Ursolic Acid's Alluring Journey: One Triterpenoid vs. Cancer Hallmarks.

Cancer is a multifactorial disease characterized by various hallmarks, including uncontrolled cell growth, evasion of apoptosis, sustained angiogenesis, tissue invasion, and metastasis, among others. Traditional cancer therapies often target specific hallmarks, leading to limited efficacy and the development of resistance. Thus, there is a growing need for alternative strategies that can address multiple hallmarks concomitantly. Ursolic acid (UA), a naturally occurring pentacyclic triterpenoid, has recently emerged as a promising candidate for multitargeted cancer therapy. This review aims to summarize the current knowledge on the anticancer properties of UA, focusing on its ability to modulate various cancer hallmarks. The literature reveals that UA exhibits potent anticancer effects through diverse mechanisms, including the inhibition of cell proliferation, induction of apoptosis, suppression of angiogenesis, inhibition of metastasis, and modulation of the tumor microenvironment. Additionally, UA has demonstrated promising activity against different cancer types (e.g., breast, lung, prostate, colon, and liver) by targeting various cancer hallmarks. This review discusses the molecular targets and signaling pathways involved in the anticancer effects of UA. Notably, UA has been found to modulate key signaling pathways, such as PI3K/Akt, MAPK/ERK, NF-κB, and Wnt/ß-catenin, which play crucial roles in cancer development and progression. Moreover, the ability of UA to destroy cancer cells through various mechanisms (e.g., apoptosis, autophagy, inhibiting cell growth, dysregulating cancer cell metabolism, etc.) contributes to its multitargeted effects on cancer hallmarks. Despite promising anticancer effects, this review acknowledges hurdles related to UA's low bioavailability, emphasizing the need for enhanced therapeutic strategies.

Chemical composition and biological potential of Thymus Willdenowii Boiss. & Reut. essential oil.

The fresh aerial parts of Thymus willdenowii Boiss. & Reut. (syn. Thymus hirtus Willd.) were hydrodistilled in a Clevenger type apparatus and analyzed by GC and GC-MS. 44 Components were identified representing 97.3%, with 1,8-cineole (34.62%), camphor (18.55%), α-pinene (9.46%) and camphene (5.38%) as the main components. T. willdenowii essential oil was not cytotoxic (CC50 = 97.65 µg/mL) towards Vero non-tumoural cells, exhibiting good antibacterial and antiproliferative (30.8 ± 3.1% inhibition) potentials against four tested pathogenic bacteria and Human colorectal cell line HT-29, respectively. The essential oil did not show a DPPH radical scavenging activity, by Electron Spin Resonance spectroscopy (ESR), and it lacks antiviral effect towards coxsackievirus B3.

Public health implication of solid waste generated by households in Bekwarra Local Government area.

BACKGROUND: This study was conducted in Bekwarra Local Government Area of Cross River State, Nigeria, to determine the public health implication of solid waste generated by households. METHODS: A cross sectional descriptive design was employed, using a semi-structured questionnaire together with an observation checklist to elicit information from the respondents. Proportionate sampling was used to select 400 respondents of 18 years and above for the study area. Data collected were analysed using the Microsoft Excel 2007 and Statistical Package for Social Sciences (SPSS) software version 20. RESULTS: Respondents knowledge concerning solid waste disposal was assessed and the results showed that majority of the respondents 193 (63.7%) had high level of knowledge of solid waste disposal, while 170 (42.5%) had average level of knowledge of solid waste disposal. Wastes produced by households in the study include vegetables (95.5%), ash (94%), clothing/rag (94.2%), wood (95%), and animal waste (86.2%) had the highest abundance. Diseases associated with these wastes produced by households include cholera (18.2%), malaria (47.2%), lassa fever (10.7%) and diarrhea (23.9%) with malaria been the most prevalence infection. CONCLUSION: The result shows solid waste posed a serious health hazard and lead to the spread of infectious diseases. These issues can be addressed through health education and enlightenment of the people on waste disposal.

Association of calcium density in the thoracic aorta with risk factors and clinical events.

OBJECTIVES: In the ascending aorta, calcification density was independently and inversely associated with cardiovascular disease (CVD) risk prediction. Until now, the density of thoracic aorta calcium (TAC) was estimated as the Agatston score divided by the calcium area (DAG). We thought to analyze TAC density in a full Hounsfield unit (HU) range and to study its association with TAC volume, traditional risk factors, and CVD events. METHODS: Non-enhanced CT images of 1426 patients at intermediate risk were retrospectively reviewed. A calcium density score was estimated as the average of the maximum HU attenuation in all calcified plaques of the entire thoracic aorta (DAV). RESULTS: During a mean 4.0 years follow-up, there were 26 events for a total of 674 patients with TAC > 0. TAC volume and DAV were positively correlated (R = 0.72). The median DAV value was 457 HU (IQ 323-603 HU) and was exponentially related to DAG (R = 0.86). DAV was inversely associated with systolic pressure (p < 0.05), pulse pressure (p < 0.01), hypertension (p < 0.05), and 10-year FRS (p < 0.001) after adjusting for TAC volume. When TAC volume and DAV were included in a logistic model, a significant improvement was shown in CVD risk estimation beyond coronary artery calcium (CAC) (AUC = 0.768 vs 0.814, p < 0.05). In multivariable Cox models, TAC volume and DAV showed an independent association with CVD. CONCLUSIONS: In intermediate risk patients, TAC density was inversely associated with several risk factors after adjustment for TAC volume. A significant improvement was observed over CAC when TAC volume and density were added into the risk prediction model. KEY POINTS: • Calcifications in the aorta can be non-invasively assessed using CT images • A higher calcium score is associated with a higher cardiovascular risk • Measuring the calcifications size and the density separately can improve the risk prediction.

Antitumoral activity of Ficus carica L. on colorectal cancer cell lines.

In traditional medicine, Ficus carica (also known as fig) latex is recognized as a remedy with various therapeutic effects. In the present study we investigated the antitumor activity of Ficus carica extracts and latex. We evaluated the effects of increasing concentrations of Ficus carica extracts and latex on HCT-116 and HT-29 human colorectal cell proliferation using MTT assay and apoptosis induction by evaluating PARP cleavage by Western blot analysis. Peel, pulp, leaves, whole fruit and latex extracts of Ficus carica exerted significant antiproliferative effects on HCT-116 (IC50 values 239, 343, 177, 299, 206 µg/ml) and HT-29 cells (IC50 values 207, 249, 230, 261, 182 µg/ml) after 48h of treatment. Furthermore, treatment with different extracts of Ficus carica induced apoptosis in both HT-29 and HCT-116 cancer cells. Leaves and latex extracts of Ficus carica showed the strongest antiproliferative activities. Overall, our results showed that these natural products are strong apoptosis inducers which suggest their use of for therapeutic purposes.

Age-related changes of thoracic aorta geometry used to predict the risk for acute type B dissection.

AIMS: Risk models that use a single aortic diameter threshold have failed to successfully predict acute type B aortic dissection (TBAD). We sought to identify meaningful age-indexed anatomical variables to predict TBAD risk. METHODS AND RESULTS: A geometric deformable model, consisting of virtual elastic balloons that inflate inside a vessel lumen, was developed to quantify thoracic aorta geometry. In the presence of TBAD, true and total artery lumen morphology were assessed. A stepwise logistic model was built to predict TBAD risk. Initial covariates included age, gender, body mass index and all anatomic variables not directly related to the dissected segment. Patients with acute TBAD (n=34, 62±12years old, 57% male gender) were compared with subjects with symptoms of dissection, but with a subsequent negative diagnosis (n=51, 62±12years old, 76% male gender). Patient risk factors did not differ between groups. Most aortic anatomical variables were age-dependent. Aortic size was larger in every segment of the dissected with respect to non-dissected aortas (p<0.001). Variables entering the TBAD risk prediction model were aortic arch diameter, thoracic aorta length and age (predictability=0.9764, r=0.85), confirmed by a bootstrap internal validation. In dissected aortas, the true lumen volume was correlated to age (r=0.72). CONCLUSIONS: TBAD probability increases with a larger aortic arch diameter and a longer thoracic aorta, whereas threshold values increase with age. The aortic morphology was age-dependent. After dissection, true lumen volume correlated to age. The use of threshold values indexed to age should be encouraged to better prevent and eventually treat TBAD.

Asociación entre el calcio de la aorta torácica y la geometría de esta en una cohorte de sujetos asintomáticos con riesgo cardiovascular aumentado / Association between thoracic aorta calcium and thoracic aorta geometry in a cohort of asymptomatic participants at increased cardiovascular risk

Introducción y objetivos: La detección del calcio de la aorta torácica mejora la predicción del riesgo cardiovascular, en cuanto a los eventos cardiacos y no cardiacos, respecto a la obtenida solo con los factores de riesgo tradicionales. En este trabajo se ha investigado la influencia de la morfometría de la aorta torácica en la presencia y la magnitud de las calcificaciones aórticas. Métodos: Se realizaron exploraciones por tomografía computarizada cardiaca sin contraste en 970 participantes asintomáticos con riesgo cardiovascular aumentado. Se utilizó un algoritmo automático para estimar la geometría de toda la aorta torácica y se cuantificó la puntuación de Agatston del calcio aórtico. Se utilizó un modelo no paramétrico para analizar los percentiles de la puntuación de calcio según la edad. Se calcularon modelos de regresión logística para identificar asociaciones anatómicas con las concentraciones de calcio. Resultados: Las calcificaciones se concentraron en el cayado aórtico y la aorta descendente. Las mayores cantidades de calcio se asociaron con una aorta agrandada, desplegada, con menor estrechamiento y más tortuosa. El tamaño de la aorta ascendente no mostró correlación con la puntuación de calcio de la aorta, mientras que el tamaño de la aorta descendente es el parámetro que mostró mayor asociación: el riesgo de tener una puntuación de calcio global superior al percentil 90 fue 3,62 veces (intervalo de confianza, 2,30-5,91; p < 0,001) mayor por cada 2,5 mm de aumento del diámetro de la aorta descendente. La reducción gradual del diámetro, la tortuosidad, el despliegue y los volúmenes del cayado aórtico y la aorta descendente estaban correlacionados con mayor cantidad de calcio. Conclusiones: Las calcificaciones se hallaron predominantemente en el cayado aórtico y la aorta descendente y mostraron asociación positiva con el tamaño de la aorta descendente y el cayado aórtico, pero no con el tamaño de la aorta ascendente. Estas observaciones indican que la dilatación aórtica puede tener mecanismos diferentes y, por consiguiente, requiere estrategias preventivas distintas según el segmento considerado (AU)

Introduction and objectives: Thoracic aorta calcium detection is known to improve cardiovascular risk prediction for cardiac and noncardiac events beyond traditional risk factors. We investigated the influence of thoracic aorta morphometry on the presence and extent of aortic calcifications. Methods: Nonenhanced computed tomography heart scans were performed in 970 asymptomatic participants at increased cardiovascular risk. An automated algorithm estimated the geometry of the entire thoracic aorta and quantified the aortic calcium Agatston score. A nonparametric model was used to analyze the percentiles of calcium score by age. Logistic regression models were calculated to identify anatomical associations with calcium levels. Results: Calcifications were concentrated in the aortic arch and descending portions. Higher amounts of calcium were associated with an enlarged, unfolded, less tapered and more tortuous aorta. The size of the ascending aorta was not correlated with aortic calcium score, whereas enlargement of the descending aorta had the strongest association: the risk of having a global calcium score > 90th percentile was 3.62 times higher (confidence interval, 2.30-5.91; P < .001) for each 2.5-mm increase in descending aorta diameter. Vessel taper, tortuosity, unfolding and aortic arch and descending volumes were also correlated with higher amounts of calcium. Conclusions: Thoracic aorta calcium was predominantly found at the arch and descending aorta and was positively associated with the size of the descending aorta and the aortic arch, but not with the size of the ascending aorta. These findings suggest that aortic dilatation may have different mechanisms and may consequently require different preventive strategies according to the considered segments (AU)

Resistance to ursolic acid-induced apoptosis through involvement of melanogenesis and COX-2/PGE2 pathways in human M4Beu melanoma cancer cells.

Melanoma is one of the most aggressive forms of cancer with a continuously growing incidence worldwide and is usually resistant to chemotherapy agents, which is due in part to a strong resistance to apoptosis. Previously, we had showed that B16-F0 murine melanoma cells undergoing apoptosis are able to delay their own death induced by ursolic acid (UA), a natural pentacyclic triterpenoid compound. We had demonstrated that tyrosinase and TRP-1 up-regulation in apoptotic cells and the subsequent production of melanin were implicated in an apoptosis resistance mechanism. Several resistance mechanisms to apoptosis have been characterized in melanoma such as hyperactivation of DNA repair mechanisms, drug efflux systems, and reinforcement of survival signals (PI3K/Akt, NF-κB and Raf/MAPK pathways). Otherwise, other mechanisms of apoptosis resistance involving different proteins, such as cyclooxygenase-2 (COX-2), have been described in many cancer types. By using a strategy of specific inhibition of each ways, we suggested that there was an interaction between melanogenesis and COX-2/PGE2 pathway. This was characterized by analyzing the COX-2 expression and activity, the expression of tyrosinase and melanin production. Furthermore, we showed that anti-proliferative and proapoptotic effects of UA were mediated through modulation of multiple signaling pathways including Akt and ERK-1/2 proteins. Our study not only uncovers underlying molecular mechanisms of UA action in human melanoma cancer cells but also suggest its great potential as an adjuvant in treatment and cancer prevention.

Association Between Thoracic Aorta Calcium and Thoracic Aorta Geometry in a Cohort of Asymptomatic Participants at Increased Cardiovascular Risk.

INTRODUCTION AND OBJECTIVES: Thoracic aorta calcium detection is known to improve cardiovascular risk prediction for cardiac and noncardiac events beyond traditional risk factors. We investigated the influence of thoracic aorta morphometry on the presence and extent of aortic calcifications. METHODS: Nonenhanced computed tomography heart scans were performed in 970 asymptomatic participants at increased cardiovascular risk. An automated algorithm estimated the geometry of the entire thoracic aorta and quantified the aortic calcium Agatston score. A nonparametric model was used to analyze the percentiles of calcium score by age. Logistic regression models were calculated to identify anatomical associations with calcium levels. RESULTS: Calcifications were concentrated in the aortic arch and descending portions. Higher amounts of calcium were associated with an enlarged, unfolded, less tapered and more tortuous aorta. The size of the ascending aorta was not correlated with aortic calcium score, whereas enlargement of the descending aorta had the strongest association: the risk of having a global calcium score > 90th percentile was 3.62 times higher (confidence interval, 2.30-5.91; P < .001) for each 2.5-mm increase in descending aorta diameter. Vessel taper, tortuosity, unfolding and aortic arch and descending volumes were also correlated with higher amounts of calcium. CONCLUSIONS: Thoracic aorta calcium was predominantly found at the arch and descending aorta and was positively associated with the size of the descending aorta and the aortic arch, but not with the size of the ascending aorta. These findings suggest that aortic dilatation may have different mechanisms and may consequently require different preventive strategies according to the considered segments.

Resistance to 3-HTMC-Induced Apoptosis Through Activation of PI3K/Akt, MEK/ERK, and p38/COX-2/PGE2 Pathways in Human HT-29 and HCT116 Colorectal Cancer Cells.

Increasing incidence and mortality of colorectal cancer brings the necessity to uncover new possibilities in its prevention and treatment. Chalcones have been identified as interesting compounds having chemopreventive and antitumor properties. In this study, we investigated the effects of the synthetic chalcone derivative 3-hydroxy-3',4,4',5'-tetra-methoxy-chalcone (3-HTMC) on proliferation, cell cycle distribution, apoptosis, and its mechanism of action in human colorectal HT-29 (COX-2 sufficient) and HCT116 (COX-2 deficient) cancer cells. We showed that 3-HTMC decreased cell viability in a dose-dependent manner with a more potent antiproliferative effect on HCT116 than HT-29 cells. Flow cytometric analysis revealed G2 /M cell cycle accumulation in HT-29 cells and significant G2 /M arrest in HCT116 cells with a subsequent apoptosis shown by appearance of Sub-G1 peak. We demonstrated that 3-HTMC treatment on both cell lines induced apoptotic process associated with overexpression of death receptor DR5, activation of caspase-8 and -3, PARP cleavage, and DNA fragmentation. In addition, 3-HTMC induced activation of PI3K/Akt and MEK/ERK principal survival pathways which delay 3-HTMC-induced apoptosis in both cell lines. Furthermore, COX-2 overexpression in HT-29 cells contributes to apoptosis resistance which explains the difference of sensitivity between HT-29 and HCT116 cells to 3-HTMC treatment. Even if resistance mechanisms to apoptosis reduced chalcone antitumoral potential, our results suggest that 3-HTMC may be considered as an interesting compound for colorectal cancer therapy or chemoprevention. J. Cell. Biochem. 117: 2875-2885, 2016. © 2016 Wiley Periodicals, Inc.

Crataegus azarolus Leaves Induce Antiproliferative Activity, Cell Cycle Arrest, and Apoptosis in Human HT-29 and HCT-116 Colorectal Cancer Cells.

Limited success has been achieved in extending the survival of patients with metastatic colorectal cancer (CRC). There is a strong need for novel agents in the treatment and prevention of CRC. Therefore, in the present study we evaluated the antiproliferative and pro-apoptotic potential of Crataegus azarolus ethyl acetate extract in HCT-116 and HT-29 human colorectal cancer cell lines. Moreover, we attempted to investigate the signaling pathways that should be involved in its cytotoxic effect. The Crataegus azarolus ethyl acetate extract-induced growth inhibitory effect was associated with DNA fragmentation, sub-G1 peak, loss of mitochondrial potential, and poly (ADP-ribose) polymerase (PARP) cleavage. In addition, ethyl acetate extract of Crataegus azarolus induced the cleavage of caspase-8. It has no effect on steady-state levels of total Bcl-2 protein. Whereas Bax levels decreased significantly in a dose-dependent manner in both tested cell lines. Taken together, these findings confirm the involvement of the extrinsic pathway of apoptosis. The apoptotic cell death induced by ethyl acetate extract of Crataegus azarolus was accompanied by an enhancement of the p21 expression but not through p53 activation in human colorectal cancer cells. The above-mentioned data provide insight into the molecular mechanisms of Crataegus azarolus ethyl acetate extract-induced apoptosis in CRC. Therefore, this compound should be a potential anticancer agent for the treatment of CRC.

Deformable Surface Model for the Evaluation of Abdominal Aortic Aneurysms Treated with an Endovascular Sealing System.

Rupture of abdominal aortic aneurysms (AAA) is responsible for 1-3% of all deaths among the elderly population in developed countries. A novel endograft proposes an endovascular aneurysm sealing (EVAS) system that isolates the aneurysm wall from blood flow using a polymer-filled endobag that surrounds two balloon-expandable stents. The volume of injected polymer is determined by monitoring the endobag pressure but the final AAA expansion remains unknown. We conceived and developed a fully deformable surface model for the comparison of pre-operative sac lumen size and final endobag size (measured using a follow-up scan) with the volume of injected polymer. Computed tomography images were acquired for eight patients. Aneurysms were manually and automatically segmented twice by the same observer. The injected polymer volume resulted 9% higher than the aneurysm pre-operative lumen size (p < 0.05), and 11% lower than the final follow-up endobag volume (p < 0.01). The automated method required minimal user interaction; it was fast and used a single set of parameters for all subjects. Intra-observer and manual vs. automated variability of measured volumes were 0.35 ± 2.11 and 0.07 ± 3.04 mL, respectively. Deformable surface models were used to quantify AAA size and showed that EVAS system devices tended to expand the sac lumen size.

Association of thoracic aorta calcium and non cardiac vascular events in cardiac disease-free individuals.

OBJECTIVE: Thoracic aorta calcium (TAC) is measurable on the same computed tomography (CT) scan as coronary artery calcium (CAC) but has still unclear clinical value. We assessed TAC and CAC relations with non-cardiac vascular events history in a cohort of subjects at risk for cardiovascular disease. METHODS: We analyzed retrospectively 1000 consecutive subjects having undergone CAC detection by non-contrast multi-slice CT with measurement field longer than usual in order to measure total TAC including aortic arch calcium. We also determined partial TAC restricted to ascending and descending thoracic aorta sites by removing arch calcium from total TAC. Calcium deposits were measured with a custom made software using Agatston score. RESULTS: Compared with the rest of the cohort, the 30 subjects with non-cardiac vascular event history had higher median values [95% CI] of total TAC (282 [28-1809] vs 39 [0-333], p < 0.01) and partial TAC (4 [0-284] vs 0 [0-5], p < 0.01) but no different value of CAC (73 [0-284] vs 16 [0-148]). Odds ratio [95% CI] of having non-cardiac vascular event per 1-SD increase in log-transformed calcium value was significant for total TAC but not for CAC, if total TAC and CAC were entered separately (1.56 [1.12-2.24], p < 0.01 and 1.13 [0.86-1.50], respectively) or together (1.57 [1.10-2.32], p < 0.01 and 0.98 [0.73-1.32], respectively) in the logistic adjusted model. CONCLUSION: TAC assessment simultaneous with CAC detection provides complementary information on the extra coronary component of cardiovascular risk beyond CAC's coronary risk prediction. Further studies are required to prospectively confirm this result.

Calcifications of the thoracic aorta on extended non-contrast-enhanced cardiac CT.

BACKGROUND: The presence of calcified atherosclerosis in different vascular beds has been associated with a higher risk of mortality. Thoracic aorta calcium (TAC) can be assessed from computed tomography (CT) scans, originally aimed at coronary artery calcium (CAC) assessment. CAC screening improves cardiovascular risk prediction, beyond standard risk assessment, whereas TAC performance remains controversial. However, the curvilinear portion of the thoracic aorta (TA), that includes the aortic arch, is systematically excluded from TAC analysis. We investigated the prevalence and spatial distribution of TAC all along the TA, to see how those segments that remain invisible in standard TA evaluation were affected. METHODS AND RESULTS: A total of 970 patients (77% men) underwent extended non-contrast cardiac CT scans including the aortic arch. An automated algorithm was designed to extract the vessel centerline and to estimate the vessel diameter in perpendicular planes. Then, calcifications were quantified using the Agatston score and associated with the corresponding thoracic aorta segment. The aortic arch and the proximal descending aorta, "invisible" in routine CAC screening, appeared as two vulnerable sites concentrating 60% of almost 11000 calcifications. The aortic arch was the most affected segment per cm length. Using the extended measurement method, TAC prevalence doubled from 31% to 64%, meaning that 52% of patients would escape detection with a standard scan. In a stratified analysis for CAC and/or TAC assessment, 111 subjects (46% women) were exclusively identified with the enlarged scan. CONCLUSIONS: Calcium screening in the TA revealed that the aortic arch and the proximal descending aorta, hidden in standard TA evaluations, concentrated most of the calcifications. Middle-aged women were more prone to have calcifications in those hidden portions and became candidates for reclassification.

Factors associated with major cardiovascular events in patients with systemic necrotizing vasculitides: results of a longterm followup study.

OBJECTIVE: Systemic necrotizing vasculitides (SNV) are associated with more frequent subclinical atherosclerosis, suggesting that SNV might be associated with a higher risk of major cardiovascular events (MCVE). We aimed to identify factors predictive of MCVE in patients with SNV. METHODS: Patients in remission from SNV were assessed for CV risk factors and subclinical atherosclerosis. MCVE was defined as myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, and/or death from CV causes. MCVE-free survival curves were compared using the log-rank test. RESULTS: Forty-two patients were followed for 7.1±2.6 years. Eight patients (18.9%) had MCVE. The respective 5- and 10-year MCVE rates were 9.5% and 26.8%. National Cholesterol Education Program/Adult Treatment Panel III (NCEP/ATP III)-defined high-risk status [hazard ratio (HR) 5.02 (95% CI: 1.17-27.4), p=0.03], BMI>30 kg/m2 [HR 4.84 (95% CI: 1.46-116), p=0.02], and plaque detection in the abdominal aorta (p=0.01) were significantly associated with MCVE. SNV characteristics, corticosteroid maintenance therapy, and C-reactive protein>5 mg/l were not associated with MCVE. Plaque in the aorta was significantly associated with high-risk status (p<0.001), while BMI and high-risk status were independent variables. Thus, a BMI>30 kg/m2 and/or a high-risk status were strongly associated with MCVE (p=0.004). Carotid intima-media thickness (IMT) identified patients with early MCVE and was correlated with the time to MCVE (r2=0.68, p=0.01). CONCLUSION: These results suggest that factors associated with a higher MCVE risk in patients with SNV are NCEP/ATP III-defined high-risk status and BMI>30 kg/m2. Carotid IMT could help identify patients with SNV at risk of early MCVE.

Identifying the principal modes of variation in human thoracic aorta morphology.

PURPOSE: Diagnosis and management of thoracic aorta (TA) disease demand the assessment of accurate quantitative information of the aortic anatomy. We investigated the principal modes of variation in aortic 3-dimensional geometry paying particular attention to the curvilinear portion. MATERIALS AND METHODS: Images were obtained from extended noncontrast multislice computed tomography scans, originally intended for coronary calcium assessment. The ascending, arch, and descending aortas of 500 asymptomatic patients (57 ± 9 y, 81% male) were segmented using a semiautomated algorithm that sequentially inscribed circles inside the vessel cross-section. Axial planes were used for the descending aorta, whereas oblique reconstructions through a toroid path were required for the arch. Vessel centerline coordinates and the corresponding diameter values were obtained. Twelve size and shape geometric parameters were calculated to perform a principal component analysis. RESULTS: Statistics revealed that the geometric variability of the TA was successfully explained using 3 factors that account for ∼80% of total variability. Averaged aortas were reconstructed varying each factor in 5 intervals. Analyzing the parameter loadings for each principal component, the dominant contributors were interpreted as vessel size (46%), arch unfolding (22%), and arch symmetry (12%). Variables such as age, body size, and risk factors did not substantially modify the correlation coefficients, although some particular differences were observed with sex. CONCLUSIONS: We conclude that vessel size, arch unfolding, and symmetry form the basis for characterizing the variability of TA morphology. The numerical data provided in this study as supplementary material can be exploited to accurately reconstruct the curvilinear shape of normal TAs.

Triterpene saponins of Genista ulicina Spach.

From the n-BuOH extract of the aerial parts of Genista ulicina, six triterpene saponins, 3-O-ß-D-glucopyranosyl-olean-12-ene-3ß,27,28,30-tetraol, 3-O-ß-D-glucopyranosyl-olean-12-ene-3ß,27,28,29-tetraol, 3,29-di-O-ß-D-glucopyranosyl-olean-12-ene-3ß,27,28,29-tetraol, 3-O-ß-D-glucopyranosyl-olean-12-ene-3ß,28,29-triol-27-oic acid, 3-O-ß-D-glucopyranosyl-olean-12-ene-3ß,27,28-triol-29-oic acid, and 3-O-ß-D-glucopyranosyl-14-H-27-nor-olean-12-ene-3ß,28,29-triol, were isolated together with eight known triterpene saponins and six flavonoids. Their structures were established mainly by means of spectroscopic methods (1D and 2D-NMR as well as HR-ESI-MS). The n-BuOH extract, investigated for its antitumor growth inhibition of human colon cancer HT-29 cells, presented no significant activity (IC50>100 µg).

Phytochemical potential of Daphne gnidium in inhibiting growth of melanoma cells and enhancing melanogenesis of B16-F0 melanoma.

In this study, we have investigated inhibitory capacity of ethyl acetate, total oligomer flavonoid (TOF), aqueous extracts and beta amyrin acetate, a triterpene isolated from ethyl acetate extract obtained from leaves of Daphne gnidium, on mouse melanoma (B16-F0 and B16-F10 cells) proliferation. Influence of these products on percentage cell distribution in cycle phases and melanogenesis was also studied. Cell viability was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and flow cytometry was used to analyse effects of tested compounds on progression through the cell cycle. In addition, amounts of melanin and tyrosinase were measured spectrophotometrically at 475 nm. Ethyl acetate, TOF and aqueous extracts exhibited significant anti-proliferative activity after incubation with the two types of tumour skin cells B16-F0 and B16-F10. Furthermore, cell cycle analysis revealed that cells treated with ethyl acetate and TOF extracts were arrested predominantly in G2-M phase. Ethyl acetate extract has also the ability to enhance melanogenesis and tyrosinase activity of B16-F0 melanoma cells.