The recently identified Th anatos- a ssociated p rotein (THAP) domain is an atypical zinc finger motif with sequence-specific DNA-binding activity. Emerging data suggest that THAP proteins may function in chromatin-dependent processes, including transcriptional regulation, but the roles of most THAP proteins in normal and aberrant cellular processes remain largely unknown. In this work, we identify THAP11 as a transcriptional regulator differentially expressed in human colon cancer. Immunohistochemical analysis of human colon cancers revealed increased THAP11 expression in both primary tumors and metastases. Knockdown of THAP11 in SW620 colon cancer cells resulted in a significant decrease in cell proliferation, and profiling of gene expression in these cells identified a novel gene set composed of 80 differentially expressed genes, 70% of which were derepressed by THAP11 knockdown. THAP11 was found to associate physically with the transcriptional coregulator HCF-1 (host cell factor 1) and recruit HCF-1 to target promoters. Importantly, THAP11-mediated gene regulation and its chromatin association require HCF-1, while HCF-1 recruitment at these genes requires THAP11. Collectively, these data provide the first characterization of THAP11-dependent gene expression in human colon cancer cells and suggest that the THAP11–HCF-1 complex may be an important transcriptional and cell growth regulator in human colon cancer.

Epithelial-mesenchymal transition or EMT is an extremely dynamic process involved in conversion of epithelial cells into mesenchymal cells, stimulated by an ensemble of signaling pathways, leading to change in cellular morphology, suppression of epithelial characters and acquisition of properties such as enhanced cell motility and invasiveness, reduced cell death by apoptosis, resistance to chemotherapeutic drugs etc. Significantly, EMT has been found to play a crucial role during embryonic development, tissue fibrosis and would healing, as well as during cancer metastasis. Over the years, work from various laboratories have identified a rather large number of transcription factors including the master regulators of EMT, with the ability to regulate the EMT process directly.  In this review, we put together these EMT transcription factors and discussed their role in the process. We have also tried to focus on their mechanism of action, their inter-dependency, and the large regulatory network they form. Subsequently, it has become clear that the composition and structure of the transcriptional regulatory network behind EMT probably varies based upon various physiological and pathological contexts, or even in a cell/tissue type dependent manner.

Leukocytes are recruited at the site of infection or injury as a part of the innate immune system, and play a very critical role in fighting the invading microorganisms and/or healing wounds. Neutrophils are the most abundant leukocytes in healthy humans and are the principal cell types that arrive at the target site in the initial phase of this process. Previous studies from our laboratory have shown that the amino acid glutamate is a novel chemotaxis-inducing factor for human neutrophils. In this report, we provide evidences that clearly demonstrate that the glutamate-induced neutrophil cell migration activity is mediated by the class I metabotropic glutamate receptors. Our results further show that a specific integrin β2 (ITG β2) receptor, namely LFA1 (α(L)β(2)) is activated upon glutamate treatment and is required for further downstream signaling events leading to increased migration of human neutrophil cells. Following glutamate stimulation, LFA1 is phosphorylated by the Src Kinase Lck at the Y735 residue, which triggers a downstream signaling cascade leading to activation of PI3K, Syk, Vav and finally the Rho family GTPase, Rac2. Interestingly, glutamate was previously found to be present in elevated levels in wound fluid. Furthermore, glutamate level was also found to go up following inflammation. Taken together, our study suggests a novel mode of neutrophil recruitment to the target site following an infection or injury.

The development of drug delivery systems with microencapsulated therapeutic agents is a promising approach to the sustained and controlled delivery of various drug molecules. The incorporation of dual release kinetics to such delivery devices further adds to their applicability. Herein, novel core-shell scaffolds composed of sodium deoxycholate and trishydroxymethylaminomethane (NaDC-Tris) have been developed with the aim of delivering two different drugs with variable release rates using the same delivery vehicle. Data obtained from XRD studies, sol-gel transition temperature measurement, rheology and fluorescence studies of the core-shell systems indicate a significant alteration in the core and the shell microstructural properties in a given system as compared to the pure hydrogels of identical compositions. The release of the model drugs Fluorescein (FL) and Rhodamine B (RhB) from the shell and the core, respectively, of the two core-shell designs studied exhibited distinctly different release kinetics. In the 25@250 core-shell system, 100% release of FL from the shell and 19% release of RhB from the core was observed within the first 5 hours, while 24.5 hours was required for the complete release of RhB from the core. For the 100@250 system, similar behaviour was observed with varied release rates and a sigmoidal increase in the core release rate upon disappearance from the shell. Cell viability studies suggested the minimal toxicity of the developed delivery vehicles towards NMuMG and WI-38 cells in the concentration range investigated. The reported core-shell systems composed of a single low molecular weight gelator with dual release kinetics may be designed as per the desired application for the consecutive release of therapeutic agents as required, as well as combination therapy commonly used to treat diseases such as diabetes and cancer.

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