Baicalin can enhance odonto/osteogenic differentiation of inflammatory dental pulp stem cells by inhibiting the NF-κB and ß-catenin/Wnt signaling pathways.

BACKGROUND: Scutellaria baicalensis Georgi is a famous traditional Chinese medicine, which is widely used in treating fever, upper respiratory tract infection and other diseases. Pharmacology study showed it can exhibit anti-bacterial, anti-inflammation and analgesic effects. In this study, we investigated the effect of baicalin on the odonto/osteogenic differentiation of inflammatory dental pulp stem cells (iDPSCs). METHODS AND RESULTS: iDPSCs were isolated from the inflamed pulps collected from pulpitis. The proliferation of iDPSCs was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2,5-tetrazolium bromide (MTT) assay and flow cytometry. Alkaline phosphatase (ALP) activity assay, alizarin red staining, Real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blot assay were conducted to examine the differentiation potency along with the involvement of nuclear factor kappa B(NF-κB) and ß-catenin/Wnt signaling pathway. MTT assay and cell-cycle analysis demonstrated that baicalin had no influence on the proliferation of iDPSCs. ALP activity assay and alizarin red staining demonstrated that baicalin could obviously enhance ALP activity and calcified nodules formed in iDPSCs. RT-PCR and Western blot showed that the odonto/osteogenic markers were upregulated in baicalin-treated iDPSCs. Moreover, expression of cytoplastic phosphor-P65, nuclear P65, and ß-catenin in iDPSCs was significantly increased compared with DPSCs, but the expression in baicalin-treated iDPSCs was inhibited. In addition, 20 µM Baicalin could accelerate odonto/osteogenic differentiation of iDPSCs via inhibition of NF-κB and ß-catenin/Wnt signaling pathways. CONCLUSION: Baicalin can promote odonto/osteogenic differentiation of iDPSCs through inhibition of NF-κB and ß-catenin/Wnt pathways, thus providing direct evidence that baicalin may be effective in repairing pulp with early irreversible pulpitis.

pH-Responsive Hyperbranched Polymer Nanoparticles to Combat Intracellular Infection by Disrupting Bacterial Wall and Regulating Macrophage Polarization.

Intracellular bacterial infections pose a serious threat to public health. Macrophages are a heterogeneous population of immune cells that play a vital role in intracellular bacterial infection. However, bacteria that survive inside macrophages could subvert the cell signaling and eventually reduce the antimicrobial activity of macrophages. Herein, dual pH-responsive polymer (poly[(3-phenylprop-2-ene-1,1-diyl)bis(oxy)bis(enthane-2,1-diyl)diacrylate-co-N-aminoethylpiperazine] (PCA)) nanoparticles were developed to clear intracellular bacteria by activating macrophages and destructing bacterial walls. The presence of acid-labile acetal linkages and tertiary amine groups in the polymer's backbone endow hyperbranched PCA dual pH-response activity that shows acid-induced positive charge increase and cinnamaldehyde release properties. The biodegraded PCA nanoparticles could significantly inhibit the growth of bacteria by damaging the bacterial walls. Meanwhile, PCA nanoparticles could uptake by macrophages, generate reactive oxygen species (ROS), and remodel the immune response by upregulating M1 polarization, leading to the reinforced antimicrobial capacity. Furthermore, PCA nanoparticles could promote bacteria-infected wound healing in vivo. Therefore, these dual pH-responsive PCA nanoparticles enabling bacteria-killing and macrophage activation provide a novel outlook for treating intracellular infection.

High-Performance Nonfullerene Polymer Solar Cells Based on a Wide-Bandgap Polymer without Extra Treatment.

Nonfullerene polymer solar cells (PSCs) are developed based on a fluorinated thienyl-based wide-bandgap (WBG) polymer PBBF as the electron donor and nonfullerene small molecule IDIC as the electron acceptor. PBBF exhibits a strong absorption in the range of 300-605 nm with a wide optical bandgap of 2.05 eV, which is complementary with that of IDIC. Meanwhile, it possesses a deeper highest occupied molecular orbital energy level of  -5.52 eV and a higher hole mobility of 7.3 × 10-4  cm2 V-1  s-1 compared to the nonfluorinated polymer PBDTT. The PSCs based on PBBF:IDIC without extra treatment show a power conversion efficiency (PCE) of 8.5% with a V oc of 0.95 V, a J sc of 15.3 mA cm-2 , and an FF of 58.8%, which is much higher than that of the devices based on PBDTT:IDIC (a PCE of 5.3% with a V oc of 0.88 V, a J sc of 13.7 mA cm-2 , and an FF of 43.9%). These results indicate that PBBF is a promising WBG polymer donor material for the photovoltaic applications in nonfullerene PSCs.

Bioactive Peptide-Mimicking Polymer Nanoparticles for Bacteria Imaging and Chemo/Immunotherapy of Intracellular Infection.

Intracellular bacterial infections are extremely difficult to be treated because intracellular bacteria have developed resistant mechanisms to escape the immune attack and antibiotic therapy. It remains challenging to develop antibiotic-free materials and relative strategies for treating intracellular bacterial infections. Herein, a new host-defense peptide-mimicking polymer nanoparticle, inspired by cell-penetrating peptides, was developed to eradicate intracellular bacteria by its outstanding antibacterial and pro-inflammatory immunomodulatory. The polymer nanoparticle (TPE-Parg) was prepared through ring-opening polymerization of N6-carbobenzoxy-l-lysine N-carboxyanhydride (Cbz-l-Lys NCA) using 1-(4-aminophenyl)-1,2,2-triphenylethene (TPE-NH2) as the initiator, followed by deprotection of the Cbz-l-Lys NCA group and guanidinium modification. The impact of cationic functional groups and chain length variation on the antibacterial activity of polymer nanoparticle were investigated in detail. The results confirmed that the optimal polymer nanoparticle could not only image bacteria with aggregation-induced blue fluorescence, but also kill planktonic bacteria with low cytotoxicity. Furthermore, the nanoparticle could induce macrophages to generate nitric oxide (NO) and activate the immune system to eliminate intracellular bacteria. The nanoparticle further showed its potent in vivo antibacterial activity in an intracellular Staphylococcus aureus infection model fabricated on mice hypodermic. The obtained multifunctional host-defense peptide-mimicking polymer nanoparticles with potent antibacterial activity (chemotherapy) and pro-inflammatory immunomodulatory (immunotherapy) are excellent alternatives for intracellular antibacterial therapy and provide a direction for developing innovative antimicrobials.

pH-Responsive Fluorescent Polymer-Drug System for Real-Time Detection and In Situ Eradication of Bacterial Biofilms.

Bacterial biofilms encased in extracellular polymeric substances to create protected microenvironments are typically challenging to disperse by common antibiotics and cannot be in situ visualized under current modalities. Herein, a pH-responsive branched polymer [poly(MBA-AEPZ)-AEPZ-NA] capable of overcoming antibiotic resistance and real-time visualizing biofilms for fluorescence imaging-guided infection control is reported. The positively charged polymer can effectively penetrate bacterial biofilms, neutralize the anionic character, and then disrupt the structural integrity, thus significantly promoting the transport of antibiotics into biofilms. The polymer shows a weak fluorescence emission intensity under physiological conditions (pH 7.4) but emits intense green-light emission within the localized biofilm microenvironment (pH 5.5) to real-time visualize bacterial biofilms. A therapeutic system made of the polymer and a model antibiotic can significantly reduce the dosages of the drug, thereby minimizing biofilm-induced drug resistance. Notably, a green fluorescent polymer responding to localized pH conditions is demonstrated in living zebrafish. This work confirmed that combinations of the pH-responsive branched polymer and antibiotics could be administered to overcome drug resistance and realize fluorescence imaging-guided treatment of bacterial biofilm infections.

pH-Responsive non-antibiotic polymer prodrugs eradicate intracellular infection by killing bacteria and regulating immune response.

Intracellular bacterial infections pose enormous challenges to food safety and public health. Antibiotic-based polymer prodrugs have been used to treat intracellular bacterial infection. However, the overuse of antibiotics may lead to the emergence of antibiotic resistance. In this work, we aimed to develop antibiotic-free pH-responsive polymeric prodrugs to combat intracellular S. aureus infection. Amphiphilic poly(ethylene glycol)-b-poly[(3-phenylprop-2-ene-1,1-diyl)bis(oxy)bis(enthane-2,1- diyl)diacrylate] (PEG-b-PCAE) was obtained by radical polymerization and they could self-assemble to form micelles. PEG-b-PCAE micelles could uptake by macrophage. Upon exposure to the acidic phagolysosome, PEG-b-PCAE micelles could release cinnamaldehyde (CA) through hydrolysis of the acetal linkage. PEG-b-PCAE could kill intracellular bacteria by damaging the bacterial membrane. Furthermore, PEG-b-PCAE micelles could generate reactive oxygen species (ROS) in macrophages and subsequently activate immune system to clear bacteria by inducing macrophages differentiation to M1 phenotype. PEG-b-PCAE micelles could accelerate the wound healing process of the S. aureus-infected model in vivo. It is anticipated that multifunctional antibiotic-free PEG-b-PCAE micelles with intrinsic antibacterial activities hold promise for improved outcomes in intracellular S. aureus infections.

Synthesis and Characterization of Epoxidized Silkworm Pupae Oil and Its Application as Polyvinyl Chloride.

More and more industries demand environmental friendliness. Silkworm pupae oil (SPO), extracted from the desilked silkworm pupae, can serve as a promising substrate alternative to use in plasticization. This study aimed to prepare epoxidized silkworm pupae oil (ESPO) and investigate their effects on the thermal stability and plasticization of polyvinyl chloride (PVC) films. A chemo-enzymatic method of ESPO was developed in the presence of Lipase SMG1-F278N and H2O2 in natural deep eutectic solvents (DESs). Lipase SMG1-F278N could initiate the epoxidation reaction effectively at room temperature with a negligible loss of activities 10 batches. A maximum oxirane value of 6.94% was obtained. The formation of oxirane ring in ESPO was confirmed by FTIR and 13C NMR spectra. Moreover, ESPO showed a better thermal stability and lower freezing point than epoxidized soybean oil (ESO). It was demonstrated that ESPO had a good frost resistance. In addition, ESPO showed a significantly improved plasticizing effect on flexible polyvinyl chloride (PVC). Compared with ESO, ESPO could increase the tensile elongation at break effectively. A significantly lower migration rate of plasticizer was observed in PVC plasticized with ESPO.

Simultaneous inhibition of planktonic and biofilm bacteria by self-adapting semiconducting polymer dots.

Biofilm infections present an enormous challenge in today's healthcare settings. Currently, pH-switchable antibacterial agents are being developed to eradicate biofilms. However, most pH-switchable antibacterial agents are less lethal to planktonic bacteria under neutral conditions, and cannot prevent the dispersed bacteria from seeding acute infection again. Herein, this work reports the applications of semiconducting polymer dots (Pdots) with a double adhesion mechanism in imaging and inhibiting bacteria inside (weak acidic conditions) and outside (neutral conditions) biofilms. Clew-like Pdots were prepared by covalently linking phenylboronic acid (PBA) and pH-responsive naphthalimide (NA) ramification in semiconducting polymers. Under neutral conditions, the Pdots combined with bacteria through the formation of boronate esters between PBA and diols. Under weakly acidic conditions, the partial borate bond fractured, and the Pdots adhered onto the bacterial surface through the positively charged NA in Pdots. Furthermore, the Pdots display negligible toxicity to mammalian cells and tissues. More importantly, the Pdots can selectively damage the bacterial membrane and inhibit bacteria in vivo. This work highlights the feasibility of using semiconducting Pdots to image and inhibit bacteria inside and outside biofilms, which represents a highly effective strategy to cope with biofilm infections.

Water-soluble branched polymer for combined chemo-immunotherapy of bacterial infections.

Bacterial infection is one of the most significant public health challenges due to the limited choices of antibiotics which can overcome antibiotic-resistant bacteria. The promising nonantibiotic therapeutic alternatives for antibiotic-resistant bacterial infection are urgently needed to reduce the disease burden. Herein, the water-soluble branched poly(amino ester) with inherently antibacterial (chemotherapy) and enhanced inflammatory response activity (immunotherapy) was prepared via Michael addition polymerization to combat bacterial infection. These polymers can not only damage bacteria walls, leading to the death of bacteria but also activate macrophages to low-output nitric oxide (NO), TNF-α and interleukin (IL)-1ß to kill and clean bacteria. Importantly, these polymers can efficiently inhibit aminoglycoside-resistant P. aeruginosa even at a low dose of 500 nmol L-1. Furthermore, these polymers can treat subcutaneous bacterial infections in vivo. In this study, we first report a water-soluble branched polymer to combat bacteria through the combination of chemotherapy and immunotherapy, which will open a new path to design promising potential therapeutic alternatives for bacterial infection.

Acetic acid transporter-mediated, oral, multifunctional polymer liposomes for oral delivery of docetaxel.

Nanoparticle-structuring aimed at the acetic acid (A) transporter on intestinal epithelial cells and tumor cells is a new potential strategy to enhance oral bioavailability and anti-tumor efficacy. In this study, chitosan (CS) was modified with hydrophilic A and hydrophobic lipoic acid (L), to produce ACSL. A novel ACSL-modified multifunctional liposomes (Lip) loaded with docetaxel (DTX; DTX-ACSL-Lip) was then prepared and characterized. DTX-ACSL-Lip recorded higher pH sensitivity and slower release than DTX-Lip and showed dithiothreitol (DTT) response release. DTX-ACSL-Lip uptake by Caco-2 cells was also significantly enhanced mainly viaA transporters compared with DTX-Lip. ACSL modification of DTX-Lip also improved oral bioavailability by 10.70-folds, with a 3.45-fold increase in Cmax and a 1.19-fold prolongation in retention time of DTX in the blood. Moreover, the grafting degree of A significantly affected cell uptake and oral bioavailability. They also showed a significant (1.33-fold) increase in drug intratumoral distribution, as well as an increase in tumor growth inhibition rate from 54.34% to 87.51% without weight loss, compared with DTX-Lip. Therefore, modification of DTX-Lip with ACSL can significantly enhance the oral bioavailability and anti-tumor efficacy of DTX without obvious toxicity, confirming the potential of the dual strategy of targeting A transporter and controlled drug release in tumor cells in oral therapy of tumor.

[Influence of Six Digestion Methods on the Determination of Polystyrene Microplastics in Organisms Using the Fluorescence Intensity].

Microplastic pollution has become a global environmental problem and is a cause of great concern. To evaluate the biological effects of microplastics, microplastics in organisms need to be accurately quantified. The quantification of microplastics in organisms using the fluorescence intensity is common; the digestion of biological samples is an important pretreatment method. However, the microplastics may be destroyed by digestion, which affects the fluorescence intensity of the microplastics and results in large deviations between measured and true values. In this study, six commonly used digestive agents were studied:KOH, NaOH, H2O2, HNO3, HNO3:HCl, and HNO3:HClO4. The effect of different digestion methods on the fluorescence intensity and surface morphology of microplastics was studied and the most suitable protocol was selected. The results show that, among the six different digestion methods, KOH digestion (100 g·L-1, 60℃) has the least influence on the fluorescence intensity of the microplastics and does not affect their surface morphology. The other five digestion methods lead to different degrees of reduction of the fluorescence intensity of microplastics and damage the microplastics' surface (aggregation, bubbles, scratches, and depressions). In addition, the KOH digestion method was used to extract microplastics from biological samples. The recovery rate was ≥ 96.3%±0.5%, indicating that the KOH digestion method is suitable for fluorescent microplastics in biological samples.

Comparative performances of lactoferrin-loaded liposomes under in vitro adult and infant digestion models.

There remain gaps in our understanding of the fate of liposomes in the infant gastrointestinal tract, especially regarding essential proteins such as lactoferrin. Models in vitro that mirrored digestion in the stomach and intestine of infants and adults were used to explore the behaviour of lactoferrin-loaded liposomes. The liposomes behaved differently in these environments, with less hydrolysis of encapsulated lactoferrin under infant model conditions. Compared to the adult model (1000 ±â€¯66 µM mL-1), fewer free fatty acids were released (500 ±â€¯43 µM mL-1) from liposomal bilayers and there was less alteration in functional groups of phospholipids membranes, based on pH and FTIR after infant model digestion. Particle tracking analysis and TEM supported the reduced damage of particle structure under infant model conditions. This work provides information on the stability of functional protein-loaded liposomes during digestion, and shows the potential of liposomes to be nutrient carriers in infant foods.