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131.
Moonseong Heo David B. Allison Myles S. Faith Shankuan Zhu Kevin R. Fontaine 《Obesity (Silver Spring, Md.)》2003,11(2):209-216
Objective: To estimate the association between body mass index (BMI) and health‐related quality of life (HRQL) and examine whether joint pain and obesity‐related comorbidities mediate the BMI‐HRQL association. Research Methods and Procedures: Population‐based survey data from the 1999 Behavioral Risk Factor Surveillance Survey. Adults (N = 155, 989) were classified according to BMI as underweight (<18.5 kg/m2), desirable weight (18.5 to 24.9 kg/m2), overweight (25 to 29.9 kg/m2), obese class I (30 to 34.9 kg/m2), obese class II (35 to 39.9 kg/m2), and obese class III (≥40 kg/m2). Data including general health status, unhealthy days in the past 30 caused by physical problems and mental problems, and total unhealthy days in the past 30 were collected. Results: After adjusting for age, sex, race, smoking, education, and income, we observed J‐shaped associations between BMI and HRQL. Compared with desirable weight adults, underweight, overweight, and obesity classes I, II, and III adults [odds ratio (OR) = 1.57, 1.19, 1.95, 2.72, and 4.36, respectively] were significantly (p < 0.001) more likely to report fair/poor general health status. For unhealthy days caused by physical problems, the corresponding ORs were 1.51, 1.15, 1.66, 2.27, and 3.61 (p < 0.001). For unhealthy days caused by mental problems, the ORs were 1.35, 1.14 1.43, 1.57, and 2.25 (p < 0.001). For total unhealthy days, the corresponding ORs were 1.27, 1.09, 1.37, 1.73, and 2.46 (p < 0.01). Adding joint pain and obesity‐related comorbidities into models attenuated BMI‐HRQL associations. Discussion: Associations between BMI and HRQL indices were J‐shaped. Joint pain and comorbidities may mediate BMI‐HRQL associations. 相似文献
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Hung-Yun Lin Mingzeng Sun Cassie Lin Heng-Yuan Tang David London Ai Shih Faith B. Davis Paul J. Davis 《The Journal of steroid biochemistry and molecular biology》2009,113(3-5):182-188
Androgens have important physiological effects in women. Not only are they the precursor hormones for estrogen biosynthesis in the ovaries and extragonadal tissues, but also act directly via androgen receptors (ARs) throughout the body. Studies of the role of androgens on breast cancer development are controversial and the mechanisms involved are not fully understood. In this report we demonstrate that a non-aromatizable androgen metabolite, dihydrotestosterone (DHT), stimulated cell proliferation in vitro of both estrogen receptor-α (ER-α)-positive MCF-7 cells and ER-α-negative MDA-MB-231 human breast cancer cells. A contribution of ER to the proliferative effect of DHT in MCF-7 cells was supported by actions of small interfering RNA (siRNA) ER-α transfection and of the specific inhibitor of ER, ICI 182,780 to block DHT-induced proliferation. A contribution of the possible conversion of DHT to androstane-3α, 17β-diol was not excluded in these MCF-7 cell studies. In MDA-MB-231 cells, a novel mechanism was implicated, in that anti-integrin αvβ3 or an Arg-Gly-Asp (RGD) peptide targeted at a small molecule binding domain of the integrin eliminated the DHT effect on cell proliferation. Anti-integrin αvβ3 did not affect DHT action on MCF-7 cells. A contribution from classical androgen receptor to the DHT effect in each cell line was excluded. A proliferative DHT signal is transduced in both ER-α-positive and ER-α-negative breast cancer cells, but by discrete mechanisms. 相似文献
134.
c-Myc overexpression and endocrine resistance in breast cancer 总被引:5,自引:0,他引:5
135.
Hammach A Barbosa A Gaenzler FC Fadra T Goldberg D Hao MH Kroe RR Liu P Qian KC Ralph M Sarko C Soleymanzadeh F Moss N 《Bioorganic & medicinal chemistry letters》2006,16(24):6316-6320
A new class of benzimidazolone p38 MAP kinase inhibitors was discovered through high-throughput screening. X-ray crystallographic data of the lead molecule with p38 were used to design analogues with improved binding affinity and potency in a cell assay of LPS-induced TNF production. Herein, we report the SAR of this new class of p38 inhibitors. 相似文献
136.
Background
Enteroaggregative Escherichia coli (EAEC) are defined by their stacked-brick adherence pattern to human epithelial cells. There is no all-encompassing genetic marker for EAEC. The category is commonly implicated in diarrhea but research is hampered by perplexing heterogeneity.Methodology/Principal Findings
To identify key EAEC lineages, we applied multilocus sequence typing to 126 E. coli isolates from a Nigerian case-control study that showed aggregative adherence in the HEp-2 adherence assay, and 24 other EAEC strains from diverse locations. EAEC largely belonged to the A, B1 and D phylogenetic groups and only 7 (4.6%) isolates were in the B2 cluster. As many as 96 sequence types (STs) were identified but 60 (40%) of the EAEC strains belong to or are double locus variants of STs 10, 31, and 394. The remainder did not belong to predominant complexes. The most common ST complex, with predicted ancestor ST10, included 32 (21.3%) of the isolates. Significant age-related distribution suggests that weaned children in Nigeria are at risk for diarrhea from of ST10-complex EAEC. Phylogenetic group D EAEC strains, predominantly from ST31- and ST394 complexes, represented 38 (25.3%) of all isolates, include genome-sequenced strain 042, and possessed conserved chromosomal loci.Conclusions/Significance
We have developed a molecular phylogenetic framework, which demonstrates that although grouped by a shared phenotype, the category of ‘EAEC’ encompasses multiple pathogenic lineages. Principal among isolates from Nigeria were ST10-complex EAEC that were associated with diarrhea in children over one year and ECOR D strains that share horizontally acquired loci. 相似文献137.
Infection with the Lyme disease pathogen suppresses innate immunity in mice with diet‐induced obesity
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Nataliya Zlotnikov Ashkan Javid Mijhgan Ahmed Azad Eshghi Tian Tian Tang Anoop Arya Anil Bansal Fatima Matar Maitry Parikh Rhodaba Ebady Adeline Koh Nupur Gupta Peng Song Yang Zhang Susan Newbigging Gary P. Wormser Ira Schwartz Robert Inman Michael Glogauer Tara J. Moriarty 《Cellular microbiology》2017,19(5)
Obesity is a major global public health concern. Immune responses implicated in obesity also control certain infections. We investigated the effects of high‐fat diet‐induced obesity (DIO) on infection with the Lyme disease bacterium Borrelia burgdorferi in mice. DIO was associated with systemic suppression of neutrophil‐ and macrophage‐based innate immune responses. These included bacterial uptake and cytokine production, and systemic, progressive impairment of bacterial clearance, and increased carditis severity. B. burgdorferi‐infected mice fed normal diet also gained weight at the same rate as uninfected mice fed high‐fat diet, toll‐like receptor 4 deficiency rescued bacterial clearance defects, which greater in female than male mice, and killing of an unrelated bacterium (Escherichia coli) by bone marrow‐derived macrophages from obese, B. burgdorferi‐infected mice was also affected. Importantly, innate immune suppression increased with infection duration and depended on cooperative and synergistic interactions between DIO and B. burgdorferi infection. Thus, obesity and B. burgdorferi infection cooperatively and progressively suppressed innate immunity in mice. 相似文献
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Widiez T Hartman TG Dudai N Yan Q Lawton M Havkin-Frenkel D Belanger FC 《Plant molecular biology》2011,76(6):475-488
Caffeoyl CoA O-methyltransferases (OMTs) have been characterized from numerous plant species and have been demonstrated to be involved in
lignin biosynthesis. Higher plant species are known to have additional caffeoyl CoA OMT-like genes, which have not been well
characterized. Here, we identified two new caffeoyl CoA OMT-like genes by screening a cDNA library from specialized hair cells
of pods of the orchid Vanilla planifolia. Characterization of the corresponding two enzymes, designated Vp-OMT4 and Vp-OMT5, revealed that in vitro both enzymes preferred
as a substrate the flavone tricetin, yet their sequences and phylogenetic relationships to other enzymes are distinct from
each other. Quantitative analysis of gene expression indicated a dramatic tissue-specific expression pattern for Vp-OMT4, which was highly expressed in the hair cells of the developing pod, the likely location of vanillin biosynthesis. Although
Vp-OMT4 had a lower activity with the proposed vanillin precursor, 3,4-dihydroxybenzaldehyde, than with tricetin, the tissue
specificity of expression suggests it may be a candidate for an enzyme involved in vanillin biosynthesis. In contrast, the
Vp-OMT5 gene was mainly expressed in leaf tissue and only marginally expressed in pod hair cells. Phylogenetic analysis suggests
Vp-OMT5 evolved from a cyanobacterial enzyme and it clustered within a clade in which the sequences from eukaryotic species
had predicted chloroplast transit peptides. Transient expression of a GFP-fusion in tobacco demonstrated that Vp-OMT5 was
localized in the plastids. This is the first flavonoid OMT demonstrated to be targeted to the plastids. 相似文献