Anthracycline-induced cardiotoxicity and the cardiac-sparing effect of liposomal formulation

The anthracyclines are a group of antibiotics that are among the most potent chemotherapeutic agents. They are highly effective against a broad spectrum of malignancies, including lymphoma, gastric cancer, small cell lung cancer, sarcoma, and breast cancer. Unfortunately, these agents also exhibit a well-recognized cumulative-dose related cardiotoxic profile that limits the extent to which they can be used safely. In clinical practice, most clinicians limit the cumulative dose of doxorubicin (the most widely used agent in this group) to 400-450 mg/m2, but considerable cardiac damage is now known to occur at cumulative dosages considerably below this level. Regimens using newer combinations of agents, the most widely studied of which is the monoclonal antibody trastuzumab, are known to augment the cardiotoxicity of anthracyclines. The application of nanotechnology to medicine involves the use of devices that will interact with the body at the molecular level. These methods can lead to target and tissue specific clinical application, often with minimal or reduced side effects. Liposomal preparations incorporate such technology, thereby altering some important characteristics of the parent compound and facilitating concentration at the tumor site. In the case of liposomal doxorubicin, cardiotoxicity is reduced significantly. This review summarizes the important information on the liposomal preparation of anthracyclines.     

Evolutionary analysis of enzymes using Chisel

MOTIVATION: Availability of large volumes of genomic and enzymatic data for taxonomically and phenotypically diverse organisms allows for exploration of the adaptive mechanisms that led to diversification of enzymatic functions. We present Chisel, a computational framework and a pipeline for an automated, high-resolution analysis of evolutionary variations of enzymes. Chisel allows automatic as well as interactive identification, and characterization of enzymatic sequences. Such knowledge can be utilized for comparative genomics, microbial diagnostics, metabolic engineering, drug design and analysis of metagenomes. RESULTS: Chisel is a comprehensive resource that contains 8575 clusters and subsequent computational models specific for 939 distinct enzymatic functions and, when data is sufficient, their taxonomic variations. Application of Chisel to identification of enzymatic sequences in newly sequenced genomes, analysis of organism-specific metabolic networks, 'binning' of metagenomes and other biological problems are presented. We also provide a thorough analysis of Chisel performance with other similar resources and manual annotations on Shewanella oneidensis MR1 genome.     

Spatial Assessment of Heavy Metals in Surface Soil from Klang District (Malaysia): An Example from a Tropical Environment

Heavy metals (Al, Cd, Co, Cr, Cu, Fe, Pb, Zn) in surface soil of Klang district were determined and multivariate analysis was used to understand their potential sources. The total and bioavailability of concentrations were used in identifying the potential risks to the ecology and human health. The means for the total heavy metal concentrations were found to be in the order of Fe > Al > Zn > Pb > Cu > Cr > Co > Cd, while the means for the bioavailability concentrations were found to be in the order of Al > Fe > Zn > Cu > Co > Cd > Pb > Cr. Principal Component Analysis showed Principal Component 1 as being of natural origin whereas Principal Components 2, 3, and 4 were associated with mixed anthropogenic sources, such as traffic and industrial emissions, organic matter, and granulometric fractions. Potential ecological risk assessment indicated an overall low ecological risk. Spatial assessment of non-carcinogenic risks showed that the Hazard Index values were more than one in Johan Setia, due to biomass burning of peat swamps exploited for agricultural development. While for spatial assessment of carcinogenic risks, the Lifetime Cancer Risk values were in the limit (1 × 10^?5), indicating low cancer inducing risks. Nevertheless, with intense development pressure in the Klang district could overlap pollution inputs in the future.     

Cell memory‐based therapy

Current cell therapies, despite all of the progress in this field, still faces major ethical, technical and regulatory hurdles. Because these issues possibly stem from the current, restricted, stereotypical view of cell ultrastructure and function, we must think radically about the nature of the cell. In this regard, the author's theory of the cell memory disc offers ‘memory‐based therapy’, which, with the help of immune system rejuvenation, nervous system control and microparticle‐based biodrugs, may have substantial therapeutic potential. In addition to its potential value in the study and prevention of premature cell aging, age‐related diseases and cell death, memory therapy may improve the treatment of diseases that are currently limited by genetic disorders, risk of tumour formation and the availability and immunocompatibility of tissue transplants.     

Genome sequence of the fish pathogen Flavobacterium columnare ATCC 49512

Flavobacterium columnare is a Gram-negative, rod-shaped, motile, and highly prevalent fish pathogen causing columnaris disease in freshwater fish worldwide. Here, we present the complete genome sequence of F. columnare strain ATCC 49512.     

Cell population based mass spectrometry using platinum nanodots for algal and fungal studies

For the first time, we applied cell-population based mass spectrometry (CP-MS) for biosensing intact eukaryotic cells of Chlamydomonas reinhardtii and Saccharomyces cerevisiae. Cell counts ranging from 1 × 10(7) to 1.28 × 10(2) were analyzed using MALDI-MS to obtain the threshold detection sensitivity. Platinum nanodots (Pt NDs) were used to enhance the detection sensitivity of CP-MS. Pt NDs were able to improve the detection sensitivity of CP-MS from 3200 cells/mL to 640 cells/mL (5-fold) for Chlamydomonas. For yeast cells, the detection sensitivity was also increased from 400,000 cells/mL to 3200 cells/mL (125-fold) when Pt NDs were used. Using the Clin Pro tool, the obtained results from MALDI-MS data were validated. Statistical analysis of the mass data was performed using MYSTAT software.     

A Computational analysis on Lectin and Histone H1 protein of different pulse species as well as comparative study with rice for balanced diet

The issue of balanced nutrition is of great concern to human. Meat and fish are the best sources of protein. The affordability of these resources for people in developing countries is less. Thus, there is an increasing interest in pulses and its derivates as an alternative to fish and meat. Lectin and histone H1 are the most common proteins in various pulses and our interest is in identifying the dominant essential amino acids in them for use as supplements. However, actin and lectin are common among Oryza Sativa and cicer arietinum. We describe the amount of lectin and histone H1 in cicer arietinum, Lens culinaris and Pisum sativum in a comparative manner. cicer arietinum was found to contain more essential amino acids than Lens culinaris and Pisum sativum. The secondary structures of lectin and histone H1 protein were analyzed to gain functional inferences in these species. The comparative study shows the relatively poor presence of the amino acid methionine in most pulses. However, Oryza Sativa was found to contain sufficient methionine. The study shows that pulses (especially cicer arietinum) were a suitable alternative source to meat and fish for Lectin and Histone H1 balance. Hence, pulses could be suggested with rice for balanced protein diet.     

Caspase-3 Protects Stressed Organs against Cell Death

The ability to generate appropriate defense responses is crucial for the survival of an organism exposed to pathogenesis-inducing insults. However, the mechanisms that allow tissues and organs to cope with such stresses are poorly understood. Here we show that caspase-3-knockout mice or caspase inhibitor-treated mice were defective in activating the antiapoptotic Akt kinase in response to various chemical and environmental stresses causing sunburns, cardiomyopathy, or colitis. Defective Akt activation in caspase-3-knockout mice was accompanied by increased cell death and impaired survival in some cases. Mice homozygous for a mutation in RasGAP that prevents its cleavage by caspase-3 exhibited a similar defect in Akt activation, leading to increased apoptosis in stressed organs, marked deterioration of their physiological functions, and stronger disease development. Our results provide evidence for the relevance of caspase-3 as a stress intensity sensor that controls cell fate by either initiating a RasGAP cleavage-dependent cell resistance program or a cell suicide response.