Exosomes: Small Vesicles with Important Roles in the Development, Metastasis and Treatment of Breast Cancer

Breast cancer (BC) has now overtaken lung cancer as the most common cancer, while no biopredictive marker isolated from biological fluids has yet emerged clinically. After traditional chemotherapy, with the huge side effects brought by drugs, patients also suffer from the double affliction of drugs to the body while fighting cancer, and they often quickly develop drug resistance after the drug, leading to a poor prognosis. And the treatment of some breast cancer subtypes, such as triple negative breast cancer (TNBC), is even more difficult. Exosomes (Exos), which are naturally occurring extracellular vesicles (EVs) with nanoscale acellular structures ranging in diameter from 40 to 160 nm, can be isolated from various biological fluids and have been widely studied because they are derived from the cell membrane, have extremely small diameter, and are widely involved in various biological activities of the body. It can be used directly or modified to make derivatives or to make some analogs for the treatment of breast cancer. This review will focus on the involvement of exosomes in breast cancer initiation, progression, invasion as well as metastasis and the therapeutic role of exosomes in breast cancer

3D Bio-Printing Fabrication and Properties of Graphene Dispersion-based Hybrid Scaffolds

Abstract Peripheral nerve is an important tissue of human body, which is distributed in various parts of human body, and has the function of connecting central nervous system and other organs. The self-repair ability of the nervous system is poor. However, 3D bio-printed neural tissue-engineered scaffolds offer a promising solution. In this study, graphene (Gr) was dispersed by a certain method, and then blended with gelatin (Gel) and sodium alginate (SA) to prepare a mixed bio-ink. Performance of different ratios of bio-ink was evaluated to determine the best printing ratio of the material. Four groups of Gr/Gel/SA scaffolds (The concentrations of graphene were 0%, 0.02%, 0.08% and 0.2% (w/v%), respectively) were prepared by using 3D printing technology. The mechanical strength, contact angle, degradation rate and water absorption of bio-scaffolds were compared to select the most suitable scaffold to support cell proliferation and differentiation, PC12 cells were used to study the biocompatibility of the scaffolds. This article aims to get the most optimized scaffolds.</p

Effect of Heat Input on Microstructure and Corrosion Resistance of CP-Ti Laser Beam Welded Joints

The TA1 welded joints with different heat inputs were obtained by a fiber laser and their microstructure, mechanical properties and corrosion resistance in simulated saliva solution were studied. The results show that the microstructure in fusion zone (FZ) is needle-like α′ martensite and lath-shape α′ martensite, and that of the heat-affected zone (HAZ) is zigzag α phase. With the increase of heat input, the volume fraction of needle-like α′ martensite decrease and the microstructure is coarsened in FZ, but there is almost no change in the microstructure of the HAZ. The order of the corrosion resistance of welded joints with different heat inputs is the same as FZ > HAZ > base material (BM), and the heat input has a more influence on the corrosion resistance of FZ. The binary multiple linear regression relationship between the corrosion current density/charge transfer resistance and the length/width of α′ martensite was established, indicating that the width of α′ martensite is the main factor affecting the corrosion resistance

Induced pluripotent stem cells generated from human adipose-derived stem cells using a non-viral polycistronic plasmid in feeder-free conditions.

Induced pluripotent stem cells (iPSCs) can be generated from somatic cells by ectopic expression of defined transcription factors (TFs). However, the optimal cell type and the easy reprogramming approaches that minimize genetic aberrations of parent cells must be considered before generating the iPSCs. This paper reports a method to generate iPSCs from adult human adipose-derived stem cells (hADSCs) without the use of a feeder layer, by ectopic expression of the defined transcription factors OCT4, SOX2, KLF4 and C-MYC using a polycistronic plasmid. The results, based on the expression of pluripotent marker, demonstrated that the iPSCs have the characteristics similar to those of embryonic stem cells (ESCs). The iPSCs differentiated into three embryonic germ layers both in vitro by embryoid body generation and in vivo by teratoma formation after being injected into immunodeficient mice. More importantly, the plasmid DNA does not integrate into the genome of human iPSCs as revealed by Southern blotting experiments. Karyotypic analysis also demonstrated that the reprogramming of hADSCs by the defined factors did not induce chromosomal abnormalities. Therefore, this technology provides a platform for studying the biology of iPSCs without viral vectors, and can hopefully overcome immune rejection and ethical concerns, which are the two important barriers of ESC applications

Screening Ionic Liquids for Dissolving a Melamine Formaldehyde Resin Prepolymer to Fabricate Flame-Retardant Fibers

The melamine fiber has been widely used because of its excellent flame retardancy. We tried to fabricate melamine fibers using ionic liquids (ILs) as solvents, melamine formaldehyde resin prepolymer (pre-MF) as flame-retardant material, and cellulose as the supporter. The best ILs for dissolving water-insoluble pre-MF were screened by COSMO-RS, in view of the richness of ILs and the complexity of pre-MF. The logarithmic activity coefficients (ln gamma) of three models were calculated to evaluate the dissolution ability of pre-MF in 432 ILs. According to the results of ln gamma and excess enthalpies, anions play a leading role in the dissolution process of pre-MF in ILs, while cations have little effect on it. The solubility experiments of pre-MF in 8 ILs were determined, which are consistent with the trend of ln gamma predicted. It is important that the ILs composed of OAc-, Dec(-), HCOO-, DEP-, DBP-, DMP-, Ben(-), Cl-, and Br- and different cations studied in this work have good dissolution ability for pre-MF. Besides, MF/cellulose composite flame-retardant fibers were prepared finally using EmimDEP as the solvent and cellulose as the supporter with good mechanical properties and flame retardancy: the breaking strength and limiting oxygen index are 2.24 cN/dtex and 31%, respectively

Evaluation of inhibitory effects of geniposide on a tumor model of human breast cancer based on 3D printed Cs/Gel hybrid scaffold

Traditional Chinese medicine therapy, which can serve as adjuvant therapy for cancer treatment, has no obvious side effects on the human body. Geniposide (GEN), one of the main iridoid glycosides in gardenia fruit, has been widely reported to have anti-cancer effects. In this study, we aimed to inspect whether GEN could inhibit proliferation and promote the apoptosis of human breast cancer cells (MCF-7). In order to better predict the efficacy of GEN, we have prepared the Cs/Gel composite scaffolds by 3D printing technology to mimic the MCF-7 cell growth microenvironment. The prepared Cs/Gel scaffold has good mechanical properties and biocompatibility, which can provide a more accurate platform for drug screening. The semi-inhibitory concentration (IC50) evaluated by CCK-8 assay was 16.06 mg/mL (24 h), 14.85 mg/mL (48 h), and 13.14 mg/mL (72 h). After exposed to GEN for 48 h, the cancer cell survival rate reduced from 69.15 +/- 2.86% (13 mg/mL) to 20.97 +/- 3.24% (16 mg/mL). Although the inhibitory effect was weaker in the 3D culture system, it also managed to inhibit cell proliferation and induce cell apoptosis. Besides, Live/Dead staining, Hematoxylin-Eosin (H&E) staining and SEM evaluation were also conducted to estimate the anti-cancer effect of GEN in 2D and 3D cultures. The results indicate that GEN has an anti-cancer effect based on a timeand dose-dependent manner

Migration to gliomas of bone mesenchymal stem cells transfected with cytosine deaminase gene following transplantation in vivo

This experiment sought to observe the migration and distribution of bone mesenchymal stem cells transfected with the cytosine deaminase gene (BMSCs-CD/eGFP) after transplantation in vivo through three pathways. In addition, we examined the tropism of these cells to glioma. Intracranial C6 glioma models were established in Sprague-Dawley rats using an intracranial stereotactic inoculation method. When tumors were 7 days old, rats were inoculated with 1x10(6) BMSCs-CD/eGFP cells via the tumor-bearing internal carotid artery, the contralateral hemisphere and the tumor-bearing glioma. Fluorescence microscopy revealed that BMSCs-CD/eGFP exhibited a strong capacity for migration to tumors. BMSCs-CD/eGFP transplanted via the tumor-bearing internal carotid artery were observed to distribute in glioma tissues. BMSCs-CD/eGFP inoculated via the ipsilateral glioma mainly located within and at the edge of glioma tissues. BMSCs-CD/eGFP inoculated via the contralateral hemisphere mainly distributed at the proximal end of the tumor at the incubation site

Numerical simulation of fluid field and in vitro three-dimensional fabrication of tissue-engineered bones in a rotating bioreactor and in vivo implantation for repairing segmental bone defects

In this paper, two-dimensional flow field simulation was conducted to determine shear stresses and velocity profiles for bone tissue engineering in a rotating wall vessel bioreactor (RWVB). In addition, in vitro three-dimensional fabrication of tissue-engineered bones was carried out in optimized bioreactor conditions, and in vivo implantation using fabricated bones was performed for segmental bone defects of Zelanian rabbits. The distribution of dynamic pressure, total pressure, shear stress, and velocity within the culture chamber was calculated for different scaffold locations. According to the simulation results, the dynamic pressure, velocity, and shear stress around the surface of cell-scaffold construction periodically changed at different locations of the RWVB, which could result in periodical stress stimulation for fabricated tissue constructs. However, overall shear stresses were relatively low, and the fluid velocities were uniform in the bioreactor. Our in vitro experiments showed that the number of cells cultured in the RWVB was five times higher than those cultured in a T-flask. The tissue-engineered bones grew very well in the RWVB. This study demonstrates that stress stimulation in an RWVB can be beneficial for cell/bio-derived bone constructs fabricated in an RWVB, with an application for repairing segmental bone defects

Migration to gliomas of bone mesenchymal stem cells transfected with cytosine deaminase gene following transplantation in vivo

This experiment sought to observe the migration and distribution of bone mesenchymal stem cells transfected with the cytosine deaminase gene (BMSCs-CD/eGFP) after transplantation in vivo through three pathways. In addition, we examined the tropism of these cells to glioma. Intracranial C6 glioma models were established in Sprague-Dawley rats using an intracranial stereotactic inoculation method. When tumors were 7 days old, rats were inoculated with 1x10(6) BMSCs-CD/eGFP cells via the tumor-bearing internal carotid artery, the contralateral hemisphere and the tumor-bearing glioma. Fluorescence microscopy revealed that BMSCs-CD/eGFP exhibited a strong capacity for migration to tumors. BMSCs-CD/eGFP transplanted via the tumor-bearing internal carotid artery were observed to distribute in glioma tissues. BMSCs-CD/eGFP inoculated via the ipsilateral glioma mainly located within and at the edge of glioma tissues. BMSCs-CD/eGFP inoculated via the contralateral hemisphere mainly distributed at the proximal end of the tumor at the incubation site