Publications by authors named "Yunlong Chen"

40 Publications

Identification of a Four Cancer Stem Cell-related Gene Signature and Establishment of a Prognostic Nomogram Predicting Overall Survival of Pancreatic Adenocarcinoma.

Comb Chem High Throughput Screen 2022 Jan 20. Epub 2022 Jan 20.

Department of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China | Guangdong Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, China.

Background: Cancer stem cells (CSCs) are now being considered as the initial component in the development of pancreatic adenocarcinoma (PAAD). Our aim was to develop a CSCrelated signature to assess the prognosis of PAAD patients for the optimization of treatment.

Materials And Methods: Differentially expressed genes (DEGs) between pancreatic tumor and normal tissue in the Cancer Genome Atlas (TCGA) were screened out, and the weighted gene correlation network analysis (WGCNA) was employed to identify the CSC-related gene sets. Then, univariate, Lasso Cox regression analyses and multivariate Cox regression were applied to construct a prognostic signature using the CSC-related genes. Its prognostic performance was validated in TCGA and ICGC cohorts. Furthermore, Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors in PAAD, and a prognostic nomogram was established.

Results: The Kaplan-Meier analysis, ROC curve and C-index indicated the good performance of the CSC-related signature at predicting overall survival (OS). Univariate Cox regression and multivariate Cox regression revealed that the CSC-related signature was an independent prognostic factor in PAAD. The nomogram was superior to the risk model and AJCC stage in predicting OS. In terms of mutation and tumor immunity, patients in the high-risk group had higher tumor mutation burden (TMB) scores than patients in the low-risk group, and the immune score and the ESTIMATE score were significantly lower in the high-risk group. Moreover, according to the results of principal component analysis (PCA) and Gene Set Enrichment Analysis (GSEA), the low-risk and high-risk groups displayed different stemness statuses based on the risk model.

Conclusion: Our study identified four CSC-related gene signatures and established a prognostic nomogram that reliably predicts OS in PAAD. The findings may support new ideas for screening therapeutic targets to inhibit stem characteristics and the development of PAAD.
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http://dx.doi.org/10.2174/1386207325666220113142212DOI Listing
January 2022

Peripheral leukemia burden at time of apheresis negatively affects the clinical efficacy of CART19 in refractory or relapsed B-ALL.

Mol Ther Methods Clin Dev 2021 Dec 27;23:633-643. Epub 2021 Oct 27.

Department of Hematology, Beijing Boren Hospital, Beijing 100070, China.

Our previous clinical study achieved complete remission (CR) rates of >90% following chimeric antigen receptor T cells targeting CD19 (CART19) treatment of refractory/relapsed B cell acute lymphoblastic leukemia (r/r B-ALL); however, the influence of the leukemia burden in peripheral blood (PB) blasts remains unclear. Here, we retrospectively analyzed 143 patients treated with CART19 (including 36 patients with PB blasts) to evaluate the effect of peripheral leukemia burden at the time of apheresis. One hundred seventeen patients with high disease burdens achieved 91.5% CR or incomplete count recovery CR and 86.3% minimal residual disease-negative CR, and 26 patients with low disease burdens obtained 96.2% MRD CR. Collectively, 9 of 36 (25%) patients with PB blasts and 2 of 107 (1.87%) patients without PB blasts did not respond to CART19 therapy. The leukemia burden in PB negatively influenced cell characteristics, including the transduction efficiency of CD3 T cells and their fold expansion, and cell dynamics, including peak CART19 proportion and absolute count, fold expansion, and persistence duration. Further studies showed that these patients had higher programmed death-1 expression in CART19 products. Our data imply that PB blasts negatively affected CART19 production and the clinical efficacy of CART19 therapy in patients with r/r B-ALL.
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http://dx.doi.org/10.1016/j.omtm.2021.10.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640733PMC
December 2021

Tug-of-war: molecular dynamometers against living cells for analyzing sub-piconewton interaction of a specific protein with the cell membrane.

Chem Sci 2021 Nov 2;12(43):14389-14395. Epub 2021 Sep 2.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University Nanjing 210023 China

Protein-membrane interactions play important roles in signal transductions and functional regulation of membrane proteins. Here, we design a molecular dynamometer (MDM) for analyzing protein-membrane interaction on living cells. The MDM is constructed by assembling an artificial lipid bilayer and alkylated Cy3-DNA azide (azide-Cy3-C) on a silica bubble. After a functional aptamer is covalently anchored onto the corresponding target protein on a living cell through UV irradiation, azide-Cy3-C is conjugated with the aptamer through a click reaction to produce a "tug-of-war" between the MDM and the cell due to the buoyancy of the silica bubble. This induces the detachment of the protein from the cell membrane or the alkane terminal from the MDM enabling sub-piconewton embedding force measurement by changing the alkane chain length and simple fluorescence analysis. The successful analysis of embedding force variation of a protein on the cell membrane upon post-translational modifications demonstrates the practicability and expansibility of this method for mechanics-related research in biological systems.
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http://dx.doi.org/10.1039/d1sc03059kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8580102PMC
November 2021

ASO Visual Abstract: Laparoscopic in Situ Anatomical Mesohepatectomy for Solitary Massive HCC Using Combined Intrafascial and Extrafascial Approaches with Indocyanine Green Navigation (with Video).

Ann Surg Oncol 2021 Oct 25. Epub 2021 Oct 25.

Department of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

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http://dx.doi.org/10.1245/s10434-021-10968-1DOI Listing
October 2021

Laparoscopic in Situ Anatomical Mesohepatectomy for Solitary Massive HCC Using Combined Intrafascial and Extrafascial Approaches With Indocyanine Green Navigation (with Video).

Ann Surg Oncol 2021 Oct 13. Epub 2021 Oct 13.

Department of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Background: Laparoscopic anatomic mesohepatectomy for patients with hepatocellular carcinoma (HCC) remains technically challenging, especially for those with a massive tumor larger than 10 cm.

Methods: In this study, a 65-year-old man with a 13 × 10-cm solitary liver tumor located at segments 4, 5, and 8 underwent laparoscopic mesohepatectomy. To reduce the possibility of releasing cancer cells from the primary tumor, the in situ resection strategy for tumor removal was implemented. The intrafascial approach was used to dissect the right Glissonean pedicle, to transect the right anterior hepatic artery, and to ligate the right anterior portal vein. The extrafascial and transfissural approach was performed along the umbilical fissure to transect the Glissonean pedicle of segment 4. Indocyanine green (ICG) then was applied using "reverse staining" to visualize the resection extent and the right posterior hepatic duct (RPHD). During parenchymal resection, the right anterior Glissonean pedicle was adequately exposed and transected via the extrafascial approach above the plane of the RPHD. Finally, the right coronary ligament was dissected, and the tumor was removed.

Results: The operation was completed in 360 min, with a blood loss of 200 mL. The histopathologic diagnosis indicated a moderately differentiated HCC. The patient was discharged on postoperative day 8 without any complications.

Conclusion: Laparoscopic in situ anatomic mesohepatectomy using combined intra- and extrafascial approaches with ICG navigation may be feasible for patients with a centrally located solitary massive HCC.
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http://dx.doi.org/10.1245/s10434-021-10886-2DOI Listing
October 2021

Insights into Enhancer RNAs: Biogenesis and Emerging Role in Brain Diseases.

Neuroscientist 2021 Oct 6:10738584211046889. Epub 2021 Oct 6.

Laboratory of Molecular Translational Medicine, Center for Translational Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.

Enhancers are cis-acting elements that control the transcription of target genes and are transcribed into a class of noncoding RNAs (ncRNAs) termed enhancer RNAs (eRNAs). eRNAs have shorter half-lives than mRNAs and long noncoding RNAs; however, the frequency of transcription of eRNAs is close to that of mRNAs. eRNA expression is associated with a high level of histone mark H3K27ac and a low level of H3K27me3. Although eRNAs only account for a small proportion of ncRNAs, their functions are important. eRNAs can not only increase enhancer activity by promoting the formation of enhancer-promoter loops but also regulate transcriptional activation. Increasing numbers of studies have found that eRNAs play an important role in the occurrence and development of brain diseases; however, further research into eRNAs is required. This review discusses the concept, characteristics, classification, function, and potential roles of eRNAs in brain diseases.
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http://dx.doi.org/10.1177/10738584211046889DOI Listing
October 2021

Mass Spectrometric Biosensing: A Powerful Approach for Multiplexed Analysis of Clinical Biomolecules.

ACS Sens 2021 10 16;6(10):3517-3535. Epub 2021 Sep 16.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

Rapid and sensitive detection of clinical biomolecules in a multiplexed fashion is of great importance for accurate diagnosis of diseases. Mass spectrometric (MS) approaches are exceptionally suitable for clinical analysis due to its high throughput, high sensitivity, and reliable qualitative and quantitative capabilities. To break through the bottleneck of MS technique for detecting high-molecular-weight substances with low ionization efficiency, the concept of mass spectrometric biosensing has been put forward by adopting mass spectrometric chips to recognize the targets and mass spectrometry to detect the signals switched by the recognition. In this review, the principle of mass spectrometric sensing, the construction of different mass tags used for biosensing, and the typical combination mode of mass spectrometric imaging (MSI) technique are summarized. Future perspectives including the design of portable matching platforms, exploitation of novel mass tags, development of effective signal amplification strategies, and standardization of MSI methodologies are proposed to promote the advancements and practical applications of mass spectrometric biosensing.
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http://dx.doi.org/10.1021/acssensors.1c01394DOI Listing
October 2021

A pore-forming protein-induced surface-enhanced Raman spectroscopic strategy for dynamic tracing of cell membrane repair.

iScience 2021 Sep 14;24(9):102980. Epub 2021 Aug 14.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P.R. China.

The plasma membrane repair holds significance for maintaining cell survival and homeostasis. To achieve the sensitive visualization of membrane repair process for revealing its mechanism, this work designs a perforation-induced surface-enhanced Raman spectroscopy (SERS) strategy by conjugating Raman reporter (4-mercaptobenzoic acid) loaded gold nanostars with pore-forming protein streptolysin O (SLO) to induce the SERS signal on living cells. The SERS signal obviously decreases with the initiation of membrane repair and the degradation of SLO pores due to the departure of gold-nanostar-conjugated SLO. Thus, the designed strategy can dynamically visualize the complete cell membrane repair and provide a sensitive method to demonstrate the SLO endocytosis- and exocytosis-mediated repairing mechanism. Using DOX-resistant MCF-7 cells as a model, a timely repair-blocking technology for promoting the highly efficient treatment of drug-resistant cancer cells is also proposed. This work opens an avenue for probing the plasma membrane repairing mechanisms and designing the precision therapeutic schedule.
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http://dx.doi.org/10.1016/j.isci.2021.102980DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403736PMC
September 2021

Comprehensive analysis of an immune-related ceRNA network in identifying a novel lncRNA signature as a prognostic biomarker for hepatocellular carcinoma.

Aging (Albany NY) 2021 07 8;13(13):17607-17628. Epub 2021 Jul 8.

Department of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

The function of competitive endogenous RNA (ceRNA) network in the immune regulation of hepatocellular carcinoma (HCC) is unclear. Our study aimed to construct an immune-related ceRNA network and develop an immune-related long noncoding RNA (lncRNA) signature to assess the prognosis of HCC patients and to optimize the treatment methods. We firstly constructed a ceRNA regulatory network for HCC using differentially expressed lncRNAs, mRNAs and microRNAs (miRNAs) from the Cancer Genome Atlas. A signature was constructed by 11 immune-related prognostic lncRNAs from the ceRNA network. The survival analysis and receiver operating characteristic analysis validated the reliability of the signature. Multivariate Cox regression analysis revealed that the signature could act an independent prognostic indicator. This signature also showed high association with immune cell infiltration and immune check blockades. LINC00491 was identified as the hub lncRNA in the signature. and evidence demonstrated that silencing of LINC00491 significantly inhibited HCC growth. Finally, 59 lncRNAs, 21 miRNAs, and 26 mRNAs were obtained to build the immune-related ceRNA network for HCC. In conclusion, our novel immune-related lncRNA prognostic signature and the immune-related ceRNA network might provide in-depth insights into tumor-immune interaction of HCC and promote better individual treatment strategies in HCC patients.
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http://dx.doi.org/10.18632/aging.203250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312417PMC
July 2021

Safety and efficacy of S1 monotherapy or combined with nab-paclitaxel in advanced elderly pancreatic cancer patients: A meta-analysis.

Medicine (Baltimore) 2021 Jun;100(25):e26342

Department of Hepatobiliary Surgery, the First Affiliated Hospital of Dalian Medical University.

Objective: To evaluate the therapeutic efficacy and safety of S1 monotherapy or combination with nab-paclitaxel for the treatment of elderly patients with metastatic or locally advanced pancreatic adenocarcinoma.

Method: PubMed, Embase, Cochrane Central Library, China Biology Medicine, and China National Knowledge Infrastructure databases were searched without time limits according to the inclusion criteria. RevMan (Version 5.3) software was used for data extraction and meta-analysis. Objective response rate (ORR) and disease control rate (DCR) were used to evaluate therapeutic effects while side effects including leukopenia, thrombocytopenia, neurotoxicity, vomit, and alopecia were extracted for evaluation. There was no need for ethical review in this study because no ethical experiments were conducted and all data used were public data. All relevant data are within the paper and its Supporting Information files.

Results: Four retrospective studies comprising 308 elderly patients with metastatic or locally advanced pancreatic adenocarcinoma were included in the analysis. One hundred fifty-one patients underwent S1 monotherapy and 157 received S1 combined nab-paclitaxel. Meta-analysis indicated that compared with S1 monotherapy, S1 combined with nab-paclitaxel had higher ORR (OR 2.25, 95% CI: 1.42-3.55; P = .0005) and DCR (OR 2.94, 95% CI: 1.55-5.58; P = .0009). The adverse reaction of leukopenia was higher in the combined therapy group (OR 1.85, 95% CI: 1.09-3.13, P = .02), but no significant difference was found in thrombocytopenia, neurotoxicity, vomiting, and alopecia between the 2 groups (P > .05).

Conclusion: Nab-paclitaxel plus S1 was more efficient in terms of ORR and DCR than S1 monotherapy in elderly pancreatic ductal adenocarcinoma patients while the side effect was controllable with a higher probability of leukopenia. Thus, combined nab-paclitaxel and S1 could be safely used in elderly patients.
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http://dx.doi.org/10.1097/MD.0000000000026342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238291PMC
June 2021

Anti-atopic dermatitis effects of dictamni cortex: Studies on in vitro and in vivo experimental models.

Phytomedicine 2021 Feb 29;82:153453. Epub 2020 Dec 29.

School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong SAR, China; Hong Kong Institute of Integrative Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address:

Background: Dictamni Cortex (DC), a Chinese herbal medicine with wind dispelling and itchiness relieving effects, is the most popular single herb prescribed for the treatment of atopic dermatitis (AD), as it is used in up to 12.68% of all herbal prescriptions for AD.

Purpose: The present study aimed to evaluate the anti-AD effect of Dictamni Cortex extract (DCE) and elucidate the underlying molecular mechanisms of its action using the 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like mouse model and a relevant in vitro experimental model.

Methods: Female Balb/c mice were sensitized with 200 μl 0.5% DNCB for three days. After sensitization, mice were challenged with 200 μl 1% DNCB on the same dorsal skin and also 20 μl 1% DNCB on each ear every 3 days, and orally administrated by gavage with DCE (0.6, 1.2 and 2.4 g/kg) daily from day 14 to day 29 for 16 consecutive days. At the end of experiment, the clinical scores for AD on the mice were calculated to evaluate the therapeutic effect of DCE; and serum, ears and dorsal skin of the mice were collected for mechanistic study. The anti-allergic activity of DCE was also evaluated using antigen-induced RBL-2H3 cell line. The release of selected cytokines, chemokines and β-hexosaminidase was measured to determine the anti-allergic activity of DCE. In addition, intracellular Ca level, MAPKs and Lyn phosphorylations were further investigated to reveal its anti-allergic molecular mechanisms.

Results: Our results demonstrated that DCE could markedly improve the AD-like symptoms in AD-like mice by inhibiting the mast cell infiltration, suppressing the production of Th2-associated cytokine (IL-4) and pro-inflammatory cytokines (TNF-α), and enhancing the protein expression of filaggrin through inhibition of the MAPKs and NF-κB pathways. Moreover, DCE suppressed mast cell degranulation through decreasing the intracellular Ca level and inactivation of Lyn, Syk and PLCγs, suggesting DCE could regulate mast-cell-mediated allergic response.

Conclusion: Our experimental results unambiguously indicate that DCE possesses potent anti-allergic effect, and help place the application of DC for the treatment of AD on a scientific footing.
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http://dx.doi.org/10.1016/j.phymed.2020.153453DOI Listing
February 2021

Is seafloor litter contributing to sea anemone blooms?

Sci Total Environ 2021 Mar 11;759:143479. Epub 2020 Nov 11.

Key Laboratory of Sustainable Development of Marine Fisheries, Ministry of Agriculture and Rural Affairs, Shandong Provincial Key Laboratory of Fishery Resources and Ecological Environment, Yellow Sea Fisheries Research Institute, Chinese Academy of Fishery Sciences, Qingdao, China; Function Laboratory for Marine Fisheries Science and Food Production Processes, Pilot National Laboratory for Marine Science and Technology, Qingdao, China. Electronic address:

Increasing marine litter have become a global environmental disaster. The accumulation of seafloor litter (generally includes anthropogenic litter and natural debris) could change the habitat of benthic organisms and thereby affecting their population dynamics including spatial distribution. Metridium senile fimbriatum (i.e., M. senile), a fast-growing sea anemone, has become a dominant species of benthic community in the north Yellow Sea in recent years. In this study, we tested the hypothesis that the distribution of M. senile is positively correlated with that of seafloor litter, using data collected on seafloor litter and M. senile from three fisheries-independent bottom trawl surveys in the Yellow Sea in May, August and November 2019. Gradient Forest Model (GFM) was used to select appropriate response variables for characterizing the distribution of M. senile, and evaluate the influences of potential environmental factors on M. senile distribution. Surface area of anthropogenic litter (represented as 'Anthropogenic litter'), surface area of natural debris (represented as 'Natural debris') and latitude (Lat) were identified as the most significant variables influencing the distribution of M. senile. Furthermore, Generalized Additive Mixed Model (GAMM) was applied to model the abundance distribution of M. senile in terms of significant environmental variables, and evaluate its correlations with 'Anthropogenic litter' and 'Natural debris'. The best fitting GAMM showed that the abundance of M. senile has a significantly positive association with 'Anthropogenic litter' and 'Natural debris'. We therefore speculated that accumulation of seafloor litter might contribute to the bloom of M. senile, given that seafloor litter could serve as "vectors" for M. senile dispersal and provide with a preferable "natural habitat" for their settlement.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143479DOI Listing
March 2021

HTLV screening of blood donors using chemiluminescence immunoassay in three major provincial blood centers of China.

BMC Infect Dis 2020 Aug 6;20(1):581. Epub 2020 Aug 6.

National Center for Clinical Laboratories, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

Background: Human T-cell lymphotropic virus (HTLV) remains a major safety concern for blood supplies. Despite many HTLV positive cases being reported in southeastern China, the detection of HTLV has not been prioritized in routine blood screening. Additionally, data on the prevalence of HTLV infection among blood donors is also limited. The objective of this study was to investigate the prevalence of HTLV among blood donors in three Chinese provinces through their representative blood centers, to evaluate the feasibility of chemiluminescence immunoassay (CLIA) for blood screening.

Methods: From November 2018 to March 2019, blood plasma samples were collected from Hebei, Changsha, and Shenzhen blood centers and were screened for the HTLV-1/2 antibody using a CLIA and enzyme-linked immunosorbent assay (ELISA). This was followed by confirmatory tests using INNO-LIA HTLV I/II.

Results: A total of 59,929 blood donations were collected and screened for HTLV-1/2. The reactive rate of CLIA and ELISA among donations in the Shenzhen blood center (0.0943%, 27/28,621) was higher than Hebei (0.0248%, 4/16,144), and Changsha (0.0198%, 3/15,164) (p < 0.05). After confirmation, 3 samples were confirmed as indeterminate for HTLV antibodies, and only one sample from the Shenzhen blood center was confirmed as HTLV-1. The overall prevalence of HTLV-1/2 was 1.67 per 100,000 (1/59,929). The HTLV-infected blood came from a 32-year-old first-time female donor with a high school degree, who belonged to the SHE ethnic minority and was born in the Fujian province.

Conclusions: In summary, the overall prevalence of HTLV-1/2 among blood donors in the three blood centers in China remains relatively low. However, blood donations with positive or indeterminate results for HTLV antibodies reminded us of the importance of HTLV screening among blood donors in China.
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http://dx.doi.org/10.1186/s12879-020-05282-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409689PMC
August 2020

Administration of umbilical cord mesenchymal stem cells in patients with severe COVID-19 pneumonia.

Crit Care 2020 07 11;24(1):420. Epub 2020 Jul 11.

Department of Cardiology, Xinqiao Hospital of Army Medical University, 183 Xinqiao Street, Chongqing, 400037, China.

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http://dx.doi.org/10.1186/s13054-020-03142-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7351637PMC
July 2020

Combination of Left Ventricular End-Diastolic Diameter and QRS Duration Strongly Predicts Good Response to and Prognosis of Cardiac Resynchronization Therapy.

Cardiol Res Pract 2020 17;2020:1257578. Epub 2020 Jan 17.

Institute of Cardiovascular Diseases, Xinqiao Hospital, Army Medical University (Third Military Medical University), 183 Xinqiao Street, Chongqing 400037, China.

Background: Approximately 20-40% of recipients of cardiac resynchronization therapy (CRT) do not respond to it based on the current patient selection criteria. The purpose of this study was to identify baseline parameters that can predict CRT response and to evaluate the effect of those predictive parameters on long-term prognosis.

Methods: This was a retrospective, nonrandomized, noncontrolled cohort study. Patients who received CRT in our centre were divided into responders and nonresponders by the definition of CRT response (an increase in left ventricular ejection fraction (LVEF) of ≥5% and improvement of ≥1 New York Heart Association (NYHA) class from baseline to the 6-month follow-up).

Results: Of the 101 patients, 68 were responders and 33 were nonresponders. Left ventricular end-diastolic diameter (LVEDD; OR: 0.88, 95% CI: 0.81-0.95, =0.001) and QRS duration (OR: 1.07, 95% CI: 1.04-1.10, < 0.001) were independent predictors of CRT response. The combination of LVEDD and QRS duration was more valuable for predicting CRT response (AUC 0.836; 95% CI: 0.76-0.91; < 0.001). Moreover, the combination of LVEDD ≤ 71 mm and QRS duration ≥ 170 ms had a low incidence of all-cause mortality, HF hospitalisation, and the composite endpoint. In addition, baseline LVEDD had a positive correlation with QRS duration (=0.199, =0.046). Responders to CRT had better LV reverse remodeling.

Conclusion: The combination of LVEDD and QRS duration provided more robust prediction of CRT response. Moreover, the combination of LVEDD ≤ 71 mm and QRS duration ≥ 170 ms was associated with a low incidence of all-cause mortality, HF hospitalisation, and the composite endpoint. Our results may be useful to provide individualized patient selection for CRT.
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http://dx.doi.org/10.1155/2020/1257578DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201746PMC
January 2020

Huang-Lian-Jie-Du extract ameliorates atopic dermatitis-like skin lesions induced by 2,4-dinitrobenzene in mice via suppression of MAPKs and NF-κB pathways.

J Ethnopharmacol 2020 Mar 31;249:112367. Epub 2019 Oct 31.

School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, N.T, Hong Kong SAR, China; Brain Research Centre, School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China; Institute of Integrative Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address:

Ethnopharmacological Relevance: Huang-Lian-Jie-Du Decoction (HLJDD), is a well-known traditional Chinese herbal formula first written in the Tang dynasty. In Chinese medicine practice, HLJDD is commonly prescribed to treat various inflammatory skin diseases, such as atopic dermatitis (AD) and psoriasis.

Aim Of The Study: The present study aimed at investigating the therapeutic effect of HLJDD extract (HLJDE) and to elucidate the underlying molecular mechanisms of action in the 1-chloro-2,4-dinitrobenzene (DNCB)-induced AD-like mice.

Materials And Methods: Female Balb/c mice were sensitized with DNCB for three days. After sensitization, mice were challenged with DNCB every three days and orally administrated with HLJDE (150, 300 and 600 mg/kg) daily from day 14 to day 29 for consecutive 16 days. At the end of experiment, the clinical AD scores of the mice were calculated to evaluate the therapeutic effect of HLJDE, and serum, ears and dorsal skin of the mice were collected for unravelling molecular mechanisms.

Results: HLJDE significantly reduced the clinical symptoms in the AD-like mice by inhibiting eosinophil and mast cell infiltration, suppressing the production of Th2-associated cytokine (IL-4) and pro-inflammatory cytokines (TNF-α). In addition, HLJDE significantly suppressed the NF-κB and MAPKs pathways. Moreover, HLJDE was able to accentuate filaggrin expression in the skin lesion when compared to the sensitized mouse without treatment.

Conclusion: HLJDE significantly improved the AD-like symptoms on the DNCB-sensitized mice through mitigating the production of inflammatory mediators via suppressing MAPKs and NF-κB pathways. Additionally, the elevated expression of filaggrin in the skin lesion by HLJDE contributes to the recovery of dysfunctional skin barrier on the DNCB-sensitized mice.
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http://dx.doi.org/10.1016/j.jep.2019.112367DOI Listing
March 2020

Heart Failure Duration Combined with Left Atrial Dimension Predicts Super-Response and Long-Term Prognosis in Patients with Cardiac Resynchronization Therapy Implantation.

Biomed Res Int 2019 24;2019:2983752. Epub 2019 Jun 24.

Department of Cardiology, Xinqiao Hospital, Army Medical University (Third Military Medical University), 183 Xinqiao Street, Chongqing 400037, China.

Background: Response to cardiac resynchronization therapy (CRT) varies significantly among patients. This study aimed to identify baseline characteristics that could predict super-response to CRT and to evaluate the long-term prognosis in super-responders.

Methods: We retrospectively reviewed the data of 73 consecutive patients who received CRT. Patients were considered as super-responders after 6-month follow-up when NYHA class reduction to I or II combined with left ventricular ejection fraction (LVEF) ≥ 50% was observed. Patients were divided into super-responders group and non-super-responders group. All-cause mortality or hospitalization for heart failure (HF) was referred to the combined end point.

Results: 17 (23.3%) patients were super-responders. HF duration, left atrial dimension (LAD), and left bundle branch block (LBBB) were independent predictors of super-response to CRT. The combination of HF duration and LAD could provide more robust prediction of super-response than standalone HF duration (0.899 versus 0.789, Z = 2.207, P = 0.027) or standalone LAD (0.899 versus 0.775, Z = 2.487, P = 0.013). super-responders had excellent LV reverse remodeling. The cumulative incidences of combined end point were significantly lower in the super-responders group, LAD ≤ 42mm group, and combination of HF duration ≤ 48 months and LAD ≤ 42mm group. LBBB remained associated with a lowered risk of the combined end point (HR: 0.19, 95% CI: 0.07-0.57, P = 0.003), whereas LAD was associated with a raised risk of the combined end point (HR: 1.09, 95% CI: 1.02-1.17, P = 0.014).

Conclusions: HF duration, LAD, and LBBB independently predicted super-response. The combination of HF duration and LAD makes more robust prediction of CRT super-response. Super-responders had excellent LV reverse remodeling and decreased the incidences of the combined end point. LBBB and LAD were independently associated with the combined end point.
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http://dx.doi.org/10.1155/2019/2983752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613035PMC
December 2019

Fluorescent visual quantitation of cell-secreted sialoglycoconjugates by chemoselective recognition and hybridization chain reaction.

Analyst 2019 Aug 3;144(15):4545-4551. Epub 2019 Jul 3.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.

Sialic acid (SA), usually located at the termini of glycan chains, is one of the most important monosaccharide blocks for glycosylation of proteins. The expression level of sialoglycoconjugates (SiaGCs) in cellular secretome is of great significance in diagnosis of tumor malignancy. This work developed a fluorescent visual method for the detection of SiaGCs secreted from living cells by a boronic acid modified chip based chemoselective recognition and hybridization chain reaction. The cell-secreted SiaGCs, which were labeled with the azide group through a metabolic labeling technique during cell culture, were captured by the chip through chemoselective recognition of boronic acid toward SA. After further conjugating the azide group with an alkyne modified DNA probe, the captured SiaGCs could be conveniently endowed with the amplified fluorescent signal through a hybridization chain reaction of a pair of dye-labeled DNA hairpins, which led to a quantitative imaging method for detection of SiaGCs. The average amount of metabolically labeled SiaGCs secreted from a single HeLa cell and MCF-7 cell was 2.18 × 10 and 3.98 × 10 mol, respectively. The proposed method could be utilized to monitor the variation of the secreted SiaGCs during drug treatment, providing a useful tool for investigating the glycosylation and glycan-related biological processes.
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http://dx.doi.org/10.1039/c9an00572bDOI Listing
August 2019

A multifunctional SERS sticky note for real-time quorum sensing tracing and inactivation of bacterial biofilms.

Chem Sci 2018 Jul 31;9(27):5906-5911. Epub 2018 May 31.

State Key Laboratory of Analytical Chemistry for Life Science , School of Chemistry and Chemical Engineering , Nanjing University , Nanjing 210023 , P. R. China . Email:

Quorum sensing (QS) is crucial for bacterial survival and activity. Although detecting related signaling metabolites can reveal QS, a versatile platform for convenient real-time imaging of their secretion in the context of bacterial biofilms along with inhibition to the growth of biofilms is still highly desired. Here we develop a flexible sticky note with a sandwich structure by encapsulating gold nanostars between two pieces of hexagonal boron nitride layers, which can be easily pasted on natural biofilms to monitor in real-time the secreted signaling molecule by SERS imaging with high sensitivity and spatiotemporal resolution. Using and its pyocyanin secretion as a model and an internal standard for self-calibration of SERS signals, the sticky note achieves reliable quantification and a rapid response to the secretion as early as 1 h biofilm growth. With antibiotic loading, the multifunctional SERS sticky note also demonstrated effective inactivation of the bacterial biofilm with simultaneous evaluation of the inactivation effect. This multifunctional SERS sticky note provides a versatile platform for investigating bacterial behaviors and developing antibacterial therapeutics.
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http://dx.doi.org/10.1039/c8sc02078gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050527PMC
July 2018

In Situ Cellular Glycan Analysis.

Acc Chem Res 2018 04 29;51(4):890-899. Epub 2018 Mar 29.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering , Nanjing University , Nanjing 210023 , P. R. China.

Glycan decorates all mammalian cell surfaces through glycosylation, which is one of the most important post-modifications of proteins. Glycans mediate a wide variety of biological processes, including cell growth and differentiation, cell-cell communication, immune response, pathogen interaction, and intracellular signaling events. Besides, tumor cells aberrantly express distinct sets of glycans, which can indicate different tumor onsets and progression processes. Thus, analysis of cellular glycans may contribute to understanding of glycan-related biological processes and correlation of glycan patterns with disease states for clinical diagnosis and treatment. Although proteomics and glycomics have included great efforts for in vitro study of glycan structures and functions using lysis samples of cells or tissues, they cannot offer real-time qualitative or quantitative information, especially spatial distribution, of glycans on/in intact cells, which is important to the revelation of glycan-related biological events. Moreover, the complex lysis and separation procedures may bring unpredictable loss of glycan information. Focusing on the great urgency for in situ analysis of cellular glycans, our group developed a series of methods for in situ analysis of cellular glycans in the past 10 years. By construction of electrochemical glycan-recognizable probes, glycans on the cell surface can be quantified by direct or competitive electrochemical detection. Using multichannel electrodes or encoded lectin probes, multiple glycans on the cell surface can be dynamically monitored simultaneously. Through design of functional nanoprobes, the cell surface protein-specific glycans and intracellular glycan-related enzymes can be visualized by fluorescence or Raman imaging. Besides, some biological enzymes-based methods have been developed for remodeling or imaging of protein-specific glycans and other types of glycoconjugates, such as gangliosides. Through tracing the changes of glycan expression induced by drugs or gene interference, some glycan-related biological processes have been deduced or proved, demonstrating the reliability and practicability of the developed methods. This Account surveys the key technologies developed in this area, along with the discussion on the shortages of current methodology as well as the possible strategies to overcome those shortages. The future trend in this topic is also discussed. It is expected that this Account can provide a versatile arsenal for chemical and biological researchers to unravel the complex mechanisms involved in glycan-related biological processes and light new beacons in tumor diagnosis and treatment.
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http://dx.doi.org/10.1021/acs.accounts.7b00617DOI Listing
April 2018

Functional Dual-Color Indicator To Achieve in Situ Visualization of Intracellular Glycosylation.

Anal Chem 2018 03 16;90(5):3073-3078. Epub 2018 Feb 16.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering , Nanjing University , Nanjing 210023 , P. R. China.

A functional dual-color indicator is designed for in situ visualization of intracellular glycosylation. Using O-GlcNAcylation as model, the indicator is constructed on a poly-GlcNAc-coated gold nanoparticle (AuNP) by assembling dye labeled lectin (FSWGA) and then another dye-labeled GlcNAc (FGlcNAc) through the two opposite subunits of FSWGA. These dyes possess negligible overlapping emission and can be quenched by AuNP. In the presence of intracellular dissociated GlcNAc residue and O-GlcNAcylated proteins, the assembled FGlcNAc and the conjugate of FSWGA with FGlcNAc are released from AuNP through the dynamic competitive conjugation, which lights up the fluorescence of two dyes, respectively, and provides a simple technique for simultaneously monitoring the level of O-GlcNAcylated proteins and the total amount of GlcNAc groups in living cells. The practicality of the protocol for visually monitoring the biological pathway between intracellular O-GlcNAcylation and cell surface differentiation-related proteins demonstrates a convenient and powerful tool for research of glycosylation equilibrium and related biological processes.
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http://dx.doi.org/10.1021/acs.analchem.7b03587DOI Listing
March 2018

Quantitative Screening of Cell-Surface Gangliosides by Nondestructive Extraction and Hydrophobic Collection.

Angew Chem Int Ed Engl 2018 01 19;57(3):785-789. Epub 2017 Dec 19.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P.R. China.

A screening strategy involving designed extractors and collectors was used for the nondestructive quantitation of gangliosides on cell surfaces. The extractors were constructed by functionalizing maleimide silica bubbles with a DNA probe, which contains an endonuclease cleavage site and a boronic acid end to extract cell-surface sialic acid-containing compounds through simple centrifugation. After the extractors containing the extracted compounds were incubated with endonuclease, the released oligonucleotide-gangliosides were selectively collected by silanized collector bubbles through hydrophobic interactions. The in vitro fluorescent signals from the collectors were used for the quantitation of cell-surface gangliosides. By combining with sialidase cleavage, a protocol for the identification of ganglioside subtypes was developed. The successful monitoring of the regeneration of cell-surface gangliosides demonstrates the potential of this strategy in probing related biological processes.
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http://dx.doi.org/10.1002/anie.201710984DOI Listing
January 2018

Urine Metabonomics Reveals Early Biomarkers in Diabetic Cognitive Dysfunction.

J Proteome Res 2017 09 9;16(9):3180-3189. Epub 2017 Aug 9.

Chinese Materia Medica College, Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine , Tianjin 300193, People's Republic of China.

Recently, increasing attention has been paid to diabetic encephalopathy, which is a frequent diabetic complication and affects nearly 30% of diabetics. Because cognitive dysfunction from diabetic encephalopathy might develop into irreversible dementia, early diagnosis and detection of this disease is of great significance for its prevention and treatment. This study is to investigate the early specific metabolites biomarkers in urine prior to the onset of diabetic cognitive dysfunction (DCD) by using metabolomics technology. An ultra-high performance liquid-chromatography-quadrupole time-of-flight-mass spectrometry (UPLC-Q/TOF-MS) platform was used to analyze the urine samples from diabetic mice that were associated with mild cognitive impairment (MCI) and nonassociated with MCI in the stage of diabetes (prior to the onset of DCD). We then screened and validated the early biomarkers using OPLS-DA model and support vector machine (SVM) method. Following multivariate statistical and integration analysis, we found that seven metabolites could be accepted as early biomarkers of DCD, and the SVM results showed that the prediction accuracy is as high as 91.66%. The identities of four biomarkers were determined by mass spectrometry. The identified biomarkers were largely involved in nicotinate and nicotinamide metabolism, glutathione metabolism, tryptophan metabolism, and sphingolipid metabolism. The present study first revealed reliable biomarkers for early diagnosis of DCD. It provides new insight and strategy for the early diagnosis and treatment of DCD.
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http://dx.doi.org/10.1021/acs.jproteome.7b00168DOI Listing
September 2017

Polyadenine-Modulated DNA Conformation Monitored by Surface-Enhanced Raman Scattering (SERS) on Multibranched Gold Nanoparticles and Its Sensing Application.

Chemistry 2017 Jul 20;23(39):9332-9337. Epub 2017 Jun 20.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry & Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.

This work proposes a facile way to modulate the conformation of DNA from the "Lie-Down" to the "Stand-Up" conformation on the surface of multibranched gold nanoparticles (AuNPs). This is realized by regulating the length of polyadenine (polyA) linked to the DNA sequence and/or the hybridization of this sequence with the target DNA, and can be monitored by the Raman signal owing to the excellent performance of multibranched AuNPs (AuNSs) as a surface-enhanced Raman scattering (SERS) substrate and the distance change between the Raman reporter and the substrate. The probable mechanism, which depends on the repulsion of polyA from the sequence and the tip assembly, has also been probed through theoretical simulation using the finite difference time domain method. By virtue of this strategy, a conformation-transformation-based [email protected] sensor is constructed for the identification of a specific oligonucleotide, which has been used for the detection of DNA sequences associated with Severe Acute Respiratory Syndrome (SARS). This strategy leads to a novel sensing platform with good extendibility for DNA analysis, and provides a powerful protocol for facilitating the cognition of DNA conformation on metal surfaces.
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http://dx.doi.org/10.1002/chem.201700883DOI Listing
July 2017

Plasmonic coupling of dual gold nanoprobes for SERS imaging of sialic acids on living cells.

Chem Commun (Camb) 2016 Aug;52(70):10640-3

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, P. R. China.

This work reports a benzoic group functionalized gold nanoflower as a bridge probe for both recognition of target sialic acids and assembly of poly(N-acetylneuraminic acid) modified gold nanoparticles, which leads to plasmonic coupling of two kinds of gold nanoprobes in a single-core-multi-satellite nanostructure to produce a sensitive surface-enhanced Raman scattering (SERS) signal for the imaging of sialic acids on living cells.
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http://dx.doi.org/10.1039/c6cc04147gDOI Listing
August 2016

Total flavonoids of Willd inhibit inflammatory responses in LPS-activated macrophages via suppression of the NF-κB and MAPK signaling pathways.

Exp Ther Med 2016 Mar 29;11(3):1116-1122. Epub 2015 Dec 29.

Research Base of TCM Syndrome, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350108, P.R. China.

Nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways play a central role in inflammatory responses. Total flavonoids of Hedyotis diffusa Willd (TFHDW) are active compounds derived from Hedyotis diffusa Willd, which has been long used in Chinese traditional medicine for the treatment of various inflammatory diseases, including ulcerative colitis and bronchitis; however, the precise mechanisms underlying the effects of TFHDW are largely unknown. In the present study, the anti-inflammatory effect of TFHDW was evaluated and the underlying molecular mechanisms were investigated in an inflammatory model comprising lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. The results indicated that TFHDW inhibited the inflammatory response as it significantly reduced the LPS-induced expression of pro-inflammatory nitric oxide, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β in a concentration-dependent manner, without causing cytotoxicity. In addition, the mRNA expression of inducible nitric oxide synthase, TNF-α, IL-6 and IL-1β was suppressed by treatment with TFHDW in LPS-stimulated RAW 264.7 cells. Moreover, TFHDW treatment significantly inhibited the LPS-induced activation of NF-κB via the suppression of inhibitor of κB (IκB) phosphorylation, and reduced the phosphorylation of MAPK signaling molecules (p38, c-Jun N-terminal protein kinase and extracellular signal-regulated kinase 1/2), which resulted in the inhibition of cytokine expression. These findings suggest that TFHDW exerted anti-inflammatory activity via suppression of the NF-κB and MAPK signaling pathways.
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http://dx.doi.org/10.3892/etm.2015.2963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774565PMC
March 2016

Anti-inflammatory and anti-allergic effects and underlying mechanisms of Huang-Lian-Jie-Du extract: Implication for atopic dermatitis treatment.

J Ethnopharmacol 2016 Jun 11;185:41-52. Epub 2016 Mar 11.

School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong SAR. Electronic address:

Ethnopharmacological Relevance: Huang-Lian-Jie-Du Decoction (HLJDD), a well-known Chinese herbal formula recorded in the Tang dynasty, is composed of Coptidis rhizoma (Huang-Lian), Scutellariae radix (Huang-Qin), Phellodendri Chinensis cortex (Huang-Bai) and Gardenia fructus (Zhi-Zi). It has clinical efficacy of purging fire for removing toxin and is commonly used for the treatment of disease including Alzheimer's disease, stroke and gastrointestinal disorders. HLJDD is also frequently applied for the treatment of various skin diseases, such as atopic dermatitis (AD) and various types of eczema. The aim of this study is to investigate the anti-inflammatory and anti-allergic actions of Huang-Lian-Jie-Du ethanolic extract (HLJDE) and to elucidate underlying molecular mechanisms of action using relevant in vitro experimental models.

Materials And Methods: The anti-inflammatory effects of HLJDE were investigated through evaluating the change of nitric oxide (NO) and the production of several cytokines and chemokines in lipopolysaccharide (LPS)-stimulated RAW264.7 cell line. Expression of mitogen-activated protein kinases (MAPKs), NF-κB p65 phosphorylation, inhibitor-κBα (IκBα) degradation were further investigated to elucidate its anti-inflammatory molecular mechanisms. Meanwhile, the anti-allergic activities of HLJDE was also evaluated using antigen-induced RBL-2H3 cell line. β-hexosaminidase and histamine release and selected cytokines and chemokines were measured to evaluate the anti-allergic activities of HLJDE. In addition, intracellular Ca(2+)level, MAPKs and Lyn phosphorylation were further investigated to reveal its anti-allergic molecular mechanisms.

Results: HLJDE could significantly suppress the secretion of NO, IL-1β, IL-4, MCP-1 and GM-CSF in RAW264.7 cells in a dose-dependent manner. In addition, HLJDE also markedly reduced the phosphorylation of MAPKs, and inhibited the transcriptional activity of NF-κB and IκBα degradation. Furthermore, HLJDE exerted marked anti-allergic activity through inhibiting the release of β-hexosaminidase and histamine. The release of cytokines and chemokines (IL-4, TNF-α, MCP-1) from activated RBL-2H3 cells were also attenuated by pretreatment with HLJDE. The inhibitory effects on intracellular Ca(2+)level, and reduced phosphorylation of MAPKs and Lyn are believed to be the anti-allergic mechanisms.

Conclusions: HLJDE exerted significant anti-inflammatory and anti-allergic effects through suppressing the production of allergic and inflammatory mediators via the NF-κB and MAPKs inactivation and IκBα degradation in the LPS-stimulated RAW24.7 cells, inactivation of MAPKs and Lyn pathway in antigen-induced RBL-2H3 cells. The present study provides in vitro experimental evidence to support the use of HLJDE for the clinical treatment of AD.
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http://dx.doi.org/10.1016/j.jep.2016.03.028DOI Listing
June 2016

Liberation of Protein-Specific Glycosylation Information for Glycan Analysis by Exonuclease III-Aided Recycling Hybridization.

Anal Chem 2016 Mar 17;88(5):2923-8. Epub 2016 Feb 17.

State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University , Nanjing 210023, People's Republic of China.

A strategy for information liberation of protein-specific glycosylation is designed via an exonuclease III-aided recycling "hybridization and cleavage" process with glycan and protein probes, which achieves homogeneous quantification of cell surface glycan. The protein probe contains matching and spacer DNA sequences and an aptamer specific to target protein. The glycan probe contains a complementary sequence modified with neighboring fluorescein and quencher, a spacer sequence, and a dibenzocyclooctyne-amine end to bind azide-tagged glycan. Upon sequential binding to their targets, the complementary sequences of two probes approach enough for their hybridization, which leads to the cleavage of hybridized glycan probe by exonuclease III and followed recycling "hybridization and cleavage" process of protein probe with other adjacent glycan probes to release the labeled fluorescein for obtaining the information on protein-specific glycosylation. This protocol has been used to in situ quantify EpCAM-specific sialic acid on MCF-7 cell surface and monitor its variation during drug treatment. This work demonstrates a powerful quantification tool for research of glycosylation.
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http://dx.doi.org/10.1021/acs.analchem.5b04883DOI Listing
March 2016

Protein-specific Raman imaging of glycosylation on single cells with zone-controllable SERS effect.

Chem Sci 2016 Jan 16;7(1):569-574. Epub 2015 Oct 16.

State Key Laboratory of Analytical Chemistry for Life Science , School of Chemistry and Chemical Engineering , Nanjing University , Nanjing 210023 , P. R. China . Email: ; ; Tel: +86 25 89683593.

A zone-controllable SERS effect is presented for Raman imaging of protein-specific glycosylation on a cell surface using two types of newly designed nanoprobes. The signal probe, prepared using a Raman signal molecule and dibenzocyclooctyne-amine to functionalize a 10 nm Au nanoparticle, exhibits a negligible SERS effect and can recognize and link the azide-tagged glycan a click reaction. The substrate probe, an aptamer modified 30 or 40 nm Au nanoparticles, can specifically recognize the target protein to create an efficient SERS zone on the target protein. By controlling the size of the substrate probe to match the expression zone of the protein-specific glycan, an efficient SERS signal can be generated. This method has been successfully used for imaging of sialic acids on the target protein EpCAM on an MCF-7 cell surface and for the monitoring of the expression variation of protein-specific glycosylation during drug treatment. The concept of zone control can also be used to measure the distance between glycoproteins on a cell surface. This protocol shows promise in uncovering glycosylation-related biological processes.
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http://dx.doi.org/10.1039/c5sc03560kDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5519952PMC
January 2016

Effect of Chaihushugan San on expression of the Raf/mitogen-activated protein kinase/extracellular signal-regulated kinase pathway in the hippocampi of perimenopausal rats induced by immobilization stress.

J Tradit Chin Med 2015 Aug;35(4):445-52

Objective: We wished to study the impact of Chaihushugan San (CSS) on the behavior of perimenopausal rats with liver-Qi stagnation (LQS) and to investigate the effect of CSS on signal transduction of the Raf/mitogen-activated protein kinase (MEK)/ extracellular signal-regulated kinase (ERK) cascade in the hippocampi of rats induced by immobilization.

Methods: Twenty 52-week-old female rats were divided into two groups by the random number table method: model control group (MCG) and CSS group (CSSG), with 10 rats in each group. Ten-week-old female rats were used as the normal control group (NCG). CSS effects were assessed using rats exposed to immobilization stress by measuring body weight and sucrose consumption, serum hormone levels, and observing performance in the open field test (OFT). Molecular mechanisms were examined by measuring the effect of CSS on expression of Raf1, MEK1/2 and ERK1/2 mRNA in hippocampi using quantitative real-time polymerase chain reaction and by measuring levels of these proteins and related phospho-proteins using Western blotting.

Results: Perimenopausal rats with LQS had decreased locomotor activity; reduced sucrose consumption; and increased serum levels of corticotropin releasing hormone (CRH) and corticosterone (CORT). Activation of hippocampal Raf/MEK/ERK cascade was suppressed significantly in the MCG, and activation was increased after 21 days of CSS treatment.

Conclusion: CSS has significant effects upon relief of the symptoms of LQS in immobilization-induced rats. The mechanism underlying this action might (at least in part) be mediated by reversal of disruption of the Raf/MEK/ERK pathway.
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http://dx.doi.org/10.1016/s0254-6272(15)30123-0DOI Listing
August 2015
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