A year in review: The most popular medical research of 2017
Published Wednesday 20 December 2017
https://www.medicalnewstoday.com/articles/320405.php
アメリカ及び周辺事情を冒頭記載。その中、"fidge spinner"(指（ハンド）スピナー)を何故か取り上げている。
“この、ハゲー＆白髪”の原因遺伝子
KROX20
Identification of hair shaft progenitors that create a niche for hair pigmentation
Chung-Ping Liao, et al.
GENES & DEVELOPMENT 31:1–13
http://genesdev.cshlp.org/content/early/2017/05/02/gad.298703.117.full.pdf
Hair differentiates from follicle stem cells through progenitor cells in the matrix. In contrast to stem cells in the bulge, the identities of the progenitors and the mechanisms by which they regulate hair shaft components are poorly understood. Hair is also pigmented by melanocytes in the follicle. However, the niche that regulates follicular melanocytes is not well characterized. Here, we report the identification of hair shaft progenitors in the matrix that are differentiated from follicular epithelial cells expressing transcription factor KROX20. Depletion of Krox20 lin- eage cells results in arrest of hair growth, confirming the critical role of KROX20+ cells as antecedents of structural cells found in hair. Expression of stem cell factor (SCF) by these cells is necessary for the maintenance of differen- tiated melanocytes and for hair pigmentation. Our findings reveal the identities of hair matrix progenitors that regulate hair growth and pigmentation, partly by creating an SCF-dependent niche for follicular melanocytes.
“2型糖尿病は、プリオン病的伝染性神経変性疾患の特性を有する”というショッキングな話
膵臓ラ氏島・アミロイド・ポリペプチドを構成する異常折り畳み構造(misfolded)凝集
Induction of IAPP amyloid deposition and associated diabetic abnormalities by a prion-like mechanism
Abhisek Murkherjee , et al.
JEM DOI: 10.1084/jem.20161134 | Published August 1, 2017
http://jem.rupress.org/content/214/9/2591
Although a large proportion of patients with type 2 diabetes (T2D) accumulate misfolded aggregates composed of the islet amyloid polypeptide (IAPP), its role in the disease is unknown. Here, we show that pancreatic IAPP aggregates can promote the misfolding and aggregation of endogenous IAPP in islet cultures obtained from transgenic mouse or healthy human pancreas. Islet homogenates immunodepleted with anti-IAPP–specific antibodies were not able to induce IAPP aggregation. Importantly, intraperitoneal inoculation of pancreatic homogenates containing IAPP aggregates into transgenic mice expressing human IAPP dramatically accelerates IAPP amyloid deposition, which was accompanied by clinical abnormalities typical of T2D, including hyperglycemia, impaired glucose tolerance, and a substantial reduction on β cell number and mass. Finally, induction of IAPP deposition and diabetic abnormalities were also induced in vivo by administration of IAPP aggregates prepared in vitro using pure, synthetic IAPP. Our findings suggest that some of the pathologic and clinical alterations of T2D might be transmissible through a similar mechanism by which prions propagate in prion diseases.
アメリカの食事ガイドライン(Dietary Guidelines for Americans 2015–2020)
健康的、バランスの取れた食事として、多種の果物や野菜、全粒粉、低あるいは無脂肪乳製品、タンパク質食品、油分を含み、かつ、飽和脂肪・トランス脂肪酸・添加糖・ナトリウムの制限する
若い成人で、野菜と果物の摂取量を増やすことは心理的well-beingを改善する。気分、バイタリティー、モチベーション、うつ・不安症状、他のメンタルヘルス・well-being要素の改善。
Let them eat fruit! The effect of fruit and vegetable consumption on psychological well-being in young adults: A randomized controlled trial
Tamlin S. et al.
PLOSone, Published: February 3, 2017
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0171206
This study tested the psychological benefits of a 14-day preregistered clinical intervention to increase fruit and vegetable (FV) consumption in 171 low-FV-consuming young adults (67% female, aged 18–25). Participants were randomly assigned into a diet-as-usual control condition, an ecological momentary intervention (EMI) condition involving text message reminders to increase their FV consumption plus a voucher to purchase FV, or a fruit and vegetable intervention (FVI) condition in which participants were given two additional daily servings of fresh FV to consume on top of their normal diet. Self-report outcome measures were depressive symptoms and anxiety measured pre- and post-intervention, and daily negative and positive mood, vitality, flourishing, and flourishing behaviors (curiosity, creativity, motivation) assessed nightly using a smartphone survey. Vitamin C and carotenoids were measured from blood samples pre- and post-intervention, and psychological expectancies about the benefits of FV were measured post-intervention to test as mediators of psychological change. Only participants in the FVI condition showed improvements to their psychological well-being with increases in vitality, flourishing, and motivation across the 14-days relative to the other groups. No changes were found for depressive symptoms, anxiety, or mood. Intervention benefits were not mediated by vitamin C, carotenoids, or psychological expectancies. We conclude that providing young adults with high-quality FV, rather than reminding them to eat more FV (with a voucher to purchase FV), resulted in significant short-term improvements to their psychological well-being. These results provide initial proof-of-concept that giving young adults fresh fruit and vegetables to eat can have psychological benefits even over a brief period of time.
冠動脈疾患の病態生理や治療にパラダイムシフトが必要？というエディトリアル
要するに、LDLコレステロールリスクを喧伝しすぎ！
抗インスリン抵抗性と抗炎症作用を主眼に置くべき！
Saturated fat does not clog the arteries: coronary heart disease is a chronic inflammatory condition, the risk of which can be effectively reduced from healthy lifestyle interventions
Aseem Malhotra , et al.
British Journal of Sports Medicine,
http://bjsm.bmj.com/content/51/15/1111
従来のconceptual modelは誤り！という主張。ランドマークであるシステマティックレビュー・メタアナリシス(BMJ 2015;351:h3978.doi:10.1136/bmj.h3978)で、飽和脂肪酸と1）全原因死亡率、2）冠動脈性心疾患（CHD）、3）冠動脈性心疾患死亡率、4）虚血性卒中、5）2型糖尿病の成人性人での関連性認めず。
もう一つの報告(BMJ Open 2014;4:e004487.doi:10.1136/bmjopen-2013-004487 )は、CHDの二次予防で、脂肪減少、特に、飽和脂肪酸の減少に関して、心筋梗塞、心血管疾患、全原因死亡率の減少ベネフィットを認めなかった。
CHDを有する閉経後女性の血管造影研究(Am J Clin Nutr November 2004 vol. 80 no. 5 1175-1184)で、飽和脂肪酸摂取増加による動脈硬化進展減少がみられ、一方炭水化物やPUFA摂取増加では動脈硬化進展増加が示された。
動脈の血栓形成や心発作や卒中のリスク増加するであろうプラークの由来は細菌からで、食事摂取細菌だけでなく、口腔・腸管常在細菌由来の可能性がある。食事のみが主犯容疑者ではない！
Deposition and hydrolysis of serine dipeptide lipids of Bacteroidetes bacteria in human arteries: relationship to atherosclerosis
Reza Nemati et al.
Journal of LIPID RESEARCH, First Published on August 16, 2017, doi: 10.1194/jlr.M077792
ナトリウム摂取と高血圧の関係性にも疑念
https://www.sciencedaily.com/releases/2017/04/170425124909.htm
Low-sodium diet might not lower blood pressure2600名の男女、16年間の減塩で降圧効果見られず
Findings from large, 16-year study contradict sodium limits in Dietary Guidelines for Americans
Date:
April 25, 2017
Source:
Experimental Biology 2017
Summary:
A new study that followed more than 2,600 men and women for 16 years found that consuming less sodium wasn't associated with lower blood pressure. The study adds to growing evidence that current recommendations for limiting sodium intake may be misguided.
カリウム、カルシウム、マグネシウム摂取の影響などは考察されている。
グルテン・フリーの弊害！
- 2型糖尿病リスク増加 (http://newsroom.heart.org/news/low-gluten-diets-may-be-associated-with-higher-risk-of-type-2-diabetes)
- 健康食である全粒粉摂食を無くすことそのもの (Long term gluten consumption in adults without celiac disease and risk of coronary heart disease: prospective cohort study BMJ 2017; 357 doi: https://doi.org/10.1136/bmj.j1892 (Published 02 May 2017))
- 夾雑物 (The Unintended Consequences of a Gluten-free Diet Bulka, et al. Epidemiology: May 2017 - Volume 28 - Issue 3 - p e24–e25)：ヒ素、水銀など
健康有害リスクを金と手間をかけて励む変わった人たちが多い
身体活動に関して
＜大腿部痛のため動けないから・・・記載する気がしない＞
Physical Activity Guidelines for Americans : 週毎に中等度活動性150分以上
https://health.gov/paguidelines/guidelines/summary.aspx
MNTによる調査：週5日以上推奨分数到達運動で、死亡 12のうち1、心血管疾患 20のうち1を回避
https://www.medicalnewstoday.com/articles/319514.php
2日間食事して、1日絶食というモデル
総量的なカロリー摂取制限せず間欠性断食することにより体重減少効果と代謝的な改善効果有り
血糖低下とインスリン値低下、neuronal resistanceの改善効果、マウスレベルで視床下部内興奮性障害保護作用
Intermittent fasting dissociates beneficial effects of dietary restriction on glucose metabolism and neuronal resistance to injury from calorie intake
R. Michael Anson et al.
Proc Natl Acad Sci U S A. 2003 May 13; 100(10): 6216–6220.
全体量でなく特定の栄養素、特定のアミノ酸を制限することが鍵で、microbiomeの栄養的なmodulation、世代間を含む長期的影響も関与
Promoting health and longevity through diet: from model organisms to humans.
Cell. 2015 Mar 26;161(1):106-18. doi: 10.1016/j.cell.2015.02.020.
がんの話
ポリオウィルス
Cancer immunotherapy with recombinant poliovirus induces IFN-dominant activation of dendritic cells and tumor antigen–specific CTLs
Michael C. Brown, et al.
Science Translational Medicine 20 Sep 2017: Vol. 9, Issue 408, eaan4220DOI: 10.1126/scitranslmed.aan4220
例のビタミンC
NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Identification of Vitamin C and CAPE as natural products targeting “stemness”
Oncotarget. 2017; 8:20667-20678. https://doi.org/10.18632/oncotarget.15400
caspase-independent cell death (CICD)
Mitochondrial permeabilization engages NF-κB-dependent anti-tumour activity under caspase deficiency
Evangelos Giampazolias, et al.Nature Cell Biology 19, 1116–1129 (2017)doi:10.1038/ncb3596
アポトーシスは良いことだけとは限らない、悪さもする可能性
A fate worse than death: apoptosis as an oncogenic process
Gabriel Ichim & Stephen W. G. Tait
Nature Reviews Cancer 16, 539–548 (2016)
doi:10.1038/nrc.2016.58
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