Publications by authors named "Yuhua Fan"

76 Publications

Two biologically inspired tetranuclear nickel(II) catalysts: effect of the geometry of Ni core on electrocatalytic water oxidation.

J Biol Inorg Chem 2021 Feb 5. Epub 2021 Feb 5.

Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao, 26610, Shandong, China.

Two biologically inspired tetranuclear nickel complexes [Ni(L-H)(CHCOO)]·Cl (1) and [Ni(L-H)(CHCOO)]·2CHOH (2) (L = di(pyridin-2-yl)methanediol) have been synthesized and investigated by a combination of X-ray crystallography, PXRD, electrochemistry, in-situ UV-Vis spectroelectrochemistry and DLS. Both of the two complexes feature a core composed of four Ni(II) ions with the same peripheral ligation provided by the anionic di(pyridin-2-yl)methanediol and MeCOO ligands. Whereas, complex 1 possesses one distorted cubane-like [Ni(µ-O)] core, while 2 has one extended butterfly-like [Ni(µ-O)] core. The homogeneous electrocatalytic reactivity of the two water-soluble complexes for water oxidation have been thoroughly studied, which demonstrates that both of them can efficiently electrocatalyze water oxidation with high stability under alkaline conditions, at relatively low over-potentials (η) of 420-790 mV for 1 and 390-780 mV for 2, both in the pH range of 7.67-12.32, with the high TOF of about 139 s (1) and 69 s (2) at pH = 12.32, respectively. By a series of comparative experiments for complexes 1 and 2, we proposed that their crystal geometries play an important role in their electrocatalytic reactivity for water oxidation. We verified that biomimetic cubane geometry could promote OER catalysis with two very similar compounds for the first time. Compared with 2, the biomimetic cubane topology of 1 could promote OER catalysis by facilitating efficient charge delocalization and electron-transfer.
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http://dx.doi.org/10.1007/s00775-020-01846-4DOI Listing
February 2021

Sera and lungs metabonomics reveals key metabolites of resveratrol protecting against PAH in rats.

Biomed Pharmacother 2021 Jan 15;133:110910. Epub 2020 Dec 15.

College of Basic Medical Sciences, Harbin Medical University, Daqing, 163319, China. Electronic address:

Pulmonary arterial hypertension (PAH) is a type of high morbidity and mortality disease. Currently, the intrinsic metabolic alteration and potential mechanism of PAH are still not fully uncovered. Previously, we have found that polyphenol resveratrol (Rev) reversed the remodeling of the pulmonary vasculature and decreased the number of mitochondria in pulmonary arterial smooth muscle cells (PASMCs) (Lei Yu et al. (2017)). However, potential effects of Rev on the changed metabolic molecules derived from lung tissue and serum have no fully elucidated. Thus, we conducted a systematic elaboration through the metabonomics method. Various of metabolites in different pathways including amino acid metabolism, tricarboxylic acid cycle (TCA), acetylcholine metabolism, fatty acid metabolism and biosynthesis in male Wistar rats' sera and lung tissues were explored in three groups (normal group, PAH group, PAH and Rev treatment group). We found that leucine and isoleucine degradation, valine, leucine and isoleucine biosynthesis, tryptophan metabolism and aminoacyl-tRNA biosynthesis were involved in the development of PAH. Hydroxyphenyllactic, isopalmitic acid and cytosine might be significant key metabolites. Further work in this area may inform personalized treatment approaches in clinical practice of PAH through elucidating pathophysiology mechanisms of experimental verification.
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http://dx.doi.org/10.1016/j.biopha.2020.110910DOI Listing
January 2021

Stent-Assisted Angioplasty in Spontaneous Bilateral Extracranial Internal Carotid Artery Dissection.

Front Neurol 2020 13;11:582253. Epub 2020 Nov 13.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Internal carotid artery dissection (ICAD) results from a tear in the intima or rupture of the vasa vasorum with bleeding within the media resulting in separation of the vessel wall layers and a false lumen. It may cause arterial stenosis, occlusion, or dissecting pseudoaneurysm. Currently, the treatment of ICAD is controversial, including drug therapy and endovascular stent implantation. Simultaneous spontaneous dissection of bilateral carotid artery is rarely reported. We reported a 39-year-old-man with bilateral ICAD. Although the long-term durability of endovascular stent remains to be determined, for ICAD failed with active drug treatment and combined with hemodynamic impairment, early endovascular stent should be considered.
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http://dx.doi.org/10.3389/fneur.2020.582253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691571PMC
November 2020

Regional High Wall Shear Stress Associated With Stenosis Regression in Symptomatic Intracranial Atherosclerotic Disease.

Stroke 2020 10 4;51(10):3064-3073. Epub 2020 Sep 4.

Shenzhen Research Institute, The Chinese University of Hong Kong, China (X.L.).

Background And Purpose: Understanding the mechanisms underlying progression/regression of symptomatic intracranial atherosclerotic stenosis (sICAS) will inform secondary prevention of the patients. Focal wall shear stress (WSS) may play an important role, which, however, had seldom been investigated.

Methods: Patients with acute ischemic stroke or transient ischemic attack (TIA) attributed to 50% to 99% intracranial atherosclerotic stenosis were recruited. All patients underwent cerebral computed tomography angiography at baseline, and a computational fluid dynamics model was built based on computed tomography angiography to simulate blood flow and quantify WSS in the vicinity of the sICAS lesion. All patients received optimal medical treatment and a second computed tomography angiography at 1 year. The change in the luminal stenosis from baseline to 1 year in sICAS was defined as progression (increased >10%), quiescence (±10%), or regression (decreased >10%). Associations between baseline WSS metrics and sICAS regression were analyzed.

Results: Among 39 patients (median age 62 years; 27 males), sICAS luminal stenosis progressed, remained quiescent and regressed in 6 (15.4%), 15 (38.5%), and 18 (46.2%) cases, respectively. A higher maximum WSS and larger high-WSS area, throughout the sICAS lesion or obtained separately in the proximal and distal parts of the lesion, were independently associated with regression of luminal stenosis in sICAS over 1 year.

Conclusions: A majority of sICAS lesions regress or stay quiescent in the luminal stenosis over 1 year after stroke under optimal medical treatment, when higher focal WSS may facilitate stenosis regression. Further studies of the effects of hemodynamics including WSS in altering plaque vulnerability and stroke risks are needed.
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http://dx.doi.org/10.1161/STROKEAHA.120.030615DOI Listing
October 2020

Rosuvastatin Improves Cognitive Function of Chronic Hypertensive Rats by Attenuating White Matter Lesions and Beta-Amyloid Deposits.

Biomed Res Int 2020 12;2020:4864017. Epub 2020 Aug 12.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University; Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou 510080, China.

Hypertensive white matter lesion (WML) is one of common causes of vascular cognitive impairment. In this study, we aimed to investigate the effect of rosuvastatin on cognitive impairment and its underlying mechanisms in chronic hypertensive rats. From the 8 week after establishment of stroke-prone renovascular hypertensive rats (RHRSPs), rosuvastatin (10 mg/kg) or saline as a control was administrated once daily for consecutive 12 weeks by gastric gavage. Cognitive function was assessed with the Morris water maze test and novel object recognition test. WML was observed by Luxol fast blue staining. A deposits, Claudin-5, Occludin, and ZO-1 were determined by immunofluorescence. After rosuvastatin treatment, the escape latencies were decreased and the time of crossing the hidden platform was increased in the Morris water maze, compared with the vehicle-treated RHRSP group. In a novel object recognition test, the recognition index in the rosuvastatin-treated RHRSP group was significantly larger than that in the vehicle-treated RHRSP group. Rosuvastatin treatment presented with the effects of lower WML grades, higher expression of tight junction proteins Claudin-5, Occludin, and ZO-1 in the corpus callosum, and less A deposits in the cortex and hippocampus. The data suggested that rosuvastatin improved the cognitive function of chronic hypertensive rats partly by attenuating WML and reducing A burden.
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http://dx.doi.org/10.1155/2020/4864017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441415PMC
August 2020

A Coarse-to-Fine Framework for Multiple Pedestrian Crossing Detection.

Sensors (Basel) 2020 Jul 25;20(15). Epub 2020 Jul 25.

Center for Machine Vision and Signal Analysis, University of Oulu, University of Oulu, 90570 Oulu, Finland.

When providing route guidance to pedestrians, one of the major safety considerations is to ensure that streets are crossed at places with pedestrian crossings. As a result, map service providers are keen to gather the location information about pedestrian crossings in the road network. Most, if not all, literature in this field focuses on detecting the pedestrian crossing immediately in front of the camera, while leaving the other pedestrian crossings in the same image undetected. This causes an under-utilization of the information in the video images, because not all pedestrian crossings captured by the camera are detected. In this research, we propose a coarse-to-fine framework to detect pedestrian crossings from probe vehicle videos, which can then be combined with the GPS traces of the corresponding vehicles to determine the exact locations of pedestrian crossings. At the coarse stage of our approach, we identify vanishing points and straight lines associated with the stripes of pedestrian crossings, and partition the edges to obtain rough candidate regions of interest (ROIs). At the fine stage, we determine whether these candidate ROIs are indeed pedestrian crossings by exploring their prior constraint information. Field experiments in Beijing and Shanghai cities show that the proposed approach can produce satisfactory results under a wide variety of situations.
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http://dx.doi.org/10.3390/s20154144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436173PMC
July 2020

Zn-MOFs based luminescent sensors for selective and highly sensitive detection of Fe and tetracycline antibiotic.

J Pharm Biomed Anal 2020 Sep 26;188:113444. Epub 2020 Jun 26.

Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao, Shandong, 266100, PR China. Electronic address:

Either reduced or excessive metal ions level in biological systems might induce serious metabolic diseases, and the abuse of antibiotics has seriously affected the environment. Despite the significant progress in the development of fluorescence probes over the past decade, the ability to sensitively and selectively detect these metal ions and antibiotics remains a pressing problem. Herein, we demonstrated some effective fluorescence probes for sensing metal ions and antibiotics, six novel and stable Zn(II) metal-organic frameworks (Zn-MOFs), namely [Zn(L)(1,4-bimb)] (1), [Zn(L)(4,4'-bbibp)(HO)]·2(CHCN) (2), [Zn(HL)(4,4'-bidpe)] (3), [Zn(HL)(4,4'-bibp)] (4), [Zn(HL)(3,5'-bip)] (5) and [Zn(HL)(1,3'-bit)] (6) (flexible HL = 5-(2-carboxylphenoxy)isophthalic acid, semi-flexible 1,4-bimb = 1,4-bis(imidazol-l-ylmethyl) benzene, rigid 4,4'-bbibp = 4,4'-bis(benzoimidazo-1-ly)biphenyl, semi-flexible 4,4'-bidpe = 4,4'-bis(imidazolyl)diphenyl ether, rigid 4,4'-bibp = 4,4'-bis(imidazolyl)biphenyl, rigid 3,5'-bip = bis(1-imidazoly)pyridine and rigid 1,3-bit = 1,3-bis(l-imidazoly)toluene) have been successfully synthesized via solvothermal conditions and further characterized by IR spectra, elemental analysis, powder X-ray diffraction (PXRD), single-crystal X-ray diffraction, and thermogravimetric (TG) analysis. These Zn MOFs have exhibited diversely architectural frameworks via the assistant N-donor ligands: 1, 2, 5 and 6 show unprecedented topological networks, 1 affords a 3-nodal (3, 4, 4)-connect 2-fold interpenetrating topology structure with the Point Schläfli symbol of (5·6·7·9·10)(5·6·7)(5·7·8), 2 shows a 3-nodal (3, 4, 6)-c topology with (4·8)(4·8·10·12)(8), 5 and 6 display 3-nodal (2, 2, 4)-c topology with (2·4·6)(2)(4). 3 and 4 show 4-connected sql topology with (4·6). As expected, Zn MOFs 1-6 not only revealed a highly sensitive and selective fluorescence quenching effect on Fe ions in aqueous solution, but also toughed the interference of a myriad of other metal ions. It is noteworthy that they could also be used as luminescent sensors for detection of tetracycline antibiotic.
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http://dx.doi.org/10.1016/j.jpba.2020.113444DOI Listing
September 2020

Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: executive summary and 2019 update of clinical management of cerebral venous sinus thrombosis.

Stroke Vasc Neurol 2020 06 13;5(2):152-158. Epub 2020 May 13.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University; Guangdong Provincial Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China

Aim: Cerebral venous sinus thrombosis (CVST) is a less common cerebrovascular disease that predominantly affects young patients. The incidence of CVST is 2-5/10 000 000/year, accounting for 0.5%-1% of all stroke. To reduce mortality and morbidity associated with CVST, Chinese Stroke Association commissioned the authors to write the current guideline on the management of CVST.

Methods: PubMed (MEDLINE), CNKI and Wanfang database were searched for studies related to CVST from 1 January 1990 to 31 July 2019. Data were synthesised by evidence tables. Each recommendation was fully discussed by the writing group members and reviewed by Chinese Stroke Association Stroke Fellow Committees. Levels of evidence grading algorithm of Chinese Stroke Association was used to grade each recommendation.

Results: This guideline mainly focuses on the diagnostic evaluation, therapeutic strategies and secondary prevention of CVST. CT/CTV and MRI/MRV are recommended in the initial imaging evaluation of patients with suspected CVST. Anticoagulation therapy with low-molecular weight heparin should be initiated in patients with CVST immediately. After the acute stage, warfarin is recommended for 3-6 months to prevent the recurrence of CVST and other venous thromboembolic events.

Conclusions: The guideline summarises the current evidence regarding the management of CVST, and provides references for diagnosis, treatment and secondary prevention of CVST in China.
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http://dx.doi.org/10.1136/svn-2020-000358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337369PMC
June 2020

Intermittent Theta Burst Stimulation Improves the Spatial Cognitive Function of Rats with Chronic Hypertension-induced Cerebral Small Vessel Disease.

Neuroscience 2020 06 27;437:98-106. Epub 2020 Apr 27.

Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, No. 58 Zhongshan Road 2, Guangzhou 510080, China. Electronic address:

We investigated whether intermittent theta burst stimulation (iTBS) can improve the spatial cognitive function of rats with hypertension-induced cerebral small vessel disease. To prove our hypothesis, stroke-prone renovascular hypertensive rats (RHRSPs) were treated with iTBS beginning at postoperative week 22. The Morris water maze was performed to assess spatial cognitive function. The expression of the N-methyl-d-aspartate receptor (NMDAR) subunits NR1, NR2A and NR2B, calcium/calmodulin-dependent protein kinase IIα (CaMKIIα), p-CaMKIIα and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit 1 (GluR1) in the hippocampus were evaluated by western blot analysis. The distribution of GluR1, glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule-1 (IBa-1) in the CA1 and CA3 regions and dentate gyrus (DG) of the hippocampus were evaluated by immunofluorescence analysis. Treatment with iTBS significantly improved the spatial cognitive function of RHRSPs, increased the expression of NR2B, p-CaMKIIα and GluR1 in the hippocampus, and decreased the proliferation of astrocytes and microglia. Our results showed that iTBS treatment had a beneficial effect on the cognitive impairments induced by cerebral small vessel disease, potentially through the activation of the NR2B-CaMKII pathway, an increase in GluR1 expression and the suppression of astrocyte and microglial activation.
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http://dx.doi.org/10.1016/j.neuroscience.2020.04.029DOI Listing
June 2020

Estradiol-Induced MMP-9 Expression via PELP1-Mediated Membrane-Initiated Signaling in ERα-Positive Breast Cancer Cells.

Horm Cancer 2020 04 10;11(2):87-96. Epub 2020 Feb 10.

Department of Pathology and Pathophysiology, College of Basic Medical Sciences, Harbin Medical University-Daqing, Daqing, 163319, Heilongjiang, China.

Proline-, glutamic acid-, leucine-rich protein 1 (PELP1) is a novel estrogen receptor (ER) coregulator, demonstrated distinctive characters from other ERα coregulators, and has been suggested to be involved in metastasis of several cancers. In ERα-positive breast cancer, PELP1 overexpression enhanced ruffles and filopodium-like structure stimulated by estradiol (E) through extranuclear cell signaling transduction hereby increased cell motility. However, whether PELP1 is also involved in extracellular matrix remodeling of ERα-positive breast cancer cells is still unknown. In this study, we investigated the role of PELP1 in E-induced MMP-9 expression and the underlined mechanism. The results demonstrated the following: E-induced ERα-positive MCF-7 breast cancer cell MMP-9 mRNA and protein expression in a rapid response and concentration-dependent manner. Knocked down PELP1 significantly suppressed E-induced MMP-9 expression. E-bovine serum albumin (BSA), a large molecular membrane-impenetrable conjugate of E, can also upregulate MMP-9 protein expression in MCF-7, and the action of E-BSA can be abolished by PI3K inhibitor LY294002; treating MCF-7 simultaneously with PELP1-shRNA and LY294002 did not show synergetic inhibitory effect on E-BSA-induced MMP-9 expression. Our results indicated that estrogen-induced MMP-9 expression in ER-positive breast cancer cells may be through PELP1-mediated PI3K/Akt signaling pathway.
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http://dx.doi.org/10.1007/s12672-020-00380-8DOI Listing
April 2020

Stroke Outcome Prediction by Blood Pressure Variability, Heart Rate Variability, and Baroreflex Sensitivity.

Stroke 2020 04 22;51(4):1317-1320. Epub 2020 Jan 22.

Division of Neurology, Department of Medicine and Therapeutics, The Chinese University of Hong Kong (L.X., V.C.T.M., K.S.W., T.W.L.).

Background and Purpose- Poststroke autonomic dysfunction portended an unfavorable prognosis. We investigated whether blood pressure variability (BPV), heart rate variability, and baroreflex sensitivity might predict stroke functional outcome. Methods- We calculated BPV, heart rate variability, baroreflex slope, and baroreflex effectiveness index from a 5-minute beat-to-beat blood pressure and heart rate monitoring within 7 days from the stroke onset. We compared the parameters between patients with a good outcome (modified Rankin Scale score, 0-2) and those with a poor outcome. Results- Among 142 patients (mean age, 63.9±10.2 years; 88.0% men), functional outcome was good in 112 (78.9%) and poor in 30 (21.1%). There were significant differences in admission National Institutes of Health Stroke Scale, prior stroke, high-frequency systolic BPV, low/high-frequency ratio of BPV, baroreflex sensitivity-up, and baroreflex sensitivity-total between the 2 groups (all <0.05). In multivariate analysis, National Institutes of Health Stroke Scale (OR, 1.672 [95% CI, 1.316-2.125]; <0.001), low/high-frequency ratio of systolic BPV (OR, 0.493 [95% CI, 0.250-0.973]; =0.041), and baroreflex effectiveness index-down (OR, 0.958 [95% CI, 0.924-0.992]; =0.017) independently predicted a poor functional outcome. Conclusions- A decreased low/high-frequency ratio of systolic BPV and impaired baroreflex sensitivity predicted an unfavorable stroke outcome, in addition to the established prognostic factor such as the National Institutes of Health Stroke Scale.
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http://dx.doi.org/10.1161/STROKEAHA.119.027981DOI Listing
April 2020

Urease inhibition studies of six Ni(II), Co(II) and Cu(II) complexes with two sexidentate NO-donor bis-Schiff base ligands: An experimental and DFT computational study.

J Inorg Biochem 2020 03 16;204:110959. Epub 2019 Dec 16.

Key Laboratory of Marine Chemistry Theory and Technology, Ministry of Education, College of Chemistry and Chemical Engineering, Ocean University of China, Qingdao, China. Electronic address:

Six novel complexes, [Ni(CHNO)]·2.25CHOH·0.5CHO (1), [Co(CHNO)] (2), [Cu(CHNO)]·2CHOH (3), [Ni(CHNOCl)]·2CHOH (4), [Co(CHNOCl)]·4CHOH (5) and [Cu(CHNOCl)]·2CHOH (6) with two sexidentate NO-donor bis-Schiff base ligands (CHNO = 1,2-bis(2-methoxy-6-formylphenoxy)ethane-l-tyrosine; CHNOCl = 1,2-bis(2-methoxy-6-formylphenoxy)ethane-l-4-chlorophenylalanine) have been synthesized and structurally characterized. Theoretical calculation of the six complexes was carried out by density functional theory (DFT) Becke's three-parameter hybrid (B3LYP) method employing the 6-3lG basis set, indicating that the calculation results are in accordance with experimental results. Moreover, the inhibitory activities of complexes 1-6 were tested in vitro against jack bean urease. At the same time, molecular docking was investigated to determine the probable binding mode. The experimental values and docking simulation exhibited that complexes 3 and 6 showed strong inhibitory activity (IC = 10.36 ± 1.13, 15.63 ± 3.04 μM) compared with the positive reference acetohydroxamic acid (IC = 26.99 ± 1.43 μM). Their structure-inhibitory activity relationship was further discussed from the perspective of molecular docking and theoretical calculation.
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http://dx.doi.org/10.1016/j.jinorgbio.2019.110959DOI Listing
March 2020

Peak width of skeletonized mean diffusivity and its association with age-related cognitive alterations and vascular risk factors.

Alzheimers Dement (Amst) 2019 Dec 25;11:721-729. Epub 2019 Oct 25.

Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.

Introduction: Only two studies investigated the associations between peak width of skeletonized mean diffusivity (PSMD) and age-related cognitive alterations, whereas none of the studies investigated the association with vascular risk factors.

Methods: We evaluated 801 stroke- and dementia-free elderlies with baseline and 3-year follow-up assessments. Regression analyses were used to assess the association between age-related cognitive functions and PSMD. Simple mediation models were used to study the mediation effect of PSMD between vascular risk factors and age-related cognitive outcomes.

Results: PSMD was negatively associated with processing speed at baseline and negatively associated with processing and memory scores at 3-year follow-up. The association between vascular risk factors and age-related cognition was mediated by PSMD, as well as other diffusion tensor imaging markers.

Discussion: PSMD is preferred over other diffusion tensor imaging markers as it is sensitive to age-related cognitive alterations and calculation is fully automated. PSMD is proposed as a research tool to monitor age-related cognitive alterations.
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http://dx.doi.org/10.1016/j.dadm.2019.09.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6829102PMC
December 2019

Novel lncRNA PSMG3‑AS1 functions as a miR‑143‑3p sponge to increase the proliferation and migration of breast cancer cells.

Oncol Rep 2020 Jan 25;43(1):229-239. Epub 2019 Oct 25.

Central Laboratory of The Fifth Affiliated Hospital of Harbin Medical University, Daqing, Heilongjiang 163711, P.R. China.

Long non‑coding RNAs (lncRNAs) are considered to be important regulators in breast cancer. In the present study, the potential mechanisms and functional roles of lncRNA PSMG3‑antisense (AS)1 were investigated in vivo and in vitro. The relative expression levels of lncRNA PSMG3‑AS1 and microRNA (miR)‑143‑3p were determined using reverse‑transcription quantitative PCR. The protein expression levels of collagen type 1 alpha 1 (COL1A1) and proliferating cell nuclear antigen (PCNA) were obtained using western blot analysis. Bioinformatics analysis was used to identify the relationship between PSMG3‑AS1, miR‑143‑3p and COL1A1. Colony forming and Cell Counting Kit‑8 assays were used to detect cell proliferation. Transwell and wound‑healing assays were used to determine cell migration. The results of the present study demonstrated that PSMG3‑AS1 expression was increased in breast cancer tumor tissues and cell lines, and that of miR‑143‑3p was decreased. Knockdown of PSMG3‑AS1 increased the level of miR‑143‑3p expression, which led to the mitigation of proliferation and migration capacity in breast carcinoma cells. Additionally, PSMG3‑AS1 knockdown was demonstrated to reduce the mRNA and protein expression levels of COL1A1. miR‑143‑3p mimic transfection reduced proliferation and migration in MDA‑MB‑231 and MCF‑7 cell lines. Furthermore, miR‑143‑3p inhibition significantly increased the proliferation and migration of breast cancer cells compared with the negative control group. The mRNA and protein expression levels of PCNA were reduced in the MCF‑7 cell line when transfected with miR‑143‑3p mimics and si‑PSMG3‑AS1. However, PCNA expression was increased in cells transfected with a miR‑143‑3p inhibitor. In conclusion, the results of the present study identified a novel lncRNA PSMG3‑AS1, which serves as a sponge for miR‑143‑3p in the pathogenesis of breast cancer. PSMG3‑AS1 may be used as a potential therapeutic target gene in breast cancer treatment.
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http://dx.doi.org/10.3892/or.2019.7390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6908943PMC
January 2020

Alcohol consumption, tobacco smoking, betel quid chewing and oral health associations with hypopharyngeal cancer among men in Central South China: a case-control study.

Cancer Manag Res 2019 10;11:6353-6364. Epub 2019 Jul 10.

Department of Otorhinolaryngology Head and Neck Surgery, Province Key Laboratory of Otolaryngology Critical Diseases, Xiangya Hospital of Central South University, Changsha, People's Republic of China.

Background: Hypopharyngeal cancer has relatively high incidence rates in China, especially in high-risk areas. However, data on the role of major risk factors in these areas of China are still limited.

Methods: We have evaluated the roles of alcohol, tobacco and betel quid consumption, and oral health, based on 278 hypopharyngeal cancer cases and 693 controls from two centers in Central South China. The odds ratio (OR) and 95% confidence interval (CI) values were estimated using logistic regression.

Results: We found that alcohol drinkers had a risk of hypopharyngeal cancer that was up to seven times higher than that for those who had never drunk. A very strong effect of traditional liquor as compared to other alcohol types was observed, with the OR reaching 11.26 (CI 6.53-19.41) for this cancer. Tobacco smokers were up to four times more likely to develop hypopharyngeal cancer than never smokers. The OR for betel quid chewing was 1.86 (CI 1.26-2.75) as compared to never users. Poor oral hygiene had a risk of hypopharyngeal cancer that was two times higher than that for normal oral hygiene.

Conclusion: In this study, we have shown for what is believed to be the first time the association of increased hypopharyngeal cancer incidence with alcohol, tobacco, betel quid and oral hygiene in China. Alcohol may play a larger role for hypopharyngeal cancer in this population than in populations in other areas.
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http://dx.doi.org/10.2147/CMAR.S203439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628859PMC
July 2019

Development of a magnetic core-shell FeO@TA@UiO-66 microsphere for removal of arsenic(III) and antimony(III) from aqueous solution.

J Hazard Mater 2019 10 1;378:120721. Epub 2019 Jun 1.

State Key Laboratory of Bio-Fiber and Eco-Textiles, College of Materials Science and Engineering, Collaborative Innovation Center for Marine Biobased Fibers and Ecological textiles, Institute of Marine Biobased Materials, Qingdao University, Qingdao 266071, China. Electronic address:

Removal of trivalent species of As and Sb from wastewater is crucial due to their more toxic and mobile properties. In this study, a novel magnetic core-shell microsphere FeO@TA@UiO-66 was developed via in-situ crystal growth of UiO-66 around the magnetic FeO modified by Tannic Acid (TA). Characterization of the microsphere by transmission electron microscopy (TEM) and X-ray diffraction spectroscopy (XRD) confirmed that UiO-66 was adhered on the surface of FeO functionalized by TA. Adsorption experiments showed that the magnetic FeO@TA@UiO-66 had high adsorption capacity for As(III) and Sb(III) and could be rapidly separated from aqueous media within two minutes after treatment. The adsorption kinetics and adsorption isotherms were described well by the pesudo-second order model and Langmuir model, respectively. In addition, the composite exhibited excellent removal performance for As(III) and Sb(III) in a broad solution chemistry environment, including pH and co-existing anions. Based on X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR) measurement, we proposed that the removal mechanism was mainly controlled through a synergistic interaction of surface complexation and hydrogen bonding. This study indicates the potential of the magnetic microsphere to be used as an effective material for the removal of As(III) and Sb(III) from water.
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http://dx.doi.org/10.1016/j.jhazmat.2019.05.114DOI Listing
October 2019

Resveratrol inhibits lipid accumulation in the intestine of atherosclerotic mice and macrophages.

J Cell Mol Med 2019 06 7;23(6):4313-4325. Epub 2019 Apr 7.

Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China.

Disordered intestinal metabolism is highly correlated with atherosclerotic diseases. Resveratrol protects against atherosclerotic diseases. Accordingly, this study aims to discover novel intestinal proatherosclerotic metabolites and potential therapeutic targets related to the anti-atherosclerotic effects of resveratrol. An untargeted metabolomics approach was employed to discover novel intestinal metabolic disturbances during atherosclerosis and resveratrol intervention. We found that multiple intestinal metabolic pathways were significantly disturbed during atherosclerosis and responsive to resveratrol intervention. Notably, resveratrol abolished intestinal fatty acid and monoglyceride accumulation in atherosclerotic mice. Meanwhile, oleate accumulation was one of the most prominent alterations in intestinal metabolism. Moreover, resveratrol attenuated oleate-triggered accumulation of total cholesterol, esterified cholesterol and neutral lipids in mouse RAW 264.7 macrophages by activating ABC transporter A1/G1-mediated cholesterol efflux through PPAR (peroxisome proliferator-activated receptor) α/γ activation. Furthermore, we confirmed that PPARα and PPARγ activation by WY14643 and pioglitazone, respectively, alleviated oleate-induced accumulation of total cholesterol, esterified cholesterol and neutral lipids by accelerating ABC transporter A1/G1-mediated cholesterol efflux. This study provides the first evidence that resveratrol abolishes intestinal fatty acid and monoglyceride accumulation in atherosclerotic mice, and that resveratrol suppresses oleate-induced accumulation of total cholesterol, esterified cholesterol and neutral lipids in macrophages by activating PPARα/γ signalling.
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http://dx.doi.org/10.1111/jcmm.14323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533483PMC
June 2019

Retinal image analytics detects white matter hyperintensities in healthy adults.

Ann Clin Transl Neurol 2019 01 15;6(1):98-105. Epub 2018 Nov 15.

Clinical Trials and Biostatistics Lab CUHK Shenzhen Research Institute Shenzhen China.

Objective: We investigated whether an automatic retinal image analysis (ARIA) incorporating machine learning approach can identify asymptomatic older adults harboring high burden of white matter hyperintensities (WMH) using MRI as gold standard.

Methods: In this cross-sectional study, we evaluated 180 community-dwelling, stroke-, and dementia-free healthy subjects and performed ARIA by acquiring a nonmydriatic retinal fundus image. The primary outcome was the diagnostic performance of ARIA in detecting significant WMH on MRI brain, defined as age-related white matter changes (ARWMC) grade ≥2. We analyzed both clinical variables and retinal characteristics using logistic regression analysis. We developed a machine learning network model with ARIA to estimate WMH and its classification.

Results: All 180 subjects completed MRI and ARIA. The mean age was 70.3 ± 4.5 years, 70 (39%) were male. Risk factor profiles were: 106 (59%) hypertension, 31 (17%) diabetes, and 47 (26%) hyperlipidemia. Severe WMH (global ARWMC grade ≥2) was found in 56 (31%) subjects. The performance for detecting severe WMH with sensitivity (SN) 0.929 (95% CI from 0.819 to 0.977) and specificity (SP) 0.984 (95% CI from 0.937 to 0.997) was excellent. There was a good correlation between WMH volume (log-transformed) obtained from MRI versus those estimated from retinal images using ARIA with a correlation coefficient of 0.897 (95% CI from 0.864 to 0.922).

Interpretation: We developed a robust algorithm to automatically evaluate retinal fundus image that can identify subjects with high WMH burden. Further community-based prospective studies should be performed for early screening of population at risk of cerebral small vessel disease.
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http://dx.doi.org/10.1002/acn3.688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331948PMC
January 2019

mi R -15a/15b Cluster Modulates Survival of Mesenchymal Stem Cells to Improve Its Therapeutic Efficacy of Myocardial Infarction.

J Am Heart Assoc 2019 01;8(1):e010157

1 Department of Cardiology The 2nd Hospital of Harbin Medical University Nangang District Harbin China.

Background The poor viability of transplanted mesenchymal stem cells (MSCs) hampers their therapeutic efficacy for ischemic heart disease. Micro RNA s are involved in regulation of MSC survival and function. The present study was designed to investigate the molecular effects of mi R -15a/15b on MSC survival, focusing on the role of vascular endothelial growth factor receptor 2. Methods and Results We first harvested donor luc(Luciferase)- MSC s (5×10) isolated from the luciferase transgenic mice with FVB background. Luc- MSC s were transfected with miR-15a/15b mimics or inhibitors and cultured under oxygen glucose deprivation condition for 12 hours to mimics the harsh microenvironment in infarcted heart; they were subjected to MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide?Thiazolyl Blue Tetrazolium Bromide) assay, bioluminescence imaging, quantitative reverse transcription-polymerase chain reaction, transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling assay, and flow cytometry. Furthermore, the levels of vascular endothelial growth factor receptor 2, protein kinase B, p(Phosphorylate)-protein kinase B, Bcl-2, Bax, and caspase-3 proteins were available by Western blotting assay. In vivo, acute myocardial infarction was induced in 24 mice by coronary ligation, with subsequent receipt of Luc- MSC s, Luc- MSC s+miR-15a/15b inhibitors, or PBS treatment. The therapeutic procedure and treatment effects were tracked and assessed using bioluminescence imaging and echocardiographic measurement. Next, ex vivo imaging and immunohistochemistry were conducted to verify the distribution of MSC s. We demonstrated that miR-15a/15b targeted vascular endothelial growth factor receptor 2 to modulate MSC survival, possibly via phosphatidylinositol 3-kinase/protein kinase B signaling pathway, which was proved by bioluminescence imaging, immunohistochemistry analysis, and echocardiographic measurement. Conclusions Luc- MSC s could be followed dynamically in vitro and in vivo by bioluminescence imaging, and the role of mi R -15a/b could be inferred from the loss of signals from luc- MSC s. This finding may have practical clinical implications in mi R -15a/15b-modified MSC transplantation in treating myocardial infarction.
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http://dx.doi.org/10.1161/JAHA.118.010157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405735PMC
January 2019

Orthostatic Hypotension and Albuminocytologic Dissociation as Primary Manifestations of the Paraneoplastic Syndrome.

Eur Neurol 2018 19;80(1-2):78-81. Epub 2018 Oct 19.

Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.

Background: Orthostatic hypotension (OH) is the key manifestation of autonomic dysfunction with many causes. Systemic neurological causes such as paraneoplastic syndrome are usually ignored.

Methods: We retrospectively analyzed clinical and examination data of 2 patients who were hospitalized, with onset symptom of OH and who were diagnosed as paraneoplastic syndrome.

Results: The patients were characteristic of an initial symptom of OH, positive anti-Hu antibody and albuminocytologic dissociation in the cerebrospinal fluid. Patient 2 died and Patient 1 worsened during follow-up.

Conclusions: The diagnosis of paraneoplastic syndrome is usually neglected when the onset symptoms are autonomic dysfunctions such as OH. Neurologists should improve their knowledge to diagnose accurately.
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http://dx.doi.org/10.1159/000493865DOI Listing
January 2019

Closure versus Medical Therapy for Patent Foramen Ovale in Patients with Cryptogenic Stroke: An Updated Meta-Analysis of Randomized Controlled Trials.

J Stroke Cerebrovasc Dis 2018 Dec 2;27(12):3463-3472. Epub 2018 Sep 2.

Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. Electronic address:

Background: Debate continues about whether percutaneous closure of patent foramen ovale (PFO) is a better strategy for the treatment of patients with cryptogenic stroke in comparison with medical therapy alone. We performed an updated meta-analysis of 6 randomized controlled trials (RCTs) to assess the effectiveness and safety of percutaneous closure of PFO as secondary prevention for patients with previous cryptogenic stroke compared to medical therapy.

Materials And Methods: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, conference proceedings, and Internet-based resources were retrieved in March 2018 for eligible RCTs. The primary effectiveness outcome was recurrent strokes.

Results: Six studies meeting our selection criteria were identified. Among 3560 participants, 1889 patients were assigned to PFO closure and 1671 patients to medical therapy. There were no significant differences among the baseline characteristics. The pooled incidence of recurrent strokes was 1.96% in the PFO closure group and 4.60% in the medical therapy group (Relative risk [RR] .39, 95% confidence interval [CI] .18-.82, P = .01). Newly detected atrial fibrillation occurred in 77 of 1844 (4.18%) patients in the PFO closure group and in 12 of 1667 (.72%) patients in the medical therapy group (RR 4.56, 95% CI 2.21-9.41, P <.0001). There was no difference in terms of serious adverse events, total mortality or bleeding between 2 groups.

Conclusions: Our updated meta-analysis suggests that in patients with PFO and cryptogenic stroke, the rate of recurrent stroke is significantly reduced with percutaneous closure of PFO compared to the medical therapy.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.08.008DOI Listing
December 2018

Novel TBC1D24 Mutations in a Case of Nonconvulsive Status Epilepticus.

Front Neurol 2018 31;9:623. Epub 2018 Jul 31.

Department of Neurology and Stroke Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Nonconvulsive status epilepticus (NCSE) is an uncommon clinical manifestation in patients with TBC1D24 mutations. In addition, NCSE has not been reported as a syndrome together with cerebellar ataxia and ophthalmoplegia. We herein report the clinical and genetic features of a four-year-old patient with NCSE, cerebellar ataxia, and ophthalmoplegia caused by hitherto unidentified TBC1D24 mutations. We performed 24-h video electroencephalogram (EEG), magnetic resonance imaging, and gene sequencing on the patient and her parents to determine the diagnosis. We identified a novel c.1416_1437del (p.Ser473Argfs43) mutation, as well as the previously identified c.1499C>T (p.Ala500Val) mutation in TBC1D24, by using targeted next-generation sequencing. The novel mutation (inherited from the mother) is the first reported deletion mutation longer than 20 bp in TBC1D24. The p.Ala500Val mutation inherited from father has been reported in a German patient with infantile myoclonic, for whom results from the EEG and neuroimaging were normal. These two mutations resulted in the severe phenotypes observed in our patient The identification of the novel TBC1D24 mutation and consequent complicated clinical manifestations suggest that patients with NCSE and ataxia demand more attention. We further recommend that genetic test should be administered to these patients to avoid genetic inheritance of this mutation.
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http://dx.doi.org/10.3389/fneur.2018.00623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079244PMC
July 2018

Multimodality Molecular Imaging of Cardiovascular Disease Based on Nanoprobes.

Cell Physiol Biochem 2018 31;48(4):1401-1415. Epub 2018 Jul 31.

Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China.

Recently, multimodality molecular imaging has evolved into a fast-growing research field with goals of detecting and measuring biological processes in vivo non-invasively. Researchers have come to realize that the complementary abilities of different imaging modalities over single modality could provide more precisely information for the diagnosis of diseases. At present, nanoparticles-based multimodal imaging probes have received significant attention because of their ease of preparation and straightforward integration of each modality into one entity. More importantly, nanotechnology has an increasing impact on multimodality molecular imaging of cardiovascular diseases, such as atherosclerosis and vulnerable plaque, myocardial infarction, angiogenesis, apoptosis and so on. In this review, we briefly summarize that various nanoprobes are exploited for targeted molecular imaging of cardiovascular diseases, as well as associated multimodality imaging approaches and their applications in the diagnosis and treatment of cardiovascular diseases.
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http://dx.doi.org/10.1159/000492251DOI Listing
September 2018

Metabolomics Reveals Protection of Resveratrol in Diet-Induced Metabolic Risk Factors in Abdominal Muscle.

Cell Physiol Biochem 2018 7;45(3):1136-1148. Epub 2018 Feb 7.

College of Pharmacy, Harbin Medical University-Daqing, Daqing, China.

Background/aims: Abdominal obesity is recognized as the main reason of metabolic syndrome, which is closely related to disordered skeletal and/or abdominal muscle metabolic functions. Metabolomics is a comprehensive assessment system in biological metabolites. The aim of our present study is to investigate the diet-induced metabolic risk factors by metabolic in the abdominal muscles and clarify the relationship between atheroprotective effects of Resveratrol (Rev) and abdominal muscles metabolic components during the development of atherosclerosis.

Methods: The mice were randomly divided into three groups including normal group (N), high fat diet (HFD or H) group and high fat diet with Rev treated group (HR). GC-MS combined with pattern recognition approaches were employed to obtain comprehensive metabolic signatures and related differential metabolites after 24 week HFD feeding. Oil Red O staining and Electron microscopy technology (EMT) were employed to detect the size of fatty plaques and intracellular lipid accumulation, respectively.

Results: The result indicated that 22 types of metabolites in the abdominal muscles were obviously altered by HFD feeding group. Moreover, Rev treatment obviously increased 11 different kinds of metabolites, most of which were involved in the carbohydrate, amino acid and lipid metabolisms. Importantly, these elevated different metabolites were involved in pathways mainly related to galactose metabolism, alanine, aspartate and glutamate metabolism, glyoxylate and dicarboxylate metabolism in abdominal muscles. Oil Red O staining and Electron microscopy showed less lipid accumulation in the lesions and decreased intracellular lipid deposition in the foam cells in HR group.

Conclusions: We concluded that Rev produced a beneficial effect partially by modulating multiple metabolism pathways and metabolites in the abdominal muscles, which may provide a new protective mechanism of Rev on the progression of atherosclerosis. These notably changed metabolites might be potential biomarkers or therapeutic targets during development of metabolic syndrome and atherosclerosis.
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http://dx.doi.org/10.1159/000487354DOI Listing
March 2018

Effect of Body Mass on Oxygenation and Intra-Abdominal Pressure When Using a Jackson Surgical Table in the Prone Position During Lumbar Surgery.

Spine (Phila Pa 1976) 2018 07;43(14):965-970

Division of Anesthesiology and Intensive Care, Changhai Hospital, the Second Military Medical University, Shanghai, China.

Study Design: Prospective observational study.

Objective: To test the hypothesis that different types of surgical frame and the patient's body mass index (BMI) can affect pulmonary compliance, intra-abdominal pressure (IAP), and oxygenation.

Summary Of Background Data: The oxygenation index (PaO2/FiO2) and IAP are known to be associated with BMI when patients are in the supine position. However, there are few reports on the correlation between BMI, the oxygenation index, and IAP in the prone position, especially when a Jackson surgical table is used.

Methods: Thirty-seven adult patients were divided into two groups according to BMI: normal-weight patients (n = 19, BMI: 18.5-24.9 kg m) and overweight patients (n = 18, BMI ≥ 25 kg m). After the induction of general anesthesia, patients were turned to the prone position onto either a Jackson surgical table (Mizuho OSI) or a general surgical table (MAQUET; foam pad, China). The patient's IAP, peak airway pressure, pulmonary dynamic compliance (Cdyn), and oxygenation index were recorded.

Results: In overweight patients, there was a greater increase in peak airway pressure and a greater decrease in Cdyn observed when a general surgical table was used compared with the Jackson surgical table. When the Jackson surgical table was used, there was a greater increase in the oxygenation index and a greater decrease in IAP. There was a significant negative correlation between the oxygenation index and BMI and a significant positive correlation between IAP and BMI in the prone position.

Conclusion: Turning patients from the supine to the prone position during anesthesia results in an increase in the oxygenation index and a decrease in IAP. Both of these factors are dependent upon the type of surgical frame used and the patient's BMI. The reduction in IAP was particularly significant when a Jackson surgical table was used for overweight patients.

Level Of Evidence: 4.
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http://dx.doi.org/10.1097/BRS.0000000000002505DOI Listing
July 2018

Posttranscriptional regulation of lipid metabolism by non-coding RNAs and RNA binding proteins.

Semin Cell Dev Biol 2018 09 6;81:129-140. Epub 2017 Dec 6.

Vascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Department of Comparative Medicine, Department of Pathology, Yale University School of Medicine, 10 Amistad St., New Haven, CT 06510, USA. Electronic address:

Alterations in lipoprotein metabolism enhance the risk of cardiometabolic disorders including type-2 diabetes and atherosclerosis, the leading cause of death in Western societies. While the transcriptional regulation of lipid metabolism has been well characterized, recent studies have uncovered the importance of microRNAs (miRNAs), long-non-coding RNAs (lncRNAs) and RNA binding proteins (RBP) in regulating the expression of lipid-related genes at the posttranscriptional level. Work from several groups has identified a number of miRNAs, including miR-33, miR-122 and miR-148a, that play a prominent role in controlling cholesterol homeostasis and lipoprotein metabolism. Importantly, dysregulation of miRNA expression has been associated with dyslipidemia, suggesting that manipulating the expression of these miRNAs could be a useful therapeutic approach to ameliorate cardiovascular disease (CVD). The role of lncRNAs in regulating lipid metabolism has recently emerged and several groups have demonstrated their regulation of lipoprotein metabolism. However, given the high abundance of lncRNAs and the poor-genetic conservation between species, much work will be needed to elucidate the specific role of lncRNAs in controlling lipoprotein metabolism. In this review article, we summarize recent findings in the field and highlight the specific contribution of lncRNAs and RBPs in regulating lipid metabolism.
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http://dx.doi.org/10.1016/j.semcdb.2017.11.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5975105PMC
September 2018

Cerebral Venous Collagen Remodeling in a Modified White Matter Lesions Animal Model.

Neuroscience 2017 Dec 31;367:72-84. Epub 2017 Oct 31.

Department of Neurology, First affiliated Hospital, Sun Yat-sen University, Guanghzou, China. Electronic address:

To mimic the expected pathological changes of white matter lesions (WMLs) and increase the stability, we applied modified two-vessel occlusion (modified 2VO) (1-week interval bilateral carotid artery occlusion) in stroke-prone renovascular hypertensive rats (RHRSP) and established a modified WMLs model (RHRSP/modified 2VO) that compared their phenotypes with RHRSP and sham-operated rats. In addition, we tried to differentiate small veins from small arteries through the presence of smooth muscle to study the pathological changes of small veins detailed in the model. RHRSP/modified 2VO rats showed higher stability and more extensive white matter damage without an obvious increase in mortality rate at 12 weeks after the modified 2VO operation compared to RHRSP rats. RHRSP/modified 2VO rats showed more severe small venous collagen deposition than RHRSP rats, and the majority of the deposition was collagen I and IV rather than collagen III. In addition, RHRSP/modified 2VO rats possessed cognitive impairment, mild wall thickness and blood-brain barrier disruption. Our findings suggest that the modified WMLs model (RHRSP/modified 2VO) mimics cognitive impairment and small vessel pathological changes similar to WMLs in humans. Differentiating small veins from small arteries through smooth muscle is feasible, and marked small venous deposition may play an important role in the hypertensive white matter lesions.
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http://dx.doi.org/10.1016/j.neuroscience.2017.10.031DOI Listing
December 2017

MiR-367 regulates cell proliferation and metastasis by targeting metastasis-associated protein 3 (MTA3) in clear-cell renal cell carcinoma.

Oncotarget 2017 Sep 27;8(38):63084-63095. Epub 2017 Jun 27.

Department of Urology, The First Affiliated Hospital of The Harbin Medical University, Harbin 150001, China.

Clear-cell renal cell carcinoma (ccRCC) is an aggressive and malignant kidney cancer which has the worst prognosis. Although microRNAs (miRNAs) have recently been identified as a novel class of regulators in oncogenesis and metastasis, there are few studies on their participation in ccRCC. In the present study, we observed that miR-367 expression was increased in both human ccRCC tissues and cell lines. Cell proliferation was evaluated by MTT assay and 5-Ethynyl-2'-deoxyuridine (EdU) assay kit, which indicated that inhibition of miR-367 could suppress the ccRCC proliferation. Forced expression of miR-367 substantially induced cell migration and invasion evidenced by wound-healing and transwell assays, and this carcinogenesis could be abolished by miR-367 inhibitor treatment. Further analysis identified Metastasis-Associated Protein 3 (MTA3) as a direct target of miR-367. QRT-PCR and western blot results indicated the correlative expression of miR-367 and MTA3 in ccRCC tissue samples. Overexpression of MTA3 reversed miR-367-induced cell proliferation, migration and invasion. Our data uncovered a novel molecular interaction between miR-367 and MTA3, indicating a therapeutic strategy of miR-367 for ccRCC.
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http://dx.doi.org/10.18632/oncotarget.18647DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5609905PMC
September 2017

Autonomic Neuropathy and Albuminocytologic Dissociation in Cerebrospinal Fluid As the Presenting Features of Primary Amyloidosis: A Case Report.

Front Neurol 2017 26;8:368. Epub 2017 Jul 26.

Department of Neurology and Stroke Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Objective: Primary amyloidosis is a disease with a poor prognosis and multi-organ involvement. Here, we report the clinical and pathological features of a patient with primary amyloidosis featuring autonomic neuropathy as the initial symptom and albuminocytologic dissociation in the cerebrospinal fluid (CSF).

Methods: The patient was a 60-year-old Chinese male with numbness, orthostatic hypotension, and gastrointestinal symptoms. For diagnosis, we performed an electromyogram (EMG), lumbar puncture, Bence Jones protein urine test, serum electrophoresis blood test, sural nerve and rectal membrane biopsies, transthyretin (TTR) gene sequencing, and bone marrow puncture.

Results: Congo red staining of sural nerve and rectal membrane biopsies showed amyloid deposition and apple-green birefringence was visualized under polarized light microscopy. TTR gene sequencing showed no causative mutation. Following lumbar puncture, normal CSF cell counts and elevated CSF protein concentration (1,680 mg/L) were detected. Bone marrow puncture showed that out of the total number of whole blood cells, 0.56% were abnormal plasma cells and that 87.4% of the total number of plasma cells were abnormal. EMG results showed mixed peripheral nerve damage predominately in the sensory nerve fibers.

Conclusion: Obvious symptoms of neuropathy, particularly autonomic neuropathy, albuminocytologic dissociation, and organ function damage suggested a diagnosis of amyloidosis. In such patients, neurologists should use caution to differentiate between chronic inflammatory demyelinating polyneuropathy, primary amyloidosis, and familial amyloid neuropathy.
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http://dx.doi.org/10.3389/fneur.2017.00368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5526844PMC
July 2017

Resveratrol Protects Against Pulmonary Arterial Hypertension in Rats via Activation of Silent Information Regulator 1.

Cell Physiol Biochem 2017 11;42(1):55-67. Epub 2017 May 11.

College of Pharmacy, Harbin Medical University-Daqing, Daqing, China.

Background/objectives: The polyphenol resveratrol (Rev) has been found to exhibit various beneficial effects including prevention of pulmonary arterial hypertension (PAH). The present study was designed to investigate the action and potential mechanism of Rev on PAH, focusing on the role of SIRT1 (Silent Information Regulator 1) in apoptosis of pulmonary artery smooth muscle cells (PASMCs).

Methods: PAH rats were established by exposure to hypoxia for 21 days. Rev and SRT1720 (a selective SIRT1 activator) were used to reverse PAH by gavaging rats. PASMCs were confronted with hypoxia for 24 h or 48 h and were then treated with Rev or SRT1720 in vitro. Western blot was performed to detect the protein expression of SIRT1. CCK-8 and scratch wound experiments were carried out to verify cell proliferation. In addition, the TUNEL positive assay and flow cytometry assay were used to measure PASMC apoptosis. Mitochondrial permeability transition (mPT) was identified by confocal microscopy. Right ventricular systolic pressure (RVSP) was determined with a Gould pressure transducer, and right ventricular hypertrophy (RVH) was determined by weighing the cardiac muscle.

Results: We demonstrated that Rev could reverse the remodelling of the pulmonary vasculature, thus contributing to alleviating the severity of PAH. Down-regulation of SIRT1 was observed in PAH, but administration of Rev had no obvious effect on the protein expression of SIRT1. In addition, Rev could induce mitochondrial swelling and nuclear pyknosis, leading to small, dense, and dysmorphic mitochondria in rats exposed to hypoxia alone. Rev treatment inhibited PASMC proliferation in a dose-dependent manner in vitro. Incubation with SRT1720, a specific activator of SIRT1, significantly retarded PASMC proliferation and promoted PASMC apoptosis in vitro. The mechanism could be associated with inducing mPT damage in PASMCs. Rev and SRT1720 treatment mitigated RVSP and reduced RVH.

Conclusion: Rev produced a beneficial effect partially by enhancing the activation of SIRT1, thus improving RVSP and reducing RVH. SIRT1 activation increased PASMC apoptosis by inducing mPT dysfunction, which might be a novel future strategy for the treatment of PAH.
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http://dx.doi.org/10.1159/000477115DOI Listing
July 2017