Current Signal Transduction Therapy - Volume 12, Issue 2, 2017

Background: Transforming growth factor beta (TGF-β) is a multifunctional protein that acts as a regulator of cellular function such as proliferation, migration, differentiation, apoptosis, vascular hemostasis, and development of organisms. As the TGF-β is the key player of cell proliferation and apoptosis it also involves in different diseases such as autoimmune disorder and vascular disease. The TGF-β signaling pathway starts with the activation of TGFBRII and TGFBRI that trigger the phosphorylation of Smad cascade. The Smads complexes (Smad4+R-Smad) translocate to the nucleus and induce the transcription of the target gene. The dysregulation of the TGF-β signaling pathways has been reported in many human diseases including cancer. TGF-β acts as a tumor suppressor in the early stage of cancer but in late-stage show oncogenic factor and loss antiproliferative response. Objective: This reviews article determines the mechanism of TGF-β signaling pathways, the effect of TGF-β component on different cancers and provides a brief overview how it (TGF-β) acts as a tumor suppressor and promoter. Conclusion:TGF-β signaling pathways have a multifaceted and fundamental role in human development. It acts as a double-edged sword, both tumor suppressor, and tumor promoter. The tumor suppressor role is commonly designated as antiproliferative and apoptotic effects. TGF-β stops cell cycle at the G1 phase and promotes apoptosis. However, in advance stage of the tumor, it lost suppressor activities and begin tumor promotor due to the mutation in some component of the TGF-β pathway. Thus, The TGF-β can no longer control the cell cycle and proliferate the cancer cell. The increased production of TGF-β induces tumor invasion, motility, metastasis, immunosuppression epithelial-to-mesenchymal transition and angiogenesis. To study the exact molecular mechanism of TGF-β in the cancer cell and determine the oncogenic activities can provide successful and new therapeutic approach to reestablish the ordinary function of TGF-β.

Background: Inflammatory Bowel Disease (IBD) is the hypernym of a group of chronic inflammatory relapsing gastrointestinal diseases which consist of ulcerative colitis (UC) and Crohn's disease. Although its etiology is ambiguous; it is marked by the dysregulated production of proinflammatory mediators like tumor necrosis factor (TNF)-α and interleukins (IL) etc. These accelerated inflammatory responses are triggered by various environmental and genetic factors. They significantly pose an adverse impact on patient’s life and treatment of IBD requires long-term therapy. Various signaling pathways which are mediated by different cytokines like IL-6, IL-17, IL-22, IL-31, IL-33, TNF and NF-kb etc. are responsible for the accelerated immune responses in IBD. Objective: In this review numerous signaling pathways like TL1ADR3, TLR, ErbB, VDR, TGF-β1 Smad 3, Rac1 GTPase and PI3KAKTPTEN which are of clinical importance for IBD have been elucidated with a particular emphasis on JAK-STAT pathway. Conclusion: An exhaustive study of the above mentioned signaling pathways and their influence on the inflammatory process in IBD may simplify the expertise in the homeostasis of gastrointestinal tract and aid in unveiling new avenues for the treatment of IBD.

Background: Failure of cell division control due to mutations leading to inactivation or over activation of regulatory proteins is the leading cause of cancer development. Several mitogens and growth factors have been found to regulate cancer cell cycle progression. However, all signalling pathways converge to the cell cycle machinery and thus disruption of cell cycle control offers an attractive therapeutic target for the treatment of cancer. Method: We undertook a comprehensive search of bibliographic databases through PubMed and selected the most relevant and appropriate peer-reviewed research articles. Results: There has been a breakthrough in identification of the cell cycle regulatory molecules and elucidation of their roles in subtle adjustment of the balance between proliferation and apoptosis of cancer cells. This review will shed light on the current understanding of the regulation of the cell cycle pathway links and the feasibility of targeting cell cycle for fighting metastatic cancer. Conclusion: There are cross-talks among the diverse neoplastic cell types acting together on cell cycle to ensure survival, growth and metastasis, by inhibiting apoptosis, promoting angiogenesis, and avoiding immune system. Approaches should be undertaken to synergistically block the activation of the interconnected pathways for effective cancer therapy.

Background: Targeting of virulence factors is considered as a novel strategy for antifungal drug development. We have tried to identify potential targets of Indole and Isatin in the Yeast to hyphal induction signal transduction pathways in the human pathogen Candida albicans. Objective: To study changes in gene expression during yeast to hyphal transition in the presence and absence of Indole and Isatin. Methods: Total RNA were isolated by using RNeasy® Mini Kit (QIAGEN) and converted to cDNA by using SuperScript® III for First strand synthesis for RT-PCR (Invitrogen by Life technologies). PCR reactions were done using KAPA SYBR® Fast qPCR Kit Master mix (2x) (BIOSYSTEMS). Results: The genes involved in Yeast to hyphal transition were modulated by the treatment of Indole and Isatin. Our results indicate that Indole and Isatin may target multiple steps in the yeast to hyphal signal transduction pathway. The expression of Ece1 and Hwp1 was downregulated by both the molecules in this study. Hyphal suppressor genes Nrg1, Tup1 were significantly upregulated by Indole and Isatin. Conclusion: Indole and Isatin affected the expression of multiple genes in the yeast to hyphal signal transduction pathway in Candida albicans. In conclusion both Isatin and Indole may represent potential anti-virulence agents against Candida albicans. Indole derivatives could be good candidates for drug repositioning.

Background: Mastography is a strong screening and diagnostic tool for the primitive detection of cancer in the breasts. The acquired mammogram images or stored mammogram images are often corrupted by the outliers. These outliers must be eliminated before microcalcification. Method: In the proposed scenario, an adaptive filter that uses median of minimum distance from its neighbourhood is used to eliminate the salt and pepper noise. The minimum Euclidean distance between each of the non noisy pixels allows the algorithm to choose a better value to replace the corrupted pixels. The algorithm terms the pixel to be corrupted if it holds 0 or 255; otherwise, the pixel is termed uncorrupted. The algorithm uses 3x3 window initially and increases the window size, if the entire window consists of outliers. If the uncorrupted number of pixels inside the processing window is at least 2, then the corrupted pixel is replaced by the median of minimum Euclidean distance between each non noisy pixel and the corrupted pixel. If the number of non noisy pixels inside the current processing window is 1, then the corrupted pixel is replaced by it. Results: The Mini Mias database is used to assess the performance of the (ADBMEDUTMF) Adaptive Decision based minimum Euclidean distance unsymmetrical Trimmed median filter with the other standard and recently proposed algorithms. The ADBMEDUTMF proved efficient in removing the corrupted pixels and found to operate well even at noise densities as high as 90% without inducing any artifacts. Conclusion: Exhaustive test results suggest that the ADBMEDUTMF algorithm exhibits very good noise suppression characteristics with minimum error and higher information preservation capability even at very high noise densities in different mammogram images. This makes the algorithm suitable for low level processing.

Background: Ubiquitous naturally occurring longitudinal magnetic waves may serve as a carrier for biological signal transfer. Material and Method: Scalar waves were generated by Meyl`s Experimental Scalar Wave Kit. An experimental model was developed to study the signal transfer of an antifungal drug to yeast colonies. Yeast colonies were cultivated on agar plates at a constant cultivation temperature of 28°C. Result and Conclusion: In a series of experiments, we were able to show that the mere information transfer of an antifungal substance (clotrimazole) leads to a statistically significant reduction of yeast colony growth. Same was true for a homeopathic potency and a digitalized clotrimazole information. Implications for pharmaceutical treatment and unwanted drug side effects are discussed. An experimental confirmation of these findings would coincide with a wide range of practical applications.