PHYTOMEDICINE
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2023
·
IF 7.9
Zhihao Liu,Qixiang Shang,Haimeng Li,Daozheng Fang,Zhuohuan Li,Yuqi Huang,Mimi Zhang,Kam Ming Ko,Jihang Chen
Background Diabetic kidney disease (DKD) is one of the major chronic microvascular complications of diabetes and the main cause of end-stage renal failure. Zhenwu Decoction (ZWD), an ancient classic herbal formula in Chinese medicine, has been clinically used for the treatment of kidney disease in China for many years. However, there is currently limited research investigating the application of ZWD in the treatment of DKD and the underlying chemical and biochemical mechanisms involved. Therefore, in the present study, we aimed to identify active components in ZWD and unravel the possible mechanism(s) of action for ZWD in treating DKD. Methods The protective effect of ZWD against DKD was evaluated utilizing an in vitro model of diabetic renal proximal tubulopathy. The major chemical components from ZWD were identified by LC-MS/MS. Drug targets were predicted by submitting the SMILES (Simplified Molecular Input Line Entry System) of the compounds to SEA (Similarity Ensemble Approach) search server and SwissTargetPrediction. The differentially expressed genes (DEGs) of the disease were collected and integrated from GeneCards. The constructions of “Compounds-potential targets interaction” (CTI) network and Protein-Protein Interaction (PPI) network, as well as topology analysis were conducted by Cytoscape. Gene Ontology (GO)-enrichment and Metacore pathway enrichment analysis were also performed. Lastly, molecular docking and experimental studies were adopted to validate the core target and identify an active component(s) of ZWD. Results We demonstrated that the ZWD extract could significantly rescue the palmitic acid (PA) and high glucose-induced apoptotic cell death in HK-2 cells, and the cytoprotection was accompanied by decreases in the extent of reactive oxygen species (ROS) production, mitochondrial membrane depolarization and ATP depletion. Fifty-seven compounds in the aqueous extract of ZWD were identified by LC-MS. The results of PPI analysis showed that top hub genes involved epidermal growth factor receptor (EGFR), Signal Transducer and Activator of Transcription 3 (STAT3), Serine/Threonine Kinase 1 (AKT1), Vascular Endothelial Growth Factor A (VEGFA) and Fibroblast Growth Factor 2 (FGF2). Pathway enrichment analysis revealed the involvement of S1P1 receptor signaling and EGFR pathways. The results of molecular docking analysis showed that albiflorin has a high binding affinity to EGFR. Albiflorin could also exert protective effects in an HK-2 cell model of DKD, which may be related to the inhibition of the high glucose/high lipid-induced EGFR and Akt phosphorylation. Conclusion ZWD has been shown to be effective in ameliorating cell death in an experimental model of DKD. The beneficial effect of ZWD against DKD was associated with the interactions between the active ingredients and the hub genes, such as EGFR, STAT3, AKT1, and VEGF-A. Albiflorin may be one of the active components responsible for the nephroprotective effect in ZWD.
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ACS Synthetic Biology
·
2023
·
IF 4.7
Qiuyan Sun,Fang Guo,Shichao Ren,Liang Zhang,Xinhe Liu,Chun Li,Xudong Feng
Glycosylation is an important method of modifying natural products and is usually catalyzed by uridine 5′-diphosphate (UDP)-glycosyltransferase. UDP-β-l-arabinose (UDP-Ara) confers specific functions to natural products such as pentacyclic triterpenoids. However, UDP-arabinosyltransferase with high regioselectivity toward pentacyclic triterpenoids has rarely been reported. In addition, UDP-Ara is mainly biosynthesized from UDP-α-d-glucose (UDP-Glc) through several reaction steps, resulting in the high cost of UDP-Ara. Herein, UGT99D1 was systematically characterized for specifically transferring one moiety of arabinose to the C-3 position of typical pentacyclic triterpenoids. Subsequently, 15 enzymes from plants, mammals, and microorganisms were characterized, and a four-enzyme cascade comprising sucrose synthase, UDP-Glc dehydrogenase, UDP-α-d-glucuronic acid decarboxylase, and UDP-Glc 4-epimerase was constructed to transform sucrose into UDP-Ara with UDP recycling. This system was demonstrated to efficiently produce the arabinosylated derivative (Ara-BA) of typical pentacyclic triterpenoid betulinic acid (BA). Finally, the in vitro cytotoxicity tests indicated that Ara-BA showed much higher anticancer activities than BA. The established arabinosylation platform shows the potential to enhance the pharmacological activity of natural products.
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Foods
·
2023
·Vol. 12
·期 13
·2483
·
IF 5.2
Qian Zou,Weifei Wang,Qingqing Xu,Menglei Yan,Dongming Lan,Yonghua Wang
α-Tocopherol has been widely used in medicine, cosmetics, and food industry as a nutritional supplement and antioxidant. However,α-tocopherol showed low bioaccessibility, and there is a widespreadα-tocopherol deficiency in society today. The preparation of oil-in-water emulsions with high safety and low-calorie property is necessary. The aim of this research was to investigate the effects of different protein emulsifiers (whey protein isolate (WPI), soy protein isolate (SPI), and sodium casein (SC)) on the properties of emulsions delivery system, and diacylglycerol (DAG) was picked as a low-accumulated lipid. The interfacial changes, microstructural alterations, and possible interactions of the protein-stabilized DAG emulsions were investigated during the in vitro digestion. The results show that different proteins affect the degree of digestibility andα-tocopherol bioaccessibility of the emulsions. Both WPI- and SPI-coated emulsions showed good digestibility andα-tocopherol bioaccessibility (77.64 ± 2.93%). This might be due to the strong hydrolysis resistance of WPI (β-lactoglobulin) and the good emulsification ability of SPI. The SC-coated emulsion showed the lowest digestibility andα-tocopherol bioaccessibility, this might be due to the emulsification property of hydrolysis products of SC and the potential interaction with calcium ions. This study provides new possibilities for the application of DAG emulsions in delivery systems.Keywords:diacylglycerol;in vitro digestion;bioaccessibility;α-tocopherol;delivery systems
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Surfaces and Interfaces
·
2023
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IF 6.2
Shengchen Ke,Linling Qin,Ruoxi Zhang,Weijian Zhu,Wenxiang Lu,Lu Ma,Shaolong Wu,Xiaofeng Li
It is of great importance to develop a non-invasive and portable glucose sensor to address challenges and obstacles brought by invasive glucose sensors, such as negative physical and psychological impacts to patients during the fingertip blood collection, limited environment of use for enzyme-based electrodes, and cumbersome active-driven integrated devices. Photoelectrochemical (PEC) sensors have great potential in this regard. In this work, self-driven and enzyme-free sweat glucose PEC sensing is realized by constructing TiO 2 hierarchical nanotubes modified by CuO nanoparticles (CuO@TiO 2 HNT). A sensitivity of 138.9 μA mM −1 cm −2 in the low concentration range (< 200 μM) and a detection limit of 0.7 μM (Signal/Noise=3) are achieved by the as-prepared CuO@TiO 2 HNT photoelectrode at relatively zero bias. The testing results for sweat glucose detection before and after meal consumption are consistent with those from commercial glucometers. The CuO@TiO 2 HNT photoelectrode works well at absolutely zero bias and in a wide temperature range (e.g., 0–60 °C). The extraordinary sensing performance can be mainly attributed to the following two factors: (1) the TiO 2 hierarchical nanotubes have an excellent light-capturing property and large specific surface area, and (2) the CuO nanoparticles substantially facilitate surface-carrier transfer for the glucose oxidation reaction. This work provides an enzyme-free sensing photoelectrode for self-driven sweat glucose detection and an alternative route to portable and noninvasive sensing of glucose.
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Materials Today Bio
·
2023
·
IF 8.2
Danni Dai,Jianrong Wang,Hanshu Xie,Chao Zhang
Biomineralization with amorphous calcium phosphate (ACP) is a highly effective strategy for caries prevention and defect restoration. The identification and interruption of cariogenic biofilm formation during remineralization remains a challenge in current practice. In this study, an epigallocatechin gallate (EGCG)-ACP functional nanocomposite was developed to prevent and restore demineralization by integrating the antibacterial property of EGCG and the remineralization effect of ACP. The synthesized EGCG-ACP showed good biocompatibility with L-929 cells and human gingival fibroblasts. Under neutral conditions, the sustained release of ACP from EGCG-ACP restored the microstructure and mechanical properties of demineralized enamel. Under acidic conditions, protonated EGCG released from EGCG-ACP exerted a strong antibacterial effect, and the ACP release rate doubled within 4 h, resulting in the prevention of demineralization in the presence of cariogenic bacteria. The pH-responsive features of EGCG-ACP to promote the protonation of EGCG and ACP release facilitated its performance in remineralization effect to overcome the difficulty of restoring demineralized enamel in a cariogenic acidic environment, which was evidenced by the in vivo experiment carried out in a rat oral cariogenic environment. The results of this study indicate the potential of EGCG-ACP for the prevention of enamel demineralization and provide a theoretical basis its application in populations with high caries risk.
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CHEMICAL ENGINEERING JOURNAL
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2023
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IF 15.1
Kai Sun,Jiaying Yu,Jinzhong Hu,Wanxiang Yang,Xianfeng Chu,Lucheng Chen,Xiongwei Deng,Baiwang Sun,Zhifei Wang
Ferroptosis is an emerging antitumor treatment modality with the superiority for evading apoptotic cell death pathway. However, how to elevate catalytic efficacy of Fe 2+ -mediated Fenton reaction and efficiently elicit ferroptosis remain enormously challenging. Herein, inspired by hyperthermia-enhanced Fenton reaction kinetics, we firstly designed iron-polyphenol-aspirin-coordinated nanochelates for photothermal-enhanced ferroptosis antitumor immunotherapy. Specifically, we modulated optimal mass feeding ratio of gallic acid (GA), aspirin (ASA), Fe (II) and polyvinylpyrrolidone (PVP) to construct novel nanofibrous GA-ASA-Fe (II) metalchelates named GAFs. The variations in size and structure allowed the nanomedicines to avoid the risk of premature renal clearance in vivo, compared with the reported ultrasmall GA-Fe (II) nanocomplexes (GFs). Under NIR laser irradiation, GAFs could constantly amplify toxic hydroxyl radicals ( OH) generation and deplete excessive GSH to induce more accumulation of lethal lipid peroxidation (LPO), thereby triggering ferroptosis pathway in vitro and in vivo. Besides, the introduction of ASA could inhibit cyclooxygenase-2 (COX-2) and prostaglandin E 2 (PGE 2 ), in combination with photothermal-enhanced ferroptosis tumor therapy to induce immunogenic cell death (ICD), promote maturation of dendritic cells (DCs) and activate cytotoxic T cells for synergistic antitumor immunotherapy. GAFs with laser irradiation exhibited the capacity of inhibition of pulmonary metastasis. This work presented a strategy for incorporating small molecule immunomodulator into the metal-polyphenolic coordination to ameliorate its deficiencies, thereby inspiring a new design concept for tumor treatment.
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FUEL
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2023
·
IF 7.4
Jinchuan Wang,Li Zhang,Jinping Weng,Juntao Wei,Deliang Xu,Bin Li,Shu Zhang,Mortaza Gholizadeh,Electo Silva Lora,Hong Zhang
The retention and transformation of nitrogen in hydrochars prepared from co-hydrothermal carbonization (Co-HTC) of fiberboard (FB) and glucose were mainly investigated in this study. This study showed that more than 90 wt% nitrogen has transferred into aqueous solution at 180–220 °C during the hydrothermal carbonization (HTC) of FB. When the HTC temperatures were higher than 220 °C, some dissolved nitrogen recombined into hydrochars due to the enhancement of nitrogen fixation reactions (Maillard reactions). The addition of glucose could significantly increase nitrogen retention rate in hydrochars, which was due to abundant oxygen-containing intermediates (5-HMF, furfural, etc.) formed in aqueous phase by the hydrothermal decomposition of glucose. Besides, the hydrochars with more microspheres formed on the surface could apparently enhance nitrogen fixation due to the increased contacting area. In Co-HTC, the temperature range of 220–280 °C favored the nitrogen retention in hydrochars. Additionally, nitrogen retention rate increased significantly with increasing residence time and mixture ratio of glucose in a certain extent. While the heterocyclic-N was the main nitrogen functional group in hydrochars and it transformed from pyridinic-N, pyrrolic-N to quaternary-N with higher HTC temperatures and longer residence times, additionally, some amine-N was clearly formed when the nitrogen returned from the aqueous phase into hydrochars.
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ACS Applied Materials & Interfaces
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2023
·
IF 9.5
Ziying You,Yue Yu,Tie Hua Wang,Chenglin Wang,Ding Xiong,Yu Shi,Zhenming Wang,Ling Ye
Increased intracranial pressure after traumatic brain injury (TBI) is an urgent problem in clinical practice. A pliable hydrogel is preferred for cranioplasty applications after TBI since it can protect brain tissue and promote bone healing. Nevertheless, biohydrogels for cranial bone regeneration still face challenges of poor mechanical properties, large swelling ratios, and low osteogenesis activity. Herein, inspired by Hofmeister effects, biopolymer hydrogels composed of protein and polysaccharides were treated with a Hofmeister series including a series of monovalent and divalent anions. Our results reveal that the divalent anion-cross-linked biohydrogels exhibit stronger mechanical properties and lower swelling ratios compared with monovalent-anion treated gels. Intriguingly, the divalent HPO42– anion induced biohybrid hydrogels with excellent mechanical behaviors (3.7 ± 0.58 MPa, 484 ± 76.7 kPa, and 148.3 ± 6.85 kJ/m3), anti-swelling capability (16.7%), and gradual degradation ability, significantly stimulating osteogenic differentiation and in vivo cranial bone regeneration. Overall, this study may provide new insights into the design of biomimetic hydrogels for treating cranial bone defects after TBI.
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Nano Research
·
2023
·Vol. 16
·期 8
·11042-11047
·
IF 9.9
Wang Lei,Zhang Yuehan,Sun Xiaoxuan,Li Yunhui,Zhai Junfeng,Dong Shaojun
Eco-friendly chemical oxygen demand (COD) sensors are highly desired with respect to the importance of COD determination in environmental protection. In this work, a new FTO/TiO 2 /PbO 2 (FTO = fluorine-doped tin oxide) electrode was fabricated with a two-step method and used as an eco-friendly electrochemical COD sensor. The interlayer TiO 2 was employed to strengthen the adhesion of PbO 2 on the FTO substrates by providing a large TiO 2 /PbO 2 interface area. The effects of the factors including applied potential, supporting electrolyte concentration and stirring speed on the sensing performance were investigated. Under the optimized conditions, linear responses to the COD of water with different COD sources were achieved, and a linear range from 5 to 120 mg/L was obtained in the case of sucrose as the COD source. The relative standard deviations (RSD) were determined to be less than 9% for the glucose solutions with the COD of 7.5, 12.5 and 17.5 mg/L. For real sample analysis, the obtained results were comparable with those measured with the conventional dichromate method, with a relative error less than 11%.
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JOURNAL OF CONTROLLED RELEASE
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2023
·
IF 10.8
Yuan-Fu Ding,Ziyi Wang,Cheryl H.T. Kwong,Yonghua Zhao,Greta S.P. Mok,Hua-Zhong Yu,Ruibing Wang
Camptothecin (CPT) and cisplatin (Pt) have shown synergistic effects on a variety of cancers during preclinical and clinical studies. However, the ratio of the two drugs often could not be precisely regulated in different delivery systems, which hinders the desired synergistic effect. In addition, the low delivery efficiency of the two drugs to the tumor further impedes the ideal therapeutic outcomes. Herein, we report that a platelet-mimicking supramolecular nanomedicine (SN) could precisely control of the ratio of CPT and Pt with a high tumor accumulation rate for cascade amplification of synergistic chemotherapy. The SN was fabricated via the host–guest interaction between cucurbit[7]uril conjugated hyaluronic acid (HA-CB[7]) and adamantane (ADA) respectively functionalized CPT- and Pt-based prodrugs . The ratio of CPT and Pt in the SN could be facilely regulated by simply controlling the loading ratio, based on the strong binding affinity between CB[7] and ADA, and SN60 with 60% CPT and 40% Pt showed the highest synergistic effects on 4T1 cells. To improve the tumor accumulation efficiency of SN, 5,6-dimethylxanthenone-4-acetic acid (DMXAA, a tumor vasculature-disruptive agent) was loaded into the optimized SN and then coated with platelet membrane to yield platelet-mimicking supramolecular nanomedicine ( [email protected] ). [email protected] could first passively accumulate in tumors owing to the enhanced permeability and retention (EPR) effect after intravenous administration. The initially release of DMXAA from [email protected] could induce tumor vascular disruption, and the resultant epithelial collagen exposure around the disrupted tumor vasculature provided a target for further recruitment of platelet-mimicking SN, leading to cascade amplification of tumor accumulation with synergistic chemotherapy. Hence, this platelet-mimicking supramolecular nanomedicine presents a universal supramolecular strategy to finely regulate the ratio of loaded pro-drugs, and improve the accumulation efficiency to amplify chemotherapy via platelet-mimics.
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Biomedical Materials
·
2023
·Vol. 18
·期 4
·045026
·
IF 4
Xiaobo Guo,Di Liu,Siyuan Dong,Yuyang Wang,Meng Li
Self-assembling peptides, offering favorable biocompatibility, high stability, and easy incorporation of various functionalities, have demonstrated enormous potential for the precise design of next-generation nanodrugs for non-invasive tumor therapy. Peptide-based supramolecular photodynamic therapy (PDT) has shown great promise as an emerging modality for cancer treatment, achieving substantially-enhanced photosensitizer delivery selectivity and treatment efficacy, based on peptide biological activity and self-assembly potential. Although considerable research has been conducted toward fabricating self-assembling peptide-based smart nanodrugs for PDT, few studies have investigated cellular biophysical responses as indicators of tumor function and metabolic state. Here, via atomic force microscopy (AFM)-based morphological and mechanical measurements, including optical microscopy and scanning electron microscopy, we observed, for the first time, variation in membrane stiffness of human liver (HepG2) cancer cells treated with self-assembling peptides serving as a PDT nanodrug. This biophysical information will help to establish a comprehensive understanding of the anticancer effect of peptide-based smart nanodrugs, and highlight the exceptional ability of AFM in determining cell-surface properties.
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ONCOGENE
·
2023
·Vol. 42
·期 29
·2278-2293
·
IF 8
Chen Yihuan,Dai Xiaoshuo,Chen Wei,Qiao Yan,Bai Ruihua,Duan Xiaoxuan,Zhang Kai,Chen Xinhuan,Li Xin,Mo Saijun,Cao Wenbo,Li Xiang,Liu Kangdong,Dong Ziming,Lu Jing
Cisplatin (CDDP) is the first-line drug in the clinical treatment of esophageal squamous cell carcinoma (ESCC), which has severe nephrotoxicity. Diosmetin (DIOS) can protect kidney from oxidative damage, however, its function in ESCC is unknown. This study aims to explore the effect and mechanism of DIOS on ESCC and its combined effect with CDDP. Herein, we found that DIOS significantly inhibited the progression of ESCC in vitro and in vivo. Furthermore, the anti-tumor effect of DIOS was not statistically different from that of CDDP. Mechanically, transcriptomics revealed that DIOS inhibited the E2F2/RRM2 signaling pathway. The transcriptional regulation of RRM2 by E2F2 was verified by luciferase assay. Moreover, docking model, CETSA, pull-down assay and CDK2 inhibitor assay confirmed that DIOS directly targeted CDK2, leading to significant suppression of ESCC. Additionally, the patient-derived xenografts (PDX) model showed that the combination of DIOS and CDDP significantly inhibited the growth of ESCC. Importantly, the combined treatment with DIOS and CDDP significantly reduced the mRNA expression levels of kidney injury biomarkers KIM-1 and NGAL in renal tissue, as well as the levels of blood urea nitrogen, serum creatinine and blood uric acid compared to the single treatment with CDDP. In conclusion, DIOS could be an effective drug and a potential chemotherapeutic adjuvant for ESCC treatment. Furthermore, DIOS could reduce the nephrotoxicity of CDDP to some extent.
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