Publications by authors named "Yu-Chuan Wang"

50 Publications

Associations Between Periosteal Reaction of Proximal Tibial and Medial Compartment Knee Osteoarthritis.

Orthop Surg 2021 May 7. Epub 2021 May 7.

School of Medicine, Nankai University, Tianjin, China.

Objective: To evaluate and analyze the potential relationship between periosteal reaction and medial compartment knee osteoarthritis (KOA), and to assess the independent risk factors for the development of periosteal reaction associated with medial compartment KOA.

Methods: This is a retrospective comparative study. From January 2019 to December 2019 at the Third Hospital of Hebei Medical University, a total of 363 patients (726 knees) with medial compartment KOA were enrolled in this study according to our inclusion and exclusion criteria, including 91 males and 272 females, with an mean age of 57.9 ± 12.8 years (range, 18-82 years). Among these patients, 206 patients (412 knees) were allocated to the periosteal reaction group (44 males and 162 females) and 157 patients (314 knees) were allocated to the non-periosteal reaction group (47 males and 110 females). The classification of KOA severity was based on Kellgren and Lawrence (K-L) grading system. The malalignment of the lower extremities in coronal plane was evaluated as medial proximal tibial angle (MPTA), hip-knee-ankle angle (HKA), and lateral distal femoral angle (LDFA). Patients demographics and radiographic parameters were recorded in the two groups. Intra-observer and inter-observer reliabilities of all radiological measurements were analyzed by intraclass correlation coefficients (ICCs). Univariate analyses were conducted for comparison of differences with continuous variables between patients with periosteal reaction and without periosteal reaction. Multivariate logistical regression analysis was performed to determine the independent risk factors of radiographic parameters for periosteal reaction.

Results: The overall incidence of periosteal reaction associated with medial compartment KOA was 56.7%. Furthermore, we observed that the incidence of periosteal reaction significantly increased with age and correlated with K-L grade progression (P < 0.05). There was a statistically significant difference between the two groups. In the multivariate logistical regression analysis, HKA and JLCA were identified as independent risk factors of the development of periosteal reaction in patients with medial compartment KOA (odds ratio [OR], 0.594; 95% confidence interval [CI] 0.544-0.648; P < 0.05; OR, 0.851; 95% confidence interval CI 0.737-0.983; P < 0.05; respectively), with other radiographic parameters including MTPA (OR 0.959; 95% CI 0.511-0.648; P > 0.05), LDFA (OR 0.990; 95% CI 0.899-1.089; P > 0.05), and JSW (OR 1.005; 95% CI 0.865-1.167; P > 0.05).

Conclusions: In this retrospective study, patients with lower HKA and higher JLCA were identified as independent risk factors for the development of periosteal reaction, which occurred most commonly adjacent to the lateral of proximal tibia diaphysis, and thus we concluded that periosteal reaction may be an anatomical adaptation for medial compartment KOA based upon these results.
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http://dx.doi.org/10.1111/os.12963DOI Listing
May 2021

The impacts of contact force, power and application time on ablation effect indicated by serial measurements of impedance drop in both conventional and high-power short-duration ablation settings of atrial fibrillation.

J Interv Card Electrophysiol 2021 Apr 23. Epub 2021 Apr 23.

Department of Clinical Science, University of Bergen, Bergen, Norway.

Background: This study aimed to clarify the interrelationship and additive effects of contact force (CF), power and application time in both conventional and high-power short-duration (HPSD) settings.

Methods: Among 38 patients with paroxysmal atrial fibrillation who underwent first-time pulmonary vein isolation, 787 ablation points were collected at the beginning of the procedure at separate sites. Energy was applied for 60 s under power outputs of 25, 30 or 35 W (conventional group), or 10 s when using 50 W (HPSD group). An impedance drop (ID) of 10 Ω was regarded as a marker of adequate lesion formation.

Results: ID ≥ 10 Ω could not be achieved with CF < 5 g under any power setting. With CF ≥ 5 g, ID could be enhanced by increasing power output or prolonging ablation time. ID for 30 and 35 W was greater than for 25 W (p < 0.05). Ablation with 35 W resulted in greater ID than with 30 W only when CF of 10-20 g was applied for 20-40 s (p < 0.05). Under the same power output, ID increased with CF level at different time points. The higher the CF, the shorter the time needed to reach ID of 10 Ω and maximal ID. ID correlated well with ablation index under each power, except for lower ID values at 25 W. ID with 50 W for 10 s was equivalent to that with 25 W for 40 s, but lower than that with 30 W for 40 s or 35 W for 30 s.

Conclusions: CF of at least 5 g is required for adequate ablation effect. With CF ≥ 5g, CF, power output, and ablation time can compensate for each other. Time to reach maximal ablation effect can be shortened by increasing CF or power. The effect of HPSD ablation with 50 W for 10 s is equivalent to conventional ablation with 25 W for 40 s and 30-35 W for 20-30 s in terms of ID.
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http://dx.doi.org/10.1007/s10840-021-00990-4DOI Listing
April 2021

Crystal structure and functional implication of a bacterial cyclic AMP-AMP-GMP synthetase.

Nucleic Acids Res 2021 May;49(8):4725-4737

Institute of New Drug Development, China Medical University, Taichung 406, Taiwan.

Mammalian cyclic GMP-AMP synthase (cGAS) and its homologue dinucleotide cyclase in Vibrio cholerae (VcDncV) produce cyclic dinucleotides (CDNs) that participate in the defense against viral infection. Recently, scores of new cGAS/DncV-like nucleotidyltransferases (CD-NTases) were discovered, which produce various CDNs and cyclic trinucleotides (CTNs) as second messengers. Here, we present the crystal structures of EcCdnD, a CD-NTase from Enterobacter cloacae that produces cyclic AMP-AMP-GMP, in its apo-form and in complex with ATP, ADP and AMPcPP, an ATP analogue. Despite the similar overall architecture, the protein shows significant structural variations from other CD-NTases. Adjacent to the donor substrate, another nucleotide is bound to the acceptor binding site by a non-productive mode. Isothermal titration calorimetry results also suggest the presence of two ATP binding sites. GTP alone does not bind to EcCdnD, which however binds to pppApG, a possible intermediate. The enzyme is active on ATP or a mixture of ATP and GTP, and the best metal cofactor is Mg2+. The conserved residues Asp69 and Asp71 are essential for catalysis, as indicated by the loss of activity in the mutants. Based on structural analysis and comparison with VcDncV and RNA polymerase, a tentative catalytic pathway for the CTN-producing EcCdnD is proposed.
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http://dx.doi.org/10.1093/nar/gkab165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096243PMC
May 2021

Design and synthesis of 4-anilinoquinazolines as Raf kinase inhibitors. Part 1. Selective B-Raf/B-Raf and potent EGFR/VEGFR2 inhibitory 4-(3-hydroxyanilino)-6-(1H-1,2,3-triazol-4-yl)quinazolines.

Bioorg Chem 2021 Apr 8;109:104715. Epub 2021 Feb 8.

Department of Applied Chemistry, National Chiayi University, No. 300, Syuefu Rd., Chiayi City 60004, Taiwan; The Training and Research Institute of Food and Agriculture, National Chiayi University, No. 300, Syuefu Rd., Chiayi City 60004, Taiwan. Electronic address:

This paper presents the design and synthesis of 4-(3-hydroxyanilino)-6-(1H-1,2,3-triazol-4-yl)quinazolines of scaffold 9 as selective B-Raf/B-Raf and potent EGFR/VEGFR2 kinase inhibitors. Total 14 compounds of scaffold 9 having different side chains at the triazolyl group with/without fluoro substituents at the anilino group were synthesized and investigated. Among them, 9m with a 2-carbamoylethyl side chain and C-4'/C-6' difluoro substituents was the most potent, which selectively inhibited B-Raf (IC: 57 nM) and B-Raf (IC: 51 nM) over C-Raf (IC: 1.0 μM). Compound 9m also actively inhibited EGFR (IC: 73 nM) and VEGFR2 (IC: 7.0 nM) but not EGFR and PDGFR-β (IC: >10 μM). Despite having good potency for B-Raf and B-Raf in the enzymatic assays, 9m was less active to inhibit melanoma A375 cells which proliferate due to constitutively activated B-Raf. The inferior activity of 9m for A375 was similar to that of sorafenib (6), suggesting that 9m might bind to the inactive conformations of B-Raf and B-Raf. Docking simulations could thus be performed to reveal the binding poses of 9m in B-Raf, B-Raf, and VEGFR2 kinases.
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http://dx.doi.org/10.1016/j.bioorg.2021.104715DOI Listing
April 2021

Tannic acid suppresses SARS-CoV-2 as a dual inhibitor of the viral main protease and the cellular TMPRSS2 protease.

Am J Cancer Res 2020 1;10(12):4538-4546. Epub 2020 Dec 1.

Graduate Institute of Biomedical Sciences, College of Medicine, China Medical University Taichung 40402, Taiwan.

The cell surface protein TMPRSS2 (transmembrane protease serine 2) is an androgen-responsive serine protease important for prostate cancer progression and therefore an attractive therapeutic target. Besides its role in tumor biology, TMPRSS2 is also a key player in cellular entry by the SARS-CoV viruses. The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has resulted in huge losses in socio-economy, culture, and human lives for which safe and effective cures are highly demanded. The main protease (M/3CL) of SARS-CoV-2 is a critical enzyme for viral propagation in host cells and, like TMPRSS2, has been exploited for treatment of the infectious disease. Numerous natural compounds abundant in common fruits have been suggested with anti-coronavirus infection in the previous outbreaks of SARS-CoV. Here we show that screening of these compounds identified tannic acid a potent inhibitor of both SARS-CoV-2 M and TMPRSS2. Molecular analysis demonstrated that tannic acid formed a thermodynamically stable complex with the two proteins at a K of 1.1 mM for M and 1.77 mM for TMPRSS2. Tannic acid inhibited the activities of the two proteases with an IC of 13.4 mM for M and 2.31 mM for TMPRSS2. M protein. Consistently, functional assays using the virus particles pseudotyped (Vpp) of SARS-CoV2-S demonstrated that tannic acid suppressed viral entry into cells. Thus, our results demonstrate that tannic acid has high potential of developing anti-COVID-19 therapeutics as a potent dual inhibitor of two independent enzymes essential for SARS-CoV-2 infection.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7783773PMC
December 2020

Crystal structure of the N-terminal domain of TagH reveals a potential drug targeting site.

Biochem Biophys Res Commun 2021 01 22;536:1-6. Epub 2020 Dec 22.

Institute of New Drug Development, China Medical University, Taichung, 406, Taiwan; Drug Development Center, Research Center for Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung, 40402, Taiwan. Electronic address:

Bacterial wall teichoic acids (WTAs) are synthesized intracellularly and exported by a two-component transporter, TagGH, comprising the transmembrane and ATPase subunits TagG and TagH. Here the dimeric structure of the N-terminal domain of TagH (TagH-N) was solved by single-wavelength anomalous diffraction using a selenomethionine-containing crystal, which shows an ATP-binding cassette (ABC) architecture with RecA-like and helical subdomains. Besides significant structural differences from other ABC transporters, a prominent patch of positively charged surface is seen in the center of the TagH-N dimer, suggesting a potential binding site for the glycerol phosphate chain of WTA. The ATPase activity of TagH-N was inhibited by clodronate, a bisphosphonate, in a non-competitive manner, consistent with the proposed WTA-binding site for drug targeting.
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http://dx.doi.org/10.1016/j.bbrc.2020.12.028DOI Listing
January 2021

Author Correction: PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis.

Nat Cell Biol 2020 Nov;22(11):1396

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41556-020-00599-1DOI Listing
November 2020

PD-L1-mediated gasdermin C expression switches apoptosis to pyroptosis in cancer cells and facilitates tumour necrosis.

Nat Cell Biol 2020 10 14;22(10):1264-1275. Epub 2020 Sep 14.

Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Although pyroptosis is critical for macrophages against pathogen infection, its role and mechanism in cancer cells remains unclear. PD-L1 has been detected in the nucleus, with unknown function. Here we show that PD-L1 switches TNFα-induced apoptosis to pyroptosis in cancer cells, resulting in tumour necrosis. Under hypoxia, p-Stat3 physically interacts with PD-L1 and facilitates its nuclear translocation, enhancing the transcription of the gasdermin C (GSDMC) gene. GSDMC is specifically cleaved by caspase-8 with TNFα treatment, generating a GSDMC N-terminal domain that forms pores on the cell membrane and induces pyroptosis. Nuclear PD-L1, caspase-8 and GSDMC are required for macrophage-derived TNFα-induced tumour necrosis in vivo. Moreover, high expression of GSDMC correlates with poor survival. Antibiotic chemotherapy drugs induce pyroptosis in breast cancer. These findings identify a non-immune checkpoint function of PD-L1 and provide an unexpected concept that GSDMC/caspase-8 mediates a non-canonical pyroptosis pathway in cancer cells, causing tumour necrosis.
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http://dx.doi.org/10.1038/s41556-020-0575-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653546PMC
October 2020

Structural basis of SARS-CoV-2 main protease inhibition by a broad-spectrum anti-coronaviral drug.

Am J Cancer Res 2020 1;10(8):2535-2545. Epub 2020 Aug 1.

Institute of New Drug Development, China Medical University Taichung 40402, Taiwan.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or 2019 novel coronavirus (2019-nCoV), took tens of thousands of lives and caused tremendous economic losses. The main protease (M) of SARS-CoV-2 is a potential target for treatment of COVID-19 due to its critical role in maturation of viral proteins and subsequent viral replication. Conceptually and technically, targeting therapy against M is similar to target therapy to treat cancer. Previous studies show that GC376, a broad-spectrum dipeptidyl M inhibitor, efficiently blocks the proliferation of many animal and human coronaviruses including SARS-CoV, Middle East respiratory syndrome coronavirus (MERS-CoV), porcine epidemic diarrhea virus (PEDV), and feline infectious peritonitis virus (FIPV). Due to the conservation of structure and catalytic mechanism of coronavirus main protease, repurposition of GC376 against SARS-CoV-2 may be an effective way for the treatment of COVID-19 in humans. To validate this conjecture, the binding affinity and IC value of M with GC376 was determined by isothermal titration calorimetry (ITC) and fluorescence resonance energy transfer (FRET) assay, respectively. The results showed that GC376 binds to SARS-CoV-2 M tightly (K = 1.6 μM) and efficiently inhibit its proteolytic activity (IC = 0.89 μM). We also elucidate the high-resolution structure of dimeric SARS-CoV-2 M in complex with GC376. The cocrystal structure showed that GC376 and the catalytic Cys145 of M covalently linked through forming a hemithioacetal group and releasing a sulfonic acid group. Because GC376 is already known as a broad-spectrum antiviral medication and successfully used in animal, it will be a suitable candidate for anti-COVID-19 treatment.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471349PMC
August 2020

Gastrodin protects H9c2 cardiomyocytes against oxidative injury by ameliorating imbalanced mitochondrial dynamics and mitochondrial dysfunction.

Acta Pharmacol Sin 2020 Oct 12;41(10):1314-1327. Epub 2020 Mar 12.

Institute of Interdisciplinary Integrative Biomedical Research, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.

Gastrodin (GAS) is the main bioactive component of Tianma, a traditional Chinese medicine widely used to treat neurological disorders as well as cardio- and cerebrovascular diseases. In the present study, the protective effects of GAS on H9c2 cells against ischemia-reperfusion (IR)-like injury were found to be related to decreasing of oxidative stress. Furthermore, GAS could protect H9c2 cells against oxidative injury induced by HO. Pretreatment of GAS at 20, 50, and 100 μM for 4 h significantly ameliorated the decrease in cell viability and increase in apoptosis of H9c2 cells treated with 400 μM HO for 3 h. Furthermore, we showed that HO treatment induced fragmentation of mitochondria and significant reduction in networks, footprint, and tubular length of mitochondria; HO treatment strongly inhibited mitochondrial respiration; HO treatment induced a decrease in the expression of mitochondrial fusion factors Mfn2 and Opa1, and increase in the expression of mitochondrial fission factor Fis1. All these alterations in HO-treated H9c2 cells could be ameliorated by GAS pretreatment. Moreover, we revealed that GAS pretreatment enhanced the nuclear translocation of Nrf2 under HO treatment. Knockdown of Nrf2 expression abolished the protective effects of GAS on HO-treated H9c2 cells. Our results suggest that GAS may protect H9c2 cardiomycytes against oxidative injury via increasing the nuclear translocation of Nrf2, regulating mitochondrial dynamics, and maintaining the structure and functions of mitochondria.
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http://dx.doi.org/10.1038/s41401-020-0382-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608121PMC
October 2020

Discovery of T-1101 tosylate as a first-in-class clinical candidate for Hec1/Nek2 inhibition in cancer therapy.

Eur J Med Chem 2020 Apr 7;191:112118. Epub 2020 Feb 7.

Taivex Therapeutics Corporation, 2nd Floor, Dongxing Rd., Songshan Dist., Taipei City, 10511, Taiwan.

Highly expressed in cancer 1 (Hec1) plays an essential role in mitosis and is correlated with cancer formation, progression, and survival. Phosphorylation of Hec1 by Nek2 kinase is essential for its mitotic function, thus any disruption of Hec1/Nek2 protein-protein interaction has potential for cancer therapy. We have developed T-1101 tosylate (9j tosylate, 9j formerly known as TAI-95), optimized from 4-aryl-N-pyridinylcarbonyl-2-aminothiazole of scaffold 9 by introducing various C-4' substituents to enhance potency and water solubility, as a first-in-class oral clinical candidate for Hec1 inhibition with potential for cancer therapy. T-1101 has good oral absorption, along with potent in vitro antiproliferative activity (IC: 14.8-21.5 nM). It can achieve high concentrations in Huh-7 and MDA-MB-231 tumor tissues, and showed promise in antitumor activity in mice bearing human tumor xenografts of liver cancer (Huh-7), as well as of breast cancer (BT474, MDA-MB-231, and MCF7) with oral administration. Oral co-administration of T-1101 halved the dose of sorafenib (25 mg/kg to 12.5 mg/kg) required to exhibit comparable in vivo activity towards Huh-7 xenografts. Cellular events resulting from Hec1/Nek2 inhibition with T-1101 treatment include Nek2 degradation, chromosomal misalignment, and apoptotic cell death. A combination of T-1101 with either of doxorubicin, paclitaxel, and topotecan in select cancer cells also resulted in synergistic effects. Inactivity of T-1101 on non-cancerous cells, a panel of kinases, and hERG demonstrates cancer specificity, target specificity, and cardiac safety, respectively. Subsequent salt screening showed that T-1101 tosylate has good oral AUC (62.5 μM·h), bioavailability (F = 77.4%), and thermal stability. T-1101 tosylate is currently in phase I clinical trials as an orally administered drug for cancer therapy.
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http://dx.doi.org/10.1016/j.ejmech.2020.112118DOI Listing
April 2020

An Often Easily Missed Injury in the Presence of Orthopaedic Trauma: A Case Series of Derived Injury.

Orthop Surg 2020 Feb 20;12(1):337-342. Epub 2020 Jan 20.

School of Medicine, Nankai University, Tianjin, China.

Derived disaster is a common concept in emergencies such as earthquakes. With the progress of society, the incidence of fractures caused by high-energy trauma has increased year by year. After the first injury, the possibility of derived injury caused by the original injury also increases rapidly. Orthopaedic surgeons, especially trauma orthopaedic surgeons, lack sufficient understanding and recognition of this kind of injury. The purpose of this article is to present a case series of an often missed injury pattern that is associated with an original injury. The diagnosis of derived injury may go unrecognized in a considerable number of cases and delayed treatment decreases the success rate of soft tissue repairing; therefore, a high index of suspicion and a proper early diagnosis is of paramount importance. We also describe the current surgical management used by the authors, and propose the concept of "derived injury", studying its clinical significance in traumatic orthopaedics.
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http://dx.doi.org/10.1111/os.12606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031595PMC
February 2020

A YajQ-LysR-like, cyclic di-GMP-dependent system regulating biosynthesis of an antifungal antibiotic in a crop-protecting bacterium, Lysobacter enzymogenes.

Mol Plant Pathol 2020 02 20;21(2):218-229. Epub 2019 Nov 20.

College of Plant Protection (Key Laboratory of Integrated Management of Crop Diseases and Pests), Nanjing Agricultural University, Nanjing, 210095, P.R. China.

YajQ, a binding protein of the universal bacterial second messenger cyclic di-GMP (c-di-GMP), affects virulence in several bacterial pathogens, including Xanthomonas campestris. In this bacterium, YajQ interacts with the transcription factor LysR. Upon c-di-GMP binding, the whole c-di-GMP-YajQ-LysR complex is found to dissociate from DNA, resulting in virulence gene regulation. Here, we identify a YajQ-LysR-like system in the bacterial biocontrol agent Lysobacter enzymogenes OH11 that secretes an antifungal antibiotic, heat-stable antifungal factor (HSAF) against crop fungal pathogens. We show that the YajQ homologue, CdgL (c-di-GMP receptor interacting with LysR) affects expression of the HSAF biosynthesis operon by interacting with the transcription activator LysR. The CdgL-LysR interaction enhances the apparent affinity of LysR to the promoter region upstream of the HSAF biosynthesis operon, which increases operon expression. Unlike the homologues CdgL (YajQ)-LysR system in X. campestris, we show that c-di-GMP binding to CdgL seems to weaken CdgL-LysR interactions and promote the release of CdgL from the LysR-DNA complex, which leads to decreased expression. Together, this study takes the YajQ-LysR-like system from bacterial pathogens to a crop-protecting bacterium that is able to regulate antifungal HSAF biosynthesis via disassembly of the c-di-GMP receptor-transcription activator complex.
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http://dx.doi.org/10.1111/mpp.12890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988422PMC
February 2020

A novel high maltose-forming α-amylase from Rhizomucor miehei and its application in the food industry.

Food Chem 2020 Feb 30;305:125447. Epub 2019 Aug 30.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. Electronic address:

A novel α-amylase gene (RmAmyA) from Rhizomucor miehei was cloned and expressed in Pichia pastoris. RmAmyA showed 70% amino acid identity with the α-amylase from Rhizomucor pusillus. A high α-amylase activity of 29,794.2 U/mL was found through high cell density fermentation. The molecular mass of RmAmyA was determined to be 49.9 kDa via SDS-PAGE. RmAmyA was optimally active at 75 °C and pH 6.0, and it did not require Ca to improve its activity. It exhibited broad substrate specificity towards amylose, amylopectin, soluble starch, pullulan, and cyclodextrins. High level of maltose (54%, w/w) was produced after liquefied starch was hydrolysed with RmAmyA for 16 h. Moreover, the addition of RmAmyA into Chinese steamed bread resulted in 7.7% increment in the specific volume, and 17.2% and 11.5% reduction in the chewiness and hardness, respectively. These results indicate that RmAmyA might be a potential candidate for applications in the food industry.
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http://dx.doi.org/10.1016/j.foodchem.2019.125447DOI Listing
February 2020

Dynamics of fungal communities during Gastrodia elata growth.

BMC Microbiol 2019 07 10;19(1):158. Epub 2019 Jul 10.

State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan, Yunnan University, Kunming, 650091, China.

Background: Gastrodia elata is a widely distributed achlorophyllous orchid and is highly valued as both medicine and food. Gastrodia elata produces dust-like seeds and relies on mycorrhizal fungi for its germination and growth. In its life cycle, G. elata is considered to switch from a specific single-fungus relationship (Mycena) to another single-fungus relationship (Armillaria). However, no studies have investigated the changes in the plant-fungus relationship during the growth of G. elata in the wild. In this study, high-throughput sequencing was used to characterize the fungal community of tubers in different growth phases as well as the soils surrounding G. elata.

Results: The predominant fungi were Basidiomycota (60.44%) and Ascomycota (26.40%), which exhibited changes in abundance and diversity with the growth phases of G. elata. Diverse basidiomycetes in protocorms (phase P) were Hyphodontia, Sistotrema, Tricholoma, Mingxiaea, Russula, and Mycena, but the community changed from a large proportion of Resinicium bicolor (40%) in rice-like tubers (phase M) to an unidentified Agaricales operational taxonomic unit 1(OTU1,98.45%) in propagation vegetation tubers (phase B). The soil fungi primarily included Simocybe, Psathyrella, Conocybe, and Subulicystidium. Three Mycena OTUs obtained in this study were differentially distributed among the growth phases of G. elata, accounting for less than 1.0% of the total reads, and were phylogenetically close to Mycena epipterygia and M. alexandri.

Conclusions: Our data indicated that G. elata interacts with a broad range of fungi beyond the Mycena genus. These fungi changed with the growth phases of G. elata. In addition, these data suggested that the development of the fungal community during the growth of G. elata was more complex than previously assumed and that at least two different fungi could be involved in development before the arrival of Armillaria.
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http://dx.doi.org/10.1186/s12866-019-1501-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6617676PMC
July 2019

High-level expression of a novel α-amylase from Thermomyces dupontii in Pichia pastoris and its application in maltose syrup production.

Int J Biol Macromol 2019 Apr 29;127:683-692. Epub 2019 Jan 29.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China. Electronic address:

A novel α-amylase gene (TdAmyA) with an open reading frame of 1431 bp, deducing 476 amino acids, was cloned from the thermophilic fungus Thermomyces dupontii L18. The recombinant α-amylase was successfully over-expressed in Pichia pastoris. The highest α-amylase activity of 38,314 U/mL was obtained with protein content of 28.7 mg/mL after 168 h high-cell density fermentation. Molecular mass of purified TdAmyA was 61.2 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 59.2 kDa by gel filtration. TdAmyA was a glycoprotein with 5.3% (w/w) of carbohydrate. TdAmyA exhibited maximal activity at 60 °C and pH 6.5, and was thermostable up to 55 °C within pH 4.5-10.0. It was more active towards linear starchy substrates than branched ones. The hydrolysis products were mainly comprised of maltose and maltotriose. TdAmyA produced the highest maltose content of 51.8% after 8 h hydrolysis. Thus, TdAmyA might be a candidate α-amylase for maltose syrup production.
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http://dx.doi.org/10.1016/j.ijbiomac.2019.01.162DOI Listing
April 2019

A Pilot Study on Parameter Setting of VisiTag™ Module during Pulmonary Vein Isolation.

Cardiol Res Pract 2018 29;2018:8960941. Epub 2018 Oct 29.

Department of Cardiology, Peking University First Hospital, Beijing, China.

Objectives: To identify optimal predefined criteria (OPC) for filters of the VisiTag™ module in the CARTO 3 system during pulmonary vein isolation (PVI).

Methods: Thirty patients with atrial fibrillation (AF) who experienced PVI first were enrolled. PVI was accomplished by using a Thermocool SmartTouch catheter. Ablation lesions were tagged automatically as soon as predefined criteria of the VisiTag™ module were met. OPC should be that ablation with the setting resulting in the conduction gap (CG) as few as possible, while contiguous encircling ablation line (CEAL) without the tag gap (TG) on the 3D anatomic model as much as possible.

Results: When ablation with parameter setting is being catheter movement with a 3 mm distance limit for at least 20 s and force over time (FOT) being off, there were 60 CEAL without TG on the 3D anatomic model. However, 26 CGs were found. After changing FOT setting to be a minimal force of 5 g with 50% stability time, 22 TGs were displayed. Of them, 20 TGs were accompanied by CGs. On reablation at sites of TG with changed parameter setting, 18 CGs were eliminated when 20 TGs disappeared. When reablation with FOT is being a minimal force of 10 g with 50% stability time, 6 remaining CGs were eliminated. However, there was no CEAL. With a mean of follow-up 10.93 months, 2 patients with persistent AF suffered AF recurrence.

Conclusion: A 3 mm distance limit for at least 20 s and FOT being a minimal force of 5 g with 50% stability time might be OPC for the VisiTag™ module.
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http://dx.doi.org/10.1155/2018/8960941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231390PMC
October 2018

Glutathione S-Transferase M1 and T1 polymorphisms and hypertension risk: an updated meta-analysis.

J Hum Hypertens 2019 06 12;33(6):454-465. Epub 2018 Nov 12.

Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, P.R. China.

Recently, Glutathione S-transferase M1 (GSTM1), glutathione S-transferase T1 (GSTT1), and their interaction with hypertension risk have been focused on. However, the results of previous studies have been inconsistent. Hence, the present meta-analysis was performed to explore the association. Twenty-two case-control studies met the inclusion criteria for GSTM1 (including 3577 hypertension cases and 3784 controls), twenty-two for GSTT1 (including 3741 cases and 4444 controls), and nine for their combined effects (including 1073 cases and 781 controls). Pooled analyses on the association between GSTM1 present/null polymorphism and hypertension risk were observed to be insignificant in overall and subgroup analyses. The individual who carries the GSTT1 null-genotype had a statistically significant overall population (OR = 1.28, 95% CI: 1.03, 1.60), Indians (OR = 2.45, 95% CI: 1.08, 5.59), and hospital-based controls (OR = 1.53, 95% CI: 1.21, 1.94). For the GSTM1-GSTT1 interaction, we found that the GSTM1/GSTT1 double-null-genotype was significantly associated with hypertension risks (double-null vs. double-present: OR = 2.68, 95% CI: 1.06, 6.81). To summarize, this meta-analysis indicates that Indians with the GSTT1 null-genotype has a raised hypertension risks; the GSTM1 null/GSTT1 null-genotype is association with raised hypertension risks, while the GSTM1 null-genotype is not associated with hypertension risks. In addition, I > 75% cannot be eliminated for GSTM1 in Indians or Asians, hence, it will be very important to explore the GSTM1 null-genotype and hypertension susceptibility in Indians and Asians for a large new sample, on population-based control study.
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http://dx.doi.org/10.1038/s41371-018-0133-3DOI Listing
June 2019

Anti-inflammatory activities of hepatocyte growth factor in post-ischemic heart failure.

Acta Pharmacol Sin 2018 Oct 24;39(10):1613-1621. Epub 2018 May 24.

Department of Cardiology, The Second Hospital of Shanxi Medical University, Taiyuan, 030001, China.

Hepatocyte growth factor (HGF) alleviates acute and chronic inflammation in experimental inflammatory bowel disease, glomerulonephritis, and airway inflammation. However, the anti-inflammatory effects of HGF on myocardial infarction are not defined. The current study assessed the anti-inflammatory effects of HGF in post-ischemic heart failure. The left anterior descending coronary artery was ligated in rats, and adenovirus containing human HGF (Ad-HGF) or control virus (Ad-GFP) was administered intramyocardially. The quantity of proinflammatory cytokines secreted by cardiomyocytes, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, was evaluated. Cardiac function and LV remodeling were assessed using echocardiography and collagen deposition, respectively. Left ventricular fractional shortening (LVFS) and left ventricular ejection fraction (LVEF) four weeks after injection were significantly increased in Ad-HGF-treated animals compared to the Ad-GFP group. HGF gene therapy improved ventricular geometry with a significantly decreased left ventricular end-diastolic diameter (LVEDD) and markedly reduced myocardial collagen deposition. Treatment with Ad-HGF significantly decreased the mRNA levels of TNF-α, IL-6, and IL-1β in the non-infarcted region four weeks after injection. Changes of the TNF-α, IL-6, and IL-1β levels in the non-infarcted region positively correlated with the LVEDD 4 weeks after infarction. Treatment of acute myocardial infarction (AMI) with Ad-HGF in the early stage of MI reduced the pro-inflammatory cytokine levels and preserved cardiac function. These findings indicated that Ad-HGF gene therapy alleviated ventricular remodeling after infarction by reducing inflammation.
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http://dx.doi.org/10.1038/aps.2018.14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6289380PMC
October 2018

Protective effects of theasinensin A against carbon tetrachloride-induced liver injury in mice.

Food Funct 2017 Sep;8(9):3276-3287

Citrus Research and Education Center, Department of Food Science and Human Nutrition, University of Florida, Lake Alfred, 33850, USA.

Theasinensins have been identified as a major group of unique catechin dimers mainly found in oolong tea and black tea. Among several types of theasinensins, theasinensin A (TSA), an epigallocatechin gallate (EGCG) dimer with an R-biphenyl bond, is the most abundant theasinensin prevalent in oolong tea. Previous studies have reported that TSA exhibits antioxidative, anti-inflammatory and anti-cancer activities in vitro and in vivo. However, little is known about the hepatoprotective effect of TSA. Thus, the aim of this study was to investigate the inhibitory effect of TSA on carbon tetrachloride (CCl)-induced hepatic fibrosis in mice. After intraperitoneal injection of CCl for eight weeks, histological lesions in the liver tissue and elevated serum levels of alanine aminotransferase and alkaline phosphatase were found in mice. Conversely, oral administration of TSA relieved CCl-induced liver injury as well as ameliorated liver functions. Our immunohistochemical staining results revealed that collagen deposition was profoundly reduced due to supplementation with TSA. In addition, we also found that hepatic α-smooth muscle actin (α-SMA) and matrix metallopeptidase 9 (MMP-9) expression was suppressed through the inhibition of transforming growth factor β (TGF-β). Taken together, our current findings suggest that TSA may serve as a potent bioactive constituent from oolong tea that acts against liver fibrosis through the inhibition of hepatic stellate cell (HSC) activation.
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http://dx.doi.org/10.1039/c7fo00700kDOI Listing
September 2017

[Association of serum vitamin D level with severity and treatment in children with Henoch-Schönlein purpura].

Zhongguo Dang Dai Er Ke Za Zhi 2017 Jul;19(7):796-799

Department of Pediatrics, Guizhou Provincial People's Hospital, Guiyang 550002, China.

Objective: To investigate the association of serum vitamin D [25-(OH)D] level with the severity and treatment in children with Henoch-Schönlein purpura (HSP).

Methods: A total of 50 children with newly-diagnosed HSP between January and December, 2015 were enrolled as HSP group, and 49 healthy children were enrolled as control group. Fasting serum samples were collected, and ELISA was used to measure serum 25-(OH)D level. According to the serum 25-(OH)D level, the HSP group were further divided into normal group (>20 ng/mL) (n=9), insufficiency group (15-20 ng/mL) (n=15), deficiency group (≤15 ng/mL) (n=25), and severe deficiency group (≤5 ng/mL) (n=1). The general data, clinical manifestations, hormone therapy, course of disease before admission, and length of hospital stay were compared between groups.

Results: The HSP group had a significantly lower serum 25-(OH)D level than the control group (16±6 ng/mL vs 29±5 ng/mL; P<0.01). Compared with the normal and insufficiency groups, the deficiency and severe deficiency groups had significant increases in the incidence rate of renal involvement, rate of hormone application, and median length of hospital stay (P<0.05), while there was no significant difference in course of disease before admission (P>0.05).

Conclusions: Children with HSP have a low serum 25-(OH)D level, and such children may have a high risk of renal involvement, a high rate of hormone application, and a prolonged length of hospital stay. However, further studies are needed to investigate whether vitamin D supplementation is helpful to the treatment of HSP and can shorten the course of disease in children with HSP.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7389916PMC
July 2017

Nucleotide binding by the widespread high-affinity cyclic di-GMP receptor MshEN domain.

Nat Commun 2016 08 31;7:12481. Epub 2016 Aug 31.

Institute of Biochemistry, National Chung Hsing University, Taichung 40227, Taiwan, Republic of China.

C-di-GMP is a bacterial second messenger regulating various cellular functions. Many bacteria contain c-di-GMP-metabolizing enzymes but lack known c-di-GMP receptors. Recently, two MshE-type ATPases associated with bacterial type II secretion system and type IV pilus formation were shown to specifically bind c-di-GMP. Here we report crystal structure of the MshE N-terminal domain (MshEN1-145) from Vibrio cholerae in complex with c-di-GMP at a 1.37 Å resolution. This structure reveals a unique c-di-GMP-binding mode, featuring a tandem array of two highly conserved binding motifs, each comprising a 24-residue sequence RLGxx(L/V/I)(L/V/I)xxG(L/V/I)(L/V/I)xxxxLxxxLxxQ that binds half of the c-di-GMP molecule, primarily through hydrophobic interactions. Mutating these highly conserved residues markedly reduces c-di-GMP binding and biofilm formation by V. cholerae. This c-di-GMP-binding motif is present in diverse bacterial proteins exhibiting binding affinities ranging from 0.5 μM to as low as 14 nM. The MshEN domain contains the longest nucleotide-binding motif reported to date.
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http://dx.doi.org/10.1038/ncomms12481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013675PMC
August 2016

microRNA-218 Inhibits Oxygen-induced Retinal Neovascularization via Reducing the Expression of Roundabout 1.

Chin Med J (Engl) 2016 03;129(6):709-15

Department of General Ophthalmology, Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin Key Laboratory of Ophthalmology and Visual Science, Tianjin 300020, China.

Background: The mechanisms of pathological retinal neovascularization (RNV) remain unknown. Several microRNAs were reported to be involved in the process of RNV. Oxygen-induced retinopathy (OIR) is a useful model to investigate RNV. Our present work explored the expression and the role of microRNA-128 (miR-218) in oxygen-induced RNV.

Methods: OIR was used to establish RNV model. The expression level of miR-218 in the retina from OIR mice was assessed by quantitative real-time reverse transcriptase polymerase chain reaction. Fluorescein angiography was performed in retinae of OIR mice, and RNV was quantified by hematoxylin and eosin staining to evaluate the effect of pCDH-CMV-miR-218 intravitreal injection on RNV in OIR mice. Roundabout 1 (Robo1) expression was detected by Western blotting in mouse retinal vascular endothelial cells expressing a high or low level of miR-218 and retinal tissues from OIR mice. Cell migration was evaluated by scratch wound assay.

Results: In OIR mice, the expression level of miR-218 was significantly down-regulated (P = 0.006). Retinal Robo1 expression was significantly increased at both mRNA and protein levels (P = 0.001, 0.008; respectively). miR-218 intravitreal injection inhibited retinal angiogenesis in OIR mice, and the restoration of miR-218 in retina led to down-regulation of Robo1.

Conclusions: Our experiments showed that restoration of miR-218 inhibited retinal angiogenesis via targeting Robo1. MiR-218 contributed to the inhibition of retinal angiogenesis and miR-218 might be a new therapeutic target for preventing RNV.
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http://dx.doi.org/10.4103/0366-6999.178013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4804418PMC
March 2016

Inhibitory effect of arsenic trioxide on neuronal migration in vitro and its potential molecular mechanism.

Environ Toxicol Pharmacol 2015 Nov 29;40(3):671-7. Epub 2015 Aug 29.

Department of Pediatrics, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China. Electronic address:

Primary neuron cultures were established from the brains of neonatal rats and the effects of arsenic trioxide (As2O3) on the migration of neurons and the potential mechanism of As2O3 were investigated. Boyden chamber assay was used to detect the effect of AS2O3 on neuronal migration. Matrix metalloproteinase-2 (MMP-2) and MMP-9 RNA expression and doublecortin (DCX) protein expression were measured. Neuronal migration ability was significantly lower in the 20 μmol/L group compared with the other three groups (all p < 0.001). The expression of both MMP-2 and MMP-9 was significantly inversely correlated with As2O3 concentration. The expression of DCX was significantly higher in the control group compared with the other three groups (all p ≤ 0.003). Thus, the inhibitory effect of As2O3 on the migration of primary neurons might be related to the reduction in MMP-2 and MMP-9 activities and decrease in β-actin and DCX expression.
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http://dx.doi.org/10.1016/j.etap.2015.08.026DOI Listing
November 2015

Effect of piperlongumine on drug resistance reversal in human retinoblastoma HXO-RB44/VCR and SO-Rb50/CBP cell lines.

Int J Clin Exp Pathol 2015 1;8(3):2525-34. Epub 2015 Mar 1.

Tianjin Eye Hospital, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Institute, Clinical College of Ophthalmology Tianjin Medical University Tianjin 300020, China.

Piperlongumine (PLGM) was considered as an anti-cancer agent since it was involved in suppressing of many types of cancer. To investigate the functions and mechanisms of PLGM on drug resistance reversal in human retinoblastoma cell lines, drug resistance cell lines HXO-RB44/VCR and SO-Rb50/CBP were established. We found that after treatment with PLGM, drug sensitivity and apoptosis rate of these drug resistance cancer cells were improved, cell cycle was arrested, the expressions of P-gp, MDR1, MRP1, Top-II, GST-π, Survivin, Bcl-2, CDK1, ABCB1 and ABCG1 was decreased, while the activities of caspase-3/8 and intracellular content of Rh-123 was increased. Furthermore, the activities of PI3K/AKT and PKCζ pathways were suppressed following PLGM treatment. Therefore, this study suggests that PLGM could reverse the drug resistance of human retinoblastoma cell lines HXO-RB44/VCR and SO-Rb50/CBP. This drug resistance reversing effect might exert via PI3K/AKT and PKCζ pathways.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4440067PMC
March 2016

Effect of flecainide on the extension and localization of complex fractionated electrogram during atrial fibrillation.

Scand Cardiovasc J 2015 Jun 27;49(3):168-75. Epub 2015 Apr 27.

Department of Heart Disease, Haukeland University Hospital and the Department of Clinical Science, University of Bergen , Bergen , Norway.

Aims: Complex fractionated electrogram (CFE) ablation in addition to pulmonary vein isolation is an accepted strategy for the treatment of non-paroxysmal atrial fibrillation (AF). We sought to determine the effect of flecainide on the distribution and extension of CFE areas.

Methods: Twenty-three non-paroxysmal AF patients were enrolled in this prospective study. A first CFE map was obtained under baseline conditions by sampling 5 s of continuous recording from the distal electrodes of the ablation catheter. Intravenous flecainide (1 mg/kg) was administered over 10 min and followed by 30-min observation time. A second CFE map was obtained with the same modalities. CFE-mean values, CFE areas, and atrial electrogram amplitude were retrieved from the electro-anatomical mapping system (Ensite NavX).

Results: After flecainide administration, CFE-mean values increased (111.5 ± 55.3 vs. 132.3 ± 65.0 ms, p < 0.001) with a decrease of CFE area (32.9%) in all patients. Atrial electrogram amplitude decreased significantly (0.30 ± 0.31 vs. 0.25 ± 0.20 mV, p < 0.001). We observed 80.9% preservation of CFE areas. A CFE mean of 78 ms was the best cutoff for predicting stable CFE areas.

Conclusions: Flecainide reduces the extension of CFE areas while preserving their spatial localization. A CFE-mean value <80 ms may be crucial to define and locate stable CFE areas.
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http://dx.doi.org/10.3109/14017431.2015.1036920DOI Listing
June 2015

Obesity increases the risk of renal involvement in children with Henoch-Schönlein purpura.

Eur J Pediatr 2015 Oct 22;174(10):1357-63. Epub 2015 Apr 22.

Department of Pediatrics, The Second Affiliated Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou District, Dalian, 116027, China.

Unlabelled: The main aim of this study was to evaluate the relationship between obesity and renal involvement in children with Henoch-Schönlein purpura (HSP). A retrospective study of 141 pediatric patients with HSP was conducted in our hospital. The clinical data of all patients were collected from the electronic medical record management system from January 2010 to June 2014. The possible risk factors of renal involvement, especially obesity, were analyzed using univariate and multivariate analyses. Renal involvement occurred in 45/141 of the patients. A univariate analysis showed that an age more than 7 years at onset, persistent purpura, obesity, time from symptoms onset to diagnosis more than 14 days, and decreased C3 all increased the risk of renal involvement in HSP. The forward stepwise logistic regression analysis indicated obesity (odds ratio (OR) 4.43, 95 % confidence interval (CI) 1.896 to 10.358), age more than 7 years at onset (OR 2.81, 95 % CI 1.142 to 6.907), and persistent purpura (OR 2.57, 95 % CI 1.119 to 5.909) were independent risk factors for renal involvement.

Conclusions: Our results show that obesity can increase the hazard of renal involvement in children with HSP and reconfirm that older age at onset and persistent purpura are the independent risk factors for renal involvement.

What Is Known: • There have been some reports that obesity was associated with the development of renal injury. • It is not clear whether obesity can increase the risk of renal involvement in children with HSP. What is New: • The main finding of this study is that obesity can increase the hazard of renal involvement in children with HSP.
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http://dx.doi.org/10.1007/s00431-015-2547-zDOI Listing
October 2015

Clinical and immunological features of common variable immunodeficiency in China.

Chin Med J (Engl) 2015 Feb;128(3):310-5

Department of Geriatrics, Peking University First Hospital, Beijing 100034, China.

Background: Common variable immunodeficiency (CVID) is one of the most common symptomatic primary immunodeficiency syndromes. The purpose of this article was to broaden our knowledge about CVID for better diagnosis and treatment.

Methods: Clinical and immunological features of 40 Chinese patients with CVID were analyzed retrospectively.

Results: The median age at onset was 11-year-old (range 4-51 years). The median age at diagnosis was 14.5-year-old (range 5-66 years). The average time of delay in diagnosis was 5.3 years (range 1-41 years). The most common main complaint was fever due to infections (35 cases, 87.5%). Pneumonia (28 cases, 70%) was the most common type of infections. Bronchiectasis was present in 6 patients (15%). Autoimmune disease was detected in 6 cases of CVID, and malignancy in 2 cases. The median total serum levels of IgG, IgA, and IgM at diagnosis were 1.07 g/L, 0.07 g/L, and 0.28 g/L, respectively. The percentages of CD3- /CD19 + B-cells were 1%-3.14%.

Conclusions: Infection is the most frequent presentation of CVID. Patients with unexplainable infections should receive further examination including serum immunoglobulin (Ig) and lymphocyte subset analysis. Regular and sufficient substitution with Ig is recommended.
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http://dx.doi.org/10.4103/0366-6999.150092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837860PMC
February 2015

[The clinicopathologic observation of 64 cases of eyelid and eyebrow pilomatrixoma].

Zhonghua Yan Ke Za Zhi 2013 Nov;49(11):997-1001

Clinical College of Ophthalmology, Tianjin Medical University, Tianjin Eye Institute, Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Hospital, Tianjin 300020, China.

Objective: To study the clinicopathologic characteristics of eyelid and eyebrow pilomatrixoma.

Methods: It was a retrospective case series study. The clinical and pathological characteristics of 64 cases of eyelid pilomatrixoma who were treated in Tianjin Eye Hospital or Tianjin Gongan Hospital from May 2003 to October 2012 were reviewed and analysed.

Results: In 64 cases, 21 cases were male(32.8%), 43 were female( 67.2%). The age at the time of diagnosis ranged from 1 to 66 years, 27 cases(42.1%) were before age 10 years, 13 cases(20.3%) were before age 20 years, 11 cases(17.2%) were before age 30 years, 13 cases were beyond age 30 years. The tumors were more frequent in children and younger patients, mainly involved the eyebrow and upper lid, 42 cases (65.6%) were eyebrow, 18 cases (28.1%) were upper lid, 3 cases (4.7%) were lower lid, and 1 case was inner canthus, no prominently differences between right and left eyes were showed. The clinical features mainly presented with a slowly growing asymptomatic solid mass attached to the skin, which were frequently a round nodule, clearly demarcated and more hard, with skin overlying the lesion was normal or presented some reddish or bluish discoloration. The history of the most cases were several months to one year. The greatest diameter of tumors ranged from 4 mm to 16 mm besides one case was 3.2 cm. The tumors were consisted of darkly staining basaloid cells and shadow cells, which most cases associated with polynuclear giant cell reaction and chronic inflammation. There were 24 cases(37.5%) showed varying degrees of calcification and 6 cases showed ossification, one case was presented an epidermoid cyst in the tumor and one case associated with a pilomatrixoma on homolateral upper extremity skin.

Conclusions: Pilomatrixoma is a benign neoplasm which is mainly consisted of basaloid cells and shadow cells, usually combined with inflammation, foreign body giant cells, calcification and ossification.If a child or young patient has a firm subcutaneous mass in the upper eyelid or eyebrow area, a pilomatrixoma should be suspected.
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November 2013

Dual topoisomerase I and II poisoning by chiral Ru(II) complexes containing 2-thiophenylimidazo[4,5-f][1,10]phenanthroline derivatives.

J Inorg Biochem 2014 Jan 7;130:15-27. Epub 2013 Oct 7.

MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, State Key Laboratory of Optoelectronic Materials and Technologies, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, PR China.

A series of chiral Ru(II) complexes bearing thiophene ligands were synthesized and characterized. Both Ru(II) complexes Δ/Λ-[Ru(bpy)2(pscl)](2+) (Δ/Λ-1) and Δ/Λ-[Ru(bpy)2(psbr)](2+) (Δ/Λ-2) (bpy=2,2'-bipyridine, pscl=2-(5-chlorothiophen-2-yl)imidazo[4,5-f][1,10]phenanthroline, psbr=2-(5-bromothiophen-2-yl)imidazo[4,5-f][1,10]phenanthroline) showed antitumor activities against A549, HepG2 and BEL-7402 tumor cell lines, especially HeLa tumor cell line. Moreover, Δ enantiomers were more active than Λ enantiomers, accounting for the different cellular uptake. In addition, with the extension of time, these enantiomers could finally accumulate in the nucleus, suggesting that nucleic acids were the cellular target of these enantiomers. The DNA-binding behaviors of complexes were studied using spectroscopic and viscosity measurements. Results suggested that four complexes could bind to DNA in an intercalative mode but no obvious DNA-binding selectivity between the enantiomers was observed. Topoisomerase inhibition and DNA religation assay confirmed that four complexes acted as efficient dual topoisomerase I and II poisons, DNA strand breaks had also been observed from alkaline single cell gel electrophoresis (comet assay). Δ-1 and Δ-2 inhibited the growth of HeLa cells through the induction of apoptotic cell death, as evidenced by the Alexa Fluor® 488 annexin V staining assays and flow cytometry analysis. The results demonstrated that Δ/Λ-1 and Δ/Λ-2 acted as dual topoisomerase I and II poisons and caused DNA damage that could lead to cell cycle arrest by apoptosis.
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http://dx.doi.org/10.1016/j.jinorgbio.2013.09.015DOI Listing
January 2014