JOURNAL OF NANOBIOTECHNOLOGY
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2022
·Vol. 20
·期 1
·1-16
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IF 9.429
Wang Dan,Chen Ling,Li Chengbi,Long Quanxin,Yang Qing,Huang Ailong,Tang Hua
Background Currently, there are no curative drugs for hepatitis B virus (HBV). Complete elimination of HBV covalently closed circular DNA (cccDNA) is key to the complete cure of hepatitis B virus infection. The CRISPR/Cas9 system can directly destroy HBV cccDNA. However, a CRISPR/Cas9 delivery system with low immunogenicity and high efficiency has not yet been established. Moreover, effective implementation of precise remote spatiotemporal operations in CRISPR/Cas9 is a major limitation.Results In this work, we designed NIR-responsive biomimetic nanoparticles (UCNPs-Cas9@CM), which could effectively deliver Cas9 RNP to achieve effective genome editing for HBV therapy. HBsAg, HBeAg, HBV pgRNA and HBV DNA along with cccDNA in HBV-infected cells were found to be inhibited. These findings were confirmed in HBV-Tg mice, which did not exhibit significant cytotoxicity and minimal off-target DNA damage.Conclusion sThe UCNPs-based biomimetic nanoplatforms achieved the inhibition of HBV replication via CRISPR therapy and it is a potential system for efficient treatment of human HBV diseases.Graphical Abstract
研究领域:
分子生物学
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病毒学
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纳米技术
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治疗学
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DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
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2022
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IF 12.545
Ru Cheng,Fu Zhu,Min Huang,Qiang Zhang,Hui Hong Yan,Xiao Hui Zhao,Fu Kang Luo,Chun Mei Li,Hui Liu,Gao Lin Liang,Cheng Zhi Huang,Jian Wang
As the common hepatitis viruses , hepatitis B virus (HBV) and hepatitis C virus (HCV) are important causes of liver diseases, which greatly threaten human health and public hygiene. Furthermore, due to the similar transmission routes of HBV and HCV, it is highly susceptible to suffer from the cross-infection of HBV and HCV when humans are infected by hepatitis viruses. So it is urgent to develop strategies with high sensitivity to distinguish HBV/HCV and detect their overlapping infection. Herein, a new biosensor named “hepatitis virus indicator” for simultaneous detection of HBV and HCV based on the automatic particle enumeration was developed by the combination of Exo III assisted signal amplification strategy and particle counting technology with a dark-field microscopy. The limit of detections (LOD) were as low as 0.194 pM for HBV and 0.169 pM for HCV, respectively. In addition, the proposed method was capable of simultaneously detecting HBV and HCV based on the colorful light scattering from plasmonic nanoparticles . The proposed assay was simple, sensitive and selective for the simultaneous detection of HBV and HCV, which provided a new idea for the early diagnosis of diseases, such as hepatitis A virus (HAV), hepatitis D virus (HDV) and hepatitis E virus (HEV).
研究领域:
医学
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生物传感器技术
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DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
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2024
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IF 5.7
Hang Gong,Ganping Cai,Yong Li,Ning Jiang,Chunyan Chen,Feng Chen,Changqun Cai
Background Viral epidemics have long endangered human health and had dramatic impacts on environment and society. The currently known viruses and the rapid emergence of previously unknown viruses lead to an urgent need for effective virus detection strategies. It is important to develop methods that can detect multiple related viruses simultaneously in order to improve detection efficiency and to avoid treatment delays due to misdiagnoses. However, an important practical problem for viruses simultaneously detection is mutual interference between the targets, which is caused by a certain degree of signal superposition. Results A portable ratio-based triple-emission molecular imprinting fluorescence sensor was constructed to detect hepatitis A virus (HAV) and hepatitis B virus (HBV) simultaneously, which eliminated background interference and mutual interference between the two targets, and improved detection accuracy. In this sensor, a layer containing blue fluorescent carbon quantum dots (B-CDs) coated with silicon was used as a constant luminescent core to permit ratiometric detection of signals, this layer also affords visual analysis due to its constant blue color. As signal sources to employ yellow-green and red quantum dots, HAV- and HBV-specific molecularly imprinted polymers (MIPs) were prepared by imprinting virus onto the core containing the B-CDs. Under the optimized detection conditions, the simply physically mixing HAV-MIPs and HBV-MIPs in a specific ratio, which leads to non-interfering fluorescence signals and the simultaneous detection of the two target viruses via the rich color visualization under ultraviolet light. Significance This strategy provides a simple and low-cost (0.26 ¥/sensor) method for the simultaneous detection of two hepatitis viruses, and provides an avenue for the development of portable methods for the simultaneous detection of similar highly infectious viruses. This self-service sensor also has the potential to be used by patients themselves, reducing pressures on medical staff and decreasing risks of cross-infection.
研究领域:
病毒学
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医学检测
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纳米材料科学
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DOI
PubMed
高影响因子
Analytical Methods
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2018
·Vol. 11
·期 3
·268-275
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IF 2.073
Qiongqiong Yu,Wenchao Dou,Jing Liu,Guangying Zhao,Shuai Yang,Danhua Zhu,Yalei Zhao,Lanjuan Li
An immunochromatographic assay (ICA) based on red silica nanoparticles (red-SiNPs) was developed for quantitative detection of hepatitis B surface antigen (HBsAg) in serum. Red SiNPs have unique optical properties and remarkable stability compared to red latex microspheres. Red-SiNPs functionalized with anti-HBsAg mAb1 were employed as detection immuno-probes. The sandwich-type immunoreaction structures were formed on ICA strips, and the accumulation of red SiNPs-mAb1 on the test line produced characteristic red color bands, enabling visual detection of HBsAg without instrumentation. Quantitative detection was performed by researching the relationship between the HBsAg concentration and the corresponding peak area of the gray value of the test line with a camera and image analysis software Image J. Under optimal conditions, the visual limit of detection (vLOD) of the strip for the qualitative detection of HBsAg is 1 ng mL−1, which is lower than that of the routinely used red latex microsphere-based ICA. In the quantitative detection, the peak area of the gray value of the test line and the HBsAg concentration show a good linearity when the HBsAg concentration is in the range of 5–500 ng mL−1. The calibration equation was y = 370.6118 + 9.6673x (R2 = 0.9962) and the limit of detection (LOD) of the method was 0.97 ng mL−1 (S/N = 3). Our proposed method provides promising and versatile opportunities for the rapid and quantitative screening of other proteins at relatively sensitive levels by combining a colored label with ICA.
研究领域:
医学诊断
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纳米技术
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病毒学
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DOI
高影响因子
SENSORS
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2020
·Vol. 20
·期 17
·4912
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IF 3.275
Xuexue Xu,Rongbin Nie,Jingwen Huang,Li Yang
Optical fiber based immunosensors are very attractive for biomarker detection. In order to improve the sensor response, we propose a promising strategy which combines porous-layer modification of the fiber surface and streptavidin-biotin-peroxidase nano-complex signal amplification in chemiluminescent detection. Two hepatitis B antigens, hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg), are used as the targets for analysis using the proposed sensor. Comparing to immunoassays using normal optical fiber sensors, the response of the present sensor is enhanced by a factor of 4.8 and 6.7 for detection of HBsAg and HBeAg, respectively. The limit-of-quantitation of the proposed method is as low as 0.3 fg/mL (0.01 fg/mL) with a wide linear response range of 3 fg/mL–150 ng/mL (0.1 fg/mL–160 ng/mL) for sensing HBsAg (HBeAg). Quantitative determination of HBsAg and HBeAg in human serum samples is performed, showing the applicability of the proposed method for biomarker detection.Keywords:optical fiber immunosensor;surface modification;signal amplification;hepatitis B surface antigen;hepatitis B e antigen
研究领域:
生物医学工程
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分析化学
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医学诊断
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DOI
PubMed
高影响因子
Botanical Studies
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2016
·Vol. 57
·期 1
·1-11
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IF 1.159
Shi Qiang-Qiang,Dang Jun,Wen Huai-Xiu,Yuan Xiang,Tao Yan-Duo,Wang Qi-Lan
Background
Dracocephalum heterophyllum was a traditional Tibetan medicine possesses various pharmacological effects involved in anti-inflammatory, antibacterial activities. However, its anti-hepatitis, antioxidant activity and bioactive compounds have not been reported, the objective of this research work was to investigate the pharmacological activity and bioactive compounds of D. heterophyllum extracts. Results In the present study, the anti-hepatics and antioxidant activities of four D. heterophyllum extracts (i.e. petroleum ether extracts, ethyl acetate extracts, n -BuOH extracts, and water extracts) were conducted. The main chemical constituent of petroleum ether and ethyl acetate extracts were also isolated using chromatographic techniques and identified by NMR spectroscopic methods. The anti-hepatitis assay showed that the petroleum ether and ethyl acetate extracts of D. heterophyllum significantly prolonged the mean survival times and reduced the mortality of mouse hepatitis model induced by concanavalin A (ConA). The levels of alanine transaminase, aspartate transaminase in blood serum could be decreased obviously by ethyl acetate extracts compared with ConA group (P < 0.01). The histological analysis demonstrated that the ethyl acetate extracts could inhibit apoptosis and necrosis caused by ConA. In addition, the antioxidant activities of the four extracts of D. heterophyllum were measured by DPPH assay, ABTS assay, anti-lipidperoxidation assay, ferric reducing antioxidant power assay, ferrous metal ions chelating assay and determination of total phenolic contents. The results showed that the ethyl acetate extract had the highest antioxidant activities, followed by petroleum ether extract. Finally, nine mainly compounds were isolated from the Petroleum ether and ethyl acetate extracts, including four triterpenes: oleanolic acid ( 1 ), ursolic acid ( 2 ), pomolic acid ( 3 ), 2α- hydroxyl ursolic acid ( 4 ), three flavonoids: apigenin-7- O -rutinoside ( 5 ), luteolin ( 8 ), diosmetin ( 9 ) and two phenolic acids: rosmarinic acid ( 6 ), methyl rosmarinate ( 7 ). Conclusion The Ethyl acetate extract of D. heterophyllum had the highest anti-hepatitis and antioxidants activities, followed by petroleum ether extract. The bioactive substances may be triterpenes, flavonoids and phenolic acids, the ethyl acetate extracts of D. heterophyllum may be possible candidates in developing anti-hepatitis medicine.
研究领域:
药理学
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植物学
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药物化学
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DOI
PubMed
高影响因子
Open Life Sciences
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2025
·Vol. 20
·期 1
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IF 1.7
Chengrong Huang,Hao Zhang,Jing Wang,Jianfei Li,Qian Liu,Qiyin Zong,Yunyun Zhang,Qin Wang,Qiang Zhou
A growing body of evidence has shown that hepatitis B surface antigen (HBsAg) mutations can influence the occurrence of occult hepatitis B infection (OBI), particularly amino acid substitutions in small hepatitis B surface proteins (SHBs). The mechanistic basis for these results, however, remains unclear. This study was designed to explore the potential impact and mechanisms of OBI-related SHBs mutations on serum HBsAg. Huh7 and HepG2 cells were transfected with plasmids encoding wild-type (WT) or OBI-related SHB mutation-containing sequences, after which a chemiluminescence approach was used to detect HBsAg levels in cell culture supernatants. Western blotting was further used to assess HBsAg and endoplasmic reticulum stress (ERS)-related protein levels in lysates prepared from these cells, while the localization of HBsAg within cells was assessed via immunofluorescent staining. Cells transfected with OBI-related SHB mutation-encoding plasmids exhibited lower supernatant HBsAg levels than cells transfected with WT plasmids. Intracellular and extracellular HBsAg levels in these mutant plasmid-transfected cells were lower relative to those for WT plasmid-transfected cells, and HBsAg accumulation within the ER was detected via immunofluorescent staining in cells transfected with OBI-related SHB mutation-encoding plasmids, ERS-related protein content was also significantly increased in mutant plasmid-transfected cells as compared to those in the WT group. These results suggest that proteins harboring OBI-related mutations may tend to accumulate in the ER, thereby triggering an ERS response and impairing the transcription and translation of HBsAg via the activation of the unfolded protein response and ER-associated protein degradation pathway. These effects ultimately reduce the overall assembly of HBV virions in the ER and their associated secretion.
研究领域:
病毒学
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分子生物学
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医学
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PubMed
高影响因子
Viruses-Basel
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2021
·Vol. 13
·期 12
·2383
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IF 5.048
Huawei Xia,Zeming Zhang,Fuping You
Murine hepatitis virus strain A59 (MHV-A59) was shown to induce pyroptosis, apoptosis, and necroptosis of infected cells, especially in the murine macrophages. However, whether ferroptosis, a recently identified form of lytic cell death, was involved in the pathogenicity of MHV-A59 is unknown. We utilized murine macrophages and a C57BL/6 mice intranasal infection model to address this. In primary macrophages, the ferroptosis inhibitor inhibited viral propagation, inflammatory cytokines released, and cell syncytia formed after MHV-A59 infection. In the mouse model, we found that in vivo administration of liproxstatin-1 ameliorated lung inflammation and tissue injuries caused by MHV-A59 infection. To find how MHV-A59 infection influenced the expression of ferroptosis-related genes, we performed RNA-seq in primary macrophages and found that MHV-A59 infection upregulates the expression of the acyl-CoA synthetase long-chain family member 1 (ACSL1), a novel ferroptosis inducer. Using ferroptosis inhibitors and a TLR4 inhibitor, we showed that MHV-A59 resulted in the NF-kB-dependent, TLR4-independent ACSL1 upregulation. Accordingly, ACSL1 inhibitor Triacsin C suppressed MHV-A59-infection-induced syncytia formation and viral propagation in primary macrophages. Collectively, our study indicates that ferroptosis inhibition protects hosts from MHV-A59 infection. Targeting ferroptosis may serve as a potential treatment approach for dealing with hyper-inflammation induced by coronavirus infection.Keywords:coronavirus;mouse hepatitis virus (MHV);ferroptosis;therapy
研究领域:
病毒学
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免疫学
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药理学
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PubMed
高影响因子
Nanomaterials
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2022
·Vol. 12
·期 4
·595
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IF 5.719
Yifei Yang,Zhenning Sun,Huopeng Li,Jijing Tian,Mingyong Chen,Tianlong Liu
The hepatitis E virus (HEV) is an important pathogen that threatens global public health. One-third of the world’s population lives in the epidemic area of HEV, causing 20 million infections and 70,000 deaths annually. In China, HEV transmission has changed from human-to-human transmission of HEV1 to zoonotic transmission of HEV4, causing hepatitis outbreaks throughout the country. Protecting vulnerable groups, such as practitioners related to animal husbandry and downstream consumers who are immune deficient or pregnant, from HEV infections is an urgent task. At present, the commercial human vaccine, Hecolin®(HEV 239 vaccine), is licensed for use only in China. HEV 239 vaccine is a human vaccine developed for HEV1. Although it has a cross-protective effect on HEV4, the level of immune protection is still different. To address the transformation of domestic HEV transmission modes, there is an urgent need to develop a new vaccine against zoonotic HEV4.[email protected]is a vaccine candidate in which nanomaterials are used to encapsulate viral capsid proteins for the immunization of livestock animals. Our experiments show that[email protected]has excellent biocompatibility and safety. In addition,[email protected]can effectively induce animals to produce a high titer of antibodies against HEV4, and thus has the potential to become a veterinary vaccine for the prevention of HEV. This approach provides a new concept for HE prevention to reduce the transmission of HEV in farms and protect susceptible populations.Keywords:hepatitis E virus;vaccine immunity;nanoparticles;PLGA;P206
研究领域:
病毒学
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免疫学
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纳米技术
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公共卫生
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DOI
PubMed
高影响因子
Nutrients
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2022
·Vol. 14
·期 12
·2411
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IF 6.706
Zhuohui Zhao,Zhen-Tao Deng,Suling Huang,Mengmeng Ning,Ying Feng,Yu Shen,Qin-Shi Zhao,Ying Leng
Non-alcoholic steatohepatitis (NASH) is a common chronic liver disease worldwide, with no effective therapies available. Discovering lead compounds from herb medicine might be a valuable strategy for the treatment of NASH. Here, we discovered Alisol B, a natural compound isolated fromAlisma orientalis(Sam.), that attenuated hepatic steatosis, inflammation, and fibrosis in high-fat diet plus carbon tetrachloride (DIO+CCl4)-induced and choline-deficient and amino acid-defined (CDA)-diet-induced NASH mice. RNA-seq showed Alisol B significantly suppressed CD36 expression and regulated retinol metabolism in NASH mice. In mouse primary hepatocytes, Alisol B decreased palmitate-induced lipid accumulation and lipotoxicity, which were dependent on CD36 suppression. Further study revealed that Alisol B enhanced the gene expression of RARα with no direct RARα agonistic activity. The upregulation of RARα by Alisol B reduced HNF4α and PPARγ expression and further decreased CD36 expression. This effect was fully abrogated after RARα knockdown, suggesting Alisol B suppressed CD36 via regulating RARα-HNF4α-PPARγ cascade. Moreover, the hepatic gene expression of RARα was obviously decreased in murine NASH models, whereas Alisol B significantly increased RARα expression and decreased CD36 expression, along with the downregulation of HNF4α and PPARγ. Therefore, this study showed the unrecognized therapeutic effects of Alisol B against NASH with a novel mechanism by regulating RARα-PPARγ-CD36 cascade and highlighted Alisol B as a promising lead compound for the treatment of NASH.Keywords:Alisol B;non-alcoholic steatohepatitis;RARα;CD36
研究领域:
药理学
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分子生物学
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肝病学
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PubMed
高影响因子
Chinese Medicine
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2025
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IF 5.7
Ruiyu Wu,Runping Liu,Ranyun Chen,Yijie Li,Xiaoyong Xue,Yinhao Zhang,Fanghong Li,Jiaorong Qu,Lingling Qin,Chen Wang,Xiaojiaoyang Li
Background Obesity is frequently linked to chronic systamic inflammation and presents significant challenges to public health. Aurantio-obtusin (AO) boosted the brown adipose tissue (BAT) thermogenesis in diet-induced obesity. However, the specific mechanisms by which injured mitochondria-related damage signals derived from overwhelmed BAT can transmit to liver and exacerbate metabolic disorders and whether AO can reverse this process remain unknown. Materials and methods After applying high-fat diet and glucose-fructose water (HFHS)-induced obesity mice, different BAT transplant procedures and primary BAT adipocytes, we investigated the anti-obesity effects and mechanism of AO through RNA sequencing and biology techniques. Results AO improved whole-body lipid accumulation, mitochondrial metabolism in BAT and hepatic inflammation in HFHS-induced obesity mice. Interscapular transplant of BAT-derived from obese donor mice triggered hepatic inflammation of chow diet-fed recipient mice, which was protected by AO. Furthermore, the transplantation of BAT-derived from AO-treated mice protected hepatic inflammation in obese mice. In vivo and in lipid-challenged primary BAT adipocytes, AO decreased kexin type 9 (PCSK9), prevented mPTP opening and mitochondrial DNA (mtDNA) release in extracellular vesicles (EVs) manner by inhibiting the acetylation of cyclophilin D associated with adenine nucleotide translocase, suppressing oligomerization of voltage-dependent anion channel 1 and activating mitophagy. Ultimately, AO inhibited mtDNA-containing EVs-induced cyclic GMP-AMP synthase/stimulator of interferon genes (STING) activation and hepatic inflammation, which was confirmed by Sting −/− mice. Conclusion AO not only improves thermogenesis and mitochondrial function of BAT but also prevents liver inflammation by repairing mitochondrial function and blocking the transfer of mtDNA from BAT to the liver. Graphic abstract Supplementary Information The online version contains supplementary material available at 10.1186/s13020-025-01097-y.
研究领域:
医学
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分子生物学
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代谢研究
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PubMed
高影响因子
Small
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2025
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IF 12.1
Chenggong Zhu,Qunfang Huang,Ruijie Fu,Zhen Xun,Qishui Ou,Yunlei Xianyu,Can Liu
Hepatitis B virus (HBV) infection remains a significant global public health issue, and rapid detection of HBV DNA is crucial for disease prevention and control. However, traditional methods for HBV DNA detection are limited by their reliance on precise instruments and single readout, which can hardly meet the requirements of on-site detection. In this study, the Mg 2+ -enhanced trans-cleavage activity of clustered regularly interspaced short palindromic repeats/associated protein 12a (CRISPR/Cas12a) is reported and coupled with loop-mediated isothermal amplification (LAMP) and Au@Pt nanoparticles as a signaling reporter for on-site detection of HBV DNA. This triple-modal biosensing strategy enables multiple signal readouts including UV–vis spectrum, RGB value, and temperature with high sensitivity and accuracy. The linear detection ranges using UV–vis spectroscopy, RGB color recognition, and photothermal modes are from 50 to 10,000 copies µL −1 , with the limitation of detection of 24.07, 39.65, and 23.33 copies µL −1 , respectively. This biosensing strategy is further employed for the qualitative detection of HBV DNA in 48 serum samples, achieving sensitivities of 100%, 100%, and 95.24% for triple modes. This work offers a promising tool of next-generation LAMP-CRISPR/Cas12a for the rapid and portable detection of nucleic acids.
研究领域:
生物传感器
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病毒学
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纳米技术
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分子诊断学
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CRISPR技术
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分析化学
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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）