Highly hydrophilic and dispersed TiO2 nano-system with enhanced photocatalytic antibacterial activities and accelerated tissue regeneration under visible light.

Titanium dioxide (TiO2)-based photodynamic antibacterial (PDA) agents present a novel approach for addressing drug-resistant bacterial infections and the associated tissue damage. However, the suboptimal dispersibility, negative charge, and weak photocatalytic activity under visible light of TiO2 hinder its practical applications. This study aimed to address these limitations by developing a highly hydrophilic and dispersed Zn-TiO2/reduced graphene oxide (rGO) (HTGZ) nano-system with exceptional visible light catalytic activity and tissue repair ability. HTGZ produced an antibacterial ratio over 98% within a short time, likely due to the enhanced production of reactive oxygen species under visible light. After being co-cultured for 4 days, L929 cells and BMSCs maintained over 90% activity, indicating that HTGZ had no significant cytotoxicity. Furthermore, the transcriptomic and metabolic analyses revealed that the antibacterial mechanism mainly came from the destruction of cell membranes and the disruption of various metabolic processes, such as purine metabolism and fatty acid biosynthesis. Critically, results of in vivo experiments had authenticated that HTGZ significantly promoted infected tissue regeneration by slaughtering bacteria and release Zn2+. After 14 days, the wound area was only one-third that of the control group. Overall, the enhanced antibacterial efficacy and wound-healing potential position HTGZ as a promising nano-antibacterial medication for the clinical treatment of infectious bacterial diseases.

Unloading of occlusal force aggravates alveolar bone loss in periodontitis.

BACKGROUND AND OBJECTIVE: Periodontitis (PD), a chronic infectious inflammatory disease initiated by bacteria, is associated with several local contributing factors including occlusal trauma. Previous studies have found that the traumatic occlusal force could aggravate alveolar bone loss during PD. However, the effect of reduced occlusal force during PD remains unclear. This study aimed to explore the effect of occlusal force unloading on PD onset and progression and its underlying mechanism as an effort to provide restoration suggestions for PD patients with dentition defect in clinic. This study might also propose occlusal force unloading could be a new local contributing factor for PD. MATERIALS AND METHODS: C57BL/6 mice were used to establish a PD model by the ligation of 5-0 silk around the mandibular left first molar (PD group) and an unloading experiment model by the extraction of their left maxillary first molar (EX group). The THP-1-derived macrophages were used to verify in vivo results. RESULTS: Micro-CT scanning and H&E staining results consistently showed that PD + EX group experienced the most severe alveolar bone resorption as compared to PD group and control group. Further RNA-sequencing analysis suggested that occlusal force unloading significantly enhanced osteoclastic resorption, inhibited osteoblastic activity, and promotes M1 and M2 macrophages polarization. Immunofluorescence staining (IF) results showed that compared with the PD group, PD + EX group significantly increased the ratio of M1/M2 polarization. Similar results were observed by RT-qPCR and IF in vitro: removal of compressive force led to an increased ratio of M1/M2 polarization in LPS-stimulated THP-1-derived macrophages. CONCLUSIONS: Our study demonstrated that occlusal force unloading aggravates bone resorption by increasing the ratio of M1/M2 macrophages polarization during PD, suggesting a previously unknown local contributing factor for PD, and providing a novel insight for dentists to restore missing teeth as an effort to maintain remaining dentition.

Retrospective study on the merits of bone grafts and the influence of implant protrusion length after osteotome sinus elevation surgery.

OBJECTIVES: This study aims to evaluate the endo-sinus bone remodeling of dental implants placed via osteotome sinus floor elevation (OSFE) after 6 months and using different implant protrusion lengths and bone grafts through cone beam computed tomography (CBCT). METHODS: Ninety-six patients with 124 implants were included and assigned into four groups. Group 1: implant protrusion length<4 mm with bone graft; group 2: implant protrusion length>4 mm with bone graft; group 3: implant protrusion length<4 mm without bone graft; group 4: implant protrusion length>4 mm without bone graft. Apical bone gain (ABG), cortical bone gain (CBG), bone density gain (BDG), and marginal bone loss (MBL) were observed and analyzed at baseline and 6 months after implant surgery. RESULTS: The CBG in grafted groups 1 and 2 was higher than that in non-grafted groups. The ABG and BDG were higher in non-grafted groups 3 and 4 than in grafted groups, and the levels in group 3 were higher than those in group 4. The CBG in grafted group 2 was higher than that in group 1. No significant difference was observed in MBL analysis. CONCLUSIONS: The BDG of IPL<4 mm implants was higher than IPL>4 mm implant when bone grafts were not applied. No relevance was observed between IPL and CBG. Bone grafts can accelerate endo-sinus bone remodeling by increasing CBG and dissipating the influence of IPL on BDG.

Hyperglycemia accelerates inflammaging in the gingival epithelium through inflammasomes activation.

BACKGROUND AND OBJECTIVE: Diabetes accelerates inflammaging in various tissue with an increase in senescent cell burden and senescence-associated secretory phenotype (SASP) secretion, which is a significant cause of tissue dysfunction and contributes to the diabetic complications. Recently, inflammasomes are thought to contribute to inflammaging. Here, utilizing diabetic models in vivo and in vitro, we investigated the potential association between hyperglycemia-induced inflammaging and gingival tissue dysfunction and the mechanism underlying inflammasome-associated inflammaging. MATERIALS AND METHODS: Gingival epithelium and serum were collected from control and diabetic patients and mice. The expression of p16, p21, and inflammasomes in the gingival epithelium, SASP factors in serum, and the molecular factors associated with gingival epithelial barrier function were assessed. Human oral keratinocyte (HOK) was stimulated with normal and high glucose, and pre-treated with Z-YVAD-FMK (Caspase-1 inhibitor) prior to evaluating cellular senescence, SASP secretion, and inflammasome activation. RESULTS: In vivo, hyperglycemia significantly elevated the local burden of senescent cells in the gingival epithelium and SASP factors in the serum and simultaneously reduced the expression levels of Claudin-1, E-cadherin, and Connexin 43 in the gingival epithelium. Interestingly, the inflammasomes were activated in the gingival epithelium. In vitro, high glucose-induced the inflammaging in HOK, and blocking inflammasome activation through inhibiting Caspase-1 and glucose-induced inflammaging. CONCLUSIONS: Hyperglycemia accelerated inflammaging in the gingival epithelium through inflammasomes activation, which is potentially affiliated with a decline in the gingival epithelial barrier function in diabetes. Inflammasomes-related inflammaging may be the crucial mechanism underlying diabetic periodontitis and represents significant opportunities for advancing prevention and treatment options.

Tetrahedral Framework Nucleic Acids Loaded with Aptamer AS1411 for siRNA Delivery and Gene Silencing in Malignant Melanoma.

siRNA is found to effectively knock down the target gene in cells, which is considered a promising strategy for gene therapy. However, the application of siRNA is limited due to its low efficiency of the cellular uptake. Tetrahedral framework nucleic acids (tFNAs) are synthesized by four single-stranded DNAs and show multiple biological functions in recent studies, especially suitable for drug delivery. More than 60% of malignant melanomas are associated with Braf gene mutation, an attractive therapeutic target for RNA interference. In this study, we modified anti-Braf siRNA (siBraf) with tFNAs to downregulate the target gene. Meanwhile, we directly incorporated AS1411 (a DNA aptamer) to our nanostructure, which assists tFNAs to improve the cellular uptake efficacy of siBraf significantly. The results indicated that tFNAs-AS1411-siBraf exhibited more potent activity to cleave Braf mRNA than free siBraf. This study may provide a new idea for the combination therapy of siRNA and aptamers via DNA nanomaterials to achieve gene silencing.

Protein corona formed in the gastrointestinal tract and its impacts on oral delivery of nanoparticles.

The interaction of nanoparticles (NPs) with proteins and the formation of protein corona in the biological fluids are of great interest and significance for drug delivery. In the past decade, the corona formation in the blood and its impacts on the in vitro and in vivo fate of NPs has been well investigated and reviewed. Recently, more and more attention is paid to the nano-protein interactions taking place in the gastrointestinal tract (GIT) between the orally administered NPs and the digestive enzymes. The enzyme corona formed in the GIT can significantly affect the properties, gastrointestinal transit, and oral absorption of NPs. Since oral delivery is the most preferred delivery route, comprehensively understanding the corona formation in the GIT and its impacts on oral delivery NPs are of great importance. Herein, we aim to summarize the recent updates on the nano-protein interactions between NPs and digestive enzymes, and launch an interesting discussion on the potentials of using the digestive enzyme corona for the colon targeted delivery.

Inhibition of methicillin-resistant Staphylococcus aureus (MRSA) biofilm by cationic poly (D, L-lactide-co-glycolide) nanoparticles.

The emergent need for new treatment methods for multi-drug resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) has focused attention on novel potential tools like nanoparticles (NPs). In the present study, a drug-free cationic nanoparticles (CNPs) system was developed and its anti-MRSA effects were firstly investigated. The results showed that CNPs (261.7 nm, 26.1 mv) showed time- and concentration-dependent activity against MRSA growth, killing ∼ 90% of planktonic bacterial cells in 3 h at 400 µg ml-1, and completely inhibiting biofilm formation at 1000 µg ml-1. Moreover, CNPs at 400 µg ml-1 reduced the minimum inhibitory concentration (MIC) of vancomycin on inhibition of planktonic MRSA growth (∼ 25%) and biofilm formation (∼ 50%). The CNPs-bacteria interaction force was up to 22 nN. Overall, these data suggest that CNPs have a good potential in clinical applications for the prevention and treatment of MRSA infection.

The UV absorption of graphene oxide is size-dependent: possible calibration pitfalls.

Graphene oxide (GO) is often quantified via its UV absorption, typically at around 230 nm. This is convenient but the effect of the size of GO on the accuracy of this method has been ignored so far. The authors report that the molar absorbance of GO is size-dependent. Data are presented on the absorbance of small (hydrodynamic diameter 1 µm), medium sized (1.5 µm), and large (2.2 µm) GO particles at wavelengths of 210, 230 and 250 nm. In general, linear relationship and good regression fits are obtained, but with different slope depending on size even at the same wavelength. This implies that using the UV absorption-based calibration may cause significant errors in GO quantification. Ultimately, this leads to incorrect dosages and faulty conclusions. This may also explain a variety of inconsistent results obtained in previous biological applications of GO. Graphical abstract The size of graphene oxide (GO) determines its UV absorption and the UV absorption-based calibration (GO-s, GO-m and GO-l represent the GO with small, medium and large size).

Antibiofilm effect of drug-free and cationic poly(D,L-lactide-co-glycolide) nanoparticles via nano-bacteria interactions.

AIM: Recently, nano-bio interactions and their biomedical impacts have drawn much attention, but nano-bacteria interaction and its function are unknown. Herein, we aim to synthesize drug-free and cationic nanoparticles (CNPs) and investigate CNP-bacteria interaction and its antibiofilm effect. MATERIALS & METHODS: The bioactivity of CNPs against Streptococcus mutans was examined by colony-forming units counting and scanning electron microscopy. CNP-bacteria interaction force was measured by atomic force microscopy. RESULTS: CNPs (217.7 nm, 14.7 mv) showed a concentration-dependent activity against bacteria. Particularly, CNPs at 200 µg/ml completely inhibited planktonic bacterial growth and biofilm formation, and disrupted ∼70% mature biofilm. CNP-bacteria interaction force was up to 184 nN. CONCLUSION: CNPs have great potentials for convenient local use for prevention and treatment of bacteria-related oral diseases.

Concentration-dependent protein adsorption at the nano-bio interfaces of polymeric nanoparticles and serum proteins.

AIM: A comprehensive understanding of nanoparticle (NP)-protein interaction (protein corona formation) is required. So far, many factors influencing this interaction have been investigated, like size and ζ potential. However, NPs exposure concentration has always been ignored. Herein, we aim to disclose the correlation of NPs exposure concentration with protein adsorption. MATERIALS & METHODS: Four polymeric NPs systems possessing similar sizes (230 ± 20 nm) but varied ζ potentials (-30 ∼ +40 mv) were prepared. Physicochemical properties and protein adsorption upon NP-protein interaction were characterized. RESULTS: Protein adsorption capacity and adsorbed protein types were NPs concentration-dependent. CONCLUSION: Considering the critical impacts of protein adsorption on NPs delivery, our work could be an urgent warning about the possible risks of dosage adjustment of nanoformulations.

Oral Nano-Delivery Systems for Colon Targeting Therapy.

BACKGROUND: Targeting drug delivery is an attractive research area, as it enables localized treatment, improves the efficacy of therapeutics and reduces systemic toxicity. Colon targeting delivery is particularly beneficial to the treatment of colon diseases, such as inflammatory bowel disease and colon cancer, due to the improved local drug concentrations. The traditional strategies for colon targeting delivery include time-dependent and pH-dependent technologies, etc. In recent years, nanotechnology has emerged as a novel and efficient tool for targeting drug delivery. After oral administration, nano-based formulations are able to protect drug from the harsh gastrointestinal environment and selectively increase the drug concentration at the disease site. Various orally administered drug-loaded nano-systems for colon targeting delivery have been well documented and shown great potentials in colon disease therapy. OBJECTIVE: In this work, we aim to provide a comprehensive understanding of the recent progress in the area of colon targeting delivery in combination with introduction of the pathophysiological changes of diseased colon sites and the obstacles for drug delivery.

Histological evidence that metformin reverses the adverse effects of diabetes on orthodontic tooth movement in rats.

This study evaluated the effects of metformin on orthodontic tooth movement in a rat model of type 2 diabetes mellitus. Rats were fed a high-fat diet for 4 weeks to induce fat accumulation and insulin resistance, and then injected with a low dose of streptozotocin (35 mg/kg) intraperitoneally to induce type 2 diabetes. An orthodontic appliance was placed in normoglycemic, type 2 diabetes, and type 2 diabetes with metformin-administrated rats. After 14 days, type 2 diabetes rats exhibited greater orthodontic tooth movement and had a higher number of tartrate-resistant acid phosphatase-positive osteoclasts, stronger cathepsin K expression, and weaker alkaline phosphatase immunostaining than normoglycemic rats. Metformin administration resulted in normalization of osteoclast numbers, cathepsin K immunostaining, and of tooth movement as well as partly recovery of alkaline phosphatase expression in diabetic rats. Metformin also reduced sclerostin expression and improved the immunolocalization of dentin matrix protein 1 in osteocytes of type 2 diabetes rats. These results suggest that metformin administration reversed the adverse effects of diabetes on orthodontic tooth movement.