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Objective To investigate the osteogenic properties of a methacrylated gelatin (GelMA) / bone marrow mesenchymal stem cells (BMSCs) composite hydrogel applied to the skull defect area of rats and to provide an experimental basis for the development of bone regeneration biomaterials. Methods This study was approved by the Animal Ethics Committee of Nanjing University. A novel photocurable composite biohydrogel was developed by constructing photoinitiators [lthium phenyl (2,4,6-trimethylbenzoyl) phosphinate, LAP], GelMA, and BMSCs. The surface morphology and elemental composition of the gel were examined using scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The compressive strength of the gel was evaluated using an electronic universal testing machine. After in vitro culture for 1, 2, and 5 days, the proliferation of the BMSCs in the hydrogels was assessed using a CCK-8 assay, and their survival and morphology were examined through confocal microscopy. A 5 mm critical bone deficiency model was generated in a rat skull. The group receiving composite hydrogel treatment was referred to as the GelMA/BMSCs group, whereas the untreated group served as the control group. At the 4th and 8th weeks, micro-CT scans were taken to measure the bone defect area and new bone index, while at the 8th week, skull samples from the defect area were subjected to H&E staining, van Gieson staining, and Goldner staining to evaluate the quality of bone regeneration and new bone formation. Results SEM observed that the solidified GelMA showed a 3D spongy gel network with uniform morphology, the porosity of GelMA was 73.41% and the pore size of GelMA was (28.75 ± 7.13) μm. EDX results showed that C and O were evenly distributed in the network macroporous structure of hydrogel. The hydrogel compression strength was 152 kPa. On the 5th day of GelMA/BMSCs culture, the cellular morphology transitioned from oval to spindle shaped under microscopic observation, accompanied by a significant increase in cell proliferation (159.4%, as determined by the CCK-8 assay). At 4 weeks after surgery, a 3D reconstructed micro-CT image revealed a minimal reduction in bone defect size within the control group and abundant new bone formation in the GelMA/BMSCs group. At 8 weeks after surgery, no significant changes were observed in the control group's bone defect area, with only limited evidence of new bone growth; however, substantial healing of skull defects was evident in the GelMA/BMSCs group. Quantitative analysis at both the 4- and 8-week examinations indicated significant improvements in the new bone volume (BV), new bone volume/total bone volume (BV/TV), bone surface (BS), and bone surface/total bone volume (BS/TV) in the GelMA/BMSCs group compared to those in the control group (P

Objective To evaluate the bone repair effect of 3D-printed magnesium (Mg)-loaded polycaprolactone (PCL) scaffolds in a rat skull defect model. Methods PCL scaffolds mixed with Mg microparticles were prepared by using 3D printing technology, as were pure PCL scaffolds. The surface morphologies of the two scaffolds were observed by scanning electron microscopy (SEM), and the surface elemental composition was analyzed via energy dispersive spectroscopy (EDS). The physical properties of the scaffolds were characterized through contact angle measurements and an electronic universal testing machine. This study has been reviewed and approved by the Ethics Committee. A critical size defect model was established in the skull of 15 Sprague-Dawley (SD) rats, which were divided into the PCL group, PCL-Mg group, and untreated group, with 5 rats in each group. Micro-CT scanning was performed to detect and analyze skull defect healing at 4 and 8 weeks after surgery, and samples from the skull defect area and major organs of the rats were obtained for histological staining at 8 weeks after surgery. Results The scaffolds had a pore size of (480 ± 25) μm, a fiber diameter of (300 ± 25) μm, and a porosity of approximately 66%. The PCL-Mg scaffolds contained 1.0 At% Mg, indicating successful incorporation of Mg microparticles. The contact angle of the PCL-Mg scaffolds was 68.97° ± 1.39°, indicating improved wettability compared to that of pure PCL scaffolds. Additionally, compared with that of pure PCL scaffolds, the compressive modulus of the PCL-Mg scaffolds was (57.37 ± 8.33) MPa, demonstrating enhanced strength. The PCL-Mg group exhibited the best bone formation behavior in the skull defect area compared with the control group and PCL group at 4 and 8 weeks after surgery. Moreover, quantitative parameters, such as bone volume (BV), bone volume/total volume (BV/TV), bone surface (BS), bone surface/total volume (BS/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N) and bone mineral density (BMD), of skull defects were better than those in the other groups, indicating the best bone regeneration effect. H&E, Goldner, and VG staining revealed more mineralized new bone formation in the PCL-Mg group than in the other groups, and H&E staining of the major organs revealed good biosafety of the material. Conclusion PCL-Mg scaffolds can promote the repair of bone defects and have clinical potential as a new scaffold material for the repair of maxillofacial bone defects.

Objective This article explores the relationship between congenital tooth agenesis and related gene mutations, providing a reference for early diagnosis of the disease. Methods Clinical and radiographic examinations of a rare case of congenital tooth agenesis were conducted to evaluate the abnormal morphology and quantity of the teeth, as well as the overall health of the patient. Bidirectional sequencing of the PAX9 and MSX1 genes and whole-exome sequencing were conducted to identify potential genetic abnormalities. Sanger sequencing of the newly discovered mutation site was performed on the proband's son. Subsequently, the impacts of the mutations were evaluated through computational tools and a cell-based gene transfection assay. Results This is a rare case of tooth agenesis characterized by a congenitally missing first molar, a second molar with one single root and a supernumerary second premolar in the right mandibular dentition. The c.717 C>C/T in PAX9 is synonymous. The c.119C>G in MSX1 is a missense mutation predicted to be “benign” by Polyphen. Through whole-exome sequencing, we found a novel mutation, c.637-7 C>A in intron 3 of the WNT6 gene, which is predicted by MAXENT to influence the splicing of mRNA. Both the proband and his son carry this mutation. A cell-based gene transfection assay demonstrated that it did not alter the mRNA splicing of WNT6. Conclusion The interaction between single nucleotide polymorphisms may contribute to congenital tooth agenesis.

Objective To analyze the current status, hotspots, and trends in the field of stem cell therapies for periodontal tissue engineering based on bibliometric analysis. Methods The literature on stem cell therapies for periodontal tissue engineering in animal experiments and clinical studies was searched in the Web of Science core database up to December 31, 2021. The bibliometric analysis of the relevant literature data was carried out by using the "Bibliometrix" package of R language. Results A total of 304 articles were included, and the number of publications and the citation frequency are increasing. The number of related studies from China ranks first in the world with 166 publications; the institution with the largest number of publications is the Fourth Military Medical University; the author with the largest number of publications is Jin Y; and Tissue Engineering Part A had the most related publications. The hotspots of stem cell therapies for periodontal tissue engineering are mainly focused on tissue engineering and periodontal ligament regeneration, while the frontiers are mainly focused on exosomes, gold nanoparticles, and angiogenesis. Conclusion Research on stem cell therapies for periodontal tissue engineering continues to expand, and the academic influence is gradually increasing. Future research directions should focus on periodontal ligament regeneration, exosomes, gold nanoparticles and angiogenesis.

In situ tumor vaccines (ISTVs) hold great potential in tumor immunotherapy, however, three major obstacles, including inadequate endogenous antigen uptake by dendritic cells (DCs), weak T‐cell immune responses, and stubborn immunosuppressive tumor microenvironment (TME), still need to be fully addressed. Herein, a trifecta nanovaccine (TriNV) with TME‐responsive transformable ability is developed to tri‐boost antitumor immunity. First, sufficient endogenous tumor‐associated antigens (TAAs) are liberated in situ after immunogenic cell death is induced via TriNV‐based photoimmunotherapy. In the TME, soft‐transformed TriNV improves the uptake of TAAs by DCs to enhance acquired immunity. Second, the self‐adjuvating TriNV and the TME‐responsive released Mn2+ synergistically promote DC maturation and macrophage M1 polarization by augmenting the stimulator of interferon genes activation to further amplify T‐cell immune responses. Moreover, the decomposition of MnO2 within the core of TriNV exhausts glutathione and facilitates O2 release to alleviate hypoxia in the TME, thereby overcoming the chemical obstacles of the TME to further mitigate immunosuppression. Thus, TriNV remarkably eradicates primary tumors and inhibits distant metastasis, thus demonstrating great potential as a feasible and effective ISTV nanoplatform for combating poorly immunogenic solid tumors. [ABSTRACT FROM AUTHOR]

Host immune systems serving as crucial defense lines are vital resisting mechanisms against biofilm‐associated implant infections. Nevertheless, biofilms hinder the penetration of anti‐bacterial species, inhibit phagocytosis of immune cells, and frustrate host inflammatory responses, ultimately resulting in the weakness of the host immune system for biofilm elimination. Herein, a cell‐like construct is developed through encapsulation of erythrocyte membrane fragments on the surface of Fe3O4 nanoparticle‐fabricated microbubbles and then loaded with hydroxyurea (EMB‐Hu). Under ultrasound (US) stimulation, EMB‐Hu undergoes a stable oscillation manner to act in an "exocytosis" mechanism for disrupting biofilm, releasing agents, and enhancing penetration of catalytically generated anti‐bacterial species within biofilms. Additionally, the US‐stimulated "exocytosis" by EMB‐Hu can activate pro‐inflammatory macrophage polarization and enhance macrophage phagocytosis for clearance of disrupted biofilms. Collectively, this work has exhibited cell‐like microbubbles with US‐stimulated "exocytosis" mechanisms to overcome the biofilm barrier and signal macrophages for inflammatory activation, finally achieving favorable therapeutic effects against implant infections caused by methicillin‐resistant Staphylococcus aureus (MRSA) biofilms. [ABSTRACT FROM AUTHOR]

Dendritic cell (DC)‐based cancer immunotherapy has exhibited remarkable clinical prospects because DCs play a central role in initiating and regulating adaptive immune responses. However, the application of traditional DC‐mediated immunotherapy is limited due to insufficient antigen delivery, inadequate antigen presentation, and high levels of immunosuppression. To address these challenges, engineered biomaterials have been exploited to enhance DC‐mediated immunotherapeutic effects. In this review, vital principal components that can enhance DC‐mediated immunotherapeutic effects are first introduced. The parameters considered in the rational design of biomaterials, including targeting modifications, size, shape, surface, and mechanical properties, which can affect biomaterial optimization of DC functions, are further summarized. Moreover, recent applications of various engineered biomaterials in the field of DC‐mediated immunotherapy are reviewed, including those serve as immune component delivery platforms, remodel the tumor microenvironment, and synergistically enhance the effects of other antitumor therapies. Overall, the present review comprehensively and systematically summarizes biomaterials related to the promotion of DC functions; and specifically focuses on the recent advances in biomaterial designs for DC activation to eradicate tumors. The challenges and opportunities of treatment strategies designed to amplify DCs via the application of biomaterials are discussed with the aim of inspiring the clinical translation of future DC‐mediated cancer immunotherapies. [ABSTRACT FROM AUTHOR]

Background: Dynamic changes in circulating immune-inflammatory cells have been regarded as simple and convenient prognostic biomarkers in various cancers. However, studies on the prognostic values of their ratios in oral squamous cell carcinoma (OSCC) remain limited. Materials and Methods: A total of 493 OSCC patients were included in the present study. Here, we investigated the prognostic values of the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), neutrophil-to-white blood cell ratio (NWR), and lymphocyte-to-white blood cell ratio (LWR) in OSCC. The correlations of the NLR, LMR, NWR, and LWR with clinicopathological characteristics were statistically analyzed using the Chi-square test, Kaplan-Meier curves, and univariate and multivariate Cox regression models. Result: Kaplan-Meier analyses revealed that OSCC patients with a high LMR and low NWR had prolonged overall survival (OS, P <0.001) and disease-free survival (DFS, P <0.001 and P =0.003, respectively), but there were no significant differences in metastasis-free survival (MFS, P =0.053 and P =0.052, respectively). In contrary, a high NLR and low LWR were associated with poor OS (P <0.001 and P =0.0016, respectively), DFS (P =0.0014 and 0.0012, respectively) and MFS (P =0.021 and 0.008, respectively). Additionally, Cox multivariate analyses showed that the LMR was an independent prognostic factor for both OS (P =0.007) and DFS (P= 0.017), while the LWR was an independent prognostic factor for MFS (P =0.009). Conclusion: Preoperative NLR, LMR, NWR, and LWR in the peripheral blood are significant prognostic factors for OSCC and might be helpful in predicting OSCC progression. [ABSTRACT FROM AUTHOR]

Preclinical animal models of oral squamous cell carcinoma (OSCC) have been extensively studied in recent years. Investigating the pathogenesis and potential therapeutic strategies of OSCC is required to further progress in this field, and a suitable research animal model that reflects the intricacies of cancer biology is crucial. Of the animal models established for the study of cancers, mouse tumor-bearing models are among the most popular and widely deployed for their high fertility, low cost, and molecular and physiological similarity to humans, as well as the ease of rearing experimental mice. Currently, the different methods of establishing OSCC mouse models can be divided into three categories: chemical carcinogen-induced, transplanted and genetically engineered mouse models. Each of these methods has unique advantages and limitations, and the appropriate application of these techniques in OSCC research deserves our attention. Therefore, this review comprehensively investigates and summarizes the tumorigenesis mechanisms, characteristics, establishment methods, and current applications of OSCC mouse models in published papers. The objective of this review is to provide foundations and considerations for choosing suitable model establishment methods to study the relevant pathogenesis, early diagnosis, and clinical treatment of OSCC. [ABSTRACT FROM AUTHOR]

Background: With advanced technology, short implants are more commonly used and have proven to have a relatively reliable curable efficacy. A consensus has not been reached regarding potential risk factors related to the loss of short implants. Purpose This large‐sample retrospective study concentrated not only on patient characteristics and medical procedures but also on the features of implants in order to uncover the risk factors associated with short implants. Methods: Between 2014 and 2017, a total of 7001 implants were inserted at Nanjing Stomatological Hospital, Medical School of Nanjing University. Among the all, 1236 short implants were included after being evaluated according to the inclusion and exclusion criteria. In organizing the detailed information, seven variables including bone grafting procedure, age, gender, diameter of the implant, implant position, surface treatment, and definitive restorations were taken into consideration. The χ2 test, Kaplan‐Meier test, logistic regression, and multifactorial Cox regression analysis were employed to explore the risk factors. Results: The cumulative survival rate of short implants was 96.36%, slightly lower than that of the standard implants (98.16%, P <.001). Most of the short implants (84.44%) were lost at the early stage, mainly because of infection. Based on the results, male gender, implants treated by titanium anodizing and single‐crown restoration increased the loss rate of short implants. Comparison of the short implants inserted into the maxillary and mandibular posterior area alone showed that the maxillary molar area was a risk factor for prognosis. Conclusions: Male gender, TA surface treatment, and the presence of a single crown were associated with an increasing rate of short implants loss. Examination of the implant location focused on the posterior area revealed the maxillary posterior area to be a risk factor. [ABSTRACT FROM AUTHOR]

Background: Narrow‐diameter implants (NDIs) have been proposed to address the dilemma of implant installation in cases of insufficient bone volume. However, the potential risk factors of failed NDIs, and whether reimplants with reliable efficacy are still controversial. Purpose: This study aimed to evaluate the survival/success rate of NDIs in the maxillary anterior region and that of reimplants at the same site, as well as to explore the potential risk factors of original and replaced implants. Materials and Methods: From January 2015 to April 2019, patients receiving NDIs in the anterior maxilla were enrolled in the present study. Multiple variables were assessed to exploit the risk factor of failed NDIs, including age, sex, implant sites, length, surface characteristics, and healing abutment designs. The relationship between bone augmentation and the number of missing teeth was assessed. For failed NDIs, the reasons for NDIs removal and marginal bone loss (MBL) were analyzed. The details and outcomes of reimplants were evaluated. Results: Cumulative survival rates (CSRs) and success rates of 1095 NDIs installed in 835 patients were 96.99% and 96.51%, respectively. In total, 33 of these NDIs failed. TiUnite (TU) surface was a risk factor and it affected the success rate (92.56%) and CSR (92.4%) of NDIs (P <.001). The single NDIs with bone augmentation have lower failure rate. The average MBL for 33 failed NDIs was 1.92 ± 1.91 mm. Additionally, 22 patients with 23 NDIs accepted reimplantation of previously failed NDIs, and the success rate of reimplants was 95.65%. Conclusions: Surface characteristic (TU surface) was a risk factor for failure of NDIs in the maxillary anterior region. Bone augmentation simultaneously performed during NDIs implantation was favorable for a single missing tooth. As an alternative plan, the reimplantation of failed NDIs was reliable and stable after successful bone reconstruction. [ABSTRACT FROM AUTHOR]

The PI3K/AKT signaling pathway regulates cell proliferation and differentiation in multiple types of cells. The present study aimed to investigate the effects of mechanical stress on C2C12 cell proliferation and to explore the associated mechanisms. A cyclic mechanical stress model of C2C12 myoblasts was established. Reverse transcription-quantitative PCR and western blotting assay were used to examine the PI3K signaling pathways involved in the progress of cell differentiation. Cell counting kit-8 (CCK-8) assay was used to evaluate the proliferation of C2C12 cells. Flow cytometry was employed to evaluate apoptosis following mechanical stress. The results demonstrated that mechanical stress activated the PI3K signaling pathway in C2C12 myoblasts. Mechanical stress significantly promoted phosphorylation (p-) of AKT and expression of mammalian target of rapamycin (mTOR) compared with the normal group. Mechanical stress significantly promoted 4E-binding protein 1 (4EBP1) expression in C2C12 cells compared with the normal group. The PI3K specific inhibitor LY294002 significantly decreased 4EBP1 expression and reduced p-AKT and p-mTOR expression compared with the mechanical stress group. Mechanical stress promoted C2C12 cell proliferation. Apoptosis of C2C12 significantly decreased in the mechanical stress group compared with the normal group. Cyclin D levels significantly increased in the mechanical stress group compared with the normal group. In conclusion, mechanical stress promoted biological functions of C2C12 cells by activating the PI3K/AKT signaling pathway. These results may contribute to a better understanding of the effects of mechanical stress on cells. [ABSTRACT FROM AUTHOR]

Caspase recruitment domain‐containing protein 9 (CARD9) is an adaptor protein and highly expressed in myeloid cells. Our previous study demonstrates a critical protective effect of CARD9 in the development of colitis‐associated colon cancer. Nevertheless, the effect of CARD9 in lung cancer remains unclear. Here, using a mouse Lewis lung cancer model, we found the tumor burden of CARD9−/− mice was much heavier than that in wild‐type (WT) mice. More myeloid‐derived suppressor cells (MDSCs) were accumulated and less cytotoxicity T lymphocyte was found in tumor tissues of CARD9−/− mice, compared to WT mice. Depleting MDSCs using anti‐Gr1 antibody can significantly decrease tumor burden in CARD9−/− mice. Furthermore, the noncanonical nuclear factor‐kappaB (NF‐κB) pathway was activated in CARD9−/− mice‐derived MDSCs. Deficiency of CARD9 enhanced expression of indoleamine 2,3‐dioxygenase (IDO) in MDSCs via noncanonical NF‐κB pathway. Moreover, correlations between CARD9 expressions and MDSCs relative genes (IDO, iNOS‐2 and arginase 1 [ARG‐1]) were further confirmed in tumor tissues from lung cancer patients. Taken together, we showed a CARD9‐NF‐κB‐IDO pathway in MDSCs which can inhibit the suppressive function of MDSCs and prevent lung cancer development. What's new? Myeloid‐derived suppressor cells (MDSCs) play a critical role in enabling tumor immune escape. Factors capable of counteracting MDSC activity in the tumor microenvironment remain largely unknown. Here, the authors identify caspase recruitment domain‐containing protein 9 (CARD9), a myeloid cell adaptor protein, as an inhibitor of MDSCs and indoleamine 2,3‐dioxygenase (IDO), an immunosuppressive enzyme produced by MDSCs. In mice, CARD deficiency was associated with increased lung tumor size and impaired immune response. Non‐canonical NF‐kB pathway signaling and IDO expression were enhanced in CARD‐deficient cells. The findings suggest that CARD9 is an important immune regulator in the lung tumor microenvironment. [ABSTRACT FROM AUTHOR]

Background: The factors influencing satisfaction of the patients with implant treatments are still unclear. This study aims to evaluate the patients' satisfaction and to identify influencing factors, which will improve the medical quality of oral implantology. Materials and methods: Patients who lost single teeth and received implant treatments were enrolled in Nanjing Stomatological Hospital between February 2016 and March 2018. A questionnaire survey was performed to assess patient satisfaction and data were collected at four time points. Information included gender, age, educational level, application of bone augmentation, type of prosthetic restoration, period of teeth loss, dentist qualification, and tooth position. Meanwhile, the satisfaction of the patients was evaluated by visual analog scale. Results: A total of 373 patients completed the questionnaires. The mean of overall satisfaction score was 69.05±7.10. Lower overall satisfaction score was found in patients who received bone augmentation (P<0.001) and those with a longer period of teeth loss (P<0.05). In the bone augmentation group, the elements of pain and complication were significantly associated with a decrease in the median satisfaction score (P<0.001), and a similar result was obtained form the duration of operative time and healing response (P<0.001). On the other hand, the satisfaction scores for elements including the duration of operative time and healing response (P<0.05), aesthetics and psychology (P<0.05), and chewing function (P<0.05) decreased with an extended period of teeth loss. Meanwhile, over half of respondents were more concerned about the survival time (40.70%) and success rate (20.49%) of implants. Conclusion: Bone augmentation and the period of teeth loss are negative factors affecting patient satisfaction, and the success rate and survival time of implants are considerable aspects for patients. It is essential to raise general awareness of oral hygiene and optimize the dental implant therapeutic process. [ABSTRACT FROM AUTHOR]

Background: The knowledge of the potential risk factors associated with implant loss is crucial for dental clinicians, but the opinions about the risk factors are still diverse and controversial. Purpose This retrospective study assessed the risk factors associated with implant loss, especially that in the maxillary molar location. Materials and Methods: From January 2015 to March 2017, 4338 Chinese patients received 6977 implants at Nanjing Stomatological Hospital. Information on patient age, gender, bone grafting procedure, implant location, length and diameter, and the records of lost implants were obtained. The Kaplan‐Meier method and log‐rank test were used to conduct a survival function analysis. Chi‐square test and multivariate Cox regression analysis were used to identify risk factors related to implant loss. Results: The cumulative survival rate (CSR) after 0‐32 months of observation period for all implants was 97.76%, and the CSR for maxillary molar implants was 97.00%. Maxillary molar implants showed a significantly lower CSR than the other implants (P < .05). Male sex, short implants (<10 mm) were considered as risk factors for implant loss. However, male sex and bone grafting procedure were regarded as risk factors for maxillary molar implant loss, which was slightly different from the result of all implants. Conclusions: Male sex, short implants (<10 mm) and maxillary molar location were considered as potential risk factors for implant loss, whereas male sex and bone grafting procedure were significantly associated with implant loss in maxillary molar location. [ABSTRACT FROM AUTHOR]

Background: Due to the high-quality immunogenicity of tumor-derived autophagosomes (DRibbles), we aimed to explore the antitumor ability and mechanism of DRibble-loaded dendritic cells (DRibble-DCs). Materials and methods: DRibbles extracted from the oral squamous cell carcinoma cell line SCC7 express specific LC3-II and ubiquitination marker. Immunization of mice with the DRibble-DCs vaccine led to the proliferation and differentiation of CD3+CD4+IFN-γ+ and CD3+CD8+IFN-γ+ T cells. The expression of proteins in endoplasmic reticulum stress (ERS) pathways was determined by Western blotting. Additionally, the functional properties of the DRibble-DCs were examined in mice, and regulatory T cells were measured by flow cytometry. Results: Excellent biocompatibility was observed in vitro when DCs were loaded with DRibbles. T cells of lymph nodes and spleens from mice immunized with DRibble-DCs had cytotoxic effects on SCC7 cells. DCs homeostasis and ERS-related proteins were affected by DRibbles. Moreover, the DRibble-DCs vaccine achieved significantly better antitumor efficacy than DRibbles and tumor cell lysate-loaded DCs. Conclusion: The results validated the antitumor immune responses to the DRibble-DCs vaccine in vivo and in vitro. The ERS pathway can be affected by DRibbles. [ABSTRACT FROM AUTHOR]

Objective: Many studies have shown that magnetic fields (MF) inhibit tumor growth and influence the function of immune system. However, the effect of MF on mechanism of immunological function in tumor-bearing mice is still unclear. Methods: In this study, tumor-bearing mice were prepared by subcutaneously inoculating Balb/c mice with hepatocarcinoma cell line H22. The mice were then exposed to a low frequency MF (0.4 T, 7.5 Hz) for 30 days. Survival rate, tumor growth and the innate and adaptive immune parameters were measured. Results: MF treatment could prolong survival time (n = 28, p<0.05) and inhibit tumor growth (n = 9, p<0.01) in tumor-bearing mice. Moreover, this MF suppressed tumor-induced production of cytokines including interleukin-6 (IL-6), granulocyte colony- stimulating factor (G-CSF) and keratinocyte-derived chemokine (KC) (n = 9–10, p<0.05 or 0.01). Furthermore, MF exposure was associated with activation of macrophages and dendritic cells, enhanced profiles of CD4+ T and CD8+ T lymphocytes, the balance of Th17/Treg and reduced inhibitory function of Treg cells (n = 9–10, p<0.05 or 0.01) in the mice model. Conclusion: The inhibitory effect of MF on tumor growth was related to the improvement of immune function in the tumor-bearing mice. [ABSTRACT FROM AUTHOR]

Background: We previously found that the low frequency magnetic fields (LF-MF) inhibited gastric and lung cancer cell growth. We suppose that exposure to LF-MF may modulate immune function so as to inhibit tumor. We here investigated whether LF-MF can inhibit the proliferation and metastasis of melanoma and influence immune function.Methods: The effect of MF on the proliferation, cell cycle and ultrastracture of B16-F10 in vitro was detected by cell counting Kit-8 assay, flow cytometry, and transmission electron microscopy. Lung metastasis mice were prepared by injection of 2 × 105 B16-F10 melanoma cells into the tail vein in C57BL/6 mice. The mice were then exposed to an LF-MF (0.4 T, 7.5 Hz) for 43 days. Survival rate, tumor markers and the innate and adaptive immune parameters were measured.Results: The growth of B16-F10 cells was inhibited after exposure to the LF-MF. The inhibition was related to induction of cell cycle arrest and decomposition of chromatins. Moreover, the LF-MF prolonged the mouse survival rate and inhibited the proliferation of B16-F10 in melanoma metastasis mice model. Furthermore, the LF-MF modulated the immune response via regulation of immune cells and cytokine production. In addition, the number of Treg cells was decreased in mice with the LF-MF exposure, while the numbers of T cells as well as dendritic cells were significantly increased.Conclusion: LF-MF inhibited the growth and metastasis of melanoma cancer cells and improved immune function of tumor-bearing mice. This suggests that the inhibition may be attributed to modulation of LF-MF on immune function and LF-MF may be a potential therapy for treatment of melanoma. [ABSTRACT FROM AUTHOR]

Dental implants are widely used in the field of oral restoration, but there are still problems leading to implant failures in clinical application, such as failed osseointegration, marginal bone resorption, and peri-implantitis, which restrict the success rate of dental implants and patient satisfaction. Poor osseointegration and bacterial infection are the most essential reasons resulting in implant failure. To improve the clinical outcomes of implants, many scholars devoted to modifying the surface of implants, especially to preparing different physical and chemical modifications to improve the osseointegration between alveolar bone and implant surface. Besides, the bioactive-coatings to promote the adhesion and colonization of ossteointegration-related proteins and cells also aim to improve the osseointegration. Meanwhile, improving the anti-bacterial performance of the implant surface can obstruct the adhesion and activity of bacteria, avoiding the occurrence of inflammation related to implants. Therefore, this review comprehensively investigates and summarizes the modifying or coating methods of implant surfaces, and analyzes the ossteointegration ability and anti-bacterial characteristics of emerging functional coatings in published references. [ABSTRACT FROM AUTHOR]

Background: Biofilm ecosystem around the surface of teeth or prostheses is composed of more than 700 bacteria species, which are closely related to periodontal and peri‐implant diseases. Though periodontal pathogens can be detected around the implants based on the theory of bacteria translocation, the microbiota is usually not identical between peri‐implant and periodontal sites. Moreover, it's unclear whether there are differences of bacteria composition in peri‐implant sites in diverse periodontal status. Aim/Hypothesis: To investigate the bacterial diversities in peri‐implant biofilms and the differences in bacteria composition between periodontitis and periodontal healthy patients by 16S rRNA sequencing technique. Material and Methods: Patients with or without periodontitis completed implant restoration at the first molar site for at least six months were investigated. Subgingival plaques were collected around the involved implants and the first molars. Then periodontal examination was provided, but the recorded probing depth were limited to the sampling sites. Plaque samples were transported to the laboratory and the bacterial DNA was extracted. After the V4 region of the 16S rDNA was amplified, the mixture PCR products were purified, processed and sequenced on Illumina HiSeq platform. The effective data were clustered as OTUs (Operational Taxonomic Units) and the prevalence and identity of bacteria was analyzed using Sliva database and advanced techniques. Results: 36 implants in 30 periodontitis subjects (PI) and 13 implants in 11 healthy subjects (HI) were included in our study. Peri‐implant probing depth was comparable between two groups (_I_P _i_>_I_ _i_0.05). The average OTUs was 551, corresponding to 2 kingdoms, 50 phyla, 127 classes, 185 orders, 362 families, 783 generas. The genera Filifactor, Fusobacterium, Porphyromonas, Neisseria, Fretibacterium were present in higher abundance in PI, while Corynebacterium, Actinomyces, Streptococcus, Gemella and Veillonella were higher in HI. Anosim analysis indicated bacterial diversity between PI and HI was significantly different (_I_P _i_<_I_ _i_0.05). T‐test showed phylum Actinobacteria was higher in HI (_I_P _i_<_I_ _i_0.05). Phylum Bacteroidetes, Spirochaetes, TM7 (Saccharibacteria), Synergistetes, SR1 (Absconditabacteria) and Tenericutes were higher in PI (_I_P _i_<_I_ _i_0.05). LEfSe analysis were carried out and find genera Actinomyces and Sterptococcus in HI, Porphyromonas and Treponema 2 in PI could be considered as biomarkers individually. Conclusions and Clinical Implications: The biofilm around implant was comparable between periodontitis and healthy subjects, and it was mainly consisted of Gram‐negative anaerobic bacteria. The abundance of disease‐associated generas, such as Porphyromonas, Treponema, was higher in PI while genera Actinomyces and Streptococcus were higher in HI. Periodontitis history is considered as a risk factor for implant failure, and our study illustrates that more harmful bacteria colonizes in peri‐implant sulcus in patients with periodontitis.

Antibacterial therapy targeting the regulation of macrophage polarization may be a useful approach for normalizing the immune environment and accelerating wound healing. Inspired by black phosphorus-based nanoplatforms, more stable yet less-explored violet phosphorus nanosheets (VPNSs) are expected to provide a superior solution for effectively combating bacterial infections. In this study, an average thickness of 5-7 nm VPNSs are fabricated through the liquid-phase exfoliation method to serve as an immunoregulatory dressing for the treatment of infected wounds. VPNSs attenuated excessive reactive oxygen species (ROS) and reduced the accumulation of proinflammatory M1 macrophages, showing notable antioxidant and anti-inflammatory properties. Comprehensive RNA sequencing further elucidated the potential immunoregulatory mechanisms of VPNSs, including modulation of the inflammatory response and enzyme regulator activity. Additionally, the inherent photothermal properties of the VPNSs contributed significantly to their antibacterial efficacy. When combined with near-infrared laser irradiation, VPNSs showed remarkable effectiveness in reducing infection-related complications and expediting wound healing in infected skin wound models. The rapid promotion of wound healing through ROS clearance, the regulation of macrophage polarization, and hyperthermia generation underscores the potential of the violet-phosphorus-based nanoplatforms as clinically viable agents for treating infected wounds. This study suggests that VPNSs are promising candidates for clinical anti-infective and anti-inflammatory applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

The development of nanovaccines capable of eliciting tumor-specific immune responses holds significant promise for tumor immunotherapy. However, many nanovaccine designs rely heavily on incorporating multiple adjuvants and carriers, increasing the biological hazards associated with these additional components. Here, this work introduces novel flexible nanocapsules (OVAnano) designed to mimic extracellular vesicles, primarily using the ovalbumin antigen and minimal polyethylenimine adjuvant components. These results show that the biomimetic flexible structure of OVAnano facilitates enhanced antigen uptake by dendritic cells (DCs), leading to efficient antigen and adjuvant release into the cytosol via endosomal escape, and ultimately, successful antigen cross-presentation by DCs. Furthermore, OVAnano modulates the intracellular nuclear factor kappa-B (NF-κB) signaling pathway, promoting DC maturation. The highly purified antigens in OVAnano demonstrate remarkable antigen-specific immunogenicity, triggering strong antitumor immune responses mediated by DCs. Therapeutic tumor vaccination studies have also shown that OVAnano administration effectively suppresses tumor growth in mice by inducing immune responses from CD8 + and CD4 + T cells targeting specific antigens, reducing immunosuppression by regulatory T cells, and boosting the populations of effector memory T cells. These findings underscore that the simple yet potent strategy of employing minimal flexible nanocapsules markedly enhances DC-mediated antitumor immunotherapy, offering promising avenues for future clinical applications., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Implant infections are difficult to cure by traditional antibiotic therapy due to bacterial biofilm-induced antibiotic tolerance and impaired immune responses. To efficiently treat implant infections, therapeutic agents need to kill bacteria and regulate the inflammatory response of immune cells during the biofilm elimination process. Herein, multifunctional smart hollow Cu 2 MoS 4 nanospheres (H-CMS NSs) with pH-responsive enzyme-like activities were prepared for self-adaptively eliminating biofilms and regulating the inflammation of macrophages in implant infections. During biofilm infection, the tissue microenvironment around implants is acidic. H-CMS NSs with oxidase (OXD)/peroxidase (POD)-like activities can catalyze reactive oxidative species (ROS) generation for directly killing bacteria and polarizing macrophages to a proinflammatory phenotype. Moreover, the POD-like activity and antibacterial property of H-CMS NSs can be further enhanced under ultrasound (US) irradiation. After the elimination of biofilms, the tissue microenvironment around implants shifts from acidic to neutral. H-CMS NSs show catalase (CAT)-like activity and eliminate excessive ROS, which polarizes macrophages to anti-inflammatory phenotype and promotes healing of infected tissue. This work provides a smart nanozyme with self-adaptive regulation of the antibiofilm activity and immune response by regulating ROS generation/elimination according to the different pathological microenvironments in implant infections during the different therapeutic stages.

Efficient treatment of chronic lung infections caused by Pseudomonas aeruginosa biofilms is a great challenge because of drug tolerance and immune evasion issues. Here, we develop ultrasound-responsive catalytic microbubbles with biofilm elimination and immune activation properties to combat chronic lung infection induced by P. aeruginosa biofilms. In these microbubbles, piperacillin and Fe 3 O 4 nanoparticles form a drug-loaded shell surrounding the air core. Under ultrasound stimulation, the microbubbles can physically disrupt the structure of biofilms and enhance the penetration of both Fe 3 O 4 nanoparticles and piperacillin into the biofilm. Then, Fe 3 O 4 nanoparticles chemically degrade the biofilm matrix and kill the bacteria with the assistance of piperacillin. Fe 3 O 4 nanoparticles can activate the immune response for biofilm elimination by polarizing macrophages into a pro-inflammatory phenotype. These ultrasound-responsive catalytic microbubbles efficiently treat chronic lung infections in a mouse model by combining physical/chemical/antibiotic biofilm elimination and immune activation, thus providing a promising strategy for combating bacterial biofilm infections.