Withaferin A (WA) is present abundantly in Withania somnifera, a well-known Indian medicinal plant. Here we demonstrate how WA exhibits a strong growth-inhibitory effect on several human leukemic cell lines and on primary cells from patients with lymphoblastic and myeloid leukemia in a dose-dependent manner, showing no toxicity on normal human lymphocytes and primitive hematopoietic progenitor cells. WA-mediated decrease in cell viability was observed through apoptosis as demonstrated by externalization of phosphatidylserine, a time-dependent increase in Bax/Bcl-2 ratio; loss of mitochondrial transmembrane potential, cytochrome c release, caspases 9 and 3 activation; and accumulation of cells in sub-G0 region based on DNA fragmentation. A search for the downstream pathway further reveals that WA-induced apoptosis was mediated by an increase in phosphorylated p38MAPK expression, which further activated downstream signaling by phosphorylating ATF-2 and HSP27 in leukemic cells. The RNA interference of p38MAPK protected these cells from WA-induced apoptosis. The RNAi knockdown of p38MAPK inhibited active phosphorylation of p38MAPK, Bax expression, activation of caspase 3 and increase in Annexin V positivity. Altogether, these findings suggest that p38MAPK in leukemic cells promotes WA-induced apoptosis. WA caused increased levels of Bax in response to MAPK signaling, which resulted in the initiation of mitochondrial death cascade, and therefore it holds promise as a new, alternative, inexpensive chemotherapeutic agent for the treatment of patients with leukemia of both lymphoid and myeloid origin.

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An evanescent wave optical fiber biosensor based on titania-silica-coated long period grating (LPG) is presented. The chemical overlay, which increases the refractive index (RI) sensitivity of the sensor, consists of a sol-gel-based titania-silica thin film, deposited along the sensing portion of the fiber by means of the dip-coating technique. Changing both the sol viscosity and the withdrawal speed during the dip-coating made it possible to adjust the thickness of the film overlay, which is a crucial parameter for the sensor performance. After the functionalization of the fiber surface using a methacrylic acid/methacrylate copolymer, an antibody/antigen (IgG/anti-IgG) assay was carried out to assess the performance of sol-gel based titania-silica-coated LPGs as biosensors. The analyte concentration was determined from the wavelength shift at the end of the binding process and from the initial binding rate. This is the first time that a sol-gel based titania-silica-coated LPG is proposed as an effective and feasible label-free biosensor. The specificity of the sensor was validated by performing the same model assay after spiking anti-IgG into human serum. With this structured LPG, detection limits of the order of tens of micrograms per liter (10(-11) M) are attained.

New generation antimicrobial and smart drugs are the needs of the present era in fighting microbial infection and various chronic diseases. Nowadays nanoparticles (NPs) are widely applied in biomedical fields by virtue of their surface modification, which enhances both target selectivity and function. This study is a continuation of our earlier study that demonstrated antimicrobial property of NPs against both Gram-positive and Gramnegative organisms (Goswami et al, 2015). Silver NPs were synthesized using tea leaves (Camellia sinensis) decoction and were characterized using UV-vis spectrophotometry, transmission electron microscopy (TEM) and Fouriertransformed infrared spectroscopy (FTIR). The silver NPs were stable at various environmental conditions. The stability of the particles may be due to various phytochemicals of tea that were bound to the surface of reduced silver ions as a capping agent. The antimicrobial activity of NP was investigated against three Gram-negative pathogenic bacteria (Shigella dysentriae, Salmonella infestis and Vibrio parahaemolyticus). The outer membrane of Gram-negative bacteria is a lipopolysaccharide (LPS) in nature and provides protection from various stress conditions and antibiotics. But a silver NP destroys its membrane integrity and thus helps in cell killing. Spectral changes confirmed NP interaction with hydrophobic moiety of LPS. Minimum inhibitory concentrations for S. dysentriae, S. infestis and V. parahaemolyticus were 3.75, 5.25 and 5.25 μg ml −1 , respectively. Inhibition of biofilm formation was significant with the three bacterial strains. Cytoplasmic leakage from each bacterial strain was also demonstrated on account of NP treatment. The particles demonstrated good biocompatibility. No damage of human buccal mucosal cells was recorded even at concentration of 10 mg ml −1. Thus, silver NPs would be potential oral therapeutic molecules against Gram-negative bacteria.