Mesenchymal stem cell-derived extracellular vesicles carrying miR-99b-3p restrain microglial activation and neuropathic pain by stimulating autophagy.

Neuropathic pain is a complex condition that seriously affects human quality of life. This study aimed to investigate the therapeutic mechanism of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) and try to discover new targets for alleviating neuropathic pain. Extracellular vesicles were isolated and identified via ultracentrifugation. BV-2 microglial cells were stimulated with lipopolysaccharide (LPS) in the presence or absence of MSC-EVs. Further, microglial activation and neuroinflammation were evaluated by flow cytometry, RT-qPCR, and ELISA. High-throughput sequencing analysis was performed to reveal the differentially expressed (DE) miRNAs in BV-2 microglia. Autophagy-related regulators were assessed by Western blotting and Immunofluorescence staining. Chronic constriction injury (CCI) model was used to induce neuropathic pain in rats, and the mechanical withdrawal threshold (MWT) was measured. High-throughput sequencing analysis identified 17 DE miRNAs, which were mainly enriched in PI3K-AKT and mTOR signaling pathways. MSC-EVs inhibited the activation of PI3K/AKT/mTOR signaling pathway in LPS-stimulated microglia. Moreover, MSC-EVs treatment enhanced the autophagy level in activated microglia, whereas autophagy inhibitor 3-MA reversed the suppressing effects of MSC-EVs on microglial activation and neuroinflammation. The MSC-EV-mediated transfer of miR-99b-3p was verified to promote microglial autophagy, and miR-99b-3p overexpression suppressed the expression of pro-inflammatory factors in activated microglia. During in vivo studies, intrathecal injection of MSC-EVs significantly up-regulated the expression of miR-99b-3p, and alleviated mechanical allodynia caused by activated microglia in the spinal cord dorsal horn of CCI rats. Moreover, MSC-EVs treatment repaired CCI-induced autophagic impairment by stimulating autophagy in the spinal cord. Collectively, our findings demonstrated that MSC-EVs had an analgesic effect on neuropathic pain via promoting autophagy, and these antinociceptive effects were at least in part caused by MSC-EV-mediated transfer of miR-99b-3p, thereby inhibiting microglial activation and pro-inflammatory cytokines expression.

Huc-MSCs-derived exosomes attenuate neuropathic pain by inhibiting activation of the TLR2/MyD88/NF-κB signaling pathway in the spinal microglia by targeting Rsad2.

BACKGROUND: Mesenchymal stem cells (MSCs)-derived exosomes have shown promise as a cell-free therapeutic strategy for neuropathic pain. This study was conducted to explore the potential mechanisms underlying the analgesic effects of MSC-derived exosomes in treating neuropathic pain. METHODS: Human umbilical cord MSCs (huc-MSCs)-derived exosomes were isolated and identified. BV-2 microglia were stimulated with lipopolysaccharide (LPS) in the presence or absence of exosomes. Differentially expressed proteins were identified by tandem mass tag (TMT)-based proteomic analysis. The analgesic effects of huc-MSCs-derived exosomes were evaluated in a rat model of chronic constriction injury (CCI). The underlying mechanism was investigated by flow cytometry, RT-qPCR, Western blotting, immunofluorescent staining, and small interfering RNA transfection. RESULTS: In vitro, huc-MSCs-derived exosomes suppressed LPS-induced microglial activation and inhibited activation of the TLR2/MyD88/NF-κB signaling pathway. Based on the proteomic analysis, Rsad2 was identified and confirmed to be down-regulated by huc-MSCs-derived exosomes. Importantly, knockdown of Rsad2 also inhibited microglial activation and restrained activation of the TLR2/MyD88/NF-κB signaling pathway. In vivo, intrathecal injection of exosomes ameliorated CCI-induced mechanical allodynia, down-regulated Rsad2 expression and restrained TLR2/MyD88/NF-κB signaling activation in the spinal microglia. CONCLUSION: Huc-MSCs-derived exosomes exerted analgesic effects on neuropathic pain by inhibiting activation of the TLR2/MyD88/NF-κB signaling pathway in the spinal microglia. The mechanism underlying these antinociceptive effects involved exosome-mediated interference with Rsad2 expression, thereby inhibiting microglial activation.

Clinical outcomes of bariatric surgery - Updated evidence.

Obesity has grown to become a major health problem over the past few decades. Obesity-related comorbidities, such as diabetes mellitus, hypertension, obstructive sleep apnea, and dyslipidemia, are inextricably linked with increased adverse clinical consequences and mortality. Compared with other strategies for obesity, bariatric surgery is efficient in weight loss and has been proved to exert positive effects on obesity-related risk factors. This broad improvement in risk factors has resulted in substantial remission or reductions of comorbidities and better performance on clinical outcomes, including cardiovascular diseases, cancer, and mortality. With the development of surgical procedures, the safety of bariatric surgery has been validated and the rate of peri-operative death is low all over the world. Nonetheless, surgeons ought to be careful about potential complications, such as nutrition deficiencies, psychological disorders, or new digestive tract tumors after surgery. For patients with obesity, bariatric surgery might be a precious and crucial tool to bring additional benefits including comorbidities protection and life span extension. All patients with obesity should be engaged in a union consultation group to select a suitable treatment.

Serine/Threonine-Protein Kinase 3 Facilitates Myocardial Repair After Cardiac Injury Possibly Through the Glycogen Synthase Kinase-3ß/ß-Catenin Pathway.

Background The neonatal heart maintains its entire regeneration capacity within days after birth. Using quantitative phosphoproteomics technology, we identified that SGK3 (serine/threonine-protein kinase 3) in the neonatal heart is highly expressed and activated after myocardial infarction. This study aimed to uncover the function and related mechanisms of SGK3 on cardiomyocyte proliferation and cardiac repair after apical resection or ischemia/reperfusion injury. Methods and Results The effect of SGK3 on proliferation and oxygen glucose deprivation/reoxygenation- induced apoptosis in isolated cardiomyocytes was evaluated using cardiomyocyte-specific SGK3 overexpression or knockdown adenovirus5 vector. In vivo, gain- and loss-of-function experiments using cardiomyocyte-specific adeno-associated virus 9 were performed to determine the effect of SGK3 in cardiomyocyte proliferation and cardiac repair after apical resection or ischemia/reperfusion injury. In vitro, overexpression of SGK3 enhanced, whereas knockdown of SGK3 decreased, the cardiomyocyte proliferation ratio. In vivo, inhibiting the expression of SGK3 shortened the time window of cardiac regeneration after apical resection in neonatal mice, and overexpression of SGK3 significantly promoted myocardial repair and cardiac function recovery after ischemia/reperfusion injury in adult mice. Mechanistically, SGK3 promoted cardiomyocyte regeneration and myocardial repair after cardiac injury by inhibiting GSK-3ß (glycogen synthase kinase-3ß) activity and upregulating ß-catenin expression. SGK3 also upregulated the expression of cell cycle promoting genes G1/S-specific cyclin-D1, c-myc (cellular-myelocytomatosis viral oncogene), and cdc20 (cell division cycle 20), but downregulated the expression of cell cycle negative regulators cyclin kinase inhibitor P 21 and cyclin kinase inhibitor P 27. Conclusions Our study reveals a key role of SGK3 on cardiac repair after apical resection or ischemia/reperfusion injury, which may reopen a novel therapeutic option for myocardial infarction.

Cardiotoxicity in cancer immune-checkpoint therapy: Mechanisms, clinical evidence, and management strategies.

Immune-checkpoint inhibitors (ICIs), a unique antibody-based therapeutic strategy, have revolutionized the treatment landscape of solid and hematological cancers. Despite the proven benefits of ICIs, the cardiotoxicity from unspecific immune activation (uncommon but potentially fatal) is a continuing concern. Accumulating preclinical research has demonstrated that ICIs initiate inflammation in the myocardium, while clinically significant cardiotoxicity were reported in few patients receiving ICI therapy, probably due to the low incidence and unspecific symptoms. The subtle signs and symptoms (e.g., chest pain, dizziness, and dyspnea) were likely attributed to cancer and/or non-cardiac events by previous studies, thus limiting the understanding of the incidence, outcomes, risk factors, and management of ICI-related cardiotoxicity. The heterogeneous clinical presentation and complex diagnostic procedure further make it challenging to accurately identify ICI-related cardiac events in clinical trials. Therefore, ICI-related cardiotoxicity, whose incidence is probably underestimated, has not been well recognized. In this article, we provide an overview of potential mechanisms underlying ICI-related cardiotoxicity and review accumulating clinical evidence of ICI-related cardiotoxicity, with a focus on myocarditis. Moreover, we discuss possible strategies to manage ICI-related cardiotoxicity and highlight the importance of developing cardio-oncology.

Identification of key genes in calcific aortic valve disease via weighted gene co-expression network analysis.

BACKGROUND: Calcific aortic valve disease (CAVD) is the most common subclass of valve heart disease in the elderly population and a primary cause of aortic valve stenosis. However, the underlying mechanisms remain unclear. METHODS: The gene expression profiles of GSE83453, GSE51472, and GSE12644 were analyzed by 'limma' and 'weighted gene co-expression network analysis (WGCNA)' package in R to identify differentially expressed genes (DEGs) and key modules associated with CAVD, respectively. Then, enrichment analysis was performed based on Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, DisGeNET, and TRRUST database. Protein-protein interaction network was constructed using the overlapped genes of DEGs and key modules, and we identified the top 5 hub genes by mixed character calculation. RESULTS: We identified the blue and yellow modules as the key modules. Enrichment analysis showed that leukocyte migration, extracellular matrix, and extracellular matrix structural constituent were significantly enriched. SPP1, TNC, SCG2, FAM20A, and CD52 were identified as hub genes, and their expression levels in calcified or normal aortic valve samples were illustrated, respectively. CONCLUSIONS: This study suggested that SPP1, TNC, SCG2, FAM20A, and CD52 might be hub genes associated with CAVD. Further studies are required to elucidate the underlying mechanisms and provide potential therapeutic targets.

Epigenetic role of N6-methyladenosine (m6A) RNA methylation in the cardiovascular system.

As the most prevalent and abundant transcriptional modification in the eukaryotic genome, the continuous and dynamic regulation of N6-methyladenosine (m6A) has been shown to play a vital role in physiological and pathological processes of cardiovascular diseases (CVDs), such as ischemic heart failure (HF), myocardial hypertrophy, myocardial infarction (MI), and cardiomyogenesis. Regulation is achieved by modulating the expression of m6A enzymes and their downstream cardiac genes. In addition, this process has a major impact on different aspects of internal biological metabolism and several other external environmental effects associated with the development of CVDs. However, the exact molecular mechanism of m6A epigenetic regulation has not been fully elucidated. In this review, we outline recent advances and discuss potential therapeutic strategies for managing m6A in relation to several common CVD-related metabolic disorders and external environmental factors. Note that an appropriate understanding of the biological function of m6A in the cardiovascular system will pave the way towards exploring the mechanisms responsible for the development of other CVDs and their associated symptoms. Finally, it can provide new insights for the development of novel therapeutic agents for use in clinical practice.

Shenfu injection attenuates lipopolysaccharide-induced myocardial inflammation and apoptosis in rats.

Shenfu injection (SFI), a Chinese medicinal product, shows potent efficacy in treating sepsis. The aim of the present study was to clarify the protective effects of SFI against lipopolysaccharide (LPS)-induced myocardial inflammation and apoptosis. Experiments were carried out in Sprague-Dawley (SD) rats treated with LPS or LPS + SFI, and in H9C2 cardiomyocytes. The sepsis-associated myocardial inflammation and apoptosis was induced by the intraperitoneal injection of LPS (20 mg·kg-1). SFI attenuated the increased expression of tumor necrosis factor (TNF)-α and interleukin (IL)-1ß induced by LPS both in serum and heart. In LPS group, cell viability was reduced, and reversed after SFI administration. LPS treatment increased the expression levels of cleaved-caspase 3 and Bax, and those of Bcl2 and Bcl2/Bax. These two trends were reversed by SFI administration. The expression levels of phosphorylated mitogen-activated protein kinase kinase (p-MEK) and phosphorylated extracellular regulated protein kinases (p-ERK) were increased by LPS, and reversed by SFI. MEK inhibitor U0126 attenuated the apoptosis induced by LPS. These results indicate that SFI could treat LPS-induced cardiac dysfunction. In conclusion, SFI attenuates the inflammation and apoptosis induced by LPS via downregulating the MEK and ERK signaling pathways.

Alamandine attenuates hypertension and cardiac hypertrophy in hypertensive rats.

Oral administration of the peptide alamandine has antihypertensive and anti-fibrotic effects in rats. This work aimed to determine whether subcutaneous alamandine injection would attenuate hypertension and cardiac hypertrophy, and improve the function of a major target of hypertension-related damage, the left ventricle (LV), in spontaneously hypertensive rats (SHRs). This was examined in vivo in SHRs and normotensive rats subjected to 6-week subcutaneous infusion of alamandine or saline control, and in vitro in H9C2-derived and primary neonatal rat cardiomyocytes treated with angiotensin (Ang) II to model cardiac hypertrophy. Tail artery blood pressure measurement and transthoracic echocardiography showed that hypertension and impaired LV function in SHRs were ameliorated upon alamandine infusion. Alamandine administration also decreased the mass gains of heart and lung in SHRs, suppressed cardiomyocyte cross-sectional area expansion, and inhibited the mRNA levels of atrial natriuretic peptide and brain natriuretic peptide. The expression of alamandine receptor Mas-related G protein-coupled receptor, member D was increased in SHR hearts and in cardiomyocytes treated with Ang II. Alamandine inhibited the increases of protein kinase A (PKA) levels in the heart in SHRs and in cardiomyocytes treated with Ang II. In conclusion, the present study showed that alamandine administration attenuates hypertension, alleviates cardiac hypertrophy, and improves LV function. PKA signaling may be involved in the mechanisms underlying these effects.

Correlation between Serum Calcineurin Activity and Left Ventricular Hypertrophy in Hypertensive Patients and Its Clinical Significance.

OBJECTIVE: The aim of this study is to investigate the correlation between calcineurin (CaN) and hypertension with left ventricular hypertrophy (HLVH) and to evaluate its potential clinical significance. DESIGN: The study involved 160 patients diagnosed with hypertension and 42 controls. Based on the exclusion criteria, 42 were not eligible for this study. The remaining 118 hypertensive patients were categorized into 2 subgroups based on left ventricular mass index and relative ventricular wall thickness: a normal model subgroup with hypertension (HNM) and an HLVH subgroup. Serum CaN levels were determined by enzyme-linked immunosorbent assay, while serum CaN activity was determined by malachite green colorimetric assay. RESULTS: Among the HNM and HLVH subgroups, a positive correlation was demonstrated between serum CaN activity, but not serum CaN level, and HLVH. Moreover, the HLVH subgroup displayed a remarkable increase in the levels of brain natriuretic peptide, cystatin C, urinary albumin/creatinine ratio, and left atrium diameter compared to the HNM subgroup and controls. CONCLUSION: There was a positive correlation between serum CaN activity and LVH in hypertensive patients. Activated CaN could play an important role in the pathophysiologic mechanism of HLVH. Serum CaN activity could be a clinically useful diagnostic and prognostic biomarker for LVH.

Bixin ameliorates high fat diet-induced cardiac injury in mice through inflammation and oxidative stress suppression.

Diabetic cardiomyopathy is known as an essential complication of diabetes, a main reason leading to mortality for diabetic patients, and novel therapeutic strategies for treatment are urgently required. Bixin (BX), isolated from the seeds of Bixa orellana, is a carotenoid, possessing anti-inflammatory, anti-tumor and anti-oxidant activities. In our study, we attempted to calculate the role of bixin in cardiac injury progression, and reveal the possible molecular mechanism. Bixin treatment ameliorated cardiac dysfunction through inhibiting fibrosis, inflammation and reactive oxygen species (ROS) generation. It reduced fibrosis levels via collagen deposition down-regulation. Inflammatory response was attenuated by reducing pro-inflammatory cytokines secretion via Toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) signaling pathway inactivation in mice induced by high fat diet. Also, in in vitro studies, lipopolysaccharide (LPS)-treated cardiac muscle cells exhibits pro-inflammatory cytokines over-expression, which was reduced by bixin through blocking TLR4/NF-κB pathway. Additionally, oxidative stress triggered by high fat in vivo and LPS in vitro was down-regulated for bixin administration via nuclear factor-E2-related factor 2 (Nrf2) signaling pathway activation. Our study suggested that bixin might be a novel and protective agent with therapeutic activity against cardiac injury by suppressing fibrosis, inflammation and oxidative stress.

Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats.

Li P, Huang P, Yang Y, Liu C, Lu Y, Wang F, Sun W, Kong X. Renal sympathetic denervation attenuates hypertension and vascular remodeling in renovascular hypertensive rats. J Appl Physiol 122: 121-129, 2017. First published October 14, 2016; doi:10.1152/japplphysiol.01019.2015-Sympathetic activity is enhanced in patients with essential or secondary hypertension, as well as in various hypertensive animal models. Therapeutic targeting of sympathetic activation is considered an effective antihypertensive strategy. We hypothesized that renal sympathetic denervation (RSD) attenuates hypertension and improves vascular remodeling and renal disease in the 2-kidney, 1-clip (2K1C) rat model. Rats underwent 2K1C modeling or sham surgery; then rats underwent RSD or sham surgery 4 wk later, thus resulting in four groups (normotensive-sham, normotensive-RSD, 2K1C-sham, and 2K1C-RSD). Norepinephrine was measured by ELISA. Echocardiography was used to assess heart function. Fibrosis and apoptosis were assessed by Masson and TUNEL staining. Changes in mean arterial blood pressure in response to hexamethonium and plasma norepinephrine levels were used to evaluate basal sympathetic nerve activity. The 2K1C modeling success rate was 86.8%. RSD reversed the elevated systolic blood pressure induced by 2K1C, but had no effect on body weight. Compared with rats in the 2K1C-sham group, rats in the 2K1C-RSD group showed lower left ventricular mass/body weight ratio, interventricular septal thickness in diastole, left ventricular end-systolic diameter, and left ventricular posterior wall thickness in systole, whereas fractional shortening and ejection fraction were higher. Right kidney apoptosis and left kidney hypertrophy were not changed by RSD. Arterial fibrosis was lower in animals in the 2K1C-RSD group compared with those in the 2K1C-sham group. RSD reduced plasma norepinephrine and basal sympathetic activity in rats in the 2K1C-RSD group compared with rats in the 2K1C-sham group. These results suggest a possible clinical efficacy of RSD for renovascular hypertension. NEW & NOTEWORTHY: The effects of renal sympathetic denervation (RSD) on hypertension, cardiac function, vascular fibrosis, and renal apoptosis were studied in the 2K1C rat model. Results showed that RSD attenuated hypertension, improved vascular remodeling, and reduced vascular fibrosis through decreased sympathetic activity in the 2K1C rat model, but it did not change the kidney size, renal apoptosis, or renal caspase-3 expression. These results could suggest possible clinical efficacy of RSD for renovascular hypertension.

Overexpression of FABP3 promotes apoptosis through inducing mitochondrial impairment in embryonic cancer cells.

Fatty acid-binding protein 3 (FABP3) is a low-molecular-weight protein with a distinct tissue distribution that may play an important role in fatty acid transport, cell growth, cellular signaling, and gene transcription. Previously, we have found that FABP3 was involved in apoptosis-associated congenital cardiac malformations, but the underlying mechanisms have not yet been described. In the present study, we investigated the characteristics of mitochondrial dysfunction in embryonic cancer cells (P19 cells) that overexpressed FABP3. We demonstrated that in FABP3-overexpressing P19 cells a lower cellular ATP production was accompanied by a dramatic decrease in mitochondrial membrane potential (MMP), despite the lack of a substantial decrease in the mtDNA copy number. In addition, FABP3 overexpression also led to an imbalance in mitochondrial dynamics and to excess intracellular reactive oxygen species production. Collectively, our results indicated that overexpression of FABP3 in P19 cells caused mitochondrion dysfunction that might be responsible for the development of FABP3-induced apoptosis.

Silencing of FABP3 promotes apoptosis and induces mitochondrion impairment in embryonic carcinoma cells.

Fatty acid binding protein 3 (FABP3) (also known as H-FABP) is a member of the intracellular lipid-binding protein family, and is mainly expressed in cardiac muscle tissue. The in vivo function of FABP3 is proposed to be in fatty acid metabolism, trafficking, and cell signaling. Our previous study found that FABP3 is highly regulated in patients with ventricular septal defect (VSD), and may play a significant role in the development of human VSD. In the present study, we aimed to investigate the impact of FABP3 knockdown by RNA interference (RNAi) on apoptosis and mitochondrial function of embryonic carcinoma (P19) cells. The results revealed that downregulated FABP3 expression promoted apoptosis, and resulted in mitochondrial deformation, increased mitochondrial membrane potential (MMP), and decreased intracellular ATP synthesis. In addition, the knockdown of FABP3 also led to excess intracellular ROS production. However, there was no obvious influence on the amount of mitochondrial DNA. Collectively, our results indicated that FABP3 knockdown promoted apoptosis and caused mitochondrial dysfunction in P19 cells, which might be responsible for the development of human VSD.

Expressing murine p56Hck(ca) promotes HeLa cells' motility and invasion via triggering redistribution of F-actin and microtubules.

Hck is the unique example among the Src PTKs to be expressed as two isoforms, which are generated by alternative translation. The two isoforms differs from each other by a 21 N-terminal amino acids sequence which supports myristoylation. Though it has been shown that these different acylation states govern the different subcellular localization of the isoforms and each Hck isoform could play a specific role, little study focus on the function of p56Hck. To investigated the role of p56Hck isoform in cell migration, GFP targeted p56Hck plasmid and its constitutively active form were constructed and transiently transfected into HeLa cells, F-actin staining and Indirect immunofluorescence for microtubules were then performed. Phagokinetic track motility assay and In vitro invasion assays were also investigated after transiently transfection respectively. In this study, we found ectopically expressing a constitutively active form of 56Hck will lead to membrane protrusion and F-actin reorganization in HeLa cells. Both 56Hck and its constitutive active form will lead to redistribution of microtubules and enhancement of cell motility and cell invasion. Hck inhibitor PP2 supplementation eliminated cell motility and cell invasion of p56Hck while PP3, a negative control of PP2 didn't eliminate cell motility and cell invasion of p56Hck. It is indicated that enhanced cell motility and cell invasion in p56Hck ectopically expressed HeLa cells are the results of reorganization of F-actin and microtubules.

Differential expression of microRNAs in cardiac myocytes compared to undifferentiated P19 cells.

microRNA (miRNA) expression is tightly controlled in a tissue-specific and developmental stage-specific manner; some are highly and specifically expressed in cardiovascular tissues. miRNA expression profiling, using miRNA microarrays facilitates studying the biological function of miRNAs. We investigated changes in miRNA expression profiles during differentiation of P19 cells into cardiac myocytes in order to elucidate the mechanisms of heart development. The morphology of P19 cells during differentiation was observed using an inverted microscope. Western blot analysis was performed to detect cardiac troponin I (cTnI) expression. Total RNA was extracted from P19 cells for microarray and real-time quantitative reverse transcription-polymerase chain reaction (real-time qRT-PCR) analyses to determine the miRNA expression profile. The miRNA microarray revealed differential expression of 49 miRNAs, of which 26 were down-regulated and 23 were up-regulated in differentiated cardiac myocytes, compared to normal P19 cells. This was confirmed by real-time qRT-PCR. We also utilized target prediction analysis to identify gene targets. Some miRNAs may have important roles in cardiac development and congenital heart defects (CHDs). Further analysis of miRNA function to confirm their target genes during cardiac development will determine the potential for novel miRNA-based therapeutic strategies.

Ginsenoside Rg1 promotes endothelial progenitor cell migration and proliferation.

AIM: To investigate the effect of ginsenoside Rg1 on the migration, adhesion, proliferation, and VEGF expression of endothelial progenitor cells (EPCs). METHODS: EPCs were isolated from human peripheral blood and incubated with different concentrations of ginsenoside Rg1 (0.1, 0.5, 1.0, and 5.0 micromol/L) and vehicle controls. EPC migration was detected with a modified Boyden chamber assay. EPC adhesion was determined by counting adherent cells on fibronectin-coated culture dishes. EPC proliferation was analyzed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In vitro vasculogenesis was assayed using an in vitro vasculogenesis detection kit. A VEGF-ELISA kit was used to measure the amount of VEGF protein in the cell culture medium. RESULTS: Ginsenoside Rg1 promoted EPC adhesion, proliferation, migration and in vitro vasculogenesis in a dose- and time-dependent manner. Cell cycle analysis showed that 5.0 micromol/L of ginsenoside Rg1 significantly increased the EPC proliferative phase (S phase) and decreased the resting phase (G(0)/G(1) phase). Ginsenoside Rg1 increased vascular endothelial growth factor production. CONCLUSION: The results indicate that ginsenoside Rg1 promotes proliferation, migration, adhesion and in vitro vasculogenesis.

A correlative study between prevalence of chondromalacia patellae and sports injury in 4068 students.

OBJECTIVE: To study the prevalence of chondromalacia patella among college students and the correlation with sports injury. METHODS: 354 students from gymnastic department and 429 from nongymnastic department with knee joint pain were selected. 184 students from gymnastic department and 342 from nongymnastic department were checked randomly by a surgeon. 77 patients (37 males, 40 females) from gymnastic department and 119 patients (62 males, 57 females) from nongymnastic department were diagnosed as chondromalacia patellae. The amount of exercise and the occurrence of sports injury were investigated in each student. All data were analyzed with SPSS 10.0 statistical software. RESULTS: The prevalence of chondromalacia patella was 20.1% in female students and 11.6% in male students from gymnastic department, and 5.61% in female students and 4.92% in male students from nongymnastic department. The amount of exercise and the occurrence of sports injury to the knee joint in students from gymnastic department were greater than those from nongymnastic department. CONCLUSIONS: In both female and male students, the prevalence of chondromalacia patella is higher in gymnastic department than nongymnastic department. Sports injury is an important cause of chondromalacia patella.