Anti-Angiogenic and Vasculoprotective Effect of Punica Granatum Root

AIM AND OBJECTIVE: Angiogenesis is a process of formation of new blood vessels from a pre-existing vasculature. It plays a vital role in embryonic development and numerous pathological conditions including cancer, rheumatoid arthritis, diabetes retinopathy, age related macular degeneration and neurological disorders such as Parkinsonism and Alzheimer‟s disease (Folkman 1990; Folkman 1995). In cancer, the growth and metastasis of tumour are dependent on angiogenesis (Hazel 2003). Cancer cells can generate various pro-angiogenic factors such VEGF, FGF, EGF. These factors promote the migration, proliferation and tube formation of endothelial cells which are essential steps for angiogenesis. The newly formed blood vessels can promote cancer growth by supplying nutrients, oxygen and most importantly facilitate cancer cell metastasis to other localities (Sassa and Hatta 2009; Homayouni 2009). In diabetic patients, hyperglycemia is the triggering factor for tissue alterations such as damage to capillary endothelial cells in the retina and BRB breakdown (Zhang et al. 2014; Brownlee 2005) and one of the key players is vascular endothelial growth factor (VEGF), which promotes angiogenesis, abnormal vascular permeability, and eventually, an inflammatory response. Thus interrupting the process of angiogenesis has become one of the promising approaches in the treatment and prevention of cancer progression and diabetic retinopathy. Drug development from natural products has become a rapidly emerging and highly promising strategy to identify novel anti-angiogenic and anti-tumour agents. Plant derived compounds have played an important role in the development of several clinically useful anticancer agents. Over 62 % of biologically active substances currently used as anticancer agents are derived from natural sources, including plants, marine organism and microorganism. Today over 300 anti-angiogenic molecules targeting different signalling pathways are being tested for their anticancer properties at preclinical and clinical stages (Sassa and Hatta, 2009; Homayouni, 2009). Although the results of clinical trials are encouraging the effects were modest (Lu and Bergers, 2013). Therefore, the search and discovery of novel anti-angiogenic principle that selectively target the angiogenic process could bring hope to millions of sufferers with cancer. Punica granatum belonging to family Punicaceae is more commonly known as pomegranate (Salgado et al. 2006). Punica granatum is a large shrub which grows 12-16 feet, has many spiny branches with lance shaped glossy leaves. The bark of the tree turns gray as the tree ages. The flowers are large, red, white, or variegated having a tubular calyx that eventually becomes the fruit. Pomegranate is considered “A pharmacy unto itself” (Jurenka 2008). Pomegranate has many potential effects including bactericidal, antifungal, antiviral, immune modulation, vermifuge, stimulant, refrigerant, astringent, stomachic, styptic, laxative, diuretic and antihelminthic. It has also been widely used in treatment of cardiovascular diseases, diabetes, diarrhea, dysentery, asthma, bronchitis, cough, bleeding disorders, fever, inflammation, acquired immune deficiency syndrome, dyspepsia, ulcers, bruises, sores, mouth lesions, skin lesions, malaria, prostate cancer, atherosclerosis, hypertension, hyper lipidemia, denture stomatitis, male infertility, vaginitis, erectile dysfunction, Alzheimer's disease, obesity, and neonatal hypoxic-ischemic brain injury (Abdollahzdeh et al 2011; Jurenka 2008; Prakash et al. 2011). Punica granatum Linn roots are found to be rich in ellagitannins, including punicalin and punicalagin, numerous piperidine alkaloids (Tanaka et al. 1986; Neuhofer 1993). They are known for antihelmintic and vermifuge properties (Naqvi et al. 1991) and were found to be effective against melanoma in mice (Suresh et al. 2012). From the literature review, it was noted that fruit extract, peel extract (Dana et al. 2015) and pomegranate juice (Tibullo et al. 2016) possessed ant-angiogenic activity and it was noted that very limited study has been carried out in roots of Punica granatum. Moreover, no scientific report is available regarding antiangiogenic and vasculoprotective potential of Punica granatum roots to the best of my knowledge. Based on this, the present study was planned to evaluate anti-angiogenic and vaculoprotective property of Punica granatum roots in chorioallantoic membrane model. SUMMARY AND CONCLUSION: The effect of punica granatum roots on angiogenesis and vasoprotection was evaluated by chorioallantoic membrance (CAM) model. Powdered Punica granatum roots were extracted with ethanol by hot continuous extraction method. The crude ethanol extract of Punica granatum was subjected to preliminary photochemical examination and quantitative analysis. The free radical scavenging activity of extract was evaluated by DPPH radical scavenging and nitric oxide scavenging activity. It was observed that the extract was rich in alkaloids, flavonoids, tannins, saponins, glycoside and possessed a potent free radical scavenging activity. The extract was screened for angiogenesis modulation in chorioallantoic membranel. In CAM model, a significant decrease in average number of blood vessels was noted in extract treated group compared to vehicle control eggs. The extract was subjected to fractionation using solvents of increasing potency and the fractions were subjected to evaluation of anti-angiogenesis activity in CAM. Among the fractions, the ethyl acetate fraction showed a potent angiogenesis inhibition compared to vehicle control. Based on these results the ethyl acetate fraction was evaluated against glucose induced vascular changed in CAM model. To induce hyperglycemia in developing embryo, a single intravitellus injection of 5 mg glucose/g whole egg was introduced. The treatment groups received ethyl acetate fraction and 5 mg glucose/g whole egg. On day 12 of incubation, the blood glucose levels were measured in blood samples taken from CAM vessels and vascular changes were examined in CAM. Hyperglycaemia with vascular leakage, haemorrhagic spots (microaneurysms), proliferation of new vessels (neovascularization), superficial lesions were spotted in untreated eggs. Ethyl acetate fraction 100 μg showed a significant protection against glucose induced microvascular abnormalities with a significant decrease in blood glucose level and reduced average number of blood vessels. These findings demonstrate the anti-angiogenic and vasculoprotective effect of Punica granatum against hyperglycaemia induced vascular changes in CAM model. In conclusion, root extract of Punica granatum possess a significant angiogenesis inhibition in chorioallantoic membrane assay and vasuloprotective effect in glucose induced vascular change. The possible mechanism of antiangiogenesis and vasoprotective actions are might be due to the presence of active principles that possess a potent antioxidant property of roots, as antioxidants are potent inhibitors of angiogenesis and might be due to the presence of inhibitors that repress the expression of VEGF and VEGF like growth factors thereby inhibiting the formation of new blood vessels and maintaining a vascular stability by inhibiting capillary degeneration and permeability. Thus the isolation of antiangiogenic active principle from Punica granatum roots could bring hope to millions of sufferers with cancer and diabetic retinopathy. Further work is in progress to identify the bioactive compounds and delineate the underlying mechanism of antiangiogenesis and vasoprotection

System Reliability Estimation of Divert Attitude Control System of a Launch Vehicle using Bayesian Networks

Divert attitude and control system (DACS) is a one-shot system and provides attitude correction and translation of the Launch vehicle. DACS consists of many flight critical sub systems which are arranged in a series configuration. The traditional Reliability block diagram and Fault tree diagram methods are unsuitable for reliability modelling, when considering uncertainty among the components and system. Bayesian network is the natural choice to model dependencies among the components and system. DACS being one shot system, it is very expensive and time consuming to test more number of systems during the design and development. Hence the data is drawn from component level, subsystem level and expert opinion is used for reliability estimation. In this paper, Bayesian network modelling of DAC system was carried out for estimating the reliability using multi-level data. An algorithm is developed for computation of Conditional probabilities in Bayesian network. Posterior probability distribution of components is calculated using Markov Chain Monte Carlo (MCMC) simulations and results are compared with Junction tree based exact inference algorithm. MATLAB code is developed to estimate the reliability of DAC system

Lower bounds on the dilation of plane spanners

(I) We exhibit a set of 23 points in the plane that has dilation at least $1.4308$, improving the previously best lower bound of $1.4161$ for the worst-case dilation of plane spanners. (II) For every integer $n\geq13$, there exists an $n$-element point set $S$ such that the degree 3 dilation of $S$ denoted by $\delta_0(S,3) \text{ equals } 1+\sqrt{3}=2.7321\ldots$ in the domain of plane geometric spanners. In the same domain, we show that for every integer $n\geq6$, there exists a an $n$-element point set $S$ such that the degree 4 dilation of $S$ denoted by $\delta_0(S,4) \text{ equals } 1 + \sqrt{(5-\sqrt{5})/2}=2.1755\ldots$ The previous best lower bound of $1.4161$ holds for any degree. (III) For every integer $n\geq6$, there exists an $n$-element point set $S$ such that the stretch factor of the greedy triangulation of $S$ is at least $2.0268$.Comment: Revised definitions in the introduction; 23 pages, 15 figures; 2 table

Viewpoint: The Human Capital Approach to Inference

The purpose of this essay is to discuss the “human capital” approach to inference. Observed decisions by experts can be used to organize data on their decisions using simple machine learning techniques. The fact that the human capital of these experts is heterogeneous implies that errors in decision making are inevitable, which in turn allows us to identify the conditional average treatment effect for a wider class of situations than would be possible with randomized control trials. This point is illustrated with some data from medical decision making in the context of treating depression, heart disease, and adverse childbirth events

EDDY CURRENT THERMOGRAPHY FOR RAIL INSPECTION

Abstract With the tendency of the railway transportation into heavy haul, more frequent usage of rail tracks and increased axle load, the problem of surface damage and fatigue is dominant on rails. Rolling contact fatigue (RCF), which leads to crack formation in rail track heads, is becoming a growing concern in the transportation industry. It occurs on or very close to the rail head surface, and is a significant cause of rail failure. The detection of cracks in RAILS is a critical requirement in the Railway industry. Cracks, if undetected will lead to rail fractures and consequently may lead to catastrophic accidents. Thus with the development and operation of high speed trains, condition based maintenance and monitoring becomes an important approach for the improvement of reliability and safety of rail transportation. Eddy Current Thermography (ECT) is an emerging NDT method especially for conductive material like rails which combines the advantages of eddy current testing and IR Thermography. Due to electrical conductivity, thermal conductivity and high permeability of rails, ECT is very suitable for its damage detections. This technology describes an inspection methodology which utilizes scanning induction Thermography in which coil is excited by a high frequency alternating current and induced eddy current are generated in sample placed near the coil. The thermographic camera is arranged to capture data indicative of a thermal response resulting from the flow of electrical current through the copper coil which scans the rail track. A computer system is configured to process the data from the thermographic camera to generate an indication of a presence of a discontinuity in the rails

Encoding conformance checking artefacts in SAT

Conformance checking strongly relies on the computation of artefacts, which enable reasoning on the relation between observed and modeled behavior. This paper shows how important conformance artefacts like alignments, anti-alignments or even multi-alignments, defined over the edit distance, can be computed by encoding the problem as a SAT instance. From a general perspective, the work advocates for a unified family of techniques that can compute conformance artefacts in the same way. The prototype implementation of the techniques presented in this paper show capabilities for dealing with some of the current benchmarks, and potential for the near future when optimizations similar to the ones in the literature are incorporated.Peer ReviewedPostprint (author's final draft

Encoding conformance checking artefacts in SAT

Conformance checking strongly relies on the computation of artefacts, which enable reasoning on the relation between observed and modeled behavior. This paper shows how important conformance artefacts like alignments, anti-alignments or even multi-alignments, defined over the edit distance, can be computed by encoding the problem as a SAT instance. From a general perspective, the work advocates for a unified family of techniques that can compute conformance artefacts in the same way. The prototype implementation of the techniques presented in this paper show capabilities for dealing with some of the current benchmarks, and potential for the near future when optimizations similar to the ones in the literature are incorporated.Peer ReviewedPostprint (author's final draft

Resonating Valence Bond Wave Functions for Strongly Frustrated Spin Systems

The Resonating Valence Bond (RVB) theory for two-dimensional quantum antiferromagnets is shown to be the correct paradigm for large enough ``quantum frustration''. This scenario, proposed long time ago but never confirmed by microscopic calculations, is very strongly supported by a new type of variational wave function, which is extremely close to the exact ground state of the $J_1{-}J_2$ Heisenberg model for $0.4 \lesssim J_2/J_1\lesssim 0.5$. This wave function is proposed to represent the generic spin-half RVB ground state in spin liquids.Comment: 4 Pages, 5 figures, accepted for publication in PR

PEAK FACTOR IN THE DESIGN OF WATER DISTRIBUTION-AN ANALYSIS

ABSTRACT Water distribution system , being an important components of a water supply system, consumes nearly 75% of installation cost. Population, minimum residual pressure, peak factor and demand variation mostly decide the pipe size and cost. Peak factor value adopted for the design of distribution system differs country to country around the world. A critical review of peak factor used by different countries has been made. The cost of the net work increases with the peak factor. In India, the actual peak factor observed in the field fluctuates from 3 to 12 due to intermittent water suppl. Peak factor 5 to 6 is found to be suitable for ensuring the reliability of the distribution system