Mechanisms of antimicrobial and antiendotoxin activities of a triazine-based amphipathic polymer.

TZP4 is a triazine-based amphipathic polymer designed to mimic the amphipathic structure found in antimicrobial peptides. TZP4 showed potent antimicrobial activity comparable to melittin against antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus and multidrug-resistant Pseudomonas aeruginosa. TZP4 showed high resistance to proteolytic degradation and low tendency to develop drug resistance. The results from membrane depolarization, SYTOX Green uptake, flow cytometry, and gel retardation revealed that the mechanism of antimicrobial action of TZP4 involved an intracellular target rather than the bacterial cell membrane. Furthermore, TZP4 suppressed the messenger RNA levels of inducible nitric oxide synthase and tumor necrosis factor-α (TNF-α) and inhibited the release of nitric oxide and TNF-α in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. BODIPY-TR-cadaverine displacement and dissociation of fluorescein isothiocyanate (FITC)-labeled LPS assays revealed that TZP4 strongly bound to LPS and disaggregated the LPS oligomers. Flow cytometric analysis demonstrated that TZP4 inhibits the binding of FITC-conjugated LPS to RAW264.7 cells. These observations indicate that TZP4 may exert its antiendotoxic activity by directly binding with LPS and inhibiting the interaction between LPS and CD14+ cells. Collectively, TZP4 is a promising drug candidate for the treatment of endotoxic shock and sepsis caused by Gram-negative bacterial infections.

Comparison of 4-L Polyethylene Glycol and 2-L Polyethylene Glycol Plus Ascorbic Acid in Patients with Inactive Ulcerative Colitis.

BACKGROUND: Although colonoscopy preparation may cause symptom flares in patients with ulcerative colitis (UC), little is known about the standard preparation regimen in this population. AIM: We aimed to compare 4L polyethylene glycol (4L-PEG) with 2L polyethylene glycol plus ascorbic acid (2L-PEG-Asc) in quiescent UC patients. METHODS: Patients with inactive UC undergoing colonoscopy for surveillance or checkup of mucosal healing were prospectively enrolled at 5 tertiary hospitals. They were randomly assigned to 4L-PEG and 2L-PEG-Asc groups. The Boston Bowel Preparation Scale (BBPS) was used for the preparation quality. Symptoms were assessed using the Simple Clinical Colitis Activity Index (SCCAI) before colonoscopy, at 1 and 4 weeks after the procedure. RESULTS: Overall, 109 patients were included in the study (4L-PEG group 53, 2L-PEG-Asc group 56, the mean age at diagnosis 42.25 years, male 77). The quality of preparation was comparable between the groups (BBPS ≥ 6, 96.2 vs. 92.9%, p = 0.679). Although 26 patients (23.8%) had increased SCCAI scores within 4 weeks after colonoscopy, resulting in a medication dose-up or add-on in 3 patients (2.7%), the rise in scores was not different between the groups. No serious adverse events during preparation were observed in either group. However, the 2L-PEG-Asc group was more likely to be willing to repeat the preparation with the same agent than the 4L-PEG group (82.1 vs. 64.2%, respectively, p = 0.034). CONCLUSION: PEG-based regimens with different volumes are equally effective and safe in inactive UC patients. 2L-PEG-Asc is more acceptable in this population as indicated by the willingness for further usage.

Bioreducible polymer-delivered siRNA targeting MMP-9: suppression of granulation tissue formation after bare metallic stent placement in a rat urethral model.

PURPOSE: To evaluate the effectiveness of small interfering RNA (siRNA) targeting matrix metalloproteinase 9 (MMP-9) in suppressing granulation tissue formation caused by bare metallic stent placement in a rat urethral model. MATERIALS AND METHODS: All experiments were approved by the committee of animal research. In 20 Sprague-Dawley male rats (weight range, 300-350 g), a self-expanding metallic bare stent was inserted in the urethra with fluoroscopic guidance. One group of 10 rats (group A) was treated with MMP-9 siRNA/bioreducible branched polyethylenimine-disulfide cross-linked-indocyanine green (bioreducible BPEI-SS-ICG), while the other group of 10 rats (group B) received control siRNA/bioreducible BPEI-SS-ICG treatment. All rats were sacrificed at 4 weeks. The therapeutic effectiveness of the MMP-9 siRNA/bioreducible BPEI-SS-ICG complex was assessed by comparing the two results of retrograde urethrography, histologic examination, and quantification of MMP-9 by using zymography and Western blot analysis between the two groups. The Mann-Whitney U test was used to evaluate differences. RESULTS: Stent placement was successful in all rats without a single case of migration at follow-up. Retrograde urethrography performed 4 weeks after stent placement demonstrated significantly larger luminal diameters of the urethra within the stents in group A compared with those in group B (P = .011). Histologic analysis revealed that the mean percentage of granulation tissue area (P < .001), mean number of epithelial layers (P < .001), and mean thickness of submucosal fibrosis (P < .001) were significantly decreased in group A compared with group B. Meanwhile, the mean density of inflammatory cell infiltration did not significantly differ between the two groups (P = .184). Quantitative analysis disclosed MMP-9 levels to be lower in group A relative to group B, indicating positive inhibition of MMP-9 by MMP-9 siRNA/bioreducible BPEI-SS-ICG. CONCLUSION: MMP-9 siRNA/bioreducible BPEI-SS-ICG is effective for inhibiting granulation tissue formation after bare metallic stent placement in a rat urethral model.

IN-1233-eluting covered metallic stent to prevent hyperplasia: experimental study in a rabbit esophageal model.

PURPOSE: To investigate the efficacy of an IN-1233-eluting covered stent in preventing tissue hyperplasia in a rabbit esophageal model. MATERIALS AND METHODS: The local animal research committee approved all experiments. Esophageal stents were placed in 40 male New Zealand rabbits (weight range, 2.8-3.2 kg). The drug group (D) received IN-1233-eluting covered stents (n = 20); the control group (C) received polyurethane-covered stents (n = 20). Drug loading of IN-1233-eluting covered stent was 10%. Four study groups were formed: C and D animals sacrificed at 4 (D4, C4) and 8 (D8, C8) weeks after stent placement (n = 10). Esophagography was used to assess the percentage of diameter stenosis. Histologic findings of the drug and control stents were compared. The Mann-Whitney U test was used to evaluate differences. RESULTS: The mean percentage ± standard deviation of diameter stenosis was significantly lower in D groups than in C groups at both 4 (C4 = 36.15% ± 12.63, D4 = 7.83% ± 8.12 [P < .001]) and 8 (C8 = 50.21% ± 20.43, D8 = 27.78% ± 14.40 [P = .019]) weeks. Percentage of granulation tissue area (C4 = 33.07% ± 19.11, D4 = 21.59% ± 18.22 [P = .028]; C8 = 44.70% ± 21.71, D8 = 31.97% ± 22.54 [P = .131]), number of epithelial layers (C4 = 4.77 ± 1.55, D4 = 3.37 ± 1.73 [P = .002]; C8 = 5.50 ± 1.38, D8 = 4.50 ± 1.63 [P = .057]), and thickness of submucosal fibrosis (C4 = 2.42 mm ± 1.08, D4 = 1.62 mm ± 0.77 [P = .006]; C8 = 2.89 mm ± 1.00, D8 = 2.07 mm ± 0.71 [P = .007]) were lower in D than in C groups. Inflammatory cell infiltration was significantly higher in D than in C groups (C4 = 2.63 ± 0.81, D4 = 3.33 ± 1.09 [P = .032]; C8 = 2.20 ± 0.81, D8 = 3.00 ± 0.95 [P = .012]). CONCLUSION: The use of an IN-1233-eluting covered stents decreased tissue hyperplasia secondary to stent placement in a rabbit esophageal model.

Metabolic engineering of Escherichia coli for enhanced biosynthesis of poly(3-hydroxybutyrate) based on proteome analysis.

We have previously analyzed the proteome of recombinant Escherichia coli producing poly(3-hydroxybutyrate) [P(3HB)] and revealed that the expression level of several enzymes in central metabolism are proportional to the amount of P(3HB) accumulated in the cells. Based on these results, the amplification effects of triosephosphate isomerase (TpiA) and fructose-bisphosphate aldolase (FbaA) on P(3HB) synthesis were examined in recombinant E. coli W3110, XL1-Blue, and W lacI mutant strains using glucose, sucrose and xylose as carbon sources. Amplification of TpiA and FbaA significantly increased the P(3HB) contents and concentrations in the three E. coli strains. TpiA amplification in E. coli XL1-Blue lacI increased P(3HB) from 0.4 to 1.6 to g/l from glucose. Thus amplification of glycolytic pathway enzymes is a good strategy for efficient production of P(3HB) by allowing increased glycolytic pathway flux to make more acetyl-CoA available for P(3HB) biosynthesis.

Synthesis of nylon 4 from gamma-aminobutyrate (GABA) produced by recombinant Escherichia coli.

In this study, we developed recombinant Escherichia coli strains expressing Lactococcus lactis subsp. lactis Il1403 glutamate decarboxylase (GadB) for the production of GABA from glutamate monosodium salt (MSG). Syntheses of GABA from MSG were examined by employing recombinant E. coli XL1-Blue as a whole cell biocatalyst in buffer solution. By increasing the concentration of E. coli XL1-Blue expressing GadB from the OD600 of 2-10, the concentration and conversion yield of GABA produced from 10 g/L of MSG could be increased from 4.3 to 4.8 g/L and from 70 to 78 %, respectively. Furthermore, E. coli XL1-Blue expressing GadB highly concentrated to the OD600 of 100 produced 76.2 g/L of GABA from 200 g/L of MSG with 62.4 % of GABA yield. Finally, nylon 4 could be synthesized by the bulk polymerization using 2-pyrrolidone that was prepared from microbially synthesized GABA by the reaction with Al2O3 as catalyst in toluene with the yield of 96 %.

Vertical augmentation of a severely atrophied posterior mandibular alveolar ridge for a dental implant using a patient-specific 3D printed PCL/BGS7 scaffold: A technical note.

Vertical bone augmentation for dental implants in the posterior mandibular region with significant bone resorption is challenging. For this purpose, methods such as block bone grafting with screw fixation, particulate bone grafting with titanium mesh or barrier membrane, and distraction osteogenesis have been used, and autogenous block bone grafting is considered the gold standard. However, the autogenous block bone grafting has the following disadvantages: bone harvesting is challenging, and block bone contouring according to the recipient site is time-consuming and laborious. Therefore, in this study, we report the use of particulate bone with a polycaprolactone/bioactive glass-7 scaffold, designed, and three-dimensionally printed preoperatively, to resolve the above-mentioned challenges.

Efficacy and safety of 1 L polyethylene glycol plus ascorbic acid for bowel preparation in elderly: comparison with oral sulfate solution.

BACKGROUND/AIMS: Recently, 1 L of polyethylene glycol (PEG) plus ascorbic acid (Asc) has been introduced in Korea as a colonoscopy preparation agent. Data on its efficacy and safety in older adults have been limited. We aimed to evaluate the safety and efficacy of 1 L PEG/Asc in older adults by comparing it with oral sulfate solution (OSS). METHODS: A prospective multicenter randomized study was conducted with subjects aged ≥ 65 years who underwent colonoscopy. The participants were randomized to receive 1 L PEG/Asc or OSS. The primary endpoint was successful bowel preparation, defined as total Boston Bowel Preparation Scale ≥ 6, and ≥ 2 at each segment. Patient satisfaction, adverse events, and renal function changes were compared between the groups. RESULTS: Among the 106 patients, 104 were finally included in the analysis. Overall, successful bowel preparation was achieved in 96.2% of both 1 L PEG/Asc and OSS groups. The satisfaction scores for taste, total amount ingested, overall feeling, and willingness to repeat the same regimen were not significantly different between the groups. Adverse events of moderate or higher severity occurred in 16 and 10 cases in the 1 L PEG/Asc and OSS group, respectively. There were no significant changes in electrolyte levels or renal function from baseline. CONCLUSION: The successful bowel preparation rate was > 90% in both groups without severe adverse effects and significant changes in renal function. As a new low-dose preparation regimen for colonoscopy in older adults, 1 L PEG/Asc, is as effective and safe as OSS.

Dysfunction in parkin aggravates inflammatory bone erosion by reinforcing osteoclast activity.

BACKGROUND: Parkin dysfunction associated with the progression of parkinsonism contributes to a progressive systemic skeletal disease characterized by low bone mineral density. However, the role of parkin in bone remodeling has not yet been elucidated in detail. RESULT: We observed that decreased parkin in monocytes is linked to osteoclastic bone-resorbing activity. siRNA-mediated knockdown of parkin significantly enhanced the bone-resorbing activity of osteoclasts (OCs) on dentin without any changes in osteoblast differentiation. Moreover, Parkin-deficient mice exhibited an osteoporotic phenotype with a lower bone volume accompanied by increased OC-mediated bone-resorbing capacity displaying increased acetylation of α-tubulin compared to wild-type (WT) mice. Notably, compared to WT mice, the Parkin-deficient mice displayed increased susceptibility to inflammatory arthritis, reflected by a higher arthritis score and a marked bone loss after arthritis induction using K/BxN serum transfer, but not ovariectomy-induced bone loss. Intriguingly, parkin colocalized with microtubules and parkin-depleted-osteoclast precursor cells (Parkin-/- OCPs) displayed augmented ERK-dependent acetylation of α-tubulin due to failure of interaction with histone deacetylase 6 (HDAC6), which was promoted by IL-1ß signaling. The ectopic expression of parkin in Parkin-/- OCPs limited the increase in dentin resorption induced by IL-1ß, accompanied by the reduced acetylation of α-tubulin and diminished cathepsin K activity. CONCLUSION: These results indicate that a deficiency in the function of parkin caused by a decrease in parkin expression in OCPs under the inflammatory condition may enhance inflammatory bone erosion by altering microtubule dynamics to maintain OC activity.

Transcatheter renal artery embolization with N-butyl cyanoacrylate.

BACKGROUND: Despite its long history, the application of N-butyl cyanoacrylate (NBCA) has been limited compared to other materials such as particulate agents and coils. This possibly owes to a widespread misconception that NBCA is difficult to handle and carries a high risk of complications due to its liquid nature and rapid polymerization time. However, recent reports have shown that, with knowledge and experience, NBCA is safe and effective to use in visceral arteries. PURPOSE: To review the outcome of transcatheter embolization of the renal artery using NBCA for varied etiologies in the kidney. MATERIAL AND METHODS: Fourteen patients with varied etiologies in the kidney underwent renal artery embolization using NBCA as the sole embolic agent (64%) or in combination with an additional embolic material (36%). A review of medical charts and images were performed to gather information regarding underlying etiologies, clinical presentation, and outcome of embolization. RESULTS: Technical success was achieved in all patients (100%) while clinical success was achieved in 12 (85.7%). One failed case was managed by repeat embolization using microcoils, while the other underwent partial nephrectomy after failed reattempt at embolization. Three patients with recurrent bleeding after previously having undergone embolization using microcoils or gelatin sponge particles were successfully managed the second time using NBCA. NBCA embolization was also effective in three patients with hemostatic abnormality. Complications attributable to NBCA embolization were renal atrophy in one patient and microcatheter tip fracture in another. CONCLUSION: The application of NBCA for transcatheter embolization of varied etiologies involving the renal artery is feasible and safe in the hands of an experienced interventional radiologist. It offers immediate and effective occlusion of the pathologic vessel and, while it can be used exclusively on its own, it can also be used to complement other embolic materials.

Sphingosine-1-phosphate hinders the osteogenic differentiation of dental pulp stem cells in association with AKT signaling pathways.

Sphingosine-1-phosphate (S1P) is an important lipid mediator that regulates a diverse range of intracellular cell signaling pathways that are relevant to tissue engineering and regenerative medicine. However, the precise function of S1P in dental pulp stem cells (DPSCs) and its osteogenic differentiation remains unclear. We here investigated the function of S1P/S1P receptor (S1PR)-mediated cellular signaling in the osteogenic differentiation of DPSCs and clarified the fundamental signaling pathway. Our results showed that S1P-treated DPSCs exhibited a low rate of differentiation toward the osteogenic phenotype in association with a marked reduction in osteogenesis-related gene expression and AKT activation. Of note, both S1PR1/S1PR3 and S1PR2 agonists significantly downregulated the expression of osteogenic genes and suppressed AKT activation, resulting in an attenuated osteogenic capacity of DPSCs. Most importantly, an AKT activator completely abrogated the S1P-mediated downregulation of osteoblastic markers and partially prevented S1P-mediated attenuation effects during osteogenesis. Intriguingly, the pro-inflammatory TNF-α cytokine promoted the infiltration of macrophages toward DPSCs and induced S1P production in both DPSCs and macrophages. Our findings indicate that the elevation of S1P under inflammatory conditions suppresses the osteogenic capacity of the DPSCs responsible for regenerative endodontics.

Efficacy, safety and tolerability of oral sulphate tablet for bowel preparation in patients with inflammatory bowel disease: A multicentre randomized controlled study.

BACKGROUND AND AIMS: We evaluated the efficacy, safety and tolerability of novel oral sulphate tablets [OSTs] vs 2 L of polyethylene glycol and ascorbate [PEG/Asc] in patients with inflammatory bowel disease [IBD]. PATIENTS AND METHODS: A total of 110 patients with clinically inactive IBD were enrolled in this single-blind multicentre non-inferiority study. Patients were randomly assigned to the OST or 2 L PEG/Asc group and we applied a split-dose regimen. The primary efficacy endpoint was bowel cleansing success rate defined as Harefield Cleansing Scale Grade A or B. The secondary endpoints were perfect preparation rate, the presence of air bubbles, safety as assessed by laboratory abnormalities and self-reported adverse events, or IBD symptom flare-ups. Tolerability was assessed by a pre-procedural visual analog scale [VAS] interview. RESULTS: Both groups showed high cleansing success rates [98.1%] and there was no significant difference in perfect preparation rate. The proportion of a bubble score 0 was significantly higher in the OST group [94.5% vs 50.0%, p < 0.001]. There was no significant intergroup difference in vomiting or bloating. Symptom flare-ups occurred in two OST group patients. No clinically significant blood test abnormalities were noted in either group. Ease of ingestion and taste scores were significantly higher in the OST group. More patients in the OST group [94.5%] wanted to take the same preparation agent for their next colonoscopy. CONCLUSIONS: Both OST and 2 L PEG/Asc demonstrated high successful cleansing and safety in patients with inactive IBD. OST achieved higher satisfaction than 2 L PEG/Asc. Our results suggest that the OST split-dose regimen is effective and safe for patients with inactive IBD.

HDAC6 Inhibition Corrects Electrophysiological and Axonal Transport Deficits in a Human Stem Cell-Based Model of Charcot-Marie-Tooth Disease (Type 2D).

Charcot-Marie-Tooth disease type 2D (CMT2D), is a hereditary peripheral neuropathy caused by mutations in the gene encoding glycyl-tRNA synthetase (GARS1). Here, human induced pluripotent stem cell (hiPSC)-based models of CMT2D bearing mutations in GARS1 and their use for the identification of predictive biomarkers amenable to therapeutic efficacy screening is described. Cultures containing spinal cord motor neurons generated from this line exhibit network activity marked by significant deficiencies in spontaneous action potential firing and burst fire behavior. This result matches clinical data collected from a patient bearing a GARS1P724H mutation and is coupled with significant decreases in acetylated α-tubulin levels and mitochondrial movement within axons. Treatment with histone deacetylase 6 inhibitors, tubastatin A and CKD504, improves mitochondrial movement and α-tubulin acetylation in these cells. Furthermore, CKD504 treatment enhances population-level electrophysiological activity, highlighting its potential as an effective treatment for CMT2D.

Temporary placement of covered retrievable expandable nitinol stents with barbs in high-risk surgical patients with benign prostatic hyperplasia: work in progress.

PURPOSE: To report the use of a newly constructed, covered, retrievable, expandable nitinol stent with barbs to overcome the problem of stent migration associated with conventional covered prostatic expandable stents and to evaluate prospectively the technical feasibility and clinical effectiveness of the stents in patients with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A covered retrievable expandable nitinol stent with four barbs was placed with use of an 18-F stent delivery system in seven consecutive patients with symptomatic BPH who had high operative risks. Age range of patients was 62-83 years (mean 74 years). In cases in which the stent migrated, it was replaced with a stent with eight barbs. The stents were routinely removed 4 months after placement using a 21-F stent removal set. RESULTS: Stent placement was technically successful and well tolerated in six of the seven patients. The remaining patient needed a second stent placement after removal of the first stent. The stent with four barbs migrated into the urinary bladder in four patients (57%); three of these patients received a second stent with eight barbs with good results, and the fourth patient did not need further treatment because his symptoms improved. Routine removal of the stent 4 months after placement was performed in three of the seven patients with good results. CONCLUSIONS: Retrievable stents with eight barbs seem to overcome the problem of stent migration associated with conventional prostatic expandable stents. Preliminary results suggest that stents with barbs are both feasible and effective in patients with BPH.

Tumor overgrowth after expandable metallic stent placement: experience in 583 patients with malignant gastroduodenal obstruction.

OBJECTIVE: The objective of our study was to assess the incidence, predictive factors, and treatment of tumor overgrowth after placement of expandable metallic dual stents in patients with malignant gastroduodenal obstruction. MATERIALS AND METHODS: Expandable metallic dual stents were inserted under fluoroscopic guidance in 583 patients with symptomatic malignant gastroduodenal obstruction. We retrospectively reviewed prospectively collected patient records to determine the incidence and treatment of tumor overgrowth after stent placement and used multivariate analysis to determine factors predicting tumor overgrowth. RESULTS: Tumor overgrowth occurred after stent placement in 22 of 583 patients (3.8%) (range, 41-634 days; mean, 179.0 days). Duodenal lesions (odds ratio [OR], 4.505; p = 0.002), longer survival time (OR, 1.003; p = 0.001), and length of obstruction (OR, 0.783; p = 0.035) were independent predictors of tumor overgrowth. Twenty of the 22 patients were successfully treated by placement of a second dual stent, whereas the other two patients refused placement of a second stent or other further treatment. Overall, 19 of 20 patients (95%) showed improvement in symptoms after second stent placement. Duodenal perforation occurred in one of the 20 patients 125 days after placement of a second stent and was treated surgically. CONCLUSION: Tumor overgrowth seems to be an uncommon complication of expandable metallic dual stent placement in patients with malignant gastroduodenal obstruction. Tumor overgrowth is associated with duodenal lesions, longer survival time, and shorter stricture length. Tumor overgrowth can be successfully managed by coaxial insertion of a second dual-expandable metallic stent into the obstructed first stent.

Structure and phase behavior of a confined nanodroplet composed of the flexible chain molecules.

A polymer density functional theory has been employed for investigating the structure and phase behaviors of the chain polymer, which is modelled as the tangentially connected sphere chain with an attractive interaction, inside the nanosized pores. The excess free energy of the chain polymer has been approximated as the modified fundamental measure-theory for the hard spheres, the Wertheim's first-order perturbation for the chain connectivity, and the mean-field approximation for the van der Waals contribution. For the value of the chemical potential corresponding to a stable liquid phase in the bulk system and a metastable vapor phase, the flexible chain molecules undergo the liquid-vapor transition as the pore size is reduced; the vapor is the stable phase at small volume, whereas the liquid is the stable phase at large volume. The wide liquid-vapor coexistence curve, which explains the wide range of metastable liquid-vapor states, is observed at low temperature. The increase of temperature and decrease of pore size result in a narrowing of liquid-vapor coexistence curves. The increase of chain length leads to a shift of the liquid-vapor coexistence curve towards lower values of chemical potential. The coexistence curves for the confined phase diagram are contained within the corresponding bulk liquid-vapor coexistence curve. The equilibrium capillary phase transition occurs at a higher chemical potential than in the bulk phase.

The evaluation of resin infiltration for masking labial enamel white spot lesions.

OBJECTIVE: The aim of this study was to clinically assess the effectiveness of masking white spot enamel lesions using a resin infiltration technique that was recently developed to arrest incipient caries in a micro-invasive concept. METHODS: Twenty teeth with a Developmental Defect of Enamel (DDE) and 18 teeth with Post-orthodontic Decalcification (POD) were selected and treated with resin infiltration. Standardized photographs were taken before, immediately after, and 1 week after treatment and were analysed using image analysing software to calculate the ΔE values. The results were classified into three groups: completely masked, partially masked, and unchanged. RESULTS: Among the 20 teeth with DDE, five teeth (25%) were classified as completely masked, whereas seven (35%) and eight teeth (40%) were partially masked and unchanged, respectively. Among the 18 teeth with POD, 11 teeth (61%) were completely masked, six teeth (33%) were partially masked, and one tooth (6%) was unchanged. In some teeth, the result was more improved after 1 week than immediately after infiltration. CONCLUSION: The masking effect was dramatic in some cases but not in others. The long-term colour stability of the result should be followed up through continuous clinical and scientific studies.

Amphiphilic Triazine Polymer Derivatives as Antibacterial And Anti-atopic Agents in Mice Model.

Considering the emergence of bacterial resistance and low proteolytic stability of antimicrobial peptides (AMPs), herein we developed a series of ultra-short triazine based amphipathic polymers (TZP) that are connected with ethylene diamine linkers instead of protease sensitive amide bond. The most potent oligomers, TZP3 and TZP5 not only displayed potent antibacterial action on various drug-resistant pathogens but also exhibited a strong synergic antibacterial activity in combination with chloramphenicol against multidrug-resistant Pseudomonas aeruginosa (MDRPA). Since most of atopic dermatitis (AD) infections are caused by bacterial colonization, we evaluated the potency of TZP3 and TZP5 on AD in vitro and in vivo. In vitro AD analysis of these two polymers showed significant inhibition against the release of ß-hexosaminidase and tumor necrosis factor (TNF-α) from RBL-2H3 cells. In AD-like skin lesions in BALB/c mice model, these two polymers displayed significant potency in suppressing dermal and epidermal thickness, mast cell infiltration and pro-inflammatory cytokines expression. Moreover, these polymers exhibited remarkable efficacy over the allergies caused by the imbalance of Th1/Th2 by regulating total IgE and IgG2a. Finally, the impact of treatment effects of these polymers was examined through analyzing the weights and sizes of spleen and lymph node of AD-induced mice.

Simple, efficient, and reproducible gene transfection of mouse embryonic stem cells by magnetofection.

Embryonic stem (ES) cells are recognized as an excellent cell culture model for studying developmental mechanisms and their therapeutic modulations. The aim of this work was to define whether using magnetofection was an efficient way to manipulate stem cells genetically without adversely affecting their proliferation or self-renewal capacity. We compared our magnetofection results to those of a conservative method using FuGENE 6. Using enhanced green fluorescent protein (eGFP) as a reporter gene in D3 mouse ES (mES) cells, we found that magnetofection gave a significantly higher efficiency (45%) of gene delivery in stem cells than did the FuGENE 6 method (15%), whereas both demonstrated efficient transfection in NIH-3T3 cells (60%). Although the transfected D3 (D3-eGFP) mES cells had undergone a large number of passages (>50), a high percentage of cells retained ES markers such as Oct-4 and stage-specific embryonic antigen-1 (SSEA-1). They also retained the ability to form embryoid bodies and differentiated in vitro into cells of the three germ layers. eGFP expression was sustained during stem cell proliferation and differentiation. This is the first transfection report using magnetofection in ES cells. On the basis of our results, we conclude that magnetofection is an efficient and reliable method for the introduction of foreign DNA into mouse ES cells and may become the method of choice.