Ligustilide-loaded liposome ameliorates mitochondrial impairments and improves cognitive function via the PKA/AKAP1 signaling pathway in a mouse model of Alzheimer's disease.

BACKGROUND: Oxidative stress is an early event in the development of Alzheimer's disease (AD) and maybe a pivotal point of interaction governing AD pathogenesis; oxidative stress contributes to metabolism imbalance, protein misfolding, neuroinflammation and apoptosis. Excess reactive oxygen species (ROS) are a major contributor to oxidative stress. As vital sources of ROS, mitochondria are also the primary targets of ROS attack. Seeking effective avenues to reduce oxidative stress has attracted increasing attention for AD intervention. METHODS: We developed liposome-packaged Ligustilide (LIG) and investigated its effects on mitochondrial function and AD-like pathology in the APPswe/PS1dE9 (APP/PS1) mouse model of AD, and analyzed possible mechanisms. RESULTS: We observed that LIG-loaded liposome (LIG-LPs) treatment reduced oxidative stress and ß-amyloid (Aß) deposition and mitigated cognitive impairment in APP/PS1 mice. LIG management alleviated the destruction of the inner structure in the hippocampal mitochondria and ameliorated the imbalance between mitochondrial fission and fusion in the APP/PS1 mouse brain. We showed that the decline in cAMP-dependent protein kinase A (PKA) and A-kinase anchor protein 1 for PKA (AKAP1) was associated with oxidative stress and AD-like pathology. We confirmed that LIG-mediated antioxidant properties and neuroprotection were involved in upregulating the PKA/AKAP1 signaling in APPswe cells in vitro. CONCLUSION: Liposome packaging for LIG is relatively biosafe and can overcome the instability of LIG. LIG alleviates mitochondrial dysfunctions and cognitive impairment via the PKA/AKAP1 signaling pathway. Our results provide experimental evidence that LIG-LPs may be a promising agent for AD therapy.

Thermosensitive Hydrogel Wound Dressing Loaded with Bacteriophage Lysin LysP53.

Wound infections are prone to attacks from infectious pathogens, including multidrug resistant bacteria that render conventional antimicrobials ineffective. Recently, lysins have been proposed as alternatives to conventional antimicrobials to tackle the menace of multidrug resistance pathogens. The coupling of lysins with a material that will cover the wound may prove beneficial in both protecting and treating wound infections. Hence, in this study, a Gram-negative lysin, LysP53, was coupled with a thermosensitive hydrogel, poloxamer P407, and its efficacy to treat wound infection was tested. In vitro, the addition of LysP53 to the poloxamer did not affect its thermosensitive characteristics, nor did it affect the hydrogel structure. Moreover, the lysin hydrogel could hydrolyze the peptidoglycan, demonstrating that it may have bactericidal activity. Up to 10.4% of LysP53 was released from the hydrogel gradually within 24 h, which led to a 4-log reduction of stationary phase Acinetobacter baumannii. Lastly, the lysin hydrogel was found safe with no cytotoxic effects observed in cells. Ex vivo, LysP53 hydrogel could inhibit bacterial growth on a pig skin decolonization model, with 3-log differences compared to non-treated groups. Overall, our results suggest that lysin-loaded hydrogels may provide a novel solution to treat wound infections caused by resistant bacteria.

Differential diagnosis of gastric cancer and gastritis: the role of contrast-enhanced ultrasound (CEUS).

OBJECTIVES: To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) in differential diagnosis of gastric cancer and gastritis, with histological results as reference standard. METHODS: From September 2011 to August 2014, 82 patients (50 males and 32 females; mean age ± SD, 59.5 ± 15.0 years; range 19-91 years) with gastric cancer or gastritis were included in this Ethics Committee-approved prospective study. Conventional ultrasonography (US) and CEUS were applied to distinguish the two lesions, and both qualitative and quantitative features were evaluated. RESULTS: Of the 82 histopathologic-proven lesions, 58 were cancer and 24 were gastritis. For US, the gastric wall stratification was not preserved in about one-third of cancer (21/58, 36.2%) compared with gastritis (0/24, 0%) (p < 0.001). Blurred, angular, or spiculated serosa margin and increased echogenicity in perigastric fat appeared only in cancer (10/58, 17.2%), and all of them proved to be pathologic T3 or T4 stage. On CEUS, gastric cancer usually manifested as diffused enhancement without comb-teeth-like vessels (parallel curvilinear structures representing arterial branching within the gastric wall) (56/58, 96.6%), while these vessels presented in most gastritis (19/24, 79.2%, p < 0.001). For quantitative analysis, the malignant lesions showed later and lower enhancement (p < 0.001), and they also had slower speed to reach the peak intensity (p < 0.001). On CEUS, the absence of comb-teeth-like vessel is most reliable for diagnosing malignancy, and the sensitivity, specificity, and accuracy were 96.5%, 79.2%, and 91.5%, respectively. CONCLUSIONS: Our results demonstrated the usefulness and accuracy of US and CEUS in differential diagnosis of gastric cancer and gastritis. CEUS has the potential to make the diagnosis more accurate.

[Effect of surface modified nano-diamond on viscosity of dental adhesives].

PURPOSE: Different surface modified ultrafine-diamond (UFD) was added into dental adhesives as filler ,then the influence of dental adhesive properties was observed. The main matrix of dental adhesive was high polymer resin. METHODS: Different content of non-modified UFD(n-UFD) or modified UFD(m-UFD) were added into dental adhesives, then the viscosity of materials were measured. The data was processed with SPSS17.0 software package. RESULTS: The viscosity of dental adhesives was decreased when the proportion of UFD was less than 0.1wt%, especially when it was 0.1wt%; but was significantly improved when the proportion was more than 0.1wt%. The effect of UFD and surface-modified UFD on the viscosity was significantly different. CONCLUSIONS: The results show that silane coupling was chemically-grafted on the surface of UFD, the dispersion and stability of UFD in ethanol was improved; And a quantity of UFD with special content could reduce the viscosity of dental adhesives and improve the flowability obviously. The m-UFD was superior to n-UFD.

[Bi-axial flexure strength and fracture mode of alumina glass-infiltrated core/veneer ceramic composites].

PURPOSE: To determine the bi-axial flexural strength and fracture mode of bilayered alumina glass-infiltrated core and the veneering porcelain. METHODS: Forty disk specimens were made from alumina glass-infiltrated core (HSDC-A) and veneer porcelain (Vintage AL), and equally divided into four groups as follows: monolithic specimens of veneer(MV),monolithic specimens of core material(MC),bilayered specimens with the veneer on top (BC) and bilayered specimens with core material on top(BV). Mean flexure strength, standard deviation and associated Weibull modulus were determined using bi-axial flexure (ball-on-ring) for each group. The results were analyzed with one-way ANOVA and the Weibull distribution with SPSS 13.0 software package. Both optical and scanning electron microscopy were employed for identification of the fracture mode and origin. RESULTS: The strength in the group MC and BC were significantly stronger than that in the group MV and BV. The frequency of specimen delamination, Hertzian cone formation and sub-critical radial cracking in the bilayered discs were dependent on the surface loaded in tension. CONCLUSION: Material which lies on the bottom surface dictates the strength and fracture mode of the specimens. Supported by Shenzhen Municipal Technological Project (Grant No.200903082).

[Use of casting inlays with pulp chamber retention to restore extensive damaged crowns of molars].

PURPOSE: To evaluate the effect of casting inlays with pulp chamber retention to restore extensively damaged crowns of molars. METHODS: After root canal treatment, sixty-one extensively damaged molar crowns were restored by casting inlays with pulp chamber retention. All the patients revisited after treatment at regular intervals and routine clinical examinations were performed. RESULTS: During the follow-up period from 1 to 5 years, all the 61 restorations functioned well. However, gingivitis, secondary caries or food impaction due to ill-fitting margins of prosthesis were observed in some cases. CONCLUSIONS: Casting inlays with pulp chamber retention is a simple, economic and effective method to restore extensively damaged crowns of molars. Strict choices of indication, precise preparations of the teeth and well-made prosthesis are the key points for long-term successful restorations.