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The failure to treat and control the growth of metastases is the main cause of death in breast cancer (BC) patients. Compared to the traditional method of analyzing circulating tumor DNA (ctDNA), capturing intact circulating tumor cells (CTCs) allows us to more accurately characterize mutations and identify suitable targeted therapies. We used CellCollector to collect peripheral CTCs. Thirty metastatic breast cancer (MBC) patients were enrolled, and 17 were analyzed with next-generation sequencing (NGS) methods. Clinical characteristics were analyzed along with the CTCs enumeration and detection rates. Whole-genome amplification (WGA) was used to amplify the CTC genomic DNA of 127 genes. Patients younger than 45 years old, with brain metastasis, with three or more metastatic sites, or with HER2-positive had the highest number of CTCs collected. The CTCs detection rate was also correlated to the number of metastasis sites. Different metastasis sites such as the brain, viscus, bone, and soft tissue contained specific high-frequency gene mutations. AKT3, MYC, and NT5C2 mutations were only found in brain metastases. APC, BCL2L11, ESRP1, FLT3 mutations were only in the visceral metastases. KEAP1, KIT, MET were the specific mutation genes in patients with bone and soft tissue metastases. These findings provide evidence that we can detect gene mutation information for obtaining the biological characteristics by CTCs using CellCollector. Different metastasis sites contain specific high-frequency mutation genes, which provide guidance to the accurate gene therapy.

In the current study, we present three designer self-assembling peptides (SAPs) by appending RADA 16-I with epitopes IKVAV, RGD, and YIGSR, which have different net charges and amphiphilic properties at neutral pH. The self-assembly of the designer SAPs is intensively investigated as a function of pH, canion type, and assembly time. The morphologies of the designer SAPs were studied by atomic force microscope. The secondary structure was investigated by circular dichroism. The dynamic viscoelasticity of designer SAP solutions was examined during titration with different alkaline reagents. Our study indicated that both electrostatic and hydrophilic/hydrophobic interactions of the motifs exhibited influences on the self-assembly, consequentially affecting the fiber morphologies and rheological properties. Moreover, NaOH induced a quicker assembly/reassembly of the designer SAPs than Tris because of its strong ionic strength. Therefore, our study gained comprehensive insight into the self-assembling mechanism as references for developing RADA 16-I-based functional SAPs.

Aim: To investigate the influence of ion pairing of carboxylated multiwalled carbon nanotubes (MWCNT-COOH) and polycations on the layer-by-layer assembly of nanocomposites and their biocompatibility for biomedical applications., Materials & Methods: Strong polycation poly(dimethyldiallylammonium chloride), and weak polycations chitosan and polyethyleneimine were selected to assembly with MWCNT-COOH. The MWCNT-COOH/polycation nanocomposites were analyzed by their physicochemical, electrical properties and biocompatibility., Results: The ion pairing of CNTs/polyelectrocytes played a critical role in the layer-by-layer assembly. Strong interactions between MWCNTs and poly(dimethyldiallylammonium chloride) produced thicker nanocomposites with rougher surfaces, higher MWCNT mass and better conductance. All the MWCNT multilayered nanocomposites were of good biocompatibility., Conclusion: The MWCNT multilayered nanocomposites hold high potential for biomedical applications.

As novel, promising, man-made nanomaterials with extraordinary properties, carbon nanotubes have been attracting massive attention in regenerative medicine. However, published reports on their potential cytotoxic effects are not concordant and are even conflicting. In the current study, the cytotoxic effects of carboxyl-modified multi-walled carbon nanotubes (COOH-MWCNTs), as well as their influences on the cell adhesion of NIH-3T3 fibroblasts, were thoroughly investigated. Live/dead cell viability assay and cell counting kit-8 assay both indicated that the viability of the NIH-3T3 cells exposed to COOH-MWCNTs in the culture medium was dependent on the latter's concentration. Cell viability increased at COOH-MWCNT concentrations below 50 μg ml(-1) and then decreased with increasing concentration. Scanning electron microscopy and immunofluorescent staining of the NIH-3T3 cells revealed that the cells were well adherent to the substrate after exposure to the COOH-MWCNTs for 48 h. Western blot demonstrated that COOH-MWCNT exposure enhanced the expression of adhesion-associated proteins compared with normal cells, peaking at an intermediate concentration. Our study showed that the cytotoxicity of COOH-MWCNTs, as well as their effects on NIH-3T3 fibroblast adhesion, was dose dependent. Therefore, COOH-MWCNT concentrations in the cell culture medium should be considered in the biomedical application of COOH-MWCNTs.

Self-assembling peptide (SAP) RADA16-I (Ac-(RADA)4-CONH2) has been suffering from a main drawback associated with low pH, which damages cells and host tissues upon direct exposure. In this study, we presented a strategy to prepare nanofiber hydrogels from two designer SAPs at neutral pH. RADA16-I was appended with functional motifs containing cell adhesion peptide RGD and neurite outgrowth peptide IKVAV. The two SAPs were specially designed to have opposite net charges at neutral pH, the combination of which created a nanofiber hydrogel (-IKVAV/-RGD) characterized by significantly higher G' than G″ in a viscoelasticity examination. Circular dichroism, Fourier transform infrared spectroscopy, and Raman measurements were performed to investigate the secondary structure of the designer SAPs, indicating that both the hydrophobic/hydrophilic properties and electrostatic interactions of the functional motifs play an important role in the self-assembling behavior of the designer SAPs. The neural progenitor cells (NPCs)/stem cells (NSCs) fully embedded in the 3D-IKVAV/-RGD nanofiber hydrogel survived, whereas those embedded within the RADA 16-I hydrogel hardly survived. Moreover, the -IKVAV/-RGD nanofiber hydrogel supported NPC/NSC neuron and astrocyte differentiation in a 3D environment without adding extra growth factors. Studies of three nerve injury models, including sciatic nerve defect, intracerebral hemorrhage, and spinal cord transection, indicated that the designer -IKVAV/-RGD nanofiber hydrogel provided a more permissive environment for nerve regeneration than the RADA 16-I hydrogel. Therefore, we reported a new mechanism that might be beneficial for the synthesis of SAPs for in vitro 3D cell culture and nerve regeneration.

One of the most complex systems in the human body is the nervous system, which is divided into the central and peripheral nervous systems. The regeneration of the CNS is a complex and challenging biological phenomenon hindered by the low regenerative capacity of neurons and the prohibition factors in response to nerve injuries. To date, no effective approach can achieve complete recovery and fully restore the functions of the nervous system once it has been damaged. Developments in neuroscience have identified properties of the local environment with a critical role in nerve regeneration. Advances in biomaterials and biomedical engineering have explored new approaches of constructing permissive environments for nerve regeneration, thereby enabling optimism with regard to nerve-injury treatment. This article reviews recent progress in nanoengineered environments for aiding nerveinjury repair and regeneration, including nanofibrous scaffolds, functional molecules, and stem cells.

Objective: To summarize the disposal methods and the reasons of complications in operation of totally implantable central venous port (TICVP)., Methods: A total of 2 007 patients were enrolled in this observational, single-center study between December 2008 and March 2013. TICVP implantation was performed with one small skin incision and subcutaneous puncture of subclavian or jugular vein. Patient's profiles, indications of port system, early and delayed complications, and disposal methods were evaluated. There were 38 male and 1 969 female patients, aged from 21 to 85 years, with a mean of 47.6 years., Results: The mean duration of the TICVP system was (242 ± 12) days, ranging from 9 to 1 243 days. The achievement rate of puncture in the right jugular vein (99.76%) was the highest. Sonographic approach using the internal jugular vein were better than the external landmark-guided technique (99.80% vs. 96.34%, χ² = 29.905, P = 0.000). The rate of immediate complication was 0.80%, which included pneumothorax, hemothorax, lymphatic fistula and thrombosis. Early complications rate was 0.10%, which included pocket hematoma, catheter migration, venous thrombosis, port pocket infection, fibrin sheath formation. Late complications rate was 7.87%, which included catheter fracture, pinch-off syndrome, catheter-related bloodstream infection, fibrin sheath formation, catheter migration, extravasation, port inversion and port reveal. The rate of removal due to complications was 1.34% (27/2 007), and the early complication was higher (χ² = 8.053, P = 0.011)., Conclusions: The low incidence of complications suggests that TICVP is safe and reliable for long term intermittent venous access. The results support the use of TICVP in the oncology patients and patients requiring long-term intravenous therapy.