Current clinical treatment of infection, the main etiological factor in the development of gastritis, gastric ulcers, and gastric carcinoma, requires a combination of at least two antibiotics and one proton pump inhibitor. However, such triple therapy suffers from progressively decreased therapeutic efficacy due to the drug resistance and undesired killing of the commensal bacteria due to poor selectivity. Here, we report the development of antimicrobial polypeptide-based monotherapy, which can specifically kill under acidic pH in the stomach while inducing minimal toxicity to commensal bacteria under physiological pH. Specifically, we designed a class of pH-sensitive, helix-coil conformation transitionable antimicrobial polypeptides (HCT-AMPs) (PGA)--(PHLG-MHH), bearing randomly distributed negatively charged glutamic acid and positively charged poly(γ-6--(methyldihexylammonium)hexyl-l-glutamate) (PHLG-MHH) residues. The HCT-AMPs showed unappreciable toxicity at physiological pH when they adopted random coiled conformation. Under acidic condition in the stomach, they transformed to the helical structure and exhibited potent antibacterial activity against , including clinically isolated drug-resistant strains. After oral gavage, the HCT-AMPs afforded comparable killing efficacy to the triple-therapy approach while inducing minimal toxicity against normal tissues and commensal bacteria, in comparison with the remarkable killing of commensal bacteria by 65% and 86% in the ileal contents and feces, respectively, following triple therapy. This strategy renders an effective approach to specifically target and kill in the stomach while not harming the commensal bacteria/normal tissues.

This study was carried out to test the hypothesis that Tongxinluo (TXL) as a Chinese herbal medicine enhances stability of vulnerable plaque dose dependently via lipid-lowering and anti-inflammation effects, similar to a high-dose simvastatin therapy. After abdominal aortic balloon injury, 75 rabbits were fed a 1% cholesterol diet for 10 wk and were then divided into five groups for 8-wk treatment: control group, low-dose TXL group, moderate-dose TXL group, high-dose TXL group, and high-dose simvastatin group. At the end of week 16, an adenovirus containing p53 was injected into the abdominal aortic plaques. Two weeks later, plaque rupture was induced by pharmacological triggering. The incidence of plaque rupture in all treatment groups (14.3%, 7.1%, 7.7%, and 7.1%) was significantly lower than that in control group (73.3%; P>0.01). TXL dose-dependently lowered serum lipid levels and inhibited systemic inflammation. Corrected acoustic intensity and fibrous cap thickness of the aortic plaques were significantly increased, whereas plaque area, plaque burden, vulnerable index, and expression of oxidized low-density lipoprotein (ox-LDL) receptor 1, matrix metalloproteinase 1 (MMP-1), MMP-3, tissue inhibitor of MMP 1, and NF-kappaB in plaques were markedly reduced in all treatment groups when compared with the control group. Similar to high-dose simvastatin group, high-dose TXL group exhibited a low serum level of low-density lipoprotein cholesterol and ox-LDL, a low expression level of systemic and local inflammatory factors and a low plaque vulnerability index, with no differences in the incidence of plaque rupture among all treatment groups. TXL dose-dependently enhances the stability of vulnerable plaques and prevents plaques from rupture. Simvastatin and TXL offer similar protection in terms of lipid-lowering, anti-inflammation, and antioxidation effects.

These recent findings emphasize the importance of intraplaque hemorrhage as a contributor of free cholesterol in plaques and point to its provocative role in lesion destabilization.

The tumour suppressor gene p53 codes for a transcription factor that activates genes involved in cell growth arrest (p21, GADD45) and apoptosis (e.g. Bax, Fas, Abstract This study aims to develop a new animal model of vulnerable plaques and investigate the potential mechanisms of exogenous p53-induced plaque instability. Forty rabbits underwent aortic balloon injury, were fed a 1% cholesterol diet for 10 weeks and then normal chow for 6 weeks. Rabbits were divided into Ad5-CMV.p53-treated group (n ϭ 16), Ad5-CMV.lac Z-treated group (n ϭ 16) and blank control group (n ϭ 8). Under the guidance of intravascular ultrasound, a 50-l suspension of adenovirus containing p53 or lac Z was injected into the largest plaque of the first two groups, respectively, and these rabbits received pharmacological triggering 2 weeks later. In 76.9% of rabbits with p53 transfection, plaque rupture was found, which was significantly (P Ͻ 0.05) higher than that in the Ad5-CMV.lac Z-treated plaques (23.1%), or blank controls plaques (0%

Real-time monitoring of mental stress biomarkers in sweat provides the possibility to evaluate mental status in a precise manner. In general, wearable sweat sensors suffer from inconvenient sweat collection, low levels of diagnostic biomarkers in sweat, sophisticated signal processing, and challenges with data visualization. To overcome these challenges, herein an integrated wearable sweat-sensing patch for continuous analysis of stress biomarkers (cortisol, Mg 2+ , and pH) at rest is demonstrated. The sweat sensing patch comprised a microfluidic chip, a highly sensitive sensing platform, an on-site signal processing circuitry (SPCs), and a smartphone installed with a homedeveloped display software. The sweat collection at rest is realized using a microfluidic chip without perspiration assistance. A ternary composite electrode is designed to obtain good conductivity, high surface area, and massive reactive sites, thereby yielding excellent electrochemical performances and high sensitivity to trace stress biomarkers. The on-site SPC has the function of signal transduction, conditioning, processing, and wireless transmission. The detection results can be displayed on a smartphone through the software. This work represents a significant scientific and technological advancement toward indexing mental stress status and can be used as an innovative tool for psychological diagnosis.

Peroxisome proliferator-activated receptor (PPAR)-␥ modulators, a class of antidiabetic drugs, have been associated with cardiovascular risks in type 2 diabetes in humans. The objective of this study was to explore possible cardiovascular risk biomarkers associated with PPAR-␥ in rodents that could provide an alert for risk to humans. Normal, myocardial infarction-induced heart failure (HF) or Zucker diabetic fatty (ZDF) rats were used. Rats (n ϭ 5-6) were treated with either vehicle or rosiglitazone (RGZ; 3 or 45 mg/kg/day p.o.) for 4 weeks. Biomarkers for potential cardiovascular risks were assessed, including 1) ultrasound for cardiac structure and function; 2) neuroendocrine and hormonal plasma biomarkers of cardiovascular risk; 3) pharmacogenomic profiling of cardiac and renal tissue by targeted tissue low-density gene array representing ion channels and transporters, and components of the renin-angiotensin-aldosterone system; and 4) immunohistochemistry for cardiac fibrosis, hypertrophy, and inflammation (macrophages and tumor necrosis factor-␣). HF was confirmed by increase in cardiac brain natriuretic peptide expression (p Ͻ 0.01) and echocardiography. Adequate exposure of RGZ was confirmed by pharmacokinetics (plasma drug levels) and the pharmacodynamic biomarker adiponectin. In normal or HF rats, RGZ had no negative effects on any of the biomarkers investigated. Similarly, RGZ had no significant effects on gene expression except for the increase in interleukin-6 mRNA expression in the heart and decrease in epithelial sodium channel ␤ in the kidney. In contrast, echocardiography showed improved cardiac structure and function after RGZ in ZDF rats. Taken together, this study suggests a limited predictive power of these preclinical models in respect to observed clinical adverse effects associated with RGZ.

Background and purpose:Previous studies demonstrated that intraplaque haemorrhage increased the contents of cholesterol and oxidants in atherosclerotic plaques. The present study was aimed to test the hypothesis that enhanced expression of haem oxygenase-1 (HO-1) may stabilize vulnerable plaques. Experimental approach: Intravascular ultrasound (IVUS) was performed to identify three similar abdominal aortic plaques in each of 58 fat-fed New Zealand rabbits after aortic balloon injury. With the guidance of IVUS, 50 mL autologous erythrocytes (RBC) or normal saline (NS) were injected from adventitia into two of the pre-selected plaques, respectively, whereas the third plaque served as a blank control. All rabbits were randomly divided into two groups, receiving intraperitoneal injection of haemin and saline respectively. Key results: Compared with NS or control plaques, RBC plaques had more macrophage infiltration and lipid content, thinner plaque fibrous cap, and higher expression of inflammatory factors and incidence of plaque rupture. RBC plaques in the haemin group had about a 50% lower incidence of plaque rupture than those in the control group. Conclusions and implications:Haem oxygenase-1 may eliminate haem or other oxidants, exert unexpected anti-oxidative and anti-inflammatory effects and serve as a promising approach to the direct inhibition of erythrocyte-induced plaque instability.British Journal of Pharmacology (2010) 160, 1484-1495; doi:10.1111/j.1476-5381.2010.00799.x Keywords: atherosclerosis; erythrocyte; vulnerable plaque; haem oxygenase-1; intraplaque hemorrhage Abbreviations: EEMA, external elastic membrane area; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; HDL, highdensity lipoprotein; HO-1, haem oxygenase-1; IVUS, intravascular ultrasound; LA, lumen area; LDL, lowdensity lipoprotein; MCP-1, monocyte chemoattractant protein-1; MDA, malondialdehyde; MMP, matrix metalloproteinase; NF-kB, nuclear transcription factor kB; NS, normal saline; PB, plaque burden; PBS, phosphate buffered saline; RBC, erythrocyte; SDS-PAGE, sodium dodecyl sulphate-polyacrylamide gel electrophoresis; SOD, superoxide dismutase; TC, total cholesterol; TG, triglycerides; TIMP-1, tissue inhibitor of metalloproteinase 1; VCAM-1, vascular cell adhesion molecule-1 IntroductionPathological studies have demonstrated that vulnerable plaques induced by intraplaque hemorrhage are frequently associated with increased density of microvessels (Burke et al., 1999;Kockx et al., 2003) and presence of erythrocyte membranes within the necrotic core (Kolodgie et al., 2003). The number of vasa vasorum was increased twofold and fourfold in vulnerable and ruptured plaques, respectively, as compared with stable plaques. The cholesterol content of the erythrocyte membrane was also found to contribute to the progression of atherosclerosis (Torkhovskaia et al., 1983;Miwa et al., 2003). Lipid contents derived from erythrocytes were associated with large necrotic cores of atherosclerotic plaques with intraplaque hemorrhage (Kolodgie et al., 200...

Biofortification is an effective way to increase micronutrient levels in food crops. This study investigated selenium enrichment as a biofortification strategy in soybean sprouts. Chitosan oligosaccharide selenium nanoparticles (COS-Se NPs) were synthesized and used in soybean sprout culture to study their effects on the sprouts. The results showed that the enrichment factor value (EF) was higher when the concentration was 2.36−9.43 mg•L −1 compared with other concentrations, and the enrichment factor (EF) reached a maximum value of 0.9782 at a COS-Se NP concentration of 4.72 mg•L −1 . Translocation factors (TF radicle-hypocotyl and TF hypocotyl-cotyledon ) reached maximum values of 0.7866 and 0.9723 at 25.15 mg•L −1 and 15.09 mg•L −1 , respectively, suggesting the relationship between enrichment of nanoselenium and concentration was not proportional. Most of the organic selenium was present mainly in the protein fraction, and albumin and glutelin were the main protein-bound seleniums. The contents of protein and biomacromolecule selenium reached higher values at a COS-Se NP concentration of 2.36−9.43 mg•L −1 . Furthermore, the COS-Se NPs at 2.36−9.43 mg•L −1 concentration significantly affected the nutrient parameters in soybean sprouts. Different concentrations of COS-Se NPs were observed to have different effects on the mineral element content of the bean sprouts. In vitro digestion and dialysis experiments showed that the bioavailability of K, Mg, P, and Se was at a high level, while that of Fe and Ca was at a low level in soybean sprouts. Overall, no significant impact on the bioaccessibility of most elements was observed during the enrichment process compared to the control group. This work shows that the selenium enrichment strategy can be a potential soybean sprout production method and help solve the problem of nutritional deficiencies with selenium and reduce malnutrition.