-
Harvey Park posted an update 6 months ago
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.Constipation is a highly prevalent functional gastrointestinal disorder that may significantly affect the quality of life and health care costs. Treatment for constipation has been broadly reviewed by cognitive therapies, medications, and surgical interventions. Gut microbiota such as Bifidobacterium, Clostridium, Bacteroidetes, and Lactobacilli have been demonstrated in functional gastrointestinal disorders and prebiotics play a role in augmenting their presence. Prebiotics are ingredients in foods that remain undigested that may stimulate bacteria. There are variety of prebiotics however there only a handful of studies that describes their efficacy for chronic constipation. The purpose of this study is to review the available literature on the utility of different commercially available prebiotics in patients with functional and chronic idiopathic constipation. To fulfill the objectives of the study, published articles in the English language on databases such as Pubmed, Ovid Medline, and EMBASE were searched. The terms prebiotics, constipation, chronic constipation, functional constipation was used. We reviewed and included 21 randomized controlled trials exploring the role of prebiotics in constipated adults. Prebiotics are effective treatments for chronic idiopathic constipation and showed improvement in the stool consistency, number of bowel moments and bloating. Although which prebiotic formulary would promote improved symptoms of constipation is still not clear. . Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND Cancer is the leading cause of death in the current decade. With the advancement in scientific technologies various treatments had been introduced but they suffer from numerous side effects. The root cause of cancer is alteration in the cell cycle which generates cancerous cells. Development of new lead which specifically target cancerous cells is needed to reduce the side effect and to overcome multidrug resistance. OBJECTIVE Design and development of anticancer leads targeting colchicine site of microtubules using structurally screened phytofragments is the primary objective of this work. MATERIAL AND METHODS Bioactive fragments of phytoconstituents were identified from a large dataset of phytochemicals. The identified phytofragments were used to design structures which were screened for virtual interactions with colchicine site of microtubules. Selected set of designed molecules was further screened for drug like properties and toxicity. The designed molecules which surpassed virtual filters were then synthesized, characterized and further screened for anticancer potential against HEPG2 liver cancer cellline. RESULT A novel series of chalcones was designed by phytofragment based drug design. Cathepsin G Inhibitor I The synthesized compounds showed profound anticancer activity comparable to standard, 5-fluoro uracil. In the present communication, rational development of anticancer leads targeting colchicine site of microtubules has been done by integrating pocket modeling and virtual screening with synthesis and biological screening. CONCLUSION In this present work, we found that compound S4 and S3 showed specific interaction with colchicine site of microtubules and desirable anticancer activity. Further optimization of the lead could yield drug like candidate with reduced side effects and may overcome multidrug resistance. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.CDK9 is an important cell-cycle control enzyme essential in transcription, elongation, and mRNA maturation. Overexpression of CDK9 has been reported in several diseases, including acute lymphoblastic leukemia, chronic lymphocytic leukemia, and malignant melanoma. Recent research revealed that CDK9-inhibitors have a major impact on the induction of apoptosis in hepatocellular carcinoma (HCC) cell lines. Despite surprisingly promising results in in vitro and in vivo research, no CDK9 related therapy is currently allowed in cases of HCC. Furthermore, due to their high specificity, the inhibitors had no effects on unaltered hepatocytes and no toxic effects were shown. Considering that they were well tolerated and showed relatively few severe side-effects in mice, CDK9-inhibitors would seem to be promising targets in HCC biomarker-guided immunotherapy. Studies have verified that CDK9 has a pivotal role in c-Myc-mediated tumor growth and CDK9 inhibitors inhibit not only its progression but diametrically decrease both the mass and size of HCC nodules. CDK9-inhibitors seem to be a promising target in HCC treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.BACKGROUND Alzheimer’s disease (AD) is a neurodegenerative disorder histopathologically characterized by the accumulation of amyloid β (Aβ) peptides and inflammation associated with activated microglia. These features are well investigated in the central nervous system using AD-model mice; however, peripheral inflammation in these mice has not been investigated well. OBJECTIVE We evaluated the inflammatory responses, especially myeloid dendritic cells (mDCs), in peripheral lymphoid tissues in AD-model mice to determine their association with Aβ deposition. METHODS We collected lymphocytes from mesenteric lymphoid nodes (MLNs) and Peyer’s patches (PPs) of 5×FAD transgenic mice used as an AD model. Lymphocytes were analyzed using a flow cytometer to characterize mDCs and T cells. Collected lymphocytes were treated with Aβ1-42 ex vivo to evaluate the inflammatory response. RESULTS We observed elevated levels of inflammatory cytokines and chemokines including interleukin (IL)-12 and macrophage inflammatory protein-1α in mDCs from MLNs and PPs and reduced levels of programmed death-ligand-1, an immunosuppressive co-stimulatory molecule, on the surface of mDCs from 5×FAD mice. Additionally, we found increases in interferon (IFN)-γ-producing CD4- or CD8- positive T cells in MLNs were increased in 5×FAD mice. Moreover, ex vivo treatment with Aβ peptides increased the production of IL-12 and IFN-γ by lymphocytes from 5×FAD mice. CONCLUSION The present study showed that pro-inflammatory mDC and T cells were induced in MLNs and PPs of 5×FAD mice. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.