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Träfflista för sökning "WFRF:(Zhao Ming) ;lar1:(ki)"

Sökning: WFRF:(Zhao Ming) > Karolinska Institutet

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1.
  • Abbafati, Cristiana, et al. (författare)
  • 2020
  • Tidskriftsartikel (refereegranskat)
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2.
  • Kanoni, Stavroula, et al. (författare)
  • Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
  • 2022
  • Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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3.
  • Boeger, Carsten A., et al. (författare)
  • CUBN Is a Gene Locus for Albuminuria
  • 2011
  • Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 22:3, s. 555-570
  • Tidskriftsartikel (refereegranskat)abstract
    • Identification of genetic risk factors for albuminuria may alter strategies for early prevention of CKD progression, particularly among patients with diabetes. Little is known about the influence of common genetic variants on albuminuria in both general and diabetic populations. We performed a meta-analysis of data from 63,153 individuals of European ancestry with genotype information from genome-wide association studies (CKDGen Consortium) and from a large candidate gene study (CARe Consortium) to identify susceptibility loci for the quantitative trait urinary albumin-to-creatinine ratio (UACR) and the clinical diagnosis microalbuminuria. We identified an association between a missense variant (I2984V) in the CUBN gene, which encodes cubilin, and both UACR (P = 1.1 x 10(-11)) and microalbuminuria (P = 0.001). We observed similar associations among 6981 African Americans in the CARe Consortium. The associations between this variant and both UACR and microalbuminuria were significant in individuals of European ancestry regardless of diabetes status. Finally, this variant associated with a 41% increased risk for the development of persistent microalbuminuria during 20 years of follow-up among 1304 participants with type 1 diabetes in the prospective DCCT/EDIC Study. In summary, we identified a missense CUBN variant that associates with levels of albuminuria in both the general population and in individuals with diabetes.
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5.
  • Graslund, S, et al. (författare)
  • Protein production and purification
  • 2008
  • Ingår i: Nature methods. - : Springer Science and Business Media LLC. - 1548-7105 .- 1548-7091. ; 5:2, s. 135-146
  • Tidskriftsartikel (refereegranskat)
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6.
  • Han, Xiaolei, et al. (författare)
  • Accelerometer-assessed sedentary behaviour among Chinese rural older adults : Patterns and associations with physical function
  • 2022
  • Ingår i: Journal of Sports Sciences. - : Informa UK Limited. - 0264-0414 .- 1466-447X. ; 40:17, s. 1940-1949
  • Tidskriftsartikel (refereegranskat)abstract
    • Sedentary behaviour is associated with a range of adverse health conditions. Population-based studies have rarely examined the distribution and associated factors of accelerometer-measured sedentary behaviour patterns in rural-dwelling older adults. This population-based study included 2096 rural-dwelling older adults (age ≥60 years; 59.0% women) derived from baseline participants of the MIND-China Study. Total sedentary time and patterns (e.g., uninterrupted bouts and breaks) were derived from the hip-worn accelerometers for 7 days. Physical function was assessed using the Short Physical Performance Battery test. Data were analysed using general linear models. Overall, participants spent 58.8% of daily waking time in sedentary behaviour, with nearly half of sedentary time being accumulated through sedentary bouts of 30+ minutes. Men spent more total and accumulated sedentary time than women in each sedentary bout duration, while women had more daily 1+ minute sedentary bouts than men (all P < 0.001). Controlling for moderate-to-vigorous physical activity and other confounders, more prolonged sedentary time and fewer breaks were significantly associated with poor physical function, balance, lower limb strength, and walking speed (all P < 0.001). In older adults living in rural communities, prolonged sedentary behaviour and less frequent breaks are associated with poor physical function.
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7.
  • Khalifa, Shaden A. M., et al. (författare)
  • Screening for natural and derived bio-active compounds in preclinical and clinical studies : One of the frontlines of fighting the coronaviruses pandemic
  • 2021
  • Ingår i: Phytomedicine. - : Elsevier BV. - 0944-7113 .- 1618-095X. ; 85
  • Forskningsöversikt (refereegranskat)abstract
    • Background: Starting December 2019, mankind faced an unprecedented enemy, the COVID-19 virus. The world convened in international efforts, experiences and technologies in order to fight the emerging pandemic. Isolation, hygiene measure, diagnosis, and treatment are the most efficient ways of prevention and intervention nowadays. The health organizations and global care systems screened the available resources and offered recommendations of approved and proposed medications. However, the search for a specific selective therapy or vaccine against COVID-19 remains a challenge.Methods: A literature search was performed for the screening of natural and derived bio-active compounds which showed potent antiviral activity against coronaviruses using published articles, patents, clinical trials website (https://clinicaltrials.gov/) and web databases (PubMed, SCI Finder, Science Direct, and Google Scholar).Results: Through the screening for natural products with antiviral activities against different types of the human coronavirus, extracts of Lycoris radiata (L'Her.), Gentiana scabra Bunge, Dioscorea batatas Decne., Cassia tora L., Taxillus chinensis (DC.), Cibotium barometz L. and Echinacea purpurea L. showed a promising effect against SARSCoV. Out of the listed compound Lycorine, emetine dihydrochloride hydrate, pristimerin, harmine, conessine, berbamine, 4'-hydroxychalcone, papaverine, mycophenolic acid, mycophenolate mofetil, monensin sodium, cycloheximide, oligomycin and valinomycin show potent activity against human coronaviruses. Additionally, it is worth noting that some compounds have already moved into clinical trials for their activity against COVID-19 including fingolimod, methylprednisolone, chloroquine, tetrandrine and tocilizumab.Conclusion: Natural compounds and their derivatives could be used for developing potent therapeutics with significant activity against SARS-COV-2, providing a promising frontline in the fighting against COVID-19.
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8.
  • Wang, Shaoying, et al. (författare)
  • Characterizing lipid profiles associated with asymptomatic intracranial arterial stenosis in rural-dwelling adults : A population-based study
  • 2020
  • Ingår i: Journal of Clinical Lipidology. - : Elsevier BV. - 1933-2874 .- 1876-4789. ; 14:3, s. 371-380
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Although individual lipid parameters have been frequently examined in association with asymptomatic intracranial arterial stenosis (aICAS), few population-based studies have investigated the lipid profiles associated with aICAS among Chinese adults. OBJECTIVE: This study aims to characterize the lipid profiles associated with aICAS in rural-dwelling adults in China. METHODS: This population-based study included 2027 persons who were aged >= 40 years and free of stroke. Data were collected via interviews, clinical examinations, and laboratory testing. We diagnosed aICAS by integrating transcranial color Doppler with magnetic resonance angiography. Data were analyzed using binary and multinomial logistic regression models. RESULTS: Of the 2027 participants, 154 were detected with aICAS. The multiadjusted odds ratio (95% confidence interval) of aICAS was 1.41 (0.997-2.00) for high small dense low-density lipoprotein cholesterol, 1.44 (1.02-2.04) for high lipoprotein(a), 1.71 (1.21-2.44) for low apolipoprotein A-1, 1.43 (1.00-2.04) for low high-density lipoprotein cholesterol (HDL-C), 1.61 (1.14-2.27) for high apolipoprotein B/apolipoprotein A-1 ratio, 1.95 (1.38-2.76) for high low-density lipoprotein cholesterol/HDL-C ratio, and 1.51 (1.06-2.14) for high total cholesterol/HDL-C ratio. When severity of aICAS was analyzed, high levels of lipoprotein(a), small dense low-density lipoprotein cholesterol, and lipid ratios were significantly associated with an increased likelihood of moderate-to-severe aICAS (P < .05). An increasing number of abnormal lipid measurements was associated with an increased likelihood of aICAS (P for trend <.001). CONCLUSION: These findings suggest that lipid profiles for aICAS among rural residents in China are characterized by high atherogenic cholesterol, low antiatherogenic cholesterol, and high ratios of atherogenic-to-antiatherogenic cholesterol or lipoproteins.
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9.
  • Yang, Yifeng, et al. (författare)
  • Weak acidic stable carbazate modified cellulose membranes target for scavenging carbonylated proteins in hemodialysis
  • 2020
  • Ingår i: Carbohydrate Polymers. - : Elsevier. - 0144-8617 .- 1879-1344. ; 231
  • Tidskriftsartikel (refereegranskat)abstract
    • Carbazate groups were grafted on the commercial cellulose membrane (CM) to specifically scavenge the carbonylated proteins for hemodialysis. It confirmed that carbazate groups were successfully covalently attached on the CMs by XPS and EDS, and the modified CMs still saved their original morphology and crystalline structures by SEM and XRD. Furthermore, the modified CMs presented favorable physicochemical stability at wide pH range from 2.5 to 7.4. It was also found that the carbazate modified CMs could selectively remove carbonylated proteins from acrolein treated bovine serum albumin (BSA) or ESRD patient's blood serum in PBS buffer. The modified CMs showed the potential to be utilized as the substitute of dialysis membranes in hemodialysis.
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10.
  • Zhao, Ming (författare)
  • Neurorestorative strategies involving neurogenesis, neuronal precursors and stem cells in animal models of Parkinson's disease
  • 2009
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • The general aims of the thesis is to provide evidence for neurogenesis in the adult substantia nigra pars compacta (SNpc), where the dopamine-producing neurons lost in Parkinson's disease (PD) reside; to optimize methods used for detecting newborn nerve cells in adult brain regions with a low rate of neurogenesis; to explore the mechanism of nerve cell death in animal models of parkinsonism and early degenerative and restorative changes in nigral cell populations; and to develop a therapeutic approach that could translate into a future restorative disease-modifying strategy in PD. Paper I. We provide evidence for the generation of dopaminergic projection neurons in adult SNpc, and estimate the low rate of turnover in this brain region. We administered the thymidine-analogue 5-bromodeoxyuridine (BrdU) or [3H]-thymidine using various regimen strategies to establish the generation of new neurons in SNpc in the confocal light and electron microscope. To trace the origin of the newly generated cells from stem cells lining the cerebroventricular system, we labeled ependymal cells with 1,1´-dioctadecyl-6,6´-di-(4-sulfophenyl)-3,3,3´,3´-tetramethylindocarbocyanine (DiI) or rhodamine-conjugated latex beads. The results obtained in this work show that (1) the size of the nigral nerve cell population remains constant during a large part of the mouse life span; (2) neurogenesis occurs in the substantia nigra and the BrdU-labeled neurons do not represent DNA repair; (3) the newly generated neurons project to the striatum and integrate into synaptic circuits; (4) there is increased neurogenesis after a partial 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced lesion. Paper II. Methodological differences may explain discrepancies between research reports on adult mammalian neurogenesis in the brain outside the widely accepted neurogenic regions, i.e. hippocampus and olfactory bulb/subventricular zone. We describe a method to dissolve and administer BrdU at high concentrations (150 mg/mL) into the adult mouse right cerebral ventricle to demonstrate neuronal incorporation of this thymidine analogue in CNS regions with a low rate of neurogenesis. The dosage regimen, duration and survival time of the mouse after the end of the nucleotide analogue administration all are critical, since e.g. exposure to low doses (paper I) did not result in a robust neuronal label. Techniques to optimize BrdU detection include tissue denaturation to fully expose the incorporated nuclear thymidine analogue for immunohistochemical staining. On the other hand, strategies to protect other tissue antigens against deterioration by this denaturation (HCl and pepsin) are necessary. Nigral neuronal incorporation of another proliferative marker, [3H]-thymidine confirmed the presence of neurogenesis in adult mammalian substantia nigra under physiological conditions. Paper III. To understand early neurodegenerative and neurorestorative post-lesion events in SNpc after a single dose of MPTP, we analyzed cell death by apoptosis as well as parallel dynamic changes in nigral populations of neurons, glia and progenitor cells. At the time of the peak of the MPTP-induced apoptosis, condensed neuronal nuclei containing fragmented DNA and activated caspases in the cytoplasm was found in nigral neurons, but neither in glial nor progenitor cells. Ultrastructural analysis confirmed the neuronal phenotype of cells with apoptotic morphologies. Moreover, the dynamic changes during the first 7 days after a single MPTP-induced lesion indicate that neuronal apoptosis is slow, lasting over several days, and that parallel changes in neuronal and glial progenitor populations occur, possibly representing both neurodegenerative and neurorestorative events. Stereological cell counts of nigral neurons using antibodies against tyrosine hydroxylase and neuronal-specific nuclear protein combined with Nissl staining all provide evidence that neurons are lost by a single dose of MPTP, in contrast to earlier reports indicating that neurons do not die in this lesion model, but merely lose expression of the rate limiting enzyme for dopamine synthesis. Paper IV. Intracerebroventricular administration of platelet-derived growth factor (PDGF)-BB for two weeks in parkinsonian animal models result in long-lasting dopaminergic restoration and functional recovery. We used several animal models, all inducing partial lesions in the nigrostriatal dopamine system, including mice and monkeys lesioned with MPTP and rats with a 6-hydroxydopamine (6OHDA)-injection in the right medial forebrain bundle. PDGF-BB promoted proliferation of neural progenitor cells in the subventricular zone in all animal species used. When the proliferation inhibitor cytosine-D-arabinofuranoside was coadministered with PDGF-BB in the 6-OHDA lesioned rats for two weeks, both structural and behavioral restoration was blocked. A link between the anti-parkinsonian effect of PDGF-BB and proliferation points to a new strategy in the search for disease-modifying agents that could lead to the development of new therapies against PD.
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