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プロサイモシンα由来ペプチドはシスプラチン誘発急性腎障害を軽減する
Background: Prothymosin alpha (ProTα) is a nuclear protein expressed in virtually all mammalian tissues. Previous studies have shown that ProTα exhibits protective effects against ischemia-induced cell death in various cell types. Recently, the 6-residue peptide P6Q (NEVDQE), the modified form of the active 6-residue core (51–56) in ProTα, has also been shown to have protective effects against retinal ischemia. However, it remains to be elucidated whether P6Q is effective against acute kidney injury (AKI). Therefore, we investigated the renoprotective effect of P6Q on cisplatin-induced AKI. Methods: Cultured HK-2 cells were treated with cisplatin for 24 h and pretreatment with ProTα or P6Q was carried out 30 min before cisplatin treatment. Cell viability was evaluated using the MTT assay. In an in vivo study, 8-week-old male Wistar rats were divided into control, cisplatin treated, and cisplatin treated with P6Q injection groups. In the last of these, P6Q was injected intravenously before cisplatin treatment. Then, we evaluated the renoprotective effect of P6Q. Results: In the study on cultured cells, pretreatment with ProTα or P6Q prevented cisplatin-induced cell death. In the in vivo study, pretreatment with P6Q significantly attenuated cisplatin-induced increase in serum creatinine and blood urea nitrogen levels, renal tubular cell injury, and apoptosis. Moreover, P6Q attenuated the mitochondrial apoptotic pathway and accelerated Akt phosphorylation after cisplatin-induced renal damage. Conclusion:
Taken together, our findings indicate that P6Q can attenuate cisplatin-induced AKI and suppress the mitochondrial apoptotic pathway via Akt phosphorylation. These data suggest that P6Q has potential as a preventative drug for cisplatin-induced AKI.長崎大学学位論文 学位記番号:博(医歯薬)甲第1213号 学位授与年月日:令和2年3月4日Author: Kenta Torigoe, Yoko Obata, Miki Torigoe, Satoru Oka, Kazuo Yamamoto, Takehiko Koji, Hiroshi Ueda, Hiroshi Mukae & Tomoya NishinoCitation: Clinical and Experimental Nephrology, Article in Press
北部ベトナムにある国立三次医療機関の診断未確定発熱入院患者におけるツツガムシ病診断上の課題
Background: Scrub typhus (ST) is a leading cause of non-malarial febrile illness in Southeast Asia, but evidence of its true disease burden is limited because of difficulties of making the clinical diagnosis and lack of adequate diagnostic tests. To describe the epidemiology and clinical characteristics of ST, we conducted an observational study using multiple diagnostic assays at a national tertiary hospital in Hanoi, Vietnam. Methodology/Principal findings: We enrolled 1,127 patients hospitalized with documented fever between June 2012 and May 2013. Overall, 33 (2.9%) patients were diagnosed with ST by PCR and/or screening of ELISA for immunoglobulin M (IgM) with confirmatory tests: 14 (42.4%) were confirmed by indirect immunoperoxidase assay (IIP), and 19 (57.6%) were by IIP and PCR. Living by farming, conjunctival injection, eschar, aspartate aminotransferase elevation, and alanine aminotransferase elevation were significantly associated with ST cases (adjusted odds ratios (aORs): 2.8, 3.07, 48.8, 3.51, and 4.13, respectively), and having a comorbidity and neutrophilia were significantly less common in ST cases (aORs: 0.29 and 0.27, respectively). The majority of the ST cases were not clinically diagnosed with rickettsiosis (72.7%). Dominant IIP reactions against a single antigen were identified in 15 ST cases, whereas indistinguishably high reactions against multiple antigens were seen in 11 ST cases. The most frequently observed dominant IIP reaction was against Karp antigen (eight cases) followed by Gilliam (four cases). The highest diagnostic accuracy of IgM ELISA in acute samples was 78%. In a phylogenetic analysis of the 56-kDa type-specific antigen gene, the majority (14 cases) were located in the Karp-related branch followed by the Gilliam-related (two cases), Kato-related (two cases), and TA763-related clades (one case).
Conclusions/Significance: Both the clinical and laboratory diagnoses of ST remain challenging at a tertiary hospital. Implementation of both serological and nucleic acid amplification assays covering endemic O. tsutsugamushi strains is essential.長崎大学学位論文 学位記番号:博(医歯薬)甲第1214号 学位授与年月日:令和2年3月4日Author: Shungo Katoh, Ngo Chi Cuong, Sugihiro Hamaguchi, Pham Thanh Thuy, Do Duy Cuong, Le Kim Anh, Nguyen Thi Hien Anh, Dang Duc Anh, Eiichiro Sando, Motoi Suzuki, Hiromi Fujita, Michio Yasunami, Keisuke Yoshihara, Lay-Myint Yoshida, Daniel Henry Paris, Koya AriyoshiCitation: PLOS Neglected Tropical Diseases, 13(12), e0007928; 201
ナノバブルと超音波照射を用いた腹腔内組織への高効率な遺伝子導入法の開発
In this study, we demonstrate the low toxicity and highly efficient and spatially improved transfection of plasmid DNA (pDNA) with liposomal nanobubbles (bubble liposomes [BLs]) using ultrasound (US) irradiation in mice. Naked pDNA with BLs was intraperitoneally injected, followed by US irradiation. The injection volume, the duration of US irradiation, and the dose of BLs were optimized. Both BLs and US irradiation were essential to achieve high transgene expression from naked pDNA. We observed transgene expression in the entire peritoneal tissues, including the peritoneal wall, liver, spleen, stomach and small and large intestines. The area of transfection could be controlled with focused US irradiation. There were few changes in the morphology of the peritoneum, the peritoneal function or serum alanine aminotransferase levels, suggesting the safety of BLs with US irradiation. Using a tissue-clearing method, the spatial distribution of transgene expression was evaluated. BLs with US irradiation delivered pDNA to the submesothelial layer in the peritoneal wall, whereas transgene expression was restricted to the surface layer in the liver and stomach. Therefore, BLs with US irradiation could be an effective and safe method of gene transfection to the peritoneum.長崎大学学位論文 学位記番号:博(医歯薬)甲第1233号 学位授与年月日:令和2年3月19日Author: Koyo Nishimura, Shintaro Fumoto, Yuki Fuchigami, Masayori Hagimori, Kazuo Maruyama & Shigeru KawakamiCitation: Drug Delivery, 24(1), pp.737-744; 201
トヨカマイシンは培養肝細胞における遊離脂肪酸が誘導する脂肪変性及びアポトーシスを抑制し、マウスにおける非アルコール性脂肪肝疾患を改善する
長崎大学学位論文 [学位記番号]博(医歯薬)甲第1273号 [学位授与年月日]令和2年9月2
老化肝星細胞から分泌される細胞外小胞は、分化THP-1細胞からのEGF発現増加を介し肝癌細胞増殖能を促進させる
長崎大学学位論文 [学位記番号]博(医歯薬)甲第1274号 [学位授与年月日]令和2年9月2
Comprehensive Prospective Analysis of the Factors Contributing to Aspiration Pneumonia Following Endoscopic Submucosal Dissection in Patients with Early Gastric Neoplasms
ndoscopic submucosal dissection (ESD) has become the first-line treatment for early gastric neoplasms; however, a subset of patients treated by this method develop aspiration pneumonia. We conducted a comprehensive prospective analysis of the factors contributing to post-ESD aspiration pneumonia in early gastric neoplasms in this study, with special focus on whether pre-treatment oral care can prevent aspiration pneumonia. Sixty-one patients who underwent ESD for gastric neoplasms were randomly assigned to the oral care or control groups. ESD was performed under deep sedation. Of 60 patients whose data were available for analysis, 5 (8.3%) experienced pneumonia confirmed either by chest radiography or computed tomography. Although no difference in the rate of pneumonia was found between
the control and oral care groups, the post-oral care bacteria count was significantly higher in the saliva of patients who developed pneumonia compared to those without pneumonia. In addition, the presence of vascular brain diseases and the dose of meperidine were also significantly associated with the occurrence of pneumonia. These results suggest that the number of oral bacteria as well as pre-existing
vascular brain diseases and high-dose narcotics can affect the incidence of post-ESD pneumonia
Prevotella intermedia ジペプチダーゼAの基質特異性の決定と新規オートプロセシング機構
Prevotella intermedia, a gram-negative anaerobic rod, is frequently observed in subgingival polymicrobial biofilm from adults with chronic periodontitis. Peptidases in periodontopathic bacteria are considered to function as etiological reagents. Pre. intermedia OMA14 cells abundantly express an unidentified cysteine peptidase specific for Arg-4-methycoumaryl-7- amide (MCA). BAU17746 (locus tag, PIOMA14_I_1238) and BAU18827 (locus tag, PIOMA14_II_0322) emerged as candidates of this peptidase from the substrate specificity and sequence similarity with C69-family Streptococcus gordonii Arg-aminopeptidase. The recombinant form of the former solely exhibited hydrolyzing activity toward Arg-MCA, and BAU17746 possesses a 26.6% amino acid identity with the C69-family Lactobacillus helveticus dipeptidase A. It was found that BAU17746 as well as L. helveticus dipeptidase A was a P1-position Arg-specific dipeptidase A, although the L. helveticus entity, a representative of the C69 family, had been reported to be specific for Leu and Phe. The fulllength form of BAU17746 was intramolecularly processed to a mature form carrying the N-terminus of Cys15. In conclusion, the marked Arg-MCA-hydrolyzing activity in Pre. intermedia was mediated by BAU17746 belonging to the C69-family dipeptidase A, in which the mature form carries an essential cysteine at the N-terminus.長崎大学学位論文 学位記番号:博(医歯薬)甲第1215号 学位授与年月日:令和2年3月19日Author: Mohammad Tanvir Sarwar, Yuko Ohara-Nemoto, Takeshi Kobayakawa, Mariko Naito and Takayuki K. NemotoCitation: Biological Chemistry, Article in Pres
Effect of Metofluthrin-Impregnated Spatial Repellent Devices Combined with New Long-Lasting Insecticidal Nets (Olyset® Plus) on Pyrethroid-Resistant Malaria Vectors and Malaria Prevalence: Field Trial in South-Eastern Malawi
Long-lasting insecticidal nets (LLINs) experience some operational problems that reduce their effectiveness, such as limited spaces for hanging, biting of mosquitoes outdoors, a shift of key biting time from midnight to dawn or dusk, and development of pyrethroid resistance in mosquitoes. The concept of spatial repellency may be a countermeasure to overcome the above issues. The effect of the combined use of metofluthrin-impregnated spatial repellent devices (MSRDs) and LLINs (Olyset® Plus) on malaria prevalence and vector mosquitoes were examined in malaria endemic villages in south-eastern Malawi. The intervention reduced the infection rate in children as well as the number of pyrethroid-resistant vector mosquitoes. To achieve effective malaria control, continued intervention using MSRDs with 2 strips per 10 m2 at 3-month intervals to reduce the density of malaria mosquitoes is recommended