Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are well-established therapeutics for gastrointestinal neoplasias, but complications after EMR/ESD, including bleeding and perforation, result in additional treatment morbidity and even threaten the lives of patients. Thus, designing biomaterials to treat gastric bleeding and wound healing after endoscopic treatment is highly desired and remains a challenge. Herein, a series of injectable pH-responsive self-healing adhesive hydrogels based on acryloyl-6-aminocaproic acid (AA) and AA-g-N-hydroxysuccinimide (AA-NHS) were developed, and their great potential as endoscopic sprayable bioadhesive materials to efficiently stop hemorrhage and promote the wound healing process was further demonstrated in a swine gastric hemorrhage/wound model. The hydrogels showed a suitable gelation time, an autonomous and efficient self-healing capacity, hemostatic properties, and good biocompatibility. With the introduction of AA-NHS as a micro-cross-linker, the hydrogels exhibited enhanced adhesive strength. A swine gastric hemorrhage in vivo model demonstrated that the hydrogels showed good hemostatic performance by stopping acute arterial bleeding and preventing delayed bleeding. A gastric wound model indicated that the hydrogels showed excellent treatment effects with significantly enhanced wound healing with type I collagen deposition, α-SMA expression, and blood vessel formation. These injectable self-healing adhesive hydrogels exhibited great potential to treat gastric wounds after endoscopic treatment.
In this study, high-performance flexible strain sensors based on carbon nanotube (CNT) and graphene nanoplatelet (GNP) filled thermoplastic polyurethane (TPU) composites were fabricated via Fused Filament Fabrication (FFF) 3D printing. The introduction of GNPs generated a more complete conductive network of the composites due to the improved nanofiller dispersion. Due to the synergy of CNTs and GNPs, the printed CNT/GNP(3:1)/TPU sensor shows higher sensitivity (GF = 136327.4 at 250% strain), larger detectable range (0~250% strain), and better stability (3000 cycles) compared with the CNT/TPU and GNP/TPU sensors with a nanofiller content of 2 wt%. Furthermore, the printed sensors can accurately detect strains at different frequencies (0.01~1 Hz). A modelling study based on tunneling theory was conducted to analysis the strain sensing mechanism, and the theoretical results agreed well with the experimental data. The capability of the sensors in monitoring physiological activities and speech recognition has also been demonstrated.
Matrix metalloproteinase-9 is a member of the Matrix metalloproteinases (MMP) family, which is overexpressed in some solid tumor and thought to enhance the tumor invasion and metastasis ability. Our study is to investigate the association of MMP-9 expression with disease-free survival and overall survival of patients with gastric cancer. Clinical gastric cancer specimens and adjacent normal tissues from 286 patients who had not received neoadjuvant chemotherapy were investigated by immunohistochemistry assay. Staining evaluation results were analyzed statistically in relation to various clinicopathological characters, disease-free survival and overall survival. High level of MMP-9 expression was detected in gastric cancer, significantly more than in adjacent normal epithelial cells. In gastric cancer, MMP-9 was significantly positively correlated with depth of invasion, lymph node metastasis and distant metastasis. However, no correlations between MMP-9 expression and patients' age, sex, tumor location or differentiation status were detected. The disease-free survival and overall survival were significantly shorter for patients with MMP-9 positive than those with MMP-9 negative tumors. Multivariate analysis identified MMP-9 was an independent prognostic factor for both disease-free survival and overall survival. Our findings provided convincing evidence for MMP-9 as an important role in human gastric cancer recurrence and prognosis. It might also serve as a novel target for both prognostic prediction and therapeutics.Matrix metalloproteinases (MMPs) are a group of zinc-dependent proteins that are found in the extracellular milieu of various tissues.1 They are a multigene family of highly homologous enzymes sharing a similar structure, involved in extracellular matrix (ECM) proteins7-10 remodelling processes. 2-5To date, at least 26 known human MMPs have been discovered.6 Based on sequence homology and substrate specificities, the MMPs can be divided into several distinct subclasses: collagenases, gelatinases, stromelysins and matrilysins. 7 MMPs are frequently overexpressed in various human cancers and have long been associated with malignancy. [8][9][10] However, MMPs exhibit considerable promiscuity with respect to their substrates, leading to considerable redundancy in biologic functions, in which the effects on tumor aggressiveness were of vital importance. 11 The development of tumor invasion and metastasis is a complicated and continuous process with multiple steps. To invade and metastasize tumor cells must break through ECM and basement membrane of the epithelium; then infiltrate blood vessels and lymphatics to build up secondary cancer cell colonies at distant sites. There has been a great deal of interest in the role of MMPs in cancer invasion and metastasis due to their ECM degrading capacity.1,2 Thus, MMPs have for long been viewed as key modulators of tumor progression and metastasis. A substantial subsequent study has provided evidence for an association between MMPs expression and tumor aggressive...
NDRG2 (N-Myc downstream-regulated gene 2) is aberrantly expressed in colorectal cancer (CRC) and related to tumor differentiation status. In the present study, we investigated the association between NDRG2 mRNA levels in primary CRC to determine whether levels of NDRG2 mRNA could predict relapse and survival. A hospital-based study cohort of 226 CRC patients was involved in the study. NDRG2 mRNA levels were determined by real-time PCR. Correlations of NDRG2 mRNA expression with tumor clinicopathologic features, disease-free survival, and overall survival of the patients were studied. Significant decreased expression of NDRG2 mRNA was detected in tumor specimens. NDRG2 mRNA expression significantly correlated with differentiation status (P < 0.001), lymph node metastasis (P < 0.001), and tumor node metastasis stage (P < 0.001). Patients with reduced level of NDRG2 mRNA had a statistically significantly shorter disease-free survival and overall survival duration than patients with preserved expression of NDRG2 mRNA. In multivariate analysis, NDRG2 mRNA level was found to be an independent prognostic factor for both disease-free survival and overall survival of CRC patients. The present research provided the first evidence that decreased NDRG2 mRNA expression in primary human CRC might be a powerful, independent predictor of recurrence and outcome.
The role of NDRG4 in human malignancies is largely unknown. We investigated the role of NDRG4 protein in colorectal cancer and its prognostic value in a hospital-based retrospective training cohort of 272 patients and a prospective validation cohort of 708 patients were. Cell line was transfected with an NDRG4 expression construct to confirm the suppression of PI3K-AKT activity by NDRG4. Appropriate statistical methods were utilized for analysis. Results showed that NDRG4 protein expression was significantly decreased from normal mucosa, chronic colitis, ulcerative colitis, atypical hyperplasia to colorectal cancer. Significant negative correlations were found between NDRG4 staining and p-AKT. Patients with positive NDRG4 staining had favorable survival in both study cohorts. In multivariate analysis, NDRG4 staining proved to be an independent predictor of overall survival. Moreover, the prognostic role of NDRG4 was stratified by p-AKT. Overexpression of NDRG4 in colorectal cancer cell can significantly suppress PI3K-AKT activity, even after EGF stimulation. These results indicated NDRG4 protein expression was decreased in colorectal cancer. It may play its tumor suppressive role in carcinogenesis and progression through attenuation of PI3K-AKT activity. Therefore, high risk colorectal cancer patients could be better identified based on the combination of NDRG4 and PI3K-AKT activity.
Photo‐electronic devices based on reactive oxygen species (ROS) generation suffer a crucial limitation in wound treatment due to their sandwich structure, which prevents the contact of ROS with wound tissue. In this work, the first anti‐sandwich structured visible‐light/electricity dual‐responsive wound dressing is constructed for treatment of methicillin‐resistant Staphylococcus aureus (MRSA), based on selenoviologen‐appendant polythiophene (SeV2+‐PT)‐containing polyacrylamide hydrogels. The new wound dressing is named an anti‐sandwich structured photo‐electronic wound dressing (PEWD). The unique structure of PEWD enables its use in synergistic electrodynamic and photodynamic therapy (EDT and PDT), providing rapid, on‐demand, and sustained generation of ROS in situ via short‐time light irradiation and/or wireless‐controlled electrification. The PEWD possesses good flexibility, excellent biocompatibility, and fast response, as well as sustained ROS generation in a physiological environment. Animal experiments demonstrate effective ROS generation in 6 s under irradiation and electrification, inhibiting infection at an early stage, and substantially shortening the healing time of bacterial infection (to within 7 days). This proof‐of‐concept research holds great promise in developing new flexible PEWD, and novel strategies to improve wound treatment.
The development of supramolecular hosts with effective host–guest properties is crucial for their applications. Herein, we report the preparation of a porphyrin-based metallacage, which serves as a host for a series of polycyclic aromatic hydrocarbons (PAHs). The association constant between the metallacage and coronene reaches 2.37 × 10 7 M –1 in acetonitrile/chloroform (ν/ν = 9/1), which is among the highest values in metallacage-based host–guest complexes. Moreover, the metallacage exhibits good singlet oxygen generation capacity, which can be further used to oxidize encapsulated anthracene derivatives into anthracene endoperoxides, leading to the release of guests. By employing 10-phenyl-9-(2-phenylethynyl)anthracene whose endoperoxide can be converted back by heating as the guest, a reversible controlled release system is constructed. This study not only gives a type of porphyrin-based metallacage that shows desired host–guest interactions with PAHs but also offers a photooxidation-responsive host–guest recognition motif, which will guide future design and applications of metallacages for stimuli-responsive materials.
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