Oral infection with periodontal pathogens induced chronic obstructive pulmonary disease-like lung changes in mice.

BACKGROUND: Epidemiological studies have demonstrated that periodontitis is an independent risk factor for chronic obstructive pulmonary disease (COPD). However, the mechanism underlying the association between these two diseases remains unclear. The lung microbiota shares similarities with the oral microbiota, and there is growing evidence to suggest that the lung microbiome could play a role in the pathogenesis of COPD. This study aimed to investigate whether periodontal pathogens could contribute to the pathogenesis of COPD in a mouse model. METHODS: We established mouse models with oral infection by typical periodontal pathogens, porphyromonas gingivalis (Pg group) or fusobacterium nucleatum (Fn group), over a three-month period. Mice that did not receive oral infection were set as the control group (C group). We assessed the level of alveolar bone resorption, lung function, and histological changes in the lungs of the mice. Additionally, we measured the levels of inflammatory factors and tissue damage associated factors in the lung tissues. RESULTS: Lung function indices, including airway resistance, peak inspiratory/expiratory flow and expiratory flow-50%, were significantly reduced in the Fn group compared to the C group. Additionally, histological examination revealed an increased number of inflammatory cells and bullae formation in the lung tissue sections of the Fn group. Meanwhile, levels of inflammatory factors such as IL-1ß, IL-6, IFN-γ, and TNF-α, as well as tissue damage associated factors like matrix metalloproteinase-8 and neutrophil elastase, were significantly elevated in the lung tissue of the Fn group in comparison to the C group. The Pg group also showed similar but milder lung changes compared to the Fn group. Pg or Fn could be detected in the lungs of both oral infected groups. CONCLUSION: The results indicated that oral periodontal pathogens infection could induce COPD-like lung changes in mice, and they may play a biological role in the association between periodontitis and COPD.

[Systemic Influencing Factors of Dentition Defect in Type 2 Diabetes Mellitus Patients with Periodontitis].

Objective: To analyze the influencing factors of dentition defect in people with type 2 diabetes mellitus (T2DM) and periodontitis and to provide evidence-based support for improving the oral health and quality of life of T2DM patients. Methods: A total of 169 patients with T2DM and periodontitis were selected by convenience sampling. According to the number of remaining teeth, the subjects were divided into two groups, group A (number of remaining teeth in the mouth≥20, n=115) and group B (the number of remaining teeth in the mouth<20, n=54). Questionnaire surveys, systemic and oral examinations, and laboratory blood tests were performed. Systematic influencing factors of dentition defect in people with T2DM and periodontitis were analyzed with logistic regression. Results: Compared with patients in group A, patients in group B had higher findings in age, systolic blood pressure (SBP), prevalence of coronary heart disease and hyperlipidemia, glycosylated hemoglobin (HbA1c), periodontal probing depth (PD), and clinical attachment loss (CAL). Furthermore, their behaviors and awareness of oral health were not as good as those of patients in group A. Logistic regression showed that age, HbA1c, and SBP were independent risk factors for the number of remaining teeth in the mouth <20 among T2DM patients with periodontitis ( P<0.05). Conclusion: Increasing age, lower HbA1c, and increased SBP are the most important influencing factors for the number of remaining teeth in the mouth <20 in T2DM patients with periodontitis. Clinical practitioners should give more attention to the general health status of the patients and strengthen health education, thereby improving patients' quality.

Relationship between periodontal status and dyslipidemia in patients with type 2 diabetic nephropathy and chronic periodontitis: A cross-sectional study.

OBJECTIVE: The aim of this study was to investigate the association between periodontitis and total serum cholesterol level in patients with type 2 diabetic nephropathy (T2DN). BACKGROUND: Periodontitis is now recognized as the sixth complication of diabetes and can also affect other complications of diabetes, including nephropathy and coronary artery diseases. Studies have considered dyslipidemia as a risk factor for exacerbation of periodontitis. METHODS: A total of 119 T2DN patients with chronic periodontitis were included in this observational study. Participants were stratified into the Normal (serum total cholesterol <5.17 mmol/L, n = 89) and the Dyslipidemia groups (serum total cholesterol ≥5.17 mmol/L, n = 30). Participants completed a validated questionnaire that collected information on oral hygiene behaviors and knowledge of oral health and underwent a clinical oral examination. The number of remaining teeth, probing depth (PD), clinical attachment level (CAL), and bleeding index (BI) was recorded. Physical examination and laboratory tests (fasting plasma glucose, serum glycosylated hemoglobin (HbA1c), total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglyceride, and high-sensitivity C-reactive protein levels) were performed. RESULTS: Means of CAL and BI were significantly higher in the Dyslipidemia group compared with the Normal group. In the Dyslipidemia group, PD and percent of sites with PD ≥4 mm were positively correlated with urinary albumin/creatinine ratios; PD and percent of sites with PD ≥4 and PD ≥5 mm were positively correlated with HbA1c level; a number of remaining teeth were negatively correlated with serum LDL-C level. After adjusting for age, gender, body mass index, smoking, FPG, and serum HbA1c and triglyceride levels, BI was found to be positively associated with dyslipidemia in T2DN patients with periodontitis. CONCLUSION: T2DN patients with chronic periodontitis had a 2.355-fold higher risk of developing dyslipidemia, implying an important relationship between periodontitis and blood lipid control among T2DN patients.

Human adipose-derived stem cells and simvastatin-functionalized biomimetic calcium phosphate to construct a novel tissue-engineered bone.

To repair bone defects, we evaluate the in-vitro and in-vivo osteogenic activities of a novel tissue-engineered bone (TEB) by elaborately combining biomimetic calcium phosphate (BioCaP) granules with internally-incorporated simvastatin (SIM) and human adipose-derived stem cells (hASCs). First, we constructed BioCaP with SIM internally incorporated (SIM-BioCaP). Then we characterized the morphology and chemical composition of SIM-BioCaP. The release kinetics of SIM was monitored in vitro spectroscopically. Thereafter, we explored the in-vitro cellular responses of hASCs to SIM-BioCaP by performing scanning electron microscopy observation, proliferation assay, alkaline phosphatase (ALP) activity assay, alizarin red staining and real-time PCR. Finally, we investigated the in-vivo osteogenic activities of the novel TEB in a subcutaneous bone induction model in nude mice. We found that SIM was successfully incorporated internally in BioCaP and showed a slow release manner without significantly affecting the attachment and proliferation of hASCs. The released SIM from BioCaP could significantly enhance the proliferation, ALP activities, mineralized nodules formation and osteogenic genes of hASCs. The in-vivo tests showed this TEB could induce new bone formation while the other groups could not. Taken together, the present data show that this novel TEB represented a very promising construct to treat critical-volume bone defects.

Stability of diazepam's phase II metabolites in dried blood spots on filter paper.

Phase II metabolites play an important role in diazepam-related cases. The study aimed to assess the stability of diazepam's phase II metabolites in dried blood spots on filter paper. METHODS: A piece of filter paper was spotted with 100 µL of whole blood (added 1% sodium fluoride as needed) obtained from participant who received 5 mg diazepam orally, air dried for 2 h at room temperature, and then stored at different conditions. Whole spots were cut at 0.1 cm from the outer edge of blood spots at post-consumption time-points of prior (zero), 5, 16, 35, 61, 120 days and 1, 1.5 years. Analytes were extracted with methanol/water mixture (8:2, v/v) and determined using HPLC-MS/MS. Decomposition rules were analyzed by a statistical software "SPSS". RESULTS: Temazepam glucuronide remained stable (0.5-18.6% loss) at 20 â„ƒ and at 20 â„ƒ with 1% sodium fluoride for 16 days, while it was unstable after 5 days at 4 â„ƒ (21.1-26.2% loss) and - 20 â„ƒ (28.9 - 34.4% loss). After 35 days, temazepam glucuronide concentrations began to fluctuate significantly under all conditions, and an obvious increase (290.4-355.1%) was observed in 1.5 years. Oxazepam glucuronide was always unstable after 5 days, the percentage loss was even 100% when it was stored for 61 days and 1.5 years. CONCLUSIONS: Dried blood spots on ordinary filter paper are recommended to be stored at 20 â„ƒ or 20 â„ƒ with 1% sodium fluoride within 16 days. Samples should be analyzed immediately or stored in sterile and dry media.

Polydopamine-coated nanocomposite theranostic implants for localized chemotherapy and MRI imaging.

Sustained and localized delivery of chemotherapeutics in postoperative cancer treatment leads to a radical improvement in prognosis and a much decreased risk of tumor recurrence. In this work, polydopamine (PDA)-coated superparamagnetic iron oxide nanoparticle (SPION)-loaded polycaprolactone and poly(lactic-co-glycolic acid) fibers were developed as a potential implant to ensure safe and sustained release of the chemotherapeutic drug methotrexate (MTX), as well as provide local contrast for magnetic resonance imaging (MRI). Fibres were prepared by co-axial electrospinning and loaded with MTX-layered double hydroxide (LDH) nanocomposites in the core, yielding organic-inorganic hybrids ranging from 1.23 to 1.48 µm in diameter. After surface coating with PDA, SPIONs were subsequently loaded on the fibre surface and found to be evenly distributed, providing high MRI contrast. In vitro drug release studies showed the PDA coated fibres gave sustained release of MTX over 18 days, and the release profile is responsive to conditions representative of the tumor microenvironment such as slightly acidic pH values or elevated concentrations of the reducing agent glutathione (GSH). In vitro studies with Caco-2 and A549 cells showed highly effective killing with the PDA coated formulations, which was further enhanced at higher levels of GSH. The fibres hence have the potential to act as an implantable drug-eluting platform for the sustained release of cytotoxic agents within a tumor site, providing a novel treatment option for post-operative cancer patients.

Microbiota in Gingival Crevicular Fluid Before and After Mechanical Debridement With Antimicrobial Photodynamic Therapy in Peri-Implantitis.

OBJECTIVES: This study aims to compare the microbiota of gingival crevicular fluid (GCF) before and after mechanical debridement (MD) with antimicrobial photodynamic therapy (aPDT) and determine the core efficient microbiota in peri-implantitis after treatment. METHODS: We recruited 9 patients (14 implants) treated with MD+aPDT for peri-implantitis at our center from February 1, 2018, to February 1, 2019. GCF was collected using filter paper strip before and after the treatment. The bacterial 16S rRNA was amplified and sequenced using an Illumina MiSeq platform to characterize the GCF. Bioinformatics and statistical analyses were performed using QIIME2 and R. RESULTS: A total of 4,110,861 high-quality sequences were obtained from GCF samples. Based on the reference database, 1,120 amplicon sequence variants (ASVs) were finally harvested. Principal coordinates analysis indicated significant differences in the bacterial community structure between the 180 days after-treatment group and pre-treatment group. Difference analysis and least discriminant analysis showed that the differences were mainly reflected in non-dominant bacteria between these two groups. The non-dominant genera with significantly different distribution between the 180 days after-treatment group and the pre-treatment group included Lactobacillus, Pedobacter, Bulleidia, Centipeda, Desulfovibrio, Ochrobactrum, Staphylococcus, Microbacterium, Brevundimonas, Desulfobulbus, and Parvimonas. Moreover, a total of 29 predictive functional categories at KEGG level 2 were identified. The significant difference pathways at KEGG level 2 between after-treatment and pre-treatment were concentrated in infectious disease-related pathways. CONCLUSIONS: Patients with peri-implantitis have significant changes in the low-abundance bacteria of the GCF before and after MD+aPDT. MD+aPDT may change the composition of GCF microbiota by increasing the abundance of cluster 1 (beneficial) and decreasing that of cluster 4 (harmful), which may decrease metabolic response to infection and thus improve peri-implantitis.

[Correlation between social psychology and personality characteristics and treatment options for adult patients with skeletal malocclusion].

OBJECTIVE: This study aims to explore factors affecting the dental aesthetic social psychology of patients with skeletal malocclusion and to measure the relationship between the objective orthodontic requirements and the subjective treatment requirements of patients. This work provides a reference for doctors to measure patients' orthodontic treatment needs. METHODS: Adult patients with skeletal malocclusion were chosen as the research object. Questionnaire survey was used to analyze factors influencing the psychosocial impact of dental aesthetics questionnaire (PIDAQ), index of orthodontic treatment need (IOTN), and Eysenck personality questionnaire-revised short scale for Chinese (EPQ-RSC). The relationship among PIDAQ, IOTN, EPQ-RSC, and treatment options was also evaluated. RESULTS: Seventy-two valid questionnaires were collected from adult patients with skeletal malocclusion. 1) The PIDAQ scores significantly differed among different occupations (P<0.05) but were not affected by other general conditions such as gender and age. 2) Patients of different dental health component (DHC) grade and ages had different AC self-assessment scores (P<0.01, P<0.05). The AC self-assessment score was positively correlated with the PIDAQ score (P<0.05). 3) Males accounted for a higher proportion of patients who received treatment. Younger patients (18-28 years old) were more likely to receive treat-ment when their own dental aesthetics were poor. People with the higher monthly expenditure accounted for the larger proportion of surgical patients. 4) The PIDAQ score had no significant effects on the choice of opera-tion (P>0.05). People with low educational level were more likely to receive surgery if their psychosocial impacts of dental aes-thetics were serious. 5) The score of psychoticism scale of EPQ-RSC and the educa-tional level had a mutual influence on the PIDAQ score (P<0.01). Moreover, the neuroticism scale and AC self-assessment scores had a mutual influence on the PIDAQ score (P<0.05). However, this study did not find a correlation between personality traits and treatment options. CONCLUSIONS: Many factors, such as personal natural conditions, subjective aesthetic evaluation of teeth, and psychosocial impacts of dental aesthetics, affect patients' treatment options. Personality characteristics can play a certain role in dental aesthetics social psychology.

Tissue-Engineered Bone Immobilized with Human Adipose Stem Cells-Derived Exosomes Promotes Bone Regeneration.

Exosomes, nanoscale extracellular vesicles functioning as cell-to-cell communicators, are an emerging promising therapeutic in the field of bone tissue engineering. Here, we report the construction and evaluation of a novel cell-free tissue-engineered bone that successfully accelerated the restoration of critical-sized mouse calvarial defects through combining exosomes derived from human adipose-derived stem cells (hASCs) with poly(lactic-co-glycolic acid) (PLGA) scaffolds. The exosomes were immobilized on the polydopamine-coating PLGA (PLGA/pDA) scaffolds under mild chemical conditions. Specifically, we investigated the effects of hASC-derived exosomes on the osteogenic, proliferation, and migration capabilities of human bone marrow-derived mesenchymal stem cells in vitro and optimized their osteoinductive effects through osteogenic induction. Furthermore, an in vitro assay showed exosomes could release from PLGA/pDA scaffold slowly and consistently and in vivo results showed this cell-free system enhanced bone regeneration significantly, at least partially through its osteoinductive effects and capacities of promoting mesenchymal stem cells migration and homing in the newly formed bone tissue. Therefore, overall results demonstrated that our novel cell-free system comprised of hASC-derived exosomes and PLGA/pDA scaffold provides a new therapeutic paradigm for bone tissue engineering and showed promising potential in repairing bone defects.

Osteoinductive Effects of Free and Immobilized Bone Forming Peptide-1 on Human Adipose-Derived Stem Cells.

Most synthetic polymeric materials currently used for bone tissue engineering lack specific signals through which cells can identify and interact with the surface, resulting in incompatibility and compromised osteogenic activity. Soluble inductive factors also have issues including a short half-live in vivo. Bone forming peptide-1 is a truncated peptide from the immature form of bone morphogenetic protein-7 (BMP-7) that displays higher osteogenic activity than full-length, mature BMP-7. In this study, we used a mussel-inspired immobilization strategy mediated by polymerization of dopamine to introduce recently discovered stimulators of bone forming peptide-1 (BFP-1) onto the surface of poly-lactic-co-glycolic acid (PLGA) substrate to form a biomaterial that overcomes these challenges. Human adipose-derived stem cells (hASCs), being abundant and easy accessible, were used to test the osteogenic activity of BFP-1 and the novel biomaterial. Under osteoinductive conditions, cells treated with both BFP-1 alone and BFP-1-coated biomaterials displayed elevated expression of the osteogenic markers alkaline phosphatase (ALP), osteocalcin (OC), and RUNX2. Furthermore, hASCs associated with poly-dopamine-assisted BFP-1-immobilized PLGA (pDA-BFP-1-PLGA) scaffolds promoted in vivo bone formation in nude mice. Our novel materials may hold great promise for future bone tissue engineering applications.

Smartphone quantifies Salmonella from paper microfluidics.

Smartphone-based optical detection is a potentially easy-to-use, handheld, true point-of-care diagnostic tool for the early and rapid detection of pathogens. Paper microfluidics is a low-cost, field-deployable, and easy-to-use alternative to conventional microfluidic devices. Most paper-based microfluidic assays typically utilize dyes or enzyme-substrate binding, while bacterial detection on paper microfluidics is rare. We demonstrate a novel application of smartphone-based detection of Salmonella on paper microfluidics. Each paper microfluidic channel was pre-loaded with anti-Salmonella Typhimurium and anti-Escherichia coli conjugated submicroparticles. Dipping the paper microfluidic device into the Salmonella solutions led to the antibody-conjugated particles that were still confined within the paper fibers to immunoagglutinate. The extent of immunoagglutination was quantified by evaluating Mie scattering from the digital images taken at an optimized angle and distance with a smartphone. A smartphone application was designed and programmed to allow the user to position the smartphone at an optimized angle and distance from the paper microfluidic device, and a simple image processing algorithm was implemented to calculate and display the bacterial concentration on the smartphone. The detection limit was single-cell-level and the total assay time was less than one minute.