Safety and Efficacy of Drug-Coated Balloon in the Treatment of Below-the-Knee Artery: A Meta-analysis.

INTRODUCTION: Chronic limb threat ischemia is associated with cardiovascular events, resulting in high amputation, morbidity and mortality rates. This study aims to accomplish a comprehensive summary of randomized controlled trials and single-center trials related to drug-coated balloons (DCBs) in the treatment of below-the-knee (BTK) artery disease, and to provide a recommendation for the application of DCBs in BTK artery disease. METHODS: Five electronic databases were used to retrieve relevant articles on the safety and effectiveness of DCBs in the treatment of BTK artery disease. A random-effects model was applied to calculate the standard mean deviation, odds ratio (OR) and their 95% of confidence interval (CI). RESULTS: As of April 8, 2021, a total of 241 articles were retrieved, but only 13 articles were finally included for meta-analysis. The 12 mo follow-up study found that major adverse events , all-cause mortality, major amputation ,and target lesion revascularization had no statistically significant difference between the DCBs group and the control group (target lesion revascularization: OR = 0.68, 95% CI: 0.36, 1.31; all-cause mortality: OR = 1.30, 95% CI: 0.69, 2.46; major amputation: OR = 1.34, 95% CI: 0.64, 2.79; target lesion revascularization: OR = 0.72, 95% CI: 0.35, 1.45). CONCLUSIONS: The meta-analysis results of randomized controlled trials focusing on comparing DCBs and other treatments suggest that DCBs do not have significant advantages in the treatment of BTK artery disease when compare with percutaneous transluminal angioplasty (PTA), but better than control intervention except PTA in both safety and efficacy end points. However, the results of meta-analysis of single-arm trial reported DCBs in treating BTK artery lesions are significantly improved compared with the meta-analysis concentrating on PTA.

Biobutanol production from sugarcane bagasse by Clostridium beijerinckii strains.

Acetone-butanol-ethanol (ABE) fermentation was performed with sugarcane bagasse (SCB) hydrolysate using Clostridium beijerinckii strains. A cost-effective SCB medium was developed with no enzymatic hydrolysis and no supplementation of extra carbon source or expensive nitrogen source. One of the C. beijerinckii strains studied was able to produce butanol with butanol productivity of 1.23 g/L/day with butanol yield of 0.18 g/g of sugars from the developed medium. High utilization rate of both glucose and xylose was observed in SCB medium during ABE fermentation. This study shows that SCB is a promising substrate for cellulosic biobutanol production.

In vitro protoscolicidal effects of high-intensity focused ultrasound enhanced by a superabsorbent polymer.

Echinococcus granulosus, the etiologic agent of cystic echinococcosis in humans and other animal hosts, is distributed worldwide. Echinococcosis is an increasing public health and socioeconomic concern. The present work evaluated whether or not a superabsorbent polymer (SAP) could enhance the damage efficacy of high-intensity focused ultrasound (HIFU) on the viability of E. granulosus protoscolices in vitro. HIFU of 100 W acoustic power and 0.01 g superabsorbent polymer were used to treat 5,000 protoscolices in 2-ml protoscolices suspension. After different HIFU exposure time (5, 10, 20, 30, 40, 50, and 60 s, respectively), the temperature of protoscolices suspension was taken, and the treated protoscolices were stained by trypan-blue exclusion assay, and their structures were observed by light microscopy. To better understand the biological mechanisms responsible for the deaths of protoscolices, the activity of succinate dehydrogenase (SDH) of the protoscolices treated with HIFU was examined. The temperature of protoscolices suspension treated with HIFU rose slowly, and the death rate of protoscolices was 73.7 % in the group of HIFU treatment time of 40 s; however, with the same HIFU treatment time of 40 s, the temperature of protoscolices suspension in the group of HIFU combined with SAP rose quickly, and the death rate of protoscolices was 100 %. The same protoscolicidal effect (100 %) of HIFU of 100 W acoustic power combined with SAP was also observed in the groups of HIFU treatment time of 50 and 60 s, respectively. The dead protoscolices were stained to blue, shrunken and black calcareous corpuscles, and disordered and decreasing hooks though of intact membrane, as well as some protoscolices lost hooks and tore open on membrane were observed. In the group of HIFU combined with SAP, it was found that the superabsorbent polymer was surrounded by the spoiled, and the destruction of protoscolices was much stronger than in the group of HIFU. The dead protoscolices exhibited the reduction or absence of SDH staining intensity in the parenchymal cell and calcareous corpuscles after HIFU irradiation, where a large number of necrotic cells were evident. These results suggested that HIFU could induce the damage and loss of viability of protoscolices; SAP could enhance the HIFU energy focused and cause more severe destruction efficacy on protoscolices; and mitochondrial energetic function is involved in the regulation of cell-death pathways of protoscolices.

The damages of high intensity focused ultrasound to transplanted hydatid cysts in abdominal cavities of rabbits with aids of ultrasound contrast agent and superabsorbent polymer.

The present study investigates the damages of high intensity focused ultrasound (HIFU) to transplanted hydatid cysts in abdominal cavities of rabbits with aids of ultrasound contrast agent (UCA) and superabsorbent polymer (SAP) alone or in combination. A rabbit model with transplanted hydatid cyst was established by implanting hydatid cyst isolated from infected sheep liver, and HIFU was used to ablate the transplanted cysts with the aid of UCA and SAP alone or in combination. The hydatid cyst with thin wall, good elasticity, approximately spherical, and a diameter of approximately 30 mm was selected for the following experiments. According to our previous studies, a mixture of 0.1 g SAP and 0.5 ml anhydrous ethanol, and the solution of 0.1 ml UCA SonoVue, or both materials were injected into different cyst before HIFU ablation, respectively. The cyst inoculated with the SAP and UCA alone or in combination was immediately implanted into the abdominal cavity of rabbit for HIFU ablation at a dosage of 100 W acoustic powers. The ablation mode was spot scanning at the speed of 3 mm/s. Every target point was scanned three times; every ablating time lasted 3 s. The distance of each ablated layer was 5 mm. The total ablation time depended on the volume of cyst. The comparison of ultrasound image for each layer of hydatid cyst was made before and after HIFU ablation. The protoscolices in ablated cysts were stained by trypan blue exclusion assay, and their structures were observed by light microscopy. To estimate ablation effects of HIFU to the walls of hydatid cysts, the ultrastructure changes of cyst walls were examined by electron microscopy. The pathological changes of rabbits' skins through which ultrasound penetrated were observed to investigate the side effects of HIFU ablation. The results demonstrated that HIFU had some lethal effects to hydatid cysts in vivo, namely, echo enhancements of ultrasound images of cysts, increases in mortality rate of protoscolices from 15.19 % (HIFU alone) to 48.66 % (HIFU + SAP), 38.67 % (HIFU + UCA), and 67.75 % (HIFU + SAP + UCA), respectively, serious structural damages of protoscolices, and destructions or even disappearance of laminated layers and germinal layers in the walls of hydatid cysts ablated by HIFU aided with UCA and SAP alone or in combination. This study demonstrated that destructive effects of HIFU to transplanted hydatid cyst could be enhanced by UCA and SAP alone, but the destruction of HIFU aided with a combination of UCA and SAP to hydatid cysts was more effective than those aided with UCA or SAP alone. The enhanced thermal and cavitation effects of HIFU induced by UCA and SAP might be involved in the enhanced destructive effects of HIFU on hydatid cysts. There were no evidences of pathological changes on rabbits' skins overlying the hydatid cysts after HIFU ablation. The results suggested that the rabbit model with transplanted hydatid cyst may serve as an optional animal model for the experiments of HIFU ablation to hydatid cyst in vivo, and the materials of UCA and SAP were proved as enhancing agents of HIFU ablation to hydatid cysts, and HIFU at a dosage of 100 W acoustic powers was a safe and feasible parameter to ablate the hydatid cysts in this special animal model. These results laid a theoretical foundation for improving HIFU therapy for cystic echinococcosis by inoculation of UCA and SAP into hydatid cysts.

[Enhancement of in vitro protoscolicidal effects of high-intensity focused ultrasound by a superabsorbent polymer and ultrasound contrast agent].

This study evaluated whether or not a superabsorbent polymer (SAP) combined with ultrasound contrast agent (UCA) could enhance damage efficacy of high intensity focused ultrasound (HIFU) on Echinococcus granulosus protoscoleces in vitro. Thirty test tubes each with 6 000-7 500 protoscolices were divided into 5 groups: group A (blank control) without HIFU treatment, group B treated with HIFU (50 W) only, group C treated with 10 microl UCA and HIFU, group D treated with 0.01 g SAP and HIFU, group E treated with 10 microl UCA, 0.01 g SAP, and HIFU. In group B, echo enhancement of ultrasound image, suspension temperature (26.0 degrees C +/- 0.2 degrees C) and protoscoleces mortality (30.4%) were higher than that of group A (18.0 degrees C +/- 0.1 degrees C, 1.9%) (P < 0.01). Compared with group B, the echo enhancement of ultrasound image, suspension temperature (27.0 degrees C +/- 0.2 degrees C, 28.2 degrees C +/- 0.2 degrees C) and protoscoleces mortality (50.0%, 53.7%) of groups C and D increased significantly (P < 0.01). In group E, more protoscoleces were stained in red and their internal structures were indistinct. By chi-square test, the protoscoleces mortality of group E (69.7%) was higher than that of groups C and D (P < 0.01). There was no significant difference in suspension temperature among the 3 groups.

Molecularly Stimuli-Responsive Self-Assembled Peptide Nanoparticles for Targeted Imaging and Therapy.

Self-assembly has emerged as an extensively used method for constructing biomaterials with sizes ranging from nanometers to micrometers. Peptides have been extensively investigated for self-assembly. They are widely applied owing to their desirable biocompatibility, biodegradability, and tunable architecture. The development of peptide-based nanoparticles often requires complex synthetic processes involving chemical modification and supramolecular self-assembly. Stimuli-responsive peptide nanoparticles, also termed "smart" nanoparticles, capable of conformational and chemical changes in response to stimuli, have emerged as a class of promising materials. These smart nanoparticles find a diverse range of biomedical applications, including drug delivery, diagnostics, and biosensors. Stimuli-responsive systems include external stimuli (such as light, temperature, ultrasound, and magnetic fields) and internal stimuli (such as pH, redox environment, salt concentration, and biomarkers), facilitating the generation of a library of self-assembled biomaterials for biomedical imaging and therapy. Thus, in this review, we mainly focus on peptide-based nanoparticles built by self-assembly strategy and systematically discuss their mechanisms in response to various stimuli. Furthermore, we summarize the diverse range of biomedical applications of peptide-based nanomaterials, including diagnosis and therapy, to demonstrate their potential for medical translation.

Restoration of spinal cord biophysical microenvironment for enhancing tissue repair by injury-responsive smart hydrogel.

Spinal cord injury (SCI) represents a central nervous system disaster, resulting in the destruction of spinal cord structure and function and the formation of an adverse microenvironment at the SCI site. Various biomaterial-based therapeutic strategies have been developed to repair SCI by bridging spinal cord lesions. However, constructing a favorable biophysical microenvironment with biomaterials for spinal cord regeneration remains challenging because of the unmatched mechanical and electrical transmission properties with native spinal cords and the supra- or subtherapeutic dose release of biological molecules independent of SCI activity. Herein, we developed a new hydrogel with mechanical properties and conductivities comparable to those of native spinal cords by controlling gelatin and PPy concentrations. To endow the hydrogel with a biological function, glutathione (GSH) was conjugated on the hydrogel through gelatin-derived amine groups and GSH-derived sulfhydryl groups to prepare an MMP-responsive hydrogel with a recombinant protein, GST-TIMP-bFGF. The MMP-responsive conductive hydrogel could release bFGF on-demand in response to the SCI microenvironment and provide a favorable biophysical microenvironment with comparable mechanical and electrical properties to native spinal cords. In SCI model rats, the MMP-responsive bionic mechanical and conductive hydrogel could inhibit MMPs levels, promote axon regeneration and angiogenesis, and improve locomotion function recovery after SCI.

Supramolecular Hydrogel-Wrapped Gingival Mesenchymal Stem Cells in Cutaneous Radiation Injury.

Radiation-induced skin wound/dermatitis is one of the common side effects of radiotherapy or interventional radiobiology. Gingiva-derived mesenchymal stem cells (GMSCs) were indicated to have therapeutic potentials in skin diseases. However, stem cells are prone to spread and difficult to stay in the skin for a long time, limiting their curative effects and application. This study investigated the therapeutic efficacy of Nap-GDFDFpDY (pY-Gel) self-assembled peptide hydrogel-encapsulated GMSCs to treat 137Cs γ-radiation-induced skin wounds in mice. The effects were evaluated by skin damage score, hind limb extension measurement and histological and immunohistochemical analysis. In vivo studies showed that pY-Gel self-assembled peptide hydrogel-encapsulated GMSCs could effectively improve wound healing in irradiated skin tissues. In addition, it was found that GMSCs conditioned medium (CM) could promote the proliferation, migration and DNA damage repair ability of skin cells after irradiation in human keratinocyte cell line HaCaT and normal human dermal fibroblasts (HFF). Mechanistically, GMSCs-CM can promote the expression of epidermal growth factor receptor (EGFR), signal transducers and activators of transcription 3 (STAT3) and matrix metalloproteinases (MMPs), suggesting that activation of the EGFR/STAT3 signaling pathway may be involved in the repair of skin cells after exposure to radiations. In conclusion, pY-Gel self-assembled peptide hydrogel-encapsulated GMSCs have a beneficial therapeutic effect on radiation-induced cutaneous injury and may serve as a basis of novel cells therapeutic approach.

Tooth Loss and Risk of Lung Cancer among Urban Chinese Adults: A Cohort Study with Meta-Analysis.

Epidemiological evidence on tooth loss and lung cancer risk remains limited, especially for smoking-specific associations. To investigate the association between tooth loss and lung cancer risk by smoking status, we first analyzed data from the Shanghai Men's Health Study (n = 49,868) and the Shanghai Women's Health Study (n = 44,309). Cox regression models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer risk in relation to tooth loss. We also conducted a meta-analysis to summarize epidemiologic findings to date, incorporating results from the current study and six previously published studies. For 7.3 median follow-up years, 973 incident lung cancer cases (613 men and 360 women) were ascertained. After adjustment for major covariates, tooth loss was associated with an increased risk of lung cancer among men (HR [95% CI] for >10 teeth vs. none = 1.59 [1.21−2.11]) but not among women (0.86 [0.50−1.46]). The positive association was stronger among male current smokers (1.75 [1.26−2.45], p-interaction by smoking status = 0.04). In a meta-analysis incorporating 4052 lung cancer cases and 248,126 non-cases, tooth loss was associated with a 1.64-fold increased risk of developing lung cancer (relative risk [RR, 95% CI] for the uppermost with the lowest category = 1.64 [1.44−1.86]). The positive association was more evident among current smokers (1.86 [1.41−2.46]), but no significant associations were found among never or former smokers. Our findings suggest that tooth loss may be associated with an increased risk of lung cancer, and the association could be modified by smoking status.

Paeoniflorin-loaded pH-sensitive liposomes alleviate synovial inflammation by altering macrophage polarity via STAT signaling.

Macrophage polarization plays a prominent role in the pathogenesis of rheumatoid arthritis (RA) and could be regulated by natural extracts paeoniflorin (Pae) but with low bioavailability. In the present study, Pae-loaded liposomes (Pae-LS) with co-conjugation of folate and PEG were prepared for the improvement of therapeutic benefits. We evaluated biophysical characterizations of Pae-LS and macrophage uptake of liposomes, as well as gain insight into whether Pae-LS can improve synovial inflammation in CIA rats and how Pae-LS promoted RAW 264.7 macrophages phenotype switch. We found that Pae-LS showed physical stability, sustained release, long circulation, pH-responsive properties, and higher uptake by active macrophages than free Pae. Furthermore, Pae-LS could repress STAT1 phosphorylation to reduce the levels of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and iNOS expression, as well as lead to a marked increase in anti-inflammatory cytokine (IL-10) and CD206 levels via elevated p-STAT6. In contrast to free Pae, Pae-LS treatment was more effective in alleviating synovial inflammation and hyperplasia in the ankle joint of CIA rats. Our study revealed Pae-LS could effectively suppress synovial inflammation of CIA rats by regulating macrophage polarization via STAT signaling and had the potential for RA treatment as liposome delivery carriers systems.

Processing nanocellulose foam into high-performance membranes for harvesting energy from nature.

Nanocellulose membranes exhibit good stability and high strength. However, the conventional synthetic routes rely on solvent volatilization of a nanocellulose suspension or solution. The complete hydrogen bonding that occurs in this process leads to a dense structure and poor strength in water. Hereby, lignosulfonate and polycation were mixed to form a complex and then attached to cellulose. The freeze-dried nanocellulose foam was hot-pressed to membrane, resulting in simultaneous co-crosslinking and membrane formation. The membrane had a porous structure with a high mechanical performance, excellent stability and a fast shape recovery. This also represents a method for processing functional nanocellulose membranes, as further demonstrated by the hybrid membrane with exceptional solar-driven seawater desalination and water-flow electricity generation properties. This work established facile methods for tackling the structural weakness of the conventional nanocellulose membrane, and opens the door to the application of nanocellulose membrane with a combination of mechanical stability and functionality.

The influx/efflux mechanisms of d-peptide ligand of nAChRs across the blood-brain barrier and its therapeutic value in treating glioma.

A d-peptide ligand of the nicotine acetylcholine receptors (nAChRs), termed DCDX, enables drug delivery to the brain when incorporated into liposomes and has shown promise as a nanocarrier for treating brain diseases. However, few reports have described the mechanisms whereby DCDX-modified liposomes traverse the blood-brain barrier (BBB). Here, we studied the molecular mechanisms enabling DCDX (and its associated liposomes) to cross an in vitro BBB using a simulated cerebral endothelium monolayer formed by brain capillary endothelial cells (bEnd.3 cells). We also examined the mechanisms whereby DCDX-modified liposomes cross the BBB in vivo using the brain efflux-index method. Transport of DCDX and its modified liposomes was dominantly mediated via the lipid raft/caveolae endocytic pathway. Both the endoplasmic reticulum (ER) and Golgi complex participated in delivering DCDX-modified liposomes to the plasma membrane (PM). DCDX-modified liposomes also participated in the endosome/lysosome pathway (with high-efficiency BBB crossing observed in vitro), while competing for the ER/Golgi/PM pathway. In addition, nAChR α7 did not promote the transportation of DCDX-modified liposomes in vivo or in vitro, as assessed with α7-knockout mice and by performing α-bungarotoxin (α-Bgt) binding-competition experiments. P-glycoprotein (P-gp) was identified as the main efflux transporter across the BBB, in vivo and in vitro. Using a xenograft nude mouse model of human glioblastoma multiforme, blocking the efflux function of P-gp with verapamil enhanced the therapeutic efficiency of DCDX-modified liposomes that were formulated with doxorubicin against glioblastoma. The findings of this study reveal novel mechanisms underlying crossing of the BBB by DCDX-modified liposomes, suggesting that DCDX-modified liposomes can potentially serve as a powerful therapeutic tool for treating glioma.

Engineering PLGA nano-based systems through understanding the influence of nanoparticle properties and cell-penetrating peptides for cochlear drug delivery.

The properties of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) and penetration enhancers play a deciding role in the inner ear drug delivery of NPs across the round window membrane (RWM). Thus, PLGA nano-based systems with a variety of particle sizes and surface chemistries and those combined with cell-penetrating peptides (CPPs) as penetration enhancers were devised to explore their impact on the cochlear drug delivery in vivo. First, we demonstrated that the properties of NPs dictated the extent of NP cochlear entry by near-infrared fluorescence imaging. NPs with the sizes of 150 and 300nm had faster entry than that of 80nm NPs. At 0.5h, among the NPs unmodified and modified with chitosan (CS), poloxamer 407 (P407) and methoxy polyethylene glycol, CS-PLGA-NPs (positive surface charge) carried payload to the cochlea fastest, whereas P407-PLGA-NPs (surface hydrophilicity) showed the greatest distribution in the cochlea at 24h. Compared to other CPPs (TAT, penetratin and poly(arginine)8), low molecular weight protamine (LMWP) performed an outstanding enhanced NP cellular uptake in HEI-OC1 cells and cochlear entry. More importantly, NPs with optimized properties and CPPs may be combined to improve RWM penetration. For the first time, we confirmed that the combination of P407-PLGA-NPs (mean diameter: 100-200nm) and LMWP provided a synergistic enhancement in NP entry to the organ of Corti and stria vascularis without inducing pathological alteration of cochlear tissues and RWM. Taken together, we propose an effective PLGA nano-based strategy for enhanced drug delivery to the inner ear tissues that combines hydrophilic molecule-modified NPs and CPPs, ultimately opening an avenue for superior inner ear therapy.

[Effect of porcelain firing cycle on microstructure and corrosion resistance of 4 metal ceramic alloys].

OBJECTIVE: To determine the effect of porcelain firing cycle on microstructure of 4 metal ceramic alloys, and to analyze the changes of their corrosion resistance in the artificial saliva. METHODS: We simulated the process of firing and repolishing when fabricating porcelain-fused-to-metal restoration in clinic,and then observed the microstructures of Ni-Cr, Ni-Cr-Ti, Co-Cr alloys and high gold alloy by field emission scanning electron microscopy and energy dispersive spectroscopy. The electrochemical corrosion behavior of alloys in artificial saliva was analyzed by polarization curves and corrview 2 corrosion analysis software. The data of self-corrosion potential and transpassive potential were obtained and analyzed. RESULTS: After the porcelain firing cycle, the surface composition changed slightly, and the morphological in the 3 predominate base metal alloys also changed. The self-corrosion potential turned to more negative, and the transpassive potential declined. CONCLUSION: The procedure of porcelain firing cycle can affect the surface microstructure and increase the corrosion of 4 metal-ceramic alloys.

Nanomedicine strategy for optimizing delivery to outer hair cells by surface-modified poly(lactic/glycolic acid) nanoparticles with hydrophilic molecules.

Targeted drug delivery to outer hair cells (OHCs) in the cochlea by nanomedicine strategies forms an effective therapeutic approach for treating hearing loss. Surface chemistry plays a deciding role in nanoparticle (NP) biodistribution, but its influence on such distribution in the cochlea remains largely unknown. Herein, we report the first systematic comparison of poly(lactic/glycolic acid) nanoparticles (PLGA NPs) with or without surface modification of hydrophilic molecules for optimizing the delivery to OHCs both in vitro and in vivo. NPs that were surface modified with poloxamer 407 (P407), chitosan, or methoxy poly(ethylene glycol) and the unmodified NPs were highly biocompatible with L929 and House Ear Institute-organ of Corti 1 cells as well as cochlear tissues. Interestingly, among all the examined NPs, P407-PLGA NPs showed the greatest cellular uptake and prominent fluorescence in cochlear imaging. More importantly, we provide novel evidence that the surface-modified NPs reached the organ of Corti and were transported into the OHCs at a higher level. Together, these observations suggest that surface modification with hydrophilic molecules will allow future clinical applications of PLGA NPs, especially P407-PLGA NPs, in efficient hearing loss therapy.

[Experimental study of total nutrient admixture promoting transfection of plasmid DNA mediated with liposomes to colorectal cancer cells].

OBJECTIVE: To study total nutrient admixture (TNA) promoting plasmid DNA transfection mediated with liposomes to colorectal cancer cells. METHODS: Dispensing varied transfection agents of liposome + DNA plasmid pEGFP-N(1), TNA + liposomes + pEGFP-N(1), TNA + pEGFP-N(1), liposomes merely, and TAN sole. Human colorectal cancer cell LoVo and HR-8348 were treated with the agents respectively. Green fluorescence protein (GFP) gene as a report gene was detected. RESULTS: GFP was not detected in cancer cells treated with agents of merely liposomes and TAN. Transfection rates of GFP in two groups of cancer cells treated with agent of TNA + liposomes + pEGFP-N(1) were 33%, 38% respectively. With liposome + pEGFP-N(1), the rates of transfection in two cells were 22%, 24% respectively. The expression of GFP was 1% in the two groups of tumor cells treated with TNA + pEGFP-N(1). With agent of TNA + liposomes + pEGFP-N(1), a high transfection rate of GFP gene was obtained. And no negative effect was observed to stabilization of TAN solution. CONCLUSION: TNA may enhance transfection rate of plasmid DNA mediated with liposome, and may be beneficial to the treatment of cancer.

Enhanced local bioavailability of single or compound drugs delivery to the inner ear through application of PLGA nanoparticles via round window administration.

In this paper, the potential of poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles (NPs) for carrying single or compound drugs traversing the round window membrane (RWM) was examined after the round window (RW) administration of different NPs to guinea pigs. First, coumarin-6 was incorporated into PLGA NPs as a fluorescent probe to investigate its ability to cross the RWM. Then, PLGA NPs with salvianolic acid B (Sal B), tanshinone IIA (TS IIA), and total panax notoginsenoside (PNS) including notoginsenoside R1 (R1), ginsenoside Rg1 (Rg1), and ginsenoside Rb1 (Rb1) were developed to evaluate whether NPs loaded with compound drugs would pass through the RWM and improve the local bioavailability of these agents. PLGA NPs loaded with single or compound drugs were prepared by the emulsification solvent evaporation method, and their particle size distribution, particle morphology, and encapsulation efficiency were characterized. In vitro release study showed sustained-release profiles of Sal B, TS IIA, and PNS from the NPs. The pharmacokinetic results showed that NPs applied to the RWM significantly improved drug distribution within the inner ear. The AUC0-t of coumarin-6 in the perilymph (PL) following RW administration of NPs was 4.7-fold higher than that of coumarin-6 solution, and the Cmax was 10.9-fold higher. Furthermore, the AUC(0-t) of R1, Rg1, and Rb1 were 4.0-, 3.1-, and 7.1-fold greater, respectively, after the application of NPs compared to the compound solution, and the Cmax were, respectively, 14.4-, 10.0-, and 16.7-fold higher. These findings suggest that PLGA NPs with unique properties at the nanoscale dimensions have a powerful ability to transport single or compound drugs into the PL through the RWM and remarkably enhance the local bioavailability of the encapsulated drugs in the inner ear. The use of PLGA NPs as nanoscale delivery vehicles to carry drugs across the RWM may be a promising strategy for the treatment of inner ear diseases.

Liposome-mediated induction of apoptosis of human hepatoma cells by c-myc antisense phosphorothioate oligodeoxynucleotide and 5-fluorouracil.

BACKGROUND: The aim of this study was to investigate the effect of a c-myc antisense oligodeoxynucleotide and 5-fluorouracil on the expression of c-myc, invasion and proliferation of HEPG-2 liver cancer cells. MATERIALS AND METHODS: HEPG-2 cells were treated with lipiosome-mediated c-myc ADSON and 5-fluorouracil. The proliferation inhibition rate and invasion were measured by MTT and invasion assay, respectively. Cell apoptosis was detected by flow cytometry and expression of c-myc by RT-PCR and immunohistochemistry. RESULTS: The proliferation inhibition rate was significantly higher in the antisense oligodeoxynucleotide added-5-fluorouracil group than single antisense oligodeoxynucleotide or 5-fluorouracil group (p<0.05). G0/G1 cells in the antisense oligodeoxynucleotide group and S cells in the 5-fluorouracil groups were significantly increased than that in the control group, respectively (P<0.01). The amplification strips of PCR products in 5-FU, ASODN and combination groups were significantly weaker than that in the control group (P<0.01). The percentage of c-myc-protein- positive cells were significantly lower in antisense oligodeoxynucleotide, 5-fluorouracil and combination groups than that in the control group (P<0.01). CONCLUSIONS: A liposome-mediated c-myc antisense oligodeoxynucleotide and 5-fluorouracil can inhibit the proliferation and invasion of liver cancer cells by reducing the expression of c-myc. A c-myc antisense oligodeoxynucleotide can increase the sensitivity of liver cancer cells to 5-fluorouracil and decrease the dosage of the agent necessary for efficacy, providing an experimental basis for the clinical therapy of liver cancer.

[Effects of surface treatment on the fracture resistance of teeth restored with fiber posts and core system].

OBJECTIVE: To evaluate the effects of different surface treatment on the fracture resistance of teeth restored with fiber posts and core system. METHODS: 24 fiber posts were divided into three groups according to different surface treatment techniques, including sandblasting, etching with hydrogen peroxide, and no treatment performed (the control group). All fiber posts were luted with a composite resin luting agent in the canal roots. The teeth were restored with composite resin cores and metal crowns. After cementation, the teeth were subjected to simulated aging conditions consisting of mechanical loading cycles and thermal cycles. All teeth were loaded in a mechanical testing machine, and the fracture load and fracture mode of each teeth were recorded. RESULTS: The fracture resistances of sandblasting and hydrogen peroxide groups were higher than the control group (P<0.05), while the fracture resistances of two test groups had no significant differences (P>0.05). Fracture modes of all fiber post groups were nearer to the coronal third of the root. CONCLUSION: Sandblasting and etching with hydrogen peroxide can improve the fracture resistance of teeth.