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Objective: To study the characteristics and risk factors of carotid atherosclerosis in populations at high risk of stroke in urban and rural areas of North China. Methods: A cross-sectional study was conducted to investigate high stroke risk populations in representative urban and rural areas sampled from 12 regions of China. A pre-designed questionnaire, ultrasound, and laboratory examinations were performed to evaluate risk factors. Results: A total of 30,175 patients were included in the study. The overall prevalence of carotid atherosclerosis was 54.53%, among which intimal thickening and plaque were 39.22 and 41.25%, respectively. The prevalence of carotid atherosclerosis in the urban group was higher than in the rural group. Multivariate logistic regression analysis revealed that male gender, age, smoking, hypertension, dyslipidemia, stroke, atrial fibrillation, systolic blood pressure, and levels of fasting blood glucose, total cholesterol, and low-density lipoprotein cholesterol were the common independent risk factors for carotid atherosclerosis in both groups. Higher education, high salt consumption, passive smoking, family history of stroke, and transient ischemic attack were unique independent risk factors, and high-density lipoprotein cholesterol was a protective factor for carotid atherosclerosis in the urban population. Conclusion: This study suggests that risk factors for carotid atherosclerosis differ between urban and rural populations in North China.

Objective The Chinese stroke emergency map (SEM) was implemented in 2017 to reduce prehospital and hospital delays for acute ischemic stroke (AIS) patients suitable for intravenous recombinant tissue plasminogen activator (rt‐PA) thrombolysis. However, data on the time delay following the implementation of an SEM in China are limited. Methods Data for suspected stroke patients from the SEM registry center of Taiyuan, Shanxi Province, from August 2017 to July 2019, patients’ characteristics, thrombolysis rate, and functional outcome at 90 days were analyzed. Results One thousand seven hundred and eighty six patients who arrived at hospitals within 4.5 hr of onset were included; 35.9% arrived by emergency medical services (EMSs), and 1,207 (67.6%) of the population received intravenous rt‐PA. As a result of the SEM, the number of patients treated with rt‐PA increased from 63.9% in phase 1 (August 2017 to July 2018) to 70.5% in phase 2 (August 2018 to July 2019). The median onset‐to‐door and onset‐to‐needle times decreased by five minutes (100 [IQR: 62–135] vs. 105 [IQR: 70–145], p = .005) and nine minutes (158 [IQR: 124–197] vs. 167 [IQR: 132–214], p = .001), respectively. Patients in phase 2 achieved greater independent function outcome at 90 days (79.9% vs. 72.1%; adjusted odds ratio, 2.010; 95% confidence interval, 1.444–2.798). The binary logistic regression models revealed that shorter onset‐to‐needle time (OR: 0.994; 95% CI: 0.992–0.997; p, The implementation of a stroke emergency map effectively reduced prehospital delays and improved function outcomes. Future efforts should attempt to increase EMS usage.

Lin28a is a pluripotent factor that promotes somatic cell reprogramming. Unlike other pluripotent factors, Lin28a expression is transient and accumulated in primed embryonic stem (ES) cells, but its exact function and mechanism in the conversion of ES cells from naïve to primed state remain unclear. Here, we present evidence for Dppa3, a protein originally known for its role in germ cell development, as a downstream target of Lin28a in naïve–primed conversion. Using rescue experiment, we demonstrate that Dppa3 functions predominantly downstream of Lin28a during naïve–primed state conversion. Higher level of Lin28a prevents let-7 maturation and results in Dnmt3a/b (target of let-7) upregulation, which in turn induces hypermethylation of the Dppa3 promoter. Dppa3 demarcates naïve versus primed pluripotency states. These results emphasize that Lin28a plays an important role during the naïve–primed state conversion of ES cells, which is partially mediated by a Lin28a–let-7–Dnmt3a/b–Dppa3 axis.

Background.Proton pump inhibitor (PPI) and other acid-suppressing drugs are widely used in the treatment of gastrointestinal ulcer, upper gastrointestinal bleeding, gastritis, and gastric cancer (GC). About 80% of GC patients receive acid suppression treatment. PPI suppresses the production of gastric acid by inhibiting the function of H+/K+-ATPase in gastric parietal cells and raises the pH value to achieve therapeutic purposes. Some studies have found that PPI had a certain antitumor effect in the proliferation and apoptosis of tumor cells. But the effects of environmental pH on the growth of GC cells and its mechanism are unknown. Therefore, we hoped to find the effects of culture medium pH on the biological behavior of GC cells by in vitro experiments and provide guidance for the use of acid-suppressing drugs in GC patients.Aims.We aimed to observe the effects of pH changes in GC cell culture medium on the cell biological behavior of cancer cells and to analyze the potential mechanisms. We hoped to find out the effect of acid suppression on the growth of GC cells.Methods. The GC cell lines (SGC-7901 and MKN45) were used as the research object. We adjusted the pH value in the cell culture medium to observe the changes in cell viability (MTT), apoptosis (flow cytometry), and invasion (Transwell) at pH 6, pH 7, and pH 8. qRT-PCR and western blot (WB) assays were used to determine the expression changes of genes and proteins (mTOR, AKT, Wnt, Glut, and HIF-1α) at pH 6, pH 7, and pH 8.Results.The results of MTT showed that the viability of SGC-7901 and MKN45 in the pH 8.0 group was significantly weaker than that in the pH 6.0 or pH 7.0 group (P<0.001). Flow cytometry results showed that the apoptosis of SGC-7901 and MKN45 in the pH 8.0 group was more obvious than that in the pH 6.0 or pH 7.0 group (P<0.001). The results of Transwell showed that the invasion ability of SGC-7901 and MKN45 in the pH 8.0 group was significantly weaker than that in the pH 6.0 or pH 7.0 group (P<0.001). As shown by PCR and WB results, with the increase of pH, the expression of mTOR, AKT, Wnt, Glut, and HIF-1αin SGC-7901 and MKN45 was downregulated (P<0.05).Conclusions. Compared with the microacid environment, the microalkaline environment inhibited the viability, invasion, and expression of genes and proteins (mTOR, AKT, Wnt, Glut, and HIF-1α) but promoted the apoptosis of GC cells and thus inhibited the growth of GC.

Three Cu(II) complexes of [Cu(L1)(Br)2]·CH3CN (1), [Cu(L2)2(OAc)](PF6)·2C2H5OH (2), and [Cu(L1)(L2)](PF6)2 (3) (L1 = 2-(6-(pyridine-2-yl)-4-p-tolylpyridin-2-yl)pyridine, L2 = 2-(4-(pyridine-2-yl)-6-p-tolylpyridin-2-yl)pyridine) were designed and synthesized as anti-cancer drugs. All complexes were structurally characterized by X-ray crystallography showing that three complexes were the mononuclear compounds with the triclinic crystal system p 1 ¯ space group. The interaction between each of these three complexes and calf thymus DNA (CT-DNA) was investigated via spectroscopic techniques and viscosity measurement, which indicated that these complexes could bind to CT-DNA by intercalation. Moreover, DNA cleavage experiment showed that, in the natural light under an aerobic environment, all complexes could cleave DNA in the absence of exogenous oxidant agent, and that singlet oxygen (1O2) might serve as the major cleavage active species. Protein binding experiment indicated that 1–3 could bind to bovine serum albumin (BSA) with moderate bonding via the static quenching mechanism. In addition, the IC50 values of these three complexes were significantly lower which denoted highly anti-cancer activities in comparison to cisplatin. And each of these complexes could individually inhibit proliferation potential of cancer cells by promoting G1-phase cell cycle arrest (G1 arrest) and inducing apoptosis through the production of reactive oxygen species (ROS) and the activation of caspase-3

// Dan Wang 1, 3, * , Hui Sang 1, 3, * , Kaiyue Zhang 2 , Yan Nie 2 , Shuang Zhao 1, 3 , Yan Zhang 2, 3 , Ningning He 2 , Yuebing Wang 2 , Yang Xu 2 , Xiaoyan Xie 4 , Zongjin Li 1, 2 , Na Liu 1, 2 1 Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Sciences, Nankai University, Tianjin, China 2 School of Medicine, Nankai University, Tianjin, China 3 College of Life Sciences, Nankai University, Tianjin, China 4 Stem Cells and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, Beijing, China * These authors contributed equally to this work Correspondence to: Na Liu, email: liuna@nankai.edu.cn Zongjin Li, email: zongjinli@nankai.edu.cn Keywords: embryonic stem cell, ground state, Stat3 signal pathway, imaging Received: November 24, 2016 Accepted: March 01, 2017 Published: March 10, 2017 ABSTRACT Embryonic stem cells (ES cells) can be maintained its undifferentiated state with feeder cells or LIF, which can activate Jak/Stat3 pathway. Recently, it has been reported a new culture condition comprising serum-free medium with ERK and GSK3β inhibitors (2i) could drive ES cells into a state of pluripotency more like inner cell mass (ICM) in mouse blastocysts called ground state. However, although 2i could sustain ES cells self-renewal, LIF is routinely added. The roles of Stat3 activation are still unclear now. Here we investigated whether Jak/Stat3 might also contribute to the induction of ground state pluripotency. We introduced a lentiviral construct with 7-repeat Stat3-binding sequence to drive Renilla luciferase into ES cells, which can be used as a reporter to detect Stat3 activation by noninvasive bioluminescence imaging. Using this ES cells, we investigated the role of Stat3 activation in ground state maintenance. The results showed that Stat3 could be activated by 2i. Stattic, a chemical inhibitor of Stat3 phosphorylation, could effectively inhibit Stat3 activation in ES cells. When Stat3 activation was suppressed, ground state related genes were down regulated, and ES cells could not be maintained the ground state pluripotency even in 2i medium. All of these results indicate Stat3 activation is required in ground state maintenance.

Background: The accuracy of three-dimensional (3D) reconstructions from cone-beam computed tomography (CBCT) has been particularly important in dentistry, which will affect the effectiveness of diagnosis, treatment plan, and outcome in clinical practice. The aims of this study were to assess the linear, volumetric, and geometric accuracy of 3D reconstructions from CBCT and to investigate the influence of voxel size and CBCT system on the reconstructions results. Methods: Fifty teeth from 18 orthodontic patients were assigned to three groups as NewTom VG 0.15 mm group (NewTom VG; voxel size: 0.15 mm; n = 17), NewTom VG 0.30 mm group (NewTom VG; voxel size: 0.30 mm; n = 16), and VATECH DCTPRO 0.30 mm group (VATECH DCTPRO; voxel size: 0.30 mm; n = 17). The 3D reconstruction models of the teeth were segmented from CBCT data manually using Mimics 18.0 (Materialise Dental, Leuven, Belgium), and the extracted teeth were scanned by 3Shape optical scanner (3Shape A/S, Denmark). Linear and volumetric deviations were separately assessed by comparing the length and volume of the 3D reconstruction model with physical measurement by paired t- test. Geometric deviations were assessed by the root mean square value of the imposed 3D reconstruction and optical models by one-sample t-test. To assess the influence of voxel size and CBCT system on 3D reconstruction, analysis of variance (ANOVA) was used (μ = 0.05). Results: The linear, volumetric, and geometric deviations were −0.03 ± 0.48 mm, −5.4 ± 2.8%, and 0.117 ± 0.018 mm for NewTom VG 0.15 mm group; −0.45 ± 0.42 mm, −4.5 ± 3.4%, and 0.116 ± 0.014 mm for NewTom VG 0.30 mm group; and −0.93 ± 0.40 mm, −4.8 ± 5.1%, and 0.194 ± 0.117 mm for VATECH DCTPRO 0.30 mm group, respectively. There were statistically significant differences between groups in terms of linear measurement (P < 0.001), but no significant difference in terms of volumetric measurement (P = 0.774). No statistically significant difference were found on geometric measurement between NewTom VG 0.15 mm and NewTom VG 0.30 mm groups (P = 0.999) while a significant difference was found between VATECH DCTPRO 0.30 mm and NewTom VG 0.30 mm groups (P = 0.006). Conclusions: The 3D reconstruction from CBCT data can achieve a high linear, volumetric, and geometric accuracy. Increasing voxel resolution from 0.30 to 0.15 mm does not result in increased accuracy of 3D tooth reconstruction while different systems can affect the accuracy.

Malignant tumors are often multifactorial. Epidemiological studies have shown that hyperglycemia raises the prevalence and mortality of certain malignancies, like breast, liver, bladder, pancreatic, colorectal, endometrial cancers. Hyperglycemia can promote the proliferation, invasion and migration, induce the apoptotic resistance and enhance the chemoresistance of tumor cells. This review focuses on the new findings in the relationship between hyperglycemia and tumor development.

In Shanghai, one of the biggest modern cities in the world, community-based health care providers are largely underutilized. As a result, valuable medical resources are wasted. The present study examined the relationship between the variables of perceived risk and patient anxiety on intentions to use community health clinics, because these two variables are closely related to decision making. A survey measuring these variables was distributed near community health clinics in Shanghai ( n = 869), and structural equation models were constructed to analyze the data. Results show that patient anxiety was associated with contracting diseases and positively related to the intention to seek services from community-based providers, whereas their perceived risk of these providers had a negative relationship with such an intention. Moreover, the knowledge that some community clinics were not as good as large hospitals was positively related to perceived risk. Policy implications are discussed based on the findings.

Background Auditory function and cochlear morphology have previously been described in a porcine model with spontaneous WS2-like phenotype. In the present study, cochlear histopathology was further investigated in the inner ear of the developing spontaneous deafness pig. Results We found that the stria vascularis transformed into a complex tri-laminar tissue at embryonic 85 days (E85) in normal pigs, but not in the MITF−/− pigs. As the neural crest (NC) of cochlea was derived by melanocytes. MITF mutation caused failure of development of melanocytes which caused a subsequent collapse of cochlear duct and deficits of the epithelium after E100. Furthermore, the spiral ganglion neurons of cochlea in the MITF−/− pigs began to degenerate at postnatal 30 days (P30). Thus, our histopathological results indicated that the malformation of the stria vascularis was a primary defect in MITF−/− induced WT pigs which was resulted from the loss of NC-derived melanocytes. Subsequently, the cochleae underwent secondary degeneration of the vestibular organs. As the degeneration of spiral ganglion neurons happened after P30, it suggests that WS patients should be considered as candidates for cochlear implant. Conclusions Our porcine model of MITF-M mutation may provide a crucial animal model for cochlear implant, cell therapy in patients with congenital hereditary hearing loss.

Previously, we found that Celastrus orbiculatus Thunb. (COT) decreases athero-susceptibility in lipoproteins and the aorta of guinea pigs fed a high-fat diet, and increases high-density lipoprotein (HDL). In the present study, we investigated the effect of COT in reducing lipid accumulation and promoting reverse cholesterol transport (RCT) in vivo and vitro. Healthy male mice were treated with high-fat diet alone, high-fat diet with COT (10.0 g/kg/d), or general fodder for 6 weeks. Serum levels of total cholesterol (TC), triglyceride (TG), HDL-C, non-HDL-C, and (3)H-cholesterol in plasma, liver, bile, and feces were determined. Pathological changes and the levels of TC and TG in liver were examined. The expression of hepatic genes and protein associated with RCT were analyzed. COT administration reduced lipid accumulation in the liver, ameliorated the pathological changes, and lessened liver injury, the levels of TG, TC, and non-HDL-C in plasma were decreased significantly, and COT led to a significant increase in plasma HDL-C and apolipoprotein A (apoA1). (3)H-cholesterol in plasma, liver, bile, and feces was also significantly increased in COT-treated mice compared to controls. Both mRNA and protein expression of SRB1, CYP7A1, LDLR, ATP-binding cassette transporters ABCA1, ABCG5, and LXRα were improved in COT-treated mice. An in vitro isotope tracing experiment showed that COT and its bioactive ingredients, such as celastrol, ursolic acid, oleanolic acid, and quercetin, significantly increased the efflux of (3)H-cholesterol. They also increased the expression of SRB1, ABCA1, and ABCG1 significantly in macrophages. Our findings provided a positive role of COT in reducing lipid accumulation by promoting RCT. These effects may be achieved by activating the SRB1 and ABC transporter pathway and promoting cholesterol metabolism via the CYP7A1 pathway in vivo. The effective ingredients in vitro are celastrol, ursolic acid, oleanolic acid, and quercetin.

This study aims to investigate urban-rural differences in characteristics and risk factors of ischemic stroke in northern China. The present cross-sectional study was based on the High-risk Population Screening and Intervention Project for Stroke. The cluster sampling method was used to select urban and rural screening sites in northern China. By collecting information and screening the data, patients with ischemic stroke were obtained and a control group with similar gender, age, and regional distribution was selected among the nonischemic stroke patients. Then, the demographic and risk factors of patients with ischemic stroke were described and analyzed. The prevalence of ischemic stroke in northern China was 2.88%, with a greater prevalence in rural areas than in urban areas (3.32% vs 2.43%), and a greater prevalence in males than in females (3.06% vs 2.73%). Furthermore, rural stroke patients were younger than urban stroke patients. Hypertension, family history of stroke, and smoking were the top 3 independent risk factors for ischemic stroke. Overweight/obesity and low education were associated with increased ischemic stroke in urban areas, while low education was associated with less ischemic stroke in rural areas. In addition, the prevalence of alcoholism, dyslipidemia, diabetes, and obvious overweight/obesity was greater in urban areas, while high-salt diet and low education and income were more prevalent in rural regions. Moreover, the smoking index was higher in rural areas than in urban areas. The characteristics and risk factors of ischemic stroke differ between rural and urban areas, which could be used to design specific preventative measures.

Celastrus orbiculatus Thunb. (COT), a traditional Chinese herb, has anti-inflammatory and anti-oxidative properties. In this study, we examined the protective effect of COT on the initiation of atherosclerosis induced by high fat diet and explored the underlying mechanisms. We established guinea pig models of hyperlipidemia and treated them with three dosages of COT or 20 mg/kg/d simvastatin (a positive control drug) for 8 weeks. Plasma lipid analysis indicated that COT decreased total cholesterol (TC), non-high-density lipoprotein cholesterol (non-HDL-C), triglyceride (TG), apolipoprotein B100 (apoB100) and apolipoprotein E (apoE) levels and increased high density lipoprotein cholesterol (HDL-C) level. The analysis of the hepatic gene involving cholesterol metabolism by quantitative real-time PCR revealed that COT upregulated the mRNA abundance of LDL receptor (LDL-R), scavenger receptor class B type 1 (SR-B1), cholesterol 7α-hydroxylase A1 (CYP7A1) and the 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR). Oil red O staining showed COT significantly reduced lipid deposition in the arterial wall. Moreover, ELISA assay revealed COT lowered the levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in plasma. Meanwhile, the level of Nitric oxide (NO) in plasma was increased by COT. Immunohistochemistry and Western blot analysis showed the expression of CD68 and active NF-kB p65 proteins in the arterial wall was decreased by COT. The content of Malondialdehyde (MDA) and activity of Superoxide dismutase (SOD) in plasma were determined and the data indicated COT suppressed oxidative stress reaction. These results reveal that administration of COT decreases athero-susceptibility through lowering plasma lipid, attenuating inflammation, and suppressing oxidative stress in guinea pig fed high fat diet.

Objective It is to characterize the underlying molecular mechanisms of the anti-atherosclerotic effects of hydrogen (dihydrogen; H 2 ), a novel antioxidant. In particular, to examine the effects of hydrogen on athero-susceptibility in lipoproteins and aorta of apolipoprotein E knockout (apoE−/−) mice. Methods and results Plasma analysis by enzymatic method and spectrophotometric measurement showed that eight weeks intraperitoneally injection of hydrogen-saturated saline remarkably decreased plasma total and non-high-density lipoprotein (non-HDL) cholesterol, and malondialdehyde in apoE−/− mice fed either chow or high fat diet. Western blot analysis showed hydrogen treatment reduced the contents of apolipoprotein B (apoB), a major protein constituent of non-HDL in either plasma or hepatic tissues. Moreover, ELISA assay revealed that the production of tumor necrosis factor-α and interleukin-6 were significantly suppressed by hydrogen in RAW264.7 macrophages, after stimulation with the isolated non-HDL from treated or untreated mice. Immunohistochemistry of aortic valve sections revealed that hydrogen suppressed the expression of several proinflammatory factors and decreased vessel wall infiltration of macrophages. Besides, real-time PCR and Western blot analysis disclosed that hepatic scavenger receptor class B type I (SR-BI), ATP-binding cassette (ABC) transporters ABCG8, ABCB4, ABCB11, and macrophage SR-BI, were all induced by hydrogen treatment. Finally arterial wall lipid disposition displayed by oil red O staining was reduced significantly in aortic root and whole aorta en face in hydrogen administrated mice. In addition, hydrogen significantly improved HDL functionality in C57BL/6J mice assessed in two independent ways, namely (i) stimulation of cholesterol efflux from macrophage foam cells by measuring HDL-induced [ 3 H]cholesterol efflux, and (ii) protection against LDL oxidation as a measure of Cu 2+ -induced TBARS formation. Conclusion These results reveal that administration of hydrogen-saturated saline decreases athero-susceptibility in apoB-containing lipoprotein and aortic atherosclerosis in apoE−/− mice and improves HDL functionality in C57BL/6J mice.

Endothelial progenitor cells (EPCs) derived from bone marrow are known to be heterogeneous. In this study, we tried to find favorable conditions that induce the differentiation of mononuclear cells (MNCs) from bone marrow into EPCs. The differentiation capacity of MNCs from rat bone marrow was investigated in different conditions, such as different media, different induction times and different culture surfaces. The cell morphology and endothelial biomarkers associated with differentiated MNCs were studied. Our results indicated that MNCs cultured in EGM-2MV (Endothelial cell basal medium-2, plus SingleQuots of growth supplements) developed a bursiform shape, a late EPC-like morphology, while MNCs cultured in complete medium (CM, M199 with 10% FBS, 20 ng/mL VEGF and 10 ng/mL bFGF) showed a spindle shape, an early EPC-like morphology. Cells of both morphologies were able to incorporate DiI-ac-LDL and bind lectin in vitro. MNCs cultured in EGM-2MV exhibited a higher proliferation rate and higher eNOS expression than MNCs cultured in CM. MNCs cultured in EGM-2MV had the ability to form tubes on Matrigel. Flow cytometry results indicated that CD133 expression was highest at day 12 and that the greatest number of cells positive for both FLK-1 and CD133 appeared at day 20 from cells cultured in dishes without fibronectin coating. In addition, the expression levels of CD133, CD31 and FLK-1/CD133 were not significantly different between cells of different shapes. Our experiments suggest that MNCs from bone marrow can be differentiated into late EP-like cells in EGM-2MV, which have the ability to rapidly proliferate. These MNCs can also be differentiated into early EP-like cells in CM. Additionally, fibronectin may not be necessary for the differentiation of EPCs to mature ECs after three generations. Differentiated MNCs from bone marrow in EGM-2MV have the characteristics of EPCs, although the expression levels of EPC markers were lower than previously reported.

Metabolic syndrome (MetS) is a constellation of cardiovascular risk factors, including central obesity, dysglycemia, hypertension, and dyslipidemia. The anti-inflammatory properties of high density lipoprotein (HDL) can be compromised in MetS. Exercise is recognized as an important factor in the prevention and treatment of MetS.This study was designed to investigate whether walk/run training without any specific diet could enhance anti-inflammation capacity of HDL from MetS patients.This was a case control study.The study was conducted in a Zhoudian community, Taian.Thirty nine patients with MetS were recruited and divided into a control group (n = 12) remaining in an untrained state and exercise group (n = 27) performing a 10-week walk/run training program.The anti-inflammation capacities of HDL3 (HDL subfractions) from MetS patients with or without exercise were investigated by co-incubating with TNF- α-injured endothelial cells in vitro.The training did not influence serum lipoprotein level in MetS patients and cholesterol efflux capacity of circulating HDL. However, walk/run training increased paraoxonase-1 (PON1) activity and decreased the levels of malondialdehyde in either serum or isolated HDL from MetS patients prominently. More importantly, HDL3 isolated from MetS patients with 10 weeks training protected endothelial cells against tumor necrosis factor-a (TNF-a) -induced injury, decreased monocyte chemotactic protein-1 levels in media and vascular cell adhesion molecule-1 expression markedly. Furthermore, HDL3 isolated from MetS patients with walk/run training inhibited the TNF-á-induced monocyte adhesion to endothelial cells and obviously increased nitric oxide production by activating endothelial nitric oxide synthase.Walk/run training leads to a significant improvement in HDL anti-inflammation capacity in subjects with MetS without restricted diet, the mechanism underlying which at least partially is due to increased PON1 activity in HDL, NO production, and eNOS expression in endothelial cells.

The study aimed to investigate the effect of niacin on vascular inflammatory lesionsin vivoandin vitroas well as its lipid-regulating mechanism.In vivostudy revealed that niacin downregulated the levels of inflammatory factors (IL-6 and TNF-α) in plasma, suppressed protein expression of CD68 and NF-κB p65 in arterial wall, and attenuated oxidative stress in guinea pigs that have been fed high fat diet.In vitrostudy further confirmed that niacin decreased the secretion of IL-6 and TNF-αand inhibited NF-κB p65 and notch1 protein expression in oxLDL-stimulated HUVECs and THP-1 macrophages. Moreover, niacin attenuated oxLDL-induced apoptosis of HUVECs as well. In addition, niacin significantly lessened lipid deposition in arterial wall, increased HDL-C and apoA levels and decreased TG and non-HDL-C levels in plasma, and upregulated the mRNA amount of cholesterol 7α-hydroxylase A1 in liver of guinea pigs. These data suggest for the first time that niacin inhibits vascular inflammationin vivoandin vitrovia downregulating NF-κB signaling pathway. Furthermore, niacin also modulates plasma lipid by upregulating the expression of factors involved in the process of reverse cholesterol transport.

We have found that hydrogen (dihydrogen; H2) has beneficial lipid-lowering effects in high-fat diet-fed Syrian golden hamsters. The objective of this study was to characterize the effects of H2-rich water (0.9–1.0 l/day) on the content, composition, and biological activities of serum lipoproteins on 20 patients with potential metabolic syndrome. Serum analysis showed that consumption of H2-rich water for 10 weeks resulted in decreased serum total-cholesterol (TC) and LDL-cholesterol (LDL-C) levels. Western blot analysis revealed a marked decrease of apolipoprotein (apo)B100 and apoE in serum. In addition, we found H2 significantly improved HDL functionality assessed in four independent ways, namely, i) protection against LDL oxidation, ii) inhibition of tumor necrosis factor (TNF)-α-induced monocyte adhesion to endothelial cells, iii) stimulation of cholesterol efflux from macrophage foam cells, and iv) protection of endothelial cells from TNF-α-induced apoptosis. Further, we found consumption of H2-rich water resulted in an increase in antioxidant enzyme superoxide dismutase and a decrease in thiobarbituric acid-reactive substances in whole serum and LDL. In conclusion, supplementation with H2-rich water seems to decrease serum LDL-C and apoB levels, improve dyslipidemia-injured HDL functions, and reduce oxidative stress, and it may have a beneficial role in prevention of potential metabolic syndrome.

The present study was performed to investigate the effects of the combination therapy of pinocembrin and simvastatin on the atherosclerotic lesions development in the ApoE−/− mice. Methods Eight-week-old male ApoE−/− mice were fed high fat diet (HFD) and treated with simvastatin (10 mg/kg per day), pinocembrin (20 mg/kg per day), or the combination therapy (simvastatin 5 mg/kg per day and pinocembrin 20 mg/kg per day) for 14 weeks. The serum lipid levels, nitric oxide (NO), endothelin (ET), superoxide dismutase (SOD) and malondialdehyde (MDA) were determined with spectrophotometric measurement and ELISA assay. Vascular endothelial growth factor (VEGF) in serum and aortic root was detected. En face analyses of atherosclerotic lesion in whole aorta and aortic root sections were performed with plaque staining using oil red O. Results The combination treatment with simvastatin and pinocembrin resulted in significantly decreased levels of serum total cholesterol, triglycerides and low-density lipoprotein cholesterol, augmented NO levels and SOD activity, inhibited ET and VEGF expression. Immunohistochemistry of aortic valve sections revealed that the combination therapy also suppressed the expression of VEGF induced by HFD. In addition, HFD-induced arterial wall lipid disposition displayed by oil red O staining was reduced significantly in aortic root and whole aorta en face in the combination administrated mice. The effect of the combination was superior to simvastatin alone. Conclusion The combination of simvastatin and pinocembrin synergistically inhibited atherosclerotic lesion development in ApoE−/− mice with hyperlipidemia, which is partially dependent on the protective of vascular endothelium.

[Purpose] To investigate the effects and potential mechanisms of preconditioning of high-density lipoprotein (HDL3) on lipopolysaccharide (LPS)-induced injure to human umbilical vein endothelial cells (HUVEC). [Methods] HUVECs were pretreated with HDL3 at the concentration of 50 or 100 or 200mg/L for 18 hours, washed and stimulated with LPS (1.0 mg/L) for additional 6 hours. Cell viability was measured by MTT assay. Annexin V/PI double staining was used to measure the cell apoptotic rate by flow cytometry. The numbers of THP-1 adhesion to HUVECs were observed under fluorescence microscope and the content of VCAM-1 in culture medium was measured by ELISA. The level of NF-κB p65 in cell nuclei was determined by Western blotting. [Results] LPS reduced cell viability and induced apoptosis in HUVECs. The cytotoxic effects of LPS were significantly inhibited by HDL3 pretreatment. In addition, HDL3 also significantly suppressed the LPS-induced adhesion of THP-1 to HUVECs. Meanwhile, exposure of HUVECs to LPS resulted in a significant increase in the levels of VCAM-1 in culture media and NF-κB p65 in cell nuclei. HDL3 blocked these effects in a concentration-dependent manner. [Conclusion] HDL3 can protect HUVECs from LPS-induced injure and the mechanism at least partially involves its ability to suppress the secretion of VCAM-1 and the activation of NF-κB.

Background: The inhibition of tumor cell growth without toxicity to normal cells is an important target in cancer therapy. One possible way to increase the efficacy of anticancer drugs and to decrease toxicity or side effects is to develop traditional natural products, especially from medicinal plants. Paris polyphylla Smith has shown anti-tumour effects by inhibition of tumor promotion and inducement of tumor cell apoptosis, but mechanisms are still not well understood. The present study was to explore the effect of Paris polyphylla Smith extract (PPSE) on connexin26 and growth control in human esophageal cancer ECA109 cells. Methods: The effects of PPSE on Connexin26 were examined by RT-PCR, western blot and immunofluorescence; cell growth and proliferation were examined by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Results: PPSE inhibited the growth and proliferation on esophageal cancer ECA109 cells, while increasing the expression of connexin26 mRNA and protein; conversely, PPSE decreased Bcl-2 and increased Bad. Conclusion: This study firstly shows that PPSE can increase connexin26 expression at mRNA and protein level, exerting anti-tumour effects on esophageal cacner ECA109 cells via inhibiting cell proliferation and inducing cell apoptosis.

Background The present study was undertaken to investigate the effects and underlying mechanism of ethanolic extract of propolis (EEP) on the development of atherosclerotic lesions in ApoE−/− mice. Methods Eight-week-old male ApoE−/− mice fed a high-fat diet were treated with EEP (160 mg/kg/d) or vehicle (the same dose) respectively for 14 weeks. The serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were determined by enzymatic methods. Non-HDL-C was calculated as TC minus HDL-C. Serum interleukin-6 (IL-6), interleukin-17 (IL-17), endothelin (ET), inducible nitric oxide synthase (iNOS) and vascular endothelial growth factor (VEGF) were determined with enzyme-linked immunosorbent assay methods. Nitric oxide (NO) content was measured with an enzymatic nitrate reductase assay. Analyses of atherosclerotic lesions in whole aorta and aortic root sections were performed with plaque staining using Oil Red O. Results Compared with the vehicle-treated group, serum contents of total cholesterol (TC), triglycerides (TG) and non-HDL-C reduced significantly by 31.88%, 21.01%, and 27.11% respectively in the EEP-treated group. Administration of EEP decreased the level of IL-6 and increased the level of IL-17 in ApoE−/− mice with a high-fat diet. Compared with the vehicle-treated group,EEP significantly reduced the levels of ET and VEGF,and showed a trend to increase NO and inhibit iNOS. In the ApoE−/− mice fed a high-fat diet, EEP significantly reduced atherosclerotic lesion development in the aortic root and whole aorta. Conclusion EEP can inhibit atherosclerotic lesion formation in ApoE−/− mice fed a high-fat diet possibly through modulating cholesterol, regulating inflammatory reaction,inhibiting ET and VEGF, and protecting vascular endothelial cells.