Yajun Wang, Kai Kang, Yilu Lin, Qi-qi Lai, Yujia Tang, Xintong Wang, Di Wu, Huiying Liu, Huan Meng, Libin Huang, Yang Gao
This study investigated the protective effect of Shenfu injection (SI) on septic acute kidney injury (AKI) induced by lipopolysaccharide (LPS) and its underlying mechanism. A mouse model of septic AKI was established, and various dosages of SI (2 mL/kg, 4 mL/kg, and 8 mL/kg) were administered as treatment. HE staining and TUNEL assay were conducted for pathological analysis. The content of ATP was detected by the biochemical kit. The mitochondrial membrane potential (MMP) was detected by flow cytometry. Western blotting was used for the detecting expression of apoptosis and inflammation related proteins. To explore the molecular mechanism, septic mice were treated by SI (8 mL/kg) combined with ML385 (30 mg/kg). The number and morphology of mitochondria were observed by the transmission electron microscope (TEM). The increased renal volume, paler renal cortex, and necrotic renal tubules observed in septic AKI mice were significantly alleviated by treatment with either 4 mL/kg or 8 mL/kg of SI. Furthermore, signally declined ATP content and increased MMP value in septic AKI mice were markedly reversed by 8 mL/kg SI. Additionally, the increased IL-6, p-p65, cle-caspase-3, and Bax levels, as well as the decreased Bcl-2 level, observed in septic AKI mice were notably rescued by 8 mL/kg SI. The protective function of SI on pathological changes and mitochondria in septic AKI mice was abolished by ML385. These findings suggested that SI alleviated LPS-induced septic AKI by regulating the Nrf2/NF-κB axis.
本研究探讨了参附注射液（SI）对脂多糖（LPS）诱导的脓毒性急性肾损伤（AKI）的保护作用及其内在机制。建立了小鼠脓毒性急性肾损伤模型，并给予不同剂量（2 mL/kg、4 mL/kg 和 8 mL/kg）的神茯注射液进行治疗。HE染色和TUNEL检测用于病理分析。生化试剂盒检测 ATP 含量。流式细胞术检测线粒体膜电位（MMP）。Western 印迹法用于检测凋亡和炎症相关蛋白的表达。为探索分子机制，脓毒症小鼠接受 SI（8 mL/kg）联合 ML385（30 mg/kg）治疗。透射电子显微镜（TEM）观察了线粒体的数量和形态。使用 4 mL/kg 或 8 mL/kg 的 SI 治疗后，脓毒性 AKI 小鼠肾脏体积增大、肾皮质变白和肾小管坏死的情况明显缓解。此外，脓毒症 AKI 小鼠体内 ATP 含量明显降低，MMP 值明显增加，而 8 mL/kg SI 则可明显逆转。此外，脓毒症 AKI 小鼠体内观察到的 IL-6、p-p65、cle-caspase-3 和 Bax 水平的升高以及 Bcl-2 水平的降低在 8 毫升/千克 SI 的作用下也得到了明显的缓解。ML385 可取消 SI 对脓毒症 AKI 小鼠病理变化和线粒体的保护功能。这些研究结果表明，SI 通过调节 Nrf2/NF-κB 轴缓解了 LPS 诱导的脓毒性 AKI。
{"title":"Shenfu Injection Alleviates Lipopolysaccharide-Induced Septic Acute Kidney Injury by Regulating the Nrf2/NF-κ B Axis","authors":"Yajun Wang, Kai Kang, Yilu Lin, Qi-qi Lai, Yujia Tang, Xintong Wang, Di Wu, Huiying Liu, Huan Meng, Libin Huang, Yang Gao","doi":"10.1166/jbn.2024.383","DOIUrl":"https://doi.org/10.1166/jbn.2024.383","url":null,"abstract":"This study investigated the protective effect of Shenfu injection (SI) on septic acute kidney injury (AKI) induced by lipopolysaccharide (LPS) and its underlying mechanism. A mouse model of septic AKI was established, and various dosages of SI (2 mL/kg, 4 mL/kg, and 8 mL/kg) were administered\u0000 as treatment. HE staining and TUNEL assay were conducted for pathological analysis. The content of ATP was detected by the biochemical kit. The mitochondrial membrane potential (MMP) was detected by flow cytometry. Western blotting was used for the detecting expression of apoptosis and inflammation\u0000 related proteins. To explore the molecular mechanism, septic mice were treated by SI (8 mL/kg) combined with ML385 (30 mg/kg). The number and morphology of mitochondria were observed by the transmission electron microscope (TEM). The increased renal volume, paler renal cortex, and necrotic\u0000 renal tubules observed in septic AKI mice were significantly alleviated by treatment with either 4 mL/kg or 8 mL/kg of SI. Furthermore, signally declined ATP content and increased MMP value in septic AKI mice were markedly reversed by 8 mL/kg SI. Additionally, the increased IL-6, p-p65, cle-caspase-3,\u0000 and Bax levels, as well as the decreased Bcl-2 level, observed in septic AKI mice were notably rescued by 8 mL/kg SI. The protective function of SI on pathological changes and mitochondria in septic AKI mice was abolished by ML385. These findings suggested that SI alleviated LPS-induced septic\u0000 AKI by regulating the Nrf2/NF-κB axis.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141023896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Han Ding, Song Liu, Zhi-Guo Ding, Zhaojun Wang, Xingsheng Lu
Ras-related protein Rab24, a member of the small GTPase family, plays a vital role in regulating intracellular protein trafficking. Recent research has uncovered dysregulation of Rab24 in hepatocellular carcinoma (HCC), but its clinical implications and tumor-related effects require further investigation. We aimed to investigate Rab24’s expression patterns and its role in HCC progression. We analyzed Rab24 expression in HCC and adjacent tissues at the transcriptional, mRNA, and protein levels. The prognostic significance of Rab24 in HCC was assessed through univariate and multivariate analyses, along with Kaplan–Meier survival analysis. Rab24’s impact on cell proliferation was investigated through cellular and xenograft experiments. Our findings revealed elevated Rab24 expression in HCC tissues compared to adjacent liver tissues. High Rab24 expression correlated with larger tumor size and advanced tumor stage. Additionally, HCC patients with high Rab24 expression experienced poorer overall survival, with Rab24 identified as an independent prognostic factor. Manipulating Rab24 expression in HCC cell lines demonstrated its role in promoting tumor proliferation. Silencing Rab24 significantly reduced xenograft growth in vivo. This study highlights the significant association between high Rab24 expression and poorer HCC prognosis, suggesting Rab24’s potential as a novel clinical biomarker and therapeutic target.
{"title":"Ras-Related Protein Rab24 is a Predictor for Hepatocellular Carcinoma Prognosis and Promotes Tumor Growth","authors":"Han Ding, Song Liu, Zhi-Guo Ding, Zhaojun Wang, Xingsheng Lu","doi":"10.1166/jbn.2024.3831","DOIUrl":"https://doi.org/10.1166/jbn.2024.3831","url":null,"abstract":"Ras-related protein Rab24, a member of the small GTPase family, plays a vital role in regulating intracellular protein trafficking. Recent research has uncovered dysregulation of Rab24 in hepatocellular carcinoma (HCC), but its clinical implications and tumor-related effects require\u0000 further investigation. We aimed to investigate Rab24’s expression patterns and its role in HCC progression. We analyzed Rab24 expression in HCC and adjacent tissues at the transcriptional, mRNA, and protein levels. The prognostic significance of Rab24 in HCC was assessed through univariate\u0000 and multivariate analyses, along with Kaplan–Meier survival analysis. Rab24’s impact on cell proliferation was investigated through cellular and xenograft experiments. Our findings revealed elevated Rab24 expression in HCC tissues compared to adjacent liver tissues. High Rab24\u0000 expression correlated with larger tumor size and advanced tumor stage. Additionally, HCC patients with high Rab24 expression experienced poorer overall survival, with Rab24 identified as an independent prognostic factor. Manipulating Rab24 expression in HCC cell lines demonstrated its role\u0000 in promoting tumor proliferation. Silencing Rab24 significantly reduced xenograft growth in vivo. This study highlights the significant association between high Rab24 expression and poorer HCC prognosis, suggesting Rab24’s potential as a novel clinical biomarker and therapeutic\u0000 target.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141044215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Angiogenesis plays a key role in promoting the growth and metastasis of breast tumors. Tumor exosomes (EXs) contribute to angiogenesis in various tumor tissues by transferring their carried RNAs. MiR-423-5p was enriched in multiple tumors and implicated in tumor growth. In this study, we investigated the roles and underlying mechanisms of tumor-derived EXs and their carried miR-423-5p in regulating human umbilical vein endothelial cell (HUVEC) functions. EXs derived from MCF-7 cells (MCF-7 EXs) or with miR-423-5p knockdown (MCF-7 EXsSimiR-423-5p) were collected and incubated with ECs, and then the proliferation, migration, and tube formation abilities of ECs were detected. We found that miR-423-5p was enriched in breast cancer, MCF-7 cell lines and their derived EXs. After coculture with HUVECs, MCF-7 EXs merged into HUVECs and subsequently increased the miR-423-5p expression, proliferation, migration, and tube formation abilities of HUVECs, paralleling the increased EFNA3 and Notch1 expression, which was partially abolished by miR-423-5p knockdown. Altogether, our data suggest that MCF-7 EXs enriched with miR-423-5p promote the angiogenic function of vascular endothelial cells by activating the miR-423-5p/EFNA3/Akt signaling pathway.
{"title":"Tumor-Derived Exosomes Promote the Angiogenic Function of Vascular Endothelial Cells by Activating the miR-423-5p/EFNA3 Signaling Pathway","authors":"Zhongzeng Liang, Yuanqi Zhang, Chaosheng Huang, Zeming Yan, Huilai Miao","doi":"10.1166/jbn.2024.3833","DOIUrl":"https://doi.org/10.1166/jbn.2024.3833","url":null,"abstract":"Angiogenesis plays a key role in promoting the growth and metastasis of breast tumors. Tumor exosomes (EXs) contribute to angiogenesis in various tumor tissues by transferring their carried RNAs. MiR-423-5p was enriched in multiple tumors and implicated in tumor growth. In this study,\u0000 we investigated the roles and underlying mechanisms of tumor-derived EXs and their carried miR-423-5p in regulating human umbilical vein endothelial cell (HUVEC) functions. EXs derived from MCF-7 cells (MCF-7 EXs) or with miR-423-5p knockdown (MCF-7 EXsSimiR-423-5p) were collected\u0000 and incubated with ECs, and then the proliferation, migration, and tube formation abilities of ECs were detected. We found that miR-423-5p was enriched in breast cancer, MCF-7 cell lines and their derived EXs. After coculture with HUVECs, MCF-7 EXs merged into HUVECs and subsequently increased\u0000 the miR-423-5p expression, proliferation, migration, and tube formation abilities of HUVECs, paralleling the increased EFNA3 and Notch1 expression, which was partially abolished by miR-423-5p knockdown. Altogether, our data suggest that MCF-7 EXs enriched with miR-423-5p promote the angiogenic\u0000 function of vascular endothelial cells by activating the miR-423-5p/EFNA3/Akt signaling pathway.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141045553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jie Yang, Chao Wang, Chuan Zhou, Zijian Da, Fenghai Zhou
This study investigates immunogenic cell death (ICD)-related gene expression patterns in prostate adenocarcinoma (PRAD), explores the potential for ICD activation to induce anticancer effects, and identifies molecular subtypes in PRAD. Datasets from TCGA and GEO were analyzed using R software to assess ICD-related gene expression changes. Up-regulated genes included EIF2AK3, FOXP3, BAX, PDIA3, CALR, and CASP8, while down-regulated genes included IL1R, PIK3CA, IL17A, and others. Western blot confirmation supported the up-regulation of EIF2AK3, FOXP3, BAX, PDIA3, CALR, and CASP8. Clustering 497 samples based on 33 ICD-related genes revealed three molecular subtypes, with distinct gene functions and varying PD-L1 expression levels. The PRAD tumor microenvironment exhibited an abundance of resting dendritic cells and rare activated dendritic cells. This study suggests that diverse ICD-related genes are expressed in PRAD, leading to the classification of three molecular subtypes, which could guide precise molecular-level treatments. Additionally, the presence of resting dendritic cells in the PRAD tumor microenvironment hints at the potential for ICD-based therapies to activate these cells for anti-tumor effects.
{"title":"Characterization of Immunogenic Cell Death Related Molecular Subtypes and Its Therapeutic Implications for Prostate Adenocarcinoma","authors":"Jie Yang, Chao Wang, Chuan Zhou, Zijian Da, Fenghai Zhou","doi":"10.1166/jbn.2024.3830","DOIUrl":"https://doi.org/10.1166/jbn.2024.3830","url":null,"abstract":"This study investigates immunogenic cell death (ICD)-related gene expression patterns in prostate adenocarcinoma (PRAD), explores the potential for ICD activation to induce anticancer effects, and identifies molecular subtypes in PRAD. Datasets from TCGA and GEO were analyzed using\u0000 R software to assess ICD-related gene expression changes. Up-regulated genes included EIF2AK3, FOXP3, BAX, PDIA3, CALR, and CASP8, while down-regulated genes included IL1R, PIK3CA, IL17A, and others. Western blot confirmation supported the up-regulation of EIF2AK3, FOXP3, BAX, PDIA3, CALR,\u0000 and CASP8. Clustering 497 samples based on 33 ICD-related genes revealed three molecular subtypes, with distinct gene functions and varying PD-L1 expression levels. The PRAD tumor microenvironment exhibited an abundance of resting dendritic cells and rare activated dendritic cells. This study\u0000 suggests that diverse ICD-related genes are expressed in PRAD, leading to the classification of three molecular subtypes, which could guide precise molecular-level treatments. Additionally, the presence of resting dendritic cells in the PRAD tumor microenvironment hints at the potential for\u0000 ICD-based therapies to activate these cells for anti-tumor effects.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141031412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ying Zhang, Li Li, Weiling Wang, Man Li, Aihong Cao, Yanyan Hu
This study investigates the potential of TPX2 in mitigating diabetic cardiomyopathy by modulating the Akt/FoxO1 signaling pathway. Diabetic cardiomyopathy was induced in rats using streptozotocin, and heart structure and function were assessed through echocardiography and HE staining. TPX2 expression in myocardial tissue was measured using qRT-PCR. Lentivirus was used to overexpress TPX2 specifically in myocardial tissue, followed by reassessment of cardiac structure and function. Immunohistochemical staining was employed to evaluate Caspase3 expression. In the diabetic cardiomyopathy group, rat hearts exhibited evident damage in structure and function, with increased Caspase3 expression in myocardial tissue. Conversely, TPX2 overexpression effectively improved heart structure and function while inhibiting Caspase3 upregulation. In H9C2 cells cultured with high glucose, TPX2 overexpression counteracted reduced cell activity and increased apoptosis rates. It also downregulated the mRNA levels of apoptosis-related factors (Bax, Caspase3, Caspase9) and promoted anti-apoptotic factor Bcl-2 mRNA. TPX2 overexpression inhibited Caspase3 and Caspase9 activities, upregulated Akt mRNA and protein expression, and inhibited FoxO1 mRNA and protein expression. This suggests that TPX2 may regulate the Akt/FoxO1 signaling pathway, reducing apoptosis and cardiomyocyte toxicity induced by high glucose. These findings offer potential drug targets and therapeutic strategies for diabetic cardiomyopathy treatment.
{"title":"Antiapoptotic Effect of Target Protein for Xklp2 on Diabetic Rat Cardiomyocytes","authors":"Ying Zhang, Li Li, Weiling Wang, Man Li, Aihong Cao, Yanyan Hu","doi":"10.1166/jbn.2024.3832","DOIUrl":"https://doi.org/10.1166/jbn.2024.3832","url":null,"abstract":"This study investigates the potential of TPX2 in mitigating diabetic cardiomyopathy by modulating the Akt/FoxO1 signaling pathway. Diabetic cardiomyopathy was induced in rats using streptozotocin, and heart structure and function were assessed through echocardiography and HE staining.\u0000 TPX2 expression in myocardial tissue was measured using qRT-PCR. Lentivirus was used to overexpress TPX2 specifically in myocardial tissue, followed by reassessment of cardiac structure and function. Immunohistochemical staining was employed to evaluate Caspase3 expression. In the diabetic\u0000 cardiomyopathy group, rat hearts exhibited evident damage in structure and function, with increased Caspase3 expression in myocardial tissue. Conversely, TPX2 overexpression effectively improved heart structure and function while inhibiting Caspase3 upregulation. In H9C2 cells cultured with\u0000 high glucose, TPX2 overexpression counteracted reduced cell activity and increased apoptosis rates. It also downregulated the mRNA levels of apoptosis-related factors (Bax, Caspase3, Caspase9) and promoted anti-apoptotic factor Bcl-2 mRNA. TPX2 overexpression inhibited Caspase3 and Caspase9\u0000 activities, upregulated Akt mRNA and protein expression, and inhibited FoxO1 mRNA and protein expression. This suggests that TPX2 may regulate the Akt/FoxO1 signaling pathway, reducing apoptosis and cardiomyocyte toxicity induced by high glucose. These findings offer potential drug targets\u0000 and therapeutic strategies for diabetic cardiomyopathy treatment.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141057526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fe3O4 nanoparticles can be used in diagnostic imaging and therapeutic applications. However, poor solubility limits its use in tumors. In this study, we used ferric oxide and nanoparticles to covalently bind ferric oxide nanoparticles as a strategy for treatment of cervical cancer metastases. We aimed to evaluate their biological effects on cervical cancer metastases in vivo. Confocal microscopy was used to detect transfection efficiency, ferric oxide or ferric oxide nanoparticles were used to intervene cervical cancer cell lines, and flow cytometry explored cell apoptosis. The mouse model of cervical cancer metastasis was further treated with ferric oxide or ferric tetroxide nanoparticles through intraperitoneal injection. The tumor volume was counted and size was measured. Cell proliferation and apoptosis were detected by IHC and Western-blot was used to detect protein expression. Nanoparticles significantly enhanced the cellular uptake of Fe3O4, which inhibited cell proliferation and promoted cell apoptosis. In the in vivo transplanted tumor model, the same was observed in mice. In the mice model, ferric oxide nanoparticles significantly inhibited the growth of tumors, slowed down tumor growth rate, and accelerated apoptosis. Our research results showed that nanoparticles contributed to the uptake of oxidized particles, and Fe3O4 nanoparticles regulated studied tumors by enhancing cytotoxicity, thereby inhibiting cell proliferation and promoting cell apoptosis, achieving Fe3O4 nanoparticles. The particles significantly inhibited tumor growth, slowed down multiplication rate, and accelerated apoptosis, suggesting that Fe3O4 nanoparticles have a significant inhibitory effect on cervical cancer transplanted tumors.
{"title":"Ferric Oxide Nanoparticles Enhance Cytotoxicity and Reduce the Occurrence and Development of Cervical Cancer Metastases","authors":"Qiujin Cheng, Yanhua Song, Fu Zheng","doi":"10.1166/jbn.2024.3878","DOIUrl":"https://doi.org/10.1166/jbn.2024.3878","url":null,"abstract":"Fe3O4 nanoparticles can be used in diagnostic imaging and therapeutic applications. However, poor solubility limits its use in tumors. In this study, we used ferric oxide and nanoparticles to covalently bind ferric oxide nanoparticles as a strategy for treatment\u0000 of cervical cancer metastases. We aimed to evaluate their biological effects on cervical cancer metastases in vivo. Confocal microscopy was used to detect transfection efficiency, ferric oxide or ferric oxide nanoparticles were used to intervene cervical cancer cell lines, and flow\u0000 cytometry explored cell apoptosis. The mouse model of cervical cancer metastasis was further treated with ferric oxide or ferric tetroxide nanoparticles through intraperitoneal injection. The tumor volume was counted and size was measured. Cell proliferation and apoptosis were detected by\u0000 IHC and Western-blot was used to detect protein expression. Nanoparticles significantly enhanced the cellular uptake of Fe3O4, which inhibited cell proliferation and promoted cell apoptosis. In the in vivo transplanted tumor model, the same was observed in mice.\u0000 In the mice model, ferric oxide nanoparticles significantly inhibited the growth of tumors, slowed down tumor growth rate, and accelerated apoptosis. Our research results showed that nanoparticles contributed to the uptake of oxidized particles, and Fe3O4 nanoparticles\u0000 regulated studied tumors by enhancing cytotoxicity, thereby inhibiting cell proliferation and promoting cell apoptosis, achieving Fe3O4 nanoparticles. The particles significantly inhibited tumor growth, slowed down multiplication rate, and accelerated apoptosis, suggesting\u0000 that Fe3O4 nanoparticles have a significant inhibitory effect on cervical cancer transplanted tumors.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141041493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shouxian Peng, Weiguang Wang, Rong Ling, Shechang Zou, Dongping Li, Hong Guo
Our study aimed to explore whether YT521-B homology domain family protein 2 (YTHDF2)-dependent m6A is involved in oxidative stress induced by I/R in vitro. We established a cell model of I/R by oxygen-glucose deprivation/re-oxygenation (OGD/R) in HT22 cell line. The shRNAs were used to silence YTHDF2 and Nrf2. The expression of YTHDF2 and Nrf2, levels of m6A, and the indicators related to oxidative stress (GSH, SOD and MDA) was detected in different cell groups. CCK8, flow cytometry, and ki67 fluorescence staining was used to evaluate the cell viability and apoptosis. The levels of YTHDF2, m6A and MDA were increased in cells, while the levels of GSH and SOD were reduced by OGD/R. Also, the apoptosis in cells was increased after OGD/R, and with decreased cell viability. The knockdown of YTHDF2 could reduce the level of m6A, increase the expression of Nrf2. Moreover, the levels of GSH and SOD were increased after exposure to YTHDF2-shRNA, while the level of MDA was decreased, and the cell viability was increased. Our study showed that YTHDF2-Dependent N6A mediates cerebral I/R injury via oxidative stress in vitro, which may constitute a new target for stroke.
{"title":"Human YTH Domain Family 2 (YTHDF2)-Dependent N6-Methyladenosine Mediates Cerebral Ischemia/Reperfusion Injury via Oxidative Stress","authors":"Shouxian Peng, Weiguang Wang, Rong Ling, Shechang Zou, Dongping Li, Hong Guo","doi":"10.1166/jbn.2024.3828","DOIUrl":"https://doi.org/10.1166/jbn.2024.3828","url":null,"abstract":"Our study aimed to explore whether YT521-B homology domain family protein 2 (YTHDF2)-dependent m6A is involved in oxidative stress induced by I/R in vitro. We established a cell model of I/R by oxygen-glucose deprivation/re-oxygenation (OGD/R) in HT22 cell line. The shRNAs were\u0000 used to silence YTHDF2 and Nrf2. The expression of YTHDF2 and Nrf2, levels of m6A, and the indicators related to oxidative stress (GSH, SOD and MDA) was detected in different cell groups. CCK8, flow cytometry, and ki67 fluorescence staining was used to evaluate the cell viability and apoptosis.\u0000 The levels of YTHDF2, m6A and MDA were increased in cells, while the levels of GSH and SOD were reduced by OGD/R. Also, the apoptosis in cells was increased after OGD/R, and with decreased cell viability. The knockdown of YTHDF2 could reduce the level of m6A, increase the expression of Nrf2.\u0000 Moreover, the levels of GSH and SOD were increased after exposure to YTHDF2-shRNA, while the level of MDA was decreased, and the cell viability was increased. Our study showed that YTHDF2-Dependent N6A mediates cerebral I/R injury via oxidative stress in vitro, which may constitute\u0000 a new target for stroke.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141047690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiangwei Ke, Kuai Chen, Zhiqiang Liu, Ximei Yang, Xiaolu Hu
Congenital esophageal atresia (EA) is an abnormality induced by the incomplete differentiation of the foregut in infants, and is frequently accompanied by tracheoesophageal fistula (TEF). Our understanding of the pathogenesis of EA-TEF is limited, additionally, there is still a lack of standard animal or cell models for in vitro EA-TEF investigation. Therefore, we analyzed esophageal tissue samples from 10 children with EA-TEF via Exome sequencing (ES) to identify gene variants. And esophageal organoid units (EOUs) were established as an in vitro model of EA by culturing esophageal tissues from Adriamycin-challenged rats. The ES results indicated 11 mutated genes, including the frameshift variants of ZNF717 and PABPC1. The EA organoids expressed the esophageal marker proteins CK13 and CK4 and showed a significantly slower rate of growth and dysplasia of cell development. In EA organoids, the transcription of SOX2, ZNF717, and PABPC1 was downregulated at varying levels, while NOGGIN transcription was markedly upregulated. Furthermore, when siRNA-ZNF717 or siRNA-PABPC1 was transfected into normal esophageal organoids, the proliferation of esophageal cells was significantly decreased. In conclusion, we found that normal ZNF717 and PABPC1 expressions are essential to the esophageal development, whereas the variant or deficiency of these genes might lead to EA-TEF.
{"title":"ZNF717 or PABPC1 Gene Variants Contribute to Congenital Esophageal Atresia by Interfering with Normal Esophageal Growth","authors":"Jiangwei Ke, Kuai Chen, Zhiqiang Liu, Ximei Yang, Xiaolu Hu","doi":"10.1166/jbn.2024.3836","DOIUrl":"https://doi.org/10.1166/jbn.2024.3836","url":null,"abstract":"Congenital esophageal atresia (EA) is an abnormality induced by the incomplete differentiation of the foregut in infants, and is frequently accompanied by tracheoesophageal fistula (TEF). Our understanding of the pathogenesis of EA-TEF is limited, additionally, there is still a lack\u0000 of standard animal or cell models for in vitro EA-TEF investigation. Therefore, we analyzed esophageal tissue samples from 10 children with EA-TEF via Exome sequencing (ES) to identify gene variants. And esophageal organoid units (EOUs) were established as an in vitro model of\u0000 EA by culturing esophageal tissues from Adriamycin-challenged rats. The ES results indicated 11 mutated genes, including the frameshift variants of ZNF717 and PABPC1. The EA organoids expressed the esophageal marker proteins CK13 and CK4 and showed a significantly slower rate\u0000 of growth and dysplasia of cell development. In EA organoids, the transcription of SOX2, ZNF717, and PABPC1 was downregulated at varying levels, while NOGGIN transcription was markedly upregulated. Furthermore, when siRNA-ZNF717 or siRNA-PABPC1 was transfected into\u0000 normal esophageal organoids, the proliferation of esophageal cells was significantly decreased. In conclusion, we found that normal ZNF717 and PABPC1 expressions are essential to the esophageal development, whereas the variant or deficiency of these genes might lead to EA-TEF.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141039688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To clarify the role of long non-coding RNA (lncRNA) MIAT in regulating proliferative and migratory abilities in VSMCs extracted from hypertension mice via downregulating microRNA-505-5p (miR-505-5p). Serum levels of MIAT and miR-505-5p in enrolled 20 hypertension patients and 20 healthy volunteers were detected. VSMCs were extracted from hypertension mice and healthy mice. Regulatory effects of MIAT and miR-505-5p on proliferative and migratory abilities in VSMCs were examined. At last, the interaction between MIAT and miR-505-5p was explored by dual-luciferase reporter assay and rescue experiments. Serum level of MIAT was higher in hypertension patients than those of healthy subjects, while miR-505-5p was downregulated. MIAT level was negatively correlated to miR-505-5p level in serum of hypertension patients. Knockdown of MIAT suppressed proliferative and migratory abilities in VSMCs extracted from hypertension mice. In addition, knockdown of MIAT upregulated E-cadherin and downregulated Vimentin and Snail-1. MiR-505-5p was verified to be the target binding MIAT. Knockdown of miR-505-5p reversed regulatory effects of MIAT on VSMCs phenotypes. LncRNA MIAT stimulates VSMCs in hypertension mice to proliferate and migrate through downregulating miR-505-5p, which may be a promising target for diagnosis and treatment of hypertension.
{"title":"LncRNA Myocardial Infarction-Associated Transcript (MIAT)/miR-505-5p Axis Regulates Proliferation and Migration of Vascular Smooth Muscle Cells of Hypertension Mice","authors":"Hua Yang, Hongfei Song, Pan Xiong","doi":"10.1166/jbn.2024.3824","DOIUrl":"https://doi.org/10.1166/jbn.2024.3824","url":null,"abstract":"To clarify the role of long non-coding RNA (lncRNA) MIAT in regulating proliferative and migratory abilities in VSMCs extracted from hypertension mice via downregulating microRNA-505-5p (miR-505-5p). Serum levels of MIAT and miR-505-5p in enrolled 20 hypertension patients and 20 healthy\u0000 volunteers were detected. VSMCs were extracted from hypertension mice and healthy mice. Regulatory effects of MIAT and miR-505-5p on proliferative and migratory abilities in VSMCs were examined. At last, the interaction between MIAT and miR-505-5p was explored by dual-luciferase reporter assay\u0000 and rescue experiments. Serum level of MIAT was higher in hypertension patients than those of healthy subjects, while miR-505-5p was downregulated. MIAT level was negatively correlated to miR-505-5p level in serum of hypertension patients. Knockdown of MIAT suppressed proliferative and migratory\u0000 abilities in VSMCs extracted from hypertension mice. In addition, knockdown of MIAT upregulated E-cadherin and downregulated Vimentin and Snail-1. MiR-505-5p was verified to be the target binding MIAT. Knockdown of miR-505-5p reversed regulatory effects of MIAT on VSMCs phenotypes. LncRNA\u0000 MIAT stimulates VSMCs in hypertension mice to proliferate and migrate through downregulating miR-505-5p, which may be a promising target for diagnosis and treatment of hypertension.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141047552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ang Li, Chenglin Qin, Hefei Chen, Yong Zhou, Yonghua Xu, Min Xu, Wenzhang Zha
Hepatocellular carcinoma (HCC) is a major contributor to global cancer-related deaths. The chromatin binding protein MCM5, part of the MCM family, plays a crucial role in regulating DNA replication, a key driver of cancer. Database analysis revealed elevated MCM5 levels in HCC, associated with shorter patient survival. Silencing MCM5 impedes liver cancer cell proliferation by halting the cell cycle at G1 phase. In vivo experiments confirm this effect, demonstrating that MCM5 knockdown suppresses HCC growth. Mechanistic studies unveil MCM5′s impact on HCC development via the PI3K/AKT/mTOR signaling pathway. Reversing liver cancer growth is possible by adding AKT agonist SC79. Additionally, inhibiting mettl3 with stm2457 downregulates MCM5, further suppressing liver cancer growth. In summary, high MCM5 expression in liver cancer correlates with poor prognosis and drives disease progression. Targeting MCM5 with mettl3 inhibitors presents a promising therapeutic strategy for HCC.
{"title":"Minichromosome Maintenance Complex Component 5 Modified by Mettl3 Inhibits the Proliferation of Liver Cancer by Regulating PI3K/AKT/mTOR Axis","authors":"Ang Li, Chenglin Qin, Hefei Chen, Yong Zhou, Yonghua Xu, Min Xu, Wenzhang Zha","doi":"10.1166/jbn.2024.3815","DOIUrl":"https://doi.org/10.1166/jbn.2024.3815","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a major contributor to global cancer-related deaths. The chromatin binding protein MCM5, part of the MCM family, plays a crucial role in regulating DNA replication, a key driver of cancer. Database analysis revealed elevated MCM5 levels in HCC, associated\u0000 with shorter patient survival. Silencing MCM5 impedes liver cancer cell proliferation by halting the cell cycle at G1 phase. In vivo experiments confirm this effect, demonstrating that MCM5 knockdown suppresses HCC growth. Mechanistic studies unveil MCM5′s impact on HCC development\u0000 via the PI3K/AKT/mTOR signaling pathway. Reversing liver cancer growth is possible by adding AKT agonist SC79. Additionally, inhibiting mettl3 with stm2457 downregulates MCM5, further suppressing liver cancer growth. In summary, high MCM5 expression in liver cancer correlates with poor prognosis\u0000 and drives disease progression. Targeting MCM5 with mettl3 inhibitors presents a promising therapeutic strategy for HCC.","PeriodicalId":15260,"journal":{"name":"Journal of biomedical nanotechnology","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140354305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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