Publications by authors named "Jianwen Guo"

31 Publications

River Basin Cyberinfrastructure in the Big Data Era: An Integrated Observational Data Control System in the Heihe River Basin.

Sensors (Basel) 2021 Aug 11;21(16). Epub 2021 Aug 11.

National Tibetan Plateau Data Center, Institute of Tibetan Plateau Research, Chinese Academy of Sciences, Beijing 100101, China.

River basin cyberinfrastructure with the Internet of Things (IoT) as the core has brought watershed data science into the big data era, greatly improving data acquisition and sharing efficiency. However, challenges in analyzing, processing, and applying very large quantities of observational data remain. Given the observational needs in watershed research, we studied the construction of river basin cyberinfrastructure and developed an integrated observational data control system (IODCS). The IODCS is an important platform for processing large quantities of observational data, including automated collection, storage, analysis, processing, and release. This paper presents various aspects of the IODCS in detail, including the system's overall design, function realization, big data analysis methods, and integrated models. We took the middle reaches of the Heihe River Basin (HRB) as the application research area to show the performance of the developed system. Since the system began operation, it has automatically received, analyzed, and stored more than 1.4 billion observational data records, with an average of more than 14 million observational data records processed per month and up to 21,011 active users. The demonstrated results show that the IODCS can effectively leverage the processing capability of massive observational data and provide a new perspective for facilitating ecological and hydrological scientific research on the HRB.
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http://dx.doi.org/10.3390/s21165429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8401438PMC
August 2021

Would integrated Western and traditional Chinese medicine have more benefits for stroke rehabilitation? A systematic review and meta-analysis.

Stroke Vasc Neurol 2021 Aug 26. Epub 2021 Aug 26.

Hong Kong Association for Integration of Chinese-Western Medicine Limited, Hong Kong SAR, China.

Background: Stroke is a major cause of death or long-term disability worldwide. Many patients with stroke receive integrative therapy consisting of Western medicine (WM) and routine rehabilitation in conjunction with Chinese medicine (CM), such as acupuncture and Chinese herbal medicine. However, there is no available evidence on the effectiveness of the combined use of WM and CM interventions in stroke rehabilitation.

Aims: The purpose of this meta-analysis is to evaluate the results of all individual studies to assess the combined use of CM and WM in stroke rehabilitation compared with WM only.

Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed. MEDLINE, EMBASE, Cochrane and China National Knowledge Infrastructure (CNKI) were searched. The included outcomes were dependency, motor function, depression and swallowing function. Subgroup analysis was performed, and publication bias was assessed using funnel plots.

Summary Of Review: 58 studies and 6339 patients were included in the meta-analysis. Subgroup analysis revealed that combined therapy comprising both acupuncture and WM had a superior effect on improving dependency and swallowing function compared with standard WM therapy alone. Potential superiority of combined therapy comprising CM and WM in improving depression compared with standard WM therapy was also found.

Conclusions: Our results indicate that the combined use of CM and WM could be more efficacious in stroke rehabilitation compared with the use of WM therapy alone. However, most studies were short in duration (2 to 4 weeks) and prone to different types of biases, which prevents making any conclusion regarding the long-term effects and raises concerns regarding true efficacy in context of high likelihood of Hawthorn bias. So, more randomised controlled trials with more rigorous design and longer duration of treatment and follow-up need to be conducted to compare WM alone versus WM and CM combined.

Prospero Registration Number: CRD42020152050.
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http://dx.doi.org/10.1136/svn-2020-000781DOI Listing
August 2021

Altered Actinobacteria and Firmicutes Phylum Associated Epitopes in Patients With Parkinson's Disease.

Front Immunol 2021 2;12:632482. Epub 2021 Jul 2.

Department of Neurology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

Recent evidence suggests that inflammation was participated in the pathogenesis of PD, thus, to understand the potential mechanism of gut microbiota in the pathogenesis of Parkinson's disease (PD), we performed a metagenomic analysis of fecal samples from PD patient and controls. Using a two-stage metagenome-wide association strategy, fecal DNA samples from 69 PD patients and 244 controls in three groups (comprising 66 spouses, 97 age-matched, and 81 normal samples, respectively) were analyzed, and differences between candidate gut microbiota and microbiota-associated epitopes (MEs) were compared. In the study, 27 candidate bacterial biomarkers and twenty-eight candidate epitope peptides were significantly different between the PD patients and control groups. Further, enriched 4 and 13 MEs in PD were positively associated with abnormal inflammatory indicators [neutrophil percentage (NEUT.1), monocyte count/percentage (MONO/MONO.1), white blood cell count (WBC)] and five candidate bacterial biomarkers (c_Actinobacteria, f_Bifidobacteriaceae, , o_Bifidobacteriales, p_Actinobacteria) from Actinobacteria phylum, and they were also positively associated with histidine degradation and proline biosynthesis pathways, respectively. Additionally, enriched 2 MEs and 1 ME in PD were positively associated with above inflammatory indicators and two bacteria (f_Lactobacillaceae, ) from Firmicutes phylum, and they were also positively associated with pyruvate fermentation to propanoate I and negatively associated with isopropanol biosynthesis, respectively. Of these MEs, two MEs from GROEL2, RPSC were derived from , triggered the T cell immune response, as previously reported. Additionally, other candidate epitope peptides derived from and may also have potential immune effects in PD. In all, the altered MEs in PD may relate to abnormalities in immunity and glutamate and propionate metabolism, which furthers our understanding of the pathogenesis of PD.
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http://dx.doi.org/10.3389/fimmu.2021.632482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8284394PMC
September 2021

Reducing False-Positives in Lung Nodules Detection Using Balanced Datasets.

Front Public Health 2021 19;9:671070. Epub 2021 May 19.

School of Mechanical Engineering, Dongguan University of Technology, Dongguan, China.

Malignant pulmonary nodules are one of the main manifestations of lung cancer in early CT image screening. Since lung cancer may have no early obvious symptoms, it is important to develop a computer-aided detection (CAD) system to assist doctors to detect the malignant pulmonary nodules in the early stage of lung cancer CT diagnosis. Due to the recent successful applications of deep learning in image processing, more and more researchers have been trying to apply it to the diagnosis of pulmonary nodules. However, due to the ratio of nodules and non-nodules samples used in the training and testing datasets usually being different from the practical ratio of lung cancer, the CAD classification systems may easily produce higher false-positives while using this imbalanced dataset. This work introduces a filtering step to remove the irrelevant images from the dataset, and the results show that the false-positives can be reduced and the accuracy can be above 98%. There are two steps in nodule detection. Firstly, the images with pulmonary nodules are screened from the whole lung CT images of the patients. Secondly, the exact locations of pulmonary nodules will be detected using Faster R-CNN. Final results show that this method can effectively detect the pulmonary nodules in the CT images and hence potentially assist doctors in the early diagnosis of lung cancer.
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http://dx.doi.org/10.3389/fpubh.2021.671070DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170487PMC
June 2021

Effect and safety of Chinese herbal medicine granules in patients with severe coronavirus disease 2019 in Wuhan, China: a retrospective, single-center study with propensity score matching.

Phytomedicine 2021 May 5;85:153404. Epub 2020 Nov 5.

Department of Emergency, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China; Guangdong Provincial Key Laboratory of Research on Emergency in TCM, Guangzhou, China; State Key Laboratory of Dampness Syndrome of Chinese Medicine, the Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address:

Background: Chinese herbal medicine (CHM) has been used for severe illness caused by coronavirus disease 2019 (COVID-19), but its treatment effects and safety are unclear.

Purpose: This study reviews the effect and safety of CHM granules in the treatment of patients with severe COVID-19.

Methods: We conducteda single-center, retrospective study on patients with severe COVID-19 in a designated hospital in Wuhan from January 15, 2020 to March 30, 2020. The propensity score matching (PSM) was used to assess the effect and safety of the treatment using CHM granules. The ratio of patients who received treatment with CHM granules combined with usual care and those who received usual care alone was 1:1. The primary outcome was the time to clinical improvement within 28 days, defined as the time taken for the patients' health to show improvement by decline of two categories (from the baseline) on a modified six-category ordinal scale, or to be dischargedfrom the hospital before Day 28.

Results: Using PSM, 43 patients (45% male) aged 65.6 (57-70) yearsfrom each group were exactly matched. No significant difference was observed in clinical improvement of patients treated with CHM granules compared with those who received usual (p = 0.851). However, the use of CHM granules reduced the 28-day mortality (p = 0.049) and shortened the duration of fever (4 days vs. 7 days, p = 0.002). The differences in the duration of cough and dyspnea and the difference in lung lesion ratio on computerized tomography scans were not significant.Commonly,patients in the CHM group had an increased D-dimer level (p = 0.036).

Conclusion: Forpatients with severe COVID-19, CHM granules, combined with usual care, showed no improvement beyond usual care alone. However, the use of CHM granules reduced the 28-day mortality rate and the time to fever alleviation. Nevertheless, CHM granules may be associated with high risk of fibrinolysis.
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http://dx.doi.org/10.1016/j.phymed.2020.153404DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642753PMC
May 2021

Evidence-based Chinese medicine for the response to public health emergencies: The Guangzhou declaration.

J Evid Based Med 2021 Feb 7;14(1):3-4. Epub 2021 Feb 7.

Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Clinical School of Guangzhou University of Chinese Medicine, Guangzhou, China.

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http://dx.doi.org/10.1111/jebm.12422DOI Listing
February 2021

Pyridine-2,6-dicarboxaldehyde-Enabled N-Terminal In Situ Growth of Polymer-Interferon α Conjugates with Significantly Improved Pharmacokinetics and In Vivo Bioactivity.

ACS Appl Mater Interfaces 2021 Jan 31;13(1):88-96. Epub 2020 Dec 31.

Department of Geriatric Dentistry, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing 100081, China.

Polymer-protein conjugates are a class of biohybrids with unique properties that are highly useful in biomedicine ranging from protein therapeutics to biomedical imaging; however, it remains a considerable challenge to conjugate polymers to proteins in a site-specific, mild, and efficient way to form polymer-protein conjugates with uniform structures and properties and optimal functions. Herein we report pyridine-2,6-dicarboxaldehyde (PDA)-enabled N-terminal modification of proteins with polymerization initiators for in situ growth of poly(oligo(ethylene glycol)methyl ether methacrylate) (POEGMA) conjugates uniquely at the N-termini of a range of natural and recombinant proteins in a mild and efficient fashion. The formed POEGMA-protein conjugates showed highly retained in vitro bioactivity as compared with free proteins. Notably, the in vitro bioactivity of a POEGMA-interferon α (IFN) conjugate synthesized by this new chemistry is 8.1-fold higher than that of PEGASYS that is a commercially available and Food and Drug Administration (FDA) approved PEGylated IFN. The circulation half-life of the conjugate is similar to that of PEGASYS but is 46.2 times longer than that of free IFN. Consequently, the conjugate exhibits considerably improved antiviral bioactivity over free IFN and even PEGASYS in a mouse model. These results indicate that the PDA-enabled N-terminal grafting-from method is applicable to a number of proteins whose active sites are far away from the N-terminus for the synthesis of N-terminal polymer-protein conjugates with high yield, well-retained activity, and considerably improved pharmacology for biomedical applications.
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http://dx.doi.org/10.1021/acsami.0c15786DOI Listing
January 2021

A novel doublet extreme learning machines for Delta 3D printer fault diagnosis using attitude sensor.

ISA Trans 2021 Mar 17;109:327-339. Epub 2020 Oct 17.

School of Mechanical Engineering, Dongguan University of Technology, Dongguan, 523808, China.

Extreme learning machine (ELM) has better operation efficiency in fault diagnosis. However, the recognition accuracy of ELM algorithm is actually affected by the activation function. Moreover, most of the testing dataset are coming from high precision and expensive sensors. In this paper, raw data are collected by a low-cost attitude sensor, which is installed on the mobile platform of a delta 3D printer. A doublet activation function is proposed to improve the performance of ELM, named doublet ELM (DELM). The proposed method is evaluated using experimental data collected from the 3D printer, and its advantages are demonstrated by comparing with other activation functions. The experimental results indicate that the proposed method leads to the highest accuracy in different hidden nodes and the testing classification rate achieves 93% and 96% using only 8.33% of the dataset for model training, for R75 and R90 sub-datasets, respectively. Moreover, compared with peer methods, such as random forest, echo state network, and so on, the results show that the present DELM exhibits the best performance in small-sample and improves the accuracy of the 3D printer fault diagnosis.
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http://dx.doi.org/10.1016/j.isatra.2020.10.024DOI Listing
March 2021

Data-Driven Anomaly Detection Approach for Time-Series Streaming Data.

Sensors (Basel) 2020 Oct 2;20(19). Epub 2020 Oct 2.

Key Laboratory of Remote Sensing of Gansu Province, Northwest Institute of Eco-Environment and Resources, Chinese Academy of Sciences, Lanzhou 730000, China.

Recently, wireless sensor networks (WSNs) have been extensively deployed to monitor environments. Sensor nodes are susceptible to fault generation due to hardware and software failures in harsh environments. Anomaly detection for the time-series streaming data of sensor nodes is a challenging but critical fault diagnosis task, particularly in large-scale WSNs. The data-driven approach is becoming essential for the goal of improving the reliability and stability of WSNs. We propose a data-driven anomaly detection approach in this paper, named median filter (MF)-stacked long short-term memory-exponentially weighted moving average (LSTM-EWMA), for time-series status data, including the operating voltage and panel temperature recorded by a sensor node deployed in the field. These status data can be used to diagnose device anomalies. First, a median filter (MF) is introduced as a preprocessor to preprocess obvious anomalies in input data. Then, stacked long short-term memory (LSTM) is employed for prediction. Finally, the exponentially weighted moving average (EWMA) control chart is employed as a detector for recognizing anomalies. We evaluate the proposed approach for the panel temperature and operating voltage of time-series streaming data recorded by wireless node devices deployed in harsh field conditions for environmental monitoring. Extensive experiments were conducted on real time-series status data. The results demonstrate that compared to other approaches, the MF-stacked LSTM-EWMA approach can significantly improve the detection rate (DR) and false rate (FR). The average DR and FR values with the proposed approach are 95.46% and 4.42%, respectively. MF-stacked LSTM-EWMA anomaly detection also achieves a better F score than that achieved by other methods. The proposed approach provides valuable insights for anomaly detection in WSNs by detecting anomalies in the time-series status data recorded by wireless sensor nodes.
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http://dx.doi.org/10.3390/s20195646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582627PMC
October 2020

Temperature-triggered micellization of interferon alpha-diblock copolypeptide conjugate with enhanced stability and pharmacology.

J Control Release 2020 12 6;328:444-453. Epub 2020 Sep 6.

Department of Geriatric Dentistry, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing 100081, PR China; Biomedical Engineering Department, Peking University, Beijing 100191, PR China. Electronic address:

Polypeptides are useful in designing protein-polypeptide conjugates for therapeutic applications; however, they are not satisfactory in improving the stability of therapeutic proteins and extending their in vivo half-life. Here we show that thermally-induced self-assembly (TISA) of elastin-like polypeptide diblock copolymer fused interferon alpha (IFNα-ELP) into a spherical micelle can dramatically enhance the proteolytic stability of IFNα. Notably, the circulation half-life of IFNα-ELP micelle (54.7 h) is 124.3-, 5.7-, and 1.4-time longer than those of free IFNα (0.44 h), freely soluble IFNα-ELP (9.6 h), and PEGylated IFNα (39.0 h), respectively. Importantly, in a mouse model of ovarian tumor, IFNα-ELP micelle exhibited significantly enhanced tumor retention and antitumor efficacy over free IFNα, freely soluble IFNα-ELP, and even PEGylated IFNα. These findings provide a thermoresponsive supramolecular strategy of TISA to design protein-diblock copolypeptide conjugate micelles with enhanced stability and pharmacology.
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http://dx.doi.org/10.1016/j.jconrel.2020.08.065DOI Listing
December 2020

The add-on effect of Chinese herbal medicine on COVID-19: A systematic review and meta-analysis.

Phytomedicine 2021 May 11;85:153282. Epub 2020 Jul 11.

Guangdong Provincial Hospital of Chinese Medicine, Guangdong Provincial Academy of Chinese Medical Sciences, The Second Clinical School of Guangzhou University of Chinese Medicine, Guangzhou, China; Guangdong Provincial Key Laboratory of Research on Emergency in TCM, Guangzhou, China. Electronic address:

Background: Chinese herbal medicine (CHM) is thought to be a potential intervention in the treatment of coronavirus disease (COVID-19).

Purpose: This study aimed to investigate the efficacy and safety of CHM or CHM combination therapy for COVID-19.

Study Design: Systematic review and meta-analysis METHODS: We searched for relevant studies in the CNKI, CBM, Wanfang Data, PubMed, Cochrane Library, Embase, and other resources from their inception to April 15, 2020. Randomized controlled trials, cohort studies, and case-control studies on CHM or CHM combination therapy for COVID-19 were included. Meta-analysis was performed according to the Cochrane Handbook.

Results: Overall, 19 studies with 1474 patients were included. Meta-analysis showed that the overall clinical effectiveness (OR = 2.67, 95% CI 1.83-3.89, I = 0%), improvement in the CT scan (OR = 2.43, 95% CI 1.80-3.29, I = 0%), percentage of cases turning to severe/critical (OR = 0.40, 95% CI 0.24-0.67, I = 17.1%), reverse transcription-polymerase chain reaction (RT-PCR) negativity rate (OR = 2.55, 95% CI 1.06-6.17, I = 56.4%) and disappearance rate of symptoms (fever, cough, and fatigue) were superior by combined CHM treatment of COVID-19. However, there was no statistical difference between the two groups in terms of length of hospital stay (WMD = -0.46, 95% CI -3.87 - 2.95, I = 99.5%), and rate of adverse effects (OR = 1.21, 95% CI 0.48-3.07, I = 43.5%). The quality of evidence was very low to low.

Conclusion: The combined treatment of COVID-19 with Chinese and Western medicine may be effective in controlling symptoms and reducing the rate of disease progression due to low quality evidence.
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http://dx.doi.org/10.1016/j.phymed.2020.153282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831541PMC
May 2021

The transcriptional reprograming and functional identification of WRKY family members in pepper's response to Phytophthora capsici infection.

BMC Plant Biol 2020 Jun 3;20(1):256. Epub 2020 Jun 3.

National Education Minister Key Laboratory of Plant Genetic Improvement and Comprehensive Utilization, Fujian Agriculture and Forestry University, Fuzhou, 350002, Fujian, China.

Background: Plant transcription factors (TFs) are key transcriptional regulators to manipulate the regulatory network of host immunity. However, the globally transcriptional reprogramming of plant TF families in response to pathogens, especially between the resistant and susceptible host plants, remains largely unknown.

Results: Here, we performed time-series RNA-seq from a resistant pepper line CM334 and a susceptible pepper line EC01 upon challenged with Phytophthora capsici, and enrichment analysis indicated that WRKY family most significantly enriched in both CM334 and EC01. Interestingly, we found that nearly half of the WRKY family members were significantly up-regulated, whereas none of them were down-regulated in the two lines. These induced WRKY genes were greatly overlapped between CM334 and EC01. More strikingly, most of these induced WRKY genes were expressed in time-order patterns, and could be mainly divided into three subgroups: early response (3 h-up), mid response (24 h-up) and mid-late response (ML-up) genes. Moreover, it was found that the responses of these ML-up genes were several hours delayed in EC01. Furthermore, a total of 19 induced WRKY genes were selected for functional identification by virus-induced gene silencing. The result revealed that silencing of CaWRKY03-6, CaWRKY03-7, CaWRKY06-5 or CaWRKY10-4 significantly increase the susceptibility to P. capsici both in CM334 and EC01, indicating that they might contribute to pepper's basal defense against P. capsici; while silencing of CaWRKY08-4 and CaWRKY01-10 significantly impaired the disease resistance in CM334 but not in EC01, suggesting that these two WRKY genes are prominent modulators specifically in the resistant pepper plants.

Conclusions: These results considerably extend our understanding of WRKY gene family in pepper's resistance against P. capsici and provide potential applications for genetic improvement against phytophthora blight.
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http://dx.doi.org/10.1186/s12870-020-02464-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7271409PMC
June 2020

Head-to-tail macrocyclization of albumin-binding domain fused interferon alpha improves the stability, activity, tumor penetration, and pharmacology.

Biomaterials 2020 08 23;250:120073. Epub 2020 Apr 23.

Department of Geriatric Dentistry, Beijing Laboratory of Biomedical Materials, Peking University School and Hospital of Stomatology, Beijing, 100081, China; Biomedical Engineering Department, Peking University, Beijing, 100191, China. Electronic address:

Genetic fusion of a therapeutic protein to albumin can improve its stability and pharmacokinetics, but it usually leads to considerably reduced bioactivity and poor tumor penetration due to increased steric hindrance, resulting in limited antitumor efficacy. Herein we report head-to-tail macrocyclization of albumin-binding domain fused interferon alpha (IFN-ABD) to form a cyclic fusion protein (c-IFN-ABD) with well-retained albumin-binding affinity. Notably, c-IFN-ABD showed not only greater thermal and enzymatic stability and thus antiproliferative activity than IFN-ABD and IFN due to the macrocyclization, but also exhibited considerably better pharmacokinetics than IFN and cyclic IFN owing to the albumin-binding affinity. More importantly, c-IFN-ABD showed deeper tumor penetration, greater tumor retention, and thus higher antitumor efficiency than all the controls without significant systemic side effects in mice bearing melanoma. These results implicate that head-to-tail macrocyclization of ABD fused therapeutic proteins is an enabling strategy for the design of highly potent protein therapeutics for tumor therapy.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120073DOI Listing
August 2020

Generative Transfer Learning for Intelligent Fault Diagnosis of the Wind Turbine Gearbox.

Sensors (Basel) 2020 Mar 2;20(5). Epub 2020 Mar 2.

School of Mechanical Engineering, Dongguan University of Technology, Dongguan 523808, China.

Intelligent fault diagnosis algorithms based on machine learning and deep learning techniques have been widely used in industrial applications and have obtained much attention as well as achievements. In real industrial applications, working loads of machines are always changing. Hence, directly applying the traditional algorithms will cause significant degradation of performance with changing conditions. In this paper, a novel domain adaptation method, named generative transfer learning (GTL), is proposed to tackle this problem. First, raw datasets were transformed to time-frequency domain based on short-time Fourier transformation. A domain discriminator was then built to distinguish whether the data came from the source or the target domain. A target domain classification model was finally acquired by the feature extractor and the classifier. Experiments were carried out for the fault diagnosis of a wind turbine gearbox. The t-distributed stochastic neighbor embedding technique was used to visualize the output features for checking the effectiveness of the proposed algorithm in feature extraction. The results showed that the proposed GTL could improve classification rates under various working loads. Compared with other domain adaptation algorithms, the proposed method exhibited not only higher accuracy but faster convergence speed as well.
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http://dx.doi.org/10.3390/s20051361DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7085519PMC
March 2020

Polymerization-Induced Coassembly of Enzyme-Polymer Conjugates into Comicelles with Tunable and Enhanced Cascade Activity.

Nano Lett 2020 02 9;20(2):1383-1387. Epub 2020 Jan 9.

Department of Geriatric Dentistry, Beijing Laboratory of Biomedical Materials , Peking University School and Hospital of Stomatology , Beijing 100081 , China.

Living organisms utilize spatially organized enzyme complexes to carry out signal transduction and metabolic pathways in an efficient and specific way. Herein, inspired by natural enzyme complexes, we report the polymerization-induced coassembly (PICA) of enzyme-polymer conjugates into comicelles with tunable and enhanced cascade activity by using the cascade reaction implemented by glucose oxidase (GOX) and horseradish peroxidase (HRP) as a model system. Notably, the cascade activity of GOX/HRP-polymer comicelles monotonically increases with the GOX/HRP ratio. The cascade activity of GOX/HRP-polymer comicelles is up to 4.9 times higher than that of free GOX and HRP mixtures at the same GOX/HRP ratio. We further demonstrate that our system can quickly detect glucose in contrast with a commercially available glucose assay kit. These findings provide a new and general method of PICA for the controlled construction of artificial enzyme complexes with tunable and enhanced activity in enzyme cascades for advanced biomedical applications.
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http://dx.doi.org/10.1021/acs.nanolett.9b04959DOI Listing
February 2020

The add-on effect of dengzhan shengmai capsules on secondary prevention of ischemic stroke: A multicentre, randomised, placebo-controlled clinical trial.

Complement Ther Med 2019 Oct 24;46:189-194. Epub 2019 Aug 24.

Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China. Electronic address:

Objective: The Dengzhan Shengmai (DZSM) capsule is a commercially available type of Chinese herbal medicine frequently administered to improve neurological impairment after stroke. Its ability to prevent recurrent stroke, however, has not been determined. This study therefore evaluated the ability of DZSM as an add-on to conventional secondary preventive agents to prevent recurrent ischemic stroke.

Methods: In this randomised, double-blind, placebo-controlled trial, conducted at 83 hospitals in Mainland China, 3143 patients in 14-180 days after the initial onset of ischemic stroke, were randomly allocated to the DZSM (0.36 g, twice daily for 12 months) or the placebo group. All patients in both groups received standard secondary preventive medications. The primary outcome was the 1-year incidence of stroke. Between group differences were assessed using the Cox proportional hazards model.

Results: Intent-to-treat analysis showed that 58 (3.8%) participants in the DZSM group and 82 (5.4%) in the placebo group experienced new stroke events (hazard ratio = 0.70, 95% confidence interval = 0.50-0.98, P = 0.036). The type and incidence of adverse events were similar in the DZSM and placebo groups.

Conclusions: The addition of DZSM capsules to standard secondary preventive agents provides additional benefits after the initial onset of ischemic stroke, reducing recurrent stroke without increasing severe adverse events. However, further study is needed to elucidate the role of DZSM on the updated practice of conventional secondary prevention for ischemic stroke.
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http://dx.doi.org/10.1016/j.ctim.2019.08.015DOI Listing
October 2019

Thermoresponsive and Protease-Cleavable Interferon-Polypeptide Conjugates with Spatiotemporally Programmed Two-Step Release Kinetics for Tumor Therapy.

Adv Sci (Weinh) 2019 Aug 14;6(16):1900586. Epub 2019 Jun 14.

Department of Geriatric Dentistry Beijing Laboratory of Biomedical Materials Peking University School and Hospital of Stomatology Beijing 100081 P. R. China.

Protein-polymer conjugates show improved pharmacokinetics but reduced bioactivity and tumor penetration as compared to native proteins, resulting in limited antitumor efficacy. To address this dilemma, genetic engineering of a body temperature-responsive and matrix metalloproteinase (MMP)-cleavable conjugate of interferon alpha (IFNα) and elastin-like polypeptide (ELP) is reported with spatiotemporally programmed two-step release kinetics for tumor therapy. Notably, the conjugate could phase separate to form a depot postsubcutaneous injection, leading to 1-month zero-order release kinetics. Furthermore, it could selectively be cleaved by MMPs that are overexpressed in tumors to release IFNα from ELP and thus to recover the bioactivity of IFNα. Consequently, it exhibits dramatically enhanced tumor accumulation, tumor penetration, and antitumor efficacy as compared to free IFNα in two mouse models of melanoma and ovarian tumor. These findings may provide an intelligent technology of thermoresponsive and protease-cleavable protein-polymer conjugates with spatiotemporally programmed two-step release kinetics for tumor treatment.
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http://dx.doi.org/10.1002/advs.201900586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6702759PMC
August 2019

Safety and Efficacy of the C-117 Formula for Vulnerable Carotid Artery Plaques (Spchim): A Randomized Double-Blind Controlled Pilot Study.

Evid Based Complement Alternat Med 2019 17;2019:9746492. Epub 2019 Jul 17.

The 2nd Teaching Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Traditional Chinese Medicine), 111 Da'de Road, Yuexiu District, Guangzhou, Guangdong Province 510120, China.

Objective: To investigate the safety and efficacy of the Herbal Medicine C-117 (C-117) formula in the treatment of carotid atherosclerotic vulnerable plaques.

Methods: This was a prospective, single-centre, randomized, double-blind study. A total of 120 eligible patients were randomly divided into two groups to receive the C-117 formula or placebo. As the basic treatment, both groups were treated according to the using statins to regulate blood lipids, blood pressure lowering drugs, drugs for controlling blood sugar, and antiplatelet drugs according to the indications. The primary outcomes were the change in stability, the mean change of the plaque Crouse score, and the area and number of bilateral carotid artery plaques before and after 6 months of treatment. The secondary outcomes were the total number of cardiocerebrovascular events during the treatment and follow-up and the mean changes of lipid levels.

Result: After 180 days of treatment, the plaque Crouse score(95% CI, 0.39 (0.01-0.77), P=0.046) and plaque area (95% CI, 2.14 (-10.10-14.39), P=0.727) were lower in the C-117 formula group than that before treatment. The plaque Crouse score of the control group (95% CI, 0.17 (-0.24-0.57), P=0.417) was lower than that before treatment, while the plaque area (95% CI, -0.35 (-9.35-8.65), P=0.938) increased, but without statistical significance. There was no significant difference in the reduction of the intima-media thickness (IMT), plaque Crouse score, or plaque area between the two groups after treatment (P>0.05). Subgroup analysis of patients whose Lipitor medication time ≥ 20% of the 6-month treatment showed that the levels of total cholesterol, triglycerides, and low-density lipoprotein were lower in the two groups after treatment than before, and the low-density lipoprotein levels in the C-117 formula group significantly decreased (95% CI, 2.99 (-0.08-0.39), P=0.005), but there was no statistical difference between the two groups after treatment (P>0.05). No serious adverse events occurred in the two groups after 180 days of treatment.

Conclusion: The C-117 formula may be antiatherosclerotic by strengthening statins to reduce the low-density lipoprotein levels and reducing the carotid plaque Crouse scores. Clinical trials with large sample sizes, long-term interventions, and follow-up are needed to investigate the efficacy of the C-117 formula.

Clinical Trials Registration: This trial is registered with clinicaltrials.gov identifier: NCT03072225 (registered retrospectively on 1st March 2017).
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http://dx.doi.org/10.1155/2019/9746492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662507PMC
July 2019

Safety and efficacy of herbal medicine for acute intracerebral hemorrhage (CRRICH): a multicentre randomised controlled trial.

BMJ Open 2019 05 9;9(5):e024932. Epub 2019 May 9.

Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.

Objective: To evaluate the safety and efficacy of removing blood stasis (RBS) herbal medicine for the treatment of acute intracerebral haemorrhage (AICH) within a 6-hour time window.

Study Design: A randomised, multicentre, double-blind, placebo-controlled study performed in 14 hospitals in China.

Participants And Interventions: Patients with AICH were randomly assigned to receive a placebo, the ICH-1 (Intracerebral Haemorrhage) formula (eight herbs, including the RBS herbs and ) or the ICH-2 formula (six herbs without the RBS herbs and ) within 6 hours of ICH onset.

Outcomes: The primary safety outcome was the incidence of haematoma enlargement at 24 hours and at 10 days after treatment. The secondary outcome was the incidence of poor prognosis (mortality or modified Rankin Scale score ≥5) assessed at 90 days after symptom onset.

Results: A total of 324 subjects were randomised between October 2013 and May 2016: 105 patients received placebo; 108 patients received the ICH-1 formula; and 111 patients received the ICH-2 formula. The incidence of haematoma enlargement at 24 hours was 7.8% in the placebo group, 12.3% in the ICH-1 group and 7.5% in the ICH-2 group; the incidence of haematoma enlargement on day 10 was 1.1% in the placebo group, 1.1% in the ICH-1 group, and 3.1% in the ICH-2 group, with no significant differences among the groups (P>0.05). The mortality rates were 3.8% in the placebo group, 2.8% in the ICH-1 group, and 0.9% in the ICH-2 group; the incidences of poor prognosis were 7.1% in the placebo group, 6.0% in the ICH-1 group and 4.8% in the ICH-2 group at 3 months, with no significant differences among the groups (p>0.05). However, the overall frequency of treatment-emergent adverse events in the ICH-1 group (12.1%) was higher among the three groups (5.8% and 2.8%, respectively, p0.05). All three cases of serious adverse events were in the ICH-1 group.

Conclusions: Ultra-early administration of ICH-1 formula for AICH patients did not exert significant beneficial effects on clinical outcomes but increased the risk of bleeding, which probably resulted from the inclusion of RBS herbal medicines in ICH-1.

Trialregistration Number: NCT01918722.
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http://dx.doi.org/10.1136/bmjopen-2018-024932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528012PMC
May 2019

One-month zero-order sustained release and tumor eradication after a single subcutaneous injection of interferon alpha fused with a body-temperature-responsive polypeptide.

Biomater Sci 2018 Dec;7(1):104-112

Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.

Most therapeutic proteins except antibodies necessitate frequent dosing at high concentrations due to their short circulation half-lives, leading to limited therapeutic efficacy, serious adverse side effects and poor patient compliance. Herein we report a strategy of thermoresponsive polypeptide fusion to genetically engineer a super-long-acting interferon alpha fused with a body-temperature-responsive polypeptide. After a single subcutaneous injection in a mouse model, this interferon alpha can in situ form a depot to show a one-month zero-order sustained release, which would enable a once-trimonthly dosing in humans. As a result, it exhibits greatly enhanced tumor accumulation and tumor eradication as well as substantially improved tolerability and biosafety. This strategy provides a promising solution to dramatically enhance the pharmacological performance of therapeutic proteins with short circulation half-lives while reducing the side effects.
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http://dx.doi.org/10.1039/c8bm01096jDOI Listing
December 2018

Clinical Evaluation of Herbal Medicine (ICH-012) in Treating Acute Cerebral Haemorrhage: Safety and Efficacy from 6- to 72-Hour Time Window (CRRICHTrial-II).

Evid Based Complement Alternat Med 2018 26;2018:3120179. Epub 2018 Aug 26.

Brain Center, The Guangdong Provincial Hospital of Chinese Medicine, The Second Teaching Hospital of Guangzhou University of Chinese Medicine, China.

Background: Hypertensive intracerebral haemorrhage (HICH), which is characterized by rapid change, high morbidity, and mortality, is extremely dangerous. Both medical and surgical treatments lack definitive evidence and remain controversial. A prospective RCT that we have conducted has shown that the usage of the herbal medicine ICH-012 within 6 h of the event may increase the risk of haematoma enlargement and gastrointestinal bleeding. However, the volume of haematoma remains stable after 6 h. Thus, we will increase the time window to the period from 6 to 72 h after onset to evaluate the safety and efficacy of ICH-012 treating ICH (ClinicalTrial.gov ID: NCT03354026).

Methods/design: The CRRICHTrial-II study, a prospective, double-blinded, controlled, multicentre RCT, includes three groups: A, B, and C. Group A patients were treated with 8 herbal medicines (with 2 herbal medicines of Hirudo and Tabanus as well as 6 other combined herbal medicines of Group B) and Group C were placebo. Patients should meet all the inclusion criteria: age between 18 and 80 and diagnosis of HICH by brain CT scan between 6 and 72 h from the onset. The CT scan will be taken at four critical time points: baseline, between 6 and 72h, 24h after onset, and between 10 and 14 days after onset. The drug intervention lasts 10 days, and there is a follow-up visit taken after 90 days. The haematoma enlargement after 24 h onset as demonstrated by CT is the primary outcome.

Discussion: A large amount of data from high-quality RCTs is needed for the extensive clinical application of herbal medicine. The CRRICHTrial-II will evaluate the safety and effectiveness of ICH-012 in a safer time window between 6 and 72 h and investigate the possible mechanisms of action and direction of herbal medicine in the haematoma growth after HICH. ClinicalTrial.gov, ID: NCT03354026, is registered on 23rd Nov. 2017.
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http://dx.doi.org/10.1155/2018/3120179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6129335PMC
August 2018

Polymerization Induced Self-Assembly of a Site-Specific Interferon α-Block Copolymer Conjugate into Micelles with Remarkably Enhanced Pharmacology.

J Am Chem Soc 2018 08 9;140(33):10435-10438. Epub 2018 Aug 9.

Department of Biomedical Engineering, School of Medicine , Tsinghua University , Beijing 100084 , China.

Conjugating a hydrophilic and protein-resistant polymer to a protein is a widely used strategy to extend the in vivo half-life of the protein; however, the benefit of the half-life extension is usually limited by the bioactivity decrease. Herein we report a supramolecular self-assembly strategy of site-specific in situ polymerization induced self-assembly (SI-PISA) to address the dilemma. An amphiphilic block copolymer (POEGMA-PHPMA) was directly grown from the C-terminus of an important therapeutic protein interferon-α (IFN) to in situ form IFN-POEGMA-PHPMA conjugate micelles. Notably, the in vitro bioactivity of the micelles was 21.5-fold higher than that of the FDA-approved PEGylated interferon-α PEGASYS. Particularly, the in vivo half-life of the micelles (83.8 h) was 1.7- and 100-fold longer than those of PEGASYS (49.5 h) and IFN (0.8 h), respectively. In a tumor-bearing mouse model, the micelles completely suppressed tumor growth with 100% animal survival, whereas at the same dose, PEGASYS and IFN were much less effective. These findings suggest that SI-PISA is promising as a next-generation technology to remarkably enhance the pharmacological performance of therapeutic proteins with short circulation half-lives.
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http://dx.doi.org/10.1021/jacs.8b06013DOI Listing
August 2018

Tumour-homing chimeric polypeptide-conjugated polypyrrole nanoparticles for imaging-guided synergistic photothermal and chemical therapy of cancer.

Theranostics 2018 3;8(10):2634-2645. Epub 2018 Apr 3.

Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084, China.

Near-infrared (NIR)-absorbing conjugated polymer nanoparticles are interesting for imaging-guided combination therapy, especially for synergistic photothermal therapy and chemotherapy; however, most of them target tumours passively through the enhanced permeability and retention (EPR) effect, leading to low utilization efficiency. To address this problem, we report an active tumour-targeting strategy of tumour-homing chimeric polypeptide-conjugated NIR-absorbing conjugated-polymer nanoparticles as a new class of drug nanocarriers for imaging-guided combination therapy of cancer. A tumour-homing chimeric polypeptide C-ELP-F3 was genetically engineered, and chemoselectively conjugated to polypyrrole (PPy) nanoparticles via a facile thiol-maleimide coupling reaction to form ELP-F3 conjugated PPy (PPy-ELP-F3) nanoparticles. Doxorubicin (DOX) was physically adsorbed onto PPy-ELP-F3 nanoparticles to yield DOX-loaded PPy-ELP-F3 (DOX/PPy-ELP-F3) nanoparticles. The physicochemical properties of DOX/PPy-ELP-F3 were characterized. The pharmacokinetics of DOX/PPy-ELP-F3 was studied in a mouse model. The photoacoustic imaging and photothermal imaging of tumours were tested in a melanoma-bearing mouse model. The photothermal-chemical combination therapy of tumours was investigated by using melanoma cells and in a melanoma-bearing mouse model. DOX/PPy-ELP-F3 nanoparticles showed enhanced cytotoxicity to melanoma cells and improved tumour-targeting efficiency , as compared with both DOX/PPy-ELP nanoparticles without the tumour-homing function and free DOX. The photothermal effect of DOX/PPy-ELP-F3 nanoparticles could accelerate the release of DOX from PPy-ELP-F3. Under the guidance of photoacoustic and photothermal imaging, the synergy of photothermal and chemical therapy could completely abolish tumours without detectable systemic toxicity. Tumour-homing chimeric polypeptide-conjugated NIR-absorbing conjugated-polymer nanoparticles are promising as a new multifunctional drug delivery platform for highly-efficient imaging guided combination therapy.
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http://dx.doi.org/10.7150/thno.24705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5956998PMC
May 2019

Deferoxamine therapy for intracerebral hemorrhage: A systematic review.

PLoS One 2018 22;13(3):e0193615. Epub 2018 Mar 22.

The 2nd Teaching Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangdong Province Key Laboratory of Emergency Medicine of TCM, Guangzhou, Guangdong, China.

Intracerebral hemorrhage (ICH) is a significant cause of morbidity and mortality worldwide. Several recent controlled trials have reported that deferoxamine (DFX) therapy appears to be effective for ICH. The aim of this study was to perform a systematic review of DFX therapy for ICH patients and evaluate the efficacy and safety of DFX therapy for ICH patients. We searched Medline, Embase, the Cochrane Database of Systematic Reviews, clinicaltrials.gov, all Chinese databases and the reference lists of all included studies and review articles. We then performed a systematic review of studies involving the administration of DFX following ICH. Only two studies were included, a prospective, randomized clinical trial and a prospective,observational cohort study with concurrent groups. Qualitative analysis of each study revealed one randomized controlled trial of moderate quality with a moderate risk of bias and one observational cohort study of moderate quality with a moderate risk of bias. DFX may be an effective treatment for edema in patients with ICH. However, due to the small number of trials and small sample sizes of these trials, insufficient evidence exists to determine the effect of DFX on neurologic outcomes after ICH and the safety of this intervention. Further investigation is required before DFX can become a routine treatment for ICH.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0193615PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863956PMC
June 2018

Clinical re-evaluation of removing blood stasis therapy in treating acute intracerebral hemorrhage safety and efficacy: a protocol for a randomized, controlled, multicenter study (CRRICH Trial).

Springerplus 2016 1;5(1):1466. Epub 2016 Sep 1.

No. 1 Neurology Department, The 2nd Teaching Hospital of Guangzhou University of Chinese Medicine, Guangdong Provincal Hospital of Chinese Medicine, Guangdong Province Key Laboratory of Emergency medicine of TCM., 111 Da'de Road, Yuexiu District, Guangzhou, Guangdong China.

Background: Hypertensive intracerebral hemorrhage (HICH) is one of the most devastating forms of stroke. Currently, no specific therapies for HICH except general medical care. However, in China, medicine of promoting blood circulation (PBC) and removing blood stasis (RBS) are widely and efficiently used to treat HICH and become a potentially effective treatment for the secondary effects of HICH to alleviate brain injury, accelerate neuronal recovery, and improve the prognosis. In order to evaluate the safety and effect of PBC and RBS herbal drugs, we design a prospective, randomized, open, double-blind controlled clinical trial on the hematoma enlargement in HICH patients treating with PBC and RBS herbal medicine within 6 h time window from the symptom onset.

Methods/design: A multicenter, three-group, prospective, randomized, double-blinded and placebo-controlled clinical trial. Patients aged 18 or older with HICH confirmed by CT scan within 6 h from the onset are included. 360 patients will be randomized to 3 groups (PBC & RBS & Placebo) within 6 h of ictus. Stratified block randomization is undertaken using a sequentially numbered and opaque envelope. All subjects must take medicine within 6 h of ictus and have another CT scan at about 24 h to confirm hematoma expansion. A postal questionnaire to the patients to evaluate their recorvery at 3 months. Primary outcome is the percent change in the volume of hematoma at 24 h. Secondary outcomes include: mortality, disability, serious adverse events, etc.

Conclusions: The CRRICH Trial is expected to confirm the safety and effect of acute intracerebral hemorrhage treated within 6 h of ictus with "RBS" therapy and to determine whether the traditional therapy can cause hematoma growth after intracerebral hemorrhage.

Discussions: This is the first  prospective, multicenter, randomized, placebo-controlled clinical trial to investigate herbal medicine whether can induce the incidence of hematoma enlargement of AICH patient within the 6 h time window from onset. We need the data to keep the herbal clinical usage safety. Trial registration clinicaltrials.gov: NCT01918722.
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http://dx.doi.org/10.1186/s40064-016-3136-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007233PMC
September 2016

Can Herbal Medicine Cause Hematoma Enlargement of Hypertensive Intracerebral Hemorrhage within 24 hrs Time Window? A Retrospective Study of 256 Cases from a Single Center in China.

Evid Based Complement Alternat Med 2015 19;2015:868731. Epub 2015 Feb 19.

No. 1 Neurology Department, Guangdong Province Hospital of TCM, The Second Teaching Hospital of Guangzhou University of Traditional Chinese Medicine, 111 Da'de Road, Yuexiu District, Guangzhou, Guangdong Province 510120, China.

A retrospective review was performed of consecutive patients presenting with HICH within 24 hours of ictus presenting between March 2008 and March 2013 who were diagnosed as having HICH by CT scan. Of the 256 patients who matched study inclusion standard, 43 patients hematoma was enlarged (16.8%). The number of the patients who did not take PBC or RBC herbal medicine, took the PBC herbal medicine, and took RBS herbal medicine was 19 (44.2%), 2 (4.7%), and 22 (51.2%) in hematoma enlargement group and 78 (36.6%), 26 (12.2%), and 109 (51.2%) in nonhematoma enlargement group, individually. There was no significant difference between two groups (P = 0.671). PBC and RBS herbal medicine did not increase the incidence of hematoma expansion of ICH within 24 hours after onset of symptom.
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http://dx.doi.org/10.1155/2015/868731DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4351003PMC
March 2015

Effect of P38 MAPK on the apoptosis of human lung adenocarcinoma cell induced by the spider venom.

Thorac Cancer 2010 07 12;1(2):77-82. Epub 2010 Apr 12.

Tumor Institute, No.4 Hospital of Hebei Medical University, Shijiazhuang, China Research Center, No.4 Hospital of Hebei Medical University, Shijiazhuang, China College of life Science, Hebei Normal University, Shijiazhuang, China.

Background: The venom of spiders may inspire new drugs to treat carcinoma. The aim of this study was to investigate the effect of P38 MAPK on tumor necrosis factor-related apoptosis of lung adenocarcinoma cell line by spider venom.

Methods: Lung adenocarcinoma A549 cells were cultured in PRMI-1640 medium and the apoptosis rate was observed after treatment with spider venom with a flow cytometer. The expression of P38 MAPK protein in lung cancer cells was analyzed using Western blot.

Results: After targeting spider venom intervention, the expression of P38 MAPK in the cells compared to the control group was significantly down-regulated. The anticancer potency of spider venom is associated with decreased expression of P38 MAPK of lung adenocarcinoma cancer cells.
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http://dx.doi.org/10.1111/j.1759-7714.2010.00009.xDOI Listing
July 2010

Aberrant methylation of thrombospondin-1 and its association with reduced expression in gastric cardia adenocarcinoma.

J Biomed Biotechnol 2010 15;2010:721485. Epub 2010 Mar 15.

Department of Laboratory of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.

Aim: Investigate the promoter methylation of the Thrombospondin-1 (TSP1) gene in gastric cardia adenocarcinoma (GCA).

Methods: MSP approach, immunohistochemistry method, and RT-PCR were used respectively to examine the promoter methylation of TSP1, its protein and mRNA expression in tumors and corresponding normal tissues. The expression and concentration of TGF-beta1 were examined respectively by immunohistochemistry and ELISA method. The status of T cell immunity was examined by Flow cytometry analysis.

Results: TSP1 was methylated in 34/96 (35.4%) tumor specimens, which was significantly higher than that in corresponding normal tissues (P < .001). Protein and mRNA expression of TSP1 in GCA tumor tissues were reduced significantly and were associated with TSP1 methylation. The protein expression of TGF-beta1 was significantly higher in tumor tissues (P < .001) and was associated with TNM stage and histological differentiation. The concentration of active and total TGF-beta1 did not show significant difference between the GCA patients with hypermethylation of TSP1 and without methylation of TSP1 (P > .05). The function of T cell immunity was significantly different between the GCA patients with hypermethylation of TSP1 and without methylation of TSP1.

Conclusions: Epigenetic silencing of TSP1 gene by promoter hypermethylation may play an important role in GCA.
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http://dx.doi.org/10.1155/2010/721485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2838370PMC
June 2010

Dual interference with novel genes mfgl2 and mTNFR1 ameliorates murine hepatitis virus type 3-induced fulminant hepatitis in BALB/cJ mice.

Hum Gene Ther 2010 Aug;21(8):969-77

Department and Institute of Infectious Disease, Huazhong University of Science and Technology, 430074 Wuhan, People's Republic of China.

Our studies and those of many others have implicated hepatocyte necrosis and apoptosis mediated by fibrinogen-like protein-2 (fgl2) prothrombinase and tumor necrosis factor receptor (TNFR) in the development of fulminant viral hepatitis, a disease with a mortality rate greater than 80% in cases lacking immediate organ transplantation. This study was designed to explore the efficacy of dual short hairpin RNA (shRNA) interference with fgl2 and TNFR1 in the treatment of murine hepatitis virus strain 3 (MHV-3)-induced fulminant hepatitis in mice. Plasmids p-mfgl2shRNA and p-mTNFR1shRNA, complementary to the sequences for mfgl2 and mTNFR1, were constructed. Plasmids pEGFP-mfgl2 and pEGFP-mTNFR1 expressing mfgl2-EGFP (enhanced green fluorescent protein) and mTNFR1-EGFP fusion proteins were also constructed to screen the inhibitory effect of p-mfgl2shRNA and p-mTNFR1shRNA on mfgl2 and mTNFR1 expression. Cotransfection of individual shRNA plasmids and pcDNA3.0-mfgl2 and pcDNA3.0-mTNFR1 expression constructs into Chinese hamster ovary (CHO) cells significantly inhibited mfgl2 and mTNFR1 gene expression, as evidenced by fluorescence microscopy, reverse transcription-polymerase chain reaction, and Western blotting. In vivo hydrodynamic delivery of dual-interference shRNA plasmids for mfgl2 and mTNFR1 significantly decreased mfgl2 and mTNFR1 expression; markedly ameliorated fibrin deposition, hepatocyte necrosis, and apoptosis; and prolonged survival against fulminant viral hepatitis induced by MHV-3 in BALB/cJ mice compared with mfgl2 or TNFR1 single-gene interference. These results indicate that in vivo interference with genes for more than one key target provides superior treatment efficacy compared with single-gene interference.
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http://dx.doi.org/10.1089/hum.2009.177DOI Listing
August 2010

[UV-induced DNA mutation of peach aphid].

Ying Yong Sheng Tai Xue Bao 2006 Jul;17(7):1245-9

College of Plant Protection, Northwest Sci-Tech University of Agriculture and Forestry, Yangling, China.

By using PCR technique and microsatellite marks, this paper studied the DNA polymorphism of peach aphid (Myzus persicae) under UV-radiation. The fragments of three primers were amplified, and the gene diversity and the rate of loci polymorphisms of their genomic DNA, which could reflect the damage degree of DNA after UV-radiation, were measured. The results revealed that after treated with different radiation intensity (15, 30, 45 W) and duration (2, 4, 6 h) , the UV-induced DNA mutations were genetic and could be delivered to F2 generation. The mutations depended on the interaction of radiation intensity and duration. Variance analysis on the gene diversity and the rate of loci polymorphisms showed that there existed a significant difference between UV-treated and control groups, except the rate of loci polymorphisms under 2 h radiation. The average value of the control was higher than that of 2 h radiation treatment. According to the cluster analysis of the genetic distance, the aphids were divided into three groups, i. e., control group, 2 h (15, 30 W) treatment group, and the other, which was consistent with the result of variance analysis.
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July 2006
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