Real-world impact of chemotherapy on overall survival in craniomaxillofacial osteosarcoma.

OBJECTIVES: The goal of this study was to identify the survival benefit of chemotherapy in craniomaxillofacial osteosarcoma (CMFO) patients based on a US population. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to select patients with CMFO from 1988 to 2016. Age and tumor size were grouped by X-tail. Cox analysis were used to estimate hazards ratios (HR) among patients. All of patients were divided into two cohorts by using Propensity Score Matching (PSM) method to evaluate the effect of chemotherapy. All prognostic factors were included in the nomograms which predict the median survival time. RESULTS: 410 patients were included in our study. The results of survival rate, Kaplan-Meier and Cox regression were showed no significant difference between the group of chemotherapy performed and the group without chemotherapy. PSM analysis also demonstrated the limited survival advantage of chemotherapy. Moreover, all factors were further incorporated to construct the novel nomograms and its concordance indices (C-index) for internal validation of OS prediction were 0.749 (95 %CI:0.731-0.767). CONCLUSIONS: Our study did not show the advantage of chemotherapy on the overall survival outcome of CMFO. Although neoadjuvant chemotherapy was currently recommended in clinical treatment, more rigorous randomized controlled trials are still needed. Nomograms would assist clinicians in making more accurate survival evaluation and choosing the optimal medical treatment.

Genome-wide DNA methylation profiling of gastric cardia cancer.

BACKGROUND AND AIM: Aberrant DNA methylation has been found in various cancer types including gastric cancer, yet the genome-wide DNA methylation profile of gastric cardia cancer (GCC) remains unclear. Therefore, we aimed to profile the DNA methylation pattern of GCC and identify promising diagnostic epigenetic biomarkers. METHODS: We investigated the genome-wide DNA methylation pattern in eight pairs of GCC and adjacent normal tissues using Illumina 850K microarrays. Subsequently, bisulfite-pyrosequencing and quantitative real-time PCR were performed on eight pairs of GCC-adjacent normal tissues for validation. Finally, we performed immunohistochemistry to examine ADHFE1 expression on 126 pairs of GCC-adjacent normal samples. RESULTS: DNA methylome analysis showed global hypomethylation and local hypermethylation of promoter cytosine-phosphate-guanine (CpG) islands (CGIs) in GCC tissues compared with gastric cardia normal mucosa (P < 2.2 × 10-16 ). Differential methylation analysis identified a total of 91 723 differentially-methylated probes (DMPs), and the candidate gene with the largest average DNA methylation difference mapped to ADHFE1 (mean Δß = 0.53). Subsequently, three DMPs in the ADHFE1 promoter were validated by pyrosequencing. Notably, the mean methylation level of the three candidate DMPs (ADHFE1_cg08090772, ADHFE1_cg19283840, and ADHFE1_cg20295442) was negatively associated with ADHFE1 mRNA expression level (Spearman rho = -0.64, P = 0.01). Moreover, both mRNA (P = 0.0213) and protein (P < 0.0001) expression of ADHFE1 were significantly decreased in GCCs compared with the adjacent normal tissues. CONCLUSIONS: Our results reveal DNA methylation aberrations in GCC and that ADHFE1 gene DNA methylation contributes to the risk of GCC, thus providing novel mechanistic insights into gastric cardia cancer carcinogenesis.

Engineered fabrication of EGCG-UV absorber conjugated nano-assemblies for antioxidative sunscreens with broad-band absorption.

Applying sunscreen is a common, convenient, and effective measure to protect skin from ultraviolet (UV) damage, but most of UV absorbers in the present commercially available sunscreens are accompanied with the insufficiencies in terms of efficacy and biosafety. The use of nanotechnology to combine conventional UV absorbers with biocompatible natural products is a feasible strategy to combat these deficiencies. Herein, a simple, green and engineering preparation of broad-band sunscreens was demonstrated by the molecular assembly of a UV absorber aminobenzoic acid (ABA) and polyphenol extracted from green tea (EGCG). Spherical and negatively-charged EGCG/ABA nanoparticles (EA NPs) were simply synthesized with a wide range of particle size from 54.6 to 715.1 nm. These NPs had the satisfactory biocompatibility and antioxidative activity, and could protect fibroblasts from oxidative-stress damage. The formulations containing 10 wt% EA NPs further exhibited broad-spectrum UV absorption and lower UV transmittance than commercial sunscreens. It is believed that this study would spur the utilization of natural reproducible sources for developing biosafe sunscreens with strong anti-UV capability. Indeed, this simple nanotechnology aimed at tackling the biosafe risk of conventional UV absorbers provides a feasible solution strategy with green tea extracts.

Size Changeable Nanomedicines Assembled by Noncovalent Interactions of Responsive Small Molecules for Enhancing Tumor Therapy.

The size of nanocarriers strongly affects their performance in biological systems, especially the capacity to overcome various barriers before delivering the payloads to destinations. However, the optimum size varies at different delivery stages in cancer therapy due to the complicated tumor microenvironment. Relatively large particles are favored for long-term circulation in vivo, while smaller particles contribute to deep penetration into tumor tissues. This dilemma in the size of particles stimulates the development of stimuli-responsive size-shrinking nanocarriers. Herein, we report a facile strategy to construct a tumor-triggered tannic acid (TA) nanoassembly with improved drug delivery efficiency. Cystamine (CA), a small molecule with a disulfide bond, is thus used to mediate TA assembling via cooperative noncovalent interactions, which endows the nanoassembly with intrinsic pH/GSH dual-responsiveness. The obtained TA nanoassemblies were systematically investigated. DOX encapsulated nanoassembly labeled TCFD NP shows high drug loading efficiency, pH/GSH-responsiveness and significant size shrinkage from 122 to 10 nm with simultaneous drug release. The in vitro and in vivo experimental results demonstrate the excellent biocompatibility, sufficient intracellular delivery, enhanced tumor retention/penetration, and superior anticancer efficacy of the small-molecule-mediated nanoassembly. This noncovalent strategy provides a simple method to fabricate a tumor-triggered size-changeable delivery platform to overcome biological barriers.

E-waste polycyclic aromatic hydrocarbon (PAH) exposure leads to child gut-mucosal inflammation and adaptive immune response.

Polycyclic aromatic hydrocarbon (PAH) exposure alters immunological responses. Research concerning PAH exposure on intestinal immunity of children in electronic waste (e-waste) areas is scarce. The aim of this study was to evaluate the effects of polycyclic aromatic hydrocarbon (PAH) pollutants on intestinal mucosal immunity of children in e-waste areas. Results showed higher hydroxylated PAH (OH-PAH) concentrations in e-waste-exposed children, accompanied with higher sialyl Lewis A (SLA) level, absolute lymphocyte and monocyte counts, decreased of percentage of CD4+ T cells, and had a higher risk of diarrhea. OH-PAH concentrations were negative with child growth. 1-OHNap mediated through WBCs, along with 1-OHPyr, was correlated with an increase SLA concentration. 2-OHFlu, 1-OHPhe, 2-OHPhe, 1-OHPyr, and 6-OHChr were positively correlated with secretory immunoglobulin A (sIgA) concentration. Our results indicated that PAH pollutants caused inflammation, affected the intestinal epithelium, and led to transformation of microfold cell (M cell). M cells initiating mucosal immune responses and the subsequent increasing sIgA production might be an adaptive immune respond of children in the e-waste areas. To our knowledge, this is the first study of PAH exposure on children intestinal immunity in e-waste area, showing that PAH exposure plays a negative role in child growth and impairs the intestinal immune function.

Lead (Pb) exposure and heart failure risk.

Lead (Pb) is a heavy metal with widespread industrial use, but it is also a widespread environmental contaminant with serious toxicological consequences to many species. Pb exposure adversely impacts the cardiovascular system in humans, leading to cardiac dysfunction, but its effects on heart failure risk remain poorly elucidated. To better understand the pathophysiological effects of Pb, we review potential mechanisms by which Pb exposure leads to cardiac dysfunction. Adverse effects of Pb exposure on cardiac function include heart failure risk, pressure overload, arrhythmia, myocardial ischemia, and cardiotoxicity. The data reviewed clearly establish that Pb exposure can play an important role in the occurrence and development of heart failure. Future epidemiological and mechanistic studies should be developed to better understand the involvement of Pb exposure in heart failure.

Biocompatible, Antioxidant Nanoparticles Prepared from Natural Renewable Tea Polyphenols and Human Hair Keratins for Cell Protection and Anti-inflammation.

Excessive reactive oxygen species (ROS) can cause oxidative stress of tissues and adversely influence homeostasis of the body. Epigallocatechin gallate (EGCG) with an antioxidative effect can effectively eliminate the ROS, but an evident weakness associated with it is the relatively poor cytocompatibility. Combining with other biomacromolecules such as human hair keratin (KE) and using nanotechnology to prepare nanoparticles can improve this situation. By covalent bonding, we assembled KE and EGCG into KE-EGCG nanoparticles (NANO) with size of about 50 nm and characterized them by DLS, UV, FTIR, NMR, and XPS. Free radical scavenging experiments show that antioxidant properties of the obtained NANO are superior to that of vitamin C. Cell culture experiments also show that the NANO can effectively protect the proliferation of L929 cells and HUVEC cells. In addition, we also used RAW264.7 cells to establish a H2O2-induced cell injury model and an lipopolysaccharide-induced cellular inflammatory model to evaluate the antioxidant and anti-inflammatory properties of NANO. The results show that the NANO can effectively prevent cells from oxidative damage and reduce inflammatory expression of the cells, indicating that the NANO have a good antioxidative and anti-inflammatory effect on cells which can be applied to many diseases related to oxidative stress.

Synthesis and characterization of injectable self-healing hydrogels based on oxidized alginate-hybrid-hydroxyapatite nanoparticles and carboxymethyl chitosan.

Injectable hydrogels are of great interest in tissue engineering, and those incorporating hydroxyapatite (HA) are especially acclaimed in the application of bone repair. Synthetic micro-HA were generally used for this purpose and in some cases, surface modification of HA was further applied to improve the interfacial compatibility of rigid inorganic HA with soft organic matrix. In this study, the injectable hydrogels based on oxidized alginate hybrid HA nanoparticles and carboxymethyl chitosan were achieved via Schiff base reaction. Physicochemical characterization confirmed that oxidized HA/Alg hybrids (OHAH) were successfully prepared. Rheological measurements verified the formation of hydrogels based on the dynamic imine bonding, and the gelation time showed a negative correlation to the concentration and oxidation time of OHAH, while the storage moduli exhibited a positive correlation. The self-healing property of these hydrogels was validated by the splicing experiments and rheological experiments. The lyophilized hydrogels showed porous structures with numerous HA nanoparticles distributed on the surface of pore wall. MTT assays and live/dead staining of cell experiments confirmed the cytocompatibility of these hydrogels. The injectable hydrogels with self-healing and tunable gelling properties were ingeniously prepared with functionalized alginate-mediated HA hybrid nanoparticles, and these hydrogels are promising for applications in bone tissue engineering.

Natural polysaccharide-incorporated hydroxyapatite as size-changeable, nuclear-targeted nanocarrier for efficient cancer therapy.

Targeted delivery of anticancer drugs is one of the most promising methods for cancer therapy. However, barriers including complicated procedures, costly preparation, and toxic side effects have restricted the development of nuclear-targeted nanocarriers. Natural polysaccharides as extracellular matrix constituents or analogs play an important role in biomineralization. Herein, a simple, polysaccharide-intervened preparation of hydroxyapatite (HA) hybrid nanoparticles (NPs) with low crystallinity was used as a bio-safe carrier for targeting the delivery of doxorubicin (DOX) for efficient anticancer therapy. The poorly crystallized hybrid HA NPs were specifically taken up by cancer cells (HeLa cells), and subsequently, the abrupt degradation of HA nanoparticles would cause a change in the osmotic pressure, leading to the explosive death of cancer cells. Furthermore, the hybrid HA NPs were size changeable and capable of directly delivering the anti-cancer drug into the nucleus of cancer cells, thereby efficiently killing cancer cells. In addition, the HA/ALG NPs reduce the toxicity of DOX to L929 cells and cause little negative effect on normal tissue cells. The in vitro and in vivo experiments confirmed that the size-changeable HA-ALG/DOX could be a promising nuclear-targeted delivery nanocarrier for efficient cancer therapy.

General Nanomedicine Platform by Solvent-Mediated Disassembly/Reassembly of Scalable Natural Polyphenol Colloidal Spheres.

The current strategy using the assembly of medicines and active functional molecules to develop nanomedicines often requires both molecules to have a specific matched chemical molecular structure; however, this is often difficult to predict, execute, and control in practical applications. Herein, we reported a general solvent-mediated disassembly/reassembly strategy for preparing nanomedicines based on epigallocatechin gallate (EGCG) active molecules. The polyphenol colloidal spheres (CSs) were self-assembled from molecular condensed EGCG in aqueous solution but disassembled in organic solvents and reassembled in aqueous solution. The solvent-mediated disassembly and reassembly capability of CSs gave rise to the active binding of condensed EGCG to various hydrophilic and hydrophobic guest molecules. The maximum encapsulation and drug-loading rate of reassembled CSs/DOX were 90 and 44%, respectively, and the nanomedicines could reverse drug resistance of tumor cells and exhibit enhanced therapeutic effects for breast cancer. Last but not least, 37.3 g of polyphenol CSs was massively produced at one time with a yield of 74.6%, laying a solid foundation for the practical applications of reassembled nanomedicines. The present strategy leading to a general nanomedicines platform was concise and highly efficient for both hydrophilic and hydrophobic drugs, making a breakthrough for low loading dilemma of current nanomedicines, and would open up a new direction for the preparation of nanocarriers, nanocomposites, and nanomedicines from natural polyphenols.