Weight loss in nonalcoholic fatty liver disease patients in an ambulatory care setting is largely unsuccessful but correlates with frequency of clinic visits

Background and Aims: Nonalcoholic fatty liver disease (NALFD) is a leading cause of liver disease. Weight loss improves clinical features of NAFLD; however, maintenance of weight loss outside of investigational protocols is poor. The goals of this study were to characterize patterns and clinical predictors of long-term weight loss in ambulatory patients with NAFLD

Synthesis and anti–microbial activity of 1,2,3–triazole tethered nitroguiacol ethers

Nitro aromatic/nitrophenols have been widely distributed in nature and are mostly isolated from marine microorganisms and had shown a broad spectrum of anti–microbial activities against a wide range of microbial pathogens. The objective of the present work is to Synthesize some new 1,2,3–triazole tethered nitroguiacol ethers and evaluated of their anti–bacterial and anti–fungal activities. A focused library of 1,2,3-triazole tethered nitroguiacol ethers were prepared by employing Cu (I) catalyzed click chemistry reaction and evaluated for their antimicrobial activities by broth microdilution method. Among the tested compounds, compounds 8e, 8f, 8g, and 8i exhibited broad–spectrum activity against selected pathogenic strains, with the MIC of 8 µg/mL for gram–positive bacteria (Staphylococcus aureus), 16 µg/mL for Pseudomonas aeruginosa (gram–negative bacteria), and Candida species, respectively. Future investigations with this class of compounds may lead to the development of potential candidates for antimicrobial drug discovery.Â

Telomere length and survival in primary cutaneous melanoma patients

Dermatology-oncolog

Telomerase promoter mutations in cancer: an emerging molecular biomarker?

João Vinagre, Vasco Pinto and Ricardo Celestino contributed equally to the manuscript.Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomerase reactivation, such immortalization could be due to telomere maintenance through the “alternative mechanism of telomere lengthening” (ALT) but the mechanisms underlying both forms of reactivation remained elusive. Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer. The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review, we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction. In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target

Smad phosphoisoform signals in acute and chronic liver injury: similarities and differences between epithelial and mesenchymal cells

Hepatocellular carcinoma (HCC) usually arises from hepatic fibrosis caused by chronic inflammation. In chronic liver damage, hepatic stellate cells undergo progressive activation to myofibroblasts (MFB), which are important extracellular-matrix-producing mesenchymal cells. Concomitantly, perturbation of transforming growth factor (TGF)-β signaling by pro-inflammatory cytokines in the epithelial cells of the liver (hepatocytes) promotes both fibrogenesis and carcinogenesis (fibro-carcinogenesis). Insights into fibro-carcinogenic effects on chronically damaged hepatocytes have come from recent detailed analyses of the TGF-β signaling process. Smad proteins, which convey signals from TGF-β receptors to the nucleus, have intermediate linker regions between conserved Mad homology (MH) 1 and MH2 domains. TGF-β type I receptor and pro-inflammatory cytokine-activated kinases differentially phosphorylate Smad2 and Smad3 to create phosphoisoforms phosphorylated at the COOH-terminal, linker, or both (L/C) regions. After acute liver injury, TGF-β-mediated pSmad3C signaling terminates hepatocytic proliferation induced by the pro-inflammatory cytokine-mediated mitogenic pSmad3L pathway; TGF-β and pro-inflammatory cytokines synergistically enhance collagen synthesis by activated hepatic stellate cells via pSmad2L/C and pSmad3L/C pathways. During chronic liver disease progression, pre-neoplastic hepatocytes persistently affected by TGF-β together with pro-inflammatory cytokines come to exhibit the same carcinogenic (mitogenic) pSmad3L and fibrogenic pSmad2L/C signaling as do MFB, thereby accelerating liver fibrosis while increasing risk of HCC. This review of Smad phosphoisoform-mediated signals examines similarities and differences between epithelial and mesenchymal cells in acute and chronic liver injuries and considers Smad linker phosphorylation as a potential target for the chemoprevention of fibro-carcinogenesis

New developments in osteoarthritis. Posttraumatic osteoarthritis: pathogenesis and pharmacological treatment options

Joint trauma can lead to a spectrum of acute lesions, including osteochondral fractures, ligament or meniscus tears and damage to the articular cartilage. This is often associated with intraarticular bleeding and causes posttraumatic joint inflammation. Although the acute symptoms resolve and some of the lesions can be surgically repaired, joint injury triggers a chronic remodeling process in cartilage and other joint tissues that ultimately manifests as osteoarthritis in a majority of cases. The objective of the present review is to summarize information on pathogenetic mechanisms involved in the acute and chronic consequences of joint trauma and discuss potential pharmacological interventions. The focus of the review is on the early events that follow joint trauma since therapies for posttraumatic joint inflammation are not available and this represents a unique window of opportunity to limit chronic consequences

The evaluation of acoustic characteristic performance on natural sound absorbing materials from cogon grass waste

In the past few decades, synthetic fibers are been used widely in the field of sound absorption due to their superior characteristics such as durable and chemical resistant. However, there are several disadvantages of synthetic fibers such as non-biodegradability and hazards to the health of human. In this research, the natural sound absorber from cogon grass was investigated. The objective of the research was to evaluate the performance of cogon grass physical characteristics on its acoustical behavior, to evaluate the effect of sodium hydroxide (NaOH) treatment times on physical and acoustical characteristics of cogon grass, to investigate the decay effects after it was left over for twelve months and lastly to compare and verify the acoustical results with theoretical models based on (Delany-Bazley and Miki Model). The measurement of acoustical characteristics which are sound absorption coefficient (SAC) and noise reduction coefficient (NRC) were done by using impedance tube method (ITM). The samples of cogon grass were tested in a way of the untreated and treated with NaOH in varied soaked hours which are one, two, three, four and five hours. Scanning electron microscope (SEM) and density kit were used to investigate physical characteristics. The research confirmed that physical characteristics of tortuosity and airflow resistivity values tend to increase with the increment of treatment times, but the density and porosity tend to decrease. Untreated samples were tested with varied thicknesses of 10, 20, 30, 40 and 50mm. The results show SAC value increases when the thickness of the sample was increased. Treated samples results show the least treated sample (1 hour) reached the maximum SAC value and indicated the highest value of NRC which is 0.50. The results also show a reduction in sound absorption value after the samples were left for twelve months. Verification parts demonstrated that Delany-Bazley and Miki Model can predict approximately pattern compared with ITM results because of the theoretical models are developed by a simple empirical model approach. Overall, cogon grass samples have the good characteristics to be an acoustic material component