Analysis of Risk Factors for Velopharyngeal Insufficiency and Palatal Fistula After Sommerlad-Furlow Palatoplasty.

This study aimed to introduce a surgery technique-Sommerlad-Furlow palatoplasty (SFP) and analyze the risk factors of velopharyngeal insufficiency (VPI) and palatal fistula after SFP. Cases after SFP under the age of 5 between 2011 and 2021 were reviewed, and the cases with complete follow-up information were included. Univariate and multivariate logistic regression were used to evaluate the effects of surgical age, surgery technique, surgeon's experience, and cleft type on velopharyngeal function and the occurrence of palatal fistula. SFP is a safe and effective procedure to increase the palatal length and reconstruct the levator veli palatini sling. The speech outcome after SFP was associated with cleft type and age at operation. Age = 1.285 years is the best cutoff value. The fistula occurrence was associated with cleft type only.

The reciprocity of skeletal muscle and bone: an evolving view from mechanical coupling, secretory crosstalk to stem cell exchange.

Introduction: Muscle and bone constitute the two main parts of the musculoskeletal system and generate an intricately coordinated motion system. The crosstalk between muscle and bone has been under investigation, leading to revolutionary perspectives in recent years. Method and results: In this review, the evolving concept of muscle-bone interaction from mechanical coupling, secretory crosstalk to stem cell exchange was explained in sequence. The theory of mechanical coupling stems from the observation that the development and maintenance of bone mass are largely dependent on muscle-derived mechanical loads, which was later proved by Wolff's law, Utah paradigm and Mechanostat hypothesis. Then bone and muscle are gradually recognized as endocrine organs, which can secrete various cytokines to modulate the tissue homeostasis and remodeling to each other. The latest view presented muscle-bone interaction in a more direct way: the resident mesenchymal stromal cell in the skeletal muscle, i.e., fibro-adipogenic progenitors (FAPs), could migrate to the bone injury site and contribute to bone regeneration. Emerging evidence even reveals the ectopic source of FAPs from tissue outside the musculoskeletal system, highlighting its dynamic property. Conclusion: FAPs have been established as the critical cell connecting muscle and bone, which provides a new modality to study inter-tissue communication. A comprehensive and integrated perspective of muscle and bone will facilitate in-depth research in the musculoskeletal system and promote novel therapeutic avenues in treating musculoskeletal disorders.

Enhanced Cellular Delivery of Tildipirosin by Xanthan Gum-Gelatin Composite Nanogels.

Tildipirosin has no significant inhibitory effect on intracellular bacteria because of its poor membrane permeability. To this end, tildipirosin-loaded xanthan gum-gelatin composite nanogels were innovatively prepared to improve the cellular uptake efficiency. The formation of the nanogels via interactions between the positively charged gelatin and the negatively charged xanthan gum was confirmed by powder X-ray diffraction and Fourier transform infrared. The results indicate that the optimal tildipirosin composite nanogels possessed a 3D network structure and were shaped like a uniformly dispersed ellipse, and the particle size, PDI, and ζ potential were 229.4 ± 1.5 nm, 0.26 ± 0.04, and -33.2 ± 2.2 mV, respectively. Interestingly, the nanogels exhibited gelatinase-responsive characteristics, robust cellular uptake via clathrin-mediated endocytosis, and excellent sustained release. With those pharmaceutical properties provided by xanthan gum-gelatin composite nanogels, the anti-Staphylococcus aureus activity of tildipirosin was remarkably amplified. Further, tildipirosin composite nanogels demonstrated good biocompatibility and low in vivo and in vitro toxicities. Therefore, we concluded that tildipirosin-loaded xanthan gum-gelatin composite nanogels might be employed as a potentially effective gelatinase-responsive drug delivery for intracellular bacterial infection.

Lightweight Differentiated Transmission Based on Fuzzy and Random Modeling in Underwater Acoustic Sensor Networks.

Energy-efficient and reliable underwater acoustic communication attracts a lot of research due to special marine communication conditions with limited resources in underwater acoustic sensor networks (UASNs). In their final analysis, the existing studies focus on controlling redundant communication and route void that greatly influence UASNs' comprehensive performances. Most of them consider directional or omnidirectional transmission for partial optimization aspects, which still have many extra data loads and performance losses. This paper analyzes the main issue sources causing redundant communication in UASNs, and proposes a lightweight differentiated transmission to suppress extra communication to the greatest extent as well as balance energy consumption. First, the layered model employs layer ID to limit the scale of the data packet header, which does not need depth or location information. Second, the layered model, fuzzy-based model, random modeling and directional-omnidirectional differentiated transmission mode comb out the forwarders step by step to decrease needless duplicated forwarding. Third, forwarders are decided by local computation in nodes, which avoids exchanging controlling information among nodes. Simulation results show that our method can efficiently reduce the network load and improve the performance in terms of energy consumption balance, network lifetime, data conflict and network congestion, and data packet delivery ratio.

Intestinal Barrier Protective Study of Jujube Peel Polyphenols/Zein Complexes by a Combined Caco-2 Cell and Caenorhabditis elegans Model: A Perspective of Proteomics.

Jujube peels have been recognized as a promising resource of several bioactive ingredients. The main composition of jujube peel polyphenols (JPP) has been identified as rutin, kaempferol-3-O-rutinosid, and salicylic acid. The JPP/zein complexes, whose bioavailability reached 69.73% ± 5.06% in vitro, have been formed successfully. The Caco-2 cell and Caenorhabditis elegans (C. elegans) models have been combined to detect the intestinal barrier protective effect of JPP and its complexes. Results showed that JPP/zein complexes contain better protection capability than JPP in both models. In the Caco-2 cell model, the complex relieved intestinal barrier damage by regulating the tight junction proteins. Moreover, the lysosome pathway has been activated, further regulating immune responses and lipid transportation, improving the barrier function of C. elegans after incubation with JPP/zein complexes according to the proteomics study. This work provides new insights into intestinal barrier protection with bioactive compounds.

Rheological properties, gel properties and 3D printing performance of soy protein isolate gel inks added with different types of apricot polysaccharides.

A soybean protein isolate (SPI)-apricot polysaccharide gel with hypolipidemic activity that can be used for 3D printing was prepared and the mechanism of its gel formation was studied in this work. The results demonstrated that adding apricot polysaccharide to SPI could effectively improve the bound water content, viscoelastic properties and rheological properties of the gels. Low-field NMR, FT-IR spectroscopy and surface hydrophobicity confirmed that the interactions between SPI and apricot polysaccharide were mainly realized by electrostatic interactions, hydrophobic and hydrogen bonding. Furthermore, adding modified polysaccharide treated by ultrasonic-assisted Fenton method to SPI on the basis of low-concentration apricot polysaccharide contributed to improving the 3D printing accuracy and stability of the gel. Consequently, the gel formed by adding apricot polysaccharide (0.5 %, m/v) and modified polysaccharide (0.1 %, m/v) to SPI had the best hypolipidemic activity (the binding rate of sodium taurocholate and sodium glycocholate were 75.33 % and 72.86 %, respectively) and 3D printing characteristics.

Insight into the self-assembly behavior of α-zein by multi-spectroscopic and molecular simulations: An example of combination with the main component of jujube peel pigments - Rutin.

Zein has been widely used as a kind of carrier material for its self-assembly capability, while the mechanism of this process is still elusive. Rutin, one of the flavonoids, has been confirmed as the main ingredient of pigments in jujube peels. In this work, the binding mechanism in the zein/rutin complexes has been systematically studied by using multi-spectroscopic methods and molecular simulations. Results have shown that the encapsulation efficiency of complexes has researched the maximum, 67.30 % ± 1.50 %, when the concentration of rutin is 60 µM. Furthermore, the spherical morphology of complexes has been provided by microstructure characterization. Multi-spectroscopic indicated that a static quenching, alongside strong affinity, occurred in the process of interaction. Hydrophobic interaction has been further proven as the main force in zein/rutin complexes from the results of molecular dynamics simulation. This work is vital to fully utilize zein for the delivery of bio-compounds.

Proteomic analysis reveals the mechanism of green regulation in garlic puree induced by purple light stress.

Greening is an undesirable appearance in garlic puree during processing. Our previous study indicated that purple light could induce the greening changes in garlic. In order to investigate the mechanism of green regulation in garlic puree, purple light-induced greening and nongreening garlic puree were used as materials to investigate the differentially expressed proteins (DEPs) by sodium dodecyl-sulfate polyacrylamide gel electrophoresis and data-independent acquisition (DIA) technology. The results showed that a total of 186 DEPs were detected by DIA, with 73 DEPs were up-regulated in greening garlic puree and 113 of them were down-regulated in greening garlic puree. Most DEPs were belonged to 20 functional categories, and mainly participated in post-translational modification and transport of proteins, molecular chaperones (12.93%) and signal transduction mechanisms (10.20%), energy production and transformation (6.80%), carbohydrate transport and metabolism (5.44%) and amino acid transport and metabolism (4.08%), indicating that the biological metabolic pathway, metabolic direction, and metabolic strength efficiency significantly changed in garlic puree after greening. Besides, the physiological and biochemical experiments showed that purple light significantly induced the γ-glutathione transpeptidase activity and prompted the conversion of thiosulfinate into garlic green pigment. This study explained the general molecular mechanism of greening changes of garlic puree in response to purple light. Practical Application Greening is an undesirable appearance in garlic puree during processing, which deteriorate the qualities of garlic. This study provides a comprehensive understanding of green regulation in garlic puree based on proteomics analysis.

Enhanced extraction of bioactive natural products using ultrasound-assisted aqueous two-phase system: Application to flavonoids extraction from jujube peels.

The ultrasound-assisted aqueous two-phase extraction (UA-ATPE) was employed to develop an effective technique for the extraction of flavonoids from jujube peels (JPs). The extraction conditions were further optimized as K2HPO4 35% (w/w), ethanol 20% (w/w), solid-liquid ratio 1:30 g/mL (w/v), ultrasonic power 200 W, and extraction time 50 min. Moreover, rutin, quercetin 3-ß-d-glucoside, and kaempferol-3-O-rutinosid were identified as the main flavonoids by UPLC-MS/MS. Finally, the extraction mechanism of UA-ATPE was explored, which is salting out effect, hydrogen bonding, van der Waals force, and ultrasound promoted the mass transfer of solvent to cells of JPs, then extraction behavior occurred. The mechanical destruction of JPs cells by ultrasound also further accelerated the release of flavonoids. Flavonoids were captured by W/W emulsion in the bottom phase and distributed to the top phase. Overall, this study proposes a green and clean method, UA-ATPE, to extract flavonoids from JPs, while revealing the mechanism of UA-ATPE.

Jujube peel polyphenols synergistically inhibit lipopolysaccharide-induced inflammation through multiple signaling pathways in RAW 264.7 cells.

Jujube has great potential as food and traditional drugs in several countries. To study the anti-inflammatory influence of jujube peel polyphenols in lipopolysaccharide (LPS) induced RAW 264.7 cells through mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB) and nuclear erythroid 2-related factor 2 (Nrf2) signaling pathways. In this study, the phenolic composition of polyphenols in jujube peel was analyzed using LC-MS/MS, and which was confirmed that the main polyphenols were p-coumaric acid, catechin and rutin. Meanwhile, jujube peel polyphenols attenuated the generation of TNF-α, IL-1ß, IL-6, NO and PGE2 by inhibiting MAPK and NF-κB signaling pathways. Additionally, jujube peel polyphenol activate Nrf2 from the cytoplasm to the nucleus, regulate antioxidant enzymes and pro-inflammatory cytokines, and reduce oxidative stress and inflammatory responses. Results obtained from this study suggest that jujube peel polyphenols may alleviate oxidative stress and inflammation by inhibiting MAPK and NF-κB and activating Nrf2 signaling pathways. Furthermore, jujube peel polyphenols have a synergistic effect in the treatment of LPS-induced inflammatory in RAW 264.7 cells. In conclusion, this study not only reveals the mechanism by which jujube peel polyphenols inhibit LPS-induced inflammation in RAW 264.7 cells, but also provides guidance for the development of new anti-inflammatory drugs.

Head muscle fibro-adipogenic progenitors account for the tilted regeneration towards fibrosis.

Branchiomeric head muscle is ontogenetically and phylogenetically distinct from somitic limb muscle, and they exhibit different regenerative capacity. Unique satellite cell property of head muscle could explain the impaired myofiber formation, but the underlying mechanism for fibrosis is still elusive. In this work, we first established a freezing-induced skeletal muscle regeneration model and made comparisons between the regeneration characteristics in tibialis anterior (TA) muscle and masseter (MAS) muscle. The process of myogenesis and fibrogenesis were investigated by histological, immunohistochemical and cellular analysis, to characterize the role of muscle satellite cell (MuSCs) and fibro-adipogenic progenitors (FAPs) in TA and MAS muscle regeneration. Our results revealed that FAPs infiltrated the fibrotic area during MAS muscle regeneration. In contrast to the rapid rise and fall of FAPs number at the early regeneration stages in TA muscle, the number of MAS FAPs increased to a plateau without descending till 14 days after injury. It is the first time that the pivotal role of FAPs in head muscle regeneration was characterized. The persistence of FAPs without timely clearance in the first two weeks of regeneration could be accountable for the head muscle fibrosis.

Ultrasound-assisted adsorption/desorption of jujube peel flavonoids using macroporous resins.

The work explored the process of ultrasound-assisted adsorption/desorption to efficiently purify jujube peel flavonoids (JPFs) using macroporous resins (MRs). The impact of ultrasound power and temperature on the adsorption/desorption features of JPFs on MRs were studied. The maximum adsorption (80.21 ± 2.11 mg/g) /desorption (76.22 ± 1.68 mg/g) capacity of total flavonoids content were obtained. The pseudo-second-order kinetic and Freundlich isotherm models better described the whole process of ultrasound-assisted adsorption. The adsorption process was spontaneous, physical, and dominated by multilinear intraparticle diffusion. Ultrasound mainly enhanced the adsorption capacity by strengthening the formation of hydrogen bonds and increasing the surface roughness of MRs. Besides, the principal individual flavonoid ((+)-Catechin, (-)-Epicatechin, Rutin, Quercetin-3-O-robinobioside) content of JPFs in ultrasound treatment was 2-3 times that of shaking treatment, and biological activities were significantly increased. Overall, as a low-cost green technology, ultrasound can improve the properties of MRs and better purify JPFs.

The Traditional Chinese Medicine Compound Huangqin Qingre Chubi Capsule Inhibits the Pathogenesis of Rheumatoid Arthritis Through the CUL4B/Wnt Pathway.

The pathogenesis of rheumatoid arthritis (RA) is still not fully clarified, and the development of therapeutic drugs for RA is particularly urgent. Our group studies a possibility that circ_ 0015756/miR-942-5p may participate in the pathogenesis of RA through disordered Cullin 4B (CUL4B) and the traditional Chinese medicine compound Huangqin Qingre Chubi Capsule (HQC) may inhibit the pathogenesis of RA through the CUL4B/Wnt pathway. Data showed that the expression of circ_0015756 increased not only in fibroblast-like synoviocytes (FLS) of RA, but also in synovium and FLS of CIA mice, and the expression of miR-942-5p decreased. Abnormal circ_0015756 up-regulated the CUL4B expression and activated the canonical Wnt signaling pathway by inhibiting the expression of miR-942-5p. Circ_0015756 participated in the pathogenesis of RA and promoted the abnormal proliferation of FLS. Further, circ_0015756 activated the secretion of IL-1 and IL-8 and promoted the production of RA pathological gene MMP3 and fibronectin. Further analysis showed that HQC inhibited the pathogenesis of RA through the CUL4B/Wnt pathway, and the specific target was CUL4B. HQC interfered with the effects of circ_0015756 on the pathogenesis of RA by inhibiting the CUL4B, showing a good therapeutic effect on RA.

Cocktail enzyme-assisted alkaline extraction and identification of jujube peel pigments.

Jujube peel (JP) is rich in pigments, which appears red to deep red in color. This study optimized conditions for cocktail enzyme-assisted extraction of jujube peel pigments based on response surface method (RSM). A Box-Behnken design (BBD) was utilized to analyze the effects of buffer liquid volume (BLV), pH, temperature, and incubation time on the total polyphenols content (TPC), total flavonoids content (TFC) and color (L*, a*, b*). Optimal extraction conditions, for the highest concentrations of TPC, TFC and a* values, were 16 mL BLV, pH 7.0, temperature 43 °C, and incubation time 97 min. Finally, concentrations and identities of the eight main constituents (p-coumaric acid, (-)-epicatechin, quercetin-3-O-robinobioside, rutin, kaempferol 3-O-robinobioside, quercetin 3-O-α-l-arabinosyl-(1 â†’ 2)-α-l-rhamnoside, quercetin 3-O-ß-d-xylosyl-(1 â†’ 2)-α-l-rhamnoside, quercetin) in jujube peel pigments were determined using UPLC-MS/MS. The study provides guidance for valorisation of jujube peel, specifically valuable food-safe pigments, during industrial production.

DNA hypermethylation of SFRP2 influences the pathology of rheumatoid arthritis through the canonical Wnt signaling in model rats.

In this work, the expression of secreted frizzled related protein 2 (SFRP2) in rheumatoid arthritis (RA) model rats and the mechanisms of SFRP2 on the RA pathogenesis were investigated. Data suggested that SFRP2 was significantly down-regulated in RA model rats compared with normal control, and overexpression of SFRP2 suppressed the RA pathogenesis and the canonical Wnt signaling in fibroblast-like synovial cells (FLS) from RA model rats, whereas knockdown of SFRP2 got an opposite observation. Interestingly, 5-azadC treatment up-regulated the SFRP2 expression, inhibited the FLS proliferation, suppressed the expression of IL-6 and IL-8 and the fibronectin production, suggesting that the decreased SFRP2 in RA model rats was due to the DNA methylation. Furthermore, DNMT1 knockdown up-regulated the SFRP2 expression, DNMT1 overexpression inhibited the SFRP2, and the quantitative methylation-specific PCR (qMSP) confirmed that the DNMT1 has direct methylation roles for the SFRP2 promoter, leading to a regulation of FLS proliferation and fibronectin expression in RA model rats. In addition, up-regulated MeCP2 was involved in the SFRP2 regulation and the pathogenesis of RA model rats, and MeCP2 and DNMT1 have synergistic inhibition roles in the SFRP2 expression. Combination of DNMT1 and DNA methylation may be a promising treatment strategy for individuals with RA in which SFRP2 is down-regulated.

Secretion expression of human neutrophil peptide 1 (HNP1) in Pichia pastoris and its functional analysis against antibiotic-resistant Helicobacter pylori.

Human neutrophil peptide 1 (HNP1) is a small (3.44 kDa) cationic peptide that is a distinct member of the defensin family. HNP1 plays a crucial role in controlling bacterial infections, particularly by antibiotic-resistant bacteria, through membrane perforation patterns. The structural characteristics of HNP1's three intramolecular disulfide bridges cause difficulty in its synthesis via chemical methods. In this study, bioactive recombinant HNP1 was produced using the Pichia pastoris (P. Pichia) expression system. HNP1 was fused with the polyhedrin of Bombyx mori and enhanced green fluorescent protein (EGFP) to prevent HNP1 toxicity in yeast host cells under direct expression. An enterokinase protease cleavage site (amino acid sequence DDDDK) was designed upstream of the HNP1 peptide to obtain the antibacterial peptide HNP1 with native structure after it was cleaved by the enterokinase. The fusion HNP1 protein (FHNP1) was successfully expressed and had a molecular mass of approximately 62.6 kDa, as determined using SDS-PAGE and Western blot. Then, the recovered FHNP1 was digested and purified; Tricine-SDS-PAGE results showed that HNP1 was successfully released from FHNP1. Functional analysis of induction against antibiotic-resistant Helicobacter pylori (H. pylori) showed that it was challenging for HNP1 to acquire resistance to the antibiotic-resistant H. pylori. Moreover, in vitro studies showed that HNP1 exerted a strong effect against antibiotic-resistant H. pylori activity. Furthermore, the animal model of H. pylori infection established in vivo showed that HNP1 significantly reduced the colonization of antibiotic-resistant H. pylori in the stomach. Our study indicated that this could be a new potential avenue for large-scale production of HNP1 for therapeutic application against the antibiotic-resistant H. pylori infection in humans.

Fusion expression of the PGLa-AM1 with native structure and evaluation of its anti-Helicobacter pylori activity.

Helicobacter pylori (H. pylori) shows increasingly enhanced resistance to various antibiotics, and its eradication has become a major problem in medicine. The antimicrobial peptide PGLa-AM1 is a short peptide with 22 amino acids and exhibits strong antibacterial activity. In this study, we investigated whether it has anti-H. pylori activity for the further development of anti-H. pylori drugs to replace existing antibiotics. However, the natural antimicrobial peptide PGLa-AM1 shows a low yield and is difficult to separate, limiting its application. A good strategy to solve this problem is to express the antimicrobial peptide PGLa-AM1 using gene engineering at a high level and low cost. For getting PGLa-AM1 with native structure, in this study, a specific protease cleavage site of tobacco etch virus (TEV) was designed before the PGLa-AM1 peptide. For convenience to purify and identify high-efficiency expression PGLa-AM1, the PGLa-AM1 gene was fused with the polyhedrin gene of Bombyx mori (B. mori), and a 6 × His tag was designed to insert before the amino terminus of the fusion protein. The fusion antibacterial peptide PGLa-AM1 (FAMP) gene codon was optimized, and the gene was synthesized and cloned into the Escherichia coli (E. coli) pET-30a (+) expression vector. The results showed that the FAMP was successfully expressed in E. coli. Its molecular weight was approximately 34 kDa, and its expression level was approximately 30 mg/L. After the FAMP was purified, it was further digested with TEV protease. The acquired recombinant antimicrobial peptide PGLa-AM1 exerted strong anti-H. pylori activity and therapeutic effect in vitro and in vivo.

Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability.

Metronidazole (MNZ) is an effective agent that has been employed to eradicate Helicobacter pylori (H. pylori). The emergence of broad MNZ resistance in H. pylori has affected the efficacy of this therapeutic agent. The concentration of MNZ, especially the mutant prevention concentration (MPC), plays an important role in selecting or enriching resistant mutants and regulating therapeutic effects. A strategy to reduce the MPC that can not only effectively treat H. pylori but also prevent resistance mutations is needed. H. pylori is highly resistant to lysozyme. Lysozyme possesses a hydrolytic bacterial cell wall peptidoglycan and a cationic dependent mode. These effects can increase the permeability of bacterial cells and promote antibiotic absorption into bacterial cells. In this study, human lysozyme (hLYS) was used to probe its effects on the integrity of the H. pylori outer and inner membranes using as fluorescent probe hydrophobic 1-N-phenyl-naphthylamine (NPN) and the release of aspartate aminotransferase. Further studies using a propidium iodide staining method assessed whether hLYS could increase cell permeability and promote cell absorption. Finally, we determined the effects of hLYS on the bactericidal dynamics and MPC of MNZ in H. pylori. Our findings indicate that hLYS could dramatically increase cell permeability, reduce the MPC of MNZ for H. pylori, and enhance its bactericidal dynamic activity, demonstrating that hLYS could reduce the probability of MNZ inducing resistance mutations.

Resveratrol Protects against Helicobacter pylori-Associated Gastritis by Combating Oxidative Stress.

Helicobacter pylori (H. pylori)-induced oxidative stress has been shown to play a very important role in the inflammation of the gastric mucosa and increases the risk of developing gastric cancer. Resveratrol has many biological functions and activities, including antioxidant and anti-inflammatory effect. The purpose of this study was to probe whether resveratrol inhibits H. pylori-induced gastric inflammation and to elucidate the underlying mechanisms of any effect in mice. A mouse model of H. pylori infection was established via oral inoculation with H. pylori. After one week, mice were administered resveratrol (100 mg/kg body weight/day) orally for six weeks. The mRNA and protein levels of iNOS and IL-8 were assessed using RT-PCR, Western blot and ELISA. The expression levels of IκBα and phosphorylated IκBα (which embodies the level and activation of NF-κB), Heme Oxygenase-1 (HO-1; a potent antioxidant enzyme) and nuclear factor-erythroid 2 related factor 2 (Nrf2) were determined using Western blot, and lipid peroxide (LPO) level and myeloperoxidase (MPO) activity were examined using an MPO colorimetric activity assay, thiobarbituric acid reaction, and histological-grade using HE staining of the gastric mucosa. The results showed that resveratrol improved the histological infiltration score and decreased LPO level and MPO activity in the gastric mucosa. Resveratrol down-regulated the H. pylori-induced mRNA transcription and protein expression levels of IL-8 and iNOS, suppressed H. pylori-induced phosphorylation of IκBα, and increased the levels of HO-1 and Nrf2. In conclusion, resveratrol treatment exerted significant effects against oxidative stress and inflammation in H. pylori-infected mucosa through the suppression of IL-8, iNOS, and NF-κB, and moreover through the activation of the Nrf2/HO-1 pathway.

Development of RGD-Functionalized PEG-PLA Micelles for Delivery of Curcumin.

Curcumin (Cur), a hydrophobic polyphenolic compound, possesses a wide range of biological activities. However, its prominent application in cancer treatment is limited due to low aqueous solubility and rapid metabolism. Recently, micelle-based drug delivery system has been proven to be an attractive alternative for poorly soluble drugs. In order to improve the application of Cur as an anti-cancer agent, in this study, we synthesized the αvß3 integrin-targeted peptide (RGD) functionalized polymer (RGD-PEG-PLA). The RGD conjugated Cur loaded micelles (Cur-RPP) were prepared using the thin-film hydration method with modification and the preparation process was optimized with a central composite design. The obtained Cur-RPP presented spherical shape with a particle size of 20 nm and high drug loading (4.70%). Compared with the Cur propylene glycol solution, the in vitro release of Cur from the prepared micelles showed the sustained-release property. Cellular uptake of Cur-RPP was found to be higher than that of non-RGD modified micelles due to the binding effect between αvß3 integrin and RGD in human umbilical vein endothelial cells (HUVEC) and mouse melanoma cell lines (B16). In B16 tumor-bearing mice, Cur-RPP showed the stronger inhibiting effect on growth of tumor compared with non-RGD modified micelles. It could be concluded from these results that the RGD modified micelles might be a potential carrier for Cur.