Effect of licofelone against NSAIDs-induced gastrointestinal ulceration and inflammation

The present study was aimed to evaluate the effect of licofelone, a dual inhibitor of cycloxygenase1/2-5-lipoxygenase against indomethacin-induced gastric damage in rats and mice in order to assess the role of leukotrienes if any, in non-steroidal anti-inflammatory drugs (NSAIDs)-induced gastrointestinal inflammation. Acute pretreatment with licofelone reversed the indomethacin-induced gastric ulceration, neutrophil adhesion in mesentery venules, neutrophil count in blood, lipid peroxides and vascularity in the stomachs of mice and rats. Further, chronic pretreatment of licofelone also prevented indomethacin-induced gastric morphological changes and cellular infiltration in mesentery venules. Moreover, acute administration of indomethacin elevated leukotriene B4 levels in gastric mucosa, which was reversed by pretreatment with licofelone The results suggest that licofelone offered gastroprotection against NSAIDs-induced gastropathy through its effect on leukotrienes and by inhibiting extravasation of neutrophils.     

The KIF3 motor transports N-cadherin and organizes the developing neuroepithelium

In the developing brain, the organization of the neuroepithelium is maintained by a critical balance between proliferation and cell-cell adhesion of neural progenitor cells. The molecular mechanisms that underlie this are still largely unknown. Here, through analysis of a conditional knockout mouse for the Kap3 gene, we show that post-Golgi transport of N-cadherin by the KIF3 molecular motor complex is crucial for maintaining this balance. N-cadherin and beta-catenin associate with the KIF3 complex by co-immunoprecipitation, and colocalize with KIF3 in cells. Furthermore, in KAP3-deficient cells, the subcellular localization of N-cadherin was disrupted. Taken together, these results suggest a potential tumour-suppressing activity for this molecular motor.     

Purification and physiochemical characterization of melanin pigment from Klebsiella sp. GSK

The bacterium capable of producing melanin pigment in the presence of L-tyrosine was isolated from crop field soil sample and identified as Klebsiella sp. GSK based on morphological, biochemical and 16S rDNA sequencing. The polymerization of this pigment occurs outside the cell wall, which has granular structure as melanin ghosts. The chemical characterization of pigment particles showed acid resistant, alkali soluble, insoluble in most of the organic solvents and water. The pigment gets bleached when subjected to the action of oxidants as well as reductants. This pigment was precipitated with FeCl3, ammoniacal silver nitrate and potassium ferricynide. The pigment showed high absorbance in the UV region and decreased absorbance when shifted towards the visible region. The melanin pigment was further charecterized by FT-IR and EPR spectroscopy. A key enzyme 4-hydroxyphenylacetic acid hydroxylase catalyzes the formation of melanin pigment by hydroxylation of L-tyrosine was detected in this bacterium. Inhibition studies with specific inhibitor kojic acid and KCN proved that melanin is synthesized by DOPA-Melanin pathway.     

In vitro effect of some Indian honeys on Staphylococcus aureus from wounds

Staphylococcus aureus is the most frequently isolated pathogen from wounds with multiple resistances to antibiotics. Honey has been demonstrated and reported to be effective antibacterial agent on Gram positive and Gram negative organisms. Hence, the present study was conducted to evaluate the in vitro antibacterial effect of Indian honeys on Staphylococcus aureus obtained from wounds. A total of 123 Staphylococcus aureus isolates along with ATCC 25923 were categorized as sensitive, multi drug resistant (MDR) and non-MDR strains. Out of total nine Indian honeys (three each of unifloral, multifloral and branded marketed honey) used, three unifloral and three multifloral honey samples showed antibacterial activity against all the organisms tested by Agar diffusion method but not the branded marketed honeys. The MIC values of all honey samples for all studied Staphylococcus aureus isolates ranged between 5-15% (v/v). Unifloral honey samples showed higher antibacterial activity than multifloral honey. The single sample of Jambhul honey showed the highest activity. Thus, Indian honeys were found to be effective for their antimicrobial activity on sensitive, non-MDR, MDR and ATCC strains of S. aureus.     

A Rich1/Amot complex regulates the Cdc42 GTPase and apical-polarity proteins in epithelial cells

Using functional and proteomic screens of proteins that regulate the Cdc42 GTPase, we have identified a network of protein interactions that center around the Cdc42 RhoGAP Rich1 and organize apical polarity in MDCK epithelial cells. Rich1 binds the scaffolding protein angiomotin (Amot) and is thereby targeted to a protein complex at tight junctions (TJs) containing the PDZ-domain proteins Pals1, Patj, and Par-3. Regulation of Cdc42 by Rich1 is necessary for maintenance of TJs, and Rich1 is therefore an important mediator of this polarity complex. Furthermore, the coiled-coil domain of Amot, with which it binds Rich1, is necessary for localization to apical membranes and is required for Amot to relocalize Pals1 and Par-3 to internal puncta. We propose that Rich1 and Amot maintain TJ integrity by the coordinate regulation of Cdc42 and by linking specific components of the TJ to intracellular protein trafficking.