Periodontitis causally affects the brain cortical structure: A Mendelian randomization study.

OBJECTIVE: To estimate whether genetically proxied periodontitis causally impacts the brain cortical structure using Mendelian randomization (MR). BACKGROUND: Periodontitis is one of the most prevalent inflammatory conditions globally, and emerging evidence has indicated its influences on distal organs, including the brain, whose disorders are always accompanied by magnetic resonance imaging (MRI)-identified brain cortical changes. However, to date, no available evidence has revealed the association between periodontitis and brain cortical structures. METHODS: The instrumental variables (IVs) were adopted from previous genome-wide association study (GWAS) studies and meta-analyses of GWAS studies of periodontitis from 1844 to 5266 cases and 8255 to 12 515 controls. IVs were linked to GWAS summary data of 51 665 patients from the ENIGMA Consortium, assessing the impacts of genetically proxied periodontitis on the surficial area (SA) or the cortical thickness (TH) of the global and 34 MRI-identified functional regions of the brain. Inverse-variance weighted was used as the primary estimate; the MR pleiotropy residual sum and outlier (MR-PRESSO), the MR-Egger intercept test, and leave-one-out analyses were used to examine the potential horizontal pleiotropy. RESULTS: Genetically proxied periodontitis affects the SA of the medial orbitofrontal cortex, the lateral orbitofrontal cortex, the inferior temporal cortex, the entorhinal cortex, and the temporal pole, as well as the TH of the entorhinal. No pleiotropy was detected. CONCLUSIONS: Periodontitis causally influences the brain cortical structures, implying the existence of a periodontal tissue-brain axis.

Salivary microbiomes vary among orthodontic appliances and associate with clinical periodontal parameters.

OBJECTIVE: To investigate the salivary bacterial communities during the first 6-month orthodontic treatment with Clear Aligners (CA) and Fixed Appliances (FA), and its correlation with clinical periodontal parameters. MATERIALS AND METHODS: Saliva and periodontal parameters were sampled from individuals wearing CA or FA before treatment (T0), and after 3- (T3) and 6-month (T6) treatments. Salivary bacterial communities characterized based on the 16S rRNA V3-V4 region were compared between FA and CA and correlated with clinical periodontal parameters. RESULTS: Probing Depth (PD) significantly increased at T6 in the FA group versus T0, whereas it remained stable in the CA group. The Shannon and Pielou indices were significantly higher in the FA group and significantly positively correlated with periodontal inflammation parameters. ß-diversity analysis revealed distinct communities between the FA group and CA group at T6. The relative abundances of 3 genera and 15 species were significantly higher in the FA group. Among the above appliance-type related taxa, bacterial genera Selenomonas, Stomatobaculum, Olsenella and Faecalicoccus and bacterial species Selenomonas_sputigena, Dialister_invisus, Olsenella_profus, Prevotella_buccae, Cryptobacterium_curtum and Clostridium_spiroforme were significantly positively associated with periodontal parameters. CONCLUSIONS: Orthodontic treatments trigger appliance-related salivary bacterial communities, highlighting the importance of developing appliance-orientated periodontal strategies during orthodontic treatments. Salivary bacterial communities harboured by patients wearing FA possess higher bacterial parameters which were associated with increasing PD, PI and Gingival Index.

From teeth to brain: dental caries causally affects the cortical thickness of the banks of the superior temporal sulcus.

OBJECTIVES: Dental caries is one of the most prevalent oral diseases and causes of tooth loss. Cross-sectional studies observed epidemiological associations between dental caries and brain degeneration disorders, while it is unknown whether dental caries causally affect the cerebral structures. This study tested whether genetically proxied DMFS (the sum of Decayed, Missing, and Filled tooth Surfaces) causally impacts the brain cortical structure using Mendelian randomization (MR). METHODS: The summary-level GWAS meta-analysis data from the GLIDE consortium were used for DMFS, including 26,792 participants. ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) consortium GWAS summary data of 51,665 patients were used for brain structure. This study estimated the causal effects of DMFS on the surface area (SA) and thickness (TH) of the global cortex and functional cortical regions accessed by magnetic resonance imaging (MRI). Inverse-variance weighted (IVW) was used as the primary estimate, the MR pleiotropy residual sum and outlier (MR-PRESSO), the MR-Egger intercept test, and leave-one-out analyses were used to examine the potential horizontal pleiotropy. RESULTS: Genetically proxied DMFS decreases the TH of the banks of the superior temporal sulcus (BANSSTS) with or without global weighted (weighted, ß = - 0.0277 mm, 95% CI: - 0.0470 mm to - 0.0085 mm, P = 0.0047; unweighted, ß = - 0.0311 mm, 95% CI: - 0.0609 mm to - 0.0012 mm, P = 0.0412). The causal associations were robust in various sensitivity analyses. CONCLUSIONS: Dental caries causally decrease the cerebral cortical thickness of the BANKSSTS, a cerebral cortical region crucial for language-related functions, and is the most affected brain region in Alzheimer's disease. This investigation provides the first evidence that dental caries causally affects brain structure, proving the existence of teeth-brain axes. This study also suggested that clinicians should highlight the causal effects of dental caries on brain disorders during the diagnosis and treatments, the cortical thickness of BANKSSTS is a promising diagnostic measurement for dental caries-related brain degeneration.

Supramolecular Core-Shell Nanoassemblies with Tumor Microenvironment-Triggered Size and Structure Switch for Improved Photothermal Therapy.

Photothermal therapy (PTT) is demonstrated to be an effective methodology for cancer treatment. However, the relatively low photothermal conversion efficiency, limited tumor accumulation, and penetration still remain to be challenging issues that hinder the clinical application of PTT. Herein, the core-shell hierarchical nanostructures induced by host-guest interaction between water-soluble pillar[5]arene (WP5) and polyethylene glycol-modified aniline tetramer (TAPEG) are constructed. The pH-responsive performance endows the core-shell nanostructures with size switchable property, with an average diameter of 200 nm in the neutral pH and 60 nm in the acidic microenvironment, which facilitates not only tumor accumulation but also tumor penetration. Moreover, the structure switch of WP5⊃TAPEG under acidic microenvironment and the dual mechanism regulated extending of п conjugate, inclusion in the hydrophobic cavity of WP5 and the dense distribution in the core-shell structured assemblies, dramatically enhance the absorption in the near-infrared-II region and, further, the photothermal conversion efficiency (60.2%). The as-designed intelligent nanoplatform is demonstrated for improved antitumor efficacy via PTT.

Minimally invasive bone augmentation through subperiosteal injectable hydroxylapatite/laponite/alginate nanocomposite hydrogels.

Bone augmentation has an enormous demand in oral clinical treatment. Although there are various options available for clinical management to address it, these approaches could increase patient suffering due to surgical trauma and even cause psychological trauma to the patients. Moreover, presently, there is still a lack of well-considered microinvasive bone augmentation systems to deal with this challenge. Herein, we newly developed a subperiosteal injectable and osteogenesis-promoting hydroxylapatite/laponite/alginate nanocomposite hydrogels to address the insufficient microinvasive bone augmentation strategies. The physical performances (like swelling profiles, degradation behaviors, mechanical properties, and surface morphologies) of the gels were determined, and can be slightly tuned through altering concentrations of laponite. The cytocompatibility test results show outstanding biocompatibility of the hydrogels. Furthermore, the in vitro testing for bone-inducing activity and in vivo determination of bone-augmentation in the rat cranial subperiosteum exhibit that the hydrogels significantly promoted rat periosteum-derived mesenchymal stromal cells (P-MSCs) osteogenic differentiation in vitro and bone augmentation in vivo. Therefore, the research reveals that the nanocomposite hydrogels possessing subperiosteal microinvasive injectability, osteogenesis-enhancing capability, and clinical applicability have extremely great potential application in subperiosteal microinvasive bone augmentation.

A simple liposome-based bionic bacterium for tumor treatment by re-education of tumor-associated microphages in combination with chemotherapy.

Re-education of tumor-associated macrophages (TAMs) into M1-like macrophages (Mφ1) has become one of the aims of tumor immunotherapy. Injection of live bacteria has been applied for this purpose; however, an acute innate immune response might be caused in this progress, and therefore a bacteria-based strategy with great security is needed. In this study, the bacterial walls of Staphylococcus aureus were inserted into the bilayer of liposome to construct liposome-based bionic bacteria (Bio-Bac), and doxorubicin (DOX) was encapsulated to form DOX@Bio-Bac. DOX@Bio-Bac re-educated the THP-1-derived TAMs into Mφ1 in vitro, and subsequently inhibited the migration and invasion of CAL27 cells. In a mouse model of hepatocellular carcinoma with lymphatic metastasis, the re-education of TAMs was proved, and an effective inhibition of tumor growth and metastasis in mice was observed. The liposome-based bionic bacteria constructed in this study provide a new strategy for re-education of TAMs, replacing the bacterial therapy reported previously, and a more effective anti-tumor effect can be obtained by combining the chemotherapy drugs with this bionic bacterium.

Gold nanorod@void@polypyrrole yolk@shell nanostructures: Synchronous regulation of photothermal and drug delivery performance for synergistic cancer therapy.

Synergistic therapy has been emerging as new trend for effective tumor treatment due to synchronous function and cooperative reinforcement of multi therapeutic modalities. Herein, gold nanorods (GNRs) encapsulated into polypyrrole (PPy) shell with tunable void space (GNRs@Void@PPy) showing yolk@shell nanostructures were innovatively designed. The exploitation of dual near-infrared (NIR) absorptive species offered synergistic enhancement of photothermal performance. In addition, the manipulation of the void space between them provided additional benefits of high drug encapsulation efficiency (92.6%) and, interestingly, tumor microenvironment and NIR irradiation triggered targeted drug releasing. Moreover, the GNRs@Void@PPy exhibited excellent biocompatibility, and optimal curative effect by chemo-photothermal synergistic therapy was achieved through both in vitro and in vivo antitumor activity investigation.

Penetrating Macrophage-Based Nanoformulation for Periodontitis Treatment.

Periodontitis is a chronic inflammatory disease caused by the interaction of oral microorganisms with the host immune response. Porphyromonas gingivalis (P.g.) acts as a key mediator in subverting the homeostasis of the local immune system. On the one hand, P.g. inhibits phagocytosis and the killing capacity of immune cells. On the other hand, P.g. increases selective cytokine release, which is beneficial to its further proliferation. Here, we prepared a penetrating macrophage-based nanoformulation (MZ@PNM)-encapsulating hydrogel (MZ@PNM@GCP) that responded to the periodontitis microenvironment. MZ@PNM targeted P.g. via the Toll-like receptor complex 2/1 (TLR2/1) on its macrophage-mimicking membrane, then directly killed P.g. through disruption of bacterial structural integrity by the cationic nanoparticles and intracellular release of an antibacterial drug, metronidazole (MZ). Meanwhile, MZ@PNM interrupted the specific binding of P.g. to immune cells and neutralized complement component 5a (C5a), preventing P.g. subversion of periodontal host immune response. Overall, MZ@PNM@GCP showed potent efficacy in periodontitis treatment, restoring local immune function and killing pathogenic bacteria, while exhibiting favorable biocompatibility, all of which have been demonstrated both in vivo and in vitro.

Emerging research and clinical development trends of liposome and lipid nanoparticle drug delivery systems.

Liposomes are spherical-enclosed membrane vesicles mainly constructed with lipids. Lipid nanoparticles are loaded with therapeutics and may not contain an enclosed bilayer. The majority of those clinically approved have diameters of 50-300 nm. The growing interest in nanomedicine has fueled lipid-drug and lipid-protein studies, which provide a foundation for developing lipid particles that improve drug potency and reduce off-target effects. Integrating advances in lipid membrane research has enabled therapeutic development. At present, about 600 clinical trials involve lipid particle drug delivery systems. Greater understanding of pharmacokinetics, biodistribution, and disposition of lipid-drug particles facilitated particle surface hydration technology (with polyethylene glycol) to reduce rapid clearance and provide sufficient blood circulation time for drug to reach target tissues and cells. Surface hydration enabled the liposome-encapsulated cancer drug doxorubicin (Doxil) to gain clinical approval in 1995. Fifteen lipidic therapeutics are now clinically approved. Although much research involves attaching lipid particles to ligands selective for occult cells and tissues, preparation procedures are often complex and pose scale-up challenges. With emerging knowledge in drug target and lipid-drug distribution in the body, a systems approach that integrates knowledge to design and scale lipid-drug particles may further advance translation of these systems to improve therapeutic safety and efficacy.

Electromembrane extraction of salivary polyamines followed by capillary zone electrophoresis with capacitively coupled contactless conductivity detection.

Electromembrane extraction (EME) as a novel sample preparation technique was firstly applied for the purification and enrichment of four polyamines mainly present in saliva samples. These four target analytes, putrescine, cadaverine, spermidine, and spermine, were directly determined by CZE with capacitively coupled contactless conductivity detection (CZE-C(4)D) after EME procedure. Several factors affecting extraction efficiency, electrophoretic separation, and detection were investigated. Under the optimum conditions, four polyamines were baseline separated within 22 min, exhibiting a linear calibration over three orders of magnitude (r>0.999); the highest enrichment factor could reach 106-fold (for spermidine), and the LODs were in the range of 1.4-7.0 ng mL(-1). The proposed EME/CZE-C(4)D method has been successfully applied to analyze human saliva samples with recoveries in the range of 78-97%.