Converting One-Face α‑Helix Mimetics into Amphiphilic α‑Helix Mimetics as Potent Inhibitors of Protein–Protein Interactions

Many biologically active α-helical peptides adopt amphiphilic helical structures that contain hydrophobic residues on one side and hydrophilic residues on the other side. Therefore, α-helix mimetics capable of mimicking such amphiphilic helical peptides should possess higher binding affinity and specificity to target proteins. Here we describe an efficient method for generating amphiphilic α-helix mimetics. One-face α-helix mimetics having hydrophobic side chains on one side was readily converted into amphiphilic α-helix mimetics by introducing appropriate charged residues on the opposite side. We also demonstrate that such two-face amphiphilic α-helix mimetics indeed show remarkably improved binding affinity to a target protein, compared to one-face hydrophobic α-helix mimetics. We believe that generating a large combinatorial library of these amphiphilic α-helix mimetics can be valuable for rapid discovery of highly potent and specific modulators of protein-protein interactions

Baseline demographic and clinical characteristics of literature cases.

<p>Baseline demographic and clinical characteristics of literature cases.</p

Morus tiliaefolia Makino

原著和名: ケグハ科名: クワ科 = Moraceae採集地: 島根県 隠岐 島後 (隠岐 島後)採集日: 1976/5/9採集者: 萩庭丈壽整理番号: JH007815国立科学博物館整理番号: TNS-VS-95781

The relationship between drinking alcohol and esophageal, gastric or colorectal cancer: A nationwide population-based cohort study of South Korea

<div><p>Background</p><p>Epidemiologic findings of low-volume alcohol consumption in relation to gastrointestinal cancers including gastric cancer are inconsistent.</p><p>Methods</p><p>The association between alcohol intake and esophageal, gastric and colorectal cancer risk was examined in a population-based prospective cohort of 23,323,730 adults in Korea who had undergone a biennial evaluation provided by the National Health Insurance Corporation between the years 2009 and 2012. After median 5.4 years of follow-up, 9,171 esophageal, 135,382 gastric and 154,970 colorectal cancer cases were identified. Cox regression models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (95% CI).</p><p>Results</p><p>Light drinking as well as moderate to heavy alcohol consumption significantly increased the risks of the three gastrointestinal cancers (HR 1.51; 95% CI, 1.43–1.60; HR 1.08; 95% CI, 1.06–1.09; HR 1.12; 95% CI, 1.11–1.14) compared with non-drinkers after adjusting for age, sex, smoking, exercise, income, body mass index, and diabetes. The synergistically increased cancer risk between excessive amount of alcohol consumption and currently smoking or underweight individuals was observed only in the esophageal cancers.</p><p>Conclusions</p><p>Light drinking including even one alcoholic drink a day is associated with increased risks of esophageal, gastric and colorectal cancer.</p></div

Included studies and outcomes of interest.

<p>Included studies and outcomes of interest.</p

The relationship between drinking alcohol and esophageal, gastric or colorectal cancer: A nationwide population-based cohort study of South Korea - Fig 2

<p>Esophagus, stomach and colorectal cancer risks based on the combined effect of the amount of alcohol consumption and smoking status (A) Esophageal cancer, (B) Gastric cancer, (C) colorectal cancer.</p

Subgroup analysis of the risk of esophageal, stomach and colorectal cancers according to alcohol consumption.

<p>Subgroup analysis of the risk of esophageal, stomach and colorectal cancers according to alcohol consumption.</p

Flowchart showing the enrolment process for the study cohort.

<p>NHIC, National Health Insurance Corporation.</p

Effects of Statin Therapy on Clinical Outcomes of Survivors of Acute Myocardial Infarction with Severe Systolic Heart Failure

<div><p>Objective</p><p>Large randomized trials have failed to show a beneficial effect of statin treatment in chronic HF. The investigators tried to evaluate the long-term effects of statin therapy in patients with new onset heart failure (HF) following acute myocardial infarction (AMI).</p><p>Methods</p><p>Between January 2008 and December 2011, a total of 13,616 AMI patients were enrolled in the Korea Acute Myocardial Infarction Registry (KAMIR) which was a prospective, multi-center, nationwide, web-based database of AMI in Korea. From this database, we studied 1,055 patients with AMI who had newly developed severe acute HF [left ventricular ejection fraction ≤ 40%] and were discharged alive. The patients were divided into two groups, a statin group (n = 756) and a no-statin group (n = 299). We investigated the one-year major adverse cardiovascular events (MACEs), including all-cause mortality, MI, and any revascularization of each group. We then performed a propensity-score matched analysis.</p><p>Results</p><p>In the original cohort, one-year MACEs were similar between the two groups (16.5% vs. 14.7% in the statin or no-statin groups; <i>p</i> = 0.47). Propensity-score matching yielded 256 pairs, and in that population we observed comparable results in terms of MACEs (18.0% vs. 12.5% in the statin or no-statin groups, <i>p</i> = 0.11) and mortality (5.1% vs. 3.5% in the statin or no-statin groups, <i>p</i> = 0.51). Cox-regression analysis revealed that statin therapy was not an independent predictor for occurrence of a MACE [Hazard ratio (HR) 1.11, 95% CI 0.79–1.57, <i>p</i> = 0.54] or all-cause mortality (HR 1.42, 95% CI 0.75–2.70, <i>p</i> = 0.28).</p><p>Conclusion</p><p>Statin therapy was not associated with a reduction in the long-term occurrence of MACEs or mortality in survivors of AMI with severe acute HF in this retrospective cohort study.</p></div

The effect of change in the amount of alcohol consumption and the risk of developing esophageal, stomach and colorectal cancer.

<p>The effect of change in the amount of alcohol consumption and the risk of developing esophageal, stomach and colorectal cancer.</p