Evaluation of the efficacy of polyethylene glycol in combination with different doses of linaclotide in a fractionated bowel preparation for colonoscopy: a prospective randomized controlled study.

BACKGROUND AND AIM: The ideal bowel cleansing program still needs to be explored. The aim was to compare the bowel cleansing effect and patient tolerance of low-dose polyethylene glycol (PEG) combined with different doses of linaclotide in fractionated bowel preparation. METHODS: The subjects were randomly assigned to the 3LPEG group, 2LPEG + 2L group, or 2LPEG + L group. The primary outcome was to use the Ottawa Bowel Preparation Scale (OBPS) to evaluate the efficacy of bowel cleansing, and the secondary outcomes were the detection rate of adenomas and polyps, adverse reactions, tolerance, and defecation dynamics; subsets of patients with chronic constipation and irritable bowel syndrome were also analyzed. RESULTS: A total of 753 patients were randomly assigned. In ITT analysis, the success of preparation of the 2LPEG + 2L group was better than that of the 2LPEG + L group or the 3LPEG group (92.0% vs. 82.3% vs. 82.1%; P = 0.002). Compared with the 3LPEG group, the 2LPEG + L group showed similar but non-inferior results (82.3% vs. 82.1%, P > 0.05). The 2LPEG + 2L group was similar to the 2LPEG + L group in terms of adverse reaction, tolerance, willingness to reuse, and sleep quality, but both were superior to the 3LPEG group. In a subgroup analysis of chronic constipation, the 2LPEG + 2L group had the best cleansing effect on the right colon and mid colon, while in the subgroup analysis of irritable bowel syndrome, the tolerance was better in the 2LPEG + 2L group and the 2LPEG + L group than the 3LPEG group. CONCLUSIONS: 2LPEG + 2L is a feasible bowel preparation regimen.

Nanostructure of DiR-Loaded Solid Lipid Nanoparticles with Potential Bioimaging Functions.

The fluorescence dye-loaded nanoparticles are widely used as bioimaging agents in the field of nanotheranostics. However, the nanoparticles for nanotheranostics usually consist of synthetic materials, such as metal, silica, and organic polymers, which are often biologically incompatible and may arouse toxicity issues. Herein, the potential of near-infrared probe DiR-containing solid lipid nanoparticle suspensions (DiR-SLNS) as the bioimaging agent, which was prepared by lipids and surfactants with excellent biocompatibility, was investigated in this study. The nanostructure of DIR-SLNS system and the distribution of DiR were studied by dissipative particle dynamics (DPD) simulations. The stability of physicochemical properties and fluorescence spectra of DIR-SLNS system were investigated using dynamic laser scattering (DLS), nanoparticle tracking analysis (NTA), and fluorescence spectra. The fluorescence intensity-concentration correlation of DIR-SLNS was also evaluated. As a result, DiR-SLNS demonstrated a "core-shell"-like nanostructure and DiR was mainly distributed in the cetyl palmitate (CP) core rather than the surface of SLNS, which was beneficial to its potential applications in bioimaging. DiR-SLNS exhibited remarkable physicochemical stability as the nanoparticles maintained ~ 90% fluorescence intensity during the 10-day storage time. The correlation between fluorescence intensity and concentration was established and validated using a linear regression model. This study proposed a type of promising candidates in nano-scale with higher safety and fluorescence stability for bioimaging.

Collagen-based scaffolds with high wet-state cyclic compressibility for potential oral application.

Soft tissue substitutes have been developed to treat gingival recessions to avoid a second surgical site. However, products of pure collagen for clinical application lack their original mechanical strengths and tend to degrade fast in vivo. In this study, a collagen-based scaffold crosslinked with oxidized sodium alginate (OSA-Col) was developed to promote mechanical properties. Compared with commercial products collagen matrix (CM) and collagen sponge (CS), OSA-Col scaffolds presented higher wet-state cyclic compressibility, early anti-degradation ability, similar hemocompatibility and cytocompatibility. Furthermore, in the subcutaneous implantation experiment, OSA2-Col3 scaffolds showed better anti-degradation performance than CS scaffolds and superior neovascularization than CM scaffolds. These results demonstrated that OSA2-Col3 scaffolds had potential as a new soft tissue substitute for the treatment of gingival recessions.

A Multiepitope Peptide, rOmp22, Encapsulated in Chitosan-PLGA Nanoparticles as a Candidate Vaccine Against Acinetobacter baumannii Infection.

BACKGROUND: The development of vaccines is a promising and cost-effective strategy to prevent emerging multidrug-resistant (MDR) Acinetobacter baumannii (A. baumannii) infections. The purpose of this study was to prepare a multiepitope peptide nanovaccine and evaluate its immunogenicity and protective effect in BALB/c mice. METHODS: The B-cell and T-cell epitopes of Omp22 from A. baumannii were predicted using bioinformatics methods and identified by immunological experiments. The optimal epitopes were conjugated in series by 6-aminocaproic acid and chemically synthesized multiepitope polypeptide rOmp22. Then, rOmp22 was encapsulated by chitosan (CS) and poly (lactic-co-glycolic) acid (PLGA) to prepare CS-PLGA-rOmp22 nanoparticles (NPs). The immunogenicity and immunoprotective efficacy of the vaccine were evaluated in BALB/c mice. RESULTS: CS-PLGA-rOmp22 NPs were small (mean size of 272.83 nm) with apparently spherical structures, positively charged (4.39 mV) and nontoxic to A549 cells. A high encapsulation efficiency (54.94%) and a continuous slow release pattern were achieved. Compared with nonencapsulated rOmp22, CS-PLGA-rOmp22 immunized BALB/c mice induced higher levels of rOmp22-specific IgG in serum and IFN-γ in splenocyte supernatant. Additionally, lung injury and bacterial burdens in the lung and blood were suppressed, and potent protection (57.14%-83.3%) against acute lethal intratracheal A. baumannii challenge was observed in BALB/c mice vaccinated with CS-PLGA-rOmp22. CONCLUSION: CS-PLGA-rOmp22 NPs elicited specific IgG antibodies, Th1 cellular immunity and protection against acute lethal intratracheal A. baumannii challenge. Our results indicate that this nanovaccine is a desirable candidate for preventing A. baumannii infection.

Polymalate (PMA) biosynthesis and its molecular regulation in Aureobasidium spp.

It has been well documented that different strains of Aureobasidium spp. can synthesize and secrete over 30.0 g/L of polymalate (PMA) and the produced PMA has many potential applications in biomaterial, medical and food industries. The substrates for PMA biosynthesis include glucose, xylose, fructose, sucrose and glucose or fructose or xylose or sucrose-containing natural materials from industrial and agricultural wastes. Malate, the only monomer for PMA biosynthesis mainly comes from TCA cycle, cytosolic reduction TCA pathway and the glyoxylate cycle. The PMA synthetase (a NRPS) containing A like domain, T domain and C like domain is responsible for polymerization of malate into PMA molecules by formation of ester bonds between malates. PMA biosynthesis is regulated by the transcriptional activator Crz1 from Ca2+ signaling pathway, the GATA-type transcription factor Gat1 from nitrogen catabolite repression and the GATA-type transcription factor NsdD.

Prevotella intermedia induces matrix metalloproteinase-9 expression in human periodontal ligament cells.

Matrix metalloproteinases (MMPs) play pivotal roles in inflammatory diseases including chronic periodontitis. The effects of Prevotella intermedia, a major periodontal pathogen, on MMP-9 production in primary human periodontal ligament (hPDL) cells were examined in the present study. MMP-9 mRNA expression was measured by semiquantitative reverse transcriptase PCR and its protein secretion was assayed by gelatin zymography. Prevotella intermedia ATCC 25611 supernatant time and dose-dependently induced MMP-9 expression. In contrast, Porphyromanas gingivalis ATCC 33277 supernatants, Escherichia coli lipopolysacchride and IL-1beta exhibited no stimulatory effects on MMP-9 production in hPDL cells. Mitogen-activated protein kinases [MAPK, including extracellular signal-related kinases (ERK), c-jun N-terminal kinases (JNK) and p38] inhibitors exerted no effect on the P. intermedia-induced MMP-9 production, indicating that P. intermedia induced MMP-9 production through an MAPK-independent pathway. Our results demonstrated that P. intermedia may contribute to periodontal tissue destruction during chronic periodontitis by inducing MMP-9 production in hPDL cells.

Spectroscopic examination of enamel staining by coffee indicates dentin erosion by sequestration of elements.

The mechanism of coffee eliciting erosion on teeth is unclear as few studies have investigated the direct effect of coffee on enamel and dentin structures. The present study identified how coffee, the most popular beverage worldwide, induces staining and erosion on teeth. We show the grade of erosion of molars and incisors in Sprague Dawley rats from two different age groups, young (four weeks) and old (six months). We quantified the concentration of metals contained in coffee by mass spectrometry (ICP-MS). To determine elemental content in enamel (i.e. superficial) and dentin (i.e. substructure), we used Laser-induced Breakdown Spectroscopy (LIBS) and X-ray fluorescence (XRF) spectroscopy, respectively. For LIBS, a significant decrease of Ca, P, and Na was observed in the young coffee group relative to age-matched controls, whereas a significant increase in Mn, Fe, and K was observed. In the old coffee group, a significant increase of Mg, Fe, and K was observed along with a decrease of Mg, Ca, P, Na, Sr and Zn. For XRF, a significant decrease of the Ca/P ratio in the coffee group was observed. Spectroscopy results were correlated with scanning electron microscopy (SEM) and histological analysis. The SEM analysis showed pores and open spaces between young and old coffee groups, respectively. Thinning of enamel layers, loss of continuity in the enamel-dentin-junction, and wide spaces in dentin tubules with coffee use was found histologically. Coffee induces decalcification of teeth that corresponds to erosion, exposing the dentin structure by reducing enamel. Coffee immersion demonstrated an intrinsic staining in dentin by metal deposition.

Prevotella intermedia stimulates tissue-type plasminogen activator and plasminogen activator inhibitor-2 expression via multiple signaling pathways in human periodontal ligament cells.

Prevotella intermedia is an important periodontal pathogen that induces various inflammatory and immune responses. In this study, we investigated the effects of P. intermedia on the plasminogen system in human periodontal ligament (hPDL) cells and explored the signaling pathways involved. Using semi-quantitative reverse transcription (RT)-PCR and quantitative real-time RT-qPCR, we demonstrated that P. intermedia challenge increased tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor (PAI)-2 expression in a concentration- and time-dependent manner, but exerted no influence on urokinase-type plasminogen activator and PAI-1mRNA expression in hPDL cells. Prevotella intermedia stimulation also enhanced tPA protein secretion as confirmed by enzyme-linked immunosorbent assay. Western blot results revealed that P. intermedia treatment increased phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase (p38). ERK, JNK and protein kinase C inhibitors significantly attenuated the P. intermedia-induced tPA and PAI-2 expression. Furthermore, p38 and phosphatidylinositol 3-kinase inhibitors markedly decreased PAI-2 expression, whereas they showed no or little inhibition on tPA expression. In contrast, inhibition of protein kinase A greatly enhanced the upregulatory effect of P. intermedia on tPA and PAI-2 expression. Our results suggest that P. intermedia may contribute to periodontal tissue destruction by upregulating tPA and PAI-2 expression in hPDL cells via multiple signaling pathways.

[Study on the height of marginal ridge to cusp in posterior teeth and its effect on brackets placement].

OBJECTIVE: To measure the vertical height of mesio-distal marginal ridge to cusp in posterior teeth, which may be helpful to brackets positioning. METHODS: The study groups comprised of 60 patients (30 men, 30 women, mostly aged 12-14 years) who underwent orthodontic treatment without tooth extraction and matched the Andrews normal occlusion standard after treatment. Study model of each patient was made. Three-dimensional laser measurer was used to evaluate the vertical height of mesio-distal marginal ridge to mesial cusp in posterior teeth. The data were stored in a personal computer and submitted to statistical analysis of paired t test. RESULTS: No statistical significant difference was found in the same teeth between men and women. Not only in maxilla but also in mandible, there was no significant difference between the left and the right (P>0.05). The average vertical height of maxillary first premolars was (1.70+/-0.50) mm, the maxillary second premolars was (1.24+/-0.45) mm, and for maxillary first molars, the result was (0.83+/-0.40) mm. The difference between each result was statistically significant (P9< 0.01). The average vertical height of mandibular first premolars was (2.25+/-0.45) mm, the mandibular second premolars was (1.55+/-0.45) mm, and for mandibular first molars, the result was (1.18+/-0.40) mm. The difference between each result was statistically significant (P<0.0 1). CONCLUSION: The vertical height of brackets position in posterior teeth should be considered to guarantee that mesio-distal marginal ridges of deferent posterior teeth located in the same plane, so that satisfying goal could be achieved, If the vertical height in the first molar was X mm, the vertical height in the second premolar should be (X+0.5) mm, and (X+1.0) mm might be suit for the first premolar.