacular adhesion.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"22 1","pages":"25"},"PeriodicalIF":6.4,"publicationDate":"2020-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12575-020-00138-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38713287","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}