Publications by authors named "Yan-Fang Zhang"

76 Publications

Geometric, electronic, and optical properties of MoS/WSSe van der Waals heterojunctions: a first-principles study.

Nanotechnology 2021 Jun 11;32(35). Epub 2021 Jun 11.

Institute of Physics and University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.

Van der Waals (vdW) heterojunctions constructed by vertical stacking two-dimensional transition metal dichalcogenides hold exciting promise in realizing future atomically thin electronic and optoelectronic devices. Recently, a Janus WSSe structure has been successfully synthesized by using chemical vapor deposition, selective epitaxy atomic replacement, and pulsed laser deposition methods. Herein, based on first-principles calculations, we introduce the structures and performances of MoS/WSSe vdW heterojunctions with different interfaces and stacking modes. The vdW heterojunctions possess indirect band gaps for S-S interfaces, while direct band gaps for Se-S interfaces. Besides, the potential drop indicates an efficient separation of photogenerated charges. Interestingly, the opposite built-in electric fields formed in the vdW heterojunctions with a S-S interface and a Se-S interface suggest different charge transfer paths, which would motivate further theoretical and experimental investigations on charge transfer dynamics. Moreover, the electronic property is adjustable by applying external in-plane strains, accomplishing with indirect to direct bandgap transition and semiconductor to metal transition. The findings are helpful for the design of multi-functional high-performance electronic and optoelectronic devices based on the MoS/WSSe vdW heterojunctions.
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http://dx.doi.org/10.1088/1361-6528/ac0569DOI Listing
June 2021

Hydromorphone Protects against CO Pneumoperitoneum-Induced Lung Injury via Heme Oxygenase-1-Regulated Mitochondrial Dynamics.

Oxid Med Cell Longev 2021 9;2021:9034376. Epub 2021 Apr 9.

Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin 300100, China.

Various pharmacological agents and protective methods have been shown to reverse pneumoperitoneum-related lung injury, but identifying the best strategy is challenging. Herein, we employed lung tissues and blood samples from C57BL/6 mice with pneumoperitoneum-induced lung injury and blood samples from patients who received laparoscopic gynecological surgery to investigate the therapeutic role of hydromorphone in pneumoperitoneum-induced lung injury along with the underlying mechanism. We found that pretreatment with hydromorphone alleviated lung injury in mice that underwent CO insufflation, decreased the levels of myeloperoxidase (MPO), total oxidant status (TOS), and oxidative stress index (OSI), and increased total antioxidant status (TAS). In addition, after pretreatment with hydromorphone, upregulated HO-1 protein expression, reduced mitochondrial DNA content, and improved mitochondrial morphology and dynamics were observed in mice subjected to pneumoperitoneum. Immunohistochemical staining also verified that hydromorphone could increase the expression of HO-1 in lung tissues in mice subjected to CO pneumoperitoneum. Notably, in mice treated with HO-1-siRNA, the protective effects of hydromorphone against pneumoperitoneum-induced lung injury were abolished, and hydromorphone did not have additional protective effects on mitochondria. Additionally, in clinical patients who received laparoscopic gynecological surgery, pretreatment with hydromorphone resulted in lower serum levels of club cell secretory protein-16 (CC-16) and intercellular adhesion molecule-1 (ICAM-1), a lower prooxidant-antioxidant balance (PAB), and higher heme oxygenase-1 (HO-1) activity than morphine pretreatment. Collectively, our results suggest that hydromorphone protects against CO pneumoperitoneum-induced lung injury via HO-1-regulated mitochondrial dynamics and may be a promising strategy to treat CO pneumoperitoneum-induced lung injury.
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http://dx.doi.org/10.1155/2021/9034376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053056PMC
May 2021

[Morin Improves Experimental Autoimmune Thyroiditis in Rats via NLRP3/Caspase-1 Pathway].

Sichuan Da Xue Xue Bao Yi Xue Ban 2021 Mar;52(2):229-234

Department of Respiratory and Critical Care Medicine, Huaihe Hospital Affiliated to Henan University, Kaifeng 475000, China.

Objective: To investigate the effects of morin-regulated NLRP3/Caspase-1 pathway on experimental autoimmune thyroiditis in rats.

Methods: The rats were randomly assigned to 6 groups: control group, experimental autoimmune thyroiditis group (EAT), low-, medium- and high-dose morin groups (post-modeling gavage of 50, 100 and 200 mg/kg morin hydrate per day for 6 weeks) and tripterygium wilfordii polyglycosides group (LGT group, post-modeling gavage of 6.25 mg/kg tripterygium wilfordii polyglycosidesper day for 6 weeks). Except for the control group, the rat model of experimental autoimmune thyroiditis was established by subcutaneous injection of 0.1 mL incomplete Freund's adjuvant containing porcine thyroglobulin. The levels of serum thyroglobulin (TgAb), thyroid peroxidase antibody (TPOAb), triiodothyronine (T3) and tetraiodothyronine (T4) in serum were detected by radioimmunoassay. The mRNA levels of interleukin-17 ( -17), interleukin-4 ( -4) and interferon γ ( - ) were detected by reverse transcription-polymerase chain reaction. The levels of serum protein carbonyl content, 8-hydroxydeoxyguanosine (8-OHdG), and malondialdehyde (MDA) activity were checked with test kits. Expressions of NLRP3, apoptosis-related speck-like protein (ASC), and Caspase-1 were detected by Western blot.

Results: Compared with the EAT group, serum levels of TPOAb, TgAb, T3, and T4 in low-, medium- and high-dose Morin groups and LGT group were reduced ( <0.01) and the mRNA levels of -17, and -4 were increased ( <0.01), the protein hydroxyl content, MDA activity, and 8-OHdG levels were reduced ( <0.01). The levels of NLRP3, ASC and Caspase-1 were reduced ( <0.01), the levels of 8-OHdG were significantly reduced ( <0.01), and the levels of NLRP3, ASC and Caspase-1 were significantly reduced ( <0.01). There were statistically significant differences between the data from the low-dose and the medium-dose Morin groups and the data of the LGT group ( <0.05), while data from the high-dose Morin group showed no significant difference compared with the data of the LGT group. Data from low-, medium- and high-dose Morin groups showed no statistically significant differences ( <0.05).

Conclusion: The findings suggest that Morin improved experimental autoimmune thyroiditis in rats through regulating NLRP3/Caspase-1 pathway.
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http://dx.doi.org/10.12182/20210160507DOI Listing
March 2021

Correction to: The Impact of Smoking, Sex, Infection, and Comedication Administration on Oral Olanzapine: A Population Pharmacokinetic Model in Chinese Psychiatric Patients.

Eur J Drug Metab Pharmacokinet 2021 May;46(3):373-374

The National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Lane, Dewai Avenue, Xicheng District, Beijing, 100088, China.

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http://dx.doi.org/10.1007/s13318-021-00680-6DOI Listing
May 2021

The Impact of Smoking, Sex, Infection, and Comedication Administration on Oral Olanzapine: A Population Pharmacokinetic Model in Chinese Psychiatric Patients.

Eur J Drug Metab Pharmacokinet 2021 May 6;46(3):353-371. Epub 2021 Mar 6.

The National Clinical Research Center for Mental Disorders and Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, No. 5 Ankang Lane, Dewai Avenue, Xicheng District, Beijing, 100088, China.

BACKGROUND AND OBJECTIVE: Prior olanzapine population pharmacokinetic (PPK) models have focused on the effects of sex and smoking on olanzapine clearance. This PPK model in Chinese adult psychiatric patients also investigated the influence of comedications and co-occurrence of infections on olanzapine clearance, and explored how to personalize oral olanzapine dosage in the clinical setting.

Methods: A total of 1546 serum concentrations from 354 patients were collected in this study. A one-compartment model with first-order absorption was employed to develop the PPK model using a nonlinear mixed-effects modeling approach. Covariates included demographic parameters, co-occurrence of infection and concomitant medications (including dangguilonghui tablets, a Chinese herbal medicine for constipation). Bootstrap validation (1000 runs) and external validation of 50 patients were employed to evaluate the final model. Simulations were performed to explore the personalization of olanzapine dosing after stratification by sex, smoking, and comedication with valproate.

Results: Typical estimates for the absorption rate constant (K), apparent clearance (CL/F), and apparent distribution volume (V/F) were 0.30 h, 12.88 L/h, and 754.41 L, respectively. Olanzapine clearance was increased by the following variables: 1.23-fold by male sex, 1.23-fold by smoking, 1.23-fold by comedication with valproate, 1.16-fold by sertraline, and 2.01-fold by dangguilonghui tablets. Olanzapine clearance was decreased by the following variables: 0.75-fold by co-occurrence of infection, 0.70-fold by fluvoxamine, and 0.78-fold by perphenazine. The model evaluation indicated that the final model's performance was good, stable, and precise.

Conclusion: This study contributes to the personalization of oral olanzapine dosing, but further studies should be performed to verify the effects of infection and comedications, including valproate and dangguilonghui.
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http://dx.doi.org/10.1007/s13318-021-00673-5DOI Listing
May 2021

[Effect of Sini San prescription on apoptosis and proliferation of hepatocellular carcinoma HepG2 cells].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2020 Sep;36(5):489-493

The College of Basic Medicine Sciences, Shaanxi University of Chinese Medicine, Xianyang 712046.

To investigate the effects of Sini San prescription(SNS) on the proliferation and apoptosis of HepG2 cells and its molecular mechanism. The morphological changes of hepatocellular carcinoma HepG2 cells treated by SNS were observed by inverted microscope. MTT assay was used to detect the inhibitory effect of SNS on cell proliferation. Fluorescence staining and flow cytometry were employed to analyze the effect of SNS on apoptosis of HepG2 cells. Rho123 (Rhodamine 123) staining method was performed to detect the changes of mitochondrial membrane potential, and Western blot was used to evaluate the expression of proteins related to apoptosis. The number of hepatocellular carcinoma HepG2 cells were significantly decreased (<0.01) and cells showed typical apoptotic cell morphology after treated with serum contained SNS. The inhibition rate of HepG2 cells was increased with the increase of concentration of serum contained SNS. The number of cells in G1 phase was significantly increased, while G2 phase was decreased after treated with serum contained SNS(<0.05).The apoptosis rate and mitochondrial membrane potential of HepG2 cells were significantly increased and decreased after treated with serum contained SNS(<0.05). The expression levels of Bax, caspase-3,-9 and cyt-c were significantly increased, while the expression of bcl-2 was decreased in HepG2 cells treated with serum contained SNS(<0.05). Sini San prescription can inhibit the proliferation of HepG2 cells and induce apoptosis by mitochondrial pathway.
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http://dx.doi.org/10.12047/j.cjap.5839.2020.104DOI Listing
September 2020

Initiation of Acupoint Molecular Mechanisms for Manual Acupuncture Analgesia-Nuclear Factor κB Signaling Pathway.

Chin J Integr Med 2020 Nov 2. Epub 2020 Nov 2.

School of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, China.

Objective: To identify the prominent molecular signaling in acupoints and explore their roles in initiating the analgesia effect of manual acupuncture (MA).

Method: A three-step study was conducted, the experiment 1 was a genome-wide analysis of the tissue at acupoint Zusanli (ST 36), including 12 Wistar rats which were divided into control, control+MA1, and control+MA7 groups. In the experiment 2, the paw withdrawal latency (PWL), immunohistochemistry and Western blot analysis of phospho-nuclear factor kappa B (NFκB) p65 (p-p65), phospho-NFκB p50 (p-p50) at ST 36 were performed on rats of saline, saline+MA, and complete Freund's adjuvant (CFA)+MA groups (n=6). In experiment 3, 24 rats were divided into saline+DMSO, CFA+DMSO, CFA+DMSO+MA, and CFA+BAY 11-7082+MA groups, the PWL and immunofluorescence assay of NFκB p65 at ST 36 was conducted.

Result: (1) The gene: inhibitor of NFκB (Nfkbia), interleukin-1β (Il1b), interleukin-6 (Il6), chemokine c-x-c motif ligand 1 (Cxcl1), monocyte chemoattractant protein-1 (MCP-1/Ccl2) expressions in the control+MA7 group were significantly increased (P<0.05 or P<0.01), and the expression of NFκB p65 (Rela), NFκB p50 (Nfkb1) were increased in the control+MA7 group (P<0.05). (2) CFA+MA groups showed increased PWL from day 1 to 7 (P<0.01 vs. CFA), and the Western blot results were consistent with immunohistochemistry, the expression of NFκB p-p65 and NFκB p-p50 were significantly increased in the MA-related groups compared with control and CFA groups (P<0.05). (3) Compared with the CFA+DMSO+MA group, the PWL of the CFA+ BAY 11-7082+MA group decreased significantly and continued until day 5 and 7 (P<0.05 and P<0.01, respectively), and the NFκB p65 expression of CFA+BAY 11-7082+MA was significantly reduced compared with CFA+DMSO+MA (P<0.01).

Conclusion: Local NFκB signaling cascade in acupoint caused by MA is an important step in initiating the analgesic effect, which would provide new evidence for the initiation of MA-effect and improve the understanding of the scientific basis of acupuncture analgesia.
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http://dx.doi.org/10.1007/s11655-020-3435-6DOI Listing
November 2020

Deficiency of Tfh Cells and Germinal Center in Deceased COVID-19 Patients.

Curr Med Sci 2020 Aug 29;40(4):618-624. Epub 2020 Aug 29.

Institute of Pathology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

The COVID-19 pandemic caused by SARS-CoV2 is characterized by a remarkable variation in clinical severity ranging from a mild illness to a fatal multi-organ disease. Understanding the dysregulated human immune responses in the fatal subjects is critical for management of COVID-19 patients and the pandemic. In this study, we examined the immune cell compositions in the lung tissues and hilar lymph nodes using immunohistochemistry on 6 deceased COVID-19 patients and 4 focal organizing pneumonia (FOP) patients who underwent lung surgery and served as controls. We found a dominant presence of macrophages and a general deficiency of T cells and B cells in the lung tissues from deceased COVID-19 patients. In contrast to the FOP patients, Tfh cells and germinal center formation were largely absent in the draining hilar lymph nodes in the deceased COVID-19 patients. This was correlated with reduced IgM and IgG levels compared to convalescent COVID-19 patients. In summary, our data highlight a defect of germinal center structure in deceased COVID-19 patients leading to an impaired humoral immunity. Understanding the mechanisms of this deficiency will be one of the key points for the management of this epidemic.
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http://dx.doi.org/10.1007/s11596-020-2225-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412778PMC
August 2020

Clinical characteristics and outcomes of autoimmune encephalitis patients associated with anti-glutamate decarboxylase antibody 65.

Clin Neurol Neurosurg 2020 09 10;196:106082. Epub 2020 Jul 10.

Department of Neurology, The Nanjing Brain Hospital Affiliated Nanjing Medical University, 210029, Nanjing, China.

Objective: This study was to investigate the clinical characteristics and prognosis of autoimmune encephalitis (AE) associated with anti-Glutamic Acid Decarboxylase 65 (GAD65).

Patients And Methods: From Jan 2016 to Aug 2018, three patients diagnosed as anti-GAD65 AE in our hospital were retrospectively analyzed for their general demographic characteristics, clinical presentation, cerebrospinal fluid (CSF) cytology, brain imaging, EEG, treatment and prognosis.

Results: We found that Anti-GAD65 AE may be more common in young and middle-aged women, with initial presentations of refractory status epilepticus or cognitive decline following the disease progresses, but with less psychiatric symptoms than other types of AEs. The abnormal signals of MRI may be obvious in bilateral frontal, temporal lobe and hippocampus.

Conclusion: The production of anti-GAD65 may have a certain latency period, and it is usually negative at the onset stage. More studies need to be performed on larger populations and further understand the potential mechanisms underlying the above clinical features of anti-GAD65 AE.
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http://dx.doi.org/10.1016/j.clineuro.2020.106082DOI Listing
September 2020

Direct Visualization of Hydrogen-Transfer Intermediate States by Scanning Tunneling Microscopy.

J Phys Chem Lett 2020 Feb 10;11(4):1536-1541. Epub 2020 Feb 10.

Institute of Physics and University of the Chinese Academy of Sciences, Chinese Academy of Sciences , Beijing 100190 , China.

Hydrogen atoms bonded within molecular cavities often undergo tunneling or thermal-transfer processes that play major roles in diverse physical phenomena. Such transfers may or may not entail intermediate states. The existence of such fleeting states is typically determined by indirect means, while their direct visualization has not been achieved, largely because their concentrations under equilibrium conditions are negligible. Here we use density-functional-theory calculations and scanning-tunneling-microscopy (STM) image simulations to predict that, under specially designed nonequilibrium conditions of voltage-enhanced high transfer rates, the -intermediate of the two-hydrogen transfer process in metal-free naphthalocyanine molecules adsorbed on Ag(111) surfaces would be visualizable in a composite image of double-C morphology. As guided by the theoretical predictions, at adjusted scanning temperature and bias, STM experiments achieve a direct visualization of the -intermediate. This work demonstrates a practical way to directly visualize elusive intermediates, which enhances understanding of the quantum dynamics of hydrogen atoms.
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http://dx.doi.org/10.1021/acs.jpclett.0c00046DOI Listing
February 2020

Differential Diagnosis of Autoimmune Encephalitis from Infectious Lymphocytic Encephalitis by Analysing the Lymphocyte Subsets of Cerebrospinal Fluid.

Anal Cell Pathol (Amst) 2019 3;2019:9684175. Epub 2019 Dec 3.

Department of Neurology, The Affiliated Nanjing Brain Hospital of Nanjing Medical University, 210029 Nanjing, China.

This study is aimed at investigating the lymphocyte subsets of cerebrospinal fluid (CSF) to provide possible differential diagnostic values and better understand the pathophysiological mechanism underlying autoimmune encephalitis (AE) and infectious lymphocytic encephalitis. A series of CD markers, including CD3/4/8/20 representing different types and developmental stages of lymphocytes, were used to count the corresponding subpopulations of CSF from clinical and laboratory confirmed cases of anti-N-methyl-D-aspartate receptor AE (NMDAR-AE), herpes simplex virus encephalitis (HSVE), and tuberculous meningitis (TBM). The percentages of lymphocytes observed and the CD4 : CD8 ratios were compared between the three groups. There were no significant differences of the percentage of total lymphocytes, CD3 cells, and CD4 cells of CSF among each group. However, there were strongly statistical differences of the CD4 : CD8 ratio in CSF of each group with 0.6 : 1 in NMDAR-AE, 0.9 : 1 in HSVE, and 3.2 : 1 in TBM. The percentage of CD20 B lymphocytes in NMDAR-AE was statistically higher than that of other groups. The distinct percentages of lymphocyte subpopulations of CSF appeared to be characteristic and could potentially serve as diagnostic indicators. Further verification and research will be necessary to clarify the significance and nature of CD4 : CD8 ratios and B lymphocytes in CSF between AE and the infectious lymphocytic encephalitis.
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http://dx.doi.org/10.1155/2019/9684175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914943PMC
May 2020

Illumina Sequencing Reveals Candidate Genes of Carotenoid Metabolism in Three Pummelo Cultivars () with Different Pulp Color.

Int J Mol Sci 2019 May 7;20(9). Epub 2019 May 7.

Fruit Research Institute, Fujian Academy of Agricultural Sciences, Fuzhou 350013, China.

Pummelo () is one of important fruit trees, which belongs to species. The fruits of different pummelo cultivars have different colors and differ in the contents of carotenoid. Our results clearly showed that 'Huangjinmiyou' (HJMY) has the highest content of β-carotene, followed by 'Hongroumiyou' (HRMY) and 'Guanximiyou' (GXMY). Lycopene is dominantly accumulated in HRMY. However, the molecular mechanism underlying the carotenoid accumulation in pummelo flesh is not fully understood. In this study, we used the RNA-Seq technique to investigate the candidate genes of carotenoid metabolism in the flesh of pummelo cv. GXMY and its mutants HRMY and HJMY in three development periods of fruit. After data assembly and bioinformatic analysis, a total of 357 genes involved in biosynthesis of secondary metabolites were isolated, of which 12 differentially expressed genes (DEGs) are involved in carotenoid biosynthesis. Among these 12 DEGs, phytoene synthase (), lycopene β-cyclase (), lycopene Ɛ-cyclase (), carotenoid cleavage dioxygenases (), 9-cis-epoxycarotenoid dioxygenase (), aldehyde oxidase 3 (), and ABA 8'-hydroxylases () are the most distinct DEGs in three pummelo cultivars. The co-expression analysis revealed that the expression patterns of several transcription factors such as , , , and are highly correlated with DEGs, which are involved in carotenoid biosynthesis. In addition, the expression patterns of 22 DEGs were validated by real-time quantitative PCR (RT-qPCR) and the results are highly concordant with the RNA-Seq results. Our results provide a global vision of transcriptomic profile among three pummelo cultivars with different pulp colors. These results would be beneficial to further study the molecular mechanism of carotenoid accumulation in pummelo flesh and help the breeding of citrus with high carotenoid content.
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http://dx.doi.org/10.3390/ijms20092246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539737PMC
May 2019

[Analysis of epidemiological characteristics of drug induced liver injury associated with Baixianpi Preparations].

Zhongguo Zhong Yao Za Zhi 2019 Mar;44(5):1048-1052

Department of Pharmacy,Dongzhimen Hospital Afliated to Beijing University of Traditional Chinese Medicine Beijing 100700,China.

A retrospective study was performed in drug-induced liver injury(DILI) cases associated with Dictamni Cortex(Baixianpi,BXP) Preparations,which were treated at grade Ⅲ class A liver disease hospitals from 2008 to 2016 and spontaneously reported for adverse reactions between 2012 and 2016 at HILI Cloud(hilicloud.net). The results showed 25 DLII cases associated with BXP Preparations treated at grade Ⅲ class A liver disease hospitals during the 9 years,including only 14 cases in line with the clinical diagnostic criteria of Guidelines for the Diagnosis and Treatment of Herb-Induced Liver Injury. And 74 DILI cases associated with BXP Preparations spontaneously reports adverse reactions,and 18. 92% of them had unreasonable medication,including polypharmacy(21. 43%),overdose(28. 57%) and repeated dosage(50%). And 47 DILI cases used BXP Preparations to treat psoriasis and vitiligo(a total of59. 57%). The time range of taking BXP Preparations until liver injury occurred was 1-366 d,with the median of 18 d. The dose of BXP Preparations was estimated to be 0. 09-12 g·d-1. And the cumulative dosage of taking drugs until liver injury occurred was 1. 1-336 g. Obvious associations with time-toxicity as well as quantity-toxicity could not be found based on the wide range of time-toxicity relations and quantity-toxicity relations. On the basis of the study,we found that DILI cases associated with BXP Preparations commonly occurred in patients with immune diseases,such as psoriasis and vitiligo,indicating specific individual differences. The results suggested that DILI cases associated with BXP Preparations would be correlated with the property of idiosyncratic drug-induced liver injury. In conclusion,the risk of liver injury clinically caused by BXP Preparations should be paid more attention,and the studies on the mechanism of idiosyncratic drug-induced liver injury must be enhanced,and those on risk factors,like irrational drug use,should be strengthened. Moreover,the evaluation of the risk-to-benefit ratio is supposed to be performed for the sake of improving the risk prevention and control standards for BXP preparations,and ensuring safe and rational clinical application of BXP Preparations.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20181217.001DOI Listing
March 2019

In Vitro Evaluation of Hemoperfusion for Chlorpyrifos Poisoning.

Biomed Environ Sci 2018 Dec;31(12):922-926

Shenzhen Prevention and Treatment Center for Occupational Disease, Shenzhen 518020, Guangdong, China.

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http://dx.doi.org/10.3967/bes2018.126DOI Listing
December 2018

SUR2B/Kir6.1 channel openers correct endothelial dysfunction in chronic heart failure via the miR-1-3p/ET-1 pathway.

Biomed Pharmacother 2019 Feb 5;110:431-439. Epub 2018 Dec 5.

The 307 Military Hospital, Academy of Military Medical Sciences, Beijing, 100850, China; Cardiovascular Drug Research Center, Thadweik Academy of Medicine, Beijing, 100039, China. Electronic address:

The SUR2B/Kir6.1 channel openers iptakalim and natakalim reverse cardiac remodeling and ameliorate endothelial dysfunction by re-establishing the balance between the nitric oxide and endothelin systems. In this study, we investigated the microRNAs (miRs) involved in the molecular mechanisms of SUR2B/Kir6.1 channel opening in chronic heart failure. Both iptakalim and natakalim significantly upregulated the expression of miR-1-3p, suggesting that this miR is closely associated with the therapeutic effects against chronic heart failure. Bioinformatic analysis showed that many of the 183 target genes of miR-1-3p are involved in cardiovascular diseases, suggesting that miR-1-3p plays a vital role in such diseases and vascular remodeling. Target gene prediction showed that miR-1-3p combines with the 3' untranslated region (UTR) of endothelin-1 (ET-1) mRNA. Iptakalim and natakalim upregulated miR-1-3p expression and downregulated ET-1 mRNA expression in vitro. The dual luciferase assay confirmed that there is a complementary binding sequence between miR-1-3p and the 3' UTR 158-165 sequence of ET-1 mRNA. To verify the effect of miR-1-3p on ET-1, lentiviral vectors overexpressing or inhibiting miR-1-3p were constructed for the transduction of rat primary cardiac microvascular endothelial cells. The results showed that natakalim enhanced the miR-1-3p level. miR-1-3p overexpression downregulated the expression of ET-1, whereas miR-1-3p inhibition had the opposite effect. Therefore, we verified that SUR2B/Kir6.1 channel openers could correct endothelial imbalance and ameliorate chronic heart failure through the miR-1-3p/ET-1 pathway in endothelial cells. Our study provides comprehensive insights into the molecular mechanisms behind the SUR2B/Kir6.1 channel's activity against chronic heart failure.
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http://dx.doi.org/10.1016/j.biopha.2018.11.135DOI Listing
February 2019

Predictors of poor outcomes in 488 patients with herb-induced liver injury.

Turk J Gastroenterol 2019 01;30(1):47-58

Institute of Industrial, Environmental and Social Medicine, Goethe University School of Medicine, Frankfurt, Germany.

Background/aims: Herb-induced liver injury (HILI) can lead to chronic liver injury, liver transplantation, or even death. This study aimed to identify the predictors of poor HILI outcomes, especially chronic HILI.

Materials And Methods: Clinical data of 488 patients with HILI were retrospectively analyzed from a Chinese center between January 2010 and January 2014. Logistic regression and C-statistic were used to identify risk factors and prognostic models for HILI outcomes.

Results: In all patients, 69 (14.1%) developed chronic HILI, and 20 (4.1%) died due to liver injury or underwent liver transplantation. To predict the fatal HILI prognosis, the model for end-stage liver disease (MELD) with a C-statistic of 0.981 (95%CI 0.968-0.995) was better than Hy's law (C-statistic 0.569; 95%CI 0.449-0.689). The latency, course of peak alanine aminotransferase decreasing >50% after discontinuation of herb application, peak triglyceride value, and platelet count at liver injury onset were identified as independent risk factors for chronicity with the adjusted odds ratios of 1.268 (95% confidence interval [CI] 1.034-1.554), 2.303 (95%CI 1.588-3.340), 0.580 (95%CI 0.343-0.978), and 0.183 (95%CI 0.091-0.368), respectively. A prognostic model for chronic HILI based on these four factors yielded the best prediction with a C-statistic of 0.812 (95%CI 0.755-0.868), compared with MELD (C-statistic 0.506; 95%CI 0.431-0.581) and Hy's law (C-statistic 0.418; 95%CI 0.343-0.492).

Conclusion: Model for end-stage liver disease can be used to predict the fatal prognosis of HILI. A long latency, slow recovery, and low triglyceride value and platelet counts are important determinants for chronic HILI.
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http://dx.doi.org/10.5152/tjg.2018.17847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6389292PMC
January 2019

Design Rules for Self-Assembly of 2D Nanocrystal/Metal-Organic Framework Superstructures.

Angew Chem Int Ed Engl 2018 Oct 11;57(40):13172-13176. Epub 2018 Sep 11.

The Molecular Foundry, Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA, 94720, USA.

We demonstrate the guiding principles behind simple two dimensional self-assembly of MOF nanoparticles (NPs) and oleic acid capped iron oxide (Fe O ) NCs into a uniform two-dimensional bi-layered superstructure. This self-assembly process can be controlled by the energy of ligand-ligand interactions between surface ligands on Fe O NCs and Zr O (OH) (fumarate) MOF NPs. Scanning transmission electron microscopy (TEM)/energy-dispersive X-ray spectroscopy and TEM tomography confirm the hierarchical co-assembly of Fe O NCs with MOF NPs as ligand energies are manipulated to promote facile diffusion of the smaller NCs. First-principles calculations and event-driven molecular dynamics simulations indicate that the observed patterns are dictated by combination of ligand-surface and ligand-ligand interactions. This study opens a new avenue for design and self-assembly of MOFs and NCs into high surface area assemblies, mimicking the structure of supported catalyst architectures, and provides a thorough fundamental understanding of the self-assembly process, which could be a guide for designing functional materials with desired structure.
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http://dx.doi.org/10.1002/anie.201807776DOI Listing
October 2018

Dynamic changes in the immunological characteristics of T lymphocytes in surviving patients with severe fever with thrombocytopenia syndrome (SFTS).

Int J Infect Dis 2018 May 14;70:72-80. Epub 2018 Mar 14.

Department of Infectious Diseases, Institute of Infection and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China. Electronic address:

Objective: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease with high mortality. T cell deficiency has recently been described, but the changes in T cell functionality during acute SFTS virus (SFTSV) infection and the mechanisms leading to T lymphocyte death remain largely unknown. This study was conducted to evaluate T cell functionality and the expression of apoptotic/proliferation and activation/inhibition markers during acute SFTSV infection.

Methods: Twenty-eight surviving SFTS patients were sequentially sampled during their entire hospital stay. SFTSV RNA copies were investigated using real-time RT-PCR. The expression levels of apoptotic markers (annexin V and CD95) and proliferation and activation markers (Ki-67, HLA-DR, and CD25) and the expression levels of programmed cell death-1 (PD-1), interferon gamma (IFN-γ), and granzyme B in T cells were evaluated by flow cytometry for the SFTS patients.

Results: In parallel with T cell depletion, higher annexin V and CD95 expression was observed in SFTS patients. Additionally, the expression levels of Ki-67, HLA-DR, CD25, and PD-1 and the levels of IFN-γ and granzyme B in T lymphocytes were markedly increased in the SFTS patients.

Conclusions: T cell proliferation, activation, and functional enhancement were apparent despite the observation of T cell apoptosis, suggesting that these processes are involved in the complex protective response to SFTSV infection.
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http://dx.doi.org/10.1016/j.ijid.2018.03.010DOI Listing
May 2018

Interatomic Spin Coupling in Manganese Clusters Registered on Graphene.

Phys Rev Lett 2017 Oct 27;119(17):176806. Epub 2017 Oct 27.

Institute of Physics and University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing 100190, China.

Different interatomic spin interactions in graphene-regulated Mn atomic clusters are investigated by low-temperature scanning tunneling microscopy and magnetic-field-dependent inelastic spin excitation spectroscopy. All dimers observed exhibit an antiferromagnetic (AFM) singlet ground state and spin transition from the singlet to triplet states, but their AFM coupling strength shows a unique dependence on their site registration on the graphene. Intriguing spin coupling can be found in the graphene-mediated Mn trimers, which manifest multilevel spin excitations. In combination with Heisenberg spin modeling and first-principles numerical simulation, an exclusive noncollinear spin configuration of the Mn trimer regulated by the graphene template can be determined, and our observed experimental exchange energies cannot be understood by a direct spin exchange mechanism, but suggest a nonlocal Ruderman-Kittel-Kasuya-Yosida indirect spin exchange mechanism through substrate modulation, which has not yet been achieved in graphene so far.
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http://dx.doi.org/10.1103/PhysRevLett.119.176806DOI Listing
October 2017

Prokaryotic expression of the extracellular domain of porcine programmed death 1 (PD-1) and its ligand PD-L1 and identification of the binding with peripheral blood mononuclear cells .

Can J Vet Res 2017 Apr;81(2):147-154

Biotechnology Research Center, School of Life Science and Technology, Xinxiang University, Xinxiang, Henan Province 453003, China (Zhu, Yue, He, Li, Yang, Han, Zhang, Sun, Guo, Wang); College of Veterinary and Animal Sciences, Henan Institute of Science and Technology, Xinxiang, Henan Province 453003, China (Yang, Han, Yin, Wang).

Programmed cell death protein 1 (PD-1), a costimulatory molecule of the CD28 family, has 2 ligands, PD-L1 and PD-L2. Our previous studies showed that the expression of PD-1 and PD-L1 is up-regulated during viral infection in pigs. Extensive studies have shown that blockade of the PD-1/PD-L1 pathways by anti-PD-L1 antibody or soluble PD-1 restores exhausted T-cells in humans and mice. In the present study the extracellular domains of PD-1 and PD-L1 were used to evaluate the binding of PD-1 and PD-L1 with peripheral blood mononuclear cells (PBMCs). We amplified the cDNA encoding the extracellular domains of PD-1 and PD-L1 to construct recombinant expression plasmids and obtain soluble recombinant proteins, which were then labeled with fluorescein isothiocyanate (FITC). The His-PD-1 and His-PD-L1 recombinant proteins were expressed in the form of inclusion bodies with a relative molecular weight of 33.0 and 45.0 kDa, respectively. We then prepared polyclonal antibodies against the proteins with a multi-antiserum titer of 1:102 400. Binding of the proteins with PBMCs was evaluated by flow cytometry. The fluorescence signals of His-PD-1-FITC and His-PD-L1-FITC were greater than those for the FITC control. These results suggest that the soluble recombinant proteins may be used to prepare monoclonal antibodies to block the PD-1/PD-L1 pathway.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370541PMC
April 2017

Pregnane X Receptor Not Nuclear Factor-kappa B Up-regulates P-glycoprotein Expression in the Brain of Chronic Epileptic Rats Induced by Kainic Acid.

Neurochem Res 2017 Aug 16;42(8):2167-2177. Epub 2017 Mar 16.

Department of Neurology, Nanjing Medical University, Affiliated Nanjing Brain Hospital, 210029, Nanjing, China.

Drug-resistance epilepsy (DRE) is attributed to the brain P-glycoprotein (P-gp) overexpression. We previously reported that nuclear factor-kappa B (NF-κB) played a critical role in regulating P-gp expression at the brain of the acute seizure rats. This study was extended further to investigate the interaction effect of NF-κB and pregnane X receptor (PXR) on P-gp expression at the brain of chronic epileptic rats treated with carbamazepine (CBZ). The chronic epileptic models were induced by the micro-injection of kainic acid (KA) into rats' hippocampus. Subsequently, the successful models were treated with different intervention agents of CBZ; PMA(a non-specific PXR activity inhibitor) or PDTC(a specific NF-κB activity inhibitor) respectively. The expression levels of P-gp and its encoded gene mdr1a/b were significantly up-regulated on the brain of KA-induced chronic epilepsy rats or the epilepsy rats treated with CBZ for 1 week, meanwhile with a high expression of PXR. The treatment of PMA dramatically reduced both PXR and P-gp expressions at the protein and mRNA levels in the chronic epilepsy brain. By compared to the epilepsy model group, the P-gp expression was not markedly attenuated by the inhibition of NF-κB activity with PDTC treatment, nevertheless with a decrease of NF-κB expression in this intervention group. Higher levels of proinflammatory cytokines(IL-1β, IL-6, TNF-α) were found both in the brain tissue and the serum in the epilepsy rats of each group. There was a declined trend of the pro-inflammatory cytokines expression of the PDTC treatment group but with no statistical significance. This study demonstrates for the first time that P-gp up-regulation is due to increase PXR expression in the chronic phase of epilepsy, differently from that NF-κB signaling may induce the P-gp expression in the acute seizure phase. Our results offer insights into the mechanism underlying the development of DRE using or not using CBZ treatment.
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http://dx.doi.org/10.1007/s11064-017-2224-xDOI Listing
August 2017

Sequence of Silicon Monolayer Structures Grown on a Ru Surface: from a Herringbone Structure to Silicene.

Nano Lett 2017 02 23;17(2):1161-1166. Epub 2017 Jan 23.

Institute of Physics, Beijing Key Laboratory for Nanomaterials and Nanodevices, Chinese Academy of Sciences , Beijing 100190, P. R. China.

Silicon-based two-dimensional (2D) materials are uniquely suited for integration in Si-based electronics. Silicene, an analogue of graphene, was recently fabricated on several substrates and was used to make a field-effect transistor. Here, we report that when Ru(0001) is used as a substrate, a range of distinct monolayer silicon structures forms, evolving toward silicene with increasing Si coverage. Low Si coverage produces a herringbone structure, a hitherto undiscovered 2D phase of silicon. With increasing Si coverage, herringbone elbows evolve into silicene-like honeycomb stripes under tension, resulting in a herringbone-honeycomb 2D superlattice. At even higher coverage, the honeycomb stripes widen and merge coherently to form silicene in registry with the substrate. Scanning tunneling microscopy (STM) was used to image the structures. The structural stability and electronic properties of the Si 2D structures, the interaction between the Si 2D structures and the Ru substrate, and the evolution of the distinct monolayer Si structures were elucidated by density functional theory (DFT) calculations. This work paves the way for further investigations of monolayer Si structures, the corresponding growth mechanisms, and possible functionalization by impurities.
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http://dx.doi.org/10.1021/acs.nanolett.6b04804DOI Listing
February 2017

Pharmacological evidence: a new therapeutic approach to the treatment of chronic heart failure through SUR2B/Kir6.1 channel in endothelial cells.

Acta Pharmacol Sin 2017 Jan 28;38(1):41-55. Epub 2016 Nov 28.

Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China.

Both iptakalim (Ipt) and natakalim (Nat) activate the SUR2B/Kir6.1 channel, an ATP-sensitive potassium channel (KATP) subtype, with high selectivity. In this study we investigated the therapeutic effects of Ipt and Nat against isoproterenol-induced chronic heart failure (ISO-CHF) in rats, and demonstrated a new therapeutic approach to the treatment of CHF through activation of the SUR2B/Kir6.1 channel in endothelial cells. In ISO-CHF rats, oral administration of Nat (1, 3, 9 mg·kg·d) or Ipt (3 mg·kg·d) for 60 days significantly improved cardiac dysfunction, reversed cardiac remodeling, significantly attenuated the pathological increases in BNP levels, and improved endothelial dysfunction by adjusting the balance between endothelin and NO systems. The therapeutic effects of Nat were prevented by the selective KATP blocker glibenclamine (Gli, 50 mg·kg·d), confirming that these effects were mediated through activation of the SUR2B/Kir6.1 channel in endothelial cells. The molecular mechanisms underlying the therapeutic effects of Nat were further addressed using proteomic methods. We identified 724 proteins in the plasma of ISO-CHF rats; 55 proteins were related to Nat. These differentially expressed proteins were mainly involved in single-organism processes and the regulation of biological quality relative to CHF, including proteasome (Psm) and ATP protein clusters. We screened out PRKAR2β, GAS6/eNOS/NO and NO/PKG/VASP pathways involved in the amelioration of CHF among the 24 enriched pathways. We further confirmed 6 protein candidates, including PRKAR2β, GAS6 and VASP, which were involved in the endothelial mechanisms, and ATP, TIMP3 and AGT, which contributed to its cardiovascular actions. This study demonstrates a new pharmacological approach to the treatment of CHF through activation of the SUR2B/Kir6.1 channel in endothelial cells, and that the eNOS/VASP pathways are involved in its signaling mechanisms.
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http://dx.doi.org/10.1038/aps.2016.118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220542PMC
January 2017

[Construction of T vectors based on Xcm I recognition site and optimization of PCR fragments for ligation].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2016 Jan;32(1):46-50

Objective: To construct T vectors based on Xcm I recognition site and optimize the PCR fragments for its ligation.

Methods: We firstly cloned the human histone H4 cDNA containing one Xcm I recognition site at both its 5' and 3' end into pCDNA 3.0 vector and then generated T vector with pCDNA 3.0 backbone by cutting the recombinant plasmid with Xcm I. To increase the ligation efficiency, the primers were firstly phosphorylated before DNA fragments amplification and then the PCR products were treated with Taq DNA polymerase and dATP after PCR amplification. Two DNA fragments with the length of 312 bp and 1 329 bp were ligated to it and the ligation mixture was transformed into E. coli DH5α competent cells and the positive rates of the transformants were evaluated by PCR and DNA agarose gel electrophoresis.

Results: Our results showed that the T vector produced by our method could ligate to the target DNA fragments with high efficiency. Besides, the phosphorylation state of the primers used for PCR amplification is also an important factor determining the cloning efficiency. What's more, as for longer DNA fragments, retreatment with Taq DNA polymerase and dATP after PCR amplification and purification could improve the ligation efficiency significantly.

Conclusion: Our protocol may overcome the dependence on blue/white screening to get positive clones and provide a potent way to generate T vectors and ligate them to the target PCR fragment.
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January 2016

Synergisms of cardiovascular effects between iptakalim and amlodipine, hydrochlorothiazide or propranolol in anesthetized rats.

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2015 Nov;31(6):532-40

The primary object of this fundamental research was to survey the synergistic cardiovascular effects of iptakalim, a novel ATP-sensitive potassium channel (K(ATP)) opener, and clinical first-line antihypertensive drugs, such as calcium antagonists, thiazide diuretics and β receptor blockers by a 2 x 2 factorial-design experiment. It would provide a theoretical basis for the development of new combined antihypertensive therapy program after iptakalim is applied to the clinic. Amlodipine besylate, hydrochlorothiazide and propranolol were chosen as clinical first-line antihypertensive drugs. Blood pressure, heart rate (HR) and cardiac functions were observed in anesthetized normal rats by an eight-channel physiological recorder. The results showed that iptakalim monotherapy in a low dose could produce significant antihypertensive effect. There was no interaction between iptakalim and amlodipine on the maximal changes of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MABP), the left ventricular systolic pressure (LVSP), and the left ventricular end-diastolic pressure (LVEDP) (P > 0.05). However, the effects of combination iptakalim/amlodipine on the maximal changes of SBP, DBP, MABP, LVSP and LVEDP were more obvious than those of iptakalim or amlodipine monotherapy. And there was strong positive interaction between iptakalim and amlodipine on the maximal changes of HR (P>0.05). According to the maximal changes of DBP, MABP, LVSP and LVEDP (P < 0.05) of combination iptakalim with hydrochlorothiazide, there was strong positive interaction between them. But there was no interaction between iptakalim and hydrochlorothiazide on the maximal drop of SBP and HR (P > 0.05). According to the maximal drops of DBP, MABP of combination iptakalim with propranolol, there was strong positive interaction between them (P < 0.05). But there was no interaction between iptakalim and propranolol on the maximal changes of SBP, LVSP, LVEDP and HR (P > 0.05). In conclusion, it was the first time to study the effects of amlodipine, hydrochlorothiazide or propranolol, which had different mechanisms of action from iptakalim, on cardiovascular effects of iptakalim in anesthetized normal rats. This study proved that the combination of iptakalim with hydrochlorothiazide or propranolol respectively had significant synergism on lowering blood pressure, while the combination of iptakalim/amlodipine had additive action on lowering blood pressure. Meanwhile the antihypertensive effect was explicit, stable and long-lasting. Iptakalim thus appears suitable for the clinical treatment of hypertensive people who need two or more kinds of antihypertensive agents.
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November 2015

MELAS and Kearns-Sayre overlap syndrome due to the mtDNA m. A3243G mutation and large-scale mtDNA deletions.

eNeurologicalSci 2016 Sep 25;4:15-18. Epub 2016 Apr 25.

Nanjing Medical University, Affiliated Nanjing Brain Hospital, Department of Neurology, 210029 Nanjing, China.

This paper reported an unusual manifestation of a 19-year-old Chinese male patient presented with a complex phenotype of mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) syndrome and Kearns-Sayre syndrome (KSS). He was admitted to our hospital with the chief complaint of "acute fever, headache and slow reaction for 21 days". He was initially misdiagnosed as "viral encephalitis". This Chinese man with significant past medical history of intolerating fatigue presented paroxysmal neurobehavioral attacks that started about 10 years ago. During this span, 3 or 4 attack clusters were described during which several attacks occurred over a few days. The further examination found that the hallmark signs of this patient included progressive myoclonus epilepsy, cerebellar ataxia, hearing loss, myopathic weakness, ophthalmoparesis, pigmentary retinopathy and bifascicular heart block (Wolff-Parkinson-White syndrome). By young age the disease progression is characterized by the addition of migraine, vomiting, and stroke-like episodes, symptoms of MELAS expression, which indicated completion of the MELAS/KSS overlap syndrome. The m. A3243G mitochondrial DNA mutation and single large-scale mtDNA deletions were found in this patient. This mutation has been reported with MELAS, KSS, myopathy, deafness and mental disorder with cognitive impairment. This is the first description with a MELAS/KSS syndrome in Chinese.
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http://dx.doi.org/10.1016/j.ensci.2016.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803102PMC
September 2016

[Molecular of pulmonary arterioles relaxation through SUR2B/Kir6.1 channel opening].

Zhongguo Ying Yong Sheng Li Xue Za Zhi 2016 Mar;32(3):238-241

Cardiovascular Drug Research Center, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850.

Objective: To study the dilatation characteristics of ATP-sensitive potassium channel (K) SUR2B/Kir6.1 subtype opener iptakalim (Ipt) in pulmonary arterioles, and to explore its possible mechanism.

Methods: Vessels pressure-diameter monitoring perfusion technique was used to observe the dilatation effects of Ipt in rats fourth pulmonary arterioles (=6~8). After the pulmonary arterioles were pre-treated with removing endothelium or pre-incubated with K channel blocker glibenclamide (Gli), cyclo-oxygenase (COX) inhibitor indomethacin (Indo) and nitric oxide synthase (NOS) inhibitor L-Nω-Nitro-arginine methyl ester(L-NAME), the dilatation effects of Ipt were observed.

Results: Pulmonary arterioles could be relaxed by Ipt, the maximal relaxation rate was (60.53±2.08)%. Compaired with control group, the effects of Ipt in endothelium denuded arterioles were significantly decreased, the maximal relaxation rate was (9.47±1.56)% (<0.01). The maximal relaxation rate were decreased to(17.49±1.47)%,(37.00±3.88)% and(24.91±2.30)% respectively after Gli,Indo,L-NAME were pre-incubated (<0.01).

Conclusions: Pulmonary arterioles can be relaxed by Ipt. The selective activation of K SUR2B/Kir6.1 subtype by Ipt was involved in its mechanisms. The endothelium-dependently dilatation of Ipt was related to nitric oxide (NO) and prostacyclin (PGI) released by endothelial cells.
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http://dx.doi.org/10.13459/j.cnki.cjap.2016.03.013DOI Listing
March 2016

Cancer-associated fibroblasts promote the progression of endometrial cancer via the SDF-1/CXCR4 axis.

J Hematol Oncol 2016 Feb 6;9. Epub 2016 Feb 6.

Department of Gynecology and Obstetrics, Tianjin Medical University General Hospital, NO 154, Anshan Road, He Ping District, Tianjin, 300052, China.

Background: Cancer-associated fibroblasts (CAFs) are believed to play an essential role in cancer initiation and development. However, little research has been undertaken to evaluate the role of CAFs in endometrial cancer (EC) progression. We aim to detect the functional contributions of CAFs to promote progression of EC.

Methods: Stromal fibroblasts were isolated from endometrioid adenocarcinomas and normal endometrial tissues. The conditioned media of cultured CAFs and normal fibroblasts (NFs) were collected to detect the level of stromal cell-derived factor-1alpha (SDF-1α), macrophage chemoattractant protein-1 (MCP-1), migration inhibitory factor (MIF), colony stimulating factor-1 (CSF-1), and interleukin-1 (IL-1) by ELISA. The CAFs or NFs were cocultured with EC cell lines to determine the proliferation, migration, and invasion by MTT assays and transwell chambers. Xenograft models were used to observe tumor growth. Matrix metalloproteinases (MMP)-2 and MMP-9 activity was evaluated by zymography. AMD3100 (a chemokine receptor 4 (CXCR4) antagonist) was used to block the SDF-1/CXCR4 axis. Neutralizing antibodies were used to detect PI3K/Akt and MAPK/Erk pathways by western blotting. SDF-1α and CXCR4 expressions were analyzed in xenotransplanted tumors and 348 cases by immunohistochemistry.

Results: CAFs promoted proliferation, migration, and invasion as well as in vivo tumorigenesis of admixed EC cells significantly more than NFs by secreting SDF-1α. These effects were significantly inhibited by AMD3100. CAFs promoted EC progression via the SDF-1α/CXCR4 axis to activate the PI3K/Akt and MAPK/Erk signalings in a paracrine-dependent manner or increase MMP-2 and MMP-9 secretion in an autocrine-dependent manner. SDF-1α and CXCR4 expression upregulation accompanied clinical EC development and progression. High SDF-1α expression levels were associated with deep myometrial invasion, lymph node metastasis, and poor prognosis in EC.

Conclusions: Our data indicated that CAFs derived from EC tissues promoted EC progression via the SDF-1/CXCR4 axis in a paracrine- or autocrine-dependent manner. SDF-1α is a novel independent poor prognostic factor for EC patients' survival. Targeting the SDF-1/CXCR4 axis might provide a novel therapeutic strategy for EC treatment.
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http://dx.doi.org/10.1186/s13045-015-0231-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744391PMC
February 2016

Expression, purification, crystallization and crystallographic analysis of the N-terminal domain of translocated intimin receptor.

Acta Crystallogr F Struct Biol Commun 2016 Jan 1;72(Pt 1):49-52. Epub 2016 Jan 1.

Department of Cardiothoracic Surgery, The 306 Hospital, No. 9 Anxiang North Road, Chaoyang District, Beijing 100101, People's Republic of China.

Translocated intimin receptor (Tir) is an Escherichia coli-encoded protein that is transported into the host cell through a sophisticated bacterial type III secretion system (T3SS). Tir anchors the infected cell membrane twice using both its N- and C-termini from inside the host cytoplasm for signalling. It plays a key role in enterohemorrhagic Escherichia coli (EHEC) infection, attaching and effacing (A/E) lesions and intracellular signal transduction. Here, the overexpression, purification and crystallization of its N-terminal intracellular domain are reported. The crystal belonged to the orthorhombic space group I4122, with unit-cell parameters a = b = 59.79, c = 183.11 Å. The asymmetric unit contained one molecule, with a solvent content of 51% and a VM of 2.55 Å(3) Da(-1).
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http://dx.doi.org/10.1107/S2053230X15023274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708050PMC
January 2016