Publisher Correction: MiR-21 and miR-183 can simultaneously target SOCS6 and modulate growth and invasion of hepatocellular carcinoma (HCC) cells.

Correction to: Eur Rev Med Pharmacol Sci 2015; 19 (17): 3208-3217. PMID: 26400524-published online on September 14, 2015. After publication, a reader brought to our attention a mistake in Figure 4. The journal found that Figure 3 was mistakenly inserted twice in the galley proof, resulting in the publication of the same figure for Figures 3 and 4. The publisher is, therefore, substituting Figure 4 with the correct figure provided at the time of submission as follows: There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/9429.

Single-cell RNA sequencing identifies molecular targets associated with poor in vitro maturation performance of oocytes collected from ovarian stimulation.

STUDY QUESTION: What is the transcriptome signature associated with poor performance of rescue IVM (rIVM) oocytes and how can we rejuvenate them? SUMMARY ANSWER: The GATA-1/CREB1/WNT signalling axis was repressed in rIVM oocytes, particularly those of poor quality; restoration of this axis may produce more usable rIVM oocytes. WHAT IS KNOWN ALREADY: rIVM aims to produce mature oocytes (MII) for IVF through IVM of immature oocytes collected from stimulated ovaries. It is not popular due to limited success rate in infertility treatment. Genetic aberrations, cellular stress and the absence of cumulus cell support in oocytes could account for the failure of rIVM. STUDY DESIGN, SIZE, DURATION: We applied single-cell RNA sequencing (scRNA-seq) to capture the transcriptomes of human in vivo oocytes (IVO) (n = 10) from 7 donors and rIVM oocytes (n = 10) from 10 donors. The effects of maternal age and ovarian responses on rIVM oocyte transcriptomes were also studied. In parallel, we studied the effect of gallic acid on the maturation rate of mouse oocytes cultured in IVM medium with (n = 84) and without (n = 85) gallic acid. PARTICIPANTS/MATERIALS, SETTING, METHODS: Human oocytes were collected from donors aged 28-41 years with a body mass index of <30. RNA extraction, cDNA generation, library construction and sequencing were performed in one preparation. scRNA-seq data were then processed and analysed. Selected genes in the rIVM versus IVO comparison were validated by quantitative real-time PCR. For the gallic acid study, we collected immature oocytes from 5-month-old mice and studied the effect of 10-µM gallic acid on their maturation rate. MAIN RESULTS AND THE ROLE OF CHANCE: The transcriptome profiles of rIVM/IVO oocytes showed distinctive differences. A total of 1559 differentially expressed genes (DEGs, genes with at least 2-fold change and adjusted P < 0.05) were found to be enriched in metabolic processes, biosynthesis and oxidative phosphorylation. Among these DEGs, we identified a repression of WNT/ß-catenin signalling in rIVM when compared with IVO oocytes. We found that oestradiol levels exhibited a significant age-independent correlation with the IVO mature oocyte ratio (MII ratio) for each donor. rIVM oocytes from women with a high MII ratio were found to have over-represented cellular processes such as anti-apoptosis. To further identify targets that contribute to the poor clinical outcomes of rIVM, we compared oocytes collected from young donors with a high MII ratio with oocytes from donors of advanced maternal age and lower MII ratio, and revealed that CREB1 is an important regulator. Thus, our study identified that GATA-1/CREB1/WNT signalling was repressed in both rIVM oocytes versus IVO oocytes and in rIVM oocytes of lower versus higher quality. Consequently we investigated gallic acid, as a potential antioxidant substrate in human rIVM medium, and found that it increased the mouse oocyte maturation rate by 31.1%. LARGE SCALE DATA: Raw data from this study can be accessed through GSE158539. LIMITATIONS, REASONS FOR CAUTION: In the rIVM oocytes of the high- and low-quality comparison, the number of samples was limited after data filtering with stringent selection criteria. For the oocyte stage identification, we were unable to predict the presence of oocyte spindle, so polar body extrusion was the only indicator. WIDER IMPLICATIONS OF THE FINDINGS: This study showed that GATA-1/CREB1/WNT signalling was repressed in rIVM oocytes compared with IVO oocytes and was further downregulated in low-quality rIVM oocytes, providing us the foundation of subsequent follow-up research on human oocytes and raising safety concerns about the clinical use of rescued oocytes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Collaborative Research Fund, Research Grants Council, C4054-16G, and Research Committee Funding (Research Sustainability of Major RGC Funding Schemes), The Chinese University of Hong Kong. The authors have no conflicts of interest to declare.

Correlation between serum microRNA-136 levels and RAAS biochemical markers in patients with essential hypertension.

OBJECTIVE: The aim of this study was to investigate the correlation between microRNA-136 levels and biochemical markers of renin-angiotensin-aldosterone system (RAAS) in patients with essential hypertension (EH). PATIENTS AND METHODS: The subjects were divided into EH group (n=110) and healthy control group (n=110). MicroRNA-136 expression, angiotensin-converting enzyme (ACE) activity, and expression of renin (RA) and angiotensin II (Ang II), and aldosterone (ALD) in peripheral blood serum were examined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR), equine glycylglycine glycine method, magnetic particle chemistry, and radioimmunoassay, respectively. In addition, the correlation between microRNA-136 and RAAS biochemical markers was estimated by Pearson linear regression. Meanwhile, ROC curve analysis was carried out to evaluate the potential of microRNA-136 for the diagnosis of EH. Follow-up data were recorded for assessing the influence of microRNA-136 on the prognosis in patients with EH. RESULTS: It was found that microRNA-136 expression was remarkably elevated in peripheral blood serum of patients with EH, and the expression levels of biochemical markers of RASS, such as ACE, RA, Ang II, and ALD were also found higher than those in healthy controls. Meanwhile, a significant positive correlation was confirmed between microRNA-136 level and ACE activity, RA, Ang II, as well as ALD levels in patients with EH. In addition, the area under the ROC curve (AUC) was calculated as 0.8662, with a sensitivity of 82.73% and a specificity of 80.91%. After two-months medication intervention, patients with EH expressing a high level of microRNA-136 had better therapeutic efficacy than those with a low level. CONCLUSIONS: In peripheral blood serum, microRNA-136 expression was dramatically negatively correlated with biochemical markers of RASS. High level of microRNA-136 predicts a good prognosis in patients with EH following medication. Therefore, microRNA-136 can be used as a potential biomarker for the diagnosis of EH.

Allergen sensitisation among chronic respiratory diseases in urban and rural areas of the south of Viet Nam.

OBJECTIVE: To evaluate the prevalence of and risk factors for allergen sensitisation among patients with chronic respiratory disease (CRD) in southern Viet Nam. DESIGN: An environmental questionnaire and skin prick tests for airborne and food allergens were administered to patients with CRD, defined as individuals with respiratory symptoms and lung function defects. RESULTS: Of 610 CRD patients, 56% had chronic obstructive pulmonary disease and 31% were asthma patients; 80% were males. The most frequent sensitisers were dust mites (Dermatophagoides farinae 22%, Blomia tropicalis 19%, D. pteronyssinus 18%) and cockroach droppings (13%). Among study participants, 37% were from rural settings and 36% from urban areas, whereas 27% had migrated from rural to urban areas. Compared with people from rural areas, being born in an urban area was a risk factor for sensitisation to mites (OR 1.56, 95%CI 1.11-2.20, P < 0.02). In multivariate analysis, place of birth remained a risk factor for mite sensitisation. Compared with the native urban population, the risk of mite sensitisation was not significantly different among patients born in rural areas and those migrating to urban areas. CONCLUSION: Dust mites and cockroach droppings were the most frequent allergens among people with CRD in the south of Viet Nam. Compared with the urban population, being native to a rural area was protective against mite sensitisation, but this effect ceased to be significant after migration from rural to urban areas.

MiR-21 and miR-183 can simultaneously target SOCS6 and modulate growth and invasion of hepatocellular carcinoma (HCC) cells.

OBJECTIVE: Both miR-21 and miR-183 are upregulated in hepatocellular carcinoma (HCC) and are considered as oncomiR. However, their oncogenic roles are still not fully understood. This study aimed to explore the regulative role of miR-21 and miR-183 over suppressors of cytokine signaling 6 (SOCS6), a negative regulator of cytokine receptor signaling. MATERIALS AND METHODS: qRT-PCR analysis was performed to assess miR-21 and miR-183 expression in tumor tissues obtained from HCC patients and in HCC cell lines HepG2 and Hep3B. Their regulation over SOCS6 is verified using dual luciferase assay and Western blot analysis. The function of miR-21/miR-183-SOCS6 axis in cell growth, invasion and apoptosis was studied. RESULTS: MiR-21 and miR-183 expression in HCC tissues than in adjacent normal tissues. Knockdown of miR-21 and miR-183 in HepG2 and Hep3B cells could decrease cell viability, increase cell apoptosis and decrease cell invasion. Based on the dual luciferase assay and Western blot analysis, we confirmed that both miR-21 and miR-183 can simultaneously target SOCS6 and modulate its expression at protein level. Overexpression of SOCS6 without 3'UTR could significantly lower cell growth rate and invasion capability, but increase relative caspase 3/7 activity and the ratio of apoptotic cells. However, these effects could not be blocked by miR-21 or miR-183 mimics. CONCLUSIONS: This study revealed a novel miR-21/miR-183-SOCS6 axis that might play an important role in modulating cell growth and invasion of HCC cells.

Anterior ankle-foot orthosis effects on postural stability in hemiplegic patients.

OBJECTIVES: To evaluate the effects of an anterior ankle-foot orthosis (AFO) on static and dynamic postural stability in hemiplegic patients. DESIGN: A cross-sectional assessment of hemiplegic subjects with and without an AFO. SETTING: Outpatient department of a rehabilitation hospital. PATIENTS: A convenience sample of 24 subjects who had been prescribed an anterior AFO. OUTCOME MEASURES: Postural sway index and postural symmetry (body weight distribution through the affected leg) when standing were measured as static postural stability. Maximal balance range in anterior-posterior and lateral directions and the affected leg's weight bearing after weight shift to affected side were measured as dynamic postural stability. RESULTS: When wearing the anterior AFO, there was no significant difference and small effect size (r<0.3) in postural sway index (p = .35), postural symmetry (p = .21), and maximal balance range in anterior-posterior direction (p = .46). There was a significant improvement and large effect size (r>0.5) in lateral weight shifting (p<.01) and weight bearing through the affected leg after weight shifted to the affected side (p<.01). CONCLUSIONS: The significant effects of the anterior AFO in long-term hemiplegic patients were on lateral weight shifting and weight bearing through affected leg after weight shifted to the affected side. Postural sway, postural symmetry, and anterior-posterior weight shifting were not significantly affected.