Publications by authors named "Li Tu"

43 Publications

Virus-inspired nanosystems for drug delivery.

Nanoscale 2021 Nov 25;13(45):18912-18924. Epub 2021 Nov 25.

Fujian Provincial Key Laboratory of Innovative Drug Target Research, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China.

With over millions of years of evolution, viruses can infect cells efficiently by utilizing their unique structures. Similarly, the drug delivery process is designed to imitate the viral infection stages for maximizing the therapeutic effect. From drug administration to therapeutic effect, nanocarriers must evade the host's immune system, break through multiple barriers, enter the cell, and release their payload by endosomal escape or nuclear targeting. Inspired by the virus infection process, a number of virus-like nanosystems have been designed and constructed for drug delivery. This review aims to present a comprehensive summary of the current understanding of the drug delivery process inspired by the viral infection stages. The most recent construction of virus-inspired nanosystems (VINs) for drug delivery is sorted, emphasizing their novelty and design principles, as well as highlighting the mechanism of these nanosystems for overcoming each biological barrier during drug delivery. A perspective on the VINs for therapeutic applications is provided in the end.
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http://dx.doi.org/10.1039/d1nr05872jDOI Listing
November 2021

The Involvement of Neutrophil Extracellular Traps in Disease Activity Associated With IgA Vasculitis.

Front Immunol 2021 3;12:668974. Epub 2021 Sep 3.

Department of Pediatrics, The First Affiliated Hospital, Guangxi Medical University, Nanning, China.

Objectives: This aim of this study was to determine whether neutrophil extracellular traps (NETs) are involved in the pathogenesis of IgA vasculitis (IgAV) and investigate whether the circulating NETs levels are associated with disease activity in children.

Methods: We performed a case-control study and collected blood samples from 193 children with different stages of IgAV (61 were at the onset stage, 64 at the remission stage, 43 at the active stage, and 25 were undergoing drug withdrawal). A total of 192 healthy children were recruited as controls. Circulating cell free DNA (cf-DNA) was obtained from the plasma and quantified by using the Quant-iT PicoGreen DNA quantification kit. NETs-associated myeloperoxidase-DNA (MPO-DNA), citrullinated-histone H3 (cit-H3), neutrophil elastase (NE), and the deoxyribonuclease I (DNase I) concentrations were measured using enzyme-linked immunosorbent assays. The presence of NETs in the kidney and gastrointestinal tissues of onset and active IgAV patients was determined by multiple immunofluorescence staining in 15 IgAV nephritis patients and 9 IgAV patients without IgAV nephritis, respectively. NETs degradation potency of collected sera samples from IgAV patients were checked . Relationships between circulating levels of cf-DNA with MPO-DNA, NE, and DNase I and the patients were analyzed.

Results: Circulating levels of cf-DNA in onset and active IgAV patients were significantly higher than those in remission and drug withdrawal patients as well as healthy controls. The results were similar for MPO-DNA and NE. The levels of circulating cf-DNA correlated significantly with MPO-DNA, NE and DNase I. A significantly decreased degradation of NETs from the onset and active IgAV patients was observed, but was normal in healthy controls. Furthermore, presence of NETs was also confirmed in all renal and gastrointestinal tissues obtained from the onset and active IgAV patients but not control samples.

Conclusions: Our data showed that NETs were released into the circulation of IgAV patients and are involved in the disease activity. The circulating levels of NETs maybe used to assess disease severity in children with IgAV.
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http://dx.doi.org/10.3389/fimmu.2021.668974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446352PMC
October 2021

Gold-based nanomaterials for the treatment of brain cancer.

Cancer Biol Med 2021 May 18. Epub 2021 May 18.

CAS Center for Excellence in Nanoscience, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology, Beijing 100190, China.

Brain cancer, also known as intracranial cancer, is one of the most invasive and fatal cancers affecting people of all ages. Despite the great advances in medical technology, improvements in transporting drugs into brain tissue have been limited by the challenge of crossing the blood-brain barrier (BBB). Fortunately, recent endeavors using gold-based nanomaterials (GBNs) have indicated the potential of these materials to cross the BBB. Therefore, GBNs might be an attractive therapeutic strategy against brain cancer. Herein, we aim to present a comprehensive summary of current understanding of the critical effects of the physicochemical properties and surface modifications of GBNs on BBB penetration for applications in brain cancer treatment. Furthermore, the most recent GBNs and their impressive performance in precise bioimaging and efficient inhibition of brain tumors are also summarized, with an emphasis on the mechanism of their effective BBB penetration. Finally, the challenges and future outlook in using GBNs for brain cancer treatment are discussed. We hope that this review will spark researchers' interest in constructing more powerful nanoplatforms for brain disease treatment.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2020.0524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185869PMC
May 2021

Erratum: Epidemiology of and prognostic factors for patients with sarcomatoid carcinoma: a large population-based study.

Am J Cancer Res 2021 15;11(4):1800-1802. Epub 2021 Apr 15.

Lung Cancer Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University Chengdu, Sichuan, P. R. China.

[This corrects the article on p. 3801 in vol. 10, PMID: 33294268.].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085883PMC
April 2021

Integrated analysis of gait parameters and gene expression profiles in a murine model of subarachnoid hemorrhage.

Genes Brain Behav 2021 06 9;20(5):e12728. Epub 2021 Mar 9.

Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.

Gait analysis has been widely used to examine the behavioral presentation of numerous neurological disorders. Thorough murine model evaluation of the subarachnoid hemorrhage (SAH)-associated gait deficits is missing. This study measures gait deficits using a clinically relevant murine model of SAH to examine associations between gait variability and SAH-associated gene expressions. A total of 159 dynamic and static gait parameters from the endovascular perforation murine model for simulating clinical human SAH were determined using the CatWalk system. Eighty gait parameters and the mRNA expression levels of 35 of the 88 SAH-associated genes were differentially regulated in the diseased models. Totals of 42 and 38 gait parameters correlated with the 35 SAH-associated genes positively and negatively with Pearson's correlation coefficients of >0.7 and <-0.7, respectively. p-SP1 expression in the motor cortex in SAH animal models displays a significant correlation with a subset of gait parameters associated with muscular strength and coordination of limb movements. Our data highlights a strong correlation between gait variability and SAH-associated gene expression. p-SP1 expression could act as a biomarker to monitor SAH pathological development and a therapeutic target for SAH.
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http://dx.doi.org/10.1111/gbb.12728DOI Listing
June 2021

Regulation of Autophagy Orchestrates Pyroptotic Cell Death in Molybdenum Disulfide Quantum Dot-Induced Microglial Toxicity.

ACS Biomater Sci Eng 2020 03 24;6(3):1764-1775. Epub 2020 Feb 24.

Department of Biomaterials, Research Center of Biomedical Engineering of Xiamen & Key Laboratory of Biomedical Engineering of Fujian Province, College of Materials, Xiamen University, Xiamen 361005, P. R. China.

Molybdenum disulfide quantum dots (MoS QDs) represent an emerging class of two-dimensional (2D) atomically layered transition metal dichalcogenide nanostructures with few nanometers in lateral size, which show attractive potential as versatile platforms for theranostic applications in various neurological disorders. However, the potential impacts of MoS QDs on microglia remain unclear. In this report, we showed that exposure of microglia to MoS QDs triggered NLRP3 inflammasome activation as revealed by the cleavage of the inactive precursor of caspase-1 to its active form and the increased release of downstream pro-inflammatory cytokines, resulting in microglia cell death that occurred through caspase-1-dependent pyroptosis. We also found that MoS QDs activated autophagy, and suppression of autophagy by specific inhibitors potentiated MoS QD-induced pyroptosis. Additionally, MoS QDs stimulated mitochondria-derived reactive oxygen species (mtROS) generation in BV-2 cells. However, ROS scavengers could diminish the MoS QD-mediated NLRP3 inflammasome activation and pyroptotic cell death in microglia. Overall, our findings identified pyroptosis as a cellular response to MoS QD exposure in microglial cells, affording novel insights into the neurotoxicity of MoS QDs and facilitating the rational design and application of functional MoS QDs in neuroscience.
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http://dx.doi.org/10.1021/acsbiomaterials.9b01932DOI Listing
March 2020

Epidemiology of and prognostic factors for patients with sarcomatoid carcinoma: a large population-based study.

Am J Cancer Res 2020 1;10(11):3801-3814. Epub 2020 Nov 1.

Lung Cancer Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University Chengdu, Sichuan, China.

Sarcomatoid carcinoma (SC) is regarded as a rare malignant neoplasm associated with poor outcomes. This study aimed to explore the epidemiological characteristics and prognostic factors of SC, and establish a clinical predictive model. The Surveillance, Epidemiology, and End Results database was used for data inquiry of patients with SC. Relevant population materials were used for age-adjusted incidence, limited-duration prevalence and prognostic analyses, and also for nomogram construction and validation. A total of 17,917 cases of SC were identified. Among them, 12,276 (68.52%) were women and 14,265 (79.62%) were white. Most cases occurred in the female genital system, accounting for 41.10% of all SCs. The median age at diagnosis was 68 years. The incidence and prevalence of SC increased substantially over time. The age-adjusted incidence increased from 0.31/100,000 in 1973 to 1.26/100,000 by 2014, a 4.06-fold change. Among site groups, the incidence of SC in the female genital and the respiratory system increased most significantly ( < 0.001). As for stage and grade, the incidence increased the most in distant and high-grade SC, respectively ( < 0.001). Moreover, the survival duration varied significantly by site, histology, stage and grade ( < 0.001). The multivariable analyses showed that the year of diagnosis, age, sex, race, grade, stage, and site were all significant prognostic factors ( < 0.001). Among these, stage and primary tumor site were the most valuable indicators of outcomes. Furthermore, a nomogram comprising age, histology, grade, stage and site were established to predict the 3-/5-year survival probability. The concordance indexes of the nomogram were 0.745 (95% confidence interval [CI]: 0.737-0.753) and 0.743 (95% CI: 0.728-0.756) for the internal and external validations, respectively. The calibration plot demonstrated satisfactory consistency between the actual and predicted outcomes in both the internal and external validations. In conclusion, increasing incidence and prevalence of SC was observed in our study, suggesting that SC is more prevalent than previously reported. Clinicians should be familiar with the characteristics of these tumors. Furthermore, the established nomogram could accurately predict the 3-/5-year survival rate of patients with SC, which may be of value for patient counselling and risk stratification.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716166PMC
November 2020

LncRNA MALAT1 facilitates inflammasome activation via epigenetic suppression of Nrf2 in Parkinson's disease.

Mol Brain 2020 09 24;13(1):130. Epub 2020 Sep 24.

Department of Emergency, Guizhou Provincial People's Hospital, No.83 Zhongshan East Road, Guiyang, 550002, Guizhou Province, P.R. China.

The goal of the present study was to elucidate the mechanism by which long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) promotes inflammation in Parkinson's disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to induce PD development in C57BL/6 mice, and tyrosine hydroxylase (TH) expression was analysed by immunohistochemical analysis. Western blot and qPCR analyses were conducted to assess the expression of protein and mRNA levels, respectively. Lipopolysaccharide/adenosine triphosphate (LPS/ATP) was used to activate microglia in vitro. Chromatin immunoprecipitation (ChIP), RNA pull-down and RNA immunoprecipitation chip (RIP) assays were performed to investigate the interaction among specific molecules. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to evaluate cell viability and proliferation. Flow cytometry was performed to analyse cell apoptosis after staining. The dichlorofluorescein diacetate (DCFH-DA) assay was used to measure the generation of reactive oxygen species (ROS) in cells. The results showed that MALAT1 was highly expressed in the brains of MPTP-induced PD model mice and in LPS/ATP-induced microglia cells. Knockdown of MALAT1 inhibited elevated nuclear factor (erythroid-derived 2)-like-2 factor (NRF2) expression, thereby inhibiting inflammasome activation and ROS production. MALAT1 was shown to promote neuroinflammation by recruiting enhancer of zeste homologue 2 (EZH2) to the promoter of NRF2, suppressing Nrf2 expression. In summary, MALAT1 epigenetically inhibits NRF2, thereby inducing inflammasome activation and reactive oxygen species (ROS) production in PD mouse and microglial cell models.
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http://dx.doi.org/10.1186/s13041-020-00656-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7513532PMC
September 2020

HOTAIR Accelerates Dyskinesia in a MPTP-Lesioned Mouse Model of PD via SSTR1 Methylation-Mediated ERK1/2 Axis.

Mol Ther Nucleic Acids 2020 Jul 15;22:140-152. Epub 2020 Jul 15.

Emergency Department of Internal Medicine, Guizhou Provincial People's Hospital, Guiyang 550002, P.R. China. Electronic address:

Homeobox transcript antisense RNA (HOTAIR), has been associated with neuroprotective effects in Parkinson's disease (PD). However, the underlying mechanisms still remain unclear. Hence, this present study attempted to clarify the functional relevance of HOTAIR in PD. We established an in vivo mouse model of PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and an in vitro cell model of PD by treating dopaminergic neuron MN9D cells with 1-methyl-4-phenylpyridinium species (MPP). The expressions of somatostatin receptor 1 (SSTR1) and HOTAIR were altered to examine their effects on MN9D cell viability and apoptosis, as well as on movement impairments in MPTP-induced PD mouse model. The results indicated that HOTAIR expression was upregulated and SSTR1 was downregulated in in vivo and in vitro PD models. HOTAIR could bind to the promoter region of SSTR1, resulting in an increase of SSTR1 methylation through the recruitment of DNA methyltransferases in PD cell models. Notably, overexpression of HOTAIR and silencing of SSTR1 enhanced dopaminergic neuron apoptosis in MN9D cells and exacerbated dyskinesia in MPTP-induced PD mouse model. Collectively, overexpressed HOTAIR stimulates DNA methylation of SSTR1 to reduce SSTR1 expression, thereby accelerating dyskinesia and facilitating dopaminergic neuron apoptosis in a MPTP-lesioned PD mouse model via activation of the ERK1/2 axis.
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http://dx.doi.org/10.1016/j.omtn.2020.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494946PMC
July 2020

Self-recognizing and stimulus-responsive carrier-free metal-coordinated nanotheranostics for magnetic resonance/photoacoustic/fluorescence imaging-guided synergistic photo-chemotherapy.

J Mater Chem B 2020 07;8(26):5667-5681

CAS Key Laboratory of Design and Assembly of Functional Nanostructures, and Fujian Provincial Key Laboratory of Nanomaterials, Fujian Institute of Research on the Structure of Matter, Chinese Academy of Sciences, Fuzhou 350002, China. and Department of Translational Medicine, Xiamen Institute of Rare Earth Materials, Chinese Academy of Sciences, Xiamen 361024, China.

Carrier-free nanotheranostics directly assembled by using clinically used photosensitizers and chemotherapeutic drugs are a promising alternative to tumor theranostics. However, the weak interaction-driven assembly still suffers from low structural stability against disintegration, lack of targeting specificity, and poor stimulus-responsive property. Moreover, almost all exogenous ligands possess no therapeutic effect. Enlightened by the concept of metal-organic frameworks, we developed a novel self-recognizing metal-coordinated nanotheranostic agent by the coordination-driven co-assembly of photosensitizer indocyanine green (ICG) and chemo-drug methotrexate (MTX, also served as a specific "targeting ligand" towards folate receptors), in which ferric (FeIII) ions acted as a bridge to tightly associate ICG with MTX. Such carrier-free metal-coordinated nanotheranostics with high dual-drug payload (∼94 wt%) not only possessed excellent structural and physiological stability, but also exhibited prolonged blood circulation. In addition, the nanotheranostics could achieve the targeted on-demand drug release by both stimuli of internal lysosomal acidity and external near-infrared laser. More importantly, the nanotheranostics could self-recognize the cancer cells and selectively target the tumors, and therefore they decreased toxicity to normal tissues and organs. Consequently, the nanotheranostics showed strongly synergistic potency for tumor photo-chemotherapy under the precise guidance of magnetic resonance/photoacoustic/fluorescence imaging, thereby achieving highly effective tumor curing efficiency. Considering that ICG and bi-functional MTX are approved by the Food and Drug Administration, and FeIII ions have high biosafety, the self-recognizing and stimulus-responsive carrier-free metal-coordinated nanotheranostics may hold potential applications in tumor theranostics.
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http://dx.doi.org/10.1039/d0tb00850hDOI Listing
July 2020

Neuroprotection of GLP-1/GIP receptor agonist via inhibition of mitochondrial stress by AKT/JNK pathway in a Parkinson's disease model.

Life Sci 2020 Sep 20;256:117824. Epub 2020 May 20.

Department of Emergency, Guizhou Provincial People's Hospital, Guiyang 550004, PR China. Electronic address:

Objectives: To investigate the effect of glucagon-like peptide-1 (GLP-1) receptor and glucose dependent insulinotrophic polypeptide (GIP) receptor dual agonist DA-JC4 on alleviating Parkinson's disease (PD) and unveil related cellular mechanisms.

Methods: Rotenone was injected to generate a rat PD model, on which the effect of DA-JC4 on motor functions was evaluated by rotational behavioral assay and open field test. The survival of dopaminergic neurons was analyzed, in addition to assays for mitochondrial stress and quantification of neurotransmitter levels using high performance liquid chromatography (HPLC). In cultured hippocampal neurons, the effect of DA-JC4 on mitochondrial stress and related cellular mechanism was analyzed by Flow cytometry, western blotting and reactive oxygen species (ROS).

Results: DA-JC4 significantly improved motor functions in PD rats, and elevated levels of major neurotransmitters. By histological analysis, DA-JC4 protected dopaminergic neurons from rotenone-induced cell death, which was associated with reduced mitochondrial stress. Experiments in cultured rat hippocampal neurons validated the neuroprotective role of DA-JC4 against cell apoptosis and mitochondrial stress induced by rotenone. The protective effect of DA-JC4 was later found to be dependent on AKT/JNK signal pathway, as treatment using AKT inhibitor or JNK activator abolished such effects.

Conclusion: Our results showed that the dual agonist of GLP-1/GIP receptor could ameliorate motor dysfunctions of PD by protecting dopaminergic neurons which was mediated by relieved mitochondrial stress and apoptosis via AKT/JNK signal pathway.
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http://dx.doi.org/10.1016/j.lfs.2020.117824DOI Listing
September 2020

Lung CSC-derived exosomal miR-210-3p contributes to a pro-metastatic phenotype in lung cancer by targeting FGFRL1.

J Cell Mol Med 2020 06 12;24(11):6324-6339. Epub 2020 May 12.

Lung Cancer Center, Cancer Center, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, China.

Lung cancer has the highest mortality rate among human cancers, and the majority of deaths can be attributed to metastatic spread. Lung cancer stem cells (CSCs) are a component of the tumour microenvironment that contributes to this process. Exosomes are small membrane vesicles secreted by all types of cells that mediate cell interactions, including cancer metastasis. Here, we show that lung CSC-derived exosomes promote the migration and invasion of lung cancer cells, up-regulate expression levels of N-cadherin, vimentin, MMP-9 and MMP-1, and down-regulate E-cadherin expression. Moreover, we verified that these exosomes contribute to a pro-metastatic phenotype in lung cancer cells via miR-210-3p transfer. The results of bioinformatics analysis and dual-luciferase reporter assays further indicated that miR-210-3p may bind to fibroblast growth factor receptor-like 1 (FGFRL1); silencing FGFRL1 enhanced the metastatic ability of lung cancer cells, whereas overexpressing FGFRL1 suppressed metastasis. Taken together, our results provide new insights into a potential molecular mechanism whereby lung CSC-derived exosomal miR-210-3p targets FGFRL1 to promote lung cancer metastasis. FGFRL1 may be a promising therapeutic target in lung cancer.
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http://dx.doi.org/10.1111/jcmm.15274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294132PMC
June 2020

Functional near-infrared spectroscopy (fNIRS) as a tool to assist the diagnosis of major psychiatric disorders in a Chinese population.

Eur Arch Psychiatry Clin Neurosci 2021 Jun 11;271(4):745-757. Epub 2020 Apr 11.

Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Insitute, Shanghai, People's Republic of China.

Advances in neuroimaging have promised the development of specific and objective biomarkers for the diagnosis and treatment of psychiatric disorders. Recently, functional near-infrared spectroscopy (fNIRS) has been used during cognitive tasks to measure cortical dysfunction associated with mental illnesses such as Schizophrenia (SCH), Major-Depressive disorder (MD) and Bipolar Disorder (BD). We investigated the ability of fNIRS as a clinically viable tool to successfully distinguish healthy individuals from those with major psychiatric disorders. 316 patients with major psychiatric disorders (198 SCH/54 MD/64 BP) and 101 healthy controls were included in this study. Changes in oxygenated-hemoglobin during a Chinese language verbal fluency test were measured using a 52-channel fNIRS machine over the bilateral temporal and frontal lobe areas. We evaluated the ability of two task-evoked features selected from prior studies the Integral and Centroid values, to identify individuals with major diagnoses. Both the integral value of frontal and centroid value of temporal showed sensitivity in classifying individuals with mental disorders from healthy controls. However, using a combined index featuring both the integral value and centroid value to differentiate psychiatric disorders from healthy controls with an AUC of 0.913, differentiate individuals with mood disorders from healthy controls showed an AUC of 0.899, while for schizophrenia the AUC was 0.737. Our data suggest that fNIRS can be used as a candidate biomarker during differential diagnosis individuals with mood or psychosis disorders and offer a step towards individualization of treatment.
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http://dx.doi.org/10.1007/s00406-020-01125-yDOI Listing
June 2021

Early detection and management of immune-related myocarditis: Experience from a case with advanced squamous cell lung carcinoma.

Eur J Cancer 2020 05 2;131:5-8. Epub 2020 Apr 2.

Department of Medical Oncology, Lung Cancer Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China. Electronic address:

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http://dx.doi.org/10.1016/j.ejca.2020.02.046DOI Listing
May 2020

Tumor-Specific Endogenous Fe-Activated, MRI-Guided Self-Targeting Gadolinium-Coordinated Theranostic Nanoplatforms for Amplification of ROS and Enhanced Chemodynamic Chemotherapy.

ACS Appl Mater Interfaces 2020 Apr 18;12(13):14884-14904. Epub 2020 Mar 18.

Department of Biomaterials, College of Materials, Research Center of Biomedical Engineering of Xiamen & Key Laboratory of Biomedical Engineering of Fujian Province & Fujian Provincial Key Laboratory for Soft Functional Materials Research, Xiamen University, Xiamen 361005, China.

Low drug payload and lack of tumor-targeting for chemodynamic therapy (CDT) result in an insufficient reactive oxygen species (ROS) generation, which seriously hinders its further clinical application. Therefore, how to improve the drug payload and tumor targeting for amplification of ROS and combine it with chemotherapy has been a huge challenge in CDT. Herein, methotrexate (MTX), gadolinium (Gd), and artesunate (ASA) were used as theranostic building blocks to be coordinately assembled into tumor-specific endogenous Fe-activated and magnetic resonance imaging (MRI)-guided self-targeting carrier-free nanoplatforms (NPs) for amplification of ROS and enhanced chemodynamic chemotherapy. The obtained ASA-MTX-Gd NPs exhibited extremely high drug payload (∼96 wt %), excellent physiological stability, long circulating ability (half-time: ∼12 h), and outstanding tumor accumulation. Moreover, ASA-MTX-Gd NPs could be specifically uptaken by tumor cells via folate (FA) receptors and subsequently be disassembled via lysosomal acidity-induced coordination breakage, resulting in drug burst release. Most strikingly, the produced ASA could be catalyzed by tumor-specific overexpressed endogenous Fe ions to generate sufficient ROS for enhancing the main chemodynamic efficacy, which could exert a synergistic effect with the assistant chemotherapy of MTX. Interestingly, ASA-MTX-Gd NPs caused a lower ROS generation and toxicity on normal cell lines that seldom expressed endogenous Fe ions. Under MRI guidance with assistance of self-targeting, significantly superior synergistic tumor therapy was performed on FA receptor-overexpressed tumor-bearing mice with a higher ROS generation and an almost complete elimination of tumor. This work highlights ASA-MTX-Gd NPs as an efficient chemodynamic-chemotherapeutic agent for MRI imaging and tumor theranostics.
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http://dx.doi.org/10.1021/acsami.0c00970DOI Listing
April 2020

Neuroprotective effect and mechanism of baicalin on Parkinson's disease model induced by 6-OHDA.

Neuropsychiatr Dis Treat 2019 31;15:3615-3625. Epub 2019 Dec 31.

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

Objective: This research was aimed to investigate the effects of baicalin on 6-hydroxydopamine (6-OHDA)-induced rat model of Parkinson's disease (PD) and the main mechanism of baicalin based on metabolomics.

Methods: The rat model of PD was induced by 6-OHDA. The protective effects of baicalin on rat model of PD were evaluated by open field test and rotarod test. The anti-PD efficacy of baicalin was evaluated by examining the morphologic changes of neurons and the level of monoamine neurotransmitters in the striatum, the number and morphology of tyrosine hydroxylase (TH)-positive neurons, and oxidative stress. Combined with metabolomics methods, the pharmacodynamic mechanism of baicalin on PD pathogenesis was also explored.

Results: Baicalin treatment improved the rod time and voluntary movement in rat model of PD (<0.05) by the open field test and rotarod test. In addition, baicalin also protected from oxidative stress injury (<0.05), and regulated the content of monoamine neurotransmitters dopamine, 3,4-dihydroxyphenylacetic acid, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid (<0.05) and the number and morphology of TH-positive cells in 6-OHDA-induced PD model rats. By metabolomics, multivariate statistical analysis, and receiver operating characteristic curve analysis, we found that two metabolites N-acetyl aspartic acid and glutamic acid had a good diagnostic value. Quantitative analysis of metabolites showed a regulatory function of baicalin.

Conclusion: Baicalin has significant protective effect on 6-OHDA-induced PD rats, which may play a protective role through an antioxidant, promoting the release of neurotransmitters and regulating the metabolism of N-acetyl aspartate and glutamate.
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http://dx.doi.org/10.2147/NDT.S165931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997193PMC
December 2019

Mechanisms underlying direct actions of hyperlipidemia on myocardium: an updated review.

Lipids Health Dis 2020 Feb 8;19(1):23. Epub 2020 Feb 8.

Department of Cardiovascular Diseases, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510080, People's Republic of China.

Hyperlipidemia is a common metabolic disorder and one of risk factors for cardiovascular disease. Clinical studies have shown that hyperlipidemia increases the risk of non-ischemic heart failure, while decreasing serum lipids can reverse heart dysfunction. Apart from indirectly affecting the function of the heart by promoting the development of atherosclerosis, hyperlipidemia also affects the systolic function and cardiac electrophysiological response of the heart directly, which may be related to gradual accumulation of cardiac lipids and consequent systemic oxidative stress, proinflammatory state and mitochondrial dysfunction. However, the mechanism underlying direct effects of hyperlipidemia on the heart are not fully understood. In this review, we provide an updated summary of recent experimental and clinical studies that focus on elucidating the mechanisms of the action of hyperlipidemia on cardiac function, the relationship between heart failure and serum lipids, and protective effects of lipid-lowering drugs on the heart. The exciting progress in this field supports the prospect of guiding early protection of the heart to benefit the patients with chronic hyperlipidemia and familial hyperlipidemia.
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http://dx.doi.org/10.1186/s12944-019-1171-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007679PMC
February 2020

Up-regulation of microRNA-375 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in Parkinson's disease by inhibiting SP1.

Aging (Albany NY) 2020 01 11;12(1):672-689. Epub 2020 Jan 11.

Department of Emergency, Guizhou Provincial People's Hospital, Guiyang 550004, PR. China.

Background: This study is conducted to investigate the protective role of elevated microRNA-375 (miR-375) in dopaminergic neurons in Parkinson's disease through down-regulating transcription factor specificity protein 1 (SP1).

Results: The successfully modeled rats with Parkinson's disease showed aggregated neurobehavioral change, increased neuroinflammatory response and oxidative stress, and lowered dopamine content. Parkinson's disease rats treated with overexpressed miR-375 displayed improved neurobehavioral change, ameliorated neuroinflammatory response and oxidative stress, heightened dopamine content and abated neuronal apoptosis by down-regulating SP1. Up-regulation of SP1 reversed the protective effect of upregulated miR-375 on Parkinson's disease.

Conclusion: Up-regulation of miR-375 ameliorated the damage of dopaminergic neurons, reduced oxidative stress and inflammation in Parkinson's disease by inhibiting SP1.

Methods: Parkinson's disease rat model was established by targeted injection of 6-hydroxydopamine to damage the substantia nigra striatum. The successfully modeled Parkinson's disease rats were intracerebroventricularly injected with miR-375 mimics or pcDNA3.1-SP1. The functions of miR-375 and SP1 in neurobehavioral change, neuroinflammatory response, oxidative stress, dopamine content and expression of apoptosis-related proteins in the substantia nigra of Parkinson's disease rats were evaluated. The target relation of miR-375 and SP1 was confirmed by bioinformatics analysis and dual luciferase reporter gene assay.
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http://dx.doi.org/10.18632/aging.102649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6977707PMC
January 2020

Study of the association between gait variability and gene expressions in a mouse model of transient focal ischemic stroke.

Int J Neurosci 2020 Jan 13;130(1):52-63. Epub 2019 Oct 13.

Neurology Department, The Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guang Zhou, China.

Gait variability analysis has been clinically adopted to characterize the presentation of various neurological diseases. However, literature and practice lack a comprehensive murine model assessment of the gait deficits that result from transient focal ischemic stroke. Further, correlations between gait parameters and the gene expression profiles associated with brain ischemia have yet to be identified. This study quantitatively assesses gait deficits through a murine model of transient focal cerebral ischemia on day 7 to determine associations between gait deficits and ischemia-related gene expressions.: A total of 182 dynamic and static gait parameters from the transient middle cerebral artery occlusion (MCAO) murine model for simulating human transient focal ischemic stroke on day 7 were measured using the CatWalk system. Pearson's correlation analysis and genes associated with ischemia were identified from the existing literature to aid the investigation of the relationship between gait variability and gene expression profiles. Thirty-nine gait parameters and the mRNA expression levels of four of the eight ischemia-associated genes exhibited more significant change in the MCAO models ( < 0.005) on day 7. Twenty-six gait parameters exhibited strong correlations with four ischemia-associated genes. This examination of gait variability and the strong correlation to the gene expression profiles associated with transient focal brain ischemia on day 7 provides a quantitative and reliable assessment of the MCAO model's motor performance. This research provides valuable insights into the study of disease progression and offers novel therapeutic interventions in the murine modeling of ischemic stroke.
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http://dx.doi.org/10.1080/00207454.2019.1663188DOI Listing
January 2020

MiR-34c acts as a tumor suppressor in non-small cell lung cancer by inducing endoplasmic reticulum stress through targeting HMGB1.

Onco Targets Ther 2019 16;12:5729-5739. Epub 2019 Jul 16.

Department of Respiratory Medicine, Peking University Shenzhen Hospital, Shenzhen 518000, People's Republic of China.

Objective: To investigate the role of miR-34c in lung cancer.

Methods: The levels of microRNA-34c (miR-34c) expression in non-small cell lung cancer (NSCLC) tissue and cell lines were examined by the qRT-PCR assay. High mobility group box 1 (HMGB1) expression in NSCLC was assessed by immunohistochemical analysis (IHC), qRT-PCR, and Western blot assays. The effects of miR-34c overexpression or HMGB1 knockdown on cell proliferation and apoptosis were evaluated by CCK-8 and flow cytometry analysis, respectively. Cellular reactive oxygen species (ROS) production in NSCLC cells was detected using a ROS kit. The levels of Bax, p-ERK, eIF2α, GADD153, and IRE1α expression in treated NSCLC cells were measured by Western blot assays. In addition, the interaction between miR-34c and HMGB1 was verified by the dual-luciferase reporter assay.

Results: miR-34c was only slightly expressed, while HMGB1 was highly expressed in NSCLC tissues and cell lines. Overexpression of miR-34c or knockdown of HMGB1 inhibited cell proliferation, promoted cell apoptosis, and induced ER stress in NSCLC cells. In terms of mechanism, miR-34c negatively regulated HMGB1 expression by directly targeting the 3'-untranslated region (UTR) of HMGB1 mRNA. In addition, we proved that HMGB1 overexpression could block the effects of miR-34c on NSCLC cell proliferation, apoptosis, and ER stress.

Conclusion: miR-34c may suppress NSCLC tumors by targeting HMGB1 mRNA, promoting endoplasmic reticulum stress, and increasing ROS levels. Our findings suggest that miR-34c has a role in NSCLC.
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http://dx.doi.org/10.2147/OTT.S206932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647009PMC
July 2019

Downregulation of lncRNA UCA1 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in Parkinson's disease through the inhibition of the PI3K/Akt signaling pathway.

Int Immunopharmacol 2019 Oct 10;75:105734. Epub 2019 Jul 10.

Department of Emergency, Guizhou Provincial People's Hospital, Guiyang 550004, PR China. Electronic address:

This study is conducted to investigate the role of lncRNA urothelial carcinoma-associated 1 (UCA1) in the protection of dopaminergic neurons in Parkinson's disease (PD) through regulating the PI3K/Akt signaling pathway. PD rat model was induced by injection of 6-hydroxydopamine (6-OHDA) to damage the substantia nigra striatum. The successfully modeled PD rats were introduced with siRNA-negative control (NC) or UCA1-siRNA. The expression of UCA1 in neurobehavioral change, neuroinflammatory response and oxidative stress of PD rats were explored. The effect of UCA1 on the PI3K/Akt signaling pathway and downstream proteins IκBα and ERK was also investigated. The rats with PD exhibited aggregated neurobehavioral change, increased neuroinflammatory response and oxidative stress. Down-regulation of UCA1 up-regulated the expression of TH positive cells and DA content, reduced the apoptosis of substantia nigra neurons, the apoptosis of substantia nigra neurons and oxidative stress and improved the neuroinflammatory response in PD rats. Down-regulation of UCA1 inhibited the activation of the PI3K/AKT signaling pathway in substantia nigra of PD rats. Our study suggests that the downregulated lncRNA UCA1 ameliorates the damage of dopaminergic neurons, reduces oxidative stress and inflammation in PD rats through the inhibition of the PI3K/Akt signaling pathway.
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http://dx.doi.org/10.1016/j.intimp.2019.105734DOI Listing
October 2019

CuS/Prussian blue core-shell nanohybrid as an electrochemical sensor for ascorbic acid detection.

Nanotechnology 2019 08 4;30(32):325501. Epub 2019 Apr 4.

Department of Biomaterials, College of Materials, Xiamen University, Xiamen 361005, People's Republic of China.

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http://dx.doi.org/10.1088/1361-6528/ab1613DOI Listing
August 2019

Zoledronic acid inhibits the growth of cancer stem cell derived from cervical cancer cell by attenuating their stemness phenotype and inducing apoptosis and cell cycle arrest through the Erk1/2 and Akt pathways.

J Exp Clin Cancer Res 2019 Feb 21;38(1):93. Epub 2019 Feb 21.

Lung Cancer Center, Laboratory of Lung Cancer, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.

Background: Zoledronic acid is the most potent osteoclast inhibitor and is widely used for advanced cancer patients with bone metastasis, but its role on cancer stem cells (CSCs) remains unclear. In the present study, we aimed to identify the stemness phenotypic characteristics of CSCs derived from cervical cancer cells and explore the anti-cancer efficiency of zoledronic acid on these cells, as well as the possible molecular mechanisms.

Methods: Stemness phenotypic identification of cervical cancer cells derived CSCs was performed via sphere formation efficiency (SFE), tumorigenesis, immunofluorescence staining, Transwell assay, and western blot. Anti-cancer efficiency of zoledronic acid on these cells (including proliferation, stemness phenotype, apoptosis, and cell cycle) was carried out through MTT assay, SFE, transwell, DAPI staining, flow cytometry, immunofluorescence, TUNEL staining, and western blot, both in vitro and in vivo.

Results: Enhanced self-renewal ability, including SFE and tumorigenesis, was verified in cervical cancer cells derived CSCs compared to parental cervical cancer cells. Specifically, the expression of ALDH1, Sox2, CD49f, Nanog, and Oct4 was significantly up-regulated in cervical cancer cells derived CSCs. Furthermore, enhanced migratory ability was observed in these cells along with up-regulated N-cadherin and Vimentin and down-regulated E-cadherin. Zoledronic acid inhibited cervical cancer cells derived CSCs proliferation in vitro and in vivo. The stemness phenotype of these CSCs including tumor sphere formation, migration, as well as the expression of the aforementioned associated markers was also suppressed. In addition, zoledronic acid significantly induced apoptosis and cell cycle arrest of cervical cancer cells derived CSCs in a dose-dependent manner. Mechanistically, the expression of phosphorylated Erk1/2 and Akt was significantly increased in cervical cancer cells derived CSCs compared to parental cervical cancer cells. Zoledronic acid inhibited phosphorylated Erk1/2 and Akt in cervical cancer cells derived CSCs. IGF-1, a potent stimulator for Erk1/2 and PI3K/Akt, attenuated the aforementioned anti-cancer effect of zoledronic acid.

Conclusions: Zoledronic acid inhibited the growth of cervical cancer cells derived CSCs through attenuating their stemness phenotype, inducing apoptosis, and arresting cell cycle. The suppression of phosphorylated Erk1/2 and Akt was involved in this process.
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http://dx.doi.org/10.1186/s13046-019-1109-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6385443PMC
February 2019

Molybdenum Disulfide Quantum Dots Attenuates Endothelial-to-Mesenchymal Transition by Activating TFEB-Mediated Lysosomal Biogenesis.

ACS Biomater Sci Eng 2019 Feb 17;5(2):1057-1070. Epub 2018 Dec 17.

Department of Surgery, First Affiliated Hospital of Xiamen University, Xiamen 361004, P.R. China.

A defective lysosome-autophagy degradation pathway contributes to a variety of endothelial-to-mesenchymal transition (EndMT)-related cardiovascular diseases. Molybdenum disulfide quantum dots (MoS QDs) are nanoscale sizes in the planar dimensions and atomic structures of transition metal dichalcogenides (TMDs) materials with excellent physicochemical and biological properties, making them ideal for various biomedical applications. In this study, water-soluble MoS QDs with an average diameter of about 3.4 nm were synthesized by using a sulfuric acid-assisted ultrasonic method. The as-prepared MoS QDs exhibited low cytotoxicity of less than 100 μg/mL in both human umbilical vein endothelial cells and human coronary artery endothelial cells and showed novel biological properties to prevent EndMT and promote angiogenesis in vitro. We found that MoS QDs treatment-induced transcription factor (TFEB) mediated lysosomal biogenesis, which could cause autophagy activation. Importantly, using in vitro transforming growth factor (TGF)-β-induced EndMT model, we demonstrated that the cardiovascular protective effect of MoS QDs against EndMT acted through triggering TFEB nucleus translocation and restoring an impairment of autophagic flux, whereas genetic suppression of TFEB impaired the protective action of MoS QDs against EndMT. Taken together, these results gain novel insights into the mechanisms by which MoS QDs regulate EndMT and facilitate the development of MoS-based nanoagents for the treatment of EndMT-related cardiovascular diseases.
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http://dx.doi.org/10.1021/acsbiomaterials.8b01253DOI Listing
February 2019

Favorable progression-free survival in women with two different histopathological subtypes of bilateral breast cancer.

J Cancer Res Ther 2018 ;14(7):1627-1631

Department of Medical Oncology, Cancer Center, Lung Cancer Center and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China.

Purpose: The aim of this study was to classify bilateral breast cancers (BBCs) into two groups according to histopathological or molecular subtypes of the two breast diseases in each patient and to study their characteristics in relation to survival outcomes.

Methods: Fifty-six BBC patients were enrolled in the study. They were classified according to whether the two breast diseases were of the same or different histopathological subtypes (defined as S-his or D-his groups) and molecular subtypes (defined as S-mole and D-mole groups). Progression-free survival (PFS), overall survival (OS), and important characteristics were then compared between the groups.

Results: We observed that the PFS and OS of the S-mole and D-mole groups failed to reach a significant difference. However, D-his BBC patients enjoyed longer PFS than their S-his counterparts, although the OS was similar. To explore the reason for the extended PFS in D-his BBC patients, we first focused on the possible prognostic contribution by various histopathological subtypes in the groups. We compared the proportion of infiltrating ductal carcinoma, infiltrating lobular carcinoma, and other breast cancer subtypes in the D-his and S-his groups, and demonstrated that they were not associated with longer PFS. We then examined age, menopausal status, tumor, node, and metastasis (TNM) stage, expressions of estrogen receptor (ER), progesterone receptor (PR) and Ki67, and metastasis to lymph nodes, viscera, and bone. The results indicated no significant between-group differences in age, TNM stage, ER/PR expression, and metastasis to viscera and bone. However, significantly lower levels of Ki67and decreased lymph node metastasis rate were associated with D-his BBC patients, which might explain the observed longer PFS.

Conclusions: In comparison to S-his, D-his BBC patients had longer PFS, which was associated with lower levels of Ki67 and a decreased lymph node metastasis rate.
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http://dx.doi.org/10.4103/jcrt.JCRT_997_17DOI Listing
February 2019

Assessment of Concurrent Chemoradiotherapy plus Induction Chemotherapy in Advanced Nasopharyngeal Carcinoma: Cisplatin, Fluorouracil, and Docetaxel versus Gemcitabine and Cisplatin.

Sci Rep 2018 10 22;8(1):15581. Epub 2018 Oct 22.

Department of Head and Neck Oncology, Cancer Center, and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, 610041, Sichuan, China.

Induction chemotherapy treatment for nasopharyngeal carcinoma (NPC) is controversial. The aim of this study was to evaluate the treatment outcomes and toxicities between two induction chemotherapy regimens, with both followed by concurrent chemoradiotherapy. The first strategy used docetaxel, cisplatin and fluorouracil for induction chemotherapy (TPF), and the second utilised gemcitabine and cisplatin (GP). A retrospective analysis was performed on eligible NPC patients attending our hospital between May 2009 and Dec 2014. A total of 113 patients were enrolled with 58 patients receiving TPF and 55 receiving GP induction chemotherapy. Ninety-four patients (83.2%) were alive after 36-months follow-up. The median overall survival (OS) and progression-free survival (PFS) time were 48.3 and 39.7 months, respectively. The 3-year OS for the TPF regimen was 87.9% and 87.4% with GP chemotherapy (P = 0.928). The 3-year PFS of the TPF treatment was 84.5%, while it was 83.5% for the GP group (P = 0.551). Univariate analysis showed that lymph node metastasis was a significant PFS prognostic factor, while N3 stage was an independent predictor of PFS and distant failure-free survival (DMFS) in multivariate analysis. There were no significant differences in adverse toxicities or treatment efficacy between the chemotherapy regimens in the treatment of locoregionally advanced NPC.
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http://dx.doi.org/10.1038/s41598-018-33614-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6197284PMC
October 2018

CXCR2 is a novel cancer stem-like cell marker for triple-negative breast cancer.

Onco Targets Ther 2018 6;11:5559-5567. Epub 2018 Sep 6.

Lung Cancer Center, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, People's Republic of China,

Background: Breast cancer is the leading cause of mortality from cancer in women worldwide, and cancer stem-like cell (CSC) is responsible for failure treatment of breast cancer. It plays an important role in resistant disease and metastasis. CD44/CD24 and ALDH are well-accepted protein markers of breast CSC, and it was reported that distinct subtypes of breast CSC were identified by the 2 markers. It is possible that there are various kinds of breast CSC which could be identified by different markers, and CSC markers utilized at present are not enough to fully understand breast CSC. Finding out more novel CSC markers is necessary. CXCR2 is involved in breast cancer metastasis, treatment resistance, and recurrence and has positive cross-talk with known breast CSC protein markers. It can be concluded that CXCR2 is related to breast CSC, and further study is in need.

Results: In this study, we assessed expression of CXCR2 with immunohistochemistry in breast cancer tissues from 37 patients and discovered that level of CXCR2 was significantly lower in triple-negative breast cancer (TNBC) compared with non-TNBC. CXCR2 expression decreased in estrogen receptor-negative or HER2-negative breast cancer, but not progesterone receptor-negative counterparts. By immunofluorescence, we observed high coexpression rate of CXCR2 and CSC-related proteins, including NANOG and SOX2. To prove our speculation that CXCR2 was a novel CSC marker for TNBC, we used 4T1 cell, which is a TNBC cell line, to analyze CXCR2-positive subpopulations and observed that CXCR2-positive 4T1 cells showed characteristics of CSC, including resistance to cisplatinum, radiation, and hypoxia, low proportion (around 1%), much more tumor xenografts, tumor spherule formation, and higher levels of CSC-related mRNA compared with CXCR2-negative cells.

Conclusion: CXCR2 is an acceptable and newly discovered CSC marker for only TNBC.
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http://dx.doi.org/10.2147/OTT.S174329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134958PMC
September 2018

Admission Serum Calcium Level as a Prognostic Marker for Intracerebral Hemorrhage.

Neurocrit Care 2019 02;30(1):81-87

Department of Emergency, Guizhou Provincial People's Hospital, No. 83, Zhongshan East Road, Guiyang, 550002, Guizhou Province, People's Republic of China.

Background: Prognostic significance of serum calcium level in patients with intracerebral hemorrhage is not well studied. The aim of the study was to identify if a relationship between admission serum calcium level and prognosis exists in patients with intracerebral hemorrhage.

Methods: A total of 1262 confirmed intracerebral hemorrhage patients were included. Demographic data, medical history, medicine history, laboratory data, imaging data, clinical score, and progress note were collected from their medical records. All images of head computed tomography were reanalyzed. Ninety-day prognosis was recorded, and poor outcome was defined as death or major disability caused by intracerebral hemorrhage.

Results: During the 90-day follow-up period, 504 patients died and 226 patients suffered from major disability. Death and major disability were combined as poor prognosis. The remaining 532 patients showed good prognosis. Admission serum calcium level was lower in the patients with poor prognosis than in the patients with good prognosis (2.41 ± 0.23 mmol/l, 2.55 ± 0.26 mmol/l, P < 0.001). Admission INR and hematoma volume were higher in the patients with poor prognosis than in the patients with good prognosis (INR: 1.74 ± 0.29, 1.70 ± 0.29, P = 0.029; hematoma volume: 11.6 ± 4.4 ml, 10.7 ± 4.1 ml, P < 0.001). There was no difference in admission APTT level between the two prognosis groups (28.4 ± 5.6 s, 27.8 ± 5.4 s, P = 0.056). A multivariate COX regression analysis reported that admission serum calcium level ≤ 2.41 mmol/l was associated with the increased risk of poor prognosis (death or major disability) in the patients (HR 1.45, 95% CI 1.32-1.60). In addition, there was a significant linear association of serum calcium level with coagulation function markers and hematoma volume on admission (APTT: r = - 0.091, P = 0.001; INR: r = - 0.063, P = 0.025; hematoma volume: r = -0.108, P < 0.001).

Conclusions: Admission serum calcium level might be a prognostic marker for intracerebral hemorrhage. Potential mechanism involved calcium-induced coagulation function abnormality.
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http://dx.doi.org/10.1007/s12028-018-0574-0DOI Listing
February 2019

[Fine root morphology and chemistry characteristics in different branch orders of Castanopsis platyacantha and their responses to nitrogen addition].

Ying Yong Sheng Tai Xue Bao 2017 Nov;28(11):3461-3468

College of Fore-st, Sichuan Agricultural University, Chengdu 611130, China.

Fine root morphology and chemistry characteristics of dominant species Castanopsis platya-cantha in an evergreen broad-leaved forest in subtropical China and their response to nitrogen (N) addition were determined in order 1st to 5th. With the increase of root order, C. platyacantha root diameter, tissue density (RTD), and K content increased, and specific root length (SRL), speci-fic surface area (SRA) and contents of N, P and Mg decreased. Nitrogen addition significant increased N content and decreased Mg content and C/N of fine roots. Root tissue Ca content had a decrease trend under N addition treatments. There were neither significant effects on the contents of C, P, K, Na, Al, Mn, Fe of fine roots, nor on fine root diameter, SRL, SRA and RTD. Root P content had a significant liner relationship with root morphology in the all treatments. Nitrogen addition changed the linear relationships between tissue Mg content and root morphology from no significant relationship to significant relationship, and linear relationships between tissue N content and root morphology from significant relationship to no significant relationship. N addition would affect the root tissue nutrient contents and could enhance P and Mg requirement of plants.
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http://dx.doi.org/10.13287/j.1001-9332.201711.004DOI Listing
November 2017

Bexarotene attenuates early brain injury via inhibiting micoglia activation through PPARγ after experimental subarachnoid hemorrhage.

Neurol Res 2018 Aug 24;40(8):702-708. Epub 2018 Apr 24.

b Department of Emergency , Guizhou Provincial People's Hospital , Guizhou , China.

Objectives Early brain injury (EBI) is considered to be one of the main causes of poor outcome in subarachnoid hemorrhage (SAH) patients. Bexarotene is an agonist of retinoid X receptor and plays a protective role in central nervous system diseases. However, the exact role of bexarotene in SAH has not been reported. Therefore, the present study was to determine whether bexarotene administration attenuate EBI after SAH in mice and to explore the underlying mechanism. Methods SAH was induced in C57BL/6 mice by endovascular perforation. Bexarotene was administrated intraperitoneally. Neurological score, cell death, microglia activation, and pro-inflammatory cytokines were detected at 24 h after SAH. The expression of PPARγ was measured by Western blot. Results Results showed that bexarotene significantly improved neurological score after SAH. In addition, the number of cell death and activated microglia were significantly reduced by bexarotene administration. Compared with vehicle-treated mice, bexarotene-treated mice showed reduced pro-inflammatory cytokines after SAH. The expression of PPARγ was significantly increased with bexarotene treatment compared with vehicle-treated controls. Discussion The present study demonstrats that bexarotene administration protects against EBI after SAH, inhibiting cell death, attenuating microglia activation, and alleviating neuroinflammation. The underlying mechanism may partially involve the activation of PPARγ.
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http://dx.doi.org/10.1080/01616412.2018.1463900DOI Listing
August 2018
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