Drug Design Development and Therapy
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2022
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IF 4.319
Qin Yin,Yi-jin Wu,Shu Pan,Dan-dan Wang,Meng-qing Tao,Wei-ya Pei,Jian Zuo
Background Studies have shown that α-mangostin (MG) could exert anti-rheumatic effects in vivo by restoring immunity homeostasis, and have indicated that activation of the choline anti-inflammatory pathway (CAP) may contribute to this immunomodulatory property. The current study was designed to further investigate the effects of MG on the CAP in peripheral immune cells and clarify its relevance to the potential anti-rheumatic actions.Methods The catalytic activity of acetylcholinesterase (AChE) and expression of α7-nicotinic cholinergic receptor (α7nAChR) in peripheral blood mononuclear cells (PBMCs) from rats with collagen-induced arthritis (CIA) or human volunteers were evaluated after MG treatment. Consequent influences on the immune environment were assessed by flow cytometry and ELISA analyses. Indirect effects on joints resulting from these immune changes were studied in a co-culture system comprised of fibroblast-like synoviocytes (FLSs) and PBMCs.Results MG promoted α7nAChR expression in PBMCs both in vivo and in vitro, and inhibited the enzymatic activity of AChE simultaneously. Activation of the CAP was accompanied by a significant decrease in Th17 cells (CD4+IL-17A+), while no obvious changes concerning the distribution of other T-cell subsets were noticed upon MG treatment. Meanwhile, MG decreased the secretion of TNF-α and IL-1β under inflammatory conditions. PBMCs from MG-treated CIA rats lost the potential to stimulate NF-κB activation and pro-inflammatory cytokine production of FLSs in the co-culture system.Conclusion Overall, the evidence suggested that MG can improve the peripheral immune milieu in CIA rats by suppressing Th17-cell differentiation through CAP activation, and achieve remission of inflammation mediated by FLSs.
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BREAST CANCER RESEARCH AND TREATMENT
·
2023
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IF 3.8
Lei Lei,Huang Yuan,Shi Lei,Ye Weiwu,Lv Xianmei,Ying Lisha,Yu Xingfei,Cheng Skye Hung-Chun,Zheng Yabing
Purpose Endocrine therapy is the anti-tumor therapy for human breast cancer but endocrine resistance was a major burden. It has been reported that Palbociclib and fulvestrant can be used in combination for the treatment of patients who are experiencing endocrine resistance. However, the underlying mechanism is unclear. In this study, we aimed to investigate the mechanism by which Palbocicilib affected ER-positive breast cancer, combined with fulvestrant. Methods We first detected the effect of palbociclib on cell survival, growth and cycle distribution separately by MTT, colony formation and flow cytometry. Then SNHG17 was screened as palbociclib-targeted LncRNA by LncRNA-seq, and the SNHG17-targeted mRNAs were selected by mRNA-seq for further determination. Subsequently, the underlying mechanism by which palbociclib promoted the cytotoxicity of fulvestrant was confirmed by qRT-PCR, western blot, and immunoprecipitation. Eventually, the xenograft model and immunohistochemistry experiments were used to validate the sensitization effect of palbociclib on fulvestrant and its mechanism in vivo. Results Palbociclib significantly enhanced the cytotoxicity of fulvestrant in fulvestrant-resistant breast cancer cell lines. Interestingly, this might be related to the lncRNA SNHG17 and the Hippo signaling pathway. And our subsequent western blotting experiments confirmed that overexpressing SNHG17 induced the down-regulation of LATS1 and up-regulated YAP expression. Furthermore, we found that the increased sensitivity of breast cancer cells was closely associated with the LATS1-mediated degradation of ER-α. The following animal experiments also indicated that overexpressing SNHG17 obviously impaired the anti-cancer effect of co-treatment of palbociclib and fulvestrant accompanied by decreased LATS1 and increased ER-α levels. Conclusion Palbociclib might sensitize the cytotoxicity of fulvestrant in ER-positive breast cancer cells by down-regulating SNHG17 expression, and then resulted in the LATS1-inactivated oncogene YAP and LATS1-mediated degradation of ER-α.
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MICROCHEMICAL JOURNAL
·
2023
·
IF 4.8
Kunfeng Xue,Bingyong Lin,Qiukai Tang,Yuanyuan Yao,Yueliang Wang,Lifen Chen,Zuguang Li,Yanbo Zeng,Lei Li,Longhua Guo
Establishing a simple, sensitive, and accurate α-fetoprotein (AFP) detection methods is of great significance for the early diagnosis of hepatocellular carcinoma (HCC). Surface-enhanced Raman spectroscopy (SERS) has been identified as one of the most promising techniques for clinical monitoring. However, accurate detection of AFP is still challenging due to the poor stability of SERS substrate and the low abundance of AFP in the early stages of HCC. Herein, we developed an ultrasensitive and highly stable paper-based 3D SERS immunoassay array for AFP detection, combining the superior advantages of self-assembled AuNBPs@Ag nanorods, filter paper, and sandwich immunoassay. In the immunoassay array, 4-mercaptobenzoic acid (4-MBA) linked to the secondary antibody was employed as the Raman reporter, while the array modified with antibodies was used to capture AFP. The SERS immunoassay array sensor exhibited a wide linear range (3 pg mL −1 to 10 µg mL −1 ), low detection limit (0.086 pg mL −1 ), good specificity, and high signal reproducibility (RSD < 5 %). Meanwhile, the sensor is further used for accurate detection of trace AFP in serum, which paves an avenue for the fabrication of SERS substrates with high stability and provides a new outlook for their application in the early diagnosis of cancer.
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ACS Applied Energy Materials
·
2023
·
IF 6.4
Yaqiao Liu,Shuozhen Hu,Zhaoqun Gao,Xinsheng Zhang,Shigang Sun
Photoelectrochemical (PEC) water oxidation is considered to be a promising approach to converting solar energy into clean chemical fuels. α-Fe2O3 is a potential photoanode material for water oxidation with a high theoretical photocurrent density (12.6 mA cm–2) driven by visible light. Constructing α-Fe2O3-based heterojunction with other semiconductors is a promising strategy to improve the actual photoelectrocatalytic activity. In this work, nitrogen-doped Ta2O5 is introduced to synthesize N-Ta2O5-h@α-Fe2O3 nanorod heterojunction with different band structures. At the interface, electrons transfer from N-Ta2O5-h to α-Fe2O3, which forms a built-in electric field. The heterojunction structure contributes to inhibiting the severe recombination of photogenerated electron–hole pairs. By controlling the duration of mild heat treatment, the N-Ta2O5-h nanorods with different Fermi energy levels and contents of oxygen vacancies are obtained. A mild heat treatment in N2 is proved to enlarge the ΔE by leveling up the Fermi level and to promote the content of oxygen vacancies for the N-Ta2O5-h@α-Fe2O3 heterojunction as the heat-treatment time increases. The PEC water oxidation performance of the N-Ta2O5-h@α-Fe2O3 heterojunction increases when the mild-heat-treatment time is 2 h and decreases for 6 h treatment. Eventually, N-Ta2O5-2@α-Fe2O3 exhibits an enhanced photocurrent density of 3.10 mA cm–2 (4.4 times higher than that of bare α-Fe2O3), an efficiently boosted charge separation (2.0 times higher than bare α-Fe2O3), and a high chemical stability after a long-term test.
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INDUSTRIAL CROPS AND PRODUCTS
·
2023
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IF 5.9
Weiming Chai,Qiuxia Pan,Qiuhan Bai,Yifeng Wu,Wenshuang Wei,Linjun Wang,Du Zhu
Dimocarpus longan Lour. is a valuable industrial crop for its broad applications in food , traditional Chinese medicine, and other fields. In this paper, condensed tannins were isolated from the leave of D. longan Lour., and their structure, anti-tyrosinase, anti-melanogenesis, anti-browning, anti-α-glucosidase, and anti-glycation properties were methodically clarified. The joint application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), electrospray ionization time-of-flight mass spectrometer (ESI + TOF MS), and high-performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) confirmed that the longan leave condensed tannins (LLCTs) were polymers of procyanidins (majority) and prodelphinidins . The polymers powerfully inhibit tyrosinase (TY) with a competitive mechanism. These compounds altered the microenvironment of the binding site through hydrophobic interaction and hydrogen bond, and caused conformational modification of the enzyme by changing the polypeptide framework and secondary structure, leading to a decrease in TY activity. Cell assays further suggested that LLCTs exhibited a strong inhibition against intracellular TY activity and melanin production, and caused apoptosis in B16F10 cells. Anti-browning studies demonstrated that LLCTs suppress the browning of fresh-cut apples. Furthermore, the LLCTs exhibited an impressive inhibition on both α-glucosidase and nonenzymatic glycation . Therefore, this study confirms the potential of LLCTs as new inhibitors of tyrosinase, melanogenesis , browning, α-glucosidase, and nonenzymatic glycation, which provided a theoretical basis for the potential utilization of these polymers in the cosmetics, pharmaceutical, and food industries.
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CHEMICAL ENGINEERING JOURNAL
·
2023
·
IF 15.1
Muhammad Arif,Ayaz Mahsud,Amjad Ali,Shipeng Liao,Jiawei Xia,Hai Xiao,Mohammad Azam,Tahir Muhmood,Zhansheng Lu,Yinjuan Chen
The construction of visible-light-driven hybrid heterostructure photocatalysts is of great significance for environmental remediation, although the utilization of strong visible-light response photocatalysts with high efficiency and stability remains a major challenge. On the other hand, defect engineering is an excellent way to introduce metal cation vacancies in materials, thereby ensuing in highly enhanced catalytic performance. Inspired by this, we effectively constructed a built-in interface α-MnO 2 /Bi 2 WO 6 heterostructure with abundant intimate interfaces and defective Mn 3+ /Mn 4+ active sites for photocatalytic tetracycline hydrochloride (TC-HCl), hexavalent chromium Cr 6+ reduction, and Escherichia coli ( E. coli ) inactivation. The experimental results, such as the active species test and X-ray photoelectron spectroscopy, indicated that the defective sites Mn 3+ /Mn 4+ , surface oxygen vacancies, and Bi (3+x)+ boosted the visible light absorption, and highly enhanced the photoinduced charge separation/transfer. Furthermore, experimental and DFT calculations reveal the high charge density at the built-in interface heterostructure and the Z-scheme charge transfer mechanism during the photocatalytic process. The results further reveal that O 2 − and 1 O 2 are the main reactive active species contributing to the photocatalytic reaction. The exceptional TC-HCl decomposition activity of the α-MnO 2 /Bi 2 WO 6 heterostructure (97.56%, 2.31, and 2.04 times higher than bulk), enhanced reaction kinetics (K app = 0.041 min −1 , 6.4, and 5.2 times higher than bulk), removal rate of 80.3%, Cr 6+ reduction to Cr 3+ (98.56%, K app = 0.0599 min −1 ), and almost 100% bacterial inactivation compared to bulk α-MnO 2 (42.22%) and Bi 2 WO 6 (47.76%), were mainly due to the enhanced charge separation/transfer at the built-in interface and high charge density. This study opens new horizons for constructing Z-scheme MnO-based interface heterostructures with abundant defect sites for exceptional photocatalytic applications.
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EXPERIMENTAL CELL RESEARCH
·
2023
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IF 3.7
Lei Huang,Shunyi Lu,Mengxuan Bian,Jiayi Wang,Jieqin Yu,Jun Ge,Jian Zhang,Qintong Xu
Oxidative stress is one of the most important factors in changing bone homeostasis. Redox homeostasis plays a key role in the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) and the angiogenesis ability of human umbilical vein endothelial cells (HUVECs) for bone regeneration. Currently, this study assessed the effects of punicalagin (PUN) on BMSCs and HUVECs. Cell viability was determined by CCK-8 assay. A flow cytometry analysis was adopted to detect macrophage polarization. The production of reactive oxygen stress (ROS), glutathione (GSH), malonaldehyde (MDA) and superoxide dismutase (SOD) activities were evaluated by using commercially-available kits. Osteogenic capacity of BMSCs was evaluated by ALP activity, ALP staining and ARS staining. The expression of osteogenic-related proteins (OCN, Runx-2, OPN) and Nrf/HO-1 levles were evaluated by Western blotting. Osteogenic-related genes (Osterix, COL-1, BMP-4, ALP) were evaluated by RT-PCR. Migration ability and invasion ability of HUVECs were evaluated by wound healing assay and Transwell assay. Angiogenic ability was detected by tube formation assay and the expression of angiogenic-related genes (VEGF, vWF, CD31) were evaluated by RT-PCR. Results showed that PUN alleviated oxidative stress by TNF-α, enhanced osteogenic differentiation in BMSCs and angiogenesis in HUVECs. Moreover, PUN regulate immune microenvironment by promoting the polarization of M2 macrophages and reduce the oxidative stress related products by activating Nrf2/HO-1 pathway. Altogether, these results suggested that PUN can promote osteogenic capacity of BMSCs, angiogenesis of HUVECs, alleviate oxidative stress via Nrf2/HO-1 pathway, offering PUN as a novel antioxidant agent for treating bone loss diseases.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2023
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IF 8.2
Xixi Bai,Xiaoyang Sun,Yue Yu,Yuheng Guo,Linyu Nian,Chongjiang Cao,Shujie Cheng
Raffinose family oligosaccharides (RFOs) in food are the main factors causing flatulence in Irritable Bowel Syndrome (IBS) patients and the development of effective approaches for reducing food-derived RFOs is of paramount importance. In this study, polyvinyl alcohol (PVA)-chitosan (CS)-glycidyl methacrylate (GMA) immobilized α-galactosidase was prepared by the directional freezing-assisted salting-out technique, aimed to hydrolyze RFOs. SEM, FTIR, XPS, fluorescence and UV characterization results demonstrated that α-galactosidase was successfully cross-linked in the PVA-CS-GMA hydrogels, forming a distinct porous stable network through the covalent bond between the enzyme and the carrier. Mechanical performance and swelling capacity analysis illustrated that α-gal @ PVA-CS-GMA not only had suitable strength and toughness for longer durability, but also exhibited high water content and swelling capacity for better retention of catalytic activity. The enzymatic properties of α-gal @ PVA-CS-GMA showed an improved Km value, pH and temperature tolerance range, anti-enzymatic inhibitor (melibiose) activity compared to the free α-galactosidase and its reusability was at least 12 times with prolonged storage stability. Finally, it was successfully applied in the hydrolysis of RFOs in soybeans. These findings provide a new strategy for the development of α-galactosidase immobilization system to biological transform the RFOs components in the food for diet intervention of IBS.
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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2023
·
IF 6.1
Xiang Wang,Yejun Deng,Yang Zhang,Caihong Zhang,Lujie Liu,Yong Liu,Jianxin Jiang,Pujun Xie,Lixin Huang
Food-derived α-glucosidase inhibitory peptides have gained significant interest in treating type 2 diabetes mellitus (T2DM) owing to their favorable safety profiles. Molecular docking combined with molecular dynamics simulation was performed to screen α-glucosidase inhibitory peptides from Ginkgo biloba seed cake (GBSC), and two novel peptides (Met-Pro-Gly-Pro-Pro (MPGPP) and Phe-Ala-Pro-Ser-Trp (FAPSW)) were acquired. The results of molecular docking and molecular dynamics simulation suggested that FAPSW and MPGPP could generate stable complexes with 3wy1, and the electrostatic and van der Waals forces played contributory roles in FAPSW and MPGPP binding to 3wy1. The α-glucosidase inhibition assay corroborated that FAPSW and MPGPP had good α-glucosidase inhibition capacity, with IC50 values of 445.34 ± 49.48 and 1025.68 ± 140.78 μM, respectively. In vitro simulated digestion results demonstrated that FAPSW and MPGPP strongly resisted digestion. These findings lay a theoretical foundation for FAPSW and MPGPP in treating T2DM.
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COLLOIDS AND SURFACES B-BIOINTERFACES
·
2019
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IF 3.973
Jun Zhao,Chun-Liu Yu,Wei Fang,Ji-Duan Lin,Guo Chen,Xiao-Qin Wang
Self-assembled polypseudorotaxanes (PPRXs) fabricated with α -cyclodextrin and poly(ethylene glycol) (PEG) or its thiolated derivatives were candidate functional materials for enzyme soft-immobilization, encapsulation and controlled-release. The study of their interaction with Jack bean urease (JBU) indicated that they inconspicuously influenced the activity and stability of JBU during long storage, up to 30 days. The macro-species were inaccessible to JBU’s active site and the steric effect might play a significant role in the stabilization of JBU, when compared with the small-molecular sulfhydryl inhibitor thioglycolic acid. Circular dichroism and fluorescence spectra analyses revealed that thiolated PEG 400 -(SH) 2 and its assembly PPRX 400 (SH) brought in perturbations to certain α -helical or β -sheet domains of JBU, making JBU’s conformation more flexible. The resulting partial unfolding of domains exposed several hydrophobic clusters and varied JBU’s surface hydrophobicity. It also rendered the chromophores more hydrophilic and more bared to the polar environment, leading to the typical bathochromic-shift and quenching in intrinsic and synchronous fluorescence spectra. Moreover, the surface hydrophobicity profile of JBU was depicted by fluorescent probe monitoring and the unique “hydrophobic cave” motif was proposed by analyzing JBU’s structural data from the Protein Data Bank. It should be pointed out that conformational variations mainly occurred at the surface region of JBU, while the buried active bi-nickel center was not markedly influenced by the macro-species. The results demonstrated that the PPRXs might act as a proper carrier for JBU encapsulation or soft-immobilization.
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TALANTA
·
2018
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IF 4.244
Di Wu,Na Hu,Jichao Liu,Guangsen Fan,Xiuting Li,Jing Sun,Chunji Dai,Yourui Suo,Guoliang Li,Yongning Wu
Recently, exploitation of nanozymes for signal amplification has aroused extensive research interesting in the fields of analytical chemistry and nanoscience. Herein, we introduced a new sensing strategy based on the ascorbic acid (AA) precisely regulated Ag 3 PO 4 nanozyme for signal amplification. AA can reduce the partial Ag + on the surface of Ag 3 PO 4 nano-particles to form Ag° particles and result in the formation of Ag°/Ag 3 PO 4 heterostructure. Due to surface plasmon resonance (SPR), the Ag° particles in heterostructure can act as the co-catalysts to enhance the electron-hole separation and the interfacial charge transfer, leading to a highly efficient oxidase mimicking activity for catalyzing the oxidation of the substrate of 3,3,5,5-tetramethylbenzidine (TMB) under visible light. Impressively, the activity enhancement of Ag 3 PO 4 nano-peroxidase was linearly depended on the AA concentrations. Based on this feature, we employed it for multiple biological detections. For example, L -ascorbic acid-2-O-α- D -glucopyranosyl (AAG) was designed for α-glucosidase substrate, which can be hydrolyzed by α-glucosidase and lead to AA release. Further, the signal of α-glucosidase activity can be efficiently enlarged by Ag 3 PO 4 nanozyme. Taking advantages of the powerful signal amplification by Ag 3 PO 4 nanozymes, we developed the multiple sensing assays for monitoring AA in rat brain microdialysates, detection of α-glucosidase activity and its inhibitors (anti-diabetic drugs). The assay allowed the ultrasensitive colorimetric detection of α-glucosidase inhibitor with an ultra-low detection limit of 10 nM, and a naked-eye detection of the inhibitor concentration as low as 1 μM. The sensing strategy based on AA precisely regulated Ag 3 PO 4 nano-peroxidase provides a promising candidate platform for highly stable and efficient cascaded signal amplification in biosensing field.
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ANESTHESIA AND ANALGESIA
·
2018
·Vol. 127
·期 3
·775
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IF 3.463
Gui Yulong,Li Aiyuan,Zhang Jie,Li Guan,Ruan Xia,Guo Qulian,Zou Wangyuan
BACKGROUND: Neuropathic pain is an intractable and complex disease. Recent studies have shown a close relationship between endoplasmic reticulum (ER) stress and neuropathic pain. Here, we investigated the effect of α-asarone, an ER stress inhibitor, on chronic constriction injury (CCI)–induced neuropathic pain. METHODS: Two parts were included in this study. In part 1, rats were assigned to 7 groups: the sham group, the sham + α-asarone 20 mg/kg group, the CCI group, the CCI + vehicle group, the CCI + α-asarone 5 mg/kg group, the CCI + α-asarone 10 mg/kg group, and the CCI + α-asarone 20 mg/kg group. After surgery, the rats were treated with α-asarone or normal saline daily. Pain thresholds were measured, and samples of the L3–6 spinal cord were taken for western blotting and immunofluorescence on day 7. In part 2, rats were intrathecally implanted with PE-10 tubes and divided into 4 groups: the CCI + α-asarone 20 mg/kg group, the CCI + α-asarone 20 mg/kg + vehicle group, the CCI + α-asarone 20 mg/kg + SR9243 group, and the CCI group. Five rats in each group were separated for behavioral tests 1 hour after intrathecal injection. The rest of them were killed for western blotting on day 7. RESULTS: In this study, CCI surgery significantly induced mechanical allodynia and thermal hyperalgesia. CCI surgery significantly induced activation of ER stress (PERK-eIF2α, IRE1α, CHOP, and XBP-1s) in rats. However, treatment with 20 mg/kg of α-asarone significantly alleviated CCI-induced activation of ER stress. Behavioral results showed that daily treatment with 20 mg/kg of α-asarone significantly alleviated CCI-induced nociceptive behaviors, on day 7 (mechanical allodynia, P = .016, 95% confidence interval, 0.645–5.811; thermal hyperalgesia, P = .012, 95% confidence interval, 0.860–6.507). Furthermore, α-asarone induced upregulated expression of liver X receptor β (LXRβ) and downstream proteins in the spinal cord. The LXR antagonist SR9243 completely inhibited the anti-ER stress and antinociceptive effects of α-asarone in rats. CONCLUSIONS: α-Asarone relieved CCI-induced neuropathic pain in an LXR-dependent manner. α-Asarone may be a potential agent for treatment of neuropathic pain.
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