1.An Fe-Cu bimetallic organic framework as a microwave sensitizer for treating tumors using combined microwave thermotherapy and chemodynamic therapy
Zhu XINYANG ; He CHAO ; Tan LONGFEI ; Qi XUN ; Niu MENG ; Meng XIANWEI ; Zhong HONGSHAN
Journal of Pharmaceutical Analysis 2024;14(7):1063-1075
Microwave thermotherapy(MWTT),as a treatment for tumors,lacks specificity and requires sensitizers.Most reported microwave sensitizers are single metal-organic frameworks(MOFs),which must be loaded with ionic liquids to enhance the performance in MWTT.Meanwhile,MWTT is rarely combined with other treatment modalities.Here,we synthesized a novel Fe-Cu bimetallic organic framework FeCuMOF(FCM)by applying a hydrothermal method and further modified it with methyl polyethylene glycol(mPEG).The obtained FCM@PEG(FCMP)showed remarkable heating performance under low-power microwave irradiation;it also acted as a novel nanospheres enzyme to catalyze H2O2 decompo-sition,producing abundant reactive oxygen species(ROS)to deplete glutathione(GSH)and prevent ROS clearance from tumor cells during chemodynamic treatment.The FCMP was biodegradable and demonstrated excellent biocompatibility,allowing it to be readily metabolized without causing toxic effects.Finally,it was shown to act as a suitable agent for T2 magnetic resonance imaging(MRI)in vitro and in vivo.This new bimetallic nanostructure could successfully realize two tumor treatment modalities(MWTTand chemodynamic therapy)and dual imaging modes(T2 MRI and microwave thermal imaging).Our findings represent a breakthrough for integrating the diagnosis and treatment of tumors and pro-vides a reference for developing new microwave sensitizers.
2.IL-33 up-regulates eIF3a expression by activating NF-κB signaling pathway to mediate the proliferation and differentiation of mouse pulmonary myofibroblasts and aggravate pulmonary fibrosis.
Yunxing GAO ; Yu FU ; Xiao CHEN ; Zepeng LI ; Xiaowei HE ; Xianwei LI
Chinese Journal of Cellular and Molecular Immunology 2023;39(8):693-700
Objective To investigate the effects and mechanism of Interleukin-33 (IL-33) mediated proliferation and differentiation of pulmonary myofibroblasts (MFbs) in pulmonary fibrosis (PF). Methods C57BL/6 mice were randomly divided into four groups: a control group, a bleomycin (BLM) group, a BLM combined with IL-33 group and a BLM combined with anti-IL-33 antibody group, 12 mice in each group. The PF model was induced by intratracheal injection of BLM (5000 U/kg). The degrees of fibrosis were examined using HE and Masson staining. ELISA was used to measure the plasma levels of IL-33. Immunohistochemical staining was used to measure the expression of alpha smooth muscle actin (α-SMA) in lung tissue. Primary pulmonary fibroblasts were isolated and cultured from lung tissues of mice. The cells were divided into four groups: a control group, an IL-33 group, an IL-33 combined with dimethyl sulfoxide (DMSO) group and an IL-33 combined with pyrrolidine dithiocarbamate (PDTC) group. The cells were treated with DMSO or PDTC for 1 hour and then with IL-33 for 48 hours. Cell proliferation was measured by 5-ethynyl-2'-deoxyuridine (EdU) assay and cell cycle was measured by flow cytometry. TranswellTM assay was used to analyze cell migration. Real-time quantitative PCR was used to measure the expression of collagen type I (Col1), Col3 and α-SMA mRNA. The protein levels of IL-33, Col1, Col3, α-SMA, eukaryotic initiation factor 3a (eIF3a), phosphorylated IκBα (p-IκBα) (total lysate), p-NF-κB p65(total lysate) and NF-κB p65 (nucleus) were measured by Western blot analysis. Results In vivo, compared with the control group, the expressions of IL-33, p-IκBα (total lysate), p-NF-κB p65 (total lysate), NF-κB p65(nucleus), eIF3a, α-SMA, Col1 and Col3 in the BLM group significantly increased. Compared with the BLM group, the expressions of p-IκBα (total lysate), p-NF-κB p65 (total lysate), NF-κB p65 (nucleus), eIF3a, α-SMA, Col1 and Col3 in the IL-33 group increased further and the PF was further aggravated. But the effect of anti-IL-33 antibody was just opposite to that of IL-33. In vitro, IL-33 markedly induced the proliferation and migration of pulmonary fibroblasts, and significantly up-regulated the expression of p-IκBα (total lysate), p-NF-κB p65(total lysate), NF-κB p65 (nucleus), eIF3a, α-SMA, Col1 and Col3. But all these effects of IL-33 were reversed by pyrrolidine dithiocarbamate. Conclusion The results suggest that IL-33 may promote the expression of eIF3a by activating NF-κB signaling pathway, thus inducing the proliferation and differentiation of MFbs and promoting the occurrence and development of PF.
Animals
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Mice
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Bleomycin/metabolism*
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Cell Differentiation
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Cell Proliferation
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Dimethyl Sulfoxide/pharmacology*
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Fibroblasts
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Interleukin-33/pharmacology*
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Mice, Inbred C57BL
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Myofibroblasts/metabolism*
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NF-kappa B/metabolism*
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NF-KappaB Inhibitor alpha/metabolism*
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Pulmonary Fibrosis
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Signal Transduction
3.Factors Associated with Macular Staphyloma Area on Ultra-widefield Fundus Images
Xinmei ZHANG ; Emmanuel Eric PAZO ; Aoqi ZHANG ; Lanting YANG ; Guangzheng DAI ; Xianwei WU ; Yang XIA ; Amit MESHI ; Wei HE ; Tiezhu LIN
Korean Journal of Ophthalmology 2022;36(3):210-217
Purpose:
To assess the feasibility of applying ultra-widefield fundus (UWF) images for macular staphyloma area (MSA) measurement and investigate the associated factors with MSA.
Methods:
This is a retrospective study. MSA was measured by UWF imaging. Central foveal thickness, subfoveal choroidal thickness, subfoveal scleral thickness were measured on spectral domain optical coherence tomography. Intraclass correlation coefficients of MSA measurement would be evaluated. Multiple linear regression analysis was used to analyze the associated factors with MSA.
Results:
In total, 135 eyes of 92 patients were enrolled. The mean age was 64.73 ± 10.84 years. Mean MSA on UWF image was 279.67 ± 71.70 mm2. Intraclass correlation coefficients of MSA measurement was 0.965 (95% confidence interval [CI], 0.946 to 0.977; p < 0.001). In the multiple linear regression analysis, after adjusting for subfoveal choroidal thickness, best-corrected visual acuity, central foveal thickness, and subfoveal scleral thickness, the factors independently related to MSA were axial length (β = 8.352; 95% CI, 3.306 to 13.398; p = 0.001), sex (β = -26.673; 95% CI, -51.759 to -1.586; p = 0.037), age (β = 1.184; 95% CI, 0.020 to 2.348; p = 0.046).
Conclusions
It is feasible to measure MSA on UWF image. Female, longer axial length, and older age may indicate larger MSA.
4.Value of contrast-enhanced ultrasound combined with serum CXCL8 and CXCR2 in the evaluation of postoperative efficacy of transcatheter arterial chemoembolization for primary liver cancer
Yumin ZHANG ; Xianwei ZHAO ; Qianjin HE ; Jieneng CHEN
Journal of International Oncology 2022;49(10):592-596
Objective:To investigate the application value of contrast-enhanced ultrasound combined with serum CXC chemokine ligand 8 (CXCL8) and CXC chemokine receptor 2 (CXCR2) levels detection in the efficacy evaluation of patients with primary liver cancer after transcatheter arterial chemoembolization (TACE) .Methods:A total of 80 patients with primary liver cancer who were diagnosed and treated in Huanggang Central Hospital of Hubei Province from June 2019 to January 2022 were selected as the research objects. The therapeutic efficacy was evaluated 2 months after TACE treatment. According to the pathological diagnosis, the patients were divided into complete inactivation group ( n=30) and residual lesion group ( n=50) . The levels of serum CXCL8 and CXCR2 were measured by enzyme linked immunosorbent assay (ELISA) double antibody sandwich method, and contrast-enhanced ultrasonography was performed on the patients. Receiver operating characteristic (ROC) curve was applied to analyze the value of serum CXCL8 and CXCR2 in evaluating the efficacy of TACE in patients with primary liver cancer. Kappa test was applied to test the consistency of contrast-enhanced ultrasound and contrast-enhanced ultrasound combined with serum CXCL8 and CXCR2 in evaluating the efficacy of TACE in patients with primary liver cancer and the results of pathological diagnosis. Results:Compared with the complete inactivation group, the levels of serum CXCL8 [ (7.12±1.68) ng/ml vs. (5.07±1.25) ng/ml] and CXCR2 [ (3.62±0.79) ng/ml vs. (2.43±0.67) ng/ml] in the residual lesion group were obviously higher ( t=5.79, P<0.001; t=6.89, P<0.001) . The areas under the curve of CXCL8 and CXCR2 in evaluating the efficacy of TACE in patients with primary liver cancer were 0.827 and 0.801 respectively, the specificities were 73.3% and 76.7%, and the sensitivities were 70.0% and 72.0% respectively. The concordance between contrast-enhanced ultrasound and pathological diagnosis was moderate, and the Kappa value was 0.49 ( P<0.001) . The concordance between contrast-enhanced ultrasound combined with serum CXCL8 and CXCR2 and pathological diagnosis was high, and the Kappa value was 0.62 ( P<0.001) . The sensitivity of contrast-enhanced ultrasound combined with serum CXCL8 and CXCR2 in evaluating the efficacy of TACE in patients with primary liver cancer was 90.0%, which was higher than the sensitivity of contrast-enhanced ultrasound (72.0%, χ2=5.26, P=0.022) , CXCL8 (70.0%, χ2=6.25, P=0.012) and CXCR2 (72.0%, χ2=5.26, P=0.022) . Conclusion:Contrast-enhanced ultrasound can detect residual lesions after TACE in patients with primary liver cancer to a certain extent, and its combination with serum CXCL8 and CXCR2 can effectively improve the evaluation efficiency of the efficacy of TACE treatment in patients with primary liver cancer.
5.Microorganisms in the typical anaerobic digestion system of organic solid wastes: a review.
Xingsheng YANG ; Shang WANG ; Qing HE ; Zhujun WANG ; Zhaojing ZHANG ; Chengying JIANG ; Liping MA ; Xianwei LIU ; Baolan HU ; Yongmei LI ; Ye DENG
Chinese Journal of Biotechnology 2021;37(10):3425-3438
The facultative anaerobic and strict anaerobic microorganisms enriched and acclimated during the anaerobic digestion process are crucial for the efficiency of the anaerobic digestion system. Most of the problems encountered during running anaerobic digestion processes could be effectively improved via stimulation of microbial metabolic activity. Benefited from the rapid development of microbiome techniques, deeper insights into the microbial diversity in anaerobic digestion systems, e.g. the microbe-microbe interactions and microbe-environment interactions, have been gained. A complex and intricate metabolic network exists in the anaerobic digestion system of solid organic wastes. However, little is known about these interactions and the underlying mechanisms. This review briefly summarized the representative interactions between microbial communities during anaerobic digestion process discovered to date. In addition, typical issues encountered during the anaerobic digestion of solid organic wastes and how microbes can tackle and alleviate these issues were discussed. Finally, future priorities on microbiome research were proposed based on present contribution of microbiome analysis in anaerobic digestion system.
Anaerobiosis
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Bioreactors
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Methane
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Microbial Interactions
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Microbiota
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Solid Waste
6.Comparison of structural characteristics and anticoagulation activity of enoxaparin sodium with different degree of 1,6-anhydro derivatives.
He ZHU ; Youjing LIü ; Xianwei HAN ; Shilong LIU ; Jiejie HAO ; Xiaoliang ZHAO ; Guangli YU
Acta Pharmaceutica Sinica 2014;49(7):1049-53
The fine structure of enoxaparin sodium samples with different degree of 1,6-anhydro derivatives were analyzed with polyacrylamide gel electrophoresis, high performance liquid chromatography, ultraviolet spectroscopy, infrared spectroscopy and nuclear magnetic resonance spectroscopy. A further study of anticoagulation activity of enoxaparins was performed, including those on their inhibition activities of coagulation factor Xa (FXa) and thrombin (FIIa). The results showed that the anti-FXa and -FIIa activities of enoxaparins with different degree of 1,6-anhydro derivatives (20.0%-39.7%) with similar structure characteristics, had decreasing tendency when the degree of 1,6-anhydro derivatives increased. Especially, the anti-FXa activity was sensitive to the change of the degree of 1,6-anhydro derivatives.
7.Th17 Cells and IL-17 are Increased in Patients with Brain Metastases from the Primary Lung Cancer
HE GAIPING ; ZHANG BIN ; ZHANG BAOWEN ; QIAO LIANGJIE ; TIAN ZHONGLAN ; ZHAI GUOYAN ; XIN XIANWEI ; YANG CHUN ; LIU PEIGANG ; ZHANG YONG ; XU LINGLING
Chinese Journal of Lung Cancer 2013;(9):476-481
Background and objective Th17 cells are important T helper cells, which are characterized by their production of IL-17. hT17 cells play an important role in host defense against microbial infections, autoimmune diseases and cancer. hTe aim of this study is to investigate the percentage of hT17 in peripheral blood lymphocyte and the level of IL-17 in serum and cerebrospinal lfuid (CSF) in patients with brain metastases from lung cancer. Methods Twenty-two patients with brain metastases from lung cancer and 20 health controls were analyzed. hTe percentage of hT17 cell was detected with lfow cytometry using CD3+CD4+IL-23R+marker, the level of IL-17 was measured with ELISA method. Results hTe percentage of hT17 cells in patients with brain metastases from lung cancer was 4.65%±0.72%, which was remarkably higher than that in con-trols (2.71%±0.54%, P=0.04). hTere was no signiifcant difference between non-small cell lung cancer (NSCLC) patients and small cell lung cancer (SCLC) patients. Serum IL-17 was remarkably increased in patients with brain metastases from lung can-cer (117.4±16.43 pg/mL vs 72.55±8.19 pg/mL, P=0.02). No signiifcant difference of the serum IL-17 was observed between NSCLC and SCLC patients. hTe level of IL-17 in CSF from patients with brain metastases from lung cancer was signiifcant higher than that from lung cancer patients without brain metastases (73.21±7.52 pg/mL vs 50.25±8.04 pg/mL, P=0.04). Con-clusion hT17 cells and IL-17 increase in patients with brain metastases from lung cancer. It may involve in the pathogenesis of brain metastases from lung cancer.
8.p27 gene methylation and clinicopathologic features of colorectal carcinoma
Jixian CHEN ; Jie ZHANG ; Zhenhua REN ; Dixin XUE ; Weili WU ; Renhu ZHANG ; Ming YU ; Daozhe LIN ; Xiao LIN ; Jianwu HUANG ; Meizhen LIANG ; Xianwei HE
Chinese Journal of General Surgery 2011;26(4):332-334
Objective To investigate the relationship between p27 gene methylation and pathology of colorectal carcinoma. Methods p27 gene methylation promotor region and p27 protein expression were detected respectively by methylation specificity polymerase chain reaction and immunohistochemical staining SP in 106 cases of colorectal carcinoma and each adjacent normal mucous membrane tissue and 22 cases of colorectal adenoma tissue. Results The positive expression rate of p27 gene methylation was statistically different in colorectal carcinoma tissue compared with normal mucous membrane and colorectal adenoma tissue (P<0.05). Their positive expression rate were 59.4% (63/106), 18.2% (4/22) and 3.8%(4/106) respectively in colorectal carcinoma tissue,colorectal adenoma and normal mucous membrane tissue (P < 0. 05). p27 gene methylation in poorly differentiated group was significantly higher than that in welldifferentiated group (48.0% vs. 24. 7%, P <0. 05), in Dukes-A + B stage group was significantly lower than that in Dukes C + D stage group(20. 0% vs. 41.2%, P < 0. 05 ), and it was higher in lymph nodes metastases group than that in lymph nodes negative group(41.5% vs. 23. 1%, P <0. 05), that in positive serosa infiltration group was higher than negative serosa infiltration group(32. 5% vs. 24. 1%, P > 0. 05 ).Conclusions Methylated p27 gene protein expression in colorectal carcinoma was significantly higher than normal mucous membrane and colorectal adenoma tissue. The methylation rate of p27 gene in colorectal carcinoma was significantly associated with tumor differentiation, invasive depth, Dukes stage, lymph node metastasis.
9.Changes of cardiac rhythms in a swine model of adult asphyxial cardiac arrest
Ying SHEN ; Tangwei LIU ; Menghua CHEN ; Jingyu LU ; Junhui ZHENG ; Jinlong HE ; Xianwei ZHANG
Chinese Journal of Emergency Medicine 2008;17(6):614-617
Objective To observe the changes of cardiac rhythms in a swine model of adult asphyxia! cardiac arrest. Method Sixteen Pigs were aphyxiated by endotracheal tube clamping until 8 min after loss of aortic pulsations. Resuscitation was then provided and swinds were assigned to received 0.045 mg/kg epinephrine intravenously after 3 min of basic life support. The animals with restoration of spontaneous circulation within 20 min from CPR were defined as successfully resuscitated, while the rest were identified as unresuscitation. Electrocardiogram ( EGG) were monitored from the start of asphyxia to the start of the CPR. Results When loss of pulsations occurred, 2 of 16 animals had ventricular fibrillation; 10 pigs exhibited pulseless electrical activity, and 4 pigs had asystole. During the 8 min after the loss of aortic pulsations, pulseless electrical activity converted to VF in 7 pigs. Immidiatedly prior to resuscitation, VF occurred in 9 pigs, asystole in 4 pigs, and PEA in 3 pigs. Conclusions Most of animals in this swine model of asphyxial cardiac arrest presented PEA, but most of them converted to VF especially late in the asphyxial process.
10.Recovery of IgG binding capability of human FcγRⅡa refolded by rapid dilution expressed in E. coli
Jun XI ; Caiping ZHANG ; Lina ZHANG ; Xianwei MIAO ; Songlin QIAO ; Hong ZHANG ; Liyang HE ; Leiming YOU ; Yanjun ZHENG
Chinese Journal of Microbiology and Immunology 2008;28(12):1059-1063
Objective To study the effect of soluble, refolded, recombinant extracellular domain of the human Fc gamma receptor Ⅱ a (huFcγRⅡa) on the binding of human IgG to cells. Methods Extra-cellular domain of the huFcγRⅡ a gene was amplified from recombinant plasmid pe3huR Ⅱ by PCR and then cloned into pET-28a vector. The recombinant plasmid pETshuR Ⅱ was transformed into E. coli BL21 (DE3) after identified by PCR and doubly digested. The inclusion bodies of fusion protein were extracted and purified by washing, dissolved in 6 mol/L guanidine buffer, and refolded by rapid dilution technique. The refolding protein activity was tested by ELISA and flow cytometry. Results Extraceilular domain of the huFcγRⅡa gene was successfully cloned into pET-28a. The results of SDS-PAGE showed that the molecular mass (Mr) of the expressed protein was 24.8 × 103, and the expression rate was 30%. The purity of recom-binant shuR Ⅱ was up to 90% after washing. ELISA showed that the recombinant shuR Ⅱ was able to bind human IgG in a dose dependent manner, shuRⅡ could competitively inhibit the binding of human IgG to huFcγRⅡa expressed on the surface of COS-7 cells by flow cytometry. Conclusion The results demon-strate that it is possible to obtain large quantities of recombinant shuR Ⅱ which has comparable binding prep-erties to those of the whole membrane bound huFcγR Ⅱ a.

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