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    In vitro effects of febrifugine on Schistosoma mansoni adult worms

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    Background: Reports on the antischistosomal effect of several antimalarial drugs such as artesunate, mefloquine, and amodiaquine suggest that febrifugine, which exerts an antimalarial effect, can also be expected to possess antischistosomal potential. The present study investigates the antischistosomal effects of febrifugine. Methods: In experiment 1, Schistosoma mansoni adult worm pairs were incubated in a medium alone as a control or supplemented with febrifugine at 0.05, 0.1, 0.2, and 0.5 μg/ml for 14 days. The morphology of the worms and the egg production of the female worms were observed simultaneously. In experiment 2, the incubation was conducted as in experiment 1, except that the febrifugine concentrations were reduced to 0.005, 0.01, and 0.02 μg/ml. In addition, S. mansoni adult worms were incubated with either 0.5 μg/ml febrifugine or none as a control for 5 days and stained with neutral red dye. Results: Febrifugine significantly reduced the survival of S. mansoni male and female worms at concentrations of 0.02-0.5 μg/ml following incubation for 14 days and remarkably inhibited the daily egg output of the female worms. The non-treated male and female worms remained morphologically normal within the period of 14 days, whereas male and female worms treated with febrifugine at different concentrations gradually twisted and subsequently died. In addition, S. mansoni adult worms were incubated with either 0.5 μg/ml febrifugine or none as a control for 5 days and stained with neutral red dye. Non-treated male worms were morphologically normal and stained dark red with neutral red, while febrifugine-treated male worms appeared similar to those in the control group and were stained at a slightly lower level of dark red than the non-treated male worms. Non-treated female worms were morphologically normal, and their intestinal tract and vitellaria were stained deep red and dark red, respectively. In contrast, febrifugine-treated female worms were morphologically damaged, and their intestinal tract and vitellaria remained mostly unstained and stained dark red, respectively. Conclusion: Febrifugine exerts potent antischistosomal effects and can be expected to contribute to the development of a novel antischistosomal drug

    Selective inhibition of PI3K110α as a novel therapeutic strategy for cetuximab‑resistant oral squamous cell carcinoma

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    High expression of the 110 kDa catalytic subunit of the class IA PI3K (PI3Kp110α) may play an important role in cetuximab resistance exhibited by both colorectal cancer and head and neck squamous cell carcinoma. Therefore, the present study aimed to examine the association between the expression of proteins in the PI3Kp110α pathway and cetuximab resistance, and the antitumor effects of alpelisib (PI3K inhibitor) and cetuximab in oral squamous cell carcinoma (OSCC) cells. The association between PI3Kp110α protein expression levels and the tumor response to cetuximab was determined using immunohistochemistry. OSCC cells were treated with alpelisib, cetuximab, or in combination, and the effects were examined in vitro and in vivo. PI3Kp110α protein expression was significantly associated with the tumor response to cetuximab (P<0.05) and 1‑year progression‑free survival and overall survival (P<0.05). Combined treatment of alpelisib and cetuximab resulted in enhanced antitumor effects in vitro compared with either agent administered alone. In particular, the expression level of N‑cadherin, an epithelial‑mesenchymal transition‑related protein, was decreased, suggesting that the invasion potential of cetuximab‑resistant cells decreased. Furthermore, the expression of proteins in the PI3K pathway were decreased in tumors from mice with OSCC xenografts treated with alpelisib and cetuximab in combination. These results indicate that novel regimens of systemic therapy (such as chemotherapy), with combinations of cetuximab and alpelisib, may be beneficial for patients with cetuximab‑resistant OSCC

    屋内放射能汚染の効果的除染のための清掃用素材及び方法

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    長崎大学学位論文 学位記番号:博(医歯薬)乙第60号 学位授与年月日:令和2年9月2

    Effect of tank shape on survival and growth of Pacific bluefin tuna Thunnus orientalis larvae

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    We examined the effect of rearing tank shape on survival and growth of Pacific bluefin tuna Thunnus orientalis larvae. Cylindrical (1.7 × 103 cm2 water surface area; 30 cm deep) and rectangular (1.8 × 103 cm2 water surface area; 28 cm deep) tanks (n = 3 each) were filled with 50 l of seawater. One air stone with a 100 ml/min aeration rate was set at the bottom center of each tank. Light intensity at the water surface was 2000 lx with a photoperiod of 24 L:0D. Larvae were introduced into each tank at a rate of 10 individuals/l at 2 days post-hatching (dph). Rotifers were fed at 10 individuals/ml and their distribution in tanks was measured. Survival of larvae in cylindrical tanks (CT; 52.7 ± 5.1%) at 8 dph was higher than that in rectangular tanks (RT; 0.8 ± 0.7%, p < .01). Meanwhile, larvae growth was not significantly different between tank shapes either in body length (CT: 4.23 ± 0.26 mm; RT: 4.09 ± 0.20 mm) or dry weights (CT: 95.1 ± 17.6 μg; RT: 67.7 ± 10.9 μg). The swimbladder inflation rate of larvae also did not differ significantly between tank shapes (CT: 16.5 ± 14.5%; RT: 56.9 ± 3.47%). Rotifer distribution was higher at tank bottom in both shapes (p < .05). Two-phase bubbly flow simulations in the tanks revealed that the low-flow area was larger in the RT. The low-flow area at tank bottom varied by tank shape, occurring at the edge of the tank wall on the bottom in the CT, and from the center of the tank (air stone) to the tank wall in the RT. These low-flow areas at tank bottom coincided with areas of higher rotifer distribution, which may be a cause of sinking syndrome in fish larvae. Our results indicate that small-scale (50-l) PBT larviculture experiments can be conducted using a CT with the present aeration system, and that an RT requires an improved aerator in place of the single air stone

    キレート型カルベン配位子を持つ発光性異種多核金属錯体に関する研究

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    長崎大学学位論文 学位記番号:博(工)甲第82号 学位授与年月日:令和2年3月19

    Circulating CD34+ cells and active arterial wall thickening among elderly men: A prospective study

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    Age-related physical changes, such as low-grade inflammation and increased oxidative stress, induce endothelial repair and cause active arterial wall thickening by stimulating the production of CD34+ cells (the principal mediators of atherosclerosis). Despite this, aggressive endothelial repair (progressing atherosclerosis) might cause a wasting reduction in CD34+ cells, which could result in a lower capacity of endothelial repair and hypertension. As yet, no prospective study has clarified the association of circulating CD34+ cells with active arterial wall thickening. We conducted a prospective study of 363 men aged 60–69 years who participated in a general health check-up at least twice from 2014–2017. The circulating CD34+ cell count was significantly positively associated with active arterial wall thickening among subjects without hypertension (n = 236), but not among subjects with hypertension (n = 127). The fully adjusted odds ratios (ORs) of active arterial wall thickening for the logarithmic circulating CD34+ cell count were 1.83 (1.19, 2.84) and 0.69 (0.36, 1.32) for subjects without and with hypertension, respectively. Circulating CD34+ cells are positively associated with active arterial wall thickening in subjects without hypertension. This study demonstrates a means to clarify the mechanisms of endothelial repair in elderly subjects

    Stereoselective synthesis of (+)-5-thiosucrose and (+)-5-thioisosucrose

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    +)-5-Thiosucrose 1, a novel isosteric sulfur analog of sucrose, was synthesized stereoselectively for the first time via indirect β-d-fructofuranosidation involving selective β-d-psicofuranosidation, followed by stereo-inversion of the secondary hydroxy group at the C-3 position on the furanose ring. Glycosidation of protected 5-Thio-d-glucose with a d-psicofuranosyl donor provided β-d-psicofuranosyl 5-Thio-α-d-glucopyranoside and that with d-fructofuranosyl donor gave α-d-fructofuranosyl 5-Thio-α-d-glucopyranoside. Two anomeric stereocenters of the glycosyl donor and acceptor were controlled correctly to provide a single disaccharide among four possible anomeric isomers in the glycosylation. Conversion of the resulting disaccharides afforded (+)-5-Thiosucrose 1 and (+)-5-Thioisosucrose 2 in excellent yields, respectively. Inhibitory activities of 1 and 2 against α-glucosidase in vitro were also examined

    Ceramics in Guadalajara, Mexico

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    We will introduce some collection of ceramics in Guadalajara and a ceramic workshop in Tonalá near Guadalajara. Tokugawa shogunate banned Christianity and completed sakoku system that was a kind of sea ban system in Japan in 1639. As a result, the exchange between Japan and the Catholic countries, such as Spain and Portugal, officially discontinued. However we can find some evidence of material exchange between Japan and New Spain. For example, many pieces of Japanese porcelains were exported from Nagasaki to New Spain in the second half of 17th century and the first half of 18th century. One pair of jar colored with enamel in the cathedral church in Guadalajara is one of the evidences. They were jars that were produced in the first half of 18th century in Arita, Japan. Under the sakoku system, they were imported from Nagasaki to Mexico. Chinese porcelain and Japanese porcelain had crossed the Pacific Ocean. On the other hand ceramic production technology came from Europe to New Spain. Tonala ware near Guadalajara is ceramic made by introducing European technology

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