Anti-CASP9 polyclonal antibody

A major concern associated with the use of drugs is their adverse side effects. Specific examples of the drugs of concern include antibiotic agents and non-steroidal anti-inflammatory drugs. Despite the presence of a high degree of efficacy for specific conditions, these drugs may deteriorate the surrounding tissues that are exposed to them. Often, carprofen is used for joint inflammation; however, it may stimulate cartilage degradation which can then lead to osteoarthritis progression. In this study, hyaluronan was combined with carprofen treatment in three different applications (pre-treatment, co-treatment and post-treatment) on normal canine chondrocytes to determine whether Hyaluronan (HA) is capable of mitigating the degree of chondrotoxicity of carprofen. Our findings revealed that carprofen at IC20 (0.16 mg/mL) decreased viability and increased nitric oxide (NO) production. Importantly, carprofen induced the apoptosis of canine chondrocytes via the up-regulation of Bax, Casp3, Casp8, Casp9 and NOS2 as compared to the control group. Although the co-treatment of HA and carprofen appeared not to further alleviate the chondrotoxicity of carprofen due to the presence of a high number of apoptotic chondrocytes, post-treatment with HA (carprofen treatment for 24 h and then changed to HA for 24 h) resulted in a decrease in chondrocyte apoptosis by the down-regulation of Bax, Casp3, Casp8, Casp9, NOS2, along with NO production when compared with the treatment of carprofen for 48 h (P < 0.05). These results suggest that HA can be used as a therapeutic agent to mitigate the degree of chondrotoxicity of carprofen.

BackgroundNonsyndromic oral clefts are craniofacial malformations, which include cleft lip with or without cleft palate. The etiology for oral clefts is complex with both genetic and environmental factors contributing to risk. Previous genome-wide association (GWAS) studies have identified multiple loci with small effects; however, many causal variants remain elusive. MethodsIn this study, we address this by specifically looking for rare, potentially damaging variants in family-based data. We analyzed both whole exome sequence (WES) data and whole genome sequence (WGS) data in multiplex cleft families to identify variants shared by affected individuals. ResultsHere we present the results from these analyses. Our most interesting finding was from a single Syrian family, which showed enrichment of nonsynonymous and potentially damaging rare variants in two genes: CASP9 and FAT4. ConclusionNeither of these candidate genes has previously been associated with oral clefts and, if confirmed as contributing to disease risk, may indicate novel biological pathways in the genetic etiology for oral clefts.