European Journal of Histochemistry最新文献

The present study was undertaken to provide more information on the peripheral RNA containing ring of ringshaped nucleoli (RSNo). Human lymphocytes of blood donors and patients suffering from B chronic lymphocytic leukemia mostly characterized by RSNo represented very convenient cell models for such study. According to the light microscopy the peripheral RNA ring possessed several highly condensed foci. Such regions represented accumulated dense RNA fibrillar components (DFCs) seen by the electron microscopy. In contrary, the incidence of dense granular RNA-containing components (GCs) in surrounding portions of the RNA ring was small. Thus, the structural and morphological organization of the peripheral RNA ring of RSNo apparently reflects sites of micro-segregated foci of DFCs and a small incidence of GCs. That structural organization of the peripheral RNA ring of RSNo appeared to be a prerequisite for further regressive nucleolar changes resulting in the development of micronucleoli in terminal lymphocytes.

Endometriosis is an estrogen-dependent inflammatory gynecological disease whose pathogenesis is unclear. C-C motif chemokine ligand 18 (CCL18), a chemokine, is involved in several inflammatory diseases. In this study, we aimed to investigate the role of CCL18 in endometriosis and its underlying mechanisms. Human endometrium and peritoneal fluid were obtained from women with and without endometriosis for molecular studies. The expression level of CCL18 in each tissue sample was examined by RNA sequencing analysis, quantitative PCR analysis and immunohistochemistry staining. The effects of CCL18 on cell migration, tube formation and neurite growth were investigated in vitro using primary endometrial cells, human umbilical vein endothelial cells (HUVECs) and dorsal root ganglion (DRG) neurons, respectively. Moreover, the development of endometriosis in mice was studied in vivo by blocking CCL18. CCL18 was shown to be overexpressed in endometrial foci and peritoneal fluid in women with endometriosis and was positively correlated with endometriosis pain. In vitro, CCL18 promoted the migration of ectopic endometrial cells, tube formation of HUVECs, and nerve outgrowth of DRG neurons. More importantly, inhibition of CCL18 significantly suppressed lesion development, angiogenesis, and nerve infiltration in a mouse model of endometriosis. In conclusion, CCL18 may play a role in the progression of endometriosis by increasing endometrial cell migration and promoting neuroangiogenesis.

Papillary thyroid carcinoma (PTC) is the most prevalent malignancy of the thyroid. Fibroblast growth factor receptor 1 (FGFR1) is highly expressed in PTC and works as an oncogenic protein in this disease. In this report, we wanted to uncover a new mechanism that drives overexpression of FGFR1 in PTC. Analysis of FGFR1 expression in clinical specimens and PTC cells revealed that FGFR1 expression was enhanced in PTC. Using siRNA/shRNA silencing experiments, we found that FGFR1 downregulation impeded PTC cell growth, invasion, and migration and promoted apoptosis in vitro, as well as suppressed tumor growth in vivo. Bioinformatic analyses predicted the potential USP7-FGFR1 interplay and the potential binding between YY1 and the FGFR1 promoter. The mechanism study found that USP7 stabilized FGFR1 protein via deubiquitination, and YY1 could promote the transcription of FGFR1. Our rescue experiments showed that FGFR1 re-expression had a counteracting effect on USP7 downregulation-imposed in vitro alterations of cell functions and in vivo suppression of xenograft growth. In conclusion, our study identifies the deubiquitinating enzyme USP7 and the oncogenic transcription factor YY1 as potent inducers of FGFR1 overexpression. Designing inhibitors targeting FGFR1 or its upstream inducers USP7 and YY1 may be foreseen as a promising strategy to control PTC development.

This corrects the article published in the European Journal of Histochemistry 2014;58:2262. doi: 10.4081/ejh.2014.2262.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder involving motor neuron (MN) loss in the motor cortex, brainstem and spinal cord leading to progressive paralysis and death. Due to the pathogenetic complexity, there are no effective therapies available. In this context the use of mesenchymal stem cells and their vesicular counterpart is an emerging therapeutic strategy to counteract neurodegeneration. The extracellular vesicles derived from adipose stem cells (ASC-EVs) recapitulate and ameliorate the neuroprotective effect of stem cells and, thanks to their small dimensions, makes their use suitable to develop novel therapeutic approaches for neurodegenerative diseases as ALS. Here we investigate a therapeutic regimen of ASC-EVs injection in SOD1(G93A) mice, the most widely used murine model of ALS. Repeated intranasal administrations of high doses of ASC-EVs were able to ameliorate motor performance of injected SOD1(G93A) mice at the early stage of the disease and produce a significant improvement at the end-stage in the lumbar MNs rescue. Moreover, ASC-EVs preserve the structure of neuromuscular junction without counteracting the muscle atrophy. The results indicate that the intranasal ASC-EVs administration acts in central nervous system sites rather than at peripheral level in SOD1(G93A) mice. These considerations allow us to identify future applications of ASC-EVs that involve different targets simultaneously to maximize the clinical and neuropathological outcomes in ALS in vivo models.

Artificial light can affect eyeball development and increase myopia rate. Matrix metalloproteinase 2 (MMP-2) degrades the extracellular matrix, and induces its remodeling, while tissue inhibitor of matrix MMP-2 (TIMP-2) inhibits active MMP-2. The present study aimed to look into how refractive development and the expression of MMP-2 and TIMP-2 in the guinea pigs' remodeled sclerae are affected by artificial light with varying spectral compositions. Three weeks old guinea pigs were randomly assigned to groups exposed to five different types of light: natural light, LED light with a low color temperature, three full spectrum artificial lights, i.e. E light (continuous spectrum in the range of ~390-780 nm), G light (a blue peak at 450 nm and a small valley 480 nm) and F light (continuous spectrum and wavelength of 400 nm below filtered). A-scan ultrasonography was used to measure the axial lengths of their eyes, every two weeks throughout the experiment. Following twelve weeks of exposure to light, the sclerae were observed by optical and transmission electron microscopy. Immunohistochemistry, Western blot and RT-qPCR were used to detect the MMP-2 and TIMP-2 protein and mRNA expression levels in the sclerae. After four, six, eight, ten, and twelve weeks of illumination, the guinea pigs in the LED and G light groups had axial lengths that were considerably longer than the animals in the natural light group while the guinea pigs in the E and F light groups had considerably shorter axial lengths than those in the LED group. Following twelve weeks of exposure to light, the expression of the scleral MMP-2 protein and mRNA were, from low to high, N group, E group, F group, G group, LED group; however, the expression of the scleral TIMP-2 protein and mRNA were, from high to low, N group, E group, F group, G group, LED group. The comparison between groups was statistically significant (p<0.01). Continuous, peaks-free or valleys-free artificial light with full-spectrum preserves remodeling of scleral extracellular matrix in guinea pigs by downregulating MMP-2 and upregulating TIMP-2, controlling eye axis elongation, and inhibiting the onset and progression of myopia.