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BIOSENSORS & BIOELECTRONICS · 2019 · IF 9.518

Peptide-functionalized upconversion nanoparticles-based FRET sensing platform for Caspase-9 activity detection in vitro and in vivo

Lin Liu,Hua Zhang,Zhenxin Wang,Daqian Song

In the present work, peptide-functionalized upconversion@silica nanoparticle (termed as UCNP@SiO 2 @Cy5-pep)-based fluorescence resonance energy transfer (FRET) sensing platform has been fabricated for the detection of caspase-9 activity in vitro and in vivo. A Cy5 labeled peptide containing specific motif LEHD for caspase-9 cleavage was designed and conjugated with UCNP@SiO 2 through covalent attachment . The red upconversion luminescence (UCL) emission of UCNP@SiO 2 can be quenched by Cy5 while the green UCL emission of UCNP@SiO 2 remains undisturbed. After the cleavage of LEHD by caspase-9, the Cy5 departed from UCNP@SiO 2 surface, resulting in recovery of red UCL emission of UCNP@SiO 2 . The UCNP@SiO 2 @Cy5-pep has been successfully used to monitoring the changes of caspase-9 activity levels in apoptotic cancerous cells (MG-63 and SW480) by cisplatin-induction. Under same experimental conditions, it is found that the intracellular caspase-9 activity level of cisplatin-treated MG-63 cells is higher than that of cisplatin-treated SW480. This result is consistent with that of commercial caspase-9 activity kits. The UCL signal intensity ratio of red emission to green emission of UCNP (termed as R/G) is linearly dependent on the amount of MG-63 cells within the range of 5 × 10 3 to 1 × 10 6  cells (i.e., 0.5–100 U mL −1 caspase-9) with a limit of detection (LOD) of 675 cells (i.e., 0.068 U mL −1 caspase-9). Furthermore, the practicability of UCNP@SiO 2 @Cy5-pep is demonstrated by detection of caspase-9 activities in tumor tissues in vivo, and satisfactory results are obtained.

CAS / MDL: 106627-54-7 14913-33-8
研究领域: 生物化学 · 纳米医学 · 肿瘤学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Acta Biomaterialia · 2022 · IF 10.633

45S5 Bioglass® works synergistically with siRNA to downregulate the expression of matrix metalloproteinase-9 in diabetic wounds

Ying Li,Xin Zhang,Dan He,Zhijie Ma,Ke Xue,Haiyan Li

Diabetic chronic wounds are difficult to heal because of the presence of excessive inflammation and high overexpression of matrix metalloproteinase-9 (MMP-9), which greatly affects the quality of life of patients with diabetes and increases the risk of death. Thus, the regulation of excessive inflammation and inhibition of MMP-9 overexpression are effective strategies to improve diabetic wound healing. The present study is the first to demonstrate that ion products of 45S5 Bioglass® (BG) can work with small interfering RNA of MMP9 (MMP9-siRNA) to reduce MMP-9 expression in tissue-forming cells and enhance the synthesis of extracellular matrix proteins (ECMs). Specifically, the BG ionic products can stimulate macrophages to convert to M2 phenotype, thereby creating a proregenerative inflammation microenvironment to indirectly suppress the expression of MMP-9 in tissue-forming cells. Chitosan nanoparticles encapsulating MMP9-siRNA (MMP9-siNP) can directly lower MMP-9 expression in tissue-forming cells. In addition, BG ionic products can promote the vascularization of endothelial cells and ECM protein synthesis by fibroblasts. Thus, injectable BG/sodium alginate (BG/SA) hydrogels loaded with MMP9-siNP can significantly accelerate the healing process of full-thickness excision wounds of diabetic rats by decreasing MMP-9 expression, improving collagen synthesis , and enhancing angiogenesis in the wounds, thereby demonstrating their great application potential in treating diabetic chronic wounds. Statement of significance Excessive inflammation and high overexpression of MMP-9 have been considered as factors that severely hinder the healing process of diabetic chronic wounds. Effective strategies are required for the regulation of excessive inflammation and inhibition of MMP-9 overexpression to enhance diabetic wound healing. In the present work, an injectable bioglass/sodium alginate (BG/SA) hydrogel loaded with MMP9-siNP was developed; this hydrogel significantly accelerated the healing process of full-thickness excision wounds of diabetic rats by decreasing MMP-9 expression, improving collagen accumulation, and enhancing angiogenesis in the wounds. Thus, the BG/SA hydrogel loaded with MMP9-siNP has great potential for use in healing of diabetic chronic wounds.

CAS / MDL: 7758-29-4
研究领域: 生物材料 · 伤口愈合 · 糖尿病 · 组织工程 · 纳米技术 · 药剂学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ACTA HISTOCHEMICA · 2019 · IF 1.719

miR-9-5p attenuates ischemic stroke through targeting ERMP1-mediated endoplasmic reticulum stress

Lumei Chi,Dan Jiao,Guangxian Nan,Honghua Yuan,Jing Shen,Yu Gao

Ischemic stroke (IS) is a cerebrovascular disease with serious neurological function impairment, which may activate endoplasmic reticulum (ER) stress. However, the underlying regulatory mechanism of ER stress under IS remains unclear. miR-9-5p is enriched in the brain tissues and plays a role in the pathological process of IS. Therefore, the purpose of this study is to explore the effect of miR-9 on ER stress and underlying mechanism in IS. Here, a middle cerebral artery occlusion (MCAO) rat model was utilized to examine the alteration of brain pathology, and the expressions of miR-9 and ER stress-related proteins. Then SH-SY5Y cells with oxygen-glucose deprivation (OGD) were performed to further evaluate the functional role of miR-9 and preliminary mechanism. The results showed that miR-9 levels were decreased in the ischemic region of rats after MCAO. MCAO significantly increased the brain infract volume, reduced Nissl bodies and cell apoptosis , and increased ER stress-related proteins (ERMP1, GRP78, p-PERK, p-eIF2α and CHOP). Furthermore, overexpression of miR-9 by miR-9 mimics increased cell viability , inhibited LDH activity and cell apoptosis, and inactivated ER stress in OGD-neurons. Luciferase activity results showed that miR-9 negatively regulated ERMP1 expression by directly targeting ERMP1 3′ UTR. Subsequently, we found that ERMP1 overexpression reversed the inhibition of miR-9 on GRP78-PERK−CHOP pathway in OGD neurons. In summary, our results suggest that the attenuation of miR-9 on ischemic injury may be involved in targeting ERMP1-mediated ER stress, which provides an available target for IS treatment.

CAS / MDL: 302-79-4
研究领域: 神经科学 · 分子生物学 · 病理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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ANALYST · 2023 ·Vol. 148 ·期 23 ·5905-5914 · IF 4.2

A simple electrochemical strategy for the detection of the cancer marker CA19-9 by signal amplification using copper organic framework nanocomposite

Tingting Zhang,Yan Ma,Yuzhong Zhang

In this work, label-free electrochemical immunosensing of the cancer biomarker carbohydrate antigen 19-9 (CA19-9) is reported using [Fe(CN)6]3−/4− as a signal probe and a copper organic framework (Cu-BTC) nanocomposite for the amplification of the signal. The immunosensor was fabricated by the following process. First, the Cu-BTC nanomaterial with a larger surface area and good biocompatibility was synthesized to improve the dispersion of gold nanoparticles (Au NPs). Then, nitrogen-doped graphene (N-GR) was combined with Cu-BTC to form the nanocomposite. The synthesized Cu-BTC@N-GR@AuNPs@CS nanocomposite was employed to modify the surface of the immunosensor to accelerate the electron transfer rate and improve the immobilization amount of CA19-9 antibodies (Ab). Various techniques, including TEM, SEM and XPS were used to characterize Cu-BTC and nanocomposites. Differential pulse voltammetry (DPV) was used to measure the electrochemical response of the immunosensor in [Fe(CN)6]3−/4−. The signal intensity of the immunosensor was linearly changed upon increasing the concentration of CA19-9 antigen from 10 μU mL−1 to 100 U mL−1, and a detection limit of 4.2 μU mL−1 was achieved. Furthermore, the immunosensor showed good stability, reproducibility and specificity, indicating its potential application in clinical analysis.

研究领域: 生物医学工程 · 分析化学 · 肿瘤学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Oleo Science · 2022 · IF 1.628

Immobilization of Candida antarctica Lipase A onto Macroporous Resin NKA-9: Esterification and Glycerolysis Performance Study

Lihong He,Jiawei Zheng,Siting Feng,Li Xu,Nanjing Zhong

In this study, lipase A from Candida antarctica (CALA) was immobilized onto the macroporous resin NKA-9. Immobilization conditions (pH, time and CALA concentration) were studied, enzymatic activity and immobilization efficiency (IE) up to 968.89 U/g and 53.19% were respectively obtained under optimal conditions (immobilization pH 5.0, time 5 h and CALA concentration at 30 mg/mL). Then, the NKA-9 supported CALA (CALA@NKA-9) samples were used to catalyze glycerolysis in solvent-free system. With 0.25 g of the present CALA@NKA-9 (soybean oil 3.52 g and glycerol 0.184 g) and after 12 h reaction at 50 °C, diacylglycerols (DAG) content up to 64.37% and triacylglycerols (TAG) conversion at 83.33% were obtained. The relationship between temperature and TAG conversion was LnV 0 = 13.9310-6.4212/T for CALA@NKA-9. Meanwhile, the activation energy (Ea) of CALA@NKA-9 was calculated to be 53.39 kJ/mol. In addition, reusability in the glycerolysis reaction was also evaluated, and 57.82% of the initial glycerolysis activity was retained after 9 consecutive applications. Furthermore, the CALA@NKA-9 was also used to catalyze the esterification (esterification of fatty acids with glycerol), however, the present CALA@NKA-9 cannot initiate the esterification. Therefore, the present CALA@NKA-9 is shown to be potential for DAG production through glycerolysis reaction.

研究领域: 生物技术 · 酶工程 · 化学工程 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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SEPARATION AND PURIFICATION TECHNOLOGY · 2022 · IF 9.136

High-performance Fe3O4-terephthalaldehyde magnetic-nanocomposite for removal phenanthrene and 9-phenanthrol: A comprehensive experimental and theoretical analysis

Zhengwen Wei,Yifan Du,Xiang-fei Lü,Wei Wang,Roberta Del Sole,Giuseppe Mele,Zhen-Yi Jiang

Ascribing to the serious environmental and health risks caused by phenanthrene (PENE) and its dangerous degradation intermediate, 9-phenanthrol (9-PENE), solving their contamination problem was extremely urgent. In this work, a novel Fe 3 O 4 -terephthalaldehyde (Fe 3 O 4 -TERE) magnetic nanomaterial was fabricated by introducing aromatic rings onto Fe 3 O 4 nanoparticles through encapsulation and grafting technique. The Fe 3 O 4 core provided convenience for the subsequent recycling and regeneration. The grafted aromatic carbons could act as adsorption active sites to form π–π interaction with PENE/9-PENE’s aromatic rings, thus improving the capture performance. The properties of the prepared magnetic nanomaterials were investigated via multiple characterization techniques. As expected, the Fe 3 O 4 -TERE could be utilized for effectively reducing the contamination risk of PENE and 9-PENE. Furthermore, the Fe 3 O 4 -TERE possessed with excellent regeneration performance. The abundant homogeneous reaction sites of Fe 3 O 4 -TERE provided possibility for the monolayer adsorption of PENE and 9-PENE. There were multiple microscopic interactions and driving forces jointly or individually participated the multi-stage adsorption reaction. Moreover, density functional theory calculations not only analyzed the validity and existence form of the π–π interaction under different adsorption configuration modes, but also provided deeply perspectives related to the microscopic bonding mechanism. This work proposed a promising fabrication strategy for magnetic nanomaterials used for removing and remediation of polycyclic aromatic hydrocarbons contamination, as well as provided profound theoretical perspectives for analyzing the adsorption mechanism.

研究领域: 环境科学 · 材料科学 · 理论化学
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ORGANIC GEOCHEMISTRY · 2023 · IF 3

The occurrence and geochemical origin of 9-alkyl HDBTs substituted by long isoprenoid alkyl chains in crude oil

Jianxun Wu,Abdelrahman A. Hamid,Weilai Zhang,Shuofan Li,Yahe Zhang,Yuhong Liao,Quan Shi

1,1,4a,6-tetramethyl-9-alkyl-1,2,3,4,4a,9b-hexahydrodibenzo[b,d]thiophene (9-alkyl HDBT) was initially found in highly desulfurized diesel oils. This and related organic sulfur compounds (OSCs) have a special shielding structure that make them extremely resistant to hydrodesulfurization. The structure of 9-alkyl HDBTs is likely directly inherited from biological precursors related to terpenoids, but their origins have not been determined. In this study, OSCs were isolated from a low sulfur crude oil from the Junggar Basin in China by the methylation/demethylation method and characterized by gas chromatography-mass spectrometry. A series of 9-alkyl HDBTs substituted with long isoprenoid alkyl chains were identified in the OSCs. Raney nickel desulfurization was conducted to assist the structural identification. The presence of 9-alkyl HDBTs with a β -carotene carbon skeleton and the predominance in specific carbon numbers of alkyl-substituted 9-alkyl HDBTs support a carotenoid origin of such OSCs. Possible geochemical pathways are proposed for the formation of these OSCs via β -carotene, involving processes such as sulfur incorporation, cyclization, aromatization, hydrogenation, and cleavage.

研究领域: 石油化学 · 地球化学 · 生物化学
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DIGESTIVE DISEASES AND SCIENCES · 2022 ·Vol. 67 ·期 10 ·4780-4796 · IF 3.487

KISS-1, Mediated by Promoter Methylation, Suppresses Esophageal Squamous Cell Carcinoma Metastasis via MMP2/9/MAPK Axis

Duan Houyu,Ding Xiang,Luo Hesheng

Background and Aims KISS-1 is an established tumor suppressor that inhibits metastases in various malignancies. However, little is known regarding its role in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to identify the possible mechanisms of KISS-1 in ESCC metastasis. Methods The expression levels of KISS-1 mRNA and protein in ESCC samples and cell lines were analyzed by qRT-PCR, IHC, and western blotting. Bisulfite sequencing PCR (BSP) and methylation-specific PCR (MSP) were used to analyze the methylation pattern of KISS-1 promoter in ESCC cells with or without 5-Aza-dC treatment. The role of KISS-1 in the progression and metastasis of ESCC was analyzed through in vitro functional assays. Results KISS-1 mRNA and protein were markedly downregulated in ESCC tissues and cell lines compared to the respective controls. Hypermethylation of KISS-1 promoter correlated to its lower expression levels in ESCC, and KISS-1 demethylation inhibited tumor progression. Ectopic KISS-1 overexpression inhibited tumor cell metastasis in vitro. In addition, KISS-1 overexpression downregulated the matrix metalloproteinase 2 and 9 (MMP2 and 9) and inhibited epithelial–mesenchymal transition (EMT). Finally, KISS-1 downregulated phosphorylated extracellular regulated protein kinase 1/2 (ERK1/2) and phosphorylated p38 mitogen-activated protein kinase (MAPK) without affecting their total expression levels in the ESCC cells. MAPK/ERK and p38 MAPK agonists reversed the suppressive effects of KISS-1. Conclusions The hypermethylation of KISS-1 promoter partly contributed to its downregulation in ESCC. KISS-1 inhibits the metastasis of ESCC cells by targeting the MMP2/9/ERK/p38 MAPK axis.

CAS / MDL: 2353-33-5
研究领域: 肿瘤学 · 分子生物学 · 癌症遗传学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF CHEMICAL AND ENGINEERING DATA · 2023 · IF 2.6

Solubility Measurement and Modeling of 9-Phenylcarbazole in Various Organic Solvents at Different Temperatures toward Efficient Process Design of Solvent Antisolvent Precipitation

Junwei Yang,Jingzhou Guo,Jiwen Fu,Yuan Pu,Dan Wang

9-Phenylcarbazole (PCz) is widely used for synthesizing functional molecules in display material industry and synthetic crystal industry. This study aimed to gain reliable experimental data for PCz solubility in common organic solvents under atmospheric pressure in the temperature range of 278.15 to 313.15 K. The selected solvents are methanol, ethanol, n-propanol, isopropanol, n-butanol, n-hexane, cyclohexane, acetonitrile, 1,4-dioxane, tetrahydrofuran, dichloromethane, and trichloromethane. Evaluating the existing models for solid–liquid equilibrium showed that the Apelblat equation was reliable and that the maximum value of mean square deviation between experimental and calculated data was 0.016. This knowledge was referenced for designing the solvent antisolvent (SAS) precipitation processing. Purified products of PCz with a mass fraction purity of over 98.11% was obtained via SAS precipitation in a rotating packed bed with intensified micromixing. Bulk crystals of PCz with high quality were grown from acetonitrile via the deposited crystallization processing.

研究领域: 化学工程 · 材料科学
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RAPID COMMUNICATIONS IN MASS SPECTROMETRY · 2015 ·Vol. 29 ·期 14 ·1328-1334 · IF 2.253

Direct detection of the anti-cancer drug 9-phenylacridine in tissues by graphite rod laser desorption vacuum-ultraviolet post-ionization mass spectrometry

Ping Liu,Yongjun Hu,Jiaxin Chen,Qing Yang

Rationale Traditionally, drug analysis in biological tissue by mass spectrometry has required complicated sample pre-treatment, which not only wasted time, but also had adverse effects on the results. In order to assist assessment of potential drugs rapidly and accurately, a direct analytical method for drug detection in tissues is needed. The development of such a method is described in this study. Methods An anti-cancer drug, 9-phenylacridine (ACPH), injected into the kidney of mice, was directly analysed from tissues placed on the surface of a graphite rod by near-infrared (1064 nm) laser desorption single photon ionization mass spectrometry (LD/SPI-MS). Results The LD/SPI-MS method was successfully validated by direct analysis of ACPH in kidney sections of mice, without any complicated and time-consuming sample pre-treatment. The sensitivity of detection was down to about 100 fmol per spot and the wide linear dynamic range allowed quantitative detection of ACPH in complex biological samples. A drug-time curve was acquired of ACPH in the kidney of mice after the drug had been injected into the caudal vein. Conclusions It was demonstrated that the anti-tumor drug ACPH could be directly and rapidly detected by LD/SPI-MS in biological tissues without any time-consuming pre-treatment procedure. This method could potentially be applied to the selective localization and analysis of small molecule drugs in tissues and to the study of the pharmacokinetics of new drugs. Copyright © 2015 John Wiley & Sons, Ltd.

CAS / MDL: 602-56-2
研究领域: 分析化学 · 药理学 · 肿瘤学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Analytical Methods · 2024 ·Vol. 17 ·期 1 ·84-91 · IF 2.7

A simple SERS sensor based on antibody-modified Fe3O4@Au MNPs for the detection of CA19-9 in CRC patients

Miaowen Xu,Gaoyang Chen,Yong Huang,Hangyu Song,Zheng Wu,Fengjuan Jiang,Lei Fu,Caili Bi,Xiaowei Cao,Wei Wei

This paper presents functionalized magnetic nanoparticles (Fe3O4@Au MNPs) combined with the surface-enhanced Raman spectroscopy (SERS) technique for sensitive detection of colorectal cancer (CRC) protein biomarker carbohydrate antigen 19-9 (CA19-9). Fe3O4@Au MNPs were constructed by the PEI-mediated seed growth method. Then, the signal molecule 5-5′-dithiobis (succinimidyl-2-nitrobenzoic acid) was used as a bridging agent to link CA19-9 antibody, and the SERS sensor was prepared. Using this sensor, detection of CA19-9 can be realized with only a one step sampling reaction. Fe3O4@Au MNPs combine the advantages of magnetic materials and noble metal nanoparticles, effectively amplifying the signal by creating numerous “hot spots” within the Au particle gaps and enhancing magnetic enrichment. Consequently, this approach lowers the detection limit (LOD) and enhances detection sensitivity. The ratio of characteristic peak intensities I1392/I1069 was selected for calculation, and a linear equation was constructed with a LOD as low as 0.27 U mL−1 by quantitative detections of the standard antigen. Finally, the sensor was used to analyze the clinical serum samples from CRC patients and healthy individuals, and the detection results were consistent with the actual results. This method exhibits notable advantages, including simplicity, high sensitivity, specificity, stability and reproducibility. It is expected to provide a new promising analytical method for clinical CA19-9 immunoassay.

CAS / MDL: 16903-35-8 7558-80-7
研究领域: 生物医学工程 · 肿瘤学 · 纳米技术
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Journal of Materials Chemistry B · 2020 ·Vol. 9 ·期 5 ·1336-1350 · IF 5.344

Combination of mitochondria targeting doxorubicin with Bcl-2 function-converting peptide NuBCP-9 for synergistic breast cancer metastasis inhibition

Jiatao Yang,Qiuyi Li,Rui Zhou,Minglu Zhou,Xi Lin,Yucheng Xiang,Dandan Xie,Yuan Huang,Zhou Zhou

Distant organ metastasis is the main cause of death in breast cancer patients. Evidences have shown that mitochondria also play a crucial role in tumor metastasis, except for as apoptosis center. However, the treatment of tumor growth and metastasis was reported to be limited by mitochondria-associated protein Bcl-2, which are gatekeepers of apoptosis and are found to reside in mitochondria mainly. Herein, we designed a mitochondria-targeting doxorubicin delivery system as well as a mitochondrial distributed Bcl-2 function-converting peptide NuBCP-9 delivery system, which are both based on N-(2-hydroxypropyl)methacrylamide copolymers, to achieve a synergistic effect on tumor regression and metastasis inhibition by combination therapy. After mitochondria were damaged by mitochondria-targeting peptide-modified doxorubicin, apoptosis was effectively enhanced by mitochondrial specifically distributed NuBCP-9 peptides, which converted Bcl-2 function from anti-apoptotic to pro-apoptotic and paved the way for the development of mitochondrial impairment. The combination treatment exhibited significant damage to mitochondria, including excess reactive oxygen species (ROS), the permeabilization of mitochondrial outer membrane (MOMP), and apoptosis initiation on 4T1 breast cancer cells. Meanwhile, besides enhanced tumor growth suppression, the combination treatment also improved the inhibition of 4T1 breast cancer metastasis both in vitro and in vivo. By increasing the expression of cytochrome C and decreasing the expression of Bcl-2, metal matrix protease-9 (MMP-9) as well as vascular endothelial growth factor (VEGF), the combination treatment successfully decreased 84% lung metastasis. Overall, our work provided a promising strategy for metastatic cancer treatment through mitochondria-targeting anti-cancer drug delivery and combination with mitochondrial distributed Bcl-2 function-converting peptide.

研究领域: 肿瘤学 · 药理学 · 细胞生物学 · 癌症治疗
✓ 已验证 DOI PubMed 高影响因子
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