Superior Therapeutic Efficacy of Nanoparticle Albumin Bound Paclitaxel Over Cremophor-Bound Paclitaxel in Experimental Esophageal Adenocarcinoma

Esophageal adenocarcinoma (EAC) is the fastest growing cancer in the western world and the overall 5 year survival rate of EAC is below 20%. Most patients with EAC present with locally advanced or widespread metastatic disease, where current treatment is largely ineffective. Therefore, new therapeutic approaches are urgently needed. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is a novel albumin-stabilized, cremophor-free and water soluble nanoparticle formulation of paclitaxel, and the potential role of nab-paclitaxel has not been tested yet in experimental EAC. Here we tested the antiproliferative and antitumor efficacy with survival advantage of nab-paclitaxel as monotherapy and in combinations in in-vitro, and in murine subcutaneous xenograft and peritoneal metastatic survival models of human EAC. Nab-paclitaxel significantly inhibited in-vitro cell proliferation with higher in-vivo antitumour efficacy and survival benefit compared to paclitaxel or carboplatin treatments both in mono- and combination therapies. Nab-paclitaxel treatment increased expression of mitotic-spindle associated phospho-stathmin, decreased expression of proliferative markers and enhanced apoptosis. This study demonstrates that nab-paclitaxel had stronger antiproliferative and antitumor activity in experimental EAC than the current standard chemotherapeutic agents which supports the rationale for its clinical use in EAC.     

In vitro clonal propagation of<Emphasis Type="Italic"> Clerodendrum serratum</Emphasis> (Linn.) Moon (barangi): a rare and threatened medicinal plant

An in vitro process for rapid clonal propagation of Clerodendrum serratum (Linn.) Moon, a rare and threatened medicinal shrub, has been developed. Nodal stem segments having axillary bud, taken from field-grown plant, showed bud-break within 15 days of culture on modified Murashige and Skoog (MS) (Physiol Plant 15:473–497, 1962) medium supplemented with 0.25 mg/l each of 6-benzylaminopurine and indole-3-acetic acid along with 15 mg/l adenine sulphate (AdS). Regenerated shoots could be further multiplied on the same agarified morphogenetic medium in presence of 0.5 mg/l 2-chloroethyltrimethyl ammonium chloride with increased concentration of AdS, i.e., 30 mg/l. A group of five shoots used as inoculum produced on an average 4.98 new shoots per original shoot after 4 weeks of subculture. Shoots excised from cultures of proliferating shoots were rooted in half-strength MS medium having 1 mg/l indole-3-propionic acid. In vitro rooted shoots—plantlets—grew luxuriantly under field conditions and came to flowering after 10 months of transplantation. The genetic fidelity of in vitro-raised field-grown plants and their mother plant was ascertained by random amplified polymorphic DNA markers. The protocol developed holds good for in vitro cloning of C. serratum.     

Correlates of substitution rate variation in mammalian protein-coding sequences

Background  

Rates of molecular evolution in different lineages can vary widely, and some of this variation might be predictable from aspects of species' biology. Investigating such predictable rate variation can help us to understand the causes of molecular evolution, and could also help to improve molecular dating methods. Here we present a comprehensive study of the life history correlates of substitution rate variation across the mammals, comparing results for mitochondrial and nuclear loci, and for synonymous and non-synonymous sites. We use phylogenetic comparative methods, refined to take into account the special nature of substitution rate data. Particular attention is paid to the widespread correlations between the components of mammalian life history, which can complicate the interpretation of results.     

Piperine,an active ingredient of white pepper,suppresses the growth of multidrug-resistant toxigenic Vibrio cholerae and other pathogenic bacteria

Emergence and rapid spread of multidrug-resistant (MDR) bacteria including Vibrio cholerae are a global public health issue. Much attention has been paid to natural compounds, such as spices and herbs to find novel antimicrobial compounds as they are considered to be cheaper alternatives to develop as a drug. Here, we show that methanol extract of white pepper could inhibit the growth of V. cholerae O1 El Tor variant, responsible for the recent outbreaks/epidemics. Furthermore, we demonstrate for the first time that piperine, the major component of white pepper, showed a dose-dependent bactericidal effect on V. cholerae growth irrespective of their biotypes and serogroups in the presence of 200 and 300 µg ml⁻¹ of piperine, respectively. Piperine also inhibited the growth of MDR strains of Pseudomonas aeruginosa, Escherichia coli isolated from poultry and enterohemorrhagic/enteroaggregative E. coli O104 in the presence of 200 µg ml⁻¹. Interestingly, we did not observe any significant inhibitory effect of piperine on E. coli strains isolated from healthy person even up to 200 µg ml⁻¹. Our data suggest that piperine could be a novel antimicrobial agent in therapeutic and preventive applications against infections caused by pathogenic bacteria including MDR strains.     

Protection of potato virus X infection by plant extracts

Extracts from the roots ofBoerhaavia diffusa L., stems ofCuscuta reflexa Roxb. or leaves ofEuphorbia hirta L. have shown a potential protective effect on the infection of potato virus X, in hypersensitive and systemic hosts. The inhibition by these extracts was systemic and sensitive to actinomycin D.