Synthesis and antitumor activity evaluation of coumarin Mannich base derivatives.

Twenty-one new coumarin Mannich base derivatives (11a-u) were synthesized, which exhibited antiproliferation activities in HepG2 (liver cancer), A549 (lung cancer), MCF-7 (breast cancer), and HT-29 (colon cancer). Most of the target compounds showed the most potent activity against HepG2 cells compared with other cancer cells, compound 11g showed the strongest antiproliferative activity (2.10 µM) against HepG2, even superior to the positive control drug 5-FU(5.49 µM). The nitric oxide (NO) release of all compounds in HepG2 cells was determined, of which compound 11g showed high levels of NO release (10.8 µM). Notably, the solubility of compound 11g increased 13-fold compared with the lead 8. The preliminary cytotoxicity studies suggest that 11g had little effect on LO2 cells(normal liver cells, >50 µM). The effect of compound 11g on the apoptosis of HepG2 cells was also studied, and the results showed that the induction effect of compound 11g on apoptosis is a concentration-dependent manner. Our results indicate that compound 11g might be a promising lead for further studies.

Handheld photoacoustic imaging of indocyanine green clearance for real-time quantitative evaluation of liver reserve function.

Preoperative assessment of liver function reserve (LFR) is essential for determining the extent of liver resection and predicting the prognosis of patients with liver disease. In this paper, we present a real-time, handheld photoacoustic imaging (PAI) system-based noninvasive approach for rapid LFR assessment. A linear-array ultrasound transducer was sealed in a housing filled with water; its front end was covered with a plastic wrap. This PAI system was first implemented on phantoms to confirm that the photoacoustic (PA) intensity of indocyanine green (ICG) in blood reflects the concentration of ICG in blood. In vivo studies on normal rabbits and rabbits with liver fibrosis were carried out by recording the dynamic PA signal of ICG in their jugular veins. By analyzing the PA intensity-time curve, a clear difference was identified in the pharmacokinetic behavior of ICG between the two groups. In normal rabbits, the mean ICG clearance rate obtained by PAI at 15 min after administration (PAI-R15) was below 21.6%, whereas in rabbits with liver fibrosis, PAI-R15 exceeded 62.0% because of poor liver metabolism. The effectiveness of the proposed method was further validated by the conventional ICG clearance test and pathological examination. Our findings suggest that PAI is a rapid, noninvasive, and convenient method for LFR assessment and has immense potential for assisting clinicians in diagnosing and managing patients with liver disease.

Multifunctional Electrospinning Polyhydroxyalkanoate Fibrous Scaffolds with Antibacterial and Angiogenesis Effects for Accelerating Wound Healing.

To treat large-scale wounds or chronic ulcers, it is highly desirable to develop multifunctional wound dressings that integrate antibacterial and angiogenic properties. While many biomaterials have been fabricated as wound dressings for skin regeneration, few reports have addressed the issue of complete skin regeneration due to the lack of vasculature and hair follicles. Herein, an instructive poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB) fibrous wound dressing that integrates an antibacterial ciprofloxacin (CIP) and pro-angiogenic dimethyloxalylglycine (DMOG) is successfully prepared via electrospinning. The resultant dressings exhibit suitable flexibility with tensile strength and elongation at break up to 4.08 ± 0.18 MPa and 354.8 ± 18.4%, respectively. The in vitro results revealed that the groups of P34HB/CIP/DMOG dressings presented excellent biocompatibility on cell proliferation and significantly promote the spread and migration of L929 cells in both transwell and scratch assays. Capillary-like tube formation is also significantly enhanced in the P34HB/CIP/DMOG group dressings. Additionally, dressings from the P34HB/CIP and P34HB/CIP/DMOG groups show a broad spectrum of antimicrobial action against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. In vivo studies further demonstrated that the prepared dressings in the P34HB/CIP/DMOG group not only improved wound closure, increased re-epithelialization and collagen formation, as well as reduced inflammatory response but also increased angiogenesis and remodeling, resulting in complete skin regeneration and hair follicles. Collectively, this work provides a simple but efficient approach for the design of a versatile wound dressing with the potential to have a synergistic effect on the rapid stimulation of angiogenesis as well as antibacterial activity in full-thickness skin repair.

[Photoacoustic imaging study on spatial structure of microvessels around acupoints in mice with acute myocardial ischemia].

OBJECTIVE: To observe the changes of microvascular structure of acupoints caused by myocardial ischemia, so as to explore the application of photoacoustic imaging technology in the research of acupoint sensitization. METHODS: Twelve BALB/c mice were randomly divided into normal, sham operation and acute myocardial ischemia (AMI) model groups, with 4 mice in each group. AMI model was established by ligating the left anterior descending coronary artery. Electrocardiogram (ECG) was recorded by physiological signal acquisition system at 12 h and on the 14th day after modeling, and serum cardiac troponin T (cTnT) and creatine kinase isoenzyme MB (CK-MB) levels were detected by enzyme-linked immunosorbent assay. The microvascular structure changes of acupoints "Feishu"(BL13), "Jueyinshu"(BL14), "Quze"(PC3) and "Chize"(LU5) were observed by photoacoustic imaging technology, and distance (DM), inflection count metric (ICM), sum of angle metric(SOAM)and microvessel density (MVD) were calculated by microvascular quantification algorithm. RESULTS: Compared with the normal and sham operation groups, the ST segment of ECG was obviously elevated, serum cTnT and CK-MB were significantly increased in AMI model group at 12 h and on the 14th day after AMI (P<0.01). The ICM of BL14 in AMI model group was significantly decreased on the 14th day than that on the 7th day after AMI. Compared with the normal group, the ICM of BL14 was significantly increased in AMI model group on the 7th day after AMI(P<0.05). There were no significant changes in DM, ICM, SOAM and MVD at other acupoints on the 7th and 14th day (P>0.05) among the three groups. CONCLUSION: The change of ICM may be one of the characteristics of acupoint sensitization and photoacoustic imaging technology can be used to study the structure of acupoint microvessels.

[Steady-state spectroscopy on complementary tissue structural and functional information extraction].

Steady-state spectroscopy is prevailing for complementary tissue structural and functional information extraction The goal of the present study is to experimentally validate the merit of this technique for optical properties and intrinsic fluorescence extraction from tissue mimicking phantoms. Phantom studies were carried out in which HbO2 was used as absorber, polystyrene sphere was used as scatterer, and stilbene was used for fluorescence emission Two sets of phantoms corresponding to two absorption levels and one scattering level were made, and 4 fluorophore concentrations were titrated in each set. The results indicate that both optical properties and intrinsic fluorescence can be extracted with high accuracy, implying that it's feasible to extract complementary structural and functional information with steady-state spectroscopy.