Stem Cells International最新文献

{"title":"miR-4780 Derived from N2-Like Neutrophil Exosome Aggravates Epithelial-Mesenchymal Transition and Angiogenesis in Colorectal Cancer.","authors":"Liang Wang, Yuqiang Shan, Sixin Zheng, Jiangtao Li, Peng Cui","doi":"10.1155/2023/2759679","DOIUrl":"10.1155/2023/2759679","url":null,"abstract":"<p><p>Despite significant advances in diagnostic methods and treatment strategies, the prognosis for patients with advanced colon cancer remains poor, and mortality rates are often high due to metastasis. Increasing evidence showed that it is of significant importance to investigate how the tumor microenvironment participates in the development of colorectal cancer (CRC). In this manuscript, neutrophils were sequentially stimulated with all-trans retinoic acid and transforming growth factor-<i>β</i> in turn to induce the neutrophil polarization. Differentially expressed miRNA in neutrophil exosomes have been sequenced by microarray profile, and the effect of N2-like neutrophil-derived exosomal miR-4780 on epithelial-mesenchymal transition (EMT) and angiogenesis was investigated. In our results, we found that neutrophils were enriched in CRC tumor tissue and that CD11b expression correlated with tumor site and serous membrane invasion. At the same time, we demonstrated that internalization of N2 exosomes exacerbated the viability, migration, and invasion of CRC cell lines and inhibited apoptosis. To further investigate the molecular mechanism, we analyzed the miRNA expression profile in the N2-like neutrophils, which led to the selection of hsa-miR-4780 for the subsequent experiment. The overexpression of miR-4780 from N2-like neutrophil-derived exosomes exacerbated EMT and angiogenesis. Moreover, miR-4780 can regulate its target gene SOX11 to effect EMT and angiogenesis in CRC cell lines. CRC with liver metastasis model also validated that aberrant expression of miR-4780 in N2-like neutrophil exosomes exacerbated tumor metastasis and development of tumor via EMT and angiogenesis. In conclusion, our current findings reveal an important mechanism by which mR-4780 from N2-like neutrophil exosomes exacerbates tumor metastasis and progression via EMT and angiogenesis.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2023 ","pages":"2759679"},"PeriodicalIF":4.3,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9996310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Mesenchymal Stem Cell-Derived Exosomes and miR17-5p Inhibitor on Multicellular Liver Fibrosis Microtissues.","authors":"Farnaz Sani,&nbsp;Mina Soufi Zomorrod,&nbsp;Negar Azarpira,&nbsp;Masoud Soleimani","doi":"10.1155/2023/8836452","DOIUrl":"10.1155/2023/8836452","url":null,"abstract":"<p><strong>Background: </strong>Although several studies have been conducted on modeling human liver disease, it is still challenging to mimic nonalcoholic fatty liver disease in vitro. Here, we aimed to develop a fibrotic liver microtissue composed of hepatocytes, hepatic stellate, and endothelial cells. In addition, the therapeutic effects of umbilical cord mesenchymal stem cell-derived exosomes (UC-MSC-EXO) and anti-miR17-5p as new antifibrotic drugs were investigated.</p><p><strong>Methods: </strong>To create an effective preclinical fibrosis model, multicellular liver microtissues (MLMs) consisting of HepG2, LX2, and HUVECs were cultured and supplemented with a mixture of palmitic acid and oleic acid for 96 hr. Then, MLMs were exposed to UC-MSC-EXO and anti-miR17-5p in different groups. The results of cell viability, reactive oxygen species (ROS) production, liver enzyme levels, inflammation, and histopathology were analyzed to assess the treatment efficacy. Furthermore, the expression of collagen I (COL I) and <i>α</i>-smooth muscle actin (<i>α</i>-SMA) as critical matrix components, transforming growth factor beta (TGF-<i>β</i>), and miR-17-5p were measured.</p><p><strong>Results: </strong>Free fatty acid supplementation causes fibrosis in MLMs. Our results demonstrated that UC-MSC-EXO and anti-miR17-5p attenuated TGF-<i>β</i>1, interleukin-1<i>β</i>, and interleukin-6 in all experimental groups. According to the suppression of the TGF-<i>β</i>1 pathway, LX2 activation was inhibited, reducing extracellular matrix proteins, including COL I and <i>α</i>-SMA. Also, miR-17-5p expression was elevated in fibrosis conditions. Furthermore, we showed that our treatments decreased alanine aminotransferase and aspartate aminotransferase, and increased albumin levels in the culture supernatant. We also found that both MSC-EXO and MSC-EXO + anti-miR17-5p treatments could reduce ROS production.</p><p><strong>Conclusion: </strong>Our findings indicated that anti-miR17-5p and MSC-EXO might be promising therapeutic options for treating liver fibrosis. Furthermore, EXO + anti-miR had the best effects on boosting the fibrotic markers. Therefore, we propose this novel MLM model to understand fibrosis mechanisms better and develop new drugs.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2023 ","pages":"8836452"},"PeriodicalIF":4.3,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10421706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9989951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Donor Mesenchymal Stem Cells Program Bone Marrow, Altering Macrophages, and Suppressing Endometriosis in Mice.","authors":"Shutaro Habata, Ramanaiah Mamillapalli, Abdullah Ucar, Hugh S Taylor","doi":"10.1155/2023/1598127","DOIUrl":"10.1155/2023/1598127","url":null,"abstract":"<p><p>Endometriosis is a chronic inflammatory gynecological disorder regulated by estrogen and characterized by the growth of endometrial tissue outside the uterus. We have previously demonstrated that mesenchymal stem cells (MSCs) contribute directly to endometriosis. Here, we investigated an indirect effect; we hypothesized that MSCs may also impact the bone marrow (BM) by regulating bone marrow-derived inflammatory cells. Endometriosis was induced in mice by transplanting uterine tissue into recipient mice followed by BM transplant. Control or MSC conditioned BM was injected retro-orbitally. Direct administration of MSCs outside of the setting of BM conditioning did not alter endometriosis. Coculture of an undifferentiated macrophage cell line with MSCs in vitro led to a reduction of M1 and increased M2 macrophages as determined by fluorescence-activated cell sorting and western blot. Conditioning of BM with MSCs and transplantation into a mouse model inhibited endometriotic lesion development and reduced lesion volume by sevenfold compared to BM transplant without MSCs conditioning. Immunohistochemistry and immunofluorescence showed that MSC conditioned BM reduced the infiltration of macrophages and neutrophils into endometriotic lesions by twofold and decreased the proportion of M1 compared to M2 macrophages, reducing inflammation and likely promoting tissue repair. Expression of several inflammatory markers measured by quantitative real-time polymerase chain reaction, including tumor necrosis factor alpha and CXCR4, was decreased in the conditioned BM. Donor MSCs were not detected in recipient BM or endometriotic lesions, suggesting that MSCs actively program the transplanted BM. Taken together, these data show that individual characteristics of BM have an unexpected role in the development of endometriosis. BM remodeling and alterations in the inflammatory response are also potential treatments for endometriosis. Identification of the molecular basis for BM programing by MSCs will lead to a better understanding of the immune system contribution to this disease and may lead to new therapeutic targets for endometriosis.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2023 ","pages":"1598127"},"PeriodicalIF":3.8,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403325/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9954341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesenchymal Stem Cells Inhibit Epithelial-to-Mesenchymal Transition by Modulating the IRE1<i>α</i> Branch of the Endoplasmic Reticulum Stress Response.","authors":"Ruixi Luo, Yaqiong Wei, Peng Chen, Jing Zhang, La Wang, Wenjia Wang, Ping Wang, Weiyi Tian","doi":"10.1155/2023/4483776","DOIUrl":"10.1155/2023/4483776","url":null,"abstract":"<p><strong>Background: </strong>Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial lung disease, and it carries a poor prognosis due to a lack of efficient diagnosis methods and treatments. Epithelial-mesenchymal transition (EMT) plays a key role in IPF pathogenesis. Endoplasmic reticulum (ER) stress contributes to fibrosis via EMT-mediated pathways. Mesenchymal stem cell (MSC) transplantation is a promising treatment strategy for pulmonary fibrosis and ameliorates lung fibrosis in animal models via paracrine effects. However, the specific mechanisms underlying the effect of transplanted MSCs are not known. We previously reported that MSCs attenuate endothelial injury by modulating ER stress and endothelial-to-mesenchymal transition. The present study investigated whether modulation of ER stress- and EMT-related pathways plays essential roles in MSC-mediated alleviation of IPF.</p><p><strong>Methods and results: </strong>We constructed a A549 cell model of transforming growth factor-<i>β</i>1 (TGF-<i>β</i>1)-induced fibrosis. TGF-<i>β</i>1 was used to induce EMT in A549 cells, and MSC coculture decreased EMT, as indicated by increased E-cadherin levels and decreased vimentin levels. ER stress participated in TGF-<i>β</i>1-induced EMT in A549 cells, and MSCs inhibited the expression of XBP-1s, XBP-1u, and BiP, which was upregulated by TGF-<i>β</i>1. Inhibition of ER stress contributed to MSC-mediated amelioration of EMT in A549 cells, and modulation of the IRE1<i>α</i>-XBP1 branch of the ER stress pathway may have played an important role in this effect. MSC transplantation alleviated bleomycin (BLM)-induced pulmonary fibrosis in mice. MSC treatment decreased the expression of ER stress- and EMT-related genes and proteins, and the most obvious effect of MSC treatment was inhibition of the IRE1<i>α</i>/XBP1 pathway.</p><p><strong>Conclusions: </strong>The present study demonstrated that MSCs decrease EMT by modulating ER stress and that blockade of the IRE1<i>α</i>-XBP1 pathway may play a critical role in this effect. The current study provides novel insight for the application of MSCs for IPF treatment and elucidates the mechanism underlying the preventive effects of MSCs against pulmonary fibrosis.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2023 ","pages":"4483776"},"PeriodicalIF":3.8,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10397497/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9949049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal Decrease of Macrophage ALKBH5 Expression Causes Abnormal Polarization and Inhibits Osteoblast Differentiation.","authors":"Junquan Weng,&nbsp;Haidong Fan,&nbsp;Huijuan Liu,&nbsp;Su Tang,&nbsp;Yuyan Zheng","doi":"10.1155/2023/9974098","DOIUrl":"10.1155/2023/9974098","url":null,"abstract":"<p><p>Peri-implant tissue inflammation is an inflammatory injury that occurs in the soft and hard tissues surrounding the implant and is the main cause of short- or long-term failure of implant prosthetic restorations, which is compounded by bone loss and bone destruction in the alveolar bone of diabetes patients with peri-implantitis. However, the mechanisms underlying the persistence of diabetic peri-implantitis, as well as the essential connections and key molecules that regulate its start and progression, remain unknown. In this study, we discovered that M1 macrophage polarization was abnormally enhanced in diabetic peri-implantitis and influenced the osteogenic differentiation of mesenchymal stem cells. RNA sequencing revealed that ALKBH5 expression was abnormally reduced in diabetic peri-implantitis. Further mechanism study showed that ALKBH5 and its mediated m⁶A can influence osteogenic differentiation, which in turn influences the persistence of diabetic peri-implantitis. Our findings present a new mechanism for the suppression of osteoblast development in diabetic peri-implantitis and a new treatment strategy to promote anabolism by inhibiting ALKBH5.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2023 ","pages":"9974098"},"PeriodicalIF":4.3,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10372297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9911478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human Umbilical Mesenchymal Stem Cells-Derived Microvesicles Attenuate Formation of Hypertrophic Scar through Multiple Mechanisms","authors":"Qun Qian, N. Zhu, Wenzhe Li, Songlin Wan, Dongcheng Wu, Yun-hua Wu, Weicheng Liu","doi":"10.1155/2023/9125265","DOIUrl":"https://doi.org/10.1155/2023/9125265","url":null,"abstract":"Mesenchymal stem cells and the derived extracellular microvesicles are potential promising therapy for many disease conditions, including wound healing. Since current therapeutic approaches do not satisfactorily attenuate or ameliorate formation of hypertrophic scars, it is necessary to develop novel drugs to achieve better outcomes. In this study, we investigated the effects and the underlying mechanisms of human umbilical mesenchymal stem cells (HUMSCs)-derived microvesicles (HUMSCs-MVs) on hypertrophic scar formation using a rabbit ear model and a human foreskin fibroblasts (HFF) culture model. The results showed that HUMSCs-MVs reduced formation of hypertrophic scar tissues in the rabbit model based on appearance observation, and hematoxylin and eosin (H&E), Masson, and immunohistochemical stainings. HUMSCs-MVs inhibited invasion of HFF cells and decreased the levels of the α-SMA, N-WASP, and cortacin proteins. HUMSCs-MVs also inhibited cell proliferation of HFF cells. The MMP-1, MMP-3, and TIMP-3 mRNA levels were significantly increased, and the TIMP-4 mRNA level and the NF-kB p65/β-catenin protein levels were significantly decreased in HFF cells after HUMSCs-MVs treatment. The p-SMAD2/3 levels and the ratios of p-SMAD2/3/SMAD2/3 were significantly decreased in both the wound healing tissues and HFF cells after HUMSCs-MVs treatment. CD34 levels were significantly decreased in both wound healing scar tissues and HFF cells after HUMSCs-MVs treatment. The VEGF-A level was also significantly decreased in HFF cells after HUMSCs-MVs treatment. The magnitudes of changes in these markers by HUMSCs-MVs were mostly higher than those by dexamethasone. These results suggested that HUMSCs-MVs attenuated formation of hypertrophic scar during wound healing through inhibiting proliferation and invasion of fibrotic cells, inflammation and oxidative stress, Smad2/3 activation, and angiogenesis. HUMSCs-MVs is a potential promising drug to attenuate formation of hypertrophic scar during wound healing.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44281132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors Associated with 28-day Critical Illness Development During the First Wave of COVID-19.","authors":"Uluhan Sili, Pınar Ay, Hüseyin Bilgin, Ahmet Topuzoğlu, Elif Tükenmez-Tigen, Buket Ertürk-Şengel, Dilek Yağçı-Çağlayık, Baran Balcan, Derya Kocakaya, Şehnaz Olgun-Yıldızeli, Fethi Gül, Beliz Bilgili, Rabia Can-Sarınoğlu, Ayşegül Karahasan-Yağcı, Lütfiye Mülazimoğlu-Durmuşoğlu, Emel Eryüksel, Zekaver Odabaşı, Haner Direskeneli, Sait Karakurt, Volkan Korten","doi":"10.36519/idcm.2023.206","DOIUrl":"10.36519/idcm.2023.206","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to define the predictors of critical illness development within 28 days postadmission during the first wave of the COVID-19 pandemic.</p><p><strong>Materials and methods: </strong>We conducted a prospective cohort study including 477 PCR-positive COVID-19 patients admitted to a tertiary care hospital in Istanbul from March 12 to May 12, 2020.</p><p><strong>Results: </strong>The most common presenting symptoms were cough, dyspnea, and fatigue. Critical illness developed in 45 (9.4%; 95% CI=7.0%-12.4%) patients. In the multivariable analysis, age (hazard ratio (HR)=1.05, <i>p</i><0.001), number of comorbidities (HR=1.33, <i>p</i>=0.02), procalcitonin ≥0.25 µg/L (HR=2.12, <i>p</i>=0.03) and lactate dehydrogenase (LDH) ≥350 U/L (HR=2.04, <i>p</i>=0.03) were independently associated with critical illness development. The World Health Organization (WHO) ordinal scale for clinical improvement on admission was the strongest predictor of critical illness (HR=4.15, <i>p</i><0.001). The patients hospitalized at the end of the study period had a much better prognosis compared to the patients hospitalized at the beginning (HR=0.14; <i>p</i>=0.02). The C-index of the model was 0.92.</p><p><strong>Conclusion: </strong>Age, comorbidity number, the WHO scale, LDH, and procalcitonin were independently associated with critical illness development. Mortality from COVID-19 seemed to be decreasing as the first wave of the pandemic advanced.</p><p><strong>Graphic abstract: </strong>Graphic Abstract.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2016 1","pages":"94-105"},"PeriodicalIF":0.0,"publicationDate":"2023-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86383685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Biological Properties and Clinical Application of Mesenchymal Stem Cells from the Mesoderm and Ectoderm.","authors":"Zhenning Wang,&nbsp;Meng Huang,&nbsp;Yu Zhang,&nbsp;Xiaoxia Jiang,&nbsp;Lulu Xu","doi":"10.1155/2023/4547875","DOIUrl":"10.1155/2023/4547875","url":null,"abstract":"<p><p>Since the discovery of mesenchymal stem cells (MSCs) in the 1970s, they have been widely used in the treatment of a variety of diseases because of their wide sources, strong differentiation potential, rapid expansion in vitro, low immunogenicity, and so on. At present, most of the related research is on mesoderm-derived MSCs (M-MSCs) such as bone marrow MSCs and adipose-derived MSCs. As a type of MSC, ectoderm-derived MSCs (E-MSCs) have a stronger potential for self-renewal, multidirectional differentiation, and immunomodulation and have more advantages than M-MSCs in some specific conditions. This paper analyzes the relevant research development of E-MSCs compared with that of M-MSCs; summarizes the extraction, discrimination and culture, biological characteristics, and clinical application of E-MSCs; and discusses the application prospects of E-MSCs. This summary provides a theoretical basis for the better application of MSCs from both ectoderm and mesoderm in the future.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2023 ","pages":"4547875"},"PeriodicalIF":4.3,"publicationDate":"2023-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10276766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9653931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-125b-5p/STAT3 Axis Regulates Drug Resistance in Osteosarcoma Cells by Acting on ABC Transporters.","authors":"Yang Yang, Yueyuan Chen, Jiajia Liu, Bo Zhang, Linlin Yang, Jianhua Xue, Zexu Zhang, Lili Qin, Rongpeng Bian","doi":"10.1155/2023/9997676","DOIUrl":"10.1155/2023/9997676","url":null,"abstract":"<p><strong>Background: </strong>The poor prognosis of the highly malignant tumor osteosarcoma stems from its drug resistance and therefore exploring its resistance mechanisms will help us identify more effective treatment options. However, the effects of miR-125b-5p on drug resistance in osteosarcoma cells are still unclear.</p><p><strong>Methods: </strong>To study the effects of miR-125b-5p on drug resistance in osteosarcoma cells. Osteosarcoma-resistant miR-125b-5p was obtained from the databases GeneCards and g:Profiler. CCK8, western blot, and transwell were applied for the detection of the miR-125b-5p effects on proliferation, migration, invasion, apoptosis, and drug resistance in osteosarcoma. Bioinformatics is aimed at demonstrating the targeting factor miR-125b-5p, performing protein interaction enrichment analysis by Metascape, and finally validating by binding sites.</p><p><strong>Results: </strong>Upregulation of miR-125b-5p restrains proliferation, migration, and invasion of osteosarcoma and promotes apoptosis. In addition, miR-125b-5p can restore drug sensitivity in drug-resistant osteosarcoma. miR-125-5p restrains the signal transducer and inhibits the transcription 3 (STAT3) expression activator via targeting its 3'-UTR. STAT3 affects drug-resistant osteosarcoma to regulate the ABC transporter.</p><p><strong>Conclusion: </strong>miR-125b-5p/STAT3 axis mediates the drug resistance of osteosarcoma by acting on ABC transporter.</p>","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":"2023 ","pages":"9997676"},"PeriodicalIF":4.3,"publicationDate":"2023-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10163973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9813282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Construction of an Excellent 7 mRNAsi-Related Gene Model Based on Cancer Stem Cells for Predicting Survival Outcome of Cervical Cancer","authors":"Yang Liu, Lin Yang, Hao Liang, Jianhua Zeng, Yuanyuan Hua, Huancheng Wu","doi":"10.1155/2023/8383058","DOIUrl":"https://doi.org/10.1155/2023/8383058","url":null,"abstract":"Background. Cervical cancer (CC) is one of the most frequent female malignancy. Cancer stem cells (CSCs) positively affect survival outcomes in cancer patients, but in cervical cancer, the mechanism of tumor stem cells is still uncertain. Methods. RNA-seq data and related clinical follow-up of patients suffering from CC were from TCGA. Consensus clustering screened prognostic mRNAsi-related genes and identified molecular subtypes for CC. Based on the overlapping differentially expressed genes (DEGs) in subtypes, we employed LASSO and multivariate Cox regression to screen prognostic-related genes and established the RiskScore system. The patients were grouped by RiskScore, the prognosis was analyzed by the Kaplan-Meier (K-M) curve among the various groups, and the precision of the RiskScore was assessed by the ROC curve. Finally, the potential worth of RiskScore in immunotherapy/chemotherapy response was assessed by evaluating TIDE scores and chemotherapy drug \u0000 \u0000 \u0000 \u0000 IC\u0000 \u0000 \u0000 50\u0000 \u0000 \u0000 \u0000 values. Results. We noticed that patients with low mRNAsi had a shorter survival and then identified three molecular subtypes (C1-3), with the C1 having the worst prognosis and the lowest mRNAsi. Finally, we identified 7 prognostic-related genes (SPRY4, PPP1R14A, MT1A, DES, SEZ6L2, SLC22A3, and CXCL8) via LASSO and Cox regression analysis. We established a 7-gene model defined RiskScore to predict the prognosis of CC patients. K-M curve indicated that low RiskScore patients had improved prognosis, and ROC curves indicated that RiskScore could precisely direct the prognostic evaluation for those suffering from the cancer. This was also confirmed in the GSE44001 and GSE52903 external cohorts. Patients were more sensitive to immunotherapy if with low RiskScore, and RiskScore exhibited precise assessment ability in predicting response to immunological therapy in CC patients. Conclusion. CC stemness is associated with patient prognosis, and the RiskScore constructed based on stemness characteristics is an independent prognostic index, which is expected to be a guide for immunotherapy, providing a new idea for CC clinical practice.","PeriodicalId":21962,"journal":{"name":"Stem Cells International","volume":" ","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47513177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}