ACS Biomaterials Science & Engineering
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2025
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IF 5.5
Yanjia Zhang,FangFei Xue,Yunzheng Du,Biao Wang,Mengya Chen,Lichun Wang,Nan Li,Yamin Chai,Zuoliang Dong,Lailiang Ou
At present, AIDS remains a significant global health issue that requires ongoing attention. Although there is no practical cure for AIDS, hemoadsorption can effectively remove the virus from the blood and may serve as a promising treatment strategy. In this research, cellulose acetate/metal–organic framework composite beads (CA/MIL-125) with interconnected macropores were first fabricated using a one-step phase inversion method and then applied as a viral hemoadsorbent for the treatment of AIDS. The results showed that CA/MIL-125 exhibited excellent specific surface areas (221.17 m2 g–1) and an interconnected macropore structure, which allows HIV molecules to be transported freely within the pores of the beads. The CA/MIL-125 composite beads reached a 97.37% adsorption rate of HIV in plasma, which was 90 times higher than that of pure cellulose acetate (CA) microspheres, demonstrating that MIL-125 played a dominant role in HIV adsorption. Furthermore, the adsorption of CA/MIL-125 on HIV primarily obeys the pseudo-second-order kinetics and Freundlich model, with a maximum adsorption capacity (Qm) of 642.2 ng g–1. Tests for hemolysis, coagulation time, and cytotoxicity confirmed that CA/MIL-125 had good blood compatibility and biocompatibility. This study presents an effective strategy for HIV adsorption through hemoperfusion, suggesting a promising new treatment approach for AIDS.
研究领域:
生物医学工程
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病毒学
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材料科学
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纳米技术
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血液学
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产品关联
DOI
PubMed
高影响因子
CELLULOSE
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2019
·Vol. 26
·期 13
·8087-8099
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IF 3.917
Zhang Su-Feng,Liu Li-Na,Tang Rui-Hua,Liu Zhi,He Xiao-Cong,Qu Zhi-Guo,Li Fei
Abstract Lateral flow assays (LFAs) have been extensively used as point-of-care testing platforms because they are inexpensive, portable, simple, and rapid, which particularly improve their availability in resource-poor settings. However, the poor sensitivity of LFAs restricts their further applications. Herein, we proposed a novel and simple method to enhance the detection sensitivity of LFAs by embedding cotton thread-based barriers into paper and further integrating them into strips to decrease the flow rate of sample and extend the reaction time. The number and hydrophilicity of the embedded cotton threads were sequentially optimized. The flow rate of liquid in cotton thread-embedded LFAs was mathematically simulated using a circuit-like model and the simulation results are consistent with the experimental results. With using human immunodeficiency virus nucleic acid as a model target, the cotton thread-embedded LFAs presented a fourfold enhancement in detection sensitivity compared to that of the unmodified LFAs. The strategy of embedding cotton threads into paper possesses great potential for fabricating other paper-based microfluidic devices in the future. Graphic abstract
研究领域:
医学诊断
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生物工程
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DOI
高影响因子
Microorganisms
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2023
·Vol. 11
·期 5
·1183
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IF 4.5
Sana Shabbir,Yanzhou Hu,Xiaoyun He,Kunlun Huang,Wentao Xu
Nanoparticles (NPs), having exceptional physicochemical and electrical characteristics with lower toxicity, have evolved as dynamic drug delivery carriers in living organisms. Potentially, the intragastric gavage of silica nanoparticles (SiNPs) affects gut microbiota profiles in immunodeficient mice. In this study, the impact of SiNPs of variable size and dosage was investigated in cyclophosphamide (Cy)-induced immunodeficient mice, specifically on their immune functions and gut microbiota, through physicochemical and metagenomic analysis. SiNPs of different sizes and doses were gavaged to Cy-induced immunodeficient mice for 12 days at an interval of 24 h to investigate their effects on immunological functions and the gut microbiome of mice. Our results showed that SiNPs had no significant toxicological effects on the cellular and hematological activities of immunodeficient mice. Furthermore, after the administration of different levels of SiNPs, no immune dysfunction was found in the immunosuppressed mice groups. However, gut-microbial studies and comparisons of characteristic bacterial diversity and compositions demonstrated that SiNPs significantly affect the abundance of different bacterial communities. LEfSe analysis revealed that SiNPs significantly increased the abundance ofLactobacillus,Sphingomonas,Sutterella,Akkermansia, andPrevotella, and potentially reducedRuminococcusandAllobaculum. Thus, SiNPs significantly regulate and modify the configuration of the gut microbiota in immunodeficient mice. These dynamic variations in the intestinal bacterial community, abundance, and diversity provide new insight into the regulation and administration of silica-based NPs. This would be helpful for the further demonstration of the mechanism of action and prediction of the potential effects of SiNPs.Keywords:Cy-immunodeficiency;silica nanoparticles;intragastric gavage;immune dysfunctioning;RNA sequencing;microbial diversity
研究领域:
纳米技术
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免疫学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
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2022
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IF 4.601
Jialing Huang,Yunqing Qi,Xiaowen Zeng,Wei Huang,Da Chen
Measurement of immunoglobulin subclasses is a useful tool for exploring humoral immune deficiency in the presence of total immunoglobulins within reference intervals. Conventional methods for immunoglobulin measurement are mostly immunoassays, which are of low throughput and laborious to run multiple immunoglobulin subclass tests. Liquid chromatography-mass spectrometry (LC-MS) has emerged as a promising technology for the measurement of protein biomarkers in biological matrices, owing to its high specificity, selectivity, multiplexing, and wide dynamic range. In fully taking these advantages, we developed here a LC-MS based methodology for simultaneous quantitation of the primary immunoglobulin isotypes (IgG, IgA, IgM) and their subclasses in human plasma. Method validation demonstrated that the proposed method showed good linearity with R > 0.99, high precision with coefficients of variation for inter- and intra-assay less than 15%, as well as high accuracy with relative errors less than 8.7%. The developed method was further applied to maternal and cord blood collected at delivery for assessment of maternal and fetal immune status. The immunoglobulin profiles and the features of transplacental transport of maternal immunoglobulin subclasses were comparable to the findings from previous reports, further demonstrating the reliability of this method. Therefore, our method provides a competitive approach to high-throughput detection of multiple immunoglobulin subclasses for biomonitoring or epidemiological studies.
研究领域:
免疫学
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临床化学
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妊娠研究
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蛋白质组学
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产品关联
DOI
PubMed
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2022
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IF 7.129
Tianxiu Qiu,Huan Wang,Lei Liu,Jiong Chen
Azoxystrobin (AZ) is one of the most widely used strobilurin fungicides in the world, and its residue has seriously endangered aquatic ecological security. Our previous data showed that AZ exposure may reduce the resistance of fish to rhabdovirus infection in aquatic environment. Here, we further reported a potential long-term adverse effect of AZ exposure on the antiviral and immunosuppressive recovery in fish, and observed that mitochondrial dynamic balance was disturbed by AZ in which excessive mitochondrial fission occurred in response to decreased ATP levels. When a recovery operation was performed in AZ-exposed cells and fish, infectivity of our model virus, spring viraemia of carp virus (SVCV), was significantly decreased in vitro (using the epithelioma papulosum cyprini [EPC] fish cell line) and in vivo (using zebrafish) in a time-dependent manner. Also, the expression of eight innate antiviral immune genes ( IFNs , ISG15 , MX1 , RIG-I , IRF3 , Nrf2 and HO-1 ) showed a similar change to SVCV replication between the longer exposure period and the expression recovery. Additionally, AZ facilitated horizontal transmission of SVCV in a static cohabitation challenge model, predicting the increase of the potential for the viral outbreak. Therefore, our data suggest that long-term effect of AZ on irreparable impairment in fish made AZ residue potentially greater for ecological risks.
研究领域:
水生毒理学
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免疫学
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病毒学
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环境科学
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产品关联
DOI
PubMed
高影响因子
TALANTA
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2020
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IF 5.339
Jiao Zhou,Lei Han,Yu Ling,Lei Wang,Nian Bing Li,Hong Qun Luo
Relying on the specific coordination of Ag + and mismatched cytosine-cytosine (C–C), the high-efficiency inhibition of urease by Ag + ion, and the rapid and sensitive response of phenol red to pH, a sensitive ratiometric sensor has been designed for visual detection of human immunodeficiency virus gene (HIV DNA). This sensor utilizes the HIV DNA to initiate catalytic hairpin assembly (CHA) process, releasing Ag + to inhibit subsequent urease-catalyzed urea hydrolysis and prevent the pH of the solution from rising. The CHA process and the absorbance ratio of phenol red at different wavelengths (A 559 /A 432 ) amplify the signal, allowing the sensor to detect HIV DNA from 10 to 130 nM in a sensitive and highly selective manner with a low detection limit of 7.8 nM. In addition, this sensor can visually distinguish different concentrations of HIV DNA within a certain range and possesses a good recovery in 1% of serum samples, which will provide new ideas for biosensor design, dipstick test, blood test, and other clinical disease prevention.
研究领域:
生物技术
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纳米技术
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分析化学
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分子生物学
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医学诊断
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产品关联
DOI
PubMed
高影响因子
Nature Biomedical Engineering
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2023
·Vol. 7
·期 9
·1129-1141
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IF 28.1
Li Xianlei,Gong Ningqiang,Tian Falin,Zhang Shangkun,Zhang Yuxuan,Wang Yufei,Qing Guangchao,Wang Yongchao,Li Fangzhou,Xu Yihui,Zhang Linlin,Wang Jinjin,Ni Qiankun,Gan Yaling,Gu Chaojiang,Jiang Huaidong,Huang Xingxu,Shi Xinghua,Zhang Tongcun,Wu Yan,Liang Xing-Jie
The infusion of chimaeric antigen receptor (CAR) T cells can trigger the release of life-threatening supraphysiological levels of pro-inflammatory cytokines. However, uncertainty regarding the timing and severity of such cytokine release syndrome (CRS) demands careful monitoring of the conditions required for the administration of neutralizing antibodies. Here we show that a temperature-sensitive hydrogel conjugated with antibodies for the pro-inflammatory cytokine interleukin-6 (IL-6) and subcutaneously injected before the infusion of CAR-T cells substantially reduces the levels of IL-6 during CRS while maintaining the therapy’s antitumour efficacy. In immunodeficient mice and in mice with transplanted human haematopoietic stem cells, the subcutaneous IL-6-adsorbing hydrogel largely suppressed CAR-T-cell-induced CRS, substantially improving the animals’ survival and alleviating their levels of fever, hypotension and weight loss relative to the administration of free IL-6 antibodies. The implanted hydrogel, which can be easily removed with a syringe following a cooling-induced gel–sol transition, may allow for a shift in the management of CRS, from monitoring to prevention.
研究领域:
肿瘤学
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免疫治疗
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生物医学工程
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药理学
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DOI
PubMed
高影响因子
Bioengineering & Translational Medicine
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2022
·Vol. 8
·期 1
·e10327
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IF 10.684
Zi-Yan Xu,Jin-Jian Huang,Ye Liu,Can-Wen Chen,Gui-Wen Qu,Ge-Fei Wang,Yun Zhao,Xiu-Wen Wu,Jian-An Ren
Organoids hold inestimable therapeutic potential in regenerative medicine and are increasingly serving as an in vitro research platform. Still, their expanding applications are critically restricted by the canonical culture matrix and system. Synthesis of a suitable bioink of bioactivity, biosecurity, tunable stiffness, and printability to replace conventional matrices and fabricate customized culture systems remains challenging. Here, we envisaged a novel bioink formulation based on decellularized extracellular matrix (dECM) from porcine small intestinal submucosa for organoids bioprinting, which provides intestinal stem cells (ISCs) with niche-specific ECM content and biomimetic microstructure. Intestinal organoids cultured in the fabricated bioink exhibited robust generation as well as a distinct differentiation pattern and transcriptomic signature. This bioink established a new co-culture system able to study interaction between epithelial homeostasis and submucosal cells and promote organoids maturation after transplantation into the mesentery of immune-deficient NODSCID-gamma (NSG) mice. In summary, the development of such photo-responsive bioink has the potential to replace tumor-derived Matrigel and facilitate the application of organoids in translational medicine and disease modeling.
研究领域:
再生医学
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组织工程
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干细胞生物学
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
Iranian Journal of Basic Medical Sciences
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2023
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IF 2.2
Yutao Zhang,Yongming Yang,Likun Zan,Jing Wang,Lei Yan,Lili Zhao,Lixia Chen,Yanfeng Xi,Wenqi Bai,Xihua Yang
Objective(s): Patient-derived xenograft (PDX) model becomes a more and more important tool for tumor research. This study aimed to establish a colorectal cancer PDX model and verify its applicability. Materials and Methods: Fresh human colorectal cancer tissue was surgically removed and subcutaneously inoculated into immunodeficient mice to establish the PDX model. Hematoxylin and eosin (HE) staining and immunohistochemical staining were used to evaluate the model. The successful PDX model was selected to study the efficacy of capecitabine in treating colorectal cancer. Results: HE staining showed that the PDX mice model of colorectal cancer could preserve the histological characteristics of the primary tumor. Immunohistochemistry staining showed α-fetoprotein (AFP), carcinoembryonic antigen (CEA), and E-cadherin were strongly positively expressed in primary human and PDX tumor tissues, with a high degree of similarity. Capecitabine significantly inhibited PDX tumor growth and reduced the expression of AFP and CEA proteins in the tumor tissues (all P s <0.05). Conclusion: We successfully established a colorectal cancer PDX model, and the PDX model could retain the histological and biological characteristics of the primary tumor. Using this PDX model, we revealed that capecitabine at a dose of 300–400 mg/kg can effectively treat colorectal cancer, and no significant difference in toxicity was found among different dose groups. The current work provides a feasible framework for establishing and validating the PDX tumor model to better facilitate the evaluation of drug efficacy and safety.
研究领域:
肿瘤学
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药理学
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分子生物学
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癌症研究
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DOI
PubMed
高影响因子
Cell and Bioscience
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2023
·Vol. 13
·期 1
·1-15
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IF 7.5
Yu Juan,Yu Nianye,Tian Yao,Fang Yifan,An Bin,Feng Guihai,Wu Jun,Wang Liu,Hao Jie,Wang Liqiang,Zhou Qi,Li Wei,Wang Yukai,Hu Baoyang
Background Research on human pluripotent stem cells (hPSCs) has shown tremendous progress in cell-based regenerative medicine. Corneal endothelial dysfunction is associated with the loss and degeneration of corneal endothelial cells (CECs), rendering cell replacement a promising therapeutic strategy. However, comprehensive preclinical assessments of hPSC-derived CECs for this cell therapy remain a challenge. Results Here we defined an adapted differentiation protocol to generate induced corneal endothelial cells (iCECs) consistently and efficiently from clinical-grade human embryonic stem cells (hESCs) with xeno-free medium and manufactured cryopreserved iCECs. Cells express high levels of typical CECs markers and exhibit transendothelial potential properties in vitro typical of iCECs. After rigorous quality control measures, cells meeting all release criteria were available for in vivo studies. We found that there was no overgrowth or tumorigenicity of grafts in immunodeficient mice. After grafting into rabbit models, the surviving iCECs ameliorated edema and recovered corneal opacity. Conclusions Our work provides an efficient approach for generating iCECs and demonstrates the safety and efficacy of iCECs in disease modeling. Therefore, clinical-grade iCECs are a reliable source for future clinical treatment of corneal endothelial dysfunction.
研究领域:
再生医学
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干细胞生物学
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眼科
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临床前研究
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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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
Frontiers in Immunology
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2023
·
IF 7.3
Xi Zhang,Tiaoxia Wang,Xiaona Zhu,Yong Lu,Mingpeng Li,Zhihong Huang,Deping Han,Longzhen Zhang,Yang Wu,Liantao Li,Frank Klawonn,Renata Stripecke
Introduction Epstein-Barr virus (EBV) is a widely spread pathogen associated with lymphoproliferative diseases, B/ T/ NK cell lymphomas, nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC). EBV lytic reactivations contribute to the genomic instability, inflammation and tumorigenesis of NPC, promoting cancer progression. Patients with NPC refractory to standard therapies show dismal survival. EBV gp350 is an envelope protein detectable in NPC specimens intracellularly and on the cell membrane of malignant cells, and is a potential viral antigen for T cell-directed immunotherapies. The potency of T cells engineered with a chimeric antigen receptor (CAR) targeting gp350 against EBV + lymphoproliferative disease was previously shown. Methods Here, we advanced towards preclinical and non-clinical developments of this virus-specific CAR-T cell immunotherapy against NPC. Different gp350CAR designs were inserted into a lentiviral vector (LV) backbone. Results A construct expressing the scFv 7A1-anti−gp350 incorporating the CD8 transmembrane and CD28.CD3ζ signaling domain (ZT002) was selected. High titer ZT002 (~1x10 8 TU/ml) was manufactured in HEK 293T/17 suspension cells in serum free media as large-scale production under good manufacturing practices (GMP). A LV multiplicity of infection (MOI) of 1 resulted in high frequencies of functional gp350CAR + T cells (>70%) at a low (<2) vector copy numbers in the genome. ZT002 was therefore used to establish gp350CAR-T batch run production methods. GMP upscaling and validation of T cell transduction and expansion in several runs resulted in average 3x10 9 gp350CAR-T cells per batch. >80% CD3 + gp350CAR-T cells bound to purified gp350 protein. In vitro cytotoxicity and cytokine secretion assays (IFN-γ and TNF-α) confirmed the specificity of gp350CAR-T cells against gp350 + NPC, GC and lymphoma cell targets. Immunocompromised B-NDG mice (NOD.CB17- PrkdcscidIl2rgtm1 /Bcgen) were challenged s.c. with a EBV + NPC C666.1 cell line expressing gp350 and then treated with escalating doses of gp350CAR-T cells or with non-transduced T cells. gp350CAR-T cells promoted antitumor responses, bio-distributed in several tissues, infiltrated in tumors and rejected gp350 + tumor cells. Discussion These results support the use of gp350CAR-T cells generated with ZT002 as an Innovative New Drug to treat patients with solid and liquid EBV-associated malignancies.
研究领域:
免疫治疗
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肿瘤学
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分子生物学
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病毒学
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临床前研究
✓ 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）