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Anti-inflammatory mechanisms of the novel cytokine interleukin-38 in allergic asthma

Cellular & Molecular Immunology 2020年第6期17卷 631-646页

作者： Xiaoyu Sun Tianheng Hou Edwin Cheung tiffany nga-teng iu Victor Wai-Hou Tam Ida Miu-Ting Chu Miranda Sin-Man Tsang Paul Kay-Sheung Chan Christopher Wai-Kei Lam Chun-Kwok Wong Department of Chemical Pathology The Chinese University of Hong KongHong KongChina Cancer Centre/Centre of Precision Medicine Research and Training Faculty of Health SciencesUniversity of MacaoMacaoChina Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Microbiology The Chinese University of Hong KongHong KongChina Faculty of Medicine and State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacaoChina Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong KongHong KongChina

We elucidated the anti-inflammatory mechanisms of IL-38 in allergic *** bronchial epithelial cells and eosinophils were cocultured upon stimulation with the viral RLR ligand poly(I:C)/LyoVec or infection-related cytokine TNF-αto induce expression of cytokines/chemokines/adhesion *** dust mite(HDM)-induced allergic asthma and humanized allergic asthma NOD/SCID murine models were established to assess anti-inflammatory mechanisms in ***-38 significantly inhibited induced proinflammatory IL-6,IL-1β,CCL5,and CXCL10 production,and antiviral interferon-βand intercellular adhesion molecule-1 expression in the coculture *** cytometry and RNA-sequencing analysis revealed that IL-38 could antagonize the activation of the intracellular STAT1,STAT3,p38 MAPK,ERK1/2,and NF-κB pathways,and upregulate the expression of the host defense-related gene POU2AF1 and anti-allergic response gene *** injection of IL-38 into HDM-induced allergic asthma mice could ameliorate airway hyperreactivity by decreasing the accumulation of eosinophils in the lungs and inhibiting the expression of the Th2-related cytokines IL-4,IL-5,and IL-13 in the bronchoalveolar lavage fluid(BALF)and lung *** examination indicated lung inflammation was alleviated by reductions in cell infiltration and goblet cell hyperplasia,together with reduced Th2,Th17,and innate lymphoid type 2 cell numbers but increased proportions of regulatory T cells in the lungs,spleen,and lymph ***-38 administration suppressed airway hyperreactivity and asthma-related IL-4 and IL-5 expression in humanized mice,together with significantly decreased CCR3^(+) eosinophil numbers in the BALF and lungs,and a reduced percentage of human CD4^(+)CRTH2^(+)Th2 cells in the lungs and mediastinal lymph ***,our results demonstrated the anti-inflammatory mechanisms of IL-38 and provided a basis for the development of a regulatory cytokine-based treatment for allergic

关键词： allergic asthma eosinophils IL-38 ILC2s Tregs

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Characterization of the Xenopus homolog of animmediate early gene associated with cell activation: sequence analysis and regulation of its expression by thyroid hormone during amphibian metamorphosis

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Cell Research 1997年第2期7卷 179-193页

作者： VIVIA CT LIANG tiffany SEDGWICK YUN BOSHI(Laboratory of Molecular Embryology NICHD/NIH, Bldg.18T, Rm. 106 Bethesda, MD 20892-5431 USA) Laboratory of Molecular Embryology NICHD/NIH USA

The complex transformation of a tadpole to a frogduring amphibian development is under the control of thyroid hormone (T3). T3 is known to regulate gene transcription through its nuclear receptors. We have previouslyisolated many genes which are up-regulated by T3 in theintestine of Xenopus laevis tadpoles. We have now cloneda full- length cDNA for one such gene (iu12). Sequenceanalysis shows that the iu12 cDNA encodes a plasmamembrane protein with 12 transmembrane domains andhomologous to a mammalian gene associated with cell activation and organ development. Similarly, we have foundthat iu12 is activated during intestinal remodeling whenboth cell death and proliferation take place. Furthermore,iu12 is an early T3-response gene and its expression in theintestine during T3-induced metamorphosis mimics thatduring normal development. These results argue for a roleof iu12 in the signal transduction pathways leading to intestinal metamorphosis.

关键词： Thyroid hormone Xenopus laevis cell proliferation organogenesis transcription factor

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Overuse and underuse of calcium and vitamin D in women with osteoporosis: A survey in a primary care setting

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Open Journal of Preventive Medicine 2013年第9期3卷 570-575页

作者： Milagros Silva Adam Romeiser David W. Baker Aashish K. Didwania tiffany Brown Joseph M. Feinglass Ji Young Lee Nancy C. Dolan Division of General Internal Medicine Department of Medicine Northwestern University Feinberg School of Medicine Chicago USA

Introduction: Optimal calcium and vitamin D intake is important components of the treatment of osteoporosis. The national average calcium and vitamin D intake for women over age 50 is below the recommended levels for optimal bone health. The aim of this study was to assess whether deficiencies in calcium and vitamin D intake exist in women with osteoporosis in a general medicine practice, as well as evaluate whether physicians accurately document calcium and vitamin D supplementation in the health record. Methods: Using the Electronic Health Record (EHR), we identified all female patients age 50 and older with the diagnosis of osteoporosis who were seen at the study site clinic, an urban academic general medicine practice, between January 1st, 2010 and December 1st, 2010. Women were randomly selected to receive an invitation to participate in a telephone survey on osteoporosis treatment. Results: One hundred and sixteen women completed the telephone survey. The mean calcium intake was 1524 mg per day. Forty-nine percent of women surveyed reported taking less than 1200 mg/day of supplemental calcium. When considering reported calcium intake from diet, 33% percent consumed less than 1200 mg/day and 52% percent consumed more than 1500 mg/day. Twenty eight percent of patients were taking less than 800 iu/day of vitamin D;only four percent were taking more than 4000 iu/day. Agreement between patients’ self-reported intake of calcium, vitamin D and multivitamin supplements and physicians’ documentation of these supplements was 52% for calcium, 53% for vitamin D and 61% for multivitamin. Conclusion: Among women with osteoporosis getting regular care in a general medicine practice, approximately a third are getting less than the recommended daily amount of calcium and a quarter less than the recommended amount of vitamin D. In addition, a significant proportion of women are getting excessive daily amounts of calcium, which may also be a quality concern. Rates of agreement b

关键词： Calcium Supplementation Ambulatory Electronic Health Record Vitamin Supplementation Osteoporosis

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Effectiveness of Ledipasvir/Sofosbuvir with / without Ribavarin in Liver Transplant Recipients with Hepatitis C

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Journal of Clinical and Translational Hepatology 2017年第2期5卷 101-108页

作者： Sammy Saab Justin Rheem Melissa A.Jimenez tiffany M.Fong Michelle H.Mai Caterina A.Kachadoorian Negin L.Esmailzadeh Sherona N.Bau Susan Kang Samantha D.Ramirez Jonathan Grotts Gina Choi Francisco A.Durazo Mohammed M.El-Kabany Steven-Huy B.Han Ronald W.Busuttil Departments of Medicine at the University of California at Los Angeles Los Angeles California USA Departments of Surgery at the University of California at Los Angeles Los Angeles California USA Department of Medicine at Harbor-University of California at Los Angeles Medical Center Torrance California USA Departments of Surgery at the University of California at Los Angeles Los Angeles California USA Department of Biostatistics at the University of California at Los Angeles Los Angeles California USA

Background and Aims:Recurrent infection of hepatitis C virus (HCV) in liver transplant (LT) recipients is universal and associated with significant morbidity and ***:We retrospectively evaluated the safety and efficacy of ledipasvir/sofosbuvir with and without ribavirin in LT recipients with recurrent genotype 1 hepatitis ***:Eighty-five LT recipients were treated for recurrent HCV with ledipasvir/sofosbuvirwith and without ribavirin for 12 or 24 *** mean (± standard deviation [SD]) time from LT to treatment initiation was 68 (±71) *** mean (± SD) age of the cohort was 63 (±8.6) years *** recipients were male (70%).Baseline alanine transaminase,total bilirubin,and HCV ribonucleic acid (RNA) values (± SD) were 76.8 (±126)mg/dL,0.8 (±1.3) U/L,and 8,010,421.9 (±12,420,985)iu/mL,*** of 43 recipients who were treated with ribavirin required drug cessation due to side effects,with 4 of those being anemia *** recipient discontinued the ledipasvir/***-one percent of recipients had undetectable viral levels at 4 weeks after starting therapy,and all recipients had complete viral suppression at the end of *** sustained viral response at 12 weeks after completion of therapy was 94%.Conclusion:Ledipasvir and sofosbuvir with and without ribavirin therapy is an effective and well-tolerated interferon-free treatment for recurrent HCV infection after *** is not uncommon in LT recipients receiving ribavirin.

关键词： Liver transplantation Immunosuppressant Hepatitis C Direct-acting agents Sustained viral response

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Quantitative hepatitis B surface antigen in predicting recurrence of hepatitis B-related hepatocellular carcinoma after liver transplantation

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Hepatoma Research 2018年第9期4卷 159-170页

作者： James Fung Danny Ka-Ho Wong Yasuhito Tanaka Regina Lo tiffany Wong Kenneth Siu-Ho Chok AIbert Chi-Yan Chan Tan-To Cheung Wing-Chiu Dai KeIvin Ng Kevin Ng Man Kwan Irene Ng Wai-Kay Seto Ching-Lung Lai Man-Fung Yuen Chung-Mau Lo The Liver Transplant Center Queen Mary HospitalHong KongChina Department of Medicine the University of Hong KongHong KongChina State Key Laboratory for Liver Research the University of Hong KongHong KongChina Department of Virology and Liver Unit Graduate School of Medical sciencesNagoya City UniversityNagoya 467-8601Japan Department of Pathology the University of Hong KongHong KongChina Department of Surgery the University of Hong KongHong KongChina

Aim:Recurrence of hepatocellular carcinoma (HCC) after liver transplantation (LT) for chronic hepatitis B (CHB) can be associated with reappearance of hepatitis B surface antigen (HBsAg). The current study determined the significance of HBsAg qualitatively and quantitatively using a highly sensitive assay in recurrent HCC after transplantation. Methods:Consecutive patients with HBV-related HCC with LT were included. Oral nucleos(t)ide analogues without hepatitis B immune globulin were used as hepatitis B virus (HBV) prophylaxis. Quantitative HBsAg levels were performed at time of transplant, at 1 month, 3 and 6 months post transplant using a highly sensitive (hs)-HBsAg assay. Results:One hundred and fourteen patients were included, with a median follow-up of 80 months, with 24 cases of HCC recurrence, and a cumulative rate of 20.7% at 5 years. There was significant correlation between time of tumor recurrence and time of HBsAg reappearance (r = 0.551,P = 0.027). Early HCC recurrence was associated with higher median level of hs-HBsAg at the time of transplant (72.85vs. 69.70 iu/mL,P = 0.018). Using a hs-HBsAg cut-off level of 0.0005 iu/mL, patients with levels above this threshold at 3 and 6 months were associated with higher rate of early HCC recurrence (28.6%vs. 3.0% and 26.9%vs. 2.9% respectively, bothP =0.0006). There was no significant difference in HCC recurrence between positive and negative HBsAg using the conventional qualitative HBsAg assay. Conclusion:Serum hs-HBsAg levels of≥ 0.0005 iu/mL at 3 to 6 months after LT is associated with higher rates of early HCC recurrence, and may be useful as an early tumor marker.

关键词： Hepatitis B hepatocellular carcinoma transplantation hepatitis B surface antigen recurrence

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