Vascular endothelial growth factor-modified macrophages accelerate reendothelialization and attenuate neointima formation after arterial injury in atherosclerosis-prone mice.

Vascular endothelial growth factor (VEGF) is a promising molecule for cardiovascular diseases therapy. But lack of a targeted delivery system limits its translation into clinical application. This study aimed to develop stably overexpressing VEGF macrophages for targeted VEGF delivery to injured arteries and determine their potential for repairing of the damaged endothelium. Wire-induced carotid artery injury model was established in atherosclerosis-prone mice. It was observed that the VEGF-modified macrophages were recruited to the site of vascular injury and incorporated into new endothelium formation. VEGF-modified macrophages therapy accelerated reendothelialization and attenuated neointima formation. The VEGF protein level in tissues of injured arteries treated with VEGF-modified macrophages was increased. The upregulated C-C chemokine receptor type 5 (CCR5) and unaltered CCR2 protein levels were verified in VEGF-modified macrophages in vitro. Moreover, enhanced nitric oxide (NO) production in the culture medium of VEGF-modified macrophages was demonstrated. Our results indicated that VEGF-modified macrophages acted as vectors of VEGF targeting injured arteries, promoting the repairing directly by incorporating into new endothelium formation and indirectly by secreting sustainable VEGF and producing NO locally. This study represents a novel therapeutic application of targeted cell therapy with VEGF-modified macrophages for cardiovascular diseases.

Puerarin Attenuates Insulin Resistance by Inhibiting Endoplasmic Reticulum Stress and Suppresses Inflammation by Modulating the JNK and IKKß/NF-κB Pathways in Epididymal White Adipose Tissue of Mice on a High-Fat Diet.

SCOPE: Obesity is associated with insulin resistance (IR), which is characterized by endoplasmic reticulum (ER) stress in multiple organs. ER stress in adipose tissue causes metabolic disturbances and activates inflammatory signaling pathways. Puerarin, an isoflavone extracted from Pueraria lobata, exhibits antioxidant, anti-inflammatory, and antidiabetic effects. This study explores the potential mechanisms underlying puerarin's role in mitigating insulin resistance in high-fat diet (HFD)-induced obese mice. METHODS AND RESULTS: In this study, insulin resistant in mice is induced by a high-fat diet, followed by treatment with puerarin. The results demonstrate that puerarin effectively attenuates insulin resistance, including weight loss, improvement of glucose tolerance and insulin sensitivity, and activation of insulin signaling pathway. Additionally, puerarin administration suppresses ER stress by down-regulation of ATF6, ATF4, CHOP, GRP78 expressions in epididymal white adipose tissue (eWAT), along with decreased phosphorylation IRE1α, PERK, and eIF2α. Furthermore, puerarin exerts anti-inflammatory effects by inhibiting JNK and IKKß/NF-κB pathways, leading to reduction of TNF-α and IL-6. CONCLUSION: These findings suggest that puerarin mitigates insulin resistance by inhibiting ER stress and suppressing inflammation through the JNK and IKKß/NF-κB pathways. This highlights the promising clinical application of puerarin in the treatment of insulin resistance.

Ultrafast inactivation of SARS-CoV-2 with 266 nm lasers.

Disinfection eliminates pathogenic microorganisms and ensures a biosafe environment for human beings. The rapid spread of COVID-19 is challenging traditional disinfection methods in terms of reducing harmful side effects and conducting faster processes. Spraying large-scale chemical disinfectants is harmful to individuals and the environment, while UV lamp and light-emitting diode (LED) disinfection still requires a long exposure time due to the low irradiance and highly divergent beam characteristics. Given that a laser maintains a high irradiance over a long distance, we studied the effectiveness of lasers as a new disinfection method, and the results show the capability for ultrafast inactivation of SARS-CoV-2 virus with a 266 nm laser. This work confirms UV lasers as a good candidate for disinfection.

A theoretical study on the formation and oxidation mechanism of hydroxyalkylsulfonate in the atmospheric aqueous phase.

Hydroxymethanesulfonate (HMS) is an important organosulfur compound in the atmosphere. In this work, we studied the formation mechanism of HMS via the reaction of formaldehyde with dissolved SO2 using the quantum chemistry calculations. The results show that the barrier (9.7 kcal mol-1) of the HCHO + HSO3 - reaction is higher than that (1.6 kcal mol-1) of the HCHO + SO3 2- reaction, indicating that the HCHO + SO3 2- reaction is easier to occur. For comparison, the reaction of acetaldehyde with dissolved SO2 also was discussed. The barriers for the CH3CHO + HSO3 - reaction and CH3CHO + SO3 2- reaction are 16.6 kcal mol-1, 2.5 kcal mol-1, respectively. This result suggests that the reactivity of HCHO with dissolved SO2 is higher than that of CH3CHO. The further oxidation of CH2(OH)SO3 - and CH3CH(OH)SO3 - by an OH radical and O2 shows that the SO5˙- radical can be produced.

Variations in carotid artery intima-media thickness during the cardiac cycle in children.

BACKGROUND: There is paucity of research looking at variations in carotid artery intima-media thickness (CIMT) during the cardiac cycle in children. The aim of this study was to ascertain variations, if any, in CIMT during the cardiac cycle in a population of high-risk children. METHODS: Forty-nine children aged 6 to 19 years with dyslipidemia and other atherosclerosis-promoting risk factors underwent a carotid ultrasound. CIMT was measured using commercially available, semiautomated edge-detection software. The region of interest was the far wall of the common carotid artery. CIMT was measured at various points during the cardiac cycle using the electrocardiogram (EKG) as a reference. CIMT measurements two frames before, during, and after the QRS complex (end diastole) were analyzed separately (designated as "QRS CIMT") from the other CIMT measurements (designated as "non-QRS CIMT"). Demographics, heart rate, blood pressure, anthropometric measures, lumen diameter, family history, and presence of other atherosclerosis-promoting risk factors were documented. RESULTS: "QRS CIMT" was significantly thicker than "non-QRS CIMT" (P = .01), with the age group 10 to 14 years showing the most significant variation between "QRS CIMT" and "non-QRS CIMT" (P = .005). CIMT values between right and left carotid arteries differed by 2.5%. Age, systolic blood pressure, and blood glucose were significant predictors of mean CIMT by simple linear regression; systolic blood pressure was the only significant predictor of mean CIMT by stepwise multiple linear regression analysis. CONCLUSION: CIMT measurements vary during the cardiac cycle in children. It is thicker during the QRS complex on EKG. Carotid ultrasound should be performed with an EKG, and CIMT should be measured at the same point on the EKG to overcome this variation. Furthermore, we recommend that CIMT be measured at the R-wave on EKG because this is an easily discernible point in the cardiac cycle.

"Vascular age" is advanced in children with atherosclerosis-promoting risk factors.

BACKGROUND: Obesity and familial dyslipidemia in children are associated with accelerated atherosclerosis by pathological examination. We sought to determine whether these children had increased carotid artery intima-media thickness (CIMT), a measure of subclinical atherosclerosis similar to 45-year-old adults. Adult CIMT percentile tables were used for comparison because normative CIMT data for children are limited. METHODS AND RESULTS: Seventy children, ages 6 to 19 years, with obesity- and atherosclerosis-promoting risk factors such as dyslipidemia, hypertension, insulin resistance, and tobacco smoke exposure, or with familial dyslipidemia, underwent carotid artery ultrasound. Advanced "vascular age" (VA) was defined as having maximum CIMT that was > or =25th percentile for race- and sex-matched 45-year-old adults. Mean age was 13.0+/-3.3 years. Forty (57%) of 70 children had body mass index > or =95th percentile for age and sex. Maximum CIMT for obese children was 0.53+/-0.05 mm and for familial dyslipidemic children was 0.52+/-0.04 mm. Advanced VA was seen in 30 (75%) of obese children and 22 (73%) of familial dyslipidemic children. Thirty (75%) of obese children had >3 mutable atherosclerosis-promoting risk factors; these children had a nonsignificantly higher maximum CIMT compared with obese children with < or =3 risk factors (0.54+/-0.06 mm versus 0.52+/-0.03 mm, P=0.07). Obese children with high fasting triglyceride levels were more likely to have advanced VA. CONCLUSIONS: VA is advanced and comparable in obese children with atherosclerosis-promoting risk factors and in children with familial dyslipidemia. Advanced VA is prevalent in obese children with high fasting triglyceride levels.