High patatin like phospholipase domain containing 8 expression as a biomarker for poor prognosis of colorectal cancer.

BACKGROUND: Patatin like phospholipase domain containing 8 (PNPLA8) has been shown to play a significant role in various cancer entities. Previous studies have focused on its roles as an antioxidant and in lipid peroxidation. However, the role of PNPLA8 in colorectal cancer (CRC) progression is unclear. AIM: To explore the prognostic effects of PNPLA8 expression in CRC. METHODS: A retrospective cohort containing 751 consecutive CRC patients was enrolled. PNPLA8 expression in tumor samples was evaluated by immunohistochemistry staining and semi-quantitated with immunoreactive scores. CRC patients were divided into high and low PNPLA8 expression groups based on the cut-off values, which were calculated by X-tile software. The prognostic value of PNPLA8 was identified using univariate and multivariate Cox regression analysis. The overall survival (OS) rates of CRC patients in the study cohort were compared with Kaplan-Meier analysis and Log-rank test. RESULTS: PNPLA8 expression was significantly associated with distant metastases in our cohort (P = 0.048). CRC patients with high PNPLA8 expression indicated poor OS (median OS = 35.3, P = 0.005). CRC patients with a higher PNPLA8 expression at either stage I and II or stage III and IV had statistically significant shorter OS. For patients with left-sided colon and rectal cancer, the survival curves of two PNPLA8-expression groups showed statistically significant differences. Multivariate analysis also confirmed that high PNPLA8 expression was an independent prognostic factor for overall survival (hazard ratio HR = 1.328, 95%CI: 1.016-1.734, P = 0.038). CONCLUSION: PNPLA8 is a novel independent prognostic factor for CRC. These findings suggest that PNPLA8 is a potential target in clinical CRC management.

One-Step Approach to Prepare Transparent Conductive Regenerated Silk Fibroin/PEDOT:PSS Films for Electroactive Cell Culture.

Silk fibroin (SF)-based electroactive biomaterials with favorable electroconductive property and transparency have great potential applications for cell culture and tissue engineering. Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) is an excellent candidate as a conductive component, which has been widely used in the field of bioelectronics; however, it is hard to be directly coated onto the surface of regenerated SF (RSF) materials with good stability under a cell culture environment. In this study, a one-step facile PEDOT:PSS modification approach for RSF films based on a suitable post-treatment process of RSF was developed. PEDOT:PSS was successfully embedded and fixed into the shallow surface of an RSF film, forming a tightly conjunct conductive layer on the film surface based on the conformation transition of RSF during the post-treatment process. The conductive layer demonstrated a PSS-rich surface and a PEDOT-rich bulk structure and showed excellent stability under a cell culture environment. More specifically, the robust RSF/PEDOT:PSS film achieved in the post-treatment formula with 70% ethanol proportion possessed best comprehensive properties such as a sheet resistance of 3.833 × 103 Ω/square, a conductivity of 1.003 S/cm, and transmittance over 80% at maximum in the visible range. This kind of electroactive biomaterial also showed good electrochemical stability and degradable properties. Moreover, pheochromocytoma-derived cell line (PC12) cells were cultured on the RSF/PEDOT:PSS film, and an effective electrical stimulation cell response was demonstrated. The facile preparation strategy and the good electroconductive property and transparency make this RSF/PEDOT:PSS film an ideal candidate for neuronal tissue engineering and further for biomedical applications.

Transparent Conductive Silk Film with a PEDOT-OH Nano Layer as an Electroactive Cell Interface.

Bioelectronics based on biomaterial substrates are advancing toward biomedical applications. As excellent conductors, poly(3,4-ethylenedioxythiophene) (PEDOT) and its derivatives have been widely developed in this field. However, it is still a big challenge to obtain a functional layer with a good electroconductive property, transparency, and strong adhesion on the biosubstrate. In this work, poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT-OH) was chemically polymerized and deposited on the surface of a regenerated silk fibroin (RSF) film in an aqueous system. Sodium dodecyl sulfate (SDS) was used as the surfactant to form micelles which are beneficial to the polymer structure. To overcome the trade-off between transparency and the electroconductive property of the PEDOT-OH coating, a composite oxidant recipe of FeCl3 and ammonium persulfate (APS) was developed. Through electrostatic interaction of oppositely charged doping ions, a well-organized conductive nanoscale coating formed and a transparent conductive RSF/PEDOT-OH film was produced, which can hardly be achieved in a traditional single oxidant system. The produced film had a sheet resistance (Rs) of 5.12 × 104 Ω/square corresponding to a conductivity of 8.9 × 10-2 S/cm and a maximum transmittance above 73% in the visible range. In addition, strong adhesion between PEDOT-OH and RSF and favorable electrochemical stability of the film were demonstrated. Desirable transparency of the film allowed real-time observation of live cells. Furthermore, the PEDOT-OH layer provided an improved environment for adhesion and differentiation of PC12 cells compared to the RSF surface alone. Finally, the feasibility of using the RSF/PEDOT-OH film to electrically stimulate PC12 cells was demonstrated.

A trade-off between antifouling and the electrochemical stabilities of PEDOTs.

Strong nonspecific protein/cell adhesion on conducting polymer (CP)-based bioelectronic devices can cause an increase in the impedance or the malfunction of the devices. Incorporating oligo(ethylene glycol) or zwitterionic functionalities with CPs has demonstrated superior performance in the reduction of nonspecific adhesion. However, there is no report on the evaluation of the antifouling stability of oligo(ethylene glycol) and zwitterion-functionalized CPs under electrical stimulation as a simulation of the real situation of device operation. Moreover, there is a lack of understanding of the correlation between the molecular structure of antifouling CPs and the antifouling and electrochemical stabilities of the CP-based electrodes. To address the aforementioned issue, we fabricated a platform with antifouling poly(3,4-ethylenedioxythiophene) (PEDOT) featuring tri(ethylene glycol), tetra(ethylene glycol), sulfobetaine, or phosphorylcholine (PEDOT-PC) to evaluate the stability of the antifouling/electrochemical properties of antifouling PEDOTs before and after electrical stimulation. The results reveal that the PEDOT-PC electrode not only exhibits good electrochemical stability, low impedance, and small voltage excursion, but also shows excellent resistance toward proteins and HAPI microglial cells, as a cell model of inflammation, after the electrical stimulation. The stable antifouling/electrochemical properties of zwitterionic PEDOT-PC may aid its diverse applications in bioelectronic devices in the future.

All-Organic Conductive Biomaterial as an Electroactive Cell Interface.

Various attractive materials are being used in bioelectronics recently. In this paper, hydroxymethyl-3,4-ethylenedioxythiophene (EDOT-OH) has been in situ integrated and polymerized on the surface of the regenerated silk fibroin (RSF) film to construct a biocompatible electrode. In order to improve the efficiency of in situ polymerization, sodium dodecyl sulfate (SDS) was adopted as surfactant to construct a well-organized and stable poly(hydroxymethyl-3,4-ethylenedioxythiophene) (PEDOT-OH) coating, whereas ammonium persulfate was used as oxidant. The effects of dosages of surfactant and oxidant, initial pH value, and monomer concentration on the polymerization were studied. Under the optimal conditions, the RSF/PEDOT-OH film exhibited a square resistance of 3.28 × 105 Ω corresponding to a conductance of 6.1 × 10-3 S/cm. Scanning electron microscope images indicated that PEDOT-OH was deposited uniformly on the surface of the RSF film with SDS. Furthermore, Fourier transform infrared spectroscopy confirmed that interactions existed between the peptide linkages of silk fibroin (SF) macromolecules and PEDOT-OH. The RSF/PEDOT-OH film displayed favorable electrochemical stability, biocompatibility, and fastness. This study provides a feasible method to endow conductivity to RSF materials in various forms. In addition, the conductive layer and biocompatible silk substrate make the RSF/PEDOT-OH biomaterial highly suitable for potential applications in bioelectric devices, sensors, and tissue engineering.

Robust silk fibroin/bacterial cellulose nanoribbon composite scaffolds with radial lamellae and intercalation structure for bone regeneration.

A big challenge in bone regeneration is preparation of an appropriate bone extracellular matrix that mimics the robust mechanical properties of the lamellar structure of natural bones as well as the in vivo micro-environment of bone cells. In this work, silk fibroin (SF)/bacterial cellulose nanoribbon (BCNR) composite scaffolds were prepared using various BCNR contents via a multi-staged freeze-drying method. The scaffolds showed a radial lamellar pattern and gradient lamellae gap distance, the structure of which could transfer nutrient solution and metabolic waste through a capillary effect, and can guide cells from the outer to the inner area of the scaffolds. The gap distance and thickness of the lamellae increased with increasing BCNRs contents. Parts of BCNRs attached to the surfaces of lamellae while others penetrated into it. The intercalation structure led to an eight-fold enhancement in compression modulus and six-fold increase in compression strength. These robust three-dimensional composite scaffolds with improved in vitro bioactivity, bone-cell adhesion, and proliferation are highly promising for further applications in bone defect repairs.