JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2026
·
IF 6.7
Caiyan Zhang,Fengxian Sui,Meiyan Liu,Yalin Xie,Jiadi Su,Jing Gao,Ye Lin,Yang Yang,Xiaoming Hou
Oleic acid (OA)-enriched diet significantly enhances CD36 expression and promotes milk fat production in the mammary gland. However, the mechanisms by which OA upregulates this process are unknown. Here, GC-MS analysis and molecular docking were used to assess OA-CD36 binding, while gene expression and ChIP assays clarified the OA-mediated regulation of CD36 and milk fat synthesis. The results showed that CD36 is highly expressed in the lactating mammary tissues of dairy cows and positively regulates milk fat production. OA enters dairy cow mammary epithelial cells via direct binding to CD36. OA stimulation elevates the CD36 expression and translocation. ChIP assays confirmed CD36 as a target gene of NRF2. OA also enhances NRF2 expression and nuclear translocation, which in turn upregulates CD36 expression and function. This study elucidates the NRF2–CD36 axis as a regulator of OA-driven milk fat synthesis in mammary tissue, offering practical value for dairy industry nutritional strategies.
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高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Yi Duan,Mengqiong Deng,Bin Liu,Xianwei Meng,Jinghan Liao,Yijie Qiu,Zhihua Wu,Jiangtao Lin,Yi Dong,Yourong Duan,Ying Sun
The challenge of drug resistance in intrahepatic cholangiocarcinoma (ICC) is intricately linked with lipid metabolism reprogramming. The hepatic lipase (HL) and the membrane receptor CD36 are overexpressed in BGJ398-resistant ICC cells, while they are essential for lipid uptake, further enhancing lipid utilization in ICC. Herein, a metal-organic framework-based drug delivery system (OB@D-pMOF/CaP-AC, DDS), has been developed. The specifically designed DDS exhibits a successive targeting property, enabling it to precisely target ICC cells and their mitochondria. By specifically targeting the mitochondria, DDS produces reactive oxygen species (ROS) through its sonodynamic therapy effect, achieving a more potent reduction in ATP levels compared to non-targeted approaches, through the impairment of mitochondrial function. Additionally, the DDS strategically minimizes lipid uptake through the incorporation of the anti-HL drug, Orlistat, and anti-CD36 monoclonal antibody, reducing lipid-derived energy production. This dual-action strategy on both mitochondria and lipids can hinder energy utilization to restore drug sensitivity to BGJ398 in ICC. Moreover, an orthotopic mice model of drug-resistant ICC was developed, which serves as an exacting platform for evaluating the multifunction of designed DDS. Upon in vivo experiments with this model, the DDS demonstrated exceptional capabilities in suppressing tumor growth, reprogramming lipid metabolism and improving immune response, thereby overcoming drug resistance. These findings underscore the mitochondria-targeted DDS as a promising and innovative solution in ICC drug resistance.
研究领域:
肿瘤学
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药学
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分子生物学
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生物医学工程
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PubMed
高影响因子
NEUROSCIENCE
·
2026
·
IF 3.3
Xiaoyu Lin,Wanliang Du,Ruile Fang,Ying Ma,Yongjun Wang,Jialei Yang
Systemic inflammation worsens ischemic stroke by increasing brain injury, neurological deficits, and neuroinflammation. • Systemic inflammation enhances microglial NF-κB activity and promotes p65/β-catenin interaction. • Systemic inflammation downregulates microglial Wnt/β-catenin/CD36 axis and impairs microglial efferocytosis. • Lithium chloride restores Wnt/β-catenin signaling and microglial efferocytosis, improving stroke outcome under systemic inflammation. Systemic inflammation is associated with worse outcomes after ischemic stroke, but the underlying mechanisms remain poorly understood. Microglial efferocytosis limits post-stroke inflammation and promotes recovery, whereas Wnt/β-catenin signaling has been implicated in neuroprotection and in regulation of CD36, a key efferocytotic receptor. Here, we investigated whether systemic inflammation is associated with alterations in microglial Wnt/β-catenin/CD36 axis and efferocytosis during ischemic injury. Mice were pretreated with lipopolysaccharide (LPS) before transient middle cerebral artery occlusion/reperfusion (tMCAO/R), and BV2 microglia were exposed to LPS before oxygen-glucose deprivation/reoxygenation (OGD/R). LPS pretreatment markedly increased infarct volume, worsened neurological deficits, and amplified post-ischemic neuroinflammatory responses. These effects were accompanied by enhanced microglial NF-κB signaling, increased p65/β-catenin interaction, and reduced nuclear β-catenin, consistent with suppression of Wnt/β-catenin signaling. Reduced CD36 expression and impaired microglial efferocytosis were observed in parallel. Notably, pharmacological activation of Wnt/β-catenin signaling with lithium chloride (LiCl) restored CD36 expression and microglial efferocytosis under LPS-pretreated conditions, and was accompanied by smaller infarcts, improved neurological function, and attenuated neuroinflammation. Collectively, these findings show that LPS pretreatment exacerbates ischemic stroke and is associated with enhanced microglial NF-κB signaling, dysregulation of the Wnt/β-catenin/CD36 axis, and impaired microglial efferocytosis. These results support defective microglial efferocytosis as a potential biological link between systemic inflammation and aggravated ischemic injury and identify Wnt/β-catenin signaling as a candidate pathway for further therapeutic investigation Download: Download high-res image (128KB) Download: Download full-size image
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高影响因子
MOLECULAR ECOLOGY
·
2023
·Vol. 32
·期 11
·2884-2897
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IF 4.9
Jia-Xu Li,Zhong Tian,Xing-Feng Liu,Bei Li,Hao-Min An,Colin S. Brent,Jia-Lu Wang,Xiao-Ping Wang,Wen Liu
Many animals, including insects, exhibit plasticity of body colour in response to environmental changes. Varied expression of carotenoids, major cuticle pigments, significantly contributes to body colour flexibility. However, the molecular mechanisms by which environmental cues regulate carotenoid expression remain largely unknown. In this study, we used the ladybird Harmonia axyridis as a model to investigate the photoperiodic-responsive plasticity of elytra coloration and its endocrine regulation. It was found that H. axyridis females under long-day conditions develop elytra that are much redder than those under short-day conditions, resulting from the differential accumulation of carotenoids. Exogenous hormone application and RNAi-mediated gene knockdown indicate that carotenoid deposition was directed through the juvenile hormone (JH) receptor-mediated canonical pathway. Moreover, we characterized an SR-BI/CD36 ( SCRB ) gene SCRB10 as the carotenoid transporter responding to JH signalling and regulating the elytra coloration plasticity. Taken together, we propose that JH signalling transcriptionally regulates the carotenoid transporter gene for the photoperiodic coloration plasticity of elytra in the beetles, which reveals a novel role of the endocrine system in the regulation of carotenoid-associated animal body coloration under environmental stimuli.
研究领域:
昆虫学
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分子生物学
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内分泌学
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高影响因子
FOOD CHEMISTRY
·
2021
·
IF 7.514
Zhuqing Dai,Jiangfeng Song,Ye Chen,Lei Feng,Yayuan Xu,Dajing Li,Caie Wu,Zhongyuan Zhang,Jun Liu
This study aims to develop novel lutein nanoparticles encapsulized by stevioside (LUT-STE, 165 ± 2 nm average particles size) and systematically evaluate its bioavailability. Multiple spectroscopy and NMR analyses showed lutein and stevioside could interact through hydrogen bonds, C H π interaction and van der Waals forces. Molecular docking simulation showed lutein was well distributed in the hydrophobic cavity of stevioside. Analyzed by Caco-2 cellular models, the transported amount of LUT-STE was 2.39 times that of lutein in 120 min with a P app (B → A)/ P app (A → B) value of 0.63 ± 0.04. Nystatin and dynasore significantly reduced the cellular uptake of LUT-STE by 41.3% and 57.7%, respectively. Compared with free lutein, LUT-STE increased the C max in mice plasma by 5.01-fold and promoted the accumulation in multiple organs. LUT-STE promoted the protein expressions of CD36, NPC1L1 and PPARγ in both cell and animal models. In conclusion, stevioside entrapment significantly promote the bioavailability of lutein through multiple transmembrane pathways.
研究领域:
药学
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营养学
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分子生物学
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药理学
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高影响因子
MOLECULAR PHARMACEUTICS
·
2026
·
IF 4.5
Wanyu Jin,Shujun Xu,Hongyan Zhang,Yujie Li,Mengna Shi,Ninghui Ma,Xin Zhang,Lujia Zhu,Yang Xiong
The limited efficacy of programmed death-ligand-1 (PD-L1) monoclonal antibodies (aPD-L1) in triple-negative breast cancer (TNBC) is largely attributable to the immunosuppressive tumor microenvironment (TME). Notably, the abundance of cancer-associated adipocytes (CAAs) constitutes a distinctive feature of the TNBC microenvironment, contributing significantly to its immunosuppressive nature. CAAs upregulate cluster of differentiation 36 (CD36), a fatty acid translocase on tumor cells, thereby promoting excessive fatty acids (FAs) uptake and lipid droplet (LD) accumulation, which starve immune cells and reinforce immunosuppression through this metabolic adaptation. Berberine (BBR), a bioactive alkaloid derived from Rhizoma coptidis, has previously been shown to ameliorate lipid metabolism disorders through downregulation of CD36 in metabolic diseases such as hepatic steatosis. We therefore hypothesize that BBR inhibits CD36-mediated FAs uptake and reduces LD accumulation in tumor cells, representing a novel mechanism that remains unexplored in the context of TNBC. In this study, we demonstrated that BBR counteracts the tumor-promoting effects of CAAs in 4T1 cells by inhibiting CD36 upregulation and its mediated FAs uptake, thereby reducing CAA-induced LD accumulation and ultimately suppressing tumor cell proliferation. Furthermore, BBR remodeled the TME by enhancing CD8+ T cell recruitment and activity, while reducing immunosuppressive factors. In order to improve the sustained release of BBR at the tumor site and overcome its poor aqueous solubility, we created a thermosensitive hydrogel-based nanoparticle system (BBR-NPs-GEL). This injectable hydrogel demonstrated favorable thermosensitive gelation and shear-thinning behavior, making it suitable for localized administration. It exhibited a gelation temperature of 35.3 ± 0.2 °C and a sustained release profile with 52% of BBR released within 48 h. In 4T1Fluc tumor-bearing mice, BBR-NPs-GEL significantly suppressed tumor growth and remodeled the TME, as evidenced by increased infiltration of CD8+ T cells (+8.49%), activation of dendritic cells (+8.39%), and a shift toward M1-macrophages (+39.9%), accompanied by a reduction in M2-macrophages (−19.13%). Importantly, when combined with aPD-L1 therapy, the treatment elicited synergistic antitumor effects, resulting in enhanced tumor regression. This combination strategy effectively overcame metabolic immunosuppression and reversed immune resistance in TNBC.
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高影响因子
CANCER CHEMOTHERAPY AND PHARMACOLOGY
·
2024
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IF 2.7
Ma Xuan,Sun Zhenou,Chen Hui,Cao Lixing,Zhao Shuang,Fan Lihong,Zhao Chong,Yin Shutao,Hu Hongbo
Purpose 18β-glycyrrhetinic acid (GA), the main metabolite of glycyrrhizic acid extracted from the root of licorice, has been reported to possess anti-cancer and immunomodulatory activity, but the mechanisms are not well understood. Recent studies have shown that ferroptosis of immune cells is involved in tumor-associated immune suppression. The purpose of this study was to investigate whether the enhanced immune response via inhibiting immune cell ferroptosis contributed to the anticancer effect of 18β-GA. Methods Lewis Lung carcinoma mouse model and Murine CD8 + T cell culture model were used to examine the changes of immune response and ferroptosis of immune cells. Results We found that 18β-GA was effective against lung cancer accompanied by enhanced activation of tumor-infiltrating CD8 + T cells in Lewis Lung carcinoma mouse model. Furthermore, we demonstrated that the boosted immune response by GA was attributed to its ability to inhibit arachidonic acid (AA)-mediated CD8 + T ferroptosis via suppressing CD36 expression. Conclusion The findings of the present study unraveled a novel mechanism underlying the anti-cancer and immunomodulatory activity of 18β-GA and support that 18β-GA holds potential to be used as an immune enhancer for lung cancer prevention or treatment.
研究领域:
肿瘤学
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免疫学
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药理学
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高影响因子
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY
·
2019
·
IF 1.99
Haocan Luo,Xu-Fang Liang,Jiao Li,Yanpeng Zhang,Qianqian Xiao,Binbin Peng,Zhilu Zhang
In order to evaluate fatty acid (FA) sensing systems based on binding to FAT/CD36 in hypothalamus of Chinese perch ( Siniperca chuatsi ) and its sensitivity to FAs with the same chain length and different unsaturation levels. The effects of Stearate (SA; C18:0), oleate (OA; C18:1 n-9), linoleic acid (LA; C18:2 n-6), and α-linolenic acid (ALA; C18:3 n-3) on hypothalamic FA sensing were evaluated by intracerebroventricular (ICV) administration. Food intake was assessed after 2, 4, 6, 8 and 12 h. Gene expression associated with FA sensing mechanism such as cd36 , pparα and srebp1c , and neuropeptides controlling appetite such as pomca , cart , agrp2 and npy were assessed after 6 h. The ICV treatment of OA, LA and ALA activated FAT/CD36 and PPARα, rather than SA, and modulated gene expression levels of hypothalamic neuropeptides associated with appetite. And then, OA, LA and ALA inhibited food intake, which was consistent with the activation of hypothalamus FA sensing. Our data indicated some mechanisms of the hypothalamic FA sensing systems also existed in Chinese perch. It's worth noting that polyunsaturated fatty acids (PUFA) could also activate hypothalamic FA sensing mechanisms in Chinese perch. The unsaturation of FA appears to be extremely important for FA sensing mechanisms, since no major influences in Chinese perch after SA treatment. Our findings will contribute to the study of long-chain FAs sensing mechanisms in fish hypothalamus and highlight the importance of PUFAs in fish species.
研究领域:
营养学
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神经生物学
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水产动物学
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高影响因子
Nanoscale
·
2020
·Vol. 12
·期 3
·2133-2141
·
IF 6.895
Dongling Li,Haihong Yu,Zhouyi Guo,Shengtao Li,Yang Li,Yanxian Guo,Huiqing Zhong,Honglian Xiong,Zhiming Liu
Carcinoma-associated fibroblasts (CAFs), one of the most important components of a tumor microenvironment (TME), play a significant role in the complex tumorigenesis process. Herein, the evolution of CAFs in TME is elaborately investigated by surface-enhanced Raman spectroscopy (SERS), a molecular fingerprint technique. Two-dimensional (2D) nanocomposites consisting of gold nanoparticles and a supramolecular “PCsheet” self-assembled between 2D nanosheets and oxidized phosphatidylcholine (PC) are fabricated as SERS-active probes to specifically recognize the CD36 receptor on the cytomembrane of the fibroblasts, a reliable landmark of CAF development. The 2D SERS substrates can also illuminate the fingerprint information around the CD36 protein with high detection sensitivity, which helps elucidate the biochemical component transition in the protein mini-domain during carcinoma progression. Visualized data are then supplied by label-free SERS imaging to exploit the distribution of biomolecules on the plasma membrane. In addition, the repressed expression of CD36 in TME is detected in lung metastasis tumor-bearing mice. This study based on the 2D SERS technique opens up an alternative avenue for unveiling carcinoma-associated molecular events.
研究领域:
肿瘤学
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生物医学工程
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分子生物学
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高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2020
·
IF 2.985
Peng Ma,Rongrong Huang,Jingyao Jiang,Yuan Ding,Tingting Li,Yu Ou
C-phycocyanin (C-PC) is a kind of photosynthetically assisted pigment, which is ubiquitous in cyanobacteria cells. We investigated the effect of C-PC on non-alcoholic fatty liver disease (NAFLD) and its mechanism. Through oil red O staining, TC/TG detection, liver SOD/MDA detection and liver H&E staining, we found that C-PC could significantly reduce the lipid accumulation in the steatosis L02 cells and the liver of non-alcoholic steatohepatitis (NASH) mice, and improve the antioxidant capacity of liver. The results of Western Blotting showed that C-PC upregulated the expression of AMPK phosphorylation and downregulated SREBP-1c and its target genes ACC and FAS expression levels. Furthermore, C-PC also upregulated the expression of transcription factor PPARα , which was regulated by AMPK, and its target genes CPT1 level. In addition, C-PC could promote AMPK phosphorylation in hepatocytes while increasing the phosphorylation level of ACC in vivo and in vitro. Besides, C-PC could also improve the liver inflammatory infiltration by upregulated the expression of PPARγ and downregulated the expression of CD36 , IL6 and TNFα . These results indicate that C-PC may improve hepatic lipid accumulation and inflammation in the non-alcoholic fatty liver mice by activating AMPK pathway of hepatocytes. The finding provides important help for the research and development of C-PC in the nutraceuticals and therapeutics of NAFLD.
研究领域:
药理学
·
肝病学
·
营养保健品
·
分子生物学
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高影响因子
npj Regenerative Medicine
·
2023
·Vol. 8
·期 1
·1-17
·
IF 7.2
Zhao Chuanrong,Yang Qianru,Tang Runze,Li Wang,Wang Jin,Yang Fangfang,Zhao Jianan,Zhu Juanjuan,Pang Wei,Li Ning,Zhang Xu,Tian Xiao Yu,Yao Weijuan,Zhou Jing
Healing of the cutaneous wound requires macrophage recruitment at the sites of injury, where chemotactic migration of macrophages toward the wound is regulated by local inflammation. Recent studies suggest a positive contribution of DNA methyltransferase 1 (Dnmt1) to macrophage pro-informatory responses; however, its role in regulating macrophage motility remains unknown. In this study, myeloid-specific depletion of Dnmt1 in mice promoted cutaneous wound healing and de-suppressed the lipopolysaccharides (LPS)-inhibited macrophage motility. Dnmt1 inhibition in macrophages eliminated the LPS-stimulated changes in cellular mechanical properties in terms of elasticity and viscoelasticity. LPS increased the cellular accumulation of cholesterol in a Dnmt1-depedent manner; cholesterol content determined cellular stiffness and motility. Lipidomic analysis indicated that Dnmt1 inhibition altered the cellular lipid homeostasis, probably through down-regulating the expression of cluster of differentiation 36 CD36 (facilitating lipid influx) and up-regulating the expression of ATP-binding cassette transporter ABCA1 (mediating lipid efflux) and sterol O-acyltransferase 1 SOAT1 (also named ACAT1, catalyzing the esterification of cholesterol). Our study revealed a Dnmt1-dependent epigenetic mechanism in the control of macrophage mechanical properties and the related chemotactic motility, indicating Dnmt1 as both a marker of diseases and a potential target of therapeutic intervention for wound healing.
研究领域:
免疫学
·
细胞生物学
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分子生物学
·
药理学
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PubMed
高影响因子
Food Bioscience
·
2025
·
IF 5.9
Abdul Mueed,He Ma,Abdul Basit,Philippe Madjirebaye,Akhtar Ali,Shoaib Khan,Jing Li,Ze-yuan Deng
Flaxseed cyclolinopeptides (CLs) inhibit the lipid oxidation during in vitro digestion of high-fat meat. However, the effect of CLs on high-fat diet (HFD) induced lipid impairment metabolism remains unclear. Therefore, this study aimed to investigate the impact of CLs on HFD-induced lipid metabolism in the liver and pancreas of mice. The results demonstrated that the CLs administration significantly improved serum lipids (TG, TC, and LDL-C) in the HFD-induced model ( p < 0.05). Histological analysis using H&E and immunofluorescence staining revealed that CLs significantly restored pancreatic structure, and enhanced the secretion of insulin and glucagon. Furthermore, CLs intervention significantly improved antioxidant capacity in both the liver and pancrease by increasing the level of GSH-Px, T-GSH and GSH while decreasing GSSG and MDA levels in HFD-induced model. Lipidomic analysis further revealed that CLs treatment significantly reduced the levels of several lipid metabolites, including lysophosphatidylcholines (LPC), phosphatidylinositols (PI), lysophosphatidylethanolamines (LPE), phosphatidylethanolamines (PE), fatty acyls (FA), and diacylglycerols (DG), while increasing the levels of sphingomyelins (SM) and phosphatidylcholines (PC) compared to the model group. Pathway enrichment analysis indicated that CLs promoted the fatty acids metabolism and biosynthesis of unsaturated fatty acid, as supported by the upregulated expression of lipid metabolism gene/protien (CPT1, SLC7A11 and GPX4) and downregulated expression of lipid tranporter gene/protien (CD36, ACSL4, LPCAT3, and P35). Collectively, these findings suggest that CLs effectively enhance hepatic and pancreatic functiona and inhibit lipid accumulation in liver and pancreas through modulation of the CD36/p53/ACSL4 signalling pathway.
研究领域:
营养科学
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生物化学
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分子生物学
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药理学
·
代谢性疾病
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高影响因子
危险品化学品经营许可证（带存储）