Associations between serum biomarkers of cartilage metabolism and serum hyaluronic acid, with risk factors, pain categories, and disease severity in knee osteoarthritis: a pilot study.

Background: Specific serum biomarkers of cartilage metabolism such as cartilage oligomeric matrix protein (sCOMP) and procollagen type II C-terminal propeptide (sPIICP) as well as hyaluronan (sHA), a biomarker of synovitis, have been implicated in the pathophysiology of knee osteoarthritis (OA). However, the associations of these biomarkers with the severity of the disease and OA risk factors, including age and obesity remain inconclusive. This analysis examines the associations between these serum biomarkers and the radiographic severity of OA and knee pain, as wells as obesity, the age and gender of the participants, and other OA risk factors.

Novel multifunctional and multitarget homo- (Fe) and heterobimetallic [(Fe,M) with M = Re or Mn] sulfonyl hydrazones.

The synthesis and characterization of the novel ferrocenyl sulfonyl hydrazide [Fe(η5-C5H5){(η5-C5H4)-S(O)2-NH-NH2}] (2) is reported. Additional studies on its reactivity using acetone or the ferrocenyl-, cyrhetrenyl- or cymantrenyl-aldehydes have allowed us to isolate and characterize [Fe(η5-C5H5){(η5-C5H4)-S(O)2-NH-N[double bond, length as m-dash]CMe2}] (3), the bis(ferrocenyl) derivative [Fe(η5-C5H5){[(η5-C5H4)-S(O)2-NH-N[double bond, length as m-dash]CH-(η5-C5H4)]Fe(η5-C5H5)}] (4) and the heterodimetallic compounds [Fe(η5-C5H5){[(η5-C5H4)-S(O)2-NH-N[double bond, length as m-dash]CH-(η5-C5H4)]M(CO)3}] with M = Re (5a) or Mn (5b). The X-ray crystal structures of compounds 3, 5a and 5b are also reported.

A novel type of organometallic 2-R-2,4-dihydro-1H-3,1-benzoxazine with R = [M(η-CH)(CO)] (M = Re or Mn) units. Experimental and computational studies of the effect of substituent R on ring-chain tautomerism.

The syntheses, characterization, X-ray crystal structures, electrochemical properties and anticancer and antichagasic activities of the first examples of 2-substituted 2,4-dihydro-1H-3,1-benzoxazines with half-sandwich organometallic arrays, [M(η5-C5H4)(CO)3] (M = Re or Mn), at position-2 are described. Experimental and computational studies based on DFT calculations on the open forms [Schiff bases of general formulae R-CH[double bond, length as m-dash]N-C6H4-2-CH2OH] (5), with R = ferrocenyl (a), phenyl (b), cyrhetrenyl (c) or cymantrenyl (d), and their tautomeric forms (2-substituted 2,4-dihydro-1H-3,1 benzoxazines) have allowed us to establish the influence of substituents a-d and solvents on: (a) the extent of tautomeric equilibria (5a-5d) ↔ (6a-6d) and (b) their electrochemical properties and the electronic distribution on the open and closed forms. Despite the formal similarity between 6c and 6d, their anticancer and antiparasitic activities are markedly different.

Site-Specific Antibody Drug Conjugates Using Streamlined Expressed Protein Ligation.

Antibody-Drug Conjugates (ADCs) have been shown to produce clinical benefit in cancer patient thanks to their ability to target highly cytotoxic small molecules to tumor cells. However, the development of these complex molecules faces significant challenges due to the need to combine a large biologic drug with a small molecule drug to generate the desired bioconjugate. We describe here the use of a protein ligation methodology, based on the native chemical ligation reaction to generate site-specific Antibody-Drug Conjugates, which does not require the incorporation of unnatural modifications into the antibody.

Toward Angiogenesis Inhibitors Based on the Conjugation of Organometallic Platinum(II) Complexes to RGD Peptides.

A novel conjugate between a cyclometalated platinum(II) complex with dual antiangiogenic and antitumor activity and a cyclic peptide containing the RGD sequence (-Arg-Gly-Asp-) has been synthesized by combining solid- and solution-phase methodologies. Although peptide conjugation rendered a non-cytotoxic compound in all tested tumor cell lines (± α β and α β integrin receptors), the antiangiogenic activity of the Pt-c(RGDfK) conjugate in human umbilical vein endothelial cells at sub-cytotoxic concentrations opens the way to the design of a novel class of angiogenesis inhibitors through conjugation of metallodrugs with high antiangiogenic activity to cyclic RGD-containing peptides or peptidomimetic analogues.