Chikungunya emergency in China: microevolution and genetic analysis for a local outbreak

A small-scale local chikungunya outbreak occurred in a Guangdong village of southern China in October 2010. The five chikungunya viruses (CHIKV) isolated from the epidemic and three other imported cases obtained from the same period were sequenced and analyzed for phylogenesis. The results demonstrated that all of the eight sequences were clustered in the Eastern, Central, Southern, and African group. However, the local strains and imported isolates showed different sequence variations. A226V in E1 gene and V264A in E2 gene were detected in all three imported isolates, the unique substitutions S250P in E1 gene and H313Y in E2 genes could be observed in four of the five local strains. These significant variations might be some of the causes for the outbreak. It would be an important event for CHIKV to have mutated adaption to the local mosquitoes in China, Aedes albopictus and Aedes aegypti.     

Protective effect of blueberry anthocyanins in a CCl4-induced injury model in human embryonic liver cells

This study investigates the possible mechanism of the protective effects of blueberry anthocyanins on human embryonic liver L-02 cells. Results of the WST-8 method showed that different concentrations of blueberry anthocyanins protected the human embryonic liver L-02 cells against CCl₄-induced injury in a dose-dependent manner with IC₅₀ at 6.2×g/L. Cell clone formation inhibition assay demonstrated that cell clones increased with increased concentration of anthocyanins. Propidium iodide (PI) staining analysis showed that anthocyanins can decrease cell cycle in the G1 phase. DNA ploidy analysis showed a weakened percentage of hypodiploid cells in a dose-dependent manner. Moreover, Annexin V-FITC/PI staining analysis showed a dose-dependent effect of anthocyanins on late apoptotic and necrotic cells. Western blot assay showed gradually decreased caspase-3 protein expression levels with increased anthocyanin concentration. In summary, these findings provided pharmacological evidence supporting the clinical application and protective effect of blueberry anthocyanins against acute liver injury.     

Protein kinase C-δ mediates sepsis-induced activation of complement 5a and urokinase-type plasminogen activator signaling in macrophages

Objective and design

Activations of the complement C5a (C5a) and the urokinase-type plasminogen activator (uPA) are commonly seen together during sepsis. However, the mechanism linking these two important pathways remains elusive.

Material, methods and treatment

We used the C57BL/6 J mice model of sepsis induced by cecal ligation puncture (CLP) procedure, injected anti-C5aR or rottlerin through the tail vein to neutralize C5aR or PKC-δ, and then isolated peritoneal macrophages. Total RNA was isolated from the cells and analyzed by quantitative PCR.

Results

Our study revealed that neutralizing C5aR markedly inhibited sepsis-induced uPA receptor (uPAR) expression and its downstream signaling in macrophage. Similarly, neutralizing uPAR suppressed sepsis activation of C5a signaling. Importantly, inhibition of PKC-δ largely blocked sepsis-induced expression of C5aR and uPAR.

Conclusions

Our study demonstrates a crosstalk between the complement C5a signaling and the fibrinolytic uPA pathways, which may depend on each other to maintain their expression and signaling, and reveals a central role of PKC-δ in mediating sepsis-induced activation of these pathways.     

Label‐free molecular probe based on G‐quadruplex and strand displacement for sensitive and selective detection and naked eye discrimination of exon 2 deletion of AIMP2

Exon 2 deletion of aminoacyl tRNA synthetase complex‐interacting multifunctional protein 2 (AIMP2) is a genetic deletion related to various cancers, for instance ovarian and lung cancers. It can be worked as an indicator of cancer for diagnosis of diseases. Here, we developed a label‐free method based on the formation of split G‐quadruplex in the presence of target DNA combined with strand displacement to detect exon 2 deletion of AIMP2 (DE2) sensitively and selectively. This method is easy‐operating and cost‐saving. Moreover, it has observed discrimination of gene deletion from wild‐types by naked eyes. The results demonstrate that this strategy can be further used for the detection of different gene deletions to achieve early diagnosis of diseases and allow better prognosis.     

Liver fat accumulation measured by high-speed T2-corrected multi-echo magnetic resonance spectroscopy can predict risk of cholelithiasis

BACKGROUND Liver fat accumulation is associated with increased cholesterol synthesis and hypersecretion of biliary cholesterol, which may be related to the development of cholelithiasis.AIM To investigate whether liver fat accumulation measured by high-speed T2-corrected multi-echo magnetic resonance spectroscopy(MRS) is a risk factor for cholelithiasis.METHODS Forty patients with cholelithiasis and thirty-one healthy controls were retrospectively enrolled. The participants underwent high-speed T2-corrected multi-echo single-voxel MRS of the liver at a 3 T MR scanner. The proton density fat fraction(PDFF) and R~2 value were calculated. Serum parameters and waist circumference(WC) were recorded. Spearman's correlation analysis was used to analyze the relationship between PDFF, R~2, and WC values. Multivariate logistic regression analysis was carried out to determine the significant predictors of the risk of cholelithiasis. Receiver operating characteristic curve(ROC) analysis was used to evaluate the discriminative performance of significant predictors.RESULTS Patients with cholelithiasis had higher PDFF, R~2, and WC values compared with healthy controls(5.8% ± 4.2% vs 3.3% ± 2.4%, P = 0.001; 50.4 ± 24.8/s vs 38.3 ±8.8/s, P = 0.034; 85.3 ± 9.0 cm vs 81.0 ± 6.9 cm, P = 0.030; respectively). Liver iron concentration extrapolated from R~2 values was significantly higher in the cholelithiasis group(2.21 ± 2.17 mg/g dry tissue vs 1.22 ± 0.49 mg/g dry tissue, P = 0.034) than in the healthy group. PDFF was positively correlated with WC(r = 0.502, P 0.001) and R~2(r = 0.425, P 0.001). Multivariate logistic regression analysis showed that only PDFF was an independent risk factor for cholelithiasis(odds ratio = 1.79, 95%CI: 1.22-2.62, P = 0.003). ROC analysis showed that the area under the curve of PDFF was 0.723 for discriminating cholelithiasis from healthy controls, with a sensitivity of 55.0% and specificity of 83.9% when the cut-off value of PDFF was 4.4%.CONCLUSION PDFF derived from high speed T2-corrected multi-echo MRS can predict the risk of cholelithiasis.     

Early Warning of Acute Altitude Sickness by Physiological Variables and Noninvasive Cardiovascular Indicators

Objective To examine if the variations at sea level would be able to predict subsequent susceptibility to acute altitude sickness in subjects upon a rapid ascent to high altitude.Methods One hundred and six Han nationality male individuals were recruited to this research. Dynamic electrocardiogram, treadmill exercise test, echocardiography, routine blood examination and biochemical analysis were performed when subjects at sea level and entering the plateau respectively. Then multiple regression analysis was performed to construct a multiple linear regression equation using the Lake Louise Score as dependent variable to predict the risk factors at sea level related to acute mountain sickness (AMS).Results Approximately 49.05% of the individuals developed AMS. The tricuspid annular plane systolic excursion (22.0±2.66 vs. 23.2±3.19 mm, t=1.998, P=0.048) was significantly lower in the AMS group at sea level, while count of eosinophil [(0.264±0.393)×10⁹/L vs. (0.126±0.084)×10⁹/L, t=-2.040, P=0.045], percentage of differences exceeding 50 ms between adjacent normal number of intervals (PNN50, 9.66%±5.40% vs. 6.98%±5.66%, t=-2.229, P=0.028) and heart rate variability triangle index (57.1±16.1 vs. 50.6±12.7, t=-2.271, P=0.025) were significantly higher. After acute exposure to high altitude, C-reactive protein (0.098±0.103 vs. 0.062±0.045 g/L, t=-2.132, P=0.037), aspartate aminotransferase (19.7±6.72 vs. 17.3±3.95 U/L, t=-2.231, P=0.028) and creatinine (85.1±12.9 vs. 77.7±11.2 mmol/L, t=-3.162, P=0.002) were significantly higher in the AMS group, while alkaline phosphatase (71.7±18.2 vs. 80.6±20.2 U/L, t=2.389, P=0.019), standard deviation of normal-to-normal RR intervals (126.5±35.9 vs. 143.3±36.4 ms, t=2.320, P=0.022), ejection time (276.9±50.8 vs. 313.8±48.9 ms, t=3.641, P=0.001) and heart rate variability triangle index (37.1±12.9 vs. 41.9±11.1, t=2.020, P=0.047) were significantly lower. Using the Lake Louise Score as the dependent variable, prediction equation were established to estimate AMS: Lake Louise Score=3.783+0.281×eosinophil-0.219×alkaline phosphatase+0.032×PNN50.Conclusions We elucidated the differences of physiological variables as well as noninvasive cardiovascular indicators for subjects after high altitude exposure compared with those at sea level. We also created an acute high altitude reaction early warning equation based on the physiological variables and noninvasive cardiovascular indicators at sea level.