Publications by authors named "Yue Wan"

102 Publications

Integrated gut microbiota and fecal metabolomics reveal the renoprotective effect of Rehmanniae Radix Preparata and Corni Fructus on adenine-induced CKD rats.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Jun 24;1174:122728. Epub 2021 Apr 24.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, PR China. Electronic address:

Rehmanniae Radix Preparata (RR) and Corni Fructus (CF), well-known traditional Chinese medicines (TCMs), were generally used together in the clinical practices to treat chronic kidney disease (CKD) with synergistic effects for thousands of years, but their combination mechanism remains largely unknown so far. Recent evidences have implicated intestinal flora as potential targets for the therapy of CKD. In this study, the CKD rat model was induced by adenine. The levels of proteinuria, serum creatine (SCr), blood urea nitrogen (BUN) and creatinine clearance (Ccr) were used to assess the cooperation effect of RR and CF. Furthermore, high-throughput 16S ribosomal RNA (rRNA) gene sequencing combined with fecal metabonomics based on UPLC-Q-TOF-MS/MS were applied to explore the variations of intestinal flora and their metabolic profiles. 16S rRNA gene sequencing data indicated that CKD rats treated with RR, CF and RC showed the differences in the composition of gut microbiota. The abundance of beneficial bacteria including Ruminococcaceae UCG-014, Ruminococcus 1, Prevotellaceae_NK3B31_group, Lachnospiraceae NK4A136 group and Lachnospiraceae UCG-001 were elevated in various degrees, while the opportunistic pathogen such as Desulfovibrio was markedly decreased after the treatment. Moreover, fecal metabolite profiles revealed 15 different metabolites associated with CKD. These metabolites were mainly involved in the related metabolic pathways such as amino acid metabolism, bile acids metabolism and glycerophospholipid metabolism. The results implied that gut flora and their metabolites might play a vital role in the progress of CKD, which provided a potential target for the development of novel drugs for the therapy of CKD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jchromb.2021.122728DOI Listing
June 2021

Selection of a picomolar antibody that targets CXCR2-mediated neutrophil activation and alleviates EAE symptoms.

Nat Commun 2021 05 5;12(1):2547. Epub 2021 May 5.

Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, China.

Receptors and their ligands are important therapeutic targets for about one third of marketed drugs. Here, we describe an epitope-guided approach for selection of antibodies that modulate cellular signaling of targeted receptors. We chose CXC chemokine receptor 2 (CXCR2) in the G-protein coupled receptor superfamily as receptor and a CXCR2 N-terminal peptide for antibody selection. We obtain a highly selective, tight-binding antibody from a 10-member antibody library using combinatorial enrichment. Structural and Hydrogen-Deuterium-Exchange mass spectrometry analyses demonstrate antibody interaction with an N-terminal region of CXCR2 that is part of the IL-8 epitope. The antibody strongly inhibits IL-8-induced and CXCR2-mediated neutrophil chemotaxis in vitro and alleviates hCXCR2-dependent experimental autoimmune encephalomyelitis symptoms in mice. As inappropriate neutrophil migration accompanies many diseases including inflammatory bowel disease, glomerulonephritis, allergic asthma, chronic obstructive pulmonary disease, and cancer, this antibody has potential for development as a therapeutic agent, akin to anti-TNF antibodies. However, an important difference here is that the antibody targets the chemokine receptor and competes with natural ligand, rather than targeting the ligand itself.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-22810-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100106PMC
May 2021

The synergic renoprotective effect of Rehmanniae Radix Preparata and Corni Fructus on adenine-induced chronic kidney disease rats based on integrated plasma metabolomics and network pharmacology approach.

Life Sci 2021 Aug 27;278:119545. Epub 2021 Apr 27.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing 210023, PR China. Electronic address:

Aims: Rehmanniae Radix Preparata (RR) and Corni Fructus (CF) are commonly used together for the treatment of chronic kidney disease (CKD) in the clinical practices for thousands of years. However, little information on their synergy mechanism is available.

Main Methods: In this study, an integrated approach combining ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based metabonomics and network pharmacology was adopted to elucidate the cooperation mechanism of RR and CF on the amelioration of CKD. Furthermore, the targets from network pharmacology and metabolism pathways were jointly analyzed. Finally, the activities of key metabolic enzymes were experimentally validated by ELISA.

Key Findings: Metabolic profiling indicated that the metabolic disturbance in plasma was markedly alleviated after treatment. Nine putative biomarkers mainly involving in phenylalanine, tyrosine and tryptophan biosynthesis and tyrosine metabolism were identified. Moreover, the compound-target-pathway network of RR and CF for CKD treatment was constructed by network pharmacology, which was related to tyrosine metabolism and arginine and proline metabolism. The results were partly consistent with the findings of plasma metabolomics.

Significance: In conclusion, this study solidly supported and enhanced current understanding of the synergy effects of RR and CF on CKD. Meanwhile, it also confirmed the feasibility of combining metabolomics and network pharmacology to identify active components and elucidate the pharmacological effects of traditional Chinese medicines (TCMs).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.lfs.2021.119545DOI Listing
August 2021

Charge transport physics of a unique class of rigid-rod conjugated polymers with fused-ring conjugated units linked by double carbon-carbon bonds.

Sci Adv 2021 Apr 28;7(18). Epub 2021 Apr 28.

Optoelectronics Group, Cavendish Laboratory, JJ Thomson Avenue, Cambridge CB3 0HE, UK.

We investigate the charge transport physics of a previously unidentified class of electron-deficient conjugated polymers that do not contain any single bonds linking monomer units along the backbone but only double-bond linkages. Such polymers would be expected to behave as rigid rods, but little is known about their actual chain conformations and electronic structure. Here, we present a detailed study of the structural and charge transport properties of a family of four such polymers. By adopting a copolymer design, we achieve high electron mobilities up to 0.5 cm V s Field-induced electron spin resonance measurements of charge dynamics provide evidence for relatively slow hopping over, however, long distances. Our work provides important insights into the factors that limit charge transport in this unique class of polymers and allows us to identify molecular design strategies for achieving even higher levels of performance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/sciadv.abe5280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081371PMC
April 2021

Analysis and validation of human targets and treatments using a hepatocellular carcinoma-immune humanized mouse model.

Hepatology 2021 Mar 18. Epub 2021 Mar 18.

Institute of Molecular and Cell Biology, Agency for Science, Technology and Research (A*STAR), 138673, Singapore, Singapore.

Background & Aims: Recent development of multiple treatments for human hepatocellular carcinoma (HCC) has allowed us to select combination therapy to enhance the effectiveness of monotherapy. Optimal selection of therapies bases on both HCC and its microenvironment. Therefore, it is critical to develop and validate new pre-clinical animal models for testing clinical therapeutic solutions.

Approach & Results: We established cell line-based or patient-derived xenograft hepatocellular carcinoma-immune humanized subcutaneous and orthotopic mouse models. Mice were injected with human specific antibodies to deplete human immune cell. We analyzed the transcription profiles of HCC cells and human immune cells by Real-Time PCR and RNA-sequencing. The protein level of HCC tumor cells/tissues or human immune cells was determined by flow cytometry, western blot and immunohistochemistry. The HCC tumor size was measured after single, dual and triple-combination treatment using C188-9, bevacizumab, and pembrolizumab. In our study, human immune cells in the tumor microenvironment were strongly selected and modulated by HCC, which promoted the activation of the IL-6/JAK2/STAT3 signal pathway in tumor cells and led to augmented HCC proliferation and angiogenesis by releasing angiogenic cytokines in HCC-immune humanized mice. In particular, intratumor hCD14 cells could produce IL-33 via DAMP-TLR4-AP1, which up-regulated IL-6 in other intratumor immune cells and activated the JAK2/STAT3 pathway in HCC. Specific knockdown of CD14 gene in human monocytes could impair IL-33 production induced by cell lysates. Subsequently, we evaluated the in vivo anti-HCC effect of C188-9, bevacizumab, and pembrolizumab. The results showed that the anti-HCC effect of triple-combination therapy was superior to that of single or dual treatments.

Conclusions: HCC-immune humanized mouse models are suitable for identifying targets from cancer and immune components and testing combinational therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hep.31812DOI Listing
March 2021

miR-582-5p Is a Tumor Suppressor microRNA Targeting the Hippo-YAP/TAZ Signaling Pathway in Non-Small Cell Lung Cancer.

Cancers (Basel) 2021 Feb 11;13(4). Epub 2021 Feb 11.

Laboratory of Precision Oncology and Cancer Evolution, Genome Institute of Singapore, A*STAR, Singapore 138672, Singapore.

The Hippo-YAP/TAZ signaling pathway is an evolutionarily conserved signaling pathway involved in a broad spectrum of biological processes, including tumorigenesis. Whilst aberrant Hippo-YAP/TAZ signaling is frequently reported in various cancers, the genetic alterations of this pathway are relatively rare, suggesting regulation at the post-transcriptional level. MicroRNAs play key role in tumorigenesis by regulating gene expression post-transcriptionally. Amongst the cancer-relevant microRNAs, miR-582-5p suppresses cell growth and tumorigenesis by inhibiting the expression of oncogenes, including AKT3, MAP3K2 and NOTCH1. Given the oncogenic role of YAP/TAZ in solid tumors, we scrutinized the possible interplay between miR-582-5p and Hippo-YAP/TAZ signaling. Correlation analysis in NSCLC cells revealed a positive relationship between the expression of mature miR-582-5p and the proportion of phosphorylated YAP/TAZ. Intriguingly, YAP/TAZ knockdown reduced the expression of mature miR-582-5p but increased that of primary miR-582. Overexpression of miR-582-5p resulted in increased phosphorylation of YAP/TAZ with a concomitant reduction in cell proliferation and enhanced apoptosis. Mechanistically, we find that miR-582-5p targets actin regulators NCKAP1 and PIP5K1C, which may be responsible for the observed alteration in F-actin, known to modulate YAP/TAZ. We postulate that regulation of the actin cytoskeleton by miR-582-5p may attenuate YAP/TAZ activity. Altogether, this study reveals a novel mechanism of YAP/TAZ regulation by miR-582-5p in a cytoskeleton-dependent manner and suggests a negative feedback loop, highlighting the therapeutic potential of restoring miR-582-5p expression in treating NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13040756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918774PMC
February 2021

Understanding nutritional intake of Chinese farmers from the perspective of sustainable livelihood analysis.

Environ Sci Pollut Res Int 2021 Mar 1. Epub 2021 Mar 1.

College of Economics and Management, Nanjing Agricultural University, No. 1 WeiGang Street, Nanjing, 210095, China.

Based on the framework of sustainable livelihood analysis and using the China Health and Nutrition Survey (CHNS) data, this paper examines the connection between livelihood assets and farmers' nutritional intake. Results show that capital endowment and nutritional intake of farmers with diversified production are greater than those who specialize; capital endowment and nutritional intake of horticultural households are greater than those who engage in agriculture. Compared with non-economically disadvantaged households, higher livelihood assets have significant association with improved fat and protein intake of economically disadvantaged households. Compared with diversified farmers, more livelihood assets have significant association with improved energy and carbohydrate intake of agricultural households. Compared with those who specialize, additional livelihood assets have significant association with improved fat and protein intake of farmers with diversified production.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-021-12872-3DOI Listing
March 2021

Apurinic/apyrimidinic endonuclease 1/reduction-oxidation effector factor-1 (APE1) regulates the expression of NLR family pyrin domain containing 3 (NLRP3) inflammasome through modulating transcription factor NF-κB and promoting the secretion of inflammatory mediators in macrophages.

Ann Transl Med 2021 Jan;9(2):145

Radiation Oncology Center, Chongqing University Cancer Hospital, Chongqing, China.

Background: Inflammatory mediators play an important role in the occurrence, development, and metastasis of tumors. The aim of the present study was to elucidate the effect of apurinic/apyrimidinic endonuclease 1/reduction-oxidation effector factor-1 (APE1) on inflammatory mediator secretion, which is dependent on the APE1-mediated NLR family pyrin domain containing 3 (NLRP3) regulatory mechanism.

Methods: The human myeloid leukemia mononuclear cell line (THP-1) cells were cultured and polarized to M2 subset macrophages. Enzyme-linked immunosorbent assay was used for determining tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-18, IL-10, and IL-33 levels. Reverse transcription-polymerase chain reaction and western blot were used for evaluating TNF-α, NLR family pyrin domain containing 1 (NLRP1), NLRP3, caspase-1, and apoptosis-associated speck-like protein containing a card expression. Plasmid silencing gene (APE1) was synthesized and packaged into lentiviral. For activating inflammasomes, M2-type THP-1 cells were transfected with lentiviral vector APE1 incubated with lipopolysaccharide (LPS) (100 ng/mL)/ inhibitor (E3330, 20 µM) and ATP. Electrophoretic mobility shift assay and dual-luciferase reporter assay were used for determining the interaction between NLRP3 and nuclear factor-κB (NF-κB) molecule.

Results: APE1 significantly induced LPS-induced pro-inflammatory cytokine production, including TNF-α, IL-1β, and IL18, compared with THP-1 cells without APE1 treatment (P<0.05). APE1 promoted LPS-induced NLRP3 inflammasome activation by modulating the gene transcription of NLRP3-associated molecules. APE1 enhanced LPS-induced NLRP3 inflammasome activation by regulating NLRP3 and caspase-1 protein expression. APE1 improved NLRP3 activity by modulating the interaction between NLRP3 and NF-κB, and the modulation of NF-κB. APE1 promoted LPS-induced NLRP3 inflammasome activation through an NF-κB-dependent pathway.

Conclusions: APE1 regulates the expression of NLRP3 by modulating transcription factor NF-κB and further promoting the secretion of inflammatory mediators IL-1β and IL-18 in macrophages. The findings of the present study provide theoretical and experimental bases for the design of tumor-associated macrophage (TAM)-targeted therapy, with APE1 as the target molecule.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm-20-7752DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867945PMC
January 2021

A Powerful HPLC-ELSD Method for Simultaneous Determination of Fecal Bile Acids in T2DM Rats Interfered by Sanhuang Xiexin Tang.

J Chromatogr Sci 2021 Feb 2. Epub 2021 Feb 2.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China.

Bile acids (BAs) as important endogenous ligands can activate farnesoid X receptor (FXR) and G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) signaling to regulate glycolipid metabolism. In this study, a simple, reliable and sensitive analysis method for simultaneous determination of four BAs from rat feces based on high-performance liquid chromatography with evaporative light scattering detector (HPLC-ELSD) was developed. Chromatographic analysis was performed with the mobile phases of acetonitrile and 0.2% formic acid. All the standard curves exhibited good linearity (R2 ≥ 0.99). The relative standard deviations of precision, stability and repeatability varied from 1.27 to 3.96%, 2.20 to 3.89% and 3.00 to 4.31%, respectively. The validated method was successfully applied to investigate the variation of four BAs in feces from T2DM rats after oral administration of Sanhuang Xiexin Tang (SXT). Data showed that SXT could remarkably increase the contents of conjunct BAs and decrease the contents of free BAs, which might contribute to ameliorate the symptoms of T2DM rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/chromsci/bmaa144DOI Listing
February 2021

Effect of Endovascular Treatment Alone vs Intravenous Alteplase Plus Endovascular Treatment on Functional Independence in Patients With Acute Ischemic Stroke: The DEVT Randomized Clinical Trial.

JAMA 2021 01;325(3):234-243

Department of Neurology, Ganzhou People's Hospital, Zhanggong District, Ganzhou, China.

Importance: For patients with large vessel occlusion strokes, it is unknown whether endovascular treatment alone compared with intravenous thrombolysis plus endovascular treatment (standard treatment) can achieve similar functional outcomes.

Objective: To investigate whether endovascular thrombectomy alone is noninferior to intravenous alteplase followed by endovascular thrombectomy for achieving functional independence at 90 days among patients with large vessel occlusion stroke.

Design, Setting, And Participants: Multicenter, randomized, noninferiority trial conducted at 33 stroke centers in China. Patients (n = 234) were 18 years or older with proximal anterior circulation intracranial occlusion strokes within 4.5 hours from symptoms onset and eligible for intravenous thrombolysis. Enrollment took place from May 20, 2018, to May 2, 2020. Patients were enrolled and followed up for 90 days (final follow-up was July 22, 2020).

Interventions: A total of 116 patients were randomized to the endovascular thrombectomy alone group and 118 patients to combined intravenous thrombolysis and endovascular thrombectomy group.

Main Outcomes And Measures: The primary end point was the proportion of patients achieving functional independence at 90 days (defined as score 0-2 on the modified Rankin Scale; range, 0 [no symptoms] to 6 [death]). The noninferiority margin was -10%. Safety outcomes included the incidence of symptomatic intracerebral hemorrhage within 48 hours and 90-day mortality.

Results: The trial was stopped early because of efficacy when 234 of a planned 970 patients had undergone randomization. All 234 patients who were randomized (mean age, 68 years; 102 women [43.6%]) completed the trial. At the 90-day follow-up, 63 patients (54.3%) in the endovascular thrombectomy alone group vs 55 (46.6%) in the combined treatment group achieved functional independence at the 90-day follow-up (difference, 7.7%, 1-sided 97.5% CI, -5.1% to ∞)P for noninferiority = .003). No significant between-group differences were detected in symptomatic intracerebral hemorrhage (6.1% vs 6.8%; difference, -0.8%; 95% CI, -7.1% to 5.6%) and 90-day mortality (17.2% vs 17.8%; difference, -0.5%; 95% CI, -10.3% to 9.2%).

Conclusions And Relevance: Among patients with ischemic stroke due to proximal anterior circulation occlusion within 4.5 hours from onset, endovascular treatment alone, compared with intravenous alteplase plus endovascular treatment, met the prespecified statistical threshold for noninferiority for the outcome of 90-day functional independence. These findings should be interpreted in the context of the clinical acceptability of the selected noninferiority threshold.

Trial Registration: Chinese Clinical Trial Registry: ChiCTR-IOR-17013568.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jama.2020.23523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816099PMC
January 2021

Monkeys fight more in polluted air.

Sci Rep 2021 Jan 12;11(1):654. Epub 2021 Jan 12.

Lab of Animal Behavior & Conservation, School of Life Sciences, Nanjing University, Nanjing, 210023, China.

Air pollution is a global environmental problem, and its effects on human behavior, psychology, and health have been well studied. However, very few studies were done on if and how air pollution affects animal behavior, for example, social conflict. Many physiological and psychological evidences suggest a possible positive relationship between air pollution and animal social conflict, thus we established a multiple linear regression model using a captive monkey group to explore if monkeys behave more aggressively in polluted air. Our results confirmed that daily social fighting behaviors occurred more when air is polluted. Temperature has a nonlinear effect on monkey social conflict, with a fighting peak at 25-29 °C. To our knowledge, this is the first report that animal social conflict, like humans, is also affected by air pollution and temperature.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-80002-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804853PMC
January 2021

The Chemistry and Applications of Heteroisoindigo Units as Enabling Links for Semiconducting Materials.

Acc Chem Res 2020 Dec 17;53(12):2855-2868. Epub 2020 Nov 17.

State Key Laboratory of Optoelectronic Materials and Technologies, Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education, School of Materials and Engineering, Sun Yat-Sen University, Guangzhou 510275, China.

ConspectusBecause of their low-temperature processing properties and inherent mechanical flexibility, semiconducting materials are promising candidates for enabling flexible displays, renewable energy, biological sensors, and healthcare. Progress has been made in materials performance by developing judicious materials design strategies. For example, improvements in electron transport have required new electron-deficient aromatics. Among them, isoindigo (IID) is an important functional group utilized in conjugated aromatics, where the structure combines two sets of five-membered electron-withdrawing lactam rings, exhibiting enhanced solubility, excellent chemical and thermal stabilities, broad absorption, and intriguing electron affinity.In the past decade, researchers have mainly focused on IID-based materials. However, the effect of heteroatom modification of the IID core has rarely been systemically investigated. In conventional conjugated polymers, single bonds connect the monomers, leading to energetic disorder and torsion defects, while ladder-type polymers are often intractable because of their fused nature. In this regard, the molecular design of new π scaffolds based on IID is central to the development of high-performance semiconductor polymers. Especially, a complete refresh of molecular design strategies and novel conjugated polymers with unique structures are needed to circumvent the disadvantages of the conventional ladder-type polymers.In this Account, we systematically summarize our recent progress in the design, synthesis, and structure-property relationships of IID- and particularly hetero-IID-based functional materials. More specifically, starting with molecular engineering of hetero-IIDs with variable electronic effects, conjugation lengths, and numbers of heterorings, we discuss the effect of the heteroring on the absorption spectra and energy levels. Additionally, we investigate a series of electron-withdrawing substitution of IIDs and hetero-IIDs and their molecular self-assembly behavior and the device performance. Furthermore, we discuss a series of IID-bis(EDOT) copolymers with hydrophilic ethylene glycol side chains for accumulation-mode organic thin-film electrochemical transistors, in which the relationships among the molecular structure, operational stability, film morphology, and device performance were revealed. Compared with IID polymers, the HOMO levels and optical band gaps of the thiophene and thienothiophene IID copolymers markedly decrease, and these polymers exhibit ambipolar charge transport. When we further expanded the IID core to a thieno[3,2-][1]benzothiophene isoindigo (TBTI) core, such as in TBTIT, bulk-heterojunction solar cells employing this polymer class as the electron donor achieved good efficiency for additive- and annealing-free device conditions. When we introduced electron-deficient pyridine on the IID core, both the LUMO and HOMO energy levels of the copolymers markedly decreased, which significantly improved the electron mobility. In addition, we compare the correlation between the polymer structures of IID and hetero-IID copolymers with thiophene and benzothiophene as comonomers and their absorption spectra and energy levels. In particular, we evaluate the planarity and the dihedral angle between the repeat units, with systematic analysis by theoretical calculations to support our design concepts. We discuss polymer designs arising from simple aldol condensation, where the rigid backbone conformation has been locked by the double bonds. Our polymers display broad absorption from the visible to the NIR-II region, and more importantly, the high electron affinities of these polymers provide a platform to realize ambient-stable electron transport in solution-processed organic thin-film transistors. These exciting results are expected to open doors to new horizons of semiconducting materials in terms of other charming applications and the design and synthesis of superior materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.accounts.0c00480DOI Listing
December 2020

Enterohepatic circulation of bile acids and their emerging roles on glucolipid metabolism.

Steroids 2021 01 5;165:108757. Epub 2020 Nov 5.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, PR China. Electronic address:

Bile acids (BAs) are amphiphilic molecules with a nonpolar steroid carbon skeleton and a polar carboxylate side chain. Recently, BAs have aroused the attention of scholars due to their potential roles on metabolic diseases. As important endogenous ligands, BAs are wildly active in the enterohepatic circulation, during which microbiota play a significant role in promoting the hydrolysis and dehydroxylation of BAs. Besides, many pathways initiated by BAs including glucolipid metabolism and inflammation signaling pathways have been reported to regulate the host metabolism and maintain immune homeostasis. Herein, the characteristics on the enterohepatic circulation and metabolism of BAs are systematically summarized. Moreover, the regulation mechanism of the glucolipid metabolism by BAs is intensively discussed. Worthily, FXR and TGR5, which are involved in glucolipid metabolism, are the prime candidates for targeted therapies of chronic metabolic diseases such as diabetes and hypercholesterolemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.steroids.2020.108757DOI Listing
January 2021

Determination of isoform-specific RNA structure with nanopore long reads.

Nat Biotechnol 2021 03 26;39(3):336-346. Epub 2020 Oct 26.

Stem Cell and Regenerative Biology, Genome Institute of Singapore, A*STAR, Singapore, Singapore.

Current methods for determining RNA structure with short-read sequencing cannot capture most differences between distinct transcript isoforms. Here we present RNA structure analysis using nanopore sequencing (PORE-cupine), which combines structure probing using chemical modifications with direct long-read RNA sequencing and machine learning to detect secondary structures in cellular RNAs. PORE-cupine also captures global structural features, such as RNA-binding-protein binding sites and reactivity differences at single-nucleotide variants. We show that shared sequences in different transcript isoforms of the same gene can fold into different structures, highlighting the importance of long-read sequencing for obtaining phase information. We also demonstrate that structural differences between transcript isoforms of the same gene lead to differences in translation efficiency. By revealing isoform-specific RNA structure, PORE-cupine will deepen understanding of the role of structures in controlling gene regulation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41587-020-0712-zDOI Listing
March 2021

The safety and efficacy of staged angioplasty for treating carotid stenosis with a high risk of hyperperfusion: A single-center retrospective study.

Interv Neuroradiol 2020 Oct 9;26(5):637-642. Epub 2020 Aug 9.

Department of Neurology, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China.

Objective: Hyperperfusion syndrome (HPS) following carotid artery stenting (CAS) is a rare but life-threatening complication. Staged angioplasty (SAP) is an alternative method that prevents HPS by preventing a sudden increase in cerebral blood flow. In this study, we investigated the safety and efficacy of SAP.

Methods: A total of 114 patients with carotid stenosis underwent CAS treatment in our hospital between September 2014 and September 2019. Patients with severe stenosis and poor collateral circulation shown on digital subtraction angiography (DSA) and hypoperfusion of the ipsilateral diseased blood vessel shown on computed tomography perfusion (CTP) imaging were subjected to SAP treatment (the SAP group), and other patients received regular CAS treatment (the RS group).

Results: Twenty-two patients (19.3%) with a high risk of HPS underwent SAP treatment, 1 of whom had carotid dissection after stage I balloon angioplasty and underwent regular CAS. This patient had HPS after surgery. None of the other patients in either group had HPS. One patient in the SAP group (4.5%) had hyperperfusion phenomenon (HPP) after stage II stenting, and 2 patients in the RS group (2.2%) had HPP. One patient in the SAP group (4.5%) and 4 patients in the RS group (4.3%) had symptomatic ischemic complications postoperatively. None of the differences between the 2 groups were statistically significant. Three patients had reduced modified Rankin Scale (mRS) scores at 90 days after discharge.

Conclusion: This research suggests that SAP appears to be an effective method to prevent HPS for patients with a high risk of HPS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1591019920946507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645180PMC
October 2020

Computational modelling of flavivirus dynamics: The ins and outs.

Methods 2021 01 8;185:28-38. Epub 2020 Jun 8.

Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), 30 Biopolis Street, Matrix #07-01, 138671, Singapore; Department of Biological Sciences (DBS), National University of Singapore (NUS), 16 Science Drive 4, Building S3, Singapore. Electronic address:

Enveloped viruses such as the flaviviruses represent a significant burden to human health around the world, with hundreds of millions of people each year affected by dengue alone. In an effort to improve our understanding of the molecular basis for the infective mechanisms of these viruses, extensive computational modelling approaches have been applied to elucidate their conformational dynamics. Multiscale protocols have been developed to simulate flavivirus envelopes in close accordance with biophysical data, in particular derived from cryo-electron microscopy, enabling high-resolution refinement of their structures and elucidation of the conformational changes associated with adaptation both to host environments and to immunological factors such as antibodies. Likewise, integrative modelling efforts combining data from biophysical experiments and from genome sequencing with chemical modification are providing unparalleled insights into the architecture of the previously unresolved nucleocapsid complex. Collectively, this work provides the basis for the future rational design of new antiviral therapeutics and vaccine development strategies targeting enveloped viruses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ymeth.2020.06.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7278654PMC
January 2021

DEVT: A randomized, controlled, multicenter trial of direct endovascular treatment versus standard bridging therapy for acute stroke patients with large vessel occlusion in the anterior circulation - Protocol.

Int J Stroke 2021 Feb 23;16(2):229-235. Epub 2020 May 23.

Department of Neurology, the 36639First Affiliated Hospital of Anhui Medical University, Hefei, China.

Background: Eight randomized controlled trials have consistently shown that endovascular treatment plus best medical treatment improves outcome after acute anterior proximal intracranial large vessel occlusion strokes. Whether intravenous thrombolysis prior to endovascular treatment in patients with anterior circulation, large vessel occlusion is of any additional benefits remains unclear.

Objective: This study compares the safety and efficacy of direct endovascular treatment versus intravenous recombinant tissue-type plasminogen activator bridging with endovascular treatment (bridging therapy) in acute stroke patients with intracranial internal carotid artery or middle cerebral artery-M1 occlusion within 4.5 h of symptom onset.

Methods And Design: The DEVT study is a randomized, controlled, multicenter trial with blinded outcome assessment. This trial uses a five-look group-sequential non-inferiority design. Up to 194 patients in each interim analysis will be consecutively randomized to direct endovascular treatment or bridging therapy group in 1:1 ratio over three years from about 30 hospitals in China.

Outcomes: The primary end-point is the proportion of independent neurological function defined as modified Rankin scale score of 0 to 2 at 90 days. The primary safety measure is symptomatic intracerebral hemorrhage at 48 h and mortality at 90 days.

Trial Registry Number: ChiCTR-IOR-17013568 (www.chictr.org.cn).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1747493020925349DOI Listing
February 2021

Lizhong decoction ameliorates ulcerative colitis in mice via modulating gut microbiota and its metabolites.

Appl Microbiol Biotechnol 2020 Jul 17;104(13):5999-6012. Epub 2020 May 17.

Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, People's Republic of China.

Ulcerative colitis (UC), a kind of inflammatory bowel disease, is generally characterized by chronic, persistent, relapsing, and nonspecific ulceration of the bowel, which is widespread in the world. Although the pathogenesis of UC is multifactorial, growing evidence has demonstrated that gut microbiota and its metabolites are closely related to the development of UC. Lizhong decoction (LZD), a well-known classical Chinese herbal prescription, has been used to clinically treat UC for long time, but its mechanism is not clear. In this study, 16S rRNA gene sequencing combining with untargeted metabolomics profiling was used to investigate how LZD worked. Results indicated that LZD could shape the gut microbiota structure and modify metabolic profiles. The abundance of opportunistic pathogens such as Clostridium sensu stricto 1, Enterobacter, and Escherichia-Shigella correlated with intestinal inflammation markedly decreased, while the levels of beneficial bacteria including Blautia, Muribaculaceae_norank, Prevotellaceae UCG-001, and Ruminiclostridium 9 elevated in various degrees. Additionally, fecal metabolite profiles reflecting microbial activities showed that adenosine, lysoPC(18:0), glycocholic acid, and deoxycholic acid notably decreased, while cholic acid, α-linolenic acid, stearidonic acid, and L-tryptophan significantly increased after LZD treatment. Hence, based on the systematic analysis of 16S rRNA gene sequencing and metabolomics of gut flora, the results provided a novel insight that microbiota and its metabolites might be potential targets for revealing the mechanism of LZD on amelioration of UC.Key Points • The potential mechanism of LZD on the amelioration of UC was firstly investigated.• LZD could significantly shape the structure of gut microbiota.• LZD could notably modulate the fecal metabolic profiling of UC mice. Graphical abstract.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00253-020-10665-1DOI Listing
July 2020

Selective Cl-Decoration on Nanocrystal Facets of Hematite for High-Efficiency Catalytic Oxidation of Cyclohexane: Identification of the Newly Formed Cl-O as Active Sites.

ACS Appl Mater Interfaces 2020 Jun 26;12(23):26733-26745. Epub 2020 May 26.

College of Chemical Engineering, Xiangtan University, Xiangtan 411105, China.

Understanding the structure-reactivity relationship at the atomic scale is of great theoretical importance for rational design of highly active catalysts, which has long been a central concern in catalysis communities and interface science. Herein, we developed a high-efficiency catalyst for catalytic oxidation of CH by poststructural decoration on well-defined single-crystal facets of hematite. Especially for Cl-decorated {012} facets, the conversion and KA oil selectivity are improved about 3.4 times and 2 times, respectively. A better catalytic performance of the newly formed active site is derived from the charge difference between Cl and the neighboring outmost O atoms, which is affected by the geometric and electronic structures of the original catalyst surface. Based on the experimental results and the theoretical analysis, we concluded that the contribution of various O terminations to Cl-decoration follows the order O(I) > O(III) > O(II). Cl-decorated {001} facets show the highest intrinsic activity, whereas Cl-decorated {012} facets show the best catalytic performance because of their more active sites for Cl-decoration.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsami.0c06870DOI Listing
June 2020

Anisotropy of Charge Transport in a Uniaxially Aligned Fused Electron-Deficient Polymer Processed by Solution Shear Coating.

Adv Mater 2020 Jun 4;32(23):e2000063. Epub 2020 May 4.

Optoelectronics Group, Cavendish Laboratory, JJ Thomson Avenue, Cambridge, CB3 0HE, UK.

Precise control of the microstructure in organic semiconductors (OSCs) is essential for developing high-performance organic electronic devices. Here, a comprehensive charge transport characterization of two recently reported rigid-rod conjugated polymers that do not contain single bonds in the main chain is reported. It is demonstrated that the molecular design of the polymer makes it possible to achieve an extended linear backbone structure, which can be directly visualized by high-resolution scanning tunneling microscopy (STM). The rigid structure of the polymers allows the formation of thin films with uniaxially aligned polymer chains by using a simple one-step solution-shear/bar coating technique. These aligned films show a high optical anisotropy with a dichroic ratio of up to a factor of 6. Transport measurements performed using top-gate bottom-contact field-effect transistors exhibit a high saturation electron mobility of 0.2 cm V s along the alignment direction, which is more than six times higher than the value reported in the previous work. This work demonstrates that this new class of polymers is able to achieve mobility values comparable to state-of-the-art n-type polymers and identifies an effective processing strategy for this class of rigid-rod polymer system to optimize their charge transport properties.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202000063DOI Listing
June 2020

RNA Conformation Capture by Proximity Ligation.

Annu Rev Genomics Hum Genet 2020 08 22;21:81-100. Epub 2020 Apr 22.

Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, United Kingdom.

RNA proximity ligation is a set of molecular biology techniques used to analyze the conformations and spatial proximity of RNA molecules within cells. A typical experiment starts with cross-linking of a biological sample using UV light or psoralen, followed by partial fragmentation of RNA, RNA-RNA ligation, library preparation, and high-throughput sequencing. In the past decade, proximity ligation has been used to study structures of individual RNAs, networks of interactions between small RNAs and their targets, and whole RNA-RNA interactomes, in models ranging from bacteria to animal tissues and whole animals. Here, we provide an overview of the field, highlight the main findings, review the recent experimental and computational developments, and provide troubleshooting advice for new users. In the final section, we draw parallels between DNA and RNA proximity ligation and speculate on possible future research directions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1146/annurev-genom-120219-073756DOI Listing
August 2020

Assessment of Endovascular Treatment for Acute Basilar Artery Occlusion via a Nationwide Prospective Registry.

JAMA Neurol 2020 05;77(5):561-573

Department of Neurology, Yunfu People's Hospital, Yunfu, China.

Importance: Several randomized clinical trials have recently established the safety and efficacy of endovascular treatment (EVT) of acute ischemic stroke in the anterior circulation. However, it remains uncertain whether patients with acute basilar artery occlusion (BAO) benefit from EVT.

Objective: To evaluate the association between EVT and clinical outcomes of patients with acute BAO.

Design, Setting, And Participants: This nonrandomized cohort study, the EVT for Acute Basilar Artery Occlusion Study (BASILAR) study, was a nationwide prospective registry of consecutive patients presenting with an acute, symptomatic, radiologically confirmed BAO to 47 comprehensive stroke centers across 15 provinces in China between January 2014 and May 2019. Patients with acute BAO within 24 hours of estimated occlusion time were divided into groups receiving standard medical treatment plus EVT or standard medical treatment alone.

Main Outcomes And Measures: The primary outcome was the improvement in modified Rankin Scale scores (range, 0 to 6 points, with higher scores indicating greater disability) at 90 days across the 2 groups assessed as a common odds ratio using ordinal logistic regression shift analysis, adjusted for prespecified prognostic factors. The secondary efficacy outcome was the rate of favorable functional outcomes defined as modified Rankin Scale scores of 3 or less (indicating an ability to walk unassisted) at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage and 90-day mortality.

Results: A total of 1254 patients were assessed, and 829 patients (of whom 612 were men [73.8%]; median [interquartile] age, 65 [57-74] years) were recruited into the study. Of these, 647 were treated with standard medical treatment plus EVT and 182 with standard medical treatment alone. Ninety-day functional outcomes were substantially improved by EVT (adjusted common odds ratio, 3.08 [95% CI, 2.09-4.55]; P < .001). Moreover, EVT was associated with a significantly higher rate of 90-day modified Rankin Scale scores of 3 or less (adjusted odds ratio, 4.70 [95% CI, 2.53-8.75]; P < .001) and a lower rate of 90-day mortality (adjusted odds ratio, 2.93 [95% CI, 1.95-4.40]; P < .001) despite an increase in symptomatic intracerebral hemorrhage (45 of 636 patients [7.1%] vs 1 of 182 patients [0.5%]; P < .001).

Conclusions And Relevance: Among patients with acute BAO, EVT administered within 24 hours of estimated occlusion time is associated with better functional outcomes and reduced mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1001/jamaneurol.2020.0156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042866PMC
May 2020

Fused Pyrazine- and Carbazole-Containing Azaacenes: Synthesis and Properties.

Chempluschem 2019 Sep 23;84(9):1257-1262. Epub 2019 Jul 23.

Key Laboratory for Polymeric Composite and Functional Materials of Ministry of Education School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou, 510275, P. R. China.

A new family of azaacenes has been designed and synthesized by incorporating the electron-withdrawing sp -hybridized nitrogen of pyrazine and electron-donating nitrogen of carbazole in a molecular skeleton. Two different conjugated lengths of 8-ring aza-nonacene and 10-ring aza-undecene have been achieved by an efficient condensation reaction. The unique optoelectronic properties of these molecules were investigated using both experimental and theoretical techniques. The azaacenes show visible-region absorption and near-infrared (NIR) fluorescence. These compounds can serve as hole-transport semiconductors for solution-processed organic field-effect transistors (OFETs). Single-crystal transistor devices of one of the aza-nonacenes exhibit hole charge transport behavior with a hole mobility of 0.07 cm /Vs and an on/off current ratio of 1.3x10 .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cplu.201900383DOI Listing
September 2019

Endovascular treatment versus standard medical treatment for vertebrobasilar artery occlusion (BEST): an open-label, randomised controlled trial.

Lancet Neurol 2020 02 9;19(2):115-122. Epub 2019 Dec 9.

Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.

Background: Previous randomised trials have shown an overwhelming benefit of mechanical thrombectomy for treating patients with stroke caused by large vessel occlusion of the anterior circulation. Whether endovascular treatment is beneficial for vertebrobasilar artery occlusion remains unknown. In this study, we aimed to investigate the safety and efficacy of endovascular treatment of acute strokes due to vertebrobasilar artery occlusion.

Methods: We did a multicentre, randomised, open-label trial, with blinded outcome assessment of thrombectomy in patients presenting within 8 h of vertebrobasilar occlusion at 28 centres in China. Patients were randomly assigned (1:1) to endovascular therapy plus standard medical therapy (intervention group) or standard medical therapy alone (control group). The randomisation sequence was computer-generated and stratified by participating centres. Allocation concealment was implemented by use of sealed envelopes. The primary outcome was a modified Rankin scale (mRS) score of 3 or lower (indicating ability to walk unassisted) at 90 days, assessed on an intention-to-treat basis. The primary safety outcome was mortality at 90 days. Secondary safety endpoints included the rates of symptomatic intracranial haemorrhage, device-related complications, and other severe adverse events. The BEST trial is registered with ClinicalTrials.gov, NCT02441556.

Findings: Between April 27, 2015, and Sept 27, 2017, we assessed 288 patients for eligibility. The trial was terminated early after 131 patients had been randomly assigned (66 patients to the intervention group and 65 to the control group) because of high crossover rate and poor recruitment. In the intention-to-treat analysis, there was no evidence of a difference in the proportion of participants with mRS 0-3 at 90 days according to treatment (28 [42%] of 66 patients in the intervention group vs 21 [32%] of 65 in the control group; adjusted odds ratio [OR] 1·74, 95% CI 0·81-3·74). Secondary prespecified analyses of the primary outcome, done to assess the effect of crossovers, showed higher rates of mRS 0-3 at 90 days in patients who actually received the intervention compared with those who received standard medical therapy alone in both per-protocol (28 [44%] of 63 patients with intervention vs 13 [25%] of 51 with standard therapy; adjusted OR 2·90, 95% CI 1·20-7·03) and as-treated (36 [47%] of 77 patients with intervention vs 13 [24%] of 54 with standard therapy; 3·02, 1·31-7·00) populations. The 90-day mortality was similar between groups (22 [33%] of 66 patients in the intervention vs 25 [38%] of 65 in the control group; p=0·54) despite a numerically higher prevalence of symptomatic intracranial haemorrhage in the intervention group.

Interpretation: There was no evidence of a difference in favourable outcomes of patients receiving endovascular therapy compared with those receiving standard medical therapy alone. Results might have been confounded by loss of equipoise over the course of the trial, resulting in poor adherence to the assigned study treatment and a reduced sample size due to the early termination of the study.

Funding: Jiangsu Provincial Special Program of Medical Science.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1474-4422(19)30395-3DOI Listing
February 2020

Arthroscopic Stabilization of Unstable Os Subfibulare.

Arthrosc Tech 2019 Sep 12;8(9):e1007-e1012. Epub 2019 Sep 12.

Department of Orthopaedics and Traumatology, Princess Margaret Hospital, Hong Kong SAR, China.

Os subfibulare is an ossicle at the tip of the lateral malleolus. The ossicle is sometimes symptomatic and presents with local pain or lateral ankle instability. The purpose of this Technical Note is to describe the details of arthroscopic stabilization of the os subfibulare. It is indicated for symptomatic mechanical lateral ankle instability resulting from an unstable os subfibulare. The technique has the advantages of minimally invasive surgery, evaluation and treatment of concomitant ankle pathology, and preservation of integrity of the anterior talofibular ligament.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eats.2019.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819746PMC
September 2019

Arthroscopic Debridement and Microfracture of Osteochondral Lesion of the Talar Head.

Arthrosc Tech 2019 Sep 11;8(9):e969-e973. Epub 2019 Sep 11.

Department of Orthopaedics and Traumatology, North District Hospital, Hong Kong, China.

Osteochondral lesions of the talar head can be classified into 4 types according to their location. A type 1 lesion is located at the anterior part of the talar head. Surgical debridement and microfracture are indicated for symptomatic type 1 lesions if conservative treatment fails to relieve the pain. The purpose of this technical note was to describe the details of arthroscopic debridement and microfracture of the symptomatic type 1 osteochondral lesion of the talar head and the kissing lesion at the navicular bone. The procedure is performed through the standard portals of talonavicular arthroscopy and has the advantages of minimally invasive surgery of better cosmetic results and less surgical trauma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eats.2019.05.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6819872PMC
September 2019

Tamoxifen promotes white matter recovery and cognitive functions in male mice after chronic hypoperfusion.

Neurochem Int 2019 12 5;131:104566. Epub 2019 Oct 5.

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China. Electronic address:

Cerebral white matter lesions (WMLs) induced by chronic cerebral hypoperfusion are one of the major components of stroke pathology and closely associated with cognitive impairment. However, the repair and related pathophysiology of white matter after brain injury remains relatively elusive and underexplored. Successful neuroregeneration is a method for the potential treatment of central nervous system (CNS) disorders. A non-steroidal estrogen receptor modulator, Tamoxifen, is an effective inhibitor of cell-swelling-activated anion channels and can mimic neuroprotective effects of estrogen in experimental ischemic stroke. However, its remains unclear whether Tamoxifen has beneficial effects in the pathological process after WMLs. In the present study, we investigated the efficacy of Tamoxifen on multiple elements of oligovascular niche of the male C57BL/6 mice brain after bilateral carotid artery stenosis (BCAS) - induced WMLs. Tamoxifen was injected intraperitoneally once daily from 1 day after BCAS until 1 day before sacrificed. Following chronic hypoperfusion, BCAS mice presented white matter demyelination, loss of axon-glia integrity, activated inflammatory response, and cognitive impairments. Tamoxifen treatment significantly facilitated functional restoration of working memory impairment in mice after white matter injury, thus indicating a translational potential for this estrogen receptor modulator given its clinical safety and applicability for WMLs, which lack of currently available treatments. Furthermore, Tamoxifen treatment reduced microglia activation and inflammatory response, favored microglial polarization toward to the M2 phenotype, enhanced oligodendrocyte precursor cells proliferation and differentiation, and promoted remyelination after chronic hypoperfusion. Together, our data indicate that Tamoxifen could alleviate white matter injury and play multiple targets protective effects following chronic hypoperfusion, which is a promising candidate for the therapeutic target for ischemic WMLs and other demyelination diseases associated cognitive impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuint.2019.104566DOI Listing
December 2019

Overview of endovascular thrombectomy accessibility gap for acute ischemic stroke in Asia: A multi-national survey.

Int J Stroke 2020 07 3;15(5):516-520. Epub 2019 Oct 3.

Institute of Neurology, Yichang Central People's Hospital, China Three Gorges University Yichang, Yichang, China.

Endovascular thrombectomy revolutionized the treatment of acute ischemic stroke. Nevertheless, access to endovascular thrombectomy is limited in many parts of the world. Asia holds 60% of the world's population and its countries carry some of the highest stroke disease burden. To understand the availability of endovascular thrombectomy and intravenous thrombolysis in this region, we interviewed stroke neurologists and neuro-interventionists of 19 Asian countries, and found a large disparity in access to endovascular thrombectomy and intravenous thrombolysis between high- and low-income countries. Lack of neuro-interventionists, comprehensive stroke units, stroke triage systems and high treatment cost are the major obstacles to wider accessibility of endovascular thrombectomy, especially among developing countries. The potential solutions to provide equitable access to stroke revascularization therapy are discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1747493019881345DOI Listing
July 2020