STUDY QUESTION
What are the roles of the microRNA miR-210—an miRNA that is up-regulated in endometriotic cyst stromal cells (ECSCs)—in the pathogenesis of endometriosis?
SUMMARY ANSWER
Up-regulated ...miR-210 expression in ECSCs is involved in their proliferation, resistance to apoptosis and angiogenesis through signal transducer and activator of transcription (STAT) 3.
WHAT IS KNOWN ALREADY
In the pathogenesis of endometriosis, a number of roles for microRNAs (miRNAs) are becoming apparent.
STUDY DESIGN, SIZE, DURATION
ECSCs and normal endometrial stromal cells (NESCs) were isolated from ovarian endometriotic tissues (patients aged 24–40 years undergoing salpingo-oophorectomy or evisceration for the treatment of ovarian endometriotic cysts, n = 10) and the eutopic endometrial tissues without endometriosis (premenopausal patients aged 35–45 years undergoing hysterectomies for subserousal leiomyoma, n = 13), respectively.
PARTICIPANTS/MATERIALS, SETTING, METHODS
We used a global gene expression microarray technique to identify downstream targets of miR-210, and we assessed the functions of miR-210 in the pathogenesis of endometriosis by using the miR-210-transfected NESCs.
MAIN RESULTS AND THE ROLE OF CHANCE
Gene expression microarray analysis revealed that one of the key target molecules of miR-210 is STAT3. In the NESCs, in comparison to the control, miR-210 transfection resulted in the induction of cell proliferation (P < 0.0005), the production of vascular endothelial cell growth factor (VEGF) (P < 0.0005) and the inhibition of apoptosis (P < 0.05) through STAT3 activation increased levels of mRNA (P < 0.0005), and protein (P < 0.005). In the ECSCs, inhibitors of STAT3 inhibited the cell proliferation and VEGF production (P < 0.05), and induced the apoptosis of these cells (P < 0.05).
LIMITATIONS, REASONS FOR CAUTION
The roles of aberrant miR-210 expression were investigated only in the stromal component of ectopic and eutopic endometrium. Control endometrial tissues were obtained from premenopausal patients who had subserosal leiomyoma and NESC gene expression patterns may be altered in these women. Furthermore, the effects of STAT3 inhibitors were evaluated only in ECSCs and not in NESCs.
WIDER IMPLICATIONS OF THE FINDINGS
The present findings indicate that miR-210 induces NESCs to differentiate into the endometriotic phenotype and we speculate that up-regulated miR-210 expression in ECSCs is involved in the creation of the endometriosis-specific cellular dysfunctions through epigenetic mechanisms. The data indicate that STAT3 inhibitors may be promising candidates for the treatment of endometriosis.
STUDY FUNDING/COMPETING INTEREST(S)
This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (no. 13237327 to K.N., no. 25861500 to Y.K. and no. 23592407 to H.N.). There are no conflicts of interest to declare.
Architects and engineers are beginning to consider a new dimension of indoor air: the structure and composition of airborne microbial communities. A first step in this emerging field is to understand ...the forces that shape the diversity of bioaerosols across space and time within the built environment. In an effort to elucidate the relative influences of three likely drivers of indoor bioaerosol diversity – variation in outdoor bioaerosols, ventilation strategy, and occupancy load – we conducted an intensive temporal study of indoor airborne bacterial communities in a high‐traffic university building with a hybrid HVAC (mechanically and naturally ventilated) system. Indoor air communities closely tracked outdoor air communities, but human‐associated bacterial genera were more than twice as abundant in indoor air compared with outdoor air. Ventilation had a demonstrated effect on indoor airborne bacterial community composition; changes in outdoor air communities were detected inside following a time lag associated with differing ventilation strategies relevant to modern building design. Our results indicate that both occupancy patterns and ventilation strategies are important for understanding airborne microbial community dynamics in the built environment.
STUDY QUESTION
What is the global expression pattern of microRNAs (miRNAs) in endometriotic stromal cells and is miR-196b involved in the pathogenesis of endometriosis?
SUMMARY ANSWER
Several miRNAs ...are aberrantly expressed in endometriotic cyst stromal cells (ECSCs), including miR-196b whose expression is repressed in endometriotic stromal cells.
WHAT IS KNOWN ALREADY
Although, histologically, endometriotic tissues and normal proliferative endometrium are similar, a number of distinct molecular differences have been reported to date. The anti-apoptotic and excessive proliferative properties of endometriotic cells are considered to be involved in the development and progression of endometriosis.
STUDY DESIGN AND SIZE DURATION
ECSCs and normal endometrial stromal cells (NESCs) were isolated from ovarian endometriotic tissues and eutopic endometrial tissues, respectively and compared.
PARTICIPANTS/MATERIALS, SETTING AND METHODS
Aberrantly expressed miRNAs in ECSCs were identified by a global miRNA microarray technique. The roles of miR-196b in ECSC proliferation, apoptosis, and c-myc and B-cell lymphoma/leukemia (Bcl)-2 mRNA expression were investigated with precursor hsa-miR-196b transfection. The methylation status of the miR-196b gene in ECSCs and the effect of a DNA demethylating agent on miR-196b expression were also examined.
MAIN RESULTS AND THE ROLE OF CHANCE
miRNA microarray analysis identified eight down-regulated miRNAs (including miR-196b) and four up-regulated miRNAs in ECSCs. Compulsory expression of miR-196b directed the inhibition of proliferation and the induction of apoptosis in ECSCs. miR-196b was found to suppress c-myc and Bcl-2 mRNA expression in ECSCs, and there was a significant correlation between miR-196b and HOXA10 expression in ECSCs and NESCs. The miR-196b gene was hypermethylated in ECSCs when compared with NESCs, and the treatment with a DNA demethylating agent restored the expression of miR-196b in ECSCs.
LIMITATIONS AND REASONS FOR CAUTION
miRNA expression profiles were investigated only in the stromal component of ectopic and eutopic endometrium samples. In addition to miR-196b, the roles of other miRNAs aberrantly expressed in ECSCs should be examined.
WIDER IMPLICATIONS OF THE FINDINGS
The present findings suggest that aberrant miRNA expression plays an important role in the pathogenesis of endometriosis as a part of epigenetic mechanisms, that expression of miR-196b in ECSCs is repressed by DNA hypermethylation of the miR-196b gene and this repression may be involved in the development of proliferative and anti-apoptotic characteristics of endometriosis.
STUDY FUNDING
This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (no. 20591920 to K.N. and no. 23592407 to H.N.) and The Uehara Memorial Foundation (to K.N.).
Abstract
Basin-scale monthly and annual evapotranspiration (ET) is estimated for Urmia Lake Basin by applying the Global Change Observation Mission for Climate (GCOM-C) global ETindex estimation ...algorithm to thermal imagery observed by the GCOM-C satellite. In total, 297 satellite images acquired during 2018-2019 were used in this study. ET estimation accuracy was examined for an area dominated by apple fields using traditional surface irrigation. The estimated ET was 15% lower than the standard crop ET, which was computed using a procedure suggested by the Food and Agriculture Organization of the United Nations on a monthly timescale, and was 8% lower on an annual timescale. Comparison of estimated ET with a satellite-based ET map derived by using the Mapping EvapoTranspiration at high Resolution with Internalized Calibration (METRIC) model showed a similar difference. The 8%–15% differences among the different sources of ET were small, given that a similar or wider range of uncertainty is frequently available even in ground-based ET measurements. Comparison between the estimated ET and the MODIS ET Product (MOD16) revealed a greater difference in the evaluated area of the apple fields. Given the climatic ET demands and the irrigation practices of the area, ET estimation accuracy is more likely to be higher using the dataset derived from this study than using MOD16. The GCOM-C satellite started routine surface observations in January 2018. Its contribution to agricultural water management, such as by estimating ET as presented in this study, will increase as the amount of historical data stored continues to accumulate.
Neuromuscular blocking agents have been implicated in 60–70% of anaphylactic events associated with anaesthesia. We report two cases of probable hypersensitivity reaction to sugammadex and an ...additional suspected but less supported case of possible immune-mediated reaction or other adverse reaction. The patients were given a bolus of sugammadex 100 mg immediately before extubation. In all three patients, a possible allergic reaction was suspected within 4 min of sugammadex administration, but with different degrees of severity. Skin testing was positive in two of these patients. Hypersensitivity to sugammadex unaccompanied by cardiovascular or respiratory symptoms might be missed during the course of anaesthesia. Careful monitoring for possible allergic responses is required in patients who have received sugammadex.
Summary
To investigate the pathogenesis of localized autoimmune damage in Sjögren's syndrome (SS) by examining the expression patterns of cytokines, chemokines and chemokine receptors at sites of ...autoimmune damage. mRNA expression of these molecules in the labial salivary glands (LSGs) and peripheral blood mononuclear cells (PBMCs) from 36 SS patients was examined using a real‐time polymerase chain reaction‐based method. Subsets of the infiltrating lymphocytes and chemokines/chemokine receptors expression in the LSG specimens were examined by immunohistochemistry. Cytokines/chemokine concentrations in the saliva were analysed using flow cytometry or enzyme‐linked immunosorbent assay. mRNA expression of T helper type 1 (Th1) cytokines, chemokines and chemokine receptors was higher in LSGs than in PBMCs. In contrast, mRNA expression of Th2 cytokines, chemokines thymus and activation‐regulated chemokine (TARC/CCL17), macrophage‐derived chemokine (MDC/CCL22) and chemokine receptor (CCR4) was associated closely with strong lymphocytic accumulation in LSGs. Furthermore, TARC and MDC were detected immunohistochemically in/around the ductal epithelial cells in LSGs, whereas CCR4 was detected on infiltrating lymphocytes. The concentrations of these cytokines/chemokines were significantly higher in the saliva from SS patients than those from controls, and the concentrations of Th2 cytokines/chemokines were associated closely with strong lymphocytic accumulation in LSGs. These results suggest that SS might be initiated and/or maintained by Th1 and Th17 cells and progress in association with Th2 cells via the interaction between particular chemokines/chemokine receptors. Furthermore, the measurement of cytokines/chemokines in saliva is suggested to be useful for diagnosis and also to reveal disease status.
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