Association of PM2.5 Components with Acceleration of Aging: Moderating Role of Sex Hormones.

Fine particulate matter (PM2.5) has been linked to aging risk, and a lack of knowledge about the relationships between PM2.5 components and aging risk impeded the development of healthy aging. Participants were recruited through a multicenter cross-sectional study in the Beijing-Tianjin-Hebei region in China. Middle-age and older males and menopausal women completed the collection of basic information, blood samples, and clinical examinations. The biological age was estimated by Klemera-Doubal method (KDM) algorithms based on clinical biomarkers. Multiple linear regression models were applied to quantify the associations and interactions while controlling for confounders, and a restricted cubic spline function estimated the corresponding dose-response curves of the relationships. Overall, KDM-biological age acceleration was associated with PM2.5 component exposure over the preceding year in both males and females, with calcium [females: 0.795 (95% CI: 0.451, 1.138); males: 0.712 (95% CI: 0.389, 1.034)], arsenic [females: 0.770 (95% CI: 0.641, 0.899); males: 0.661 (95% CI: 0.532, 0.791)], and copper [females: 0.401 (95% CI: 0.158, 0.644); males: 0.379 (95% CI: 0.122, 0.636)] having greater estimates of the effect than total PM2.5 mass. Additionally, we observed that the associations of specific PM2.5 components with aging were lower in the higher sex hormone scenario. Maintaining high levels of sex hormones may be a crucial barrier against PM2.5 component-related aging in the middle and older age groups.

Association between the MCP-1 -2518 A > G (rs1024611) polymorphism and susceptibility to type 2 diabetes mellitus and diabetic nephropathy: a meta-analysis.

BACKGROUND: Studies evaluating the association between monocyte chemoattractant protein-1 (MCP-1) -2518 A > G (rs1024611) polymorphism and type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) are contradictory. The present study aims to provide a comprehensive assessment and more reliable estimation of the relationship between the MCP-1 rs1024611 polymorphism and T2DM and DN risk. METHODS: Eligible articles were retrieved from the PubMed, Web of Science, EMBASE, Cochrane, and China National Knowledge Infrastructure databases. The effect summary odds ratios (ORs) and 95% confidence intervals (CIs) were obtained to calculate the summary effect size. Heterogeneity was analyzed by subgroup analysis and meta-regression. Publication bias was tested using funnel plots and Egger's test. RESULTS: In total, sixteen studies were included. Thirteen studies involving 2,363 patients with T2DM and 4,650 healthy controls found no significant association between the MCP-1 rs1024611 polymorphism and T2DM in the overall population. Ethnicity stratification found an association between the GG + GA genotype and decreased T2DM risk in Caucasians (OR = 0.79, 95% CI: 0.66-0.93, P = 0.006; PQ = 0.372). No significant risks were found in the Asian population for any genetic models. Seven studies found an association between the GG + GA genotype and DN risk in the Asian population (OR = 1.37, 95% CI: 1.11-1.71, P = 0.004, PQ = 0.222). No significant risks were found in the Caucasian population with any genetic models. There were no statistically significant differences in genotype distribution between patients with T2DM and DN in Asians or Caucasians. Meta-regression revealed that genotyping method was a major driver of heterogeneity in five genetic models (GG + GA vs. AA: P = 0.032; GG vs. GA + AA: P = 0.028; GG vs. AA: P = 0.035; GG vs. GA: P = 0.041; G vs. A: P = 0.041). CONCLUSION: The MCP-1 rs1024611 polymorphism is associated with susceptibility to T2DM in Caucasians and DN in Asians. Larger, well-designed cohort studies are needed in the future to verify this association.

The impact of hazes on schizophrenia admissions and the synergistic effect with the combined atmospheric oxidation capacity in Hefei, China.

OBJECTIVES: Currently, most epidemiological studies on haze focus on respiratory diseases, cardiovascular diseases, etc. However, the relationship between haze and mental health has not been adequately explored. The purpose of this study was to investigate the influence of hazes on schizophrenia admissions and to further explore the potential interaction effect with the combined atmospheric oxidative indices (Ox and Oxwt). METHODS: We collected 5328 cases during the cold season from 2013 to 2015 in Hefei, China. By integrating the Poisson Generalized Linear Models with the Distributed Lag Non-linear Models, the association between haze and schizophrenia admissions was evaluated. The interaction between hazes and two combined oxidation indexes was tested by stratifying hazes and Ox, and Oxwt. RESULTS: Haze was found to be significantly linked to an increased risk of hospitalization for schizophrenia, and a 9-day lag effect on schizophrenia (lag 3-lag 11), with the largest effect on lag 6 (RR = 1.080, 95% confidence interval (CI): 1.046-1.116). Males, females, and <40 y (people under 40 years old) were sensitive to hazes. Furthermore, in the stratified analysis, we found synergies between two combined oxidation indexes and hazes. The interaction relative risk (IRR) and relative excess risk due to interaction (RERI) between Ox and hazes were 1.170 (95% CI: 1.071-1.277) and 0.149 (95% CI: 0.045-0.253), respectively. For Oxwt, the IRR and RERI were 1.179 (95% CI: 1.087-1.281) and 0.159 (95% CI: 0.056-0.263), respectively. It is noteworthy that this synergistic effect was significant in males and <40 y when examining the various subgroups in the interaction analysis. CONCLUSIONS: Our findings suggest that exposure to haze significantly increases the risk of hospitalization for schizophrenia. More significant public health benefits can be obtained by prioritizing haze periods with high combined atmospheric oxidation capacity.

Deep Cerebellar Nuclei Functional Connectivity with Cerebral Cortex in Temporal Lobe Epilepsy With and Without Focal to Bilateral Tonic-Clonic Seizures: a Resting-State fMRI Study.

We aimed to explore the altered functional connectivity patterns within cerebello-cerebral circuits in temporal lobe epilepsy (TLE) patients with and without focal to bilateral tonic-clonic seizures (FBTCS). Forty-two patients with unilateral TLE (21 with and 21 without FBTCS) and 22 healthy controls were recruited. We chose deep cerebellar nuclei as seed regions, calculated static and dynamic functional connectivity (sFC and dFC) in the patients with and without FBTCS and healthy controls, and compared sFC and dFC among the three groups. Correlation analyses were used to assess relationships between the significantly altered imaging features and patient clinical parameters. Compared to the group without FBTCS, the FBTCS group showed decreased sFC between the right dentate nuclei and left hemisphere regions including the middle frontal gyrus, superior temporal gyrus, superior medial frontal gyrus and posterior cingulate gyrus, and significantly increased dFC between the right interposed nuclei and contralateral precuneus. Relative to HCs, the FBTCS group demonstrated prominently decreased sFC between the right dentate nuclei and left middle frontal gyrus. No significant correlations between the altered imaging features and patient clinical parameters were observed. Our results suggest that the disrupted cerebello-cerebral FC might be related to cognitive impairment, epileptogenesis, and propagation of epileptic activities in patients with FBTCS.

A study of brain functional network and alertness changes in temporal lobe epilepsy with and without focal to bilateral tonic-clonic seizures.

BACKGROUND: Temporal lobe epilepsy (TLE) is commonly refractory. Epilepsy surgery is an effective treatment strategy for refractory epilepsy, but patients with a history of focal to bilateral tonic-clonic seizures (FBTCS) have poor outcomes. Previous network studies on epilepsy have found that TLE and idiopathic generalized epilepsy with generalized tonic-clonic seizures (IGE-GTCS) showed altered global and nodal topological properties. Alertness deficits also were found in TLE. However, FBTCS is a common type of seizure in TLE, and the implications for alertness as well as the topological rearrangements associated with this seizure type are not well understood. METHODS: We obtained rs-fMRI data and collected the neuropsychological assessment data from 21 TLE patients with FBTCS (TLE- FBTCS), 18 TLE patients without FBTCS (TLE-non- FBTCS) and 22 controls, and constructed their respective functional brain networks. The topological properties were analyzed using the graph theoretical approach and correlations between altered topological properties and alertness were analyzed. RESULTS: We found that TLE-FBTCS patients showed more serious impairment in alertness effect, intrinsic alertness and phasic alertness than the patients with TLE-non-FBTCS. They also showed significantly higher small-worldness, normalized clustering coefficient (γ) and a trend of higher global network efficiency (gE) compared to TLE-non-FBTCS patients. The gE showed a significant negative correlation with intrinsic alertness for TLE-non-FBTCS patients. CONCLUSION: Our findings show different impairments in brain network information integration, segregation and alertness between the patients with TLE-FBTCS and TLE-non-FBTCS, demonstrating that impairments of the brain network may underlie the disruptions in alertness functions.

The local neural markers of MRI in patients with temporal lobe epilepsy presenting ictal panic: A resting resting-state postictal fMRI study.

OBJECTIVES: Temporal lobe epilepsy (TLE) is one of the most common focal epilepsies. Some patients with TLE have ictal panic (IP), which is often confused with panic attack (PA) in panic disorder (PD). Previous studies have described temporal lobe epilepsy with ictal panic (TLEIP), but the specific mechanisms remain unclear. Here, we used resting-state functional magnetic resonance imaging (rs-fMRI) to investigate local brain abnormalities in patients with TLEIP and tried to find neural markers to explore the mechanism of IP in patients with TLE. METHODS: A total of 40 patients with TLE, including 28 patients with TLE and 12 patients with TLEIP along with 30 age- and gender-matched healthy controls were included. We collected clinical/physiological/neuropsychological and rs-fMRI data. Fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and degree centrality (DC) were calculated. ANOVA was used to find different areas and t-tests used to compare differences among fALFF, ReHo, and DC. Correlation analyses explored the relationship between local brain abnormalities and patient characteristics. RESULTS: No significant differences in age and gender were found among the three groups, nor were there differences in education level, Montreal Cognitive Assessment (MOCA) and Hamilton Anxiety Scale (HAMA) between the TLEIP and TLE groups. All the onset sites of patients with TLEIP were on the right. In addition to fear, other symptoms observed included nausea, palpitations, rising epigastric sensation, and dyspnea. There were no correlations between duration of IP and HAMA (p = 0.659). Moreover, all IP durations were <2 min and most <1 min. Compared to the HCs group, the ReHo value of the TLEIP group in the right middle frontal gyrus was significantly decreased (GRF correction, two-tailed, voxel level P < 0.005, cluster level P < 0.05). Compared to the HCs and TLE groups, the DC value of the TLEIP group in the left middle temporal gyrus (MTG) was significantly increased (GRF correction, two-tailed, voxel level P < 0.005, cluster level P < 0.05). No regions showed any significant fALFF difference between HCs and TLE groups (GRF correction, two-tailed, voxel level P < 0.005, cluster level P < 0.05). CONCLUSIONS: This research describes local brain abnormalities in patients with TLE presenting as IP. These results will be preliminarily conducive to understand the seizure mechanism of IP in patients with TLE, find out the MRI neural markers, and to further explore the neurophysiological mechanisms of IP in patients with TLE.

Effectiveness of seminar-case learning for use in practice teaching of statistics for undergraduates majoring in preventive medicine: a prospective cluster-randomized controlled trial.

BACKGROUND: The seminar-case learning (SCL) method is a case-oriented teaching model, with teachers and students as the main body of teaching, characterized by communication, interaction, and mutual inspiration. This study explored the effects of the SCL method versus traditional lecture-based learning (LBL) in the statistics curriculum for undergraduate students majoring in preventive medicine. Research questions were: 1) whether the scores of students in the experimental group (the SCL model) were higher than those in the control group (the LBL model); 2) whether the students' satisfaction in the experimental group was better than that in the control group; and 3) whether the self-report benefit of students in the experimental group was better than that in the control group. METHODS: We conducted a two-armed cluster-randomized education intervention trial in practice teaching of health statistics among undergraduates majoring in preventive medicine. Two administrative classes (classes 1-4 and classes 5-8) were divided into the experimental group and the control group according to the principle of drawing lots. The students in two groups received the same statistical theory course. For the arrangement of statistical practice course, the experimental group adopted the SCL model, and the control group used the LBL model. The teaching effect was evaluated via an examination and an anonymous questionnaire survey. RESULTS: Scores for noun explanation questions in the experimental group showed no statistical significance with that of the control group(U = 2911.0, P = 0.964). The scores of single choice, calculation, and case analysis questions, and the total scores were significantly higher than that of the control group (P < 0.05). Students' satisfaction with arrangements of the practice course in the experimental group (92.41%) was significantly higher than that of in the control group (77.03%), the difference was statistically significant (χ2 = 7.074, P = 0.008). The self-report benefit of students in the experimental group was better than that in the control group (P < 0.05). CONCLUSION: As an effective method of high-quality education, the SCL model is worthy of further promotion in the practice teaching of preventive medicine.

[Relationship between sleep-wake circadian chronotype and anxiety and depression of medical students in a university in Wuhu City in 2020].

OBJECTIVE: To explore the circadian rhythm of sleep-wake and its relationship with anxiety and depression among medical students. METHODS: A stratified cluster random sampling method was adopted in this study, 2231 medical students in grades 1 to 3 from a medical college in Wuhu City(1004 boys and 1227 girls, aged(19.09±1.13) years) were selected in November 2020. The sleep wake circadian chronotype and mental health of medical students were evaluated by the Morningness-Eveningness Questionnaire 19(MEQ-19), the Patient Health Questionnaire 2(PHQ-2), and the Generalized Anxiety Disorder scale(GAD-2), respectively. RESULTS: The detection rates of evening chronotype, intermediate circadian chronotype, and morning chronotype were 59.84%(n=1335), 37.92%(n=846), and 2.24%(n=50), respectively. The detection rates of anxiety, depression, and anxiety combined with depression were 12.86%(n=287), 14.12%(n=315), and 9.59%(n=214), respectively. After adjusting for gender, age, grade, class performance in the last half semester, and learning burden, the result of multivariate logistic regression analysis showed that compared with medical students with intermediate circadian chronotype, medical students with evening chronotype were more likely to have anxiety(OR_(adj. )=1.403, 95% CI 1.066-1.846, P=0.016) and depression(OR_(adj. )=1.639, 95% CI 1.251-2.146, P < 0.001). CONCLUSION: The detection rate of anxiety and depression in medical students is high. The circadian chronotype of medical students is mainly evening chronotype, which is a risk factor affecting anxiety and depression among medical students.

Association between TNF-α G-308A (rs1800629) polymorphism and susceptibility to chronic periodontitis and type 2 diabetes mellitus: A meta-analysis.

BACKGROUND AND OBJECTIVE: Although the association between tumor necrosis factor-α (TNF-α) G-308A (rs1800629) polymorphism and chronic periodontitis (CP), chronic periodontitis with type 2 diabetes mellitus (DP) is assumed, results of this association have been contradictory. The aim of this study was to assess the relationship between rs1800629 polymorphism and CP/DP susceptibility. METHODS: We searched for studies on PubMed, Web of Science, MEDLINE, Chinese National Infrastructure, and WanFang databases. Study selection was performed using specific inclusion and exclusion criteria and fulfilled the PECO (participant, exposure, comparison, and outcome) format. The relationship between rs1800629 polymorphism and CP/DP susceptibility was evaluated by the effect summary odds ratio (OR) and 95% confidence intervals (CIs). Allele, dominant, and recessive genetic models were computed to assess the strength of the association. RESULTS: A total of 25 case-control studies were included in the analysis. In the Asian population, TNF-α rs1800629 polymorphism was found to be significantly associated with CP in the overall analyses and for all genetic contrasts, while no significant risks were found among Caucasian populations for all genetic contrasts. The TNF-α rs1800629 polymorphism was also associated with increased DP risk in Asians under the fixed-effects model, but not in the recessive comparison. CONCLUSION: The meta-analysis suggested that TNF-α rs1800629 polymorphism might affect the risk of CP and DP, particularly in individuals of Asian descent.

Circulating ERBB3 levels are inversely associated with the risk of overweight-related hypertension: a cross-sectional study.

BACKGROUND: Hypertension and overweight are independent risk factors for cardiovascular disease, and overweight increase the risk of developing high blood pressure. ERBB3( also known as HER3) plays a considerable role in the development of cardiovascular diseases. However, the effect of ERBB3 levels in hypertensive overweight patients is unknown. The aim of this study was to assess the association between ERBB3 levels and hypertension in overweight Chinese patients. METHODS: We evaluated the height,weight, blood pressure, biochemical indicators, and ERBB3 levels in 128 Chinese adults aged 33-79 years. Plasma ERBB3 levels were assessed by the enzyme-linked immunosorbent assay, and body mass index(BMI) was calculated as body weight divided by height squared. Participants were allocated into three groups according to blood pressure and BMI: healthy control (CNT, n = 31; normotensive and non-overweight), hypertension (HT, n = 33; hypertension and non-overweight), and hypertension with overweight (HTO, n = 64; hypertension and overweight). Statistical significance was defined as a two-tailed P < 0.05. RESULTS: There was no significant difference in mean ERBB3 levels among the three groups, although a linear decrease from CNT (1.13 ± 0.36), HT (1.03 ± 0.36), to HTO (0.84 ± 0.26 ng/mL) was observed in men (P = 0.007). Among the drinking population, the ERBB3 level was significantly reduced in the HTO group as compared with those of the CNT and HT groups (0.76 ± 0.23 versus 1.18 ± 0.37 and 1.20 ± 0.30, respectively). ERBB3 levels were negatively correlated with diastolic blood pressure in men (r= - 0.293, P = 0.012), smoking (r= - 0.47, P = 0.004), and drinking (r = - 0.387, P = 0.008). BMI in men and among drinkers, and uric acid among drinkers were negatively correlated with ERBB3 levels. Multivariate conditional logistic regression showed that plasma ERBB3 levels were associated with a reduced risk of HTO in men [odds ratio (OR) 0.054; 95 % confidence interval (CI): 0.007-0.412) and drinkers (OR 0.002; 95 % CI: 0.000-0.101). CONCLUSIONS: ERBB3 may contribute to the pathogenesis of hypertension in overweight patients, with BMI, gender, and drinking all potentially modulating the process.

Association between serum alanine and aspartate aminotransferase and blood pressure: a cross-sectional study of Chinese freshmen.

BACKGROUND: High blood pressure is a well-recognized risk factor for cardiovascular events, and the incidence of hypertension is increasing among young people. This study investigated the relationship between ALT and AST levels and hypertension among freshmen in China. METHODS: This cross-sectional study was conducted in the Anhui Province from September to November 2018. A total of 3114 freshmen underwent a physical examination including testing of biochemical indicators and a standardized questionnaire. RESULTS: The overall prevalence of elevated ALT and AST were 6.8% and 2.3% among freshmen. The mean ALT and AST levels were higher in males (22.59 ± 21.98 vs.12.62 ± 10.30 U/L; 23.55 ± 12.24 vs. 20.02 ± 5.75 U/L, respectively). The prevalence of hypertension was significantly higher in men (16.1%) than in women (1.9%). The mean values of BMI, SBP, DBP, TC, TG, and LDL-C were found to be increased with elevated levels of serum ALT and AST in the quartiles (P for trend < 0.05). After adjusting for covariates, the risk of hypertension was significantly higher in the highest ALT quartile than in the lowest quartile (OR (95% CI) of 1.681 (1.028, 2.751) in males; 2.802 (1.102, 7.124) in females). A strong linear relationship was found between serum ALT levels and the odds of hypertension after adjustment for potential confounders only in total population and females (P for trend < 0.05). CONCLUSIONS: These findings suggest that ALT level is significantly associated with hypertension both in male and female freshmen.

Downregulation of Arntl mRNA Expression in Women with Hypertension: A Case-Control Study.

BACKGROUND: Previous studies have reported that disturbance of endogenous circadian rhythms enhances the chance of hypertension and suggested that circadian clock genes could have a crucial function in the onset of the disease. This case-control study was aimed to investigate the association of the mRNA expression of aryl hydrocarbon receptor nuclear translocator like (Arntl), clock circadian regulator (Clock), and period circadian regulators 1 and 2 (Per1 and Per2) with hypertension and blood pressure levels. METHODS: A total of 172 subjects were recruited in this study, including 86 hypertension and 86 nonhypertension controls. The mRNA expression levels in peripheral blood mononuclear cells were determined by real-time quantitative polymerase chain reaction. The differences in Arntl, Clock, Per1, and Per2 mRNA expression were compared between the 2 groups, and the relationship between mRNA expression and cardiometabolic risk profiles was also assessed. RESULTS: We found that the mRNA expression of Arntl was downregulated in the hypertension cases compared with controls in women (1.10 [0.66, 1.71] vs. 1.30 [0.99, 2.06], p = 0.031). There was a significant negative correlation between the Arntl mRNA expression and SBP (r = -0.301, p = 0.004) and DBP (r = -0.222, p = 0.034) in women. In men, a negative correlation between the Per1 mRNA expression and SBP (r = -0.247, p = 0.026) was found. CONCLUSIONS: The Arntl mRNA expression may play an important role in progression of hypertension in women.

Three-dimensional changes of the upper airway in patients with Class II malocclusion treated with functional appliances: a systematic review and meta-analysis.

BACKGROUND/OBJECTIVE: To evaluate the three-dimensional (3D) changes of the upper airway in patients with Class II malocclusion treated with functional appliances (FAs). SEARCH METHODS AND ELIGIBILITY CRITERIA: A comprehensive search of seven electronic databases was conducted from the date of inception to 12 July 2020. Manual search was also performed in relevant Chinese and English periodicals. Prospective and retrospective studies evaluating the 3D airway changes after FAs applied on growing patients with skeletal Class II malocclusion were included. DATA COLLECTION AND ANALYSIS: Risk of bias assessment of each included study was performed referring to ROBINS-I. The effects of FAs on upper airway were evaluated by meta-analysis using STATA software. The outcome variables were the changes of oropharyngeal airway volumes (OAVs), nasopharyngeal airway volumes (NAVs), minimum cross-sectional area (MCA) and antero-posterior position of hyoid bone (HB). The overall quality of evidence for each outcome was rated based on Grading of Recommendations Assessment, Development and Evaluation recommendations. RESULTS: Nine studies were ultimately included in the systematic review and five were included and analyzed in meta-analysis. The results indicated that the pooled mean differences among these studies were 2162.80 [95 per cent confidence interval (CI): 1264.97, 3060.62), 382.20 (95 per cent CI: 140.95, 623.44), 59.91 (95 per cent CI: 41.45, 78.38), and 0.63 (95 per cent CI: -1.97, 3.23) for changes of OAVs, NAVs, MCA, and antero-posterior position of HB, respectively. CONCLUSION: Weak evidence suggests that FAs can increase OAVs, NAVs, and MCA in growing patients with Class II malocclusion. Weak evidence also suggests that antero-posterior position of HB cannot be affected by FAs. Further studies are necessary to assess the stability of its effect on the upper airway in the long term. REGISTRATION: The review protocol was not registered prior to the study.

Social network strategy as a promising intervention to better reach key populations for promoting HIV prevention: a systematic review and meta-analysis.

INTRODUCTION: Key populations such as men who have sex with men (MSM), drug users and sex workers are at high risk of HIV infection, but they are marginalised and hidden. Social network strategy (SNS) is purposeful to use social networks to generate social influence, accelerate behaviour change and achieve desirable outcomes among individuals or communities and have been increasingly used for HIV interventions. This study aims to investigate the effects of SNS on HIV prevention among key populations. METHODS: We searched six databases, including PubMed, Web of Science, Embase, Cochrane Library, ScienceDirect and Wiley for randomised controlled trials published between January 1999 and May 2019. Eligibility criteria included SNS conducted among key populations for HIV interventions, with a comparator group. Outcomes included changes in HIV high-risk behaviour, HIV seroconversion and other HIV outcomes. We used the risk ratio (RR) or mean difference with associated 95% confidence interval (CI) to assess the comparative efficacy between SNS and control methods on the selected outcomes. The GRADE system was used to assess the quality of evidence for the studies. RESULTS: Of 2818 citations identified, 28 trails from 24 papers met the inclusion criteria. The results showed that SNS was associated with less unprotected intercourse (RR 0.79, 95% CI 0.72 to 0.86) and sex with multiple partners (0.46, 95% CI 0.33 to 0.65). Additionally, relative to the control methods, SNS significantly reduced HIV seroconversion (0.65, 95% CI 0.53 to 0.81), improved HIV testing uptake (1.11, 95% CI 1.07 to 1.15) and promoted participant retention (1.03, 95% CI 1.00 to 1.06) among key populations. The Grading of Recommendations Assessment, Development and Evaluation system showed that trails were of moderate quality. CONCLUSIONS: This review provides evidence that SNS can reach key populations who are currently not being reached by existing programmes and deliver HIV interventions through social networks, which decreases HIV sexual risk behaviour and HIV incidence and increases HIV testing uptake and participant retention. TRIAL REGISTRATION NUMBER: CRD42019140533.

Upregulation of long non-coding RNA MEG3 in type 2 diabetes mellitus complicated with vascular disease: a case-control study.

Previous studies have indicated that long non-coding RNAs (lncRNAs) were closely related to diabetes. In this study, we aimed to explore the possible role and mechanism of lncRNA MEG3 in the occurrence and development of type 2 diabetes mellitus (T2DM) and its vascular complications. A case-control study involving 115 subjects was conducted, including 53 T2DM patients (37 patients with vascular complication and 16 patients without vascular complications) and 62 healthy subjects. We performed real-time polymerase chain reaction (RT-PCR) analysis of the lncRNA MEG3 and miR-146a levels in peripheral blood mononuclear cells (PBMCs) in the 115 samples. We found that the expression of lncRNA MEG3 was upregulated in the T2DM patients with vascular complication (DC group) compared with T2DM patients without vascular complication (D group) (P < 0.05) and the control group (P < 0.01). miR-146a levels in DC group were significantly lower compared with control group. There was a significant positive correlation between the expression of lncRNA MEG3 and glucose (GLU) (r = 0.301, P = 0.0011) and hemoglobin A1C (HbA1c) (r = 0.477, P = 0.0006). Our study suggests MEG3 may play as an important role in progression of diabetes-related vascular complications, contributing to a novel understanding of pathogenesis and prognosis for diabetes and its complications.

Leucine-Rich Repeat Neuronal Protein 1 Regulates Differentiation of Embryonic Stem Cells by Post-Translational Modifications of Pluripotency Factors.

Stem cell surface markers may facilitate a better understanding of stem cell biology through molecular function studies or serve as tools to monitor the differentiation status and behavior of stem cells in culture or tissue. Thus, it is important to identify additional novel stem cell markers. We used glycoproteomics to discover surface glycoproteins on human embryonic stem cells (hESCs) that may be useful stem cell markers. We found that a surface glycoprotein, leucine-rich repeat neuronal protein 1 (LRRN1), is expressed abundantly on the surface of hESCs before differentiation into embryoid bodies (EBs). Silencing of LRRN1 with short hairpin RNA (shLRRN1) in hESCs resulted in decreased capacity of self-renewal, and skewed differentiation toward endoderm/mesoderm lineages in vitro and in vivo. Meanwhile, the protein expression levels of the pluripotency factors OCT4, NANOG, and SOX2 were reduced. Interestingly, the mRNA levels of these pluripotency factors were not affected in LRRN1 silenced cells, but protein half-lives were substantially shortened. Furthermore, we found LRRN1 silencing led to nuclear export and proteasomal degradation of all three pluripotency factors. In addition, the effects on nuclear export were mediated by AKT phosphorylation. These results suggest that LRRN1 plays an important role in maintaining the protein stability of pluripotency factors through AKT phosphorylation, thus maintaining hESC self-renewal capacity and pluripotency. Overall, we found that LRRN1 contributes to pluripotency of hESC by preventing translocation of OCT4, NANOG, and SOX2 from nucleus to cytoplasm, thereby lessening their post-translational modification and degradation. Stem Cells 2018;36:1514-1524.

Anti-Proliferative Effect of Wogonin on Ovary Cancer Cells Involves Activation of Apoptosis and Cell Cycle Arrest.

BACKGROUND The present study was designed to investigate the effect of wogonin on Caov-3 and A2780 ovary cancer cell proliferation and the mechanisms involved. MATERIAL AND METHODS Cell viability changes and apoptosis induction by wogonin were assessed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenytetrazolium bromide) assay and fluorescence microscopy. Morphological examination of cells was performed using transmission electron microscopy. RESULTS Wogonin exhibited inhibitory effect on Caov-3 and A2780 cancer cell proliferation in a concentration-based manner. Caov-3 and A2780 cell proliferation was reduced to 18% and 21%, respectively on treatment with 200 µM concentration of wogonin. Treatment with wogonin significantly enhanced the percentage of A2780 cells showing apoptosis. The nuclear membrane degradation and condensation of chromatin material was evident in A2780 cells on treatment with wogonin. Treatment of A2780 cells with wogonin suppressed the migration potential significantly. The proportion of A2780 cells in G1/G0 phase was markedly raised on exposure to wogonin for 48 hours. CONCLUSIONS In summary, this study demonstrated that wogonin acts as an ovary cancer cell proliferation inhibiting agent through activation of apoptosis. Wogonin, therefore, can be investigated further for the development of ovary cancer treatment.

Electronic vs steric effects on the stability of anionic species: a case study on the ortho and para regioisomers of organofullerenes.

The stability of the anionic species of the ortho and para regioisomers of (MeO)BnC(2n) (Me = methyl, Bn = benzyl, n = 30 or 35) has been examined. The results show that the ortho adducts (electronically favored regioisomers) are stable upon receiving one or two electrons, while the para ones (sterically favored adducts) decompose by removing the methoxy group under similar conditions. Computational calculations indicate that the stability of the anionic species is significantly affected by the electronic structure, where the [5,6]-double bond is responsible for the instability of the reduced species of the para adducts. Further study with 1,15-(MeO)2-2,4-Bn2C60, an adduct with both the ortho and para positioned methoxy, shows that the reduced species is stable, indicating that the 1,2,4,15-configuration is an electronically preferential structure even though it has a [5,6]-double bond.

An updated meta-analysis of transforming growth factor-ß1 gene: three polymorphisms with gastric cancer.

To derive a more precise estimation of the relationship between TGF-ß1 polymorphisms and gastric cancer (GC) risk, we conducted a meta-analysis of all available case-control studies relating the C-509 T, T869C, and G 915C polymorphisms of the TGF-ß1 gene to the risk of developing GC. The effect summary odds ratio (OR) and 95% confidence intervals (CIs) were obtained. Funnel plots and Egger's test were used to estimate publication bias. Finally, 11 studies were included in the final meta-analysis. With respect to C-509 T polymorphism, it was found that significantly increased GC risk was associated with the TT genotype in the recessive genetic model in overall analysis (TT vs. CC + CT: OR = 1.23, 95% CI 1.09-1.38, P(heterogeneity) = 0.13) and in Asian population (TT vs. CC + CT: OR = 1.24, 95% CI 1.10-1.39, P(heterogeneity) = 0.18). With respect to T869C and G915C polymorphisms, no significant association with GC risk was demonstrated in overall analysis and subgroup analyses according to ethnicity for all genetic models. This meta-analysis suggested that the T allele of TGF-ß1 509C/T polymorphism is probably the susceptibility factor for GC.

Construction of a sensitive SWCNTs integrated SPR biosensor for detecting PD-L1+ exosomes based on Fe3O4@TiO2 specific enrichment and signal amplification.

Programmed cell death-ligand 1 positive (PD-L1+) exosomes play a crucial role in the realm of cancer diagnosis and treatment. Nevertheless, due to the intricate nature of biological specimens, coupled with the heterogeneity, low refractive index (RI), and scant surface coverage density of exosomes, traditional surface plasmon resonance (SPR) sensors still do not meet clinical detection requirements. This study utilizes the exceptional electrical and optical attributes of single-walled carbon nanotubes (SWCNTs) as the substrate for SPR sensing, thereby markedly enhancing sensitivity. Furthermore, sp2 hybridized SWCNTs have the ability to load specific recognition elements. Additionally, through the coordination interaction of Ti with phosphate groups and the ferromagnetism of Fe3O4, efficient exosomes isolation and enrichment in complex samples are achievable with the aid of an external magnetic field. Owing to the high-quality and high-RI of Fe3O4@TiO2, the response signal experiences amplification, thus further improving the performance of the SPR biosensor. The linear range of the SPR biosensor constructed by this method is 1.0 × 103 to 1.0 × 107 particles/mL, with a limit of detection (LOD) of 31.9 particles/mL. In the analysis of clinical serum samples, cancer patients can be differentiated from healthy individuals with an Area Under Curve (AUC) of 0.9835. This study not only establishes a novel platform for exosomes direct detection but also offers new perspectives for the sensitive detection of other biomarkers.