Paracrine effects of mesenchymal stem cells in cisplatin-induced renal injury require heme oxygenase-1

Multipotent mesenchymal stem cells (MSC) have become a popular and promising therapeutic approach in many clinical conditions. MSC are beneficial in animal models of acute kidney injury (AKI), by mediating differentiation-independent paracrine properties, and have prompted ongoing clinical trials to evaluate the safety and efficacy of MSC. Heme oxygenase-1 (HO-1) is induced in response to stress including AKI and has important anti-apoptotic, anti-inflammatory, and proangiogenic properties in these settings. We therefore examined whether HO-1 plays a role in the beneficial effects of MSC in AKI. We isolated MSC from bone marrow of age-matched HO-1+/+ and HO-1-/- mice. Our studies indicate that while differentiation of MSC into osteo- and adipocytic lineages did not differ between cells isolated from HO-1+/+ and HO-1-/- mice, MSC from HO-1-/- mice had significantly lower angiogenic potential. Moreover, HO-1-/- MSC demonstrated reduced expression and secretion of several important growth and proangiogenic factors (stromal cell-derived factor-1, vascular endothelial growth factor-A, and hepatocyte growth factor) compared with MSC derived from HO-1+/+ mice. In addition, conditioned medium of HO-1+/+ MSC rescued functional and morphological changes associated with cisplatin-induced AKI, while the HO-1-/--conditioned medium was ineffectual. Our studies indicate that HO-1 plays an important role in MSC-mediated protection. The results expand understanding of the renoprotective effects of MSC and may provide novel strategies to better utilize MSC in various disease models.     

Novel lipase-catalysed highly selective acetylation studies on D-arabino- and D-threo-polyhydroxyalkyltriazoles

Capabilities of lipases from Candida antarctica, Candida rugosa and porcine pancreas have been evaluated for regioselective acetylation of 2-phenyl-4-(D-arabino-tetrahydroxybutyl)-2H-1,2,3-triazole, 2-phenyl-4-(D-arabino-O-1',2'-isopropylidene-3',4'-dihydroxybutyl)-2H-1,2,3-triazole and 2-phenyl-4-(D-threo-trihydroxypropyl)-2H-1,2,3-triazole, precursors for the synthesis of triazolylacyclonucleosides. C. antarctica lipase and porcine pancreatic lipase exhibited exclusive selectivity for the acetylation of primary hydroxyl group over secondary hydroxyl group(s) in all the three cases.     

Oleanane triterpenoids in the prevention and therapy of breast cancer: current evidence and future perspectives

Breast cancer is one of the most frequently diagnosed cancers and major cause of death in women in the world. Emerging evidence underscores the value of dietary and non-dietary phytochemicals, including triterpenoids, in the prevention and treatment of breast cancer. Oleanolic acid, an oleanane-type pentacyclic triterpenoid, is present in a large number of dietary and medicinal plants. Oleanolic acid and its derivatives exhibit several promising pharmacological activities, including antioxidant, anti-inflammatory, hepatoprotective, cardioprotective, antipruritic, spasmolytic, antiallergic, antimicrobial and antiviral effects. Numerous studies indicate that oleanolic acid and other oleanane triterpenoids modulate multiple intracellular signaling pathways and exert chemopreventive and antitumor activities in various in vitro and in vivo model systems. A series of novel synthetic oleanane triterpenoids have been prepared by chemical modifications of oleanolic acid and some of these compounds are considered to be the most potent anti-inflammatory and anticarcinogenic triterpenoids. Accumulating studies provide extensive evidence that synthetic oleanane derivatives inhibit proliferation and induce apoptosis of various cancer cells in vitro and demonstrate cancer preventive or antitumor efficacy in animal models of blood, breast, colon, connective tissue, liver, lung, pancreas, prostate and skin cancer. This review critically examines the potential role of oleanolic acid, oleanane triterpenoids and related synthetic compounds in the chemoprevention and treatment of mammary neoplasia. Both in vitro and in vivo studies on these agents and related molecular mechanisms are presented. Several challenges and future directions of research to translate already available impressive preclinical knowledge to clinical practice of breast cancer prevention and therapy are also presented.     

Nodes occupying central positions in human tissue specific PPI networks are enriched with many splice variants

The functional repertoire of genes in the eukaryotic organisms is enhanced by the phenomenon of alternative splicing. Hence, a node in a tissue specific protein–protein interaction (TS PPIN) network can be thought of as an ensemble of various spliced protein products of the corresponding gene expressed in that tissue. Here we demonstrate that the nodes that occupy topologically central positions characterized by high degree, betweenness, closeness, and eigenvector centrality values in TS PPINs of Homo sapiens are associated with high number of splice variants. We also show that the high “centrality” of these genes/nodes could in part be explained by the presence of a large number of promiscuous domains.     

Titanium Dioxide Nanoparticles As Guardian against Environmental Carcinogen Benzo[alpha]Pyrene

Polycyclic aromatic hydrocarbons (PAH), like Benzo[alpha]Pyrene (BaP) are known to cause a number of toxic manifestations including lung cancer. As Titanium dioxide Nanoparticles (TiO₂ NPs) have recently been shown to adsorb a number of PAHs from soil and water, we investigated whether TiO₂ NPs could provide protection against the BaP induced toxicity in biological system. A549 cells when co-exposed with BaP (25 µM, 50 µM and 75 µM) along with 0.1 µg/ml,0.5 µg/ml and 1 µg/ml of TiO₂ NPs, showed significant reduction in the toxic effects of BaP, as measured by Micronucleus Assay, MTT Assay and ROS Assay. In order to explore the mechanism of protection by TiO₂ NP against BaP, we performed in silico studies. BaP and other PAHs are known to enter the cell via aromatic hydrocarbon receptor (AHR). TiO₂ NP showed a much higher docking score with AHR (12074) as compared to the docking score of BaP with AHR (4600). This indicates a preferential binding of TiO₂ NP with the AHR, in case if both the TiO₂ NP and BaP are present. Further, we have done the docking of BaP with the TiO₂ NP bound AHR-complex (score 4710), and observed that BaP showed strong adsorption on TiO₂ NP itself, and not at its original binding site (at AHR). TiO₂ NPs thereby prevent the entry of BaP in to the cell via AHR and hence protect cells against the deleterious effects induced by BaP.     

Putative Location of Common Region and Coat Protein Gene of Blackgram Isolate of Mungbean Yellow Mosaic Geminivirus

Reciprocal cross hybridization between DNA-A and ONA-B molecules showed that MYMV genome contains certain regions common to each other. “Common region” of MYMV belongs to the 0.55 kb Kpnl-Clal fragment of DNA-A and 0.25 kb Xbal-Hind III fragment of DNA-B. Hybridization of DNA-A restriction fragments with the full length coat protein region probe to Indian cassava mosaic virus (ICMV) showed the location of MYMV coat protein coding region in DNA-A. The greater extent of homology of ICMV coat protein region falls within the 400 base pair region of Clal-Clal fragment in DNA-A of MYMV-Bg. The homology between ICMV and MYMV-Bg coat protein gene appeared to be less than 50%. Cross hybridization between DNA-A and DNA-B molecules helped to trim out the homologous region and the DNA-A and DNA-B specific probes could be tailored.     

Lancet Dynamics in Greater Horseshoe Bats,Rhinolophus ferrumequinum

Echolocating greater horseshoe bats (Rhinolophus ferrumequinum) emit their biosonar pulses nasally, through nostrils surrounded by fleshy appendages (‘noseleaves’) that diffract the outgoing ultrasonic waves. Movements of one noseleaf part, the lancet, were measured in live bats using two synchronized high speed video cameras with 3D stereo reconstruction, and synchronized with pulse emissions recorded by an ultrasonic microphone. During individual broadcasts, the lancet briefly flicks forward (flexion) and is then restored to its original position. This forward motion lasts tens of milliseconds and increases the curvature of the affected noseleaf surfaces. Approximately 90% of the maximum displacements occurred within the duration of individual pulses, with 70% occurring towards the end. Similar lancet motions were not observed between individual pulses in a sequence of broadcasts. Velocities of the lancet motion were too small to induce Doppler shifts of a biologically-meaningful magnitude, but the maximum displacements were significant in comparison with the overall size of the lancet and the ultrasonic wavelengths. Three finite element models were made from micro-CT scans of the noseleaf post mortem to investigate the acoustic effects of lancet displacement. The broadcast beam shapes were found to be altered substantially by the observed small lancet movements. These findings demonstrate that—in addition to the previously described motions of the anterior leaf and the pinna—horseshoe bat biosonar has a third degree of freedom for fast changes that can happen on the time scale of the emitted pulses or the returning echoes and could provide a dynamic mechanism for the encoding of sensory information.     

Boosted UV Sensitivity of Er-Doped In2O3 Thin Films Using Plasmonic Ag Nanoparticle-Based Surface Texturing

Plasmonics - Ag nanoparticles (NPs) were deposited on the sol-gel-processed Erbium-doped Indium Oxide (In2O3:Er) thin films (TFs) using thermal evaporation cum glancing angle deposition technique...