Cleavage of Cartilage Oligomeric Matrix Protein (COMP) by ADAMTS4 generates a neoepitope associated with osteoarthritis and other forms of degenerative joint disease.

Osteoarthritis (OA) is a highly prevalent joint disease, affecting millions of people worldwide and characterized by degradation of articular cartilage, subchondral bone remodeling and low-grade inflammation, leading to pain, stiffness and disability. Cartilage Oligomeric Matrix Protein (COMP) is a major structural component of cartilage and its degradation has been proposed as a marker of OA severity/progression. Several proteases cleave COMP in vitro, however, it is unclear which of these COMPase activities is prevalent in an osteoarthritic joint.

Soluble Proteoglycans and Proteoglycan Fragments as Biomarkers of Pathological Extracellular Matrix Remodeling.

Proteoglycans and their proteolytic fragments diffuse into biological fluids such as plasma, serum, urine, or synovial fluid, where they can be detected by antibodies or mass-spectrometry. Neopeptides generated by the proteolysis of proteoglycans are recognized by specific neoepitope antibodies and can act as a proxy for the activity of certain proteases. Proteoglycan and proteoglycan fragments can be potentially used as prognostic, diagnostic, or theragnostic biomarkers for several diseases characterized by dysregulated extracellular matrix remodeling such as osteoarthritis, rheumatoid arthritis, atherosclerosis, thoracic aortic aneurysms, central nervous system disorders, viral infections, and cancer.

Microbial richness and air chemistry in aerosols above the PBL confirm 2,000-km long-distance transport of potential human pathogens.

The existence of viable human pathogens in bioaerosols which can cause infection or affect human health has been the subject of little research. In this study, data provided by 10 tropospheric aircraft surveys over Japan in 2014 confirm the existence of a vast diversity of microbial species up to 3,000 m height, which can be dispersed above the planetary boundary layer over distances of up to 2,000 km, thanks to strong winds from an area covered with massive cereal croplands in Northeast (NE) Asia. Microbes attached to aerosols reveal the presence of diverse bacterial and fungal taxa, including potential human pathogens, originating from sewage, pesticides, or fertilizers.

Front-line liquid biopsy for early molecular assessment and treatment of hospitalized lung cancer patients.

Background: Molecular characterization is pivotal for managing non-small cell lung cancer (NSCLC), although this process is often time-consuming and patients' conditions might worsen while molecular analyses are processed. Our primary aim was to evaluate the performance of "up-front" next-generation sequencing (NGS) through liquid biopsy (LB) of hospitalized patients with newly detected lung neoplasm in parallel with conventional diagnosis. The secondary aim included longitudinal monitoring through LB of patients with oncogenic alterations at baseline.

Design, synthesis and biological evaluation of arylsulfonamides as ADAMTS7 inhibitors.

The proteolytic activity of the enzyme ADAMTS7 was recently shown to enhance the progression of atherosclerosis, in line with human genetic findings suggesting that ADAMTS7 has a role in the pathophysiology of coronary heart disease. Targeting the active site of ADAMTS7 with a small molecule inhibitor, therefore, has therapeutic potential. Here, we report the design and synthesis of a novel hydroxamate-based arylsulfonamide that is a potent and selective ADAMTS7 inhibitor.