The delivery of miR-21a-5p by extracellular vesicles induces microglial polarization via the STAT3 pathway following hypoxia-ischemia in neonatal mice.

Extracellular vesicles (EVs) from mesenchymal stromal cells (MSCs) have previously been shown to protect against brain injury caused by hypoxia-ischemia (HI). The neuroprotective effects have been found to relate to the anti-inflammatory effects of EVs. However, the underlying mechanisms have not previously been determined. In this study, we induced oxygen-glucose deprivation in BV-2 cells (a microglia cell line), which mimics HI in vitro, and found that treatment with MSCs-EVs increased the cell viability. The treatment was also found to reduce the expression of pro-inflammatory cytokines, induce the polarization of microglia towards the M2 phenotype, and suppress the phosphorylation of selective signal transducer and activator of transcription 3 (STAT3) in the microglia. These results were also obtained in vivo using neonatal mice with induced HI. We investigated the potential role of miR-21a-5p in mediating these effects, as it is the most highly expressed miRNA in MSCs-EVs and interacts with the STAT3 pathway. We found that treatment with MSCs-EVs increased the levels of miR-21a-5p in BV-2 cells, which had been lowered following oxygen-glucose deprivation. When the level of miR-21a-5p in the MSCs-EVs was reduced, the effects on microglial polarization and STAT3 phosphorylation were reduced, for both the in vitro and in vivo HI models. These results indicate that MSCs-EVs attenuate HI brain injury in neonatal mice by shuttling miR-21a-5p, which induces microglial M2 polarization by targeting STAT3.

Interaction of General or Central Obesity and Hypertension on Diabetes: Sex-Specific Differences in a Rural Population in Northeast China.

PURPOSE: Some studies have established an association between hypertension or obesity and the risk of diabetes. This study aimed to examine the interaction of hypertension and obesity on diabetes. PARTICIPANTS AND METHODS: The data of 11,731 Chinese men and women were analyzed from the 2012-2013 Northeast China Rural Cardiovascular Health Study. The interaction was examined by both additive and multiplicative scales. General obesity was measured by body mass index (BMI); central obesity was defined by waist circumference (WC), waist-to-height ratio (WHtR) and waist-to-hip ratio (WHpR). RESULTS: After controlling for potential confounders, the odds ratios for diabetes were 3.864 (3.205-4.660), 4.500 (3.673-5.514), 4.932 (3.888-6.255) and 4.701 (3.817-5.788) for the combinations of hypertension and BMI, WC, WHtR or WHpR, respectively, which had the highest risk of diabetes among the four combinations. Notwithstanding the multiplicative interactions showed statistically significant in all analyses, the results of additive interactions were not consistent, suggesting the diabetes risk from female BMI (relative excess risk due to interaction (RERI): 1.136, 95% CI: 0.127-2.146, attributable proportion due to interaction (AP): 0.267, 95% CI: 0.057-0.477, synergy index (S):1.536, 95% CI: 1.017-2.321) or female WHpR (RERI: 1.076, 95% CI: 0.150-2.002, AP:0.205, 95% CI: 0.037-0.374, S:1.340, 95% CI: 1.012-1.775) was additive to the risk from hypertension. CONCLUSION: The findings suggest that high BMI and high WHpR have synergistic interactions with hypertension on the risk of diabetes for females. The results of this study also suggest that BMI and WHpR, rather than WC, should be used for the diagnosis of metabolic syndrome in Chinese population.

KIF23 enhances cell proliferation in pancreatic ductal adenocarcinoma and is a potent therapeutic target.

BACKGROUND: In recent research, high expression of kinesin family member 23 (KIF23), one of the kinesin motor proteins involved in the regulation of cytokinesis, has been shown to be related to poor prognosis in glioma and paclitaxel-resistant gastric cancer, as a results of the enhancement of proliferation, migration, and invasion. In this study, we analyzed the role of KIF23 in the progression of pancreatic ductal adenocarcinoma. METHODS: A bioinformatic method was used to analyze the KIF23 mRNA level in pancreatic tumor tissues compared with normal pancreatic tissues and to analyze the connection between high KIF23 expression and prognosis. We examined the expression of KIF23 using immunohistochemistry and analyzed the connection between the expression of KIF23 and clinicopathological features in pancreatic ductal adenocarcinoma patients. In addition, a colony formation assay, MTT assay, and western blot assay were performed in vitro, along with a mouse xenograft model in vivo, to analyze the effect of KIF23 on proliferation. Further, the correlation between KIF23 and CDCA8 was analyzed by TCGA and immunohistochemical data. RESULTS: Bioinformatic results showed that KIF23 mRNA expression was higher in pancreatic tumor tissues than in normal pancreatic tissues and a poor prognosis has been linked to the high expression of KIF23. Immunohistochemistry revealed that KIF23 was highly expressed at the protein level and high expression of KIF23 correlated with adverse clinicopathological features. Our experimental results demonstrated that knockdown of KIF23 could inhibit the proliferation of pancreatic cells. Further, a positive correlation between KIF23 and CDCA8 expression existed, and KIF23 might promote pancreatic cancer proliferation by affecting CDCA8 expression. CONCLUSIONS: Our data showed that high expression of KIF23 is associated with a poor prognosis, and KIF23 might be a potential therapeutic target for pancreatic ductal adenocarcinoma.

Indeterminate domain 3 negatively regulates plant erectness and the resistance of rice to sheath blight by controlling PIN-FORMED gene expressions.

Plant architecture and disease resistance are the key factors that control the production of yield. However, the mechanism behind these factors is largely unknown. In this study, we identified that indeterminate domain 3 (IDD3) was obviously induced by inoculation of Rhizoctonia solani AG1-IA. Plants that overexpressed IDD3 (IDD3 OX) were more susceptible, while idd3 mutants showed a similar response to sheath blight disease compared with wild-type plants. Interestingly, IDD3 OX plants developed a wider tiller angle and exhibited altered shoot gravitropism, while idd3 knock-out mutants showed no visible morphological differences compared with the wild-type plants. IDD3 is ubiquitously expressed in different tissues and stages, and the IDD3 transcript was induced by exogenously applied auxin. Expression of the PIN-FORMED (PIN) and Aux/IAA genes was altered in IDD3 OX compared with wild-type plants. Furthermore, IDD3 OX plants are sensitive to auxin and the polar auxin transporter inhibitor N-1-naphthylphalamic acid (NPA). Further yeast-one hybrid, chromatin immunoprecipitation (ChIP) and transient assays revealed that IDD3 directly represses PIN1b via promoter binding. Inoculation with R. solani indicated that PIN1b RNAi plants are more susceptible to sheath blight disease (ShB) compared with the wild-type. Taken together, our analyses suggest that IDD3 controls plant architecture and the resistance of rice to ShB via the regulation of PIN auxin transporter genes.

The impact of monocyte to high-density lipoprotein ratio on reduced renal function: insights from a large population.

Aim: To investigate whether monocyte to HDL cholesterol ratio (MHR) can improve the risk stratification of reduced renal function by estimating atherosclerosis. Patients & methods: The cross-sectional study included 8159 subjects (males: 45.73%, mean age: 54.12 years) from Northeast China in 2013. Results: Each standard deviation increase of MHR brought 42.9% additional risk of reduced renal function in males. In females, MHR strongly correlated with reduced renal function before it reached a breakpoint (MHR = 0.25). Additionally, net reclassification improvement identified the value of MHR (0.199; 95% CI: 0.030-0.369; p = 0.021) to improve the risk classification of renal function reduction. Conclusion: This study implicates that MHR is independently associated with reduced renal function and can refine the risk stratification of renal function reduction.

Clinical significance of Stathmin1 expression and epithelial-mesenchymal transition in curatively resected gastric cancer.

In our previous study, it was demonstrated that the Stathmin1 (STMN1) is overexpressed in gastric cancer (GC) and that its high expression level is associated with tumor invasion and metastasis. Epithelial-mesenchymal transition (EMT) has also been shown to be critically involved in GC invasion and metastasis. Certain studies have indicated that STMN1 may serve an important role in the EMT process. However, the association between STMN1 expression and EMT-associated markers, as well as clinicopathological characteristics of patients with GC, remains unclear. The aim of the present study was to investigate the clinicopathological significance and prognostic value of STMN1 and EMT-associated markers in GC. The expression of STMN1 and the EMT-associated proteins E-cadherin (E-Cad) and vimentin (VIM) were analyzed by immunohistochemistry in GC and adjacent non-tumorous tissues. Associations between the expression of these markers and clinicopathological parameters were analyzed. The association between STMN1 expression and EMT-associated markers was investigated in the GC cell lines BGC-803 and SGC-7901. The results revealed that STMN1 was expressed in 63.5% of the 167 GC tissues, which was significantly higher than the percentage observed in the adjacent non-tumorous tissues (P=0.003). The STMN1 expression was demonstrated to be positively associated with the VIM levels (P=0.001) and negatively associated with the E-Cad levels (P=0.022) in GC tissues. The STMN1 expression was associated with Lauren's Classification, invasion depth, lymph node metastasis and pathological Tumor-Node-Metastasis (pTNM) stage (P<0.05). In the univariate analyses, the high E-Cad expression was a positive prognostic indicator for overall survival, whereas the high STMN1 and VIM expression was a negative indicator. COX multiple regression analysis demonstrated that the pTNM stage [hazard ratio (HR) 1.912, 95% confidence interval (CI): 1.282-2.851, P=0.001] and E-Cad expression (HR 0.403, 95% CI: 0.249-0.650, P=0.000) were independent prognostic factors. It was also revealed that the expression level of E-Cad decreased, while the expression level of VIM increased by depleting STMN1 levels in GC cells. The present results suggest that the aberrant expression of STMN1 may promote tumor progression through EMT in GC.

Estimate of prevalent diabetes from cardiometabolic index in general Chinese population: a community-based study.

BACKGROUND: Cardiometabolic index (CMI) defines adiposity based on triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) ratio and waist-to-height ratio (WHtR). This newly proposed metric has been used to detect multiple cardiovascular risk factors, but data relative to diabetes in the general population are lacking. This study aims to validate CMI's utility of discriminating diabetes and compares it with other indexes among general Chinese population. METHODS: Analyses were based on a cross-sectional study of 11,478 participants that underwent assessment of metabolic and anthropometric parameters in rural areas of northeastern China in 2013. CMI was calculated by TG/HDL-C × WHtR. Multivariate logistic regressions were performed to clarify CMI's association with diabetes, ROC analyses were engaged to investigate CMI's discriminating ability for diabetes. RESULTS: The prevalence of diabetes was 9.93% in males while 10.76% in females, and increased with CMI's increment. After full adjustment, each SD increment of CMI had odds ratios (ORs) for diabetes of 1.471 (1.367-1.584) and 1.422 (1.315-1.539) in females and males, respectively. Compared with bottom categories of CMI, the top quartiles had ORs of 3.736 (2.783-5.015) in females and 3.697 (2.757-4.958) in males. The ROC results showed an excellent discriminating power of CMI (AUC: 0.702 for females, 0.664 for males). CONCLUSIONS: An increasing CMI was correlated with higher odds of diabetes, supporting CMI as a useful and economic measure to screen and quantify diabetes in general Chinese population. Monitoring and promoting achievement of dyslipidemia and abdominal obesity based on CMI may improve subclinical and cardiovascular outcomes.

[Study on Total Triterpenoids Content of Enrichment Mineral Elements of Inonotus Obliquus].

Objective: To study the influence of different mineral elements enrichment of calcium, iron, and zinc on the growth of the mycelium from Inonotus obliquus, to explore the influence on total triterpenoids content of Inonotus obliquus. Methods: Mineral elements were enriched on Inonotus obliquus, total triterpenoids extraction methods and determination methods were optimized, and total triterpenoids content of Inonotus obliquus were compared through different mineral elements enrichment. Results: The mycelial growth and yield were promoted obviously when 1 000 mg/L Ca(NO3)2 was added in the culture medium, and the calcium enrichment rate could reach to 0.07%. The most appropriate iron source was Fe2(SO4)3, and the iron enrichment rate could reach to 0.29% when 300 mg/L Fe2(SO4)3 was added. 175 mg/L Zn SO4 led to the strongest mycelium growth vigor, and the zinc enrichment rate could reach to 0.57%. The total triterpenoids content of Inonotus obliquus was the highest (0.058 mg/mL) as enrichment of calcium element, the total triterpenoids content of Inonotus obliquus was the least (0.04 mg/mL) as enrichment of iron elements. Conclusion: The total triterpenoids content of Inonotus obliquus was the highest when calcium element was enriched. This study provides a new method and basic data for the factory production of Inonotus obliquus.

[Comparative Analysis of Different Inonotus obliquus].

OBJECTIVE: To screen optimal Inonotus obliquus strains that is suitable to cultivation, extracting effective components on industrialized production, genetics and breeding. METHODS: Inonotus obliquus mycelia from different countries were used. High quality strain was screened by comparing the antagonism between Inonotus obliquus and penicillium. The contents of crude fat, crude ash, crude protein and crude fiber were analyzed. RESULTS: It was showed that antagonism ability of Finnish birch was the strongest, its mycelia diameter was up to 53. 27 mm. It was also showed that nutritional ingredient was abundant in artificial cultured Inonotus obliquus strains. The contents of crude fat and crude protein in Finnish birch were higher, which was 1. 93% and 20. 23%, respectively. The contents of crude fat and crude protein in NBRC8681 strains were lower, which was 1. 55% and 19. 85%, respectively. The content of crude ash of JL04 strains was higher(8. 76%). The content of crude ash of NBRC8681 strains was lower(6. 8%). Crude fiber content was higher in HLJ01 strains, its content reached to 45. 09%. The least content appeared in MAFF420101 strains, whose crude fiber content was only 38. 27%. CONCLUSION: The strains of Finnish birch, HLJ01 and JL04 are suitable to exploitation.

Comparison of bevacizumab and ranibizumab in age-related macular degeneration: a systematic review and meta-analysis.

AIM: To compare the effectiveness and safety between bevacizumab and ranibizumab in the treatment of age-related macular degeneration (AMD) through a systematic review and meta-analysis. METHODS: We performed a comprehensive search of randomized controlled trials (RCTs), non-RCTs, case-control and cohort studies that compared bevacizumab and ranibizumab using PubMed and the Cochrane Library. After the related data were extracted by two investigators independently, pooled weighted mean differences (WMDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were estimated using a random-effects or a fixed-effects model. RESULTS: A total of four RCTs involving 1927 patients and eleven retrospective case series involving 2296 patients were included. For the primary outcomes, no significant differences were found between ranibizumab group and bevacizumab group in visual acuity (WMD: -0.04; 95%CI: -0.08 to 0.00; P=0.06), best corrected visual acuity (WMD: -0.05; 95%CI: -0.10 to 0.00; P=0.05), retina thickness (WMD: -4.69; 95%CI: -13.15 to 3.76; P=0.86) and foveal thickness (WMD: 10.91; 95%CI: -14.73 to 36.56; P=0.40). The pooled analyses in the evaluation of safety showed that compared to bevacizumab, ranibizumab was associated with decreased risks of ocular inflammation (RR: 0.45; 95% CI: 0.23 to 0.89; P=0.02) and venous thrombotic events (RR: 0.27; 95%CI: 0.08 to 0.89; P=0.03). However, there were no significant differences observed in deaths (P=0.69) and arterial thromboembolic events (P=0.71) between the two groups. CONCLUSION: With equal clinical efficacy, ranibizumab was found to be associated with less adverse events compared to bevacizumab, indicating that ranibizumab might be a safer management.

[Comparison of component from different species of Inonotus obliquus].

In this paper, water content, mineral element and active ingredient concentration on fifteen Inonotus obliquus which comes from all over the world were studied. In the aspect of water content, the free water content of Finnish birch was the highest, reaching 77.21%, significantly better than that of other strains. The free water content of JL04 is the lowest, only 54.6%. The bound water content of HLJ01 which from Heilongjiang is the highest, reaching 10. 74% , significant differences among other strains. The bound water content of Birch Russia was the lowest. In the aspect of mineral element, the calcium content of NBRC9788 was the high- est (3.49 mg · g(-1)), significantly better than other strains. The second was Finnish birch. The lowest was CX02. The phosphorus content of NBRC9788 was the highest (210.12 µg · g(-1)), significantly superior to other strains. The lowest was JL04. In the aspect of active ingredient concentration, the triterpenoids content of HLJ01 was highest (23.7 mg · g(-1)), significantly better than other strains. It was good strains for biological products research and development and then was Finnish birch. The betulin content of MAFF420165 and MAFF420308 was low, they were not suitable for production. The polysaccharide content of Finnish birch was the highest (9.7%), significantly better than the other strains, it is one of the most ideal and good strains to develop polysaccharide. The polysaccharide content from MAFF420308 and MAFF420256 was 1.2%, lower than other strains. We suggest that avoid using these strains in the study of polysaccharide product development.

Association between obesity and ECG variables in children and adolescents: A cross-sectional study.

Obesity exhibits a wide variety of electrocardiogram (ECG) abnormalities in adults, which often lead to cardiovascular events. However, there is currently no evidence of an association between obesity and ECG variables in children and adolescents. The present study aimed to explore the associations between obesity and ECG intervals and axes in children and adolescents. A cross-sectional observational study of 5,556 students aged 5-18 years was performed. Anthropometric data, blood pressure and standard 12-lead ECGs were collected for each participant. ECG variables were measured manually based on the temporal alignment of simultaneous 12 leads using a CV200 ECG Work Station. Overweight and obese groups demonstrated significantly longer PR intervals, wider QRS durations and leftward shifts of frontal P-wave, QRS and T-wave axes, while the obese group also demonstrated significantly higher heart rates, compared with normal weight groups within normotensive or hypertensive subjects (P<0.05). Abdominal obesity was also associated with longer PR intervals, wider QRS duration and a leftward shift of frontal ECG axes compared with normal waist circumference (WC) within normotensive or hypertensive subjects (P<0.05). Gender was a possible factor affecting the ECG variables. Furthermore, the ECG variables, including PR interval, QRS duration and frontal P-wave, QRS and T-wave axes, were significantly linearly correlated with body mass index, WC and waist-to-height ratio adjusted for age, gender, ethnicity and blood pressure. However, there was no significant association between obesity and the corrected QT interval (P>0.05). The results of the current study indicate that in children and adolescents, general and abdominal obesity is associated with longer PR intervals, wider QRS duration and a leftward shift of frontal P-wave, QRS and T-wave axes, independent of age, gender, ethnicity and blood pressure.

[Association of two SNPs in 3'UTR of ETS1 gene with systemic lupus erythematosus in a northern Chinese Han population].

OBJECTIVE: To assess the association between 2 single nucleotide polymorphisms (SNPs) of ETS1 gene and susceptibility to systemic lupus erythematosus (SLE) in a northern Chinese Han population. METHODS: Two SNPs within the ETS1 gene mapped to 11q23 were selected based on HapMap data. Genotyping was conducted with Taqman method in 231 patients with SLE and 474 healthy controls from Qilu Hospital, Shandong and analyzed with PLINK1.07 software. Haplotypes were analyzed with SHEsis software. RESULTS: A statistically significant difference was detected in the distribution of rs1128334 and rs4937333 genotypes between the two groups (all P< 0.01). For rs1128334, the frequency of the minor allele was 0.291 and 0.428 in controls and cases, respectively. For rs4937333, the minor allele frequency was 0.381 and 0.476 in controls and cases respectively. An A-C haplotype was found to be strongly associated with increased risk for SLE, while another haplotype G-C may reduce this risk. CONCLUSION: Our study has suggested that rs1128334 and rs4937333 are strongly associated with the risk for SLE in northern Chinese Han population.

Association between child and adolescent obesity and parental weight status: a cross-sectional study from rural North China.

OBJECTIVE: To investigate the relationship between child and adolescent obesity, and parental weight status. METHODS: Height and weight were measured in Chinese children and adolescents aged 6-17 years old. Information was collected concerning parental weight and height, and possible covariates, using a questionnaire. The body mass index (BMI) of each study participant and their parents was calculated. On the basis of the BMI, parents were categorized as normal, overweight or obese, and children and adolescents were categorized as normal or obese. RESULTS: Of the 5,041 participants included in the study, 6.82% were obese. Child or adolescent obesity was significantly associated with parental obesity. When both parents were obese, there was a 3.62-fold increased risk of obesity compared with those whose parents were of normal weight. Obesity in fathers was associated with a heightened risk of obesity in female children, whereas obesity in mothers was associated with a heightened risk of obesity in male children. CONCLUSIONS: Parental obesity was a predictor of obesity in children and adolescents. It is therefore of key importance to prevent obesity in children who have one or more obese parents.

Effects of television viewing on body fatness among Chinese children and adolescents.

BACKGROUND: Numerous studies have shown that time spent on television (TV) viewing is positively associated with obesity. The aim of this study was to examine the potential association between excessive TV viewing and obesity, especially abdominal obesity, among children and adolescents in mainland of China. METHODS: A total of 4708 children and adolescents aged 6 to 16 years were recruited for the study. Anthropometric measures were conducted by trained personnels. A self-report questionnaire was designed to gather information on TV time, physical activity, diet habits, maternal body mass index (BMI), birth weight, and on general demographics, including age and gender, and socio-economic status. RESULTS: The prevalence of obesity in this group was 6.5%. Linear regression analysis indicated that high TV viewing time (≥ 1.5 h/d) was significantly associated with higher BMI, waist circumference (WC), and waist-to-height ratio (WHtR). In addition, the high TV time group had 1.3 times the odds of obesity as compared to the low TV time group. Likewise, high TV viewing time increased the OR value 1.32 and 1.21 times higher in WC- and WHtR-defined obesity. Within the non-obesity group, high TV viewing time was also positively associated with higher WC and WHtR. All these correlations remained significant after adjustment for the confounding variables. CONCLUSIONS: Excessive TV viewing might increase the risk of obesity among Chinese youth. Reducing TV viewing time may be beneficial to improve health outcomes, both in the short- and long term. This finding should be taken into account in future designs of intervention policies to prevent childhood and adolescent obesity in China.