DEVELOPMENT AND PHARMACOKINETICS OF CURCUMIN LOADED BETA CAROTENE NANOPARTICLES IN RATS

Objective: The main objective of this research work is to improve the bioavailability of curcumin using beta carotene nanoparticles in experimental animals. Methods: Curcumin-loaded beta carotene nanoparticles (NPs) have been prepared by emulsion–diffusion–evaporation method. Beta carotene and ethyl acetate were used to formulate NPs, and poly (vinyl alcohol) was used as a stabilizer. The emulsion diffusion evaporation method was used to prepare the nanoparticles and bioavailability and various pharmacokinetic parameters were compared with curcumin suspension in rats. Results: The nanoparticles were successfully prepared using beta carotene and curcumin and the drug loading was almost 93% of the initial weight. Particle sizes were below 200 nm with negative zeta potentials. Comparing the pharmacokinetic parameters of curcumin loaded nanoparticles (Cmax, Tmax, Kel, and AUC were 105 µg/ml, 2 h, 0.23/h, and 1629 µg.hr/ml) with pure curcumin (Cmax, Tmax, Kel and AUC 16 µg/ml, 1h, 0.275/h and 58 µg.hr/ml) indicated a drastic improvement in bioavailability of curcumin. Conclusion: The relative bioavailability was almost increased 30 times with beta carotene nanoparticles

Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015 : a systematic analysis for the Global Burden of Disease Study 2015

Background Improving survival and extending the longevity of life for all populations requires timely, robust evidence on local mortality levels and trends. The Global Burden of Disease 2015 Study (GBD 2015) provides a comprehensive assessment of all-cause and cause-specific mortality for 249 causes in 195 countries and territories from 1980 to 2015. These results informed an in-depth investigation of observed and expected mortality patterns based on sociodemographic measures. Methods We estimated all-cause mortality by age, sex, geography, and year using an improved analytical approach originally developed for GBD 2013 and GBD 2010. Improvements included refinements to the estimation of child and adult mortality and corresponding uncertainty, parameter selection for under-5 mortality synthesis by spatiotemporal Gaussian process regression, and sibling history data processing. We also expanded the database of vital registration, survey, and census data to 14 294 geography-year datapoints. For GBD 2015, eight causes, including Ebola virus disease, were added to the previous GBD cause list for mortality. We used six modelling approaches to assess cause-specific mortality, with the Cause of Death Ensemble Model (CODEm) generating estimates for most causes. We used a series of novel analyses to systematically quantify the drivers of trends in mortality across geographies. First, we assessed observed and expected levels and trends of cause-specific mortality as they relate to the Socio-demographic Index (SDI), a summary indicator derived from measures of income per capita, educational attainment, and fertility. Second, we examined factors affecting total mortality patterns through a series of counterfactual scenarios, testing the magnitude by which population growth, population age structures, and epidemiological changes contributed to shifts in mortality. Finally, we attributed changes in life expectancy to changes in cause of death. We documented each step of the GBD 2015 estimation processes, as well as data sources, in accordance with Guidelines for Accurate and Transparent Health Estimates Reporting (GATHER). Findings Globally, life expectancy from birth increased from 61.7 years (95% uncertainty interval 61.4-61.9) in 1980 to 71.8 years (71.5-72.2) in 2015. Several countries in sub-Saharan Africa had very large gains in life expectancy from 2005 to 2015, rebounding from an era of exceedingly high loss of life due to HIV/AIDS. At the same time, many geographies saw life expectancy stagnate or decline, particularly for men and in countries with rising mortality from war or interpersonal violence. From 2005 to 2015, male life expectancy in Syria dropped by 11.3 years (3.7-17.4), to 62.6 years (56.5-70.2). Total deaths increased by 4.1% (2.6-5.6) from 2005 to 2015, rising to 55.8 million (54.9 million to 56.6 million) in 2015, but age-standardised death rates fell by 17.0% (15.8-18.1) during this time, underscoring changes in population growth and shifts in global age structures. The result was similar for non-communicable diseases (NCDs), with total deaths from these causes increasing by 14.1% (12.6-16.0) to 39.8 million (39.2 million to 40.5 million) in 2015, whereas age-standardised rates decreased by 13.1% (11.9-14.3). Globally, this mortality pattern emerged for several NCDs, including several types of cancer, ischaemic heart disease, cirrhosis, and Alzheimer's disease and other dementias. By contrast, both total deaths and age-standardised death rates due to communicable, maternal, neonatal, and nutritional conditions significantly declined from 2005 to 2015, gains largely attributable to decreases in mortality rates due to HIV/AIDS (42.1%, 39.1-44.6), malaria (43.1%, 34.7-51.8), neonatal preterm birth complications (29.8%, 24.8-34.9), and maternal disorders (29.1%, 19.3-37.1). Progress was slower for several causes, such as lower respiratory infections and nutritional deficiencies, whereas deaths increased for others, including dengue and drug use disorders. Age-standardised death rates due to injuries significantly declined from 2005 to 2015, yet interpersonal violence and war claimed increasingly more lives in some regions, particularly in the Middle East. In 2015, rotaviral enteritis (rotavirus) was the leading cause of under-5 deaths due to diarrhoea (146 000 deaths, 118 000-183 000) and pneumococcal pneumonia was the leading cause of under-5 deaths due to lower respiratory infections (393 000 deaths, 228 000-532 000), although pathogen-specific mortality varied by region. Globally, the effects of population growth, ageing, and changes in age-standardised death rates substantially differed by cause. Our analyses on the expected associations between cause-specific mortality and SDI show the regular shifts in cause of death composition and population age structure with rising SDI. Country patterns of premature mortality (measured as years of life lost [YLLs]) and how they differ from the level expected on the basis of SDI alone revealed distinct but highly heterogeneous patterns by region and country or territory. Ischaemic heart disease, stroke, and diabetes were among the leading causes of YLLs in most regions, but in many cases, intraregional results sharply diverged for ratios of observed and expected YLLs based on SDI. Communicable, maternal, neonatal, and nutritional diseases caused the most YLLs throughout sub-Saharan Africa, with observed YLLs far exceeding expected YLLs for countries in which malaria or HIV/AIDS remained the leading causes of early death. Interpretation At the global scale, age-specific mortality has steadily improved over the past 35 years; this pattern of general progress continued in the past decade. Progress has been faster in most countries than expected on the basis of development measured by the SDI. Against this background of progress, some countries have seen falls in life expectancy, and age-standardised death rates for some causes are increasing. Despite progress in reducing age-standardised death rates, population growth and ageing mean that the number of deaths from most non-communicable causes are increasing in most countries, putting increased demands on health systems. Copyright (C) The Author(s). Published by Elsevier Ltd.Peer reviewe

Givotia rottleriformis

2.1. Identification of benzoylsalicylic acid in seed coats of G. <i> <i>rottleriformis</i> </i> <p>We extracted the total seed coat compounds in methanol (MeOH) and the methanolic crude seed coat extract was fractionated by open silica column chromatography (see Experimental procedure, Section 4.3.1) and the eluted fractions (1–7) were tested for their SAR inducing bioactivities against TMV in tobacco (Supplementary Table S2). Among all the fractions, a fraction number 3 was effective in reducing the development of TMV-induced lesion number and diameter. This active fraction showed a group of peaks with different retention times (RT) when resolved by RP-HPLC (Fig. 1a). The major compound of the peak from fraction 3 that eluted at RT 22.8 min (Fig. 1a) was purified and tested for its purity by analytical HPLC with RT at 17.6 min (Fig. 1b). The purified compound was found to be active against TMV and was characterized as benzoylsalicylic acid (CCDC with accession number 90056) using single crystal X-ray diffraction analysis (Supplementary Fig. S2a and b). Further structural analysis of purified BzSA was carried out using IR and NMR (Supplementary Fig. S3a–c). The mass of the purified BzSA was determined by GC–MS/MS as 242 Da (Supplementary Fig. S4).</p> <p> Although the seed coats of <i>Givotia</i> are a rich source of BzSA (0.5 mg /gm DW), the other parts like leaves (0.1 mg /gm DW) and bark (0.15 mg /gm DW) also contained this compound (Supplementary Fig. S5a and b). The higher accumulation of BzSA, a phenolic compound, in seed coats of <i>G. rottleriformis</i> could be due to its importance in seed germination, seedling growth and interaction with soil microbes. It is well known from the literature that phenolics function as signals in plant–microbe interactions (Raskin, 1992). Emerging evidence implicates the role of SA in seed germination, flowering, thermogenesis, plant growth and development, and tolerance to abiotic stresses such as drought, chilling, heavy metal toxicity, heat and osmotic stress in plants (Khan et al., 2015; Rivas-San Vicente and Plasencia, 2011).</p> <p> The chemical structure of BzSA along with SA and ASA are depicted in Fig. 2a–c. The possibility of BzSA biosynthesis depends on the availability of free SA and benzoyl-CoA (Fig. 2d). Literature suggests that SA and benzoyl-CoA are present in plants and the biosynthesis of SA in plants takes place <i>via</i> CoA-dependent or independent way, and during this process benzoyl-CoA is formed as intermediate by the oxidation of cinnamic acid (CA) to benzoic acid (BA) (Ribnicky et al., 1998). Previously, it has been reported that the majority of the endogenously synthesized SA are rapidly converted and stored as biologically inactive derivatives <i>via</i> glucosylation and methylation since accumulation of SA has adverse physiological consequences (Dempsey et al., 2011; Park et al., 2007; Vlot et al., 2009). Recent studies have shown 2,3-dihydroxybenzoic acid (2,3 DHBA) as a hydroxy derivative of SA (Zhang et al., 2013). However, the benzoylation of SA has not been reported so far. In this study, we report benzoylation of SA for the first time in plants.</p>Published as part of <i>Kamatham, Samuel, Neela, Kishore Babu, Pasupulati, Anil Kumar, Pallu, Reddanna, Singh, Surya Satyanarayana & Gudipalli, Padmaja, 2016, Benzoylsalicylic acid isolated from seed coats of Givotia rottleriformis induces systemic acquired resistance in tobacco and Arabidopsis, pp. 11-22 in Phytochemistry 126</i> on pages 12-13, DOI: 10.1016/j.phytochem.2016.03.002, <a href="http://zenodo.org/record/10484904">http://zenodo.org/record/10484904</a&gt

Givotia rottleriformis

<i>2.2. Detection of SA precursors in seed coats of G. rottleriformis</i> <p>The other compounds of fraction 3 were identified as BA that eluted at RT 14.7 min, salicylic acid (SA) at RT 15.3 min, benzaldehyde (BD) at RT 19.4 min, and CA at RT 21.4 min (Fig. 1 and Supplementary Fig. S6a–d). The purified BA and SA were also analysed by IR and NMR (Supplementary Figs. S7a and b and S8a–c). We also detected methyl salicylate (MeSA) and methyl benzoate (MeBA) in active fraction 3 (Supplementary Fig. S9). The conjugates of the SA and BA have already been reported previously (Chong et al., 2001; Lee et al., 1995). The biosynthesis of SA and its role in disease resistance has been established in various plants (Meuwly et al., 1995; Ribnicky et al., 1998; Silverman et al., 1995; Vogt, 2010; Wildermuth et al., 2001). The precursors of SA pathway were identified as CA, BD, benzoyl-CoA and BA (Boatright et al., 2004; Gao et al., 2015; Ribnicky et al., 1998). Though the biosynthesis of SA is well known in plants (Ribnicky et al., 1998; Seyfferth and Tsuda, 2014; Wildermuth et al., 2001), identification of SA along with its precursors and its new derivative BzSA in the present study adds new information with respect to metabolism of SA in plants.</p>Published as part of <i>Kamatham, Samuel, Neela, Kishore Babu, Pasupulati, Anil Kumar, Pallu, Reddanna, Singh, Surya Satyanarayana & Gudipalli, Padmaja, 2016, Benzoylsalicylic acid isolated from seed coats of Givotia rottleriformis induces systemic acquired resistance in tobacco and Arabidopsis, pp. 11-22 in Phytochemistry 126</i> on page 13, DOI: 10.1016/j.phytochem.2016.03.002, <a href="http://zenodo.org/record/10484904">http://zenodo.org/record/10484904</a&gt

MrdH, a Novel Metal Resistance Determinant of Pseudomonas putida KT2440, Is Flanked by Metal-Inducible Mobile Genetic Elements▿ †

We report here the identification and characterization of mrdH, a novel chromosomal metal resistance determinant, located in the genomic island 55 of Pseudomonas putida KT2440. It encodes for MrdH, a predicted protein of ∼40 kDa with a chimeric domain organization derived from the RcnA and RND (for resistance-nodulation-cell division) metal efflux proteins. The metal resistance function of mrdH was identified by the ability to confer nickel resistance upon its complementation into rcnA mutant (a nickel- and cobalt-sensitive mutant) of Escherichia coli. However, the disruption of mrdH in P. putida resulted in an increased sensitivity to cadmium and zinc apart from nickel. Expression studies using quantitative reverse transcription-PCR showed the induction of mrdH by cadmium, nickel, zinc, and cobalt. In association with mrdH, we also identified a conserved hypothetical gene mreA whose encoded protein showed significant homology to NreA and NreA-like proteins. Expression of the mreA gene in rcnA mutant of E. coli enhanced its cadmium and nickel resistance. Transcriptional studies showed that both mrdH and mreA underwent parallel changes in gene expression. The mobile genetic elements Tn4652 and IS1246, flanking mrdH and mreA were found to be induced by cadmium, nickel, and zinc, but not by cobalt. This study is the first report of a single-component metal efflux transporter, mrdH, showing chimeric domain organization, a broad substrate spectrum, and a location amid metal-inducible mobile genetic elements

Engineered Deinococcus radiodurans R1 with NiCoT genes for bioremoval of trace cobalt from spent decontamination solutions of nuclear power reactors

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