Normal hematological indices, blood chemistry and histology and ultrastructure of pancreatic islets in the wild Indian bonnet monkeys (Macaca radiata radiata)

The present study is aimed at determining some haematological and biochemical parameters in the wild Indian bonnet monkeys as also the microscopic and ultrastructural characteristics of their pancreatic islets. Adult wild Indian bonnet monkeys (Macaca radiata radiata) of both sexes weighing between 2.5 and 4 kg were used in these experiments. Their platelet, reticulocyte and total leukocyte counts and the blood concentrations of hemoglobin and plasma proteins and the serum concentrations of aspartate amino transferase, alanine amino transferase and calcium are similar to the values reported for M. mulatta. Plasma glucose is lower when compared with reported values of M. mulatta and M. fascicularis. Insulin levels are comparable with those of M. mulatta and M. nigra. Histology of islets is similar to that of humans. Ovoid cell collections of islet cells are scattered throughout the pancreas. Ultrastructure of A, B and D cells is similar to humans. These findings suggest that this relatively underutilized macaques may be a suitable model for biomedical research.     

Structural and Kinetic Analysis of Nucleoside Triphosphate Incorporation Opposite an Abasic Site by Human Translesion DNA Polymerase η

The most common lesion in DNA is an abasic site resulting from glycolytic cleavage of a base. In a number of cellular studies, abasic sites preferentially code for dATP insertion (the “A rule”). In some cases frameshifts are also common. X-ray structures with abasic sites in oligonucleotides have been reported for several microbial and human DNA polymerases (pols), e.g. Dpo4, RB69, KlenTaq, yeast pol ι, human (h) pol ι, and human pol β. We reported previously that hpol η is a major pol involved in abasic site bypass (Choi, J.-Y., Lim, S., Kim, E. J., Jo, A., and Guengerich, F. P. (2010 J. Mol. Biol. 404, 34–44). hpol η inserted all four dNTPs in steady-state and pre-steady-state assays, preferentially inserting A and G. In LC-MS analysis of primer-template pairs, A and G were inserted but little C or T was inserted. Frameshifts were observed when an appropriate pyrimidine was positioned 5′ to the abasic site in the template. In x-ray structures of hpol η with a non-hydrolyzable analog of dATP or dGTP opposite an abasic site, H-bonding was observed between the phosphate 5′ to the abasic site and water H-bonded to N1 and N6 of A and N1 and O6 of G nucleoside triphosphate analogs, offering an explanation for what appears to be a “purine rule.” A structure was also obtained for an A inserted and bonded in the primer opposite the abasic site, but it did not pair with a 5′ T in the template. We conclude that hpol η, a major copying enzyme with abasic sites, follows a purine rule, which can also lead to frameshifts. The phenomenon can be explained with H-bonds.     

Two novel CTNS mutations in cystinosis patients in Thailand

Cystinosis is an autosomal recessive disorder characterized by defective transport of cystine across the lysosomal membrane and resulting in renal, ophthalmic, and other organ abnormalities. Mutations in the CTNS gene cause a deficiency of the transport protein, cystinosin. We performed mutation analysis of CTNS in six cystinosis patients from four families in Thailand. Using PCR sequencing of the entire coding regions, we identified all eight mutant alleles, including two mutations, p.G309D and p.Q284X, that have not been previously reported. This study expands the mutational and population spectrum of nephropathic cystinosis.     

Clusterin as modulator of carcinogenesis: A potential avenue for targeted cancer therapy

Clusterin (CLU) is an evolutionary conserved molecular chaperone present in different human tissues and fluids and established to be a significant cancer regulator. It controls several cancer-associated cellular events, including cancer cell proliferation, stemness, survival, metastasis, epithelial-mesenchymal transition, therapy resistance, and inhibition of programmed cell death to support cancer growth and recurrence. This multifunctional role of CLU makes it an ideal target for cancer control. More importantly, genetic and antisense-mediated (OGX-011) inhibition of CLU enhances the anticancer potential of different FDA-approved chemotherapeutic drugs at the clinical level, improving patient's survival. In this review, we have discussed the detailed mechanism of CLU-mediated modulation of different cancer-associated signaling pathways. We have also provided updated information on the current preclinical and clinical findings that drive trials in various cancer types for potential targeted cancer therapy.     

Cure of tuberculosis using nanotechnology: An overview

Mycobacterium tuberculosis is the causative agent of tuberculosis (TB), a major health issue of the present era. The bacterium inhabits the host macrophage and other immune cells where it modulates the lysosome trafficking protein, hinders the formation of phagolysosome, and blocks the TNF receptor-dependent apoptosis of host macrophage/monocytes. Other limitations such as resistance to and low bioavailability and bio-distribution of conventional drugs aid to their high virulence and human mortality. This review highlights the use of nanotechnology-based approaches for drug formulation and delivery which could open new avenues to limit the pathogenicity of tuberculosis. Moreover phytochemicals, such as alkaloids, phenols, saponins, steroids, tannins, and terpenoids, extracted from terrestrial plants and mangroves seem promising against M. tuberculosis through different molecular mechanisms. Further understanding of the genomics and proteomics of this pathogenic microbe could also help overcome various research gaps in the path of developing a suitable therapy against tuberculosis.     

Histone Deacetylases: A Saga of Perturbed Acetylation Homeostasis in Cancer

In the current era of genomic medicine, diseases are identified as manifestations of anomalous patterns of gene expression. Cancer is the principal example among such maladies. Although remarkable progress has been achieved in the understanding of the molecular mechanisms involved in the genesis and progression of cancer, its epigenetic regulation, particularly histone deacetylation, demands further studies. Histone deacetylases (HDACs) are one of the key players in the gene expression regulation network in cancer because of their repressive role on tumor suppressor genes. Higher expression and function of deacetylases disrupt the finely tuned acetylation homeostasis in both histone and non-histone target proteins. This brings about alterations in the genes implicated in the regulation of cell proliferation, differentiation, apoptosis and other cellular processes. Moreover, the reversible nature of epigenetic modulation by HDACs makes them attractive targets for cancer remedy. This review summarizes the current knowledge of HDACs in tumorigenesis and tumor progression as well as their contribution to the hallmarks of cancer. The present report also describes briefly various assays to detect histone deacetylase activity and discusses the potential role of histone deacetylase inhibitors as emerging epigenetic drugs to cure cancer.     

Attenuation of doxorubicin-induced cardiotoxicity and genotoxicity by an indole-based natural compound 3,3′-diindolylmethane (DIM) through activation of Nrf2/ARE signaling pathways and inhibiting apoptosis

The most crucial complication related to doxorubicin (DOX) therapy is nonspecific cytotoxic effect on healthy normal cells. The clinical use of this broad-spectrum chemotherapeutic agent is restricted due to development of severe form of cardiotoxicity, myelosuppression, and genotoxicity which interfere with therapeutic schedule, compromise treatment outcome and may lead to secondary malignancy. 3,3′-diindolylmethane (DIM) is a naturally occurring plant alkaloid formed by the hydrolysis of indolylmethyl glucosinolate (glucobrassicin). Therefore, the present study was undertaken to investigate the protective role of DIM against DOX-induced toxicity in mice. DOX was administered (5?mg/kg b.w., i.p.) and DIM was administered (25?mg/kg b.w., p.o.) in concomitant and 15 days pretreatment schedule. Results showed that DIM significantly attenuated DOX-induced oxidative stress in the cardiac tissues by reducing the levels of free radicals and lipid peroxidation, and by enhancing the level of glutathione (reduced) and the activity of antioxidant enzymes. The chemoprotective potential of DIM was confirmed by histopathological evaluation of heart and bone marrow niche. Moreover, DIM considerably mitigated DOX-induced clastogenicity, DNA damage, apoptosis, and myeloid hyperplasia in bone marrow niche. In addition, oral administration of DIM significantly (p?相似文献