Cephalogram synthesis and landmark detection in dental cone-beam CT systems.

Due to the lack of a standardized 3D cephalometric analysis methodology, 2D cephalograms synthesized from 3D cone-beam computed tomography (CBCT) volumes are widely used for cephalometric analysis in dental CBCT systems. However, compared with conventional X-ray film based cephalograms, such synthetic cephalograms lack image contrast and resolution, which impairs cephalometric landmark identification. In addition, the increased radiation dose applied to acquire the scan for 3D reconstruction causes potential health risks. In this work, we propose a sigmoid-based intensity transform that uses the nonlinear optical property of X-ray films to increase image contrast of synthetic cephalograms from 3D volumes. To improve image resolution, super resolution deep learning techniques are investigated. For low dose purpose, the pixel-to-pixel generative adversarial network (pix2pixGAN) is proposed for 2D cephalogram synthesis directly from two cone-beam projections. For landmark detection in the synthetic cephalograms, an efficient automatic landmark detection method using the combination of LeNet-5 and ResNet50 is proposed. Our experiments demonstrate the efficacy of pix2pixGAN in 2D cephalogram synthesis, achieving an average peak signal-to-noise ratio (PSNR) value of 33.8 with reference to the cephalograms synthesized from 3D CBCT volumes. Pix2pixGAN also achieves the best performance in super resolution, achieving an average PSNR value of 32.5 without the introduction of checkerboard or jagging artifacts. Our proposed automatic landmark detection method achieves 86.7% successful detection rate in the 2 mm clinical acceptable range on the ISBI Test1 data, which is comparable to the state-of-the-art methods. The method trained on conventional cephalograms can be directly applied to landmark detection in the synthetic cephalograms, achieving 93.0% and 80.7% successful detection rate in 4 mm precision range for synthetic cephalograms from 3D volumes and 2D projections, respectively.

Astragoloside IV Loaded Polycaprolactone Membrane Repairs Blood Spinal Cord Barrier and Recovers Spinal Cord Function in Traumatic Spinal Cord Injury.

Traumatic Spinal Cord Injury (SCI) is a serious challenge of CNS which may oftenly result in permanent paralysis and disability. The disruption of blood spinal cord barrier (BSCB) is a major step in the secondary injury of SCI. Until recently there are no restorative therapies for traumatic SCI. BSCB is considered to be a therapeutic target for SCI, however few biomaterials have been developed to restore the disrupted BSCB in SCI. In this study, an AST-PCL membrane was fabricated with a steady release of Astragoloside IV (AST) and its effects on BSCB repair as well as the functional recovery of SCI were evaluated. Firstly, this study demonstrated that AST-PCL (polycaprolactone) degradation media protects endothelial cells from apoptosis by down-regulating the expression of cleaved Caspase 3 and decreasing the ratio of Bax/Bcl-2, it also attenuates the stress fiber formation in vitro. Secondly, the rat model of traumatic SCI showed that AST-PCL treatment inhibits the disruption of BSCB permeability, as detected by MRI, Evan's Blue extravasation and water content. Thirdly, this study found that AST-PCL up-regulates the level of tight junction proteins including Occludin, Claudin5 and ZO-1. Furthermore, it is also demonstrated that AST-PCL treatment down-regulates Matrix metalloproteinase-9 secretion and diminishes neutrophil infiltration. Finally, this study found that AST-PCL treatment could significantly inhibit apoptosis, decrease tissue damage and improve functional recovery in SCI rats. Taken together, this study shows that AST-PCL might be an efficient biomaterial for BSCB repair and a potential drug therapy for SCI.

Targeting Therapy of Neuropilin-1 Receptors Overexpressed Breast Cancer by Paclitaxel-Loaded CK3-Conjugated Polymeric Micelles.

Chemotherapy for breast cancer is significantly restricted by the tumor's physio-pathological complexity. Here we have constructed a targeted nano-system based on PEGylated poly (D, L-lactide) (PEG-PDLLA) using a novel ligand, CLKADKAKC (CK3) peptide, for active targeting to Neuropilin-1-rich breast cancer cells. CK3 increased the cellular uptake of micelles 4.7-fold compared with the free drug and nearly 2.2-fold compared with the unmodified micelles (PM), respectively. Furthermore, in vivo imaging revealed that CK3-modified micelles (CK3-PM) had excellent specific tumor cells targeting and the drug accumulation was also enhanced. When paclitaxel (PTX) was loaded into micelles, CK3-PM-PTX induced the strongest inhibition and apoptosis against MDA-MB-231 cells in vitro and in vivo. These results demonstrated that CK3-modified PEG-PDLLA micelles developed in this study could be a potential targeted vehicle for enhancing the chemotherapy of breast cancers.

PEG-derivatized octacosanol as micellar carrier for paclitaxel delivery.

In this study, PEG-derivatized octacosanol copolymer was successfully developed to improve the anti-tumor activity and eliminate toxicity of the commercial formulation of paclitaxel (PTX). MPEG2K-C28, the conjugation of monomethoxy Poly(ethylene glycol) 2000 and octacosanol, was readily soluble in aqueous solution and self-assembled to form micelles with small sizes (< 20 nm) that are efficient in encapsulating PTX with a drug loading of 9.38 ± 0.18% and an encapsulation efficiency of 93.90 ± 2.12%. Meanwhile, octacosanol is very safe for humans and amazingly exhibits antitumor activity through inhibition activity of matrix metalloproteinases (MMPs) and translocation of the transcription factor (nuclear factor-kappa B, NF-κB) to the nucleus, which may be able to promote synergistic effects with PTX. A sustained and slower in vitro release behavior was observed in the (PTX micelles) than that of Taxol. PTX micelles exhibited more potent cytotoxicity than Taxol in the 4T1 breast cancer cell line. More interestingly, MPEG2K-C28 selectively inhibited the growth of 4T1 cells rather than the normal cells (HEK293 and L929 cell lines), indicating the antitumor activity of octacosanol remained after conjugation with MPEG. Acute toxicity evaluations indicated that MPEG2K-C28 was a safe drug carrier. Pharmacokinetic study revealed that PTX micelles improved the T1/2 and AUC of PTX (compared with Taxol) from 1.910 ± 0.139 h and 13.999 ± 1.109 mg/l × h to 2.876 ± 0.532 h and 76.462 ± 8.619 mg/l × h in vivo, respectively. The maximal tolerated dose (MTD) for PTX micelles (ca. 120 mg PTX/kg) in mice was significantly higher than that for Taxol (ca. 20mg PTX/kg). PTX micelles exhibited slightly better antitumor activity than Taxol but safer in 4T1 breast cancer model in vivo. The cell apoptosis in the immunofluorescent studies and the cell proliferation in the immunohistochemical studies also proved the results. In conclusion, MPEG2K-C28 is a simple, safe and effective drug delivery carrier for PTX, and has some therapeutic effects in 4T1 cells in vitro. PTX micelles showed significant antitumor activity in vivo with low systemic toxicity in 4T1 breast cancer. MPEG2K-C28 micelles entrapping PTX deserve more studies in the future.