Hormone-mediated Signaling Pathways Research Articles

Plant Stress and Biotechnology

Plant Stress and Biotechnology

Circulating MicroRNAs Identified in a Genome-Wide Serum MicroRNA Expression Analysis as Noninvasive Biomarkers for Endometriosis

There is currently no reliable noninvasive biomarker for the clinical diagnosis of endometriosis. Previous analyses have reported that circulating microRNAs (miRNAs) can serve as biomarkers for a number of diseases. The study aims to detect the serum miRNAs that are differentially expressed between endometriosis patients and negative controls to evaluate the potential of these miRNAs as diagnostic markers for endometriosis. A total of 765 serum miRNAs were profiled using a TaqMan microRNA array in a pool of 10 endometriosis patients and a pool of 10 negative controls, and a set of selected miRNAs were further analyzed in a validation cohort consisting of sera from 60 patients and 25 controls including 10 samples used in array profiling. The relative expression levels of miR-199a and miR-122 were found to be up-regulated in endometriosis patient samples compared with control samples, whereas miR-145*, miR-141*, miR-542-3p, and miR-9* were down-regulated in endometriosis patients. Importantly, the relative expression of miR-199a (P < 0.05) and miR-122 can be used to discriminate between severe and mild endometriosis. We also found that miR-199a is well correlated with pelvic adhesion and lesion distribution (P < 0.05) and associated with hormone-mediated signaling pathways. Furthermore, we investigated the diagnostic value of these molecules and confirmed the optimal combination of miR-199a, miR-122, miR-145*, and miR-542-3p with area under the curve of 0.994 (95% confidence interval = 0.984-1.000, P < 0.001) and a cutoff point (0.4950) of 93.22% sensitivity and 96.00% specificity. Our study demonstrated that the circulating miRNAs miR-199a, miR-122, miR-145*, and miR-542-3p could potentially serve as noninvasive biomarkers for endometriosis. miR-199a may also play an important role in the progression of the disease. This is the first report that circulating miRNAs serve as biomarkers of endometriosis.

Rejuvenation of the aging thymus: growth hormone-mediated and ghrelin-mediated signaling pathways

One of the major fundamental causes for the aging of the immune system is the structural and functional involution of the thymus, and the associated decline in de novo naïve T-lymphocyte output. This loss of naïve T-cell production weakens the ability of the adaptive immune system to respond to new antigenic stimuli and eventually leads to a peripheral T-cell bias to the memory phenotype. While the precise mechanisms responsible for age-associated thymic involution remain unknown, a variety of theories have been forwarded including the loss of expression of various growth factors and hormones that influence the lymphoid compartment and promote thymic function. Extensive studies examining two hormones, namely growth hormone (GH) and ghrelin (GRL), have demonstrated their contributions to thymus biology. In the current review, we discuss the literature supporting a role for these hormones in thymic physiology and age-associated thymic involution and their potential use in the restoration of thymic function in aged and immunocompromised individuals.

Salicylate‐mediated interactions between pathogens and herbivores

Plants employ hormone-mediated signaling pathways to defend against pathogens and insects. We tested predictions about the relative effect of jasmonate and salicylate pathways and how they mediate interactions between pathogens and herbivores. We employed two pathogens of tomato, Pseudomonas syringae (Pst) and tobacco mosaic virus (TMV), that are known to elicit distinct components of the two pathways, and we address the consequences of their induction for resistance in wild-type and salicylate-deficient transgenic plants in field experiments. We report that Pst infection induced jasmonic acid and proteinase inhibitors (PIs), and reduced the growth of Spodoptera exigua caterpillars on wild-type and salicylate-deficient plants. Pst and TMV both induced salicylic acid in wild-type but not salicylate-deficient plants. Although TMV did not affect jasmonic acid or PIs, infection increased caterpillar growth on wild-type plants, but not on salicylate-deficient plants. Aphid population growth was higher on salicylate-deficient compared to wild-type plants, and lower on salicylate-induced plants compared to controls. Natural aphid colonization was reduced on TMV-infected wild types, but not on salicylate-deficient plants. In sum, jasmonate-mediated resistance is induced by some pathogens, independent of salicylate, and salicylate-mediated induction by other pathogens results in induced susceptibility to a chewer and resistance to an aphid. We conclude with a predictive model for the expression of defense pathways and their consequences.

Distinct molecular mechanisms underlying clinically relevant subtypes of breast cancer: gene expression analyses across three different platforms

BackgroundGene expression profiling has been used to define molecular phenotypes of complex diseases such as breast cancer. The luminal A and basal-like subtypes have been repeatedly identified and validated as the two main subtypes out of a total of five molecular subtypes of breast cancer. These two are associated with distinctly different gene expression patterns and more importantly, a significant difference in clinical outcome. To further validate and more thoroughly characterize these two subtypes at the molecular level in tumors at an early stage, we report a gene expression profiling study using three different DNA microarray platforms.ResultsExpression data from 20 tumor biopsies of early stage breast carcinomas were generated on three different DNA microarray platforms; Applied Biosystems Human Genome Survey Microarrays, Stanford cDNA Microarrays and Agilent's Whole Human Genome Oligo Microarrays, and the resulting gene expression patterns were analyzed. Both unsupervised and supervised analyses identified the different clinically relevant subtypes of breast tumours, and the results were consistent across all three platforms. Gene classification and biological pathway analyses of the genes differentially expressed between the two main subtypes revealed different molecular mechanisms descriptive of the two expression-based subtypes: Signature genes of the luminal A subtype were over-represented by genes involved in fatty acid metabolism and steroid hormone-mediated signaling pathways, in particular estrogen receptor signaling, while signature genes of the basal-like subtype were over-represented by genes involved in cell proliferation and differentiation, p21-mediated pathway, and G1-S checkpoint of cell cycle-signaling pathways. A minimal set of 54 genes that best discriminated the two subtypes was identified using the combined data sets generated from the three different array platforms. These predictor genes were further verified by TaqMan® Gene Expression assays.ConclusionWe have identified and validated the two main previously defined clinically relevant subtypes, luminal A and basal-like, in a small set of early stage breast carcinomas. Signature genes characterizing these two subtypes revealed that distinct molecular mechanisms might have been pre-programmed at an early stage in different subtypes of the disease. Our results provide further evidence that these breast tumor subtypes represent biologically distinct disease entities and may require different therapeutic strategies. Finally, validated by multiple gene expression platforms, including quantitative PCR, the set of 54 predictor genes identified in this study may define potential prognostic molecular markers for breast cancer.