Heat shock protein 90 targeting therapy

Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone that plays a role in stabilizing and activating more than 200 client proteins. It is required for the stability and function of numerous oncogenic signaling proteins that determine the hallmarks of cancer. Since the initial discovery of the first Hsp90 inhibitor in the 1970s, multiple phase II and III clinical trials of several Hsp90 inhibitors have been undertaken. This review provides an overview of the current status on clinical trials of Hsp90 inhibitors and future perspectives on novel anticancer strategies using Hsp90 inhibitors

<ORIGINAL ARTICLE>Long-term follow-up of combined maxillary protraction appliance and chincap treatment

著しい骨格性反対咬合症例の治療において,我々は上顎前方牽引装置とchin capの併用により,顎関係の改善を行うことを含めた長期的管理を行っている。今回我々は骨格性反対咬合と診断され,治療を行った女子3症例の長期的観察を通し検討,考察を行った。これらの症例において,第一段階では上顎前方牽引装置とchin capにより顎関係を改善した。上顎前方牽引装置除去後,上顎は成長期間中位置変化を殆ど示さなかった。その間,下顎は予測よりも大きな成長を示した。咬合関係はすべての症例において成人期まで維持されていた。しかしこれらの症例は思春期成長の後も,下顎の前方成長により,わずかな後戻引頃向を示した。以上のことから,後戻りを予防するために反対咬合の治療においてはオーバーコレクションと第一段階後の下顎の成長のコントロールが必要であると考えられた。In an attempt to distinguish between long-term treatment effects and growth change, the present study evaluates the real post-treatment changes following maxillary protraction treatment after correction for the orthopedic effects which three female patients were investigated. Our proposed treatment plan for skeletal Class III patients consists of 3 stages. In the firststage, a maxillary protraction appliance and a chincap are used together to correct the intermaxillary relationship. After removal of the maxillary protraction appliance, the maxilla remains relatively stable during the growth stage. However, the mandible tends to experience overgrowth, which results in a relapse. The occlusal relationship was maintained until the adultstage in all cases. However, they experienced slight relapse, manifested by mandibular forward growth following removal of the maxillary protraction appliance. Therefore, overcorrection of reversed occlusion and control of mandibular growth after the first stage must be performed in order to prevent relapse

Protein engineering of Candida rugosa lipase

Lipases (EC 3.1.1.3) catalyze the hydrolysis of emulsified long-chain triacylglycerol at the lipid–water interface. Candida rugosa lipase (CRL) is one of important industrial enzymes that are widely used in biotechnological applications such as the production of fatty acids and the synthesis of various esters. The catalytic efficiency and substrate specificity are seemed to be the key factors for industrial applications. Several approaches have been used to increase the stability of different lipases. For example, the immobilized CRL on carriers led to significant improvement in the catalyst’s activity and stability (Ref 1). In this study, we have focused on protein engineering to improve the properties of CRL. Please click Additional Files below to see the full abstract

Enhancement of protein thermostability by three consecutive mutations using loop-walking method and machine learning

We developed a method to improve protein thermostability, "loop-walking method". Three consecutive positions in 12 loops of Burkholderia cepacia lipase were subjected to random mutagenesis to make 12 libraries. Screening allowed us to identify L7 as a hot-spot loop having an impact on thermostability, and the P233G/L234E/V235M mutant was found from 214 variants in the L7 library. Although a more excellent mutant might be discovered by screening all the 8000 P233X/L234X/V235X mutants, it was difficult to assay all of them. We therefore employed machine learning. Using thermostability data of the 214 mutants, a computational discrimination model was constructed to predict thermostability potentials. Among 7786 combinations ranked in silico, 20 promising candidates were selected and assayed. The P233D/L234P/V235S mutant retained 66% activity after heat treatment at 60 degrees C for 30 min, which was higher than those of the wild-type enzyme (5%) and the P233G/L234E/V235M mutant (35%)