MEDICAL ONCOLOGY
·
2022
·Vol. 39
·期 7
·1-12
·
IF 3.738
Chen Zhuo,Wu Jing,Wang Liang,Zhao Hua,He Jie
Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. More and more studies have shown that the tumor immune microenvironment (TME) of TNBC is closely related to its poor prognosis and early metastasis. We try to explain how tumor-associate macrophages (TAMs), an important component of the TME, function in the matrix of TNBC. Therefore, we induced THP-1 cells to become M1-TAMs and M2-TAMs, investigated their influence on breast cancer cells. 82 TNBC paraffin samples were made into tissue microarrays. The expression of macrophages makers were measured by immunohistochemistry. Scratch assay, Transwell assay, CCK-8 cell proliferation assay were performed in the co-culture system of breast cancer cells lines and macrophages to observe the invasion and proliferation ability of breast cancer cell lines. Western Blot (WB) was performed to detect the expression of E-cadherin (CDH1) and N-cadherin (CDH2). M2-TAMs were more numerous than M1-TAMs in the matrix of TNBC cancer nests and associated with poor prognosis. M2-TAMs promoted the invasion, migration, and proliferation of TNBC cells. M1-TAMs had inhibitory effects. In MCF-7 cells, WB showed a decrease in CDH1 and an increase in CDH2. In MDA-MB-231 cells and BT549 cells, CDH2 expression was reduced and CDH1 expression was increased. All of the above results were statistically significant, p < 0.001. M2-TAMs were more numerous in TNBC and associated with poor prognosis. M2-TAMs promoted the invasion, migration, and proliferation of breast cancer cells. The mechanism may be related to the epithelial-mesenchymal transition.
研究领域:
肿瘤学
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免疫学
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细胞生物学
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病理学
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PubMed
高影响因子
Journal of Animal Science and Biotechnology
·
2026
·Vol. 17
·期 1
·169
·
IF 7.9
Li Jiahao,Wang Zhengli,Ma Xiaoxue,Nie Cunxi,Liu Tingting,Li Yuanyuan,Zhang Wenju
Background Diarrhea in suckling lambs is associated with gut microbiota dysbiosis, impaired intestinal barrier function, and enhanced inflammatory responses. However, the specific intestinal microbes and microbial metabolites linked to intestinal homeostasis in suckling lambs remain unclear. Results In this study, diarrheic lambs showed significantly higher serum diamine oxidase (DAO) activity, D-lactate (D-LA), and pro-inflammatory cytokine levels than healthy lambs. We then compared gut microbial composition and metabolite profiles between healthy and diarrheic suckling lambs. Diarrheal lambs exhibited gut microbiota dysbiosis, characterized by an elevated Bacillota (syn. Firmicutes)/Bacteroidota (syn. Bacteroidetes) ratio, reduced abundance of beneficial commensals including Phocaeicola vulgatus and Bacteroides fragilis , and proliferation of the opportunistic pathogen Clostridium perfringens . Metabolomic analysis showed that, in diarrheic lambs, the tryptophan metabolism pathway was reduced with lower levels of indole-3-carboxaldehyde (IAld) and 5-hydroxyindole-3-acetic acid (5-HIAA) than in healthy lambs. Fecal microbiota transplantation experiments showed that transplantation of microbiota from diarrheic lambs partially recapitulated the donor-associated microbial, metabolic, and inflammatory phenotypes in recipient mice. Finally, functional validation using a dextran sulfate sodium (DSS)-induced colitis model revealed that supplementation with IAld and 5-HIAA significantly alleviated DSS-induced intestinal inflammation and barrier damage, accompanied by downregulated expression of genes related to the Tlr4-Myd88-Nfκb signaling pathway. Conclusions Our findings indicate that the gut microbiota-derived tryptophan metabolites IAld and 5-HIAA alleviated inflammation and improved intestinal epithelial barrier function by enhancing tight junction integrity, while also reducing the expression of Tlr4/Myd88/Nfκb pathway-related inflammatory signaling molecules.
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Plants-Basel
·
2025
·Vol. 14
·期 7
·1126
·
IF 4.1
Haonan Li,Michael Ackah,Frank Kwarteng Amoako,Aaron Tettey Asare,Jianbin Li,Zhenjiang Wang,Qiang Lin,Changyu Qiu,Mengdi Zhao,Weiguo Zhao
Vegetative propagation of mulberry (Morus albaL.) via sapling methods, due to the ability to exponentially multiply lateral buds on stem cuttings to enhance rapid shoot formation, is crucial for sericulture industries. The sprouting of mulberry using stubbles is an emerging method for rapid and mass production of mulberry leaves, but the growth mechanisms associated with its use remain obscure. This study is the first to report how the differential stubble lengths from mulberry plants alter and modulate phytohormones and the associated mechanisms. This study seeks to evaluate the growth mechanisms by elucidating the phytohormone signature modulation in response to differential stubble lengths of 0 cm, 5 cm, 10 cm, 20 cm, and a control via targeted metabolomics analysis in mulberry leaves. The results consistently show that the use of differential stubble lengths of mulberry promoted growth, the number of buds, aboveground biomass, and branch and leaf weights by improving the net photosynthesis, transpiration rate, stomatal conductance, and intercellular CO2relative to the control. The differential stubble lengths not only caused contrasting responses in the contents of plant hormones, including salicylic acid (SA), abscisic acid (ABA), indole-3-acetic acid (IAA), jasmonic acid (JA), and gibberellin (GA), but also modulated higher elemental contents relative to the control. The results further reveal significant and positive correlations between the phytohormones and all growth, biomass, and photosynthetic parameters, highlighting the role of phytohormones in the sprouting and rejuvenation of mulberry stubbles. Meanwhile, the targeted metabolomics analysis identified a total of 11 differentially accumulated phytohormones in response to the differential stubble lengths, which were significantly implicated and enriched in three major pathways, including the biosynthesis of plant hormones (ko01070), metabolic pathways (ko01100), and the plant hormone signal transduction pathway (ko04575). The use of stubbles for rapid leaf production in mulberry plants is of great importance to improve early sprouting and cutting survival, as well as shortening growth and rooting time, and is highly recommended for the sericulture industries.
研究领域:
植物学
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代谢组学
·
农学
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Yidong Zhou,Zhijian Ke,Hangting Ye,Mengting Hong,Yifei Xu,Mingliang Zhang,Wankui Jiang,Qing Hong
Carbaryl is a widely used carbamate pesticide in agriculture. The strain Rhizobium sp. X9 possesses the typical carbaryl degradation pathway in which carbaryl is mineralized via 1-naphthol, salicylate, and gentisate. In this study, we cloned a carbaryl hydrolase gene cehA and a novel two-component 1-naphthol hydroxylase gene cehC1C2. CehA mediates carbaryl hydrolysis to 1-naphthol and CehC1, an FMNH2 or FADH2-dependent monooxygenase belonging to the HpaB superfamily, and hydroxylates 1-naphthol in the presence of reduced nicotinamide-adenine dinucleotide (FMN)/flavin adenine dinucleotide (FAD), and the reductase CehC2. CehC1 has the highest amino acid similarity (58%) with the oxygenase component of a two-component 4-nitrophenol 2-monooxygenase, while CehC2 has the highest amino acid similarity (46%) with its reductase component. CehC1C2 could utilize both FAD and FMN as the cofactor during the hydroxylation, although higher catalytic activity was observed with FAD as the cofactor. The optimal molar ratio of CehC1 to CehC2 was 2:1. The Km and Kcat/Km values of CehC1 for 1-naphthol were 74.71 ± 16.07 μM and (8.29 ± 2.44) × 10–4 s–1·μM–1, respectively. Moreover, the enzyme activities and substrate spectrum between CehC1C2 and previously reported 1-naphthol hydroxylase McbC were compared. The results suggested that McbC had a higher 1-naphthol hydroxylation activity, while CehC1C2 had a broader substrate spectrum.
研究领域:
环境微生物学
·
生物化学
·
农药生物降解
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PubMed
高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2023
·
IF 11.4
Haoyue Tan,Pan Gao,Yiwen Luo,Xiao Gou,Pu Xia,Pingping Wang,Lu Yan,Shaoqing Zhang,Jing Guo,Xiaowei Zhang,Hongxia Yu,Wei Shi
Although previous studies have confirmed the association between phthalate esters (PAEs) exposure and endocrine disorders in humans, few studies to date have systematically assessed the threats of new PAE alternatives to endocrine disruptions. Herein, zebrafish embryos were continuously exposed to two PAEs [di-n-butyl phthalate (DBP) and diisobutyl phthalate (DiBP)], two structurally related alternatives [diiononyl phthalate (DINP) and diisononyl hexahydrophthalate (DINCH)], and two non-PAE substitutes [dipropylene glycol dibenzoate (DGD) and glyceryl triacetate (GTA)], and the endocrine-disrupting effects were investigated during the early stages (8–48 hpf). For five endogenous hormones, including progesterone, testosterone, 17β-estradiol, triiodothyronine (T3), and cortisol, the tested chemicals disturbed the contents of at least one hormone at environmentally relevant concentrations (≤3.9 μM), except DINCH and GTA. Then, the concentration-dependent reduced zebrafish transcriptome analysis was performed. Thyroid hormone (TH)- and androgen/estrogen-regulated adverse outcome pathways (AOPs) were the two types of biological pathways most sensitive to PAE exposure. Notably, six compounds disrupted four TH-mediated AOPs, from the inhibition of deiodinases (molecular initiating event, MIE), a decrease in T3 levels (key event, KE), to mortality (adverse outcome, AO) with the quantitatively linear relationships between MIE-KE (|r| = 0.96, p = 0.002), KE-AO (|r| = 0.88, p = 0.02), and MIE-AO (|r| = 0.89, p = 0.02). Multiple structural analyses showed that benzoic acid is the critical toxicogenic fragment. Our data will facilitate the screening and development of green alternatives.
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高影响因子
ENVIRONMENTAL SCIENCE & TECHNOLOGY
·
2021
·
IF 9.028
Hongchao Li,Zihao Zhao,Jieshu Qian,Bingcai Pan
The catalytic activation of peroxymonosulfate (PMS) is under intensive investigation with potentials as an alternative advanced oxidation process (AOP) in wastewater treatment. Among all catalysts examined, Co(II) exhibits the highest reactivity for the activation of PMS, following the conventional Fenton-like mechanism, in which free radicals (i.e., sulfate radicals and hydroxyl radicals) are reckoned as the reactive species. Herein, we report that the primary reactive species (PRS) is proposed to be a Co(II)–PMS complex (Co(II)–OOSO3–), while free radicals and Co(III) species act as the secondary reactive species (SRS) that play a minor role in the Co(II)/PMS process. This Co(II)–OOSO3– exhibits several intriguing properties including ability to conduct both one-electron-transfer and oxygen-atom-transfer reactions with selected molecules, both nucleophilic and electrophilic in nature, and strongly pH-dependent reactivity. This study provides novel insights into the chemical nature of the Co(II)-catalyzed PMS activation process.
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高影响因子
MOLECULES
·
2020
·Vol. 25
·期 19
·4441
·
IF 3.267
Guang-Xue Liu,Feng Xu,Ming-Ying Shang,Xuan Wang,Shao-Qing Cai
Asari Radix et Rhizoma (ARR) is an important traditional Chinese medicine. Volatile organic compounds (VOCs) are the main active constituents of ARR. Research on the metabolite profile of VOCs and the difference of absorbed constituents in vivo after an administration of ARR decoction and powder will be helpful to understand the pharmacological activity and safety of ARR. In this study, headspace solid-phase microextraction gas chromatography mass spectrometry (HS–SPME–GC–MS) was applied to profile the VOCs from ARR in rats in vivo. A total of 153 VOCs were tentatively identified; 101 were original constituents of ARR (98 in the powder-treated group and 43 in the decoction-treated group) and 15 were metabolites, and their metabolic reactions were mainly oxidation and reduction, with only two cases of methylation and esterification, and 37 unclassified compounds were identified only in the ARR-treated group. Of the 153 VOCs identified, 131 were reported in rats after oral administration of ARR for the first time, containing 79 original constituents, 15 metabolites, and 37 unclassified compounds. In the powder-treated group, methyleugenol, safrole, 3,5-dimethoxytoluene (3,5-DMT), 2,3,5-trimethoxytoluene (2,3,5-TMT), and 3,4,5-trimethoxytoluene (3,4,5-TMT) were the main absorbed constituents, the relative contents of which were significantly higher compared to the decoction-treated group, especially methyleugenol, safrole, and 3,5-DMT. In the decoction-treated group, 3,4,5-TMT, 2,3,5-TMT, kakuol, and eugenol were the main constituents with a higher content and wider distribution. The results of this study provide a reference for evaluating the efficacy and safety of ARR.Keywords:Asari Radix et Rhizoma;volatile compounds;distribution;HS–SPME–GC–MS;metabolite profile
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PHYTOMEDICINE
·
2019
·
IF 4.18
Wen-Zhen Dang,Hui Li,Bing Jiang,Kutty Selva Nandakumar,Kai-Fei Liu,Li-Xin Liu,Xiao-Chen Yu,Hui-Jing Tan,Chun Zhou
Background Anti-malarial drug artesunate (ART), a semi-synthetic derivative of artemisnin, has immunosuppressive effects on several autoimmune diseases, including Systemic lupus erythematosus (SLE), Rheumatoid arthritis (RA), and Colitis . However, molecular mechanisms of ART, especially on follicular helper T cells (Tfh), central players in SLE pathology, are far from clear. Purpose The object for this work is to investigate the therapeutic effect of ART on lupus-prone MRL/ lpr mice and its regulatory function on Tfh cells . Study design and methods MRL/ lpr mice were used to explore therapeutic effects of ART on lupus-prone MRL/ lpr mice and its regulatory functions on Tfh cells. Then, experiments of renal function were accomplished using the biochemical kits. Effects of ART on histopathology of kidneys, inflammatory factors and autoantibodies were examined using H&E staining, ELISA and real-time PCR. Flow cytometry and western blot analysis were used to examine effects of ART on Tfh differentiation and Jak2–Stat3 signaling pathway . Results Upon oral administration , ART significantly prolonged the survival of MRL/ lpr mice, ameliorated the lupus nephritis symptoms, decreased the levels of anti-dsDNA antibodies deposited in the kidney, and the levels of pathogenic cytokines (IL-6, IFN-γ and IL-21). After ART treatment , T-cell compartment in the spleen of MRL/ lpr mice was restored in terms of reduction in the number of Tfh cells and in the maintenance of the ratio of Tfr to follicular regulatory T cells (Tfh). In addition, ART has significantly inhibited the phosphorylation levels of Jak2 and Stat3 in the MRL/ lpr mice. Conclusion ART showed therapeutic effects on lupus-prone MRL/ lpr mice by inhibiting the differentiation of Tfh cells as well as altering the activation status of Jak2–Stat3 signaling cascade.
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高影响因子
MICROCHIMICA ACTA
·
2019
·Vol. 186
·期 12
·1-10
·
IF 5.479
Huang Shan,Yang Erli,Yao Jiandong,Chu Xu,Liu Yi,Xiao Qi
A rapid, sensitive, and selective fluorometric assay is described for the determination of chromium(VI) in real waters and living cells. The method is making use of nitrogen, phosphorus, and sulfur tri-doped carbon dots (NPS-CDs) which have absorption/emission maxima at 360/505 nm/nm. Cr(VI) has an absorption maximum at 350 nm and causes an inner filter effect (IFE) on the blue fluorescence of the NPS-CDs. The NPS-CDs were hydrothermally synthesized using p -aminobenzenesulfonic acid and tetrakis(hydroxymethyl)phosphonium chloride as precursors. The NPS-CDs were characterized by transmission electron microscopy, X-ray diffraction, and several spectroscopic methods. They are biocompatible and negligibly cytotoxic when tested with HeLa cells and MCF-7 cells even after 48 h of incubation. The NPS-CDs were used as fluorescent probes for Cr(VI). The detection limit is 0.23 μM (three times standard deviation versus slope), and the linear response covers the 1 to 500 μM chromate concentration range. The NPS-CDs were applied to the determination of Cr(VI) in real waters and living cells (HeLa and MCF-7) and gave satisfying results.
Schematic representation of hydrothermal synthesis of nitrogen, phosphorus, and sulfur tri-doped carbon dots (NPS-CDs) for Cr(VI) detection via inner filter effect (IFE). NPS-CDs were applied to the determination of Cr(VI) in living cells (HeLa and MCF-7) with satisfying results.
研究领域:
分析化学
·
环境科学
·
生物医学
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PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Zhang Xuguang,Zhang Yuxin,Zhou Mingyan,Xie Yiqiang,Dong Xiujuan,Bai Feihu,Zhang Junqing
(R)-5-hydroxy-1,7-diphenyl-3-heptanone (DPHC) from the natural plant Alpinia officinarum has been reported to have antioxidation and antidiabetic effects. In this study, the therapeutic effect and molecular mechanism of DPHC on type 2 diabetes mellitus (T2DM) were investigated based on the regulation of oxidative stress and insulin resistance (IR) in vivo and in vitro. In vivo, the fasting blood glucose (FBG) level of db/db mice was significantly reduced with improved glucose tolerance and insulin sensitivity after 8 weeks of treatment with DPHC. In vitro, DPHC ameliorated IR because of its increasing glucose consumption and glucose uptake of IR-HepG2 cells induced by high glucose. In addition, in vitro and in vivo experiments showed that DPHC could regulate the antioxidant enzyme levels including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), thereby reducing the occurrence of oxidative stress and improving insulin resistance. Western blotting and polymerase chain reaction results showed that DPHC could promote the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), the heme oxygenase-1 (HO-1), protein kinase B (AKT), and glucose transporter type 4 (GLUT4), and reduced the phosphorylation levels of c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 (IRS-1) on Ser307 both in vivo and in vitro. These findings verified that DPHC has the potential to relieve oxidative stress and IR to cure T2DM by activating Nrf2/ARE signaling pathway in db/db mice and IR-HepG2 cells.
研究领域:
药理学
·
分子生物学
·
糖尿病研究
·
细胞生物学
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PubMed
高影响因子
Redox Biology
·
2017
·
IF 6.337
Dan-Qian Chen,Gang Cao,Hua Chen,Dan Liu,Wei Su,Xiao-Yong Yu,Nosratola D. Vaziri,Xiu-Hua Liu,Xu Bai,Li Zhang,Ying-Yong Zhao
Changes in plasma concentration of small organic metabolites could be due to their altered production or urinary excretion and changes in their urine concentration may be due to the changes in their filtered load, tubular reabsorption, and/or altered urine volume. Therefore, these factors should be considered in interpretation of the changes observed in plasma or urine of the target metabolite(s). Fasting plasma and urine samples from 180 CKD patients and 120 age-matched healthy controls were determined by UPLC-HDMS-metabolomics and quantitative real-time RT-PCR techniques. Compared with healthy controls, patients with CKD showed activation of NF-κB and up-regulation of pro-inflammatory and pro-oxidant mRNA and protein expression as well as down-regulation of Nrf2-associated anti-oxidant gene mRNA and protein expression, accompanied by activated canonical Wnt/β-catenin signaling. 124 plasma and 128 urine metabolites were identified and 40 metabolites were significantly altered in both plasma and urine. Plasma concentration and urine excretion of 25 metabolites were distinctly different between CKD and controls. They were related to amino acid, methylamine, purine and lipid metabolisms. Logistic regression identified four plasma and five urine metabolites. Parts of them were good correlated with eGFR or serum creatinine. 5-Methoxytryptophan and homocystine and citrulline were good correlated with both eGFR and creatinine. Clinical factors were incorporated to establish predictive models. The enhanced metabolite model showed 5-methoxytryptophan, homocystine and citrulline have satisfactory accuracy, sensitivity and specificity for predictive CKD. The dysregulation of CKD was related to amino acid, methylamine, purine and lipid metabolisms. 5-methoxytryptophan, homocystine and citrulline could be considered as additional GFR-associated biomarker candidates and for indicating advanced renal injury. CKD caused dysregulation of the plasma and urine metabolome, activation of inflammatory/oxidative pathway and Wnt/β-catenin signaling and suppression of antioxidant pathway.
研究领域:
肾病学
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代谢组学
·
分子生物学
·
临床化学
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高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Xiao Wang,Shang Wang,Jiankun Yi,Yunshuo Li,Jianan Liu,Jun Wang,Jinghui Xi
Insects rely on olfaction to locate their host plants by antennae in complex chemical environments. Odorant receptor (OR) genes are thought to play a crucial role in the process. ORs function together with odorant coreceptors to determine the specificity and sensitivity of olfactory reception. The dark black chafer, Holotrichia parallela Motschulsky (Coleoptera: Scarabaeidae), is a destructive underground pest. To understand the molecular basis of H. parallela olfactory reception, an olfactory-biased expressed odorant receptor HparOR27 and HparOrco (HparOR40) were identified from antennal transcriptome analysis and prediction of the sequence structure. Tissue expression analysis showed that HparOR27 was mainly expressed in adult antennae throughout developmental stages. The functions of HparOR27 were analyzed using the Xenopus laevis oocyte expression system. HparOR27 was broadly responsive to three host plant volatiles, including hexanal, lauric acid, and tetradecane. Electroantennogram tests confirmed that three ligands were electrophysiologically active in antennae of female adults. A Y-tube olfactometer test indicated that hexanal was a repellent for adults of both sexes. Taken together, our data support the identification of odorant receptors and provide a molecular basis for eco-friendly pest control.
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高影响因子
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