The feasibility of contrast-enhanced CT to identify the adhesive renal venous tumor thrombus of renal cell carcinoma.

OBJECTIVE: To identify adhesive renal venous tumor thrombus (RVTT) of renal cell carcinoma (RCC) by contrast-enhancement CT (CECT). MATERIALS AND METHODS: Our retrospective study included 53 patients who underwent preoperative CECT and pathologically confirmed RCC combined with RVTT. They were divided into two groups based on the intra-operative findings of RVTT adhesion to the venous wall, with 26 cases in the adhesive RVTT group (ARVTT) and 27 cases in the non-adhesive group (NRVTT). The location, maximum diameter (MD) and CT values of tumors, the maximum length (ML) and width (MW) of RVTT, and length of inferior vena cava tumor thrombus were compared between the two groups. The presence of renal venous wall involvement, renal venous wall inflammation, and enlarged retroperitoneal lymph node was compared between the two groups. A receiver operating characteristic curve was used to analyze the diagnostic performance. RESULTS: The MD of RCC and the ML and MW of the RVTT were all larger in the ARVTT group than in the NRVTT group (p = 0.042, p < 0.001, and p = 0.002). The proportion of renal vein wall involvement and renal vein wall inflammation were higher in the ARVTT group than in NRVTT groups (both p < 0.001). The multivariable model including ML and vascular wall inflammation to predict ARVTT could achieve the best diagnostic performance with the area under the curve, sensitivity, specificity, and accuracy of 0.91, 88.5%, 96.3%, and 92.5%, respectively. CONCLUSION: The multivariable model acquired by CECT images could be used to predict RVTT adhesion. CLINICAL RELEVANCE STATEMENT: For RCC patients with tumor thrombus, contrast-enhanced CT could noninvasively predict the adhesion of tumor thrombus, thus predicting the difficulty of surgery and contributing to the selection of an appropriate treatment plan. KEY POINTS: • The length and width of the tumor thrombus could be used to predict its adhesion to the vessel wall. • Adhesion of the tumor thrombus can be reflected by inflammation of the renal vein wall. • The multivariable model from CECT can well predict whether the tumor thrombus adhered to the vein wall.

miR-488-3p Represses Malignant Behaviors and Facilitates Autophagy of Osteosarcoma Cells by Targeting Neurensin-2.

OBJECTIVE: Osteosarcoma (OS) is a primary bone sarcoma that primarily affects children and adolescents and poses significant challenges in terms of treatment. microRNAs (miRNAs) have been implicated in OS cell growth and regulation. This study sought to investigate the role of hsa-miR-488-3p in autophagy and apoptosis of OS cells. METHODS: The expression of miR-488-3p was examined in normal human osteoblasts and OS cell lines (U2OS, Saos2, and OS 99-1) using RT-qPCR. U2OS cells were transfected with miR-488-3p-mimic, and cell viability, apoptosis, migration, and invasion were assessed using CCK-8, flow cytometry, and Transwell assays, respectively. Western blotting and immunofluorescence were employed to measure apoptosis- and autophagy-related protein levels, as well as the autophagosome marker LC3. The binding sites between miR-488-3p and neurensin-2 (NRSN2) were predicted using online bioinformatics tools and confirmed by a dual-luciferase assay. Functional rescue experiments were conducted by co-transfecting miR-488-3p-mimic and pcDNA3.1-NRSN2 into U2OS cells to validate the effects of the miR-488-3p/NRSN2 axis on OS cell behaviors. Additionally, 3-MA, an autophagy inhibitor, was used to investigate the relationship between miR-488-3p/NRSN2 and cell apoptosis and autophagy. RESULTS: miR-488-3p was found to be downregulated in OS cell lines, and its over-expression inhibited the viability, migration, and invasion while promoting apoptosis of U2OS cells. NRSN2 was identified as a direct target of miR-488-3p. Over-expression of NRSN2 partially counteracted the inhibitory effects of miR-488-3p on malignant behaviors of U2OS cells. Furthermore, miR-488-3p induced autophagy in U2OS cells through NRSN2-mediated mechanisms. The autophagy inhibitor 3-MA partially reversed the effects of the miR-488-3p/NRSN2 axis in U2OS cells. CONCLUSION: Our findings demonstrate that miR-488-3p suppresses malignant behaviors and promotes autophagy in OS cells by targeting NRSN2. This study provides insights into the role of miR-488-3p in OS pathogenesis and suggests its potential as a therapeutic target for OS treatment.

Study Progress on Inorganic Fibers from Industry Solid Wastes and the Key Factors Determining Their Characteristics.

Compared to basalt and glass fibers, the production of inorganic fiber from industry solid wastes is an effective method to not only save natural resources but also recycle waste resources. Because the preparation of the fibers requires high temperature treatment, the production process is associated with high energy consumption and high carbon emissions. How to resolve these problems is a current research challenge in this field. Herein, we reviewed the study progress on these fibers and further discussed the key factors determining their characteristics, including chemical composition, melt structure, and viscosity of melt. In production, the matching of solid waste blends containing enough total content of SiO2 and Al2O3, and a suitable amount of MgO and CaO, is beneficial to the structure control of the melt. The study found that the melt consisted of Q2 and Q3; and that Q3 content more than Q2 was more suitable for fiber production and its performance improvement. Such a melt structure can be achieved by controlling the degree of depolymerization and the temperature. New ultrasonic technology can shorten the homogenization time; its application is hoped to save energy and reduce carbon emissions. These conclusions will offer important guidance for the development of inorganic fibers from industry solid wastes in the future.

Aberrant pulmonary immune response of obese mice to periodontal infection.

Obesity and periodontitis constitute mutual risk factors in respiratory disorders; this study aimed to explore the pulmonary immune response to periodontal infection using combined animal models with diet-induced obesity (DIO). Thirty-two C57 BL/6J mice were randomly divided into low-fat (LF) or high-fat (HF) diet groups and fed an LF diet as a control or an HF diet to induce obesity. The 30-week mice in the diet group were divided into periodontal ligation group (10 days using Porphyromonas gingivalis ATCC 33277) or sham-ligation group. The expressions of the macrophage-specific maker (F4/80), macrophage chemotactic protein1 (MCP1), and inflammatory cytokines in lung tissues were analyzed. The mRNA and protein levels of F4/80, MCP1, interleukin (IL)-1ß, and IL-6 expressions were significantly upregulated by obesity in lung tissues. However, the mRNA and protein levels of F4/80, MCP1, and IL-6 were downregulated by periodontitis in DIO mice relative to that of the HF control group. Periodontitis increased tumor necrosis factor-α level of lung tissues under LF, while IL-10 was not affected by obesity regardless of periodontitis. Periodontitis may aggravate pulmonary immune response in obese rodents. This may relate to the imbalance of the pro- and anti-inflammatory cytokine status of lung lesions, which tends to attenuate the infiltration of alveolar macrophages.

Preparation, thermal stability and mechanical properties of inorganic continuous fibers produced from fly ash and magnesium slag.

A large number of industrial solid waste resources urgently need to be recycled, so, fast-expanding the utilization area of these waste resources is a pressing task in today's China. The production of various slag wool fibers is an effective way due to the huge demand of thermal insulation materials. Besides, the preparation of slag continuous fibers is also a good choice because of its wide application fields. Two fly ash-based continuous fibers were successfully prepared by fly ash and magnesium slag, or add less feldspar, through melting at high temperature, following spinning into continuous fibers. Their samples were treated at different temperatures from 100 to 700 °C, and then investigate tensile strength and thermal resistance. As the same fly ash-based fibers, the tensile strength of two fibers in this study increase 115% and 28.3% than the fibers previously reported. Their utilization rates of solid waste resources are up to 100% and 80%, and far higher than 45% of the same fiber reported. FT-IR, SEM, Solid-state NMR analysis indicates that thermal action makes the 29Si structure without Al(Q3,Q2, and Q1) transfer to 29Si structure containing Al(Q4(3Al),Q4(2Al), Q4(1Al)), meanwhile, AlVI (AlO6 octahedron) was destroyed completely and converted into AlV (AlO5) and AlIV (Al[SiO]3). Only some Al atoms participated in the formation of network structure in fiber, they contributed to the strength of fibers.

Clinical Application of CT Navigation in treatment of Lumbar Spondylolisthesis with Minimally Invasive Surgery - Transforaminal Lumbar Interbody Fusion.

OBJECTIVE: To explore the clinical effect of the application of CT navigation in the treatment of lumbar spondylolisthesis with minimally invasive surgery - transforaminal lumbar interbody fusion (MIS-TLIF). METHODS: A retrospective study was conducted on 30 patients with lumbar spondylolisthesis who were continuously treated in linyi central hospital from May 2018 to March 2019.The patients were divided into two groups,15 patients treated with MIS-TLIF with the aid of CT navigation during the operation were included into an observation group. Another 15 patients were treated with open transforaminal lumbar interbody fusion as the control group. The baseline information, including gender, age and course of disease, perioperative period and imaging conditions, and VAS and ODI scores of patients in the two groups were collected and analyzed. RESULTS: Fifteen patients were included into the observation group, including 9 male and 6 female patients with an average age of 52.60 ± 6.31 and a course of disease of 16.33 ± 6.00 months. The other 15 patients were included into the observation group, including seven male and eight female patients with an average age of 52.87 ± 7.38 and a course of disease of 19.13 ± 9.89 months. The difference in the gender, age and course of disease between the two groups had no statistical significance (P > 0.05). However, the difference in the duration of operation and intraoperative blood loss between the two groups had statistical significance (P< 0.05). There were no statistically significant differences in wound complications, neurological complications, preoperative slippage rate, postoperative slippage rate, slippage reduction rate and screw placement accuracy (P > 0.05). VAS scores of the two groups were statistically significant from six months after surgery (P < 0.01). There was no significant difference in ODI between the two groups at any time point (P >, 0.05). VAS and ODI scores were improved at each time point compared with those before surgery. CONCLUSION: The minimally invasive transforaminal lumbar fusion performed with the aid of CT navigation during the operation shortens the duration of operation and the amount of bleeding, reduces the back pain, is beneficial to the early postoperative functional exercise, and speeds up the postoperative recovery.

Aberrant Periodontal and Systemic Immune Response of Overweight Rodents to Periodontal Infection.

This study aimed to explore periodontal and systemic immune response of overweight hosts to periodontitis. Forty C57 BL/6J male mice were divided into high (HF) or low fat (LF) diet groups and fed with the two diets, respectively, for 8 weeks. Each diet group was then divided into periodontitis (P) or control (C) groups (n = 10 per group) for 10-day ligation or sham-ligation. Overweight-related parameters including body weight were measured. Alveolar bone loss (ABL) was morphometrically analyzed and periodontal osteoclasts were stained. Periodontal immune response including leukocyte and macrophage number and inflammatory cytokines were analyzed by histology and quantitative PCR. Serum cytokine and lipid levels were quantified using electrochemiluminescence immunoassays, enzyme-linked immunosorbent assays, and biochemistry. It was found that HF group had 14.4% body weight gain compared with LF group (P < 0.01). ABL and periodontal osteoclast, leukocyte, and macrophage number were higher in P group than C group regardless of diet (P < 0.05). ABL and periodontal osteoclast number were not affected by diet regardless of ligation or sham-ligation. Leukocyte and macrophage number and protein level of tumor necrosis factor α (TNF-α) in periodontium and serum interleukin-6 level were downregulated by HF diet in periodontitis mice (P < 0.05). Periodontal protein level of TNF-α was highly correlated with serum interleukin-6 and low-density lipoprotein cholesterol levels (P < 0.01). These findings indicated that impaired immune response occurs both periodontally and systemically in preobesity overweight individuals. Given a well-reported exacerbating effect of obesity on periodontitis, overweight, if let uncontrolled, might place the individuals at potential risk for future periodontal tissue damage.

A survey on the prevalence and risk indicators of erosive tooth wear among adolescents in Guangzhou, South China.

BACKGROUND: Erosive tooth wear (ETW) has become a crucial oral health problem over the decades in China. OBJECTIVES: To explore the prevalence and risk indicators of ETW among adolescents in Guangzhou, south China. METHODS: A cross-sectional survey of 720 participants was conducted in Guangzhou, using an equal-sized, stratified, multistage random sampling approach. The participants were from two different age groups (12- and 15-year-olds), 360 per group. The ratio of males to females was 1:1 in each group. ETW was recorded utilising the basic erosive wear examination (BEWE) index as the dependent variable. Independent variables included age, gender, region, socioeconomic status, dietary factors, oral health measures and others. RESULTS: The prevalence rates (weighted) of ETW and dentin exposure (DE) were 56.1% and 26.2% among adolescents in Guangzhou, with mean teeth (weighted) of 1.8 ± 2.5 and 0.6 ± 1.5, respectively. No matter the prevalence or the mean teeth, the 15-year-olds were higher than the 12-year-olds; the mean teeth of ETW of males was higher than that of females; the mean teeth of ETW and DE of the adolescents of low socioeconomic status were higher than those of high socioeconomic status. Medium to high risk levels were found for 10.1%. In the multiple regression model, age, gender and taking acidic foods/drinks before sleep were associated with ETW. CONCLUSIONS: Moderate ETW in the permanent dentition was common among adolescents in Guangzhou. However, the teeth involved were low. Dietary factors and demographics were the main risk indicators.

[Impacts of periodontitis on visceral organ weight and weight percentage in obese mice].

OBJECTIVE: This study aimed to explore the impacts of periodontitis on the visceral weight and weight percentage of obese animal models. METHODS: A total of 64 C57BL/6J mice were divided into the following diet groups: high-fat diet (HFD) group (n=36), which was fed with high-fat diet to induce obesity, and low-fat diet (LFD) group (n=28), which was fed with low-fat diet as the control. After 16 weeks on diet, each diet group was divided into periodontitis (P) and control (C) groups. The P groups were induced for periodontitis by ligation with Porphyromonas gingivalis-adhered silk for 5 or 10 days, and the C groups were sham-ligated as the control. Visceral organs were resected and weighed. The organ weight percentage was calculated. RESULTS: Compared with the LFD group, the HFD group significantly upregulated the weight and weight percentage of visceral adipose tissue and spleen (P<0.05), upregulated the weight of liver and kidney (P<0.05), and downregulated the weight percentage of liver and kidney (P<0.01). In the HFD group, the weight and weight percentage of spleen were downregulated in the P group (P<0.05), but were upregulated in the 10-day group compared with the 5-day group (P<0.05). CONCLUSIONS: Periodontitis can affect the general morphology of the viscera (especially spleen) in obese animal models. Pathological indications in terms of immunometabolism might be present in the correlation between obesity and periodontitis.

Influence of periodontitis and scaling and root planing on insulin resistance and hepatic CD36 in obese rats.

BACKGROUND: The aim of the study was to explore the influence of periodontitis and scaling and root planing (SRP) on insulin resistance and hepatic CD36 in obese rats with periodontitis. METHODS: Thirty-two specific pathogen free Sprague-Dawley rats were randomly divided into four groups of eight animals each as follows: healthy rats (healthy group), obese rats (obesity group), obese rats with periodontitis (non-therapy group), and obese rats with periodontitis who underwent periodontal SRP (therapy group). Rats were fed with a high-fat diet for 16 weeks to build an obesity model. Periodontal inflammation was induced by performing periodontal ligation with Porphyromonas gingivalis. The tissue around the maxillary second molars, bilaterally, were collected. The periodontal attachment level (from the cemento-enamel junction to the bottom of the periodontal pocket) of the second molars was measured in all groups. All rats were subjected to fasting blood glucose, insulin, and serum C-reactive protein tests (CRP). Insulin resistance was evaluated by homeostasis model assessment of insulin resistance (HOMA-IR), oral glucose tolerance test (OGTT), and area under the curve (AUC). The liver was excised to detect intrahepatic free fatty acid (FFA) levels and pathologic observation. Real-time quantification PCR, western blot, and immunohistochemistry were applied to detect hepatic CD36 expression. RESULTS: Compared with the obesity group, HOMA-IR, AUC, intrahepatic FFA, and protein expression, and mRNA levels of hepatic CD36 in the non-therapy group were significantly increased (P < 0.05). HOMA-IR, AUC, CRP, protein expression, and mRNA levels of hepatic CD36 were all significantly decreased (P < 0.05) 2-weeks after SRP. CONCLUSIONS: Periodontitis increases insulin resistance while scaling and root planning could improve insulin resistance. Hepatic CD36 regulation may be considered a potential mechanism for this phenomenon.

Metformin attenuates myocardial ischemia-reperfusion injury via up-regulation of antioxidant enzymes.

The objective was to examine the protective effect of metformin (Met) on myocardial ischemia-reperfusion (IR) injury and whether the mechanism was related to the AMPK/ antioxidant enzymes signaling pathway. Rat Langendorff test and H2O2-treated rat cardiomyocytes (H9c2) were used in this study. Met treatment significantly improved left ventricular (LV) function, reduced infarct size and CK-MB release in comparison with IR group. Decreased TUNEL staining positive cells were also observed in IR+Met group ex vivo. Met treatment markedly inhibited IR inducing cell death and significantly decreased apoptosis with few generations of reactive oxygen species (ROS) in H9c2 cells in comparison with IR group. Up-regulated expressions of phosphorylated LKB1/AMPK/ACC, as well as down-regulated expressions of apoptotic proteins (Bax and cleaved caspase 3) were found in IR+Met group when compared to the IR group. Importantly, Met significantly up-regulated the expression of antioxidant enzymes (MnSOD and catalase) during IR procedure either ex vivo or in vitro. Compound C, a conventional inhibitor of AMPK, abolished the promoting effect of Met on antioxidant enzymes, and then attenuated the protective effect of Met on IR injury in vitro. In conclusion, Met exerted protective effect on myocardial IR injury, and this effect was AMPK/ antioxidant enzymes dependent.

[Effects of non-surgical periodontal therapy on serum inflammatory markers and metabolic level in obese rats].

OBJECTIVE: To investigate the effects of non-surgical periodontal therapy on serum inflammatory factors and metabolism levels in obese rats with experimental periodontitis. METHODS: Sixteen obese rats with experimental periodontitis were randomly divided into treatment group and control group with non-surgical periodontal therapy and no treatment, respectively. Oral glucose tolerance test was performed before treatment and 2 weeks after the treatment. All the rats were sacrificed 2 weeks after treatment and the orbital vein blood was taken to detect fasting blood glucose, fasting insulin, and serum level of C-reactive protein (CRP). Results Two weeks after periodontal treatment, fasting blood glucose (t=2.445, P=0.034) and beta cell function index (t=-2.543, P=0.027) were significantly lower in the treatment group than in the control group. Compared with those in the control group, CRP level (t=2.388, P=0.028) and the area under the curve in the oral glucose tolerance test (t=12.053, P=0.000) decreased significantly in the treatment group. CONCLUSION: Non-surgical periodontal treatment can reduce serum CRP level and improve glucose metabolism in obese rats.

[Beneficial effect of periodontal therapy on insulin resistance and lipid metabolism in obese rats with periodontitis].

OBJECTIVE: To investigate the effect of periodontal therapy in controlling periodontitis and on insulin resistance and lipid metabolism in obese rats with periodontitis. METHODS: Sprague-Dawley rats were randomized into normal group (group C), obese group (group O), periodontitis combined with obesity group (group P) and periodontal treatment group (group T). The obese rats in groups P and T were subjected to ligation of the maxillary second molar with silk thread to induce experimental periodontitis, and the rats in group T received periodontal therapy after the ligation. All the rats were sacrificed at the age of 24 weeks for measurement of blood lipids, insulin and blood glucose levels, and insulin resistance index (HOMA-IR) was calculated. The expressions of insulin receptor substrate-1 (IRS-1) and IRS-2 in the liver tissues were detected using real-time quantitative polymerase chain reaction (RT-PCR). RESULTS: Compared with the obese rats in group O, the rats in group P showed significantly higher HOMA-IR and LDL-C and lower expressions of IRS-1 and IRS-2 mRNA expression and HDL-C level (P<0.05). Compared with those in group P, the mRNA expressions of IRS-1 and IRS-2 and HDL-C level were significantly increased and LDL-C level, TC level and HOMA-IR were all decreased in group T (P<0.05), but the level of TG was comparable between the two groups. Pathological examination revealed lessened inflammatory cell infiltration and tissue destruction in the upper jaw of the rats in group T; the rats in group P presented with the most obvious upper jaw destruction and steatosis and inflammatory cell infiltration in the liver. CONCLUSION: Periodontal inflammation can downregulate the expression of IRS-1 and IRS-2 and increase insulin resistance and dyslipidemia in obese rats. Periodontal therapy produces a beneficial effect in improving insulin resistance and reducing dyslipidemia in obese rats.

Postoperative Weight Loss Masks Metabolic Impacts of Periodontitis in Obese Rodents.

BACKGROUND: Postoperative weight loss (POWL) is expected to occur in combined models of obesity and periodontitis. This study explores the confounding effects of POWL on the impact of ligation-induced periodontitis on glucose and lipid metabolism in obese animals. METHODS: Combined mouse models of diet-induced obesity (DIO) and ligation-induced periodontitis (5- or 10-day ligation) were studied. Fasting serum glucose (FSG), fasting insulin (Fins), and lipids including triglyceride (TG), total cholesterol (TC), and low- and high-density lipoprotein cholesterol (HDLC), were detected via biochemistry and enzyme-linked immunosorbent assay. POWL and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Analysis of covariance was performed to identify confounding effects of POWL. RESULTS: The obesity, periodontitis, and 10-day groups exhibited greater POWL than corresponding controls (P <0.01). Without considering POWL, conflicting results were found, including: 1) contradictory changes in HDLC caused by obesity or periodontitis; and 2) unequal levels of FSG, TC, and HDLC between days 5 and 10 in the sham-ligation controls. Moreover, upregulating effects of periodontitis were found only on TG in the DIO mice, whereas those on Fins, HOMA-IR, and HDLC were statistically veiled. After the confounding effects of POWL were filtered, periodontitis promoted increased levels of not only TG but also Fins, HOMA-IR, and HDLC in the DIO mice (P <0.05). CONCLUSIONS: When analyzing the interrelationship between obesity and periodontitis, the confounding effects of an imbalanced POWL should be considered. Otherwise, impact of periodontitis on metabolic dysregulation in obese animals may be underestimated.

Study on the consistency of the position of the brackets on the digital occlusal model and the actual position af-ter indirect bonding / 口腔疾病防治

Objective@#To provide the experimental basis for the coherence of the indirect bond position by comparing the position of the bracket on the digital occlusal model and the position of the transfer to the initial plaster model.@*Methods@#Fifteen digitized models were selected for the brackets on the dental denture model, the brackets were transferred to the initial plaster model by indirect bond transfer trays, The line distance between each bracket position in digital dental model and initial plaster model was measured with OrthoRx software. @*Results @#The difference between the position of the orthodontic brackets and the position of the initial plaster model was less than 0.20 mm, and the difference was statistically significant (P < 0.05). @*Conclusion @#The position of the bracket on the digital occlusal model is consistent with that of the original plaster model, which provides a theoretical basis for digital indirect bonding.

Resveratrol attenuates myocardial ischemia/reperfusion injury through up-regulation of vascular endothelial growth factor B.

The objective was to examine the protective effect of resveratrol (RSV) on myocardial ischemia/reperfusion (IR) injury and whether the mechanism was related to vascular endothelial growth factor B (VEGF-B) signaling pathway. Rat hearts were isolated for Langendorff perfusion test and H9c2 cells were used for in vitro assessments. RSV treatment significantly improved left ventricular function, inhibited CK-MB release, and reduced infarct size in comparison with IR group ex vivo. RSV treatment markedly decreased cell death and apoptosis of H9c2 cells during IR. We found that RSV was responsible for the up-regulation of VEGF-B mRNA and protein level, which caused the activation of Akt and the inhibition of GSK3ß. Additionally, RSV prevented the generation of reactive oxygen species (ROS) by up-regulating the expression of MnSOD either in vitro or ex vivo. We also found that the inhibition of VEGF-B abolished the cardioprotective effect of RSV, increased apoptosis, and led to the down-regulation of phosphorylated Akt, GSK3ß, and MnSOD in H9c2 cells. These results demonstrated that RSV was able to attenuate myocardial IR injury via promotion of VEGF-B/antioxidant signaling pathway. Therefore, the up-regulation of VEGF-B can be a promising modality for clinical myocardial IR injury therapy.

Macrophages Play a Key Role in the Obesity-Induced Periodontal Innate Immune Dysfunction via Nucleotide-Binding Oligomerization Domain-Like Receptor Protein 3 Pathway.

BACKGROUND: Obesity is associated with infiltration of macrophages into adipose tissue. However, effects of obesity on macrophage infiltration and activation in periodontal tissues with periodontitis are still to be elucidated. METHODS: A diet-induced obesity 16-week mouse model was constructed, and periodontitis was induced by periodontal ligation for 10 days. The model consisted of periodontitis (P) and control (C) groups, with high fat (HF) and normal (N) diet conditions. Bone loss (BL) was analyzed by microcomputed tomography. In periodontal tissues, immunohistochemical staining and quantitative polymerase chain reaction (qPCR) detected expressions of: 1) nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) pathway; 2) macrophage-specific marker (F4/80); and 3) macrophage chemotactic protein 1 (MCP1). Bone marrow-derived macrophages (BMDMs) from the mouse model were stimulated by Porphyromonas gingivalis lipopolysaccharide (LPS) in vitro (NC/NC + LPS: BMDMs from NC group without/with LPS stimulation; HFC/HFC + LPS: BMDMs from HFC group without/with LPS stimulation). Expressions of NLRP3 pathway in BMDMs were detected by immunocytochemical staining and qPCR. RESULTS: BL increased significantly with periodontitis (NC versus NP; HFC versus HFP) and obesity (NP versus HFP). Expressions of NLRP3 pathway were significantly elevated in gingival tissues with periodontitis (NC versus NP; HFC versus HFP), but not with obesity (NC versus HFC; NP versus HFP). F4/80 and MCP1 expressions were significantly upregulated in gingival tissues with periodontitis (NC versus NP; HFC versus HFP) but significantly downregulated in the context of obesity (NP versus HFP). In vitro, NLRP3 pathway expressions were significantly upregulated in BMDMs after LPS stimulation (NC + LPS versus NC; HFC + LPS versus HFC), but significantly downregulated in HFC groups (HFC versus NC; HFC + LPS versus NC + LPS). CONCLUSION: Obesity may paralyze innate immune response of periodontium via attenuating infiltration and activation of macrophages and further aggravate periodontal disease.

Enhanced Activity of the Macrophage M1/M2 Phenotypes and Phenotypic Switch to M1 in Periodontal Infection.

BACKGROUND: Macrophages are central players in the pathogenesis of periodontitis. However, the phenotypic switch of macrophage M1/M2 remains uncertain. METHODS: Adult male mice were divided into periodontitis (P) or control (C) groups. Bone marrow-derived macrophages (BMMs) were stimulated with Porphyromonas gingivalis lipopolysaccharide (LPS). In both the periodontium and serum, macrophage M1 and M2 phenotypes were detected in vivo and in vitro via the following: 1) immunofluorescence; 2) immunohistochemistry; 3) electrochemiluminescence immunoassays; 4) quantitative polymerase chain reaction assays; and 5) enzyme-linked immunosorbent assays. The M1-type markers used included the following: 1) nitric oxide synthase (NOS)-2; 2) tumor necrosis factor-alpha; 3) interleukin (IL)-1ß; 4) IL-6; and 5) C-reactive protein. The M2-type markers were as follows: 1) arginase-1; 2) cluster of differentiation (CD) 206; and 3) IL-10. RESULTS: Compared with the C group, the P group had a 14-fold increase in F4/80(+) NOS2(+) cells and four-fold more F4/80(+) CD206(+) cells with an enhanced NOS2/CD206 ratio in the periodontium (P <0.01). NOS2(-) CD206(+) and dual NOS2(+) CD206(+) macrophages dominated in the C and P groups, respectively. The P group had significantly increased M1- and M2-type cytokines in both the periodontium and serum and also had an enhanced IL-6/IL-10 ratio in the serum (P <0.05). M1-type markers were significantly upregulated at the mRNA level, whereas M2-type markers were downregulated at both the mRNA and protein levels in BMMs after LPS stimulation (P <0.01). CONCLUSION: Periodontal inflammation is associated with an enhancement of both the M1 and M2 phenotypes of macrophages, in which a phenotypic switch of M2 to M1 might be a critical mechanism in mediating periodontal tissue damage, including alveolar bone loss.