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The current study describes the analysis of the phytochemical composition and biological activities of various polarity extracts of the Anaphalis busua plant that was collected at an altitude of 1654 m in the Himalayan terrain of Uttarakhand, India. The extracts were prepared by the cold percolation method, which was then subjected to GC-MS for phytochemical analysis. A total of 31 compounds were identified that constituted 94.95% of the total methanolic extract. Mome inositol (31.03%) was identified as the main compound in the methanolic extract. Twenty-two compounds that comprise 68.24% of the total hexane extract were identified. Tetracontane (19.33%) was present in a significant proportion. The methanolic extract demonstrated potent antioxidant activity in terms of DPPH radical scavenging and metal chelating activity that have IC50 values of 81.71±1.334 and 11.26±0.005 µg/mL, respectively, compared to standards ascorbic acid and EDTA that have IC50 values at 12.71±0.02 and 11.36±0.06 µg/mL, respectively. The methanolic extract showed potent anti-inflammatory activity with an IC50 value of 24.10±0.09 µg/mL in comparison to standard diclofenac potassium with an IC50 value of 18.95±0.03 µg/mL. In vitro studies reveal that A. busua has a strong therapeutic potential and, if further explored, may prove to be a powerful antioxidant, anti-inflammatory, and cost-effective agent compared to synthetically derived agents from pharmaceutical industries.

Background: Alpinia malaccensis, commonly known as “Malacca ginger” and “Rankihiriya,” is an important medicinal plant of Zingiberaceae. It is native to Indonesia and Malaysia and widely distributed in countries including Northeast India, China, Peninsular Malaysia and Java. Due to vide pharmacological values, it is necessary to recognize this species for its significance of pharmacological importance Objective: This article provides the botanical characteristics, chemical compounds of vegetation, ethnopharmacological values, therapeutic properties, along with the potential pesticidal properties of this important medicinal plant. Methodology: The information in this article was gathered by searching the online journals in the databases such as PubMed, Scopus, Web of Science etc. The terms such as Alpinia malaccensis, Malacca ginger, Rankihiriya, pharmacology, chemical composition, ethnopharmacology, etc., were used in different combinations. Results and Conclusion: A detailed study of the available resources for A. malaccensis confirmed its native and distribution, traditional values, chemical properties, and medicinal values. Its essential oils and extracts are the reservoir of a wide range of important chemical constituents. Traditionally, it is being used to treat nausea, vomiting and wounds along with as a seasoning agent in meat processing and as perfume. Apart from traditional values, it has been reported for several pharmacological activities such as antioxidant, antimicrobial, anti-inflammatory etc. We believe that this review will help to provide the collective information of A. malaccensis to further explore it in the prevention and treatment of various diseases and help to the systematic study of this plant to utilize its potential in various areas of human welfare.

Altered and aberrant glycosylation signatures have been linked to being a hallmark in a variety of human disorders including cancers. Cancer stem cells, capable of self-renewal and differentiation, have recently been credited with a unique notion of disease genesis and implicated as the cause for initiation and recurrence of the disease in a new regime of neoplastic transformations hypothesis. Many biomarkers relating to diagnostic and prognostic intents have been discovered using the ubiquitous and abundant surface glycan patterns on cancer stem cells. Various technological advancements have been developed to identify and determine concerns with glycosylation structure. However, the nature and purpose of the glycan moiety on these glycosylation pattern have not yet been thoroughly investigated. This review, thus, summarises the process of glycosylation in CSCs, variations in glycosylation patterns in various stem cells, aberrant glycosylation patterns in cancer, the role of glycosylation in tumour cell adhesion, cell-matrix interactions, and signalling, as well as cancer detection and treatment. The function of carbohydrates as prospective serum biomarkers, some clinically authorized biomarkers, and potential novel biomarkers relating to cancer disease diagnosis and prognosis are also discussed in the review.

Cancer, being the leading cause of death in the globe, has been one of the major thrust areas of research worldwide. In a new paradigm about neoplastic transformations, the initiation and recurrence of disease is attributed to few mutated cells in bulk of tumor called cancer stem cells (CSCs). CSCs have capacity of self-renewal and differentiation, which are known for resistance to radio and chemotherapy leading to recurrence of the disease even after treatment. Most of traditional drugs implicated in cancer therapy targeting primary tumors have substantial toxicity to the physiological system and have not been efficient in targeting these CSCs leading to poor prognosis. Targeting these CSCs in bulk of tumor might be novel strategy for cancer chemoprevention and therapeutics. Diet-derived interventions and diverse natural products are known to target these CSCs and related signaling pathways, namely, Wnt, Notch, and Hedgehog pathways, which are implicated for CSC self-renewal. PRACTICAL APPLICATIONS: Cancer remains a global challenge even in this century. Poor prognosis, survival rate, and recurrence of the disease have been the major concerns in traditional cancer therapy regimes. Targeting cancer stem cells might be novel strategy for elimination and cure of the chronic disease as they are known to modulate all stages of carcinogenesis and responsible for recurrence and resistance to chemotherapy and radiotherapy. The evidence support that natural products might inhibit, delay, or reverse the process of tumorigenesis and modulate the different signaling pathways implicated for cancer stem cells self-renewal and differentiation. Natural products have minimal toxicity compared to traditional cancer therapy drugs since they have long been utilized in our food habits without any major side effects reported. Thus, targeting cancer stem cells with natural product might be a novel strategy for drug development in cancer chemoprevention and therapeutics.

Turmeric, since in ancient Indian traditional medicinal system, has been implicated for its therapeutic and chemopreventive properties against a broad spectrum of diseases. Curcumin, the active polyphenol from turmeric, helps to obstruct the growth of many types of cancers at various stages which include prostrate, melanoma, breast, brain tumor, pancreatic, leukemia, etc. The initiation and recurrence of cancer have been attributed to few mutated cells in bulk of tumor called as cancer stem cells which have the capacity of self-renewal and differentiation. Glycogen synthase kinase-3 beta (GSK-3B) is a multifunctional serine/threonine protein kinase, originally found in mammals, an important component of diverse signaling pathways, dysregulation of which leads to affect the cancer stem cell properties. The nutritional- and phytochemical-based dietary interventions may complement current chemotherapy to prevent recurrence and relapse of cancer. The objective of present study is to investigate the effect of retinoic acid and curcumin–retinoic acid conjugates against GSK-3B protein. The in silico results indicate that molecule 3 (curcumin–retinoic acid conjugates) might be a potent inhibitor of GSK-3B and a novel future drug candidate for the treatment of cancer.

In today’s world study of computer’s language is more important. Effective and good programming skills are need full all computer science students. They can be master in programming, only through intensive exercise practices. Due to day by day increasing number of students in the class, the assessment of programming exercises leads to extensive workload for teacher/instructor, particularly if it has to be carried out manually. In this paper, we propose an automatic assessment system for programming assignments, using verification program with random inputs. One of the most important properties of a program is that, it carries out its intended function. The intended function of a program or part of a program can be verified by using inverse function’s verification program. For checking intended functionality and evaluation of a program, we have used verification program. This assessment system has been tested on basic C programming courses, and results shows that it can work well in basic programming exercises, with some initial promising results.

Oxidative/nitrosative stress plays a crucial role in Parkinson's disease (PD) by triggering mitochondrial dysfunction. Nitrosative stress is mediated by reactive species such as peroxynitrite (PN) which could damage biomolecules thereby impinging on the cellular machinery. We observed that PN (0-1000 μM) inhibited brain mitochondrial complex I (CI) activity in a dose-dependent manner with concomitant tyrosine nitration of proteins. We also observed that exposure to PN at low concentrations (62.5-125 μM) significantly decreased the mitochondrial membrane potential and affected the mitochondrial integrity at higher doses (500-750 μM) as indicated by the mitochondrial swelling experiment. Therefore, it could be surmised that compounds that prevent such mitochondrial damage might have therapeutic value in neurological conditions such as PD. We previously showed that curcumin could detoxify PN and protect against CI inhibition and protein nitration. However, the therapeutic potential of curcumin is constrained by limited bioavailability. To address this issue and obtain improved antioxidants, three bioconjugates of curcumin (Di-demethylenated piperoyl, di-valinoyl and di-glutamoyl esters) were generated and tested against PN-mediated nitrosative stress and mitochondrial damage. We found that among the bioconjugates, the glutamoyl diester of curcumin showed improved protection against PN-dependent CI inhibition and protein nitration compared to other conjugates. Di-glutamoyl curcumin protected dopaminergic neurons against 1-methyl-4-phenylpyridinium (MPP(+))-mediated neuronal death. These effects were improved compared to curcumin alone suggesting that di-glutamoyl curcumin could be a better neuroprotective agent in neurodegenerative diseases such as PD.

We analyse here achievements of DST’s Climate Change Programme run by a small team of science administrators. The programme was run in a campaign mode in which DST science administrators not only made several young scientists interested in the programme, but also played a role of co-partner in developing the project concept and plans. The main features of the programme are: (i) several young scientists have taken lead role in carrying out research in climate change; (ii) creation of research networks; (iii) a remarkable rise in quality research papers; (iv) training of over 35,000 personnel, and (v) a marked change in the style of running a programme in which DST science administrators, committee members and researchers worked together with more trust and understanding, involving frequent interactions.

A robust and sensitive ultra-low flow liquid chromatography (UFLC) method that can reproducibly, at reasonable cost, detect low concentrations of piperine from human plasma is necessary. Piperine in plasma was separated and quantified by a gradient method using ultraviolet detection at a maximal absorbance wavelength of 340 nm. An aliquot was injected onto a reversed-phase column Waters SymmetryShield, 2.1 x 100 mm, 3.5 microm, C(18) column, attached to a Waters absorbosphere, 4.6 x 30 mm, C(18) guard column and eluted with a mobile phase containing a mixture of acetonitrile/water/acetic acid (25:74.9:0.1, v/v/v) on line A and acetonitrile/acetic acid (99.9:0.1, v/v) on line B. The flow rate was 0.3 mL/min. The gradient method consisted of an opening condition of 20% pump B, with a linear increase to 37% pump B over 8 min, then a linear increase to 100% pump B at 11 min, 2 min at 100% pump B, and then a return to the opening condition (20% pump B) via a linear gradient over 2 min, followed by 5 min re-equilibration at opening conditions. The total run time was 20 min for each sample. All samples were processed protected from ambient light to avoid isomerization of piperine. The plasma assay was linear with R = 0.9995, with a lower limit of detection [signal-to-noise (S/N) > 5:1] of 100 pg of piperine loaded into the analytical system with acceptable accuracy and precision. Extraction recoveries of piperine from human plasma were 88% for quality control high (QCH), 93% for quality control medium (QCM), and 90% for quality control low (QCL), and the matrix effect was

Oxidative stress is implicated in mitochondrial dysfunction associated with neurodegeneration in Parkinson’s disease (PD). Depletion of the cellular antioxidant glutathione (GSH) resulting in oxidative stress is considered as an early event in neurodegeneration. We previously showed that curcumin, a dietary polyphenol from turmeric induced GSH synthesis in experimental models and protected against oxidative stress. Here we tested the effect of three bioconjugates of curcumin (involving diesters of demethylenated piperic acid, valine and glutamic acid) against GSH depletion mediated oxidative stress in dopaminergic neuronal cells and found that the glutamic acid derivative displayed improved neuroprotection compared to curcumin.

The monoesters of curcumin, a symmetric diphenol with valine and glycine have been prepared by a novel solid phase synthesis and its diesters with valine, glutamic acid and demethylenated piperic acid have been prepared by solution phase method. The assessment of their antimicrobial and anticancer (antiproliferative) activities suggested that diesters of curcumin are relatively more active than curcumin itself due to their increased solubility, slow metabolism and better cellular uptake. Furthermore, significant observation was that monoesters of curcumin have even better antimicrobial activity than their corresponding diesters, emphasizing the role of free phenolic group. The conjugate of curcumin with demethylenated piperic acid in which methylenedioxy ring was open also shows enhanced activity than the corresponding piperic acid conjugate, emphasizing the role of free phenolics in the transport or in the binding processes.

Synthesis of a monoester of symmetrical diphenolic compound curcumin (1,7‐bis(4‐hydroxy‐3‐methoxy phenyl)‐1,6‐heptadiene‐3,5‐dione) with glycine has been carried out by anchoring one of its free phenolic groups to an insoluble polymeric solid‐support resin controlled pore glass‐long chain alkylamine (CPG‐LCAA) via a 2‐carbon linker by solid‐phase synthesis. The other free phenolic was esterified selectively with N‐protected glycinoyl chloride to give the monoester exclusively. Subsequent deprotection of the amino group and deblocking of the monoester from polymer support by treatment with hydriodic acid (HI) gave the desired product. We earlier reported synthesis of a large number of diesters of curcumin, but selective esterification of one phenolic has been accomplished by this novel method, which can be used for preparing monoesters of any symmetric diphenol in quantitative yields.

Inflammation is a disease of vigorous uncontrolled activated immune responses. Overwhelming reports have suggested that the modulation of immune responses by curcumin plays a dominant role in the treatment of inflammation and metabolic diseases. Observations from both in-vitro and in-vivo studies have provided strong evidence towards the therapeutic potential of curcumin. These studies have also identified a plethora of biological targets and intricate mechanisms of action that characterize curcumin as a potent 'drug' for numerous ailments. During inflammation the functional influence of lymphocytes and the related cross-talk can be modulated by curcumin to achieve the desired immune status against diseases. This review describes the regulation of immune responses by curcumin and effectiveness of curcumin in treatment of diseases of diverse nature.

International audience; Innate immune recognition is based on the detection, by pattern recognition receptors (PRRs), of molecular structures that are unique to microorganisms. Lipoglycans are macromolecules specific to the cell envelope of mycobacteria and related genera. They have been described to be ligands, as purified molecules, of several PRRs, including the C-type lectins Mannose Receptor and DC-SIGN, as well as TLR2. However, whether they are really sensed by these receptors in the context of a bacterium infection remains unclear. To address this question, we used the model organism Mycobacterium smegmatis to generate mutants altered for the production of lipoglycans. Since their biosynthesis cannot be fully abrogated, we manipulated the biosynthesis pathway of GDP-Mannose to obtain some strains with either augmented (,1.7 fold) or reduced (,2 fold) production of lipoglycans. Interestingly, infection experiments demonstrated a direct correlation between the amount of lipoglycans in the bacterial cell envelope on one hand and the magnitude of innate immune signaling in TLR2 reporter cells, monocyte/macrophage THP-1 cell line and human dendritic cells, as revealed by NF-kB activation and IL-8 production, on the other hand. These data establish that lipoglycans are bona fide Microbe-Associated Molecular Patterns contributing to innate immune detection of mycobacteria, via TLR2 among other PRRs.

Background: Basal breast cancer which occurs in women with BRCA1 mutations has been suggested to arise from arrested differentiation of stem/luminal progenitor cells, whose gene profile includes Vitamin D receptor prominently. In addition to DNA repair, BRCA1 enhances luminal differentiation of breast stem cells. Vitamin D compounds have long been known to have differentiating function. We hypothesized that Vitamin D receptor exists on stem cells and that vitamin D treatment induces differentiation of stem/progenitor cells, in part due to increased BRCA1 expression. Methods: We treated normal human breast epithelial cells and MCF-7 breast cancer cells with 10 or 100 nM 1, 25 dihydroxyvitamin D3 or the less hypercalcemic vitamin D5 analogue (1alpha(OH)D5) in suspension culture in stem cell media to assess: 1) stem cell self renewal using the mammosphere assay; 2) inhibition of stem cell percentage; 3) induction of BRCA1 mRNA and 4) induction of BRCA1 protein. Results: Teatment with 100nM 1alpha(OH)D5 inhibited stem cell self renewal as assessed by mammosphere formation assay from 23spheres/high power field (HPF) to 1 per HPF at 7 days; inhibited of percentage of stem cells from 17% in vehicle control to 7% with vitamin D5. Both vitamin D3 and D5 caused an 8 fold induction of vitamin D target CYP24 gene expression; 4 fold increase in BRCA1 mRNA by real time PCR; and 4 fold increase in BRCA1 protein expression by western blot compared to actin control. Conclusion: Vitamin D3 and D5 analogue induce BRCA1 expression and inhibit stem cell percentage in normal breast cells. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1842. doi:10.1158/1538-7445.AM2011-1842