QSAR studies on Withanolide analogs for anticancer activity

Withanolides are a group of pharmacologically active compounds present in most prodigal amounts in roots and leaves of Withania somnifera (Indian ginseng), one of the most important medicinal plants of Indian systems of medicine. Withanolides are basically steroidal lactones (highly oxygenated C-28 phytochemicals) and similar to ginsenosides activity. Some of the withanolides that have been reported possess immunomodulatory, and anticancer activities. In the present investigation, a quantitative structure activity relationship (QSAR) model based on forward stepwise multiple linear regression (MLR) has been developed against the MCF7, MCF7/BUS, and SK-Br-3 human solid tumor breast cancer cell lines. Relationship correlation coefficient (r2) and cross validation correlation coefficient (r2CV) of QSAR model were 0.77 and 0.73 for MCF7, 0.91 and 0.85 for MCF7/BUS, 0.93 and 0.90 for SK-Br-3 respectively. Developed QSAR model was also evaluated for prediction accuracy through internal, external and randomization validation methods. The QSAR study indicates that chemical descriptors viz., atom count (all atoms), connectivity index (order 2, standard), for MCF7, Connectivity Index (order 0, standard), Dipole Vector X (debye), Molar Refractivity, Shape Index (basic kappa, order 2) for SK-Br-3 and Atom Count (all atoms), Dielectric Energy (kcal/mole), Total Energy (Hartree), Heat of Formation (kcal/mole) for MCF7/BUS are correlate well with the breast cancer activity, Moreover, on the basis of screening for oral bioavailability, in silico ADME and toxicity risk assessment, we concluded that compounds W3, W4, W8 have markedly higher anticancer activity compared to control. These results can offer useful references for directing the molecular design of lead compound(s) based on withanolide or analogous template with improved activity

Amelioration of planting stress by soil amendment with a hydrogel–mycorrhiza mixture for early establishment of beech (Fagus sylvatica L.) seedlings

Introduction The mortality of nursery-grown beech (Fagus sylvatica L.) seedlings after out planting into the field is usually high. Objectives The goal of this study was to characterize the response of beech seedlings to planting stress and to test if soil amendment with a mixture of hydrogel and the ectomycorrhizal fungus Paxillus involutus could rescue the establishment of stressed plants. For this purpose, bare-rooted, dormant seedlings were exposed for 0, 2 and 6 h to air before planting. Results Water loss in response to air exposure caused increasing concentrations of soluble carbohydrates in buds and fine roots suggesting only passive of osmoprotection. Short-term exposure for 2 h delayed bud burst in spring, whereas long-term stress for 6 h also increased mortality. Growth of the seedlings in amended soil improved plant performance compared with plant grown in untreated soil. In particular, mycorrhizal colonization, plant water status and biomass increased, whereas carbohydrate storage pools were decreased. Total plant nitrogen allocated to leaves but not the nitrogen or carbohydrate concentrations were correlated with the degree of ectomycorrhizal colonization. Conclusion This suggests that soil amendment enhanced nitrogen uptake via ectomycorrhizals, which in turn stimulated growth, thereby, increasing carbon consumption and preventing starch accumulation. In conclusion, soil amendment with hydrogel and an ectomycorrhizal fungus significantly improved the performance of both stressed and unstressed young beech trees

Productivity and economics of turmeric (Curcuma longa L.) in response to nitrogen applied through different sources in conjunction with bio-fertilizer consortium

A Field investigation was carried out to study the effects of organic (FYM) and inorganic nitrogen alone or in combination with bio-fertilizer consortium (Azotobacter, PSB and PGPR) on growth, yield attributes, yield and economics of turmeric (Curcuma longa L.) during 2012-13 at Punjab Agricultural University, Ludhiana. The treat-ments were comprised of 75, 100 (25 t ha-1 FYM ~ 125 kg N ha-1) and 125 per cent of recommended N and control. Results revealed that application of organic manure (FYM) had beneficial effects on the growth, yield attributes and yield of turmeric. The maximum yield of 204.4 q ha-1 was obtained with application of 125 per cent of recommended organic manure combined with the bio-fertilizers, which was statistically at par with that of 100 per cent of recom-mended organic manure alone or in combination with the bio-fertilizers. Application of bio-fertilizers improved the growth and yield of turmeric to some extent

GGN repeat length and GGN/CAG haplotype variations in the androgen receptor gene and prostrate cancer risk in south Indian men

The ethnic variation in the GGN and CAG microsatellites of the androgen receptor (AR) gene suggests their role in the substantial racial difference in prostate cancer risk. Hence, we performed a casecontrol study to assess whether GGN repeats independently or in combination with CAG repeats were associated with prostate cancer risk in South Indian men. The repeat lengths of the AR gene determined by Gene scan analysis, revealed that men with GGN repeats £21 had no significant risk compared to those with >21 repeats (OR 0.91 at 95% CI-0.52–1.58). However, when CAG repeats of our earlier study was combined with the GGN repeat data, the cases exhibited significantly higher frequency of the haplotypes CAG £19/GGN £21 (OR-5.2 at 95% CI-2.17– 12.48, P 21(OR-6.9 at 95%CI-2.85–17.01, P < 0.001) compared to the controls. No significant association was observed between GGN repeats and prostate-specific antigen levels and the age at diagnosis. Although a trend of short GGN repeats length in high-grade was observed, it was not significant (P = 0.09). Overall, our data reveals that specific GGN/CAG haplotypes (CAG £19/GGN £21 and CAG £19/GGN > 21) of AR gene increase the risk of prostate cancer and thus could serve as susceptibility marker for prostate cancer in South Indian men

A green chemistry-based classification model for the synthesis of silver nanoparticles

The assessment of the implementation of green chemistry principles in the syntheses of nanomaterials is a complex decision-making problem that necessitates the integration of several evaluation criteria. Multiple Criteria Decision Aiding (MCDA) provides support for such a challenge. One of its methods – Dominance-based Rough Set Approach (DRSA) – was used in this research to develop a model for the green chemistry-based classification of silver nanoparticle synthesis protocols into preference-ordered performance classes. DRSA allowed integration of knowledge from both peer-reviewed literature and experts (decision makers, DMs) in the field, resulting in a model composed of decision rules that are logical statements in the form: “if conditions, then decision”. The approach provides the basis for the design of rules for the greener synthesis of silver nanoparticles. Decision rules are supported by synthesis protocols that enforce the principles of green chemistry to various extents, resulting in robust recommendations for the development and assessment of silver nanoparticle synthesis that perform at one of five pre-determined levels. The DRSA-based approach is transparent and structured and can be easily updated. New perspectives and criteria could be added into the model if relevant data were available and domain-specific experts could collaborate through the MCDA procedure

Relationship Between Characteristics of Medications and Drug-Induced Liver Disease Phenotype and Outcome

Background & Aims: It is not known if specific characteristics of medication are associated with type of drug-induced liver injury (DILI) or outcome. We examined the relationships among select characteristics of medications and DILI phenotype and outcome. Methods: We analyzed 383 cases of DILI caused by a single orally administered prescription agent from the DILI Network Prospective Study with causalities of definite, highly likely, or probable. Relationship of daily dosage (≥ 50 mg vs. ≤ 49 mg), preponderance of hepatic metabolism (≥50% vs <50%), or Biopharmaceutics Drug Disposition Classification System (BDDCS) class (1–4, based on solubility and metabolism of the drug) were compared with clinical characteristics and outcomes. Results: Compared to cases of DILI in the <50 mg/day group, those associated with daily dosages ≥50 mg had shorter latency (median 38 days vs 56 days; P=.03) and a different biochemical pattern of liver injury (P=.04); no differences in pattern of injury, recovery, severity, or outcome were observed. Patients with DILI caused by medications with or without preponderant hepatic metabolism did not differ in clinical characteristics or outcomes. Compared to other classes of BDDCS, DILI caused by BDDCS class 1 medications had significantly longer latency (P<.001) and greater proportion of hepatocellular injury (P=.001). However, peak liver biochemical values and patients’ time to recovery, disease severity, and outcomes did not differ among the 4 BDDCS classes. Conclusions: Characteristics of medications (dosage, hepatic metabolism, and solubility) are associated with features of DILI such as latency and pattern of liver injury, but not with recovery, severity, or outcome

Effect of Different Stages of Umbel Picking on Seed Quality Parameters, Yield and Economics of Fennel

The fennel seeds with uniform size green colour and optimum fiber content are preferred by customer and have high demand in national as well as International Market with premium price. For this purpose, the present investigation was carried out at the Vegetable Research Farm, Department of Vegetable Science and Seed Science and Technology, Chaudhary Charan Singh Haryana Agricultural University, Hisar to find out the optimum stage at which umbel/seed should be harvested for maximum acceptable fiber content in seed. For this purpose seeds of all order umbels were harvested at 25,30,35,40,45,50,55 and 60 days after anthesis. The fiber content of seed irrespective of umbel order was found optimum when seeds/umbels were harvested at 30 and 40 days after anthesis but maximum net return was obtained at 40 days after anthesis stage. In case of other quality parameters i.e. test weight, germination percentage, seedling length; vigour index and yield were increased with each 5 days delay in harvesting after 40 days of anthesis

Association of major depression with blood pressure and vascular complications of type 2 diabetes mellitus

Background: The WHO estimates the diabetic population to increase to 366 million by 2030 worldwide, with maximum 79.4 million Indians. Depression is an undiagnosed co-morbidity leading to significant disability, non-compliance and postulated to cause poorer glycemic control leading to early disease complications. We aimed to detect depression and study its correlation with vascular complications among type 2 diabetes mellitus (T2DM) patients.Methods: In an observational study, 312 randomly selected T2DM patients were evaluated at tertiary care center in Northern India. Socio-demographic, clinical and laboratory data was collected. Montgomery Asberg depression rating scale (MADRS) was used to detect depression. Groups with and without major depression were compared for various diabetes variables. Statistical analysis was carried out using the SPSS version 14.0.Results: One third T2DM patients (32.05%) suffered from major depression. Depression was significantly associated with diabetic patients having cardiac (p 0.01), ophthalmic (p 0.04), nephropathy (p 0.01), cerebrovascular (p 0.001) complications and diabetic foot (p 0.04). However, depression showed no significant association with systolic blood pressure, neuropathic and infectious complications.Conclusions: Identification of depression and its appropriate management may go a long way in delaying diabetic vascular complications by improving treatment adherence and subsequently glycemic control.