Publications by authors named "Li-Hua Sun"

80 Publications

Quantitative Dynamic Contrast-Enhanced Magnetic Resonance Imaging for the Analysis of Microvascular Permeability in Peritumor Brain Edema of Fibrous Meningiomas.

Eur Neurol 2021 27;84(5):361-367. Epub 2021 Jul 27.

Department of Radiology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China.

Introduction: This study aims to analyze the permeability of intra- and peri-meningiomas regions and compare the microvascular permeability between peritumoral brain edema (PTBE) and non-PTBE using DCE-MRI.

Methods: This was a retrospective of patients with meningioma who underwent surgery. The patients were grouped as PTBE and non-PTBE. The DCE-MRI quantitative parameters, including volume transfer constant (Ktrans), rate constant (Kep), extracellular volume (Ve), and mean plasma volume (Vp), obtained using the extended Tofts-Kety 2-compartment model. Logistic regression analysis was conducted to explore the risk factor of PTBE.

Results: Sixty-three patients, diagnosed as fibrous meningioma, were included in this study. They were 17 males and 46 females, aged from 32 to 88 years old. Kep and Vp were significantly lower in patients with PTBE compared with those without (Kep: 0.1852 ± 0.0369 vs. 0.5087 ± 0.1590, p = 0.010; Vp: 0.0090 ± 0.0020 vs. 0.0521 ± 0.0262, p = 0.007), while there were no differences regarding Ktrans and Ve (both p > 0.05). The multivariable analysis showed that tumor size ≥10 cm3 (OR = 4.457, 95% CI: 1.322-15.031, p = 0.016) and Vp (OR = 0.572, 95%CI: 0.333-0.981, p = 0.044) were independently associated with PTBE in patients with meningiomas.

Conclusion: DCE-magnetic resonance imaging·Meningioma·Blood vessel MRI can be used to quantify the microvascular permeability of PTBE in patients with meningioma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000516921DOI Listing
July 2021

Mutation and Copy Number Alterations Analysis of KIF23 in Glioma.

Front Genet 2021 3;12:646929. Epub 2021 May 3.

Department of Neurosurgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

In glioma, kinesin family member 23 (KIF23) is up-regulated and plays a vital role in oncogenesis. However, the mechanism underlying KIF23 overexpression in malignant glioma remains to be elucidated. This study aims to find potential causes of KIF23 high expression at genome level. To clarify this issue, we obtained point mutation and copy number alterations (CNAs) of KIF23 in 319 gliomas using whole-exome sequencing. Only two glioma samples with missense mutations in KIF23 coding region were identified, while 7 patients were detected with amplification of KIF23. Additional analysis showed that KIF23 amplification was significantly associated with higher expression of KIF23. Gene ontology analysis indicated that higher copy number of KIF23 was associated TNF-α signaling pathway and mitotic cell circle checkpoint, which probably caused by subsequent upregulated expression of KIF23. Moreover, pan-cancer analysis showed that gaining of copy number was significantly associated with higher expression of KIF23, consolidating our findings in glioma. Thus, it was deduced that elevated KIF23 expression in glioma tended to be caused by DNA copy number amplification, instead of mutation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fgene.2021.646929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129563PMC
May 2021

Pharmacodynamic elucidation of glutamate & dopamine in ketamine-induced anaesthesia.

Chem Biol Interact 2020 Aug 7;327:109164. Epub 2020 Jun 7.

Department of Anesthesiology, The Second Hospital of Jilin University, 218 Ziqiang Street, Changchun, 130041, China. Electronic address:

General anaesthetics are some of the most widely used and essential therapeutic agents. However, despite over a century of research, the molecular mechanisms of general anaesthesia in the central nervous system remain elusive. Ketamine (ketamine hydrochloride) has been approved for use in general anaesthesia either alone or in combination with other medications. It is a superb drug for use in short-term medical procedures that do not require skeletal muscle relaxation, and it has approval for the induction of general anaesthesia as a pre-anaesthetic to other general anaesthetic agents. However, Several questions remain unsolved, including the exact identification of the neural substrate of consciousness and its components, the pharmacodynamic interactions between anaesthetic agents, the mechanisms of cognitive alterations that follow an anaesthetic procedure, the identification of an eventual unitary mechanism of anaesthesia-induced alteration of consciousness, the relationship between network effects and the biochemical targets of anaesthetic agents, leading to difficulties in between-studies comparisons. Thus, the glutamate and dopamine systems play distinct roles in terms of neuronal signalling, yet both have proposed to contribute significantly to the pathophysiology of neuropsychiatric diseases. Imaging of the glutamate system and other aspects of research on the dopamine system have produced less consistent findings, potentially due to methodological limitations and the heterogeneity of the disorder. In this review, we discuss the neural circuits through which the two systems interact and how their disruption may cause psychotic symptoms. We also summarize from a molecular perspective of mechanisms of action of ketamine as general anaesthetics on ligand-gated ion channels mediated modulation of dopamine in the brain region.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cbi.2020.109164DOI Listing
August 2020

Exosomal miR-21 promotes proliferation, invasion and therapy resistance of colon adenocarcinoma cells through its target PDCD4.

Sci Rep 2020 05 19;10(1):8271. Epub 2020 May 19.

Department of Gastrointestinal Surgery, The Second Hospital of Jilin University, Changchun, China.

Exosomes contain cell-specific collections of bioactive materials including proteins, lipids, and RNAs that are transported to recipient cells to exert their impacts. MicroRNAs (miRNAs) can function as tumor suppressor or oncogenic genes and miR-21 is one of the most frequently up-regulated miRNAs in solid tumors including colon cancer. The aim of this study was to investigate the role of miR-21, secreted from exosomes, in proliferation and invasion of colon cancer, along with the mechanistic details. We used a variety of biochemical techniques including ultracentrifugation-based exosome purification, electron transmission microscopy, western blot and RT-qPCR to detect the expression levels of miR-21 in exosomes purified from culture media of human colonic adenocarcinoma cell lines. We then performed functional and mechanistic studies using three colon cancer cell lines HT29, T84 and LS174 as well as the normal colon epithelial cells CRL1831. miR-21 target PDCD4 was investigated for its role in mediating miR-21 effects. Expression of miR-21 was significantly up-regulated in exosomes of colon cancer cells, compared to the normal human colon epithelial cells. Treatment of colon cancer cells with isolated exosomes or miR-21 led to an increased expression of genes involved in cell proliferation, invasion and extracellular matrix formation. miR-21 targets PDCD4, TPM1 and PTEN were down-regulated by exosomes and silencing of PDCD4 mimicked miR-21 functional effects, even the induced resistance against 5-FU. Our study suggests that targeted inhibition of exosomes, particularly those carrying miR-21, may represent a novel approach for treatment of colorectal cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-65207-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7237414PMC
May 2020

Potential role of insulin on the pathogenesis of depression.

Cell Prolif 2020 May 13;53(5):e12806. Epub 2020 Apr 13.

Jilin Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University, Changchun, China.

The regulation of insulin on depression and depression-like behaviour has been widely reported. Insulin and activation of its receptor can promote learning and memory, affect the hypothalamic-pituitary-adrenal axis (HPA) balance, regulate the secretion of neurotrophic factors and neurotransmitters, interact with gastrointestinal microbiome, exert neuroprotective effects and have an impact on depression. However, the role of insulin on depression remains largely unclear. Therefore, in this review, we summarized the potential role of insulin on depression. It may provide new insight for clarifying role of insulin on the pathogenesis of depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cpr.12806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260070PMC
May 2020

MicroRNA-153 impairs presynaptic plasticity by blocking vesicle release following chronic brain hypoperfusion.

Cell Commun Signal 2020 04 6;18(1):57. Epub 2020 Apr 6.

Department of Pharmacology (The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), College of Pharmacy of Harbin Medical University, Harbin, 150086, Heilongjiang Province, China.

Background: Chronic brain hypoperfusion (CBH) is closely related to Alzheimer's disease (AD) and vascular dementia (VaD). Meanwhile, synaptic pathology plays a prominent role in the initial stage of AD and VaD. However, whether and how CBH impairs presynaptic plasticity is currently unclear.

Methods: In the present study, we performed a battery of techniques, including primary neuronal culture, patch clamp, stereotaxic injection of the lentiviral vectors, morris water maze (MWM), dual luciferase reporter assay, FM1-43 fluorescence dye evaluation, qRT-PCR and western blot, to investigate the regulatory effect of miR-153 on hippocampal synaptic vesicle release both in vivo and in vitro. The CBH rat model was generated by bilateral common carotid artery ligation (2VO).

Results: Compared to sham rats, 2VO rats presented decreased field excitatory postsynaptic potential (fEPSP) amplitude and increased paired-pulse ratios (PPRs) in the CA3-CA1 pathway, as well as significantly decreased expression of multiple vesicle fusion-related proteins, including SNAP-25, VAMP-2, syntaxin-1A and synaptotagmin-1, in the hippocampi. The levels of microRNA-153 (miR-153) were upregulated in the hippocampi of rats following 2VO surgery, and in the plasma of dementia patients. The expression of the vesicle fusion-related proteins affected by 2VO was inhibited by miR-153, elevated by miR-153 inhibition, and unchanged by binding-site mutation or miR masks. FM1-43 fluorescence images showed that miR-153 blunted vesicle exocytosis, but this effect was prevented by either 2'-O-methyl antisense oligoribonucleotides to miR-153 (AMO-153) and miR-masking of the miR-153 binding site in the 3' untranslated region (3'UTR) of the Snap25, Vamp2, Stx1a and Syt1 genes. Overexpression of miR-153 by lentiviral vector-mediated miR-153 mimics (lenti-pre-miR-153) decreased the fEPSP amplitude and elevated the PPR in the rat hippocampus, whereas overexpression of the antisense molecule (lenti-AMO-153) reversed these changes triggered by 2VO. Furthermore, lenti-AMO-153 attenuated the cognitive decline of 2VO rats.

Conclusions: Overexpression of miR-153 controls CBH-induced presynaptic vesicle release impairment by posttranscriptionally regulating the expression of four vesicle release-related proteins by targeting the 3'UTRs of the Stx1a, Snap25, Vamp2 and Syt1 genes. These findings identify a novel mechanism of presynaptic plasticity impairment during CBH, which may be a new drug target for prevention or treatment of AD and VaD. Video Abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12964-020-00551-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7137307PMC
April 2020

Modulation of steroid metabolism and xenobiotic biotransformation responses in zebrafish (Danio rerio) exposed to triadimefon.

Environ Pollut 2020 Jul 25;262:114145. Epub 2020 Feb 25.

China National Rice Research Institute, Hangzhou, 310006, PR China. Electronic address:

The widely used fungicide triadimefon (TDF) has been detected in aquatic environments, and appears to disrupt steroid homeostasis; however, the toxic effects on fish reproduction triggered by TDF via the key receptor signaling pathways remain largely unknown. The present study showed that TDF (0.069, 0.138, 0.690 mg/L) exposure not only caused disordered germ cell maturation, but also decreased spawned egg production. In order to better understand this reproductive inhibition, we investigated the effects of TDF based on quantitative PCR, Western blot and mass spectrometry methodology in zebrafish. Due to the preferential accumulation of TDF in the liver, a general pattern of up-regulation of genes involved in biotransformation pathway was observed. A significant increase in abcb4 expression appeared to be responsible for TDF excretion. TDF-induced receptors (AhR2 and PXR) changed many genes involved in steroid metabolism, and subsequent disruptions in steroid homeostasis, which might be the key biological pathway in TDF reproductive toxicity. However, due to the different metabolic demands, the transcript profiles involved in steroid metabolism in zebrafish exhibited a sex-specific expression pattern. For example, the increase in gene expression of ahr2 was accompanied by a reduction in the rate of E2 biosynthesis resulting from the diminished cyp19a1a expression, and in turn led to down-regulation of esr1 and vtg1 in the liver, supporting the anti-estrogenic effect of TDF in male fish. In contrast, the increase in E2 production was accompanied by an increase in Esr1 protein expression caused by TDF and paralleled the increase in ahrr1 expression, suggesting that TDF may induce estrogenic activity through AhR-ER interactions in females. In addition, over-induction of cyp3a65 activity mediated through pxr, which helped to accelerate the transformation from TDF to triadimenol in the liver, appeared to elevate T metabolite rate in females. The down-regulation of fshβ transcript in males further suggested that TDF might adversely affect normal gametogenesis and induce reproductive toxicity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.envpol.2020.114145DOI Listing
July 2020

Melatonin Reduces Androgen Production and Upregulates Heme Oxygenase-1 Expression in Granulosa Cells from PCOS Patients with Hypoestrogenia and Hyperandrogenia.

Oxid Med Cell Longev 2019 20;2019:8218650. Epub 2019 Oct 20.

CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, 100101 Beijing, China.

Background/aims: Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by abnormal hormone levels in peripheral blood and poor-quality oocytes. PCOS is a pathophysiological syndrome caused by chronic inflammation and oxidative stress. The aim of this study was to investigate the mechanism of melatonin regulation on androgen production and antioxidative damage in granulosa cells from PCOS patients with hypoestrogenia and hyperandrogenia.

Methods: Cumulus-oocyte complexes were collected from PCOS patients who had low levels of estrogen in follicular fluids.

Results: Melatonin triggered upregulation of cytochrome P450 family 19 subfamily A member 1 (CYP19A1) expression via the extracellular signal-regulated kinase pathway in luteinized granulosa cells. As a result, conversion of androgen to 17-estradiol was accelerated. We also found that melatonin significantly reduced the levels of inducible nitric oxide (NO) synthetase and NO in luteinized granulosa cells. Levels of transcripts encoding NF-E2-related factor-2 and its downstream target heme oxygenase-1 were also increased, leading to anti-inflammatory and antioxidant effects. We also found that melatonin could improve oocyte development potential.

Conclusion: Our preliminary results showed that melatonin had a positive impact on oocyte quality in PCOS patients with hypoestrogenia and hyperandrogenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2019/8218650DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854986PMC
April 2020

The Role of BDNF in the Neuroimmune Axis Regulation of Mood Disorders.

Front Neurol 2019 4;10:515. Epub 2019 Jun 4.

Department of Neurosurgery, First Hospital of Jilin University, Changchun, China.

The neuroimmune system plays a crucial role in the regulation of mood disorders. Moreover, recent studies show that brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is a key regulator in the neuroimmune axis. However, the potential mechanism of BDNF action in the neuroimmune axis' regulation of mood disorders remains unclear. Therefore, in this review, we focus on the recent progress of BDNF in influencing mood disorders, by participating in alterations of the neuroimmune axis. This may provide evidence for future studies in this field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fneur.2019.00515DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559010PMC
June 2019

Delivery of Local Anesthesia: Current Strategies, Safety, and Future Prospects.

Curr Drug Metab 2019 ;20(6):533-539

Department of Anesthesiology, The Second Hospital of Jilin University, Changchun 130041, China.

Background: The systemic administration of anesthesia is associated with severe and undesirable side effects such as sedation, vomiting, nausea, allergies, respiratory problems, and neutrophil dysfunction. With the increase in the procedures of limb surgery, cosmetics, facial, skin, and cancer reconstruction, the demand for local anesthesia has increased multifold during the last one decade. Therefore, novel, safe, and cost-effective methods are being developed to deliver local anesthetics by the surgeons.

Method: To prepare a comprehensive research report on anesthesia, we performed a structured literature search of bibliographic databases for peer-reviewed articles published recently. The studies of different articles were summarized and a deductive qualitative and quantitative data analysis was applied. Subsequently, a comprehensive summary of the analysis was used to frame this review article with ample examples.

Results: A thorough analysis of the reports suggested that there have been tremendous developments of synthesizing nanoparticle-based local anesthesia drugs. The active targeting ability of nanoparticle-based drug delivery strategy can further help to deliver the desired anesthetic drug locally. It was also found that different local anesthetic drugs are developed into liposome form and show better efficacy in patients receiving anesthesia.

Conclusion: The findings of this review article endorse that safe delivery of anesthesia drugs are essential for the safety of patients. Further, nanotechnology-based strategies are extremely useful for targeted delivery of anesthetic drugs at the required dose without affecting the neighboring tissues.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2174/1389200220666190610155049DOI Listing
January 2020

MicroRNA-132 regulates total protein of Nav1.1 and Nav1.2 in the hippocampus and cortex of rat with chronic cerebral hypoperfusion.

Behav Brain Res 2019 07 15;366:118-125. Epub 2019 Mar 15.

Department of Pharmacology, State-Province Key Laboratory of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin, Heilongjiang Province, 150081, China. Electronic address:

Nav1.1 and Nav1.2 are the voltage-gated sodium channel alpha subunit1 and 2, encoded by the genes of SCN1A and SCN2A. Previous studies have shown that chronic cerebral hypoperfusion (CCH) could induce neuropathological and cognitive impairment and increased total Nav1.1 and Nav1.2protein levels, yet the detailed mechanisms are not fully understood. MicroRNAs (miRNAs) are a class of small, non-coding RNAs that are involved in the regulation of dementia. miR-132 is known to play a key role in neurodegenerative disease. Here, we determined that miR-132 regulates Nav1.1 and Nav1.2 under CCH state. In this study, the expression of miR-132 was decreased in both the hippocampus and cortex of ratsfollowing CCH generated by bilateral common carotid artery occlusion (2VO). Lentiviral-mediated overexpression of miR-132 ameliorated dementia vulnerability induced by 2VO. At the molecular level, miR-132 repressed the increased protein expression of Nav1.1 and Nav1.2 in both the hippocampus and cortex induced by 2VO. MiR-132 suppressed, while AMO-miR-132 enhanced, the level of Nav1.1 and Nav1.2 in primary cultured neonatal rat neurons (NRNs) detected by both western blot analysis and immunofluorescence analysis. Results obtained by dual luciferase assay showed that overexpression of miR-132 inhibited the expression of Nav1.1 and Nav1.2 in human embryonic kidney 293 (HEK293T) cells. Additionally, binding-site mutation failed to influence Nav1.1 and Nav1.2, indicating that Nav1.1 and Nav1.2 are potential targets for miR-132. Taken together, our findings demonstrated that miR-132 protects against CCH-induced learning and memory impairments by down-regulating the expression of Nav1.1 and Nav1.2, and SCN1A and SCN2A are the target genes of miR-132.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbr.2019.03.026DOI Listing
July 2019

Transcriptome profiling of human oocytes experiencing recurrent total fertilization failure.

Sci Rep 2018 12 17;8(1):17890. Epub 2018 Dec 17.

Department of Assisted Reproduction, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

There exist some patients who face recurrent total fertilization failure during assisted reproduction treatment, but the pathological mechanism underlying is elusive. Here, by using sc-RNA-seq method, the transcriptome profiles of ten abnormally fertilized zygotes were assessed, including five zygotes from one patient with recurrent Poly-PN zygotes, and five zygotes from a patient with pronuclear fusion failure. Four zygotes with three pronuclear (Tri-PN) were collected from four different patients as controls. After that, we identified 951 and 1697 significantly differentially expressed genes (SDEGs) in Poly-PN and PN arrest zygotes, respectively as compared with the control group. KEGG analyses indicated down regulated genes in the Poly-PN group included oocyte meiosis related genes, such as PPP2R1B, YWHAZ, MAD2L1, SPDYC, SKP1 and CDC27, together with genes associated with RNA processing, such as SF3B1, LOC645691, MAGOHB, PHF5A, PRPF18, DDX5, THOC1 and BAT1. In contrast, down regulated genes in the PN arrest group, included cell cycle genes, such as E2F4, DBF4, YWHAB, SKP2, CDC23, SMC3, CDC25A, CCND3, BUB1B, MDM2, CCNA2 and CDC7, together with homologous recombination related genes, such as NBN, XRCC3, SHFM1, RAD54B and RAD51. Thus, our work provides a better understanding of transcriptome profiles underlying RTFF, although it based on a limited number of patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-018-36275-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6297154PMC
December 2018

Establishment of an acute extraocular muscle injury model in cats.

Int J Ophthalmol 2018 18;11(9):1475-1481. Epub 2018 Sep 18.

Department of Ophthalmology, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, Shaanxi Province, China.

Aim: To describe an acute extraocular muscle injury model in cats.

Methods: Seventy-two cats were randomly divided into 6 groups (12 cats per group). Cats' left lateral recti were clamped using a surgical needle holder with a clamping strength of 2 (Groups A and D), 4 (Groups B and E) and 6 kg (Groups C and F). The right lateral recti were treated as controls. On the 4 and 7 days, hematoxylin eosin (HE) staining, immunohistochemical staining for proliferating cell nuclear antigen (PCNA), muscle force measurements and ocular alignment changes were performed to evaluate the extent of injuries.

Results: The morphological changes were graded as mild, moderate or severe by HE staining in all experiment groups. PCNA immunohistochemical staining indicated repairment of muscle fibers in the damaged area. On the 4 and 7 days after clamping, the injured lateral muscle exhibited an elevated threshold for electric stimulation. The muscle forces among groups 2, 4 and 6 kg injury at 4d (Groups A, B and C) were statistically significant (<0.05), but no significant differences were noted among groups 2, 4 and 6 kg injury at 7d (Groups D, E and F) (>0.05), respectively. In addition, medial deviation in ocular alignment was also present to various degrees in all groups.

Conclusion: A cat model of acute extraocular muscle injury can be established by rectus clamping. Different clamping strengths can make different degrees of muscle injury. This model may help the future study in the acute extraocular muscle injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18240/ijo.2018.09.08DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6133886PMC
September 2018

Protein phosphatase 2ACα gene knock-out results in cortical atrophy through activating hippo cascade in neuronal progenitor cells.

Int J Biochem Cell Biol 2018 02 20;95:53-62. Epub 2017 Dec 20.

Department of Surgery, School of Medicine, Jilin University, Changchun, 130012, China. Electronic address:

Protein phosphatase 2ACα (PP2ACα), a vital member of the protein phosphatase family, has been studied primarily as a regulator for the development, growth and protein synthesis of a lot of cell types. Dysfunction of PP2ACα protein results in neurodegenerative disease; however, this finding has not been directly confirmed in the mouse model with PP2ACα gene knock-out. Therefore, in this study presented here, we generated the PP2ACα gene knock-out mouse model by the Cre-loxP targeting gene system, with the purpose to directly observe the regulatory role of PP2ACα gene in the development of mouse's cerebral cortex. We observe that knocking-out PP2ACα gene in the central nervous system (CNS) results in cortical neuronal shrinkage, synaptic plasticity impairments, and learning/memory deficits. Further study reveals that PP2ACα gene knock-out initiates Hippo cascade in cortical neuroprogenitor cells (NPCs), which blocks YAP translocation into the nuclei of NPCs. Notably, p73, directly targeted by Hippo cascade, can bind to the promoter of glutaminase2 (GLS2) that plays a dominant role in the enzymatic regulation of glutamate/glutamine cycle. Finally, we find that PP2ACα gene knock-out inhibits the glutamine synthesis through up-regulating the activity of phosphorylated-p73 in cortical NPCs. Taken together, it concludes that PP2ACα critically supports cortical neuronal growth and cognitive function via regulating the signaling transduction of Hippo-p73 cascade. And PP2ACα indirectly modulates the glutamine synthesis of cortical NPCs through targeting p73 that plays a direct transcriptional regulatory role in the gene expression of GLS2.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biocel.2017.12.015DOI Listing
February 2018

Direct Determination of Six Cytokinin Nucleotide Monophosphates in Coconut Flesh by Reversed-Phase Liquid Chromatography-Tandem Mass Spectrometry.

J Agric Food Chem 2017 Nov 2;65(45):9909-9915. Epub 2017 Nov 2.

Rice Product Quality Inspection and Supervision Center of Ministry of Agriculture, China National Rice Research Institute , Hangzhou, Zhejiang 310006, People's Republic of China.

Coconut contains many uncharacterized cytokinins that have important physiological effects in plants and humans. In this work, a method based on liquid chromatography-tandem mass spectrometry was developed for identification and quantification of six cytokinin nucleotide monophosphates in coconut flesh. Excellent separation was achieved using a low-coverage C18 bonded-phase column with an acidic mobile phase, which greatly improved the retention of target compounds. To enable high-throughput analysis, a single-step solid-phase extraction using mixed-mode anion-exchange cartridges was employed for sample preparation. This proved to be an effective method to minimize matrix effects and ensure high selectivity. The limits of detection varied from 0.06 to 0.3 ng/mL, and the limits of quantification ranged from 0.2 to 1.0 ng/mL. The linearity was statistically verified over 2 orders of magnitude, giving a coefficient of determination (R) greater than 0.9981. The mean recoveries were from 81 to 108%; the intraday precision (n = 6) was less than 11%; and the interday precision (n = 11) was within 14%. The developed method was applied to the determination of cytokinin nucleotide monophosphates in coconut flesh samples, and four of them were successfully identified and quantified. The results showed that trans-zeatin riboside-5'-monophosphate was the dominant cytokinin, with a concentration of 2.7-34.2 ng/g, followed by N-isopentenyladenosine-5'-monophosphate (≤12.9 ng/g), while the concentrations of cis-zeatin riboside-5'-monophosphate and dihydrozeatin riboside-5'-monophosphate were less than 2.2 and 4.9 ng/g, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.7b03798DOI Listing
November 2017

Satellite-to-ground quantum key distribution.

Nature 2017 09 9;549(7670):43-47. Epub 2017 Aug 9.

Department of Modern Physics and Hefei National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, China.

Quantum key distribution (QKD) uses individual light quanta in quantum superposition states to guarantee unconditional communication security between distant parties. However, the distance over which QKD is achievable has been limited to a few hundred kilometres, owing to the channel loss that occurs when using optical fibres or terrestrial free space that exponentially reduces the photon transmission rate. Satellite-based QKD has the potential to help to establish a global-scale quantum network, owing to the negligible photon loss and decoherence experienced in empty space. Here we report the development and launch of a low-Earth-orbit satellite for implementing decoy-state QKD-a form of QKD that uses weak coherent pulses at high channel loss and is secure because photon-number-splitting eavesdropping can be detected. We achieve a kilohertz key rate from the satellite to the ground over a distance of up to 1,200 kilometres. This key rate is around 20 orders of magnitudes greater than that expected using an optical fibre of the same length. The establishment of a reliable and efficient space-to-ground link for quantum-state transmission paves the way to global-scale quantum networks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/nature23655DOI Listing
September 2017

Comparison of endoscopic ultrasound, computed tomography and magnetic resonance imaging in assessment of detailed structures of pancreatic cystic neoplasms.

World J Gastroenterol 2017 May;23(17):3184-3192

Chen Du, Ning-Li Chai, En-Qiang Linghu, Hui-Kai Li, Li-Hua Sun, Lei Jiang, Xiang-Dong Wang, Ping Tang, Jing Yang, Department of Gastroenterology and Hepatology, Chinese People's Liberation Army General Hospital, Beijing 100853, China.

Aim: To evaluate the advantages of endoscopic ultrasound (EUS) in the assessment of detailed structures of pancreatic cystic neoplasms (PCNs) compared to computed tomography (CT) and magnetic resonance imaging (MRI).

Methods: All patients with indeterminate PCNs underwent CT, MRI, and EUS. The detailed information, including size, number, the presence of a papilla/nodule, the presence of a septum, and the morphology of the pancreatic duct of PCNs were compared among the three imaging modalities. The size of each PCN was determined using the largest diameter measured. A cyst consisting of several small cysts was referred to as a mother-daughter cyst. Disagreement among the three imaging modalities regarding the total number of mother cysts resulted in the assumption that the correct number was the one in which the majority of imaging modalities indicated.

Results: A total of 52 females and 16 males were evaluated. The median size of the cysts was 42.5 mm by EUS, 42.0 mm by CT and 38.0 mm by MRI; there was no significant difference in size as assessed among the three imaging techniques. The diagnostic sensitivity and ability of EUS to classify PCNs were 98.5% (67/68) and 92.6% (63/68), respectively. These percentages were higher than those of CT (73.1%, < 0.001; 17.1%, < 0.001) and MRI (81.3%, = 0.001; 20.3%, < 0.001). EUS was also able to better assess the number of daughter cysts in mother cysts than CT ( = 0.003); however, there was no significant difference between EUS and MRI in assessing mother-daughter cysts ( = 0.254). The papilla/nodule detection rate by EUS was 35.3% (24/68), much higher than those by CT (5.8%, 3/52) and MRI (6.3%, 4/64). The detection rate of the septum by EUS was 60.3% (41/68), which was higher than those by CT (34.6%, 18/52) and by MRI (46.9%, 30/64); the difference between EUS and CT was significant ( = 0.02). The rate of visualizing the pancreatic duct using EUS was 100%, whereas using CT and MRI it was less than 10%.

Conclusion: EUS helps visualize the detailed structures of PCNs and has many advantages over CT and MRI. EUS is valuable in the diagnosis and assessment of PCNs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v23.i17.3184DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423055PMC
May 2017

Analysis of ustiloxins in rice using polymer cation exchange cleanup followed by liquid chromatography-tandem mass spectrometry.

J Chromatogr A 2016 Dec 4;1476:46-52. Epub 2016 Nov 4.

Rice Product Quality Inspection and Supervision Center of Ministry of Agriculture, China National Rice Research Institute, Hangzhou 310006, China. Electronic address:

Ustiloxins are cyclopeptide mycotoxins produced by the pathogenic fungus Ustilaginoidea virens of rice false smut. Quantification of ustiloxins is essential to assess the food safety of rice infected by rice false smut disease. This paper describes a sensitive method for the simultaneous quantification of ustiloxins A, B, C, D and F in rice grains using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Since notable matrix enhancement effects (21%-78%) occurred for all of the target analytes (except for ustiloxin A), several solid phase extraction materials were tested for their ability to retain ustiloxins from aqueous solutions prior to the LC-MS/MS analysis, including C18 sorbents, polymer anion exchange sorbents resin (PAX), and polymer cation exchange resin (PCX). The PCX resin was adopted due to its higher extraction capability and selectivity for all targets compared to others, and in this case, almost no matrix effects (-5% to 8%) were observed for all of the ustiloxins monitored. The developed method reached limits of quantification of 0.2-2ngg, and linearity was statistically verified over two orders of magnitude with regression coefficients (R)>0.991. The mean recoveries were from 85% to 109%, and the inter-day precisions (n=11) were less than 16%, with intra-day precisions (n=6) within 12%. Analysis of samples showed that ustiloxin A was the dominant species, with the content ranging from 5.5 to 273.8ngg, followed by ustiloxin B (≤88.7ngg), while concentrations of ustiloxins C, D and F were slightly lower (≤43.2ngg). To our knowledge, this is the first report on the determination and analysis of five ustiloxins simultaneously in a single analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2016.11.004DOI Listing
December 2016

Overexpression of Paxillin Correlates with Tumor Progression and Predicts Poor Survival in Glioblastoma.

CNS Neurosci Ther 2017 Jan 17;23(1):69-75. Epub 2016 Sep 17.

Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China.

Aims: To explore the prognostic and clinicopathological features of glioma with Paxillin (PXN) expression based on a large number of samples.

Methods: RNA sequencing data of 325 glioma samples from Chinese Glioma Genome Atlas (CGGA) database were obtained as discovery set. Three additional datasets were further obtained as validation sets. The protein expression pattern of PXN in glioma was measured by IHC. Kaplan-Meier survival and multivariate Cox analysis were used to estimate the survival distributions. Moreover, the functional annotation of PXN was also analyzed.

Results: In the discovery set, PXN overexpression was significantly associated with high-grade glioma as well as the higher mortality in survival analysis (log-rank test, P < 0.01). The results of the other validation datasets showed similar findings. PXN also served as an independent prognostic biomarker in glioblastoma patients. Functional assays showed that PXN contributed to glioma cell proliferation and invasion.

Conclusion: PXN plays as an oncogene in glioma progression and suggests a new potential biotarget for therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/cns.12606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6492676PMC
January 2017

Development of a lateral-flow assay (LFA) for rapid detection of Soybean mosaic virus.

J Virol Methods 2016 09 25;235:51-57. Epub 2016 May 25.

Key Laboratory of Integrated Management of Crop Diseases and Pests, Ministry of Education, Department of Plant Pathology, Nanjing Agricultural University, Nanjing 210095, China. Electronic address:

Soybean mosaic virus (SMV) is the most common virus in soybean and poses a serious threat to crop production and germplasm recession in many countries worldwide. In this study, a highly practical and rapid lateral-flow assay (LFA) was developed for the detection of SMV. The SMV coat protein (CP) was prokaryotically expressed and purified to immunize mice. After generation of hybridoma cell lines, four anti-SMV monoclonal antibodies were selected. The LFA-strip was then assembled using a double-antibody sandwich strategy. When the SMV-infected leaf sample was assayed using the assembled LFA-strip, the positive pink color appeared in the test line within 5-10min. The strip only gave positive results with SMV and not other viruses tested and could be used to detect 800 fold dilutions of infected leaf samples. The LFA could be used to detect SMV in infected leaf tissue as well as soybean seeds. To our knowledge, this is the first report of the development of a LFA for the detection of SMV. The practical, rapid and specific assay that was developed in this study can be widely applied to the diagnosis and surveillance of SMV in the laboratory and the field.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jviromet.2016.05.011DOI Listing
September 2016

Profiling of phytohormones and their major metabolites in rice using binary solid-phase extraction and liquid chromatography-triple quadrupole mass spectrometry.

J Chromatogr A 2016 Jun 4;1451:67-74. Epub 2016 May 4.

Rice Product Quality Inspection and Supervision Center of Ministry of Agriculture, China National Rice Research Institute, Hangzhou 310006, China. Electronic address:

A high-throughput method was developed using liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) for the profiling and quantification of 43 phytohormones and their major metabolites, including auxins, abscisic acid, jasmonic acid, salicylic acid, cytokinins and gibberellins in a single sample extract. Considerable matrix effects (MEs) were observed (with most ME values in the range of 29%-84%, but maximum MEs of more than 115%, even up to 206%, existed) in sample extracts for most of the compounds studied. The application of the proposed binary solid-phase extraction using polymer anion and polymer cation exchange resins, was performed to purify 25 acidic and 18 alkaline phytohormones and their major metabolites prior to the LC-MS/MS analysis, which markedly reduced the MEs to acceptable levels, with ME values in the range of ±15%. Moreover, all of the isomers of cytokinins and their metabolites were fully separated on a sub-2μm particle C18 reverse-phase column with the optimized mobile phase consisting of methanol and 5mM ammonium formate. The method showed good linearity for all 43 analytes with regression coefficients (R(2))>0.991. Limits of detection ranged from 0.19 to 7.57 fmol for auxin, gibberellins, abscisic acid and their metabolites, 29.7 fmol for jasmonic acid, 18.1 fmol for salicylic acid, and from 0.03 to 0.31 fmol for cytokinins and their metabolites. The mean recoveries for all of the analytes were from 70.7 to 118.5%, and the inter-day precisions (n=6) were less than 18.7%, with intra-day precisions (n=6) within 25.4%. Finally, 20 compounds were successfully quantified in rice sample profiles using the proposed method, which will greatly facilitate the understanding of hormone-related regulatory networks that influence rice growth and development. To our knowledge, there are limited reports that measure this level of phytohormone species in rice samples using a single analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chroma.2016.05.011DOI Listing
June 2016

MicroRNA-27a Promotes Inefficient Lysosomal Clearance in the Hippocampi of Rats Following Chronic Brain Hypoperfusion.

Mol Neurobiol 2017 05 19;54(4):2595-2610. Epub 2016 Mar 19.

Department of Pharmacology, Harbin Medical University (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), No.157 Baojian Road, Nangang District, Harbin, Heilongjiang Province, 150086, China.

Chronic brain hypoperfusion (CBH) induces the accumulation of abnormal cellular proteins, accompanied by cognitive decline, and the autophagic-lysosomal system is abnormal in dementia. Whether CBH accounts for autophagic-lysosomal neuropathology remains unknown. Here, we show that CBH significantly increased the number of autophagic vacuoles (AVs) with high LC3-II levels, but decreased SQSTM1 and cathepsin D levels in the hippocampi of rats following bilateral common carotid artery occlusion (2VO) for 2 weeks. Further studies showed that microRNA-27a (Mir27a) was upregulated at 2 weeks compared with the sham group. Additionally, LAMP-2 proteins were downregulated by Mir27a overexpression, upregulated by Mir27a inhibition, and unchanged by binding-site mutations or miR-masks, indicating that lamp-2 is the target of Mir27a. Knockdown of endogenous Mir27a prevented the reduction of LAMP-2 protein expression as well as the accumulation of AVs in the hippocampi of 2VO rats. Overexpression of Mir27a induced, while the knockdown of Mir27a reduced, the accumulation of AVs and the LC3-II level in cultured neonatal rat neurons. The results revealed that CBH in rats at 2 weeks could induce inefficient lysosomal clearance, which is regulated by the Mir27a-mediated downregulation of LAMP-2 protein expression. These findings provide an insight into a novel molecular mechanism of autophagy at the miRNA level.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12035-016-9856-8DOI Listing
May 2017

BMP7 enhances the effect of BMSCs on extracellular matrix remodeling in a rabbit model of intervertebral disc degeneration.

FEBS J 2016 05 28;283(9):1689-700. Epub 2016 Mar 28.

Department of Orthopaedics, The Second Affiliated Hospital of Harbin Medical University, China.

Intervertebral discs (IVDs) provide stability and flexibility to the spinal column; however, IVDs, and in particular the nucleus pulposus (NP), undergo a degenerative process characterized by changes in the disc extracellular matrix (ECM), decreased cell viability, and reduced synthesis of proteoglycan and type II collagen. Here, we investigated the efficacy and feasibility of stem cell therapy using bone marrow mesenchymal stem cells (BMSCs) over-expressing bone morphogenetic protein 7 (BMP7) to promote ECM remodeling of degenerated IVDs. Lentivirus-mediated BMP7 over-expression induced differentiation of BMSCs into an NP phenotype, as indicated by expression of the NP markers collagen type II, aggrecan, SOX9 and keratins 8 and 19, increased the content of glycosaminoglycan, and up-regulated β-1,3-glucuronosyl transferase 1, a regulator of chondroitin sulfate synthesis in NP cells. These effects were suppressed by Smad1 silencing, indicating that the effect of BMP7 on ECM remodeling was mediated by the Smad pathway. In vivo analysis in a rabbit model of disc degeneration showed that implantation of BMSCs over-expressing BMP7 promoted cell differentiation and proliferation in the NP, as well as their own survival, and these effects were mediated by the Smad pathway. The results of the present study indicate the beneficial effects of BMP7 on restoring ECM homeostasis in NP cells, and suggest potential strategies for improving cell therapy for the treatment of disc diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/febs.13695DOI Listing
May 2016

Hypoxia-inducible factor-1 modulates upregulation of mutT homolog-1 in colorectal cancer.

World J Gastroenterol 2015 Dec;21(48):13447-56

Yuan Qiu, Li-Hua Sun, Ke Peng, Wei-Dong Xiao, Hua Yang, Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.

Aim: To investigate the roles and interactions of mutT homolog (MTH)-1 and hypoxia-inducible factor (HIF)-1α in human colorectal cancer (CRC).

Methods: The expression and distribution of HIF-1α and MTH-1 proteins were detected in human CRC tissues by immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR). SW480 and HT-29 cells were exposed to normoxia or hypoxia. Protein and mRNA levels of HIF-1α and MTH-1 were analyzed by western blotting and qRT-PCR, respectively. In order to determine the effect of HIF-1α on the expression of MTH-1 and the amount of 8-oxo-deoxyguanosine triphosphate (dGTP) in SW480 and HT-29 cells, HIF-1α was silenced with small interfering RNA (siRNA). Growth studies were conducted on cells with HIF-1α inhibition using a xenograft tumor model. Finally, MTH-1 protein was detected by western blotting in vivo.

Results: High MTH-1 mRNA expression was detected in 64.2% of cases (54/84), and this was significantly correlated with tumor stage (P = 0.023) and size (P = 0.043). HIF-1α protein expression was correlated significantly with MTH-1 expression (R = 0.640; P < 0.01) in human CRC tissues. Hypoxic stress induced mRNA and protein expression of MTH-1 in SW480 and HT-29 cells. Inhibition of HIF-1α by siRNA decreased the expression of MTH-1 and led to the accumulation of 8-oxo-dGTP in SW480 and HT-29 cells. In the in vivo xenograft tumor model, expression of MTH-1 was decreased in the HIF-1α siRNA group, and the tumor volume was much smaller than that in the mock siRNA group.

Conclusion: MTH-1 expression in CRC cells was upregulated via HIF-1α in response to hypoxic stress, emphasizing the crucial role of HIF-1α-induced MTH-1 in tumor growth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3748/wjg.v21.i48.13447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690173PMC
December 2015

MicroRNA-9 induces defective trafficking of Nav1.1 and Nav1.2 by targeting Navβ2 protein coding region in rat with chronic brain hypoperfusion.

Mol Neurodegener 2015 Aug 11;10:36. Epub 2015 Aug 11.

Department of Pharmacology, Harbin Medical University, No.157 Baojian Road, Nangang District,Harbin, Heilongjiang Province, 15008, China.

Background: Previous studies have demonstrated that the trafficking defects of Nav1.1/Nav1.2 are involved in the dementia pathophysiology. However, the detailed mechanisms are not fully understood. Moreover, whether the impaired miRNAs regulation linked to dementia is a key player in sodium channel trafficking disturbance remains unclear. The cognitive impairment induced by chronic cerebral ischemia through chronic brain hypoperfusion (CBH) is likely reason to precede dementia. Therefore, our goal in the present study was to examine the role of microRNA-9 (miR-9) in regulating Nav1.1/Nav1.2 trafficking under CBH generated by bilateral common carotid artery occlusion (2VO).

Results: The impairment of Nav1.1/Nav1.2 trafficking and decreased expression of Navβ2 were found in the hippocampi and cortices of rats following CBH generated by bilateral 2VO. MiR-9 was increased in both the hippocampi and cortices of rats following CBH by qRT-PCR. Intriguingly, miR-9 suppressed, while AMO-miR-9 enhanced, the trafficking of Nav1.1/Nav1.2 from cytoplasm to cell membrane. Further study showed that overexpression of miR-9 inhibited the Navβ2 expression by targeting on its coding sequence (CDS) domain by dual luciferase assay. However, binding-site mutation or miR-masks failed to influence Navβ2 expression as well as Nav1.1/Nav1.2 trafficking process, indicating that Navβ2 is a potential target for miR-9. Lentivirus-mediated miR-9 overexpression also inhibited Navβ2 expression and elicited translocation deficits to cell membrane of Nav1.1/Nav1.2 in rats, whereas injection of lentivirus-mediated miR-9 knockdown could reverse the impaired trafficking of Nav1.1/Nav1.2 triggered by 2VO.

Conclusions: We conclude that miR-9 may play a key role in regulating the process of Nav1.1/Nav1.2 trafficking via targeting on Navβ2 protein in 2VO rats at post-transcriptional level, and inhibition of miR-9 may be a potentially valuable approach to prevent Nav1.1/Nav1.2 trafficking disturbance induced by CBH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13024-015-0032-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4530481PMC
August 2015

Activation of Cdk5/p25 and tau phosphorylation following chronic brain hypoperfusion in rats involves microRNA-195 down-regulation.

J Neurochem 2015 Sep;134(6):1139-51

Department of Pharmacology (the State-Province Key Laboratories of Biomedicine-Pharmaceutics of China), Harbin Medical University, Harbin, Heilongjiang, China.

Chronic brain hypoperfusion (CBH) is a common clinical feature of Alzheimer's disease and vascular dementia, but the underlying molecular mechanism is unclear. Our previous study reported that the down-regulation of microRNA-195 (miR-195) promotes amyloidogenesis via regulation of amyloid precursor protein and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) expression at the post-transcriptional level in CBH rats with bilateral common carotid artery occlusion (2VO). CBH owing to unilateral common carotid artery occlusion (UCCAO) increases tau phosphorylation levels at multiple phosphorylation sites in the brain, but the molecular mechanism is poorly understood. The purpose of this study was to investigate whether miR-195 could both deregulate amyloid metabolism and indirectly deregulate tau phosphorylation in CBH. We observed that 2VO leads to tau hyperphosphorylation at Ser202/Thr205, Ser262, Thr231, and Ser422 and to the conversion from cyclin-dependent kinase 5 (Cdk5)/p35 to Cdk5/p25 in rat hippocampi. Endogenous miR-195 was knocked down using over-expression of its antisense molecule (pre-AMO-miR-195) via a lentivirus (lenti-pre-AMO-miR-195); this knockdown increased the tau phosphorylation at Ser202/Thr205, Ser262, Thr231, Ser422, and the Cdk5/p25 activation, but over-expression of miR-195 using lenti-pre-miR-195 decreased the tau phosphorylation and Cdk5/p25 activation. Further in vitro studies demonstrated that miR-195 over-expression prevented tau hyperphosphorylation and Cdk5/p35 activity, which were increased by miR-195 inhibition. A dual luciferase reporter assay showed that miR-195 bound to the Cdk5r1 gene, which encodes p35 protein, in the 3'UTR and inhibited p35 expression. We concluded that tau hyperphosphorylation involves the down-regulation of miR-195, which is mediated by Cdk5/p25 activation in 2VO rats. Our findings demonstrated that down-regulation of miR-195 led to increased vulnerability via the regulation of multiple targets. Schematic diagram of miR-195 mediated Aβ aggregation and tau hyperphosphorylation in chronic brain hypoperfusion (CBH). First, CBH results in the elevation of nuclear factor-κB (NF-κB), which binds with the promoter sequences of miR-195 and negatively regulates the expression of miR-195. Second, down-regulated miR-195 induces up-regulation of APP and BACE1 and leads to an increase in Aβ levels. Third, some of the elevated Aβ then enter the intracellular space and activate calpain, which promotes the conversion of Cdk5/p35 to Cdk5/p25 and catalyzes the degradation of IκB; IκB is an inhibitor of NF-κB, which activates NF-κB. Cdk5/p25 directly phosphorylates Tau. Fourth, down-regulated miR-195 induces an up-regulation of p35, which provides the active substrates of p25. Our findings demonstrated that the down-regulation of miR-195 plays a key role in the increased vulnerability to dementia via the regulation of multiple targets following CBH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jnc.13212DOI Listing
September 2015

Abnormal pulmonary function and respiratory muscle strength findings in Chinese patients with Parkinson's disease and multiple system atrophy--comparison with normal elderly.

PLoS One 2014 29;9(12):e116123. Epub 2014 Dec 29.

Department of neurology, Nanjing First Hospital, Nanjing medical university, Nanjing, China.

Background: There have been limited comparative data regarding the investigations on pulmonary and respiratory muscle function in the patients with different parkinsonism disorders such as Parkinson's disease (PD) and multiple system atrophy (MSA) versus normal elderly. The present study is aiming to characterize the performance of pulmonary function and respiratory muscle strength in PD and MSA, and to investigate the association with severity of motor symptoms and disease duration.

Methods: Pulmonary function and respiratory muscle strength tests were performed in 30 patients with PD, 27 with MSA as well as in 20 age-, sex-, height-, weight-matched normal elderly controls. All the patients underwent United Parkinson's disease rating scale (UPDRS) or united multiple system atrophy rating scale (UMSARS) separately as diagnosed.

Results: Vital capacity, forced expiratory volume in 1 second and forced vital capacity decreased, residual volume and ratio of residual volume to total lung capacity increased in both PD and MSA groups compared to controls (p<0.05). Diffusing capacity was decreased in the MSA group, compared with PD and normal elderly control groups (p<0.05). Respiratory muscle strength was lower in both PD and MSA groups than in controls (p<0.05). The values representing spirometry function and respiratory muscle strength were found to have a negative linear correlation with mean score of UPDRS-III in PD and mean score of UMSARS-I in MSA. Respiratory muscle strength showed a negative linear correlation with the mean score of UMSARS-II and disease duration in MSA patients.

Conclusions: These findings suggest that respiratory dysfunction is involved in PD and MSA. Respiratory muscle strength is remarkably reduced, and some of the parameters correlate with disease duration and illness severity. The compromised respiratory function in neurodegenerative disorders should be the focus of further researches.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116123PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4278864PMC
September 2015

Utilisation of adsorption and desorption for simultaneously improving protein crystallisation success rate and crystal quality.

Sci Rep 2014 Dec 4;4:7308. Epub 2014 Dec 4.

Key Laboratory for Space Bioscience &Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an 710072, Shaanxi, PR China.

High-quality protein crystals of suitable size are an important prerequisite for applying X-ray crystallography to determine the 3-dimensional structure of proteins. However, it is often difficult to obtain protein crystals of appropriate size and quality because nucleation and growth processes can be unsuccessful. Here, we show that by adsorbing proteins onto porous polystyrene-divinylbenzene microspheres (SDB) floating on the surface of the crystallisation solution, a localised high supersaturation region at the surface of the microspheres and a low supersaturation region below the microspheres can coexist in a single solution. The crystals will easily nucleate in the region of high supersaturation, but when they grow to a certain size, they will sediment to the region of low supersaturation and continue to grow. In this way, the probability of crystallisation and crystal quality can be simultaneously increased in a single solution without changing other crystallisation parameters.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep07308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4255177PMC
December 2014

A novel method for the simultaneous analysis of seven biothiols in rice (Oryza sativa L.) using hydrophilic interaction chromatography coupled with electrospray tandem mass spectrometry.

J Chromatogr B Analyt Technol Biomed Life Sci 2015 Jan 20;976-977:19-26. Epub 2014 Nov 20.

China National Rice Research Institute, Hangzhou 310006, China; Laboratory of Quality & Safety Risk Assessment for Rice (Hangzhou), Ministry of Agriculture, Hangzhou 310006, China. Electronic address:

Analysis of biothiols is still problematic, due to their high polarity, oxidation sensitivity and time-consuming sample preparation. In this paper, a direct, rapid and sensitive method was developed for simultaneous quantification of unbound cysteine (Cys), glutathione (GSH) and phytochelatins (PCs) in rice leaf, stem and root samples by hydrophilic interaction chromatography coupled with electrospray tandem mass spectrometry (HILIC-MS/MS). Homogenized samples were extracted with water containing 50mM dithiothreitol, without derivatization and further clean-up, and the extracts were injected directly onto an Xbridge Amide-HILIC column (3.5μm, 150mm×2.1mm i.d.). The best chromatographic separation and MS sensitivity was achieved using a linear gradient elution with 10mM aqueous ammonium formate and acetonitrile as the mobile phase. In MS/MS mode the detection limit (S/N≥3) of seven biothiols was 3-105nM. Good linearities were observed (r>0.995) with linear dynamic range at least over three orders of magnitude. Recoveries for most analytes were within the range of 77-128%, with relative standard deviations less than 18.2%. The intra-day precision (n=7) was 6.1-11.7%, and the inter-day precision over 15 d (n=15) was 8.5-16.3% for all biothiols. The optimized HILIC-MS/MS method was applied to study the influence of different cadmium (Cd) concentrations (0, 1 and 50μM) on contents of Cys, GSH and PC2-6 in rice tissue. With increasing Cd concentrations in nutrient solutions, contents of PC2-4 in rice roots increased but contents of Cys and GSH decreased. Contents of PC2-4 in both rice leafs and stems increased markedly at high dose Cd (50μM) treatment compared with controls, compared with low Cd concentrations (1μM). However, both PC5 and PC6 were not detected throughout the stress experiment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchromb.2014.11.007DOI Listing
January 2015

[Economic burden and economic risk of five major chronic diseases among Chinese urban residents].

Beijing Da Xue Xue Bao Yi Xue Ban 2014 Oct;46(5):782-9

China Center for Health Economics Research, Peking University, Beijing 100871, China.

Objective: To provide scientific evidence for medical insurance and health policies allocating the limited health resources in China.

Methods: Based on the data of the national household survey by the State Council Pilot Urban Resident Basic Medical Insurance Evaluation from Nov.2007 to Nov.2011, a two-step model and the human capital method were used to estimate the economic burden of five major chronic diseases among urban residents in China. According to the economic burden, the relative economic risk (relative risk, RR) and adjusted RR were calculated. The five chronic diseases were hypertension, cardiovascular, diabetes, arthritis or rheumatism and chronic lung diseases.

Results: More than 50% of the residents with these five chronic diseases were the over 65-year-old and retired. 90% of the residents with these five chronic diseases had medical insurance except the residents with chronic lung diseases. Average co-pay from the outpatient department and the pharmacy was more than 60%, and about 50% from the inpatient department. Annual total cost per capita was the highest 8 954.29 Yuan among the residents with cardiovascular disease and the second highest 8 914.36 Yuan among the residents with diabetes. The adjusted RR of the residents with cardiovascular and diabetes were greater than 1, respectively 1.36 and 1.15.

Conclusion: The retired take up the largest percentage of population with chronic diseases, and the influence of the major five chronic diseases is more serious in north-west China. The main expenditure is from the outpatient department and the pharmacy, in which the availability of drugs reimbursed needs to be improved. The patients with cardiovascular and diabetes experience both higher economic burden and economic risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2014
-->