Publications by authors named "Yahan Zhang"

19 Publications

  • Page 1 of 1

A modified protocol for isolation of retinal microglia from the pig.

Exp Eye Res 2021 Apr 25;207:108584. Epub 2021 Apr 25.

University of Münster Medical School, Department of Ophthalmology, Münster, Germany. Electronic address:

Microglia are the resident immune cells in the retina. To investigate their properties and behaviour, a reliable and yielding procedure to culture them is necessary. We here describe a way of isolation of microglial cells from the porcine retina, as pig eyes are similar to human eyes in size, structure and vasculature, including similarities in proteins and pathways. Retina was isolated from fresh pig eyes, dissociated by a mixture of collagenase, hyaluronidase and DNAse, and passed through a cell strainer. After triple centrifugation with decreasing velocity and re-suspension, cells were seeded into poly-d-lysine coated culture flasks and cultured using DMEM and macrophage-colony stimulating factor (M-CSF). Number of cells increased gradually during the first 10-14 days, till they could be split and used for experiments. Identity of isolated cells as microglia was assessed by immunostaining against the microglia/macrophage markers Iba1, CD11b, CD68, CD45 and TMEM119. Phagocytic function of microglia could be demonstrated by phagocytosis of fluorescence beads and their response to lipopolysaccharide (LPS). As a conclusion, we developed a protocol for isolation and cultivation of pig retinal microglial cells that are suitable for research in the laboratory.
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http://dx.doi.org/10.1016/j.exer.2021.108584DOI Listing
April 2021

Design, synthesis and biological evaluation of anilide (dicarboxylic acid) shikonin esters as antitumor agents through targeting PI3K/Akt/mTOR signaling pathway.

Bioorg Chem 2021 Mar 29;111:104872. Epub 2021 Mar 29.

State Key Laboratory of Pharmaceutical Biotechnology, Institute of Plant Molecular Biology, School of Life Sciences, Nanjing University, Nanjing 210023, China; Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing 210037, China. Electronic address:

Triple-negative breast cancer (TNBC) has an unfavorable prognosis attribute to its low differentiation, rapid proliferation and high distant metastasis rate. PI3K/Akt/mTOR as an intracellular signaling pathway plays a key role in the cell proliferation, migration, invasion, metabolism and regeneration. In this work, we designed and synthesized a series of anilide (dicarboxylic acid) shikonin esters targeting PI3K/Akt/mTOR signaling pathway, and assessed their antitumor effects. Through three rounds of screening by computer-aided drug design method (CADD), we preliminarily obtained sixteen novel anilide (dicarboxylic acid) shikonin esters and identified them as excellent compounds. CCK-8 assay results demonstrated that compound M9 exhibited better antiproliferative activities against MDA-MB-231, A549 and HeLa cell lines than shikonin (SK), especially for MDA-MB-231 (M9: IC = 4.52 ± 0.28 μM; SK: IC = 7.62 ± 0.26 μM). Moreover, the antiproliferative activity of M9 was better than that of paclitaxel. Further pharmacological studies showed that M9 could induce apoptosis of MDA-MB-231 cells and arrest the cell cycle in G2/M phase. M9 also inhibited the migration of MDA-MB-231 cells by inhibiting Wnt/β-catenin signaling pathway. In addition, western blot results showed that M9 could inhibit cell proliferation and migration by down-regulating PI3K/Akt/mTOR signaling pathway. Finally, a three-dimensional quantitative structure-activity relationship (3D-QSAR) model was also constructed to provide a basis for further development of shikonin derivatives as potential antitumor drugs through structure-activity relationship analysis. To sum up, M9 could be a potential candidate for TNBC therapy.
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http://dx.doi.org/10.1016/j.bioorg.2021.104872DOI Listing
March 2021

Complexation of an Antimicrobial Peptide by Large-Sized Macrocycles for Decreasing Hemolysis and Improving Stability.

Angew Chem Int Ed Engl 2021 05 9;60(20):11288-11293. Epub 2021 Apr 9.

College of Environmental and Chemical Engineering, Shanghai University, Shanghai, 200444, P. R. China.

Traditional macrocyclic hosts have finite cavity sizes, generally 5-10 Å, which are commonly adaptive to recognize small guests rather than biological macromolecules. Here two water-soluble large-sized quaterphen[n]arenes (WQPns, n=3, 4) were designed and synthesized. These two hosts present significantly distinct recognition abilities. Specifically, they could strongly complex an antimicrobial peptide, pexiganan (PXG) with the association constants (K ) of (4.20±0.23)×10  M for PXG/WQP3 and (2.46±0.44)×10  M for PXG/WQP4. Complexation of PXG by WQP3 and WQP4 served to decrease the hemolysis of PXG in rabbit red blood cells in a statistically significant way. Furthermore, host-guest complexation was shown to substantially enhance metabolic stability of PXG in presence of proteinase K, rat plasma and liver or kidney homogenates.
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http://dx.doi.org/10.1002/anie.202102706DOI Listing
May 2021

Dexmedetomidine post-conditioning ameliorates long-term neurological outcomes after neonatal hypoxic ischemia: The role of autophagy.

Life Sci 2021 Apr 8;270:118980. Epub 2021 Jan 8.

Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang 110004, China. Electronic address:

Background: Hypoxic-ischemic brain injury (HIBI) is a major cause of mortality in neonates and can cause long-term neurological sequelae. Excessive autophagy caused by HI may cause neuronal death. Dexmedetomidine was reported neuroprotective against HIBI. Therefore, in the present study, the autophagy-related mechanisms underlying the protective effects of dexmedetomidine against cerebral HI in neonatal rats were investigated.

Methods: In the present study, the expression of autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3) B-II and Beclin1, neuronal and microglia autophagy levels, the myelin basic protein (MBP) expression, long-term neuronal density ratio, and long-term behavioral prognosis in HIBI model were investigated by ligating the left common carotid artery in neonatal rats, followed by 2-h hypoxia.

Results: Dexmedetomidine inhibited the overactivated autophagy of hippocampal neurons and microglia after HI. In addition, dexmedetomidine inhibited neuronal density decrease and axon demyelination after HI-induced overactivated autophagy. Lastly, dexmedetomidine improved the long-term neurological prognosis and was reversed by the autophagy agonist rapamycin.

Conclusion: The protective effects of dexmedetomidine on HI neonatal rats were evidenced by inhibition of excessive autophagy of neurons and microglia, thereby reducing the decline of long-term neuronal density and axon demyelination as well as improving long-term learning cognitive function.
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http://dx.doi.org/10.1016/j.lfs.2020.118980DOI Listing
April 2021

Immunostimulatory silica nanoparticle boosts innate immunity in brain tumors.

Nanoscale Horiz 2021 02 5;6(2):156-167. Epub 2021 Jan 5.

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA.

The high mortality associated with glioblastoma multiforme (GBM) is attributed to its invasive nature, hypoxic core, resistant cell subpopulations and a highly immunosuppressive tumor microenvironment (TME). To support adaptive immune function and establish a more robust antitumor immune response, we boosted the local innate immune compartment of GBM using an immunostimulatory mesoporous silica nanoparticle, termed immuno-MSN. The immuno-MSN was specifically designed for systemic and proficient delivery of a potent innate immune agonist to dysfunctional antigen-presenting cells (APCs) in the brain TME. The cargo of the immuno-MSN was cyclic diguanylate monophosphate (cdGMP), a Stimulator of Interferon Gene (STING) agonist. Studies showed the immuno-MSN promoted the uptake of STING agonist by APCs in vitro and the subsequent release of the pro-inflammatory cytokine interferon β, 6-fold greater than free agonist. In an orthotopic GBM mouse model, systemically administered immuno-MSN particles were taken up by APCs in the near-perivascular regions of the brain tumor with striking efficiency. The immuno-MSNs facilitated the recruitment of dendritic cells and macrophages to the TME while sparing healthy brain tissue and peripheral organs, resulting in elevated circulating CD8 T cell activity (2.5-fold) and delayed GBM tumor growth. We show that an engineered immunostimulatory nanoparticle can support pro-inflammatory innate immune function in GBM and subsequently augment current immunotherapeutic interventions and improve their therapeutic outcome.
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http://dx.doi.org/10.1039/d0nh00446dDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878432PMC
February 2021

Metastases to the Breast from Extramammary Nonhematological Malignancies: Case Series.

Int J Gen Med 2020 12;13:1105-1114. Epub 2020 Nov 12.

Department of Ultrasound, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, People's Republic of China.

Objective: This article aims to provide a better understanding of ultrasonography and immunohistochemistry of secondary nonhematological tumors of breast.

Methods: The study reviewed the ultrasound findings and immunohistochemical features of nonhematological metastatic breast tumor cases found in patients of West China Hospital, Sichuan University from 2007 to 2019. Each case was categorized as secondary breast malignancy using histopathological results.

Results: Fourteen cases were identified from West China Hospital database. Ten cases originated in the lung, 2 cases in the stomach, 1 case in the ovary and 1 case of neuroendocrine carcinomas. Fourteen masses were evaluated. Ultrasound findings showed that tumors were hypoechoic (14/14), irregular (13/14), indistinct margin (13/14), along a long axis parallel to the skin (11/14), lacked vascularity via color doppler flow imaging (9/14). Eight cases showed no posterior features. Calcification was found in 1 case of lung adenocarcinoma that had metastasized to the breast. Abnormal axillary lymph nodes were detected in 5 cases. Immunohistochemical analysis showed that estrogen receptor (ER) and progesterone receptor (PR) were both negative in 11 cases, including gastric and lung cancer metastasis. One case of ovarian metastasis was positive for ER and negative for PR. Six patients were positive for cytokeratin 7 (CK7) and negative for cytokeratin 20 (CK20), including lung and ovarian carcinoma metastasis. Thyroid transcription factor-1 (TTF-1) was positive in 9 of 10 pulmonary carcinoma metastases. The patient of ovarian metastasis was positive for Wilms' tumour 1 (WT-1) and carbohydrate antigen 125 (CA125). Two cases from gastric metastasis were positive for caudal-type homeobox 2 (CDX2).

Conclusion: Although breast ultrasound is not useful in distinguishing metastases from primary breast cancer, it is helpful in diagnosing breast lesions as oncological diseases and provide evidence for further examination of patients. Immunohistochemistry plays an important role in distinguishing secondary breast cancer from primary, especially in patients without tumor history.
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http://dx.doi.org/10.2147/IJGM.S276602DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670084PMC
November 2020

Investigation and probabilistic health risk assessment of trace elements in good sale lip cosmetics crawled by Python from Chinese e-commerce market.

J Hazard Mater 2021 Mar 14;405:124279. Epub 2020 Oct 14.

Research Center for Environment and Health, Zhongnan University of Economics and Law, Wuhan 430073, China; Department of Neurology, Renmin Hospital of Wuhan University, Wuhan 430073, China. Electronic address:

A growing body of evidence suggests that the lip products are polluted by heavy metals, which would inevitably cause safety problems with long-term exposure, but few studies have focused on their deeper health risk assessments. This study sets out to identify the lip cosmetics in good sale from Chinese e-commerce market utilizing Python crawler and then explore the probabilistic health risks caused by 6 trace elements in 34 most popular lip cosmetics with Monte Carlo simulation. The results found that there was no obvious non-carcinogenic risk to humans. As for high users, the carcinogenic risk levels of Cr exceeded the acceptable risk recommended by USEPA, approximately 10% and 25% for lipsticks and lip glosses, respectively. Cr was regarded as the priority metal for risk control in the present study. Finally, it was recommended that the minimum use period limit for using up one lip product ranged from 0.54 months to 5.74 months. Overall, this study appears to be the first to conduct a probabilistic health risk assessment of trace elements in lip products, which would be of significance for policy makers to take effective strategies to minimize exposure health risk and contamination.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124279DOI Listing
March 2021

Dexmedetomidine alleviates neurobehavioral impairments and myelination deficits following lipopolysaccharide exposure in early postnatal rats.

Life Sci 2020 Dec 7;263:118556. Epub 2020 Oct 7.

Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address:

Aims: White matter injury (WMI) is the main form of brain injury in preterm neonate survivors, and perinatal inflammation is implicated in the pathogenesis of WMI. It has been demonstrated that dexmedetomidine, an anesthetic adjuvant, possesses neuroprotective effects in both preclinical and clinical trials. The present study was conducted to explore whether dexmedetomidine could protect against neurobehavioral impairments and myelination deficits caused by lipopolysaccharide (LPS) exposure in the early postnatal rat brain.

Main Methods: LPS (2 mg/kg) was intraperitoneally (i.p.) injected in Sprague-Dawley rat pups on postnatal day 2 (P2). Dexmedetomidine (25 μg/kg) or vehicle was given i.p. immediately after LPS injection. STAT3 and p-STAT3 expression were detected by western blot in rat brain 24 h after drug administration. Immunostaining for GFAP to was performed to evaluate astrocytic response at 24 h post-LPS and P14. Neurobehavioral tests (the righting reflex, negative geotaxis, and wire hanging maneuver tests) were performed from P5 to P10. Histological analysis of myelin content was accessed by immunohistochemistry for CNPase and MBP at P14.

Key Findings: Our results showed that treatment with dexmedetomidine significantly ameliorated LPS-induced neurobehavioral abnormalities and myelin damage, which is accompanied by suppression of STAT3 activation and reactive astrogliosis.

Significance: Dexmedetomidine can alleviate neurobehavioral impairments and myelination deficits after LPS exposure in early postnatal rats, probably by mitigating STAT3-mediated reactive astrogliosis. Our results suggest that dexmedetomidine might be a promising agent to treat brain injury in neonates.
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http://dx.doi.org/10.1016/j.lfs.2020.118556DOI Listing
December 2020

Supramolecular combination chemotherapy: a pH-responsive co-encapsulation drug delivery system.

Chem Sci 2020 Jun 3;11(24):6275-6282. Epub 2020 Jun 3.

Department of Chemistry , Center for Supramolecular Chemistry and Catalysis , Shanghai University , Shanghai 200444 , P. R. China . Email:

Most cancer chemotherapy regimens rely on the use of two or more chemotherapeutic agents. However, achieving the best possible dosing of the individual drugs can be challenging due to differences in metabolism, uptake, and clearance among other factors. Here we describe a supramolecular strategy for achieving drug delivery in which the loading ratio of two active components is easily defined. Specifically, we report the formation of aggregates comprised of self-assembled amphiphiles between carboxylatopillar[6]arene (CP6A) and an oxaliplatin (OX)-type Pt(iv) prodrug (PtC). The association constant () for the underlying host-guest interaction at pH 7.4 ((1.16 ± 0.03) × 10 M) is an order of magnitude higher than at pH 5.0 ((1.73 ± 0.15) × 10 M). A second chemotherapeutic, doxorubicin (DOX), may be encapsulated in the resulting vesicles (PtC⊂CP6A) to give a supramolecular combination chemotherapeutic system DOX@PtC⊂CP6A. Drug release studies served to confirm that PtC and DOX are released in acidic environments. Support for a synergistic antiproliferative effect relative to PtC + DOX came from cellular studies of DOX@PtC⊂CP6A using the human liver hepatocellular carcinoma (HepG-2) cell line. studies revealed that DOX@PtC⊂CP6A is not only able to retard tumor growth efficiently but also reduce drug-related toxic side effects in BALB/c nude mice bearing HepG-2 subcutaneous tumor xenografts. These favorable findings are attributed to the formation of a ternary complex that benefits from an enhanced permeability and retention (EPR) effect while allowing for the pH-based release of PtC and DOX at the tumor site.
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http://dx.doi.org/10.1039/d0sc01756fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473403PMC
June 2020

Biodegradable Nanoparticles Based on Pseudo-Proteins Show Promise as Carriers for Ophthalmic Drug Delivery.

J Ocul Pharmacol Ther 2020 Jul/Aug;36(6):421-432. Epub 2020 Jul 7.

Research Lab of the Department of Ophthalmology, University of Münster Medical School, Münster, Germany.

Drug delivery to treat ocular diseases still is a challenge in ophthalmology. One way to achieve drug delivery that is investigated currently is topical administration of drug-loaded polymeric nanoparticles (NPs) that are able to penetrate ocular barriers. The purpose of this study was optimal preparation of NPs made from pseudo-proteins and evaluation of their ability to penetrate ocular tissues. Biodegradable NPs of various types were prepared by nanoprecipitation of pseudo-protein composed of l-leucine (L), 1,6-hexanediol (6), and sebacic acid (8) (8L6). Arginine-based cationic polyester amides 8R6 and comb-like polyester amide containing lateral PEG-2000 chains along with 8L6 anchoring fragments in the backbones were used to construct positively charged and PEGylated NPs. They were loaded with fluorescein diacetate (FDA) or rhodamine 6G (Rh6G) as fluorescent probes. Suspensions of the NPs were given to cultivated microglial cells and retinal pigment epithelial (RPE) cells as well as topically on eyes of C57BL/6 mice. Penetration of NPs into the eyes was checked by fluorescence analysis. NPs were prepared, and their properties were characterized. Cultured microglial cells and RPE cells took up the NPs. After topical administration, penetration of NPs into the cornea of the eyes was clearly seen. Small amounts of fluorescent dyes were also found in the lens, the retina, and the sclera depending on the type of NPs. The results showed that the new NPs penetrate ocular tissues after topical administration and are internalized by the cells. This raises confidence that the NPs may be useful carriers of therapeutic agents for ocular delivery.
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http://dx.doi.org/10.1089/jop.2019.0148DOI Listing
July 2020

Mechanism insights into the transformation of carbosulfan during apple drying processes.

Ecotoxicol Environ Saf 2020 Sep 30;201:110729. Epub 2020 May 30.

State Key Laboratory of Food Science and Technology, Jiangnan University, China; School of Food Science and Technology, Jiangnan University, No.1800 Lihu Avenue, Wuxi, Jiangsu Province, 214122, China. Electronic address:

The transformation of carbosulfan (CSN) in apples was investigated during oven-drying, microwave drying, and sun-drying. CSN transformed primarily into carbofuran (COA) during these drying processes. The conversion kinetics of CSN and COA was fitted by curve regression and mainly conformed to quadratic models (R = 0.70-0.97). Oven-drying promoted the transformation of CSN into COA. Microwave drying resulted in the highest scavenging capacity against CSN and COA (41%-100%). Moreover, a transformation mechanism was proposed on the basis of density functional theory (DFT) calculation. The COA originated from a series of chemical reactions involving hydroxyl substitution, cleavage, and oxidation; this result was further confirmed on the basis of molecular electrostatic potential (MEP) and molecular orbital theory. Furthermore, the toxicity and stability of CSN and COA were evaluated with the T.E.S.T. program. COA was less toxic than CSN to aquatic organisms but more toxic than CSN to rats. Therefore, COA production should be avoided during drying. Microwave drying was found to be the optimum choice for drying apples.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110729DOI Listing
September 2020

β-cryptoxanthin alleviates myocardial ischaemia/reperfusion injury by inhibiting NF-κB-mediated inflammatory signalling in rats.

Arch Physiol Biochem 2020 May 2:1-8. Epub 2020 May 2.

TEDA International Cardiovascular Hospital, Tianjin, China.

The present study aimed to explore the function and molecular mechanism of β-cryptoxanthin on myocardial ischaemia-reperfusion injury (MIRI). Left anterior descending coronary artery ligation with reperfusion was utilised to establish a MIRI rat model. The results indicated that β-cryptoxanthin decreases infarct size and ameliorates signs of pathological histology in MIRI. TNF-α, IL-1β, and IL-6 levels in the serum were attenuated in response to β-cryptoxanthin treatment, serum LDH and CK-MB activities were also decreased. Immunohistochemical analysis and western blot results suggested that p65 was translocated to the nucleus in the I/R injury rat model. However, in the β-cryptoxanthin administration group, p65 expression and activity in the nucleus were decreased in a dose-dependent manner. Furthermore, p-p38 MAPK levels in response to β-cryptoxanthin were decreased, indicating that MAPK is involved in NF-κB signalling pathway regulation. In conclusion, β-cryptoxanthin alleviates myocardial ischaemia/reperfusion injury by inhibiting NF-κB-mediated inflammatory signalling in rats.
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http://dx.doi.org/10.1080/13813455.2020.1760302DOI Listing
May 2020

Dexmedetomidine Promotes Hippocampal Neurogenesis and Improves Spatial Learning and Memory in Neonatal Rats.

Drug Des Devel Ther 2019 31;13:4439-4449. Epub 2019 Dec 31.

Department of Anesthesiology, Shengjing Hospital, China Medical University, Shenyang, People's Republic of China.

Background: Dexmedetomidine (Dex) is a highly selective α2-adrenoceptor agonist used as an off-label medication for pediatric sedation and analgesia. Recently, Dex was reported to exhibit neuroprotective efficacy in several brain injury models. Here we investigate whether neonatal Dex administration promotes hippocampal neurogenesis and enhances hippocampus-dependent spatial learning and memory under physiological conditions.

Methods: Postnatal day 7 (P7) pups were administered saline (vehicle control) or Dex (10, 20, or 40 µg/kg) by intraperitoneal injection. Neurogenesis and astrogenesis were examined in brain slices by BrdU immunostaining on P8 and changes in the expression levels of GDNF, NCAM, CREB, PSD95, and GAP43 were assessed by Western blotting on P35, respectively. Open field and Morris water maze (MWM) tests were conducted from P28 to P36 in order to assess effects on general motor activity and spatial learning, respectively.

Results: Dexmedetomidine at 20 µg/kg significantly enhanced neurogenesis and astrogenesis in hippocampus and upregulated GDNF, NCAM, CREB, PSD95, and GAP43 compared to vehicle and other Dex doses. Moreover, 20 µg/kg Dex-injected rats showed no changes in motor or anxiety-like behavior but performed better in the MWM test compared to all other groups.

Conclusion: Neonatal injection of Dex (20 µg/kg) enhances spatial learning and memory in rat pups, potentially by promoting hippocampal neurogenesis and synaptic plasticity via activation of GDNF/NCAM/CREB signaling.
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http://dx.doi.org/10.2147/DDDT.S228220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997224PMC
July 2020

A multiplex PCR assay with a common primer for the detection of eleven foodborne pathogens.

J Food Sci 2020 Mar 30;85(3):744-754. Epub 2020 Jan 30.

Laboratory of Molecular Diagnostics, College of Pharmaceutical Sciences, Soochow Univ., Suzhou, Jiangsu, China.

Salmonella enterica, Listeria monocytogenes, Shigella flexneri, Escherichia coli O157:H7, Vibrio parahaemolyticus, Staphylococcus aureus, Vibrio cholerae, Clostridium botulinum type A, Bacillus cereus, Clostridium perfringens Alpha toxin, and Yersinia enterocolitica are 11 common foodborne pathogens. Traditional bacterial culture methods for detecting pathogens are time-consuming and labor-intensive. Multiplex PCR technology, which can detect multiple targets in a single tube, has been increasingly applied to microbial detection due to its high specificity, sensitivity, and fast response. This paper is to establish a multiplex PCR technology mediated by a common primer for the detection of these 11 common foodborne pathogens in order to achieve the goal of nondirectional screening for these 11 common foodborne pathogens. The specificity of the established CP-MPCR detection system was first verified by 100 clinical isolates. The sensitivity of the CP-MPCR detection system was then detected by using cultured bacteria preparations and has been confirmed with a high sensitivity of 10 to 10 CFU/mL, among them, the sensitivity of the CP-MPCR for Vibrio cholerae and S. flexneri can even achieve 10 CFU/mL. Sixty anal swab samples collected from Suzhou CDC and 16 enrichment cultured solutions of food samples collected from the Suzhou Food Inspection and Testing Center were tested using the CP-MPCR system. A total of 32 positive results were detected. PRACTICAL APPLICATION: Food poisoning incidents occur frequently around the world, mainly because of the contamination of food by pathogenic bacteria and serious harm to human health. The method provided in this study can detect 11 foodborne pathogens in food, which can effectively prevent the spread of pathogenic microorganisms. At the same time, for the food poisoning incident that has already occurred, this method can be used for diagnosis to find out the cause.
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http://dx.doi.org/10.1111/1750-3841.15033DOI Listing
March 2020

In-situ recurrence of the primary cardiac dedifferentiated liposarcoma: To resect or not?

J Card Surg 2020 Feb 5;35(2):495-498. Epub 2019 Dec 5.

Department of Pathology, West China Hospital, Sichuan University, Chengdu, China.

Dedifferentiated liposarcoma (DDLPS) is a rare type of neoplasm which can originally rise in cardiac chamber. Owing to the recurrence and distant metastasis, the prognosis of the primary malignant cardiac tumor is extremely poor and remains a challenge for cardiac surgeons. Here, we report a patient with an intracavitary mass which was diagnosed as DDLPS by postoperative pathological examinations, experienced repeated in-situ recurrence of the malignant cardiac tumor.
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http://dx.doi.org/10.1111/jocs.14394DOI Listing
February 2020

Primary cardiac dedifferentiated liposarcoma in a middle-aged female: a case report.

J Cardiothorac Surg 2019 Aug 30;14(1):156. Epub 2019 Aug 30.

Department of Cardiovascular Surgery, West China Hospital, Sichuan University, No.37 Guo Xue Alley, Chengdu, Sichuan, People's Republic of China, 61004.

Background: Primary malignant cardiac tumors are extremely rare and can present with the same nonspecific characteristics as benign primary cardiac tumors. We herein describe a middle-aged female with an intracavitary, irregular atrial mass who experienced partial surgical resection. The atrial mass which was recognized as myxoma before surgery was finally diagnosed as dedifferentiated liposarcoma (DDLPS) by postoperative pathological examination.

Case Presentation: The patient, a 61-year-old female, presented to the emergency room because of progressive chest congestion and shortage of liberties for 6 months and orthopnoea and paroxysmal nocturnal dyspnea for 3 days. The laboratory examinations confirmed no abnormalities. The thoracic computed tomography (CT) scan showed massive hydropericardium, pleural effusion and left atrium occupying lesion. The transesophageal echocardiography (TEE) confirmed an intracavitary and irregular left atrial mass, limiting the mitral valve inflow and pulmonary venous blood reflux. The positron emission tomography/computed tomography (PET/CT) revealed high grade fluorodeoxyglucose uptake only in the intracavitary mass which near the mitral valve. According to operative exploration, the intracavitary mass had invaded the mitral annulus and posterior wall of left ventricle which cannot be resected completely, we did merely partial surgical resection to relieve the patient's symptoms. Postoperative immunohistochemical stain confirmed the diagnosis of DDLPS. The patient was transferred to the oncology department for further therapy. Unfortunately, the patient was detected with brain metastasis 1 month later and died within 5 months after the surgery.

Conclusions: Primary cardiac DDLPS is an extremely rare histological subtype of undifferentiated pleomorphic sarcomas which present the same nonspecific characteristics as benign primary cardiac tumors. Even though surgical resection combined with chemotherapy or radiotherapy remains the mainstream treatment strategy, the prognosis of cardiac malignancy is poor with high mortality. Novel management strategies need to be further explored.
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http://dx.doi.org/10.1186/s13019-019-0973-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6717363PMC
August 2019

Identification of a pyrimidinetrione derivative as the potent DprE1 inhibitor by structure-based virtual ligand screening.

Bioorg Chem 2019 04 13;85:168-178. Epub 2018 Dec 13.

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China; Wuya College of Innovation, School of Traditional Chinese Materia Medica, Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China. Electronic address:

Despite the increasing need of new antituberculosis drugs, the number of agents approved for the market has fallen to an all-time low. In response to the emerging drug resistance followed, structurally unique chemical entities will be highlighted. decaprenylphosphoryl-β-d-ribose oxidase (DprE1) participating in the biosynthesis of mycobacterium cell wall is a highly vulnerable and validated antituberculosis target. On the basis of it, a systematic strategy was applied to identify a high-quality lead compound (compound 50) that inhibits the essential enzyme DprE1, thus blocking the synthesis of the mycobacterial cell wall to kill M. tuberculosis in vitro and in vivo. Correspondingly, the rational design and synthetic strategy for compound 50 was reported. Notably, the compound 50 has been confirmed to be no toxicity. Altogether, our data suggest the compound 50 targeting DprE1 is a promising candidate for the tuberculosis (TB) therapy.
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http://dx.doi.org/10.1016/j.bioorg.2018.12.018DOI Listing
April 2019

Design, synthesis and biological evaluations of novel pyridone-thiazole hybrid molecules as antitumor agents.

Eur J Med Chem 2018 Feb 15;145:35-40. Epub 2017 Dec 15.

School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, China.

A hybrid pharmacophore approach was adopted to design and synthesize new series of pyridone-thiazole hybrid compounds. The structures of the compounds were established by IR, H NMR, C NMR, and HRMS. All the newly prepared compounds (3a-3m) were in vitro evaluated for their antiproliferative activity against three human cancer cell lines, namely Colon cancer (HCT-116), gastric carcinoma (MGC803) and hepatocellular cancer (Huh7). Bioassay results demonstrated that most of the tested compounds showed potent anti-tumor activities against various cancer cells in vitro, and some compounds exhibited stronger effects than positive control 5-Fluorouracil (5-FU). Compound 3b showed the best anti-tumor activity with IC values of 8.17 μM and 3.15 μM against HCT116 and MGC803 cell lines, respectively, which was 1.4-8.1 times more potent than 5-Fluorouracil (IC = 11.29 μM and 25.54 μM against HCT116 and MGC803 respectively). These findings suggest that compound 3b may have potential to be developed as a promising lead for the design of novel anticancer small-molecule drugs.
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http://dx.doi.org/10.1016/j.ejmech.2017.12.038DOI Listing
February 2018

Antiviral activity of a synthesized shikonin ester against influenza A (H1N1) virus and insights into its mechanism.

Biomed Pharmacother 2017 Sep 5;93:636-645. Epub 2017 Jul 5.

State Key Laboratory of Pharmaceutical Biotechnology, NJU-NJFU Joint Institute of Plant Molecular Biology, Nanjing University, Nanjing 210023, China; Co-Innovation Center for Sustainable Forestry in Southern China, Nanjing Forestry University, Nanjing 210037, China. Electronic address:

This study aimed to examine the antiviral effects of shikonin ester ((R)-1-(5, 8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-en-1-yl3-(1H- indol-3-yl) propanoate (PMM-034) against influenza A (H1N1) virus. We investigated PMM-034 anti-H1N1 activity and its effect on caspase 3 gene expression during cellular apoptosis after influenza virus infection in vitro. Neuraminidase (NA) inhibition was assessed in comparison with oseltamivir in the influenza virus standard strains A/PR/8/34 to understand the viral mechanism. MDCK and A549 cells were used to investigate influenza viral infection and the structure-activity relationship between PMM-034 and NA was evaluated by pharmacophore-based docking modeling. The production of viral protein was tested by western blot. A/PR/8/34 induced cell inhibition but this was reduced by PMM-034 to 16μg/mL and this showed a selective index of 10mM. PMM-034 inhibited NA in a dose dependent manner, similar to oseltamivir inhibition. A sharp decrease in viral nucleocapsid protein mRNA was observed in infected cells after treatment with PMM-034. Apoptosis of infected A459 cells was inhibited by PMM-034 with decreased caspase 3 levels. ARG 118, ARG 152, ARG 371 and GLU 227 in the binding pocket of NA bound to PMM-034 in the docking model. Taken together, these results suggest PMM-034 shikonin ester blocked H1N1 infection and might be a potential anti-H1N1 drug.
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http://dx.doi.org/10.1016/j.biopha.2017.06.076DOI Listing
September 2017