JOURNAL OF POLYMER RESEARCH
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2017
·Vol. 24
·期 4
·1-7
·
IF 1.615
Li Hu,Zhou Zhen,Liu Jingcheng,Zheng Xiangfei,Xu Wenjia,Ji Changwei,Shi Weidong,Liu Ren,Liu Xiaoya
Hexakis(4-formylphenoxy) cyclotriphosphazene (HAPCP), substitution reaction product of hexachlorotriphosphazene (HCTP) with p-hydroxybenzaldehyde, was reduced by sodium borohydride to afford hexakis[4-(hydroxymethyl) phenoxyl] cyclotriphosphazene (HHPCP). The hydroxyl group of this compound was then protected by the reaction with di-tert-butyl dicarbonate ester (DBDC) in the presence of 4-dimethylaminopyridine (DMAP) as catalyst to give t-butyloxy carbonyl (tBOC) protected HHPCP. Fourier-transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance ( 1 H NMR) were employed to characterize the chemical structure, indicating that the synthesis was successful. Thermal behavior was characterized by thermogravimetric analysis (TGA), the results showed that the initial thermal decomposition temperature occurred at approximately 170 °C, X-ray diffraction analysis (XRD) results showed that the tBOC protected HHPCP derivatives had amorphous form, and performed excellent film-forming property. Upon irradiation to 365 nm exposure, the photoacid generated proton H + , which can catalyze the deprotection of acid labile tBOC group. This type of novel molecular glass photoresist based on hexachlorotriphosphazene showed high sensitivity, making it possible to fabricate 1 μm line and space pattern under i-line exposure.
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JOURNAL OF MOLECULAR LIQUIDS
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2014
·
IF 2.083
Zhenyu Bao,Weijiang Zhang,Yinglai Chen,Jiao Xu,Xianbao Cui
The densities and viscosities of BF 3 ·anisole and BF 3 ·phenetole complex were determined at T = (283.15 to 303.15)K under atmospheric pressure. The molar ratios of the complexes ranged from 0.0080 to 0.9588 for BF 3 ·anisole and 0.0090 to 0.9850 for BF 3 ·phenetole. The measured densities and viscosities of both complexes were well correlated by modified Guimarães' equation and extended Jones–Dole equation, respectively. The apparent molar volumes were calculated using densities, and the limiting partial molar volumes were obtained by regression analysis. Arrhenius-type equation was adopted to get viscous flow activation energy through data fitting of viscosity values.
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FOOD AND CHEMICAL TOXICOLOGY
·
2015
·
IF 2.895
Lingchen Yang,Zezhong Yu,Jiafa Hou,Yifeng Deng,Zhenlei Zhou,Zhiyong Zhao,Jun Cui
T-2 and HT-2 toxins belong to mycotoxins which are found in human foods and animal chow. We investigated the toxicity and oxidative stress induced by T-2/HT-2 in broilers and chicken hepatocytes. Maize cultures of Fusarium poae was fed to broilers for 42 d, and the physiological index, biochemical index and expression of mRNAs related to oxidative stress were analyzed. Chicken hepatocytes were treated with different levels of T-2/HT-2, and the following parameters were detected: cell viability, GSH and MDA concentration, LDH leakage , activities of ALT/AST, ROS , GSH-PX, SOD and CAT , and expression of mRNA related to oxidative stress. In vivo, high levels of mycotoxins (4 mg/kg T-2 and 0.667 mg/kg HT-2) in feed caused significant reductions in body weight, weight gain, and serum total protein, and significant increases in feed conversion ratio, ALP , ALT/AST activities, and expression of mRNA related to oxidative stress. In vitro, cells treated with T-2/HT-2 showed reductions of GSH concentration and significant increases in LDH leakage, ALT/AST ROS, GSH-PX, SOD and CAT activities, MDA concentration, and expression of mRNA related to oxidative stress. Consequently, F. poae culture material and T-2/HT-2 induced toxicity and oxidative stress in vivo and in vitro, respectively.
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Food & Function
·
2024
·
IF 5.1
Xing Zhang,xiao chen,Fan Yang,Huming Shao,Tianliang Bai,Xuanyi Meng,Yong Wu,Anshu Yang,Hongbing Chen,Xin Li
The exposure of food allergens elicits fast changes in the intestinal microenvironment, which guides the development of allergic reactions. Investigating the key information of these changes may help in better understanding food allergy. In this research, we explored the relationship between food allergy and extracellular adenosine triphosphate (ATP), a danger molecule that has been proven to regulate the onset of allergic asthma and dermatitis but has not been studied in food allergy, by building a unique animal model based on allergen-containing diet feeding. After 7-day consumption of an allergen-containing diet, the allergic mice showed severe enteritis with raised luminal ATP levels. The luminal dysregulated ATP deteriorated food-induced enteritis by boosting Th17 cell responses and promoting mucosal neutrophil accumulation. In vitro experiments indicated that the intervention of ATP promoted the differentiation of Th17 cells and the activation of neutrophils. In addition, the diet-induced allergy showed noticeable gut dysbiosis, characterized by decreased microbial diversity and increased diet-specific microbiota signatures. As the first, we show that the food-induced enteritis is associated with an elevated concentration of luminal ATP. The dysregulated extracellular ATP exacerbated the enteritis of mice to food challenge by manipulating intestinal Th17 cells and neutrophils.
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Food Frontiers
·
2024
·
IF 7.4
Ying Yang,Mengfan Luo,Wanyi Zhou,Wenyang Tao,Jingrui Li,Jianrong Xing,Quanqin Tan,Yuxing Guo
In recent years, the development of immunosuppression has become common, and probiotics are a vital immunomodulatory strategy. This study evaluated the alleviating effect of Lactiplantibacillus plantarum ( L. plantarum ) YY-112 on cyclophosphamide-induced immune imbalance and resolved the possible mechanism of action. L. plantarum YY-112 at 10 9 CFU/mL lowered loss of body weight and alleviated splenic injury, intestinal injury, and inflammation, according to the hematoxylin and eosin staining. Biochemical results showed that 10 9 CFU/mL L. plantarum YY-112 increased interleukin-10 and immunoglobulin M levels and decreased interferon-γ levels. Additionally, the immunoregulatory effect at the molecular levels of L. plantarum YY-112 was analyzed by transcriptome sequencing. L. plantarum YY-112 significantly upregulated Cr2 and downregulated C5aR1 to regulate the complement system; downregulated S100a8 , S100a9 , and Mmp9 to inhibit neutrophil aggregation; upregulated Cd19 , Cd72 , Cd3e , Cd28 , Cd80 , Cd8a , and histocompatibility-2-related genes to regulate B- and T-cell activation; and upregulated Xiap , Malt1 , Ikbkb , Mapk11 , Mef2c , Mapk12 , Ras , and Myc to activate immune signaling pathways. Furthermore, L. plantarum YY-112 improved intestinal microbial structure and reduced enrichment of Lachnospiraceae_NK4A136_group , norank_f_Lachnospiraceae , Desulfovibrio , Colidextribacter , and Helicobacter . In conclusion, these findings offer valuable insights into the potential mechanisms through which L. plantarum YY-112 regulates immune imbalance.
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CytoJournal
·
2024
·
IF 2.5
Yan Li,Zhenwei Jia,Xiaoyang Kong,Hongbo Zhao,Xiaoyan Liu,Guirong Cui,Jianmin Luo
Objective:
We currently face a sharp increase of T-cell acute lymphoblastic leukemia (T-ALL) incidence and a challenge of unmasking its complex etiology. The deoxycytidine analog 5-Aza-2’-deoxycytidine (5-Aza-dC) is currently the most common nucleoside methyltransferase inhibitor. The objective of this study was to clarify the role of 5-Aza-dC in T-ALL cell biological behaviors and phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression.
Material and Methods:
T-ALL cell lines were divided into the experimental group with 5-Aza-dC solution treatment, and the control group without treatment. PTEN methylation was detected using methylation-specific polymerase chain reaction (MS-PCR). Following the measurement of cell proliferation, viability, apoptosis, invasion, migration, etc., quantitative reverse transcription-polymerase chain reaction (PCR) was conducted to detect PTEN, DNA methyl-transferases (DNMT1), DNMT3a, MBD2, and MeCP2 expressions; Western blot to detect PTEN, PI3K, AKT, and mTOR protein expressions. In addition, rescue experiments to inhibit and restore the expression of PTEN in different groups were performed for further identification of the results in the former parts.
Results:
MS-PCR results showed that in Jurkat cells, the target band was amplified using methylated primers for the PTEN gene promoter region; moreover, at 10 μmol/L of 5-Aza-dC for 24 h, PTEN methylation was completely removed without any un-methylated band observed. The experimental group had significantly lower cell proliferation and viability rates, higher apoptosis rates, decreased cell proportion in S phase, reduced invasion and migration; increased PTEN expression, decreased DNMT1, DNMT3a, MBD2, and MeCP2 mRNA expressions; and decreased PI3K, AKT, and mTOR protein expressions than those in the control group (all P < 0.05). Furthermore, according to the rescue experiment, silenced PTEN expression weakened the beneficial roles of 5-Aza-dC treatment, and resulted in significantly higher cell proliferation and viability rates, lower apoptosis rates, increased cell proportion in S phase, increased cell invasion and migration; decreased PTEN expression, elevated DNMT1, DNMT3a, MBD2, and MeCP2 mRNA expressions, and higher PI3K, AKT, and mTOR protein expressions (all P < 0.05). While restored PTEN expression enhanced functions of 5-Aza-dC treatment, leading to obviously lower cell proliferation and viability rates, higher apoptosis rates, increased cell proportion in G1 phase, and reduced cell invasion and migration; as well as increased PTEN expression, decreased DNMT1, DNMT3a, MBD2, and MeCP2 mRNA expressions, and lower PI3K, AKT, and mTOR protein expressions (all P < 0.05).
Conclusion:
Demethylation treatment with 5-Aza-dC can inhibit T-ALL cell malignant biological behaviors and enhance the sensitivity to chemotherapy agents possibly, which may be related to the inhibited expressions of DNMT1, DNMT3a, MBD2, and MeCP2, and restored expression activity of PTEN to negatively regulate the PI3K/AKT signal transduction. Our silencing and restoration of PTEN expressions further support our findings, highlighting that demethylation with 5-Aza-dC to restore the anti-tumor activity of the tumor suppressor gene PTEN may be a promising therapeutic option for treating T-ALL.
Keywords: 5-Aza-2’-deoxycytidine, T-cell acute lymphoblastic leukemia, PTEN, Tumor cell biological behaviors, Demethylation
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Asian Journal of Pharmaceutical Sciences
·
2024
·
IF 10.7
Ting Yang,Zihan Liu,Zixuan Fu,Xiaojie Zhang,Yongjin Cao,Qiangwei Liang,Jiale Miao,Hao Yang,Tong Zhang,Jing Hei,Weiqing Ni,Yanhua Liu
Ferroptosis can serve as a potent strategy for regulating cell death via lipid peroxidation and the imbalance of the antioxidant system resulting from iron accumulation in triple-negative breast cancer (TNBC) therapy. However, the ferroptosis accompanied with down-regulation of glutathione peroxidase 4 (GPX4) lead to CD36-mediated tumor-infiltrating CD8 + T cells uptaking fatty acids, resulting in the negative action on immunotherapeutic efficacy. Herein, the albumin nanoparticles, abbreviated as LHS NPs, were designed by co-assembly of hemin, linoleic acid-cystamine, and a CD36 inhibitor sulfosuccinimide oleate, to bi-directionally manipulated ferroptosis in tumor and CD8 + T cells for TNBC therapy. LHS NPs exerted more efficient reactive oxygen species generation, glutathione depletion and malondialdehyde production by the combinatory strategy of classical and non-classical ferroptosis modes, which amplified the positive action on ferroptosis in tumor cells. Meanwhile, LHS manipulated the negative action of ferroptosis by inhibiting the CD36 mediated-lipid peroxidation in CD8 + T cells, thereby activating the immunotherapeutic efficacy with the improvements on induction of immunogenic cell death, proliferation of CD4 + CD8 + T cells and natural killer cells, alleviation immunosuppressive regulatory T cells and myeloid-derived suppressor cells, and repolarization of the M2- to M1-phenotype tumor-associated macrophages. Thus, LHS NPs demonstrated an improved antitumor efficacy in suppressing the tumor growth and lung metastasis of 4T1-tumor mice. Our work gives novel insights for the bi-directionally manipulating ferroptosis in tumor and CD8 + T cells on TNBC chemoimmunotherapy.
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Theranostics
·
2025
·Vol. 15
·期 9
·3797
·
IF 13.3
Ying Luo,Yi Wang,Bo Liu,Yun Liu,Wenli Zhang,Sijin Chen,Xiyue Rong,Lian Xu,Qianying Du,Jia Liu,Jie Xu,Haitao Ran,Zhigang Wang,Dajing Guo
Background: Most anticancer agents induce tumor apoptosis, but they often lack immunogenicity and display limited success when combined with mainstream immunotherapies, thus killing cancer cells through multiple cell death modalities as well as switching immune-off tumors to immune-on is a strategy with great promise. To this end, we developed a CPApoptosis (cuproptosis, pyroptosis, apoptosis) nano-actuator for immunologically cold solid tumors. Methods: In this study, elesclomol (ES), a mitochondrial targeting copper transporter, was encapsulated within bacterial outer membrane vesicles (OMVs). These OMVs were then surface-modified via metal-phenolic self-assembly using Cu 2+ and tannic acid (TA). Results: The Cu 2+ and ES were released from the OMVs in a pH-dependent manner. OMV activated the non-canonical pyroptotic pathway, leading to cell membrane rupture. Cu 2+ on the one hand was transported to the mitochondria for cuproptosis facilitated by ES, on the other hand, Cu 2+ was reduced into Cu + by TA, which catalyzed ROS production to induce oxidative apoptosis. Simultaneously, TA degraded glutathione (GSH), sensitizing cells to cuproptosis. The multifactorial cell death mechanisms led to the release of immunogenic factors from lysed tumor cells, stimulating dendritic cell maturation and recruiting cytotoxic T cells. This immune response was further amplified by αPD-L1 antibody treatment. Conclusion: The CPApoptosis nano-actuator represents a promising approach to enhance current cancer therapies, inducing both tumor cell death and a robust immune response, with the potential for long-lasting protective effects.
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Cell Death & Disease
·
2025
·Vol. 16
·期 1
·1-14
·
IF 9.6
Liu Min,Li Yuanyuan,Deng Zhilin,Zhang Ke,Huang Shuying,Xia Jiamin,Feng Yi,Liang Yundan,Sun Chengfu,Liu Xindong,Li Shurong,Su Bingyin,dong Yong,Huang Sizhou
Mutation in genes involved in DNA replication continuously disrupt DNA replication and give rise to genomic instability, a critical driver of oncogenesis. To prevent leukemia, immature T lymphocytes with genomic instability often undergo rapid cell death during development. However, the mechanism by which immature T lymphocytes undergo rapid cell death upon genomic instability has been enigmatic. Here we show that zebrafish mcm5 mutation leads to DNA damage in immature T lymphocytes and the immature T cells sensitively undergo rapid cell death. Detailed analyses demonstrated that the immature T lymphocytes undergo rapid apoptosis via upregulation of tp53 and downregulation of bcl2 transcription in mcm5 mutants. Mechanistically, Mcm5 directly binds to Stat1a and facilitates its phosphorylation to enhance bcl2a expression under the conditions of DNA replication stress. However, in mcm5 mutants, the absence of the Mcm5-Stat1 complex decreases Stat1 phosphorylation and subsequent bcl2a transcription, accelerating apoptosis of immature T lymphocytes with genomic instability. Furthermore, our study shows that the role of Mcm5 in T-cell development is conserved in mice. In conclusion, our work identifies a role of Mcm5 in regulating T cell development via Stat1-Bcl2 cascade besides its role in DNA replication, providing a kind of mechanism by which immature T cells with gene mutation-induced DNA damage are rapidly cleared during T lymphocyte development.
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Nanoscale
·
2024
·
IF 5.8
Pan Li,Zihe Zhai,Jiawen Fang,Ruo Wang,Weiqi Li,Beiduo Wang,Jinglei Wang,Jiaqi Zhu,Feng Bing,Qiaoling Pan,ChangYou Gao,ShaoHong Lu
Together, tumor and virus-specific tissue-resident CD8+ memory T cells (TRMs) of hepatocellular carcinoma (HCC) patients with Hepatitis B virus (HBV) infection can provide rapid frontline immune surveillance. The quantity and activity of CD8+ TRMs were correlated with the relapse-free survival of patients with improved health. However, HBV-specific CD8+ TRMs have a more exhausted phenotype and respond more actively under anti-PDL1 or PD1 treatment of HBV+HCC patients. Vaccination strategies that induce a strong and sustained CD8+ TRMs response are quite promising. Herein, a biodegradable poly(D,L-lactide-co-glycolide) microsphere and nanosphere particle (PLGA N.M.P) delivery system co-assembled by anti-PD1 antibodies (aPD1) and loaded with ovalbumin (OVA-aPD1 N.M.P) was fabricated and characterized for size (200 nm and 1 μm diameter), charge (−15 mV), and loading efficiencies of OVA (238 μg mg−1 particles) and aPD1 (40 μg mg−1 particles). OVA-aPD1 N.M.P could stimulate the maturation of BMDCs and enhance the antigen uptake and presentation by 2-fold compared to free OVA. The nanoparticles also induced the activation of macrophages (RAW 264.7) to produce a high level of cytokines, including TNF-α, IL-6 and IL-10. In vivo stimulation of mice using OVA-aPD1 N.M.P robustly enhanced IFN-γ-producing-CD8+ T cell infiltration in tumor tissues and the secretion of IgG and IgG2a/IgG1 antibodies. OVA-aPD1 N.M.P delivered OVA to increase the activation and proliferation of OVA-specific CD8+ TRMs, and its combination with anti-PD1 antibodies promoted complete tumor rejection by the reversal of tumor-infiltrating CD8+ T cell exhaustion. Thus, PLGA N.M.P could induce a strong CD8+ TRMs response, further highlighting its therapeutic potential in enhancing an antitumor immune response.
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Chinese Medicine
·
2024
·Vol. 19
·期 1
·1-18
·
IF 5.3
Zhen Jianhua,Li Yini,Zhang Yunan,Zhou Yali,Zhao Lu,Huang Guangrui,Xu Anlong
Background Shaoyao Decoction (SYD) is a widely recognized herbal formula utilized in traditional Chinese medicine for the treatment of diarrhea. Although it has demonstrated significant effectiveness in clinical practice for treating ulcerative colitis, the precise mechanisms by which it operates remain largely elusive. Methods The active ingredients of SYD were obtained by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS), which were used to explore the potential pharmacological mechanism based on TCMSP (Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform) and PANTHER (Protein Analysis Through Evolutionary Relationships) classification system. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, mRNA sequencing, 16S rDNA sequencing and targeted metabolomics techniques were used to elucidate the mechanisms of SYD, and immunohistochemistry, immunofluorescence, enzyme linked immunosorbent assay, real time quantitative polymerase chain reaction and western blot were used to test the key targets. In addition, QGP-1 and H9 cells were performed to validate the discoveries from the animal experiments. Results In the mouse model of DSS-induced colitis, SYD effectively alleviated symptoms such as bloody stool, tissue damage, inflammation, intestinal flora dysbiosis and abnormal gene expression. Analyses of both differential expressed genes in colonic tissue and predicted 16S rDNA genes, as well as the analyses of targeted genes from TCMSP based on the active ingredients in UPLC-MS/MS of SYD, uncovered the enrichment of pathways involved in the biosynthesis and degredation of 5-hydroxytryptamine (5-HT). Interestingly, SYD suppressed the relative abundance of key genes in 5-HT synthesis, Tph1(Tryptophan hydroxylase 1) and Ddc (Dopa decarboxylase), in faeces from DSS-induced mice, leading to a reduction in the concentration of fecal 5-HT. Moreover, SYD augmented the production of butyric acid. Subsequently, increasing butyric acid influenced the metabolism of 5-HT in the organism through G protein-coupled receptor 43 by impeding its synthesis, facilitating its transport and degredation. These findings were additionally corroborated in a model utilizing enterochromaffin cell (QGP-1 cells). Furthermore, reduced levels of 5-HT hindered the activation of T lymphocytes (H9 cells) via the PKC (Protein kinase C) and NF-κB (Nuclear factor kappa-B) signaling pathways, by means of HTR1A (5-HT receptor 1A) and HTR3 (5-HT receptor 3). Additionally, diminished secretion of 5-HT resulted in reduced secretion of associated cytokines, thereby alleviating inflammation in the colon. Conclusion Through modulation of T lymphocyte activation mediated by 5-HT metabolism in the local colon via the intestinal flora and its metabolite, SYD effectively mitigated colonic inflammation in DSS-induced mice.
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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.
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