Sex-based influential factors for dental caries in patients with schizophrenia.

BACKGROUND: Schizophrenia is a common mental disorder that seriously affects patients' daily lives and brings heavy psychological and economic burdens to their families and society. The oral problems of patients with schizophrenia are gradually gaining attention, among which dental caries are among the most common oral diseases. Sex differences may be related not only to the various clinical symptoms of schizophrenia but also to different oral hygiene statuses; therefore, the main purpose of this paper is to investigate sex differences related to influencing factors for dental caries in patients with schizophrenia. METHOD: Inpatients with schizophrenia over 18 years old were included in this study, and multidimensional indicators such as demographics, symptom and cognitive impairment assessments, medications, and the caries index of decayed, missing, and filled teeth (DMFT) were collected. An analysis of sex-based influential factors for dental caries in schizophrenia patients was performed. RESULTS: Four-hundred and ninety-six patients with schizophrenia were included, with a mean age of 46.73 ± 12.23 years, of which 142 were females and 354 were males. The mean DMFT was significantly higher in males (8.81 ± 8.50) than in females (5.63 ± 6.61, p < 0.001), and the odd ratio of caries in males to females was significantly higher as well (OR = 2.305, p < 0.001). The influential factors of caries in male patients were independently associated with age and smoking status, in which current smokers were at the highest risk for developing caries, and different smoking statuses had various influencing factors for caries. The influencing factors for caries in female patients were independently associated with age, antipsychotic dose, PANSS-positive symptoms, and MMSE levels. CONCLUSION: Our findings suggest sex differences exist among influential factors for caries in patients with schizophrenia. These risk factors may even be associated with and affect the treatment and prognosis of psychiatric symptoms in patients. Therefore, oral hygiene management of patients with schizophrenia should be enhanced. These differential factors provide new visions and ideas for formulating individual interventions, treatments, and care priorities.

A novel mutation of LRSAM1 in a Chinese family with Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (CMT) disease is the most common inherited peripheral neuropathy characterized by progressive distal muscle weakness and atrophy with decreased or absent tendon reflexes. Mutations in LRSAM1 have been identified to cause CMT disease type 2P. We report a novel LRSAM1 mutation c.2021-2024del (p.E674VfsX11) in a Chinese autosomal dominant CMT disease type 2 family. The phenotype was characterized by late onset and mild sensory impairment. Electrophysiological findings showed normal or mildly to moderately reduced motor and sensory nerve conduction velocities in lower and upper limb nerves.

Assessment of acute inhalation toxicity of citric acid and sodium hypochlorite in rats.

BACKGROUND: Citric acid (CA) and sodium hypochlorite (NaOCl) have been used to disinfect animals to protect them against avian influenza and foot-and-mouth disease. OBJECTIVES: We performed a good laboratory practice (GLP)-compliant animal toxicity study to assess the acute toxic effects of CA and NaOCl aerosol exposure in Sprague-Dawley rats. METHODS: Groups of five rats per sex were exposed for 4 h to four concentrations of the two chemicals, i.e., 0.00, 0.22, 0.67, and 2.00 mg/L, using a nose-only exposure. After a single exposure to the chemicals, clinical signs, body weight, and mortality was observed during the observation period. On day 15, an autopsy, and then gross findings, and histopathological analysis were performed. RESULTS: After exposure to CA and NaOCl, body weight loss was observed but recovered. Two males died in the CA 2.00 mg/L group and, two males and one female died in the 2.00 mg/L NaOCl group. In the gross findings and histopathological analysis, discoloration of the lungs was observed in the CA exposed group and inflammatory lesions with discoloration of the lungs were observed in the NaOCl exposed group. These results suggest that the lethal concentration 50 (LC50) of CA is 1.73390 mg/L for males and > 1.70 mg/L for females. For NaOCl, the LC50 was 2.22222 mg/L for males and 2.39456 mg/L for females. CONCLUSIONS: The Globally Harmonized System is category 4 for both CA and NaOCl. In this study, the LC50 results were obtained through a GLP-based acute inhalation toxicity assessment. These results provide useful data to reset safety standards for CA and NaOCl use.

The association between sex hormones and periodontitis among American adults: A cross-sectional study.

Introduction: After adulthood, as a person grows older, the secretion of sex hormones in the body gradually decreases, and the risk of periodontitis increases. But the relationship between sex hormones and periodontitis is still controversial. Methods: We investigated the association between sex hormones and periodontitis among Americans over 30 years old. 4,877 participants containing 3,222 males and 1,655 postmenopausal females who had had periodontal examination and detailed available sex hormone levels, were included in our analysis from the 2009-2014 National Health and Nutrition Examination Surveys cycles. We applied multivariate linear regression models to estimate the connection between sex hormones and periodontitis after converting sex hormones into categorical variables through tertile. Additionally, to ensure the stability of the analysis results, we carried out a trend test, subgroup analysis, and interaction test. Results: After fully adjusting the covariates, estradiol levels were not associated with periodontitis in both males and females with a P for trend = 0.064 and 0.064, respectively. For males, we found that sex hormone-binding globulin was positively associated with periodontitis (tertile3 vs tertile1: OR=1.63, 95% CI=1.17-2.28, p = 0.004, P for trend = 0.005). Congruously, free testosterone (tertile3 vs tertile1: OR=0.60, 95% CI=0.43-0.84, p = 0.003), bioavailable testosterone (tertile3 vs tertile1: OR=0.51, 95% CI=0.36-0.71, p < 0.001), and free androgen index (tertile3 vs tertile1: OR=0.53, 95% CI=0.37-0.75, p < 0.001) was found to be negatively associated with periodontitis. Moreover, subgroup analysis of age found a closer relationship between sex hormones and periodontitis in those younger than 50 years. Conclusion: Our research suggested that males with lower bioavailable testosterone levels affected by sex hormone-binding globulin were at a higher risk of periodontitis. Meanwhile, estradiol levels were not associated with periodontitis in postmenopausal women.

Relationship between alveolar-bone morphology at the mandibular incisors and their inclination in adults with low-angle, skeletal class III malocclusion-A retrospective CBCT study.

OBJECTIVE: To quantitatively study the effect of the labial inclination of the mandibular central incisors on the surrounding cortical and cancellous-bone morphology among patients with low-angle, skeletal class III malocclusion, by using cone-beam computed-tomography (CBCT) imaging. MATERIALS AND METHODS: The CBCT images of 60 patients with low-angle, skeletal class III malocclusion were divided into lingual-inclination, upright, and labial-inclination groups. The height of the alveolar bone and the thickness and area of the cortical, cancellous, and total alveolar bone were measured separately on each side of the mandibular central incisors. RESULTS: The thickness of the labial cortical bone from 6 mm below the cementoenamel junction (CEJ) to the root apex; the thickness of the labial cancellous bone at the root apex; the total thickness of the alveolar bone at the root apex; the area of labial cortical bone; the total area of labial alveolar bone; and the height of the labial alveolar bone were highest in the labial-inclination group (all P<0.05). All these variables were positively correlated with the labial inclination of the mandibular central incisors (all P<0.05). There were no statistical differences between the groups for any of the measurements on the lingual side of the teeth (P>0.05). CONCLUSION: The morphology of the alveolar bone on the labial but not the lingual side of the mandibular central incisors was statistically significantly correlated with the labial inclination of those teeth in patients with low-angle, skeletal class III malocclusion.

Acoustic triggered nanobomb for US imaging guided sonodynamic therapy and activating antitumor immunity.

We fabricated an ultrasound activated 'nanobomb' as a noninvasive and targeted physical therapeutic strategy for sonodynamic therapy and priming cancer immunotherapy. This 'nanobomb' was rationally designed via the encapsulation of indocyanine green (ICG) and perfluoropentane (PFP) into cRGD peptide-functionalized nano-liposome. The resulting Lip-ICG-PFP-cRGD nanoparticle linked with cRGD peptide could actively targeted ID8 and TC-1 cells and elicits ROS-mediated apoptosis after triggered by low-intensity focused ultrasound (LIFU). Moreover, the phase change of PFP (from droplets to microbubbles) under LIFU irradiation can produce a large number of microbubbles, which act as intra-tumoral bomber and can detonate explode tumor cells by acoustic cavitation effect. Instant necrosis of tumor cells further induces the release of biologically active damage-associated molecular patterns (DAMPs) to facilitate antitumor immunity. More important, the 'nanobomb' in combination with anti-PD-1checkpoint blockade therapy can significantly improve the antitumor efficacy in a subcutaneous model. In addition, the liposomes may also be used as an imaging probe for ultrasound (US) imaging after being irradiated with LIFU. In summary, the US imaging-guided, LIFU activated ROS production and explosion 'nanobomb' might significantly improve the antitumor efficacy and overcome drug resistance through combination of SDT and immunotherapy, we believe that this is a promising approach for targeted therapy of solid tumor including ovarian cancer.

Targeted Wolfram-Doped Polypyrrole for Photonic Hyperthermia-Synergized Radiotherapy.

Single ionizing radiation at a tolerable dose is ineffectual in eliminating malignancies but readily generates harmful effects on surrounding normal tissues. Herein, we intelligently fabricated novel wolfram-doped polypyrrole (WPPy) through a simple oxidative polymerization method with WCl6 as an oxidizing catalyst, which possessed good biocompatibility, high photothermal conversion, and intensive radiosensitivity capacities to concurrently serve as a photothermal reagent and a radiosensitizer for hyperthermia-synergized radiotherapy (RT) against a malignant tumor. In comparison with traditional polypyrrole without noble metal doping, the innovative introduction of WCl6 not only successfully launched the polymerization of a pyrrole monomer but also endowed WPPy with additional radiosensitization. More importantly, after further decoration with an active targeted component (SP94 polypeptide), the obtained WPPy@SP94 significantly increased tumor internalization and accumulation in vitro and in vivo and induced obvious DNA damage as well as robust ROS generation under X-ray irradiation, which meanwhile synergized with strong photonic hyperthermia to effectively inhibit tumor growth by single drug injection. Moreover, such biocompatible WPPy@SP94 showed negligible adverse effects on normal cells and tissues. WPPy@SP94 developed in this study not only expands the category of polypyrrole chemical syntheses but also sheds light on WPPy@SP94-based radiosensitizers for cancer RT.

Prevalence and Clinical Correlation of Decayed, Missing, and Filled Teeth in Elderly Inpatients With Schizophrenia.

Introduction: Schizophrenia is a mental disease with a profound impact on human health. Patients with schizophrenia have poor oral hygiene, increasing their risk of systemic diseases, such as respiratory infections, and declining their quality of life. Therefore, this study aims to assess the oral health status of inpatients with schizophrenia, analyze its related factors, and thus provide scientific evidence for further exploration of corresponding control strategies. Methods: A total of 425 inpatients older than 50 years with a diagnosis of schizophrenia from two psychiatric hospitals (mean age 58.49 ± 5.72 years) were enrolled. The demographic data of the patients were checked on admission. Two independent dentists examined caries, missing teeth, and fillings. Mini-Mental State Examination (MMSE) and Global Deterioration Scale were performed as cognitive tests. Positive and Negative Syndrome Scale and Repeatable Battery for the Assessment of Neuropsychological Status rating scale were used to determine their mental status. Results: The average decayed, missing, and filled teeth index was 12.99 ± 8.86. Linear regression analysis showed that the decayed, missing, and filled teeth index had a significantly positive relationship with age (p < 0.001) and smoking (p < 0.001) and a negative relationship with MMSE (p = 0.029). The missing teeth index had a positive relationship with age (p < 0.001), smoking (p < 0.001), and Global Deterioration Scale (p = 0.014) and a negative relationship with MMSE (p = 0.004). Conclusion: The oral health of elderly patients with schizophrenia is poor, which may be related to the cognitive level of patients and affect their quality of life. The focus should be provided to the oral care of patients with schizophrenia, and investment in their specialized oral treatment should be increased.

iRGD Co-Administration with Paclitaxel-Loaded PLGA Nanoparticles Enhance Targeting and Antitumor Effect in Colorectal Cancer Treatment.

OBJECTIVE: To explore the targeting effect of PLGA-NP and iRGD co-administration with PTXPLGA NP (PTX-PLGA + iRGD) on colorectal cancer. METHODS: Whether PLGA-NP co-administration with iRGD peptide could show effective tumor-targeting ability in contrast to with PLGA-NP in colorectal cancer mice models was evaluated. Moreover, the chemotherapeutics Paclitaxel (PTX) was loaded into the PLGA-NP to impart anti-tumor efficiency to the PTX-PLGA. Whether iRGD co-administration with PTX-PLGA NP (PTX-PLGA + iRGD) in colorectal cancer models enabled PTX to achieve better anti-tumor efficiency and biocompatibility was further assessed. RESULTS: The targeting ability of PLGA-NP was enhanced in cell experiment and colorectal cancer mice models by co-administration of iRGD. As a result, PTX-PLGA + iRGD achieved better anti-tumor efficacy than PTX and PTX-PLGA. Conlusion: The nanocarrier based on PLGA with specific targeting ability could promote the clinical application of various chemotherapeutics similar to PTX. The combination of drug-loaded nanoparticles and iRGD could develop into a promising drug delivery system.

Combined inferior alveolar nerve block anaesthesia and local infiltration anaesthesia in extraction of impacted mandibular third molars: a randomised controlled trial.

Aim To compare the anaesthetic effect of combination of inferior alveolar nerve block anaesthesia and local infiltration anaesthesia with nerve block anaesthesia techniques in the extraction of mandibular third molars.Materials and methods One hundred and fifty healthy adult volunteers were divided into three groups and were administered three different local anaesthetic techniques before tooth extractions: group A (inferior alveolar nerve, lingual nerve and buccal nerve block anaesthesia with lidocaine), group B (inferior alveolar nerve, lingual nerve and buccal nerve block anaesthesia with mepivacaine) and group C (inferior alveolar nerve block anaesthesia with lidocaine and infiltration anaesthesia with mepivacaine). The patients' reported pain on anaesthesia injection and tooth extraction, the surgeon's assessment of anaesthetic effect, the severity of intra-operative bleeding and post-operative complications were evaluated.Results There was no significant difference in visual analogue scale (VAS)-pain of anaesthesia among the three groups. Compared with groups A and B, group C had reduced VAS-pain of tooth extraction scores. Additionally, the surgeon's assessment of anaesthetic effect improved and intra-operative bleeding decreased.Conclusions The combination of inferior alveolar nerve block and infiltration anaesthesia provides a stronger anaesthetic effect in the extraction of mandibular third molars.

pH-Responsive Artesunate Polymer Prodrugs with Enhanced Ablation Effect on Rodent Xenograft Colon Cancer.

PURPOSE: In this study, pH-sensitive poly(2-ethyl-2-oxazoline)-poly(lactic acid)-poly(ß-amino ester) (PEOz-PLA-PBAE) triblock copolymers were synthesized and were conjugated with an antimalaria drug artesunate (ART), for inhibition of a colon cancer xenograft model. METHODS: The as-prepared polymer prodrugs are tended to self-assemble into polymeric micelles in aqueous milieu, with PEOz segment as hydrophilic shell and PLA-PBAE segment as hydrophobic core. RESULTS: The pH sensitivity of the as-prepared copolymers was confirmed by acid-base titration with pKb values around 6.5. The drug-conjugated polymer micelles showed high stability for at least 96 h in PBS and 37°C, respectively. The as-prepared copolymer prodrugs showed high drug loading content, with 9.57%±1.24% of drug loading for PEOz-PLA-PBAE-ART4. The conjugated ART could be released in a sustained and pH-dependent manner, with 92% of released drug at pH 6.0 and 57% of drug released at pH 7.4, respectively. In addition, in vitro experiments showed higher inhibitory effect of the prodrugs on rodent CT-26 cells than that of free ART. Animal studies also demonstrated the enhanced inhibitory efficacy of PEOz-PLA-PBAE-ART2 micelles on the growth of rodent xenograft tumor. CONCLUSION: The pH-responsive artesunate polymer prodrugs are promising candidates for colon cancer adjuvant therapy.

Microarray-based analysis of the lung recovery process after stainless-steel welding fume exposure in Sprague-Dawley rats.

Repeated exposure to welding fumes promotes a reversible increase in pulmonary disease risk, but the molecular mechanisms by which welding fumes induce lung injury and how the lung recovers from such insults are unclear. In the present study, pulmonary function and gene-expression profiles in the lung were analyzed by Affymetrix GeneChip microarray after 30 days of consecutive exposure to manual metal arc welding combined with stainless-steel (MMA-SS) welding fumes, and again after 30 days of recovery from MMA-SS fume exposure. In total, 577 genes were identified as being either up-regulated or down-regulated (over twofold changes, p < 0.05) in the lungs of low-dose or high-dose groups. Differentially expressed genes were classified based on a k-means clustering algorithm and biological functions and molecular networks were further analyzed using Ingenuity Pathways Analysis. Among the genes affected by exposure to or recovery from MMA-SS fumes, the transcriptional changes of 13 genes that were highly altered by treatment were confirmed by quantitative real-time PCR. Notably, Mmp12, Cd5l, Ccl7, Cxcl5, and Spp1 related to the immune response were up-regulated only in the exposure group, whereas Trem2, IgG-2a, Igh-1a, and Igh were persistently up-regulated in both the exposure and recovery groups. In addition, several genes that might play a role in the repair process of the lung were up-regulated exclusively in the recovery group. Collectively, these data may help elucidate the molecular mechanism of the recovery process of the lung after welding fume exposure.

Recurrent exposure to welding fumes induces insufficient recovery from inflammation.

Previous studies on welding-fume-induced lung fibrosis have indicated that recovery is possible when the degree of exposure is short-term and moderate. However, this study investigated the recovery after recurrent exposure to welding fumes, as welders are invariably re-exposed to welding fumes after recovering from radiographic pneumoconiosis. Thus, to investigate the disease and recovery processes of welding-fume-induced pneumoconiosis in the case of recurrent welding-fume exposure, rats were exposed to manual metal arc-stainless steel (MMA-SS) welding fumes with a total suspended particulate (TSP) concentration of 51.4 +/- 2.8 mg/m(3) (low dose) or 84.6 +/- 2.9 mg/m(3) (high dose) for 2 h/day in an inhalation chamber for 1 mo and then allowed to recover from the inflammation for 1 mo. Thereafter, the rats were exposed again to MMA-SS with a TSP concentration of 44.1 +/- 8.8 mg/m(3) (low dose) or 80.1 +/- 9.8 mg/m(3) (high dose) for another 30 d and then allowed to recover from the inflammation for 1 mo. The recovery from the first exposure was then compared with that from the second exposure. The first and second exposures to MMA-SS welding fumes were found to produce significant increases in the lung weights and inflammatory parameters, including total cell numbers, alveolar macrophages (AMs), polymorphonuclear cells (PMNs), lymphocytes, and lactate dehydrogenase (LDH) in the bronchoalveolar lavage fluid (BALF) when compared with the unexposed controls. Following the first and second recovery, a significant reduction in inflammatory parameters of BALF was observed between the exposure and recovery groups. Histopathological observations showed foamy or pigmented macrophage accumulation, cellular debris, or pigment from burst macrophages after the first or second exposure. Following the first or second recovery, cellular debris or pigment from burst macrophages was cleared away from the lungs and accumulation of foamy or pigmented macrophages was decreased when compared to previous exposure. Reactive hyperplasia was noticed after second exposure or either recovery. However, significant differences were observed between the first and second exposure or the first and second recovery. In particular, the number of PMNs was significantly higher after the second exposure than after the first exposure. Also, all cell types in the BALF were significantly elevated in the high-dose second recovery group than in the first recovery group, indicating an incomplete recovery from second exposure. In conclusion, these results indicated that the lung damage caused by the second welding-fume exposure was more difficult to recover from than the first exposure.

Poor oral health in patients with schizophrenia: A systematic review and meta-analysis.

Increased rates of comorbid physical illness have been commonly reported in patients with schizophrenia. However, there are fewer data on dental disease in these patients. We systematically evaluated existing data on the oral health survey of schizophrenia patients through meta-analysis. Using the available databases, we performed a systematic search to identify the studies examining the oral health in schizophrenia patients from January 1997 to June 2017, based on the inclusion and exclusion criteria. Two investigators extracted the related data independently. The meta-analysis was performed by using the RevMan 5.3 software after data extraction and quality assessment. We compared the oral health results between the schizophrenia patients and the general population, including the following measures: the mean number of decayed, missing and filled teeth (DMFT). Eight studies comprising 2640 patients with schizophrenia and 19,698 healthy controls were included in the meta-analysis. The patients with schizophrenia had significantly higher scores of dental caries (mean difference [MD] = 7.77, 95% confidence interval [CI] = 3.27 to 12.27), missing teeth (MD = 7.61, 95% CI = 3.44 to 11.77), and decayed teeth (MD = 3.44, 95% CI = 2.06 to 4.82) compared to controls (all p < 0.01). By contrast, the schizophrenia patients had fewer score of filled teeth (MD = -3.06, 95% CI, -4.82 to -1.30) than the controls (p < 0.01), indicating decreased access to dental care. Our systematic review suggests that patients with schizophrenia have worse oral health than the general population, but have received less dental care services. Hence, the oral health services should be taken into account in the patients with schizophrenia.

Facile Optimization and Evaluation of PEG-PCL Block Copolymeric Nanoparticles for Anticancer Drug Delivery Using Copolymer Hybrids and Histoculture Drug Response Assays.

The traditional method of optimizing poly(ethyleneglycol)-polycaprolactone (PEG-PCL) copolymers for drug delivery requires high reaction temperatures, long reaction times, and various organic reagents. Furthermore, the in vivo evaluations of the antitumor effects of these drug delivery systems are time consuming, with animal sacrifice, and negative environmental effects. In this paper, nanoparticles (NPs) prepared from PEG-PCL/PCL hybrids were obtained by mixing PEG-PCL and PCL copolymer in different proportions and used to deliver cisplatin, a widely used anticancer drug. Histoculture drug response assay (HDRA), a predictive method typically used to evaluate chemosensitivity, was applied to evaluate the in vivo antitumor potencies of the NPs. The PEG-PCL and PCL proportions of the PEG-PCL/PCL hybrid were found to affect the NP diameter, drug loading content, encapsulation efficiency, stability, in vitro release properties, in vitro cytotoxicity, and antitumor effect in HDRA. The optimal NPs exhibited a satisfactory antitumor effect along with comparatively low side effects during an in vivo study in a murine model. The results reveal that PEG-PCL/PCL hybrids and HDRA can be used to conveniently and easily optimize and evaluate NPs prepared from block copolymers.

Treatment outcomes after reduction of the target volume of intensity-modulated radiotherapy following induction chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: A prospective, multi-center, randomized clinical trial.

PURPOSE: To investigate whether reducing the target volume of intensity-modulated radiotherapy (IMRT) after induction chemotherapy (IC) improves the quality of life (QOL) in locoregionally advanced nasopharyngeal carcinoma (NPC) without decreasing the local control and survival rate. PATIENTS AND METHODS: A total number of 212 NPC patients staged as III-IVb were randomly assigned to group A (n=97) or group B (n=115) in this prospective clinical trial. All patients received IC followed by cisplatin concurrent with IMRT. IMRT was planned using the images of pre-IC in group A and post-IC in group B. RESULTS: The dose received by normal tissues in group B was lower than that of group A (P<0.05). The recovery of the dry mouth symptoms in group B was significantly improved than group B. The quality of life (QOL) scores in group B were higher than group A. With a median follow-up of 35months, the 1-year estimated overall survival (OS), progression-free survival (PFS), locoregional failure-free survival (LRFFS), distant metastasis-free survival (DMFS) in group A versus group B were 97.9% vs 97.3%, 90.7% vs 92,2%, 99.0% vs 98.2%, 91.8% vs 94.8%. The 2-year OS, PFS, LRFFS, DMFS in group A versus group B were 93.7% vs 92.9%, 83.4% vs 84.3%, 96.8% vs 95.5%, 86.5% vs 89.5%. The 3-year OS, PFS, LRFFS, DMFS in group A versus group B were 82.3% vs 87%, 74.7% vs 83.4%, 91.8 vs 93.9%, 81.3% vs 88.6%, respectively. CONCLUSION: Reducing the IMRT target volume after IC did not reduce the local control and survival rate in locoregionally advanced NPC but the doses received by normal tissues were decreased, and the QOL scores were improved.

Development of an epitope-blocking-enzyme-linked immunosorbent assay to differentiate between animals infected with and vaccinated against foot-and-mouth disease virus.

An epitope-blocking ELISA (EB-ELISA) was developed to distinguish animals infected with foot-and-mouth-disease (FMDV) from those immunized with commercial vaccines. The assay used monoclonal antibodies to target the 3B core repeat motif (QKPLK) and purified recombinant 3AB proteins from the major B cell line epitopes of FMDV. Sera from uninfected and regularly vaccinated cattle, pigs, goats, and sheep (raised in FMDV free areas) were screened to evaluate the specificity of the EB-ELISA. The specificity scores of the assays were 99.8-100% and 100%, respectively. Reference sera from cattle, pigs, goats, and sheep experimentally infected with FMDV tested positive, with only a single exception. Antibodies formed in response to FMDV 3B appeared 1 week after infection and persisted at high levels for more than 8 weeks within the sera collected from serial bleeding of animals infected with FMDV O/SKR/2000. The EB-ELISA was used to differentiate between farms vaccinated against and those infected with FMDV (FMDV Asia serotype) during the 2005 epidemic in Mongolia by detecting antibodies against the FMDV Asia serotype in outbreak farms. This EB-ELISA method shows promise as an effective tool for FMDV control and eradication.

Novel thermosensitive polymeric micelles for docetaxel delivery.

Targeted delivery of antitumor drugs triggered by hyperthermia has significant advantages in clinical applications, since it is easy to implement and side effects are reduced. To release drugs site-specifically upon local heating often requires the drugs to be loaded into a thermosensitive polymer matrix with a low critical solution temperature (LCST) between 37 and 42 degrees C. However, the LCSTs of most thermosensitive materials were below 37 degrees C, which limits their application in clinic because they would precipitate once injected into human body and lost thermal targeting function. Herein, we prepared a novel thermosensitive copolymer (poly(N-isopropylacrylamide-co-acrylamide)-b-poly (DL-lactide)) that exhibits no obvious physical change up to 41 degrees C when heated. Docetaxel loaded micelles made of such thermosensitive polymer were prepared by dialysis method and the maximum loading content was found to be up to 27%. The physical properties, such as structure, morphology, and size distribution of the micelles with and without docetaxel were investigated by NMR, X-ray diffraction, dynamic light scattering, atomic force microscopy, etc. The efficacy of this drug delivery system was also evaluated by examining the proliferation inhibiting activity against different cell lines in vitro. After hyperthermia, the cytotoxicity of docetaxel-loaded micelles increased prominently. Our results demonstrated that this copolymer could be an ideal candidate for thermal targeted antitumor drug delivery.

Gambogic acid-loaded biomimetic nanoparticles in colorectal cancer treatment.

Gambogic acid (GA) is expected to be a potential new antitumor drug, but its poor aqueous solubility and inevitable side effects limit its clinical application. Despite these inhe rent defects, various nanocarriers can be used to promote the solubility and tumor targeting of GA, improving antitumor efficiency. In addition, a cell membrane-coated nanoparticle platform that was reported recently, unites the customizability and flexibility of a synthetic copolymer, as well as the functionality and complexity of natural membrane, and is a new synthetic biomimetic nanocarrier with improved stability and biocompatibility. Here, we combined poly(lactic-co-glycolic acid) (PLGA) with red blood-cell membrane (RBCm), and evaluated whether GA-loaded RBCm nanoparticles can retain and improve the antitumor efficacy of GA with relatively lower toxicity in colorectal cancer treatment compared with free GA. We also confirmed the stability, biocompatibility, passive targeting, and few side effects of RBCm-GA/PLGA nanoparticles. We expect to provide a new drug carrier in the treatment of colorectal cancer, which has strong clinical application prospects. In addition, the potential antitumor drug GA and other similar drugs could achieve broader clinical applications via this biomimetic nanocarrier.

Polyglycerolated nanocarriers with increased ligand multivalency for enhanced in vivo therapeutic efficacy of paclitaxel.

Despite the excellent biocompatibility and antifouling effect of poly(ethylene glycol) (PEG), the high steric hindrance, limited chemical functionality, and low ligand multivalency of PEGylated nanocarriers often lead to inefficient cell targeting and intracellular trafficking. Hence, a new structure of hydrophilic corona allowing a higher ligand density without loss of excellent biocompatibility is highly desirable. Here we introduce tumor-targeted polyglycerolated (PGylated) nanocarriers that dramatically enhance the in vivo therapeutic efficacy of incorporated paclitaxel simply by increasing the surface density of hydrophobic tumor-targeting ligands. Linear polyglycerol-poly (ε-caprolactone) block copolymer (PG-b-PCL) is used to prepare PGylated lipiodol nanoemulsions, where PG serves as a corona conjugated with a large number of folic acid (FA) for efficient tumor targeting. Unlike FA-PEGylated nanoemulsions, FA-PGylated nanoemulsions can display a larger number of FA without structural destabilization. This property enables excellent anti-cancer activities and effective tumor regression in a cervical cancer xenograft murine model at a cumulative drug dose of ∼5 mg kg-1, which is about four fold smaller than that of commercial Taxol formulation. This study highlights the importance of surface chemistry of nanocarriers that enable multivalent ligand functionalization and high tolerance to the conjugation of hydrophobic ligands, which make PG as a very effective hydrophilic corona for in vivo drug delivery.