Sustained release of 5-aminosalicylic acid from azoreductase-responsive polymeric prodrugs for prolonged colon-targeted colitis therapy.

Ulcerative colitis (UC) is a challenging inflammatory gastrointestinal disorder, whose therapies encounter limitations in overcoming insufficient colonic retention and rapid systemic clearance. In this study, we report an innovative polymeric prodrug nanoformulation for targeted UC treatment through sustained 5-aminosalicylic acid (5-ASA) delivery. Amphiphilic polymer-based 13.5 nm micelles were engineered to incorporate azo-linked 5-ASA prodrug motifs, enabling cleavage via colonic azoreductases. In vitro, micelles exhibited excellent stability under gastric/intestinal conditions while demonstrating controlled 5-ASA release over 24 h in colonic fluids. Orally administered micelles revealed prolonged 24-h retention and a high accumulation within inflamed murine colonic tissue. At an approximately 60% dose reduction from those most advanced recent studies, the platform halted DSS colitis progression and outperformed standard 5-ASA therapy through a 77-97% suppression of inflammatory markers. Histological analysis confirmed intact colon morphology and restored barrier protein expression. This integrated prodrug nanoformulation addresses limitations in colon-targeted UC therapy through localized bioactivation and tailored pharmacokinetics, suggesting the potential of nanotechnology-guided precision delivery to transform disease management.

Self-Report Amphiphilic Polymer-Based Drug Delivery System with ROS-Triggered Drug Release for Osteoarthritis Therapy.

The development of drug delivery systems with real-time cargo release monitoring capabilities is imperative for optimizing nanomedicine performance. Herein, we report an innovative self-reporting drug delivery platform based on a ROS-responsive random copolymer (P1) capable of visualizing cargo release kinetics via the activation of an integrated fluorophore. P1 was synthesized by copolymerization of pinacol boronate, PEG, and naphthalimide monomers to impart ROS-sensitivity, hydrophilicity, and fluorescence signaling, respectively. Detailed characterization verified that P1 self-assembles into 11 nm micelles with 10 µg mL-1 CMC and can encapsulate hydrophobic curcumin with 79% efficiency. Fluorescence assays demonstrated H2O2-triggered disassembly and curcumin release with concurrent polymer fluorescence turn-on. Both in vitro and in vivo studies validated the real-time visualization of drug release and ROS scavenging, as well as the therapeutic effect on osteoarthritis (OA). Overall, this nanotheranostic polymeric micelle system enables quantitative monitoring of drug release kinetics for enhanced treatment optimization across oxidative stress-related diseases.

Over-expression of a putative poplar glycosyltransferase gene, PtGT1, in tobacco increases lignin content and causes early flowering.

Family 1 glycosyltransferases catalyse the glycosylation of small molecules and play an important role in maintaining cell homeostasis and regulating plant growth and development. In this study, a putative glycosyltransferase gene of family 1, PtGT1, was cloned from poplar (Populus tomentosa Carr.). Sequence analysis showed that this gene encodes a protein of 481 amino acid residues with a conserved PSPG box at its C-terminal, suggesting that it is active in the glycosylation of plant secondary products. The PtGT1 gene was expressed in poplar stems and leaves, with a particularly high expression level in elongating stems. Transgenic tobacco plants ectopically over-expressing PtGT1 were obtained and phenotypes were analysed. Wiesner and Mäule staining showed that stem xylem of transgenic tobacco plants stained more strongly than controls. Measurement of the Klason lignins showed much higher lignin content in the transgenic lines than in control plants. Furthermore, the ectopic over-expression of PtGT1 in tobacco resulted in an early flowering phenotype. These findings offer a possible starting point towards better understanding of the function of poplar PtGT1, and provide a novel strategy for lignin engineering and flowering control in plants through the genetic manipulation of a poplar glycosyltransferase gene.

In vivo targeted delivery of antibodies into cancer cells with pH-responsive cell-penetrating poly(disulfide)s.

Cell-penetrating poly(disulfide)s (CPDs) are promising vehicles for cytosolic delivery of proteins. However, currently available arginine-rich CPD has rarely been reported for systemic delivery due to its "always" positive charge. Herein, we developed pH-responsive CPDIMD that executes tumor targeting delivery via protonation of imidazole groups within the acidic tumor microenvironment.

[Accuracy of implantation between two immediate implantation methods in mandibular molars].

PURPOSE: To compare the accuracy of implant placement between modified and traditional immediate implant placement in mandibular molar regions. METHODS: Twenty-four patients were selected for immediate implantation in the molar area including 24 implantation sites. Preoperative cone-beam CT(CBCT) was conducted and then digital software Simplant 18.0 was used to design the ideal three-dimensional position of the implants. In the experimental group, the implant socket was prepared first according to reference of the remaining natural teeth, then the implant was implanted after minimally invasive extraction. Twelve patients in the control group underwent immediate implantation by traditional immediate implant procedures. Minimally invasive extraction, then socket preparation, and final implanting were performed. All patients underwent CBCT after surgery. Implant sites designed prior to surgery and actual implant sites differences between modified and traditional immediate implant placement were measured by Simplant 18.0 and compared with SPSS 17.0 software package. RESULTS: In the experimental group and control group, the measured average deviation were as follows, the angle was (4.492±0.912)° and (7.255±1.307)°, respectively; The horizontal error of the implant shoulder was (0.379±0.083) mm and (1.229±0.270) mm, respectively; The measuring horizontal error of the implant apex was (1.263±0.267) mm and (2.183±0.264) mm, respectively; The calculative horizontal error of the implant apex was (1.324±0.203) mm and (2.709±0.383) mm, respectively; Depth error of the implant apex was (0.663±0.123) mm and (1.533±0.155) mm, respectively, which were significantly lower than those of the control group. CONCLUSIONS: Compared with the traditional method, modified immediate implantation can improve the accuracy of implantation in mandibular molars.

Reliability of acellular decalcified and decalcified teeth as bone graft material: an experimental and pathological study in rats.

OBJECTIVE: The present study aimed to investigate the reliability of acellular decalcified teeth in the development of bone scaffolds and in bone regeneration in rats. METHODS: (1) Forty-eight human teeth were divided into two groups in vitro: twenty-four were decalcified, while the remaining twenty-four were decalcified and decellularized, following which a conventional scanning-electron microscope analysis was performed. (2) In another experiment, six male SD rats aged 10-12 weeks were selected, then decalcified and acellular decalcified teeth were embedded subcutaneously in the abdomen of the rats. After 4 weeks, the rats were sacrificed for H-E staining and immunohistochemical staining to observe the inflammatory reaction around the two materials. (3) In the ectopic osteogenesis experiment, bone defects were simulated in bilateral craniotectal areas of 12 male SD rats (age 10-12 weeks), following which acellular decalcified teeth were implanted in the right bone defect. The non-implanted left side was used as blank control. At week 4 and week 8, 6 rats were randomly selected for execution, complete specimens were obtained, and micro-CT scan was performed to compare the bone mass from gross morphology. H-E staining was performed at 4 and 8 weeks to observe the surrounding inflammatory response and immunohistochemistry was performed at 8 weeks to observe the degree of new bone formation. SPSS 23.0 software package was used for statistical processing. RESULTS: (1) Under scanning electron microscope, cells in the teeth subjected to acellular decalcification completely disappeared, leaving only inorganic scaffolds. (2) After 4 weeks, the amount of inflammatory reaction in the tissues surrounding acellular decalcified teeth was significantly lower than that in the tissues surrounding decalcified teeth. (3) After four and eight weeks, the amount of bone formation in the bone defects was significantly higher in rats implanted with acellular decalcified teeth than in those in the blank control group (P<0.05). After four and eight weeks, hematoxylin-eosin staining revealed that the degree of inflammatory response was similar around acellular decalcified teeth and blank controls. Immunohistochemistry indicated that the osteocalcin levels were significantly higher around acellular decalcified teeth than that around blank controls. CONCLUSION: Acellular decalcified teeth show significantly decreased inflammatory reaction, better biocompatibility, better osteogenic potential, and better plasticity than decalcified teeth alone.

Polystyrene microplastics induce microbiota dysbiosis and inflammation in the gut of adult zebrafish.

Microplastic (MP) are environmental pollutants and have the potential to cause varying degrees of aquatic toxicity. In this study, the effects on gut microbiota of adult male zebrafish exposed for 14 days to 100 and 1000 µg/L of two sizes of polystyrene MP were evaluated. Both 0.5 and 50 µm-diameter spherical polystyrene MP increased the volume of mucus in the gut at a concentration of 1000 µg/L (about 1.456 × 1010 particles/L for 0.5 µm and 1.456 × 104 particles/L for 50 µm). At the phylum level, the abundance of Bacteroidetes and Proteobacteria decreased significantly and the abundance of Firmicutes increased significantly in the gut after 14-day exposure to 1000 µg/L of both sizes of polystyrene MP. In addition, high throughput sequencing of the 16S rRNA gene V3-V4 region revealed a significant change in the richness and diversity of microbiota in the gut of polystyrene MP-exposed zebrafish. A more in depth analysis, at the genus level, revealed that a total of 29 gut microbes identified by operational taxonomic unit (OTU) analysis were significantly changed in both 0.5 and 50 µm-diameter polystyrene MP-treated groups. Moreover, it was observed that 0.5 µm polystyrene MP not only increased mRNA levels of IL1α, IL1ß and IFN but also their protein levels in the gut, indicating that inflammation occurred after polystyrene MP exposure. Our findings suggest that polystyrene MP could induce microbiota dysbiosis and inflammation in the gut of adult zebrafish.