Pub Date : 2024-10-18DOI: 10.1007/s11033-024-09988-3
Meiling Cheng, Yingmin Zhou, Qian Wang, Bo Luo, Yanwu Lai, Jianbin Cheng, Xiuyue Zhang, Yan Huang, Desheng Li
Background: MicroRNAs can regulate various biological functions including cell proliferation, differentiation, embryo formation, and implantation. The giant panda exhibits embryonic diapause, with embryo development resuming in late pregnancy. However, the changes in microRNAs during late pregnancy remain poorly understand.
Methods and results: After mating, plasma samples were collected on day 40 of early pregnancy (EP; n = 3) and 30 days before delivery of late pregnancy (LP; n = 3). Following microRNAs screening, a total of 120 microRNAs were detected in the plasma exosomes of pregnant pandas. Nine differentially expressed microRNAs (DEmicroRNAs) were identified in LP compared to EP, including three that were upregulated and six that were downregulated. Notably, miR-25b and miR-47 were significantly downregulated in LP group. All DEmicroRNAs were predicted to target a total of 2,675 genes. Pathway enrichment analysis of these target genes revealed significant enrichment in the MAPK and Rap1 signaling pathways, which are closely related to cell proliferation, differentiation, and cell-cell and cell-matrix interactions. Analysis of protein-protein interaction networks showed that most of the hub genes (five out of eight), including Fgfr1, Fgf2, Fgf18, Erbb4, and Kras within the MAPK and Rap1 pathways are associated with the cell proliferation and differentiation. Significantly, Erbb4 was regulated by significantly differentially expressed miRNA-47.
Conclusions: We suggest that plasma exosomal microRNAs are involved in cell proliferation and differentiation during embryonic development by regulating key hub genes within MAPK and Rap1 pathways. These findings provided new insights into the development of giant panda embryos.
{"title":"MicroRNA expression profiles in plasma exosomes of late pregnant giant pandas.","authors":"Meiling Cheng, Yingmin Zhou, Qian Wang, Bo Luo, Yanwu Lai, Jianbin Cheng, Xiuyue Zhang, Yan Huang, Desheng Li","doi":"10.1007/s11033-024-09988-3","DOIUrl":"https://doi.org/10.1007/s11033-024-09988-3","url":null,"abstract":"<p><strong>Background: </strong>MicroRNAs can regulate various biological functions including cell proliferation, differentiation, embryo formation, and implantation. The giant panda exhibits embryonic diapause, with embryo development resuming in late pregnancy. However, the changes in microRNAs during late pregnancy remain poorly understand.</p><p><strong>Methods and results: </strong>After mating, plasma samples were collected on day 40 of early pregnancy (EP; n = 3) and 30 days before delivery of late pregnancy (LP; n = 3). Following microRNAs screening, a total of 120 microRNAs were detected in the plasma exosomes of pregnant pandas. Nine differentially expressed microRNAs (DEmicroRNAs) were identified in LP compared to EP, including three that were upregulated and six that were downregulated. Notably, miR-25b and miR-47 were significantly downregulated in LP group. All DEmicroRNAs were predicted to target a total of 2,675 genes. Pathway enrichment analysis of these target genes revealed significant enrichment in the MAPK and Rap1 signaling pathways, which are closely related to cell proliferation, differentiation, and cell-cell and cell-matrix interactions. Analysis of protein-protein interaction networks showed that most of the hub genes (five out of eight), including Fgfr1, Fgf2, Fgf18, Erbb4, and Kras within the MAPK and Rap1 pathways are associated with the cell proliferation and differentiation. Significantly, Erbb4 was regulated by significantly differentially expressed miRNA-47.</p><p><strong>Conclusions: </strong>We suggest that plasma exosomal microRNAs are involved in cell proliferation and differentiation during embryonic development by regulating key hub genes within MAPK and Rap1 pathways. These findings provided new insights into the development of giant panda embryos.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1007/s11033-024-09997-2
Sara Haratizadeh, Mozhdeh Nemati, Mohsen Basiri, Masoumeh Nozari
Erythropoietin (EPO) is the main hematopoietic growth factor prescribed to overcome anemia. It is also a neuroprotective agent. EPO binds to the erythropoietin receptor (EPOR), expressed on neurons and glial cells in the central nervous system (CNS), and exerts its neuroprotective potencies through the EPO-EPOR complex. The mechanism of the signal transduction pathways of EPO on glial cells is defined. EPO-EPOR complex can affect neurological disorders, such as Alzheimer's disease, Parkinson's disease, ischemia, retinal injury, stroke, hypoxia, trauma, and demyelinating diseases, through acting downstream signaling pathways. This review focuses on the roles of EPO in different types of glial cells (astrocytes, microglia, oligodendrocytes, and Schwann cells) and their relationships with signaling pathways. Information on the non-erythropoietic action of EPO and related signaling systems in connection with glial cells could enhance EPO treatment to restore different CNS disorders and propose new perspectives on the neuroprotective potential of EPO.
{"title":"Erythropoietin and glial cells in central and peripheral nervous systems.","authors":"Sara Haratizadeh, Mozhdeh Nemati, Mohsen Basiri, Masoumeh Nozari","doi":"10.1007/s11033-024-09997-2","DOIUrl":"https://doi.org/10.1007/s11033-024-09997-2","url":null,"abstract":"<p><p>Erythropoietin (EPO) is the main hematopoietic growth factor prescribed to overcome anemia. It is also a neuroprotective agent. EPO binds to the erythropoietin receptor (EPOR), expressed on neurons and glial cells in the central nervous system (CNS), and exerts its neuroprotective potencies through the EPO-EPOR complex. The mechanism of the signal transduction pathways of EPO on glial cells is defined. EPO-EPOR complex can affect neurological disorders, such as Alzheimer's disease, Parkinson's disease, ischemia, retinal injury, stroke, hypoxia, trauma, and demyelinating diseases, through acting downstream signaling pathways. This review focuses on the roles of EPO in different types of glial cells (astrocytes, microglia, oligodendrocytes, and Schwann cells) and their relationships with signaling pathways. Information on the non-erythropoietic action of EPO and related signaling systems in connection with glial cells could enhance EPO treatment to restore different CNS disorders and propose new perspectives on the neuroprotective potential of EPO.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-18DOI: 10.1007/s11033-024-09981-w
Jayanta Kumar Pal, Subhayan Sur, Smriti P K Mittal, Saurabh Dey, Monali Prakash Mahale, Arijit Mukherjee
Erythropoiesis is regulated by the differential expression of many genes. Besides being transcriptionally regulated, these genes are also with the oath of epigenetic regulation by the microRNAs (miRNAs), in particular. Various miRNAs appear to be very important for the normal process of erythropoiesis and various hematological abnormalities in humans. Therefore, the review aims to summarize the significance of miRNAs in erythropoiesis and different hematological diseases with clinical importance. Our analysis indicates that specific miRNAs regulate erythropoiesis in a stage-specific manner from hematopoietic stem cells to differentiated erythrocytes. Further, many miRNAs have been reported to be linked with various hematological diseases. The importance of miRNAs as biomarkers or therapeutic drug targets for various hematological disorders like anemia, β-thalassemia, and leukemia has been revealed through various clinical studies and clinical trials. The miR-34a mimic and miR-155 inhibitor demonstrate promising therapeutic effects in various hematological malignancies. Additionally, miR-34a, miR-538e, miR-193e, and miR-198 exhibit diagnostic potential in acute myeloid leukemia, while miR-451, miR-151-5p, and miR-1290 show diagnostic potential in B-cell acute lymphoblastic leukemia. Thus, this review encompasses the latest observations and implications of specific miRNAs in erythropoiesis and various hematological disorders. However, challenges persist in developing safe and efficient delivery strategies to target miRNAs specifically, minimizing off-target effects and enhancing therapeutic outcomes. Future mechanistic pre-clinical and clinical research would contribute to overcoming these challenges.
{"title":"Clinical implications of miRNAs in erythropoiesis, anemia, and other hematological disorders.","authors":"Jayanta Kumar Pal, Subhayan Sur, Smriti P K Mittal, Saurabh Dey, Monali Prakash Mahale, Arijit Mukherjee","doi":"10.1007/s11033-024-09981-w","DOIUrl":"https://doi.org/10.1007/s11033-024-09981-w","url":null,"abstract":"<p><p>Erythropoiesis is regulated by the differential expression of many genes. Besides being transcriptionally regulated, these genes are also with the oath of epigenetic regulation by the microRNAs (miRNAs), in particular. Various miRNAs appear to be very important for the normal process of erythropoiesis and various hematological abnormalities in humans. Therefore, the review aims to summarize the significance of miRNAs in erythropoiesis and different hematological diseases with clinical importance. Our analysis indicates that specific miRNAs regulate erythropoiesis in a stage-specific manner from hematopoietic stem cells to differentiated erythrocytes. Further, many miRNAs have been reported to be linked with various hematological diseases. The importance of miRNAs as biomarkers or therapeutic drug targets for various hematological disorders like anemia, β-thalassemia, and leukemia has been revealed through various clinical studies and clinical trials. The miR-34a mimic and miR-155 inhibitor demonstrate promising therapeutic effects in various hematological malignancies. Additionally, miR-34a, miR-538e, miR-193e, and miR-198 exhibit diagnostic potential in acute myeloid leukemia, while miR-451, miR-151-5p, and miR-1290 show diagnostic potential in B-cell acute lymphoblastic leukemia. Thus, this review encompasses the latest observations and implications of specific miRNAs in erythropoiesis and various hematological disorders. However, challenges persist in developing safe and efficient delivery strategies to target miRNAs specifically, minimizing off-target effects and enhancing therapeutic outcomes. Future mechanistic pre-clinical and clinical research would contribute to overcoming these challenges.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Back ground: 7-Methoxycoumarin (7-MC) is well recognized for its anti-inflammatory and anti-nociceptive actions. Its capacity to lessen neuropathic pain hasn't been documented yet. Hence the impact of 7-MC on vincristine-induced peripheral neuropathic pain in rodents was investigated. The investigation also looked at the impact of 7-MC in reducing neuropathic pain via voltage-gated calcium channels and phospholipase enzyme inhibition using pertinent in vitro and in silico methods.
Methods and results: Vincristine (0.1 mg/kg, i.p., daily) was administered continuously for 7 days to induce peripheral neuropathic pain in mice, with cold allodynia and thermal hyperalgesia and evaluated on the 8th day using the acetone bubble test and hot water tail immersion test. In order to derive the mechanistic approach for ameliorating neuropathic pain, the role of 7-MC in the inhibition of the phospholipase enzyme, gene expression studies on voltage-gated calcium channels using mouse BV2 microglial cells and in silico studies for its calcium channel binding affinity were also performed. The test compounds reduced vincristine-induced cold allodynia and thermal hyperalgesia in mice in a dose-dependent experiments. In vitro studies on phospholipase inhibition by 7-MC showed an IC50 of 27.08 µg/ml and down-regulated the gene expression of calcium channels in the BV2 microglial cell line. In silico docking scores for 7-MCwere higher than the standard drug gabapentin.
Conclusion: The compound 7-MC has shown promise in alleviating vincristine-induced peripheral neuropathicin mice. Studies conducted in parallel, both in silico and in vitro have demonstrated that 7-MC effectively reduces neuropathic pain. This pain reduction is achieved through two mechanisms: inhibiting the phospholipase enzyme and blocking voltage-gated calcium channels.
{"title":"Exploring the potential therapeutic benefits of 7-methoxy coumarin for neuropathy pain: an in vivo, in vitro, and in silico approach.","authors":"Binoy Varghese Cheriyan, Jaikumar Shanmugasundaram, Prakash Ramakrishnan, Kavitha Ramasamy, R Karthikeyan, Sowmyalakshmi Venkataraman, Anitha Roy, Parameswari Royapuram Parthasarathy","doi":"10.1007/s11033-024-09991-8","DOIUrl":"https://doi.org/10.1007/s11033-024-09991-8","url":null,"abstract":"<p><strong>Back ground: </strong>7-Methoxycoumarin (7-MC) is well recognized for its anti-inflammatory and anti-nociceptive actions. Its capacity to lessen neuropathic pain hasn't been documented yet. Hence the impact of 7-MC on vincristine-induced peripheral neuropathic pain in rodents was investigated. The investigation also looked at the impact of 7-MC in reducing neuropathic pain via voltage-gated calcium channels and phospholipase enzyme inhibition using pertinent in vitro and in silico methods.</p><p><strong>Methods and results: </strong>Vincristine (0.1 mg/kg, i.p., daily) was administered continuously for 7 days to induce peripheral neuropathic pain in mice, with cold allodynia and thermal hyperalgesia and evaluated on the 8th day using the acetone bubble test and hot water tail immersion test. In order to derive the mechanistic approach for ameliorating neuropathic pain, the role of 7-MC in the inhibition of the phospholipase enzyme, gene expression studies on voltage-gated calcium channels using mouse BV2 microglial cells and in silico studies for its calcium channel binding affinity were also performed. The test compounds reduced vincristine-induced cold allodynia and thermal hyperalgesia in mice in a dose-dependent experiments. In vitro studies on phospholipase inhibition by 7-MC showed an IC<sub>50</sub> of 27.08 µg/ml and down-regulated the gene expression of calcium channels in the BV2 microglial cell line. In silico docking scores for 7-MCwere higher than the standard drug gabapentin.</p><p><strong>Conclusion: </strong>The compound 7-MC has shown promise in alleviating vincristine-induced peripheral neuropathicin mice. Studies conducted in parallel, both in silico and in vitro have demonstrated that 7-MC effectively reduces neuropathic pain. This pain reduction is achieved through two mechanisms: inhibiting the phospholipase enzyme and blocking voltage-gated calcium channels.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Hypertrophic scar (HS) is associated with cosmetic defects, mobility, and functional impairments, pruritus, and pain. Previous circRNA microarray analysis identified reduced expression of circRNA_SLC8A1 in HS tissues. Therefore, this study aims to investigate the role of circRNA_SLC8A1 in modulating the abnormal behavior of HS-derived fibroblasts (HSFs) in vitro.
Methods: RT-qPCR and FISH assays were used to assess the differential expression and localization of circRNA_SLC8A1 in normal and HS tissues. Following modulation of circRNA_SLC8A1 expression, CCK-8, flow cytometry, Transwell, and wound healing assays were employed to evaluate the effects of circRNA_SLC8A1 on the biological behaviors of HSFs. The Starbase database, dual-luciferase reporter assays, and Ago2-RIP assays were utilized to predict and validate the interaction between circRNA_SLC8A1 and downstream miRNAs.
Results: CircRNA_SLC8A1 was found to be downregulated in HS tissues and was primarily localized in the cytoplasm. Overexpression of circRNA_SLC8A1 reduced cell viability, cell invasion, wound healing, and the expression of Vimentin, N-cadherin, Col I, and Col III, while enhancing apoptosis and E-cadherin expression in HSFs. CircRNA_SLC8A1 activates the Nrf2-ARE pathway by competitively binding to miRNA-27a-3p. miRNA-27a-3p and Nrf2 exhibited high and low expression, respectively in HS tissues, with an inverse correlation between their levels. Overexpression of miRNA-27a-3p counteracted the effects of circRNA_SLC8A1 in HSF proliferation, apoptosis, migration, EMT, collagen deposition, and Nrf2-ARE pathway activity.
Conclusion: CircRNA_SLC8A1 inhibits the proliferation, migration, EMT, and collagen deposition of HSF through competitive binding with miRNA-27a-3p, thereby activating the Nrf2-ARE pathway. The circRNA_SLC8A1/miRNA-27a-3p/Nrf2-ARE axis may offer a promising molecular target for HS therapy.
{"title":"CircRNA_SLC8A1 alleviates hypertrophic scar progression by mediating the Nrf2-ARE pathway.","authors":"Yichao Jin, Yongjing He, Yifei Wu, Xiaochuan Wang, Lechun Lyu, Ke Zhang, Chunping Ao, Liangheng Xu","doi":"10.1007/s11033-024-10018-5","DOIUrl":"https://doi.org/10.1007/s11033-024-10018-5","url":null,"abstract":"<p><strong>Background: </strong>Hypertrophic scar (HS) is associated with cosmetic defects, mobility, and functional impairments, pruritus, and pain. Previous circRNA microarray analysis identified reduced expression of circRNA_SLC8A1 in HS tissues. Therefore, this study aims to investigate the role of circRNA_SLC8A1 in modulating the abnormal behavior of HS-derived fibroblasts (HSFs) in vitro.</p><p><strong>Methods: </strong>RT-qPCR and FISH assays were used to assess the differential expression and localization of circRNA_SLC8A1 in normal and HS tissues. Following modulation of circRNA_SLC8A1 expression, CCK-8, flow cytometry, Transwell, and wound healing assays were employed to evaluate the effects of circRNA_SLC8A1 on the biological behaviors of HSFs. The Starbase database, dual-luciferase reporter assays, and Ago2-RIP assays were utilized to predict and validate the interaction between circRNA_SLC8A1 and downstream miRNAs.</p><p><strong>Results: </strong>CircRNA_SLC8A1 was found to be downregulated in HS tissues and was primarily localized in the cytoplasm. Overexpression of circRNA_SLC8A1 reduced cell viability, cell invasion, wound healing, and the expression of Vimentin, N-cadherin, Col I, and Col III, while enhancing apoptosis and E-cadherin expression in HSFs. CircRNA_SLC8A1 activates the Nrf2-ARE pathway by competitively binding to miRNA-27a-3p. miRNA-27a-3p and Nrf2 exhibited high and low expression, respectively in HS tissues, with an inverse correlation between their levels. Overexpression of miRNA-27a-3p counteracted the effects of circRNA_SLC8A1 in HSF proliferation, apoptosis, migration, EMT, collagen deposition, and Nrf2-ARE pathway activity.</p><p><strong>Conclusion: </strong>CircRNA_SLC8A1 inhibits the proliferation, migration, EMT, and collagen deposition of HSF through competitive binding with miRNA-27a-3p, thereby activating the Nrf2-ARE pathway. The circRNA_SLC8A1/miRNA-27a-3p/Nrf2-ARE axis may offer a promising molecular target for HS therapy.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Triple-negative breast cancer (TNBC) exhibits a lower survival rate in comparison to other BC subtypes. Utilizing dendritic cell (DC) vaccines as a form of immunotherapy is becoming a promising new approach to cancer treatment. However, inadequate immunogenicity of tumor antigens leads to unsatisfactory effectiveness of the DC vaccines. Exosomes are the basis for the latest improvements in tumor immunotherapy. This study examined whether TNBC-derived exosomes elicit immunogenicity on the maturation and function of monocyte-derived DCs and the impact of the exosome-treated monocyte-derived DCs (moDCs) on T cell differentiation.
Methods: exosomes were isolated from MDA-MB-231 TNBC cancer cells and characterized. Monocytes were separated from peripheral blood mononuclear cells and differentiated into DCs. Then, monocyte-derived DCs were treated with TNBC-derived exosomes. Furthermore, the mRNA levels of the genes and cytokines involved in DC maturation and function were examined using qRT-PCR and ELISA assays. We also cocultured TNBC-derived exosome-treated moDCs with T cells and investigated the role of the treatment in T cell differentiation by evaluating the expression of some related genes by qRT-PCR. The concentration of the cytokines secreted from T cells cocultured with exosome-treated moDCs was quantified by the ELISA assays.
Results: Our findings showed that TNBC-derived exosomes induce immunogenicity by enhancing moDCs' maturation and function. In addition, exosome-treated moDCs promote cocultured T-cell expansion by inducing TH1 differentiation through increasing cytokine production.
Conclusion: TNBC-derived exosomes could improve vaccine-elicited immunotherapy by inducing an immunogenic response and enhancing the effectiveness of the DC vaccines. However, this needs to be investigated further in future studies.
背景:三阴性乳腺癌(TNBC与其他乳腺癌亚型相比,三阴性乳腺癌(TNBC)的生存率较低。利用树突状细胞(DC)疫苗作为一种免疫疗法正成为一种前景广阔的癌症治疗新方法。然而,肿瘤抗原的免疫原性不足导致树突状细胞疫苗的效果不尽人意。外泌体是肿瘤免疫疗法取得最新进展的基础。本研究考察了 TNBC 衍生的外泌体是否会对单核细胞衍生 DC 的成熟和功能产生免疫原性,以及经外泌体处理的单核细胞衍生 DC(moDC)对 T 细胞分化的影响。方法:从 MDA-MB-231 TNBC 癌细胞中分离出外泌体并对其进行鉴定。然后,用 TNBC 衍生的外泌体处理单核细胞衍生的 DC。此外,我们还使用 qRT-PCR 和 ELISA 方法检测了参与 DC 成熟和功能的基因和细胞因子的 mRNA 水平。我们还将经 TNBC 外泌体处理的 moDCs 与 T 细胞进行了共培养,并通过 qRT-PCR 评估了一些相关基因的表达,从而研究了处理在 T 细胞分化中的作用。用ELISA检测法量化了与外泌体处理过的moDCs共培养的T细胞分泌的细胞因子的浓度:我们的研究结果表明,TNBC衍生的外泌体通过增强moDCs的成熟和功能诱导免疫原性。此外,经外泌体处理的moDCs可通过增加细胞因子的产生诱导TH1分化,从而促进共培养T细胞的扩增:结论:TNBC衍生的外泌体可通过诱导免疫原性反应和提高DC疫苗的有效性来改善疫苗诱导的免疫疗法。不过,这还需要在今后的研究中进一步探讨。
{"title":"Triple-negative breast cancer-derived exosomes change the immunological features of human monocyte-derived dendritic cells and influence T-cell responses.","authors":"Sahar Safaei, Shiva Alipour, Seyedeh Zahra Bahojb Mahdavi, Hooman Shalmashi, Vahid Khaze Shahgoli, Dariush Shanehbandi, Behzad Baradaran, Tohid Kazemi","doi":"10.1007/s11033-024-10007-8","DOIUrl":"https://doi.org/10.1007/s11033-024-10007-8","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) exhibits a lower survival rate in comparison to other BC subtypes. Utilizing dendritic cell (DC) vaccines as a form of immunotherapy is becoming a promising new approach to cancer treatment. However, inadequate immunogenicity of tumor antigens leads to unsatisfactory effectiveness of the DC vaccines. Exosomes are the basis for the latest improvements in tumor immunotherapy. This study examined whether TNBC-derived exosomes elicit immunogenicity on the maturation and function of monocyte-derived DCs and the impact of the exosome-treated monocyte-derived DCs (moDCs) on T cell differentiation.</p><p><strong>Methods: </strong>exosomes were isolated from MDA-MB-231 TNBC cancer cells and characterized. Monocytes were separated from peripheral blood mononuclear cells and differentiated into DCs. Then, monocyte-derived DCs were treated with TNBC-derived exosomes. Furthermore, the mRNA levels of the genes and cytokines involved in DC maturation and function were examined using qRT-PCR and ELISA assays. We also cocultured TNBC-derived exosome-treated moDCs with T cells and investigated the role of the treatment in T cell differentiation by evaluating the expression of some related genes by qRT-PCR. The concentration of the cytokines secreted from T cells cocultured with exosome-treated moDCs was quantified by the ELISA assays.</p><p><strong>Results: </strong>Our findings showed that TNBC-derived exosomes induce immunogenicity by enhancing moDCs' maturation and function. In addition, exosome-treated moDCs promote cocultured T-cell expansion by inducing TH1 differentiation through increasing cytokine production.</p><p><strong>Conclusion: </strong>TNBC-derived exosomes could improve vaccine-elicited immunotherapy by inducing an immunogenic response and enhancing the effectiveness of the DC vaccines. However, this needs to be investigated further in future studies.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objectives: The study investigates how antibiotics affect biofilm formation and toxin gene expression in Clostridium difficile, which is essential for its survival and persistence.
Methods: The study confirmed 25 strains of C. difficile and assessed biofilm formation. The MIC of metronidazole and vancomycin was determined through agar dilution, and the impact of sub-MIC levels on biofilm formation and eradication was investigated. Additionally, Real-time PCR was used to analyze the expression levels of target genes related to antibiotic treatment.
Results: We found that certain genes, such as the ImmA/IrrE system, were associated with increased biofilm formation in isolates. Sub-MIC antibiotic levels influenced gene expression related to biofilm activities, particularly emphasizing the importance of toxin-antitoxin systems. The results suggest that antibiotics at sub-MIC levels may play a signaling role in promoting biofilm formation and gene expression in C. difficile.
Conclusion: Our study suggests that toxin and antitoxin genes may impact C. difficile biofilm formation, while antibiotics could signal biofilm strengthening and gene expression increase.
研究目的本研究调查了抗生素如何影响艰难梭菌的生物膜形成和毒素基因表达,这对艰难梭菌的生存和持久性至关重要:研究确认了 25 株艰难梭菌,并评估了生物膜的形成。通过琼脂稀释法确定了甲硝唑和万古霉素的 MIC 值,并研究了低于 MIC 值对生物膜形成和根除的影响。此外,还使用实时 PCR 分析了与抗生素治疗相关的目标基因的表达水平:结果:我们发现,某些基因(如 ImmA/IrrE 系统)与分离株生物膜形成的增加有关。亚微克级抗生素水平影响了与生物膜活动有关的基因表达,尤其强调了毒素-抗毒素系统的重要性。结果表明,亚微克级抗生素可能在促进艰难梭菌生物膜形成和基因表达方面发挥信号作用:我们的研究表明,毒素和抗毒素基因可能会影响艰难梭菌生物膜的形成,而抗生素则可能是生物膜强化和基因表达增加的信号。
{"title":"Unveiling the impact of antibiotic stress on biofilm formation and expression of toxin-antitoxin system genes in Clostridium difficile clinical isolates.","authors":"Nasim Cheraghi, Saeed Khoshnood, Nourkhoda Sadeghifard, Niloufar Khodaei, Parisa Asadollahi, Saiyad Bastaminejad, Ebrahim Kouhsari, Nazanin Omidi, Behrooz Sadeghi Kalani","doi":"10.1007/s11033-024-09993-6","DOIUrl":"https://doi.org/10.1007/s11033-024-09993-6","url":null,"abstract":"<p><strong>Objectives: </strong>The study investigates how antibiotics affect biofilm formation and toxin gene expression in Clostridium difficile, which is essential for its survival and persistence.</p><p><strong>Methods: </strong>The study confirmed 25 strains of C. difficile and assessed biofilm formation. The MIC of metronidazole and vancomycin was determined through agar dilution, and the impact of sub-MIC levels on biofilm formation and eradication was investigated. Additionally, Real-time PCR was used to analyze the expression levels of target genes related to antibiotic treatment.</p><p><strong>Results: </strong>We found that certain genes, such as the ImmA/IrrE system, were associated with increased biofilm formation in isolates. Sub-MIC antibiotic levels influenced gene expression related to biofilm activities, particularly emphasizing the importance of toxin-antitoxin systems. The results suggest that antibiotics at sub-MIC levels may play a signaling role in promoting biofilm formation and gene expression in C. difficile.</p><p><strong>Conclusion: </strong>Our study suggests that toxin and antitoxin genes may impact C. difficile biofilm formation, while antibiotics could signal biofilm strengthening and gene expression increase.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Currently, the use of probiotics to treat inflammatory bowel diseases (IBD) is widely accepted because of their gut microbiota modulation capabilities and anti-inflammatory potential.
Objective: The aim of this study is to examine the immunomodulatory outcomes of probiotics and sulfasalazine in the acetic acid-induced colitis murine model.
Methods: The animals were randomly assigned to one of the seven groups. Following the induction of colitis, Lactobacillus acidophilus LA-5, Bifidobacterium animalis subsp. lactis BB-12, and sulfasalazine (SASP) were orally administered for 10 days. Subsequently, the in vitro anti-inflammatory effect on TNF-α and IL-10 in the supernatants of cultured spleen cells was assessed via ELISAs. Relative mRNA expression of ZO-1, MLCK, iNOS, TNFR2, ROR-γt, GATA-3, T-bet, and Foxp3 was determined using quantitative reverse‑transcription polymerase chain reaction (qRT‑PCR).
Results: The SASP plus probiotic mixture was more effective in alleviating colitis symptoms, and reducing disease activity scores, and mucosal inflammation. qRT-PCR analysis revealed a significant reduction in T-bet and RORγt levels, while Foxp3 and GATA-3 levels increased in the colons of colitis mice. In addition, the selected strains substantially inhibited the release of inflammatory markers. Administration of LA-5 + BB-12 + SASP resulted in considerably higher inhibition of NO production and cell proliferation than in the other groups (p < 0.001). Treatment with LA-5 + BB-12 + SASP also reduced TNF-α-mediated apoptosis in intestinal epithelial cells (IECs).
Conclusions: Survey results highlight that the combination regimen could be a promising strategy for IBD therapy, warranting further study of its clinical application and long-term benefits.
{"title":"Evaluation of the immunomodulatory activity of probiotics mixture and sulfasalazine against acetic acid-induced colitis in a murine model.","authors":"Mona Moshiri, Manizhe Faghih, Mehrdad Gholami, Maryam Ghasemi, Narjes Jafari, Mansooreh Mirzaei, Saeid Abediankenari","doi":"10.1007/s11033-024-10008-7","DOIUrl":"https://doi.org/10.1007/s11033-024-10008-7","url":null,"abstract":"<p><strong>Background: </strong>Currently, the use of probiotics to treat inflammatory bowel diseases (IBD) is widely accepted because of their gut microbiota modulation capabilities and anti-inflammatory potential.</p><p><strong>Objective: </strong>The aim of this study is to examine the immunomodulatory outcomes of probiotics and sulfasalazine in the acetic acid-induced colitis murine model.</p><p><strong>Methods: </strong>The animals were randomly assigned to one of the seven groups. Following the induction of colitis, Lactobacillus acidophilus LA-5, Bifidobacterium animalis subsp. lactis BB-12, and sulfasalazine (SASP) were orally administered for 10 days. Subsequently, the in vitro anti-inflammatory effect on TNF-α and IL-10 in the supernatants of cultured spleen cells was assessed via ELISAs. Relative mRNA expression of ZO-1, MLCK, iNOS, TNFR2, ROR-γt, GATA-3, T-bet, and Foxp3 was determined using quantitative reverse‑transcription polymerase chain reaction (qRT‑PCR).</p><p><strong>Results: </strong>The SASP plus probiotic mixture was more effective in alleviating colitis symptoms, and reducing disease activity scores, and mucosal inflammation. qRT-PCR analysis revealed a significant reduction in T-bet and RORγt levels, while Foxp3 and GATA-3 levels increased in the colons of colitis mice. In addition, the selected strains substantially inhibited the release of inflammatory markers. Administration of LA-5 + BB-12 + SASP resulted in considerably higher inhibition of NO production and cell proliferation than in the other groups (p < 0.001). Treatment with LA-5 + BB-12 + SASP also reduced TNF-α-mediated apoptosis in intestinal epithelial cells (IECs).</p><p><strong>Conclusions: </strong>Survey results highlight that the combination regimen could be a promising strategy for IBD therapy, warranting further study of its clinical application and long-term benefits.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: One of the probable causes of statin myotoxicity is an imbalance between protein synthesis and degradation. These processes are regulated by the PI3K/Akt/mTOR pathway and the ubiquitin‒proteasome system (UPS). The aim of this study was to assess whether the effects of atorvastatin on PI3K/Akt/mTOR pathway downstream proteins, the FoxO3a transcription factor and the UPS genes, i.e., MuRF-1 and MAFbx, depend on muscle fibre type.
Methods and results: Atorvastatin (50 mg/kg) was administered to Wistar rats. The levels of selected PI3K/Akt/mTOR pathway proteins were assayed via Western blotting, whereas MuRF-1, MAFbx and FoxO3a mRNA levels were measured using reverse transcription quantitative polymerase chain reaction (RT‒qPCR). Gomöri trichrome staining was performed to assess skeletal muscle pathology. A decrease in the P-Akt/Akt ratio was observed in the gastrocnemius muscle (MG), whereas an increase in the P-Akt/Akt ratio was observed in the soleus muscle (SOL). FoxO3a gene expression increased in the SOL and extensor digitorum longus (EDL) muscles. MuRF-1 gene expression increased in the MG, and MAFbx expression increased in the EDL. No histopathological changes were observed in any of the tested muscles.
Conclusions: In the absence of overt muscle damage, atorvastatin decreased the P-Akt/Akt ratio in the MG, indicating an increase in inactive Akt. Consistent with the decrease in Akt activation, rpS6 phosphorylation decreased. In SOL, atorvastatin increased the P-Akt/Akt ratio, indicating Akt activation. P-FoxO3a and the P-FoxO3a/FoxO3a ratio increased, suggesting that FoxO3a inactivation occurred. Moreover, in the SOL, atorvastatin did not affect the expression of atrophy-related genes. These findings indicate that atorvastatin has no adverse effect on the Akt pathway in the SOL. Our results showed that the effects of atorvastatin on the Akt signalling pathway and atrophy-related gene expression depend on muscle type.
{"title":"Skeletal muscle fibre type-dependent effects of atorvastatin on the PI3K/Akt/mTOR signalling pathway and atrophy-related genes in rats.","authors":"Anna Gawedzka, Malgorzata Knapik-Czajka, Jagoda Drag, Malgorzata Belczyk, Edyta Radwanska, Dariusz Adamek","doi":"10.1007/s11033-024-10005-w","DOIUrl":"https://doi.org/10.1007/s11033-024-10005-w","url":null,"abstract":"<p><strong>Background: </strong>One of the probable causes of statin myotoxicity is an imbalance between protein synthesis and degradation. These processes are regulated by the PI3K/Akt/mTOR pathway and the ubiquitin‒proteasome system (UPS). The aim of this study was to assess whether the effects of atorvastatin on PI3K/Akt/mTOR pathway downstream proteins, the FoxO3a transcription factor and the UPS genes, i.e., MuRF-1 and MAFbx, depend on muscle fibre type.</p><p><strong>Methods and results: </strong>Atorvastatin (50 mg/kg) was administered to Wistar rats. The levels of selected PI3K/Akt/mTOR pathway proteins were assayed via Western blotting, whereas MuRF-1, MAFbx and FoxO3a mRNA levels were measured using reverse transcription quantitative polymerase chain reaction (RT‒qPCR). Gomöri trichrome staining was performed to assess skeletal muscle pathology. A decrease in the P-Akt/Akt ratio was observed in the gastrocnemius muscle (MG), whereas an increase in the P-Akt/Akt ratio was observed in the soleus muscle (SOL). FoxO3a gene expression increased in the SOL and extensor digitorum longus (EDL) muscles. MuRF-1 gene expression increased in the MG, and MAFbx expression increased in the EDL. No histopathological changes were observed in any of the tested muscles.</p><p><strong>Conclusions: </strong>In the absence of overt muscle damage, atorvastatin decreased the P-Akt/Akt ratio in the MG, indicating an increase in inactive Akt. Consistent with the decrease in Akt activation, rpS6 phosphorylation decreased. In SOL, atorvastatin increased the P-Akt/Akt ratio, indicating Akt activation. P-FoxO3a and the P-FoxO3a/FoxO3a ratio increased, suggesting that FoxO3a inactivation occurred. Moreover, in the SOL, atorvastatin did not affect the expression of atrophy-related genes. These findings indicate that atorvastatin has no adverse effect on the Akt pathway in the SOL. Our results showed that the effects of atorvastatin on the Akt signalling pathway and atrophy-related gene expression depend on muscle type.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11486814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-17DOI: 10.1007/s11033-024-09989-2
Longxin Wang, Wencheng Zhao, Yun Jiang, Li Liu, Jianwei Chen, Fang Zhao, Xiaoyong Zhang, Keshu Zou
Background: The Pearl River and its estuary are highly exposed to anthropogenic disturbance. Because bacterial communities play an indispensable role in aquatic ecosystems, there has been an increased research focus on the statuses of these communities under human-induced perturbations.
Methods and results: This study investigated the composition, diversity, and structure of bacterial communities across 29 sites from the Guangzhou section of the Pearl River (GZ) to the Pearl River Estuary (PRE) using 16S rRNA gene amplicons. The results revealed similar dominant phyla of bacteria in both GZ and PRE, as well as significant differences in bacterial community composition and diversity between the two sections. Proteobacteria and Cyanobacteria were identified as the primary drivers of compositional differences between GZ and PRE. The Cyanobacteria Dolichospermum_NIES41 and Cuspidothrix issatschenkoi were only present in GZ, whereas the marine Gram-negative bacteria of Porticoccus litoralis and Thalassolituus oleivorans were unique to PRE.
Conclusions: Bacterial community composition and diversity exhibit both similarities and differences between GZ and PRE; Proteobacteria and Cyanobacteria are key factors underlying these variations. Bacterial communities in both GZ and PRE are strongly influenced by human activities, and salinity is an important factor in controlling their differences. This study provides a comprehensive analysis of the bacterial communities in GZ and PRE, establishing a foundation for better management of aquatic ecosystems impacted by anthropogenic activities.
背景:珠江及其河口受到人为干扰的程度很高。由于细菌群落在水生生态系统中扮演着不可或缺的角色,人们越来越关注这些群落在人为干扰下的状况:本研究使用 16S rRNA 基因扩增子调查了珠江广州段至珠江口 29 个地点细菌群落的组成、多样性和结构。结果表明,广州段和珠江口段的细菌优势菌门相似,但两段的细菌群落组成和多样性存在显著差异。蛋白质细菌和蓝藻被认为是造成 GZ 和 PRE 组成差异的主要原因。蓝藻菌 Dolichospermum_NIES41 和 Cuspidothrix issatschenkoi 只存在于 GZ,而海洋革兰氏阴性菌 Porticoccus litoralis 和 Thalassolituus oleivorans 则是 PRE 独有的:细菌群落组成和多样性在 GZ 和 PRE 之间既有相似之处,也有差异;蛋白细菌和蓝藻是造成这些差异的关键因素。广州和珠江口地区的细菌群落都受到人类活动的强烈影响,而盐度是控制两者差异的重要因素。本研究对广州和珠江口地区的细菌群落进行了全面分析,为更好地管理受人类活动影响的水生生态系统奠定了基础。
{"title":"Similarities and differences in bacterial communities between the Pearl River (Guangzhou section) and its estuary.","authors":"Longxin Wang, Wencheng Zhao, Yun Jiang, Li Liu, Jianwei Chen, Fang Zhao, Xiaoyong Zhang, Keshu Zou","doi":"10.1007/s11033-024-09989-2","DOIUrl":"https://doi.org/10.1007/s11033-024-09989-2","url":null,"abstract":"<p><strong>Background: </strong>The Pearl River and its estuary are highly exposed to anthropogenic disturbance. Because bacterial communities play an indispensable role in aquatic ecosystems, there has been an increased research focus on the statuses of these communities under human-induced perturbations.</p><p><strong>Methods and results: </strong>This study investigated the composition, diversity, and structure of bacterial communities across 29 sites from the Guangzhou section of the Pearl River (GZ) to the Pearl River Estuary (PRE) using 16S rRNA gene amplicons. The results revealed similar dominant phyla of bacteria in both GZ and PRE, as well as significant differences in bacterial community composition and diversity between the two sections. Proteobacteria and Cyanobacteria were identified as the primary drivers of compositional differences between GZ and PRE. The Cyanobacteria Dolichospermum_NIES41 and Cuspidothrix issatschenkoi were only present in GZ, whereas the marine Gram-negative bacteria of Porticoccus litoralis and Thalassolituus oleivorans were unique to PRE.</p><p><strong>Conclusions: </strong>Bacterial community composition and diversity exhibit both similarities and differences between GZ and PRE; Proteobacteria and Cyanobacteria are key factors underlying these variations. Bacterial communities in both GZ and PRE are strongly influenced by human activities, and salinity is an important factor in controlling their differences. This study provides a comprehensive analysis of the bacterial communities in GZ and PRE, establishing a foundation for better management of aquatic ecosystems impacted by anthropogenic activities.</p>","PeriodicalId":18755,"journal":{"name":"Molecular Biology Reports","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}