The postmenopausal state is associated with an increased risk of metabolic syndrome. Grape seed extract (GSE), a rich source of proanthocyanidins, has beneficial effects on low-grade inflammatory diseases in a high-fat diet-induced obesity model and therefore is a candidate to improve postmenopausal metabolic abnormalities. In the present study, the effects of dietary GSE on body weight and glucose tolerance were examined in ovariectomized (OVX) mice. Female C57BL6/J mice underwent ovariectomy or a sham operation, and OVX mice were orally administered GSE (100 mg/ kg B.W.) or the vehicle solution (OVX+V). Mice in the OVX+V group weighed significantly more than mice in the Sham group. Body weight was significantly lower in the OVX+GSE group than in the OVX+V group. The weights of subcutaneous white adipose tissue (WAT) and visceral WAT were significantly lower in the OVX+GSE group than in the OVX+V group. In glucose tolerance tests, OVX+GSE mice showed significantly lower blood glucose levels at 30 min and 60 min than those in OVX+V mice. In conclusion, we demonstrated that GSE prevents metabolic disorders, such as obesity and glucose intolerance, in OVX mice. These results support the potential therapeutic applications of GSE in postmenopausal women.

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The stability of the knee joint affects the outcome of total knee arthroplasty. Among the knees with Bi-Surface type 3 (BS3), some showed progressive mediolateral (ML) displacement in the tibiofemoral joint on the standing anteroposterior (AP) radiographs, which indicated ML instability. We aimed to clarify the coronal instability and related factors with it. We compared radiological and clinical outcomes of the 26 knees with BS3 and 38 knees with NexGen LPS (LPS). All surgeries were performed with the same surgical techniques at our institution. Radiological evaluation included the component shift ratio, which indicated coronal instability. Correlations of the component shift ratio at latest follow-up with radiological and clinical measurements were also assessed. Greater component shift ratios in the BS3 group were found, while clinical outcomes showed no significant differences in both groups. The component shift ratio increased with the posterior tibial slope, the femorotibial angle, the implant extension angle, and the knee extension at the latest follow-up. BS3 knees exhibited coronal instability on radiographs, although clinical outcomes were similar to LPS knees. Understanding the design characteristics of BS, avoiding excess posterior tibial slope, and paying attention to the soft tissue balance would be the keys to prevent the instability with this prosthesis.

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Current understanding on the mechanisms of acute stroke highlights the importance of targeting brain endothelial cells (ECs), which regulate blood–brain barrier (BBB) disruption, neuronal cell death, and immune cell infiltration. Because the transcellular pathway through ECs is activated immediately after stroke onset, understanding transporter expression should facilitate development of an efficient drug delivery system to ischemic ECs. Here, we examined BBB leakage profiles and expression of three lipoprotein receptors, lowdensity lipoprotein receptor (LDLR), scavenger receptor class B member 1 (SRB1), and LDLR-related protein 1 (LRP1), in a mouse model of permanent middle cerebral artery occlusion (MCAO). Evans blue staining showed a biphasic BBB disruption with one peak at 6 h and the other at 3 days after MCAO. The tight junction protein occludin in the ischemic cortex significantly decreased at 3 days, but not 6 h, after MCAO. LDLR, SRB1, and LRP1 mRNA levels were significantly up-regulated early after MCAO. LDLR and SRB1 proteins were colocalized predominantly in brain ECs, whereas LRP1 was localized in neurons in the ischemic cortex. The early overexpression of lipoprotein receptors after stroke suggests that lipoprotein-associated lipids could be suitable ligands for drug delivery into ECs and neurons in the acute ischemic brain.

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Background: Platelet-derived growth factors (PDGFs) have been reported to enhance proliferation of synovial mesenchymal stem cells (MSCs) without reducing their multi-lineage differentiation potential in vitro. This study was aimed to elucidate the intracellular molecular pathways activated by PDGFs. Methods: Synovial MSCs were isolated from patients who underwent total knee arthroplasty with institutional approval and patients’ permission. Cell proliferation and differentiation assays were performed in the presence of small inhibitor molecules specific for intracellular kinases. Results: Both PDGF-AA and -BB enhanced cell proliferation in medium containing reduced serum. These effects were significantly reduced by a phosphatidylinositol- 3 kinase (PI3K) inhibitor, LY290042. During chondrogenic spheroid formation in vitro, LY290042 significantly reduced the size of spheroids enhanced by PDGF-AA. LY290042 also significantly inhibited in vitro chondrogenic and osteoblastic differentiation of synovial MSCs. Conclusion: Our data indicated that activation of the PI3K-PKB/ Akt pathway by PDGFs plays an important role in both proliferation and differentiation of synovial MSCs. Hence, these data could be beneficial for optimizing the in vitro culture conditions of synovial MSCs for clinical use.

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MicroRNAs (miRNAs) are important therapeutic targets for intractable diseases and antisense oligonucleotides that silence microRNA (antagomirs) have been developed for clinical applications. Although conjugation of ligands to antagomirs is a promising means of delivering them to target tissues and cells, the efficacy of these constructs is yet to be optimized. In this study, we designed a novel antagomir construct that comprise an antagomir strand and its complementary RNA strand. We were then able to indirectly conjugate ligands to this double-stranded antagomir via the complementary RNA strand. We then used single- or doublestranded antagomirs to examine effects of ligand type, conjugation site, or chemical modifications of the antagomir strand on miRNA silencing in vitro. We found that indirect conjugation of cholesterol ligand to a double-stranded antagomir produced a construct with comparable miRNA-silencing efficacy as that of a single-stranded antagomir directly conjugated with the ligand. Our findings support application of this technology for the therapeutic regulation of miRNA.

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Japan’s aging society and its declining birthrate are threatening to upset the balance of supply and demand of blood products. We investigated the possibility of increasing the current maximum volume of platelet apheresis donation (PA) to the current maximum volume of plasmapheresis donation (PP), without changing the maximum number of platelets collected. We analyzed PA and PP anonymized data (675,406 donors) according to gender. The incidence of initial overall side effects (side effects 1), vasovagal reaction (VVR), and non-VVR were compared according to age, body weight and measured volume at each donor group using the independence test (by the chi-squared or Fisher’s exact test). Side effects were neither significantly different nor relatively high in donors both aged 30-69 years with weighing 65- <70kg in male apheresis donors and aged 25-54 years with weighing 55-<70kg in female apheresis donors. It seems there is the possibility that the both maximum volume of male PA aged 30-69 years with weighing 65-<70 kg and female PA aged 25-54 years with weighing 55-<70 kg can be considered to increase as the subject sample on a trial basis. We expect this increase will make the risks of having fewer donors in the future reduced.

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Objective: This survey was conducted to evaluate changes of students’ English competency as they progress through the academic years, and disclose the effect of outbound exchange programs (OEP) that students can visit oversea universities as an elective course. Materials and Methods: All undergraduate dental students from 1st to 6th year (n = 332), at School of Dentistry, Tokyo Medical and Dental University were invited to participate in the study, and asked to fill out a self-administered questionnaire. As an objective scale of student’s English competency, TOEFL-ITP scores were used. In total, 236 (71.1%) of students participated. Students were classified into two groups by the participation or absence of OEP. Results: Experience from OEP was associated with improved English competency. Students without the participation showed decline in English competency over time. Self-confidence in English communication coincided statistically with the objective measurement of TOEFL-ITP scores. Discussion and Conclusions: Exposure to English communication through experience in organized OEP appears to be important for improving their confidence in English communication. Greater exposure to English language for the dental students and exposure to different culture may help development of international perspectives, motivation of students for further study, and influencing their career choice.

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Combined use of follicle stimulating hormone (FSH) and luteinizing hormone (LH) is generally believed to be essential for ovarian stimulation in the patients with WHO Group I ovulation disorders. We presented an infertile case with WHO Group I successfully treated by recombinant human FSH (rhFSH) administration alone. A 32-year-old woman visited our clinic complaining secondary amenorrhea and wishing for a child. Serum LH, FSH, estradiol, and progesterone levels were 1.4 mIU/ml, 3.1 mIU/ml, <5 pg/ml, and 0.1 ng/ml respectively. Because the LH-RH provocation test was normal response, she was diagnosed as WHO Group I ovulation disorder with partial absence of GnRHmediated hypothalamic activity caused by low body weight. As lifestyle interventions (normalizing body weight and exercise) were not effective, rhFSH administration was initiated. After that, multiple follicles were developed although serum LH was less than 0.1 mIU/ml in the mid- to late-follicular phase. After human chorionic gonadotropin administration, oocytes were retrieved, fertilized and cultured in vitro. Subsequently she successfully conceived with freeze-thawed blastocyst transfer at hormone replacement cycle. Our case indicated that LH was not necessarily essential for the development of ovarian follicles at least in the mid- to late-follicular phase even in patients with WHO Group I ovulation disorder.

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