Advances in medical sciences最新文献_第9页

Corrigendum to “Genome-engineering technologies for modeling and treatment of cystic fibrosis” [Adv Med Sci (2023 Sept) 68(1) 111–120] “用于囊性纤维化建模和治疗的基因组工程技术”的勘误表[Journal of the Advances in Medical Sciences卷68/ 1,111 -120(2023),522]。

IF 2.5 4区医学

Advances in medical sciences Pub Date : 2025-03-01 Epub Date: 2025-02-12 DOI: 10.1016/j.advms.2025.01.009

Michał Dębczyński , Damian Mojsak , Łukasz Minarowski , Monika Maciejewska , Paweł Lisowski , Robert M. Mróz

引用次数: 0

Recurrent hepatocellular carcinoma is associated with the enrichment of MYC targets gene sets, elevated high confidence deleterious mutations and alternative splicing of DDB2 and BRCA1 transcripts 复发性肝细胞癌与 MYC 目标基因组的富集、高置信度的有害突变以及 DDB2 和 BRCA1 转录本的替代剪接有关。

IF 2.5 4区医学

Advances in medical sciences Pub Date : 2025-03-01 Epub Date: 2024-10-30 DOI: 10.1016/j.advms.2024.10.004

Oğuzhan Karaosmanoğlu

{"title":"Recurrent hepatocellular carcinoma is associated with the enrichment of MYC targets gene sets, elevated high confidence deleterious mutations and alternative splicing of DDB2 and BRCA1 transcripts","authors":"Oğuzhan Karaosmanoğlu","doi":"10.1016/j.advms.2024.10.004","DOIUrl":"10.1016/j.advms.2024.10.004","url":null,"abstract":"<div><h3>Purpose</h3><div>Recurrence is the main cause of hepatocellular carcinoma (HCC) related deaths. Underlying recurrence biology can be better understood by comparative analysis of the complete set of transcripts between recurrent and non-recurrent HCC. In this study, transcriptomic data (GSE56545) from 21 male patients diagnosed with either recurrent or non-recurrent HCC were reanalyzed to identify deregulated pathways, somatic mutations, fusion transcripts, alternative splicing events, and the immune context in recurrent HCC.</div></div><div><h3>Materials and methods</h3><div>DESeq2 was used for differential expression analysis, Mutect2 for somatic mutation analysis, Arriba and STAR-Fusion for fusion transcript analysis, and rMATs for alternative splicing analysis.</div></div><div><h3>Results</h3><div>The results revealed that MYC targets gene sets (Hallmark_MYC_targets_V1 and Hallmark_MYC_targets_V2) were significantly enriched in recurrent HCC. Among the MYC targets, <em>CBX3</em>, <em>NOP56</em>, <em>CDK4</em>, <em>NPM1</em>, <em>MCM5</em>, <em>MCM4</em> and <em>PA2G4</em> upregulation was significantly associated with poor survival. Somatic mutation analysis demonstrated that the numbers of high confidence deleterious mutations were significantly increased in recurrent HCC. Alternative splicing-mediated production of non-functional <em>DDB2</em> and oncogenic <em>BRCA1 D11q</em> were discovered in recurrent HCC. Finally, CD8<sup>+</sup> T-cells were significantly decreased in recurrent HCC.</div></div><div><h3>Conclusions</h3><div>These results indicated that the enrichment of MYC targets gene sets is one of the most critical factors that leads to the development of recurrent HCC. In addition, elevated deleterious mutation numbers and alternative spliced <em>DDB2</em> and <em>BRCA1</em> isoforms have been identified as prominent contributors to increasing genomic instability in male patients with recurrent HCC.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 17-26"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibition of TRPM7 by glutathione decreases oxidant and apoptotic action of cisplatin through the downregulation of Ca2+ and Zn2+ in glioblastoma cells 谷胱甘肽抑制TRPM7可通过下调胶质母细胞瘤细胞中Ca2+和Zn2+来降低顺铂的氧化和凋亡作用。

IF 2.5 4区医学

Advances in medical sciences Pub Date : 2025-03-01 Epub Date: 2025-01-30 DOI: 10.1016/j.advms.2025.01.008

Kemal Ertilav , Mustafa Nazıroğlu

{"title":"Inhibition of TRPM7 by glutathione decreases oxidant and apoptotic action of cisplatin through the downregulation of Ca2+ and Zn2+ in glioblastoma cells","authors":"Kemal Ertilav , Mustafa Nazıroğlu","doi":"10.1016/j.advms.2025.01.008","DOIUrl":"10.1016/j.advms.2025.01.008","url":null,"abstract":"<div><h3>Purpose</h3><div>Cisplatin (CiSP)-mediated stimulation of TRPM7 may induce oxidant and apoptotic activities through the upregulation of Ca<sup>2+</sup>, apoptosis, and reactive oxygen species (ROS) in glioblastoma (DBTRG-05MG) cells, whereas inhibition of TRPM7 by the antioxidant glutathione (GSH) may reduce the observed increases in DBTRG-05MG. The aim of the study was to examine how TRPM7 activation stimulates DBTRG-05MG cell death but also how it inhibits the effects of TRPM7 antagonists (GSH and carvacrol, CRV) via altering ROS toxicity and apoptosis.</div></div><div><h3>Method</h3><div>In the DBTRG-05MG, 5 groups were established: control, GSH (10 mM for 2 h), CiSP (25 μM for 24 h), CiSP + GSH, and CiSP + CRV (200 μM for 24 h).</div></div><div><h3>Results</h3><div>The amounts of cytosolic free Ca<sup>2+</sup> were further increased in the CiSP group by the stimulation of TRPM7 (naltriben), even though the GSH and CRV treatments caused them to decrease in the cells. The amounts of mitochondrial membrane dysfunction, ROS, death cell, apoptosis, free zinc ion, and caspase-3, -8, and -9 in the cells were higher in the CiSP than in the control and GSH, although their amounts were lower in the CiSP + GSH and CiSP + CRV than in the CiSP only. The CiSP-induced decreases in cell viability and GSH concentrations were increased by GSH incubation.</div></div><div><h3>Conclusions</h3><div>The stimulation of TRPM7 increased the anticancer action of CiSP, although its inhibition decreased the amount of CiSP-induced oxidative stress and DBTRG-05MG deaths through the treatment of GSH and CRV. TRPM7 stimulation could be considered a potential tumor killer channel through oxidative glioblastoma damage caused by CiSP.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 124-135"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143073295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

High levels of soluble neuropilin −1 in critically ill multiple trauma/surgical patients 多发性创伤/外科危重患者高水平可溶性神经匹林-1

IF 2.5 4区医学

Advances in medical sciences Pub Date : 2025-03-01 Epub Date: 2025-02-26 DOI: 10.1016/j.advms.2025.02.007

Charikleia S. Vrettou, Chrysi Keskinidou , Alice G. Vassiliou , Georgios Poupouzas, Edison Jahaj, Vassilios Issaris, Evangelia Theodorou, Asimenia Halioti, Vassiliki Giannopoulou, Nikolaos S. Lotsios, Anastasia Kotanidou, Ioanna Dimopoulou

{"title":"High levels of soluble neuropilin −1 in critically ill multiple trauma/surgical patients","authors":"Charikleia S. Vrettou, Chrysi Keskinidou , Alice G. Vassiliou , Georgios Poupouzas, Edison Jahaj, Vassilios Issaris, Evangelia Theodorou, Asimenia Halioti, Vassiliki Giannopoulou, Nikolaos S. Lotsios, Anastasia Kotanidou, Ioanna Dimopoulou","doi":"10.1016/j.advms.2025.02.007","DOIUrl":"10.1016/j.advms.2025.02.007","url":null,"abstract":"<div><h3>Purpose</h3><div>Critically ill trauma/surgical patients may experience excessive inflammation, immune and coagulation dysregulation, leading to multiple organ failure (MOF), carrying high mortality rates. Neuropilin-1 (NRP-1) and its soluble isoform (sNRP-1) are implicated in immune response regulation, inflammation, and vascular permeability. This study aimed to investigate the possible role of sNRP-1 in trauma/surgical patients in the intensive care unit (ICU).</div></div><div><h3>Patients and methods</h3><div>This prospective observational study was conducted in a 31-bed ICU and included 81 patients, 43 of whom were trauma/surgical patients and 38 of whom were matched medical patients, comprising the control group. sNRP-1, interleukin (IL)-6, IL-8, and IL-10 levels were measured on admission to the ICU (within 48 h).</div></div><div><h3>Results</h3><div>Trauma/surgical patients had significantly higher sNRP-1 (p = 0.027), IL-6, IL-8, and IL-10 levels (p < 0.05) compared to medical patients. In the entire cohort, sNRP-1 correlated positively with the international normalized ratio (INR) (p = 0.017), the activated partial thromboplastin time (p = 0.026), fibrinogen (p = 0.027), alanine aminotransferase (p = 0.024), and C-reactive protein (p = 0.004). Moreover, sNRP-1 correlated negatively with total protein (p = 0.035), albumin (p = 0.005), and platelets (p = 0.033).</div></div><div><h3>Conclusion</h3><div>sNRP-1 levels were elevated in critically ill trauma/surgical patients compared to matched medical ICU patients. Further research is needed to elucidate the exact role of sNRP-1 in these patients' pathophysiology.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 191-196"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143530840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting treatment resistance in cervical cancer: A new avenue for senolytic therapies 针对宫颈癌的耐药性：老年溶解疗法的新途径

IF 2.5 4区医学

Advances in medical sciences Pub Date : 2025-03-01 Epub Date: 2024-11-15 DOI: 10.1016/j.advms.2024.11.001

Madré Meyer , Carla Fourie , Haynes van der Merwe , Hennie Botha , Anna-Mart Engelbrecht

{"title":"Targeting treatment resistance in cervical cancer: A new avenue for senolytic therapies","authors":"Madré Meyer , Carla Fourie , Haynes van der Merwe , Hennie Botha , Anna-Mart Engelbrecht","doi":"10.1016/j.advms.2024.11.001","DOIUrl":"10.1016/j.advms.2024.11.001","url":null,"abstract":"<div><div>Cervical cancer poses a significant global health challenge, particularly impacting women in economically developing nations. This disparity stems from a combination of factors, including inadequate screening infrastructure and resource limitations. However, the foremost contributor is the widespread lack of awareness and limited accessibility to Human Papillomavirus (HPV) vaccination, which is a key preventative measure against cervical cancer development. Despite advancements in cervical cancer prevention, treatment resistance remains a major hurdle in achieving improved patient outcomes. Cellular senescence, specifically the senescence-associated secretory phenotype (SASP) and its bidirectional relationship with the immune system, has been implicated in resistance to conventional cervical cancer chemotherapy treatments. The exact mechanisms by which this state of growth arrest and the associated changes in immune regulation contribute to cervical cancer progression and the associated drug resistance are not entirely understood. This underscores the necessity for innovative strategies to address the prevalence of treatment-resistant cervical cancer, with one promising avenue being the utilisation of senolytics. Senolytics are agents that have promising efficacy in clearing senescent cells from tumour tissues, however neither the utilisation of senolytics for addressing senescence-induced treatment resistance nor the potential integration of immunotherapy as senolytic agents in cervical cancer treatment has been explored to date. This review provides a concise overview of the mechanisms underlying senescence induction and the pivotal role of the immune system in this process. Additionally, it explores various senolytic approaches that hold significant potential for advancing cervical cancer research.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 33-43"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142643687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combination therapy of placenta-derived mesenchymal stem cells and artificial dermal scaffold promotes full-thickness skin defects vascularization in rat animal model 胎盘间充质干细胞与人工真皮支架的联合疗法促进了大鼠动物模型全厚皮肤缺损血管的形成。

IF 2.5 4区医学

Advances in medical sciences Pub Date : 2025-03-01 Epub Date: 2024-10-17 DOI: 10.1016/j.advms.2024.10.002

Kun Zhang , Dongjie Xiao , Fang Li , Guodong Song , Guobao Huang , Yunshan Wang , Hua Liu

{"title":"Combination therapy of placenta-derived mesenchymal stem cells and artificial dermal scaffold promotes full-thickness skin defects vascularization in rat animal model","authors":"Kun Zhang , Dongjie Xiao , Fang Li , Guodong Song , Guobao Huang , Yunshan Wang , Hua Liu","doi":"10.1016/j.advms.2024.10.002","DOIUrl":"10.1016/j.advms.2024.10.002","url":null,"abstract":"<div><h3>Purpose</h3><div>Recently, placenta-derived mesenchymal stem cells (PMSCs) have garnered considerable attention in tissue repair and regeneration. The present study was conducted to evaluate the effect of PMSCs on artificial dermal scaffold (ADS) angiogenesis and their combination therapy on wound closure.</div></div><div><h3>Material and methods</h3><div>Herein, the growth and survival of PMSCs in ADS were explored. CCK8, scratch wound, and tubule formation assays were employed to investigate the effects of ADS conditioned medium (CM) and ADS-PMSCs CM on human umbilical vein endothelial cells (HUVECs). The effect of ADS-PMSCs on full-thickness skin defects healing was evaluated based on a rat model. Wound healing progresses was meticulously investigated through hematoxylin and eosin (HE), Masson's trichrome, and immunohistochemical staining analyses.</div></div><div><h3>Results</h3><div><em>In vitro</em> cell culture results demonstrated the proliferation of PMSCs in ADS. The ADS-PMSCs CM notably stimulated the proliferation, migration, and tube formation of HUVECs compared to the ADS CM group. In the rat full-thickness skin defect model, the ADS-PMSCs treatment significantly accelerated the vascularization area of ADS after 2 weeks. Besides, HE and Masson's trichrome staining results indicated that ADS-PMSCs treatment significantly enhanced fibroblast proliferation and collagen fiber 2 weeks after surgical procedure. Compared to the ADS group, collagen fiber arrangement was thicker in the ADS-PMSCs group. Immunohistochemical staining reinforced this finding, illustrating a substantial increase in CD31 expression within the ADS-PMSCs group.</div></div><div><h3>Conclusions</h3><div>The results suggest that the combination of ADS with PMSCs accelerates ADS vascularization by fostering granulation tissue development and boosting the formation of new blood vessels.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 8-16"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigation of circulating natural autoantibodies against ANXA1 and MYC as potential biomarkers in hepatocellular carcinoma 抗ANXA1和MYC的循环天然自身抗体作为肝细胞癌潜在生物标志物的研究。

IF 2.5 4区医学

Advances in medical sciences Pub Date : 2025-03-01 Epub Date: 2025-01-15 DOI: 10.1016/j.advms.2025.01.004

Jiaxin Wang , Siqi Liu , Xuan Zhang

{"title":"Investigation of circulating natural autoantibodies against ANXA1 and MYC as potential biomarkers in hepatocellular carcinoma","authors":"Jiaxin Wang , Siqi Liu , Xuan Zhang","doi":"10.1016/j.advms.2025.01.004","DOIUrl":"10.1016/j.advms.2025.01.004","url":null,"abstract":"<div><h3>Purpose</h3><div>In this study, we examined novel autoantibodies targeting tumor-associated antigens (TAAs) as biomarkers for clinical assessment of hepatocellular carcinoma (HCC) in a Chinese population.</div></div><div><h3>Methods and methods</h3><div>A total of 119 patients with HCC and 130 healthy control (HC) volunteers who were age and gender matched were enrolled. The levels of circulating IgG antibodies were detected using an enzyme-linked immunosorbent test (ELISA) developed in-house with linear peptide antigens derived from Annexin A1(ANXA1) and proto-oncogene protein (MYC). The significant level was set at <em>P</em> < 0.025 as two tests were performed.</div></div><div><h3>Results</h3><div>In comparison to the HC group, plasma level of ANXA1 autoantibodies was significantly elevated in HCC patients (<em>t</em> = −3.174, <em>P</em> = 0.002) but the change of plasma MYC autoantibody levels failed to reach the significance level (<em>P</em> > 0.025). There was a significant increase in these two plasma IgG autoantibodies in male HCC patients (ANXA1: <em>t</em> = −3.590, <em>P</em> < 0.001; MYC: <em>t</em> = −2.706, <em>P</em> = 0.007). Pearson correlation analysis demonstrated that both anti-ANXA1 and anti-MYC IgG levels had a positive correlation with BCLC staging (both <em>P</em> < 0.025) but a negative correlation with plasma albumin (Alb) (both <em>P</em> < 0.025). The area under the ROC curve (AUC) values were 0.613 for anti-ANXA1 IgG assay and 0.567 for anti-MYC IgG assay. The anti-ANAXA1 IgG assay showed a high sensitivity of 31.4 % against the specificity of 90.0 % for detection of BCLC stages C + D.</div></div><div><h3>Conclusions</h3><div>Plasma anti-ANXA1 and anti-MYC autoantibodies are likely to serve as a potential biomarker for clinical assessment of HCC prognosis, particularly in male patients.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 136-140"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142998500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Caloric restriction mimetics: Pinostilbene versus resveratrol regarding SIRT1 and SIRT6 interaction 热量限制模拟：蒎烯与白藜芦醇对SIRT1和SIRT6相互作用的影响。

IF 2.5 4区医学

Advances in medical sciences Pub Date : 2025-03-01 Epub Date: 2024-11-29 DOI: 10.1016/j.advms.2024.11.002

Anca Ungurianu , Denisa Margină , Dragoș P. Mihai , Alina C. Nicolae , Cristina M. Drăgoi , Daniela Grădinaru , Anca Zanfirescu

{"title":"Caloric restriction mimetics: Pinostilbene versus resveratrol regarding SIRT1 and SIRT6 interaction","authors":"Anca Ungurianu , Denisa Margină , Dragoș P. Mihai , Alina C. Nicolae , Cristina M. Drăgoi , Daniela Grădinaru , Anca Zanfirescu","doi":"10.1016/j.advms.2024.11.002","DOIUrl":"10.1016/j.advms.2024.11.002","url":null,"abstract":"<div><h3>Purpose</h3><div>Caloric restriction (CR), the permanent or periodic reduction of caloric intake, is a dietary strategy that promotes longevity and healthspan, yielding multiple beneficial effects, such as improved insulin sensitivity and mitochondrial function, decreased body weight, and mitigation of cardiometabolic risk factors. The purpose of our study was the <em>in silico</em> and <em>in vitro</em> assessment of the effects exerted by pinostilbene on SIRT1 and SIRT6 compared to those of resveratrol, a known activator of these enzymes.</div></div><div><h3>Materials and methods</h3><div>Molecular docking was carried out to determine the interactions with SIRT1 and SIRT6 and, further, the effect of pinostilbene on their activity was tested <em>in vitro</em> to evaluate if it parallels resveratrol's effects regarding SIRT activation.</div></div><div><h3>Results</h3><div>Molecular docking indicates that resveratrol and pinostilbene bind similarly to SIRT6, while pinostilbene may be able to activate SIRT1 more efficiently than resveratrol. <em>In vitro</em> activity assays showed that while both resveratrol and pinostilbene activate SIRT1 and SIRT6, the concentration-dependent effects differ. For resveratrol, a greater effect was observed at the medium concentration (25 μM), whereas pinostilbene showed a more pronounced activation at the lowest concentration (5 μM).</div></div><div><h3>Conclusions</h3><div>Our results offer a glimpse into the structural features and interactions of pinostilbene and resveratrol with SIRT1 and SIRT6, contributing to understanding their potential roles in various cellular processes regulated by SIRT.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 44-50"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142765449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Knockout of histone deacetylase 8 gene in breast cancer cells may alter the expression pattern of the signaling molecules 在乳腺癌细胞中敲除组蛋白去乙酰化酶 8 基因可能会改变信号分子的表达模式。

IF 2.5 4区医学

Advances in medical sciences Pub Date : 2025-03-01 Epub Date: 2024-10-20 DOI: 10.1016/j.advms.2024.10.003

Nahid Bahrami , Mohammad Abdi

{"title":"Knockout of histone deacetylase 8 gene in breast cancer cells may alter the expression pattern of the signaling molecules","authors":"Nahid Bahrami , Mohammad Abdi","doi":"10.1016/j.advms.2024.10.003","DOIUrl":"10.1016/j.advms.2024.10.003","url":null,"abstract":"<div><h3>Purpose</h3><div>Breast cancer (BC) is the most common cancer diagnosed in the world and it is also the main leading cause of cancer deaths in women. Change in epigenetic mechanisms promotes BC initiation and progression. Histone deacetylase 8 (<em>HDAC8</em>) was found to act as a potential oncogene in different malignancies. For better understanding of the HDAC8 function in BC development, we investigated the effect of <em>HDAC8</em> deletion on the expression of genes involved in signaling pathways.</div></div><div><h3>Materials and methods</h3><div>In this study, CRISPR technology was used to knockout the <em>HDAC8</em> gene in MDA-MB-468, MDA-MB-231 and MCF-7 cell lines. For this purpose, two gRNAs were designed and cloned into the PX459 vector. The gRNA-containing vectors were transfected into the BC cell lines and then the effect of this deletion on the expression of genes involved in signaling pathway was determined using quantitative real-time PCR (qRT-PCR).</div></div><div><h3>Results</h3><div>Analysis of qRT-PCR results showed a reduction in the expression of studied genes in BC cell lines after deletion of the <em>HDAC8</em> gene compared to untreated controls. Although this decline was not significant for <em>FGF2</em> and <em>FGFR1</em> genes, however the <em>mTOR</em>, <em>IGF1R</em>, <em>INSR</em>, <em>VEGFA</em> and <em>VEGFR2</em> genes showed statistically significant reduction in the studied BC cell lines. In addition, the down-regulation of <em>PDGFC</em> and <em>PDGFRA</em> genes were only significant in the TNBC cell lines.</div></div><div><h3>Conclusion</h3><div>Overall, our study showed that <em>HDAC8</em> can exert its oncogenic effects by altering the expression level of molecules involved in some signaling pathways, and inhibiting <em>HDAC8</em> can revert these effects.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 27-32"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142492805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and temporal-validation of prognostic models for 5-year risk of pneumonia, respiratory failure/collapse, and fracture among adults with cerebral palsy 针对脑瘫成人肺炎、呼吸衰竭/塌陷和骨折 5 年风险的预后模型的开发和时间验证。

IF 2.5 4区医学

Advances in medical sciences Pub Date : 2025-03-01 Epub Date: 2025-01-22 DOI: 10.1016/j.advms.2025.01.007

Daniel G. Whitney

{"title":"Development and temporal-validation of prognostic models for 5-year risk of pneumonia, respiratory failure/collapse, and fracture among adults with cerebral palsy","authors":"Daniel G. Whitney","doi":"10.1016/j.advms.2025.01.007","DOIUrl":"10.1016/j.advms.2025.01.007","url":null,"abstract":"<div><h3>Purpose</h3><div>Pneumonia, respiratory failure, and fracture are common and highly burdensome for adults with cerebral palsy (CP). To date, there are no clinically friendly tools to assess individualized risk of these outcomes for adults with CP. The objective was to develop and validate prognostic models for 5-year risk of pneumonia, respiratory failure/collapse, and fracture for adults with CP.</div></div><div><h3>Patients and methods</h3><div>This single medical center retrospective cohort study used medical records from January 1, 2012 till June 1, 2024 from adults ≥18 years old with CP. The development cohort (n = 1520) included those with a start date of follow-up from January 1, 2015 till December 31, 2015 and evidence of being treated at the medical center for ≥3 years prior to day 0. The 5-year risk of outcomes was modelled using logistic regression and variations of the following predictors that were collected during the 3-year baseline: age, sex, Whitney Comorbidity Index, pneumonia, respiratory failure/collapse, fracture, and asthma/COPD. Discrimination (c-statistic) and calibration statistics assessed the model's performance. Decision curve analysis assessed the model's clinical utility. The models were validated in a temporal validation cohort, whose start date of follow-up was January 1, 2016 to May 31, 2019 (n = 529).</div></div><div><h3>Results</h3><div>The prognostic models had good discrimination (c-statistic = 0.76–0.78), good-to-excellent calibration, and demonstrated superior clinical utility in identifying true positives and true negatives. All models demonstrated temporal validation.</div></div><div><h3>Conclusions</h3><div>Prognostic models for 5-year risk of outcomes were developed and temporally validated for adults with CP using measures that can be easily collected from medical records.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 109-116"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143035839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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