Molecular and Cellular Probes最新文献

{"title":"Advanced meta-analysis on therapeutic strategies of mesenchymal derived exosome for diabetic chronic wound healing and tissue remodeling","authors":"Gunjan ,&nbsp;Himanshu ,&nbsp;Ramendra Pati Pandey ,&nbsp;Riya Mukherjee ,&nbsp;Chung-Ming Chang","doi":"10.1016/j.mcp.2024.101974","DOIUrl":"10.1016/j.mcp.2024.101974","url":null,"abstract":"<div><h3>Background</h3><p>Exosome (EXOs) are rapidly being identified as key mediators of cell-to-cell communication. They convey biologically active molecules to target cells, serve important roles in a range of physiological and pathological processes, and have enormous potential as novel therapeutic strategies.</p></div><div><h3>Methods</h3><p>Preclinical research published between 2019 and 2023 provided the study's data searched on different medline search engine, and <span><span>clinicaltrials.gov</span><svg><path></path></svg></span> was searched for clinical data. These papers were chosen because they are relevant to the research of mesenchymal stem cell-derived exosomes (MSC-EXOs). Thematic synthesis and meta-analysis were used to perform the meta-analysis of diabetic wound healing.</p></div><div><h3>Results</h3><p>For data extraction, a total of 18 preclinical and 4 clinical trials were selected. Preclinical investigations involving EXOs across various animal wound healing models showed promising potential for treatment. Specifically, following EXO treatment, there was a notable correlation with wound closure rates, with a pooled proportion of 46 % (95 % CI: 0.34; 0.59) and τ² of 0.0593 after 3 ± 2 days, 54 % (95 % CI: 0.43; 0.65) and τ² of 0.0465 after 7 ± 2 days, and 69 % (95 % CI: 0.62; 0.76) and τ² of 0.0221 after 14 ± 2 days, with an egger's test p-value of &lt;0.01. Further investigation into heterogeneity was conducted through subgroup analysis based on the source of EXO and the animal model utilized in the study.</p></div><div><h3>Conclusions</h3><p>EXOs are proving to be viable platforms for the treatment of a wide range of disorders in clinical trials. MSC-EXOs exhibited significant diabetic wound healing capabilities across diverse outcomes including wound closure, increase angiogenesis, immunomodulatory ability and skin regeneration with its typical structure and functions.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"77 ","pages":"Article 101974"},"PeriodicalIF":2.3,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000264/pdfft?md5=18142ca238c627bd6e07bb801809086f&pid=1-s2.0-S0890850824000264-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141749527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of ZIC2 on immune infiltration and ceRNA axis regulation in lung adenocarcinoma via bioinformatics and experimental studies","authors":"Hongjie Huo,&nbsp;Yu Feng,&nbsp;Qiong Tang","doi":"10.1016/j.mcp.2024.101971","DOIUrl":"10.1016/j.mcp.2024.101971","url":null,"abstract":"<div><h3>Objective</h3><p>This study aimed to conclude the effect and mechanism of ZIC2 on immune infiltration in lung adenocarcinoma (LUAD).</p></div><div><h3>Methods</h3><p>Expression of ZIC2 in several kinds of normal tissues of TCGA data was analyzed and its correlation with the baseline characteristic of LUAD patients were analyzed. The immune infiltration analysis of LUAD patients was performed by CIBERSORT algorithm. The correlation analysis between ZIC2 and immune cell composition was performed. Additionally, the potential upstream regulatory mechanisms of ZIC2 were predicted to identify the possible miRNAs and lncRNAs that regulated ZIC2 in LUAD. <em>In vitro</em> and <em>in vivo</em> experiments were also conducted to confirm the potential effect of ZIC2 on cell proliferation and invasion ability of LUAD cells.</p></div><div><h3>Results</h3><p>ZIC2 expression was decreased in various normal tissues, but increased in multiple tumors, including LUAD, and correlated with the prognosis of LUAD patients. Enrichment by GO and KEGG suggested the possible association of ZIC2 with cell cycle and p53 signal pathway. ZIC2 expression was significantly correlated with T cells CD4 memory resting, Macrophages M1, and plasma cells, indicating that dysregulated ZIC2 expression in LUAD may directly influence immune infiltration. ZIC2 might be regulated by several different lncRNA-mediated ceRNA mechanisms. <em>In vitro</em> experiments validated the promotive effect of ZIC2 on cell viability and invasion ability of LUAD cells. In vivo experiments validated ZIC2 can accelerate tumor growth in nude mouse.</p></div><div><h3>Conclusion</h3><p>ZIC2 regulated by different lncRNA-mediated ceRNA mechanisms may play a critical regulatory role in LUAD through mediating the composition of immune cells in tumor microenvironment.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"76 ","pages":"Article 101971"},"PeriodicalIF":2.3,"publicationDate":"2024-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000239/pdfft?md5=afb0aacc5967722a8539bb9384128c97&pid=1-s2.0-S0890850824000239-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141560215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A dual-labeling molecule for efficient drug discovery of mitochondrial-lysosomal interactions","authors":"Jinfang Wu ,&nbsp;Xiaolei Wang ,&nbsp;Xiang Li ,&nbsp;Zixuan Zhu ,&nbsp;Zhongcheng Cui ,&nbsp;Tao Zhang ,&nbsp;Weiwei Zou ,&nbsp;Guanying Han","doi":"10.1016/j.mcp.2024.101968","DOIUrl":"10.1016/j.mcp.2024.101968","url":null,"abstract":"<div><p>The close association between organelle interactions, such as mitochondrial–lysosomal interactions, and various diseases, including tumors, remains a challenge for drug discovering and identification. Conventional evaluation methods are often complex and multistep labeling procedures often generate false positives, such as cell damage. To overcome these limitations, we employed a single dual-color reporting molecule called Coupa, which labels mitochondria and lysosomes as blue and red, respectively. This facilitates the evaluation and discovering of drugs targeting mitochondria–lysosome contact (MLC). Using Coupa, we validated the effectiveness of various known antitumor drugs in intervening MLC by assessing their effect on key aspects, such as status, localization, and quantity. This provides evidence for the accuracy and applicability of our dual-color reporting molecule. Notably, we observed that several structural isomers of drugs, including Urolithin (A/B/C), exhibited distinct effects on MLC. In addition, Verteporfin and TEAD were found to induce anti-tumor effects by controlling MLC at the organelle level, suggesting a potential new mechanism of action. Collectively, Coupa offers a novel scientific tool for discovering drugs that target mitochondrial–lysosomal interactions. It not only distinguished the differential effects of structurally similar drugs on the same target, but also reveals new mechanisms underlying the reported antitumor properties of existing drugs. Ultimately, our findings contribute to the advancement of drug discovery and provide valuable insights into the complex interactions between organelles in a disease context.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"76 ","pages":"Article 101968"},"PeriodicalIF":2.3,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000203/pdfft?md5=7b6d935625207b45235175c549e214bc&pid=1-s2.0-S0890850824000203-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141499476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in omics-based biomarker discovery for biliary tract malignancy Diagnosis:A narrative review","authors":"Tao Xu ,&nbsp;Lingna Lyu ,&nbsp;Junfu Zheng ,&nbsp;Lei Li","doi":"10.1016/j.mcp.2024.101970","DOIUrl":"10.1016/j.mcp.2024.101970","url":null,"abstract":"<div><p>Biliary tract neoplasms, which originate from the intrahepatic or extrahepatic biliary epithelium, are relatively rare but diagnostically challenging types of tumours, and their morbidity and mortality have increased in recent years. Due to ineffective early diagnostic methods, once detected, patients are in an advanced stage with a poor prognosis and few treatment options. With the development of omics technologies, the associations between microorganisms, bile acid and salts, noncoding RNAs and biliary tract malignancies have been gradually revealed, providing new methods for the discovery of diagnostic biomarkers. Here, we review the research advances in microbiomics, transcriptomics, metabolomics, and proteomics in the discovery of diagnostic biomarkers for biliary tract malignancies.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"76 ","pages":"Article 101970"},"PeriodicalIF":2.3,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000227/pdfft?md5=9d1d24a52fd9eb3267e39be1e548a8a7&pid=1-s2.0-S0890850824000227-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effectiveness of ruxolitinib and cyclophosphamide combination on T helper 17 and regulatory T cells in rat experimental membranous glomerulonephritis","authors":"Rahim Iranzad ,&nbsp;Maryam Hosseini ,&nbsp;Mahdi Bagheri ,&nbsp;Mohammad Sadegh Soltani-Zangbar ,&nbsp;Mohammadbagher Pirouzpanah ,&nbsp;Negin Biglari ,&nbsp;Mohammadali Zolfaghari ,&nbsp;Arash Khaki ,&nbsp;Leili Aghebati-Maleki ,&nbsp;Leila Roshangar ,&nbsp;Elham Badihi ,&nbsp;Farshid Afandideh ,&nbsp;Reihane Shahabirad ,&nbsp;Ali Akbar Shekarchi ,&nbsp;Javad Ahmadian Heris ,&nbsp;Jalal Etemadi ,&nbsp;Mehdi Yousefi","doi":"10.1016/j.mcp.2024.101969","DOIUrl":"10.1016/j.mcp.2024.101969","url":null,"abstract":"<div><p>The progression and pathogenesis of membranous glomerulonephritis (MGN) are inextricably linked to chronic inflammation. Despite improving clinical remission rates due to the application of cyclophosphamide (CYC), treatment of MGN still requires further exploration. Ruxolitinib (Ruxo) negatively affects the signaling pathways participating in the production of pro-inflammatory cytokines. Hence, we investigated whether the combination of CYC and Ruxo can modulate inflammation through influencing T helper 17 (Th17) lineages and regulatory T cells (Tregs). Passive Heymann nephritis (PHN), an experimental model of MGN, was induced in a population of rats. Then, the animals were divided into five groups: PHN, CYC-receiving, Ruxo-receiving, CYC-Ruxo-receiving PHN rats, and healthy controls. After 28 days of treatment, biochemistry analysis was performed and splenocytes were isolated for flowcytometry investigation of Th17 cells and Tregs. The correlative transcription factors of the cells, alongside their downstream cytokine gene expressions, were also assessed using real-time PCR. Furthermore, serum cytokine signatures for the lymphocytes were determined through ELISA. The combination of CYC and Ruxo significantly reduced the serum values of urea in rats versus the PHN group (24.62 ± 7.970 vs. 40.60 ± 10.81 mg/dL). In contrast to Treg's activities, the functionality of Th17 cells noticeably increased not only in PHN rats but also in CYC or Ruxo-receiving PHN animals when compared with the control (10.60 ± 2.236, 8.800 ± 1.465, 8.680 ± 1.314 vs. 4.420 ± 1.551 %). However, in comparison to the PHN group, the incidence of Th17 cells notably fell in rats receiving CYC and Ruxo (10.60 ± 2.236 vs. 6.000 ± 1.373 %) in favor of the Treg's percentage (5.020 ± 1.761 vs. 8.980 ± 1.178 %), which was verified by the gene expressions and cytokine productions correlative to these lymphocytes. The combination of CYC and Ruxo was able to decline Th17 cells in favor of Tregs improvement in PHN rats, suggesting an innovative combination therapy in MGN treatment approaches.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"76 ","pages":"Article 101969"},"PeriodicalIF":2.3,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000215/pdfft?md5=f660c977035504dede14eb1d7e181774&pid=1-s2.0-S0890850824000215-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA lnc-SPRR2G-2 contributes to keratinocyte hyperproliferation and inflammation in psoriasis by activating the STAT3 pathway and downregulating KHSRP","authors":"Yunyue Zhen ,&nbsp;Xueqing Li ,&nbsp;Shan Huang ,&nbsp;Ruijie Wang ,&nbsp;Luan Yang ,&nbsp;Yingjian Huang ,&nbsp;Jianjun Yan ,&nbsp;Jiaoying Ju ,&nbsp;He Wen ,&nbsp;Qing Sun","doi":"10.1016/j.mcp.2024.101967","DOIUrl":"10.1016/j.mcp.2024.101967","url":null,"abstract":"<div><p>Psoriasis is a chronic inflammatory disease characterized by increased keratinocyte proliferation and local inflammation. Long noncoding RNAs (lncRNAs) play important regulatory roles in many immune-mediated diseases, including psoriasis. In this study, we aimed to investigate the role and mechanism of lnc-SPRR2G-2 (SPRR2G) in M5-treated psoriatic keratinocytes.</p><p>Fluorescence in situ hybridization and quantitative real-time polymerase chain reaction (qRT-PCR) showed that lnc-SPRR2G-2 was significantly upregulated in psoriasis tissues and psoriatic keratinocytes. In psoriatic keratinocytes, functional and molecular experiment analyses demonstrated that SPRR2G regulated proliferation, cell cycle and apoptosis, and induced the expression of S100 calcium binding protein A7 (S100A7), interleukin (IL)-1β, IL-8 and C-X-C motif chemokine ligand 10 (CXCL10). The function of SPRR2G in psoriasis is related to the STAT3 signaling pathway and can be inhibited by a STAT3 inhibitor. Moreover, KH-type splicing regulatory protein (KHSRP) was proved to be regulated by lnc-SPRR2G-2 and to control the mRNA decay of psoriasis-related cytokines (<em>p</em> &lt; 0.05). In summary, we reported the functions of lnc-SPRR2G-2 and KHSRP in psoriasis. Our findings provide new insights for the further exploration of the pathogenesis and treatment of psoriasis.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"76 ","pages":"Article 101967"},"PeriodicalIF":2.3,"publicationDate":"2024-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000197/pdfft?md5=a578745942bbff469fe41fbcb19b0911&pid=1-s2.0-S0890850824000197-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141471956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baicalein attenuates oxidative damage in mice haematopoietic cells through regulation of PDGFRβ","authors":"Huanying Ren,&nbsp;Jingyi Feng,&nbsp;Minglin Hong,&nbsp;Zhuang Liu,&nbsp;Daniel Muteb Muyey,&nbsp;Yaofang Zhang,&nbsp;Zhifang Xu,&nbsp;Yanhong Tan,&nbsp;Fanggang Ren,&nbsp;Jianmei Chang,&nbsp;Xiuhua Chen,&nbsp;Hongwei Wang","doi":"10.1016/j.mcp.2024.101966","DOIUrl":"10.1016/j.mcp.2024.101966","url":null,"abstract":"<div><p>Platelet-derived growth factor receptor β (PDGFRβ) plays a crucial role in murine haematopoiesis. Baicalein (BAI), a naturally occurring flavonoid, can alleviate disease damage through anti-oxidative, anti-apoptotic, and anti-inflammatory mechanisms. However, whether BAI attenuates oxidative damage in murine haematopoietic cells by PDGFRβ remains unexplored. In this study, we utilized a <em>tert</em>-butyl hydroperoxide (TBHP)-induced BaF3 cell injury model and an ionising radiation (IR)-induced mice injury model to investigate the impact of the presence or absence of PDGFRβ on the pharmacological effects of BAI. In addition, the BAI-PDGFRβ interaction was characterized by molecular docking and dynamics simulations. The results show that a specific concentration of BAI led to increased cell viability, reduced reactive oxygen species (ROS) content, upregulated nuclear factor erythroid 2-related factor 2 (NRF2) expression, and its downstream target genes heme oxygenase 1 (HO-1) and NAD(P)H Quinone Dehydrogenase 1 (NQO1), and activated protein kinase B (AKT) pathway in cells expressing PDGFRβ plasmid and experiencing damage. Similarly, BAI elevated lineage⁻Sca1⁺cKIT⁺ (LSK) cell proportion, promoted haematopoietic restoration, enhanced NRF2-mediated antioxidant response in PDGFRβ^+/+ mice. However, despite BAI usage, PDGFRβ knockout mice (PDGFRβ^−/−) showed lower LSK proportion and less antioxidant capacity than the total body irradiation (TBI) group. Furthermore, we demonstrated an interaction between BAI and PDGFRβ at the molecular level. Collectively, our results indicate that BAI attenuates oxidative stress injury and helps promote haematopoietic cell recovery through regulation of PDGFRβ.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"76 ","pages":"Article 101966"},"PeriodicalIF":3.3,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000185/pdfft?md5=ade0e912fe1ab928c0732f7842502cee&pid=1-s2.0-S0890850824000185-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141312066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A review of local anesthetic-induced heart toxicity using human induced pluripotent stem cell-derived cardiomyocytes","authors":"Ting Jiang ,&nbsp;Chao Ma ,&nbsp;Zitong Wang ,&nbsp;Yi Miao","doi":"10.1016/j.mcp.2024.101965","DOIUrl":"10.1016/j.mcp.2024.101965","url":null,"abstract":"<div><p>Local anesthetic (LA) cardiotoxicity is one of the main health problems in anesthesiology and pain management. This study reviewed the reported LA-induced cardiac toxicity types, risk factors, management, and mechanisms, with attention to the use of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in heart toxicity research. Important scientific databases were searched to find relevant articles. We briefly assessed the reported cardiotoxic effects of different types of LA drugs, including ester- and amide-linked LA agents. Furthermore, cardiotoxic effects and clinical manifestations, strategies for preventing and managing LA-induced cardiotoxic effects, pharmacokinetics, pharmacodynamics, and sodium channel dynamics regarding individual variability and genetic influences were discussed in this review. The applications and importance of hiPSC-CMs cellular model for evaluating the cardiotoxic effects of LA drugs were discussed in detail. This review also explored hiPSC-CMs' potential in risk assessment, drug screening, and developing targeted therapies. The main mechanisms underlying LA-induced cardiotoxicity included perturbation in sodium channels, ROS production, and disorders in the immune system response due to the presence of LA drugs. Furthermore, drug-specific characteristics including pharmacokinetics and pharmacodynamics are important determinants after LA drug injection. In addition, individual patient factors such as age, comorbidities, and genetic variability emphasize the need for a personalized approach to mitigate risks and enhance patient safety. The strategies outlined for the prevention and management of LA cardiotoxicity underscore the importance of careful dosing, continuous monitoring, and the immediate availability of resuscitation equipment. This comprehensive review can be used to guide future investigations into better understanding LA cardiac toxicities and improving patient safety.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"76 ","pages":"Article 101965"},"PeriodicalIF":3.3,"publicationDate":"2024-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000173/pdfft?md5=1cb3acb73e52161bab43535f6fb19949&pid=1-s2.0-S0890850824000173-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes regulate doxorubicin resistance in breast cancer via miR-34a-5p/NOTCH1","authors":"Nan-nan Chen ,&nbsp;Ke-fan Zhou ,&nbsp;Zhuang Miao ,&nbsp;Yun-xia Chen ,&nbsp;Jing-xia Cui ,&nbsp;Su-wen Su","doi":"10.1016/j.mcp.2024.101964","DOIUrl":"10.1016/j.mcp.2024.101964","url":null,"abstract":"<div><p>Breast cancer (BRCA) is the most common cancer among women. Adriamycin (ADR), also known as doxorubicin (Dox), is a commonly used chemotherapeutic agent for BRCA patients, however, the susceptibility of tumor cells to develop resistance to Dox has severely limited its clinical use. One new promising therapeutic target for breast cancer patients is exosomes. The objective of this study was to investigate the role of exosomes in regulating Dox resistance in BRCA.</p><p>In this study, the exosomes from both types of cells were extracted by differential centrifugation. The effect of exosomes on drug resistance was assessed by laser confocal microscopy, MTT assay, and qRT-PCR. The miRNA was transfected into cells using Lipofectamine 2000, which was then evaluated for downstream genes and changes in drug resistance.</p><p>Exosomes from MCF-7 cells (MCF-7/exo) and MCF-7/ADR cells (ADR/exo) were effectively extracted in this study. The ADR/exo was able to endocytose MCF-7 cells and make them considerably more resistant to Dox. Moreover, we observed a significant difference in miR-34a-5p expression in MCF-7/ADR and ADR/exo compared to MCF-7 and MCF-7/exo. Among the miR-34a-5p target genes, NOTCH1 displayed a clear change with a negative correlation. In addition, when miR-34a-5p expression was elevated in MCF-7/ADR cells, the expression of miR-34a-5p in ADR/exo was also enhanced alongside NOTCH1, implying that exosomes may carry miRNA into and out of cells and perform their function.</p><p>In conclusion, exosomes can influence Dox resistance in breast cancer cells by regulating miR-34a-5p/NOTCH1. These findings provide novel insights for research into the causes of tumor resistance and the enhancement of chemotherapy efficacy in breast cancer.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"76 ","pages":"Article 101964"},"PeriodicalIF":3.3,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000161/pdfft?md5=94235ca57a1305f99ffe8478ee06cad6&pid=1-s2.0-S0890850824000161-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141176787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-tube Ptprc SNP genotyping of JAXBoy (CD45.1) and C57BL/6J (CD45.2) mice by endpoint PCR and gel electrophoresis","authors":"Claire E. Ryan ,&nbsp;Thomas R. Salvetti ,&nbsp;Ilana R. Baum ,&nbsp;Brandon A. Figueroa ,&nbsp;Brittany E. LeBere ,&nbsp;Michael O. Alberti","doi":"10.1016/j.mcp.2024.101962","DOIUrl":"https://doi.org/10.1016/j.mcp.2024.101962","url":null,"abstract":"<div><p>Allelic variation at the <em>Ptprc</em> gene, which encodes the pan-leukocyte marker CD45/Ly5, is commonly exploited to track hematopoietic reconstitution by flow cytometry in mixed bone marrow chimera transplant experiments. Historically, this was accomplished using bone marrow from C57BL/6 (<em>Ptprc</em>^b/CD45.2/Ly5.2) and congenic B6.SJL-<em>Ptprc</em>^a<em>Pepc</em>^b/Boy (<em>Ptprc</em>^a/CD45.1/Ly5.1) mice. Recently, the Jackson Laboratory directly CRISPR-engineered the <em>Ptprc</em>^a allele in C57BL/6J mice. This new isogenic strain, termed JAXBoy, differs from wild-type C57BL/6J mice by two nucleotides, compared to the biologically significant 37 megabase (Mb) SJL interval retained in B6.SJL-<em>Ptprc</em>^a<em>Pepc</em>^b/Boy/J mice. Currently, <em>Ptprc</em>/CD45 variants are identified by flow cytometry or allele-specific real-time PCR, both of which require specialized workflows and equipment compared to standard genotyping of endpoint PCR products by gel electrophoresis. Here, we employed allele-specific oligonucleotides in conjunction with differential incorporation of a long non-specific oligo 5′-tail to allow for simultaneous identification of the <em>Ptprc</em>^a and <em>Ptprc</em>^b alleles using endpoint PCR and gel electrophoresis. This method allows for integration of <em>Ptprc</em> genotyping into standard genotyping workflows, which use a single set of thermocycling and gel electrophoresis conditions. Importantly, the strategy of primer placement and tail addition described here can be adapted to discriminate similar single- or multi-nucleotide polymorphisms at other genomic loci.</p></div>","PeriodicalId":49799,"journal":{"name":"Molecular and Cellular Probes","volume":"75 ","pages":"Article 101962"},"PeriodicalIF":3.3,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0890850824000148/pdfft?md5=b94bb843a399787fdfbe6027d49946b4&pid=1-s2.0-S0890850824000148-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140842635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}