Food Bioscience
·
2023
·
IF 5.2
Cheng-Hai Yan,Xiao-Meng Xun,Richard A. Herman,Yu-Fan Zhan,Lu-Chan Gong,Fu-An Wu,Jun Wang
Silkworm pupae oil (SPO) was regarded as a good alternative to alpha-linolenic acid supplements, which contain a variety of triacylglyceride with high nutritional value . To investigate the connections between triacylglyceride composition and lipid gastrointestinal digestive absorption profiles, isolation and bioavailability of triacylglyceride monomers from silkworm pupae oil was analyzed. In this study, two triacylglyceride monomers rich in α -linolenic acid were separated by preparative liquid chromatography , namely LnLnLn (1,2,3- α -linolenic acid triacylglyceride) and LnLnL (1,2- α -linolenic acid, 3- linoleic acid triacylglyceride). The in vitro digestion in the pH-stat model results showed the digestive rate of LnLnLn was 0.4101 ± 0.0089 s −1 , which was significantly higher than that of SPO (0.2494 ± 0.0108 s −1 ) ( p < 0.05). The in vitro absorption in the Caco-2 cells model results showed the absorptivity of LnLnLn and LnLnL were 6.40 ± 0.19% and 6.06 ± 0.54%, which were significantly higher than SPO (5.43 ± 0.51%) ( p < 0.05). In addition, the mRNA expression levels of lipid metabolism-related proteins provide evidence for the absorption superiority of LnLnLn and LnLnL. The present work provides novel structural lipids for rapid and efficient supplementation of α -linolenic acid.
研究领域:
营养学
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生物化学
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DOI
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2019
·
IF 3.17
Pian Gong,Zhan Zhang,Yichun Zou,Qi Tian,Shoumeng Han,Zhou Xu,Jianming Liao,Ling Gao,Qianxue Chen,Mingchang Li
Tetramethylpyrazine (TMP) has been studied in depth and is widely used in the treatment of many kinds of diseases in China. However, whether it has neuroprotective effects on cerebral ischemia remains unclear. An ischemia/reperfusion (I/R) injury animal model was established via middle cerebral artery occlusion in this study. We set several different groups in which the rats were performed in different ways to explore the effects of TMP on blood-brainbarrier (BBB) disruption and determine whether TMP relieved BBB disruption through blocking the JAK/STAT signaling pathway. Our results showed that TMP could reduce the neurological functional loss, decrease the brain edema and BBB permeability, as well as increase the expression of tight junction proteins via inhibiting the activation of JAK/STAT signaling pathway. Overall, we demonstrated that TMP promoted neurological recovery after I/R injury via restoring the integrity and function of BBB.
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Toxicology Research
·
2024
·Vol. 13
·期 3
·
IF 2.2
Jin Huiyun,Liu Yanping,Lei Yuandi,Li Guilan,Huang Lian,Zhang Zhaohui
BackgroundChronic beryllium disease is characterized by granulomas and pulmonary fibrosis. Recent studies have shown that microRNAs (miRNAs) and circular RNAs (circRNAs) play critical roles in the pathogenesis and development of many diseases. However, the role of miRNAs and circRNAs in pulmonary fibrosis induced by beryllium sulfate (BeSO4) has not been elucidated.MethodsPrevious studies demonstrated hsa-miR-663b was down-regulated in the 150 μmol/L BeSO4-treated 16HBE cells, while hsa_circ_ 0004214 was up-regulated. Here we found epithelial-mesenchymal transition (EMT) involved in pulmonary fibrosis induced by BeSO4 (4, 8, and 12 mg/kg·BW) in SD rats.ResultsElevated expression of hsa-miR-663b blocked the EMT progression of 16HBE cells induced by 150 μmol/L BeSO4. Notably, the overexpression of hsa-miR-663b decreased the expression of leukemia inhibitory factor (LIF), which was predicted as a target gene of hsa-miR-663b by bioinformatics tools. Furthermore, elevated miR-663b inhibited the activation of the downstream Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway induced by BeSO4 in 16HBE cells. Previous study suggested that hsa_circ_0004214 had binding sites for hsa-miR-663b. The results indicated hsa_circ_0004214 alleviated the BeSO4-induced EMT via JAK-STAT pathway in 16HBE cells.ConclusionsCollectively, the overexpression of hsa-miR-663b and knockdown of hsa_circ_0004214 attenuated the EMT induced by BeSO4 through the inhibition of JAK-STAT signaling pathway. The aberrant expressed hsa-miR-663b and hsa_circ_0004214 stimulated by BeSO4 may exert an important function in the toxic mechanism of beryllium exposure to 16HBE cells, providing the potential therapeutic targets in chronic beryllium disease.
研究领域:
分子生物学
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毒理学
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肺科学
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基因组学
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DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
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2024
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IF 4.7
Kumar Ganesan,Cong Xu,Chunguang Xie,Yue Sui,Chuan Zheng,Fei Gao,Jianping Chen
Breast cancer (BC) is the most common cancer in women and is known for its tendency to spread to the bones, causing significant health issues and mortality. In this study, we aimed to investigate whether cryoprotective isoliquiritigenin-zein phosphatidylcholine nanoparticles (ISL@ZLH NPs) could inhibit BC-induced bone destruction and tumor metastasis in both in vitro and animal models. To evaluate the potential of ISL@ZLH NPs, we conducted various experiments. First, we assessed cell viability, colony formation, transwell migration, and wound healing assays to determine the impact of ISL@ZLH NPs on BC cell behavior. Western blotting, TRAP staining and ALP activity were performed to examine the effects of ISL@ZLH NPs on osteoclast formation induced by MDA-MB-231 cell-conditioned medium and RANKL treated RAW 264.7 cells. Furthermore, we assessed the therapeutic impact of ISL@ZLH NPs on tumor-induced bone destruction using a mouse model of BC bone metastasis. Treatment with ISL@ZLH NPs effectively suppressed BC cell proliferation, colony formation, and motility, reducing their ability to metastasize. ISL@ZLH NPs significantly inhibited osteoclast formation and the expression of factors associated with bone destruction in BC cells. Additionally, ISL@ZLH NPs suppressed JAK-STAT signaling in RAW264.7 cells. In the BCBM mouse model, ISL@ZLH NPs led to a significant reduction in osteolytic bone lesions compared to the control group. Histological analysis and TRAP staining confirmed that ISL@ZLH NPs preserved the integrity of bone structure, preventing invasive metastasis by confining tumor growth to the bone marrow cavity. Furthermore, ISL@ZLH NPs effectively suppressed tumor-induced osteoclastogenesis, a key process in BC-related bone destruction. Our findings demonstrate that ISL@ZLH NPs have the potential to inhibit BC-induced bone destruction and tumor metastasis by targeting JAK-STAT signaling pathways and suppressing tumor-induced osteoclastogenesis. These results underscore the therapeutic promise of ISL@ZLH NPs in managing BC metastasis to the bones.
研究领域:
肿瘤学
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药理学
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纳米技术
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细胞生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2022
·
IF 6.51
Xianbin Wang,Wenjun Cao,Chuanfen Sun,Yutie Wang,Mingyu Wang,Jiarong Wu
Rheumatoid arthritis (RA) is a chronic and symmetrical autoimmune disease that primarily characterized with articular synovial hyperplasia, joint swelling, cartilage and bone destruction. The in-depth understanding of the role of immune signaling pathway inhibitors provides inspiration for the construction of new and more effective strategy for RA therapy. In this study, by loading methotrexate (MTX) into an acetalated dextran biopolymer, AcDEX, we developed a pH-sensitive, MTX-loaded and molecularly targeted nanodrug [email protected] NPs) to decrease the toxicity of MTX and simultaneously enhance its therapeutic effect. The resultant [email protected] NPs showed the spherical morphology and notable pH-responsiveness with high drug loading of 88.32%. As demonstrated in vitro and in vivo , the reduced cytotoxicity of both RAW264.7 cells and LPS-activated RAW264.7 cells treated with [email protected] NPs was found compared to free MTX. Upon intravenous administration into adjuvant-induced arthritis (AIA) rat model, the nanodrug had potent pharmacokinetic and pharmacodynamic profiles, which can accumulate in RA lesions and release MTX inhibitors for regulating the JAK-STAT pathways. As a result, the [email protected] NPs achieved the cartilage and bone protective and a better anti-inflammatory effect with negligible systemic toxicity, suggesting the strong potential of safe and effective nanodrug for RA therapy as well as other autoimmune diseases.
研究领域:
药学
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纳米技术
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免疫学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
Journal for ImmunoTherapy of Cancer
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2024
·Vol. 12
·期 10
·e009416
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IF 10.3
Hua Huang,Yuwen Pan,Qiuwen Mai,Chunyu Zhang,Qiqiao Du,Yuandong Liao,Shuhang Qin,Yili Chen,Jiaming Huang,Jie Li,Tianyu Liu,Qiaojian Zou,Yijia Zhou,Li Yuan,Wei Wang,Yanchun Liang,Chao Yun Pan,Junxiu Liu,Shuzhong Yao
Background Cervical cancer remains a global health challenge. The identification of new immunotherapeutic targets may provide a promising platform for advancing cervical cancer treatment. Objective This study aims to investigate the role of CUB domain-containing protein 1 (CDCP1) in cervical cancer progression and evaluate its potential as a therapeutic target. Methods We performed comprehensive analyses using patient cohorts and preclinical models to examine the association between CDCP1 expression and cervical cancer prognosis. Then in immunodeficient and immunocompetent mouse models, we further investigated the impact of CDCP1 on the tumor immune microenvironment, focusing on its effects on tumor-infiltrating T cells, including cytotoxic T lymphocytes (CTLs) and regulatory T cells (Tregs). Mechanistic studies were performed to elucidate the pathways involved in CDCP1-mediated immune modulation, in particular its interaction with the T cell receptor CD6 and the activation of the JAK-STAT signaling pathway. Results Our results show that CDCP1 overexpression is associated with poor prognosis and T cell infliction in cervical cancer. Specifically, it affects the activity of CTLs and Tregs. Mechanistically, CDCP1 binds to CD6 and inhibits the JAK-STAT pathway of T cells. The study further demonstrates that targeting CDCP1 with the inhibitor 8-prenylnaringenin (8PN) effectively suppresses tumor growth in vivo and enhances antitumor immunity. Conclusions CDCP1 plays a critical role in cervical cancer progression by modulating the tumor immune microenvironment. Targeting CDCP1 offers a promising therapeutic strategy to improve the outcome of patients with cervical cancer.
研究领域:
肿瘤学
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免疫学
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分子生物学
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癌症治疗
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DOI
PubMed
高影响因子
MOLECULAR AND CELLULAR ENDOCRINOLOGY
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2019
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IF 3.693
Wen Qi,Liting Zhou,Tianye Zhao,Shuang Ding,Qi Xu,Xu Han,Yaming Zhao,Xinyue Song,Tianyang Zhao,Xiaohan Zhang,Lin Ye
Background Mono-2-ethylhexyl phthalate (MEHP), an important metabolite of di (2-ethylhexyl) phthalate (DEHP), can induce lipid metabolic disorder . Previous studies have shown that MEHP promotes 3T3-L1 cell differentiation ; however, the underlying mechanism is unclear. The present study was performed to investigate the effect of the TYK-2/STAT-3 pathway on lipid accumulation induced by MEHP. Methods A 3T3-L1 precursor adipocyte differentiation model was exposed to MEHP. 3-Isobutyl-1-methylxanthine (IBMX), dexamethasone (DEX), and insulin were used to establish the 3T3-L1 precursor adipocyte differentiation model. Then the model cells were exposed to MEHP for 8 d. The lipid droplet formation in 3T3-L1 cells was determined with Oil-Red-O staining, and isopropyl alcohol was used to extract the lipid droplets for quantification. Flow cytometry was used to detect the intracellular reactive oxygen species (ROS) and mitochondrial membrane potential . Quantitative real-time polymerase chain reaction (qPCR) was used to detect mRNA expression, and western blotting was used to detect the expression of proteins encoded by TYK-2/STAT-3 pathway genes and adipogenesis-related genes. Results MEHP treatment , compared with the control treatment, significantly promoted the differentiation of 3T3-L1 cells and increased the expression of STAT-3 mRNA and protein and P-STAT3 protein in the cells. In addition, MEHP down-regulated the phosphorylation of STAT-3 in mitochondria. MEHP was found to influence the mitochondrial membrane potential and intracellular ROS levels. Conclusion MEHP may affect adipocyte differentiation and lead to lipid accumulation through the TYK-2/STAT-3 pathway.
研究领域:
毒理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
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IF 8.3
Linlin Ding,Qingjie Li,Kaige Qi,Yonghui Chen,Na Hu,Sangyu Hu,Tianqi Fang,Shuang Guan,Jianfeng Wang,Jiazhang Qiu,Xuming Deng,Lei Xu
Background Salmonella pullorum ( S. pullorum ) is an enteric pathogen that impairs growth performance, leading to substantial economic losses. Evidence demonstrates that the natural flavonoid phloretin can modulate intestinal microbiota functionality, and which underpins its therapeutic efficacy in ameliorating gastrointestinal disorders. However, the protective effects of phloretin against S. pullorum infections and underlying mechanisms remain unelucidated. Purpose This study aimed to elucidate the protective effects and mechanisms of phloretin in improving defense against S. pullorum infection by modulating gut microbiota in chicks. Methods H&E staining, RT-qPCR and ELISA assays were used to assess the protective potentials of phloretin in S. pullorum -infected chicks. Then, 16S rRNA gene sequencing and untargeted metabolomics were employed to identify key microbiota and metabolites regulating the intestinal microenvironment. Moreover, fecal microbiota transplantation (FMT) and dietary metabolite supplementation were conducted to reshape the gut microbiota, elucidate the interaction between the microbiota and S. pullorum infection. Results Phloretin treatment alleviated intestinal injury and enhanced growth performance in S. pullorum -infected chicks via improved intestinal barrier integrity, suppression of inflammatory responses, and restructuring of gut microbial composition. Additionally, these beneficial effects were also observed following FMT from phloretin-treated donors. Subsequent microbial and untargeted metabolomic analysis revealed that phloretin significantly enriched abundance of the functional bacterium Faecalibacterium , and the microbiota-derived phenylalanine metabolites 3-phenylpropionic acid (3-PPA). Importantly, 3-PPA supplementation attenuates S. pullorum -induced intestinal barrier damaged and inflammation in chicks through modulation of the AhR/IL-22/STAT-3 signalling axis. Conclusion These findings provide new insights into the therapeutic potentials of phloretin for S. pullorum -infected chicks.
研究领域:
微生物学
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免疫学
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分子生物学
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兽医学
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代谢组学
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药理学
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DOI
PubMed
高影响因子
Nanoscale
·
2020
·Vol. 12
·期 45
·23013-23027
·
IF 6.895
Ziqian Wang,Chenyue Zhan,Fang Zeng,Shuizhu Wu
Rheumatoid arthritis (RA) is a common chronic autoimmune disease associated with progressive disability, systemic complications, and poor prognosis. The improved understanding of the roles of immune signaling pathway inhibitors has shed light on designing new and more effective approaches for RA treatment. In this work, an inflammation-responsive and molecularly targeted drug system has been developed for RA therapy. The drug carrier was synthesized by covalently grafting hydrophobic cholesterol (Chol) molecules onto a hydrophilic chondroitin sulfate (CS) chain via the inflammation-responsive diselenide bonds (SeSe). The resultant amphiphilic polymer CSSeSeChol readily forms nanoparticles (NPs) and encapsulates two kinase inhibitors tofacitinib and SP600125 in aqueous media. Upon administration into the RA mouse model, the nanodrug accumulates in RA lesions and releases the inhibitors for regulating the JAK-STAT and JNK pathways. As a result, the nanodrug exhibits satisfactory efficacy in RA treatment by suppressing the expression of relevant pro-inflammatory cytokines, blocking the activation of osteoclasts and providing protection for cartilage and joints.
研究领域:
药理学
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纳米技术
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免疫学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2025
·Vol. 18
·期 9
·1319
·
IF 4.8
Xiaoxiao Chen,Jing Tang,Shijie Zhan,Yixian Qiu,Jing Li,Weiguang Shan,Youmin Ying
Background/Objectives:Acute lung injury (ALI) is a respiratory disorder lacking specific targeted therapy. Our preliminary screening revealed that the ethanol extract of the seeds ofPodocarpus nakaii(EESPN) alleviated the symptoms of ALI in mice. The objectives of this study were to identify the active constituents in EESPN and study the mechanism involved.Methods:Column chromatography was performed to separate the chemical constituents of EESPN. The structures of the isolates were determined via spectroscopic methods. MTT assays, Western blotting, histological analysis, TUNEL assays, immunofluorescence staining, transcriptomic analysis, and quantitative real-time polymerase chain reaction (qRT–PCR) were employed to evaluate the anti-inflammatory activity and to elucidate the potential mechanism of nagilactone C (3, Nag C) in ALI treatment.Results:Twelve compounds were isolated from EESPN and structurally characterized. The structure of podolactone E (1) was confirmed via single-crystal X-ray diffraction. In vitro, Nag C showed potent anti-inflammatory activity in LPS-induced RAW 264.7 cells. Nag C liposomes significantly ameliorated LPS-induced histopathological damage to the lungs, reduced neutrophil infiltration and inflammatory cytokine levels, increased myeloperoxidase (MPO) activity, and promoted apoptosis in mice. In addition to suppressing inflammation, Nag C also significantly suppressed the phosphorylation of the NF-κB, STAT3, and STAT1 proteins.Conclusions:Nag C is an active constituent of EESPN. It may protect against LPS-induced ALI via inhibition of the STAT signaling pathway. Thus, Nag C is a promising lead compound in the development of novel STAT-targeted anti-inflammatory agents.
研究领域:
药理学
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天然产物化学
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免疫学
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呼吸医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2024
·
IF 4.4
Huan Yu,Dan Zhou,Wei Wang,Qingxia Wang,Min Li,Xiaoyun Ma
Background and Purpose: The damage or apoptosis of retinal ganglion cells (RGCs) is one of the leading causes of various blinding eye diseases, such as glaucoma, diabetic retinopathy, optic neuritis, and ischemic optic neuropathy. Oxidative stress is involved in RGCs death. Baicalin, a flavonoid compound extracted from Scutellaria baicalensis, has various beneficial effects, including anti-inflammatory, anti-apoptotic, and antioxidant properties. However, the effects of baicalin on RGCs and the underlying mechanisms require further investigation.Methods: In this study, a glutamate-induced oxidative stress damage model of R28 cells and a rat retinal injury model were established to investigate the effects of baicalin on oxidative stress damage to RGCs and try to elucidate the underlying mechanism.Results: In vitro experiments demonstrated that the survival rate of R28 cells after glutamate treatment dropped to 33.4%, while 10 μM baicalin significantly inhibited glutamate-induced damage in RGCs (P < 0.001) and enhanced cell viability through decreasing ROS levels, increasing antioxidant enzyme activity, and suppressing the expression of inflammatory factors iNOS, TNF-α, IL-6, and IL-1β (P < 0.001). In vivo, baicalin effectively mitigated structural damage to retinal tissue and RGCs morphology induced by glutamate, increasing the thickness of the retinal ganglion cell layer, improving RGCs density, and reducing overall retinal thinning in rats (P < 0.001) in a time- and dose-dependent effects. Mechanistic studies revealed that glutamate evaluated the phosphorylation levels of JAK/STAT, while baicalin effectively inhibited the activation of the JAK/STAT signaling pathway.Conclusion: This study confirmed that baicalin protects against glutamate-induced oxidative stress damage in RGCs. It effectively alleviates oxidative stress and inflammatory responses, reduces cell apoptosis, and improves the pathological changes in the retina of rat models of RGCs damage, thereby decreasing RGCs death. Further exploration of its mechanism revealed that baicalin effectively inhibits the JAK/STAT signaling pathway, protecting RGCs from oxidative stress damage. This provides an experimental basis for the application of baicalin in the treatment of RGCs damage.
研究领域:
眼科学
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药理学
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细胞生物学
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神经科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NUTRITION
·
2023
·
IF 4.4
Jiabao Tang,Xiaohua Li,Wei Li,Chun Cao
Objective Enteral nutrition (EN) is the key therapy in septic patients. Different formulas of EN have various effects on gastrointestinal sepsis. Therefore, we investigated the effects of EN supplemented with octanoic acid (OA) on lipopolysaccharide (LPS) induced intestinal injury and explored the potential mechanism. Methods First, to investigate the effects of EN supplemented with OA on LPS-induced intestinal injury, rats were randomly divided into four groups: the sham, LPS, LPS + EN, and LPS + EN + OA groups. Then, to explore whether EN supplemented with OA can prevent LPS-induced intestinal injury via the PPARγ/STAT-1/MyD88 pathway, rats were randomly divided into five groups: the sham, LPS, LPS + EN + OA, LPS + EN + OA +SR202, and LPS + pioglitazone groups. All rats received nutritional support for three days. We examined the serum levels of inflammatory factors, pathological changes, goblet cell density, intestinal tight junction protein expression, and the PPARγ/STAT-1/MyD88 pathway in the ileum and colon. In addition, the effect of OA on intestinal epithelium injury was also explored in vitro. Results EN supplemented with OA significantly decreased the serum levels of inflammatory factors and prevented intestinal barrier dysfunction compared with EN alone (P < 0.05). Inhibiting the PPARγ/STAT-1/MyD88 pathway exacerbated effects of EN supplemented with OA on intestinal injury (P < 0.05). Activation of the PPARγ/STAT-1/MyD88 pathway prevented intestinal injury (P < 0.05). OA also exerted a similar effect on intestinal epithelium injury in vitro. Conclusion EN supplemented with OA prevents LPS-induced intestinal injury via the PPARγ/STAT-1/MyD88 pathway.
研究领域:
营养学
·
胃肠病学
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免疫学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
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