Advances in medical sciences最新文献

{"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":"https://doi.org/10.1016/j.advms.2024.11.001","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-11-14","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}

{"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⁺ 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":"2024-10-30","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}

{"title":"Knockout of histone deacetylase 8 gene in breast cancer cells may alter the expression pattern of the signaling molecules","authors":"Nahid Bahrami ,&nbsp;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":"2024-10-20","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}

{"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 ,&nbsp;Dongjie Xiao ,&nbsp;Fang Li ,&nbsp;Guodong Song ,&nbsp;Guobao Huang ,&nbsp;Yunshan Wang ,&nbsp;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":"2024-10-17","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}

{"title":"Enhancing the accuracy and effectiveness of diagnosis of spontaneous bacterial peritonitis in cirrhotic patients: A machine learning approach utilizing clinical and laboratory data","authors":"Babak Khorsand ,&nbsp;Mohsen Rajabnia ,&nbsp;Ali Jahanian ,&nbsp;Mobin Fathy ,&nbsp;Somayye Taghvaei ,&nbsp;Hamidreza Houri","doi":"10.1016/j.advms.2024.10.001","DOIUrl":"10.1016/j.advms.2024.10.001","url":null,"abstract":"<div><h3>Purpose</h3><div>Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascitic fluid that develops naturally, without being triggered by any surgical conditions or procedures, and is a common complication of cirrhosis. With a potential mortality rate of 40 ​%, accurate diagnosis and prompt initiation of appropriate antibiotic therapy are crucial for optimizing patient outcomes and preventing life-threatening complications. This study aimed to expand the use of computational models to improve the diagnostic accuracy of SBP in cirrhotic patients by incorporating a broader range of data, including clinical variables and laboratory values.</div></div><div><h3>Patients and methods</h3><div>We employed 5 machine learning classification methods - Decision Tree, Support Vector Machine, Naive Bayes, K-Nearest Neighbor, and Random Forest, utilizing a variety of demographic, clinical, and laboratory features and biomarkers.</div></div><div><h3>Results</h3><div>Ascitic fluid markers, including white blood cell (WBC) count, lactate dehydrogenase (LDH), total protein, and polymorphonuclear cells (PMN), significantly differentiated between SBP and non-SBP patients. The Random Forest model demonstrated the highest overall accuracy at 86 ​%, while the Naive Bayes model achieved the highest sensitivity at 72 ​%. Utilizing 10 key features instead of the full feature set improved model performance, notably enhancing specificity and accuracy.</div></div><div><h3>Conclusion</h3><div>Our analysis highlights the potential of machine learning to enhance the accuracy of SBP diagnosis in cirrhotic patients. Integrating these models into clinical workflows could substantially improve patient outcomes. To achieve this, ongoing multidisciplinary research is crucial. Ensuring model interpretability, continuous monitoring, and rigorous validation will be essential for the successful implementation of real-time clinical decision support systems.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"70 1","pages":"Pages 1-7"},"PeriodicalIF":2.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142455754","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}

{"title":"Metabolic dysfunction-associated steatotic liver disease - A new indication for sodium-glucose Co-transporter-2 inhibitors","authors":"Grzegorz Procyk ,&nbsp;Jakub Jaworski ,&nbsp;Aleksandra Gąsecka ,&nbsp;Krzysztof J. Filipiak ,&nbsp;Josip A. Borovac","doi":"10.1016/j.advms.2024.09.001","DOIUrl":"10.1016/j.advms.2024.09.001","url":null,"abstract":"<div><p>Metabolic dysfunction–associated steatotic liver disease (MASLD) has been proposed as a new name for the previous non-alcoholic fatty liver disease (NAFLD). There are some differences between MASLD and NAFLD, e.g., diagnostic criteria. MASLD is a hepatic steatosis without harmful alcohol consumption and is caused by metabolic factors. The prevalence of MASLD varies amongst different populations. The change in lifestyle plays a fundamental role in MASLD management, while there is no registered pharmacotherapy in this indication. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have been suggested to have a beneficial effect on hepatic steatosis, hence, they have been widely investigated as potential therapeutics in MASLD. In this review, we aimed to thoroughly summarize current evidence from original research about the effects of SGLT2i use on MASLD. Almost all discussed studies advocate using SGLT2i in MASLD because of their beneficial effects. It includes the loss of body weight, which is beneficial per se, and the improvement in hepatic parameters. Most importantly, steatosis reduction has been observed in patients using SGLT2i. We highly recommend further research in this field, which we believe will eventually lead to a new indication for SGLT2i, i.e., MASLD.</p></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 407-415"},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S189611262400049X/pdfft?md5=2df69cbb5aabd7e8b0e7c398a31a299c&pid=1-s2.0-S189611262400049X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142221074","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}

{"title":"An evaluation of the effect of the use of platelet-rich fibrin on tonsillectomy results","authors":"Aslıhan Oflaz Çapar,&nbsp;Emre Solguntekin,&nbsp;Kerem Kökoğlu,&nbsp;Mehmet Ilhan Şahin","doi":"10.1016/j.advms.2024.09.004","DOIUrl":"10.1016/j.advms.2024.09.004","url":null,"abstract":"<div><h3>Purpose</h3><div>The aim of this study was to investigate the effect of liquid platelet-rich fibrin (PRF) during tonsillectomy on postoperative results.</div></div><div><h3>Patients and methods</h3><div>This study included 41 patients who underwent tonsillectomy between April 2022 and January 2023. Liquid-PRF at a dose of 1 ​cc was injected to three different points of one of the tonsil fossae, selected at random intraoperatively. The same amount of physiological saline was injected to the symmetrical points on the opposite tonsil fossa using the same size injector. Pain, wound healing, and bleeding were evaluated on postoperative days 1, 7, and 14. The data of both sides were compared statistically as the study and control sides.</div></div><div><h3>Results</h3><div>The pain scores were the highest for both sides on postoperative day 1, and gradually decreased in the following days, with no significant difference determined between the sides (p ​&gt; ​0.05). Wound healing rates in the 1st week and 2 ​nd ​week were similar for both sides. Although there were more patients who have 100 ​% epithelization in the PRF group on the postoperative day 14, the difference between the groups was not statistically significant (p ​&gt; ​0.05).</div></div><div><h3>Conclusions</h3><div>The injection of PRF following tonsillectomy had no significant effect on postoperative pain, wound healing, or bleeding.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 428-433"},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142278818","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}

{"title":"Reducing metastasis ability of gastric cancer cell line by targeting MMP16 using miR-193a-5p and 5-FU","authors":"Tahani Ahmad Almatrafi ,&nbsp;Natrayan Lakshmaiya ,&nbsp;Hailah M. Almohaimeed ,&nbsp;Srikumar Chakravarthi ,&nbsp;Ali H. Amin ,&nbsp;Ayman Jafer ,&nbsp;Amany I. Almars ,&nbsp;Ammar A. Basabrain ,&nbsp;Youssef S. Alghamdi ,&nbsp;Mohamed J. Saadh ,&nbsp;Reza Akhavan-Sigari","doi":"10.1016/j.advms.2024.09.008","DOIUrl":"10.1016/j.advms.2024.09.008","url":null,"abstract":"<div><h3>Purpose</h3><div>Co-administration of microRNAs and chemotherapy drugs effectively treats several cancers. The current study sought to investigate the function of matrix metalloproteinase 16 (MMP16) and miR-193a-5p in the pathogenesis of gastric cancer (GC).</div></div><div><h3>Materials/methods</h3><div>Sixty-five surgical patients, 15 receiving 5-fluorouracil (5-FU), provided GC and adjacent non-cancerous tissue. Following that, qPCR was used to assess the expression levels of MMP16 and miR-193a-5p in GC cells. The impact of miR-193a-5p and 5-FU administration on MMP16 mRNA expression was evaluated using qRT-PCR and Western blotting. MTT and Scratch tests were also conducted to assess their effects on cell viability and migration. Moreover, a rescue experiment using an MTT assay was performed. Using flow cytometry, the apoptotic rate was calculated. Finally, it was evaluated how MMP16 and miR-193a-5p related to the clinicopathological characteristics of the patients.</div></div><div><h3>Results</h3><div>The current study found that while MMP16 expression increased in GC patients (P ​&lt; ​0.0001), miR-193a-5p expression significantly decreased (P ​&lt; ​0.001). MMP16 down-regulation was another effect of miR-193a-5p replacement, particularly when 5-FU was added (P ​&lt; ​0.01). In addition, this study found that miR-193a-5p, by concentrating on MMP16, decreased the migration of GC cells brought on by MMP16. In GC cell lines, miR-193 and 5-FU induce apoptosis, with the 5-FU being more pronounced when combined with mir-193, according to flow cytometry results. A strong correlation was also found between clinicopathological traits associated with MMP16 and miR-193a-5p.</div></div><div><h3>Conclusions</h3><div>These findings suggest that miR-193a-5p, in conjunction with 5-FU, down-regulates MMP16 in GC, where it suppresses tumor growth.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 463-473"},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339165","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}

{"title":"Angiopoietin-like 4 facilitates human aortic smooth muscle cell phenotype switch and dysfunctions through the PI3K/Akt signaling in aortic dissection","authors":"Wei He ,&nbsp;Quan Zheng ,&nbsp;Tingfang Zou ,&nbsp;Wei Yan ,&nbsp;Xue Gao ,&nbsp;Chunle Wang ,&nbsp;Yaoyao Xiong","doi":"10.1016/j.advms.2024.09.006","DOIUrl":"10.1016/j.advms.2024.09.006","url":null,"abstract":"<div><h3>Purpose</h3><div>Vascular smooth muscle cell (VSMC) phenotype switch and dysfunctions have been reported to participate in aortic dissection (AD) progression. This study was aimed to investigate the role of angiopoietin-like 4 (ANGPTL4) in regulating VSMCs phenotype switch.</div></div><div><h3>Materials and methods</h3><div>Key genes were analyzed in AD using public datasets, and it was found that the central differential gene <em>ANGPTL4</em> was up-regulated in AD. The KEGG signaling pathway annotation was performed to validate the associated pathways, and the expression of <em>ANGPTL4</em> was verified using multiple datasets and clinical samples. Furthermore, the specific functions of ANGPTL4 on platelet-derived growth factor-BB (PDGF-BB)-treated human aortic smooth muscle cell (HASMC) phenotypes were investigated. The dynamic effects of ANGPTL4 and core signaling antagonists on HASMC phenotypes were examined.</div></div><div><h3>Results</h3><div>Hub gene <em>ANGPTL4</em> was significantly up-regulated in AD. <em>ANGPTL4</em> was linked to the PI3K/Akt signaling, angiogenesis, and neovascularization and remodeling. <em>ANGPTL4</em> overexpression further enhanced PDGF-BB effects on HASMC phenotypes, including promoted cell viability and migration, decreased contractile VSMC markers α-SMA and SM22α, elevated ECM degradation markers MMP-2 and MMP-9, and promoted phosphorylation of PI3K and Akt. <em>ANGPTL4</em> knockdown partially abolished PDGF-BB-induced contractile/synthetic VSMCs imbalance and HASMC dysfunctions. Furthermore, in <em>ANGPTL4</em>-overexpressing HASMCs pre-treated with PDGF-BB, the PI3K/Akt signaling inhibitor LY294002 also partially eliminated the effects caused by the PDGF-BB treatment and <em>ANGPTL4</em> overexpression.</div></div><div><h3>Conclusions</h3><div><em>ANGPTL4</em> is significantly up-regulated in AD. <em>ANGPTL4</em> overexpression further enhanced PDGF-BB effects on HASMC phenotype switch and dysfunctions, which might be involved in the PI3K/Akt signaling.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 474-483"},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339163","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}

{"title":"LRRC45 promotes lung cancer proliferation and progression by enhancing c-MYC, slug, MMP2, and MMP9 expression","authors":"Qian Wang ,&nbsp;Xin-Yan Liu ,&nbsp;Xiao-Qi Zhang ,&nbsp;Zheng-Xing Huo ,&nbsp;Cheng-Yu Chen ,&nbsp;Shi Chen ,&nbsp;Cheng-Yong Liu ,&nbsp;Jia Zhu ,&nbsp;Shan-Shan Liu ,&nbsp;Bing Lu","doi":"10.1016/j.advms.2024.09.007","DOIUrl":"10.1016/j.advms.2024.09.007","url":null,"abstract":"<div><h3>Background</h3><div>The leucine-rich repeat-containing (LRRC) superfamily members are known for their significant roles in tumorigenesis and cellular proliferation. However, the specific regulatory role of LRRC45 in lung cancer remains unexplored. This study investigated the impact and underlying mechanisms of LRRC45 on the proliferative, migratory, and invasive capacities of lung adenocarcinoma (LUAD) cells, potentially identifying new targets for therapeutic intervention.</div></div><div><h3>Material and methods</h3><div>The importance of LRRC45 in lung cancer was analyzed using the online databases of UCSC Xena, TCGA, TISIDB, and UALCAN, whereas to detect target gene expression, we used the qRT-PCR, Western blot, and immunofluorescence confocal. The cell growth was monitored by colony formation assay and migration was examined by cell migration assay. Finally, a xenograft mouse tumor model using A549 ​cells was used to explore the <em>in vivo</em> effect of LRRC45 in lung cancer.</div></div><div><h3>Results</h3><div>Inhibition of LRRC45 expression led to a notable decrease in proliferation, migration, and invasion of A549 and H1299 ​cells. LRRC45 silencing significantly reduced the tumor volume and improved the mice's survival. Additionally, inhibition of LRRC45 expression dramatically suppressed c-MYC, Slug, MMP2, and MMP9 expression. Overexpression of c-MYC and/or Slug in the LRRC45-deficient cells can partially or totally restore the LRRC45 deficiency-suppressed growth. Moreover, the overexpression of MMP2 and/or MMP9 could partially or totally restore LRRC45 deficiency-reduced cell metastasis.</div></div><div><h3>Conclusions</h3><div>LRRC45 could promote the proliferative, migrative, and invasive capacities of lung cancer cells by increasing c-MYC, Slug, MMP2, and MMP9 expression, indicating the therapeutic implications and potential significance of these pathways in lung cancer.</div></div>","PeriodicalId":7347,"journal":{"name":"Advances in medical sciences","volume":"69 2","pages":"Pages 451-462"},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339164","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}