Microstructural and Neurochemical Changes in the Rat Brain After Diffuse Axonal Injury.

BACKGROUND: Diffuse axonal injury (DAI) is one of the devastating types of traumatic brain injury, but is difficult to detect on conventional imaging in its early stages. PURPOSE: To test the technical feasibility and diagnostic value of diffusion kurtosis imaging (DKI) and glutamate chemical exchange saturation transfer (GluCEST) imaging in the brain after DAI. STUDY TYPE: Prospective. ANIMAL MODEL: Sixty Sprague-Dawley rats. The DAI model was induced by using the impact acceleration model of Marmarou et al with modified settings. FIELD STRENGTH/SEQUENCE: A 7.0T animal MR scanner with a fast spin-echo sequence (T2 -weighted imaging), fast spin-echo multislice sequence (DKI), echo planar imaging in the signal of the chemical exchange saturation transfer sequence (CEST), and point-resolved spectroscopy sequence (hydrogenproton magnetic resonance spectroscopy, 1 H-MRS). ASSESSMENT: Brain MRI scanned before and 2 hours after injury. DKI images were processed with MatLab and MRIcro software, GluCEST images were processed using software routines written in MatLab, and spectroscopic data were postprocessed with LCModel. STATISTICAL TESTS: The parameters of these techniques were assessed using the independent sample t-test and Pearson correlation. RESULTS: Mean kurtosis and mean diffusivity values were significantly higher than controls in the parietal lobe, hippocampus, and thalamus (P < 0.01). However, fractional anisotropy was lower only in the parietal lobe, with no detectable changes in the hippocampus and thalamus. GluCEST values of the parietal lobe, hippocampus, and thalamus were significantly higher than controls in DAI rats (P < 0.01). This change was further validated through 1 H-MRS. A positive correlation was observed between glutamate (Glu) and glutamate compound (Glx) concentrations and GluCEST values (Glu: R2 = 0.589, Glx: R2 = 0.878). DATA CONCLUSION: DKI and GluCEST might be acceptably sensitive for tracking microstructural and neurochemical changes in the brain following DAI. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:1069-1077.

The long non-coding RNA PVT1 represses ANGPTL4 transcription through binding with EZH2 in trophoblast cell.

Despite progress in diagnostics and treatment for preeclampsia, it remains the foremost cause of maternal and foetal perinatal morbidity and mortality worldwide. Over recent years, various lines of evidence have emphasized long non-coding RNAs (lncRNAs) which function as an innovative regulator of biological behaviour, as exemplified by proliferation, apoptosis and metastasis. However, the role of lncRNAs has not been well described in preeclampsia. Here, we identified a lncRNA, PVT1, whose expression was down-regulated in qRT-PCR analyses in severe preeclampsia. The effects of PVT1 on development were studied after suppression and overexpression of PVT1 in HTR-8/SVneo and JEG3 cells. PVT1 knockdown notably inhibited cell proliferation and stimulated cell cycle accumulation and apoptosis. Exogenous PVT1 significantly increased cell proliferation. Based on analysis of RNAseq data, we found that PVT1 could affect the expression of numerous genes, and then investigated the function and regulatory mechanism of PVT1 in trophoblast cells. Further mechanistic analyses implied that the action of PVT1 is moderately attributable to its repression of ANGPTL4 via association with the epigenetic repressor Ezh2. Altogether, our study suggests that PVT1 could play an essential role in preeclampsia progression and probably acts as a latent therapeutic marker; thus, it might be a useful prognostic marker when evaluating new therapies for patients with preeclampsia.

Neck circumference may be a valuable tool for screening individuals with obesity: findings from a young Chinese population and a meta-analysis.

BACKGROUND: Central obesity and overweight/obesity can result in various chronic non-communicable diseases, such as cardiovascular disease, metabolic syndrome, and diabetes mellitus. Waist circumference (WC) and body mass index (BMI) are widely used to measure obesity despite their limitations. For example, WC and BMI cannot be measured in pregnant women and subjects with abdominal ascites or masses. Therefore, this study aims to determine the efficacy of neck circumference (NC) as a tool for screening central obesity and overweight/obesity. METHODS: A total of 1169 undergraduates aged 18-25 years were studied by a cross-sectional survey in China, 2016. Questionnaires and physical examinations were used to collect data. Receiver operator characteristic (ROC) curve was performed to determine the best threshold of NC for screening central obesity and overweight/obesity. Meanwhile, a meta-analysis was conducted to estimate the efficacy of NC for screening central obesity and overweight/obesity synthetically. RESULTS: NC was moderately correlated with WC and BMI. The ROC analysis showed that 37.1 cm for male and 32.6 cm for female were the best thresholds for central obesity, and 37.4 cm and 32.2 cm for overweight/obesity, respectively. The sensitivity, specificity, area under receiver operating curve (AUC) of central obesity and overweight/obesity were higher. In the meta-analysis, the pooled sensitivity, specificity, AUC and their 95%CI of NC for screening central obesity were 0.72 (0.68~ 0.75), 0.87 (0.74~ 0.94), 0.77 (0.73~ 0.80) for male and 0.73 (0.65~ 0.80), 0.80 (0.71~ 0.86), 0.82 (0.79~ 0.86) for female. For overweight/obesity, the pooled sensitivity, specificity, AUC and corresponding 95%CI were 0.83 (0.70~ 0.91), 0.77 (0.66~ 0.85), 0.86 (0.83~ 0.89) for male and 0.82 (0.71~ 0.90), 0.84 (0.61~ 0.95), 0.89 (0.86~ 0.92) for female. CONCLUSION: NC may not be a good tool for screening individuals with central obesity. But it may be a simple and valuable tool for screening individuals with overweight/obesity, especially in females.

Body mass index had different effects on premenopausal and postmenopausal breast cancer risks: a dose-response meta-analysis with 3,318,796 subjects from 31 cohort studies.

BACKGROUND: There is sufficient evidence supporting a relationship between increased body mass index (BMI) and an increased risk for breast cancer among postmenopausal women. However, most studies have found a decreased risk for premenopausal breast cancer. This study was conducted to find out the different effects of BMI on the risk of breast cancer among premenopausal and postmenopausal women, and explore the potential factors that influence the associations. METHODS: A dose-response meta-analysis with 3,318,796 participants from 31 articles was conducted. Cohort studies that included BMI and corresponding breast cancer risk were selected through various databases including PubMed, Medline, Web of Science, the China National Knowledge Infrastructure (CNKI) and Chinese Scientific Journals (VIP). Random effects models were used for analyzing the data. RESULTS: The summary relative risks (RRs) were 1.33 (95%CI: 1.20-1.48) and 0.94(95%CI: 0.80-1.11) among postmenopausal and premenopausal women, respectively. The dose-response meta-analysis indicated a positive non-linear association between BMI and breast cancer risk among postmenopausal women, and compared to the mean level of the normal BMI category (21.5 kg/m2) the RR in total postmenopausal women were1.03 (95% CI: 1.02-1.05) per 1 kg/m2 increment. However, no statistically significant association among total premenopausal women was detected. In subgroup analysis among European premenopausal women, the summary RR was 0.79(95%CI: 0.70-0.88). The non-linear relationship showed a negative non-linear association between BMI and breast cancer risk among European premenopausal women. When compared to the mean level of the normal BMI category, the RRs were 0.98 (95%CI: 0.96-1.00) per 1 kg/m2 increment, respectively. CONCLUSIONS: In line with previous studies BMI had different effects on pre-menopausal and postmenopausal breast cancer risk. However, contrary to previous studies, a high BMI was not associated with decreased risk in total pre-menopausal women. More research is needed to better understand these differences.

[Relationship between uncoupling protein 1 gene promoter methylation and obesity in adult].

OBJECTIVE: To observe the relationship between the methylation status in promoter region of uncoupling protein 1( UCP1) gene and obesity. METHODS: A casecontrol study based on the hospital consisted 116 people was carried out, according to the body mass index( BMI), the subjects were divided into two groups, the overweight and obesity group with 50 samples( BMI≥24. 0) and the normal weight group with 66 samples( 18. 5≤BMI < 24), DNA samples were extracted from white blood cell and treated by hydrogen sulfite. Then mass spectrometry method was used to quantificationally detect the methylation level UCP1 gene promoter. The difference between the two groups was compared and the relationships between CpG sites and BMI were explored. RESULTS: Statistical analysis showed that the methylation differences between normal weight and overweight or obese group were not statistically significant, however, the CpG site UCP1-2_ Cp G_ 10. 11. 12. 13 had statistical significance in correlation coefficients with BMI according to multiple linear regression method( regression coefficient was 15. 370, P <0. 05). CONCLUSION: The UCP1 gene promoter methylation may be a factor for adult obesity.

A New Schiff Base Chemodosimeter for Fluorescent Imaging of Ferric Ions in Living Cells.

A new and efficient chemodosimeter for ferric ions has been developed. The visual and fluorescent behaviors of the compound toward various metal ions were investigated: ferric ions are distinguished from other cations by selective color change and unusual fluorescence enhancement in mixed aqueous solution. Fluorescence microscopy experiments showed that this receptor is effective for detection of Fe(3+) in vitro, developing a good image of the biological organelles. The sensing mechanism is shown to involve a hydrolysis process.

Micro- and macro-changes in early-stage type 2 diabetes mellitus without cognitive impairment: a diffusion tensor imaging (DTI) and surface-based morphometry (SBM) study.

Introduction: Brain structure and function changes are considered major brain damages in type 2 diabetes mellitus (T2DM), which likely has a close relationship with cognitive impairment. Many previous studies have shown by using brain structural and functional magnetic resonance imaging (MRI) methods that brain white and gray matter are damaged in T2DM, leading to cognitive impairment. Researches neglected patients of T2DM without cognitive dysfunction might also have brain changes. Methods: In this study, subjects with early stage T2DM with no cognitive dysfunction were enrolled to detect brain damages using the tract-based spatial statistics analysis (TBSS) method to demonstrate white matter (WM) micro changes and surface-based morphometry (SBM) method to assess cerebral cortex macro changes. Results: The whole-brain TBSS analysis revealed that there were no statistically significant changes in fractional anisotropy (FA) and mean diffusivity (MD), but the FA declined in some area of cerebral WM (p < 0.1). The SBM results showed no changes in cortical thickness (CT), cortical volume (CV), surface area (SA), and cortical sulcal curve (CSC) between these two groups, but pial local gyration index (LGI) was decreased in the precuneus (-log10, p = -3.327). Discussion: In conclusion, early stage T2DM patients without cognitive impairment had brain micro and macro structural damages, suggesting the potential use of MRI as an imaging marker to detect brain changes in early stage T2DM, which could not be observed and assessed clinically.

Association of CIDEB gene promoter methylation with overweight or obesity in adults.

OBJECTIVE: To explore the association of the methylation level of cell death-inducing DFF45-like effector B (CIDEB) gene promoter with overweight or obesity in the abdominal subcutaneous adipose tissue (SAT) and omental adipose tissue (OAT) of adults. METHODS: A total of 61 patients undergoing abdominal surgery in the hospital were selected with an average age of 51.87 years. According to the diagnostic criteria of Chinese adult obesity, the subjects were divided into normal-weight group (n = 28) and overweight/obesity group (n = 33). CIDEB promoter methylation level in abdominal SAT and OAT was detected by the MethylTarget technology, then its relationship with overweight or obesity was analyzed. RESULTS: (1) There were no statistical differences between the normal-weight group and overweight/obesity group in Methylation levels of 16 CpG sites in the CIDEB gene promoter sequence. (2) The methylation level of OAT was higher than that of SAT, and there were significant differences in 16 CpG sites. (3) There were 3 statistically significant haplotypes between the normal-weight group and overweight/obesity group (2 in SAT and 1 in OAT). CONCLUSIONS: The methylation level of CIDEB gene promoter in abdominal SAT and OAT may be related to overweight or obesity in adults, and the specific regulatory mechanism needs to be further studied.

Apparent diffusion coefficient values of cryptorchid testes and malignant transformation of cryptorchidism (MTC) (seminoma) in postpubertal patients.

OBJECTIVES: Diffusion-weighted imaging signal contrast can be quantified by apparent diffusion coefficient (ADC) maps, which reflect the diffusion properties of the examined tissue and are helpful for identifying pathology. To determine ADC values of cryptorchid testes in post-pubertal patients and assess performance for characterizing cryptorchid testes. METHODS: The medical records from 35 patients with unilateral scrotal vacuity were retrospectively reviewed. Data were analyzed in three groups: Group A, normal testes (i.e. the contralateral testes of the patients with cryptorchidism or MTC); Group B, cryptorchid testes; and Group C, malignant transformation of cryptorchidism (MTC) (seminoma). DWI used b-values of 0 and 800 s/mm2. Mean ADC values were compared using the independent samples t-test. The ability of ADC values was assessed using receiver operating characteristic curve analysis. The sensitivity, specificity, and accuracy were calculated. RESULTS: Mean ADC values for normal testes, cryptorchid testes, and MTC were 1.18 ± 0.18×10-3 mm2/s, 1.82 ± 0.40×10-3 mm2/s, and 0.80 ± 0.06×10-3 mm2/s, respectively. There were statistically significant differences in mean ADC values between normal testes and cryptorchid testes or MTC (p < 0.001). The cut-off ADC value for differentiating normal testes from cryptorchid testes was 1.47 × 10-3 mm2/s. The sensitivity, specificity, and accuracy were 88%, 91%, and 90%, respectively. The cut-off ADC value for differentiating normal testes from MTC was 1.22 × 10-3 mm2/s. The sensitivity, specificity, and accuracy were 100%, 31%, and 43%, respectively. CONCLUSION: ADC values of cryptorchid testes may be used to inform clinical decision-making and also monitor testicular function in patients who retain undescended testicles or post-operatively. ADVANCES IN KNOWLEDGE: Mean ADC values of cryptorchidism and MTC (seminoma) were used to reflect their pathological features.

Glutamate Chemical Exchange Saturation Transfer (GluCEST) Magnetic Resonance Imaging in Pre-clinical and Clinical Applications for Encephalitis.

BACKGROUND: Encephalitis is a common central nervous system inflammatory disease that seriously endangers human health owing to the lack of effective diagnostic methods, which leads to a high rate of misdiagnosis and mortality. Glutamate is implicated closely in microglial activation, and activated microglia are key players in encephalitis. Hence, using glutamate chemical exchange saturation transfer (GluCEST) imaging for the early diagnosis of encephalitis holds promise. METHODS: The sensitivity of GluCEST imaging with different concentrations of glutamate and other major metabolites in the brain was validated in phantoms. Twenty-seven Sprague-Dawley (SD) rats with encephalitis induced by Staphylococcus aureus infection were used for preclinical research of GluCEST imaging in a 7.0-Tesla scanner. For the clinical study, six patients with encephalitis, six patients with lacunar infarction, and six healthy volunteers underwent GluCEST imaging in a 3.0-Tesla scanner. RESULTS: The number of amine protons on glutamate that had a chemical shift of 3.0 ppm away from bulk water and the signal intensity of GluCEST were concentration-dependent. Under physiological conditions, glutamate is the main contributor to the GluCEST signal. Compared with normal tissue, in both rats and patients with encephalitis, the encephalitis areas demonstrated a hyper-intense GluCEST signal, while the lacunar infarction had a decreased GluCEST signal intensity. After intravenous immunoglobulin therapy, patients with encephalitis lesions showed a decrease in GluCEST signal, and the results were significantly different from the pre-treatment signal (1.34 ± 0.31 vs 5.0 ± 0.27%, respectively; p = 0.000). CONCLUSION: Glutamate plays a role in encephalitis, and the GluCEST imaging signal has potential as an in vivo imaging biomarker for the early diagnosis of encephalitis. GluCEST will provide new insight into encephalitis and help improve the differential diagnosis of brain disorders.

Noninvasive Detection of Extracellular pH in Human Benign and Malignant Liver Tumors Using CEST MRI.

PURPOSE: In this study, we aimed to use 3T magnetic resonance imaging (MRI), which is clinically available, to determine the extracellular pH (pHe) of liver tumors and prospectively evaluate the ability of chemical exchange saturation transfer (CEST) MRI to distinguish between benign and malignant liver tumors. METHODS: Different radiofrequency irradiation schemes were assessed for ioversol-based pH measurements at 3T. CEST effects were quantified in vitro using the asymmetric magnetization transfer ratio (MTRasym) at 4.3 ppm from the corrected Z spectrum. Generalized ratiometric analysis was conducted by rationing resolved ioversol CEST effects at 4.3 ppm at a flip angle of 60 and 350°. Fifteen patients recently diagnosed with hepatic carcinoma and five patients diagnosed with hepatic hemangioma [1 male; mean age, 48.6 (range, 37-59) years] were assessed. RESULTS: By conducting dual-power CEST MRI, the pH of solutions was determined to be 6.0-7.2 at 3T in vitro. In vivo, ioversol signal intensities in the tumor region showed that the extracellular pH in hepatic carcinoma was acidic(mean ± standard deviation, 6.66 ± 0.19), whereas the extracellular pH was more physiologically neutral in hemangioma (mean ± standard deviation, 7.34 ± 0.09).The lesion size was similar between CEST pH MRI and T2-weighted imaging. CONCLUSION: dual-power CEST MRI can detect extracellular pH in human liver tumors and can provide molecular-level diagnostic tools for differentiating benign and malignant liver tumors at 3T.

Imaging of glutamate in acute traumatic brain injury using chemical exchange saturation transfer.

BACKGROUND: Chemical exchange saturation transfer (CEST) is an important contrast mechanism in the field of magnetic resonance imaging. Herein, we used CEST for glutamate (GluCEST) imaging to evaluate the Glu alterations in acute mild to moderate traumatic brain injury (TBI) and correlated such alterations with the cognitive outcome at 1-month postinjury. METHODS: Thirty-two patients with well-documented mild-to-moderate TBI and 15 healthy controls (HC group) underwent 3.0-Tesla magnetic resonance imaging (MRI) with GluCEST, and magnetic resonance spectroscopy (MRS) scans. The Montreal Cognitive Assessment (MoCA) examination was administered to all study subjects at 1-month postinjury for cognitive outcome acquisition and divided TBI patients into patients with good cognitive outcome (GCO group) and with poor cognitive outcome (PCO group). RESULTS: The GluCEST% values for the occipital gray matter (OGM) and bilateral parietooccipital white matter (PWM) were higher in the PCO group compared with the HC and GCO groups (P<0.05), whereas the GluCEST% value showed no significant differences between the GCO and HC groups (P>0.05). In comparison with HCs, TBI patients had a significantly increased GluCEST% value for the OGM and bilateral PWM (P<0.05). GluCEST performed better than MRS in the prediction of cognitive outcome for TBI patients (P<0.05). CONCLUSIONS: Glu is significantly increased in acute TBI and strongly correlates with the cognitive outcome at 1month postinjury. GluCEST may supply new insight into TBI and help to improve the accuracy of short-term outcome prediction.

Diffusion Kurtosis Imaging for Detection of Early Brain Changes in Parkinson's Disease.

We aimed to evaluate microscale changes in the bilateral red nucleus and substantia nigra of patients with Parkinson's disease (PD) using diffusion kurtosis imaging (DKI). Twenty-six patients with PD [mean age, 62.5 ± 8.7 years; Hoehn-Yahr stage, 0-4.0; Unified Parkinson's Disease Rating Scale (UPDRS) scores, 8-43] and 15 healthy controls (mean age, 59.5 ± 9.4 years) underwent DKI of the substantia nigra and red nucleus. Imaging was performed using a General Electric (GE) Signa 3.0-T MRI system. Patients with PD were divided into two groups consisting of 12 patients with UPDRS scores ≥ 30 and 14 patients with UPDRS scores < 30. All DKI data processing operations were performed with commercial workstations (GE, ADW 4.6) using Functool software to generate color-coded and parametric maps of mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD). MK values in the bilateral substantia nigra were significantly lower in patients with early- and advanced-stage PD than in controls. Moreover, MK values in the left substantia nigra were significantly lower in patients with advanced-stage PD than in those with early-stage PD. Patients with advanced-stage PD also exhibited significant decreases in MK values in the bilateral red nucleus relative to controls. No significant differences in FA or MD values were observed between the PD and control groups. There were no significant correlations between MK, FA, or MD values and UPDRS scores. Our findings suggest that decreased MK values in the substantia nigra may aid in determining the severity of PD and help provide early diagnoses.

Mapping the Changes of Glutamate Using Glutamate Chemical Exchange Saturation Transfer (GluCEST) Technique in a Traumatic Brain Injury Model: A Longitudinal Pilot Study.

Glutamate excitoxicity plays a crucial role in the pathophysiology of traumatic brain injury (TBI) through the initiation of secondary injuries. Glutamate chemical exchange saturation transfer (GluCEST) MRI is a newly developed technique to noninvasively image glutamate in vivo with high sensitivity and spatial resolution. The aim of the present study was to use a rat model of TBI to map changes in brain glutamate distribution and explore the capability of GluCEST imaging for detecting secondary injuries. Sequential GluCEST imaging scans were performed in adult male Sprague-Dawley rats before TBI and at 1, 3, 7, and 14 days after TBI. GluCEST% increased and peaked on day 1 after TBI in the core lesion of injured cortex and peaked on day 3 in the ipsilateral hippocampus, as compared to baseline and controls. GluCEST% gradually declined to baseline by day 14 after TBI. A negative correlation between the GluCEST% of the ipsilateral hippocampus on day 3 and the time in the correct quadrant was observed in injured rats. Immunolabeling for glial fibrillary acidic protein showed significant astrocyte activation in the ipsilateral hippocampus of TBI rats. IL-6 and TNF-α in the core lesion peaked on day 1 postinjury, while those in the ipsilateral hippocampus peaked on day 3. These subsequently gradually declined to sham levels by day 14. It was concluded that GluCEST imaging has potential to be a novel neuroimaging approach for predicting cognitive outcome and to better understand neuroinflammation following TBI.

An Amyloid-ß Targeting Chemical Exchange Saturation Transfer Probe for In Vivo Detection of Alzheimer's Disease.

A reliable and reproducible detection of Aß deposits would be beneficial for the early diagnosis of Alzheimer's disease (AD). In the present study, the feasibility of applying chemical exchange saturation transfer (CEST) for Aß deposit detection using angiopep-2 as a probe was evaluated, and it was demonstrated that CEST could detect angiopep-2 and Aß-angiopep-2 aggregates in vitro. Furthermore, APP/PS1 mice injected with angiopep-2 exhibited a significantly higher in vivo CEST effect when compared with controls. The distribution of Aß deposits detected by CEST imaging was consistent with the histological staining results. The present study is the first to report a reliable exogenous CEST probe to noninvasively evaluate Aß deposits in APP/PS1 mice. Furthermore, these results demonstrate the potential for clinical AD diagnosis and Aß-targeted drug therapy assessment using CEST imaging with the angiopep-2 probe.

APT Weighted MRI as an Effective Imaging Protocol to Predict Clinical Outcome After Acute Ischemic Stroke.

To explore the capability of the amide-proton-transfer weighted (APTW) magnetic resonance imaging (MRI) in the evaluation of clinical neurological deficit at the time of hospitalization and assessment of long-term daily functional outcome for patients with acute ischemic stroke (AIS). We recruited 55 AIS patients with brain MRI acquired within 24-48 h of symptom onset and followed up with their 90-day modified Rankin Scale (mRS) score. APT weighted MRI was performed for all the study subjects to measure APTW signal quantitatively in the acute ischemic area (APTWipsi) and the contralateral side (APTWcont). Change of the APT signal between the acute ischemic region and the contralateral side (ΔAPTW) was calculated. Maximum APTW signal (APTWmax) and minimal APTW signal (APTWmin) were also acquired to demonstrate APTW signals heterogeneity (APTWmax-min). In addition, all the patients were divided into 2 groups according to their 90-day mRS score (good prognosis group with mRS score <2 and poor prognosis group with mRS score ≥2). In the meantime, ΔAPTW of these groups was compared. We found that ΔAPTW was in good correlation with National Institutes of Health Stroke Scale (NIHSS) score (R 2 = 0.578, p < 0.001) and 90-day mRS score (R 2 = 0.55, p < 0.001). There was significant difference of ΔAPTW between patients with good prognosis and patients with poor prognosis. Plus, APTWmax-min was significantly different between two groups. These results suggested that APT weighted MRI could be used as an effective tool to assess the stroke severity and prognosis for patients with AIS, with APTW signal heterogeneity as a possible biomarker.

Downregulated lncRNA HOXA11-AS Affects Trophoblast Cell Proliferation and Migration by Regulating RND3 and HOXA7 Expression in PE.

The long noncoding RNA HOXA11-AS displays abnormal expression in numerous human diseases. However, its function and biological mechanisms remain unclear in preeclampsia (PE). In this study, we report that HOXA11-AS is significantly downregulated in preeclamptic placental tissues and could contribute to the occurrence and development of PE. Silencing of HOXA11-AS expression could significantly suppress trophoblast cell growth and migration, whereas HOXA11-AS overexpression facilitated cell growth in the HTR-8/SVneo, JEG3, and JAR cell lines. RNA-seq analysis also indicated that HOXA11-AS silencing preferentially regulated numerous genes associated with cell proliferation and cell migration. Mechanistic analyses showed that HOXA11-AS could recruit Ezh2 and Lsd1 protein and regulate RND3 mRNA expression in the nucleus. In the cytoplasm, HOXA11-AS modulates HOXA7 expression by sponged miR-15b-5p, affecting trophoblast cell proliferation. Together, these data confirm that aberrant expression of HOXA11-AS is involved in the occurrence and development of PE and may act as a prospective diagnosis and therapeutic target in PE.

Anthropometric indices as surrogates for estimating abdominal visceral and subcutaneous adipose tissue: A meta-analysis with 16,129 participants.

AIM: To seek anthropometric indices that estimate visceral and subcutaneous adipose tissue (VAT and SAT) by meta-analysis and comparing the predictive efficacy based on different characteristics of participants. METHODS: PubMed, PubMed Central, Web of Science, China National Knowledge Infrastructure and Wanfang databases were searched for publications containing correlation coefficients of VAT and/or SAT with waist circumference (WC) and/or body mass index (BMI). The overall or subgroup pooled results were analyzed by meta and metafor packages of R with random effects model. MedCalc software was used to compare the correlation coefficients between groups. RESULTS: Twenty-nine publications were included in this meta-analysis. The correlation coefficients of VAT-WC, VAT-BMI, SAT-WC and SAT-BMI for total studies were between 0.640 and 0.785. The correlation of VAT with WC was larger than that with BMI (Z = 11.664, P < 0.001). Meanwhile, the correlation coefficients of VAT-WC were statistically different among different age groups, areas, ethnicities, body shapes, scanning levels, units and instruments of measuring VAT (P < 0.05). The overall correlation of SAT with BMI was larger than that with WC (Z = 3.805, P < 0.001). The subgroups' correlation coefficients of SAT-BMI showed statistical differences between genders, age groups, areas, ethnicities, body shapes, scanning levels, units (cm2 and cm3) and instruments of measuring SAT (P < 0.05). CONCLUSIONS: WC may be a common and simple surrogate for estimating VAT, and BMI for SAT, especially in Europeans, but not in the aged people.

Quantitative assessment of optic nerve in patients with Leber's hereditary optic neuropathy using reduced field-of-view diffusion tensor imaging.

PURPOSE: To quantitatively analyze the optic nerve alterations in chronic Leber's hereditary optic neuropathy (LHON) using reduced field-of-view diffusion tensor imaging (rFOV-DTI) and evaluate the correlation of diffusion parameters with visual functional and peripapillary retinal nerve fiber layer (RNFL) thickness. METHODS: Twenty-five patients (50 affected optic nerves) with chronic LHON and 28 healthy controls (56 normal optic nerves) were enrolled. The rFOV-DTI was performed in the bilateral optic nerves for all the subjects. The fractional anisotropy (FA), mean diffusivity (MD), principal eigenvalue (λ//), and orthogonal eigenvalue (λ⊥) were calculated for quantitative analysis. Visual field (VF) and visual acuity (VA) were measured in all subjects. The peripapillary RNFL thickness was assessed using optical coherence tomography (OCT). The correlation of DTI diffusion parameters with visual function and peripapillary RNFL thickness was evaluated. RESULTS: Compared with optic nerves in the control group, the mean FA was significant decreased (P<0.005), and the mean MD, λ//and λ⊥ significant increased (P<0.005). The average and temporal peripapillary RNFL thickness were significantly thinned in LHON patients. There was a significant correlation between optic nerve FA and VA, mean deviation of visual field (MDVF) (P<0.005). Also, optic nerve FA correlated significantly with average RNFL thickness (P<0.05) but not with MD, λ//and λ⊥ (P>0.05). However, none of the DTI parameters correlated with age and disease duration (P>0.05). CONCLUSIONS: Our study has demonstrated that rFOV-DTI could provide information of optic nerve damage in chronic LHON, and can serve as technique for detecting and evaluating pathological changes in the optic nerve in LHON.

The lncRNA TUG1 modulates proliferation in trophoblast cells via epigenetic suppression of RND3.

Due to limited treatment options, pre-eclampsia (PE) is associated with fetal perinatal and maternal morbidity and mortality. During the causes of PE, failure of uterine spiral artery remodeling which might be related to functioning abnormally of trophoblast cells, result in the occurrence and progression of PE. Recently, abnormal expression of long non-coding RNAs (lncRNAs), as imperative regulators involved in human diseases progression (included PE), which has been indicated by increasing evidence. In this research, we found that TUG1, a lncRNA, was markedly reduced in placental samples from patients with PE. Loss-function assays indicated that knockdown TUG1 significantly affected cell proliferation, apoptosis, migration and network formation in vitro. RNA-seq revealed that TUG1 could affect abundant genes, and then explore the function and regulatory mechanism of TUG1 in trophoblast cells. Furthermore, RNA immunoprecipitation and chromatin immunoprecipitation assays validated that TUG1 can epigenetically inhibit the level of RND3 through binding to EZH2, thus promoting PE development. Therefore, via illuminating the TUG1 mechanisms underlying PE development and progression, our findings might furnish a prospective therapeutic strategy for PE intervention.