Thermo-responsive magnetic liposomes for hyperthermia-triggered local drug delivery.

We prepared and characterised thermo-responsive magnetic liposomes, which were designed to combine features of magnetic targeting and thermo-responsive control release for hyperthermia-triggered local drug delivery. The particle size and zeta-potential of the thermo-responsive magnetic ammonium bicarbonate (MagABC) liposomes were about 210 nm and -14 mV, respectively. The MagABC liposomes showed encapsulation efficiencies of about 15% and 82% for magnetic nanoparticles (mean crystallite size 12 nm) and doxorubicin (DOX), respectively. The morphology of the MagABC liposomes was visualised using transmission electron microscope (TEM). The MagABC liposomes showed desired thermo-responsive release. The MagABC liposomes, when physically targeted to tumour cells in culture by a permanent magnetic field yielded a substantial increase in intracellular accumulation of DOX as compared to non-magnetic ammonium bicarbonate (ABC) liposomes. This resulted in a parallel increase in cytotoxicity for DOX loaded MagABC liposomes over DOX loaded ABC liposomes in tumour cells.

Radiographic analysis of PEEK cage and FRA in adult spinal deformity fused to sacrum.

STUDY DESIGN: Retrospective radiographic study. OBJECTIVE: To radiographically evaluate sagittal plane profile and fusion rates of polyetheretherketone (PEEK) cages versus femoral ring allografts (FRAs) in patients with adult spinal deformity fused to the sacrum. SUMMARY OF BACKGROUND DATA: FRAs have been widely used in various degenerative lumbar spine disorders and in adult deformity to achieve interbody fusions with promising results. PEEK cages have gained increasing popularity of late; however, there is little documentation to the radiographic comparisons between PEEK cages and FRAs used in patients with adult spine deformity treated with long fusions to the sacrum. METHODS: From March 2006 to February 2010, we analyzed 48 patients (mean age, 56.3±13.9 y) of 61 consecutive adult patients with global coronal and sagittal adult spine deformities who underwent first stage ALIF using PEEK cages or FRAs at L4-L5, L5-S1 segments followed by long (>6 levels) posterior instrumentation. PEEK cages and FRAs were used randomly according to surgeon's preference. Two independent observers retrospectively evaluated preoperative and postoperative disk height, foraminal height, segmental lordosis, and the interbody fusion rates at different postoperative intervals. RESULTS: Both PEEK cages and FRAs significantly (P<0.05) maintained disk space height at all follow-up times. PEEK cages maintained foraminal height and segmental lordosis, especially at L4-L5 better than FRAs at the final follow-up. At the final follow-up, PEEK cages achieved 94.9% of fusion rate, which was significantly (P<0.05) superior to FRA (84.2%), and PEEK cages were superior to FRAs in attaining earlier solid fusion. The Prolo functional scores of FRAs or/and PEEK cages were significantly improved at the final follow-up and did not show a significant difference between them. CONCLUSIONS: Both PEEK cages and FRAs can significantly increase disk space height and achieve similar clinical outcomes in treating adult spinal deformity fused to the sacrum. The radiographic results of PEEK cages were superior to FRAs in terms of an earlier solid fusion, and greater restoration of segmental lordosis.

Decreased expression of MDR1 in PEG-conjugated hemoglobin solution combined cisplatin treatment in a tumor xenograft model.

This study aims to examine the contribution of PEG-conjugated hemoglobin combined with cisplatin to the expression of HIF-1α and MDR1 in a tumor xenograft model. Cervical carcinoma models were assigned to 4 groups and treated respectively: group 1(control); group 2, cisplatin; group 3, PEG-Hb; group 4 cisplatin plus PEG-Hb. 4 weeks later, tumor volume and MVD was significantly decreased in group 4 compared with other groups. Lower expression of HIF-1α and MDR1 were detected in group4. Taken together, our data indicated that PEG-Hb plus cisplatin can promote tumor tissue oxygenation and enhance the chemotherapy sensitivity. HIF-1α regulated MDR1 pathway correlated with this process.

Artificial protein block polymer libraries bearing two SADs: effects of elastin domain repeats.

We have generated protein block polymer E(n)C and CE(n) libraries composed of two different self-assembling domains (SADs) derived from elastin (E) and the cartilage oligomeric matrix protein coiled-coil (C). As the E domain is shortened, the polymers exhibit an increase in inverse transition temperature (T(t)); however, the range of temperature change differs dramatically between the E(n)C and CE(n) library. Whereas all polymers assemble into nanoparticles, the bulk mechanical properties of the E(n)C are very different from CE(n). The E(n)C members demonstrate viscolelastic behavior under ambient conditions and assemble into elastic soft gels above their T(t) values. By contrast, the CE(n) members are predominantly viscous at all temperatures. All library members demonstrate binding to curcumin. The differential thermoresponsive behaviors of the E(n)C and CE(n) libraries in addition to their small molecule recognition abilities make them suitable for potential use in tissue engineering and drug delivery.

Elastomeric polyurethane porous film functionalized with gastrodin for peripheral nerve regeneration.

The extracellular matrix provides cells with a support structure and an attachment site in actual substrate. Its biochemical and surface properties play an important role in and have significant impact on cell attachment, proliferation, migration, differentiation, and gene expression. Leveraging the hydrophilicity and neuroprotective of gastrodin, a gastrodin/polyurethane (PU) elastomer was developed utilizing in situ polymerization and salt-leaching methods. The results showed that gastrodin/PU film had a good flexibility and supporting strength, as well as hydrophilicity. Thus film possessed highly surface area, interconnected porous structure with a pore size (10~60 µm) for cell attachment, and could provide surface cues to augment neurite extension. For PC12 cells cultured within the films, especially the 5gastrodin/PU group, presented a progressive increase with time, coupled with the upregulation of brain-derived neurotrophic factor and glial cell derived neurotrophic factor expression. This is the first report on the construction of a gastrodin/PU porous film, and the results reveal its promise as a scaffold material for neural tissue engineering.

Computational methods for recognition of cancer protein markers in saliva.

In recent years, many studies have supported that cancer tissues can make disease-specific changes in some salivary proteins through some mediators in the pathogenesis of systemic diseases. These salivary proteins have the potential to become cancer-specific biomarkers in the early diagnosis stage. How to effectively identify these potential markers is one of the challenging issues. In this paper, we propose novel machine learning methods for recognition cancer biomarkers in saliva by two stages. In the first stage, salivary secreted proteins are recognized which are considered as candidate biomarkers of cancers. We picked up 557 salivary secretory proteins from 20379 human proteins by public databases and published literatures. Then, we present a training set construction strategy to solve the imbalance problem in order to make the classification methods get better accuracy. From all human protein set, the proteins belonging to the same families as salivary secretory proteins are removed. After that, we use SVC-KM method to cluster the remaining proteins, and select negative samples from each cluster in proportion. Next, the features of proteins are calculated by tools. We collect 24 protein properties such as sequence, structure and physicochemical properties, a total of 1087 features. An innovative procedure based on the local samples is proposed for selecting the appropriate features, in order to further improve the performance of SVM classifier. Experimental results show that the average sensitivity, specificity and accuracy of salivary secretory protein recognition using selected 32 features in training set are 97.09%, 98.10%, 97.61%, respectively. The use of these methods can improve the accuracy of recognition by solving the problems of unbalanced sample size and uneven distribution in training set. In the second stage, we apply the best model to dig out the salivary secreted proteins from 58 reported cancer markers, and get a total of 42 proteins which are considered to be used for salivary diagnosis. We analyze the gene expression data of three types of cancer, and predict that 33 genes will appear in saliva after they are translated into proteins. This study provides an important computational tool to help biologists and researchers reduce the number of candidate proteins and the cost of research. So as to further accelerate the discovery of cancer biomarkers in saliva and promote the development of saliva diagnosis.

Hallermann-Streiff syndrome with uncommon ocular features, ultrasound biomicroscopy and optical coherence tomography findings: A case report.

RATIONALE: Hallermann-Streiff syndrome (HSS) is a rare congenital disorder characterized by craniofacial malformations, sparse hair, degenerative skin changes, eye abnormalities, dental defects, and proportionate short stature. PATIENT CONCERNS: A 24-year-old Chinese male patient presented to the ophthalmologist because of his sore eye and blurred vision. DIAGNOSES: The final diagnosis of presented case is HSS having the main features of the syndrome, however, associated with uncommon ocular features, ultrasound biomicroscopy (UBM) and optical coherence tomography (OCT)changes, including aphakia, glaucoma, long eye axes, cilliary abnormalities, and chorioretinal atrophy. INTERVENTIONS: Antiglaucomatous medical therapy failed to reduce the pressure in the right eye and a cyclocryotherapy was carried out. The antiglaucoma eye drops was continued in the left eye. OUTCOMES: The intraocular pressure has been reduced to the normal range, but the vision has not improved. LESSONS: In the diagnosis of HSS, we should not ignore the extraordinary information especially uncommon ophthalmic features, UBM and OCT changes. We highlight the necessity of a multidisciplinary approach for accurate diagnosis and appropriate management.

Doxorubicin loaded tumor-triggered targeting ammonium bicarbonate liposomes for tumor-specific drug delivery.

Ammonium bicarbonate (ABC) liposomes can only release drugs extracellularly while intracellular drug delivery could be more promising than extracellular release in chemotherapy. The purpose of this work was to endow the ABC liposomes with tumor-triggered targeting effect, to realize the intracellular drug release and retain the long circulation characteristics of the liposomes. The tumor-triggered targeting ABC (TT-ABC) liposomes were proposed to improve uptake of tumor cells owing to folate (FA) - specific binding. To retain the long circulation characteristics of the TT-ABC liposomes, we synthesized PEGylated phospholipid with a pH-sensitive imine bond (DSPE-PEG5000) and added it to the liposomes. After endocytosis by tumor cells via active targeting, the TT-ABC liposomes produced carbon dioxide (CO2) bubbles at elevated temperature or in the acidic endo/lysosome. The permeable defects could be created in the phospholipid bilayer by the generating CO2 bubbles, so the liposomes could quickly release the drugs intracellularly. Doxorubicin (DOX) loaded TT-ABC (DOX@TT-ABC) liposomes exhibited good stability at physiological pH (7.4) and released DOX quickly at reduced pH (6.4) and hyperthermia (42 °C). DOX@TT-ABC liposomes showed significantly enhanced cellular uptake, intracellular accumulation of DOX, and cytotoxicity at pH 6.4 and 42 °C.

PEG-conjugated hemoglobin combination with cisplatin enforced the antiangiogeic effect in a cervical tumor xenograft model.

Angiogenesis, an essential event involved in a tumor's progression and metastasis, is regulated by hypoxia. Hypoxia widely exists in solid tumors due to the abnormal vasculature of tumor tissue and insufficiency of tissue oxygenation. We speculate that hemoglobin-based oxygen carriers (HBOCs) can attenuate tissue hypoxia, thereby suppressing the angiogenesis in solid tumor in the context that HBOCs have the ability to increase tissue oxygenation. In the present study, PEG-conjugated hemoglobin solution (0.3 g/kg i.v. or 0.6 g/kg i.v.) was intravenously administrated to BALB/c nude mice bearing the cervical tumor twice a week with or without the treatment of cisplatin (5mg/kg i.p.) to investigate whether PEG-conjugated hemoglobin has a chemo-sensitization effect though anti-angiogenesis pathway. Tumor volume was measured every three days and tumor hypoxia was detected by immunohistochemistry for Hypoxyprobe-1. Anti-angiogenic effect was accessed by detection of mRNA and protein levels of vascular endothelial growth factor (VEGF), the most important angiogenic factor. Our results showed that high concentration of PEG-conjugated hemoglobin solution significantly impeded the growth of tumor when compared with the control group. Moreover, VEGF expression was declined when treated with PEG-conjugated hemoglobin, possibly through the HIF regulation system. Collectively, treatment of PEG-conjugated hemoglobin combination with cisplatin has an antiangiogenic effect, but the underlying mechanism should be further studied.

Influence of PEG-conjugated hemoglobin on tumor oxygenation and response to chemotherapy.

Hypoxic tumors are significantly more malignant, metastatic, radio- and chemoresistant. The use of artificial oxygen carriers represents a new approach to the problem of hypoxia. In the present study, female athymic BALB/c nude mice bearing the cervical carcinoma were untreated or treated with cisplatin to determine whether administration of artificial oxygen carrier (PEG-conjugated Hemoglobin, PEG-Hb) could improve the tumor oxygenation and enhance the anti-tumor efficacy of cisplatin. Pimonidazole staining was employed to detect tumor tissue oxygenation status. We found that the application of a higher dose (0.6 g/kg) PEG-Hb could significantly ameliorate the hypoxic condition in cervical carcinoma xenograft models. Co-administration of PEG-Hb (0.6 g/kg) with cisplatin produced significant tumor growth inhibition and pro-apoptotic and anti-proliferative effects as compared to cisplatin alone. These suggest the evaluated PEG-Hb in this experiment has positive effects on cisplatin or cisplatin-based chemotherapy, and further work to optimize its application is warranted.

Effect of artificial oxygen carrier with chemotherapy on tumor hypoxia and neovascularization.

UNLABELLED: In addition to transfusion alternatives, artificial oxygen carriers are a benefit in ischemia disorders. This study aimed at evaluating the possible effects of PEG-conjugated hemoglobin (PEG-Hb) plus cisplatin on tumor hypoxia and neovasculature. METHODS: HeLa cells were injected into submucosa of golden hamster cheek pouch to build tumor model. Animals were randomly assigned to 4 groups (n=10) and treated respectively: group 1, saline; group 2, cisplatin (5mg/kg); group 3, cisplatin (5mg/kg) plus PEG-Hb (0.3g/kg); group 4, cisplatin (5mg/kg) plus PEG-Hb (0.6g/kg). Tumor neovascularization morphological variation and tissue hypoxia were detected by intravital microscopy and immunostaining, respectively. RESULTS: Microvessel tortuosity and area capillary density in peritumoral areas were notably depressed in group 4 compared with group 2 (p<0.05). Hypoxia markers pimonidazole and HIF-1alpha expression were decreased significantly in group 4. CONCLUSION: PEG-Hb in high concentration can notably improve tumor tissue oxygenation and normalize neovasculature; it may be a potential adjuvant to chemotherapy in cancer.

Impact of oral hygiene on head and neck cancer risk in a Chinese population.

BACKGROUND: Although the impact of oral hygiene on head and neck cancer risk has been investigated, few studies have been conducted among the Asian population. METHODS: We conducted a multicenter case-control study to investigate this potential association. We performed unconditional multiple logistic regression models adjusted by potential confounders. RESULTS: We observed an inverse association of frequency of dental visits with head and neck cancer risk, with an adjusted odds ratio (OR) of 3.70 (95% CI 2.51-5.45) for never dental visits compared with ≥1 time/year (Ptrend < .001). We also observed a positive association between the number of missing teeth and head and neck cancer risk, with an adjusted OR for ≥5 missing teeth compared with <5 missing teeth of 1.49 (95% CI 1.08-2.04). Combining multiple oral hygiene indicators, poor oral hygiene scores increased head and neck cancer risk. CONCLUSION: Poor oral hygiene may increase head and neck cancer risk in the Chinese population. Therefore, improving oral hygiene may contribute to reducing the head and neck cancer risk in the Chinese population.

Oral lesions, chronic diseases and the risk of head and neck cancer.

OBJECTIVES: The aim of our study is to explore the role of the history of oral lesions and chronic diseases on the risk of head and neck cancer in a Chinese population. MATERIALS AND METHODS: Our case-control study included 921 head and neck cancer cases and 806 controls. We obtained medical history information by administering questionnaires to both cases and controls. We used unconditional logistic regression to estimate odds ratios for oral lesions and chronic conditions. RESULTS: Oral submucous fibrosis (OR=24.24, 95% CI=7.39-79.52), oral leukoplakia (OR=4.05, 95% CI=2.44-6.71) and repetitive dental ulcers (OR=5.12, 95% CI=3.17-8.28) increased the risk of HNC. Depression was associated with HNC risk when adjusted for several covariates (OR=2.10, 95% CI=1.06-4.15), but the association was not statistically significant after adjusting for smoking and alcohol drinking (OR=1.53, 95% CI=0.72-3.25). Also, the crude OR suggested an association between diabetes and HNC risk (OR=1.51, 95% CI=1.09-2.11), but it was not significant after adjusting for confounders. CONCLUSION: Our study reported on strong associations between HNC risk and oral leukoplakia, oral submucous fibrosis, which is consistent with prior research. We also observed repetitive dental ulcer to be associated with HNC risk. Future studies may focus on studying the association between depression and HNC, using medical records or psychological evaluation results to get more accurate information about depression, with careful assessment of tobacco and alcohol history.

[Clinical application of unilateral pedicle screw for lumbar intervertebral disc protrusion].

OBJECTIVE: To explore the feasibility and effectiveness of unilateral pedicle screw rod and single poly (ether-ether-ketone) (PEEK) Cage for lumbar intervertebral disc protrusion. METHODS: A total of 126 cases of single segment of lumbar intervertebral disc protrusion between January 2006 and June 2012 were divided into 2 groups in the randomized clinical trial. Unilateral pedicle screw fixation and single PEEK Cage was used in 63 cases (research group), and bilateral pedicle screw fixation and single PEEK Cage in 63 cases (control group). There was no significant difference in gender, age, disease duration, side, and affected segment between 2 groups (P > 0.05). Schulte evaluation criterion was used to assess bone graft fusion, Oswestry disability index (ODI) to estimate the quality of life situation, and visual analogue scale (VAS) to evaluate the improvements of lower back pain. Macnab standards was applied to assess postoperative effectiveness, and Emery ways to measure the height of intervertebral space. RESULTS: The incision length, operation time, intraoperative blood loss, hospitalization time, and hospitalization fee in research group were significantly less than those in control group (P cc 0.05). The patients were followed up 12-79 months (mean, 21.3 months) in research group, and 15-73 months (mean, 22.6 months) in control group. The postoperative lordosis was recovered well, and the height of intervertebral space was increased. No loosening or breakage of internal fixation occurred. The time of bone graft fusion was (6.8 +/- 1.3) months in research group and was (7.1 +/- 1.2) months in control group, showing no significant difference (t = 1.153, P = 0.110). The height of intervertebral space, ODI score, and VAS score were significantly improved when compared with preoperative ones in 2 groups (P < 0.05), but no significant difference was found between 2 groups at preoperation and last follow-up (P > 0.05). At 3 months after operation, postoperative effectiveness was assessed according to Macnab criterion, the excellent and good rate was 95.23% in research group (excellent in 13 cases, good in 47 cases, and fair in 3 cases) and was 71.42% in control group (excellent in 7 cases, good in 38 cases, fair in 15 cases, and poor in 3 cases); the research group was significantly superior to control group (chi2 = 6.110, P = 0.006). CONCLUSION: Unilateral pedicle screw fixation and single PEEK Cage has the advantages of small trauma, reliable fixation, shorter operation time, less bleeding, less economic cost, and early off-bed activity time. It can provide a simple and reliable choice in single segmental lumbar intervertebral disc protrusion.

[Inhibitory effect of curcumin on MMP-2 and MMP-9 expression induced by polyethylene wear particles and its mechanism].

OBJECTIVE: To observe the effect of different dosage of curcumin on expression of MMP-2 and MMP-9 in the tissue of cystiform in air-pouch mouse models after the injection of polyethylene wear particles, and to investigate its mechanism of intervening inflammatory response induced by wear particles. METHODS: Seventy-two kunming strain mice were used to establish air-pouch animal models by referring to the method of Yang et al. and injecting 3 mL suspension of ultra-high molecular weight polyethylene wear particles (concentration 1 x 10(8) cells/mL) into dorsal cyst cavity. Then the animals were randomized into 3 groups (n = 24 per group): group A (control group), 0.6 mL/day normal saline by gavage; group B (low-dosage experimental group), 0.6 mL/day curcumin solution at a concentration of 1.6 mg/mL by gavage; group C (high-dosage experimental group), 0.6 mL/day curcumin solution at a concentration of 3.2 mg/mL by gavage. General condition of the animals was observed after operation. The mice were killed 3, 7 and 14 days after operation (8 mice per group at a time), the tissue of cystiform was harvested to receive gross, histology and immunohistochemistry observation, as well as RT-PCR and Western blot detection. RESULTS: All mice survived till the end of experiment. White cystiform tissue was evident on the back of mice subcutaneously in each group. For diameter of the cyst cavity at each time point, group A was obviously greater than groups B and C, and group C was significantly less than group B. Microscope observation showed that inflammatory response in group A was stronger than that of groups B and C, and group C was obviously less than group B at 7 and 14 days. There was a significant difference between groups B and C and group A in terms of MMP-2 and MMP-9 expression at 7 and 14 days after curcumin delivery (P < 0.05), and no significant differences were evident at 3 days (P > 0.05). There was no significant difference between group B and group C in MMP-2 expression at 7 days after curcumin delivery (P > 0.05), and significant difference was evident at 14 days (P < 0.05). There was significant difference bewteen group B and group C in MMP-9 expression at 7 and 14 days after curcumin delivery (P < 0.05). Nuclear translocation of NF-kappaB P65 was inhibited remarkably after curcumin delivery, and there were significant differences among three groups at 7 and 14 days (P < 0.05), and no significant differences were evident at 3 days (P > 0.05). CONCLUSION: Ultra-high molecular weight polyethylene wear particles can stimulate expression of MMP-2 and MMP-9 in cystiform tissue. Curcumin can restrain expression of MMP-2 and MMP-9 in cystiform tissue of air-pouch animal models, and expression of MMP-2 and MMP-9 may be regulated by the activation of NF-kappaB.

[Spatial distribution of seawater dimethylsulfide in winter of Jiulong Jiang Estuary].

Cruise investigation of dimethylsulfide (DMS) emission in estuarine areas, heavily disturbed by human activities, was carried out in the winter of 2001 in Jiulong Jiang Estuary. The concentrations of chlorophyll, salinity and nutrients showed evidently spatial distribution in Jiulong Jiang Estuary, so did DMS concentrations in surface water. The average of seawater DMS was 101.0 and 242.1 ng x L(-1) in river mouth area and gulf area, respectively. DMS concentrations decreased first with the increase of seawater salinity and then increased. The highest DMS concentration occurred at river plume front of maximum turbidity zone of the estuary.