Elevated temperature extraction of ß-carotene from freeze-dried carrot powder into sunflower oil: Extraction kinetics and thermal stability.

ß-Carotene, a precursor of vitamin A, can alleviate the deficiency of this vitamin prevalent worldwide. Earlier research studies have addressed the extraction of ß-carotene at relatively low temperatures (up to 70°C) due to its perceived instability at higher temperatures, as a result of which extraction rates recorded are relatively low. This study models the net rate of ß-carotene extraction by considering both extraction and degradation kinetics. The model developed, which accounts for degradation occurring in solid and extract phases, has been experimentally validated for the extraction of ß-carotene from freeze-dried carrot powder into sunflower oil over a range of temperatures 90-150°C. This study also gives insights into the application of sunflower oil as a carrier for ß-carotene during cooking and food processing, by monitoring and modeling the thermal degradation and isomerization of ß-carotene at temperatures up to 220°C. The modeling of extraction kinetics shows that it is possible to achieve viable extraction rates by employing temperatures in the range (90-150°C) for relatively short times (<5 min). The degradation kinetics shows that almost 75% of the ß-carotene can survive heating at 180°C for 10 min-indicating the possibility of using ß-carotene enriched edible oils for frying. This study also reports on the formation of three isomers of ß-carotene identified using HPLC: trans-, 9-cis, and 13-cis. The reaction network model developed in this study was able to account for the transient variation of the concentration of all three isomers. PRACTICAL APPLICATION: ß-Carotene is a precursor of vitamin A and its consumption can potentially alleviate the deficiency of this vitamin prevalent worldwide. This study validates a model for the extraction of ß-carotene in sunflower oil, which takes into account extraction as well as degradation occurring during extraction, so that a rational method is available for the design of efficient extractors for this purpose. This paper also establishes the thermal stability of ß-carotene under frying conditions by quantifying its thermal degradation as well as isomerization.

Dasatinib loaded mucoadhesive lecithin-chitosan hybrid nanoparticles for its augmented oral delivery, in-vitro efficacy and safety.

Dasatinib (DAS) is an oral tyrosine kinase inhibitor; however, its efficacy is significantly subsided by its low oral bioavailability. The present research aimed to improve DAS's oral delivery and efficacy in triple-negative breast cancer by fabricating its mucoadhesive lecithin-chitosan hybrid nanoparticles (DAS-L/CS-NPs). DAS-L/CS-NPs were optimized using Box-Behnken design which showed mean particle size and percent entrapment efficiency of 179.7 ± 5.42 nm and 64.65 ± 0.06 %, respectively. DAS-L/CS-NPs demonstrated sustained release profile in different release media up to 48 h and showed 10 times higher apparent permeability coefficient and flux than free DAS suspension. The binding of DAS-L/CS-NPs to the mucus layer was demonstrated via ex-vivo mucoadhesion study and change in absorbance using turbidimetry. In cell culture studies, DAS-L/CS-NPs revealed a 4.14-fold decrease in IC50, significantly higher cellular uptake and mitochondrial membrane depolarization, 3.82-fold increased reactive oxygen species generation and 2.10-fold enhanced apoptosis in MDA-MB-231 cells than free DAS. In in-vivo pharmacokinetic assessment, DAS-L/CS-NPs showed a 5.08-fold and 3.74-fold rise in AUC (0-t) and Cmax than free DAS suspension, respectively. An acute toxicity study revealed a good safety profile of DAS-L/CS-NPs. In a nutshell, proposed hybrid nanoparticles are promising carriers for improved oral delivery of poorly water-soluble drugs.

Efficacy of jackfruit components in prevention and control of human disease: A scoping review.

The jackfruit (Artocarpus heterophyllus) is one of the natural remedies significantly used in folk medicine. The ethnopharmacological applications of jackfruit are mainly concerned with the management of inflammation, diarrhea, and diabetes mellitus. Flavonoids, stilbenoids, aryl benzofurans, and lectin jacalin are abundant in jackfruit species. Jacalin is a good indicator for evaluating the immunological state of HIV-1 patients. The extracts and metabolites of jackfruit, particularly those from the leaves, bark, stem, and fruit, contain several beneficial bioactive mixtures. New studies are focused on exploring these bioactive compounds used in various biological activities such as antiviral, antiplatelet, anticancer, antiatherosclerotic, immunomodulatory effects, inhibitors of 5-alpha reductase activity, and the formulation of fast-dissolving tablets (orodispersible, rapid melts porous). Multidisciplinary programs that integrate traditional and modern technology play a crucial role in the lies ahead expansion of jackfruit as the prospective inception of therapeutic compounds. This review aims to highlight significant results on the identification, production, and bioactivity of metabolites found in jackfruit, with current developments in jackfruit research in the control and prevention of human diseases.

A critical review on sustainable hazardous waste management strategies: a step towards a circular economy.

Globally, industrialisation and urbanisation have led to the generation of hazardous waste (HW). Sustainable hazardous waste management (HWM) is the need of the hour for a safe, clean, and eco-friendly environment and public health. The prominent waste management strategies should be aligned with circular economic models considering the economy, environment, and efficiency. This review critically discusses HW generation and sustainable management with the strategies of prevention, reduction, recycling, waste-to-energy, advanced treatment technology, and proper disposal. In this regard, the major HW policies, legislations, and international conventions related to HWM are summarised. The global generation and composition of hazardous industrial, household, and e-waste are analysed, along with their environmental and health impacts. The paper critically discusses recently adapted management strategies, waste-to-energy conversion techniques, treatment technologies, and their suitability, advantages, and limitations. A roadmap for future research focused on the components of the circular economy model is proposed, and the waste management challenges are discussed. This review stems to give a holistic and broader picture of global waste generation (from many sources), its effects on public health and the environment, and the need for a sustainable HWM approach towards the circular economy. The in-depth analysis presented in this work will help build cost-effective and eco-sustainable HWM projects.

Nicotinic Acid Catabolism Modulates Bacterial Mycophagy in Burkholderia gladioli Strain NGJ1.

Burkholderia gladioli strain NGJ1 exhibits mycophagous activity on a broad range of fungi, including Rhizoctonia solani, a devastating plant pathogen. Here, we demonstrate that the nicotinic acid (NA) catabolic pathway in NGJ1 is required for mycophagy. NGJ1 is auxotrophic to NA and it potentially senses R. solani as a NA source. Mutation in the nicC and nicX genes involved in NA catabolism renders defects in mycophagy and the mutant bacteria are unable to utilize R. solani extract as the sole nutrient source. As supplementation of NA, but not FA (fumaric acid, the end product of NA catabolism) restores the mycophagous ability of ΔnicC/ΔnicX mutants, we anticipate that NA is not required as a carbon source for the bacterium during mycophagy. Notably, nicR, a MarR-type of transcriptional regulator that functions as a negative regulator of the NA catabolic pathway is upregulated in ΔnicC/ΔnicX mutant and upon NA supplementation the nicR expression is reduced to the basal level in both the mutants. The ΔnicR mutant produces excessive biofilm and is completely defective in swimming motility. On the other hand, ΔnicC/ΔnicX mutants are compromised in swimming motility as well as biofilm formation, potentially due to the upregulation of nicR. Our data suggest that a defect in NA catabolism alters the NA pool in the bacterium and upregulates nicR which in turn suppresses bacterial motility as well as biofilm formation, leading to mycophagy defects. IMPORTANCE Mycophagy is an important trait through which certain bacteria forage over fungal mycelia and utilize fungal biomass as a nutrient source to thrive in hostile environments. The present study emphasizes that nicotinic acid (NA) is important for bacterial motility and biofilm formation during mycophagy by Burkholderia gladioli strain NGJ1. Defects in NA catabolism potentially alter the cellular NA pool, upregulate the expression of nicR, a negative regulator of biofilm, and therefore suppress bacterial motility as well as biofilm formation, leading to mycophagy defects.

Unraveling the therapeutic potential of natural products in the prevention and treatment of leukemia.

Leukemia is a heterogeneous group of hematological malignancies distinguished by differentiation blockage and uncontrolled proliferation of myeloid or lymphoid progenitor cells in the bone marrow (BM) and peripheral blood (PB). There are various types of leukemia in which intensive chemotherapy regimens or hematopoietic stem cell transplantation (HSCT) are now the most common treatments associated with severe side effects and multi-drug resistance in leukemia cells. Therefore, it is crucial to develop novel therapeutic approaches with adequate therapeutic efficacy and selectively eliminate leukemic cells to improve the consequences of leukemia. Medicinal plants have been utilized for ages to treat multiple disorders due to their diverse bioactive compounds. Plant-derived products have been used as therapeutic medication to prevent and treat many types of cancer. Over the last two decades, 50 % of all anticancer drugs approved worldwide are from natural products and their derivatives. Therefore this study aims to review natural products such as polyphenols, alkaloids, terpenoids, nitrogen-containing, and organosulfur compounds as antileukemic agents. Current investigations have identified natural products efficiently destroy leukemia cells through diverse mechanisms of action by inhibiting proliferation, reactive oxygen species production, inducing cell cycle arrest, and apoptosis in both in vitro, in vivo, and clinical studies. Current investigations have identified natural products as suitable promising chemotherapeutic and chemopreventive agents. It played an essential role in drug development and emerged as a possible source of biologically active metabolites for therapeutic interventions, especially in leukemia. DATA AVAILABILITY: Data will be made available on request.

Meta-QTLs, ortho-MetaQTLs and candidate genes for grain Fe and Zn contents in wheat (Triticum aestivum L.).

Majority of cereals are deficient in essential micronutrients including grain iron (GFe) and grain zinc (GZn), which are therefore the subject of research involving biofortification. In the present study, 11 meta-QTLs (MQTLs) including nine novel MQTLs for GFe and GZn contents were identified in wheat. Eight of these 11 MQTLs controlled both GFe and GZn. The confidence intervals of the MQTLs were narrower (0.51-15.75 cM) relative to those of the corresponding QTLs (0.6 to 55.1 cM). Two ortho-MQTLs involving three cereals (wheat, rice and maize) were also identified. Results of MQTLs were also compared with the results of earlier genome wide association studies (GWAS). As many as 101 candidate genes (CGs) underlying MQTLs were also identified. Twelve of these CGs were prioritized; these CGs encoded proteins with important domains (zinc finger, RING/FYVE/PHD type, flavin adenine dinucleotide linked oxidase, etc.) that are involved in metal ion binding, heme binding, iron binding, etc. qRT-PCR analysis was conducted for four of these 12 prioritized CGs using genotypes which have differed for GFe and GZn. Significant differential expression in these genotypes was observed at 14 and 28 days after anthesis. The MQTLs/CGs identified in the present study may be utilized in marker-assisted selection (MAS) for improvement of GFe/GZn contents and also for understanding the molecular basis of GFe/GZn homeostasis in wheat. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-022-01149-9.

Amorphous systems for delivery of nutraceuticals: challenges opportunities.

Amorphous solid products have recently gained a lot of attention as key solutions to improve the solubility and bioavailability of poorly soluble nutraceuticals. A pure amorphous drug is a high-energy form; physically/chemically unstable and so easily gets recrystallized into the less soluble crystalline form limiting solubility and bioavailability issues. Amorphous solid dispersion and co-amorphous are new formulation approach that stabilized unstable amorphous form through different mechanisms such as preventing mobility, high glass transition temperature and molecular interaction. Nutraceuticals have been received the utmost importance due to their health benefits. However, most of these compounds have been associated with poor oral bioavailability due to poor solubility, high lipophilicity, high melting point, poor permeability, degradability and rapid metabolism in the gastrointestinal tract (GIT) which limits its health benefits. This review provides us a systematic application of amorphous systems to the delivery of poorly soluble nutraceuticals, with the aim of overcoming their pharmacokinetic limitations and improved pharmacological potential. In particular, it describes the challenges associated with delivery of oral nutraceuticals, various methods involved in the preparation and characterization of amorphous systems and permeability enhancement of nutraceuticals are in detail.

Rays of immunity: Role of sunshine vitamin in management of COVID-19 infection and associated comorbidities.

The catastrophic pandemic engendered due to the Novel coronavirus (COVID-19) outbreak which causes severe clinical afflictions on the respiratory system has severely high morbidity and mortality rates. The requirement of novel compounds is at utmost importance due to lack of targeted drug molecule to treat the afflictions and restrict the viral infection and for the usage of prophylactic treatment to avoid the spread of the infection is of utmost importance. Vitamin D is one such naturally available multifunctional molecule, which plays an eminent role in the immune system and instigation of numerous cellular pathways further promoting health benefits and enhancing the human quality of life. This article reviews the current standpoint scenario and future prevalence of vitamin D supplementation in the management of covid-19 patients. Novel findings of Vitamin D suggest that along with regulation of cell growth, neuroprotective and mood-stabilizing effects, it regulates the immune response also modulate cytokine Interleukin-6 (IL-6) by inducing progesterone-induced blocking factor (PIBF), given the IL-6 levels are considerably high in COVID-19 patients which increases the further complications. Vitamin D also have its effect on angiotensin converting enzyme (ACEII) inhibitor through which the COVID-19 virus makes cell entry. Numerous research data elucidate the play of Vitamin D, in complications of COVID-19 including the most common comorbid conditions, neurological manifestations and immunological aspects makes it an ideal molecule for adjuvant therapy. Including Vitamin D as add-on therapy in the management of COVID-19 might aid the arrest of infection and helps fight this arduous epidemic.

Ginkgo biloba L. Prevents Hypobaric Hypoxia-Induced Spatial Memory Deficit Through Small Conductance Calcium-Activated Potassium Channel Inhibition: The Role of ERK/CaMKII/CREB Signaling.

Hypobaric hypoxia (HH) is a stressful condition, which is more common at high altitudes and can impair cognitive functions. Ginkgo biloba L. leaf extract (GBE) is widely used as herbal medicine against different disorders. Its ability to improve cognitive functions, reduce oxidative stress, and promote cell survival makes it a putative therapeutic candidate against HH. The present study has been designed to explore the effect of GBE on HH-induced neurodegeneration and memory impairment as well as possible signaling mechanisms involved. 220-250 gm (approximately 6- to 8-week-old) Sprague Dawley rats were randomly divided into different groups. GBE was orally administered to respective groups at a dose of 100 mg/kg/day throughout the HH exposure, i.e., 14 days. Memory testing was performed followed by hippocampus isolation for further processing of different molecular and morphological parameters related to cognition. The results indicated that GBE ameliorates HH-induced memory impairment and oxidative damage and reduces apoptosis. Moreover, GBE modulates the activity of the small conductance calcium-activated potassium channels, which further reduces glutamate excitotoxicity and apoptosis. The exploration of the downstream signaling pathway demonstrated that GBE administration prevents HH-induced small conductance calcium-activated potassium channel activation, and that initiates pro-survival machinery by activating extracellular signal-regulated kinase (ERK)/calmodulin-dependent protein kinase II (CaMKII) and the cAMP response element-binding protein (CREB) signaling pathway. In summary, the current study demonstrates the beneficial effect of GBE on conditions like HH and provides various therapeutic targets involved in the mechanism of action of GBE-mediated neuroprotection.

The enhanced phosphorus use efficiency in phosphate-deficient and mycorrhiza-inoculated barley seedlings involves activation of different sets of PHT1 transporters in roots.

MAIN CONCLUSION: Transcriptional activation of subfamily II PHT1 members in roots is associated with the enhanced phosphorus use efficiency and growth promotion of barley seedlings inoculated with Glomus species. The arbuscular mycorrhizal (AM) fungi symbiotic associations in cereal crops are known to regulate growth in cultivar-specific manner and induce phosphate (Pi) transporters (PHT1) in roots. In the present study, we observed that both AM colonization of roots by Glomus species and phosphate starvation enhanced phosphorus use efficiency (PUE) in barley seedlings. Our search for the full complement of PHT1 members in the recently sequenced barley genome identified six additional genes, totaling their number to 17. Both AM colonization and Pi starvation triggered activation of common as well as different PHT1s. Pi starvation led to the robust upregulation of HvPHT1;6.2/6.3 at 7d and weak activation of HvPHT1;1 in shoots at 3d time-point. In roots, only HvPHT1;1, HvPHT1;6.2/6.3, HvPHT1;7, HvPHT1;8, HvPHT1;11.2 and HvPHT12 were induced at least one of the time-points. AM colonization specifically upregulated HvPHT1;11, HvPHT1;11.2, HvPHT1;12 and HvPHT1;13.1/13.2, members belonging to subfamily II, in roots. Sucrose availability seems to be obligatory for the robust activation of HvPHT1;1 as unavailability of this metabolite generally weakened its upregulation under Pi starvation. Intriguingly, lack of sucrose supply also led to induction of HvPHT1;5, HvPHT1;8, and HvPHT1;11.2 in either roots or shoot or both. The mRNA levels of HvPHT1;5 and HvPHT1;11.2 were not severely affected under combined deficiency of Pi and sucrose. Taken together, this study not only identify additional PHT1 members in barley, but also ascertain their AM, Pi and sucrose-specific transcript accumulation. The beneficial role of AM fungi in the promotion of PUE and barley seedlings' growth is also demonstrated.

Potassium and Sodium Salt Stress Characterization in the Yeasts Saccharomyces cerevisiae, Kluyveromyces marxianus, and Rhodotorula toruloides.

Biotechnology requires efficient microbial cell factories. The budding yeast Saccharomyces cerevisiae is a vital cell factory, but more diverse cell factories are essential for the sustainable use of natural resources. Here, we benchmarked nonconventional yeasts Kluyveromyces marxianus and Rhodotorula toruloides against S. cerevisiae strains CEN.PK and W303 for their responses to potassium and sodium salt stress. We found an inverse relationship between the maximum growth rate and the median cell volume that was responsive to salt stress. The supplementation of K+ to CEN.PK cultures reduced Na+ toxicity and increased the specific growth rate 4-fold. The higher K+ and Na+ concentrations impaired ethanol and acetate metabolism in CEN.PK and acetate metabolism in W303. In R. toruloides cultures, these salt supplementations induced a trade-off between glucose utilization and cellular aggregate formation. Their combined use increased the beta-carotene yield by 60% compared with that of the reference. Neural network-based image analysis of exponential-phase cultures showed that the vacuole-to-cell volume ratio increased with increased cell volume for W303 and K. marxianus but not for CEN.PK and R. toruloides in response to salt stress. Our results provide insights into common salt stress responses in yeasts and will help design efficient bioprocesses. IMPORTANCE Characterization of microbial cell factories under industrially relevant conditions is crucial for designing efficient bioprocesses. Salt stress, typical in industrial bioprocesses, impinges upon cell volume and affects productivity. This study presents an open-source neural network-based analysis method to evaluate volumetric changes using yeast optical microscopy images. It allows quantification of cell and vacuole volumes relevant to cellular physiology. On applying salt stress in yeasts, we found that the combined use of K+ and Na+ improves the cellular fitness of Saccharomyces cerevisiae strain CEN.PK and increases the beta-carotene productivity in Rhodotorula toruloides, a commercially important antioxidant and a valuable additive in foods.

Biofortification and bioavailability of Zn, Fe and Se in wheat: present status and future prospects.

KEY MESSAGE: Knowledge of genetic variation, genetics, physiology/molecular basis and breeding (including biotechnological approaches) for biofortification and bioavailability for Zn, Fe and Se will help in developing nutritionally improved wheat. Biofortification of wheat cultivars for micronutrients is a priority research area for wheat geneticists and breeders. It is known that during breeding of wheat cultivars for productivity and quality, a loss of grain micronutrient contents occurred, leading to decline in nutritional quality of wheat grain. Keeping this in view, major efforts have been made during the last two decades for achieving biofortification and bioavailability of wheat grain for micronutrients including Zn, Fe and Se. The studies conducted so far included evaluation of gene pools for contents of not only grain micronutrients as above, but also for phytic acid (PA) or phytate and phytase, so that, while breeding for the micronutrients, bioavailability is also improved. For this purpose, QTL interval mapping and GWAS were carried out to identify QTLs/genes and associated markers that were subsequently used for marker-assisted selection (MAS) during breeding for biofortification. Studies have also been conducted to understand the physiology and molecular basis of biofortification, which also allowed identification of genes for uptake, transport and storage of micronutrients. Transgenics using transgenes have also been produced. The breeding efforts led to the development of at least a dozen cultivars with improved contents of grain micronutrients, although land area occupied by these biofortified cultivars is still marginal. In this review, the available information on different aspects of biofortification and bioavailability of micronutrients including Zn, Fe and Se in wheat has been reviewed for the benefit of those, who plan to start work or already conducting research in this area.

Effect of Boswellia Serrata Extract on Acute Inflammatory Parameters and Tumor Necrosis Factor-α in Complete Freund's Adjuvant-Induced Animal Model of Rheumatoid Arthritis.

CONTEXT: The worldwide prevalence of rheumatoid arthritis (RA) is about 1%, whereas in India, it is approximately 0.75%. The current therapy for RA includes nonsteroidal anti-inflammatory drugs corticosteroids, disease-modifying anti-rheumatic drugs and some recently developed biologic agents, but all of these are associated with adverse effects. Some herbal drugs, such as Boswellia serrata, have been reported to possess anti-inflammatory activity. AIMS: The aim of this study is to evaluate the anti-arthritic activity of Boswellia serrata extract (BSE) in complete Freund's adjuvant (CFA)-induced arthritis in rats. MATERIALS AND METHODS: Thirty-six Wistar rats were divided into six equal groups. RA was induced by intradermal injection of 0.1 ml CFA in hind paw. Body weight, ankle diameter, paw volume, arthritic index, tumor necrosis factor-α (TNF-α), and histopathological examination were assessed. The experimental data were statistically assessed by one-way analysis of variance (ANOVA). STATISTICAL ANALYSIS USED: The recorded data were analyzed using paired t-test and ANOVA test using SPSS. The data were analyzed and represented as mean difference. Value of P < 0.05 was considered statistically significant. RESULTS: BSE at dose 180 mg/kg showed statistically significant improvement in body weight and decrease in ankle diameter and arthritic index (P < 0.05); however, there was insignificant change in paw volume (P = 0.056). This improvement was comparable with Indomethacin. The level of TNF-α did not show any statistically significant change (P = 0.076). Histopathological results also exhibited a reduction in inflammatory parameters. CONCLUSIONS: BSE might have usefulness as an adjunct to conventional therapy of RA.

BOLA (BolA Family Member 3) Deficiency Controls Endothelial Metabolism and Glycine Homeostasis in Pulmonary Hypertension.

BACKGROUND: Deficiencies of iron-sulfur (Fe-S) clusters, metal complexes that control redox state and mitochondrial metabolism, have been linked to pulmonary hypertension (PH), a deadly vascular disease with poorly defined molecular origins. BOLA3 (BolA Family Member 3) regulates Fe-S biogenesis, and mutations in BOLA3 result in multiple mitochondrial dysfunction syndrome, a fatal disorder associated with PH. The mechanistic role of BOLA3 in PH remains undefined. METHODS: In vitro assessment of BOLA3 regulation and gain- and loss-of-function assays were performed in human pulmonary artery endothelial cells using siRNA and lentiviral vectors expressing the mitochondrial isoform of BOLA3. Polymeric nanoparticle 7C1 was used for lung endothelium-specific delivery of BOLA3 siRNA oligonucleotides in mice. Overexpression of pulmonary vascular BOLA3 was performed by orotracheal transgene delivery of adeno-associated virus in mouse models of PH. RESULTS: In cultured hypoxic pulmonary artery endothelial cells, lung from human patients with Group 1 and 3 PH, and multiple rodent models of PH, endothelial BOLA3 expression was downregulated, which involved hypoxia inducible factor-2α-dependent transcriptional repression via histone deacetylase 1-mediated histone deacetylation. In vitro gain- and loss-of-function studies demonstrated that BOLA3 regulated Fe-S integrity, thus modulating lipoate-containing 2-oxoacid dehydrogenases with consequent control over glycolysis and mitochondrial respiration. In contexts of siRNA knockdown and naturally occurring human genetic mutation, cellular BOLA3 deficiency downregulated the glycine cleavage system protein H, thus bolstering intracellular glycine content. In the setting of these alterations of oxidative metabolism and glycine levels, BOLA3 deficiency increased endothelial proliferation, survival, and vasoconstriction while decreasing angiogenic potential. In vivo, pharmacological knockdown of endothelial BOLA3 and targeted overexpression of BOLA3 in mice demonstrated that BOLA3 deficiency promotes histological and hemodynamic manifestations of PH. Notably, the therapeutic effects of BOLA3 expression were reversed by exogenous glycine supplementation. CONCLUSIONS: BOLA3 acts as a crucial lynchpin connecting Fe-S-dependent oxidative respiration and glycine homeostasis with endothelial metabolic reprogramming critical to PH pathogenesis. These results provide a molecular explanation for the clinical associations linking PH with hyperglycinemic syndromes and mitochondrial disorders. These findings also identify novel metabolic targets, including those involved in epigenetics, Fe-S biogenesis, and glycine biology, for diagnostic and therapeutic development.

Genome-wide analysis of genes encoding MBD domain-containing proteins from tomato suggest their role in fruit development and abiotic stress responses.

In tomato, DNA methylation has an inhibitory effect on fruit ripening. The inhibition of DNA methyltransferase by 5-azacytidine results in premature fruit ripening. Methyl CpG binding domain (MBD) proteins are the readers of DNA methylation marks and help in the recruitment of chromatin-modifying enzymes which affect gene expression. Therefore, we investigate their contribution during fruit development. In this study, we identified and analyzed 18 putative genes of Solanum lycopersicum and Solanum pimpinellifolium encoding MBD proteins. We also identified tomato MBD syntelogs in Capsicum annum and Solanum tuberosum. Sixty-three MBD genes identified from four different species of solanaceae were classified into three groups. An analysis of the conserved domains in these proteins identified additional domains along with MBD motif. The transcript profiling of tomato MBDs in wild-type and two non-ripening mutants, rin and Nr, indicated constructive information regarding their involvement during fruit development. When we performed a stage-specific expression analysis during fruit ripening, a gradual decrease in transcript accumulation in the wild-type fruit was detected. However, a very low expression was observed in the ripening mutants. Furthermore, many ethylene-responsive cis-elements were found in SlMBD gene promoters, and some of them were induced in the presence of exogenous ethylene. Further, we detected the possible role of these MBDs in abiotic stresses. We found that few genes were differentially expressed under various abiotic stress conditions. Our results provide an evidence of the involvement of the tomato MBDs in fruit ripening and abiotic stress responses, which would be helpful in further studies on these genes in tomato fruit ripening.

Therapeutic prospective of plant-induced silver nanoparticles: application as antimicrobial and anticancer agent.

Green synthesis approach for nanoparticle is environmental friendly, non-hazardous and the nanoparticles have shown enhanced biocompatibility for application in healthcare. Previous reviews have mentioned about green synthesis methods for nanoparticles and their biological activities. This review not only covers the general information about green synthesis of silver nanoparticles and characterization, but also focused on recent uses of various medicinal and nonmedical plants based AgNPs synthesis and their broad-spectrum antimicrobial and anticancer activities. In addition, this review emphasizes on elaborating underlying mechanism of anti-pathogenic microbial and anticancer activities of plant based AgNPs. Thus, present article provides a comprehensive analysis of plant-mediated synthesis of AgNPs and their potential applications in biomedical field including their mode of action and challenges in a single window.

Longevity and healthy ageing genes FOXO3A and SIRT3: Serum protein marker and new road map to burst oxidative stress by Withania somnifera.

BACKGROUND: Ageing process is characterized by a decline in function; different age related diseases and excessive age associated mortality. There has always been a quest for easily accessible biomarkers to monitor and identify the development of age-associated stress for providing new anti-ageing strategies. Forkhead box protein O3A (FOXO3A) and Sirtuin3 (SIRT3) are such potential markers which plays important role in a wide variety of cellular mechanisms and has been proposed to be an ideal candidate to study longevity and are potential candidate for healthy ageing by oxidative burst. OBJECTIVES: In this study we quantified FOXO3A and SIRT3 proteins in human serum with increasing age and in-vitro assessment of modulation of their expression by the treatment of Withania somnifera (Ashwagandha). METHODOLOGY: Four hundred seventy three subjects were enrolled for the study and were divided into three groups according to increasing age [20-30years (young), 60-79years (old) and ≥80years (oldest)]. Serum levels of FOXO3A and SIRT3 proteins were estimated by Surface Plasmon Resonance (SPR) and validated by ELISA and Western blot. The statistical analysis was done with student's unpaired t-test, one way ANOVA by Stata9 and Graph pad prism5. The expression of these proteins were also analysed in stress induced HEK-293 cell line and level was observed by treatment with stress releasing compound Ashwagandha. RESULTS: In this cross sectional observational study, the serum concentration of FOXO3A and SIRT3 declined significantly (p<0.0001) with increasing age and even after adjustment with all geriatric co-morbidities the level remain downregulated with age. In the stress inducible cell line showed reduced level of proteins which gets upregulated by the treatment of Ashwagandha. CONCLUSION: This is the first report of inverse relation of age with human serum FOXO3A and SIRT3 and can be excellent marker for ageing with good therapeutic importance for maintaining healthy ageing.

Graviola inhibits hypoxia-induced NADPH oxidase activity in prostate cancer cells reducing their proliferation and clonogenicity.

Prostate cancer (PCa) is the leading malignancy among men. Importantly, this disease is mostly diagnosed at early stages offering a unique chemoprevention opportunity. Therefore, there is an urgent need to identify and target signaling molecules with higher expression/activity in prostate tumors and play critical role in PCa growth and progression. Here we report that NADPH oxidase (NOX) expression is directly associated with PCa progression in TRAMP mice, suggesting NOX as a potential chemoprevention target in controlling PCa. Accordingly, we assessed whether NOX activity in PCa cells could be inhibited by Graviola pulp extract (GPE) that contains unique acetogenins with strong anti-cancer effects. GPE (1-5 µg/ml) treatment strongly inhibited the hypoxia-induced NOX activity in PCa cells (LNCaP, 22Rv1 and PC3) associated with a decrease in the expression of NOX catalytic and regulatory sub-units (NOX1, NOX2 and p47(phox)). Furthermore, GPE-mediated NOX inhibition was associated with a strong decrease in nuclear HIF-1α levels as well as reduction in the proliferative and clonogenic potential of PCa cells. More importantly, GPE treatment neither inhibited NOX activity nor showed any cytotoxicity against non-neoplastic prostate epithelial PWR-1E cells. Overall, these results suggest that GPE could be useful in the prevention of PCa progression via inhibiting NOX activity.

Paradigm Shift in the Surveillance and Management of Dysplasia in Inflammatory Bowel Disease (West).

Patients with long-standing inflammatory bowel disease (IBD) colitis have a 2.4-fold higher risk of developing colorectal cancer (CRC) than the general population, for both ulcerative colitis (UC) and Crohn's disease (CD) colitis. Surveillance colonoscopy is recommended to detect early CRC and dysplasia. Most dysplasia discovered in patients with IBD is actually visible. Recently published SCENIC (Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations) consensus statements provide unifying recommendations for the optimal surveillance and management of dysplasia in IBD. SCENIC followed the prescribed processes for guideline development from the Institute of Medicine (USA), including systematic reviews, full synthesis of evidence and deliberations by panelists, and incorporation of the GRADE methodology. The new surveillance paradigm involves high-quality visual inspection of the mucosa, using chromoendoscopy and high-definition colonoscopy, with endoscopic recognition of colorectal dysplasia. Lesions are described according to a new classification, which replaces the term 'dysplasia associated lesion or mass (DALM)' and its derivatives. Targeted biopsies are subsequently done on areas suspicious for dysplasia, and resections are carried out for discrete, resectable lesions.