Tanshinone IIA alleviates monocrotaline-induced pulmonary hypertension in rats through the PI3K/Akt-eNOS signaling pathway / 南方医科大学学报

OBJECTIVE@#To explore the therapeutic mechanism of tanshinone IIA in the treatment of pulmonary arterial hypertension (PAH) in rats.@*METHODS@#A total of 100 male SD rats were randomized into 5 groups (n=20), and except for those in the control group with saline injection, all the rats were injected with monocrotaline (MCT) on the back of the neck to establish models of pulmonary hypertension. Two weeks after the injection, the rat models received intraperitoneal injections of tanshinone IIA (10 mg/kg), phosphatidylinositol 3 kinase (PI3K) inhibitor (1 mg/kg), both tanshinone IIA and PI3K inhibitor, or saline (model group) on a daily basis. After 2 weeks of treatment, HE staining and α-SMA immunofluorescence staining were used to evaluate the morphology of the pulmonary vessels of the rats. The phosphorylation levels of PI3K, protein kinase B (PKB/Akt) and endothelial nitric oxide synthase (eNOS) in the lung tissue were determined with Western blotting; the levels of eNOS and NO were measured using enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#The results of HE staining and α-SMA immunofluorescence staining showed that tanshinone IIA effectively inhibited MCT-induced pulmonary artery intimamedia thickening and muscularization of the pulmonary arterioles (P < 0.01). The results of Western blotting showed that treatment with tanshinone IIA significantly increased the phosphorylation levels of PI3K, Akt and eNOS proteins in the lung tissue of PAH rats; ELISA results showed that the levels of eNOS and NO were significantly decreased in the rat models after tanshinone IIA treatment (P < 0.01).@*CONCLUSION@#Treatment with tanshinone IIA can improve MCT-induced pulmonary hypertension in rats through the PI3K/Akt-eNOS signaling pathway.

Two-dimensional Nanomaterials against β-Amyloid in the Treatment of Alzheimer’s Disease / 中国生物化学与分子生物学报

Alzheimer’s disease (AD) is a prevalent progressive neurodegenerative disorder among the elderly. In the scientific community, the β-amyloid (Aβ) hypothesis is currently a widely-accepted model for AD pathogenesis. Removing Aβ, inhibiting Aβ aggregation and depolymerizing Aβ fibrils are proposed to provide useful strategies for the treatment of AD. However, most current drugs used for anti-Aβ therapy usually have inherent drawbacks that may limit their clinical applications. With the rise of nanotechnology nowadays, the application of two-dimensional nanomaterials in medicine has rapidly attracted much attention from researchers. Two-dimensional nanomaterials not only have excellent physical and chemical properties, as well as good biocompatibility, but also can easily cross either the cell membrane or blood-brain barrier. Recently, it has been found that many two-dimensional nanomaterials can inhibit Aβ aggregation or depolymerize Aβ fibrils by intermolecular interaction, near-infrared photothermal effect, photocatalytic oxidation, chelation of copper ions, drug delivery and other mechanisms, implying its great potential in treating AD. This review will focus on the research of graphene and graphene-like two-dimensional nanomaterials such as molybdenum disulfide, graphitic carbon nitride, and black phosphorus used for anti-Aβ therapy in the treatment of AD.

Influence of road types on road traffic accidents in northern Guizhou Province, China / 中华创伤杂志(英文版)

PURPOSE@#The increasing number of deaths due to road traffic accidents (RTAs) has attracted global attention. However, the influence of road types is rarely considered in the study of RTAs. This study evaluates the influence of different road types in RTAs in northern Guizhou to provide a basis for the formulation of evidence-based policies and measures.@*METHODS@#We obtained the data from the Zunyi Traffic Management Data Platform for the years 2009-2018. The mortality rates of RTAs were calculated. Descriptive methods and Chi-square tests were used to analyze the characteristics of road traffic collisions on different road types. We also examined the associations between the mortality rate per 10,000 vehicles and the growth of per capital gross domestic product (GDP) with Spearman's rank correlation analysis. According to the passing volume and the infrastructure, we defined different types of roads, like administrative road, functional road, general urban road and urban expressway.@*RESULTS@#In 2012, the traffic mortality rate of administrative roads was 8.9 per 100,000 people, and the mortality rate of functional roads was 7.4 per 100,000 people, which decreased in 2018 to 6.1 deaths per 100,000 people and 5.2 deaths per 100,000 people, respectively. The mortality rate per 10,000 vehicles reached the highest level in 2011 (28.8 per 10,000 vehicles and 22.5 per 10,000 vehicles on administrative and functional roads, respectively). The death rate of county roads was the highest among administrative roads (χ@*CONCLUSION@#Although our research shows that RTAs in northern Guizhou have steadily declined in recent years, the range of decline is relatively small. Many measures and sustainable efforts are needed to control road traffic death and accelerate the progress in road traffic safety in northern Guizhou.

Preparation of evodiamine-glycyrrhizic acid micelles with glycyrrhizic acid as carrier and their anti-hepatic fibrosis activity / 中国中药杂志

This study aimed to prepare evodiamine-glycyrrhizic acid(EVO-GL) micelles to enhance the anti-hepatic fibrosis activity of evodiamine. Firstly, EVO-GL micelles were prepared with use of thin film dispersion method. With particle size, encapsulation efficiency, loading capacity of micelles and the solubility of evodiamine as the indexes, the effect of different factors on micelles was observed to screen the optimal preparation methods and process. Then the pharmaceutical properties and the therapeutic effects of EVO-GL micelles prepared by optimal process were evaluated on CCl_4-induced hepatic fibrosis. The results showed that the micelles prepared by the thin film dispersion method had an even size, with an average particle size of(130.80±12.40)nm, Zeta potential of(-41.61±3.12) mV, encapsulation efficiency of 91.23%±1.22%, drug loading of 8.42%±0.71%, high storage stability at 4 ℃ in 3 months, and slow in vitro release. Experimental results in the treatment of CCl_4-induced hepatic fibrosis in rats showed that EVO-GL micelles had a synergistic anti-hepatic fibrosis effect, which significantly reduced the liver function index of hepatic fibrosis rats. In conclusion, the EVO-GL micelles prepared with glycyrrhizic acid as a carrier would have a potential application prospect for the treatment of hepatic fibrosis.

Advances in inorganic nanomaterials regulated autophagy in cancer treatment / 医学研究生学报

Autophagy represents one of the essential cellular mechanism to maintain homeostasis within cells, performing multiple biological functions during tumorigenesis. Base on the unique physicochemical properties of inorganic nanomaterials, supplemented by easy modification and targeting and so on, they could be used to regulate autophagy, controlling the occurrence and development of tumor and finally achieve treatment. This article primarily reviews the application of several representative inorganic nanomaterials, such as Gold nanoparticles, Silver nanoparticles, Iron oxide nanoparticles, Fullerene C60 nanomaterials, Graphene oxide nanomaterials in regulating autophagy of tumor cells and achieving treatment in recent years.

Altered serum cytokine expression profile in systemic sclerosis and its regulatory mechanisms / 北京大学学报(医学版)

OBJECTIVE@#To analyze the expression profile of serum cytokines in patients with systemic sclerosis (SSc) and explore its possible regulatory mechanisms.@*METHODS@#Serum and DNA of peripheral blood mononuclear cells were collected from 30 SSc patients and 80 normal controls (NCs). According to the presence or absence of interstitial lung disease (ILD) in SSc, the patients were divided into SSc with ILD group and SSc without ILD group. According to the degree of skin involvement, the patients were divided into diffuse systemic scleroderma (dcSSc) group and limited systemic scleroderma (lcSSc) group. According to the presence of anti-topoisomerase-1 antibody (anti-Scl-70 antibody) in the serum of patients with SSc, they were divided into SSc Scl-70 (+) group and SSc Scl-70 (-) group. 27 cytokines in serum were detected by Luminex MAGPIX detection system and Bio-Plex Pro Human Cytokine 27-plex Assay kit: interleukin-1β (IL-1β), interleukin-1 receptor antagonist (IL-1ra), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12P70, IL-13, IL-15, IL-17, basic fiber growth factor (BASIC FGF), eotaxin, granulocyte colony stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF), interferon-γ (IFN-γ), interferon-gamma induced protein 10(IP-10), monocyte chemotactic protein 1(MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein 1β(MIP-1β), platelet-derived growth factor BB (PDGF-BB), regulated on activation in normal T-cell expressed and secreted (RANTES), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor(VEGF). Methylation sites were detected by Illumina 450K methylation chip.@*RESULTS@#Compared with NCs group, the expression of 12 cytokines (BASIC FGF, eotaxin, G-CSF, GM-CSF, IFN-γ, IL-1β, IL-1ra, IL-6, IP-10, MCP-1, TNF-α and RANTES) in the SSc group significantly increased (P<0.05), IL-5 was decreased expression in the SSc group (P<0.05), there was no significant difference in the expressions of the other 14 cytokines. Compared with lcSSc group, 9 cytokines (eotaxin, IL-5, MCP-1, IL-2, RANTES, IL17A, IL-8, MIP-1β and PDGF-BB) increased in dcSSc group, but there was no significant difference. Compared with SSc without ILD group, IL-15 increased in SSC with ILD group [18.2 (172.97) ng/L vs. 2.03(0.05) ng/L, P<0.05]. Compared with SSc Scl-70 (-) group, the expression of IP-10 decreased in SSc Scl-70 (+) group [1 030 (2 196.6) ng/L vs. 1 878 (2 964) ng/L, P<0.05]. The correlation analysis of serum cytokines with erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) showed that IL-6 was positively correlated with ESR (r =0.04, P= 0.017), MCP-1 (r=0.49, P=0.043) and MIP-1β (r=0.41, P=0.007) positively correlated with CRP. By analyzing the changes of methylation sites of cytokines, it was found that cg17744604 in IL-10 TSS1500 region, cg06111286 in IL-12P70 TSS200 region, cg07935264 in IL-1β TSS200 region, cg01467417 in IL-1ra TSS1500 region, cg03989987 in IL-1ra 5'UTR region and cg21099624 in VEGF TSS200 region were all hypomethylated.@*CONCLUSION@#There were different cytokines expression profiles in the serum of SSc patients, and the altered cytokines were correlected with the degree of skin damage and pulmonary fibrosis. Many cytokines were regulated by methylation.

Advances in epigenetic markers of dermatomyositis/polymyositis / 北京大学学报(医学版)

Idiopathic inflammatory myopathy (IIM) is a rare group of autoimmune diseases, characterized by chronic muscle weakness, muscle fatigue and infiltration of single nuclear cells in skeletal muscle. Its subtypes include dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM) and immune-mediated necrotizing myositis (IMNM), and the most common subtypes are DM and PM. PM is an autoimmune disease mainly manifested by muscle damage. When the skin is involved, it is called DM. The incidence of IIM was relatively low, which was 1.16-19 per million people/year, but the mortality was high and the prognosis was poor. The pathogenesis of IIM is still unclear. Previous studies suggest that both immune and non-immune mechanisms are involved in its pathogenesis, especially cellular and humoral immunity. In recent years, researchers have conducted a number of studies on the pathogenesis of IIM, especially in the study of DM/PM with the application of high-throughput biometrics. Epigenetics is a discipline that refers to the genetic phenomena of DNA methylation spectrum, chromatin structure state and gene expression spectrum transferred between cells without any changes in DNA sequence, including DNA methylation, chromatin modification and non-coding RNA changes. A large number of studies have shown that epigenetic modification plays an important role in many diseases, especially in cancer. Recent studies have also found a series of epigenetic markers related to the occurrence and development of DM/PM, mainly in the aspect of non-coding RNA changes, such as miR-10a, miR-206, etc. And there has also been some research on DNA methylation. However, no studies have been reported on whether chromatin modification is involved in the pathogenesis of DM/PM. The pathogenesis of DM/PM is complex and diverse. With the development of research, certain microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) may become biological markers for the early diagnosis of DM/PM. Therefore, this paper mainly expounds the research progress of the biomarkers of DM/PM from the aspect of epigenetics.

Application of multi-group structural equation model in comparative study of HBM related to recreational physical activity among population with high risk of chronic diseases and healthy people / 北京大学学报(医学版)

OBJECTIVE@#To explore mechanism of health beliefs by application of health belief model (HBM) and structural equation modeling (SEM) with regard to recreational physical activity (PA), to identify the differences of among population with high risk of chronic diseases and healthy people, and to provide the specific interventions of recreational physical activity and reference for health relevant policy-making in the future.@*METHODS@#A total of 2 736 residents with high risk of chronic diseases and 1 514 healthy people were involved. A questionnaire survey, physical examination and biochemical examination were conducted. The questionnaire based on HBM had acceptable validity and reliability. The proposed model based on the total sample size of the two groups was developed using the structural equation modeling and multi-comparison in the ways of appearance and parameters were also validated.@*RESULTS@#The median amount of recreational (PA) among population with high risk of chronic diseases and healthy people were 0.0 thousand-step equivalent with quartile of (0.0, 4.6) and 0.0 thousand-step equivalent with quartile of (0.0, 4.0) respectively. The results of SEM suggested that the direct effects of perceived objective barriers (β=-0.245), perceived subjective barriers (β=-0.057), cues to action (β=-0.043) and self-efficacy (β=0.117) on recreational (PA) were significant. Self-efficacy was the most important mediator. The multi-group comparisons indicated that the models of the two groups had the same appearance but the parameters between them were significant (δ χ2=27.4, P<0.05). The multi-group structural equation model (MSEM) indicated that two paths from cues to action and from perceived subjective barriers to recreational (PA) were not statistically significant among the population with high-risk of chronic diseases. In the two groups, one path coefficient from perceived objective barriers to subjective barriers (P=0.007) was statistically significant (P<0.05).@*CONCLUSION@#The recreational (PA) levels of both groups were lower. Health beliefs on recreational (PA) of the two groups played different roles and some paths were also different. Therefore, specific interventions and strategies should be developed for different people. For residents with high risk of chronic diseases, much more attention should be paid to reduce the objective and subjective barriers of recreational physical activity and to improve self-efficacy so as to delay or prevent the occurrence of chronic diseases and then to improve the quality of life of this kind of population.

Synergistic mechanism of traditional Chinese medicine based on target combination of PepT1 and PPARα / 中国中药杂志

Synergistic effect is main pharmacological mechanism of traditional Chinese medicine(TCM). The research method based on the key targets combination is an important method to explore the synergistic effect of TCM. Peptide transporter 1 (PepT1) is an essential target for drug uptake into the bloodstream, accounting for about 50% of the total transporter protein content from the small intestine. Peroxisome proliferator-activated receptor α(PPARα) is the lipid-lowering target of fibrates, which have a good hypolipidemic effect by activating PPARα. It has been reported that PPARα could activate the gene expression of PepT1s, and PPARα agonists can promote the uptake of PepT1 substrates, indicating their synergistic effect. In this paper, PepT1 substrates and PPARα agonists from TCM were discovered, and their synergistic mechanism was also been discussed based on the target combination of PepT1 and PPARα. The support vector machine(SVM) model of PepT1 substrates was first constructed and utilized to predict potential TCM components. Meanwhile, merged pharmacophore and docking model of PPARα agonists was used to screen the potential active ingredients from TCM. According to the analysis results of two groups, the TCM combination of Panax notoginseng and Ganoderma lucidum, as well as TCM combination of P. notoginseng and Salvia miltiorrhiza were identified to have the synergistic mechanism based on target combination of PepT1 and PPARα. In this study, synergistic mechanism of TCM was analyzed for absorption and hypolipidemic effect based on target combination, which provides a new way to explore the synergetic mechanism of TCM related to pharmacokinetics.

Preparation of paclitaxel-loaded polybutylcyanoacrylate nanoparticles / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of different preparation methods on the encapsulation efficiency (EE) and drug loading (DL) of paclitaxel-loaded polybutylcyanoacrylate nanoparticles (PTX-PBCA-NPs) and optimize the preparation of PTX-PBCA-NPs.</p><p><b>METHODS</b>With DL and EE as the major indexes, the qualities of PTX-PBCA-NPs produced by the interfacial polymerization and emulsion polymerization method were compared. The optimized prescription was obtained by orthogonal design.</p><p><b>RESULTS</b>The ranges of EE of PTX-PBCA-NPs with the two methods were both 94.39%-99.23%. The highest DL with interfacial polymerization was (1.07-/+0.03)%, as compared to (0.86-/+0.01)% with emulsion polymerization. The optimized preparation conditions resulted in the mean size of PTX-PBCA-NPs of 235.6 nm, DL of 0.80%, and EE of 95.71%.</p><p><b>CONCLUSION</b>The EE of PTX-PBCA-NPs prepared by the above two methods is consistent with the requirement of the Pharmacopoeia of China, and PTX-PBCA-NPs containing higher DL can be obtained via interfacial polymerization.</p>