Transcriptome analysis of leaves,roots and flowers of Panax notoginseng on ginsenoside and alkaloid biosynthesis and amelioration of vascular insufficiency conditions by saponins from the flower buds

OBJECTIVE To investigate the transcriptomic details on the biosynthetic pathways in different parts of the Panax notoginseng and the pharmacological activity of the saponins extracted from the flower(FS)on vascular insufficiency conditions.METHODS RNA sequencing of three different Panax notoginseng tissues was performed using next generation DNA sequencing and differential gene expression was validated by real-time PCR.In order to determine pro-angiogenic and therapeutic effects of FS on myocardial infraction(MI),FS was examined on the endothelial cell migration assay,vascular insufficiency model in zebrafish and MI model in rats.RESULTS After assembling the high quality sequencing reads into 107 340 unigenes,biochemical pathways were predicted and 9 908 unigenes were assigned to 135 KEGG pathways.Among them,270 unigenes were identified to be involved in triterpene saponin biosynthesis as well as 350 and 342unigenes were predicted to encode cytochrome P450 sand glycosyltransferases,respectively.One unigene was annotated as CYP716A53v2,probably participates in the formation of protopanaxatriol from protopanaxadiol and the differential expression of this gene was confirmed by real-time PCR.In addition,the pharmacological evaluation demonstrate that FS significantly promoted vascular endothelial growth factor(VEGF)induced the migration of human umbilical vein endothelial cells(HUVECs)and partially restored defective intersegmental vessels in a chemically induced vascular insufficiency model of zebrafish larva.Moreover,the two week posttreatment of the rat MI model with FS(25-50mg·kg-1·d-1)induced approximately 3-fold upregulation of VEGF mRNA expression,with a concomitant increase in blood vessel density in the peri-infarct area of the heart by 50.7%,compared to 41.4%in the MI group.Furthermore,TUNEL analysis indicates a reduction in the mean apoptotic nuclei per field in peri-infarct myocardium upon FS treatment.CONCLUSION We have established a global transcriptome dataset for Panax notoginseng and provided additional genetic information for further genome-wide research and analyses.Candidate genes involved in ginsenoside biosynthesis,including putative cytochrome P450 sand glycosyltransferases were obtained.The transcriptomes in different plant tissues also provide invaluable resources for future study of the differences in physiological processes and secondary metabolites in different parts of P.notoginseng.And the significant pro-angiogenic effect of FS in multiple experimental models renders the purified saponin preparation as potential preventive and therapeutic agent for cardiovascular diseases yet to be developed.

Would integrated Western and traditional Chinese medicine have more benefits for stroke rehabilitation? A systematic review and meta-analysis

Background Stroke is a major cause of death or long-term disability worldwide.Many patients with stroke receive integrative therapy consisting of Western medicine(WM)and routine rehabilitation in conjunction with Chinese medicine(CM),such as acupuncture and Chinese herbal medicine.However,there is no available evidence on the effectiveness of the combined use of WM and CM interventions in stroke rehabilitation.Aims The purpose of this meta-analysis is to evaluate the results of all individual studies to assess the combined use of CM and WM in stroke rehabilitation compared with WM only.Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed.MEDLINE,EMBASE,Cochrane and China National Knowledge Infrastructure(CNKI)were searched.The included outcomes were dependency,motor function,depression and swallowing function.Subgroup analysis was performed,and publication bias was assessed using funnel plots.Summary of review 58 studies and 6339 patients were included in the meta-analysis.Subgroup analysis revealed that combined therapy comprising both acupuncture and WM had a superior effect on improving dependency and swallowing function compared with standard WM therapy alone.Potential superiority of combined therapy comprising CM and WM in improving depression compared with standard WM therapy was also found.Conclusions Our results indicate that the combined use of CM and WM could be more efficacious in stroke rehabilitation compared with the use of WM therapy alone.However,most studies were short in duration(2 to 4 weeks)and prone to different types of biases,which prevents making any conclusion regarding the long-term effects and raises concerns regarding true efficacy in context of high likelihood of Hawthorn bias.So,more randomised controlled trials with more rigorous design and longer duration of treatment and follow-up need to be conducted to compare WM alone versus WM and CM combined.

Effect of Tai Chi Chuan on serotonin and cortisol for monitoring stress and quality of life in post-treatment breast cancer patients

Objective Immediate physical exercise has been recommended for patients in the recovery phase to improve survival and quality of life(QOL)and reduce recurrence of disease.The new NCCN Guidelines for Survivorship also highlighted the role of exercise in post-cancer health,encouraging patients to perform light physical activity following treatment.The aim of our study is to effect of Tai Chi Chuan(TCC)on serotonin and cortisol for monitoring stress and QOL in post-treatment breast cancer patients.Methods Totally85 post-treatment breast cancer patients were enrolled in this study to observe the effects of practicing TCC on recovery,as well as stress and happiness which are indicators of QOL of in patients.Peripheral blood was drawn from study subjects to analyze the levels of serotonin,cortisol and high sensitive C-reactive protein(HSCRP)at baseline,and at 3,6 and 12 months of TCC practice.Blood was drawn from healthy subjects only at baseline.A QOL questionnaire was administered to study subjects at three time points throughout the study,and once for healthy controls.The data were processed by analysis of variance of repeated measurement.Results At 3,6 and 12 months time points following regular TCC exercise,WBC,RBC,hemoglobin in blood samples showed a statistically significant difference(F=161.55,172.14,289.73;all P=0.00);the level of serotonin(biomarker for well-being),cortisol(indicator of stress)and HS-CRP(biomarker for inflammation)showed a statistical improvement(F=307.46,182.85,102.23;all P=0.00).After 3,6 and 12 months of regular TCC exercise,according to the results of QOL questionnaire,the indicators including quality of sleep,perceived hunger,fatigue,contentment,stress and social interaction presented a significant difference(F=312.98,222.64,543.90,46.05,28.10,78.92,all P<0.05),while there was no statistical difference in life dissatisfaction(F=56.61,P=0.166)Conclusions TCC physical activity for post-treatment breast cancer patients improved QOL and overall well-being,leading to improved mental,physical and psychological functioning.Regulated levels of serotonin and cortisol mediated by TCC exercises are proved to be vital for continued good health.

Enhancing cartilage repair with optimized supramolecular hydrogel-based scaffold and pulsed electromagnetic field

Functional tissue engineering strategies provide innovative approach for the repair and regeneration of damaged cartilage.Hydrogel is widely used because it could provide rapid defect filling and proper structure support,and is biocompatible for cell aggregation and matrix deposition.Efforts have been made to seek suitable scaffolds for cartilage tissue engineering.Here Alg-DA/Ac-β-CD/gelatin hydrogel was designed with the features of physical and chemical multiple crosslinking and self-healing properties.Gelation time,swelling ratio,biodegradability and biocompatibility of the hydrogels were systematically characterized,and the injectable self-healing adhesive hydrogel were demonstrated to exhibit ideal properties for cartilage repair.Furthermore,the new hydrogel design introduces a pre-gel state before photo-crosslinking,where increased viscosity and decreased fluidity allow the gel to remain in a semi-solid condition.This granted multiple administration routes to the hydrogels,which brings hydrogels the ability to adapt to complex clinical situations.Pulsed electromagnetic fields(PEMF)have been recognized as a promising solution to various health problems owing to their noninvasive properties and therapeutic potentials.PEMF treatment offers a better clinical outcome with fewer,if any,side effects,and wildly used in musculoskeletal tissue repair.Thereby we propose PEMF as an effective biophysical stimulation to be 4th key element in cartilage tissue engineering.In this study,the as-prepared Alg-DA/Ac-β-CD/gelatin hydrogels were utilized in the rat osteochondral defect model,and the potential application of PEMF in cartilage tissue engineering were investigated.PEMF treatment were proven to enhance the quality of engineered chondrogenic constructs in vitro,and facilitate chondrogenesis and cartilage repair in vivo.All of the results suggested that with the injectable self-healing adhesive hydrogel and PEMF treatment,this newly proposed tissue engineering strategy revealed superior clinical potential for cartilage defect treatment.

O-alg-THAM/gel hydrogels functionalized with engineered microspheres based on mesenchymal stem cell secretion recruit endogenous stem cells for cartilage repair

Lacking self-repair abilities,injuries to articular cartilage can lead to cartilage degeneration and ultimately result in osteoarthritis.Tissue engineering based on functional bioactive scaffolds are emerging as promising approaches for articular cartilage regeneration and repair.Although the use of cell-laden scaffolds prior to implantation can regenerate and repair cartilage lesions to some extent,these approaches are still restricted by limited cell sources,excessive costs,risks of disease transmission and complex manufacturing practices.Acellular approaches through the recruitment of endogenous cells offer great promise for in situ articular cartilage regeneration.In this study,we propose an endogenous stem cell recruitment strategy for cartilage repair.Based on an injectable,adhesive and self-healable o-alg-THAM/gel hydrogel system as scaffolds and a biophysio-enhanced bioactive microspheres engineered based on hBMSCs secretion during chondrogenic differentiation as bioactive supplement,the as proposed functional material effectively and specifically recruit endogenous stem cells for cartilage repair,providing new insights into in situ articular cartilage regeneration.