Lung Cancer Risk and Genetic Polymorphisms in DNA Repair Pathways: A Meta-Analysis

Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. We conducted a meta-analysis of epidemiologic studies on the association between genetic polymorphisms in both base excision repair and nucleotide excision repair pathways, and lung cancer. We found xeroderma pigmentosum complementation group A (XPA) G23A (odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.61–0.94), 8-oxoguanine DNA glycosylase 1 (OGG1) Ser326Cys (OR = 1.22, 95% CI = 1.02–1.45), and excision repair cross-complementing group 2 (ERCC2) Lys751Gln (OR = 1.27, 95% CI = 1.10–1.46) polymorphisms were associated with lung cancer risk. Considering the data available, it can be conjectured that if there is any risk association between a single SNP and lung cancer, the risk fluctuation will probably be minimal. Advances in the identification of new polymorphisms and in high-throughput genotyping techniques will facilitate the analysis of multiple genes in multiple DNA repair pathways. Therefore, it is likely that the defining feature of future epidemiologic studies will be the simultaneous analysis of large samples of cases and controls

Methylenetetrahydrofolate reductase polymorphisms and interaction with smoking and alcohol consumption in lung cancer risk: a case-control study in a Japanese population

<p>Abstract</p> <p>Background</p> <p>Cigarette smoking is an established risk factor of lung cancer development while the current epidemiological evidence is suggestive of an increased lung cancer risk associated with alcohol consumption. Dietary folate, which is present in a wide range of fresh fruits and vegetables, may be a micronutrient that has a beneficial impact on lung carcinogenesis. Methylenetetrahydrofolate reductase (MTHFR) plays a crucial role in regulating folate metabolism, which affects both DNA synthesis/repair and methylation. We examined if smoking or alcohol consumption modify associations between <it>MTHFR </it>polymorphisms and lung cancer risk.</p> <p>Methods</p> <p>We evaluated the role of the <it>MTHFR </it>C677T (rs1801133) and A1298C (rs1801131) polymorphisms in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI).</p> <p>Results</p> <p>The TT genotype of the C677T polymorphism was significantly associated with an increased risk of lung cancer (OR = 2.27, 95% CI = 1.42 - 3.62, P < 0.01) while the A1298C polymorphism was not associated with lung cancer risk. The minor alleles of both polymorphisms behaved in a recessive fashion. The highest risks were seen for 677TT-carriers with a history of smoking or excessive drinking (OR = 6.16, 95% CI = 3.48 - 10.9 for smoking; OR = 3.09, 95% CI = 1.64 - 5.81 for drinking) compared with C-carriers without a history of smoking or excessive drinking, but no interactions were seen. The 1298CC genotype was only associated with increased risk among non-smokers (P < 0.05), and smoking was only associated with increased risks among 1298A-carriers (P < 0.01), but no significant interaction was seen. There was a synergistic interaction between the A1298C polymorphism and drinking (P < 0.05). The highest risk was seen for the CC-carriers with excessive drinking (OR = 7.24, 95% CI = 1.89 - 27.7) compared with the A-carriers without excessive drinking).</p> <p>Conclusions</p> <p>The C677T polymorphism was significantly associated with lung cancer risk. Although the A1298C polymorphism was not associated with lung cancer risk, a significant interaction with drinking was observed. Future studies incorporating data on folate intake may undoubtedly lead to a more thorough understanding of the role of the <it>MTHFR </it>polymorphisms in lung cancer development.</p

Resuscitation of Preterm Infants with Reduced Oxygen Results in Less Oxidative Stress than Resuscitation with 100% Oxygen

The objective of this study was to determine the effects of the level of inhaled oxygen during resuscitation on the levels of free radicals and anti-oxidative capacity in the heparinized venous blood of preterm infants. Forty four preterm infants <35 weeks of gestation with mild to moderate neonatal asphyxia were randomized into two groups. The first group of infants were resuscitated with 100% oxygen (100% O2 group), while in the other group (reduced O2 group), the oxygen concentration was titrated according to pulse oximeter readings. We measured total hydroperoxide (TH) and redox potential (RP) in the plasma within 60 min of birth. The integrated excessive oxygen (∑(FiO2-0.21) × Time(min)) was higher in the 100% O2 group than in the reduced O2 group (p<0.0001). TH was higher in the 100% O2 group than in the reduced O2 group (p<0.0001). RP was not different between the 100% O2 and reduced O2 groups (p = 0.399). RP/TH ratio was lower in the 100% O2 group than in the reduced O2 group (p<0.01). We conclude that in the resuscitation of preterm infants with mild to moderate asphyxia, oxidative stress can be reduced by lowering the inspired oxygen concentration using a pulse oximeter

Efficient increase of ɣ-aminobutyric acid (GABA) content in tomato fruits by targeted mutagenesis

γ-Aminobutyric acid (GABA) is a non-proteinogenic amino acid that has hypotensive effects. Tomato (Solanum lycopersicum L.) is among the most widely cultivated and consumed vegetables in the world and contains higher levels of GABA than other major crops. Increasing these levels can further enhance the blood pressure-lowering function of tomato fruit. Glutamate decarboxylase (GAD) is a key enzyme in GABA biosynthesis; it has a C-terminal autoinhibitory domain that regulates enzymatic function, and deleting this domain increases GAD activity. The tomato genome has five GAD genes (SlGAD1–5), of which two (SlGAD2 and SlGAD3) are expressed during tomato fruit development. To increase GABA content in tomato, we deleted the autoinhibitory domain of SlGAD2 and SlGAD3 using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas)9 technology. Introducing a stop codon immediately before the autoinhibitory domain increased GABA accumulation by 7 to 15 fold while having variable effects on plant and fruit size and yield. This is the first study describing the application of the CRISPR/Cas9 system to increase GABA content in tomato fruits. Our findings provide a basis for the improvement of other types of crop by CRISPR/Cas9-based genetic modification

「明石新のり・恵方巻まつり」における特定健康診査受診勧奨事業への参加報告

　明石市は市民に対する生活習慣病の早期発見につながる特定健康診査の受診勧奨を行うため，2018年の「明石新のり・恵方巻まつり」のメインイベント時にその資料の配布を行うと共に，明石のりを使用した健康レシピの紹介とレシピに基づいた食べ物の無料提供を行うこととした。　この企画にあたり，明石のりを用いた健康レシピの作成依頼とメインイベント時の健康レシピに基づいた食べ物の調理・提供のための依頼協力が明石市からあった。本報告は，このレシピの作成・試作・検食の過程と当日の食べ物の調理・提供状況を記録に留めておくことを目的とする。　まつりに来場した方に対して明石のりを使用した食べ物200食を提供するためのレシピを種々作成した。試作と検食を重ね、最終的に白玉味噌汁を選定した。白玉味噌汁には，粉のりを添加して作成した緑色の団子2個（団子は白玉粉と絹ごし豆腐で作成）と何も添加しない白色の団子1個を入れ，他の具材としてちくわとしめじも入れた。メインイベント当日は，本学の担当者4名と明石市の担当者7名が白玉味噌汁の調理と提供に当たった

SARS-CoV-2 disrupts respiratory vascular barriers by suppressing Claudin-5 expression

臓器チップ技術を用いて新型コロナウイルスが血管へ侵入するメカニズムを解明 --Claudin-5発現抑制による呼吸器の血管内皮バリア破壊--. 京都大学プレスリリース. 2022-09-22.A study using an organ-on-a-chip reveals a mechanism of SARS-CoV-2 invasion into blood vessels --Disruption of vascular endothelial barrier in respiratory organs by decreasing Claudin-5 expression--. 京都大学プレスリリース. 2022-09-27.In the initial process of coronavirus disease 2019 (COVID-19), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects respiratory epithelial cells and then transfers to other organs the blood vessels. It is believed that SARS-CoV-2 can pass the vascular wall by altering the endothelial barrier using an unknown mechanism. In this study, we investigated the effect of SARS-CoV-2 on the endothelial barrier using an airway-on-a-chip that mimics respiratory organs and found that SARS-CoV-2 produced from infected epithelial cells disrupts the barrier by decreasing Claudin-5 (CLDN5), a tight junction protein, and disrupting vascular endothelial cadherin–mediated adherens junctions. Consistently, the gene and protein expression levels of CLDN5 in the lungs of a patient with COVID-19 were decreased. CLDN5 overexpression or Fluvastatin treatment rescued the SARS-CoV-2–induced respiratory endothelial barrier disruption. We concluded that the down-regulation of CLDN5 expression is a pivotal mechanism for SARS-CoV-2–induced endothelial barrier disruption in respiratory organs and that inducing CLDN5 expression is a therapeutic strategy against COVID-19

奄美諸島と八重山諸島における高齢者の生活と福祉ニーズ : 調査対象者の健康状態、家族の状況、社会とのかかわり状況（１）

本研究の目的は、琉球弧の北に位歴する鹿児島県の奄美諸島と南に位歴する沖縄県の八重山諸島における島嘆地域の高齢者の生活の現状と福祉ニーズを把握することである。調査対象地は、奄美諸島の中心である奄美市(島嘆都市部)および瀬戸内町の加計呂麻島、請島、与路島(島嘆集落部)、八重山諸島の中心である石垣市(島填都市部)、および竹富町西表島西部および鳩間島(島喚集落部)であった。鹿児島県の場合、特に島填集落は過疎高齢化が進行し、集落機能の低下を余儀なくされている。沖縄県の場合、鹿児島県ほどの過疎高齢化は進んでいない状況であるが、島填地域のもつ生活上の課題を共有している。いずれも、相互扶助の伝統等の地域文化あるいはその精神が残っているという共通点を持つ地域である。本稿では、調査対象者の属性、健康状態、家族の状況、社会参加状況および社会関連性指標についての分析結果を示す。居住地域と年齢の両方に回答した対象者は714人(男性284人、女性430人)であった。健康状態では、すべての調査対象地で健康な人の割合が高かった。家族の状況では、対象地ごとに特徴がみられた。集落行事への参加は島嘆集落部の方が高かったが、社会とのかかわり状況全般では島喚集落部の方が低かった。The purpose of the study was to investigate the life styles and the social welfare needs of the elderly who live on the Amami islands and the Yaeyama islands through a questionnaire survey. The regions surveyed were the urban area of the Amami Ohshima (Amami City) and the rural area of the Kakeroma islands (Setouchi Town) in Kagoshima prefecture, and the urban area of Ishigaki island (Ishigaki City) and the rural area of Iriomote island and Hatoma island (Taketomi Town) in Okinawa Prefecture. The people who dwell on these remote islands are usually under unfavorable conditions geographically and economically and the communities there are under dysfunctional state by depopulation and aging. On the other hand, these islands keep the spirit of mutual helping and the traditional cultures. From the data of 714 respondents (284 males and 430 females) , we analyzed the health states, the family situations and the social involvements. Almost 90 percent of the elderly reported that they were healthy. There was no difference in the self-rated health condition among these islands. The number of the single elderly people was higher in Setouchi Town and the number of the multigenerational households was higher in Ishigaki City. Although the percentage of the elderly who participate in community events was higher in the rural area of Setouchi Town and Taketomi Town than in the urban area of Amami City and Ishigaki City, the index of social interaction was lower in the rural area than in the urban area

奄美諸島と八重山諸島における地域住民の生活と福祉ニーズ : 奄美諸島と八重山諸島における一般成人調査より紐解く(2)

本研究は、奄美諸島と八重山諸島における、地域住民の生活と福祉ニーズを一般成人調査 より紐解こうとするものである。調査対象地として、島喚都市部からは奄美市と石垣市を、島喚集落 部としては瀬戸内町の加計呂麻島、請島、与路島と、竹富町からは西表島、鳩間島を選出した。両諸島とも相互扶助としての「結い」の精神の色濃く残る集落群であるが､鹿児島県と沖縄県の諸島では、集落の有り様に差異があることが明らかになった。本稿では食生活、保健・医療福祉サービス、地域の課題等についての分析結果を示す。飲酒に関しては、「毎日飲む」と答えた人は、都市部より、集落部において高かった。「生活習慣病に関する催しへの参加」では、「参加したことが無い」と回答した人は､都市部の方が高かった。地域で感じている問題点については、奄美市と瀬戸内町では「ハブ」の問題、集落部である瀬戸内町と竹富町では日常の買い物の不便があがっていた。総じて、集落部における地域問題の指摘が多かった。国や自治体に望む重点施策について、４地区とも「在宅介護のための、自宅を訪問するサービスの充実」を第１位にあげていた。The purpose of this study was to analyze the life styles and the social welfare needs of the adults who live on the Amami islands and the Yaeyama islands. The regions surveyed were the urban areas of Amami City and Ishigaki City, and the rural areas of the Kakeroma island, Uke island, Yoro island (Setouchi Town) and the rural areas of Iriomote island and Hatoma island (Taketomi Town). Both islands have kept the spirit of mutual helping and the traditional cultures. But it is clear that the conditions of the rural areas in Kagoshima Prefecture and Okinawa Prefecture are different. In this paper we report analyses of the eating habits, the evaluation of health-care services, welfare services, and other regional subjects. The number of the respondents who drink every day was larger in the rural areas of the island than in the urban areas. The number of people who participate in the events concerning life-style rerated diseases was larger in the urban areas. Regional issues in the Amami City and in the Setouchi Town were "habu", inconvenience of daily shopping in Setouchi Town and Taketomi Town, which are in the rural areas of the island. In general, there were many regional issues in the rural areas of the island. The four areas want the national and local governments to "improve the visiting service for homecare" in the first place

奄美諸島と八重山諸島における高齢者の生活と福祉ニーズ : 将来の生活の不安と生きがい感、食生活、保健医療・福祉サービス、地域の問題(2)

本研究の目的は、琉球弧の北に位世する鹿児島県の奄美諸励と南に位置する沖縄県の八重山諸島における島嘆地域の高齢者の生活の現状と福祉ニーズを把握することである。調査対象地は、奄美諸島の中心である奄美市(島嶼都市部)および瀬戸内町の加計呂麻島、請島、与路島(島嶼集落部)、八重山諸島の中心である石垣市(島嶼都市部)、竹富町西表島西部および鳩間島(島嶼集落部)であった。鹿児島県の場合、特に島嘆集落は過疎高齢化が進行し、集落機能の低下を余儀なくされている。沖細県の場合、鹿児島県ほどの過疎高齢化は進んでいない状況であるが、島嶼地域のもつ生活上の課題を共有している。いずれも、相互扶助の伝統等の地域文化あるいはその精神が残っているという共通点を持つ地域である。本稿では、前稿に引き続き、日常生活の不安と生きがい感､食生活､保健医療･福祉サービス、暮らし向きと地域の問題等についての分析結果とそのまとめを示す。将来の生活不安は島喚集落部の方が島嶼都市部よりも不安を感じる人が多かった。一方、生きがい感は、島嶼都市部の方が高かった。食生活では、栄養面のバランスを欠きやすい環境下にあった。保健医療では、島嶼集落部は医療サービスの地域格差への不満や問題が見られると同時に、健康に対するセルフケア意識の高さが伺えた。福祉サービスでは、島嶼集落部では天候や交通手段によるサービスの中止や困難性などが生じていた。暮らし向きと地域の問題では地域差はなく、共通して台風､交際費､老後の生活の不安があげられ、特に瀬戸内町で地域の問題を感じている人が多かった。The purpose of the study was to investigate the life styles and the social welfare needs of the　elderly who live on the Amami Islands and the Yaeyama Islands through a questionnaire survey. The regions surveyed were the urban area of the Amami Ohshima (Amami City) and the rural area of the Kakeroma Islands (Setouchi Town) in Kagoshima prefecture, and the urban area of Ishigaki Island (Ishigaki City) and the rural area of Iriomote Island and Hatoma Island (Taketomi Town) in Okinawa Prefecture. The people who dwell on these remote islands are usually under unfavorable conditions geographically and economically and the communities there are under functional decline due to depopulation and aging. On the other hand, these islands keep the spirit of mutual helping and the traditional cultures. In this paper we report analyses of the anxiety about future life, the feeling that life is worth living, the eating habits, the evaluation of health-care services and welfare services, the family finances, and other regional issues. The anxiety about future life was higher in the rural areas of the islands than in the urban areas. On the other hand, the feeling that life is worth living was higher in the urban areas of the islands than in the rural areas. Respondents were prone to eat poor-balanced meals. In the rural areas of the islands, while they expressed their dissatisfaction with regional gaps of health-care services, they showed high awareness of self-care about their own health. In the rural areas of the islands, welfare services at home were sometimes cancelled by bad weather or transportation trouble by sea. There was no difference in the family finances and regional issues between areas. Regional issues shared by all islands were the vulnerability to typhoons, high social expenses, and the anxiety about life in the future, and especially the elderly in the Setouchi Town listed more regional issues than those in other areas.area of the Kakeroma Islands (Setouchi Town) in Kagoshima prefecture, and the urban area of Ishigaki Island (Ishigaki City) and the rural area of Iriomote Island and Hatoma Island (Taketomi Town) in Okinawa Prefecture. The people who dwell on these remote islands are usually under unfavorable conditions geographically and economically and the communities there are underfunctional decline due to depopulation and aging. On the other hand, these islands keep the spirit of mutual helping and the traditional cultures.In this paper we report analyses of the anxiety about future life, the feeling that life is worth living, the eating habits, the evaluation of health-care services and welfare services, the family finances, and other regional issues. The anxiety about future life was higher in the rural areas ofthe islands than in the urban areas. On the other hand, the feeling that life is worth living was higher in the urban areas of the islands than in the rural areas. Respondents were prone to eat poor-balanced meals. In the rural areas of the islands, while they expressed their dissatisfaction with regional gaps of health-care services, they showed high awareness of self-care about their own health. In the rural areas of the islands, welfare services at home were sometimes cancelled by bad weather or transportation trouble by sea. There was no difference in the family finances and regional issues between areas. Regional issues shared by all islands were the vulnerability to typhoons, high social expenses, and the anxiety about life in the future, and especially the elderly in the Setouchi Town listed more regional issues than those in other areas