PostDoc Journal

An Updated Snapshot of Recent Advances in Transcriptomics and Genomics of Phytomedicinals

Medicinal plants have been of great importance to human health care since the advent of medicine. A huge array of molecules has been obtained from these phytopharmaceutical-yielding species that have influenced human lives since the beginning of plant-based life-saving medicines. Some of these molecules have taken the form of taxol, aspirin, and artemisinin. With the flourishing era of highthroughput next generation sequencing technologies, a hot pursuit for sequencing the genomes and transcriptomes of these life-saving plants is underway. Although few genomes have been sequenced or are currently being addressed, the number of transcriptomes sequenced has sky-rocketed in the last couple of years and continues to surge forward with immense pace, covering all important genera of medicinal plants. I have attempted to provide the current status, progress, opportunities, and challenges of these sequencing endeavors in this comprehensive and updated review. It is my hope that this information will provide both specialists and non-specialists with the current trends and future directions of this interesting category of plants.

The Wnt/β-catenin Signaling Pathway in Epithelial Mesenchymal Transition

Epithelial mesenchymal transition (EMT) is a well conserved process by which polarized, immotile epithelial cells transition into motile mesenchymal cells. EMT plays an important role during normal biological processes such as embryogenesis and wound healing. More recently, EMT has been studied for its role in cancer progression and metastasis. Understanding the molecular mechanisms that regulate EMT are key to developing novel therapeutic interventions for cancer. Dysregulated or uncontrolled activation of the Wnt/β-catenin signaling pathway promotes tumor progression and metastasis. The Wnt/β-catenin signaling pathway is one of the signaling pathways that has been implicated in EMT. In this review, major Wnt target genes that promote EMT as well as the various antagonists and microRNAs that regulate the Wnt/β-catenin pathway to influence EMT during cancer progression will be discussed.

Supporting the NIH: the Original Crowdfunding of Medical Research

There is strong support in our society for increased medical research and Americans give generously to private foundations that help fund that research. In this op-ed, I look at how these organizations fit into the national research landscape compared to funding by the NIH and I urge everyone to contact their representatives in Congress since even a small increase in the NIH budget can have a huge impact on research funding that is available to fight disease.

Targeting Interleukin-2-Inducible T-cell Kinase (ITK) in T-Cell Related Diseases

IL2-inducible T-cell kinase (ITK), a member of the Tec family tyrosine kinases, is the predominant Tec kinase in T cells and natural killer (NK) cells mediating T cell receptor (TCR) and Fc receptor (Fc R) initiated signal transduction. ITK deficiency results in impaired T and NK cell functions, leading to various disorders including malignancies, inflammation, and autoimmune diseases. In this mini-review, the role of ITK in T cell signaling and the development of small molecule inhibitors of ITK for the treatment of T-cell related disorders is examined.

Discovery of Selective Vitamin D Receptor Coregulator Inhibitor

Vitamin D Receptor (VDR) is known to be involved in calcium homeostasis and recently, for its role in cell growth and differentiation. Here, we present the research highlight for discovery of selective inhibitor which blocks the interactions between VDR and co-regulators. This review discusses the anti-cancer effect of lead inhibitors in cancer cell-lines and its role in regulation of various VDR related genes.

Genetic network underlying the induction and formation of cranial placodes in the Preplacodal Region

Vertebrate cranial sensory organs and their ganglia originate from thickened ectoderm called cranial placodes. Despite the cellular and functional diversity of cranial sense organs, their precursors derive from the ectoderm adjacent to the anterior neural plate region called preplacodal region (PPR). The PPR is characterized by the expression of a unique set of transcription factors referred as PPR genes, which include Foxi, ERNI, Datch, GATA, Dlx, Six, and Eya. The expression analysis of these genes does not correlate precisely with phenotypes in the PPR. Knockouts of all PPR genes do not show complete loss of any cranial placodes. However, Foxi3 and Dlx5 genes are expressed early in the PPR in complementary fashion, with Dlx5 localized anteriorly and Foxi3 localized posteriorly. In addition, mutants of Dlx gene family members show defective anterior cranial members do not show defects in the induction of cranial placodes. All these genes are considered as PPR genes because of their expression in the PPR, but not all of them contribute to PPR induction. Placodes, and Foxi3 knockout mice show defects in posterior placodes. On the other hand, Six and Eya gene family members, mentioned as definitive PPR genes in previous studies, are expressed after Foxi3 and Dlx5. Moreover, mutants of Six and Eya gene family Vertebrate cranial sense organs largely arise from ectodermal thickening, the placodes. Albeit diverse in function, precursors of cranial sensory placodes are intermingled initially and derive from a common region called preplacodal region (PPR) (Baker and Bronner-Fraser, 2001; Couly and Le Douarin, 1985; Couly and Le Douarin, 1988; D’Amico-Martel and Noden, 1983; Litsiou et al., 2005; Streit, 2004). Several transcription factors have been identified as fate determining genes for the PPR and/ or cranial placodes, but the gene regulatory network that establishes PPR is not well understood. Based on knockout studies of different PPR genes, I have selected to discuss Foxi, Dlx, Six, and Eya gene families in this review. I will refer to Foxi and Dlx as competence transcription factors (CTFs) and the Six and Eya as definitive placodal genes (DPGs). The purpose of this review is to understand the relationship of CTFs and DPGs during the induction of PPR and cranial placodes.

Discovery and development of dabigatran

Thrombin is key protease involved in regulation of coagulation cascade and thus, highly targeted to design the newer anticoagulant. Various direct and allosteric inhibitors of thrombin were designed but few made their way to clinic. Dabigatran is direct inhibitors of thrombin approved by FDA for clinical use. This article highlights the discovery and development of dabigatran as newer anticoagulant drug.

The Utility of Circulating microRNAs as Biomarkers in Viral Infection-Associated Cancers

Since their discovery, the role of microRNAs (miRNAs) has been expanding. These small, non-coding RNAs have been associated with gene regulation by binding to 3’ UTRs. Specific miRNA expression profiles are associated with cancer development and may serve as markers of malignancy. Many of these cancers are also associated with viral infections. As some viruses express their own miRNAs, research has begun to investigate if cellular or viralencoded miRNAs could also serve as specific markers of these virus-associated cancers. Discovery of miRNAs in both tissues and serum have been reported in patients with virus positive tumors. These miRNAs may emerge as important, non-invasive diagnostic tools for detecting tumor development and progression and improving cancer treatment.

QSAR Study of Thiophene-Anthranilamides Based Factor Xa Direct Inhibitors

QSAR studies were performed to understand the structure activity relationship (SAR) and to build the computational model to predict newer inhibitors with improved potency. In this study, a library of thiophene-anthranilamide based inhibitors of factor Xa was used to develop QSAR model. The library was divided into two sets: Training and Test sets. QSAR Model consists of four descriptors with R-square value of 0.80. Based on the statistical parameters, this model can be used to predict the newer inhibitors with improved pharmacological profile.

Aerobic Oxidation of Secondary Alcohols to Ketones Catalyzed by Ionic Liquid Functionalized TEMPO

Protocols of aerobic oxidation of secondary alcohols to ketones by using TEMPO modified by bifunctionalized imidazolium-based ionic liquids have been developed. [Imim-TEMPO][X] (X= FeCl4, CuCl2) has been proved to be efficient and recyclable catalysts with modest or excellent yields and selectivity. Therefore, relevant literatures are summarized herein.