JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2018
·Vol. 22
·期 5
·2774-2790
·
IF 4.302
Qiongli Su,Ting Tao,Lei Tang,Jun Deng,Kwame Oteng Darko,Sichun Zhou,Mei Peng,Shanping He,Qing Zeng,Alex F. Chen,Xiaoping Yang
Pyruvate kinase M2 (PKM2) regulates the final step of glycolysis levels that are correlated with the sensitivity of anticancer chemotherapeutic drugs. THP is one of the major drugs used in non-muscle-invasive bladder cancer instillation chemotherapy. However, low response ratio of THP (19.7%) treatment to human genitourinary tumours using collagen gel matrix has been observed. This study aims to investigate the effect of down-regulation of PKM2 on THP efficiency. Via inhibitor or siRNA, the effects of reduced PKM2 on the efficiency of THP were determined in 2 human and 1 murine bladder cancer cell lines, using MTT, cologenic and fluorescence approaches. Molecular mechanisms of PKM2 on THP sensitization were explored by probing p-AMPK and p-STAT3 levels via WB. Syngeneic orthotopic bladder tumour model was applied to evaluate this efficiency in vivo, analysed by Kaplan-Meier survival curves, body and bladder weights plus immunohistochemistric tumour biomarkers. PKM2 was overexpressed in bladder cancer cells and tissues, and down-regulation of PKM2 enhanced the sensitivity of THP in vitro. Activation of AMPK is essential for THP to exert anti-bladder cancer activities. On the other hand, down-regulating PKM2 activates AMPK and inhibits STAT3, correlated with THP sensitivity. Compared with THP alone (400 μmol L −1 , 50 μL), the combination with metformin (60 mmol L −1 , 50 μL) stopped growth of bladder cancer completely in vivo (combination group VS normal group P = .078). Down-regulating the expression of PKM2 enhances the anticancer efficiency of THP. This study provides a new insight for improving the chemotherapeutic effect of THP.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACOLOGY
·
2014
·
IF 1.581
Ping Mao,Xiao Wei,Mo Liqian,Xiao Xiaoyan,Song Shaolian,Tang Waijiao,Yang Xixiao
Background: Paeonol (2'-hydroxy-4'-methoxyacetophenone) is thought to possess a broad range of clinically curative effects that are likely mediated by its anti-inflammatory and antioxidant activities. Aims: To elucidate the efficacy of paeonol's anti-inflammatory and antioxidant activities and the underlying mechanism of paeonol in advanced oxidation protein product (AOPP) stimulation of THP-1 macrophages. Materials and Methods: After incubating cells with AOPP plus paeonol, nitric oxide (NO) production and the levels of inducible NO synthase (iNOS), receptor for advanced glycation end products (RAGE), CD36, scavenger receptor (SR)-A, and SR-B1 were calculated. Moreover, THP-1 macrophages were preincubated with paeonol, the free radical scavenger N-acetylcysteine (NAC), NADPH oxidase inhibitors [apocynin, diphenylene iodonium (DPI)], and the specific inhibitor of nuclear factor-κB pyrrolidine dithiocarbamate (PDTC) prior to incubation with AOPP, and the levels of intracellular reactive oxygen species (ROS) production and tumor necrosis factor-a (TNF-a), interleukin (IL)-1ß, IL-6, and monocyte chemotactic protein 1 (MCP-1) were determined. Results: Paeonol increased NO production and the mRNA level of iNOS, whereas it decreased ROS production. ROS production was also effectively attenuated by apocynin, DPI, NAC, and PDTC. Furthermore, these inhibitors and paeonol could downregulate the mRNA and protein levels of proinflammatory cytokines (TNF-a, IL-1ß, IL-6, and MCP-1). Paeonol significantly reduced the expression levels of RAGE and CD36 but increased the expression levels of SR-A and SR-B1. Conclusions: These results indicate that paeonol can decrease proinflammatory cytokines in THP-1 macrophages, likely through RAGE-, CD36-, SR-A-, and SR-B1-mediated signals involving NADPH oxidase-dependent ROS generation. This suggests that paeonol can be used as a therapeutic agent for diseases contributing to oxidative stress injury
研究领域:
药理学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CURRENT MICROBIOLOGY
·
2025
·Vol. 82
·期 11
·1-15
·
IF 2.6
Shen Wei,Wang Meng,Han Ting,Yao Yan,Ying Xinyi,Cui Yuyue,Du Peng
Previous research has indicated that the exopolysaccharide galactosaminogalactan (GAG) from Aspergillus fumigatus plays a pivotal role in the pathogenesis of experimental invasive aspergillosis by promoting virulence. However, it remains unclear whether the exopolysaccharide is directly virulent to host cells. In this study, we established a co-incubation system using human THP-1-derived macrophages and GAG extracted from A. fumigatus ATCC 1022 to assess the capacity of GAG to induce necroptosis in THP-1 cells, as well as to elucidate the underlying mechanisms of this process. Our findings indicate that the proportion of N-acetylgalactosamine in the GAG fraction derived from strain ATCC 1022 was lower, while GAG demonstrated a significantly greater ability to induce the production of the pro-inflammatory cytokines TNF-α and IL-1β, which was accompanied by the induction of necroptosis. Western blotting analysis revealed a significant increase in the phosphorylation of RIP1, RIP3, and MLKL proteins in GAG-treated THP-1 cells, and RIP1-RIP3-MLKL signaling activation and GAG-induced caspase activity-independent cell death were effectively inhibited by the TNF-α receptor-1 (TNFR1) inhibitor R-7050, the neutralizing antibody against TNF-α or necroptosis inhibitor Necrostatin-1. It's worth noting that the expression of CLEC4E, the gene encoding the Mincle receptor in macrophages, was elevated in the co-incubation system, potentially enhancing TNF-α-mediated necroptotic cell death. In addition to the RIP1-RIP3-MLKL axis, BAX, cleaved PARP, and JNK were also activated following GAG treatment, warranting further investigation into their roles in the regulation of necroptosis. Our findings demonstrate that GAG produced by A. fumigatus conidia during germination triggers necroptotic cell death in human THP-1 cells via TNF-α-mediated RIP1-RIP3-MLKL signaling.
研究领域:
微生物学
·
免疫学
·
分子生物学
·
感染性疾病
·
真菌病理学
·
细胞死亡机制
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biochemistry and Biophysics Reports
·
2023
·
IF 2.7
Ke Zhang,Youyang Liu,Yunlu Zhao,Qi Guo,Shengjun An,Shuhui Wu
Many chronic inflammatory diseases, such as autoimmune inflammation, are associated with M1 macrophages, and the key to their treatment is blocking inflammation. Oxymatrine (OMT), a traditional Chinese medicine, has a marked anti-inflammatory effect. However, its anti-inflammatory target and mechanism in M1 cells remain unclear, which limits its clinical application. In this study, we investigated the anti-inflammatory effects of oxymatrine (OMT) on the M1 inflammatory response. We also determined the relationship between OMT treatment and the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathway with OMT treatment. To this end, we induced the differentiation of human peripheral blood monocytes (THP-1) into M1 cells. THP-1 cells were induced with a phorbol ester (phorbol-12-myristate-13-acetate (PMA)) and differentiated into naïve M0 macrophages. M0 cells were induced into M1 cells using lipopolysaccharide (LPS). The experimental groups were divided into the M0 macrophage group (NC), M1 inflammatory response group (LPS group), and M1 group treated with different concentrations of OMT (LPS + OMT-L, LPS + OMT-M, LPS + OMT-H). The cells in the OMT-treated groups were treated with OMT for 6 h, followed by LPS for 24 h, and the LPS group was treated with LPS only. The resulting supernatants and cells were collected. The secretion levels of NO were detected by the Griess method and the secretion levels of TNF-α and IL-1β in the supernatants were detected by the ELISA method. The secretion levels of these inflammatory factors were reduced in every OMT-treated group compared to the LPS group (P < 0.01), and the most significant reductions were found in the OMT-H group (P < 0.0001). By western blotting, the protein expression levels of TLR4, NF-κB, NLRP3, and Caspase-1 were all found to be downregulated in the cells of OMT-treated groups compared to the LPS group (P < 0.0001). In situ changes in NLRP3 expression were observed using immunofluorescence. The fluorescence intensity of NLRP3 in M1 cells was weaker in all OMT intervention groups than in the LPS group (P < 0.001). In conclusion, OMT has significant anti-inflammatory effects on the M1 inflammatory responses, and the TLR4/NF-κB/NLRP3 pathway was blocked proportional to the concentration of OMT.
研究领域:
免疫学
·
药理学
·
细胞生物学
·
炎症性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Complementary Medicine and Therapies
·
2022
·Vol. 22
·期 1
·1-13
·
IF 2.838
Gong Linna,Miao Zhishuo,Zhang Li,Shi Birui,Xiao Zuoqi,Qiu Panzi,Liu Menghua,Zou Wei
Background Penyanqing (PYQ), a traditional Chinese medicine (TCM), has a good clinical efficacy for the treatment of pelvic inflammatory disease (PID). Previously, researches on its anti-inflammatory effect and mechanism in vitro, in silico, and in vivo have been reported by our team. However, the interrelationship between the anti-inflammatory activity and the active compounds in PYQ are not clear. Here, the pharmacokinetics-pharmacodynamics (PK-PD) study was carried out for more proper clinical use.Methods The plasma concentrations of salvianolic acid B (SAB), protocatechualdehyde (PRO), paeoniflorin (PE), astilbin (AST), ferulic acid (FE), and chlorogenic acid (CH) in SD rats after PYQ administration were determined by a selective and rapid HPLC–MS/MS method. In addition, the PK-PD on cell model was used to explore the relationship between the plasma concentration and inflammatory biomarkers (TNF-α, IL-1β).Results The results of this study showed that the six components could reach the peak blood concentration within 0.29 h, indicating the rapid absorption of it. The eliminations of AST, CH, FE, PE, and PRO were relatively fast due to their mean residence times (MRTs) within 3 h, while the elimination of SAB was slower (MRT 5.67 ± 0.66 h). Combined with a THP-1 cell model, there was a significant correlation between inflammatory factors and component plasma concentrations with correlation coefficients in the range of -0.9—-0.746. Correspondingly, the drug-containing plasma obtained at 0.25 h point exhibited the best inhibition effect on production of IL-1β and TNF-α in LPS-induced THP-1 cells.Conclusion The six main components in PYQ could be quickly absorbed, and there was a potential good correlation between their pharmacokinetics and the pharmacodynamics of PYQ.
研究领域:
药理学
·
传统中药
·
炎症研究
·
细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2020
·Vol. 21
·期 6
·2466-2474
·
IF 2.1
Lu Wang,Liran Zhu,Chenfangyuan Duan,Lu Li,Guangliang Chen
Total saponins extracted from Dioscorea collettii (TSD), extracts of the Chinese herb Dioscorea, are thought to exhibit therapeutic benefit in gouty arthritis. However, its exact mechanism remains unclear. The current study aimed to elucidate the underlying mechanisms by investigating the effects of TSD on the inflammation induced by monosodium urate (MSU) crystals in THP‑1 macrophages. The viability of THP‑1 macrophages was examined using the MTT assay and the levels of inflammatory cytokines, including interleukin (IL)‑1β, IL‑18 and tumor necrosis factor (TNF)‑α, released by the cells were quantitatively measured using ELISA kits. The results revealed that the protein level of cluster of differentiation 11b increased in THP‑1 cells treated with 100 ng/ml phorbol ester, suggesting that monocytic THP‑1 cells were successfully differentiated into macrophages. TSD decreased the levels of inflammatory cytokines, including TNF‑α, IL‑18 and IL‑1β, secreted by THP‑1 macrophages. As the release of IL‑1β and IL‑18 is dependent on the NLR family pyrin domain containing 3 (NALP3) inflammasome and caspase‑1, the current study investigated the effect of TSD on the aforementioned proteins. The results revealed that TSD decreased the protein levels of NALP3 and apoptosis‑associated speck‑like, which serve important roles in the assembly of the NALP3 inflammasome. Furthermore, NALP3 inflammasome‑related proteins were also decreased by TSD in rotenone induced THP‑1 macrophages, TSD inhibited the activation of caspase‑1 and rotenone‑induced NALP3 inflammasome activation in THP‑1 macrophages. The results obtained in the current study revealed that TSD attenuated MSU crystal‑induced inflammation by inhibiting rotenone‑induced activation of the NALP3 inflammasome and caspase‑1, suggesting that these two proteins may be novel targets for the treatment of gouty arthritis.
研究领域:
药理学
·
免疫学
·
炎症研究
·
中医药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2024
·
IF 8.5
Siqi Peng,Jing Wang,Mohamed A. Farag,Mahmoud Salah,Lianliang Liu,Yajing Fang,Weimin Zhang
This study investigated the changes in phytochemical composition and inflammatory response of crude papaya ( Carica papaya L.) seed oil (CPO) and its refined forms (degummed, PDG; deacidified, PDA; decolorized, PDC; deodorized, PDO). Oils were analyzed for their phytochemical composition, oil quality parameters, antioxidant activity , and their inflammatory response in LPS-stimulated THP-1 macrophages. At higher refining degrees, particularly after deacidification , the contents of phytochemicals (sterols, tocopherols , and polyphenols) decreased while oxidation products increased. Both CPO (0.1–1.0 mg/mL) and PDG reduced the secretion and mRNA expression of LPS-stimulated inflammatory cytokines and mediators and also blocked the activation of the NF-κB pathway. PDA, PDC, and PDO showed low anti-inflammatory or even pro-inflammatory activity. Correlation analysis showed that 4 polyphenols and 2 phytosterols were responsible for the oil's anti-inflammatory effects. These findings indicated that moderate refining is suggested for papaya seed oil processing for retaining bioactive ingredients and anti-inflammatory ability.
研究领域:
食品科学
·
药理学
·
营养学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
Food Bioscience
·
2023
·
IF 5.2
Yuxin Guo,Zheng Jia,Liting Wan,Jun Cao,Yajing Fang,Weimin Zhang
This study aimed to explore the changes in phytochemical composition and inflammatory response of Camellia vietnamensis oil (CO) during refining. Four refined CO samples [degummed (DGO), deacidified (DAO), decolorized (DCO), and deodorized (DOO)] were prepared from crude CO (CCO). Five CO samples were measured for their composition of fatty acids , sterols, tocopherols , polyphenols, and oxidation products as well as anti-inflammatory activity in lipopolysaccharide (LPS)-induced THP-1 macrophages. The content of phytochemicals was significantly decreased with the deepening of the refining degree, especially after deacidification. CCO and DGO showed anti-inflammatory activity by inhibiting the production of pro-inflammatory cytokines and activation of NF-κB induced by LPS. Deacidification and decolorization of CO decreased its anti-inflammatory activity. The accumulation of oxidation products after deodorization in CO aggravated the inflammatory response. Trans -cinnamic, kaempferol , and protocatechuic acid in CO were crucial for their anti-inflammatory effects. These findings underlined that moderate refinement is suggested to retain its bioactive ingredients and anti-inflammatory ability.
研究领域:
食品科学
·
药理学
·
生物化学
✓ 已验证
DOI
高影响因子
Emerging Contaminants
·
2026
·
IF 8.2
Shuang Zheng,Bilin Zhao,Xiaoxue Lin,Peier Peng,Jiewei Deng,Lijuan Luo,Xinyan Li,Chunyan Hao,Tiangang Luan
As emerging contaminants, alternative plasticizers (APs) are increasingly prevalent in the environment due to their use as replacements for regulated phthalates, yet their potential health risks, particularly immunotoxicity, remain poorly understood. To address this critical gap, we systematically evaluated seven environmentally pervasive and toxicologically concerning Aps (ASE, ATBC, TOTM, DEHT, DEHA, DINCH, ESBO) alongside DEHP. We adopted a comprehensive multi-modal strategy to reveal the unique immunotoxic effects of each compound and their underlying mechanisms. Our findings demonstrate that APs differentially disrupt macrophage immune functions: ASE and DEHA enhanced adhesion/phagocytosis, whereas ATBC, TOTM, DEHT, DINCH, and ESBO significantly suppressed these capacities. Mitochondrial profiling revealed that ASE, ATBC, and TOTM increased mitochondrial mass, while DEHT, DEHA, DINCH, and ESBO reduced it. Notably, ASE, DEHT, and ESBO induced mitochondrial dysfunction, characterized by diminished membrane potential (MMP) and elevated mitochondrial reactive oxygen species (mtROS), implicating mitochondrial impairment as a key mechanism of APs-induced immunotoxicity. Analysis of 92 immune-related proteins further indicated a shift toward pro-inflammatory polarization. Metabolomics analysis further linked immunotoxicity to metabolic reprogramming, revealing associated metabolic disturbances. Collectively, this study provides a systematic dissection of APs-immunotoxic mechanisms through a mitochondria-metabolism-immune axis. Our findings offer crucial evidence for the informed safety assessment and regulatory prioritization of these ubiquitous environmental plasticizers.
✓ 已验证
DOI
高影响因子
POLYMER
·
2014
·
IF 3.766
Fangxia Zhu,Qinglai Yang,Yuan Zhuang,Yuanqing Zhang,Zhifeng Shao,Bing Gong,Yu-Mei Shen
Developing smart nanocarriers for drug delivery system is advantageous for many kinds of successful biomedicinal therapy. In this study, we designed an amphiphilic block copolymers containing pH-responsive tetrahydropyran (THP) and tetrahydrofuran (THF) linkage. Their structures were confirmed by 1 H NMR and gel permeation chromatography (GPC). The release rate of encapsulated drugs depends upon the pH value and pH sensitive linkage in the backbone of copolymers . For PLA–THP–PEG micelles the cumulative release amount of doxorubicin (DOX) was 62% at pH 5.0, which is about four times higher than that at pH 7.4. Under the same conditions the release rate for PLA–THF–PEG micelles is a little faster than that of the PLA–THP–PEG micelles. Cellular uptake study demonstrates that DOX-loaded micelles can easily enter the cells and produce the desired pharmacological action and minimizing the side effect of free DOX. These findings indicate that THP and THF linked diblock copolymer micelles is a promising candidate for drug carrier.
研究领域:
生物医学
·
药剂学
·
高分子化学
✓ 已验证
DOI
高影响因子
PHARMACEUTICAL BIOLOGY
·
2025
·
IF 4.8
Yong-xiang Huang,Jin-ru Zhang,Shi-hua Fu,Zhe Liu,Hui-jun Zhong,Qing-yang Zhong,Yin-di Luo,Ying-jie Hu,Hai-peng Zhu,Bin Wen,Song Chen
Context Macrophages play a critical role in the pathogenesis of ulcerative colitis (UC). Indirubin (IDR), a natural ligand of the aryl hydrocarbon receptor (AhR), has been shown to ameliorate DSS-induced colitis in our previous study (Liu Z et al.).Objective To investigate whether IDR exerts its protective effects by regulating M1/M2 polarization and inhibiting ferroptosis in macrophages.Materials and Methods Immunohistochemistry staining targeting CD206 and F4/80 was performed to evaluate the effect of IDR on the polarization of M1/M2 macrophages in colitis. Subsequently, the effects of IDR on the M1- or M2-polarization of THP-1-derived macrophages were investigated. Furthermore, the effects of IDR on ferroptosis in the colon tissue of mice and on RSL3-induced ferroptosis in THP-1-derived macrophages were assessed. The results were verified in mouse peritoneal macrophages.Results In addition to reducing the infiltrated macrophages, IDR treatment preserved CD206+ macrophages in DSS-induced colitis. Using cultured THP-1 cells, we demonstrated that IDR inhibited M1 polarization and prompted M2 polarization. Furthermore, we showed that IDR treatment decreased levels of 4-HNE while increasing GPX4 and NRF2 in DSS-induced colitis and THP-1 cells. IDR treatments also reduced cellular reactive oxygen species (ROS) and iron content, and mitigated RSL3-induced ferroptosis in THP-1-derived macrophages. Similarly, IDR augmented M2-polarization and alleviated ferroptosis in peritoneal macrophages.Discussion and Conclusion IDR skews the polarization of macrophages from M1 to M2. Furthermore, it inhibits ferroptosis in both mice and THP-1-derived macrophages. These mechanisms may contribute to the therapeutic effects of IDR in the treatment of UC.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2016
·
IF 3.138
Li Zhang,Xinquan Liu,Yongjie Wang,Guangpu Liu,Zhen Zhang,Zhongxi Zhao,Huiling Cheng
Zizyphus jujuba has been used as a traditional Chinese medicinal herb since ancient time. Polysaccharides have been found to be important bioactive compounds in the jujube. This work was designed to investigate the physicochemical characteristics and bioactivities of polysaccharides purified from Zizyphus jujuba cv. Muzao . Water-soluble polysaccharides were extracted using an ultrasonically assisted extraction method. The purified polysaccharides (HJP) were obtained by deproteinization and decoloration. Three main fractions (HJP1, HJP2 and HJP3) were isolated using DEAE-Sepharose fast flow ion-exchange chromatography. The purified polysaccharides were found to consist of mannose, rhamnose, galactose, galacturonic acid, glucose and arabinose at various levels for different fractions. The HJP and its three main fractions displayed DPPH radical scavenging activities as well as relatively strong reducing power and HJP had stronger activities than homogeneous compositions. Moreover, the results from in vitro immunological activities studies indicated that HJP could improve the phagocytosis activity of THP-l cells and had effect on the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). In conclusion, the polysaccharides from Zizyphus jujuba cv. Muzao were discovered to have antioxidative and immunological activities.
研究领域:
药理学
·
生物化学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）