BiochemistryStereospecific conversion of prostaglandin D2 to (5Z,13E)-(15S)-9a,-11,,15-trihydroxyprosta-5,13-dien-1-oic acid (9a,l11f-prostaglandin F2) Contributed by Osamu Hayaishi, October 30, 1985 ABSTRACT A prostaglandin F (PGF) synthase was recently purified from bovine lung that catalyzed the reduction of both PGH2 and PGD2 but at different active sites on the enzyme. In view of the recent finding that PGD2 is stereospecifically reduced to a unique biologically active compound, (5Z, 13E)-(15S)-9a,11f3,15-trihydroxyprosta-5,13-dien-l-oic acid (9a,11(-PGF2 or ll-epi-PGF2a), by a human liver cytosolic enzyme, detailed characterization of the products formed from PGH2 and PGD2 by the bovine lung PGF synthase was carried out. Chromatographic characteristics of the products formed and stereochemical analysis procedures using mass spectrometry indicated that the enzyme stereospecifically reduces PGH2 to PGF2a, whereas PGD2 is stereospecifically converted to 9a,11(-PGF2. The finding that this enzyme catalyzes the formation of both C-li hydroxy epimers of PGF2, albeit from different substrates, is of interest in that these two compounds may exert different biological actions.Prostaglandin F2a (PGF2a; also called 9a,lla-PGF2) is produced by a number of mammalian organs (1, 2) and exerts a variety of biological actions (3-6). Three different biosynthetic pathways have been described for the formation of PGF2a: (i) 9,11-endoperoxide reduction of PGH2 (7-9), (ii)

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IntroductionWe designed OP3-4 (YCEIEFCYLIR), a cyclic peptide, to mimic the soluble osteoprotegerin (OPG), and was proven to bind to RANKL (receptor activator of NF-κB ligand), thereby inhibiting osteoclastogenesis. We recently found that another RANKL binding peptide, W9, could accelerate bone formation by affecting RANKL signaling in osteoblasts. We herein demonstrate the effects of OP3-4 on bone formation and bone loss in a murine model of rheumatoid arthritis.MethodsTwenty-four seven-week-old male DBA/1J mice were used to generate a murine model of collagen-induced arthritis (CIA). Then, vehicle or OP3-4 (9 mg/kg/day or 18 mg/kg/day) was subcutaneously infused using infusion pumps for three weeks beginning seven days after the second immunization. The arthritis score was assessed, and the mice were sacrificed on day 49. Thereafter, radiographic, histological and biochemical analyses were performed.ResultsThe OP3-4 treatment did not significantly inhibit the CIA-induced arthritis, but limited bone loss. Micro-CT images and quantitative measurements of the bone mineral density revealed that 18 mg/kg/day OP3-4 prevented the CIA-induced bone loss at both articular and periarticular sites of tibiae. As expected, OP3-4 significantly reduced the CIA-induced serum CTX levels, a marker of bone resorption. Interestingly, the bone histomorphometric analyses using undecalcified sections showed that OP3-4 prevented the CIA-induced reduction of bone formation-related parameters at the periarticular sites.ConclusionThe peptide that mimicked OPG prevented inflammatory bone loss by inhibiting bone resorption and stimulating bone formation. It could therefore be a useful template for the development of small molecule drugs for inflammatory bone loss.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-015-0753-8) contains supplementary material, which is available to authorized users.

Purpose: This study comprehensively reviewed the current status of digital workflows in fabricating removable partial dentures (RPDs) using evidence from clinical trials and case reports. Study selection: We performed a systematic review of the literature on the materials and fabrication of RPDs using digital technologies published in online databases from 1980 to 2020. We selected eligible articles from the search results, retrieved information on digital RPDs from these, and conducted a qualitative analysis. We report evidence from clinical papers and case reports, digital impression-taking methods, and maxillomandibular relationship (MMR) records. Results: A case report electronically published in 2019 introduced a clasp-retained RPD fabricated via a full-digital workflow without a gypsum definitive cast. Computer-aided design and computer-aided manufacturing of double-crown-retained RPDs with nonmetal materials were described in some case reports. Intraoral scanners were used to obtain digital impressions and MMR records in the fabrication of digital RPDs, which have potential advantages for reducing the number of clinical appointments and simplifying laboratory procedures. Evidence from clinical trials is scarce; a randomized controlled trial reported higher patient satisfaction with digital clasp-retained RPDs than with conventional RPDs. Conclusions: Full-digital RPDs can be fabricated without a gypsum definitive cast. However, the indication for full-digital RPDs is limited to cases with Kennedy Class III/IV partially edentulous arches with several missing teeth. Challenges in digital impression-taking and MMR recording remain to be solved to extend these indications. More evidence from clinical trials is required to evaluate the efficacy and usefulness of digital RPDs.