Silicone elastomer gel impregnated with 20(S)-protopanaxadiol-loaded nanostructured lipid carriers for ordered diabetic ulcer recovery.

Inefficient diabetic ulcer healing and scar formation remain a challenge worldwide, owing to a series of disordered and dynamic biological events that occur during the process of healing. A functional wound dressing that is capable of promoting ordered diabetic wound recovery is eagerly anticipated. In this study, we designed a silicone elastomer with embedded 20(S)-protopanaxadiol-loaded nanostructured lipid carriers (PPD-NS) to achieve ordered recovery in scarless diabetic ulcer healing. The nanostructured lipid carriers were prepared through an emulsion evaporation-solidification method and then incorporated into a network of silicone elastomer to form a unique nanostructured lipid carrier-enriched gel formulation. Interestingly, the PPD-NS showed excellent in vitro anti-inflammatory and proangiogenic activity. Moreover, in diabetic mice with full-thickness skin excision wound, treatment with PPD-NS significantly promoted in vivo scarless wound healing through suppressing inflammatory infiltration in the inflammatory phase, promoting angiogenesis during the proliferation phase, and regulating collagen deposition in the remodeling phase. Hence, this study demonstrates that the developed PPD-NS could facilitate ordered diabetic wound recovery via multifunctional improvement during different wound-healing phases. This novel approach could be promising for scarless diabetic wound healing.

[Preliminary study on pH-sensitive lipid bilayer-coated mesoporous silica nanoparticles as a novel drug carrier for antitumor drug].

This study plans to prepare lipid bilayer-coated mesoporous silica nanoparticles (LMSNs) which are pH sensitive with core-shell structure to improve the tumor cell lethality of antitumor drug. The lipid coated mesoporous silica nanoparticles loaded with irinotecan (CPT-11) (CPT-11-LMSNs) were prepared by hot water-film hydration method, and the characterized its morphology, particle size and release in vitro. Meanwhile, the intracellular uptake and cell toxicity of CPT-11-LMSNs and intracellular accumulation of CPT-11 were evaluated on human breast carcinoma cell line (MCF-7). The results indicated that the mean diameter of the spherical LMSNs was (120.27 +/- 5.91) nm. The slow release in simulated normal physiological conditions and a rapid release under simulated intracellular condition demonstrated the pH sensitivity of CPT-11-MSNs in vitro. Moreover, the CPT-11-LMSN could improve the intracellular CPT-11 cumulant 2.1 times and reduce half maximal inhibitory concentration (IC50) values of CPT-11 1.4 times compared with CPT-11-MSNs, demonstrating a stronger cell lethality.

[Preparation and characterization of irinotecan hydrochloride loaded PEO-PPO-PEO micelles and its mechanism of decreasing drug intestinal toxicity].

In this work, we developed PEO-PPO-PEO micelles loaded with irinotecan hydrochloride (CPT-11) using breast cancer resistance protein (BCRP) inhibitory material PEO20-PPO70-PEO20, and studied its mechanism of decreasing CPT-11 induced delayed diarrhea and intestinal toxicity. BCRP-overexpressing MDCKII (MDCKII/BCRP) cells were used to evaluate the effect of PEO20-PPO70-PEO20 and PEO-PPO-PEO micelles on transmembrane transport of CPT-11 in vitro. The biliary excretion, delayed diarrhea and intestinal damage of CPT-11 loaded PEO-PPO-PEO micelles of rats were investigated. The results showed that the obtained micelles could decrease the biliary excretion of CPT-11, ameliorate delayed diarrhea and intestinal toxicity of rats through inhibiting BCRP-mediated CPT-11 efflux. PEO-PPO-PEO micelles were promising carriers to reduce intestinal toxicity of CPTs.

Exploring the Value of Radiomics Features Based on B-Mode and Contrast-Enhanced Ultrasound in Discriminating the Nature of Thyroid Nodules.

BACKGROUND: With the improvement of ultrasound imaging resolution and the application of various new technologies, the detection rate of thyroid nodules has increased greatly in recent years. However, there are still challenges in accurately diagnosing the nature of thyroid nodules. This study aimed to evaluate the clinical application value of the radiomics features extracted from B-mode ultrasound (B-US) images combined with contrast-enhanced ultrasound (CEUS) images in the differentiation of benign and malignant thyroid nodules by comparing the diagnostic performance of four logistic models. METHODS: We retrospectively collected and ultimately included B-US images and CEUS images of 123 nodules from 123 patients, and then extracted the corresponding radiomics features from these images respectively. Meanwhile, a senior radiologist combined the thyroid imaging reporting and data system (TI-RADS) and the enhancement pattern of the ultrasonography to make a graded diagnosis of the malignancy of these nodules. Next, based on these radiomics features and grades, logistic regression was used to help build the models (B-US radiomics model, CEUS radiomics model, B-US+CEUS radiomics model, and TI-RADS+CEUS model). Finally, the study assessed the diagnostic performance of these radiomics features with a comparison of the area under the curve (AUC) of the receiver operating characteristic curve of four logistic models for predicting the benignity or malignancy of thyroid nodules. RESULTS: The AUC in the differential diagnosis of the nature of thyroid nodules was 0.791 for the B-US radiomics model, 0.766 for the CEUS radiomics model, 0.861 for the B-US+CEUS radiomics model, and 0.785 for the TI-RADS+CEUS model. Compared to the TI-RADS+CEUS model, there was no statistical significance observed in AUC between the B-US radiomics model, CEUS radiomics model, B-US+CEUS radiomics model, and TI-RADS+CEUS model (P>0.05). However, a significant difference was observed between the single B-US radiomics model or CEUS radiomics model and B-US+CEUS radiomics model (P<0.05). CONCLUSION: In our study, the B-US radiomics model, CEUS radiomics model, and B-US+CEUS radiomics model demonstrated similar performance with the TI-RADS+CEUS model of senior radiologists in diagnosing the benignity or malignancy of thyroid nodules, while the B-US+CEUS radiomics model showed better diagnostic performance than single B-US radiomics model or CEUS radiomics model. It was proved that B-US radiomics features and CEUS radiomics features are of high clinical value as the combination of the two had better diagnostic performance.

Poly(ADP-ribose)polymerase (PARP) inhibition and anticancer activity of simmiparib, a new inhibitor undergoing clinical trials.

Poly(ADP-ribose)polymerase (PARP)1/2 inhibitors have been proved to be clinically effective anticancer drugs. Here we report a new PARP1/2 inhibitor, simmiparib, displaying apparently improved preclinical anticancer activities relative to the first approved inhibitor olaparib. Simmiparib inhibited PARP1/2 approximately 2-fold more potently than olaparib, with more than 90-fold selectivity over the other tested PARP family members. Simmiparib and olaparib caused similar cellular PARP1-DNA trapping. Simmiparib selectively induced the accumulation of DNA double-strand breaks, G2/M arrest and apoptosis in homologous recombination repair (HR)-deficient cells. Consistently, simmiparib showed 26- to 235-fold selectivity in its antiproliferative activity against HR-deficient cells over the corresponding isogenic HR-proficient cells. Notably, its antiproliferative activity was 43.8-fold more potent than that of olaparib in 11 HR-deficient cancer cell lines. Simmiparib also potentiated the proliferative inhibition of several conventional anticancer drugs. Simmiparib reduced the poly(ADP-ribose) formation in HR-deficient cancer cells and xenografts. When orally administered to nude mice bearing xenografts, simmiparib revealed excellent pharmacokinetic properties. Simmiparib caused approximately 10-fold greater growth inhibition than olaparib against HR-deficient human cancer cell- or tissue-derived xenografts in nude mice. Collectively, these findings support the undergoing clinical trials of simmiparib.