Publications by authors named "Hong-bo Wang"

124 Publications

mTOR regulates cocaine-induced behavioural sensitization through the SynDIG1-GluA2 interaction in the nucleus accumbens.

Acta Pharmacol Sin 2021 Sep 14. Epub 2021 Sep 14.

National Chengdu Center for Safety Evaluation of Drugs, State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.

Behavioral sensitization is a progressive increase in locomotor or stereotypic behaviours in response to drugs. It is believed to contribute to the reinforcing properties of drugs and to play an important role in relapse after cessation of drug abuse. However, the mechanism underlying this behaviour remains poorly understood. In this study, we showed that mTOR signaling was activated during the expression of behavioral sensitization to cocaine and that intraperitoneal or intra-nucleus accumbens (NAc) treatment with rapamycin, a specific mTOR inhibitor, attenuated cocaine-induced behavioural sensitization. Cocaine significantly modified brain lipid profiles in the NAc of cocaine-sensitized mice and markedly elevated the levels of phosphatidylinositol-4-monophosphates (PIPs), including PIP, PIP and PIP. The behavioural effect of cocaine was attenuated by intra-NAc administration of LY294002, an AKT-specific inhibitor, suggesting that PIPs may contribute to mTOR activation in response to cocaine. An RNA-sequencing analysis of the downstream effectors of mTOR signalling revealed that cocaine significantly decreased the expression of SynDIG1, a known substrate of mTOR signalling, and decreased the surface expression of GluA2. In contrast, AAV-mediated SynDIG1 overexpression in NAc attenuated intracellular GluA2 internalization by promoting the SynDIG1-GluA2 interaction, thus maintaining GluA2 surface expression and repressing cocaine-induced behaviours. In conclusion, NAc SynDIG1 may play a negative regulatory role in cocaine-induced behavioural sensitization by regulating synaptic surface expression of GluA2.
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http://dx.doi.org/10.1038/s41401-021-00760-yDOI Listing
September 2021

Breastfeeding in Mothers with COVID-19: Insights from Laboratory Tests and Follow-Up from Early Outbreak of the Pandemic in China.

J Womens Health (Larchmt) 2021 Aug 26. Epub 2021 Aug 26.

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The outbreak of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) threatens a surging number of community groups within society, including women actively breastfeeding. Breastfeeding involves intimate behaviors, a major transmission route of SARS-CoV-2, and is integral to the close mother-baby relationship highly correlated with maternal psychological status. Twenty-three pregnant women and puerperae with either confirmed or suspected diagnoses of COVID-19 were enrolled in the study. The clinical characteristics and outcomes of the mothers and neonates were recorded. The presence of SARS-CoV-2, IgG, and IgM in breast milk, maternal blood, and infant blood, together with feeding patterns, was assessed within 1 month after delivery. Feeding patterns and maternal psychological status were also recorded in the second follow-up. No positive detection of SARS-CoV-2 was found in neonates. All breast milk samples were negative for the detection of SARS-CoV-2. The presence of IgM for SARS-CoV-2 in breast milk was correlated with IgM presence in the maternal blood. The results of IgG detection for SARS-CoV-2 were negative in all breast milk samples. All infants were in a healthy condition in two follow-ups, and antibody tests for SARS-CoV-2 were negative. The rate of breast milk feeding increased during two follow-ups. All mothers receiving a second follow-up experienced negative psychological factors and status. Our findings support the feasibility of breastfeeding in women infected with SARS-CoV-2. The additional negative psychological status of mothers due to COVID-19 should also be considered during the puerperium period.
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http://dx.doi.org/10.1089/jwh.2020.8978DOI Listing
August 2021

Natural product 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose is a reversible inhibitor of glyceraldehyde 3-phosphate dehydrogenase.

Acta Pharmacol Sin 2021 Apr 13. Epub 2021 Apr 13.

Drug Discovery and Design Center, the Center for Chemical Biology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancer cell glucose metabolism and plays a crucial role in the activation of various types of immune cells. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) catalyzes the conversion of D-glyceraldehyde 3-phosphate to D-glycerate 1,3-bisphosphate in the 6th critical step in glycolysis. GAPDH exerts metabolic flux control during aerobic glycolysis and therefore is an attractive therapeutic target for cancer and autoimmune diseases. Recently, GAPDH inhibitors were reported to function through common suicide inactivation by covalent binding to the cysteine catalytic residue of GAPDH. Herein, by developing a high-throughput enzymatic screening assay, we discovered that the natural product 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) is an inhibitor of GAPDH with K = 0.5 μM. PGG blocks GAPDH activity by a reversible and NAD and Pi competitive mechanism, suggesting that it represents a novel class of GAPDH inhibitors. In-depth hydrogen deuterium exchange mass spectrometry (HDX-MS) analysis revealed that PGG binds to a region that disrupts NAD and inorganic phosphate binding, resulting in a distal conformational change at the GAPDH tetramer interface. In addition, structural modeling analysis indicated that PGG probably reversibly binds to the center pocket of GAPDH. Moreover, PGG inhibits LPS-stimulated macrophage activation by specific downregulation of GAPDH-dependent glucose consumption and lactate production. In summary, PGG represents a novel class of GAPDH inhibitors that probably reversibly binds to the center pocket of GAPDH. Our study sheds new light on factors for designing a more potent and specific inhibitor of GAPDH for future therapeutic applications.
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http://dx.doi.org/10.1038/s41401-021-00653-0DOI Listing
April 2021

N(6)-methyladenosine-binding protein YTHDF1 suppresses EBV replication and promotes EBV RNA decay.

EMBO Rep 2021 04 19;22(4):e50128. Epub 2021 Feb 19.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.

N -methyladenosine (m A) modification of mRNA mediates diverse cellular and viral functions. Infection with Epstein-Barr virus (EBV) is causally associated with nasopharyngeal carcinoma (NPC), 10% of gastric carcinoma, and various B-cell lymphomas, in which the viral latent and lytic phases both play vital roles. Here, we show that EBV transcripts exhibit differential m A modification in human NPC biopsies, patient-derived xenograft tissues, and cells at different EBV infection stages. m A-modified EBV transcripts are recognized and destabilized by the YTHDF1 protein, which leads to the m A-dependent suppression of EBV infection and replication. Mechanistically, YTHDF1 hastens viral RNA decapping and mediates RNA decay by recruiting RNA degradation complexes, including ZAP, DDX17, and DCP2, thereby post-transcriptionally downregulating the expression of EBV genes. Taken together, our results reveal the critical roles of m A modifications and their reader YTHDF1 in EBV replication. These findings contribute novel targets for the treatment of EBV-associated cancers.
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http://dx.doi.org/10.15252/embr.202050128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025027PMC
April 2021

Role of calcitonin gene-related peptide in pain regulation in the parabrachial nucleus of naive rats and rats with neuropathic pain.

Toxicol Appl Pharmacol 2021 03 30;414:115428. Epub 2021 Jan 30.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, PR China; Neurobiology Laboratory, School of Life Sciences, Peking University, Beijing 100871, PR China. Electronic address:

Researches have shown that calcitonin gene-related peptide (CGRP) plays a pivotal role in pain modulation. Nociceptive information from the periphery is relayed from parabrachial nucleus (PBN) to brain regions implicated involved in pain. This study investigated the effects and mechanisms of CGRP and CGRP receptors in pain regulation in the PBN of naive and neuropathic pain rats. Chronic sciatic nerve ligation was used to model neuropathic pain, CGRP and CGRP 8-37 were injected into the PBN of the rats, and calcitonin receptor-like receptor (CLR), a main structure of CGRP receptor, was knocked down by lentivirus-coated CLR siRNA. The hot plate test (HPT) and the Randall Selitto Test (RST) was used to determine the latency of the rat hindpaw response. The expression of CLR was detected with RT-PCR and western blotting. We found that intra-PBN injecting of CGRP induced an obvious anti-nociceptive effect in naive and neuropathic pain rats in a dose-dependent manner, the CGRP-induced antinociception was significantly reduced after injection of CGRP 8-37, Moreover, the mRNA and protein levels of CLR, in PBN decreased significantly and the antinociception CGRP-induced was also significantly lower in neuropathic pain rats than that in naive rats. Knockdown CLR in PBN decreased the expression of CLR and the antinociception induced by CGRP was observably decreased. Our results demonstrate that CGRP induced antinociception in PBN of naive or neuropathic pain rats, CGRP receptor mediates this effect. Neuropathic pain induced decreases in the expression of CGRP receptor, as well as in CGRP-induced antinociception in PBN.
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http://dx.doi.org/10.1016/j.taap.2021.115428DOI Listing
March 2021

Combined DFT and kinetic Monte Carlo study of a bridging-spillover mechanism on fluorine-decorated graphene.

Phys Chem Chem Phys 2021 Jan;23(3):2384-2391

Laboratory of Advanced Materials Physics and Nanodevices, School of Physics and Technology, University of Jinan, Jinan, Shandong 250022, China.

In this work, combining first-principles calculations with kinetic Monte Carlo (KMC) simulations, we constructed an irregular carbon bridge on the graphene surface and explored the process of H migration from the Pt catalyst to carbon bridge, and further migration to the graphene surface. The calculated reaction diagrams show that the hydrogen atoms can easily migrate from the Pt cluster to the carbon bridge with a low barrier of 0.22-0.86 eV, and KMC simulations indicate that the migration reactions can take place at intermediate temperatures (91.9-329.5 K). Our research clarified the role of the carbon bridge: (1) the close combination of Pt clusters and carbon bridges reduces H2 adsorption enthalpy, which facilitates the spillover of H atoms from the Pt cluster to the carbon bridges and (2) the unsaturated carbon atoms on the carbon bridges have radical character and tend to bind radical H atoms. The subsequent study shows that the F atoms decorated on graphene can greatly reduce the migration barrier of H atoms from the carbon bridge to graphene. With F atoms decorated, the carbon atoms are in an electron-deficient state, which have a strong ability to bind the hydrogen atoms, and it promotes the migration of H atoms to the graphene surface. The migration barrier and reaction temperature are reduced to 0.72 eV and 279 K, respectively.
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http://dx.doi.org/10.1039/d0cp05584kDOI Listing
January 2021

Maternal vitamin D deficiency impairs Treg and Breg responses in offspring mice and deteriorates allergic airway inflammation.

Allergy Asthma Clin Immunol 2020 14;16:89. Epub 2020 Oct 14.

Department of Pediatrics, the First Hospital of Jilin University, Changchun, 130021 Jilin China.

Background: Vitamin D (VitD) can regulate immune responses and maternal VitD-deficiency can affect immune responses in the offspring. This study aimed at investigating the effects of maternal VitD-deficiency during pregnancy on Treg and Breg responses in offspring mice with house dust mite (HDM)-induced allergic airway inflammation.

Methods: Female BALB/c mice were randomized and fed with normal chow or VitD-deficient diet until their offspring weaned. The offspring mice were fed with normal chow and injected with vehicle or HDM to induce allergic airway inflammation. The levels of serum 25(OH)D, cytokines and infiltrate numbers as well as percentages of Tregs and Bregs in the bronchoalveolar lavage fluid (BALF) were analyzed. The relative levels of VitD receptor (VDR), VitD-binding protein (VDBP), Cytochromes P450 (CYP) 27b1, and CYP24A1 mRNA transcripts in the lungs of different groups of mice were measured.

Results: Maternal VitD-deficiency significantly reduced serum 25(OH)D levels in offspring mice. VitD-deficiency significantly increased the relative levels of VDR, VDBP and CYP27B1 mRNA transcripts, but decreased CYP24A1 expression in the lungs of mice. In comparison with the control mice, significantly elevated levels of pro-inflammatory cytokines, increased numbers of lymphocytes and eosinophils, but decreased levels of anti-inflammatory cytokines were detected in the BALF of VitD-deficient mice. VitD-deficiency significantly increased the frequency of Th1, Th2, Th9, Th17 cells, but decreased regulatory T (Tregs) and B cells (Bregs) in the BALF of mice with allergic airway inflammation.

Conclusion: Maternal VitD-deficiency lowed serum 25(OH)D levels and enhanced HDM-induced allergic airway inflammation in the offspring by impairing Breg and Treg responses.
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http://dx.doi.org/10.1186/s13223-020-00487-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7557044PMC
October 2020

Accumulated Clinical Experiences from Successful Treatment of 1377 Severe and Critically Ill COVID-19 Cases.

Curr Med Sci 2020 Aug 29;40(4):597-601. Epub 2020 Aug 29.

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

In late December 2019, COVID-19 was firstly recognized in Wuhan, China and spread rapidly to all of the provinces of China. The West Campus of Wuhan Union Hospital, the designated hospital to admit and treat the severe and critically ill COVID-19 cases, has treated a large number of such patients with great success and obtained lots of valuable experiences based on the Chinese guideline (V7.0). To standardize and share the treatment procedures of severe and critically ill cases, Wuhan Union Hospital has established a working group and formulated an operational recommendation, including the monitoring, early warning indicators, and several treatment principles for severe and critically ill cases. The treatment experiences may provide some constructive suggestions for treating the severe and critically ill COVID-19 cases all over the world.
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http://dx.doi.org/10.1007/s11596-020-2221-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412779PMC
August 2020

Role of Calcitonin Gene-Related Peptide in Nociceptive Modulationin Anterior Cingulate Cortex of Naïve Rats and Rats With Inflammatory Pain.

Front Pharmacol 2020 26;11:928. Epub 2020 Jun 26.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, China.

It is known that calcitonin gene-related peptide (CGRP) plays a key role in pain modulation in the brain. There are high expressions of CGRP and CGRP receptor in anterior cingulate cortex (ACC), an important brain structure in pain modulation. The present study explored the role and mechanisms of CGRP and CGRP receptor in nociceptive modulation in ACC in naïve rats and inflammatory rats. Administration of different does of CGRP in ACC induced significant antinociception in a dose-dependent manner in both naïve rats and rats with inflammatory pain. The CGRP-induced antinociception was attenuated by injection of the CGRP receptor antagonist CGRP8-37 in ACC. Interestingly, both CGRP-induced antinociception and CGRP receptor expression decreased in ACC in rats with inflammatory pain compared with naïve rats. Knockdown of CGRP receptor in ACC by siRNA targeting to CGRP receptor attenuated both the CGRP receptor expression and the CGRP-induced antinociception significantly in rats. These findings demonstrate that CGRP and CGRP receptor participate in nociceptive modulation in ACC in rats, inhibiting CGRP receptor expression induces decrease in CGRP-induced antinociception in ACC.
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http://dx.doi.org/10.3389/fphar.2020.00928DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332858PMC
June 2020

Expression of angiogenic factor with G patch and FHA domains 1 (AGGF1) in placenta from patients with preeclampsia.

Folia Histochem Cytobiol 2020 30;58(2):83-89. Epub 2020 Jun 30.

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.

Introduction: Preeclampsia (PE) is a major contributor to maternal and foetal morbidity and mortality worldwide. It manifests as high blood pressure and proteinuria in women at more than 20 weeks of gestation. Abnormal levels of anti- and pro-angiogenesis factors are known to be associated with PE. In the present study, we aimed to determine the localisation of angiogenic factor with G patch and FHA domains 1 (AGGF1) in the placenta and to compare the expression levels of AGGF1 in the third-trimester placentas of preeclamptic and normotensive pregnancies.

Materials And Methods: Placental tissue samples were collected from women with PE (n = 28) and without PE (n = 28). The normotensive controls without PE were matched for gestational age at delivery with the patients with PE. The expression levels of AGGF1 in the placental tissues were evaluated using immunohistochemistry, quantitative reverse transcription polymerase chain reaction and Western blot.

Results: The immunoexpression of AGGF1 was localised in the syncytiotrophoblast tissue. Notable, the mRNA and protein expression levels of AGGF1 were decreased in preeclamptic placentas as compared with the normotensive control group (P < 0.05).

Discussion: Our results suggest that the decreased AGGF1 in preeclamptic placentas may be related to the pathogenesis of preeclampsia.
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http://dx.doi.org/10.5603/FHC.a2020.0016DOI Listing
May 2021

Revealing Crystallization-Induced Blue-Shift Emission of a Di-Boron Complex by Enhanced Photoluminescence and Electrochemiluminescence.

Angew Chem Int Ed Engl 2020 Sep 11;59(40):17461-17466. Epub 2020 Aug 11.

Key Laboratory of Optoelectronic Chemical Materials and Devices of Ministry of Education, School of Chemical and Environmental Engineering, Jianghan University, Wuhan, Hubei, 430056, China.

Elucidating the effects of crystallization-induced blue-shift emission of a newly synthesized di-boron complex (DBC) by enhanced photoluminescence (PL) and electrochemiluminescence (ECL) in the annihilation pathway was realized for the first time. The 57 nm blue-shift and great enhancement in the crystalline lattice relative to the DBC solution were attributed to the restriction of intramolecular rotation (RIR) and confirmed by PL imaging, X-ray diffraction, as well as DFT calculations. It was discovered that ECL at crystalline film/solution interfaces can be further enhanced by means of both co-reactant route and RIR. The RIR contributions with co-reactant increased ECL up to 5 times more. Very interestingly, the co-reactant system was found to give off a red-shifted light emission. Mechanistic studies reveal that a difference between location of the ECL in the co-reactant route and that in the annihilation pathway leads to an alternative emission wavelength.
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http://dx.doi.org/10.1002/anie.202007588DOI Listing
September 2020

Cardiac Troponin I Is an Independent Predictor for Mortality in Hospitalized Patients With COVID-19.

Circulation 2020 08 15;142(6):608-610. Epub 2020 Jun 15.

Departments of Cardiology (S.-F.N., M.Y., T.X., F.Y., Z.-H.W., M.L., X.-L.G., B.-J.L., S.-J.W., X.-B.Z., S.-O.H., Y.-H.L., Z.-H.Z., X.C.), Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.048789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418761PMC
August 2020

PCC0208009, an indirect IDO1 inhibitor, alleviates neuropathic pain and co-morbidities by regulating synaptic plasticity of ACC and amygdala.

Biochem Pharmacol 2020 07 23;177:113926. Epub 2020 Mar 23.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong Province, China. Electronic address:

Background And Purpose: Indoleamine 2, 3-dioxygenase 1 (IDO1) has been linked to neuropathic pain and IDO1 inhibitors have been shown to reduce pain in animals. Some studies have indicated that IDO1 expression increased after neuropathic pain in hippocampus and spinal cord, whether these changes existing in anterior cingulate cortex (ACC) and amygdala remains obscure and how IDO1 inhibition leads to analgesia is largely unknown. Here, we evaluated the antinociceptive effect of PCC0208009, an indirect IDO1 inhibitor, on neuropathic pain and examined the related neurobiological mechanisms.

Experimental Approach: The effects of PCC0208009 on pain, cognition and anxiogenic behaviors were evaluated in a rat model of neuropathic pain. Motor disorder, sedation and somnolence were also assessed. Biochemical techniques were used to measure IDO1-mediated signaling changes in ACC and amygdala.

Key Results: In rats receiving spinal nerve ligation (SNL), IDO1 expression level was increased in ACC and amygdala. PCC0208009 attenuated pain-related behaviors in the formalin test and SNL model and increased cognition and anxiogenic behaviors in SNL rats at doses that did not affect locomotor activity and sleeping. PCC0208009 inhibited IDO1 expression in ACC and amygdala by inhibiting the IL-6-JAK2/STAT3-IDO1-GCN2-IL-6 pathway. In addition, PCC0208009 reversed synaptic plasticity at the functional and structural levels by suppressing NMDA2B receptor and CDK5/MAP2 or CDK5/Tau pathway in ACC and amygdala.

Conclusion And Implications: These results support the role of IDO1-mediated molecular mechanisms in neuropathic pain and suggest that the IDO1 inhibitor PCC0208009 demonstrates selective pain suppression and could be a useful pharmacological therapy for neuropathic pain.
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http://dx.doi.org/10.1016/j.bcp.2020.113926DOI Listing
July 2020

NLRP3 inflammasome activation by estrogen promotes the progression of human endometrial cancer.

Onco Targets Ther 2019 27;12:6927-6936. Epub 2019 Aug 27.

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, People's Republic of China.

Background: Activation of NLPR3 inflammasome is associated with the development and progression of some types of malignant tumors, but its role in endometrial cancer is unclear. This study aimed to investigate the expression and function of NLRP3 inflammasome in endometrial cancer.

Materials And Methods:  The expression levels of NLRP3, its inflammasome components and estrogen receptor β in endometrial cancer and paired non-tumor tissues were detected. The effects of NLPR3 silencing or overexpression on the proliferation, migration, and invasion of Ishikawa and HEC-1A cells were determined. The impact of NLPR3 silencing on the growth of implanted tumors was determined in vivo. The effects of estrogen on NLPR3 inflammasome activation and Ishikawa cell proliferation were determined.

Results: The upregulation of NLRP3, ASC, caspase-1, and IL-1β was associated with the progression of endometrial cancer and poor survival. NLPR3 silencing inhibited the proliferation, migration, and invasion of endometrial cancer cells while NLPR3 overexpression had opposite effects. NLPR3 silencing reduced IL-1β and caspase-1 expression and the growth of implanted endometrial tumors, accompanied by decreased pro-IL-1β maturation. Estrogen enhanced NLPR3, ERβ, pro-IL-1β, IL-1β expression, and endometrial cancer cell proliferation, which were mitigated by treatment with ERβ inhibitor but not ERα inhibitor.

Conclusion: Our results suggest that estrogen acts through ERβ to enhance the activation of NLPR3 inflammasome and promote the progression of endometrial cancer. NLPR3 inflammasome may be a new therapeutic target for endometrial cancer.
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http://dx.doi.org/10.2147/OTT.S218240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717726PMC
August 2019

Phthalideisoquinoline Hemiacetal Alkaloids from That Inhibit Spontaneous Calcium Oscillations, Including Alkyl Derivatives of (+)-Egenine That Are Strikingly Levorotatory.

J Nat Prod 2019 10 10;82(10):2713-2720. Epub 2019 Oct 10.

State Key Laboratory of Natural Medicines & Jiangsu Provincial Key Laboratory for TCM Evaluation and Translational Development, School of Traditional Chinese Pharmacy , China Pharmaceutical University , Nanjing , Jiangsu 211198 , People's Republic of China.

The new phthalideisoquinoline hemiacetal alkaloids (-) and the known analogues ( and ) were isolated from the bulbs of . The new compounds were characterized by analysis of their NMR spectroscopic data, chemical degradation syntheses, X-ray crystallography, and comparison of experimental and calculated ECD data. All the isolates were screened in vitro for inhibitory activity of spontaneous calcium oscillations in primary cultured neocortical neurons. Compounds - and - were found to be active in the suppression of spontaneous calcium oscillations with IC values of 6.8, 5.6, 11.6, 10.2, 8.3, and 3.1 μM, respectively. It was also observed that the presence of hydroxy, methoxy, and ethoxy groups at the remote stereogenic center C-7' of some isolated phthalideisoquinoline hemiacetal alkaloids could alter the preferred conformation and invert the sign of optical rotation, rather than this resulting from configurational isomerism at C-1 or C-9, and that the coupling constants of these analogues varied accordingly. For example, compounds and are levorotatory, despite these molecules having the same carbon skeleton and absolute configuration as (+)-egenine. This emphasizes the potential risk of incorrectly assigning absolute configuration based only on observed coupling constants or optical rotation when comparing the data of new compounds with literature values for known analogues, especially within this class of molecules.
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http://dx.doi.org/10.1021/acs.jnatprod.9b00247DOI Listing
October 2019

A novel model of controlling PD-L1 expression in ALK anaplastic large cell lymphoma revealed by CRISPR screening.

Blood 2019 07 31;134(2):171-185. Epub 2019 May 31.

Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA.

The success of programmed cell death protein 1 (PD-1)/PD-L1-based immunotherapy highlights the critical role played by PD-L1 in cancer progression and reveals an urgent need to develop new approaches to attenuate PD-L1 function by gaining insight into how its expression is controlled. Anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALK ALCL) expresses a high level of PD-L1 as a result of the constitutive activation of multiple oncogenic signaling pathways downstream of ALK activity, making it an excellent model in which to define the signaling processes responsible for PD-L1 upregulation in tumor cells. Here, using clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 library screening, we sought a comprehensive understanding of the molecular effectors required for PD-L1 regulation in ALK ALCL. Indeed, we determined that PD-L1 induction is dependent on the nucleophosmin-ALK oncoprotein activation of STAT3, as well as a signalosome containing GRB2/SOS1, which activates the MEK-ERK and PI3K-AKT signaling pathways. These signaling networks, through STAT3 and the GRB2/SOS1, ultimately induce PD-L1 expression through the action of transcription factors IRF4 and BATF3 on the enhancer region of the gene. IRF4 and BATF3 are essential for PD-L1 upregulation, and IRF4 expression is correlated with PD-L1 levels in primary ALK ALCL tissues. Targeting this oncogenic signaling pathway in ALK ALCL largely inhibited the ability of PD-L1-mediated tumor immune escape when cocultured with PD-1-positive T cells and natural killer cells. Thus, our identification of this previously unrecognized regulatory hub not only accelerates our understanding of the molecular circuitry that drives tumor immune escape but also provides novel opportunities to improve immunotherapeutic intervention strategies.
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http://dx.doi.org/10.1182/blood.2019001043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624970PMC
July 2019

Targeting of SPP1 by microRNA-340 inhibits gastric cancer cell epithelial-mesenchymal transition through inhibition of the PI3K/AKT signaling pathway.

J Cell Physiol 2019 08 5;234(10):18587-18601. Epub 2019 Apr 5.

Department of Digestive Disease, The Second Hospital of Shandong University, Jinan, Shandong, People's Republic of China.

Gastric cancer (GC) is a common heterogeneous disease. The critical roles of microRNA-340 (miR-340) in the development and progression of GC were emphasized in accumulating studies. This study aims to examine the regulatory mechanism of miR-340 in GC cellular processes. Initially, microarray technology was used to identify differentially expressed genes and regulatory miRs in GC. After that, the potential role of miR-340 in GC was determined via ectopic expression, depletion, and reporter assay experiments. Expression of secreted phosphoprotein 1 (SPP1), miR-340, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway, and epithelial-mesenchymal transition (EMT)-related genes was measured. Moreover, to further explore the function of miR-340 in vivo and in vitro, proliferation, apoptosis, migration, invasion, and tumorigenic capacity were evaluated. SPP1 was a target gene of miR-340 which could then mediate the PI3K/AKT signaling pathway by targeting SPP1 in GC. Furthermore, miR-340 levels were reduced and SPP1 was enriched in GC tissues and cells, with the PI3K/AKT signaling pathway being activated. Inhibitory effects of upregulated miR-340 on SPP1 and the PI3K/AKT signaling pathway were confirmed in vivo and in vitro. Overexpression of miR-340 or the silencing of SPP1 inhibited GC cell proliferation, invasion, migration, and EMT process, but promoted apoptosis of GC cells. Typically, targeting of SPP1 by miR-340 may contribute to the inhibition of proliferation, migration, invasion, and EMT of GC cells via suppression of PI3K/AKT signaling pathway.
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http://dx.doi.org/10.1002/jcp.28497DOI Listing
August 2019

NLRP3 inflammasome pathway is involved in olfactory bulb pathological alteration induced by MPTP.

Acta Pharmacol Sin 2019 Aug 6;40(8):991-998. Epub 2019 Feb 6.

Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai, 264005, China.

Olfactory bulb, as one of sensory organs opening to the outside, is susceptible to toxic environment and easy to deteriorate. Recent studies in Parkinson's disease (PD) patients and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys have shown that abnormal α-synuclein is accumulated in the olfactory glomeruli, suggesting that the lesions of PD are not only confined to the substantia nigra (SN) but also located in the olfactory bulb. Thus, olfactory bulb might be the region of onset in PD pathogenesis and a targeted region for diagnosis and treatment of PD. However, the relationship between olfactory bulb and pathogenesis of PD remains unclear. In the present study, we investigated the inflammatory pathological alterations in olfactory bulb and the underlying mechanisms in chronic MPTP mice. Mice were treated with MPTP/P, i.e., MPTP (25 mg/kg, s.c.) plus probenecid (250 mg/kg, i.p.) every 4 days, for ten times. The mice displayed typical parkinsonian syndrome. Then we examined their olfactory function and the pathologic changes in olfactory bulb. The mice showed obvious olfactory dysfunction in a buried pellet test. Immunohistochemical studies revealed that tyrosine hydroxylase (TH) protein levels were significantly decreased, whereas abnormal α-synuclein was significantly increased in the olfactory bulbs. Furthermore, the olfactory bulbs in MPTP/P-treated mice showed significantly increased levels of interleukin-1β (IL-1β), caspase-1, glial fibrillary acidic protein (GFAP), Toll receptor 4 (TLR4), phosphorylation of p65, as well as activated molecules of NOD-like receptor protein 3 (NLRP3) that were associated with neuroinflammation. Our results demonstrate that MPTP/P-caused olfactory bulb damage might be related to NLRP3-mediated inflammation.
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http://dx.doi.org/10.1038/s41401-018-0209-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6786401PMC
August 2019

The mechanisms of NLRP3 inflammasome/pyroptosis activation and their role in Parkinson's disease.

Int Immunopharmacol 2019 Feb 27;67:458-464. Epub 2018 Dec 27.

Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Yantai University, Yantai 264005, China.

Parkinson's disease (PD) is a typical neurodegenerative disease and the pathological feature of which is the death of dopamine neurons in the substantia nigra region. At present, neuronal death caused by inflammatory cytokine-mediated neuroinflammation is being extensively studied. The nucleotide-binding oligomerization domain-, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome is an inflammatory complex existing in microglia. Its activation promotes the secretion of the inflammatory cytokine interleukin-1β/18 (IL-1β/18) and induces pyroptosis, a type of cell death that possesses the potential for inflammation, to rupture microglia to further release IL-1β. In this review we focus on the mechanisms of activation of the NLRP3 inflammasome and pyroptosis and their inflammatory effects on the development of PD. In addition, we focus on some inhibitors of NLRP3 inflammatory pathways to alleviate the progression of PD by inhibiting central inflammation and provide new therapeutic strategies for the treatment of PD.
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http://dx.doi.org/10.1016/j.intimp.2018.12.019DOI Listing
February 2019

Synthesis and biological evaluation of novel H6 analogues as drug resistance reversal agents.

Eur J Med Chem 2019 Jan 16;161:364-377. Epub 2018 Oct 16.

School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China. Electronic address:

Hederagenin is a naturally occurring pentacyclic triterpenoids compound with multiple pharmacological activities. We recently showed that H6, a synthetic derivative of hederagenin, could enhance the anticancer activity of paclitaxel in drug-resistant cells in vitro and in vivo, but showed poor solubility. With the aim of improving the drug resistant reversal activity of H6, here we designed and synthesized a series of novel H6 analogues. Our results showed that compound 10 at the concentration of 5 μM significantly enhanced the cytotoxicity of paclitaxel to drug-resistant KBV cells and sensitized cells to paclitaxel in arresting cells in G/M phase and inducing apoptosis. We found that compound 10 might block the drug efflux of P-gp via stimulating P-gp ATPase activity. Importantly, compound 10 enhanced the efficacy of paclitaxel against KBV cancer cell-derived xenograft tumors. Finally, we summarized a preliminary structure-activity relationship of hederagenin by the drug resistant reversal activity of H6 analogues in vitro and compound 10 and H6in vivo. This study highlights the importance of nitrogen-containing derivatives of hederagenin C-28 in the development of novel drug resistance reversal agents.
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http://dx.doi.org/10.1016/j.ejmech.2018.10.033DOI Listing
January 2019

The Effects of miR-195-5p/MMP14 on Proliferation and Invasion of Cervical Carcinoma Cells Through TNF Signaling Pathway Based on Bioinformatics Analysis of Microarray Profiling.

Cell Physiol Biochem 2018 24;50(4):1398-1413. Epub 2018 Oct 24.

Department of Obstetrics and Gynecology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Background/aims: This study is aimed at identification of miR-195-5p/MMP14 expression in cervical cancer (CC) and their roles on cell proliferation and invasion profile of CC cells through TNF signaling pathway in CC.

Methods: Microarray analysis, gene set enrichment analysis (GSEA) and DAVID were used to analyze differentially expressed miRNAs, mRNAs and signaling pathways. MiR-195-5p and MMP14 expression levels in CC cell were determined by qRT-PCR. Western blot was employed to measure MMP14 and TNF signaling pathway-relating protein level. Luciferase reporter system was used to confirm the targeting relationship between MMP14 and miR-195-5p. Cell proliferation and invasion was respectively deeded by CCK8, transwell. In vivo experiment was carried out to study the impact of MMP14 and miR-195-5p on CC development in mice.

Results: The microarray analysis and the results of qRT-PCR determined that miR-195-5p was under-expressed and MMP14 was over-expressed in CC cells. GSEA and DAVID analysis showed that TNF signaling pathway was regulated by miR-195-5p/MMP14 and activated in cervical carcinoma cells. The miR-195-5p and MMP14 have a negative regulation relation. In vivo experiment found that down-regulated MMP14 and up-regulated miR-195-5p suppressed the tumor development.

Conclusion: Our results suggest that MMP14 is a direct target of miR-195-5p, and down-regulated MMP14 and up-regulated miR-195-5p suppressed proliferation and invasion of CC cells by inhibiting TNF signaling pathway.
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http://dx.doi.org/10.1159/000494602DOI Listing
November 2018

Doxorubicin resistance induces IL6 activation in the colon cancer cell line LS180.

Oncol Lett 2018 Nov 23;16(5):5923-5929. Epub 2018 Aug 23.

Department of General Surgery, Xiangyang Central Hospital, Affiliated Hospital of Hubei College of Arts and Science, Xiangyang, Hubei 441021, P.R. China.

Despite improvements in the development of drugs for the treatment of cancer, drug resistance remains a major obstacle. In colon cancer, following an initially promising response, patients develop drug resistance, which impacts the efficacy and halts the response of cancerous cells towards drugs. In the present study, a phosphatase and tensin homolog (PTEN) knockdown model of LS180 cells, doxorubicin-resistant models of LS180 cells as well as doxorubicin-resistant LS180 (PTEN) knockdown model were established. The present study demonstrated that doxorubicin resistance led to the activation of interleukin (IL)6 signalling pathway which was enhanced by knockdown of PTEN. There was also an increase in the levels of IL8 and IL2 which were further enchanced by knockdown of PTEN. Doxorubicin resistance also led to an increase in the population of cancer stem cells in LS180 and shPTEN-treated LS180 cells. Notably, doxorubicin resistance also induced epithelial to mesenchymal transition and increased the formation of mammospheres. Furthermore, the present study also reported that IL6 receptor antibody not only decreased IL6 levels but also led to a significant decreased number of cancer stem cell like population and mammosphere formation. In conclusion, in the present study it was demonstrated that doxorubicin resistance led to activation of IL6 signalling pathway which was further elevated by the knockdown of PTEN in the colon cancer cell line LS180. Thus, inhibiting the IL6 loop may provide an alternative pathway to tackle doxorubicin resistance.
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http://dx.doi.org/10.3892/ol.2018.9360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6176352PMC
November 2018

Novel conductive polypyrrole/silk fibroin scaffold for neural tissue repair.

Neural Regen Res 2018 Aug;13(8):1455-1464

Key Laboratory of Science and Technology of Eco-textiles, Ministry of Education, Jiangnan University, Wuxi, Jiangsu Province, China.

Three dimensional (3D) bioprinting, which involves depositing bioinks (mixed biomaterials) layer by layer to form computer-aided designs, is an ideal method for fabricating complex 3D biological structures. However, it remains challenging to prepare biomaterials with micro-nanostructures that accurately mimic the nanostructural features of natural tissues. A novel nanotechnological tool, electrospinning, permits the processing and modification of proper nanoscale biomaterials to enhance neural cell adhesion, migration, proliferation, differentiation, and subsequent nerve regeneration. The composite scaffold was prepared by combining 3D bioprinting with subsequent electrochemical deposition of polypyrrole and electrospinning of silk fibroin to form a composite polypyrrole/silk fibroin scaffold. Fourier transform infrared spectroscopy was used to analyze scaffold composition. The surface morphology of the scaffold was observed by light microscopy and scanning electron microscopy. A digital multimeter was used to measure the resistivity of prepared scaffolds. Light microscopy was applied to observe the surface morphology of scaffolds immersed in water or Dulbecco's Modified Eagle's Medium at 37°C for 30 days to assess stability. Results showed characteristic peaks of polypyrrole and silk fibroin in the synthesized conductive polypyrrole/silk fibroin scaffold, as well as the structure of the electrospun nanofiber layer on the surface. The electrical conductivity was 1 × 10-1 × 10 S/cm, while stability was 66.67%. A 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay was employed to measure scaffold cytotoxicity in vitro. Fluorescence microscopy was used to observe EdU-labeled Schwann cells to quantify cell proliferation. Immunohistochemistry was utilized to detect S100β immunoreactivity, while scanning electron microscopy was applied to observe the morphology of adherent Schwann cells. Results demonstrated that the polypyrrole/silk fibroin scaffold was not cytotoxic and did not affect Schwann cell proliferation. Moreover, filopodia formed on the scaffold and Schwann cells were regularly arranged. Our findings verified that the composite polypyrrole/silk fibroin scaffold has good biocompatibility and may be a suitable material for neural tissue engineering.
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http://dx.doi.org/10.4103/1673-5374.235303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6108196PMC
August 2018

Anillin is required for tumor growth and regulated by miR-15a/miR-16-1 in HBV-related hepatocellular carcinoma.

Aging (Albany NY) 2018 Aug;10(8):1884-1901

Guangdong Provincial Key Laboratory of Liver Disease Research, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.

Anillin (ANLN) is an actin-binding protein essential for assembly of cleavage furrow during cytokinesis. Although reportedly overexpressed in various human cancers, its role in hepatocellular carcinoma (HCC) is unclear. To address this issue, we confirmed that in 436 liver samples obtained from surgically removed HCC tissues, higher ANLN expression was detected in tumor tissues than in adjacent non-tumor tissues of HCC as measured by immunohistochemistry, quantitative real-time PCR and western blotting. Correlation and Kaplan-Meier analysis revealed that patients with higher ANLN expression were associated with worse clinical outcomes and a shorter survival time, respectively. Moreover, ANLN inhibition resulted in growth restraint, reduced colony formation, and a lower sphere number in suspension culture. Mechanistically, ANLN deficiency induced an increasing number of multinucleated cells along with the activation of apoptosis signaling and DNA damage checkpoints. Furthermore, HBV infection increased ANLN expression by inhibiting the expression of microRNA (miR)-15a and miR-16-1, both of which were identified as ANLN upstream repressors by targeting its 3' untranslated region. Thus, we conclude that ANLN promotes tumor growth by ways of decreased apoptosis and DNA damage. Expression level of ANLN significantly influences the survival probability of HCC patients and may represent a promising prognostic biomarker.
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http://dx.doi.org/10.18632/aging.101510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6128427PMC
August 2018

Facile synthesis and efficient electrochemiluminescence of a readily accessible pyridopyrimidine.

Chem Commun (Camb) 2018 Sep 6;54(71):9897-9900. Epub 2018 Aug 6.

Key Laboratory of Optoelectronic Chemical Materials and Devices of Ministry of Education, School of Chemical and Environmental Engineering, Jianghan University, Wuhan, Hubei 430056, China. and Department of Chemistry, The University of Western Ontario, 1151 Richmond Street, London, ON N6A 5B7, Canada.

Through a facile one-pot three-component reaction and a subsequent acetylation strategy, a novel greenish-blue fluorescent 4-imino-4H-pyrido[1,2-a]pyrimidine-3-carbonitrile (IPPC) was synthesized. Electrochemiluminescence (ECL) of IPPC was firstly found to produce efficient emission at 500 nm with reducing coreactants. Its very similar ECL and PL spectra suggest that ECL production is mainly from the monomeric excited states.
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http://dx.doi.org/10.1039/c8cc05490hDOI Listing
September 2018

Overexpression of dedicator of cytokinesis 2 correlates with good prognosis in colorectal cancer associated with more prominent CD8 lymphocytes infiltration: a colorectal cancer analysis.

J Cell Biochem 2018 11 4;119(11):8962-8970. Epub 2018 Aug 4.

Department of Pathology, Shanghai General Hospital/Faculty of Basic Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Recently, dedicator of cytokinesis 2 (DOCK2) has been reportedly exhibited high mutation prevalence in the Asian colorectal cancer (CRC) cohort. However, the expression pattern of DOCK2 and its clinical significance in CRC were still unknown. To characterize the role of DOCK2, a tissue microarray (TMA) containing 481 archived paraffin-embedded CRC specimens was performed by immunohistochemistry. Among which, 54 primary CRC tissues showed high expression of DOCK2 protein, while others were negative. Moreover, DOCK2 expression was positively associated with invasion depth (P < .001) and tumor size (P = .016). Significantly, Kaplan-Meier survival analysis revealed that patients with higher DOCK2 expression had a longer overall survival time (P = .017). Furthermore, univariate and multivariate Cox regression analysis confirmed that DOCK2 is an independent prognostic marker in CRC (P = .049,; HR, 0.519; 95% CI, 0.270 to 0.997). In addition, we observed a strong correlation between the infiltration of CD8 T lymphocytes and DOCK2 expression (P = .0119). Our findings demonstrated that overexpressed DOCK2 might involve in recruiting CD8 T lymphocytes and serve as a novel prognostic indicator and indicated a potential therapeutic strategy by restoring DOCK2 for CRC.
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http://dx.doi.org/10.1002/jcb.27151DOI Listing
November 2018

Determination of benzo[α]pyrene in edible oil using tetraoxocalix[2]arene[2]triazine bonded silica SPE sorbent.

Food Addit Contam Part A Chem Anal Control Expo Risk Assess 2018 Jul 18;35(7):1356-1365. Epub 2018 Jun 18.

a College of Chemistry and Molecular Engineering , Zhengzhou University , Zhengzhou , PR China.

Benzo[α]pyrene (BaP) is a well-known carcinogen in edible oil. In this study, a method combined solid-phase extraction (SPE) with fluorescent detection was developed using tetraoxocalix[2]arene[2]triazine sorbent (SiO-OCA) for the clean-up and enrichment of BaP. The interaction between SiO-OCA and BaP involves a donor-acceptor complex mechanism. The experimental procedure was as follows: BaP was extracted from edible oil with DMF/HO (9:1, v/v). Then, the ratio of DMF/HO was adjusted to 1:2 prior to SPE. The final concentrate was analysed using a fluorescence detector at excitation and emission wavelengths of 255 and 420 nm. The method was fully validated. The linearity was in the range of 0.1-100 μg kg with a coefficient of 0.999. The limits of detection and quantification were 0.03 and 0.1 μg kg, respectively. The average recoveries were in the range of 88.0 - 122.3%. The intraday and interday precisions were 6.8% and 9.2%, respectively. Compared with other methods, the method reported in this article shows a good detection limit, high reproducibility and recovery and linearity over a broad concentration range. This established method was also applied to evaluate real samples. The concentration of six tested samples was below 5 μg kg.
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http://dx.doi.org/10.1080/19440049.2018.1482010DOI Listing
July 2018

Author Correction: Ephrin receptor A2 is an epithelial cell receptor for Epstein-Barr virus entry.

Nat Microbiol 2018 Sep;3(9):1075

Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology, South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.

In the version of this Letter originally published, the authors reported on the use of 2,5-dimethylpyrrolyl benzoic acid to block Ephrin receptors. In 2011, it was reported that newly synthesized 2,5-dimethylpyrrolyl benzoic acid lacked the previously reported EphA2 antagonizing activity1. However, the purchased compound did in fact have the activity initially reported, suggesting that an uncharacterized alteration occurred during storage. The authors therefore wish to clarify that the compound used in their study should be more accurately referred to as a 2,5-dimethylpyrrolyl benzoic acid derivative. All references to 2,5-dimethylpyrrolyl benzoic acid in the Letter have now been changed to reflect this.Although 2,5-dimethylpyrrolyl benzoic acid derivatives have been reported to have off-target effects2, as do most small-molecule inhibitors, the multiple complementary methods and techniques used demonstrate that EphA2 is a key Epstein-Barr virus epithelial cell receptor. The conclusions of the study are therefore unchanged.
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http://dx.doi.org/10.1038/s41564-018-0155-1DOI Listing
September 2018

Readily functionalized AAA-DDD triply hydrogen-bonded motifs.

Org Biomol Chem 2018 04;16(16):2947-2954

Key Laboratory of Optoelectronic Chemical Materials and Devices of Ministry of Education, School of Chemical and Environmental Engineering, Jianghan University, Wuhan, Hubei 430056, China.

Herein we present a new, readily functionalized AAA-DDD hydrogen bond array. A novel AAA monomeric unit (3a-b) was obtained from a two-step synthetic procedure starting with 2-aminonicotinaldehyde via microwave radiation (overall yield of 52-66%). 1H NMR and fluorescence spectroscopy confirmed the complexation event with a calculated association constant of 1.57 × 107 M-1. Likewise, the usefulness of this triple hydrogen bond motif in supramolecular polymerization was demonstrated through viscosity measurements in a crosslinked supramolecular alternating copolymer.
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http://dx.doi.org/10.1039/c8ob00479jDOI Listing
April 2018

[Therapeutic effect of BILT combined with praziquantel in treatment of chronic schistosomiasis].

Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi 2017 May;29(5):648-650

Affiliated Xiangyue Hospital of Hunan Institute of Parasitic Diseases, Yueyang 414000, China.

Objective: To investigate the clinical therapeutic effect of biological information infrared liver therapeutic apparatus (BILT) combined with praziquantel in the treatment of patients with chronic schistosomiasis.

Methods: A case-control study was conducted. A total of 142 chronic schistosomiasis patients were divided into an experimental group (BILT combined with praziquantel) with 64 cases and a control group (routine treatment with praziquantel alone) with 78 cases on the basis of the age, gender, disease duration and liver function as paired condition. Fatigue, diarrhea, abdominal distension, liver function, hyaluronic acid (HA) and laminin (LN) were as observation indexes and the observation results were compared between two groups.

Results: Before the treatment, there were no significant differences between the two groups in the indexes above-mentioned ( > 0.05). After the treatment, the incidence rates of fatigue, diarrhea, abdominal distension, abnormal liver function, and the levels of HA and LN in the experimental group were significantly lower than those in the control group ( < 0.01).

Conclusions: BILT combined with praziquantel can significantly alleviate the short-term clinical symptoms, restore liver function and also alleviate hepatic fibrosis of the patients with chronic schistosomiasis.
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http://dx.doi.org/10.16250/j.32.1374.2016260DOI Listing
May 2017
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