Asiatic Acid Inhibits Liver Fibrosis by Blocking TGF-beta/Smad Signaling In Vivo and In Vitro

Liver fibrosis is a major cause of liver failure, but treatment remains ineffective. In the present study, we investigated the mechanisms and anti-hepatofibrotic activities of asiatic acid (AA) in a rat model of liver fibrosis induced by carbon tetrachloride (CCl4) and in vitro in TGF-beta1-stimulated rat hepatic stellate cell line (HSC-T6). Treatment with AA significantly attenuated CCl4-induced liver fibrosis and functional impairment in a dosage-dependent manner, including blockade of the activation of HSC as determined by inhibiting de novo alpha smooth muscle actin (a-SMA) and collagen matrix expression, and an increase in ALT and AST (all p<0.01). The hepatoprotective effects of AA on fibrosis were associated with upregulation of hepatic Smad7, an inhibitor of TGF-beta signaling, thereby blocking upregulation of TGF-beta1 and CTGF and the activation of TGF-beta/Smad signaling. The anti-fibrosis activity and mechanisms of AA were further detected in vitro in HSC-T6. Addition of AA significantly induced Smad7 expression by HSC-T6 cells, thereby inhibiting TGF-beta1-induced Smad2/3 activation, myofibroblast transformation, and collagen matrix expression in a dosage-dependent manner. In contrast, knockdown of Smad7 in HSC-T6 cells prevented AA-induced inhibition of HSC-T6 cell activation and fibrosis in response to TGF-beta1, revealing an essential role for Smad7 in AA-induced anti-fibrotic activities during liver fibrosis in vivo and in vitro. In conclusion, AA may be a novel therapeutic agent for liver fibrosis. Induction of Smad7-dependent inhibition of TGF-beta/Smad-mediated fibrogenesis may be a central mechanism by which AA protects liver from injury

HIV Incidence among Men Who Have Sex with Men in China: A Meta-Analysis of Published Studies

Men who have sex with men (MSM) have now become one of the priority populations for prevention and control of HIV pandemic in China. Information of HIV incidence among MSM is important to describe the spreading of the infection and predict its trends in this population. We reviewed the published literature on the incidence of HIV infection among MSM in China.We identified relevant studies by use of a comprehensive strategy including searches of Medline and two Chinese electronic publication databases from January 2005 to September 2010. Point estimate of random effects incidence with corresponding 95% confidence intervals (CI) of HIV infection was carried out using the Comprehensive Meta-Analysis software. Subgroup analyses were examined separately, stratified by study design and geographic location.Twelve studies were identified, including three cohort studies and nine cross-sectional studies. The subgroup analyses revealed that the sub-overall incidence estimates were 3.5% (95% CI, 1.7%-5.3%) and 6.7% (95% CI, 4.8%-8.6%) for cohort and cross-sectional studies, respectively (difference between the sub-overalls, Q = 5.54, p = 0.02); and 8.3% (95% CI, 6.9%-9.7%) and 4.6% (95% CI, 2.4%-6.9%) for studies in Chongqing and other areas, respectively (difference between the sub-overalls, Q = 7.58, p<0.01). Syphilis infection (RR = 3.33, p<0.001), multiple sex partnerships (RR = 2.81, p<0.001), and unprotected receptive anal intercourse in the past six months (RR = 3.88, p = 0.007) represented significant risk for HIV seroconversion.Findings from this meta-analysis indicate that HIV incidence is substantial in MSM in China. High incidence of HIV infection and unique patterns of sexual risk behaviors in this population serve as a call for action that should be answered with the innovative social and public health intervention strategies, and development of biological prevention strategies

Improved ground-state modulation characteristics in 1.3 μm InAs/GaAs quantum dot lasers by rapid thermal annealing

We investigated the ground-state (GS) modulation characteristics of 1.3 μm InAs/GaAs quantum dot (QD) lasers that consist of either as-grown or annealed QDs. The choice of annealing conditions was determined from our recently reported results. With reference to the as-grown QD lasers, one obtains approximately 18% improvement in the modulation bandwidth from the annealed QD lasers. In addition, the modulation efficiency of the annealed QD lasers improves by approximately 45% as compared to the as-grown ones. The observed improvements are due to (1) the removal of defects which act as nonradiative recombination centers in the QD structure and (2) the reduction in the Auger-related recombination processes upon annealing

Decreasing the use of edible oils in China using WeChat and theories of behavior change: study protocol for a randomized controlled trial.

The consumption of edible oils in China has increased rapidly in recent years, and the total amount of edible-oil intake in the country has ranked first in the world. The choice and intake of edible oils, as a source of fats, are important factors that affect people's health. Many chronic diseases are closely associated with high-calorie and saturated-fat intake. The influence of traditional concepts that promote the use of edible oils among women, particularly housewives, plays a key role in a household's diet and nutrition because the diet-related knowledge, attitude and behaviour of housewives are dominant factors in planning and preparing their family's meals. WeChat, which was developed by Tencent, is a multipurpose messaging, social media and mobile payment application (app) in China. Described by Forbes as one of the world's most powerful apps, WeChat provides considerable convenience in disseminating knowledge. Accordingly, this study aims to design a pilot intervention to decrease the use of edible oils in Chinese households. The intervention, which is based on theories of behaviour change, will be implemented through WeChat. The study design is a randomised controlled trial that adopts knowledge, attitude and practice, social cognitive and stages of change theories as theoretical models. A total of 800 housewives between the ages of 25 and 45 years will be recruited on WeChat and from the communities in four areas (including rural and urban) in Chongqing, China. A self-administered questionnaire will be used to collect information regarding age, educational level, occupation, family members, edible-oil intake habits, knowledge of edible oils and WeChat usage habits. A total of 200 participants will be selected and randomly assigned to two equal-sized groups: group A (the intervention group) and group B (the control group). Group A will receive health education regarding edible oils for four consecutive weeks, whereas group B will be treated as the blank control. Each participant will complete a battery of knowledge, attitude and behaviour tests immediately, 3 months and 6 months after the intervention. In addition, weight, moisture rate, fat rate, visceral fat level and body mass index will be calculated using a multifunctional weighing scale, namely, Tanita BC-601 (Japan). The study is currently in the design stage. This study aims to increase knowledge and awareness of the appropriate use of edible oils, thereby encouraging participants to change behaviour by decreasing the intake of unhealthy levels of edible oils. It will be the first intervention to investigate the use of edible oils in China through WeChat. We predict that receiving health education regarding edible oils through WeChat will substantially improve the knowledge and attitude of the respondents. The members of the intervention group will have increased awareness and will be willing to decrease their use of edible oils to remain healthy. Results of this study may provide scientific evidence for the effect of health education through WeChat on edible oil-intake behaviour, thereby offering a comprehensive intervention to decrease the use of edible oils and promote a healthy lifestyle. Chinese Clinical Trial Registry (primary registry in the World Health Organisation registry network): ChiCTR-IOR-17013472 . Registered on 21 November 2017

Comparative Metaproteomic Analysis on Consecutively Rehmannia glutinosa-Monocultured Rhizosphere Soil

National Natural Science Foundation of China [30772729, 30671220, 31070403]; Natural Science Foundation of Fujian province, China [2008J0051]Background: The consecutive monoculture for most of medicinal plants, such as Rehmannia glutinosa, results in a significant reduction in the yield and quality. There is an urgent need to study for the sustainable development of Chinese herbaceous medicine. Methodology/Principal Findings: Comparative metaproteomics of rhizosphere soil was developed and used to analyze the underlying mechanism of the consecutive monoculture problems of R. glutinosa. The 2D-gel patterns of protein spots for the soil samples showed a strong matrix dependency. Among the spots, 103 spots with high resolution and repeatability were randomly selected and successfully identified by MALDI TOF-TOF MS for a rhizosphere soil metaproteomic profile analysis. These proteins originating from plants and microorganisms play important roles in nutrient cycles and energy flow in rhizospheric soil ecosystem. They function in protein, nucleotide and secondary metabolisms, signal transduction and resistance. Comparative metaproteomics analysis revealed 33 differentially expressed protein spots in rhizosphere soil in response to increasing years of monoculture. Among them, plant proteins related to carbon and nitrogen metabolism and stress response, were mostly up-regulated except a down-regulated protein (glutathione S-transferase) involving detoxification. The phenylalanine ammonia-lyase was believed to participate in the phenylpropanoid metabolism as shown with a considerable increase in total phenolic acid content with increasing years of monoculture. Microbial proteins related to protein metabolism and cell wall biosynthesis, were up-regulated except a down-regulated protein (geranylgeranyl pyrophosphate synthase) functioning in diterpenoid synthesis. The results suggest that the consecutive monoculture of R. glutinosa changes the soil microbial ecology due to the exudates accumulation, as a result, the nutrient cycles are affected, leading to the retardation of plant growth and development. Conclusions/Significance: Our results demonstrated the interactions among plant, soil and microflora in the proteomic level are crucial for the productivity and quality of R. glutinosa in consecutive monoculture system

Influence of Dll4 via HIF-1α-VEGF Signaling on the Angiogenesis of Choroidal Neovascularization under Hypoxic Conditions

Choroidal neovascularization (CNV) is the common pathological basis of irreversible visual impairment encountered in a variety of chorioretinal diseases; the pathogenesis of its development is complicated and still imperfectly understood. Recent studies indicated that delta-like ligand 4 (Dll4), one of the Notch family ligands might participate in the HIF-1α-VEGF pathway to regulate CNV angiogenesis. But little is known about the influence and potential mechanism of Dll4/Notch signals on CNV angiogenesis. Real-time RT-PCR, Western blotting were used to analyze the expression alteration of Dll4, VEGF and HIF-1α in hypoxic RF/6A cells. Immunofluorescence staining, a laser-induced rat CNV model and intravitreal injection techniques were used to confirm the relationships among these molecules in vitro and in vivo. RPE-RF/6A cell co-culture systems were used to investigate the effects of Dll4/Notch signals on CNV angiogenesis. We found that the Dll4 was involved in hypoxia signaling in CNV angiogenesis. Results from the co-culture system showed that the enhancement of Dll4 expression in RF/6A cells led to the significantly faster proliferation and stronger tube forming ability, but inhibited cells migration and invasion across a monolayer of RPE cells in hypoxic environment, while siRNA-mediated Dll4 silencing caused the opposite effects. Pharmacological disruption of Notch signaling using gamma-secretase inhibitor (GSI) produced similar, but not identical effects, to that caused by the Dll4 siRNA. In addition, the expression of several key molecules involved in the angiogenesis of CNV was altered in RF/6A cells showing constitutively active Dll4 expression. These results suggest that Dll4 play an important role in CNV angiogenesis, which appears to be regulated by HIF-1α and VEGF during the progression of CNV under hypoxic conditions. Targeting Dll4/Notch signaling may facilitate further understanding of the mechanisms that underlie CNV angiogenesis

Processing and characterization of chitosan microspheres to be used as templates for layer-by-layer assembly

Chitosan (Ch) microspheres have been developed by precipitation method, cross-linked with glutaraldehyde and used as a template for layer-by-layer (LBL) deposition of two natural polyelectrolytes. Using a LBL methodology, Ch microspheres were alternately coated with hyaluronic acid (HA) and Ch under mild conditions. The roughness of the Ch-based crosslinked microspheres was characterized by atomic force microscopy (AFM). Morphological characterization was performed by environmental scanning electron microscopy (ESEM), scanning electron microscopy (SEM) and stereolight microscopy. The swelling behaviour of the microspheres demonstrated that the ones with more bilayers presented the highest water uptake and the uncoated cross-linked Ch microspheres showed the lowest uptake capability. Microspheres presented spherical shape with sizes ranging from 510 to 840 lm. ESEM demonstrated that a rougher surface with voids is formed in multilayered microspheres caused by the irregular stacking of the layers. A short term mechanical stability assay was also performed, showing that the LBL procedure with more than five bilayers of HA/Ch over Ch cross-linked microspheres provide higher mechanical stability

A Novel Chromone Derivative with Anti-Inflammatory Property via Inhibition of ROS-Dependent Activation of TRAF6-ASK1-p38 Pathway

The p38 MAPK signaling pathway plays a pivotal role in inflammation. Targeting p38 MAPK may be a potential strategy for the treatment of inflammatory diseases. In the present study, we show that a novel chromone derivative, DCO-6, significantly reduced lipopolysaccharide (LPS)-induced production of nitric oxide, IL-1β and IL-6, decreased the levels of iNOS, IL-1β and IL-6 mRNA expression in both RAW264.7 cells and mouse primary peritoneal macrophages, and inhibited LPS-induced activation of p38 MAPK but not of JNK, ERK. Moreover, DCO-6 specifically inhibited TLR4-dependent p38 activation without directly inhibiting its kinase activity. LPS-induced production of intracellular reactive oxygen species (ROS) was remarkably impaired by DCO-6, which disrupted the formation of the TRAF6-ASK1 complex. Administering DCO-6 significantly protected mice from LPS-induced septic shock in parallel with the inhibition of p38 activation and ROS production. Our results indicate that DCO-6 showed anti-inflammatory properties through inhibition of ROS-dependent activation of TRAF6-ASK1-p38 pathway. Blockade of the upstream events required for p38 MAPK action by DCO-6 may provide a new therapeutic option in the treatment of inflammatory diseases