一抗体免疫法によるPorphyromonas. gingivalis SODの定量(プレリミナリーレポート)

Superoxide dismutase (SOD) as a free radical scavenger in Porphyromonas gingivalis is well documented. The aim of this work was to develop an enzyme-linked immunosorbent assay using recombinant P. gingivalis SOD as an antigen. The sandwich complex was detected using a secondary antibody conjugated to β-D-galactosidase. Under optimum conditions, the sensitivity and the limit of detection were determined from 25pg to 500pg. In future, the application will be extended to the expression of SOD from P. gingivalis under various growing conditions

Protocol for a randomized study of the efficacy of ibandronic acid plus eldecalcitol in patients with gastric cancer after gastrectomy: A comparative study of different routes of administration of ibandronic acid [version 2; peer review: 2 approved]

Background: Patients who undergo gastrectomy for gastric cancer are susceptible to osteoporosis. To prevent a decrease in bone mineral density, an appropriate prophylaxis is considered important to adjust the post-gastrectomy condition. In this study, we will compare two different routes of administration of ibandronic acid (oral or intravenous) plus eldecalcitol as a potentially more suitable treatment for patients at a high risk of fragile fracture. Protocol: This study protocol describes a randomized, active-controlled, non-blind, single-center, phase II trial. For patients in the investigational arm (Group A), sodium ibandronate hydrate will be administered intravenously once a month with daily oral intake of eldecalcitol; for those in the control arm (Group B), sodium ibandronate hydrate will be administered orally once a month with daily oral intake of eldecalcitol. We will recruit patients aged 45–85 years who have undergone gastrectomy for gastric cancer and are at a risk of fragility fractures. The study will include patients with existing vertebral fractures and/or femoral proximal fractures, or with lumbar and/or proximal femur bone mineral density of less than 80% of the young adult mean. The primary outcome of this study will be the change in lumbar bone mineral density. We will also evaluate the changes in femur bone mineral density, bone metabolism markers, health-related quality of life as evaluated using the EuroQol 5 Dimension (EQ-5D), and digestive symptoms as evaluated using the Gastrointestinal Symptom Rating Scale after 52 weeks of treatment. Conclusions: We believe that appropriate treatments that are adjusted to the condition of patients after gastrectomy are important for the prevention of bone mineral loss. Registration: This study was accepted by the Japan Registry of Clinical Trials (jRCT1041200059, November 6, 2021)

Porphyromonas gingivalis SOD における活性中心近傍に局在するアミノ酸残基の金属特異的活性における関与：Leu ₇2 Trp およびLeu ₇6 Phe の2残基変異による検討

The role of superoxide dismutase (SOD) as a radical scavenger in Porphyromonas gingivalis is well documented. P. gingivalis SOD (Pg SOD), which is characterized by a metal–tolerant activity, can use either iron or manganese as a cofactor. Leu ₇2 and Leu ₇6, located near the active–site metal, are characteristic amino acid sequences of Pg SOD proteins, although they are substituted to Trp in the ₇2 position and Phe in the ₇6 position in most iron–containing SOD (Fe–SOD) proteins. In the present study, we constructed a mutant of the enzyme with changes from Leu ₇2 to Trp and Leu ₇6 to Phe. This mutant SOD was examined with respect to its metal–dependent activity and structural characterization. We herein conclude the integrity of Leu ₇2 and Leu ₇6 is a necessary requisite for the metal–tolerant activity of Pg SOD

Porphyromonas gingivalis スーパーオキシドジスムターゼの構造における72位Leu をTrp に置換した影響

Porphyromonas gingivalis contains a single constitutive superoxide dismutase (SOD) that is active with either iron or manganese at the active site. The aim of this work was to evaluate the effect of the Leu ₇2 to Trp mutation on the structure of P. gingivalis SOD (Pg SOD) using lectrophoretic characterization. Leu ₇2, which is located near the active site metal, is substituted with Trp in aligned amino acid sequences of iron–containing SOD. The results of electrophoretic characterization and the expressed activity of mutant SOD suggest that mutant SOD have the same gross structure as wild–type SOD. We herein conclude that the integrity of Leu ₇2 is a necessary requisite for the metal–tolerant activity of Pg SOD

Porphyromonas gingivalis SOD の活性中心金属の近位には，トレオニンがセリンよりも優先的に選択される:155位Gly をSer に変異させた影響

Summary In this study, we analyzed the cambialistic superoxide dismutases (SODs) of Porphyromonas gingivalis (Pg–SODs) with a mutation directed at glycine position 155 to introduce serine. Glycine 155 is a highly conserved outer sphere in manganese–containing SODs (Mn–SODs), even though threonine is substituted at this position in most iron–containing SODs (Fe–SODs). Conversion of glycine 155 may affect the metal–specific activity of SODs, including that of cambialistic Pg–SODs.Previously, we reported that a Pg–SOD Gly155Thr mutant exhibited a substantially changed metalspecific activity from that of a cambialistic type to an Fe–specific type. Although serine and threonine equally contribute to protein function, serine has never been observed at position 155 in SODs. In order to elucidate this phenomenon, we created a Pg–SOD mutant Gly155Ser. The specific Fedependent activity of this mutant was almost identical to the wild–type SOD, whereas the Mndependent activity exhibited a 60% reduction. The ultraviolet–visible absorption of Fe– and Mnreconstituted mutant SODs did not exhibit characteristic absorption spectra. Similar to the wild–typeSODs, the mutant SODs exhibited a single band with identical mobilities after separation by polyacrylamide gel electrophoresis. However, their behavior after anion–exchange chromatography differed from that of the wild–type SODs. Thus, Gly155 is considered to be an essential residue for maintaining the hydrogen–bond network for Mn–specific and Fe/Mn–tolerant activity. Gly155 was possibly retained instead of Ser during the evolution of SODs owing to its increased efficiency in maintaining a dimeric structure

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (P interaction  = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications

Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.

Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications