| 1101. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 1102. |
- Ho, Joshua W. K., et al.
(författare)
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Comparative analysis of metazoan chromatin organization
- 2014
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 512:7515, s. 449-U507
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Tidskriftsartikel (refereegranskat)abstract
- Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms(1-3). Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths(4,5). To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.
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| 1103. |
- Hong Li, Yu, et al.
(författare)
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Low doses of esmolol and phenylephrine act as diuretics during intravenous anesthesia
- 2012
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Ingår i: Critical Care. - : BioMed Central. - 1364-8535 .- 1466-609X. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionThe renal clearance of infused crystalloid fluid is very low during anaesthesia and surgery, but experiments in conscious sheep indicate that the renal fluid clearance might approach a normal rate when the adrenergic balance is modified.MethodsSixty females (mean age, 32 years) undergoing laparoscopic gynecological surgery were randomized to control group and received only the conventional anesthetic drugs and 20 ml/kg of lactated Ringer's over 30 mins. The others were also given an infusion of 50 μg/kg/min of esmolol (beta1-receptor blocker) or 0.01 μg/kg/min of phenylephrine (alpha1-adrenergic agonist) over 3 hours. The distribution and elimination of infused fluid were studied by volume kinetic analysis based on urinary excretion and blood hemoglobin level.ResultsBoth drugs significantly increased urinary excretion while heart rate and arterial pressure remained largely unaffected. The urine flows during non-surgery were 43, 147, and 176 ml in the control, esmolol, and phenylephrine groups, respectively (medians, P < 0.03). When surgery had started the corresponding values were 34, 65 and 61 ml (P < 0.04). At 3 hours, averages of 9%, 20%, and 25% of the infused volume had been excreted in the three groups (P < 0.01). The kinetic analyses indicated that both treatments slowed down the distribution of fluid from the plasma to the interstitial fluid space, thereby preventing hypovolemia.ConclusionsEsmolol doubled and phenylephrine almost tripled urinary excretion during anesthesia-induced depression of renal fluid clearance.
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| 1104. |
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| 1105. |
- Hu, Qiyu, et al.
(författare)
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Developing insoluble polyoxometalate clusters to bridge homogeneous and heterogeneous water oxidation photocatalysis
- 2023
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Ingår i: Angewandte Chemie International Edition. - : John Wiley & Sons. - 1433-7851 .- 1521-3773. ; 2:32
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Tidskriftsartikel (refereegranskat)abstract
- Cluster catalysts are attractive for their atomically precise structures, defined compositions, tunable coordination environments, uniform active sites, and their ability to transfer multiple electrons, but they suffer from poor stability and recyclability. Here, we report a general approach to the direct insolubilization of a water soluble polyoxometalate (POM) [{(B-α-PW9O34)Co3(OH)(H2O)2(O3PC(O)-(C3H6NH3)PO3)}2Co]14- (Co7) and formation of a series of POM-based solid catalysts with the counter-cations Ag+, Cs+, Sr2+, Ba2+, Pb2+, Y3+, and Ce3+. They exhibit improved catalytic activities for visible-light-driven water oxidation following the trend CsCo7>SrCo7>AgCo7>CeIII Co7>BaCo7>YCo7>PbCo7. While CsCo7 exhibits mainly homogeneous catalysis, the others are predominantly heterogeneous catalysts. An optimal oxygen yield of 41.3 % and a high apparent quantum yield (AQY) of 30.6 % for SrCo7 is obtained, which is comparable to that of the parent homogeneous POM. Band gap structures, UV/Vis spectra, and real-time laser flash photolysis experiments collectively suggest that easier electron transfer from the solid POM catalyst to the photosensitizer promotes photocatalytic water oxidation performance. These solid POM catalysts exhibit good stability, which is directly confirmed by a combination of Fourier-transform infrared spectroscopy, electron microscopy, X-ray diffraction patterns, Raman spectroscopy, X-ray photoelectron spectroscopy, five cycles of tests, and poisoning experiments.
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| 1106. |
- Hua, Dong, et al.
(författare)
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Small interfering RNA-directed targeting of toll-like receptor 4 inhibits human prostate cancer cell invasion, survival, and tumorigenicity
- 2009
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Ingår i: Molecular Immunology. - : Elsevier BV. - 0161-5890 .- 1872-9142. ; 46:15, s. 2876-2884
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Tidskriftsartikel (refereegranskat)abstract
- A major cause of tumor treatment failure is cancer cell metastasis. Toll-like receptor 4 (TLR4)-mediated signaling has been implicated in tumor cell invasion, survival, and metastasis in a variety of cancers. In this study, we investigated the biological roles of TLR4 in prostate metastatic cell invasion and survival, and the potential of gene silencing of TLR4 using small interfering RNA (siRNA) for treatment of cancer. In cultured human prostate cancer cell lines, TLR4 were higher PC3 and DU145 as compared with the poorly metastatic LNCaP indicating that up-regulation of TLR4 was positively correlated with metastasis of tumor cell. In the highly metastatic cancer cell PC3, gene silencing of TLR4 using siRNA significantly inhibited TLR4 mRNA expression and protein level. Knockdown of TLR4 in PC3 cells resulted in a dramatic reduction of tumor cell migration and invasion as indicated by a Matrigel invasion assay. Furthermore, TLR4 siRNA suppressed cell viability and ultimately caused the induction of apoptotic cell death. The effects were associated with abrogating TLR4-mediated signaling to downstream target molecules such as myeloid differentiation factor 88 (MyD88), adaptor-inducing IFN-beta (TRIF), and interferon regulatory factor-1 (IRF-1). In a mouse prostate cancer model, administration with the plasmid construct expressing siRNA for TLR4 obviously inhibited established tumor growth and survival. These studies revealed evidence of a multifaceted signaling network operating downstream of TLR4-mediated tumor cell invasion, proliferation, and survival. Thus, RNA interference-directed targeting of TLR4 may raise the potential of its application for cancer therapy.
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| 1107. |
- Huang, Hongyun, et al.
(författare)
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Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)
- 2018
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Ingår i: Cell Transplantation. - : SAGE Publications. - 0963-6897 .- 1555-3892. ; 27:2, s. 310-324
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Forskningsöversikt (refereegranskat)abstract
- Cell therapy has been shown to be a key clinical therapeutic option for central nervous system diseases or damage. Standardization of clinical cell therapy procedures is an important task for professional associations devoted to cell therapy. The Chinese Branch of the International Association of Neurorestoratology (IANR) completed the first set of guidelines governing the clinical application of neurorestoration in 2011. The IANR and the Chinese Association of Neurorestoratology (CANR) collaborated to propose the current version "Clinical Cell Therapy Guidelines for Neurorestoration (IANR/CANR 2017)". The IANR council board members and CANR committee members approved this proposal on September 1, 2016, and recommend it to clinical practitioners of cellular therapy. These guidelines include items of cell type nomenclature, cell quality control, minimal suggested cell doses, patient-informed consent, indications for undergoing cell therapy, contraindications for undergoing cell therapy, documentation of procedure and therapy, safety evaluation, efficacy evaluation, policy of repeated treatments, do not charge patients for unproven therapies, basic principles of cell therapy, and publishing responsibility.
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| 1108. |
- Huang, Hongyun, et al.
(författare)
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The 2022 yearbook of neurorestoratology
- 2023
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Ingår i: JOURNAL OF NEURORESTORATOLOGY. - : Tsinghua University Press. - 2324-2426. ; 11:2
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Forskningsöversikt (refereegranskat)abstract
- There was much progress in the field of Neurorestoratology in the year of 2022. It included highlighting advances in understanding the pathogenesis of neurological diseases, neurorestorative mechanisms, and clinical treatments as compiled in the 2022 yearbook of Neurorestoratology. There is still controversy about whether amyloid b-protein and tau protein deposition are the reasons for or the results of Alzheimer's disease (AD) pathology. The fabricated images in important key articles that speculated on the reasons for AD pathogenesis were found. Cholinergic deficiency and decrease or loss in strength of glutamatergic synapse, limited or failing bidirectional cholinergic upregulation in early cognitive impairment, or progressive posterior-to-anterior cortical cholinergic denervation could result in the appearance of AD. Exploration of neurorestorative mechanisms were found in more detail ways in neuromodulation, immunomodulation, neurogenesis, neural network or circuitry reconstruction, neuroprotection, nervous structural repair, and neuroplasticity. Several kinds of cell therapies for neurological diseases showed neurorestorative effects in open-label and/or non-randomized clinical studies or trials. However, mesenchymal stromal cells and mononuclear cells did not demonstrate neurorestorative effects or improve the quality of life for patients with neurodegenerative diseases or neurotrauma including stroke, spinal cord injury (SCI), and amyotrophic lateral sclerosis in randomized, double-blind, placebo-controlled clinical trials (RDPCTs). Clinical treatments through neurostimulation/neuromodulati on and the brain-computer/ machine interface yielded positive results in AD, Parkinson's disease, stroke, SCI, cerebral palsy, and other diseases in RDPCTs. Neurorestorative surgery, pharmaceutical neurorestorative therapy and other interventions have demonstrated neurorestorative effects for various considered incurable neurological diseases in RDPCTs. Thus, this year, additional guidelines, assessment scales, and standards were set up or revised. These included guidelines of clinical neurorestorative treatments for brain trauma (2022 China version), clinical cell therapy guidelines for neurorestoration (IANR/CANR 2022), SCI or dysfunction quality of life rating scale (SCIDQLRS) (IANR 2022 version). Neurorestorative effects of varying therapeutic stra-tegies with higher standards of evidence-based medicine are now benefiting patients with currently incurable neurological diseases. Hopefully some of them may become routine therapeutic interventions for patients with these diseases in the near future.
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| 1109. |
- Huang, Jianpan, et al.
(författare)
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Altered d-glucose in brain parenchyma and cerebrospinal fluid of early Alzheimer's disease detected by dynamic glucose-enhanced MRI
- 2020
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 6:20
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Tidskriftsartikel (refereegranskat)abstract
- Altered cerebral glucose uptake is one of the hallmarks of Alzheimer's disease (AD). A dynamic glucose-enhanced (DGE) magnetic resonance imaging (MRI) approach was developed to simultaneously monitor d-glucose uptake and clearance in both brain parenchyma and cerebrospinal fluid (CSF). We observed substantially higher uptake in parenchyma of young (6 months) transgenic AD mice compared to age-matched wild-type (WT) mice. Notably lower uptakes were observed in parenchyma and CSF of old (16 months) AD mice. Both young and old AD mice had an obviously slower CSF clearance than age-matched WT mice. This resembles recent reports of the hampered CSF clearance that leads to protein accumulation in the brain. These findings suggest that DGE MRI can identify altered glucose uptake and clearance in young AD mice upon the emergence of amyloid plaques. DGE MRI of brain parenchyma and CSF has potential for early AD stratification, especially at 3T clinical field strength MRI.
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| 1110. |
- Huang, Ketuan, et al.
(författare)
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Genetic variants and Expression of Cytochrome p450 Oxidoreductase Predict Postoperative Survival in Patients with Hepatitis B Virus-Related Hepatocellular Carcinoma
- 2019
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Ingår i: Journal of Cancer. - : IVYSPRING INT PUBL. - 1837-9664. ; 10:6, s. 1453-1465
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Tidskriftsartikel (refereegranskat)abstract
- Our current study investigates the prognostic values of genetic variants and mRNA expression of cytochrome p450 oxidoreductase (POR) in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). A total of 19 candidate single nucleotide polymorphisms (SNPs) located in the exons of POR were genotyped using Sanger sequencing from 476 HBV-related HCC patients who underwent hepatectomy between 2003 and 2013. The mRNA expression of POR in 212 patients with HBV-related HCC was obtained from GSE14520 dataset. Survival analysis was performed to investigate the association of POR variants and mRNA expression with overall survival (OS) and recurrence-free survival (RFS). Nomograms were used to predict the prognosis of HBV-related HCC patients. Gene set enrichment analysis (GSEA) was used to investigate the mechanism of POR in HBV-related HCC prognosis. The polymorphism POR-rs1057868 was significantly associated with HBV-related HCC OS (CT/TT vs. CC, hazard ratio [HR] = 0.69, 95% confidence interval [CI] = [0.54, 0.88], P = 0.003), but not significantly associated with RFS (CT/TT vs. CC, P = 0.378). POR mRNA expression was also significantly associated with HBV-related HCC OS (high vs. low, HR = 0.61, 95% CI = [0.38, 0.97], P= 0.036), but not significantly associated with the RFS (high vs. low, P = 0.201). Two nomograms were developed to predict the HBV-related HCC OS. Furthermore, GSEA suggests that multiple gene sets were significantly enriched in liver cancer survival and recurrence, as well as POR-related target therapy in the liver. In conclusion, our study suggests that POR-rs1057868 and mRNA expression may serve as a potential postoperative prognosis biomarker in HBV-related HCC.
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