Results: The cytofluorimetric analysis of the expression of surfa

Results: The cytofluorimetric analysis of the expression of surface markers on S-MSCs revealed that they express the normal Selleck PKC412 pattern present on MSCs. Interestingly, these cells appeared to be successfully cryopreserved at early passages. Calcium imaging on single S-MSCs shows that these cells did not display significant spontaneous activity or a response to a depolarizing agent. However, ATP or acetylcholine-induced intracellular calcium increase via ionotropic or metabotropic receptors,

respectively. Conclusion: The results presented here reveal that S-MSCs show morphological and functional features that make them useful as an in vitro model to study cell differentiation. Copyright (C) 2009 S.

Karger AG, Basel”
“Background: Having a low level of education has been associated with worse physical performance. However, it is unclear whether this association varies by age, gender or the occupational categories of manual and non-manual work. This study examined whether there are education-related differences across four dimensions of physical performance by age, gender or occupational class and to what extent chronic diseases and lifestyle-related factors may explain such differences.\n\nMethods: Participants were a random sample of 3212 people, 60 years and older, both living in their own homes and in institutions, from the Swedish National Study on Aging and Care, in Kungsholmen, Stockholm. Trained nurses assessed physical performance in grip strength, walking speed, balance and chair stands, and gathered data on education, occupation and lifestyle-related factors, such as physical selleck inhibitor exercise, body

mass index, smoking and alcohol consumption. Diagnoses of chronic diseases were made by the examining physician.\n\nResults: Censored normal regression analyses showed that persons with university education had better grip strength, balance, chair stand time and walking speed than people with elementary school education. The differences in balance and walking speed remained statistically significant (p < 0.05) after adjustment for chronic diseases and lifestyle. However, age-stratified analyses revealed that the differences were no longer statistically significant in advanced age (80+ years). Gender-stratified analyses revealed that women with university education had significantly better grip strength, balance and walking speed compared to women with elementary school education and men with university education had significantly better chair stands and walking speed compared to men with elementary school education in multivariate adjusted models.

“The concept of hormesis in plants is critically reviewed,

“The concept of hormesis in plants is critically reviewed, taking growth stimulation by low concentrations of toxic trace elements as a reference. The importance of both non-adaptive and adaptive mechanisms underlying ion-induced hormetic growth responses is highlighted. The activation of defense mechanisms by metal ions and pathogenic elicitors and the cross talk between

the signals induced by metal ions and biotic stressors are considered. The production of reactive oxygen species and, consequently, the induction of stress-induced antioxidants, SB203580 research buy are key mechanisms in metal ion-induced hormesis in plants. It is concluded that in the current scientific literature, hormesis is used as an “umbrella” term that includes a wide range of different mechanisms. It is recommended that the term hormesis be used in plant toxicology as a descriptive term for the stimulated phase in growth response curves that is induced by low concentrations of toxic metal ions without evidence of the underlying mechanisms. If the mechanisms underlying the stimulated growth phase have been identified, specific terms, such as amelioration, defense gene activation, priming or acclimation, should be used. (C) 2013 Elsevier Ireland Ltd. All rights reserved.”
“The complex nature of plant resistance to adverse environmental conditions, such as salinity and drought

requires a better understanding of the stress-induced changes that may be involved in tolerance mechanisms. Here we investigate stress-related morpho-physiological effects during vegetative and find more reproductive growth in two Japonica rice cultivars (Bomba and Bahia) exposed to a range of NaCl concentrations from the seedling stage. The stress-related detrimental effects were observed either earlier or to a higher extent in cv. Bomba than in Bahia. Damages to the photosynthetic apparatus were related to loss of chlorophyll (Chl) and to a decrease of the maximum potential efficiency of PSII (F-v/F-m), affecting negatively net CO2 assimilation rate (P-N). Stress-related leaf anatomical alterations were A-1210477 concentration analysed during the vegetative and reproductive stages. The size of bulliform cells as well

as dimensions related to the vascular system increased under mild stress but decreased in the longer term or under higher stress level. The pattern of the anatomical alterations observed at the reproductive stage under 20 mM NaCl was reflected in poor panicle development and yield loss, with effects more pronounced in cv. Bomba than in Bahia. In summary, our results show that some physiological and, particularly, leaf anatomical responses induced by NaCl stress are distinctive indicators of sensitivity to salt stress in rice cultivars.”
“Trichosporon species are rare etiologic agents of invasive fungal infection in solid organ transplant (SOT) recipients. We report 2 well-documented cases of Trichosporon inkin invasive infection in SOT patients.

Our data suggest that BMP-2 treatment may have considerable

Our data suggest that BMP-2 treatment may have considerable

therapeutic potential in individuals with acute and chronic myocardial ischemia by improving the contractility of cardiomyocytes and preventing cardiomyocyte cell death.”
“Poly(lactic acid) (PLA) brushes were prepared through surface initiated ring-opening polymerization of L-lactide. Their degradation (depolymerization) was characterized by tracking their ellipsometric thickness as a function of time by repeated emersion from buffered, aqueous solutions. The pH and temperature both had a large effect on the rate of degradation. PLA brushes do not degrade in a manner similar to that of bulk PLA. Several experiments were performed, the results of which suggest that intramolecular transesterification (backbiting) was the pathway Cell Cycle inhibitor for the degradation of the PLA brush in basic, aqueous solution, similar to what has been observed for the depolymerization of PLA oligomers in basic solution. The PLA brushes degrade very slowly in acidic solution. This behavior is similar to the degradation of PLA oligomers NCT-501 mw in acidic solution.”
“Transesterification has proved to be the best option for obtaining biodiesel and, depending on the type of alcohol used in the reaction,

the type of biodiesel may be methyl ester or ethyl ester. Leaking biodiesel can reach water bodies, contaminating aquatic organisms, particularly fish. The objective of this study was to determine whether the soluble fraction of biodiesel (Bd), produced by both the ethylic (BdEt) and methylic (BdMt)

routes, can cause cytotoxic, biochemical and genotoxic alterations in the hepatocyte cell line of Danio rerio (ZFL). The metabolic activity of the cell was quantified by the KIT reduction method, while genotoxic damage was analyzed by the comet assay with the addition of specific endonucleases. HM781-36B ic50 The production of reactive oxygen species (ROS) and antioxidant/biotransformation enzymes activity also were determined. The results indicate that both Bd increased ROS production, glutathione S-transferase activity and the occurrence of DNA damage. BdMt showed higher cytotoxicity than BdEt, and also caused oxidative damage to the DNA. In general, both Bd appear to be stressors for the cells, causing cytotoxic, biochemical and genetic alterations in ZFL cells, but the type and intensity of the changes found appear to be dependent on the biodiesel production route. (C) 2014 Elsevier Ltd. All rights reserved.”
“Diabetic vascular pathology is largely attributable to impairments in tissue recovery from hypoxia. Circulating progenitor cells have been postulated to play a role in ischemic recovery, and deficiencies in these cells have been well described in diabetic patients.

Predefined target lesions were assessed for erythema, scaling, an

Predefined target lesions were assessed for erythema, scaling, and plaque thickness. Primary endpoint was the proportion of subjects in each treatment group who achieved treatment success after 8 weeks, analyzed on an intent-to-treat see more (ITT) basis. In the primary endpoint analysis, subjects missing 8-week outcomes data were classified as treatment failures regardless of their outcomes at earlier evaluations. As part of the sensitivity analysis, a last-observation-carried-forward (LOCF) approach to impute missing

8-week efficacy outcomes also examined treatment. Secondary endpoints included treatment success as a function of baseline ISGA score (mild or moderate), ISGA score of 0 or 1 (clear or almost clear), and effects of treatment on target lesion. Adverse events (AEs) were recorded throughout the study.\n\nResults: In the ITT population of Study I, treatment success after 8 weeks

was achieved by 14% of subjects in the calcipotriene foam group versus 7% of subjects in the vehicle foam group (p = 0.058). In the LOCF analysis, treatment success was achieved by more subjects with calcipotriene foam than with vehicle foam (15% vs 7%; p = 0.034). In Study 2, treatment success was achieved by more subjects in the calcipotriene foam group for the primary endpoint (27% vs 16%; p = 0.016) and the LOCF analysis (28% vs 16%; p = 0.010). GW4869 supplier Subjects in the calcipotriene foam group exhibited better response rates than did the vehicle foam group for most of the secondary outcomes. Calcipotriene foam was safe with an overall incidence of AEs similar to those experienced in the vehicle foam group. Application-site reactions were noted in approximately 1-2% of subjects in each group. No AE was reported in more than 2% of subjects in the calcipotriene foam group. Treatment was discontinued because of AEs in approximately 2% of subjects in both groups.\n\nConclusions: In two

identically designed, phase III clinical trials, calcipotriene 0.005% foam was safe and effective for the treatment of mild to moderate plaque-type psoriasis for up to 8 weeks.”
“For some phytophagous insects, egg maturation may be dependent on adult feeding. Accordingly, rates of egg maturation may be dependent on the quality and quantity of available food sources. In turn, oviposition behavior could be affected by diet quality via changes in egg load (number of mature eggs carried by a female). Experiments were conducted to determine whether adult feeding may affect oviposition behavior of the glassy-winged sharpshooter, Homalodisca vitripennis. No-choice tests demonstrated that eggs accumulated in glassy-winged sharpshooter abdomens as time since last oviposition increased largely as a function of feeding plant species.

We speculate that the impact of p L245F

We speculate that the impact of p.L245F GKT137831 supplier on BRAF protein

function differs either qualitatively or quantitatively from those mutations associated with CFCS. (C) 2009 Elsevier Masson SAS. All rights reserved.”
“Muramyl dipeptide (MDP), the NOD2 agonist, induces NF-kappa B and MAPK activation leading to the production of antimicrobial and proinflammatory molecules. MDP is internalized into acidified vesicles in macrophages. However, the endocytic mechanism of MDP uptake that induces NOD2 signaling is unknown. We now report the identification of an endocytosis pathway dependent on clathrin and dynamin that mediates MDP internalization and NOD2 activation. Intracellular MDP uptake was inhibited by chlorpromazine, a drug that disrupts clathrin-dependent endocytosis, but not by compounds that block pinocytosis or cellular entry via scavenger or mannose receptors. In contrast, MDP uptake and NOD2-dependent signaling were unimpaired in macrophages deficient in PepT1, a peptide transporter previously implicated in MDP internalization. Both chlorpromazine and knockdown of clathrin expression by RNA interference attenuated MDP-induced NF-kappa B and MAPK activation. Furthermore, MDP uptake and NOD2-dependent signaling learn more were impaired by inhibition of dynamin, a GTPase required for budding of clathrincoated vesicles from the plasma membrane. Finally, bafilomycin A, a specific inhibitor of the vacuolar

proton pump, blocked MDP accumulation in acidified vesicles and cytokine responses, suggesting that vacuolar maturation is important for MDP-induced NOD2 signaling. These studies provide evidence for a clathrin- and dynamin-dependent endocytosis pathway that mediates MDP uptake and NOD2 activation.

The Journal of Immunology, 2009, 182: 4321-4327.”
“Objective: The purpose of this study was to identify factors predicting growth and audiologic deterioration during follow-up (FU) in a wait and scan (W&S) policy of vestibular schwannomas (VSs) using a novel volumetric measuring tool. So far, only consecutive magnetic resonance imaging (MRI) is able to show growth objectively, and growth, combined with hearing function, generally dictates further intervention. Other factors predicting growth or hearing LY2835219 chemical structure deterioration would be invaluable and might ease clinical decision making.\n\nStudy Design: Retrospective case study.\n\nSetting: Tertiary referral center.\n\nPatients: Sixty-three patients diagnosed with VS at Maastricht University Medical Center between 2003 and 2008, with FU data available from 36 patients.\n\nIntervention(s): A W&S policy for unilateral VS with sequential contrast-enhanced T1- and T2-weighted MRI and audiograms during FU.\n\nMain Outcome Measure(s): 1. Patient and radiologic VS features potentially related to growth and auditory function during a W&S policy. 2. The correlation between increase in VS volume and audiologic deterioration during FU.

Information on self-reported tobacco use and readiness to integra

Information on self-reported tobacco use and readiness to integrate tobacco control education in the medical curriculum was collected from both the faculty and students using a pretested structured questionnaire. Multiple logistic regression analysis was done to find the associated factors. Results. Current smoking was reported by 9.0% (95% CI 6.6-12.1) of men faculty and 13.7% (CI 11.8-15.9) by men students. Faculty who were teaching tobacco-related topics [odds ratio (OR) 2.29; 95% CI 1.65-3.20] compared to those who Selleckchem JQ1 were not, faculty in government colleges (OR 1.69; CI 1.22-2.35) compared to those in private colleges and medical specialists (OR 1.79; CI 1.23-2.59) compared to surgical and non-clinical

specialists were more likely

to be ready to integrate tobacco control education in the medical curriculum. Non-smoking students (OR 2.58; CI 2.01-3.33) compared to smokers, and women students (OR 1.80; CI 1.50-2.17) compared to men were more likely to be ready to integrate a tobacco control education in the curriculum. Conclusion. Faculty and students are receptive to introduce tobacco control in the medical curriculum. Government faculty, medical specialists and faculty who already teach tobacco-related topics are likely to be early introducers of this new curriculum.”
“Background. The Facial Disability Index (FDI) is widely used for self-assessment of functional impairment and quality of life in patients with facial palsy. Objective. The study aim was to complete the validation of the FDI by generating an Italian version (IT-FDI) BLZ945 supplier and evaluating its clinimetric properties. Design. This was a longitudinal, observational measurement study. Methods. The questionnaire was translated, cross-culturally adapted, and administered to 100 consecutive participants (outpatients) with facial palsy. The ERK inhibitor libraries clinical severity of facial palsy, impairments in physical and social function, and quality of life were evaluated with the Sunnybrook Facial Grading System, IT-FDI, and 12-Item Short-Form

Health Survey. Results. The IT-FDI showed excellent test-retest reliability for every item and for total scores (intraclass correlation coefficients of 93 and .84 for physical function subscale and social/well-being function subscale, respectively). The IT-FDI confirmed the high internal consistency of the original version, with theta coefficients of .82 for the physical function subscale and .78 for the social/well-being function subscale. The physical function subscale correlated with the Sunnybrook Facial Grading System composite score (r=.44), and the social/well-being function subscale correlated with the 12-Item Short-Form Health Survey mental component (r=.55). The IT-FDI confirmed the good responsiveness of the original version, as expressed by effect size, standardized response mean, and responsiveness ratio of, respectively, 1, 1.

With a median follow-up after surgery

of 78 5 months, the

With a median follow-up after surgery

of 78.5 months, the 5-year OS and DSS were 65% and 68%, respectively. Twenty-nine patients (56%) died during follow-up, of whom 24 (46%) died of thyroid cancer. Six patients (12%) developed recurrent disease in the lateral neck, and three patients (6%) developed recurrence in the thyroid bed. Over 45 years, follicular pathology and extrapulmonary metastases Alvocidib order were predictive of lower 5-year DSS (56% vs. 100%, p < 0.001; 50% vs. 70%, p = 0.004; and 46% vs. 75%, p = 0.013, respectively).\n\nConclusion: Approximately half of patients with WDTC presenting with distant metastases die of disease within 5 years of initial diagnosis despite thyroid surgery and RAI. Age over 45 years, extrapulmonary metastases, and follicular pathology were significant predictors of the poor outcome.”
“Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue sarcoma. Although it has been regarded as a low-grade sarcoma unassociated with tumor-related death, a recent study has suggested an insidious nature with a high propensity for relapse during a long disease course. The aim of this study

was to clarify the long-term clinical features of EMC treated at a single referral center using state-of-the-art techniques.\n\nA retrospective review of 23 consecutive patients (10 males, 13 females; mean age 58 years) treated between 1979 and 2008 (mean follow-up; 109 months) was performed.\n\nSurgery for the primary tumor was performed in 22 patients, and 7 cases recurred locally due to inadequate resection. Eleven patients had metastatic disease, either at diagnosis (3) or developing later (8). The 5/10-year overall survival rates were 91/84 %, and the 5/10-year local recurrence-free Dihydrotestosterone cell line and metastasis-free survival rates for patients with localized disease were 89/62

and 89/61 %, respectively. Larger tumor size (> 10 cm) and metastases at diagnosis were significant negative prognostic factors. Four patients received ifosfamide-based chemotherapy with no objective response. There was no local recurrence in three patients who underwent R1 resection followed by adjuvant radiotherapy. Clinical palliation and retarded progression of the metastatic disease were achieved in three patients who underwent radiotherapy.\n\nEMC is indolent but has a high propensity for relapse over 5 years of follow-up. Definitive initial surgery and careful monitoring for a prolonged period are important. Radiotherapy seems beneficial in an adjuvant setting and as palliative therapy for metastatic disease.”
“A novel bioactive molecule for use in vector control is the need of the hour. Plants hold the key to such molecules which provide an alternative approach for producing a larvicidal product from plant sources. In the present study the larvicidal activity of leaf extracts of B.

For patients who did not achieve CR at interim staging, PFS for R

For patients who did not achieve CR at interim staging, PFS for R-HyperCVAD alone was 1.4 years vs not reached for R-HyperCVAD+ consolidation (either R maintenance or auto-SCT) (P = 0.02). PFS for patients with CR at interim staging was 3.3 years vs not reached (P = 0.04) after consolidation. Our data suggest potential improvement in PFS when R-HyperCVAD is consolidated with either R maintenance or auto-SCT.

This benefit appears particularly significant in those patients who do not achieve CR at interim restaging.”
“Targeted gene delivery using nonviral vectors is a highly touted scheme to reduce the potential for toxic or immunological side effects by reducing dose. In previous reports, Selleck CDK inhibitor TAT polyplexes with DNA have shown relatively poor gene delivery. The transfection efficiency has been enhanced by condensing TAT/DNA complexes to a small particle size using calcium. To explore the targetability of these condensed this website TAT complexes, LABL peptide targeting intercellular

cell-adhesion molecule-1 (ICAM-1) was conjugated to TAT peptide using a polyethylene glycol (PEG) spacer. PEGylation reduced the transfection efficiency of TAT, but TAT complexes targeting ICAM-1 expressing cells regained much of the lost transfection efficiency. Targeted block peptides properly formulated with calcium offer promise for gene delivery to ICAM-1 expressing cells at sites of injury or inflammation.”
“The loci detected by association mapping which are involved in the expression of important agronomic traits in crops often explain only a small proportion of the total genotypic variance. Here,

17 SNPs derived from 9 candidate genes from the triacylglycerol GSK126 clinical trial biosynthetic pathway were studied in an association analysis in a population of 685 diverse elite rapeseed inbred lines. The 685 lines were evaluated for oil content, as well as for glucosinolates, yield, and thousand-kernel weight in field trials at 4 locations. We detected main effects for most of the studied genes illustrating that genetic diversity for oil content can be exploited by the selection of favorable alleles. In addition to main effects, both intergenic and intragenic epistasis was detected that contributes to a considerable amount to the genotypic variance observed for oil content. The proportion of explained genotypic variance was doubled when in addition to main effects epistasis was considered. Therefore, a knowledge-based improvement of oil content in rapeseed should also take such favorable epistatic interactions into account. Our results suggest, that the observed high contribution of epistasis may to some extent explain the missing heritability in genome-wide association studies.”
“Aim:To investigate the relationship between androgens and prostate cancer in patients scheduled for radical prostatectomy. Subjects and Methods: Patients scheduled for open radical prostatectomy were enrolled.

The results suggest that rapid effects of cortisol may lead to im

The results suggest that rapid effects of cortisol may lead to impaired emotional memory contextualization, while slow effects of cortisol may confer protection against emotional memory generalization.”
“Objective: To determine the efficacy of a long-acting oxyntomodulin (OXM) analogue, OXM6421, in inhibiting food intake and decreasing body weight in lean and diet-induced obese (DIO) rodents.\n\nResearch design and methods: The

glucagon-like peptide-1 (GLP-1) receptor binding affinity and efficacy, sensitivity to enzymatic degradation in vitro and persistence in the circulation after peripheral administration were investigated for OXM6421 and compared with native OXM. The chronic effect of OXM6421 on food intake, body weight and energy expenditure was examined in lean rats, and its anti-obesity GSK2879552 research buy potential

LY411575 molecular weight was evaluated in DIO mice.\n\nResults: OXM6421 showed enhanced GLP-1 receptor binding affinity and cyclic adenosine monophosphate (cAMP) stimulation, and higher resistance to enzymatic degradation by dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidase (NEP) compared with native OXM. OXM6421 persisted longer in the circulation than OXM after peripheral administration. Acute administration of OXM6421 potently inhibited food intake in lean rodents, with cumulative effects lasting up to 24 h. In lean rats, daily subcutaneous (s.c.) administration of OXM6421 caused greater weight loss than the pair-fed animals, and a higher rate of oxygen consumption Vorinostat Epigenetics inhibitor than both the pair-fed and the saline controls. In DIO mice, continuous s.c. infusion of OXM6421 resulted in a significant weight loss, accompanied by an improvement in glucose homeostasis and an increase in circulating adiponectin levels. Once-daily s.c. administration of OXM6421 for 21 days caused sustained weight loss in DIO mice.\n\nConclusion:

OXM6421 induces negative energy balance in both lean and obese rodents, suggesting that long-acting OXM analogues may represent a potential therapy for obesity. International Journal of Obesity (2010) 34, 1715-1725; doi:10.1038/ijo.2010.110; published online 8 June 2010″
“Pactola fiji sp. n. is the first species from the tribe Eugnomini described from the Fiji Archipelago. A description, with illustrations and data about the general distribution of the genus, are provided. The genus Pactola Pascoe, 1876 now contains eleven species distributed on New Zealand, New Caledonia and Taevuni Island (Fiji Archipelago).”
“Fenton technologies for wastewater treatment have demonstrated their effectiveness in eliminating toxic compounds. This study examines how hydrogen peroxide concentration and ultraviolet (UV) light affects oxidation processes. However, total mineralization through these Fenton technologies is expensive compared with biological technologies. Therefore, partial chemical oxidation of toxic wastewaters with Fenton processes followed by biological units may increase the application range of Fenton technologies.

10 ppm O(3) (Heat + O(3)) Blood samples and nasal lavage were co

10 ppm O(3) (Heat + O(3)). Blood samples and nasal lavage were collected post-exercise and analyzed for inflammatory, epithelial damage and oxidative stress markers. Data were analyzed using repeated measures ANOVA with Tukey’s post hoc test. A significant increase in CC16 concentration (P < 0.05) and GSH/protein concentration (P < 0.05) in the upper respiratory airways was observed HDAC assay following the 8 km run in the Heat + O(3) trial compared with the control trial. There were no differences in the neutrophil counts between trials. No differences were observed for the other antioxidants analyzed.

A hot, humid and ozone-polluted environment (0.1 ppm) elicits an early epithelial damage and antioxidant protection process in the upper respiratory airways

of athletes immediately after performing 8 km time trial run.”
“A 74-year-old woman had carcinoma of her right breast for which Alvocidib order surgery was performed. Four weeks following the start of tamoxifen therapy, she developed papules and plaques over her face, trunk and limbs. A skin biopsy showed perivascular and periadnexal mixed inflammatory cellular infiltrate with fibroplasia. Notably, the dermis also showed squamous epithelial islands, which in foci were noted to be closely associated with eccrine epithelium. This was confirmed with double peroxidase alkaline phosphatase immunohistochemistry the eccrine lumina highlighted with carcinoembryonic antigen learn more (polyclonal) and the squamous metaplasia positive for cytokeratin 5/6. Eccrine squamous syringometaplasia was diagnosed. With close clinicopathological correlation, the cutaneous eruption was attributed to tamoxifen. Following discontinuation of the drug, the eruption resolved. Eccrine squamous syringometaplasia has been reported to occur in association with diverse conditions, including skin ulcers, burns and as a cutaneous adverse drug reaction, most commonly to chemotherapeutic drugs. This is believed to be the first report involving tamoxifen.”
“Hypoxia is one way of inducing differentiation due to the activation of the key regulatory factor, Hypoxia-inducible factor

1 alpha (HIF-1 alpha). However, the action of HIF-1 alpha on the differentiation of hESCs was unclear until now. To investigate the effect of hypoxia on the differentiation of hESCs, we compared the differentiation efficacy into vascular lineage cells under normoxic and hypoxic conditions. We observed HIF-1 alpha expression and the related expression of pro-angiogenic factors VEGF, bFGF, Ang-1 and PDGF in hEBs cultured under hypoxic conditions. Along with this, differentiation efficacy into vascular lineage cells was improved under hypoxic conditions. When HIF-1 alpha was blocked by echinomycin, both angiogenic factors and the differentiation efficacy were down-regulated, suggesting that the enhancement of differentiation efficacy was caused by intrinsic up-regulation of HIF-1 alpha and these pro-angiogenic factors under hypoxic condition.