BIOMEDICINE & PHARMACOTHERAPY
·
2025
·
IF 7.5
Yinlan Xu,Hejun Liu,Haonan Guo,Jinmei Zheng,Ling Tao,Weidong Wu
Non-small cell lung cancer (NSCLC) is the major type of malignant tumor in the lungs. Emerging epidemiological evidence implicates environmental copper exposure as a potential risk modulator for NSCLC progression. This study investigated the effects of low-dose Copper (Cu) exposure on A549 cells and evaluated the therapeutic potential of two natural compounds, osthole and matrine. The results demonstrated that Cu exposure (5 μg/mL, 12 h) significantly promoted the migration, invasion and colony formation of A549 cells ( P < 0.05), accompanied by a reduction in cell apoptosis, a decrease in ROS levels and an increase in mitochondrial membrane potential. Meanwhile, osthole and matrine treatment could reverse these phenotypes and arrest the cell cycle of A549 in the G1 phase. Transmission electron microscopy results revealed that Cu exposure induced slightly swollen mitochondria and as well as the increase in the number of mitochondria, while osthole and matrine treatments resulted in severe degenerative changes in mitochondria. Both qPCR and Western blot examinations indicated that Cu exposure promoted the expression of PGC-1α but inhibited the expressions of STAT1, TNF-α and IL-2. Osthole treatment could down-regulate the expression of PGC-1α and up-regulate the expressions of STAT1, TNF-α and IL-2, while matrine treatments could up-regulate the expressions of STAT1 and TNF-α and down-regulate the expressions of PGC-1α and IL-2. Taken together, these findings indicate that low-dose Cu exposure can promote the proliferation, migration, invasion and mitochondrial damage of A549 cells, while osthole and matrine treatments inhibit Cu effects by regulating the STAT1, BGC-1 α, TNF-α and IL-2.
研究领域:
肿瘤学
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环境毒理学
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药理学
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细胞生物学
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分子生物学
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天然产物化学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Nutrition
·
2022
·
IF 6.59
Han Mengyao,Zhang Zhongshan,Li Xinyue,Tong Haibin,Xu Zhiguo,Ding Zikang,Yang Anquan,Xie Min,Wang Xiaomei
To investigate the protective effect of collagen peptide from Micropterus salmoides skin (CPMs) on oxidative damage induced by cyclophosphamide in mice. Balb/c female mice were divided into blank, model (cyclophosphamide, CTX), positive control (levamisole hydrochloride), and collagen peptide low-, medium-, and high-dose groups. The results showed that CPMs increase the body mass and immune-related organ indexes, such as liver and kidneys of immunosuppressed mice. The activities of ALT, AST, UA, BUN, and MDA in the liver and kidney tissues decreased significantly, while those of SOD and GSH-Px increased significantly. CPMs can relieve the pathological damage to immune organs. CPMs significantly increase the activities of IL-2, IgG, and TNF-α in serum and SOD activity, while the MDA content was decreased compared to the model group. CPMs can exert a protective effect on cyclophosphamide-induced oxidative damage and have application prospects in the field of health food.
研究领域:
药理学
·
免疫学
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毒理学
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营养学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2019
·
IF 3.414
Lei Peng,Chenxi Hu,Chaozheng Zhang,Yingying Lu,Shuli Man,Long Ma
Ethnopharmacological relevance Conyza blinii H.Lév. is a type of natural plant distributed in southwest of China. Its dried overground section can be used in traditional Chinese medicine (TCM) for treating infections, inflammations and occasionally cancers. CBS ( Conyza blinii saponin), mainly composed of triterpenoidal saponins of Conyza blinii H.Lév. CBS is considered as the major active fraction of this species. The current investigation have focused on the mechanisms of CBS with regard to its anti-cancer activity. Hence it is of high relevance of identifying the anti-cancer efficacy of ethnomedicine . Aim of the study To understand the anti-cancer mechanism of CBS using both in vitro and in vivo experiments. Materials and methods CBS ( Conyza blinii saponin) was obtained as described previously. We tested the anti-cancer activity of CBS using in vitro HeLa cell models and in vivo animal models. We adopted immunoblot , RT-PCR (reverse transcription polymerase chain reaction), luciferase reporter assay and flow cytometry to study relevant proteins, genes, pathways and cellular ROS (reactive oxygen species) responsible for anti-cancer activity of CBS. More, 24 tumour-xenografted mice were grouped randomly as ‘control’, ‘cisplatin’ (as positive control), ‘low dose’ and ‘high dose’ groups. The IL-1β, TNF-α, PGE2 and IL-2 in the blood serum and the tumour tissue of mice were measured. Results and conclusions We have found that CBS is capable of inducing apoptotic cancer cell death via both caspase-dependent and -independent pathways. CBS inhibits the activation of TGF-β signaling pathway in a dose- and time-dependent manner. Phospho-ERK, phospho-JNK and phospho-p38 MAPK are significantly suppressed by CBS. Furthermore, some inflammation mediators including IL-1β, TNF-α and PGE2 from animal samples were found decreased in CBS-treated mice models. In contrast, the level of IL-2, a cytokine commonly used for treating cancers, increased reversely. Last, we have discovered that CBS is able to decrease the expression of Nrf2, inhibit the activation of ARE and increase ROS level in HeLa cells. In summary, we have confirmed that the anti-cancer activity of CBS is possibly related to its TGF-β, MAPK, Nrf2 signaling pathways as well as some cancer related inflammation mediators and cytokines.
研究领域:
药理学
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肿瘤学
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民族药理学
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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
Frontiers in Immunology
·
2023
·
IF 7.3
Ben Yi,Shuai Zhang,Suying Yan,Yanfei Liu,Zhiqiang Feng,Tianhao Chu,Jun Liu,Wei Wang,Jun Xue,Chunze Zhang,Yijia Wang
Introduction Tumor-infiltrating T lymphocytes in the tumor microenvironment are critical factors influencing the prognosis and chemotherapy outcomes. As a Chinese herbal medicine, Marsdenia tenacissima extract (MTE) has been widely used to treat cancer in China. Its immunoregulatory effects on tumor-associated macrophages is well known, but whether it regulates tumor-infiltrating T-cell functions remains unclear. Method We collected 17 tumor samples from MTE-administered colorectal cancer patients, 13 of which showed upregulation of CD3+/CD8+ tumor-infiltrating T cells. Further in vitro and in vivo experiments were performed to investigate the regulatory effects of MTE on tumor-infiltrating T cells and immune escape of tumors. Results Under single and co-culture conditions, MTE inhibited TGF-β1 and PD-L1 expression in the colorectal cancer (CRC) cell lines HCT116 and LoVo. In Jurkat cells, MTE inhibited FOXP3 and IL-10 expression, increased IL-2 expression, but had no effect on PD-1 expression. These findings were confirmed in vitro using subcutaneous and colitis-associated CRC mouse models. MTE also increased the density of CD3+/CD8+ tumor-infiltrating T cells and exhibited considerable tumor-suppressive effects in these two tumor mouse models. Conclusions Our findings suggested that MTE inhibits the immune escape of cancer cells, a precipitating factor increasing the immune response of T lymphocytes.
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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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
XinQian Rong,QingLong Shu
Codonopsis pilosula , an important medicinal and edible plant in traditional Chinese medicine, is used widely as a tonifying herb for various immunodeficiency diseases. A neutral polysaccharide (CPPs-D1N1) was purified from C. pilosula , composed of fructose and glucose in a molar ratio of 97.28:2.72, with an average molecular weight of 5.985 kDa. Structural analysis revealed a backbone composed of →1)-β-D-Fruf-(2 → units with some β-D-Fruf-(2 → linkages. In a murine immunosuppression model induced by cyclophosphamide injection, oral treatment with C. pilosula polysaccharide was administered, investigating changes in gut microbiota during therapy. The polysaccharide modulated serum immunoglobulins (Ig-G, Ig-M), cytokines (IL-2, IL-6, TNFα), and spleen and thymus indices in immunodeficient mice. Additionally, functional gene primer sequencing enrichment methods revealed alterations in abundance, diversity, and structure of butyrate-producing bacterial populations in the gut, with primary differential genera identified as Butyribacter , Rumanococcus , Dysosmobacter , and Ruseburia . This study provides in vivo evidence supporting the beneficial effects of C. pilosula polysaccharide oral therapy in improving gut microbiota, particularly butyrate-producing bacteria, during treatment of immunosuppressive diseases.
研究领域:
免疫学
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微生物学
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药理学
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中医药
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产品关联
DOI
PubMed
高影响因子
EXPERIMENTAL PARASITOLOGY
·
2023
·
IF 2.1
Muhammad Ehsan,Rui-Si Hu,Meng Wang,Jun-Ling Hou,Muhammad Rashid,Muhammad Irfan Malik
Legumains belonging to C_13 peptidase family of proteins, and are ubiquitously disseminated among all vertebrate and invertebrate organisms, and have been implicated in innumerable biological and cellular functionality. Herein, we characterized and evaluated immunoregulatory characteristics of Legumain-1 from Fasciola gigantica (Fg-LGMN-1) during its interaction with host immune cells . The isopropyl-ß-d-thiogalactopyranoside (IPTG) stimulated RFg-LGMN-1 protein was positively detected by rat serum containing anti-RFg-LGMN-1 polyclonal antibodies . Furthermore, the uptake of RFg-LGMN-1 by goat monocytes was successfully confirmed using Immunofluorescence Assay (IFA). The immunohistochemical analysis revealed the native localization of LGMN-1 protein on the periphery and internal structures such as suckers, pharynx, and genital pore of the adult parasite, thereby validating its presence in excretory-secretory (ES) products of F. gigantica . The RFg-LGMN-1 co-incubated with concanavalin-A (Con-A) stimulated the increase of interleukin 2 (IL-2), IL-10, and IL-17 in monocytes derived from peripheral blood mononuclear cells (PBMCs) in the concentration-dependent manner. However, the IL-4 cytokine in response to the RFg-LGMN-1 protein declined. These results illuminated the role of LGMN-1 during the parasite-host interface. Our findings elaborated additional evidence that Legumain protein play a role in the manipulating host immune responses during parasite infections. However, further evaluation of RFg-LGMN-1 protein in context of its immunomodulatory roles should be conducted to enhance our understandings of the mechanisms employed by F. gigantica to evade host immune responses.
研究领域:
免疫学
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寄生虫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2024
·
IF 2.5
Yu Duan,Qing Wang,Xiaolong Chen,Guanyun Deng,Kunyuan Huang,Fa Sun,Jianguo Zhu,Kehua Jiang
A retrospective study reported that empagliflozin reduced the risk of urinary stone events in patients with diabetes mellitus. To further investigate empagliflozin’s potential, we conducted an animal experiment to determine whether empagliflozin can prevent renal stone formation in hyperoxaluria rats. Hyperoxaluria rat models were constructed by administrating 0.75% ethylene glycol and 1% ammonium chloride in water. The empagliflozin-treated rats were gauged with empagliflozin at different concentrations, and their body weight and blood sugar data were recorded. After 30 days of treatment, we obtained 24-hour urine, kidney, and blood samples. The urine samples were subjected to component detection. Blood samples were prepared for component detection and cytokines detection. Renal samples were subjected to von Kossa staining, transmission electron microscopy, immunohistochemistry, and transcriptome sequencing analysis. Results showed that in empagliflozin-treated hyperoxaluria rats, renal crystal deposition and mitochondria injury, urinary concentration, and excretion of oxalate were significantly decreased. Additionally, plasma levels of VEGF, IL-2, IL-1β, and MCP-1 were decreased. Immunohistochemistry showed that renal expression of KIM-1, MCP-1 was significantly decreased in empagliflozin-treated hyperoxaluria rats. Transcriptome sequencing of renal tissue represented that 25 genes were down-regulated while 12 were up-regulated in empagliflozin-treated hyperoxaluria rats. These regulated genes were mainly enriched in fatty acid metabolism, insulin resistance, muscle contraction, bile secretion, and parathyroid metabolism. Our animal experiments found that empagliflozin could reduce urinary concentration and excretion of oxalate and inhibit renal inflammation, then abating renal calcium oxalate deposition in hyperoxaluria rats in a non-diabetic state.
研究领域:
药理学
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肾病学
·
泌尿学
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分子生物学
·
转化医学
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产品关联
DOI
PubMed
高影响因子
Nanomedicine
·
2024
·
IF 4.7
Jianying Song,Cong Tang,Yun Wang,Junli Ba,Kairui Liu,Jinwei Gao,Jin Chang,Jun Kang,Linling Yin
Aim: This study aimed to develop a sonodynamic–chemodynamic nanoparticle functioning on glutathione depletion in tumor immunotherapy. Materials & methods: The liposome-encapsulated 2,2-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) and copper–cysteine nanoparticles, AIPH/Cu-Cys@Lipo, were synthesized with a one-pot method. 4T1 cells were injected into female BALB/c mice for modeling. Results: AIPH/Cu-Cys@Lipo was well synthesized. It generated alkyl radicals upon ultrasound stimulation. AIPH/Cu-Cys@Lipo promoted the generation of -OH via a Fenton-like reaction. Both in vitro and in vivo experiments verified that AIPH/Cu-Cys@Lipo significantly inhibited tumor development by decreasing mitochondrial membrane potential, activating CD4+ and CD8+ T cells and promoting the expression of IL-2 and TNF-α. Conclusion: AIPH/Cu-Cys@Lipo provides high-quality strategies for safe and effective tumor immunotherapy.
研究领域:
纳米技术
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癌症研究
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免疫治疗
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生物医学工程
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药学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Siqi Li,Hui Zhang,Yujun Bao,Huanli Zhang,Jingchun Wang,Mingyang Liu,Rui Yan,Zhiqiang Wang,Xiaodan Wu,Yingxue Jin
Cancer metastasis and recurrence are closely associated with immunosuppression and a hypoxic tumor microenvironment. Chemodynamic therapy (CDT) and photothermodynamic therapy (PTT) have been shown to induce immunogenic cell death (ICD), effectively inhibiting cancer metastasis and recurrence when combined with immune adjuvants. However, the limited efficacy of Fenton’s reaction and suboptimal photothermal effect present significant challenges for successfully inducing ICD through CDT and PTT. This paper described the synthesis and immunoantitumor activity of the novel iron–copper-doped folic acid carbon dots (CFCFB). Copper-doped folic acid carbon dots (Cu-FACDs) were initially synthesized via a hydrothermal method, using folic acid and copper gluconate as precursors. Subsequently, the nanoparticles CFCFB were obtained through cross-linking and self-assembly of Cu-FACDs with ferrocene dicarboxylic acid (FeDA) and 3-bromopyruvic acid (3BP). The catalytic effect of carbon dots in CFCFB enhanced the activity of the Fenton reaction, thereby promoting CDT-induced ICD and increasing the intracellular oxygen concentration. Additionally, 3BP inhibited cellular respiration, further amplifying the oxygen concentration. The photothermal conversion efficiency of CFCFB reached 55.8%, which significantly enhanced its antitumor efficacy through photothermal therapy. Immunofluorescence assay revealed that treatment with CFCFB led to an increased expression of ICD markers, including calreticulin (CRT) and ATP, as well as extracellular release of HMGB-1, indicating the induction of ICD by CFCFB. Moreover, the observed downregulation of ARG1 expression indicates a transition in the tumor microenvironment from an immunosuppressive state to an antitumor state following treatment with CFCFB. The upregulation of IL-2 and CD8 expression facilitated the differentiation of effector T cells, resulting in an augmented population of CD8+ T cells, thereby indicating the activation of systemic immune response.
研究领域:
肿瘤学
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纳米技术
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免疫治疗
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ADVANCED MATERIALS
·
2024
·
IF 27.4
Qingshuang Zou,Ke Liao,Guangchao Li,Xin Huang,Yongwei Zheng,Gun Yang,Min Luo,Evelyn Y. Xue,Chuanqing Lan,Shuai Wang,Yao Shen,Dixian Luo,Dennis K. P. Ng,Quan Liu
The infiltration and cytotoxicity of chimeric antigen receptor (CAR)-T cells are crucial for effective elimination of solid tumors. While metallo-immunotherapy is a promising strategy that can activate the antitumor immunity, its role in promoting CAR-T cell therapy remains elusive. The first single-element nanomaterial based on chromium nanoparticles (Cr NPs) for cancer photo-metallo-immunotherapy has been reported previously. Herein, an extended study using biodegradable polydopamine as a versatile carrier for these nanoparticles, enabling synergistic CAR-T cell therapy, is reported. The results show that these nanocomposites with or without further encapsulation of the anticancer drug alpelisib can promote the CAR-T cell migration and antitumor effect. Upon irradiation with near-infrared light, they caused mild hyperthermia that can “warm” the “cold” tumor microenvironment (TME). The administration of B7-H3 CAR-T cells to NOD severe combined immunodeficiency gamma mice bearing a human hepatoma or PIK3CA-mutated breast tumor can significantly inhibit the tumor growth after the induction of tumor hyperthermia by the nanocomposites and promote the secretion of serum cytokines, including IL-2, IFN-γ, and TNF-α. The trivalent Cr 3+ ions, which are the major degradation product of these nanocomposites, can increase the CXCL13 and CCL3 chemokine expressions to generate tertiary lymphoid structures (TLSs) in the tumor tissues, facilitating the CAR-T cell infiltration.
研究领域:
肿瘤学
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免疫疗法
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纳米技术
·
生物医学工程
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癌症生物学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 14
·4890-4906
·
IF 6.6
Jianhao Liu,Xiaoman Xu,Yanying Li,Jingxia Xu,Ruogang Zhao,Siwei Liu,Jingliang Wu,Li Zhang,Bo Zhang
Comprehensively regulating the TME is now regarded as a promising approach for cancer treatment. Herein, a novel “three-in-one” effect is presented for simultaneously killing tumor cells, inhibiting the EMT of CAFs, and improving immune responses. In this study, bortezomib (BTZ) is selected for the treatment of breast cancer; it has multiple pharmacological mechanisms for killing tumor cells through the NF-κB signaling pathway, inhibiting the activity of CAFs by activating caspase-3, and enhancing the function of CD8+ T cells by regulating the expression of immune-stimulating factors. To improve the druggability of BTZ in solid tumors, BTZ-loaded lipid/glycocholic acid mixed micelles (BTZ-LGs) were prepared to verify the “three-in-one” effect in killing tumor cells, inhibiting CAFs, and improving immune responses. In the present work, BTZ-LGs were verified to show enhanced in vitro cytotoxicity in both 4T1 cells and 4T1/NIH3T3 co-cultured cells, as well as a superior in vivo treatment effect in different tumor-bearing mouse models. Additionally, BTZ-LGs could regulate the expression of α-SMA, caspase-3, E-cadherin, and N-cadherin, indicating their good inhibiting ability on both tumor cells and CAFs. More importantly, immunological analysis revealed that BTZ-LGs promoted the expression of the immunostimulatory factor IL-2 in tumor tissues, activated anti-tumor T cells, and overcame tumor-induced CD8+ T cell dysfunction. All these findings suggest that BTZ-LGs can achieve a “three-in-one” effect in terms of killing tumor cells, suppressing CAFs, and improving immune responses. This simple and multi-effective therapeutic strategy offers a promising approach for cancer therapy.
研究领域:
癌症治疗
·
药学
·
免疫学
·
细胞生物学
·
分子生物学
✓ 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）