No abstract

Sensory deprivation, such as developmental hearing loss, leads to an adjustment of synaptic and membrane properties throughout the central nervous system. These changes are thought to compensate for diminished sound-evoked activity. This model predicts that compensatory changes should be synergistic with one another along each functional pathway. To test this idea, we examined the excitatory thalamic drive to two types of cortical inhibitory interneurons that display differential effects in response to developmental hearing loss. The inhibitory synapses made by fast-spiking (FS) cells are weakened by hearing loss, whereas those made by low threshold-spiking (LTS) cells remain strong but display greater short-term depression (Takesian et al. 2010). Whole-cell recordings were made from FS or LTS interneurons in a thalamocortical brain slice, and medial geniculate (MG)-evoked postsynaptic potentials were analyzed. Following hearing loss, MG-evoked net excitatory potentials were smaller than normal at FS cells but larger than normal at LTS cells. Furthermore, MG-evoked excitatory potentials displayed less short-term depression at FS cells and greater short-term depression at LTS cells. Thus deprivation-induced adjustments of excitatory synapses onto inhibitory interneurons are cell-type specific and parallel the changes made by the inhibitory afferents.

MicroRNAs (miRNAs) are short, non-coding, conserved, oligonucleotides that are regulatory in nature and are often dysregulated in many cancers including prostate cancer. Depending on the level of complementarity between the miRNA and mRNA target, they can either inhibit translation or degrade the target mRNA. MiRNAs expression is specific to the type of cancer, its stage and level of metastasis, making miRNAs potential stage-specific biomarkers of cancer. Recent research has shown that these miRNAs have the potential to be a diagnostic and prognostic non-invasive biomarker for various cancers including prostate cancer. Various miRNAs have been reported as novel biomarkers for prostate cancer therapy. However, there is inconsistency in the data reported and no overlapping expression pattern could be found. In this review, we have highlighted the most consistently reported dysregulated miRNAs in prostate cancer from the existing literature and discussed the currently available data on their role in regulating the hallmarks of prostate cancer. These four most consistently reported dysregulated miRNAs viz. miRNA-141, miRNA-375, miRNA-221 and miRNA-21 need to be further validated in terms of their regulatory potential in regulating various pathways important for prostate cancer management.

Nephew (2010) Multivalent epigenetic marks confer microenvironmentresponsive epigenetic plasticity to ovarian cancer cells, Epigenetics, 5:8,[716][717][718][719][720][721][722][723][724][725][726][727][728][729]

Prostate cancer (PCa) is the second most common malignancy amongst men worldwide. Under PCa maintenance therapy drugs acting as antagonists/partial agonists of hormone receptors against the prostate tissue are used in clinical practices. Prominent drugs being Cyproterone acetate, Flutamide, Bicalutamide, they not only cause acute and long-term toxicity, but also develops drug resistance among patients. Our focus has been on phytochemicals which do not exhibit any cytotoxicity and have significant androgen receptor (AR) inhibition activity. As Protein- Ligand interactions play a key role in structure based drug design, so by using molecular docking, we screened 803 phytochemicals and investigated their binding affinity against AR. The three dimensional (3D) structure of AR was retrieved from Protein Data Bank, and docked with 3D Pubchem structures of 803 phytochemicals using Argus Lab. Molecular docking and drug likeness studies were made using ADMET properties while Lipinski’s rule of five was performed for the phytochemicals to evaluate their anti-prostate cancer activity. The results showed that Isobavachin exhibited best binding affinity of −13.73 kcal/mol with AR followed by Glabranin, Anthocyanin and Eriosemation. Our studies therefore reveal that these four phytochemicals could be promising candidates for further evaluation for PCa prevention or management.

No abstract

Epithelial-mesenchymal transition (EMT) is a plastic transition in tumor progression during which cancer cells undergo dramatic changes acquiring highly invasive properties. Transforming growth factor-β (TGF-β) is an inducer of EMT in epithelial cells and is obligatory for acquiring invasive phenotype in carcinoma. TGF-β plays a vital role in metastasis and tumorigenesis in prostate cancer, and mutations in the components of Wnt signaling pathways are associated with various kinds of cancers including prostate cancer. The purpose of this study was to identify alterations in Wnt signaling pathway components involved during prostate cancer progression and to determine the effect of quercetin on TGF-β-induced EMT in prostate cancer (PC-3) cell line. The expression of epithelial and mesenchymal markers and the components of Wnt signaling pathway were evaluated by real-time polymerase chain reaction. It was observed that quercetin prevented TGF-β-induced expression of vimentin and N-cadherin and increased the expression of E-cadherin in PC-3 cells, thus preventing TGF-β-induced EMT. Furthermore, the relative expression of Twist, Snail, and Slug showed that quercetin significantly decreased TGF-β-induced expression of Twist, Snail, and Slug. In the present study, the expression of epithelial markers were found to be upregulated in naive state and downregulated in induced state whereas the mesenchymal markers were found to be downregulated in naive state and upregulated in induced state. Thus, our study concludes that quercetin may prevent prostate cancer metastasis by regulating the components of Wnt pathway.

Living cells continually generate free radicals or reactive oxygen species (ROS) through the respiratory chain during energetic metabolism. ROS can either be harmful or play important physiological roles in our body. Besides being produced during normal cell metabolism there are numerous exogenous factors, such as irradiation by UV light, X-rays, gamma-rays, and atmospheric pollutants which may lead to generation of ROS. Human body has various intrinsic mechanisms to counteract oxidative stress by producing antioxidants, or through externally derived foods and/or supplements. However whenever there is excess of free radicals their accumulation in the body generates a phenomenon called oxidative stress. As we age, this oxidative and/or nitrosative damages elicit a number of late-onset diseases after ROS/RNS accumulate to certain levels. The ROS/RNS-mediated late-onset diseases can occur in any system of the body and may lead to clinical conditions such as cancer, arthritis arteriosclerosis, and neurodegenerative diseases. Oxidative stress is marked with expression of specific biomarkers whose specificity towards the various disease condition needs validation. In this review, we summarize the source, balance, maintenance and physiological functions of ROS, and its toxic mechanisms underlying a number of diseases and also the biomarkers implicated in selected human diseases.