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1.
Free Radic Biol Med ; 190: 216-225, 2022 09.
Article in English | MEDLINE | ID: mdl-35970250

ABSTRACT

Iron accumulates in the brain with age and catalyzes free radical damage to neurons, thus playing a pathogenic role in Alzheimer's disease (AD). To decrease the incidence of AD, we synthesized the iron-affinitive peptide 5YHEDA to scavenge the excess iron in the senile brain. However, the blood-brain barrier (BBB) blocks the entrance of macromolecules into the brain, thus decreasing the therapeutic effects. To facilitate the entrance of the 5YHEDA peptide, we linked the low-density lipoprotein receptor (LDLR)-binding segment of ApoB-100 to 5YHEDA (named "bs-YHEDA"). The results of intravenous injections of bs-5YHEDA into senescent mice demonstrated that bs-YHEDA entered the brain, increased ferriportin levels, reduced iron and free radical levels, decreased the consequences of neuronal necrosis and ameliorated cognitive disfunction without kidney or liver damage. bs-5YHEDA is a safe iron and free radical remover that potentially alleviates aging and Alzheimer's disease.


Subject(s)
Alzheimer Disease , Aging , Alzheimer Disease/drug therapy , Alzheimer Disease/pathology , Amyloid beta-Peptides/metabolism , Animals , Blood-Brain Barrier/metabolism , Brain/metabolism , Free Radicals , Intelligence , Iron/therapeutic use , Mice , Peptides
2.
J Biomed Nanotechnol ; 10(7): 1194-204, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24804540

ABSTRACT

Bioabsorbable drug-eluting stents (BDES) offer multiple advantages over a permanent bare metal stent (BMS) for coronary artery disease (CAD). However, current BDES remains two major issues: inferior radial strength and biocompatibility. PowerStent Absorb BDES, fabricated by co-formulating amorphous calcium phosphate (ACP) nanoparticles with poly-L-lactic acid (PLLA/ACP, 98/2, w/w) and 2% Paclitaxel (PAX, w/w) was designed to address these issues. Two cohorts of 6 miniature pigs were each implanted with PLLA/PAX (control, 2% PAX, w/w) or PowerStent Absorb BDES. After 1 month in-vivo study, histological analyses showed significantly reduced restenosis in the PowerStent Absorb BDES cohort relative to the control cohort (44.49 +/- 410.49% vs. 64.47 +/- 16.2%, p < 0.05). Stent recoil (21.57 +/- 5.36% vs. 33.81 +/- 11.49, P < 0.05) and inflammation (3.01 +/- 0.62 vs. 4.07 +/- 0.86, P < 0.01) were also obviously decreased. From in-vitro studies, PLLA/ACP/PAX stent tube maintained significantly greater radial strength than control group during 6 months in-vitro degradation (PLLA/ACP/PAX vs. PLLA/PAX: before hydrolysis: 82.4 +/- 1.9 N vs.74.8 +/- 3.8 N; 6 weeks: 73.9 +/- 1.8 N vs. 68.0 +/- 5.3 N; 3 months: 73.5 +/- 3.4 N vs.67.2 +/- 3.8 N; 6 months: 56.3 +/- 8.1 N vs. 57.5 +/- 4.9 N). Moreover, ACP facilitated the hydrolytic degradation of PLLA compared with control one (62.6% vs. 49.8%), meanwhile, it also increased the crystallinity of PLLA (58.4% vs. 50.7%) at 6 months. From SEM observations, ACP created nanometer pores that enlarge gradually to a micrometer scale as degradation proceeds. The changes of the porosity may result in greatly promoting re-endothelialization.


Subject(s)
Biocompatible Materials/chemistry , Calcium Phosphates/chemistry , Coronary Artery Disease/physiopathology , Coronary Artery Disease/therapy , Drug-Eluting Stents , Lactic Acid/chemistry , Nanoparticles/chemistry , Polymers/chemistry , Animals , Calorimetry, Differential Scanning , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/pathology , Coronary Vessels/drug effects , Coronary Vessels/pathology , Coronary Vessels/physiopathology , Female , Male , Materials Testing , Nanoparticles/ultrastructure , Paclitaxel/pharmacology , Polyesters , Radiography , Swine , Swine, Miniature
3.
J Appl Physiol (1985) ; 107(2): 488-93, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19541740

ABSTRACT

Body mass index (BMI) is often used as a surrogate estimate of percent body fat in epidemiological studies. This study tested the hypothesis that BMI is representative of body fatness independent of age, sex, ethnicity, and geographic location in prepubertal children. The study sample included a total of 605 prepubertal children (275 girls and 330 boys) of which 247 were Chinese from Jinan, Shandong, Mainland China, and 358 children were from various ethnic backgrounds in New York City (NYC): 121 Caucasians, 94 African Americans, and 143 Asians (Chinese and Korean). In this cross-sectional study, dual energy X-ray absorptiometry was used to quantify total body fat (TBF) and percent body fat (PBF). Prepubertal status was assessed by the criteria of Tanner. Multiple regression models were developed with TBF and PBF as the dependent variables and BMI, age, sex, and ethnicity as independent variables. Multiple regression analysis showed that BMI alone explained 85% and 69% of between-subject variance for TBF and PBF, respectively. Sex was a significant contributor to the models (P<0.001) with girls having higher TBF and PBF than boys. Ethnicity and geographic location were significant contributors to the model (P<0.0001) with Asians (Jinan and NYC Asians) having higher PBF than all non-Asian groups (P<0.0001), and Jinan Asians having higher TBF and PBF than NYC-Asians. Among prepubertal children, for the same BMI, Asians have significantly higher PBF compared with African Americans and Caucasians. Caution is warranted when applying BMI across sex and ethnic prepubertal groups.


Subject(s)
Adiposity/ethnology , Asian People/statistics & numerical data , Black or African American/statistics & numerical data , Body Mass Index , Obesity/ethnology , Sexual Maturation , White People/statistics & numerical data , Absorptiometry, Photon , Child , Child, Preschool , China/ethnology , Cross-Sectional Studies , Female , Humans , Korea/ethnology , Male , New York City/epidemiology , Obesity/diagnosis , Obesity/physiopathology , Predictive Value of Tests , Regression Analysis , Residence Characteristics , Sex Factors
4.
Obesity (Silver Spring) ; 15(4): 1004-11, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17426336

ABSTRACT

OBJECTIVE: The aims of this study were to investigate the body fat distribution pattern in prepubertal Chinese children and to investigate the relationship between central fat distribution and specific biomarkers of cardiovascular disease. RESEARCH METHODS AND PROCEDURES: The study was conducted in an urban Mainland Chinese (Jinan, Shandong) sample of children using a cross-sectional design. Pubertal status was determined by Tanner criteria. Measurements included weight, height, waist circumference, DXA measures of total body fat and trunk fat; fasting serum measures of glucose, insulin, triglyceride, cholesterol, high-density lipoprotein-cholesterol; and systolic and diastolic blood pressure. Multiple regression models were developed with the biomarkers of cardiovascular risk factor as the dependent variables, and adjustments were made for significant covariates, including sex, age, height, weight, waist circumference, total body fat, trunk fat, and interactions. RESULTS: A total of 247 healthy prepubertal subjects were studied. After co-varying for age, weight, height, and extremity fat (the sum of arm fat and leg fat), girls had greater trunk fat than boys (p<0.0001, R2 for model=0.95). Insulin and triglyceride were positively related to central fat measured by DXA-trunk fat (p<0.05) but not related to the waist circumference. In the blood pressure model, waist circumference was a significant predictor of both systolic blood pressure and diastolic blood pressure, while DXA-trunk fat was associated with diastolic blood pressure only. Significant interactions between sex and trunk fat, and sex and total fat, were found in relation to diastolic blood pressure. DISCUSSION: In prepubertal Chinese children, greater trunk fat was significantly associated with higher insulin and triglyceride in boys and girls and was associated with higher diastolic blood pressure in boys only.


Subject(s)
Adipose Tissue/pathology , Insulin/blood , Obesity/diagnosis , Triglycerides/blood , Age Factors , Biomarkers , Blood Pressure , Child , Child, Preschool , China , Female , Humans , Hypertension , Male , Obesity/blood , Regression Analysis
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