Protective effect of Trigonella foenum-graecum on thioacetamide induced hepatotoxicity in rats

Trigonella foenum-graecum belongs to the family Fabaceae and is indigenous to countries that lie on the eastern shores of the Mediterranean Sea and is also cultivated in India, Egypt and Africa. This study provides the evidence indicating the therapeutic effect of the extract prepared from the dried seeds of Trigonella foenum-graecum on an animal model of hepatotoxicity and on cell proliferation. Rats were induced liver cirrhosis by thioacetamide (0.03% in water for 16 weeks). Transmission electron microscopy of the liver tissue was done to evaluate liver cirrhosis. The herbal extract was administered orally for 3 weeks after induction and biochemical estimations were done. After the administration of extract the oxidative stress and lipid peroxidation were reversed. The elevated levels of alkaline phosphatase, γ-glutamyl transferase and selected biochemical markers of liver cirrhosis including drug metabolizing enzymes were also reversed. The study has implications in finding a treatment for liver cirrhosis by a natural herbal drug with no side effects.     

‘Chargaff's Rules’ for Protein Folding: Stoichiometric Leitmotif Made Visible

Abstract

The complex between cobalt hexammine and decadeoxyoligomer d(CGTACGTACG) crystallizes into the space group P6₅ with unit cell constants a = b = 17.93Å, and c = 43.41Å. The molecules have the helix axis coincident with the crystal c-axis. The decamers stack on top of each other and form a quasi-continuous helix. The structure is disordered. The asymmetric unit is a dimer (pPyr-pPur)₂ with each base pair 60% of the time a C-G and 40% of the time a T-A. Restrainted least-squares refinement led to an R-factor of 25.5% for 506 observed reflections above the two-sigma level. The structure was found to have one strand in the Z_I-conformation and the other in the Z_II-conformation. The cobalt hexammine binds to two Z_II-chains of symmetrically related molecules. On one Z_II chain, two ammonia molecules of the cobalt hexammine bind to the N7 nitrogen and 06 oxygen atoms of the guanine bases and a third ammonia to the phosphate anionic oxygen atom of the preceding pyrimidine base, resulting in an “external” binding mode. On the other Z_II chain, one ammonia molecule of the cobalt hexammine binds only to the anionic oxygens of the phosphate group of the guanine bases, leading to an “internal” binding mode. Thus, the basis of the stabilization of Z-DNA by [Co(NH₃)₆]³⁺ is its binding to only guanine nucleotides. It is surmised that statistical disordering of deoxyoligonucleotide structures which take a Z conformation, depends on the length of the oligomer. That is to say, octamers and decamers (which cannot use an integral number of molecules for a 12 base pair repeat) form disordered structures whereas tetramers and hexamers form well ordered structures.     

Prediction and Molecular Modeling of T-cell Epitopes Derived from Placental Alkaline Phosphatase for use in Cancer Immunotherapy

Abstract

In our ongoing efforts to combat cancer, peptide-based tumor vaccines are promising as one of the several alternatives used for cancer immunotherapy and immunoprevention. We have attempted to identify T-cell epitopes suitable for the development of a peptide-based cancer vaccine directed towards placental isozyme of alkaline phosphatase (PLAP), an oncofetal antigen. After identifying amino acid residues specific to PLAP and distinct from other close PLAP homologs, we have used sequence-based immunoinformatics tools (BIMAS and SYF- PEITHI) and conducted molecular modeling studies using InsightII to investigate the binding affinity of the epitopes containing the unique residues with respective MHC class I molecules. Promiscuous epitopes binding to different alleles of different class I HLA loci were analyzed to get a population coverage that is widespread. Binding affinity deduced from the modeling studies corroborated the status of most of the epitopes scoring high in BIMAS and SYFPEITHI. We have thus identified specific epitopes from PLAP that have a potential for binding to their respective MHC class I alleles with high affinity. These peptides would be analysed in experiments to demonstrate their involvement in the induction of primary cytotoxic T-cell responses in vitro, using respective HLA-restricted T-cells in our way towards the development of an effective anti-cancer vaccine in a background of diverse MHC haplotypes.     

Extending julius seizure,a bang-sensitive gene,as a model for studying epileptogenesis: Cold shock,and a new insertional mutation

The bang-sensitive (BS) mutants of Drosophila are an important model for studying epilepsy. We recently identified a novel BS locus, julius seizure (jus), encoding a protein containing two transmembrane domains and an extracellular cysteine-rich loop. We also determined that jus^{sda iso7.8}, a previously identified BS mutation, is an allele of jus by recombination, deficiency mapping, complementation testing, and genetic rescue. RNAi knockdown revealed that jus expression is important in cholinergic neurons and that the critical stage of jus expression is the mid-pupa. Finally, we found that a functional, GFP-tagged genomic construct of jus is expressed mostly in axons of the neck connectives and of the thoracic abdominal ganglia. In this Extra View article, we show that a MiMiC GFP-tagged Jus is localized to the same nervous system regions as the GFP-tagged genomic construct, but its expression is mostly confined to cell bodies and it causes bang-sensitivity. The MiMiC GFP-tag lies in the extracellular loop while the genomic construct is tagged at the C-terminus. This suggests that the alternate position of the GFP tag may disrupt Jus protein function by altering its subcellular localization and/or stability. We also show that a small subset of jus-expressing neurons are responsible for the BS phenotype. Finally, extending the utility of the BS seizure model, we show that jus mutants exhibit cold-sensitive paralysis and are partially sensitive to strobe-induced seizures.     

Fitness consequences of body melanization in Drosophila immigrans from montane habitats

We investigated eight populations of Drosophila immigrans from low to high montane localities (600–2202 m) for altitudinal variations in abdominal melanization and fitness-related traits (desiccation resistance, copulation duration, and fecundity). On the basis of common garden experiments, persistence between-population differences at 21°C suggests that observed variations in fitness-related traits have a genetic basis. Parent–offspring regression analyses showed higher heritability (h²= 0.77) for melanization patterns on all the abdominal tergites. All the traits showed significantly higher repeatability across generations. Under colder and drier environments in dispersed montane localities, abdominal melanization and desiccation resistance significantly increased (1.5–1.9 fold) along altitude. Thus, there are correlated effects of abdominal melanization on desiccation resistance. Genetic correlations, based on family means, were significantly high between abdominal melanization and other fitness traits. Furthermore, darker flies along increasing altitude resulted in a 35–40% increase in copulation duration as well as fecundity. There are significantly positive correlations of abdominal melanization with copulation duration as well as fecundity on the basis of within- as well as between-population variations. Such observations are in agreement with the thermal budget hypothesis. Present data suggest that changes in body melanization impact fitness-related traits in montane populations of Drosophila immigrans .     

Exotic tropical plant Psidium cattleianum: a review on prospects and threats

Psidium cattleianum Sabine or strawberry guava is an exotic tropical plant belonging to Myrtaceae family. Generally, this ornamental shrub is prized for its aesthetic value. However, this low-profile plant is an untapped source of therapeutically relevant phytochemicals, evident from the structural investigations. The delicious tart ripe fruits can be eaten fresh, made into a plethora of food products and pectin can be extracted from the pulp. Ameliorative attributes of this shrub viz. antioxidant, antimicrobial and antiproliferative have been reported in recent times. On the other hand, this shrub has emerged as a habitat-altering pest in Hawaii, threatening the rare endemic flora. Releasing biocontrol agents into the wilderness to hinder the unchecked proliferation of this hardy shrub is being speculated and conducted, without any obvious success till now. In this mini review the industrial and pharmaceutical prospect of this little known plant will be discussed. It is believed that, this review will serve as a useful reference and encourage future research on hitherto unknown potential of this exotic plant.     

Evolving Roles of Probiotics in Cancer Prophylaxis and Therapy

In nutraceutical science, the ingestible live microbes ‘probiotics’ are regarded for their ability to confer multiplicity of health benefits on the consumers. Wide spectrum impact of these friendly microbes on the host health has been proved very frequently. They have been confirmed to boost immunity, aid in digestion, eliminate pathogens, curb inflammatory bowel diseases, moderate side effects of antibiotic therapy, lower cholesterol and blood glycemic index and produce vitamins. This review, however, focuses on the incipient, but promising area of probiotic diet-based prevention and remedy of cancer. Researchers are in universal agreement with the critical role of probiotics in getting rid of mutagens, delaying the onset of tumors, alleviating the side effects, pepping up chemotherapy, easing the postoperative complications, foiling remission and lifting the spirit of survivors. The key findings in the emerging roles of probiotics in onco-care have been summarized; the biological pathways discussed and anticipated developments in coming times are presented.