Association of individual and combined exposures of 10 metals with periodontitis: Results from a large population-based study.

AIMS: To systematically investigate the association between individual and combined metal exposure and periodontitis. METHODS: Data encompassing complete periodontal examinations and metal detection in blood and urine samples were procured from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Three statistical methods, namely weighted logistic regression, Bayesian kernel machine regression (BKMR), and weighted quantile sum (WQS) regression, were used to evaluate the independent and combined associations between metals and periodontitis. RESULTS: Elevated concentrations of blood cadmium (odds ratio [OR]: 1.73, 95% confidence interval [CI]: 1.15-2.61) and blood lead (OR: 1.17, 95 %CI: 1.02-1.34) exhibited a positive association with periodontitis, even after adjusting for potential confounding factors. The BKMR and WQS regression suggested that the co-exposure of metals was also positively associated with periodontitis. Moreover, estradiol and albumin were identified as potential mediators in the relationship between the WQS index of the 10 metals in blood and periodontitis explaining 25.36% and 2.02% of the relationship, respectively. Furthermore, generally consistent patterns of associations between metals and periodontitis and mediating roles of estrogen and albumin were observed after a series of sensitivity analyses. CONCLUSION: This study provides evidence of positive associations between elevated levels of cadmium, lead or metal mixture and periodontitis, which may be partially mediated by sex hormones and oxidative stress indicators.

Searching for essential genes and drug discovery in breast cancer and periodontitis via text mining and bioinformatics analysis.

The primary purpose of the study was (1) to search for the essential genes associated with breast cancer and periodontitis, and (2) to identify candidate drugs targeted to these genes for expanding the potential drug indications. The genes related to both breast cancer and periodontitis were determined by text mining. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were performed on these genes, and protein-protein interaction analysis was carried out to export significant module genes. Drug-gene interaction database was employed for potential drug discovery. We identified 221 genes common to both breast cancer and periodontitis. The top six significant enrichment terms and 15 enriched signal pathways were selected. Among 24 significant genes demonstrated as a gene cluster, we found SERPINA1 and TF were significantly related to poor overall survival between the relatively high and low groups in patients. Using the final two genes, 12 drugs were identified that had potential therapeutic effects. SERPINA1 and TF were screened out as essential genes related to both breast cancer and periodontitis, targeting 12 candidate drugs that may expand drug indications. Drug discovery using text mining and analysis of different databases can promote the identification of existing drugs that have the potential of administration to improve treatment in breast cancer.

Fabrication of Synthetic Mesenchymal Stem Cells for the Treatment of Acute Myocardial Infarction in Mice.

RATIONALE: Stem cell therapy faces several challenges. It is difficult to grow, preserve, and transport stem cells before they are administered to the patient. Synthetic analogs for stem cells represent a new approach to overcome these hurdles and hold the potential to revolutionize regenerative medicine. OBJECTIVE: We aim to fabricate synthetic analogs of stem cells and test their therapeutic potential for treatment of acute myocardial infarction in mice. METHODS AND RESULTS: We packaged secreted factors from human bone marrow-derived mesenchymal stem cells (MSC) into poly(lactic-co-glycolic acid) microparticles and then coated them with MSC membranes. We named these therapeutic particles synthetic MSC (or synMSC). synMSC exhibited a factor release profile and surface antigens similar to those of genuine MSC. synMSC promoted cardiomyocyte functions and displayed cryopreservation and lyophilization stability in vitro and in vivo. In a mouse model of acute myocardial infarction, direct injection of synMSC promoted angiogenesis and mitigated left ventricle remodeling. CONCLUSIONS: We successfully fabricated a synMSC therapeutic particle and demonstrated its regenerative potential in mice with acute myocardial infarction. The synMSC strategy may provide novel insight into tissue engineering for treating multiple diseases.

Comparisons of the Computed Tomographic Scan and Panoramic Radiography Before Mandibular Third Molar Extraction Surgery.

BACKGROUND Mandibular third molar extraction surgery has a postoperative complication of hypoesthesia of the lower lip and/or chin. The objective of the study was to determine if preoperative radiographic examination by panoramic radiography and computed tomography (CT) scan can predict postoperative complications of mandibular third molar extraction surgery. MATERIAL AND METHODS In total, 479 patients who had mandibular third molar extraction surgery were included in this cross-sectional study. Patients had panoramic radiographies and CT scans to determine the relationship of the tooth, the canal, and the buccolingual position. Inferior alveolar nerve sensory impairment was detected using a two-point discrimination method. Wilcoxon test and Tukey's test were used to compare diagnostic modalities at a 99% confidence level. RESULTS Inferior alveolar nerve was more successfully quantified by CT scan compared to panoramic radiography (p<0.0001, q=8.062). Orthopantomography was better than the CT scan in detecting a close relationship of the tooth and the canal (p<0.0001, q=25.609), but the CT scan was better in detecting the buccolingual position of the teeth (p<0.0001, q=36.757). The age of patients (p<0.0001, q=36.757), postoperative bleeding (p<0.0001, q=15.981), and experience of the surgeon (p<0.0001, q=10.99) had an affected on inferior alveolar nerve sensory impairment. CONCLUSIONS Preoperative panoramic radiography, CT scan, age, the experience of the surgeon, and postoperative bleeding can predict postoperative complications for extraction of a mandibular third molar.

Armet is an effector protein mediating aphid-plant interactions.

Aphid saliva is predicted to contain proteins that modulate plant defenses and facilitate feeding. Armet is a well-characterized bifunctional protein in mammalian systems. Here we report a new role of Armet, namely as an effector protein in the pea aphid, Acyrthosiphon pisum. Pea aphid Armet's physical and chemical properties and its intracellular role are comparable to those reported for mammalian Armets. Uniquely, we detected Armet in aphid watery saliva and in the phloem sap of fava beans fed on by aphids. Armet's transcript level is several times higher in the salivary gland when aphids feed on bean plants than when they feed on an artificial diet. Knockdown of the Armet transcript by RNA interference disturbs aphid feeding behavior on fava beans measured by the electrical penetration graph technique and leads to a shortened life span. Inoculation of pea aphid Armet protein into tobacco leaves induced a transcriptional response that included pathogen-responsive genes. The data suggest that Armet is an effector protein mediating aphid-plant interactions.

Effects of Intravenous Injection of Porphyromonas gingivalis on Rabbit Inflammatory Immune Response and Atherosclerosis.

The effects of intravenous injection of Porphyromonas gingivalis (Pg) on rabbit inflammatory immune response and atherosclerosis were evaluated by establishing a microamount Pg bacteremia model combined with high-fat diet. Twenty-four New Zealand rabbits were randomly divided into Groups A-D (n = 6). After 14 weeks, levels of inflammatory factors (C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1)) in peripheral blood were detected by ELISA. The aorta was subjected to HE staining. Local aortic expressions of toll-like receptor-2 (TLR-2), TLR-4, TNF-α, CRP, IL-6, matrix metallopeptidase-9, and MCP-1 were detected by real-time PCR, and those of nuclear factor-κB (NF-κB) p65, phospho-p38 mitogen-activated protein kinase (MAPK), and phospho-c-Jun N-terminal kinase (JNK) proteins were detected by Western blot. Intravenous injection of Pg to the bloodstream alone induced atherosclerotic changes and significantly increased systemic and local aortic expressions of inflammatory factors, NF-κB p65, phospho-p38-MAPK, and JNK, especially in Group D. Injection of microamount Pg induced inflammatory immune response and accelerated atherosclerosis, in which the NF-κB p65, p38-MAPK, and JNK signaling pathways played important roles. Intravenous injection of Pg is not the same as Pg from human periodontitis entering the blood stream. Therefore, our results cannot be extrapolated to human periodontitis.

[Bioactive materials in periodontal regeneration].

Bioactive materials are a type of biomaterials that can generate special biological or chemical reactions on the surface or interface of materials. These reactions can impact the interaction between tissues and materials, stimulate cell activity, and guide tissue regeneration. In recent years, bioactive materials have been widely used in periodontal tissue regeneration. This review aims to consolidate the definition and characteristics of bioactive materials, as well as summarize their utilization in periodontal tissue regeneration. These findings shed new light on the application of bioactive materials in this field.

Impact of X-ray irradiation as an equivalent alternative to gamma for sterilization of single-use bioprocessing polymers.

Irradiation sterilization of polymeric pharmaceutical processing systems and medical devices, an essential healthcare technology, is facing critical business continuity challenges, driving the need to qualify equivalent alternative irradiation technologies, such as X-ray. Whereas the underlying there is a paucity of cross-industry published data evaluating X-ray irradiation effects on plastics as compared to gamma irradiation. That leads to regulatory uncertainty in the levels of costly validation data regulators will require and overall apprehension in the rate of X-ray irradiation adoption. The present study evaluates the impact of X-ray versus gamma irradiation on a wide range of polymers with more than 36 single-use (SU) components, using a comprehensive set of industry aligned methods for characterization of bioprocess polymers. Whereas many of these techniques readily demonstrate changes in polymer properties following irradiation, all of the polymers evaluated demonstrated that the impact of X-ray irradiation was to the same degree or less as compared to gamma. Increased publication of studies evaluating the impact to polymers of X-ray versus gamma irradiation is critical to leveraging extensive, existing validation packages on bioprocess systems and medical devices obtained following gamma irradiation, and essential in qualifying X-ray irradiation as an equivalent technology (i.e., materials are impacted to the same extent or less than gamma) that can overcome business continuity challenges to ensure continued availability of critical patient therapies.

The effects of SCARB2 and SELPLG gene polymorphisms on EV71 infection in hand, foot and mouth disease.

The same viral infection in different hosts may result in varying levels of clinical symptoms, which is related to the genetic background of the host itself. A total of 406 common cases and 452 severe cases of enterovirus 71 (EV71) infection in Yunnan Province were selected as the research subjects, and SNaPshot technology was used to detect genetic polymorphisms for 25 Tag single-nucleotide polymorphisms (TagSNPs) in the selectin P ligand (SELPLG) and scavenger receptor class B member 2 (SCARB2) genes. Our results demonstrate that SCARB2 polymorphisms (rs74719289, rs3733255 and rs17001551) are related to the severity of EV71 infection (A vs G: OR 0.330; 95% CI 0.115 - 0.947; T vs C: OR 0.336; 95% CI 0.118 - 0.958; and A vs G: OR 0.378; 95% CI 0.145 - 0.984). The SELPLG polymorphisms were not significantly different between common cases and severe cases. Therefore, we conclude that the SCARB2 gene has a protective effect on the course of hand, foot and mouth disease caused by EV71 infection and that SCARB2 gene mutations can reduce the severity of the disease.

The effects of SCARB2 and SELPLG gene polymorphisms on EV71 infection in hand, foot and mouth disease.

The same viral infection in different hosts may result in varying levels of clinical symptoms, which is related to the genetic background of the host itself. A total of 406 common cases and 452 severe cases of enterovirus 71 (EV71) infection in Yunnan Province were selected as the research subjects, and SNaPshot technology was used to detect genetic polymorphisms for 25 Tag single-nucleotide polymorphisms (TagSNPs) in the selectin P ligand (SELPLG) and scavenger receptor class B member 2 (SCARB2) genes. Our results demonstrate that SCARB2 polymorphisms (rs74719289, rs3733255 and rs17001551) are related to the severity of EV71 infection (A vs G: OR 0.330; 95% CI 0.115 - 0.947; T vs C: OR 0.336; 95% CI 0.118 - 0.958; and A vs G: OR 0.378; 95% CI 0.145 - 0.984). The SELPLG polymorphisms were not significantly different between common cases and severe cases. Therefore, we conclude that the SCARB2 gene has a protective effect on the course of hand, foot and mouth disease caused by EV71 infection and that SCARB2 gene mutations can reduce the severity of the disease.

A natural biological adhesive from snail mucus for wound repair.

The discovery of natural adhesion phenomena and mechanisms has advanced the development of a new generation of tissue adhesives in recent decades. In this study, we develop a natural biological adhesive from snail mucus gel, which consists a network of positively charged protein and polyanionic glycosaminoglycan. The malleable bulk adhesive matrix can adhere to wet tissue through multiple interactions. The biomaterial exhibits excellent haemostatic activity, biocompatibility and biodegradability, and it is effective in accelerating the healing of full-thickness skin wounds in both normal and diabetic male rats. Further mechanistic study shows it effectively promotes the polarization of macrophages towards the anti-inflammatory phenotype, alleviates inflammation in chronic wounds, and significantly improves epithelial regeneration and angiogenesis. Its abundant heparin-like glycosaminoglycan component is the main active ingredient. These findings provide theoretical and material insights into bio-inspired tissue adhesives and bioengineered scaffold designs.

Snail-inspired AFG/GelMA hydrogel accelerates diabetic wound healing via inflammatory cytokines suppression and macrophage polarization.

Diabetic foot ulcers (DFUs) are a severe and rapidly growing diabetic complication, but treating DFUs remains a challenge for the existing therapies are expensive and highly non-responsive. Recently, we discovered that a natural adhesive from snail mucus can promote skin wound healing. Herein, inspired by the finding, we developed a double-network hydrogel biomaterial that composed of snail glycosaminoglycan (AFG) and methacrylated gelatin (GelMA), in which AFG is the main bioactive component of snail mucus and GelMA provides a scaffold mimicking the proteins in snail mucus. The biomimetic hydrogel exhibited strong tissue adhesion, potent anti-inflammatory activity, and excellent biocompatibility. The biodegradable AFG/GelMA hydrogel markedly promoted chronic wound healing in both STZ-induced type 1 diabetic rat and db/db mouse models after a single treatment. Further mechanistic research showed that the hydrogel significantly attenuated inflammation by sequestrating pro-inflammatory cytokines, as well as downregulated their expression by inhibiting NF-ĸB signaling pathway, and it can also promote macrophage polarization to M2 phenotype. Taken together, the bioinspired hydrogel can effectively promote the transition of chronic wounds from inflammation to proliferation stage. These data suggest that the AFG/GelMA hydrogel is a promising therapeutic biomaterial for the treatment of chronic diabetic wounds.

Microplastic abundance and distribution in a Central Asian desert.

Microplastic pollution is widespread, affecting even the remotest places on Earth. However, observational data on microplastic deposition in deserts, which comprise 21% of the total land area, are relatively rare. The current study aims to address the knowledge gap in terms of microplastic distribution in Asian deserts. The Badain Jaran Desert in Central Asia is the second largest desert in China. We investigated microplastic distribution and deposition on dunes and lakes of this desert. Microplastics were extracted from surface sediments to determine their characteristics and polymer types by microscopic inspection and µ-FTIR. The abundance of microplastics (detection limit is approximately 40 µm) in the uninhabited area ranged from 0.7 ± 1.5 to 11.7 ± 15.5 items/kg, with an average of 6.0 ± 15.4 items/kg. Fragments and fibers accounted for 77% and 23% of the total microplastics, respectively. Epoxy resin (28%), polyethylene terephthalate (25%), phenoxy resin (25%), and polyamide (9%) were the main polymer components, whose sizes were concentrated at 50-200 µm. Back-trajectory modeling was then performed to explore the possible source direction of the microplastics. The results showed that the microplastics mainly originated from the populated areas southeast of the desert, indicating long-distance atmospheric transport and deposition in deserts. The desert-edge zone with some tourism activity contained more microplastics (8.2 ± 17.9 items/kg) than the non-tourism zone (0.9 ± 1.6 items/kg), indicating a potential contribution from tourism. The abundance in the non-tourism zone (0.9 items/kg) can be used as a reference for microplastic background values in the Central Asian deserts, as this value is critical for simulating and predicting global microplastic yields.

HA/MgO nanocrystal-based hybrid hydrogel with high mechanical strength and osteoinductive potential for bone reconstruction in diabetic rats.

Bone repair and regeneration processes are markedly impaired in diabetes mellitus (DM). Intervening approaches similar to those developed for normal healing conditions have been adopted to combat DM-associated bone regeneration. However, limited outcomes were achieved for these approaches. Hence, together with osteoconductive hydroxyapatite (HA) nanocrystals, osteoinductive magnesium oxide (MgO) nanocrystals were uniformly mounted into the network matrix of an organic hydrogel composed of cysteine-modified γ-polyglutamic acid (PGA-Cys) to construct a hybrid and rough hydrogel scaffold. It was hypothesized that the HA/MgO nanocrystal hybrid hydrogel (HA/MgO-H) scaffold can significantly promote bone repair in DM rats via the controlled release of Mg2+. The HA/MgO-H scaffold exhibited a sponge-like morphology with porous 3D networks inside it and displayed higher mechanical strength than a PGA-Cys scaffold. Meanwhile, the HA/MgO-H scaffold gradually formed a tough hydrogel with G' of more than 1000 Pa after hydration, and its high hydration swelling ratio was still retained. Moreover, after the chemical degradation of the dispersed MgO nanocrystals, slow release of Mg2+ from the hydrogel matrix was achieved for up to 8 weeks because of the chelation between Mg2+ and the carboxyl groups of PGA-Cys. In vitro cell studies showed that the HA/MgO-H scaffold could not only effectively promote the migration and proliferation of BMSCs but could also induce osteogenic differentiation. Moreover, in the 8th week after implanting the HA/MgO-H scaffold into femur bone defect zones of DM rats, more effective bone repair was presented by micro-CT imaging. The bone mineral density (397.22 ± 16.36 mg cm-3), trabecular thickness (0.48 ± 0.07 mm), and bone tissue volume/total tissue volume (79.37 ± 7.96%) in the HA/MgO-H group were significantly higher than those in the other groups. Moreover, higher expression of COL-I and OCN after treatment with HA/MgO-H was also displayed. The bone repair mechanism of the HA/MgO-H scaffold was highly associated with reduced infiltration of pro-inflammatory macrophages (CD80+) and higher angiogenesis (CD31+). Collectively, the HA/MgO-H scaffold without the usage of bioactive factors may be a promising biomaterial to accelerate bone defect healing under diabetes mellitus.

A dual PMMA/calcium sulfate carrier of vancomycin is more effective than PMMA-vancomycin at inhibiting Staphylococcus aureus growth in vitro.

Both antibiotic-impregnated poly(methyl acrylate, methyl methacrylate) (PMMA) and antibiotic-impregnated calcium sulfate have been successfully used as local antibiotic delivery vehicles for the management of chronic osteomyelitis. Here, we examined the antibiotic elution characteristics and antibacterial properties of a composite drug delivery system consisting of PMMA/calcium sulfate carrying vancomycin (dual carrier-v) against Staphylococcus aureus, with PMMA loaded with vancomycin (PMMA-v) as a control. Vancomycin gradually degraded from dual carrier-v and PMMA-v up to about 8 and 6 weeks, respectively. At different elution time points, the inhibition zones of the dual carrier-v were larger than the inhibition zones of the PMMA-v (P < 0.05). The colony inhibition rate of the dual carrier-v was 95.57%, whereas it was 77.87% for PMMA-v. Scanning electron microscopy was used to demonstrate biofilm formation on the surface of plates treated with vancomycin-unloaded PMMA, whereas there was no biofilm formation on the surface of plates treated with dual carrier-v or PMMA-v. The dual carrier-v was more effective at antibacterial adhesion at each time point after immersion in simulated body fluid as compared with PMMA-v (P < 0.05). In conclusion, our results suggest that the dual carrier-v can release higher concentrations of antibiotics and inhibit bacteria growth more effectively in vitro as compared with PMMA-v. The dual carrier-v thus may have potential as an alternative strategy for osteomyelitis management.

Localized Controlled Release of Bilirubin from ß-Cyclodextrin-Conjugated ε-Polylysine To Attenuate Oxidative Stress and Inflammation in Transplanted Islets.

Islet transplantation has been considered the most promising therapeutic option with the potential to restore the physiological regulation of blood glucose concentrations in type 1 diabetes treatment. However, islets suffer from oxidative stress and nonspecific inflammation in the early stage of transplantation, which attributed to the leading cause of islet graft failure. Our previous study reported that bilirubin exerted antioxidative and anti-inflammatory effects on hypothermic preserved islets, which inspire us to utilize bilirubin to address the survival issue of grafted islets. However, the application of bilirubin for islet transplantation is limited by its poor solubility and fast clearance. In this study, we designed a supramolecular carrier (PLCD) that could improve the solubility of bilirubin and slowly release bilirubin to protect islets after cotransplantation. PLCD was synthesized by conjugating activated ß-cyclodextrin (ß-CD) to the side chain of ε-polylysine (PLL) and acted as a carrier to load bilirubin via host-guest interactions. The constructed bilirubin supramolecular system (PLCD-BR) significantly improved the solubility and prolonged the action time of bilirubin. In vitro results confirmed that PLCD-BR coculture substantially enhanced the resistance of islets to excessive oxidative stress and proinflammatory stimulation and maximumly maintained the islet function. In vivo, PLCD could prolong drug duration at the transplant site, and the localized released bilirubin could protect the islets from oxidative stress and suppress the production of inflammatory cytokines. Crucially, islet transplantation with PLCD-BR significantly extended the stable blood glucose time of diabetic mice and produced a faster glucose clearance compared to those cotransplanted with free bilirubin. Additionally, immunohistochemical analysis showed that PLCD-BR had superior antioxidative and anti-inflammatory abilities and beneficial effects on angiogenesis. These findings demonstrate that the PLCD-BR has great potentials to support successful islet transplantation.

26Al/10Be Burial Dating of the Middle Pleistocene Yiyuan Hominin Fossil Site, Shandong Province, Northern China.

The Yiyuan hominin fossil site is one of the few localities in China where a partial skullcap and several loose teeth of Homo erectus have been discovered. Yiyuan was previously assigned broadly to the Middle Pleistocene by biostratigraphical correlation and ESR/U-series dating. Here, we report the first application of a radio-isotopic dating method to the site. 26Al/10Be burial dating results derived from two sand samples from the fossiliferous deposits show that the hominin fossils can be confidently dated to 0.64 ± 0.08 Ma (million years ago). The reliability of this age is supported by the zero age of modern fluvial sediment near the cave. Our result is consistent with the age estimation based on biostratigraphic correlation and supports the argument that the Yiyuan and Zhoukoudian Locality 1 H. erectus fossils are contemporaneous. The results presented here, along with other recent chronological studies on Chinese Middle Pleistocene hominin sites, indicate that the time span from 600-400 ka (thousand years ago) is a critical period for human evolution in East Asia. Importantly, this time bracket includes several major climatic changes that would have influenced hominins, both morphologically and behaviorally.

Characterization and antitumor efficacy of poly(L-lactid acid)-based etoposide-loaded implants.

Etoposide is widely used in the chemotherapy of a variety of malignancies. But the strong lipophilicity, poor bioavailability, and severe side effects of etoposide limit its clinical application. The aim of this study was to develop sustained-release etoposide-loaded implants and evaluate antitumor activity of the implants after intratumoral implantation. We prepared the implants containing etoposide, poly(L-lactid acid) and polyethylene glycol 4000 by the direct compression method. The implants were characterized regarding drug-excipient compatibility, content uniformity, morphology, sterility, in vitro, and in vivo release profiles. Then the antitumor activity of the implants was tested in xenograft model of A549 human non-small cell lung cancer. SEM images displayed smooth surface of the implant and indicated that etoposide was homogeneously dispersed in the polymeric matrix. The results of content uniformity met the requirements of the Chinese Pharmacopoeia. Both in vitro and in vivo release profiles of the implants were characterized by high burst release followed by sustained release of etoposide. Intratumoral implantation of etoposide-loaded implants could efficiently delay the tumor growth. Furthermore, increasing the dose of implants led to higher tumor suppression rate without adding systemic toxicity. These results indicated that etoposide-loaded implants have significant antitumor efficacy in xenograft model without dose-limiting side effects and they possess a strong potential to be used as an intratumoral chemotherapy option for lung cancer treatment.

A novel electrochemical biomimetic sensor based on poly(Cu-AMT) with reduced graphene oxide for ultrasensitive detection of dopamine.

A polymerized film of copper-2-amino-5-mercapto-1,3,4-thiadiazole (Cu(II)-AMT) complex (poly(Cu-AMT)) was successfully achieved via a simple and low-cost electrochemical methodology. Subsequently, a noncovalent nanohybrid of poly(Cu-AMT) with reduced graphene oxide (rGO) (rGO-poly(Cu-AMT)) was prepared through π-π stacking interaction as an efficient mimetic enzyme for the ultrasensitive and selective detection of dopamine (DA). The rGO-poly(Cu-AMT) nanocomposites showed considerable mimetic enzyme catalytic activity, which may be attributed to the significant promotion of the electron transfer between the substrate and graphene-based carbon materials, and also the synergistic electrocatalytic effect in mimetic enzyme between rGO sheet and poly(Cu-AMT). The electrocatalytic and sensing performances of the biomimetic sensor based on the rGO-poly(Cu-AMT) nanocomposites were evaluated in detail. The biomimetic sensor enables a reliable and sensitive determination of DA with a linear range of 0.01-40µM and a detection limit of 3.48nM at a signal-to-noise ratio of 3. In addition, we applied the proposed method to detect DA in real sample with satisfactory results. Accordingly, the rGO-poly(Cu-AMT) is one of the promising mimetic enzyme for electrocatalysis and biosensing.

Enhanced antitumor efficacy of poly(D,L-lactide-co-glycolide)-based methotrexate-loaded implants on sarcoma 180 tumor-bearing mice.

PURPOSE: Methotrexate is widely used in chemotherapy for a variety of malignancies. However, severe toxicity, poor pharmacokinetics, and narrow safety margin of methotrexate limit its clinical application. The aim of this study was to develop sustained-release methotrexate-loaded implants and evaluate antitumor activity of the implants after intratumoral implantation. MATERIALS AND METHODS: We prepared the implants containing methotrexate, poly(D,L-lactide-co-glycolide), and polyethylene glycol 4000 with the melt-molding technique. The implants were characterized with regards to drug content, morphology, in vitro, and in vivo release profiles. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were carried out to investigate the physicochemical properties of the implants. Furthermore, the antitumor activity of the implants was tested in a sarcoma 180 mouse model. RESULTS: The implants were prepared as solid rods. Scanning electron microscopy images showed a smooth surface of the implant, suggesting that methotrexate was homogeneously dispersed in the polymeric matrix. The results of DSC and FTIR indicated that no significant interaction between methotrexate and the polymer was observed in the implants. Both in vitro and in vivo release profiles of the implants were characterized by burst release followed by sustained release of methotrexate. Intratumoral implantation of methotrexate-loaded implants could efficiently delay tumor growth. Moreover, an increase in the dose of implants led to a higher tumor suppression rate without additional systemic toxicity. CONCLUSION: These results demonstrate that methotrexate-loaded implants had significant antitumor efficacy in a sarcoma 180 mouse model without dose-limiting side effects, and suggest that the implants could be potentially applied as an intratumoral delivery system to treat cancer.