Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Epigenetic dysregulation is an important emerging hallmark of cutaneous melanoma development. The global loss of DNA methylation in gene-poor regions and transposable DNA elements of cancer cells contributes to increased genomic instability. Long interspersed element-1 (LINE-1) sequences are the most abundant repetitive sequence of the genome and can be evaluated as a surrogate marker of the global level of DNA methylation. ⋯ The qualitative analysis showed a trend toward an association between LINE-1 hypomethylation and CDKN2A inactivation (p=0.05). In a quantitative approach, primary tumors, mainly the thicker ones (>4 mm), exhibited a trend toward LINE-1 hypomethylation when compared with control melanocytes. To date, this is the first study reporting in cutaneous melanomas a possible link between the dysregulation of LINE-1 methylation and the presence of driver mutations.
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Blood mercury (methyl-mercury) from environmental exposure may be related to inflammation in our body. We investigated the cut-off values of blood mercury concentration in relation to increased body mass index (BMI) and waist circumference. On the basis of data obtained from the Korea National Health and Nutrition Examination Survey (KNHANES, 2008-2012), 11,159 subjects (5543 males and 5616 females) were analyzed cross-sectionally. ⋯ BMI and waist circumference showed a significant and gradual increase as mercury quartile increased in both genders. Blood mercury concentration was weakly but significantly (p < 0.001) associated with BMI and waist circumference. Cut-off values of blood mercury concentration correlated with increased BMI and waist circumference were around 3.95 μg/L in males and 3.40 μg/L in females.
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In vitro follicle growth (IVFG) strategy is critical in the fertility preservation of cancer survivors; however, its optimal protocol needs to be developed using primate models since the availability of human samples is limited. Only a few previous studies have reported the successful IVFG of rhesus monkey ovaries using low-dose follicle-stimulating hormone (FSH) (0.3 or 3 ng/mL) and long-term culture (up to 5 weeks) and it is still uncertain in regard to the optimal culture duration and effective dose of treated gonadotropins applicable to the IVFG of rhesus preantral follicles. Recently, we have reported that the FSH to luteinizing hormone (LH) ratio affects the in vitro growth of murine ovarian follicles. ⋯ High concentration gonadotropin treatment shortened the duration required for in vitro maturation of rhesus preantral follicles. The FSH:LH=2:1 group showed a faster follicular growth and enabled the acquisition of mature oocytes, although the expression of growth differentiation factor (GDF)-9 and anti-Müllerian hormone (AMH) did not differ significantly between the two groups. Taken together, high dose gonadotropin treatment can shorten the duration of IVFG and the gonadotropin ratio is important in the IVFG of rhesus monkey ovaries.
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Lumbar spinal canal stenosis (LSCS) is the most common spinal disorder in elderly patients, causing low back and leg pain, radiculopathy, and cauda equina syndrome. Vascular endothelial growth factor (VEGF) is a potent regulator of many cellular functions including proliferation, differentiation, wound healing, and angiogenesis. The present study aimed to investigate the pattern of VEGF expression in the ligamentum flavum (LF) of patients with LSCS. 24 patients with LSCS were recruited in this prospective study. ⋯ There was no correlation between the tissue VEGF expression of non-pathological LF and patient age in patients with LSCS. Moreover, the immunohistochemical study revealed that VEGF was positively stained on fibroblasts, inflammatory cells, and endothelial cells representing neovascularization within hypertrophic LF compared to the non-pathological LF of controls. The increased expression of VEGF was associated with the degenerative changes of hypertrophic LF, suggesting that VEGF could contribute to one of the mechanisms of pathogenesis in lumbar spinal stenosis.
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Translating basic science advances into clinical meaning has been challenging for stroke research. This does not, however, mean that the investigation of basic mechanisms is irrelevant. Translation is difficult because the underlying mechanisms are complex and ill-defined. ⋯ Importantly, these cell-cell signaling pathways are also biphasic in nature, that is, mechanisms that are deleterious in the acute phase may surprisingly be required for neurovascular remodeling and plasticity during stroke recovery. Furthermore, injury-into-repair gradients are significantly influenced by a host of modifying factors and comorbidities. Rigorous dissection of these complex and recursive mechanisms should be required before they can be rationally targeted for stroke.