Search results for "Proteinase"
showing 10 items of 407 documents
Conditioned Media from Adipose-Tissue-Derived Mesenchymal Stem Cells Downregulate Degradative Mediators Induced by Interleukin-1β in Osteoarthritic C…
2013
Osteoarthritis (OA) is the most frequent joint disorder and an important cause of disability. Recent studies have shown the potential of adipose-tissue-derived mesenchymal stem cells (AD-MSC) for cartilage repair. We have investigated whether conditioned medium from AD-MSC (CM) may regulate in OA chondrocytes a number of key mediators involved in cartilage degeneration. CM enhanced type II collagen expression in OA chondrocytes while decreasing matrix metalloproteinase (MMP) activity in cell supernatants as well as the levels of MMP-3 and MMP-13 proteins and mRNA in OA chondrocytes stimulated with interleukin- (IL-) 1β. In addition, CM increased IL-10 levels and counteracted the stimulating…
Fluorovinylsulfones and -Sulfonates as Potent Covalent Reversible Inhibitors of the Trypanosomal Cysteine Protease Rhodesain: Structure–Activity Rela…
2021
Rhodesain is a major cysteine protease of Trypanosoma brucei rhodesiense, a pathogen causing Human African Trypanosomiasis, and a validated drug target. Recently, we reported the development of α-halovinylsulfones as a new class of covalent reversible cysteine protease inhibitors. Here, α-fluorovinylsulfones/-sulfonates were optimized for rhodesain based on molecular modeling approaches. 2d, the most potent and selective inhibitor in the series, shows a single-digit nanomolar affinity and high selectivity toward mammalian cathepsins B and L. Enzymatic dilution assays and MS experiments indicate that 2d is a slow-tight binder (Ki = 3 nM). Furthermore, the nonfluorinated 2d-(H) shows favorabl…
BRAF(V600E) MUTATION AND THE BIOLOGY OF PAPILLARY THYROID CANCER
2008
BRAF((V600E)) mutation is the most frequent genetic alteration in papillary thyroid carcinomas (PTCs) that are 80-90% of all thyroid cancers. We evaluated the relationship between BRAF((V600E)) and tumor, host, and environmental factors in PTCs from all geographical areas of Sicily. By PCR, BRAF((V600E)) was investigated in a series of 323 PTCs diagnosed in 2002-2005. The correlation between clinicopathological tumor, host, and environmental characteristics and the presence of BRAF((V600E)) were evaluated by both univariate and multivariate analyses. BRAF((V600E)) was found in 38.6% PTCs, with a 52% frequency in the classical PTCs and 26.4% in the tall cell variant. Univariate analysis indi…
Control of Cell Migration and Inflammatory Mediators Production by CORM-2 in Osteoarthritic Synoviocytes
2011
Background Osteoarthritis (OA) is the most widespread degenerative joint disease. Inflamed synovial cells contribute to the release of inflammatory and catabolic mediators during OA leading to destruction of articular tissues. We have shown previously that CO-releasing molecules exert anti-inflammatory effects in animal models and OA chondrocytes. We have studied the ability of CORM-2 to modify the migration of human OA synoviocytes and the production of chemokines and other mediators sustaining inflammatory and catabolic processes in the OA joint. Methodology/Principal Findings OA synoviocytes were stimulated with interleukin(IL)-1β in the absence or presence of CORM-2. Migration assay was…
High mobility group box 1 potentiates the pro-inflammatory effects of interleukin-1β in osteoarthritic synoviocytes
2010
Introduction High mobility group box 1 (HMGB1) is released by necrotic cells or secreted in response to inflammatory stimuli. Extracellular HMGB1 may act as a pro-inflammatory cytokine in rheumatoid arthritis. We have recently reported that HMGB1 is released by osteoarthritic synoviocytes after activation with interleukin-1beta (IL-1β) The present study investigated the role of HMGB1 in synovial inflammation in osteoarthritis (OA). Methods HMGB1 was determined in human synovium using immunohistochemistry, comparing normal to OA. OA synoviocytes were incubated with HMGB1 at 15 or 25 ng/ml in the absence or presence of IL-1β (10 ng/ml). Gene expression was analyzed by quantitative PCR and pro…
Patterns of transmitted HIV drug resistance in Europe vary by risk group
2014
BACKGROUND: In Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported. METHODS: HIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression. RESULTS: From the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM…
Cordycepin protects against cerebral ischemia/reperfusion injury in vivo and in vitro.
2011
Cordycepin, (3'-deoxyadenosine), a bioactive compound of Cordyceps militaris, has been shown to exhibit many pharmacological actions, such as anti-inflammatory, antioxidative and anticancer activities. Little is known about the neuroprotective action of cordycepin as well as its molecular mechanisms. In this study, cordycepin was investigated for its neuroprotective potential in mice with ischemia following 15 min of the bilateral common carotid artery occlusion and 4h of reperfusion. The effect of cordycepin was also studied in mice brain slices treated with oxygen-glucose deprivation (OGD) injury. Our results showed that cordycepin was able to prevent postischemic neuronal degeneration an…
Heterogeneous activation of MMP-9 due to prostate cancer-bone interaction.
2007
OBJECTIVES To determine whether matrix metalloproteinase (MMP)-9 activation resulting from prostate cancer cell-bone interaction is dependent on the tumor cell type and/or the nature of the bone microenvironment. METHODS In vitro co-cultures of human prostate cancer cells (PC3 and C4-2B) and mouse, human fetal, or human adult tissues were performed. In vivo the tumor cells were intratibially injected in SCID mice or intraosseously inoculated into fetal or adult bone xenografts in SCID mice. MMP-2 and MMP-9 expression and activation were determined by gelatin zymography in conditioned media obtained in vitro and in lysates derived from the in vivo studies at different time points. RESULTS Ac…
Gelatinases and their tissue inhibitors in a group of subjects with metabolic syndrome.
2013
Aim To evaluate matrix metalloproteases (MMP)-2 and MMP-9 and tissue inhibitor of metalloproteases (TIMP)-1 and TIMP-2 in a group of subjects with metabolic syndrome (MS) subdivided according to the presence or absence of diabetes mellitus. Methods We examined in 90 subjects (51 men and 39 women) with MS, defined following the International Diabetes Federation criteria, and subsequently subdivided into diabetic subjects (22 men and 11 women) and nondiabetic subjects s (29 men and 28 women), the plasma concentrations of MMP-2 and MMP-9 and of TIMP-1 and TIMP-2 using specific enzyme-linked immunosorbent assay kits. Results We found a significant increase in plasma concentrations of MMP-2, MMP…
Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe
2016
Transmitted human immunodeficiency virus drug resistance in Europe is stable at around 8%. The impact of baseline mutation patterns on susceptibility to antiretroviral drugs should be addressed using clinical guidelines. The impact on baseline susceptibility is largest for nonnucleoside reverse transcriptase inhibitors.