Journal of Functional Foods
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2020
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IF 3.701
Yuxing Guo,Tao Zhang,Jinjin Gao,Xiaoxiao Jiang,Mingxuan Tao,Xiaoqun Zeng,Zhen Wu,Daodong Pan
This research sought to assess the anticancer effects of Lactobacillus acidophilus CICC 6074 and its underlying mechanism of action. L. acidophilus CICC 6074 inhibited HT-29 cell activity and induced its apoptosis in a dose- and time-dependent manner. HT-29 cells exposed to L. acidophilus CICC 6074 showed mitochondrial membrane potential (ΔΨm) loss, as well as Cyt c is released from the mitochondria into the cytoplasm, causing Bax, Caspase-9 and Caspase-3 to be up-regulated and Bcl-2 to be down-regulated. To further explore the mechanism by which L. acidophilus CICC 6074 achieves its anti-cancer effect, a HT-29 cell-induced colon cancer mouse model was used. Compared with a colon cancer model control group, the high-dose L. acidophilus CICC 6074 group showed obvious colon cancer cell apoptosis as measured by histological morphology, electron microscopy, and terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. An in vivo study showed that L. acidophilus CICC 6074 induced colon cancer apoptosis by up-regulating Bax, down-regulating Bcl-2, releasing Cyt c from the mitochondria into the cytoplasm, and activating Caspase-3 and Caspase-9. These results demonstrate that L. acidophilus CICC 6074 exerts anticancer effects via the activation of mitochondrial pathways which then induce apoptosis. The research could provide new ideas and theoretical basis for development of probiotics functional food market.
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Aging-US
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2019
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IF 5.515
Chao Guo,Junrong Zhu,Jingwen Wang,Jialin Duan,Shanbo Ma,Ying Yin,Wei Quan,Wei Zhang,Yue Guan,Yi Ding,Aidong Wen,Yingdong Zhang
Mitochondrial dysfunction and oxidative damage are closely related to the pathogenesis of Parkinson's disease (PD). The pharmacological mechanism of protocatechuic aldehyde (PCA) for PD treatment have retained unclear. The purposes of the present study were to clarify the neuroprotective effects of post-treatment of PCA for PD treatment by mitigating mitochondrial dysfunction and oxidative damage, and to further determine whether its effects were mediated by the polo-like kinase 2/phosphorylated glycogen synthase kinase 3 β/nuclear factor erythroid-2-related factor 2 (PLK2/p-GSK3β/Nrf2) pathways. We found that PCA improved 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced behavioral deficits and dopaminergic cell loss. Moreover, PCA increased the expressions of PLK2, p-GSK3β and Nrf2, following the decrease of α-synuclein (α-Syn) in MPTP-intoxicated mice. Cell viability was increased and the apoptosis rate was reduced by PCA in 1-methyl-4-phenylpyridinium iodide (MPP + )-incubated cells. Mitochondrial membrane potential (MMP), mitochondrial complex I activity and reactive oxygen species (ROS) levels in MPP + -incubated cells were also ameliorated by treatment with PCA. The neuroprotective effects of PCA were abolished by inhibition or knockdown of PLK2, whereas overexpression of PLK2 strengthened the protection of PCA. Furthermore, GSK3β and Nrf2 were involved in PCA-induced protection. These results indicated that PCA has therapeutic effects on PD by the PLK2/p-GSK3β/Nrf2 pathway.
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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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Computational and Mathematical Methods in Medicine
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2022
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IF 2.809
Zhulin Wu,Jianyuan Kang,Wanjun Tan,Chunshan Wei,Li He,Xiaoyan Jiang,Lisheng Peng
Objective. Traditional Chinese medicine (TCM) is an important part of the comprehensive treatment of hepatocellular carcinoma (HCC), and Chinese materia medica formulas with the effect of “Yiqi Jianpi” (replenishing qi and strengthening spleen) or “Jiedu” (removing toxicity) have been proved to be effective in treating HCC. However, mechanisms of these formulas in treating HCC remain unclear. In this paper, our goal is to explore the antitumor activity and its molecular mechanisms of Yiqi Jianpi Jiedu (YQJPJD) formula against HCC. Methods. The bioactive ingredients and targets of YQJPJD formula and HCC targets were screened by five Chinese materia medicas and two disease databases, respectively. The network pharmacology was utilized to construct the relationship network between YQJPJD formula and HCC, and the mechanisms were predicted by the protein-protein interaction (PPI) network, pathway enrichment analysis, bioinformatics, and molecular docking. Numerous in vitro assays were performed to verify the effect of YQJPJD formula on HCC cells, cancer-associated targets, and PI3K/Akt pathway. Results. The network relationship between YQJPJD formula and HCC suggested that YQJPJD formula mainly regulated the potential therapeutic targets of HCC by several key bioactive ingredients (e.g., quercetin, luteolin, baicalein, and wogonin). PPI network, bioinformatics, and molecular docking analyses displayed that YQJPJD formula may play an anti-HCC effect through key targets such as MAPK3, RAC1, and RHOA. Additionally, pathway analysis demonstrated that YQJPJD formula could play an anti-HCC effect via multiple pathways (e.g., PI3K-Akt and hepatitis B). Experimental results showed that YQJPJD formula could effectively inhibit the proliferation, migration, and invasion of HCC cells and promote HCC cell apoptosis in a concentration-dependent manner. Moreover, YQJPJD formula could decrease the mRNA expression of β-catenin, MAPK3, and RHOA and the protein expression of phosphorylated PI3K and Akt. Conclusion. YQJPJD formula mainly exerts its anti-HCC effect through multiple bioactive ingredients represented by quercetin, as well as multiple pathways and targets represented by PI3K/Akt pathway, β-catenin, MAPK3, and RHOA.
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JOURNAL OF NATURAL PRODUCTS
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2013
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IF 3.285
Heng-Yi Yu,Xiao-Qiong Zhang,Xue- Li,Fan-Bo Zeng,Han-Li Ruan
In order to discover anticancer agents from natural sources, an ethanol-soluble extract of the root bark of Juglans cathayensis was investigated and showed cytotoxic effects against various human cancer cell lines. A subsequent phytochemical study on the EtOAc-soluble fraction determined 2-methoxyjuglone (1) as one of the main active constituents. Compound 1 was shown to be cytotoxic against HepG2 cells. Morphological features of apoptosis were observed in 1-treated HepG2 cells, including cell shrinkage, membrane blebbing, nuclear condensation, and apoptotic body formation. Cell cycle analysis with propidium iodide staining showed that 1 induced cell cycle arrest at the S phase in HepG2 cells. Flow cytometric analysis with annexin V and propidium iodide staining demonstrated that 1 induced HepG2 cell apoptotic events in a dose-dependent manner (0–8 μg/mL). Western blot analysis of apoptosis-related proteins revealed that 1 induces HepG2 cell apoptosis through mitochondrial cytochrome c-dependent activation of the caspase-9 and caspase-3 cascade pathway (intrinsic pathway). An in vivo experiment using tumor-bearing mice showed that treatment with 1 at 0.5 and 1.0 mg/kg per day decreased the tumor mass by 56% and 67%, respectively.
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Thoracic Cancer
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2023
·Vol. 14
·期 33
·3331-3341
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IF 2.9
Mengming Xia,Xueyi Song,Zebei Lu,Yu Wang,Quan Zhou,Peiwu Geng,Shuanghu Wang,Yunfang Zhou,Qingjun Wu,Aixia Han
Background Lenvatinib is a multitargeted tyrosine kinase inhibitor used in the treatment of a variety of solid tumors. This study aims to investigate the potential pharmacokinetic interactions between lenvatinib and various azoles (ketoconazole, voriconazole, isavuconazole and posaconazole) when orally administered to rats. Methods A total of 30 Sprague–Dawley rats were randomly allocated into five groups and administered 20 mg/kg of ketoconazole, voriconazole, isavuconazole and 30 mg/kg of posaconazole and 0.5% CMC-Na, through gavage for a duration of 7 days prior to the commencement of the experiment. On the final day, the rats were given 10 mg/kg of lenvatinib. The blood concentration of lenvatinib was determined using UPLC-MS–MS. In vitro lenvatinib were incubated with azoles and rat liver microsomes (RLMs) or human liver microsomes (HLMs). Molecular docking was lastly used to examine the binding strength of the enzymes and ligands with Autodock Vina. Results AUC and C max of lenvatinib significantly increased with each of the azoles ( p < 0.05), whereas CLz/F decreased 0.83-flod, 0.41-fold ( p < 0.05) and 0.72-fold ( p < 0.01) in voriconazole, isavuconazole and ketoconazole in rats. The IC50 of lenvatinib with the azoles were 0.237, 1.300, 0.355 and 2.403 μM in RLMs and 0.160, 1.933, 3.622 and 1.831 μM in HLMs. Molecular docking analysis suggested that azoles exhibited a strong binding ability towards the target enzymes. Conclusion It is imperative to acknowledge the potential drug–drug interactions mediated by CYP3A4 between azoles and lenvatinib, as these interactions hold significant implications for their clinical utilization.
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JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
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2023
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IF 3.6
Meng-qiu Xia,Jingbao Chen,Liu Liu,Chun-ling Tian,Wang-kai Cheng,Zhiyun Zheng,Xiao-qin Chu
Primary dysmenorrhea is a common disease in women, and oral administration of Ibuprofen (IBU) is associated with first-pass effects and gastrointestinal irritation. Here, we developed ibuprofen-loaded hexagonal liquid crystal (IBU HLC) gel for transdermal administration. In this study, the structure of prepared IBU HLC was characterized using polarizing microscopey (PLM) and small angle X ray diffraction (SAXS). In vitro drug release behavior and percutaneous penetration were investigated, and drug transdermal behavior was observed by confocal laser scanning microscope (CLSM). Finally, the pharmacokinetic profile and tissue distribution were investigated after transdermal administration. The PLM and SAXS results showed that the inner structure of IBU HLC was hexagonal phase. Moreover, in vitro release, skin permeation and CLSM demonstrated that IBU HLC had an excellent sustained-release effect, and a good transdermal penetration effect accompanied by the combination of multiple percutaneous routes. Pharmacokinetic studies indicated that IBU entered the blood circulation through abdominal transdermal administration in small amounts, mainly entering the uterus, and had a certain targeting ability. In conclusion, the IBU HLC gel would be a promising sustained-release preparation for transdermal administration to relieve dysmenorrhea with a significant drug concentration in the uterus.
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ENVIRONMENTAL TOXICOLOGY
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2023
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IF 4.5
You Xiao,Yuanyuan He,Chongsi Xu,Mei Li,Fan Hu,Wei Wang,Zhenquan Wang,Yi Cao
MoS 2 nanosheets (NSs) are novel 2D nanomaterials (NMs) being used in many important fields. Recently, we proposed the need to evaluate the influences of NMs on Kruppel-like factors (KLFs) even if these materials are relatively biocompatible. In this study, we investigated the influences of MoS 2 NSs or bulk on KLF4 signaling pathway in 3D Caco-2 spheroids in vitro and mouse intestines in vivo. Through the analysis of our previous RNA-sequencing data, we found that exposure to MoS 2 NSs or bulk activated KLF4 expression in 3D Caco-2 spheroids. Consistently, these materials also activated KLF4-related gene ontology (GO) terms and down-regulated a panel of KLF4-downstream genes. To verify these findings, we repeatedly exposed mice to MoS 2 NSs or bulk materials via intragastrical administration (1 mg/kg bodyweight, once a day, for 4 days). It was shown that oral exposure to these materials decreased bodyweight, leading to relatively higher organ coefficients. As expected, exposure to both types of materials increased Mo elements as well as other trace elements, such as Zn, Fe, and Mn in mouse intestines. The exposure also induced morphological changes of intestines, such as shortening of intestinal villi and decreased crypt depth, which may result in decreased intestinal lipid staining. Consistent with RNA-sequencing data, we found that material exposure increased KLF4 protein staining in mouse intestines and decreased two KLF4 downstream proteins, namely extracellular signal-regulated kinase (ERK) and serine/threonine kinase (AKT). We concluded that MoS 2 materials were capable to activate KLF4-signaling pathway in intestines both in vivo and in vitro.
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Bioactive Materials
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2023
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IF 18.9
Haofei Li,Yulian Shang,Qi Feng,Yang Liu,Junlin Chen,Hua Dong
Islets transplantation is a promising treatment for type 1 diabetes mellitus. However, severe host immune rejection and poor oxygen/nutrients supply due to the lack of surrounding capillary network often lead to transplantation failure. Herein, a novel bioartificial pancreas is constructed via islets microencapsulation in core-shell microgels and macroencapsulation in a hydrogel scaffold prevascularized in vivo. Specifically, a hydrogel scaffold containing methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and vascular endothelial growth factor (VEGF) is fabricated, which can delivery VEGF in a sustained style and thus induce subcutaneous angiogenesis. In addition, islets-laden core-shell microgels using methacrylated hyaluronic acid (HAMA) as microgel core and poly(ethylene glycol) diacrylate (PEGDA)/carboxybetaine methacrylate (CBMA) as shell layer are prepared, which provide a favorable microenvironment for islets and simultaneously the inhibition of host immune rejection via anti-adhesion of proteins and immunocytes. As a result of the synergistic effect between anti-adhesive core-shell microgels and prevascularized hydrogel scaffold, the bioartificial pancreas can reverse the blood glucose levels of diabetic mice from hyperglycemia to normoglycemia for at least 90 days. We believe this bioartificial pancreas and relevant fabrication method provide a new strategy to treat type 1 diabetes, and also has broad potential applications in other cell therapies.
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Molecular Pain
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2023
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IF 3.3
Yao Wu,Fangyong Wang
Previous studies have confirmed the relationship between chloride homeostasis and pain. However, the role of sodium potassium chloride co-transporter isoform 1 (NKCC1) in dorsal horn and dorsal root ganglion neurons (DRGs) in spinal cord injury (SCI)-induced neuropathic pain (NP) remains inconclusive. Therefore, we aimed to explore whether suppression of NKCC1 in the spinal cord and DRGs alleviate the NP of adult rats with thoracic spinal cord contusion. Thirty adult female Sprague-Dawley rats (8 week-old, weighing 250–280 g) were randomly divided into three groups with ten animals in each group (sham, SCI, and bumetanide groups). The paw withdrawal mechanical threshold and paw withdrawal thermal latency were recorded before injury (baseline) and on post-injury days 14, 21, 28, and 35. At the end of experiment, western blotting (WB) analysis, quantitative real-time Polymerase Chain Reaction (PCR) and immunofluorescence were performed to quantify NKCC1 expression. Our results revealed that NKCC1 protein expression in the spinal cord and DRGs was significantly up-regulated in rats with SCI. Intraperitoneal treatment of bumetanide (an NKCC1 inhibitor) reversed the expression of NKCC1 in the dorsal horn and DRGs and ameliorated mechanical ectopic pain and thermal hypersensitivities in the SCI rats. Our study demonstrated the occurrence of NKCC1 overexpression in the spinal cord and DRGs in a rodent model of NP and indicated that changes in the peripheral nervous system also play a major role in promoting pain sensitization after SCI.
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JOURNAL OF SOLID STATE CHEMISTRY
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2019
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IF 2.291
Qianqian Zhang,Haishan Wu,Wei Lin,Jiannan Wang,Yuwu Chi
Perovskite quantum dots (PQDs) are getting more and more attention for their unique optical properties such as high photoluminescence quantum yield , narrow emission spectrum, and adjustable emission wavelength . However, PQDs, especially, CH 3 NH 3 PbX 3 PQDs have very poor stability due to their easy decomposition by water and oxygen in the air. Herein, we grew nano-sized CH 3 NH 3 PbBr 3 PQDs in situ within a kind of micro-sized metal-organic frameworks (Bio-MOF-1) to obtain MOFs-protected PQD composites (PQDs-Bio-MOF-1). The MOF protection only enables the PQD composites to maintain the fluorescence characteristics of PQDs, but also obviously improves the stability of PQDs in the air, showing promising application in light-emitting diodes (LEDs).
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CHEMICO-BIOLOGICAL INTERACTIONS
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2024
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IF 4.7
Meng Luan,Bijun Zhang,Yifan Wei,Fanghua Liu,Yuhong Zhao,Yalian Yu,Qijun Wu
Enhanced drug resistance poses a significant challenge in treating ovarian cancer (OC). Phenylethyl isothiocyanate (PEITC) is involved in drug resistance in OC, but the mechanism remains unclear. In this study, we investigated the molecular regulatory mechanism of carboplatin sensitivity in OC associated with PEITC, MAF BZIP Transcription Factor F (MAFF), and Zinc finger proteins (ZNF) 711. The carboplatin sensitivity was significantly increased in OC cells after PEITC treatment. Knockdown of MAFF significantly enhanced the carboplatin sensitivity of OC cells, promoted apoptosis, inhibited colony-forming efficiency in vitro , and suppressed tumor growth in vivo . The binding site of MAFF to the ZNF711 promoter was predicted, and the knockdown of MAFF significantly increased the ZNF711 expression. Results of the dual luciferase assay and ChIP-PCR confirmed the binding of MAFF to the ZNF711 promoter. Immunofluorescence and CoIP results demonstrated the colocalization and the binding of MAFF and its interacting protein, BZIP Transcription Factor ATF-like 3 (BATF3). Similarly, we confirmed the binding of BATF3 to the ZNF711 promoter. Knockdown of BATF3 alone and simultaneous knockdown of BATF3 and MAFF showed similar regulatory effects on ZNF711 transcription and apoptosis. These suggested that the binding of MAFF to BATF3 inhibited ZNF711 transcription and reduced carboplatin sensitivity in OC.
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