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Pathogenic bacteria infection is a serious threat to human public health due to the high morbidity and mortality rates. Nano delivery system for delivering antibiotics provides an alternative option to improve the efficiency compared to conventional therapeutic agents. In addition to the drug loading capacity of nanocarriers, which is typically around 10%, further lowers the drug dose that pathological bacteria are exposed to. Moreover, nanocarriers that are not eliminated from the body may cause side effects. These limitations have motivated the development of self‐delivery systems that are formed by the self‐assembly of different therapeutic agents. In this study, a vehicle‐free antimicrobial polymer polyhexamethylene biguanide (PHMB, with bactericidal and anti‐biofilm functions) hybrid gold nanoparticle (Au NPs, with photothermal therapy (PTT)) platform (PHMB@Au NPs) is developed. This platform exhibits an excellent synergistic effect to enhance the photothermal bactericidal effect for Staphylococcus aureus under near‐infrared irradiation. Furthermore, the results showed that PHMB@Au NPs inhibit the formation of biofilms, quickly remove bacteria to promote wound healing through PTT in infection model in vivo, and even mediate the transition of macrophages from M1 to M2 type, and accelerate tissue angiogenesis. PHMB@Au NPs will have promising value as highly effective antimicrobial agents for patient management. A vehicle‐free antimicrobial polymer polyhexamethylene biguanide (PHMB, with bactericidal and anti‐biofilm functions) hybrid gold nanoparticle (Au NPs, with photothermal therapy) platform (PHMB@Au NPs) exhibits synergistic interaction and enhanced photothermal bactericidal effect and anti‐biofilm for Staphylococcus aureus under near‐infrared irradiation with superior biosecurity.

Overcoming challenges in drug targeting and modulating the immunosuppressive microenvironment are critical for treating chronic bacterial infections, which are often characterized by intracellular bacteria and biofilms. To overcome these barriers, we report a multifunctional nanomedicine (C p E@BMV). The prodrug conjugate (C p E), composed of two phenylboronic acid-modified ciprofloxacin (Cip- pba ) molecules and ellagic acid (Ea), self-assembles due to its hydrophobic nature and π–π stacking. Bacterial membrane vesicles (BMVs) derived from Escherichia coli aid in C p E assembly and structural stabilization. Upon administration, pathogen-associated molecular patterns on C p E@BMV engage toll-like receptors on macrophages, activating these cells and enhancing their phagocytic response. Once internalized, C p E responds to elevated intracellular H₂O₂ levels, releasing Cip to eliminate intracellular bacteria. Additionally, Ea scavenges excess reactive oxygen species in inflamed macrophages and modulates the expression of inflammatory factors, preventing an exaggerated inflammatory response. The C p E@BMV formulation also penetrates biofilms, eliminating bacteria and releasing antigens. These antigens are transported to draining lymph nodes, where they induce dendritic cell maturation and trigger a robust T and B cell-mediated immune response, helping restore immune balance and combat pathogens effectively in female mouse models. Therefore, our C p E@BMV provide an efficient strategy combining chemical and immunological therapies for chronic bacterial infection management. Effective delivery of therapeutic agents to the infection site and the modulation of the immunosuppressive microenvironment at the site of infection are vital for the treatment of chronic bacterial infections but remain elusive. Here, the authors address these issues by developing a nanomedicine that combines chemical and immunological therapies for chronic bacterial infection management.

Bacterial infection in skin and soft tissue has emerged as a critical concern. Overreliance on antibiotic therapy has led to numerous challenges, including the emergence of multidrug-resistant bacteria and adverse drug reactions. It is imperative to develop non-antibiotic treatment strategies that not only exhibit potent antibacterial properties but also promote rapid wound healing and demonstrate biocompatibility. Herein, a novel multimodal synergistic antibacterial system (SNO-CS@MoS 2 ) was developed. This system employs easily surface-modified thin-layer MoS 2 as photothermal agents and loaded with S-nitrosothiol-modified chitosan (SNO-CS) via electrostatic interactions, thus realizing the combination of NO gas therapy and photothermal therapy (PTT). Furthermore, this surface modification renders SNO-CS@MoS 2 highly stable and capable of binding with bacteria. Through PTT’s thermal energy, SNO-CS@MoS 2 rapidly generates massive NO, collaborating with PTT to achieve antibacterial effects. This synergistic therapy can swiftly disrupt the bacterial membrane, causing protein leakage and ATP synthesis function damage, ultimately eliminating bacteria. Notably, after effectively eliminating all bacteria, the residual SNO-CS@MoS 2 can create trace NO to promote fibroblast migration, proliferation, and vascular regeneration, thereby accelerating wound healing. This study concluded that SNO-CS@MoS 2 , a novel multifunctional nanomaterial with outstanding antibacterial characteristics and potential to promote wound healing, has promising applications in infected soft tissue wound treatment.

Background Emerging evidence shows that periodontal disease (PD) may increase the risk of Coronavirus disease 2019 (COVID-19) complications. Here, we undertook a two-sample Mendelian randomization (MR) study, and investigated for the first time the possible causal impact of PD on host susceptibility to COVID-19 and its severity. Methods Summary statistics of COVID-19 susceptibility and severity were retrieved from the COVID-19 Host Genetics Initiative and used as outcomes. Single nucleotide polymorphisms associated with PD in Genome-wide association study were included as exposure. Inverse-variance weighted (IVW) method was employed as the main approach to analyze the causal relationships between PD and COVID-19. Three additional methods were adopted, allowing the existence of horizontal pleiotropy, including MR-Egger regression, weighted median and weighted mode methods. Comprehensive sensitivity analyses were also conducted for estimating the robustness of the identified associations. Results The MR estimates showed that PD was significantly associated with significantly higher susceptibility to COVID-19 using IVW (OR = 1.024, P  = 0.017, 95% CI 1.004–1.045) and weighted median method (OR = 1.029, P  = 0.024, 95% CI 1.003–1.055). Furthermore, it revealed that PD was significantly linked to COVID-19 severity based on the comparison of hospitalization versus population controls (IVW, OR = 1.025, P  = 0.039, 95% CI 1.001–1.049; weighted median, OR = 1.030, P  = 0.027, 95% CI 1.003–1.058). No such association was observed in the cohort of highly severe cases confirmed versus those not hospitalized due to COVID-19. Conclusions We provide evidence on the possible causality of PD accounting for the susceptibility and severity of COVID-19, highlighting the importance of oral/periodontal healthcare for general wellbeing during the pandemic and beyond.

Sulforaphene (SFE) is a common nutritional supplement with antibacterial, anti-cancer, and anti-inflammatory effects. However, the effects of SFE on the cariogenicity of Streptococcus mutans and dental caries have not been reported. The objectives of this study were to investigate the caries-controlling potential of SFE. The effects of SFE on S. mutans were investigated using the broth microdilution method, crystal violet staining, SEM observation, acid tolerance assays, lactic acid quantification, and polysaccharide measurements. A rat caries model was established to evaluate the caries-controlling effects and biocompatibility of SFE in vivo. SFE inhibited S. mutans growth and biofilm formation. Furthermore, SFE restrained the cariogenic properties of S. mutans, including its acid production, acid tolerance, and extracellular polysaccharide production, without affecting the bacterial viability at sub-inhibitory levels. In the rat caries model, SFE significantly arrested the onset and development of dental caries. Moreover, no visible hemolytic phenomenon or cytotoxicity was detected in the SFE groups. After four weeks of SFE treatment, all rats remained in apparent good health with no significant differences in weight gain; their hemogram and biochemical parameters were normal; no pathological changes were observed in the oral mucosa, liver, or kidneys. In conclusion, SFE was safe and inhibited the development of caries effectively.

Background Although a great number of specific quality of life measures have been developed to analyze the impact of wearing fixed appliances, there is still a paucity of systematic appraisal of the consequences of orthodontics on quality of life. To assess the current evidence of the relationship between orthodontic treatment and quality of life. Methods Four electronic databases were searched for articles concerning the impact of orthodontic treatment on quality of life published between January 1960 and December 2013. Electronic searches were supplemented by manual searches and reference linkages. Eligible literature was reviewed and assessed by methodologic quality as well as by analytic results. Results From 204 reviewed articles, 11 met the inclusion criteria and used standardized health related quality of life and orthodontic assessment measures. The majority of studies (7/11) were conducted among child/adolescent populations. Eight of the papers were categorized as level 1 or 2 evidence based on the criteria of the Oxford Centre for Evidence-Based Medicine. An observed association between quality of life and orthodontic treatment was generally detected irrespective of how they were assessed. However, the strength of the association could be described as modest at best. Key findings and future research considerations are described in the review. Conclusions Findings of this review suggest that there is an association (albeit modest) between orthodontic treatment and quality of life. There is a need for further studies of their relationship, particularly studies that employ standardized assessment methods so that outcomes are uniform and thus amenable to meta-analysis.

Background Periodontitis is a chronic infection initiated by oral bacterial and their virulence factors, yet the severity of periodontitis is largely determined by the dysregulated host immuno-inflammatory response. Baicalein is a flavonoid extracted from Scutellaria baicalensis with promising anti-inflammatory properties. This study aims to clarify the anti-inflammatory and osteogenic effects of baicalein in periodontal ligament cells (PDLCs) treated with lipopolysaccharides (LPS). Methods Human PDLCs were incubated with baicalein (0–100 μM) for 2 h prior to LPS challenge for 24 h. MTT analysis was adopted to assess the cytoxicity of baicalein. The mRNA and protein expression of inflammatory and osteogenic markers were measured by real-time polymerase chain reaction (PCR), western blot and enzyme-linked immunosorbent assay (ELISA) as appropriate. Alkaline phosphatase (ALP) and Alizarin red S (ARS) staining were performed to evaluate the osteogenic differentiation of PDLCs. The expression of Wnt/β-catenin and mitogen-activated protein kinase (MAPK) signaling related proteins was assessed by western blot. Results MTT results showed that baicalein up to 100 μM had no cytotoxicity on PDLCs. Baicalein significantly attenuated the inflammatory factors induced by LPS, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), matrix metalloprotein-1 (MMP-1), MMP-2 and monocyte chemoattractant protein 1 (MCP-1) at both mRNA and protein level. Moreover, MAPK signaling (ERK, JNK and p38) was significantly inhibited by baicalein, which may account for the mitigated inflammatory response. Next, we found that baicalein effectively restored the osteogenic differentiation of LPS-treated PDLCs, as shown by the increased ALP and ARS staining. Accordingly, the protein and gene expression of osteogenic markers, namely runt-related transcription factor 2 (RUNX2), collagen-I, and osterix were markedly upregulated. Importantly, baicalein could function as the Wnt/β-catenin signaling activator, which may lead to the increased osteoblastic differentiation of PDLCs. Conclusions With the limitation of the study, we provide in vitro evidence that baicalein ameliorates inflammatory response and restores osteogenesis in PDLCs challenged with LPS, indicating its potential use as the host response modulator for the management of periodontitis.

Probiotic lozenges have been developed to harvest the benefits of probiotics for oral health, but their long-term consumption may encourage the transfer of resistance genes from probiotics to commensals, and eventually to disease-causing bacteria. To screen commercial probiotic lozenges for resistance to antibiotics, characterize the resistance determinants, and examine their transferability in vitro. Probiotics of all lozenges were resistant to glycopeptide, sulfonamide, and penicillin antibiotics, while some were resistant to aminoglycosides and cephalosporins. High minimum inhibitory concentrations (MICs) were detected for streptomycin (>128 µg/mL) and chloramphenicol (> 512 µg/mL) for all probiotics but only one was resistant to piperacillin (MIC = 32 µg/mL). PCR analysis detected erythromycin (erm(T), ermB or mefA) and fluoroquinolone (parC or gyr(A)) resistance genes in some lozenges although there were no resistant phenotypes. The dfrD, cat-TC, vatE, aadE, vanX, and aph(3\")-III or ant(2\")-I genes conferring resistance to trimethoprim, chloramphenicol, quinupristin/dalfopristin, vancomycin, and streptomycin, respectively, were detected in resistant probiotics. The rifampicin resistance gene rpoB was also present. We found no conjugal transfer of streptomycin resistance genes in our co-incubation experiments. Our study represents the first antibiotic resistance profiling of probiotics from oral lozenges, thus highlighting the health risk especially in the prevailing threat of drug resistance globally.

Disruption of the intestinal epithelial barrier, driven by imbalances in gut mucosal immunity and microbial homeostasis, is central to the onset and progression of inflammatory bowel disease (IBD). This study introduces a CO‐releasing polyoxometalates (POMs) nanozyme (PMC), synthesized by coordinating pentacarbonyl manganese bromide with molybdenum‐based POM nanoclusters. PMC demonstrates targeted accumulation at IBD‐affected sites, efficient scavenging of reactive oxygen species (ROS), and responsive CO release, resulting in multiple therapeutic effects. Extensive in vitro and in vivo studies have validated the exceptional capacity of PMC to repair intestinal barrier, attributed to their potent antioxidant and anti‐inflammatory properties, thereby achieving significant therapeutic efficacy in ulcerative colitis treatment. 16S rRNA sequencing indicated that PMC efficiently remodeled the gut microbiota composition. Single‐cell RNA sequencing indicates a reduction in pro‐inflammatory M1 macrophages, alongside suppressed ROS and inflammatory signaling pathways. Concurrently, an increase in reparative M2 macrophages and intestinal stem cells is observed, in addition to significant activation of the VEGF signaling pathway in macrophages and the NOTCH pathway in stem cells, underscoring the potential of PMC to restore immune balance and promote tissue repair. This study positions PMC as a promising, multifunctional therapeutic agent for IBD treatment owing to its robust intestinal barrier‐restoring capability. A CO‐releasing polyoxometalates nanozyme (PMC) is engineered by coordinating pentacarbonyl manganese bromide with molybdenum‐based polyoxometalates nanoclusters. PMC exhibits targeted accumulation at IBD sites, efficient ROS scavenging, and responsive CO release. These advantageous features facilitate the efficient restoration of intestinal barrier integrity by modulating gut mucosal immunity and remodeling microbiota homeostasis, achieving significant therapeutic efficacy in the treatment of ulcerative colitis.

Background Currently, oblique placement of long implants or the use of short implants to circumvent the maxillary sinus area and provide support for fixed prostheses are viable alternatives. The purpose of this study was to compare these two treatment concepts and ascertain which one exhibits superior biomechanical characteristics. Methods Two different treatment concept models were constructed. The first one, LT4I, consisting of two mesial vertical implants positioned in lateral incisor regions and two distal tilted implants (45°) situated in second premolar regions of the maxilla. The second model, VS4I, includes two mesial vertical implants in lateral incisor regions and two vertically positioned short implants in second premolar regions. Numerical simulations were conducted under three loading types: firstly, oblique forces upon the molars; secondly, vertical forces upon the molars; thirdly, oblique forces upon the incisors. The maximum principal stress (σ max ) and minimum principal stress (σ min ) of the bone, as well as von Mises stress of the implants, were calcuated. Results Under oblique loading on the molar, higher stress values in the bone were observed in LT4I group. Under vertical loading on molar, higher stress values in the bone were also observed in LT4I group. Furthermore, little difference was found between the two groups under oblique loading on the incisor. Conclusion Both treatment concepts can be applicable for edentulous individuals with moderate atrophic maxilla. Compared to tilted implants, short implants can transmit less occlusal force to the supporting tissues.