Siming Zhang, Xiaojia Huang, Wenbiao Zhu, Yumei Liu, Ni Qiu, Zheyou Cai, Tai Xu, Yuan Wu, Yuanlin Fan, Dongqin Qiu, Junqiang Zhu, Hongsheng Li
Trastuzumab, a first-line targeted agent for HER-2-positive breast cancer, often faces challenges due to resistance. The IGF-1R/IRS-1/AKT pathway hyperactivation has been linked to this resistance, but the primary culprit, whether epithelial cells or cancer-associated fibroblasts (CAFs), remains uncertain. To investigate, we employed seRNA-seq to differentiate CAFs and epithelial cells in trastuzumab-sensitive and resistant breast cancer samples. iTALK analysis revealed potential interactions between CAFs and epithelial cells through IGF-1. We then analyzed 43 HER-2-positive breast cancer samples treated with trastuzumab, confirming higher expression of IGF-1R/IRS-1/AKT pathway proteins using immunohistochemistry. Notably, we identified five CAFs subtypes with varying proportions in both trastuzumab-sensitive and resistant samples. Further analysis revealed elevated IGF-1 levels in CAFs of trastuzumab-resistant tissues, particularly in adipose CAFs. Immunohistochemistry staining corroborated overexpression of COL11A1 (an adipose CAF marker) and increased IGF-1R and Tyr-phosphorylated IRS-1 in HER-2-positive breast cancer, associated with poor trastuzumab response. Our findings suggest that CAFs, particularly adipose CAFs, may induce trastuzumab resistance in HER2-positive breast cancer epithelial cells through IGF-1-mediated activation of the IGF-1R/IRS-1/AKT pathway.
{"title":"Single-Cell Analysis Reveals Adipose Cancer-Associated Fibroblasts Linked to Trastuzumab Resistance in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer","authors":"Siming Zhang, Xiaojia Huang, Wenbiao Zhu, Yumei Liu, Ni Qiu, Zheyou Cai, Tai Xu, Yuan Wu, Yuanlin Fan, Dongqin Qiu, Junqiang Zhu, Hongsheng Li","doi":"10.1166/sam.2023.4536","DOIUrl":"https://doi.org/10.1166/sam.2023.4536","url":null,"abstract":"Trastuzumab, a first-line targeted agent for HER-2-positive breast cancer, often faces challenges due to resistance. The IGF-1R/IRS-1/AKT pathway hyperactivation has been linked to this resistance, but the primary culprit, whether epithelial cells or cancer-associated fibroblasts (CAFs), remains uncertain. To investigate, we employed seRNA-seq to differentiate CAFs and epithelial cells in trastuzumab-sensitive and resistant breast cancer samples. iTALK analysis revealed potential interactions between CAFs and epithelial cells through IGF-1. We then analyzed 43 HER-2-positive breast cancer samples treated with trastuzumab, confirming higher expression of IGF-1R/IRS-1/AKT pathway proteins using immunohistochemistry. Notably, we identified five CAFs subtypes with varying proportions in both trastuzumab-sensitive and resistant samples. Further analysis revealed elevated IGF-1 levels in CAFs of trastuzumab-resistant tissues, particularly in adipose CAFs. Immunohistochemistry staining corroborated overexpression of COL11A1 (an adipose CAF marker) and increased IGF-1R and Tyr-phosphorylated IRS-1 in HER-2-positive breast cancer, associated with poor trastuzumab response. Our findings suggest that CAFs, particularly adipose CAFs, may induce trastuzumab resistance in HER2-positive breast cancer epithelial cells through IGF-1-mediated activation of the IGF-1R/IRS-1/AKT pathway.","PeriodicalId":21671,"journal":{"name":"Science of Advanced Materials","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This research was aimed to analyze the biological characteristics of mifepristone solid lipid nanoparticles (MFP/SLNs) and their effects on the cardiac function of rats undergoing induction of labor at full term (FTIL). MFP was loaded into SLNs to prepare MFP/SLNs. The morphology and particle size (PS) of MFP/SLNs were observed by transmission electron microscopy (TEM), and the PS distribution (PSD) and potential distribution of MFP/SLNs were analyzed by Zeta analyzer. The drug loading (DL) and encapsulation efficiency (EE) of MFP/SLNs were calculated, and the crystal form of the drug in the carrier was detected by differential scanning calorimetry (DSC). Fifteen pregnant rats were randomly rolled into a blank (BLK) group, an MFP group, and an MFP/SLNs group, with five rats in each. Those in the MFP/SLNs and the MFP groups were administered MFP/SLNs (10 mg) and MFP by gavage on the 20th day of pregnancy. The changes in myocardial tissue of rats in the MFP/SLNs and MFP groups were observed within 24 hours after delivery and analyzed by a multifunctional true-color pathological image analysis system. The results indicated that MFP/SLNs had a spherical shape and uniform PSD, with an average PS of about 153 nm. The drug EE of MFP/SLNs exceeded 88% when the drug dosage was 50 mg. The MFP group showed obvious cytoplasmic edema in myocardial cells, an increased average mitochondrial volume density (MVD), and glycogen granule deposition. The area of myocardial cells in the MFP group was obviously larger than that in the MFP/SLNs group ( P < 0.05), and the nuclear-cytoplasmic ratio (NCR) was much smaller ( P < 0.05). These findings suggested that MFP/SLNs were successfully prepared, and MFP can cause changes in the cardiac structure of rats undergoing FTIL, resulting in hypoxic injury. However, MFP/SLNs may protect the cardiac structure and function of rats.
{"title":"Effects of Mifepristone Solid Lipid Nanoparticles on Cardiac Structure and Function in Rats Undergoing Induction of Labor at Full Term","authors":"Ruixue Liu, Fan Xie, Tian Jiang, Quan Zhu","doi":"10.1166/sam.2023.4540","DOIUrl":"https://doi.org/10.1166/sam.2023.4540","url":null,"abstract":"This research was aimed to analyze the biological characteristics of mifepristone solid lipid nanoparticles (MFP/SLNs) and their effects on the cardiac function of rats undergoing induction of labor at full term (FTIL). MFP was loaded into SLNs to prepare MFP/SLNs. The morphology and particle size (PS) of MFP/SLNs were observed by transmission electron microscopy (TEM), and the PS distribution (PSD) and potential distribution of MFP/SLNs were analyzed by Zeta analyzer. The drug loading (DL) and encapsulation efficiency (EE) of MFP/SLNs were calculated, and the crystal form of the drug in the carrier was detected by differential scanning calorimetry (DSC). Fifteen pregnant rats were randomly rolled into a blank (BLK) group, an MFP group, and an MFP/SLNs group, with five rats in each. Those in the MFP/SLNs and the MFP groups were administered MFP/SLNs (10 mg) and MFP by gavage on the 20th day of pregnancy. The changes in myocardial tissue of rats in the MFP/SLNs and MFP groups were observed within 24 hours after delivery and analyzed by a multifunctional true-color pathological image analysis system. The results indicated that MFP/SLNs had a spherical shape and uniform PSD, with an average PS of about 153 nm. The drug EE of MFP/SLNs exceeded 88% when the drug dosage was 50 mg. The MFP group showed obvious cytoplasmic edema in myocardial cells, an increased average mitochondrial volume density (MVD), and glycogen granule deposition. The area of myocardial cells in the MFP group was obviously larger than that in the MFP/SLNs group ( P < 0.05), and the nuclear-cytoplasmic ratio (NCR) was much smaller ( P < 0.05). These findings suggested that MFP/SLNs were successfully prepared, and MFP can cause changes in the cardiac structure of rats undergoing FTIL, resulting in hypoxic injury. However, MFP/SLNs may protect the cardiac structure and function of rats.","PeriodicalId":21671,"journal":{"name":"Science of Advanced Materials","volume":"12 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jingdan Hu, Jingxue Sang, Ping Li, Xinpei Wei, Zhun Wang, Kai Song
This study delineates the successful fabrication of red light-emitting carbon quantum dots (R-CQDs), approximately 3.5 nm in size, via hydrothermal methods. These carbon quantum dots (CQDs) display distinctive fluorescence properties, particularly a laser-dependency. The infrared and Raman spectra were subjected to a thorough investigation, revealing the presence of hydroxyl, amino, and carboxyl groups on the surface of the CQDs. Experimental findings indicate a significant correlation between the antibacterial effect of R-CQDs on E. coli and Yeast and their concentration. Subsequent research suggests that this antibacterial activity primarily stems from the CQDs’ disruption of cell membrane integrity, leading to the leakage of intracellular substances and consequently inhibiting the growth of these two microorganisms. The study also reveals that R-CQDs can trigger chromosomal aberrations in the root tip cells of broad beans and induce micronuclei formation. The frequency of micronuclei is directly proportional to the CQDs dosage, and an extended treatment duration results in an increased micronucleus rate. This suggests potential damage to the genetic material of broad beans by CQDs, which could adversely affect their growth and development. The study further identifies a significant impact of R-CQDs on the height of rice seedlings, causing a substantial reduction. Moreover, it was found that CQDs can infiltrate the rice body and instigate oxidative stress responses.
{"title":"Synthesis and Biological Toxicity Evaluation of Red Light-Emitting Carbon Quantum Dots","authors":"Jingdan Hu, Jingxue Sang, Ping Li, Xinpei Wei, Zhun Wang, Kai Song","doi":"10.1166/sam.2023.4530","DOIUrl":"https://doi.org/10.1166/sam.2023.4530","url":null,"abstract":"This study delineates the successful fabrication of red light-emitting carbon quantum dots (R-CQDs), approximately 3.5 nm in size, via hydrothermal methods. These carbon quantum dots (CQDs) display distinctive fluorescence properties, particularly a laser-dependency. The infrared and Raman spectra were subjected to a thorough investigation, revealing the presence of hydroxyl, amino, and carboxyl groups on the surface of the CQDs. Experimental findings indicate a significant correlation between the antibacterial effect of R-CQDs on E. coli and Yeast and their concentration. Subsequent research suggests that this antibacterial activity primarily stems from the CQDs’ disruption of cell membrane integrity, leading to the leakage of intracellular substances and consequently inhibiting the growth of these two microorganisms. The study also reveals that R-CQDs can trigger chromosomal aberrations in the root tip cells of broad beans and induce micronuclei formation. The frequency of micronuclei is directly proportional to the CQDs dosage, and an extended treatment duration results in an increased micronucleus rate. This suggests potential damage to the genetic material of broad beans by CQDs, which could adversely affect their growth and development. The study further identifies a significant impact of R-CQDs on the height of rice seedlings, causing a substantial reduction. Moreover, it was found that CQDs can infiltrate the rice body and instigate oxidative stress responses.","PeriodicalId":21671,"journal":{"name":"Science of Advanced Materials","volume":"44 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Colorectal cancer (CRC) is a prevalent malignancy worldwide, and microRNAs (miRNAs) have been recognized for their significant role in CRC progression and potential as therapeutic targets. This study aimed to investigate the impact of miR-222-3p on CRC cell proliferation, migration, and invasion, along with its target genes. HT29 cells were transfected with mimic-negative control (mimic-NC) or mimic-miR-222-3p, while the control group remained untreated. Cell proliferation, migration, and invasion were assessed using CCK-8 and Transwell assays. qRT-PCR and Western blotting were employed to measure gene mRNA and protein expression, respectively. A luciferase reporter assay verified the binding between miR-222-3p and its downstream target gene ITGB3. The results revealed that enhanced miR-222-3p expression significantly increased HT29 cell proliferation, migration, and invasion. qRT-PCR and Western blotting indicated reduced expression of ITGB3 and E-cadherin, and upregulation of Vimentin and α -SMA by miR-222-3p. The luciferase reporter assay confirmed ITGB3 as a direct target of miR-222-3p. In conclusion, miR-222-3p promotes CRC progression by regulating ITGB3 expression, suggesting its potential as a crucial biomarker and therapeutic target for colorectal cancer.
结直肠癌(CRC)是一种世界范围内普遍存在的恶性肿瘤，microRNAs (miRNAs)在结直肠癌进展中的重要作用和作为治疗靶点的潜力已得到认可。本研究旨在探讨miR-222-3p及其靶基因对结直肠癌细胞增殖、迁移和侵袭的影响。HT29细胞转染模拟阴性对照(mimi - nc)或mimi - mir -222-3p，对照组不处理。采用CCK-8和Transwell试验评估细胞增殖、迁移和侵袭。采用qRT-PCR和Western blotting分别检测基因mRNA和蛋白的表达。荧光素酶报告基因实验证实了miR-222-3p与其下游靶基因ITGB3之间的结合。结果显示，miR-222-3p表达增强可显著提高HT29细胞的增殖、迁移和侵袭能力。qRT-PCR和Western blotting显示miR-222-3p降低了ITGB3和E-cadherin的表达，上调了Vimentin和α -SMA的表达。荧光素酶报告基因检测证实ITGB3是miR-222-3p的直接靶点。总之，miR-222-3p通过调节ITGB3的表达促进结直肠癌的进展，表明其作为结直肠癌的重要生物标志物和治疗靶点的潜力。
{"title":"Mechanism of <i>hsa-miR-222-3p</i> Targeting Integrin Subunit Beta 3 to Regulate Malignant Behavior of Colorectal Cancer HT29 Cells","authors":"Meng Li, Qianyang Ni, Suyang Yu","doi":"10.1166/sam.2023.4534","DOIUrl":"https://doi.org/10.1166/sam.2023.4534","url":null,"abstract":"Colorectal cancer (CRC) is a prevalent malignancy worldwide, and microRNAs (miRNAs) have been recognized for their significant role in CRC progression and potential as therapeutic targets. This study aimed to investigate the impact of miR-222-3p on CRC cell proliferation, migration, and invasion, along with its target genes. HT29 cells were transfected with mimic-negative control (mimic-NC) or mimic-miR-222-3p, while the control group remained untreated. Cell proliferation, migration, and invasion were assessed using CCK-8 and Transwell assays. qRT-PCR and Western blotting were employed to measure gene mRNA and protein expression, respectively. A luciferase reporter assay verified the binding between miR-222-3p and its downstream target gene ITGB3. The results revealed that enhanced miR-222-3p expression significantly increased HT29 cell proliferation, migration, and invasion. qRT-PCR and Western blotting indicated reduced expression of ITGB3 and E-cadherin, and upregulation of Vimentin and α -SMA by miR-222-3p. The luciferase reporter assay confirmed ITGB3 as a direct target of miR-222-3p. In conclusion, miR-222-3p promotes CRC progression by regulating ITGB3 expression, suggesting its potential as a crucial biomarker and therapeutic target for colorectal cancer.","PeriodicalId":21671,"journal":{"name":"Science of Advanced Materials","volume":"124 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136010062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This research was aimed to investigate the effects of biodegradable letrozole (LE) sustained release (SR) polymer material on the biological behavior of uterine fibroids (UFs) and RON/PI3K signaling pathway (SPW). Poloxamer 188 (P188) and poly L lactide acid (PLLA) were selected to prepare the degradable SR electrospinning (ES) materials LE/P188/PlLA-1 (LE concentration: 6.25%), LE/P188/PLLA-2 (LE concentration: 12.25%), and LE/P188/PLLA-3 (LE concentration: 25%) with different concentrations of LE. UF cells were then co-cultured with free LE and degradable SR ES materials. Cell proliferation and apoptosis were detected by MTT and flow cytometry, respectively. The expression changes of apoptosis-related proteins (Bcl-2, Bax, and caspase-3), epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin, Vimentin), and RON/PI3K SPW-related proteins (RON and PI3K) were detected by western blot. The average diameter of LE/P188/PLLA-1, LE/P188/PLLA-2, and LE/P188/PLLA-3 were (145.6±20.8) nm, (158.1±16.3) nm, and (173.4±20.1) nm, respectively. Moreover, it possessed the obvious characteristics of LE, P188, and PLLA. LE/P188/PLLA-3 had the lowest SR rate of LE but the longest SR duration. Compared with normal cells, the proliferation inhibition rate (PIR) and apoptosis rate (AR) of LE and its degradable SR ES materials were increased ( P <0.05). While expressions of Bax, caspase-3, E-cadherin, and PI3K were increased, Bcl-2, N-cadherin, Vimentin, and RON were decreased ( P <0.05). In contrast to the free LE, the cell proliferation inhibition rate (PIR) and apoptosis promotion rate (APR) of LE degradable SR ES materials were increased, the levels of Bax, caspase-3, E-cadherin, and PI3K were increased, and the levels of Bcl-2, N-cadherin, Vimentin, and RON were decreased ( P <0.05). The results herein were concentration-dependent. The preparation of LE degradable SR ES materials with P188/PLLA can improve the therapeutic effect of LE. LE degradable SR ES materials can effectively inhibit the proliferation of UFs, promote cell apoptosis, inhibit its EMT process and activation of RON/PI3K SPW in a concentration-dependent manner.
{"title":"Effects of Recepteur D’origine Nantais/Phosphatidylinositol 3 Kinase Pathway Mediated by Polymer Biodegradable Sustained-Release Materials on Proliferation and Apoptosis of Uterine Fibroids","authors":"Jianhua Wang, Qinmei Wang, Jianmin Liu","doi":"10.1166/sam.2023.4538","DOIUrl":"https://doi.org/10.1166/sam.2023.4538","url":null,"abstract":"This research was aimed to investigate the effects of biodegradable letrozole (LE) sustained release (SR) polymer material on the biological behavior of uterine fibroids (UFs) and RON/PI3K signaling pathway (SPW). Poloxamer 188 (P188) and poly L lactide acid (PLLA) were selected to prepare the degradable SR electrospinning (ES) materials LE/P188/PlLA-1 (LE concentration: 6.25%), LE/P188/PLLA-2 (LE concentration: 12.25%), and LE/P188/PLLA-3 (LE concentration: 25%) with different concentrations of LE. UF cells were then co-cultured with free LE and degradable SR ES materials. Cell proliferation and apoptosis were detected by MTT and flow cytometry, respectively. The expression changes of apoptosis-related proteins (Bcl-2, Bax, and caspase-3), epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin, Vimentin), and RON/PI3K SPW-related proteins (RON and PI3K) were detected by western blot. The average diameter of LE/P188/PLLA-1, LE/P188/PLLA-2, and LE/P188/PLLA-3 were (145.6±20.8) nm, (158.1±16.3) nm, and (173.4±20.1) nm, respectively. Moreover, it possessed the obvious characteristics of LE, P188, and PLLA. LE/P188/PLLA-3 had the lowest SR rate of LE but the longest SR duration. Compared with normal cells, the proliferation inhibition rate (PIR) and apoptosis rate (AR) of LE and its degradable SR ES materials were increased ( P <0.05). While expressions of Bax, caspase-3, E-cadherin, and PI3K were increased, Bcl-2, N-cadherin, Vimentin, and RON were decreased ( P <0.05). In contrast to the free LE, the cell proliferation inhibition rate (PIR) and apoptosis promotion rate (APR) of LE degradable SR ES materials were increased, the levels of Bax, caspase-3, E-cadherin, and PI3K were increased, and the levels of Bcl-2, N-cadherin, Vimentin, and RON were decreased ( P <0.05). The results herein were concentration-dependent. The preparation of LE degradable SR ES materials with P188/PLLA can improve the therapeutic effect of LE. LE degradable SR ES materials can effectively inhibit the proliferation of UFs, promote cell apoptosis, inhibit its EMT process and activation of RON/PI3K SPW in a concentration-dependent manner.","PeriodicalId":21671,"journal":{"name":"Science of Advanced Materials","volume":"42 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Knee osteoarthritis (KOA) is a prevalent joint disorder characterized by articular cartilage degeneration and apoptosis. This research was aimed to demonstrate effects of calcitonin (CT) on apoptosis and Bcl-2 in KOA articular chondrocytes. In vitro cellular experiments were conducted using articular chondrocytes obtained from KOA patients, with a portion of the cells undergoing passaging and proliferation culture. The remaining cells were rolled into control group (normal chondrocytes), KOA group (chondrocytes from arthritis joints), and CT group (chondrocytes from arthritis joints treated with CT). Control and KOA groups were treated with an equivalent amount of saline solution. Apoptosis and Bcl-2 protein expression levels were assessed in each group to evaluate the impact of CT on articular chondrocytes. It was revealed that proliferation rate of human chondrocytes decreased with increasing passage number, and the exponential growth phase was shorter. After day 6, the proliferation rate drastically increased, exhibiting an exponential growth trend. Relative to KOA group, the CT group demonstrated a notable reduction in apoptosis of articular chondrocytes ( P <0.05). Bcl-2 protein level was greatly upregulated in CT group ( P < 0.05). In short, CT can inhibit apoptosis of articular chondrocytes and promote Bcl-2 expression, thereby contributing to the stability and survival of articular chondrocytes. In summary, CT has a positive effect on apoptosis and Bcl-2 expression in KOA articular chondrocytes.
{"title":"Effects of Calcitonin on Apoptosis and B-Cell Lymphoma 2 Expression in Knee Osteoarthritis Articular Chondrocytes","authors":"Wenyuan Xiang, Wenhao Zhang, Yingjie Deng, Desheng Miao, Lin Yi, Rui Fang","doi":"10.1166/sam.2023.4542","DOIUrl":"https://doi.org/10.1166/sam.2023.4542","url":null,"abstract":"Knee osteoarthritis (KOA) is a prevalent joint disorder characterized by articular cartilage degeneration and apoptosis. This research was aimed to demonstrate effects of calcitonin (CT) on apoptosis and Bcl-2 in KOA articular chondrocytes. In vitro cellular experiments were conducted using articular chondrocytes obtained from KOA patients, with a portion of the cells undergoing passaging and proliferation culture. The remaining cells were rolled into control group (normal chondrocytes), KOA group (chondrocytes from arthritis joints), and CT group (chondrocytes from arthritis joints treated with CT). Control and KOA groups were treated with an equivalent amount of saline solution. Apoptosis and Bcl-2 protein expression levels were assessed in each group to evaluate the impact of CT on articular chondrocytes. It was revealed that proliferation rate of human chondrocytes decreased with increasing passage number, and the exponential growth phase was shorter. After day 6, the proliferation rate drastically increased, exhibiting an exponential growth trend. Relative to KOA group, the CT group demonstrated a notable reduction in apoptosis of articular chondrocytes ( P <0.05). Bcl-2 protein level was greatly upregulated in CT group ( P < 0.05). In short, CT can inhibit apoptosis of articular chondrocytes and promote Bcl-2 expression, thereby contributing to the stability and survival of articular chondrocytes. In summary, CT has a positive effect on apoptosis and Bcl-2 expression in KOA articular chondrocytes.","PeriodicalId":21671,"journal":{"name":"Science of Advanced Materials","volume":"135 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In this study, the crystal structure as well as electron transport of TiN thin films were evaluated. We used DC reactive magnetron sputtering to deposit a thin layer of polycrystalline titanium nitride (TiN) on a Si (100) substrate starting from elemental Ti in a nitrogen atmosphere. The influence of nitrogen flow rate on the crystal structure, surface morphology, and electron transport of TiN were investigated systematically. It was found that the preferred orientation and conductivity of TiN thin films exhibit strong nitrogen flow rate dependence. The preferred orientation changed from (111) to (200) initially and then changed back to (111) as the nitrogen flow rate increases. However, an increase in the (200) phase leads to higher conductivity and lower surface roughness. At the optimized deposition conditions, ultra-thin (around 30 nm) TiN thin films with a low resistivity of 101.8 μ C·cm and a surface roughness of less than or equal to 0.51 nm were obtained. These superior performances, along with low running costs, suggest that TiN thin films have great potential for use as electrodes in microelectronic devices.
{"title":"Microstructural and Electrical Resistivity of TiN Electrode Films Prepared by Direct Current (DC) Reactive Magnetron Sputtering","authors":"Yu Zhang, Wen-Tao Shi, Lei Chen, Fu-Ru Zhong, Zhen-Xing Fang, Long-Fei Yuan","doi":"10.1166/sam.2023.4555","DOIUrl":"https://doi.org/10.1166/sam.2023.4555","url":null,"abstract":"In this study, the crystal structure as well as electron transport of TiN thin films were evaluated. We used DC reactive magnetron sputtering to deposit a thin layer of polycrystalline titanium nitride (TiN) on a Si (100) substrate starting from elemental Ti in a nitrogen atmosphere. The influence of nitrogen flow rate on the crystal structure, surface morphology, and electron transport of TiN were investigated systematically. It was found that the preferred orientation and conductivity of TiN thin films exhibit strong nitrogen flow rate dependence. The preferred orientation changed from (111) to (200) initially and then changed back to (111) as the nitrogen flow rate increases. However, an increase in the (200) phase leads to higher conductivity and lower surface roughness. At the optimized deposition conditions, ultra-thin (around 30 nm) TiN thin films with a low resistivity of 101.8 μ C·cm and a surface roughness of less than or equal to 0.51 nm were obtained. These superior performances, along with low running costs, suggest that TiN thin films have great potential for use as electrodes in microelectronic devices.","PeriodicalId":21671,"journal":{"name":"Science of Advanced Materials","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This research was aimed to discuss and understand the effects and mechanisms of action of Callicarpa nudiflora granules on proliferation and apoptosis of uterine leiomyoma (UL) cells. Firstly, normal uterine myometrium (UM) and UL tissues were collected, and the levels of p-Akt and Phosphatase and Tensin Homolog (PTEN) in UL tissues were detected using immunohistochemistry. Next, the UL cells were successfully obtained using enzymatic digestion, and their identification was performed using alpha-smooth muscle actin ( α -actin) immunocytochemistry. Specifically, the cells were grouped into four: a control group (CG), a low-dose group (LDG, 50 mg/L Callicarpa nudiflora solution), a medium-dose group (MDG, 100 mg/L Callicarpa nudiflora solution), and a high-dose group (HDG, 200 mg/L Callicarpa nudiflora solution). Moreover, the proliferation of UL cells was assessed using the thiazolyl blue (MTT) assay, while cell apoptosis was analyzed using flow cytometry (FCT). Real-time fluorescent quantitative PCR (fq-PCR) and Western blot assay (WBA) were utilized to determine the PAI-1, P38, TGF- β 1, E-cadherin, and Vimentin in UL cells. The results revealed that the positive rate (PR) of p-Akt in the UL tissues was much higher to that in normal UM tissues ( P < 0.001). More than 90% of UL cells were positive for α -actin. The viabilities of UL cells in the Callicarpa nudiflora treatment groups were greatly weakened to that of untreated cells ( P < 0.05). Viability of UL cells in the HDG group was the lowest, showing a great difference with P < 0.01 to the LDG group and that with P < 0.05 to the MDG group, while that between the MDG and LDG groups exhibited a great difference with P < 0.05. AR of UL cells in CG group was sharply lower to that in the Callicarpa nudiflora treatment groups, showing great differences with P < 0.05, P < 0.01, and P < 0.001, respectively. AR of UL cells in HDG group was higher to the LDG group ( P < 0.01) and MDG group ( P < 0.05), and that in LDG group was lower and exhibited a great difference with P < 0.05 to the MDG group. The HDG, LDG, and MDG groups exhibited greatly lower TGF- β 1, PAI-1, and P38 to the CG group ( P < 0.05). In the HDG group, the TGF- β 1, PAI-1, P38, and Vimentin levels were greatly lower and presented a great difference with P < 0.01 to those in the CG group and LDG group. Additionally, E-cadherin in UL cells was elevated in the LDG and MDG groups to CG group, showing P < 0.05 and P < 0.01, respectively. Such findings indicated that the Callicarpa nudiflora granules can suppress proliferation of UL cells and promote their apoptosis, which may be associated with the TGF- β 1/P38/PAI-1 singling pathway (SPW).
{"title":"Effects of <i>Callicarpa nudiflora</i> Granules on the Proliferation and Apoptosis of Uterine Fibroid Cells","authors":"Yan Xu, Yuhui Wang","doi":"10.1166/sam.2023.4551","DOIUrl":"https://doi.org/10.1166/sam.2023.4551","url":null,"abstract":"This research was aimed to discuss and understand the effects and mechanisms of action of Callicarpa nudiflora granules on proliferation and apoptosis of uterine leiomyoma (UL) cells. Firstly, normal uterine myometrium (UM) and UL tissues were collected, and the levels of p-Akt and Phosphatase and Tensin Homolog (PTEN) in UL tissues were detected using immunohistochemistry. Next, the UL cells were successfully obtained using enzymatic digestion, and their identification was performed using alpha-smooth muscle actin ( α -actin) immunocytochemistry. Specifically, the cells were grouped into four: a control group (CG), a low-dose group (LDG, 50 mg/L Callicarpa nudiflora solution), a medium-dose group (MDG, 100 mg/L Callicarpa nudiflora solution), and a high-dose group (HDG, 200 mg/L Callicarpa nudiflora solution). Moreover, the proliferation of UL cells was assessed using the thiazolyl blue (MTT) assay, while cell apoptosis was analyzed using flow cytometry (FCT). Real-time fluorescent quantitative PCR (fq-PCR) and Western blot assay (WBA) were utilized to determine the PAI-1, P38, TGF- β 1, E-cadherin, and Vimentin in UL cells. The results revealed that the positive rate (PR) of p-Akt in the UL tissues was much higher to that in normal UM tissues ( P < 0.001). More than 90% of UL cells were positive for α -actin. The viabilities of UL cells in the Callicarpa nudiflora treatment groups were greatly weakened to that of untreated cells ( P < 0.05). Viability of UL cells in the HDG group was the lowest, showing a great difference with P < 0.01 to the LDG group and that with P < 0.05 to the MDG group, while that between the MDG and LDG groups exhibited a great difference with P < 0.05. AR of UL cells in CG group was sharply lower to that in the Callicarpa nudiflora treatment groups, showing great differences with P < 0.05, P < 0.01, and P < 0.001, respectively. AR of UL cells in HDG group was higher to the LDG group ( P < 0.01) and MDG group ( P < 0.05), and that in LDG group was lower and exhibited a great difference with P < 0.05 to the MDG group. The HDG, LDG, and MDG groups exhibited greatly lower TGF- β 1, PAI-1, and P38 to the CG group ( P < 0.05). In the HDG group, the TGF- β 1, PAI-1, P38, and Vimentin levels were greatly lower and presented a great difference with P < 0.01 to those in the CG group and LDG group. Additionally, E-cadherin in UL cells was elevated in the LDG and MDG groups to CG group, showing P < 0.05 and P < 0.01, respectively. Such findings indicated that the Callicarpa nudiflora granules can suppress proliferation of UL cells and promote their apoptosis, which may be associated with the TGF- β 1/P38/PAI-1 singling pathway (SPW).","PeriodicalId":21671,"journal":{"name":"Science of Advanced Materials","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
This research was aimed to construct polyaspartic acid (PASP) surface-modified magnetic resonance imaging (MRI) contrast agent nanoparticles (NPs) and preliminarily demonstrate the feasibility of using the NPs for MRI cerebral perfusion. Ultrasmall superparamagnetic iron oxide (USPIO) NPs were fabricated by a one-step chemical coprecipitation methodology, and surface modification of USPIO NPs was performed using PASP as the surface modifier to prepare PASP-USPIO NPs. The physicochemical properties of the NPs were detected, and their specific structural ability with HUVECs was visualized by Prussian blue staining. With the contrast agent gadolinium-diethylene triamine pentaacetate (Gd-DTPA) as the control group, the intravenous bolus of USPIO and PASP-USPIO was analyzed and a brain MRI scan of New Zealand white rabbits was performed. The relative cerebral blood volume (rCBV) and maximum signal reduction ratio (SRR max ) values of cerebral gray matter and white matter were calculated based on the plotted time-signal intensity. The results showed that the USPIO and PASP-USPIO NPs were successfully prepared. The average particle sizes were 40.1±5.5 nm and 42.7±6.9 nm, respectively, and the specific saturation magnetization was 86.9 A m 2 ·kg −1 and 51.3 A m 2 ·kg −1 , respectively. Relative to USPIO, human umbilical vein endothelial cells (HUVECs) stained with Prussian blue positively in vitro in the PASP-USPIO group were notably increased, while the rate of change in the signal-to-noise ratio of imaging in vivo was substantially decreased. The time-signal intensity curves were plotted, and it was found that the rCBV of gray matter, rCBV of white matter, SRR max of gray matter, and SRR max of white matter in the USPIO group and PASP-USPIO group were greatly increased relative to control group ( P < 0.05), while the SRR max ratio of gray matter to white matter was decreased ( P < 0.05). Additionally, the rCBV in the gray matter and rCBV in the white matter of the PASP-USPIO group were drastically increased in contrast to the USPIO group ( P < 0.05). In short, the constructed PASP surface-modified USPIO NPs can become a novel MRI contrast agent for monitoring hemodynamic changes in brain tissue.
本研究旨在构建聚天冬氨酸(PASP)表面修饰磁共振成像(MRI)造影剂纳米颗粒(NPs)，并初步论证其用于MRI脑灌注的可行性。采用一步化学共沉淀法制备了超顺磁氧化铁(USPIO)纳米粒子，并以PASP为表面改性剂对USPIO纳米粒子进行表面改性，制备了PASP-USPIO纳米粒子。检测NPs的理化性质，并通过普鲁士蓝染色观察其与HUVECs的特异性结构能力。以造影剂钆-五乙酸二乙烯三胺(Gd-DTPA)为对照组，分析静脉注射USPIO和PASP-USPIO，并对新西兰大白兔进行脑MRI扫描。根据绘制的时间信号强度计算脑灰质和白质的相对脑血容量(rCBV)和最大信号减少比(SRR max)值。结果表明，成功制备了USPIO和PASP-USPIO NPs。平均粒径分别为40.1±5.5 nm和42.7±6.9 nm，比饱和磁化强度分别为86.9 A m2·kg - 1和51.3 A m2·kg - 1。与USPIO相比，PASP-USPIO组体外普鲁士蓝阳性染色的人脐静脉内皮细胞(HUVECs)明显增加，而体内成像信噪比变化率明显降低。绘制时间-信号强度曲线，发现USPIO组和PASP-USPIO组脑灰质rCBV、脑白质rCBV、脑灰质SRR max、脑白质SRR max均较对照组显著升高(P <0.05)，而脑灰质与脑白质的SRR max比值降低(P <0.05)。此外，与USPIO组相比，PASP-USPIO组的灰质rCBV和白质rCBV显著增加(P <0.05)。总之，构建的PASP表面修饰的USPIO NPs可以成为监测脑组织血流动力学变化的新型MRI造影剂。
{"title":"Feasibility Analysis of Brain Perfusion Using Polyaspartic Acid Surface-Modified Superparamagnetic Contrast Agent","authors":"Jian Liu, Bobo Zheng, Ping Zhang, Liangjie Wang","doi":"10.1166/sam.2023.4539","DOIUrl":"https://doi.org/10.1166/sam.2023.4539","url":null,"abstract":"This research was aimed to construct polyaspartic acid (PASP) surface-modified magnetic resonance imaging (MRI) contrast agent nanoparticles (NPs) and preliminarily demonstrate the feasibility of using the NPs for MRI cerebral perfusion. Ultrasmall superparamagnetic iron oxide (USPIO) NPs were fabricated by a one-step chemical coprecipitation methodology, and surface modification of USPIO NPs was performed using PASP as the surface modifier to prepare PASP-USPIO NPs. The physicochemical properties of the NPs were detected, and their specific structural ability with HUVECs was visualized by Prussian blue staining. With the contrast agent gadolinium-diethylene triamine pentaacetate (Gd-DTPA) as the control group, the intravenous bolus of USPIO and PASP-USPIO was analyzed and a brain MRI scan of New Zealand white rabbits was performed. The relative cerebral blood volume (rCBV) and maximum signal reduction ratio (SRR max ) values of cerebral gray matter and white matter were calculated based on the plotted time-signal intensity. The results showed that the USPIO and PASP-USPIO NPs were successfully prepared. The average particle sizes were 40.1±5.5 nm and 42.7±6.9 nm, respectively, and the specific saturation magnetization was 86.9 A m 2 ·kg −1 and 51.3 A m 2 ·kg −1 , respectively. Relative to USPIO, human umbilical vein endothelial cells (HUVECs) stained with Prussian blue positively in vitro in the PASP-USPIO group were notably increased, while the rate of change in the signal-to-noise ratio of imaging in vivo was substantially decreased. The time-signal intensity curves were plotted, and it was found that the rCBV of gray matter, rCBV of white matter, SRR max of gray matter, and SRR max of white matter in the USPIO group and PASP-USPIO group were greatly increased relative to control group ( P < 0.05), while the SRR max ratio of gray matter to white matter was decreased ( P < 0.05). Additionally, the rCBV in the gray matter and rCBV in the white matter of the PASP-USPIO group were drastically increased in contrast to the USPIO group ( P < 0.05). In short, the constructed PASP surface-modified USPIO NPs can become a novel MRI contrast agent for monitoring hemodynamic changes in brain tissue.","PeriodicalId":21671,"journal":{"name":"Science of Advanced Materials","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
To promote the differentiation of mesenchymal stem cells (MSCs) into osteogenic lineages, icariin (ICA) was utilized. A composite scaffold material of ICA-bone powder/poly lactic acid (PLA) was constructed using biotechnology, and its therapeutic effects on osteoporotic bone defects were visualized. During the experiment, the physicochemical properties and biocompatibility of the material were analyzed, and a rat model of osteoporotic bone defects was constructed. The prepared material was implanted into the osteoporotic bone defect region, and according to the drug-loading amount (10 −5 M, 10 −6 M, and 10 −7 M), the experimental rats were assigned into three groups (group A, group B and group C) to verify its bone defect repair performance. The results revealed that the porosity and pore size of bone powder/PLA material were (91.75±2.36)% and (213.42±16.37) μ m, respectively. The addition of the Chinese herbal medicine caused a decrease in the porosity of the ICA-bone powder/PLA material, but it still exceeded 85%. After 48 h of co-culturing with human adipose-derived stem cells (hADSCs) using various drug loading amounts (10 −5 M, 10 −6 M, and 10 −7 M) of the composite bone scaffold material, no obvious cell death was visualized. After 7 days of co-culturing, ALP staining showed that the cells grown on the prepared material surface secreted a large amount of extracellular matrix. In particular, the composite bone scaffold material with a loading amount of 10 −7 M demonstrated strong positive ALP staining. The repair progress of group C rats was faster at 4 weeks and 8 weeks after surgery versus group A and group B ( P < 0.05). According to ALP expression analysis, at 4 weeks after surgery, group C rats had higher ALP positive expression versus group A and group B rats ( P < 0.05), and at 8 weeks after surgery, group B and group C rats had higher ALP positive expression versus group A rats ( P < 0.05). These findings demonstrated that the bone powder/PLA material loaded with ICA has favorable adoption value in the repair of osteoporotic bone defects.
{"title":"Adoption of Composite Bone Scaffold Loaded with Osteoporosis Drugs in the Repair of Bone Defects in an Osteoporotic Animal Model","authors":"Honghui Tang, Fei Xue, Haitao Yue, Feng Ji","doi":"10.1166/sam.2023.4541","DOIUrl":"https://doi.org/10.1166/sam.2023.4541","url":null,"abstract":"To promote the differentiation of mesenchymal stem cells (MSCs) into osteogenic lineages, icariin (ICA) was utilized. A composite scaffold material of ICA-bone powder/poly lactic acid (PLA) was constructed using biotechnology, and its therapeutic effects on osteoporotic bone defects were visualized. During the experiment, the physicochemical properties and biocompatibility of the material were analyzed, and a rat model of osteoporotic bone defects was constructed. The prepared material was implanted into the osteoporotic bone defect region, and according to the drug-loading amount (10 −5 M, 10 −6 M, and 10 −7 M), the experimental rats were assigned into three groups (group A, group B and group C) to verify its bone defect repair performance. The results revealed that the porosity and pore size of bone powder/PLA material were (91.75±2.36)% and (213.42±16.37) μ m, respectively. The addition of the Chinese herbal medicine caused a decrease in the porosity of the ICA-bone powder/PLA material, but it still exceeded 85%. After 48 h of co-culturing with human adipose-derived stem cells (hADSCs) using various drug loading amounts (10 −5 M, 10 −6 M, and 10 −7 M) of the composite bone scaffold material, no obvious cell death was visualized. After 7 days of co-culturing, ALP staining showed that the cells grown on the prepared material surface secreted a large amount of extracellular matrix. In particular, the composite bone scaffold material with a loading amount of 10 −7 M demonstrated strong positive ALP staining. The repair progress of group C rats was faster at 4 weeks and 8 weeks after surgery versus group A and group B ( P < 0.05). According to ALP expression analysis, at 4 weeks after surgery, group C rats had higher ALP positive expression versus group A and group B rats ( P < 0.05), and at 8 weeks after surgery, group B and group C rats had higher ALP positive expression versus group A rats ( P < 0.05). These findings demonstrated that the bone powder/PLA material loaded with ICA has favorable adoption value in the repair of osteoporotic bone defects.","PeriodicalId":21671,"journal":{"name":"Science of Advanced Materials","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136009654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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