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  • 1
    Online Resource
    Online Resource
    Elevated CXCL12 expression in the bone marrow of NOD mice is associated with altered T cell and stem cell trafficking and diabetes development
    Springer Science and Business Media LLC ; 2008
    In:  BMC Immunology Vol. 9, No. 1 ( 2008-12)
    Details
    In: BMC Immunology, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2008-12)
    Abstract: Type I diabetes (TID) is an autoimmune disease resulting from destruction of the insulin-producing β-cells by autoreactive T cells. Studies have shown that polymorphisms of chemokine CXCL12 gene are linked to TID in humans. In non-obese diabetic (NOD) mice, which are predisposed to develop the disease, reduction of CXCL12 level leads to significant delays in the onset of diabetes. Despite these initial observations, however, how CXCL12 affects development of TID has not been fully investigated. Results We found that the level of CXCL12 transcript is significantly elevated in the bone marrow of NOD mice as compared to Balb/c and C57BL/6 mice. Correspondingly, naïve T cells, regulatory T cells and hematopoietic stem cells (HSC) accumulate in the bone marrow of NOD mice. Treatment of NOD mice with AMD3100, an antagonist for CXCL12's receptor CXCR4, mobilizes T cells and HSC from the bone marrow to the periphery, concomitantly inhibits insulitis and delays the onset of diabetes. Conclusion These results suggest that the elevated CXCL12 expression promotes TID in NOD mice by altering T cell and hematopoietic stem cell trafficking. The findings highlight the potential usefulness of AMD3100 to treat or prevent TID in humans.
    Type of Medium: Online Resource
    ISSN: 1471-2172
    URL: Article
    DOI: 10.1186/1471-2172-9-51
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2008
    detail.hit.zdb_id: 2041500-X
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  • 2
    Online Resource
    Online Resource
    Small Molecules Blocking the Entry of Severe Acute Respiratory Syndrome Coronavirus into Host Cells
    American Society for Microbiology ; 2004
    In:  Journal of Virology Vol. 78, No. 20 ( 2004-10-15), p. 11334-11339
    Details
    In: Journal of Virology, American Society for Microbiology, Vol. 78, No. 20 ( 2004-10-15), p. 11334-11339
    Abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV) is the pathogen of SARS, which caused a global panic in 2003. We describe here the screening of Chinese herbal medicine-based, novel small molecules that bind avidly with the surface spike protein of SARS-CoV and thus can interfere with the entry of the virus to its host cells. We achieved this by using a two-step screening method consisting of frontal affinity chromatography-mass spectrometry coupled with a viral infection assay based on a human immunodeficiency virus (HIV)-luc/SARS pseudotyped virus. Two small molecules, tetra- O -galloyl-β- d -glucose (TGG) and luteolin, were identified, whose anti-SARS-CoV activities were confirmed by using a wild-type SARS-CoV infection system. TGG exhibits prominent anti-SARS-CoV activity with a 50% effective concentration of 4.5 μM and a selective index of 240.0. The two-step screening method described here yielded several small molecules that can be used for developing new classes of anti-SARS-CoV drugs and is potentially useful for the high-throughput screening of drugs inhibiting the entry of HIV, hepatitis C virus, and other insidious viruses into their host cells.
    Type of Medium: Online Resource
    ISSN: 0022-538X , 1098-5514
    URL: Article
    DOI: 10.1128/JVI.78.20.11334-11339.2004
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2004
    detail.hit.zdb_id: 1495529-5
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  • 3
    Online Resource
    Online Resource
    Characterization of classical swine fever virus entry by using pseudotyped viruses: E1 and E2 are sufficient to mediate viral entry
    Elsevier BV ; 2004
    In:  Virology Vol. 330, No. 1 ( 2004-12), p. 332-341
    Details
    In: Virology, Elsevier BV, Vol. 330, No. 1 ( 2004-12), p. 332-341
    Type of Medium: Online Resource
    ISSN: 0042-6822
    URL: Article
    DOI: 10.1016/j.virol.2004.09.023
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2004
    detail.hit.zdb_id: 1471925-3
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Pharmacogenomics of Leukotriene Modifiers: A Systematic Review and Meta-Analysis
    MDPI AG ; 2022
    In:  Journal of Personalized Medicine Vol. 12, No. 7 ( 2022-06-29), p. 1068-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 12, No. 7 ( 2022-06-29), p. 1068-
    Abstract: Pharmacogenetics research on leukotriene modifiers (LTMs) for asthma has been developing rapidly, although pharmacogenetic testing for LTMs is not yet used in clinical practice. We performed a systematic review and meta-analysis on the impact of pharmacogenomics on LTMs response. Studies published until May 2022 were searched using PubMed, EMBASE, and Cochrane databases. Pharmacogenomics/genetics studies of patients with asthma using LTMs with or without other anti-asthmatic drugs were included. Statistical tests of the meta-analysis were performed with Review Manager (Revman, version 5.4, The Cochrane Collaboration, Copenhagen, Denmark) and R language and environment for statistical computing (version 4.1.0 for Windows, R Core Team, Vienna, Austria) software. In total, 31 studies with 8084 participants were included in the systematic review and five studies were also used to perform the meta-analysis. Two included studies were genome-wide association studies (GWAS), which showed different results. Furthermore, none of the SNPs investigated in candidate gene studies were identified in GWAS. In candidate gene studies, the most widely studied SNPs were ALOX5 (tandem repeats of the Sp1-binding domain and rs2115819), LTC4S-444A/C (rs730012), and SLCO2B1 (rs12422149), with relatively inconsistent conclusions. LTC4S-444A/C polymorphism did not show a significant effect in our meta-analysis (AA vs. AC (or AC + CC): −0.06, 95%CI: −0.16 to 0.05, p = 0.31). AA homozygotes had smaller improvements in parameters pertaining to lung functions (−0.14, 95%CI: −0.23 to −0.05, p = 0.002) in a subgroup of patients with non-selective CysLT receptor antagonists and patients without inhaled corticosteroids (ICS) (−0.11, 95%CI: −0.14 to −0.08, p 〈 0.00001), but not in other subgroups. Variability exists in the pharmacogenomics of LTMs treatment response. Our meta-analysis and systematic review found that LTC4S-444A/C may influence the treatment response of patients taking non-selective CysLT receptor antagonists for asthma, and patients taking LTMs not in combination with ICS for asthma. Future studies are needed to validate the pharmacogenomic influence on LTMs response.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm12071068
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662248-8
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  • 5
    Online Resource
    Online Resource
    Physicians’ Knowledge, Attitude, and Experience of Pharmacogenomic Testing in China
    MDPI AG ; 2022
    In:  Journal of Personalized Medicine Vol. 12, No. 12 ( 2022-12-07), p. 2021-
    Details
    In: Journal of Personalized Medicine, MDPI AG, Vol. 12, No. 12 ( 2022-12-07), p. 2021-
    Abstract: (1) Background: As prescribers, physicians play a decisive role in applying and promoting pharmacogenomic (PGx) testing in clinical practices. So far, little is known about physicians’ perspectives on PGx testing in China. The aim of this study was to assess physicians’ knowledge of, attitude towards, and experience of PGx testing in China. (2) Methods: A 39-question online survey was developed. Participants were physicians recruited through two platforms, MEDLINKER and “Dazhuanjia”. (3) Results: A total of 450 respondents completed the survey and 366 questionnaires were eligible for analysis based on the inclusion criteria. Among all included physicians, 275 (75.1%) had heard of PGx testing before. More than half rated their knowledge of PGx testing as “Fair” (61.5%) while 20.0% chose “Excellent” or “Good” and 18.6% chose “Poor” or “Terrible”. “Guidelines, consensus, and treatment paths for disease diagnosis and treatment” (72.7%) were the most preferred sources of information about PGx testing. Respondents were confident in their personal capacity to conduct PGx, with an average score of 3.30 ± 0.09 (out of 5.00). Most respondents (75.6%) believed that PGx could “help to improve efficacy and reduce the incidence of adverse reactions”. Targeted cancer therapy (score 78.95 ± 1.26 out of 100) was considered the field where PGx testing had its highest value. Lack of professionals and knowledge (n = 186, 67.6%), high costs of testing (n = 170, 61.8%), and lack of hospitals to offer PGx testing (n = 166, 60.4%) were identified as the primary obstacles to increasing the uptake of PGx testing in China. Academic conference (n = 213, 72.4%) was considered the most efficient way for physicians to obtain information about PGx testing. (4) Conclusions: Physicians in China have poor knowledge about PGx testing; nonetheless, they generally had confidence in their capacity to order PGx testing and positive attitudes towards the use of PGx testing in routine clinical practices. Future efforts to promote the uptake of PGx testing should focus on foundational education and practical training.
    Type of Medium: Online Resource
    ISSN: 2075-4426
    URL: Article
    DOI: 10.3390/jpm12122021
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662248-8
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  • 6
    Online Resource
    Online Resource
    Data_Sheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Cardiovascular Medicine Vol. 9 ( 2022-11-8)
    Details
    In: Frontiers in Cardiovascular Medicine, Frontiers Media SA, Vol. 9 ( 2022-11-8)
    Abstract: The aim of this article is to assess the risk and potential mechanisms of cardiovascular adverse events in patients treated with nilotinib or imatinib by conducting a systematic review, meta-analysis and integrative bioinformatics analysis. Materials and methods Three databases were systematically searched for studies published from inception to May 29, 2022. Differential expression analysis and weighted gene coexpression network analysis (WGCNA) were performed to search for modules of genes most associated with cardiotoxicity. Protein-protein interaction (PPI) network analysis was then performed to identify hub genes for the cardiotoxicity of nilotinib. Molecular docking was used to analyze the effects of rosuvastatin and aspirin on these targets. Results Patients treated with nilotinib as first-line treatment were associated with a higher risk of CAE (OR = 3.43 [95% CI 2.77–4.25]), CAD (OR = 5.30 [95% CI 3.85–7.29] ), ACS (OR 2.7 [95% CI 1.60–4.54]), CVA (OR 5.76 [95% CI 2.84–11.28] ), PAOD (OR 5.57 [95% CI 3.26–9.50]) and arrhythmia (OR 2.34 [1.17,4.67] ) than those treated with imatinib, while no significant difference was found in the risk of HF (OR 1.40 [95% CI 0.42–4.69]) between the two groups. Patients who were treated with more than 600 mg daily dosage of nilotinib or followed up for more than 5 years had a higher risk of ACS and CVA. IL6, CXCL8, CCL2, SOD2, NFKBIA, and BIRC3 were identified as the top 6 hub genes in the magenta module (human cardiomyocyte samples) and were mainly enriched in the NOD-like receptor signaling pathway, IL-17 signaling pathway, TNF signaling pathway, lipid and atherosclerosis signaling pathway. TYROBP and CSF1R were identified as hub genes in the turquoise module (liver samples from Mus musculus). GSEA results showed that type II diabetes mellitus, B-cell receptor, apoptosis, insulin, natural killer cell mediated cytotoxicity, mTOR, chemokine, and T-cell receptor signaling pathways were related to the higher risk of atherosclerosis caused by nilotinib. Rosuvastatin can effectively bind to most of the hub targets and proteins enriched in the inflammatory pathways above. Conclusion CML patients who start with nilotinib have a higher risk of CAE than those with imatinib. Atherosclerosis caused by the inflammatory response and glycolipid metabolism disorder is the key mechanism of nilotinib cardiotoxicity. Rosuvastatin may be an effective treatment for the cardiotoxicity of nilotinib.
    Type of Medium: Online Resource
    ISSN: 2297-055X
    URL: Article
    URL: Article
    DOI: 10.3389/fcvm.2022.966182
    DOI: 10.3389/fcvm.2022.966182.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2781496-8
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  • 7
    Online Resource
    Online Resource
    Expression cloning of functional receptor used by SARS coronavirus
    Elsevier BV ; 2004
    In:  Biochemical and Biophysical Research Communications Vol. 315, No. 2 ( 2004-03), p. 439-444
    Details
    In: Biochemical and Biophysical Research Communications, Elsevier BV, Vol. 315, No. 2 ( 2004-03), p. 439-444
    Type of Medium: Online Resource
    ISSN: 0006-291X
    URL: Article
    DOI: 10.1016/j.bbrc.2004.01.076
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2004
    detail.hit.zdb_id: 1461396-7
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Highly infectious SARS-CoV pseudotyped virus reveals the cell tropism and its correlation with receptor expression
    Elsevier BV ; 2004
    In:  Biochemical and Biophysical Research Communications Vol. 321, No. 4 ( 2004-9), p. 994-1000
    Details
    In: Biochemical and Biophysical Research Communications, Elsevier BV, Vol. 321, No. 4 ( 2004-9), p. 994-1000
    Type of Medium: Online Resource
    ISSN: 0006-291X
    URL: Article
    DOI: 10.1016/j.bbrc.2004.07.060
    RVK:
    WA 15000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2004
    detail.hit.zdb_id: 1461396-7
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    The third Intensive Care Bundle with Blood Pressure Reduction in Acute Cerebral Haemorrhage Trial (INTERACT3): an international, stepped wedge cluster randomised controlled trial
    Elsevier BV ; 2023
    In:  The Lancet Vol. 402, No. 10395 ( 2023-07), p. 27-40
    Details
    In: The Lancet, Elsevier BV, Vol. 402, No. 10395 ( 2023-07), p. 27-40
    Type of Medium: Online Resource
    ISSN: 0140-6736
    URL: Article
    DOI: 10.1016/S0140-6736(23)00806-1
    RVK:
    XA 10000
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 2067452-1
    detail.hit.zdb_id: 3306-6
    detail.hit.zdb_id: 1476593-7
    SSG: 5,21
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  • 10
    Online Resource
    Online Resource
    CXCR4 is required for the quiescence of primitive hematopoietic cells
    Rockefeller University Press ; 2008
    In:  The Journal of Experimental Medicine Vol. 205, No. 4 ( 2008-04-14), p. 777-783
    Details
    In: The Journal of Experimental Medicine, Rockefeller University Press, Vol. 205, No. 4 ( 2008-04-14), p. 777-783
    Abstract: The quiescence of hematopoietic stem cells (HSCs) is critical for preserving a lifelong steady pool of HSCs to sustain the highly regenerative hematopoietic system. It is thought that specialized niches in which HSCs reside control the balance between HSC quiescence and self-renewal, yet little is known about the extrinsic signals provided by the niche and how these niche signals regulate such a balance. We report that CXCL12 produced by bone marrow (BM) stromal cells is not only the major chemoattractant for HSCs but also a regulatory factor that controls the quiescence of primitive hematopoietic cells. Addition of CXCL12 into the culture inhibits entry of primitive hematopoietic cells into the cell cycle, and inactivation of its receptor CXCR4 in HSCs causes excessive HSC proliferation. Notably, the hyperproliferative Cxcr4−/− HSCs are able to maintain a stable stem cell compartment and sustain hematopoiesis. Thus, we propose that CXCR4/CXCL12 signaling is essential to confine HSCs in the proper niche and controls their proliferation.
    Type of Medium: Online Resource
    ISSN: 1540-9538 , 0022-1007
    URL: Article
    DOI: 10.1084/jem.20072513
    RVK:
    XA 10000
    Language: English
    Publisher: Rockefeller University Press
    Publication Date: 2008
    detail.hit.zdb_id: 1477240-1
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