P. gingivalis in oral-prostate axis exacerbates benign prostatic hyperplasia via IL-6/IL-6R pathway.

BACKGROUND: Benign prostatic hyperplasia (BPH) is the most common disease in elderly men. There is increasing evidence that periodontitis increases the risk of BPH, but the specific mechanism remains unclear. This study aimed to explore the role and mechanism of the key periodontal pathogen Porphyromonas gingivalis (P. gingivalis) in the development of BPH. METHODS: The subgingival plaque (Sp) and prostatic fluid (Pf) of patients with BPH concurrent periodontitis were extracted and cultured for 16S rDNA sequencing. Ligature-induced periodontitis, testosterone-induced BPH and the composite models in rats were established. The P. gingivalis and its toxic factor P. gingivalis lipopolysaccharide (P.g-LPS) were injected into the ventral lobe of prostate in rats to simulate its colonization of prostate. P.g-LPS was used to construct the prostate cell infection model for mechanism exploration. RESULTS: P. gingivalis, Streptococcus oralis, Capnocytophaga ochracea and other oral pathogens were simultaneously detected in the Pf and Sp of patients with BPH concurrent periodontitis, and the average relative abundance of P. gingivalis was found to be the highest. P. gingivalis was detected in both Pf and Sp in 62.5% of patients. Simultaneous periodontitis and BPH synergistically aggravated prostate histological changes. P. gingivalis and P.g-LPS infection could induce obvious hyperplasia of the prostate epithelium and stroma (epithelial thickness was 2.97- and 3.08-fold that of control group, respectively), and increase of collagen fibrosis (3.81- and 5.02-fold that of control group, respectively). P. gingivalis infection promoted prostate cell proliferation, inhibited apoptosis, and upregulated the expression of inflammatory cytokines interleukin-6 (IL-6; 4.47-fold), interleukin-6 receptor-α (IL-6Rα; 5.74-fold) and glycoprotein 130 (gp130; 4.47-fold) in prostatic tissue. P.g-LPS could significantly inhibit cell apoptosis, promote mitosis and proliferation of cells. P.g-LPS activates the Akt pathway through IL-6/IL-6Rα/gp130 complex, which destroys the imbalance between proliferation and apoptosis of prostate cells, induces BPH. CONCLUSION: P. gingivalis was abundant in the Pf of patients with BPH concurrent periodontitis. P. gingivalis infection can promote BPH, which may affect the progression of BPH via inflammation and the Akt signaling pathway.

Structural insights into cyanobacterial RuBisCO assembly coordinated by two chaperones Raf1 and RbcX.

RuBisCO is the most abundant enzyme in nature, catalyzing the fixation of CO2 in photosynthesis. Its common form consists of eight RbcL and eight RbcS subunits, the assembly of which requires a series of chaperones that include RbcX and RuBisCO accumulation factor 1 (Raf1). To understand how these RuBisCO-specific chaperones function during cyanobacterial RbcL8RbcS8 (L8S8) holoenzyme formation, we solved a 3.3-Å cryo-electron microscopy structure of a 32-subunit RbcL8Raf18RbcX16 (L8F8X16) assembly intermediate from Anabaena sp. PCC 7120. Comparison to the previously resolved L8F8 and L8X16 structures together with biochemical assays revealed that the L8F8X16 complex forms a rather dynamic structural intermediate, favoring RbcS displacement of Raf1 and RbcX. In vitro assays further demonstrated that both Raf1 and RbcX function to regulate RuBisCO condensate formation by restricting CcmM35 binding to the stably assembled L8S8 holoenzymes. Combined with previous findings, we propose a model on how Raf1 and RbcX work in concert to facilitate, and regulate, cyanobacterial RuBisCO assembly as well as disassembly of RuBisCO condensates.

Complex structure reveals CcmM and CcmN form a heterotrimeric adaptor in ß-carboxysome.

Carboxysome is an icosahedral self-assembled microcompartment that sequesters RuBisCO and carbonic anhydrases within a selectively permeable protein shell. The scaffolding proteins, CcmM, and CcmN were proposed to act as adaptors that crosslink the enzymatic core to shell facets. However, the details of interaction pattern remain unknown. Here we obtained a stable heterotrimeric complex of CcmM γ-carbonic anhydrase domain (termed CcmMNT ) and CcmN, with a 1:2 stoichiometry, which interacts with the shell proteins CcmO and CcmL in vitro. The 2.9 Å crystal structure of this heterotrimer revealed an asymmetric bundle composed of one CcmMNT and two CcmN subunits, all of which adopt a triangular left-handed ß-helical barrel structure. The central CcmN subunit packs against CcmMNT and another CcmN subunit via a wall-to-edge or wall-to-wall pattern, respectively. Together with previous findings, we propose CcmMNT -CcmN functions as an adaptor to facilitate the recruitment of shell proteins and the assembly of intact ß-carboxysome.

Molecular basis for the assembly of RuBisCO assisted by the chaperone Raf1.

The folding and assembly of RuBisCO, the most abundant enzyme in nature, needs a series of chaperones, including the RuBisCO accumulation factor Raf1, which is highly conserved in cyanobacteria and plants. Here, we report the crystal structures of Raf1 from cyanobacteria Anabaena sp. PCC 7120 and its complex with RuBisCO large subunit RbcL. Structural analyses and biochemical assays reveal that each Raf1 dimer captures an RbcL dimer, with the C-terminal tail inserting into the catalytic pocket, and further mediates the assembly of RbcL dimers to form the octameric core of RuBisCO. Furthermore, the cryo-electron microscopy structures of the RbcL-Raf1-RbcS assembly intermediates enable us to see a dynamic assembly process from RbcL8Raf18 to the holoenzyme RbcL8RbcS8. In vitro assays also indicate that Raf1 can attenuate and reverse CcmM-mediated cyanobacterial RuBisCO condensation. Combined with previous findings, we propose a putative model for the assembly of cyanobacterial RuBisCO coordinated by the chaperone Raf1.

Structural and enzymatic analyses of Anabaena heterocyst-specific alkaline invertase InvB.

Anabaena sp. PCC 7120 encodes two alkaline/neutral invertases, namely InvA and InvB. Following our recently reported InvA structure, here we report the crystal structure of the heterocyst-specific InvB. Despite sharing an overall structure similar to InvA, InvB possesses a much higher catalytic activity. Structural comparisons of the catalytic pockets reveal that Arg430 of InvB adopts a different conformation, which may facilitate the deprotonation of the catalytic residue Glu415. We propose that the higher activity may be responsible for the vital role of InvB in heterocyst development and nitrogen fixation. Furthermore, phylogenetic analysis combined with activity assays also suggests the role of this highly conserved arginine in plants and cyanobacteria, as well as some proteobacteria living in highly extreme environments.

Tooth Loss Is Associated With Increased Risk of Dementia and With a Dose-Response Relationship.

Objective: Both tooth loss and dementia are age-related and frequently-occurring diseases. Increasing attention has been given to explore the pathogenesis related to oral-brain function disorders. The present study was performed to evaluate the association between tooth loss and dementia through a dose-response meta-analysis. Methods: Relevant cohort studies were searched from online databases up until June 20, 2018, which examined the association between tooth loss and the risk of dementia. Literature selection according to inclusion and exclusion criteria, as well as data extraction from included studies were completed independently by two reviewers. Data syntheses in this meta-analysis were performed using Stata 12.0 software. Results: A total of 8 cohort studies were included, containing a total of 14,362 samples and 2,072 dementia patients. The result of the meta-analysis indicated that patients with tooth loss faced a 1.34 times greater risk of developing dementia (RR = 1.34,95% CI = 1.19-1.51). The result from this dose-response meta-analysis in a linear model, suggested that every missed tooth might increase the risk of dementia by 1.01 times (RR = 1.01, 95%CI = 1.00-1.02). Further subgroup analyses pointed out that tooth loss patients without dentures may have a higher risk of dementia than those with dentures (with denture: RR = 0.98, 95% CI = 0.87-1.10; without denture: RR = 1.53, 95% CI = 1.19-1.97); at the same time, the study design, study area and education level of the study participants, might also have some effect on the results. Conclusions: Tooth loss may be a risk factor for the development of dementia. In addition, there is a dose-response relationship with the increase of missing teeth.

Periodontal Disease and Incident Lung Cancer Risk: A Meta-Analysis of Cohort Studies.

BACKGROUND: Periodontal disease is linked to a number of systemic diseases such as cardiovascular diseases and diabetes mellitus. Recent evidence has suggested periodontal disease might be associated with lung cancer. However, their precise relationship is yet to be explored. Hence, this study aims to investigate the association of periodontal disease and risk of incident lung cancer using a meta-analytic approach. METHODS: PubMed, Scopus, and ScienceDirect were searched up to June 10, 2015. Cohort and nested case-control studies investigating risk of lung cancer in patients with periodontal disease were included. Hazard ratios (HRs) were calculated, as were their 95% confidence intervals (CIs) using a fixed-effect inverse-variance model. Statistical heterogeneity was explored using the Q test as well as the I(2) statistic. Publication bias was assessed by visual inspection of funnel plots symmetry and Egger's test. RESULTS: Five cohort studies were included, involving 321,420 participants in this meta-analysis. Summary estimates based on adjusted data showed that periodontal disease was associated with a significant risk of lung cancer (HR = 1.24, 95% CI = 1.13 to 1.36; I(2) = 30%). No publication bias was detected. Subgroup analysis indicated that the association of periodontal disease and lung cancer remained significant in the female population. CONCLUSION: Evidence from cohort studies suggests that patients with periodontal disease are at increased risk of developing lung cancer.

Cyclooxygenase-2-1195G>A Polymorphism and Head and Neck Squamous Cell Carcinoma Susceptibility: A Meta-Analysis of 1564 Cases and 2346 Controls.

BACKGROUND The aim of this study was to investigate the association between cyclooxygenase-2 (COX-2) rs689466 (-1195 G>A) polymorphism and susceptibility to head and neck squamous cell carcinoma (HNSCC) by performing a meta-analysis. MATERIAL AND METHODS PubMed and Embase were searched for relevant cohort and case-control studies up to 13 March 2015. After data extraction and methodological quality assessment for eligible studies, the overall, subgroup, sensitivity, and cumulative meta-analyses were conducted using the Comprehensive Meta-Analysis software (version 2.2). RESULTS Finally, 5 case-control studies involving 1564 HNSCC patients and 2346 healthy controls were included. For overall population, the results of 3 genetic models showed significant association, while the other 2 presented negative association [A vs. G: OR=0.97-1.09, 95%CI=0.97-1.09; AA vs. GG: OR=1.26, 95%CI=1.01-1.57; AA vs. GA: OR=1.21, 95%CI=1.01-1.45); AA vs. (GG+GA): OR=1.20, 95%CI=1.01-1.43; (AA+GA) vs. GG: OR=0.98, 95%CI=0.84-1.15]. Publication bias was not assessed due to the limited number of included studies. CONCLUSIONS This meta-analysis indicated that COX-2 rs689466 polymorphism might be associated with increased susceptibility to HNSCC. We also suggest performing more relevant studies in order to enlarge the sample size and obtain more precise results.

Meta-Analysis of Association Between Interleukin-1ß C-511T Polymorphism and Chronic Periodontitis Susceptibility.

BACKGROUND: Many studies have been conducted to explore the association between interleukin (IL)-1ß C-511T polymorphism and risk of chronic periodontitis (CP) but with different or even contradictory results. A meta-analysis was performed to further explore their association. METHODS: PubMed, Chinese National Knowledge Infrastructure, and EMBASE were searched up to September 30, 2014 for relevant case-control studies. Two authors (D-YL and L-YX) independently selected studies and extracted data from included studies. The meta-analysis was performed using comprehensive meta-analysis software. RESULTS: Nineteen case-control studies involving 2,173 patients with CP and 3,900 healthy controls were included. Using a random-effects meta-analysis model, a non-significant association between IL-1ß C-511T polymorphism and CP was identified (T versus C: odds ratio [OR] = 1.03, 95% confidence interval [CI] = 0.85 to 1.25; TT versus CC: OR = 1.03, 95% CI = 0.72 to 1.46; CT versus CC: OR = 0.96, 95% CI = 0.71 to 1.30; CT + TT versus CC: OR = 1.00, 95% CI = 0.74 to 1.34; TT versus CT + CC: OR = 1.05, 95% CI = 0.81 to 1.38), and sensitivity analysis indicated that the results were robust. Subgroup analyses also revealed a non-significant association. No publication bias was detected. CONCLUSIONS: Based on currently available evidence, IL-1ß C-511T polymorphism is not associated with the risk of developing CP. Additional research is warranted to further explore and confirm the association of genetic polymorphism and CP.

Association between p53 Arg72Pro polymorphism and the risk of human papillomavirus-related head and neck squamous cell carcinoma: a meta-analysis.

This study aimed to investigate the association between p53 Arg72Pro polymorphism and the risk of human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) by conducting meta-analysis. The PubMed database was searched for relevant studies until May 30, 2013. Relevant studies were selected and data were extracted by two independent authors. Overall, subgroup, and sensitivity analyses were then conducted using the Comprehensive Meta- Analysis v2.2 software. Wild-genotype ArgArg was considered as reference [odds ratio (OR) = 1.00]. Nine studies involving 1071 HNSCC cases were obtained. Meta-analysis results indicated no association between p53 Arg72Pro polymorphism and the risk of HPV-related HNSCC: for Pro/Pro vs. Arg/Arg, OR = 1.17, 95% confidence interval (CI) = 0.70-1.98; for Arg/Pro vs. Arg/ Arg, OR = 1.25, 95% CI = 0.97-1.72; and for (Pro/Pro + Arg/Pro) vs. Arg/Arg, OR = 1.28, 95% CI = 0.95-1.70. These meta-analysis results were supported by subgroup and sensitivity analysis results. In conclusions, p53 Arg72Pro polymorphism is a potential marker of HP infection-related HNSCC rather than a susceptibility gene polymorphism.

Periodontal disease and risk of head and neck cancer: a meta-analysis of observational studies.

BACKGROUND: Many epidemiological studies have found a positive association of periodontal disease (PD) with risk of head and neck cancer (HNC), but the findings are varied or even contradictory. In this work, we performed a meta-analysis to ascertain the relationship between PD and HNC risk. METHODS: We searched the PubMed, Embase, and Cochrane Library databases for relevant observational studies on the association between PD and HNC risk published up to March 23, 2013. Data from the included studies were extracted and analyzed independently by two authors. Meta-analysis was performed using RevMan 5.2 software. RESULTS: We obtained seven observational studies involving two cohort and six case-control studies. Random-effects meta-analysis indicated a significant association between PD and HNC risk (odds ratio = 2.63, 95% confidence interval = 1.1.68 - 4.14; p < 0.001), with sensitivity analysis showing that the result was robust. Subgroup analyses based on adjustment for covariates, study design, PD assessment, tumor site, and ethnicity also revealed a significant association. CONCLUSIONS: Based on currently evidence, PD is probably a significant and independent risk factor of HNC.

CYP1A1 Ile462Val polymorphism contributes to colorectal cancer risk: a meta-analysis.

AIM: To study the relation between CYP1A1 Ile462Val polymorphism and colorectal cancer risk by meta-analysis. METHODS: A meta-analysis was performed to investigate the relation between CYP1A1 Ile462Val polymorphism and colorectal cancer risk by reviewing the related studies until September 2010. Data were extracted and analyzed. Crude odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of relation between CYP1A1 Ile462Val polymorphism and colorectal cancer risk. RESULTS: Thirteen published case-control studies including 5336 cases and 6226 controls were acquired. The pooled OR with 95% CI indicated that CYP1A1 Ile462Val polymorphism was significantly related with colorectal cancer risk (Val/Val vs Ile/Ile: OR = 1.47, 95% CI: 1.16-1.86, P = 0.002; dominant model: OR = 1.33, 95% CI: 1.01-1.75, P = 0.04; recessive model: OR = 1.49, 95% CI: 1.18-1.88, P = 0.0009). Subgroup ethnicity analysis showed that CYP1A1 Ile462Val polymorphism was also significantly related with colorectal cancer risk in Europeans (Ile/Val vs Ile/Ile: OR = 1.22, 95% CI: 1.05-1.42, P = 0.008; dominant model: OR = 1.24, 95% CI: 1.07-1.43, P = 0.004) and Asians (Val/Val vs Ile/Ile: OR = 1.40, 95% CI: 1.07-1.82, P = 0.01; recessive model: OR = 1.46, 95% CI: 1.12-1.89, P = 0.005). CONCLUSION: CYP1A1 Ile462Val may be an increased risk factor for colorectal cancer.

[Continuous observation of canal aberrations in S-shaped simulated root canal prepared by hand-used ProTaper files].

PURPOSE: To observe the formation of canal aberrations in S-shaped root canals prepared by every file of hand-used ProTaper. METHODS: Fifteen S-shaped simulated resin root canals were selected. Each root canal was prepared by every file of hand-used ProTaper following the manufacturer instruction. The images of canals prepared by S1, S2, F1, F2 and F3 were taken and stored, which were divided into group S1, S2, F1, F2 and F3. One image of canal unprepared was superposed with the images of the same root canal in these five groups respectively to observe the types and number of canal aberrations, which included unprepared area, danger zone, ledge, elbow, zip and perforation. SPSS12.0 software pakage was used for Fisher's exact probabilities in 2x2 table. RESULTS: Unprepared area decreased following preparation by every file of ProTaper, but it still existed when the canal preparation was finished. The incidence of danger zone, elbow and zip in group F1 was 15/15, 11/15, 4/15, respectively, which was significantly higher than that in group S2(2/15,0,0) (P<0.001). Ledge appeared after prepared by F2, and increased sharply in group F3. None perforation was found in all groups. CONCLUSIONS: The incidence of canal aberrations begins to increase after prepared by finishing files of ProTaper.The presence of unprepared area suggests that it is essential to rinse canal abundantly during complicated canal preparation and canal antisepsis after preparation.

[Investigation of influence on apical sealability generated by root canal sealer placement].

OBJECTIVE: To investigate the influence of sealer placement on apical sealability in root canal treatment. METHODS: 100 extracted single root canal teeth were selected. All canals were prepared by manual Protaper instrument in a step-back way. The samples were divided into 5 groups randomly. A group: 30 samples, sealer placement by chief gutta percha; B group: 30 samples, sealer placement by K file; C group: 30 samples, sealer placement by spreader; D group: 5 samples, a positive control; E group: 5 samples, a negative control. There were 2 subsets in each experimental group which were obturated by lateral gutta percha with or without sealer. Glucose oxidase method was used to measure the apical leakage at the 1st 2nd, 4th, 7th, 10th, 15th, 20th, 25th, 30th day of the experiment. RESULTS: Apical sealability varied with different sealer placement methods (F=4.832, P=0.001). Sealer placement by chief gutta percha (A group) had the best instant apical sealability. However, lateral gutta percha with or without sealer didn't affect the apical sealibility. CONCLUSION: Placing the same kind sealer in different ways can affect the apical sealability. There were no significant differences of the apical leakage no matter the lateral gutta percha with or without sealer. In order to get better instant apical sealability and simplify the clinic operation, placing the sealer with a chief gutta percha while the lateral gutta percha without sealer is recommended.