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.

Micro-/Nanomechanics Dependence of Biomimetic Matrices upon Collagen-Based Fibrillar Aggregation and Arrangement.

The mechanical and morphological cues of fibrillar extracellular matrices (ECMs) play vital roles in controlling the cellular behaviors. Understanding and regulating the correlation of the mechanics with morphologies, at the micro-/nanoscale are of great relevance to guide the growth and differentiation of stem or progenitor cells into the desired tissues. However, the investigations directed toward acquiring such a kind of correlation are very limited and far from satisfactory. Here, rheological and nanoindentation tests were employed to appraise the mechanical behaviors of biomimetic ECMs assembled from type I collagen solutions containing the equivalent content of alginate but with different molecular weights (MWs). An alginate-molecular-weight-dependent trend was found in the fibrillogenesis process and the fibril aggregation of these collagen-alginate (CA) matrices. The present study revealed that the viscoelasticity and nonlinear elasticity of the CA matrices relied upon their specific fibrillar architectures in which a heterogeneous structure formed with varying alginate MW, including the coexistence of small fibrils and larger fibrillar bundles. The correlation of the mechanical behaviors with the inhomogeneity in the fibrillar structures was further discussed in combination with those of Ca2+ ionically cross-linked CA matrices. This study not only presented the delicate mechanics of fibrillar ECM analogues but also showed that the introduction of affiliative matters such as polysaccharides (alginate with different MWs) is a simple and convenient strategy to achieve biomimetic hydrogels with tunable viscoelastic properties.

Parry-Romberg Syndrome With Hemimasticatory Spasm: A Rare Combination.

Parry-Romberg syndrome is a rare craniofacial disorder characterized by progressive hemifacial atrophy with systematic manifestations. The combination with hemimasticatory spasm is rare, with only 9 patients reported before. In this study, a study of a young male patient with Parry-Romberg syndrome and hemimasticatory spasm on his left side was presented. Radiologic examinations showed severe atrophy limited to subcutaneous tissue and electromyography demonstrated as hemimasticatory spasm. Injection of botulinum toxin type A was applied for the treatment of hemimasticatory spasm and after 2 separated injections, the patient was significantly relieved from symptom. The theory of focal demyelination of the trigeminal nerve peripheral brunches is the possible link between hemifacial atrophy and hemimasticatory spasm, although the pathogenesis of both diseases requires further study and current therapeutic methods are still limited to symptomatic treatments. Injection of botulinum toxin type A is an effective way to treat hemimasticatory spasm and autologous fat transplant is a promising solution to correct facial asymmetry.

Delicate Assembly of Ultrathin Hydroxyapatite Nanobelts with Nanoneedles Directed by Dissolved Cellulose.

Living organisms make use of a variety of inorganic and organic components to form biogenic minerals with hierarchical structures and fascinating properties, triggering the development of biomimetic mineralization. The introduction of organic additive is a versatile strategy, and a wide range of organics have already been adopted to mimic biosystems designing and synthesizing advanced functional minerals. Insoluble cellulose is the most abundant polysaccharide in nature, but the insolubility has limited its extensive applications. In this study, we first find that concentrated calcium chloride aqueous solution is an effective solvent for cellulose, and dissolved cellulose plays a pivotal role in directing the formation of ultrathin hydroxyapatite (HA) nanobelts of ca. 10 nm in thickness. To investigate the assembling process of the belt, samples collected at different reaction times were observed. The results indicate that nanoneedles form first, and then they assemble into the prototype of nanobelts by lateral/longitudinal aggregation and arrangement. Subsequently, the nanobelts gradually become dense, transparent, and smooth via crystallographic fusion of adjacent nanoneedles, indicating the highly elaborated evolution of morphology resulted from a time-dependent process. During the evolution of nanobelts, dissolved cellulose is supposed to participate in the mineralization of HA via the bonding of its hydrophilic groups with phosphate groups and calcium ions and the interaction of cellulose molecules with HA crystal planes. These findings provide unique insight into the application of dissolved cellulose in aqueous solution and an inspiration of a bottom-up strategy for designing delicate mineral assemblies directed by insoluble organics.

Patrilineal background of the She minority population from Chaoshan Fenghuang Mountain, an isolated mountain region, in China.

The She ethnic minority population is distributed in southern China. The origin of the She population has been controversial. The purpose of this work was to investigate the genomic diversity of She. The Chaoshan She population living in the Chaoshan Fenghuang mountain is a relatively isolated population. We detected 14 Y chromosome biallelic markers (Y-SNPs) and 6 Y chromosome short tandem repeat (Y-STR) loci in Chaoshan She people. Y-SNP analysis showed the Chaoshan She was closely related to the Chaoshan Hakka, Chaoshanese, Tujia and Gaoshan national minority. Compared with the Fujian She, the Chaoshan She maintained a more southern native genetic structure. Y-STR analysis revealed the Chaoshan She population was more closely related to the Hakka population than the other Hans. We concluded the Chaoshan She population had a closer genetic relationship with the southern national minority and Hakka Han and it may be representative of She ancestors' patrilineal genetic structure.

Long-range and high-resolution correlation optical time-domain reflectometry using a monolithic integrated broadband chaotic laser.

We experimentally demonstrate a compact, long-range, high-resolution chaotic correlation optical time-domain reflectometry based on a monolithic integrated chaotic laser (MICL). The MICL can directly generate a broadband chaotic signal covering a RF frequency range of over 40 GHz. Multi-reflection events can be precisely located in a detection range of ∼47 km with a range-independent resolution of 2.6 mm.

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.

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.

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.

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.

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.

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.

Alginate-Assisted Mineralization of Collagen by Collagen Reconstitution and Calcium Phosphate Formation.

The understanding of the mineralization of collagen for bone formation is a current key theme in bone tissue engineering and is of great relevance to the fabrication of novel biomimetic bone grafting materials. The noncollagenous proteins (NCPs) play a vital role in bone formation and are considered to be responsible for regulating intrafibrillar penetration of minerals into collagen fibrils by means of their abundant polyanionic domains. In this study, alginate, as a NCPs analogue, was introduced in the mineralization of collagen to mediate the collagen self-assembly with simultaneous hydroxyapatite (HA) synthesis. The biomimetic systems were based upon the self-assembly of collagen (Col) or collagen-alginate (CA) in the absence or presence of a varying content of HA. The alginate-mediated effects were found to include the lateral aggregation of small fibrils into the extremely large bundles and the assisted deposition of HA for a larger mineralized fibril. This alginate-assisted mineralization of collagen gave rise to an exquisite 3D mineralized architecture with enhanced mechanical property. The cell viability experiments showed the excellent proliferation and spreading morphologies of rat bone mesenchymal stem cells (MSCs) on the assembled products, and a higher expression of osteogenic differentiation related transcription factor was obtained in the alginate-assisted mineralization of collagen. This study indicated that the selection of an appropriate substance, e.g., alginate as an anionic polyelectrolyte with Ca-capturing property, could be a convenient, simple solution to achieve a mineralized collagen scaffold with the reinforced mechanical property for potential applications in bone regeneration.

Preparation of Strong Antioxidative, Therapeutic Nanoparticles Based on Amino Acid-Induced Ultrafast Assembly of Tea Polyphenols.

Nanoformulations offer the opportunity to overcome the shortcomings of drug molecules, such as low solubility, side effects, insufficient stability, etc., but in most of the current nanomedicines, nanocarriers as excipients do not directly participate in the therapy procedure. Accordingly, it is promising to develop the nanotherapeutics composed entirely of pharmaceutically active molecules. Tea polyphenols, especially epigallocatechin gallate (EGCG), are a kind of natural antioxidants with various biological and health beneficial effects and are extensively investigated as nutrients and anticancer drugs. Here, the size-tunable and highly active polyphenol nanoparticles were conveniently synthesized in water and could be massively produced with a simple facility. Compared to the previous strategies, either molecular assembly via oxidative coupling or combination with other biomacromolecules, the present preparation was conducted by the amino acid-triggered Mannish condensation reactions, thus permitting the flexible molecular design of various polyphenol nanoparticles by selecting different amino acids. This straightforward and ultrafast method actually opens up a novel means to make use of naturally reproducible polyphenols. Moreover, inheriting the salient properties of EGCG, these nanoparticles show strong antioxidation capacity, 10-fold higher than the extensively investigated polydopamine nanoparticles, and they are biosafe but have therapeutic effects, according to the in vitro and in vivo assessments of anticancer activity, which is promising for various biomedical purposes.

Expression and Significance of MyD88 in Patients With Gastric Cardia Cancer in a High-Incidence Area of China.

Background: Gastric cardia cancer (GCC) arises in the area of the stomach adjoining the esophageal-gastric junction and has unique risk factors. It was suggested that the involvement of Helicobacter pylori is associated with GCC from high-risk population. Myeloid differentiation factor 88 (MyD88) is a crucial adaptor molecule in Toll-like signaling pathway recognizing H. pylori. Its role in GCC has not been elucidated yet. In this study, our purpose is to investigate the expression and significance of MyD88 in GCC tissue. Methods: Expression of MyD88 and nuclear factor κB (NF-κB) p105/p50 and infection of H. pylori were detected by immunohistochemistry in gastric cardia tissue. The correlation of MyD88 expression to NF-κB p105/p50 expression, H. pylori infection, and clinicopathologic characteristics in gastric cardia tissue was analyzed. The involvement of MyD88 in patient prognosis was also analyzed. Results: Our data showed that the expression of MyD88 elevated from normal mucosa to inflammation (p = 0.071). The expression of MyD88 was enhanced in GCC tissues by contrast to non-malignant cardia mucosa (p = 0.025). What's more, overexpression of MyD88 was detected in intestinal-type adenocarcinoma with inflammation. Patients with high MyD88 staining revealed a better differentiation (p = 0.02). MyD88 also positively correlated with NF-κB p105/p50 expression (p = 0.012) in cancer tissue. Expression of MyD88 was increased but not significantly in biopsies with H. pylori infection compared with non-infected biopsies. Multivariate analyses revealed lymph node metastasis but not MyD88 expression was an independent predictor for patient survival. Conclusion: These findings provide pathological evidence that upregulating MyD88 and inducing inflammation might be involved in gastric cardia carcinogenesis in high-risk population. MyD88 plays a role in gastric cardia carcinogenesis with NF-κB pathway activation. Higher MyD88 expression is not a major prognostic determinant in GCC, but it may relate to the tumor cell differentiation.

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.

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.

Freeze-thaw cycles for biocompatible, mechanically robust scaffolds of human hair keratins.

The keratin-based scaffolds are getting more and more attention in the application of tissue engineering. Though various approaches have been considered to improve the physical properties of these scaffolds, few succeeded in achieving the enhanced properties of the pure keratin scaffolds. Due to the presence of -OH, -NH2 , >CO, and -SH on the extracted human hair keratin (HHK), the formation of hydrogen bonds and disulfide bridges could be triggered under certain conditions, leading to the self-cross-linking of HHK materials. Herein, a simple and green strategy was introduced, via freeze-thaw cycles of keratin solutions without addition of extraneous reagents, to obtain the mechanically robust HHK scaffolds. The comparative quantitation of residual -SH among the samples treated with 1, 5, and 9 cycles confirmed the oxidation in the thaw process for forming disulfide bonds. So, the equivalent thaw time was applied in this study, and three groups of the treated samples after 1, 5, and 9 cycles with an appropriate extension thaw time were prepared to solely investigate the effects of physical cross-linking networks, primarily by formation of hydrogen bonds, on the properties of the obtained scaffolds. The systematic assessments including swelling behavior, porosity, thermal analysis, compressive measurement, and microstructural observation confirmed that the repetitive freeze-thaw treatment contributed to mechanically robust scaffolds with good porous interconnectivity. The cell culturing experiments further verified that these HHK scaffolds had desirable cytocompatibility, permitting the proper proliferation, attachment, and infiltration. Accordingly, this study provided a simple and efficient method to obtain biocompatible, mechanically robust keratin scaffolds. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1452-1461, 2019.

Size-controlled, colloidally stable and functional nanoparticles based on the molecular assembly of green tea polyphenols and keratins for cancer therapy.

While intelligent nanoparticles with therapeutic effects provide a resolving strategy for low drug loading efficacy, poor metabolism and elimination of current nanoparticulate drug delivery systems, precise preparation of colloidally stable but stimuli-responsive nanocarriers with size tunability is still a challenging task. Here, we develop a facile and sustainable method through the use of naturally reproducible green tea polyphenols and hair keratins to prepare biocompatible, colloidally stable, stimuli-responsive nanoparticles with therapeutic effects. The present strategy simply involves covalent interactions of tea catechins and keratins, giving rise to the molecular assembly of size-controlled nanoparticles (30-230 nm) which are long-term colloidally stable at physiological media but are disassembled under pathological conditions, ideally for targeted delivery of anticancer drugs. The cell experiments confirmed that these nanoparticles are bio-safe, have the inherent bioactivity of tea catechins, and that the drug-loaded nanoparticles yield a higher cancer cell inhibition rate than free drugs. In addition, the nanoparticles are found to improve the bioavailability of tea polyphenols, according to animal studies, which further demonstrates that the use of nanoparticles as drug carriers results in enhanced anticancer efficacy with negligible systemic toxicity. Given that large-scale preparation of size-controlled nanoparticles could already be easily achieved, the present study actually provides an innovative nanotechnological approach to make good use of green tea polyphenols with beneficial health effects, potentially for therapeutic and preventive purposes.