Pub Date : 2025-03-01Epub Date: 2025-02-12DOI: 10.1016/j.advms.2025.01.009
Michał Dębczyński , Damian Mojsak , Łukasz Minarowski , Monika Maciejewska , Paweł Lisowski , Robert M. Mróz
{"title":"Corrigendum to “Genome-engineering technologies for modeling and treatment of cystic fibrosis” [Adv Med Sci (2023 Sept) 68(1) 111–120]","authors":"Michał Dębczyński , Damian Mojsak , Łukasz Minarowski , Monika Maciejewska , Paweł Lisowski , Robert M. Mróz","doi":"10.1016/j.advms.2025.01.009","DOIUrl":"10.1016/j.advms.2025.01.009","url":null,"abstract":"","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Page 229"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424663","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}
Pub Date : 2025-03-01Epub Date: 2025-01-27DOI: 10.1016/j.advms.2025.01.005
Pavol Harvanik , Martina Šemeláková , Zuzana Solárová , Peter Solár
Ovarian tumours are these days one of the biggest oncogynecological problems. In addition to surgery, the treatment of ovarian cancer includes also chemotherapy in which platinum preparations are one of the most used chemotherapeutic drugs. The principle of antineoplastic effects of cisplatin (cis-diamminedichloroplatinum(II), CDDP) is its binding to the DNA and the formation of adducts. While DNA adducts induce the process of apoptosis, or inhibit the process of DNA replication, which prevents further division of tumour cells, various molecular mechanisms can reverse this process. On the other hand, with increasing scientific knowledge, it is becoming clearer that chemotherapy resistance is a very complex process. In this regard, factors and the amount of their expression may regulate the effect of resistance to chemotherapy. This review focuses on new molecular mechanisms and factors such as mitochondrial dynamics, epithelial-mesenchymal transition (EMT), cluster of differentiation, exosomes and others, that could be involved in the emergence of CDDP resistance.
{"title":"Novel factors of cisplatin resistance in epithelial ovarian tumours","authors":"Pavol Harvanik , Martina Šemeláková , Zuzana Solárová , Peter Solár","doi":"10.1016/j.advms.2025.01.005","DOIUrl":"10.1016/j.advms.2025.01.005","url":null,"abstract":"<div><div>Ovarian tumours are these days one of the biggest oncogynecological problems. In addition to surgery, the treatment of ovarian cancer includes also chemotherapy in which platinum preparations are one of the most used chemotherapeutic drugs. The principle of antineoplastic effects of cisplatin (cis-diamminedichloroplatinum(II), CDDP) is its binding to the DNA and the formation of adducts. While DNA adducts induce the process of apoptosis, or inhibit the process of DNA replication, which prevents further division of tumour cells, various molecular mechanisms can reverse this process. On the other hand, with increasing scientific knowledge, it is becoming clearer that chemotherapy resistance is a very complex process. In this regard, factors and the amount of their expression may regulate the effect of resistance to chemotherapy. This review focuses on new molecular mechanisms and factors such as mitochondrial dynamics, epithelial-mesenchymal transition (EMT), cluster of differentiation, exosomes and others, that could be involved in the emergence of CDDP resistance.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 94-102"},"PeriodicalIF":2.5,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143063219","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}
Pub Date : 2025-03-01Epub Date: 2024-10-30DOI: 10.1016/j.advms.2024.10.004
Oğuzhan Karaosmanoğlu
Purpose
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.
Materials and methods
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.
Results
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, CBX3, NOP56, CDK4, NPM1, MCM5, MCM4 and PA2G4 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 DDB2 and oncogenic BRCA1 D11q were discovered in recurrent HCC. Finally, CD8+ T-cells were significantly decreased in recurrent HCC.
Conclusions
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 DDB2 and BRCA1 isoforms have been identified as prominent contributors to increasing genomic instability in male patients with recurrent HCC.
{"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}
Pub Date : 2025-03-01Epub Date: 2025-01-30DOI: 10.1016/j.advms.2025.01.008
Kemal Ertilav , Mustafa Nazıroğlu
Purpose
Cisplatin (CiSP)-mediated stimulation of TRPM7 may induce oxidant and apoptotic activities through the upregulation of Ca2+, 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.
Method
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).
Results
The amounts of cytosolic free Ca2+ 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.
Conclusions
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.
目的：顺铂（CiSP）介导的TRPM7刺激可能通过上调胶质母细胞瘤（DBTRG-05MG）细胞中的Ca2+、凋亡和活性氧（ROS）来诱导氧化和凋亡活性，而抗氧化剂谷胱甘肽（GSH）抑制TRPM7可能会减少DBTRG-05MG的增加。该研究的目的是研究TRPM7激活如何刺激DBTRG-05MG细胞死亡，以及它如何通过改变ROS毒性和细胞凋亡来抑制TRPM7拮抗剂（GSH和carvacrol， CRV）的作用。方法：在DBTRG-05MG中建立5组：对照组、GSH （10 mM, 2h）、CiSP （25 μM, 24h）、CiSP+GSH、CiSP+CRV （200 mM, 24h）。结果：CiSP组胞质游离Ca2+的数量在TRPM7（钠triben）的刺激下进一步增加，尽管GSH和CRV处理导致它们在细胞中减少。细胞中线粒体膜超极化、ROS、死亡细胞、凋亡、游离锌离子和caspase-3、-8、-9的数量在CiSP中高于对照和GSH，但CiSP+GSH和CiSP+CRV的数量低于CiSP。GSH孵育后，cisp诱导的细胞活力和GSH浓度下降。结论：刺激TRPM7可增强CiSP的抗癌作用，但其抑制作用通过GSH和CRV的治疗降低了CiSP诱导的氧化应激和DBTRG-05MG死亡的数量。通过CiSP引起的氧化性胶质母细胞瘤损伤，TRPM7刺激可被认为是一个潜在的肿瘤杀伤通道。
{"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}
Pub Date : 2025-03-01Epub Date: 2025-02-26DOI: 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
Purpose
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).
Patients and methods
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).
Results
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).
Conclusion
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.
{"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}
Pub Date : 2025-03-01Epub Date: 2024-10-17DOI: 10.1016/j.advms.2024.10.002
Kun Zhang , Dongjie Xiao , Fang Li , Guodong Song , Guobao Huang , Yunshan Wang , Hua Liu
Purpose
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.
Material and methods
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.
Results
In vitro 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.
Conclusions
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.
{"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}
Pub Date : 2025-03-01Epub Date: 2025-01-15DOI: 10.1016/j.advms.2025.01.004
Jiaxin Wang , Siqi Liu , Xuan Zhang
Purpose
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.
Methods and methods
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 P < 0.025 as two tests were performed.
Results
In comparison to the HC group, plasma level of ANXA1 autoantibodies was significantly elevated in HCC patients (t = −3.174, P = 0.002) but the change of plasma MYC autoantibody levels failed to reach the significance level (P > 0.025). There was a significant increase in these two plasma IgG autoantibodies in male HCC patients (ANXA1: t = −3.590, P < 0.001; MYC: t = −2.706, P = 0.007). Pearson correlation analysis demonstrated that both anti-ANXA1 and anti-MYC IgG levels had a positive correlation with BCLC staging (both P < 0.025) but a negative correlation with plasma albumin (Alb) (both P < 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.
Conclusions
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.
目的：在这项研究中，我们检测了靶向肿瘤相关抗原（TAAs）的新型自身抗体作为中国人群肝细胞癌（HCC）临床评估的生物标志物。方法和方法：共纳入119例HCC患者和130例年龄和性别匹配的健康对照（HC）志愿者。采用酶联免疫吸附试验（ELISA）检测循环IgG抗体水平，该试验采用源自膜联蛋白A1（ANXA1）和原癌基因蛋白（MYC）的线性肽抗原。结果：HCC患者血浆中ANXA1自身抗体水平较HC组显著升高（t=-3.174, P = 0.002），而MYC自身抗体水平变化未达到显著水平（P = 0.025）。在男性HCC患者中，这两种血浆IgG自身抗体显著升高（ANXA1: t=-3.590, p）。结论：血浆抗ANXA1和抗myc自身抗体可能作为HCC临床预后评估的潜在生物标志物，尤其是在男性患者中。
{"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}
Pub Date : 2025-03-01Epub Date: 2024-11-15DOI: 10.1016/j.advms.2024.11.001
Madré Meyer , Carla Fourie , Haynes van der Merwe , Hennie Botha , Anna-Mart Engelbrecht
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.
{"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}
Pub Date : 2025-03-01Epub Date: 2024-11-29DOI: 10.1016/j.advms.2024.11.002
Anca Ungurianu , Denisa Margină , Dragoș P. Mihai , Alina C. Nicolae , Cristina M. Drăgoi , Daniela Grădinaru , Anca Zanfirescu
Purpose
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 in silico and in vitro assessment of the effects exerted by pinostilbene on SIRT1 and SIRT6 compared to those of resveratrol, a known activator of these enzymes.
Materials and methods
Molecular docking was carried out to determine the interactions with SIRT1 and SIRT6 and, further, the effect of pinostilbene on their activity was tested in vitro to evaluate if it parallels resveratrol's effects regarding SIRT activation.
Results
Molecular docking indicates that resveratrol and pinostilbene bind similarly to SIRT6, while pinostilbene may be able to activate SIRT1 more efficiently than resveratrol. In vitro 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).
Conclusions
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.
{"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}
Pub Date : 2025-03-01Epub Date: 2024-10-20DOI: 10.1016/j.advms.2024.10.003
Nahid Bahrami , Mohammad Abdi
Purpose
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 (HDAC8) 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 HDAC8 deletion on the expression of genes involved in signaling pathways.
Materials and methods
In this study, CRISPR technology was used to knockout the HDAC8 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).
Results
Analysis of qRT-PCR results showed a reduction in the expression of studied genes in BC cell lines after deletion of the HDAC8 gene compared to untreated controls. Although this decline was not significant for FGF2 and FGFR1 genes, however the mTOR, IGF1R, INSR, VEGFA and VEGFR2 genes showed statistically significant reduction in the studied BC cell lines. In addition, the down-regulation of PDGFC and PDGFRA genes were only significant in the TNBC cell lines.
Conclusion
Overall, our study showed that HDAC8 can exert its oncogenic effects by altering the expression level of molecules involved in some signaling pathways, and inhibiting HDAC8 can revert these effects.
{"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}
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