Progress in matrix metalloproteinase research

Matrix metalloproteinases (MMPs) are now acknowledged as key players in the regulation of both cell-cell and cell-extracellular matrix interactions. They are involved in modifying matrix structure, growth factor availability and the function of cell surface signalling systems, with consequent effects on cellular differentiation, proliferation and apoptosis. They play central roles in morphogenesis, wound healing, tissue repair and remodelling in response to injury and in the progression of diseases such as arthritis, cancer and cardiovascular disease. Because of their wide spectrum of activities and expression sites, the elucidation of their potential as drug targets in disease or as important features of the repair process will be dependent upon careful analysis of their role in different cellular locations and at different disease stages. Novel approaches to the specific regulation of individual MMPs in different contexts are also being developed.     

Croatian bibliometric analysis, 2000-2007

To develop search filters and retrieve information estimating the Croatian scientific output (SO) focusing on Public Health (PH) and Preventive Medicine (PM) in MEDLINE. A PubMed search of the MEDLINE database was performed to retrieve articles added to this database between 2000 and 2007. Search filters inspired by previous strategies were applied involving 'geographical', 'place of publication', 'subject' and 'language of publication' aspects. An evaluation of the geographical filter performance was done and sensitivity and specificity were calculated. There were obtained publications in several languages, originated in Croatia, published in Croatia and/or abroad. The Croatian SO in the field of PH-PM was obtained for the same period of time by combining search filters. The evaluation of the filter performance showed sensitivity 95.56% and specificity 100%. The filters constructed permitted the retrieval of the Croatian eight years research output. Increased tendency was observed in the global SO evolution and in the PH-PM area as well. The main languages of publication were English and Croatian. This study is a contribution to research in the field of scientific documentation and further analysis is recommended in constructing and developing search filters to retrieve and focus on specific information.     

从文献计量看海洋药物研发趋势的变化

本文对Science Citation Index Expanded （SCI-E）以及Medline数据库1998—2007年收录的海洋药物相关文章进行文献讨一量分析,统计了发文量居前10位的国家或地区、研究机构、作者以及他们各自对应文章的总被引频次和平均被引频次等数据,数据库中所收录的文献的附加关键词和主题词分布等,以反映近年来海洋药物研发趋势的变化。     

基于科技计量学的全球真菌学研究态势分析

目的 对全球真菌学研究态势进行分析.方法 检索SCI-Expanded数据库2004～2013年全球真菌学研究研究相关文献,采用Web of Science自带软件及Excel 2007等软件进行定量分析,指标包括文献量、被引频次、h指数等.结果 全球真菌学研究近年来呈上升趋势,美国具有绝对领先,中国、德国、日本也是主要的贡献国家.中国真菌学研究排名第2,但论文整体被引频次偏低;主要贡献来自于2007年以后（98.79％）,中国高校是主要的研究机构,国家自然科学基金是最主要的资助来源.结论 2007年以来中国真菌学研究正处于较好的发展时机,但研究水平仍有待提高.     

Trends in cancer mortality rates among migrants in Australia: 1981-2007

Background: Previous studies have shown that migrants have lower cancer mortality rates compared to the Australian-born population, particularly for colorectal and breast cancers, which are associated with an affluent lifestyle. This study seeks to update knowledge in this field by examining mortality from colorectal, stomach, lung, melanoma, breast and bladder cancers, as well as all cancers combined between 1981 and 2007. Methods: Data were obtained from the Australian Bureau of Statistics. Average annual age and sex-standardised mortality rates were calculated for each region of birth, period of death registration and cancer site. Results: Generally, mortality rates declined over the study period for most conditions for the majority of migrant groups. Notable exceptions included migrants from South Eastern Europe and Eastern Europe who experienced a significant increase in mortality due to all cancers combined and Australian-born individuals who recorded a significant increase in mortality due to melanoma of the skin. Migrants generally had more favourable cancer mortality outcomes, particularly for colorectal cancer and melanoma. Migrants from Southern Europe, South Eastern Europe, Chinese Asia and Southern Asia had the greatest advantage. However, migrants displayed higher rates of stomach, lung and bladder cancers than the Australian-born population. Conclusion: The migrant advantage can in part be explained by the protective effects of diet, lifestyle and reproductive behaviours. Possible explanations for why some migrants display greater mortality from stomach and bladder cancer include the consumption of abrasive, salted and preserved foods and higher rates of smoking. Greater emphasis should be placed on targeting at-risk migrant groups through screening and education programs at migrant resource centres and community groups. The study calls for further research to explain the observed trends, which has the potential to uncover important risk and protective factors.     

RECK, a novel matrix metalloproteinase regulator

Extracellular matrix (ECM) macromolecules are important for creating the cellular environments required during development and morphogenesis of tissues. Matrix metalloproteinases (MMPs) are a family of Zn-dependent endopeptidases that collectively are capable of cleaving virtually all ECM substrates, and play an important role in some physiological and pathological processes. MMP activity can be inhibited by some natural and artificial inhibitors. A newly found membrane-anchored regulator of MMPs, the reversion-inducing-cysteine-rich protein with kazal motifs (RECK), is downregulated when the cells undergo a process of malignant transformation, and is currently the subject of considerable research activity because of its specific structure and function. In this review, we have chosen to concentrate our efforts on the structure, function, regulation, and future prospect of RECK in order to provide a new target for prevention and treatment of tumours.     

Expression and function of matrix metalloproteinase (MMP)-28

Matrix metalloproteinase-28 (MMP-28, epilysin) is highly expressed in the skin by keratinocytes, the developing and regenerating nervous system and a number of other normal human tissues. In epithelial cells, over-expression of MMP-28 mediates irreversible epithelial to mesenchymal transition concomitant with loss of E-cadherin from the cell surface and an increase in active transforming growth factor beta. We recently reported the expression of MMP-28 in both cartilage and synovium where expression is increased in patients with osteoarthritis.In human chondrosarcoma cells MMP-28 was activated by proprotein convertases and the active form of the enzyme preferentially associated with the extracellular matrix in a C-terminal independent manner. over-expression of MMP-28 in chondrosarcoma cells led to altered cell morphology with increased organisation of actin. Adhesion to type II collagen and fibronectin was increased, and migration across the former was decreased. MMP-28 was localised to the cell surface, at least transiently, in a C-terminal dependent manner. Heparin prevented both extracellular matrix association and cell surface binding of MMP-28 suggesting that both are via heparan sulphate proteoglycans. Over-expression of activatable MMP-28, but not catalytically inactive EA mutant increased the expression and activity of MMP-2, and all forms of MMP-28 tested increased expression of MMP19 and TIMP3 mRNA.These data demonstrate that expression of MMP28 alters cell phenotype towards a more adhesive, less migratory behaviour. Further, MMP-28 activity may reside predominantly in the extracellular matrix, and we are currently searching for substrates in this compartment.     

A quantitative structure-activity relationship study of hydroxamate matrix metalloproteinase inhibitors derived from functionalized 4-aminoprolines

A quantitative structure-activity relationship (QSAR) study has been made on the inhibitions of some matrix metalloproteinases (MMPs) by functionalized 4-aminoproline based hydroxamates. Attempts have been made to correlate the inhibition potencies of these hydroxamates with Kier's first-order valence molecular connectivity index ((1)chi(v)) of substituents and electrotopological state (E-state) indices of some atoms. The correlations obtained for the inhibitions of all the enzymes studied, i.e. MMP-1, MMP-2, MMP-3, MMP-7, and MMP-13, were not so uniform, but suggested that in almost all the cases the substituents at the amide nitrogen may be conducive to the activity, though the whole amide group may be sterically unfavourable. Similarly, in most of the cases, the substituens at the phenyl moiety have been found to be beneficial to the inhibition potency and in many cases an electronic role of SO(2) group of the sulfonylphenyl moiety has been indicated.     

Remodeling the model organism: matrix metalloproteinase functions in invertebrates

The matrix metalloproteinase (MMP) family of extracellular proteases is conserved throughout the animal kingdom. Studies of invertebrate MMPs have demonstrated they are involved in tissue remodeling. In Drosophila, MMPs are required for histolysis, tracheal growth, tissue invasion, axon guidance, and dendritic remodeling. Recent work demonstrates that MMPs also participate in Drosophila tumor invasion. In Caenorhabditis elegans an MMP is involved in anchor cell invasion; a Hydra MMP is important for regeneration and maintaining cell identity; and a sea urchin MMP degrades matrix to allow hatching. In worms and in flies, MMPs are regulated by the JNK pathway.     

Trends in U.S. food prices, 1950-2007

The potential effect that food prices may have on the health of the U.S. population needs to be further explored, particularly in light of the rising food prices currently being observed. Declining food prices over time have been singled out as a main contributor, for example, to the rising trend in obesity. In this paper we use data from the Bureau of Labor Statistics, the American Chamber of Commerce Researchers Association, the Consumer Expenditure Survey, and the United States Department of Agriculture to analyze trends in various types of food prices, to create a food price index, and to estimate the price of a calorie. Results may be used by future researchers in estimating the health implications of these trends. We find that while the general trend in food prices has been declining, that of restaurant meal prices and prices of fruits and vegetables has risen over time. It is doubtful that the decline in food prices has been sufficiently large to account for the large increase in caloric intake that is said to have contributed to the obesity epidemic in the U.S.     

Cannabigerol: a bibliometric overview and review of research on an important phytocannabinoid

Phytochemistry Reviews - Cannabigerol (CBG) is one of the major phytocannabinoids present in Cannabis sativa L. but is presumed to be an artefact or degradation product of cannabigerolic acid...     

A unique substrate binding mode discriminates membrane type-1 matrix metalloproteinase from other matrix metalloproteinases

In our study, we characterized the substrate recognition properties of membrane type-1 matrix metalloproteinase (MT1-MMP; also known as MMP-14), a key enzyme in tumor cell invasion and metastasis. A panel of optimal peptide substrates for MT1-MMP was identified using substrate phage display. The substrates can be segregated into four groups based on their degree of selectivity for MT1-MMP. Substrates with poor selectivity for MT1-MMP are comprised predominately of the Pro-X-X- downward arrow-X(Hy) motif that is recognized by a number of MMPs. Highly selective substrates lack the characteristic Pro at the P(3) position; instead they contain an Arg at the P(4) position. This P(4) Arg is essential for efficient hydrolysis and for selectivity for MT1-MMP. Molecular modeling indicates that the selective substrates adopt a linear conformation that extends along the entire catalytic pocket of MT1-MMP, whereas non-selective substrates are kinked at the conserved P(3) Pro residue. Importantly, the selective substrates can be made non-selective by insertion of a proline kink at P(3), without significantly reducing overall k(cat)/K(m) values. Altogether the study provides a structural basis for selective and non-selective substrate recognition by MT1-MMP. The findings in this report are likely to explain several aspects of MT1-MMP biology.