Ras hyperactivation versus overexpression : Lessons from Ras dynamics in Candida albicans

We thank Prof. Neta Dean for the CIp10ADH1-Cherry plasmid and Prof. Aaron Mitchell for the BWP17 strain. We gratefully acknowledge Prof. Sudipta Maiti, TIFR, Mumbai, India for providing the data acquisition software. We also appreciate the feedback and discussions with Dr. Rohini Muthuswami, SLS, JNU as well as from the Protein Society group, New Delhi while this study was taking shape. We thank Prof. Alok Bhattacharya for Cytochalasin D. The GC-MS and fluorescence lifetime measurements were carried out at the Advanced Instrumentation Research Facility (AIRF), JNU. Confocal images were recorded either at the central instrumentation facility (CIF), SLS, JNU or at AIRF, JNU. This work was supported by project grants from Department of Biotechnology (DBT, Project grant no. BT/PR20410/BRB/10/1542/2016) and Department of Science and Technology (DST, Project grant no. SB/SO/BB-011/2014), India to S.S.K; and project grants from Department of Information Technology, (DIT, Project grant no. 12(4)/2007-PDD), India to S.S. for FCS setup. In addition, both S.S. and S.S.K. thank DBT-BUILDER for funding support (Project grant no. BT/PR5006/INF/153/2012). S.S.K. also acknowledges funding support from UGC Resource Networking grant to the School of Life Sciences. We thank DST-PURSE and JNU for assistance with funding for publication. G.S.V. and S.C.S. received a fellowship from UGC; V.A.P., B.Y., P.J., N.P., M.F.K. acknowledge CSIR for fellowships. S.L.S. received a fellowship from ICMR. D.T.H. and M.F.K. thank DBT-BUILDER for funding.Peer reviewedPublisher PD

Chronic inflammation and cancer: potential chemoprevention through nuclear factor kappa B and p53 mutual antagonism

Activation of nuclear factor-kappa B (NF- κB) as a mechanism of host defense against infection and stress is the central mediator of inflammatory responses. A normal (acute) inflammatory response is activated on urgent basis and is auto-regulated. Chronic inflammation that results due to failure in the regulatory mechanism, however, is largely considered as a critical determinant in the initiation and progression of various forms of cancer. Mechanistically, NF- κB favors this process by inducing various genes responsible for cell survival, proliferation, migration, invasion while at the same time antagonizing growth regulators including tumor suppressor p53. It has been shown by various independent investigations that a down regulation of NF- κB activity directly, or indirectly through the activation of the p53 pathway reduces tumor growth substantially. Therefore, there is a huge effort driven by many laboratories to understand the NF- κB signaling pathways to intervene the function of this crucial player in inflammation and tumorigenesis in order to find an effective inhibitor directly, or through the p53 tumor suppressor. We discuss here on the role of NF- κB in chronic inflammation and cancer, highlighting mutual antagonism between NF- κB and p53 pathways in the process. We also discuss prospective pharmacological modulators of these two pathways, including those that were already tested to affect this mutual antagonism

COMPREHENSIVE REVIEW OF SIMHANADA GUGGULU: A FORMULA FOR AMAVATA (RHEUMATOID ARTHRITIS)

Amavata is a disease characterized by gatrastabdhata caused by the combined effect of the formation of ama and prakupita vata per trikasandhi. When Ama and Vata simultaneously vitiate and enter Trika and Sandhi, it ultimately leads to stabdhata (stiffness), which is known as Amavata. The disease Amavata can be presented as very similar to Rheumatoid Arthritis.The sickness of Rheumatoid Joint pain is ongoing in nature and influences mostly the moderately aged people. It is one of the common crippling sicknesses due to its chronicity and effects. The beginning of infection is successive during the middle age with 80% of patients fostering the illness between 30 to 50 years old. Several studies show that female is more victim than male and the proportion of event between them is 3:1. It is also noted that frequency is often associated with remission of the disease in last trimester with subsequent relapse after delivery. However, in present era no appropriate medication is available that can give everlasting benefit by permanent remission of the symptoms. The treatment which are available can only give symptomatic relief for time being but their continuous use causes various adverse effects. Thus, people are looking for a safe and effective drug that gives permanent relief. The Ayurvedic system is having its pride in providing such a treatment to cure all these types of chronic ailments. Among them, Simhanada Guggulu is a well-known Guggulu preparation indicated in Amavata. It was first mentioned by Acharya Chakrapani in Chakradatta. Action of this drug works to offer pain relief and detoxification and combats loss of appetite. An attempt is made to compile the review of Ayurvedic literature of Simhanada Guggulu

Bioactive components from Gynandropsis gynandra leaves for antinociceptive activity

Gynandropsis gynandra Linn. (Capparadiaceae) leaves are used in the treatment of pain traditionally. In order to evaluate its scientific validity, leaves were extracted successively to produce various extracts. These extracts were screened for antinociceptive activity using hot plate test and acetic acid-induced writhing test in mice at the dose of 100 mg/kg, intraperitoneally. Aqueous extract was found most active in both the tests. Further it was fractionated into four major fractions and were screened by the same tests at the dose of 25 mg/kg, i.p. Results showed that AQI fraction is most active and may responsible for the antinociceptive action. GC-MS analysis of AQI fraction showed that it is a mixture of benzene acetic acid ethyl ester, octaneoic acid, dodecanal, and cholest-4-en-26-al, 3-oxo-, cyclic 26-(ethylene acetate).Colegio de Farmacéuticos de la Provincia de Buenos Aire