4-Octyl itaconate promotes alveolar ridge preservation following tooth extraction.

The search for medications that can effectively reduce alveolar bone loss following tooth extraction is of great interest. This study aimed to observe the roles of 4-octyl itaconate (4-OI) in RANKL-induced osteoclastogenesis of bone marrow macrophages (BMMs) in vitro. Mandibular second molars were extracted to evaluate whether 4-OI could alleviate alveolar bone loss. 4-OI inhibited RANKL-induced osteoclastogenesis and promoted Nrf2 expression in bone marrow macrophages in vitro. Positive Nrf2 expressions were observed in inflammatory cells and osteoclasts in vivo. Treatment with 4-octyl itaconate increased Nrf2 expression, resulting in reduced inflammatory infiltration and osteoclastic activity after tooth extraction. Furthermore, increased expression of OCN and enhanced-alveolar bone healing of extraction socket were observed in the 4-OI group compared to the control group. Our results suggested that 4-OI could serve as a promising pharmacologic candidate for alveolar ridge preservation by alleviating alveolar bone loss following tooth extraction in rats.

CKS2 modulates cell-cycle progression of tongue squamous cell carcinoma cells partly via modulating the cellular distribution of DUTPase.

BACKGROUND: CKS2 (CDC28 Protein Kinase Regulatory Subunit 2) is a gene that encodes CKS2 protein that has been characterized as a binding partner of the catalytic subunit of the cyclin-dependent kinases. However, its expression profile and regulatory effects in tongue squamous cell carcinoma has not yet been explored. METHODS: Bioinformatic analysis was conducted using bulk-seq data from The Cancer Genome Atlas and single-cell RNA-seq data from GSE103322. SCC9 and CAL27 cells were used as in vitro cell models for cellular and molecular studies. RESULTS: CKS2 expression was significantly upregulated in tongue squamous cell carcinoma tissues (N = 128) compared with adjacent normal tissues (N = 13). Its upregulation was associated with significantly shorter disease-specific survival and progression-free survival. Cellular status estimation in tumor cells indicated that CKS2 expression was moderately and positively correlated with cell-cycle progression. CKS2 inhibition in SCC9 and CAL27 cells resulted in decreased proliferation, weakened colony formation capability, and cell-cycle arrest at the G2/M phase. Immunofluorescence staining and co-Immunoprecipitation (co-IP) assay confirmed co-localization and interaction between CKS2 and DUTPase. CKS2 knockdown did not alter DUTPase expression but reduced its nuclear distribution. Both CKS2 and DUT expression were moderately correlated with their gene-level copy number. CONCLUSION: CKS2 expression is associated with unfavorable survival of patients with tongue squamous cell carcinoma. Inhibiting its expression could reduce tongue squamous cell carcinoma cell growth and induce G2/M arrest. CKS2 may interact with DUTPase and regulate its nuclear localization. Gene-level copy amplification might be an important mechanism of upregulated CKS2 and DUT in the tumor.

MicroRNA-206, IL-4, IL-13, and INF-γ levels in lung tissue and plasma are increased by the stimulation of particulate matter with a diameter of ≤2.5µm, and are associated with the poor prognosis of asthma induced pulmonary arterial hypertension patients.

BACKGROUND: This study aimed to explore the prognostic value of particulate matter with a diameter of ≤2.5 µm (PM2.5)-related microRNA-206 combined with interleukin (IL)-4, IL-13 and interferon-γ (INF-γ) in asthma induced pulmonary arterial hypertension (PAH). METHODS: Fifty SPF BALB/c mice were divided into 5 groups: control group, asthma + PAH group, low-toxic asthma + PAH group, moderately-exposed asthma + PAH group, highly-exposed asthma + PAH group. Differences of microRNA-206, IL-4, IL-13, and INF-γ expression in lung tissue and plasma were detected. A total of 98 patients with asthma induced PAH and 98 healthy persons were collected. Patients were followed up for 12 months. RESULTS: Based on microarray analyses, we found that microRNA-206 may be involved in asthma induced PAH stimulated by PM2.5. Compared with healthy people, plasma microRNA-206, IL-4, IL-13, and INF-γ levels in asthma induced PAH patients were significantly higher (P< .05). Compared with survivors, plasma microRNA-206, IL-4, IL-13, and INF-γ levels in non-survivors were significantly higher (P< .05). Survival analyses showed that compared with low microRNA-206, low IL-4, low IL-13 and low INF-γ groups, survival rate of patients in high microRNA-206 (χ2 = 4.864, P= .013), high IL-4 (χ2 = 3.774, P= .038), high IL-13 (χ2 = 8.375, P< .001) and high INF-γ groups (χ2 = 9.007, P< .001) were significantly reduced. Established prognostic evaluation model was built and the estimated probability was 0.473. Compared with estimated probability ≤ 0.473, survival rate of patients in estimated probability> 0.473 was significantly reduced (χ2 = 17.377, P< .001). CONCLUSION: Current model combining plasma microRNA-206, IL-4, IL-13, and INF-γ has potential significance for prognosis of asthma induced PAH.

Fast Handover Algorithm Based on Location and Weight in 5G-R Wireless Communications for High-Speed Railways.

With the booming development of high-speed railways (HSRs), key technologies of wireless communications need to be constantly innovated. In particular, the frontier issue of low delay of the handover for the fifth generation (5G) in fast-moving scenarios has attracted attention from both industry and academia. Based on an analysis of a large number of measured data and the location of the user equipment (UE), a fast handover algorithm is proposed to solve the problem of long delay for a train moving at high speed in a 5G-railway (5G-R). By calculating the speed of a train and its direction of movement, a reasonable handover mode is selected and the handover chain of neighboring cells is identified. The location of the train can be calculated to determine whether UE enters the defined identification zone of pre-handover. Depending on the values collected in the measurement report, the command of the handover is triggered when the weight of the target cell is greater than that of the source cell. Our experimental results show that the delay of the fast handover algorithm is reduced by 2.03%, and the success rate of the handover is increased by 0.42%. Research directions for smart railways are discussed based on these findings.

Clinical study of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen in the treatment of advanced esophageal cancer.

OBJECTIVE: this study aimed to investigate the clinical efficacy and feasibility of the treatment of advanced esophageal cancer with a combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen. METHODS: forty-five patients with advanced esophageal cancer were enrolled and were randomly divided into two groups: a treatment group and a control group. Patients in the treatment group were treated with a 125I particle-integrated esophageal covered stent and hyperbaric oxygen, while patients in the control group were treated with a 125I particle-integrated esophageal covered stent. The clinical effects and long-term survival time of the two groups were observed. RESULTS: in the treatment group, the complete remission (CR) rate and partial remission (PR) rate of local lesions were 19.2 % and 61.5 %, respectively, and the total effective rate was 80.7 %. In the control group, the CR rate and PR rate of local lesions were 10.5 % and 52.6 %, respectively, and the total effective rate was 63.1 %. The total effective rate was higher in the treatment group than in the control group, which was statistically significant (p < 0.05). CONCLUSION: the combination of a 125I particle-integrated esophageal covered stent and hyperbaric oxygen shows a good short- and long-term efficacy in the treatment of advanced esophageal cancer.

Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1 Could Serve as a Potential Serological Biomarker for the Diagnosis and Prognosis of Oral Squamous Cell Carcinoma.

PURPOSE: Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is a multifunctional protein that shows elevated expression in many cancers, including oral squamous cell carcinoma (OSCC). However, the serum APE1/REF-1 level remains unknown in such patients. The purpose of the present study was to estimate the serum APE/Ref-1 levels in patients with OSCC and measure its association with the diagnosis, clinicopathologic features, and prognosis of OSCC. PATIENTS AND METHODS: A total of 98 primary patients with OSCC and 109 age- or gender-matched normal controls were included in our case-control study. The predictor variable was the serum APE1/Ref-1 level, which was measured using an enzyme-linked immunosorbent assay. The outcome variables included diagnosis, clinicopathologic characteristics, treatment response, and OSCC prognosis. The optimal cutoff points of serum APE1/Ref-1 were identified using the X-tile program with minimum P values. Prognostic factors were evaluated using univariate and multivariate Cox regression models. RESULTS: The average patient and control age was 51.6 ± 8.7 years (63 men; 35 women) and 52.4 ± 10.3 years (67 men; 42 women), respectively. The serum APE1/Ref-1 level was significantly greater in patients with OSCC than that in the controls (4.56 ± 1.09 ng/mL vs 3.18 ± 0.88 ng/mL; P < .01). Much higher serum APE1/Ref-1 levels were observed in those with OSCC with late TNM stage, lymph node metastases, and worse pathologic differentiation. The receiver operating characteristic curve analysis illustrated that the serum APE1/Ref-1 level was a potential biomarker for differentiating OSCC, with an area under the curve of 0.83 (95% confidence interval, 0.78 to 0.88; sensitivity, 0.87; specificity, 0.68). The log-rank analysis revealed that patients with OSCC and a low APE1/Ref-1 level experienced longer disease-free survival after postoperative cisplatin chemotherapy and overall survival (P < .05). CONCLUSIONS: An elevated APE1/Ref-1 level might serve as a novel potential diagnostic biomarker for OSCC and can reflect the treatment response to cisplatin chemotherapy and prognosis.

Toll-Like Receptor 4 (TLR4) Stimulates Synovial Injury of Temporomandibular Joint in Rats Through the Activation of p38 Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway.

BACKGROUND Synovitis is an important disease that cause intractable pain in temporomandibular joint (TMJ), and the inflammation process played a crucial role in the initiation and development of temporomandibular joint disorder. A series of investigations suggested that the increasing expression of interleukin-(IL) 1ß secreted by synovial lining cells plays an important role in synovial inflammation and cartilage destruction in TMJ. In this present study, we investigated the signaling pathways which regulate the expression of IL-1ß. MATERIAL AND METHODS The occlusal interference animal model was created to induce synovial injury. Forty-eight rats were divided into 4 groups: 1) control group, 2) occlusal interference group, 3) TAK-242 (a specific inhibitor targeting the Toll-like receptor (TLR)-4) group, and 4) SB203580 (a specific inhibitor targeting the p38) group. The inflammation changes were observed, and the expression of p38 and IL-1ß in the synovial membranes were assayed. RESULTS The results showed that downstream p38 MAPK (mitogen-activated protein kinase) signaling was triggered following the activation of TLR4. Moreover, the injection of SB203580 could inhibit the inflammatory reactions and the increased expression of IL-1ß at both mRNA and protein levels. CONCLUSIONS The results prompted us that TLR4 may stimulates synovial inflammatory reactions and increased expression of IL-1ß in rats through the activation of p38 MAPK signaling pathway, p38 was an important mediator in the mechanisms of the initiation and development of synovial injury by regulating the expression of IL-1ß in synovial membranes.

Effect of Toll-Like Receptor 4 on Synovial Injury of Temporomandibular Joint in Rats Caused by Occlusal Interference.

Synovitis is an important disease that causes intractable pain in TMJ. Some investigations suggested that the increasing expression of IL-1ß secreted by synovial lining cells plays an important role in synovial inflammation and cartilage destruction in TMJ. In our previous research, the results demonstrated that TLR4 is involved in the expression of IL-1ß in SFs from TMJ with lipopolysaccharide stimulation. However, the inflammatory response that occurred in synovial membrane is not caused by bacterial infection. In the current study, we investigated whether or not TLR4 participates in the inflammatory responses and the expression of IL-1ß in synovial membrane of rats induced by occlusal interference. The results showed that obvious inflammation changes were observed in the synovial membranes and the expression of TLR4 and IL-1ß was increased at both mRNA and protein levels in the occlusal interference rats. In addition, the inflammation reactions and the increased expression of IL-1ß could be restrained by treatment with TAK-242, a blocker of TLR4 signaling. The results prompted us that the activation of TLR4 may be involved in the inflammatory reactions and increased expression of IL-1ß in patients with synovitis and participate in the mechanisms of the initiation and development of synovial injury by regulating the expression of inflammatory mediators like IL-1ß in synovial membranes.

Effects of HMGB1/TLR4 on secretion IL-10 and VEGF in human jaw bone-marrow mesenchymal stem cells.

OBJECTIVE: We aimed to investigate the regulatory effects of HMGB1/TLR4 signaling pathway on the expression of IL-10 and VEGF in human bone marrow mesenchymal stem cells. METHODOLOGY: Human JBMSCs were isolated and cultured. Then, HMGB1 was added into the JBMSCs culture medium, and the protein and mRNA expression levels of IL-10 and VEGF were assessed. Moreover, cells were pretreated with a specific TLR4 inhibitor (TAK-242), and the expression changes of IL-10 and VEGF were compared. RESULTS: Compared with the control group, exposure to HMGB1 in human JBMSCs up-regulated TLR4, IL-10, and VEGF secretion at both protein and mRNA levels (P<0. 05). In addition, the increased expression of IL-10 and VEGF could be restrained in TAK-242 group compared with the HMGB1 group (P<0.05). CONCLUSIONS: The results indicated that HMGB1 activate TLR4 signaling pathway in Human JBMSCs, which plays a regulatory role in cytokines expression.

Regulatory mechanisms of miR-212-3p on the secretion of inflammatory factors in monocyte-macrophages and the directed differentiation into osteoclasts in ankylosing spondylitis.

To explore the mechanisms of action of micro ribonucleic acid (miR)-212-3p in the secretion of inflammatory factors in monocyte-macrophages and the directed differentiation into osteoclasts (OCs) in ankylosing spondylitis (AS), proteoglycan was used to establish an AS mouse model. The mouse monocyte-macrophages were cultured in vitro, transfected with miR-212-3p mimic, and added with phosphorylated-extracellular signal-regulated kinase (p-ERK)1/2 agonist Ro67-7476 in vitro. After the cells were transfected with the miR-212-3p mimic in each group, the expressions of p-ERK1/2, matrix metalloproteinase-1 (MMP-1), MMP-3, interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) significantly declined, whereas those of tartrate-resistant acid phosphatase (TRAP), calcitonin, and p-nuclear factor of activated T cell 1 (NFATC1) significantly rose. After Ro67-7476 was added, the protein expressions of p-ERK1/2, MMP-1, MMP-3, IL-1ß, and TNF-α were significantly increased in each group, but they displayed decreasing trends in cells transfected with the miR-212-3p mimic. In contrast, the protein expressions of TRAP, calcitonin, and p-NFATC1 declined, but they showed increasing trends in cells transfected with the miR-212-3p mimic. miR-212-3p can, through inhibiting the phosphorylation of p-ERK1/2, prevent the aggregation of macrophages and the secretion of inflammatory factors. It also up-regulates the expression of OC marker proteins to facilitate the differentiation and maturation of OCs, ultimately relieving AS-induced inflammation and new bone growth-induced joint neoplasm.

MiR-217-5p inhibits smog (PM2.5)-induced inflammation and oxidative stress response of mouse lung tissues and macrophages through targeting STAT1.

OBJECTIVE: To explore the roles of macrophages' miR-217-5p in the process of PM2.5 induced acute lung injury. METHODS: GEO database and KEGG pathway enrichment analysis as well as GSEA were used to predicted the miRNA and associated target signals. And then mice and RAW246.7 macrophages treated with PM2.5 to imitate PM2.5 induced acute lung injury environment and then transfected with miR-217-5p NC or miR-217-5p mimic. The levels of inflammatory factors TNF-α and anti-inflammatory factor IL-10 of mice serum were tested by ELISA. And the pathological changes and ROS level of mouse lung tissues were stained by HE and DHE staining. The proteins expression of phosphorylated-STAT1, total-STAT1, TNF-α, IFN-γ as well as p47, gp91, NOX4 in mice or RAW264.7 cells were tested by western blot or immunofluorescence of RAW264.7 cell slides. RESULTS: The results of bioinformatics analysis indicated the miR-217 as well as STAT1 were involved PM2.5 associated lung injury. After exposure to PM2.5, the decreased levels of serum TNF-α but not IL-10, consistent with reduced macrophages' accumulation as well as decreased ROS levels in lung tissues in miR-217-5p mimic group vs miR-217-5p NC group mice, and moreover, the protein expression levels of phosphorylated--STAT1, total-STAT1, TNF-α, IFN-γ, p47, gp91 and NOX4 in mouse lung tissues and RTAW246.7 macrophages cells were all significantly reduced with miR-217-5p mimic administration. The above phenomena were reversed by specific STAT1-inhibitor HY-N8107. CONCLUSIONS: miR-217-5p suppressed the activated STAT1-signal induced inflammation and oxidative stress trigged by PM2.5 in macrophages and resulted in the decreased lung injure caused by PM2.5.

Xanthan gum protects temporomandibular chondrocytes from IL­1ß through Pin1/NF­κB signaling pathway.

Temporomandibular disorder (TMD) is a complicated and multi­factorial disease related to inflammation and cartilage destruction. Intra­articular injection of xanthan gum (XG) has been demonstrated to protect the joint cartilage and reduce osteoarthritis progression. However, the role and mechanism of XG in TMD is still unclear. In the present study, chondrocytes were isolated from rats and identified by immunofluorescence. Cells were stimulated by XG or interleukin (IL)­1ß. Cell viability was analyzed by MTT assay. Tumor necrosis factor α (TNF­α) and IL­6 levels were determined by ELISA. The expression of monocyte chemoattractive protein­1 (MCP­1), inducible nitric oxide synthase (iNOS), collagens, matrix metalloproteinases (MMPs), peptidyl­prolyl isomerase 1 (Pin1) and phosphorylated nuclear factor κB (NF­κB) p65 (p­p65) was analyzed by quantitative PCR or western blotting. MMP activity was assessed by gelatin zymography. Compared with the control, XG treatment partially reversed the IL­1ß­reduced cell viability. In addition, IL­1ß stimulation increased inflammatory cytokine expression, including TNF­α, IL­6 secretion, MCP­1 and iNOS expression, whereas XG treatment reduced the expression of these inflammatory cytokines compared with that of the IL­1ß­stimulated cells. Additionally, XG increased the expression of collagen, but reduced MMP expression and activity as compared with that in the IL­1ß group. In addition, XG treatment prevented the IL­1ß­increased Pin1 and p­p65 expression. These data suggested that XG reduced the expression of inflammatory cytokines and may maintain the balance between collagens and MMPs partially through the Pin1/NF­κB signaling pathway in IL­1ß­stimulated temporomandibular chondrocytes. Therefore, XG may be useful in the treatment of TMD.

Evolutionary conservation of Dazl genomic organization and its continuous and dynamic distribution throughout germline development in gynogenetic gibel carp.

To investigate germline development and germ cell specification, we identified a Dazl homolog (CagDazl) from gynogenetic gibel carp (Carassius auratus gibelio). Its cDNA sequence and BAC clone sequence analyses revealed the genomic organization conservation and conserved synteny of the Dazl family members and their neighborhood genes among vertebrates, especially in fish. Moreover, a polyclonal antibody specific to CagDazl was produced and used to examine its expression and distribution throughout germline development at protein level. Firstly, ovary-specific expression pattern of CagDazl was confirmed in adult tissues by RT-PCR and Western blot. In addition, in situ hybridization and immunofluorescence localization demonstrated its specific expression in germ cells, and both its transcript and protein were localized to germ plasm. Then, co-localization of CagDazl and mitochondrial cloud was found, confirming that CagDazl transcript and its protein are germ plasm component and move via METRO pathway during oogenesis. Furthermore, the CagDazl is abundant and continuous throughout germline development and germ cell specification including primordial germ cell (PGC) formation, oogonium differentiation, oocyte development, and embryogenesis, and the dynamic distribution occurs at different development stages. The data suggest that maternal CagDazl might play an important role in gibel carp PGC formation. Therefore, CagDazl is a useful and specific marker for tracing germ plasm and germ cell development in the gynogenetic gibel carp. In addition, in comparison with previous studies in sexual reproduction species, the continuous and dynamic distribution of CagDazl protein in the germ plasm throughout the life cycle seems to have significant implication in sex evolution of vertebrates.

Effects of HMGB1/TLR4 on secretion IL-10 and VEGF in human jaw bone-marrow mesenchymal stem cells

Abstract Objective: We aimed to investigate the regulatory effects of HMGB1/TLR4 signaling pathway on the expression of IL-10 and VEGF in human bone marrow mesenchymal stem cells. Methodology: Human JBMSCs were isolated and cultured. Then, HMGB1 was added into the JBMSCs culture medium, and the protein and mRNA expression levels of IL-10 and VEGF were assessed. Moreover, cells were pretreated with a specific TLR4 inhibitor (TAK-242), and the expression changes of IL-10 and VEGF were compared. Results: Compared with the control group, exposure to HMGB1 in human JBMSCs up-regulated TLR4, IL-10, and VEGF secretion at both protein and mRNA levels (P<0. 05). In addition, the increased expression of IL-10 and VEGF could be restrained in TAK-242 group compared with the HMGB1 group (P<0.05). Conclusions: The results indicated that HMGB1 activate TLR4 signaling pathway in Human JBMSCs, which plays a regulatory role in cytokines expression.

Magnesium promotes the viability and induces differentiation of neural stem cells both in vitro and in vivo.

OBJECTIVE: Neural stem cells (NSCs) are multipotent stem cells that generating various neural cells, including neurons, astrocytes and oligodendrocytes. This showed that NSCs is an ideal candidate in the application of neural disease treatment. In the current study, we established a simple and efficient method to promote the viability and induce the differentiation of NSCs by stimulating with magnesium. METHODS: The proliferation and differentiation of NSCs was determined by MTT assay and immunostaining. The behavior alteration was measured by rotorod test and Morris water maze. RESULTS: Magnesium enhanced proliferation in NSCs. The ratio of Nestin+, Ki67+ and GFAP+ progenitor cells was increased in the presence of magnesium. Besides, magnesium induced the glial differentiation instead of neuronal differentiation in NSCs. By contrast, transplantation of Mg2+-treated NSCs in vivo generated more neurons. In established PD models, transplantation of Mg2+-treated NSCs could improve the symptoms and recover the memory. CONCLUSION: We established a simple and efficient way to promote the proliferation and induce the differentiation of NSCs. More importantly, this may also facilitate to develop a new method to neural disorder treatment.

Elevated red blood cell distribution width predicts poor prognosis in patients with oral squamous cell carcinoma.

INTRODUCTION: Although red blood cell distribution width (RDW) has been reported to reflect inflammation and nutritional status and to predict prognosis in several different types of cancer, little is known about how RDW might be related to oral squamous cell carcinoma (OSCC). The present study aimed to investigate the prognostic value of preoperative RDW in OSCC patients. MATERIALS AND METHODS: We included 236 OSCC patients from Jinan Stomatological Hospital (Shandong, People's Republic of China) in this retrospective study. All enrolled patients were divided into 2 groups: high RDW (≥15%) and low RDW (<15%) according to the detected RDW values. The correlation of RDW and clinical characteristics was explored, and the prognostic significance of RDW evaluated using Kaplan-Meier curves, log-rank analysis, and the Cox proportional hazards model. RESULTS: The pretreatment median RDW among all OSCC patients was 14.4%, with a range from 11.6% to 24.5%. The RDW was found to be significantly correlated with node metastasis, tumor length, and TNM stage (P<0.05 for all). As for biochemical parameters, the results showed that higher RDW values were significantly associated with hemoglobin, mean corpuscular volume, white blood cell count, albumin, and C-reactive protein (P<0.01 for all). A significant association of RDW with the tumor marker cytokeratin 19 fragments (CYFRA21-1) and squamous cell carcinoma antigen (SCC-Ag) was also observed (P=0.02, and P=0.03; respectively). Moreover, patients with higher RDW were more likely to receive postoperative therapy (P=0.02). Kaplan-Meier survival curves showed that a high RDW was significantly associated with poor overall survival (OS) (P<0.01), especially in the early stages (I-II). Multivariate analysis revealed that an elevated RDW at diagnosis was an independent prognostic factor for shorter OS (HR =1.46, 95% CI: 1.13-2.86) after adjustment for other cancer-related prognostic factors. CONCLUSION: These data suggest that an elevated preoperative RDW (≥15%) at diagnosis may independently predict poorer OS in patients with OSCC, but better-designed studies in the future should be performed to further confirm the value of monitoring RDW.

EMMPRIN-CypA contributes to the inflammatory processes in human periodontitis through infiltrating CD68+ inflammatory cells.

Extracellular matrix metalloproteinase inducer (EMMPRIN) and its ligand cyclophilin A (CypA) levels increase in human inflammatory diseases, but EMMPRIN-CypA interactions and cell types expressing EMMPRIN and CypA in the pathogenesis of periodontitis are uncertain. Immunohistochemistry, immunofluorescence and western blotting revealed the level of EMMPRIN, CypA, and CD68 in human periodontitis. Double labelled immunofluorescence colocalized the expression of CD68 and CypA, and CD68 and EMMPRIN. Further investigation of EMMPRIN-CypA interactions and CD68+ infiltrating cells was applied using mouse monocyte cell line RAW264.7 in vitro. A higher level of EMMPRIN and CypA staining was detected in human periodontitis, compared with healthy gingiva. Many inflammatory cells, including CD68+ cells, infiltrated gingival tissues of human periodontitis. Both EMMPRIN and CypA could be localized in the CD68+ infiltrating cells. CypA could induce NF-κB activation by increasing expression of NFκB p-p65 in the nucleus of mouse monocytic cells RAW264.7 in vitro. EMMPRIN-CypA may contribute to the inflammatory processes in human periodontitis through infiltrating CD68+ inflammatory cells.

Protective effect and related mechanisms of curcumin in rat experimental periodontitis.

BACKGROUND: Curcumin exhibits anti-inflammatory effects and has been suggested as a treatment for inflammatory diseases. The aim of this study was to investigate the effects of curcumin on the lipopolysaccharide induced inflammatory response in rat gingival fibroblasts in vitro and ligation-induced experimental periodontitis in vivo, and to speculate the possible anti-inflammatory mechanism of curcumin. METHODS: The gingival fibroblasts were incubated with different concentrations of curcumin in the absence or presence of lipopolysaccharide (LPS). Concentrations of interleukin-1ß(IL-1ß), tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor kappa-B ligand (RANKL) culture supernatants of rat gingival fibroblasts were determined by enzyme linked immunosorbent assay. The nuclear fraction of rat gingival fibroblasts was extracted and nuclear factor kappa-B (NF-κB) activation was assessed by western blotting to elucidate related mechanisms. Curcumin was given every two days by oral gavage. The gingival inflammation and alveolar bone loss between the first and second molars were observed by hematoxylin and eosin staining. Collagen fibers were observed by picro-sirius red staining. Alveolar bone loss was assessed by micro-CT analysis. RESULTS: Curcumin attenuated the production of IL-1ß and TNF-α in rat gingival fibroblasts stimulated by LPS, and inhibited the LPS-induced decrease in OPG/sRANKL ratio and NF-κB activation. Curcumin significantly reduced gingival inflammation and modulated collagen fiber and alveolar bone loss in vivo. CONCLUSIONS: curcumin modulates inflammatory activity in rat periodontitis by inhibiting NF-κB activation and decreasing the OPG/sRANKL ratio induced by LPS.

Warmer and drier conditions and nitrogen fertilizer application altered methanotroph abundance and methane emissions in a vegetable soil.

Methane (CH4) is a potent greenhouse gas, and soil can both be a source and sink for atmospheric CH4. It is not clear how future climate change may affect soil CH4 emissions and related microbial communities. The aim of this study was to determine the interactive effects of a simulated warmer and drier climate scenarios and the application of different nitrogen (N) sources (urea and manure) on CH4 emissions and related microbial community abundance in a vegetable soil. Greenhouses were used to control simulated climate conditions which gave 2.99 °C warmer and 6.2% lower water content conditions. The field experiment was divided into two phases. At the beginning of phase II, half of the greenhouses were removed to study possible legacy effects of the simulated warmer and drier conditions. The responses in methanogen and methanotroph abundance to a simulated climate change scenario were determined using real-time PCR. The results showed that the simulated warmer and drier conditions in the greenhouses significantly decreased CH4 emissions largely due to the lower soil moisture content. For the same reason, CH4 emissions of treatments in phase I were much lower than the same treatments in phase II. The abundance of methanotrophs showed a more significant response than methanogens to the simulated climate change scenario, increasing under simulated drier conditions. Methanogenic community abundance remained low, except where manure was applied which provided a source of organic C that stimulated methanogen growth. Soil moisture content was a major driver for methanotroph abundance and strongly affected CH4 emissions. The application of N source decreased CH4 emissions probably because of increased methanotrophic activity. CH4 emissions were positively correlated to methanogenic abundance and negatively correlated to methanotrophic abundance. These results demonstrate that projected future climate change conditions can have a feedback impact on CH4 emissions from the soil by altering soil conditions (particularly soil moisture) and related microbial communities.

Dietary intake and risk of rheumatoid arthritis-a cross section multicenter study.

Environmental factors play an important role in the development of rheumatoid arthritis (RA). Among these factors, smoking is generally considered to be an established risk factor for RA. Data regarding the impact of diet on risk of RA development is limited. This study assessed the impact of dietary patterns on RA susceptibility in Chinese populations. This was a large scale, case-control study composed of 968 patients with RA and 1037 matched healthy controls. Subjects were recruited from 18 teaching hospitals. Socio-demographic characteristics and dietary intakes 5 years prior to the onset of RA were reported by a self-administered questionnaire. Differences in quantity of consumption between cases and controls were analyzed by Student's t test. Multiple logistic regression analysis was applied to identify independent dietary risk factor(s) responsible for RA susceptibility. Compared to healthy individuals, RA patients had decreased consumption of mushrooms (P = 0.000), beans (P = 0.006), citrus (P = 0.000), poultry (P = 0.000), fish (P = 0.000), edible viscera (P = 0.018), and dairy products (P = 0.005). Multivariate analyses revealed that several dietary items may have protective effects on RA development, such as mushrooms (aOR = 0.669; 95%CI = 0.518-0.864, P = 0.002), citrus fruits (aOR = 0.990; 95%CI = 0.981-0.999, P = 0.04), and dairy products (aOR = 0.921; 95%CI 0.867-0.977, P = 0.006). Several dietary factors had independent effects on RA susceptibility. Dietary interventions may reduce the risk of RA.