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We have synthesized a novel derivative of Digitoxin, termed "MonoD", which demonstrates cytotoxic effects in lung cancer cells with much higher potency as compared to Digitoxin. Our data show that within 1 h of MonoD treatment, H460 cells showed increased oxidative stress, increased formation of autophagic vacuoles, and increased expression of pro-autophagic markers Beclin-1 and LC3-II. Cells pretreated with MnTBAP, a superoxide scavenger not only lowered superoxide production, but also had lower levels of LC3-II and Beclin-1. Prolonged treatment with MonoD-induced apoptosis in lung cancer cells. We investigated MonoD-dependent regulation of Akt and Bcl2, proteins that are known regulators of both autophagy and apoptosis. Molecular and pharmacologic inhibitors of Bcl2 and Akt, when combined with MonoD, led to higher expression of LC3-II and Beclin-1 as compared to MonoD alone, suggesting a repressive effect for these proteins in MonoD-dependent autophagy. Pretreatment of cells with an autophagy inhibitor repressed the apoptotic potential of MonoD, confirming that early autophagic flux is important to drive apoptosis. Therapeutic entities such as MonoD that target multiple pathways such as autophagy and apoptosis may prove advantageous over current therapies that have unimodal basis for action and may drive sustained tumor regression, which is highly desirable. J. Cell. Physiol. 231: 817-828, 2016. © 2015 Wiley Periodicals, Inc.

Nanosponges (NS) show promising results in different fields such as medicine, agriculture, water purification, fire engineering and so on. The present study was designed to evaluate toxicity of different NS formulations (namely, S1-S6) synthesized with different cross-linking agents such as carbonyl diimidazole, pyromellitic dianhydride and hexamethylene diisocynate; and preparation methods in experimental animals. Acute and repeated dose toxicity studies of formulations were carried out as per OECD guidelines 423 and 407, respectively. For acute toxicity study, formulations were administered to female rats at doses of 300 and 2000 mg/kg orally. The general behaviour of the rats was continuously monitored for 1 h after dosing, periodically during the first 24 h and daily thereafter for a total of 14 days. On day 14, animals were fasted overnight, weighed, and sacrificed. After sacrification, animals were subjected to necropsy. For repeated dose toxicity study, rats of either sex were orally administered with formulations at the dose of 300 mg/kg per day for a period of 28 days. The maximally tolerated dose of all formulations was found to be 2000 mg/kg. Repeated administration of formulations for 28 days did not show any significant changes in haematological and biochemical parameters in experimental animals. These results indicate that the formulations are safe, when tested in experimental animals.

Applications such as pattern recognition, shape matching, finite element analysis need lower dimensional representation of a higher dimensional shape. Skeleton provides such one dimensional representation for a 2D or 3D shape. It can be computed for various types of inputs, such as images, solids, sketches. Although there are various methods available for computation of the skeleton, their appropriateness depends on the requirement posed by their applications. Some focus on exact computation, some are approximate, some aim at faithful backward-reconstruction; whereas some focus at proper representation for human perception. This paper focuses on a method for creation of a particular type of skeleton, called Midcurve (a skeleton that lies at the midway of a shape) for planar polygon. This method is based on the Divide-and-Conquer strategy and works in two phases - decomposition and midcurve creation. Towards the end of the paper some test case results are presented along with the conclusions.

Challenges in demonstrating durable clinical responses to molecular-targeted therapies have sparked a re-emergence in viewing cancer as an evolutionary process. In somatic evolution, cellular variants are introduced through a random process of somatic mutation and are selected for improved fitness through a competition for survival. In contrast to Darwinian evolution, cellular variants that are retained may directly alter the fitness competition. If cell-to-cell communication is important for selection, the biochemical cues secreted by malignant cells that emerge should be altered to bias this fitness competition. To test this hypothesis, we compared the proteins secreted in vitro by two human HER2+ breast cancer cell lines (BT474 and SKBR3) relative to a normal human mammary epithelial cell line (184A1) using a proteomics workflow that leveraged two-dimensional gel electrophoresis (2DE) and MALDI-TOF mass spectrometry. Supported by the 2DE secretome maps and identified proteins, the two breast cancer cell lines exhibited secretome profiles that were similar to each other and, yet, were distinct from the 184A1 secretome. Using protein-protein interaction and pathway inference tools for functional annotation, the results suggest that all three cell lines secrete exosomes, as confirmed by scanning electron microscopy. Interestingly, the HER2+ breast cancer cell line exosomes are enriched in proteins involved in antigen-processing and presentation and glycolytic metabolism. These pathways are associated with two of the emerging hallmarks of cancer: evasion of tumor immunosurveillance and deregulating cellular energetics.

Background: Gmelina arborea Roxb (Verbenaceae), also known as "Gambhari", is an important medicinal plant in the Ayurveda. There are no meticulous scientific reports on effect of the plant on inflammation and pain. Objective: To study the anti-inflammatory and anti-nociceptive properties of aqueous extracts (AE) and methanol extracts (ME) of G. arborea. Materials and Methods: The AE and ME of stembark of G. arborea was prepared by cold maceration and Soxhlet extraction technique respectively. Anti-inflammatory activity was determined in Wistar albino rats in a model of acute plantar inflammation induced by carrageenan. The anti-nociceptive activity was evaluated by using hot plate test and writhing test in Swiss albino mice. Significant differences between the experimental groups were assessed by analysis of variance. Results: AE and ME at dose of 500 mg/kg showed maximum inhibition in carrageenan induced inflammation up to 30.15 and 31.21% respectively. In hot plate test, the AE and ME showed the maximum response of 8.8 ± 0.97 (P < 0.01) and 8.2 ± 1.24 (P < 0.01) respectively at dose of 500 mg/kg when compared with control. AE showed maximum inhibition of writhing response (84.3%) as compared to ME (77.9%) in writhing test at a dose of 500 mg/kg. Conclusion: The findings suggested that G. arborea possess significant anti-inflammatory and anti-nociceptive activities.

Objective: The present study was designed to evaluate acute and repeated dose toxicity of the methanol extract (ME) of the Gmelina arborea stem bark. Materials and Methods: For the acute toxicity study, ME of G. arborea was orally administered to Swiss albino mice at a dose range of 300-5000 mg/kg. For the repeated dose toxicity study, the Wistar rats of either sex were orally administered with ME of G. arborea at the doses of 300, 1000, and 2000 mg/kg/day for a period of 28 days. The effects on body weight, food and water consumption, organ weight, hematology, clinical chemistry as well as histology were studied. Results: The administration of ME from the G. arborea bark at 300-5000 mg/kg did not produce mortality or significant changes in the clinical signs. The no-observed adverse effect level (NOAEL) of ME was 5000 mg/kg. There were no significant differences in the general condition, growth, organ weights, hematological parameters, clinical chemistry values, or gross and microscopic appearance of the organs from the treatment groups as compared to the control group. Conclusion: ME of G. arborea was found safe in acute and repeated dose toxicity studies when tested in mice and rats.

Summary The antioxidant activities of aqueous, ethanol, and Pet. ether extracts of the leaves of cassia sophera Linn, were determined by the thiocyanate method using the linoleic acid emulsion. Ether extract was the most effective antioxidant among the extracts. Like antioxidant activity, the scavenging power of ether extract was the highest and aqueous extract was the lowest. The results obtained in the present study indicate that the leaves of cassia sophera are a potential source of natural antioxidants. In addition, we could suggest that although the scavenging activity of an extract may be an indicator of its potential antioxidant activity, it is important to evaluate this plant in detail with other methods. Phytochemical isolation of the ether extract for active antioxidant moiety will be the further scope for the study.

Introduction: Diabetic Foot ulcer is the commonest burning problem in the society. Many histopathological studies show prolonged inflammatory phase in diabetic wounds. In Sushruta Samhita, Vimlāpanakarma (gentle massage) quoted, as first line of treatment for Vranashotha (inflammation). Case Report: A 70 yrs old male patient, presented with complaints of ulcer associated with severe pain and reddish skin discoloration over ventral aspect of 3 rd toe of right foot since 2 months. Vimlāpanakarma performed with Jātyādi taila around the wound for about 15-20 minutes daily for 10 days and follow-up done for period of 45 days. Discussion: By Vimlāpanakarma with Jātyādi taila there will be raised local temperature, due to which vasoconstriction is relieved and necessary nutrients, oxygen, insulin etc. are carried to the wound site, thereby improving the anoxic condition of wound. Conclusion: Vimlāpanakarma showed significant role in wound healing of Diabetic Foot ulcer, in a short period of time 10 days with no recurrence seen till 45 days follow-up.

Background: Jyotishmati, scientifically known as Celastrus paniculatus Wild (Celastraceae) is one of the most important medicinal plants in Ayurveda. The plant has shown significant pharmacological activities like anti-arthritic, wound healing, hypolipidemic, and antioxidant. Objective: To study possible effects of alcoholic extract of Celastrus paniculatus seeds (AlcE) in experimentally induced pain and inflammation in mice. Materials and Methods: The antinociceptive activity was evaluated in Swiss albino mice by tail immersion, hot plate, and acetic-acid-induced writhing tests at doses of 250, 500, and 1,000 mg/kg. Anti-inflammatory activity was evaluated in model of carrageenan-induced acute plantar inflammation in Wistar rats. Results: In tail immersion test, AlcE showed significant (P < 0.05) increase in tail withdrawal response at dose of 250 mg/kg with maximum possible effect of 15.71%. The maximum possible effect of 23.32% and 30.16% (P < 0.001) was seen at dose of 500 and 1000 mg/kg at 3 hours after administration of extract, respectively. In hot plate test, increase in paw licking time was reported at dose of 500 and 1000 mg/kg. AlcE (1,000 mg/kg) showed maximum response (6.23 ± 0.46) when compared with control (3.20 ± 0.18) at 90 min. In acetic acid induced writhings, AlcE at dose of 250, 500, and 1,000 mg/kg body weight showed 32.35%, 49.01%, and 58.82% inhibition in writhings, respectively. AlcE treated animals (500 and 1,000 mg/kg) showed significant decrease in paw edema at 3 hours and 4 hours, when compared with control animals. Conclusion: Jyotishmati seed extract possesses significant antinociceptive and anti-inflammatory activity.

The Manufacturing sector is widely recognized as a powerful instrument for socio-economic growth and balanced industrial development. The growth rate recorded by the manufacturing sector has normally been higher than that of the industrial sector as a whole. The manufacturing sector has emerged over five decades as a highly vibrant and dynamic sector of the Indian economy. World over, the contribution of the manufacturing sector to economic growth, diversification, employment generation potential, reduction of regional inequalities and higher export earnings are well recognized. The National Manufacturing Policy, which is the first such dedicated policy measure for the manufacturing sector in the country, is expected to change the manufacturing landscape of the Indian economy through increased capital formation; industrial infrastructure of global standards; technology upgradation; creation of innovation and vocational skill development infrastructure; and industry, worker, and environment-friendly regulations.