Genetic evidence strengthens the bidirectional connection between oral health status and psychiatric disorders: A two-sample Mendelian randomization study.

BACKGROUND: Observational studies cannot accurately infer the causal associations between oral health status and psychiatric disorders. METHODS: We conducted univariate and multivariate Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) associated with eight oral health statuses (periodontitis, DMFS, Nteeth, toothache, loose teeth, painful gums, bleeding gums, and mouth ulcers) and four psychiatric disorders (Schizophrenia, Major Depressive Disorder (MDD), anxiety and stress-related disorder (ASRD), and Bipolar Disorder (BIP)) as instrumental variables. Genetic data were sourced from the Gene-lifestyle interactions in dental endpoints (GLIDE), UK Biobank, Psychiatric Genomics Consortium (PGC), and Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH). The inverse variance-weighted (IVW) approach, supported by a comprehensive sensitivity analysis, was employed. RESULTS: Genetically predicted mouth ulcers were significantly linked to higher MDD (OR = 2.17, 95 % CI: 1.33--3.54, P< 0.01) and BIP risks (OR = 2.25, 95 % CI: 1.22-4.15, P = 0.01). BIP heightened bleeding gums risk (OR = 1.01, 95 % CI: 1.00-1.01, P < 0.01). These associations were adjusted for smoking status and alcohol consumption. Painful gums were significantly associated with MDD risk (OR = 96.48, 95 % CI: 2.66-3495.28, P = 0.01), while MDD raised periodontitis risk (OR = 2.15, 95 % CI: 1.24-3.75, P = 0.01), both confounded by smoking and alcohol. Relatively small effects between several variables, while others could not withstand correction for multiple tests. LIMITATIONS: The sample size and limitation to European populations limits the study generalizability. CONCLUSIONS: This study provide evidence of possible causal relationships between several oral health conditions and mental illness. Focusing on oral health and valuing mental health are important for each other and overall health.

Work Stress and Depressive Symptoms in Fishermen With a Smoking Habit: A Mediator Role of Nicotine Dependence and Possible Moderator Role of Expressive Suppression and Cognitive Reappraisal.

This study examined pathways of influence between work stress, depressive symptoms, nicotine dependence, expressive suppression, and cognitive reappraisal in fishermen with smoking habits in Qionghai, Hainan province, China (N = 1068). These fishermen responded to multiple assessments a week before leaving on a deep-sea fishing trip, including a Mental Stressor Investigation Questionnaire (MSIQ), the Center for Epidemiological Studies Depression Scale (CES-D), the Russell Reason for Smoking Questionnaire (RRSQ), and an Emotion Regulation Questionnaire (ERQ). Structural equation modeling (SEM) analyses of the collected data in Mplus 7 showed that work stress and nicotine dependence were independent predictors of depressive symptoms. The relationship between work stress and depressive symptoms was found to be partially mediated by nicotine dependence and be moderated by cognitive reappraisal. The evidence suggests it advantageous to examine the need of work stress, nicotine dependence, and cognitive reappraisal when attempting to understand depressive symptoms in fishermen with a smoking habit. These findings suggest that improving nicotine dependence through work stress management and training in cognitive reappraisal could be utilized as effective modalities for improving depressive symptoms.

Surface modification of carbon nanotubes by using iron-mediated activators generated by electron transfer for atom transfer radical polymerization.

Herein, a surface-initiated activator generated by electron transfer for an atom transfer radical polymerization (AGET ATRP) system was developed on the surface of multiwall carbon nanotubes (MWCNTs) by using FeCl3·6H2O as the catalyst, tris-(3,6-dioxoheptyl) amine (TDA-1) as the ligand and ascorbic acid (AsAc) as the reducing agent. A wide range of polymers, such as polystyrene (PS), poly(methyl methacrylate) (PMMA) and poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA), were successfully grafted onto the surfaces. The core-shell structure of MWCNTs@PS was observed by TEM. Both Raman spectra and the results of hydrolysis of MWCNTs@PS (after extraction by THF) confirmed that the PS chains were covalently tethered onto the surfaces of the MWCNTs. Due to superior biocompatibility of the iron catalyst, the strategy of modification of MWCNTs via iron-mediated AGET ATRP provided a promising method for the controllable and biocompatible modification of nanomaterials.

Effects of histone deacetylase inhibitor trichostatin A combined with cisplatin on apoptosis of A549 cell line.

BACKGROUND: Histone deacetylase (HDAC) inhibitors combined with other drugs for the treatment of malignant tumors are used more and more widely. In this study, we investigated the effect of trichostatin A (TSA), a HDAC inhibitor, in combination with cisplatin, a cytotoxic chemotherapy agent, on the apoptosis of lung cancer A549 cells. METHODS: A549 cells were treated with TSA alone, cisplatin alone or the two drugs combined. Cell viability and apoptosis were evaluated using a light microscope, methyl thiazolyl tetrazolium (MTT) (3-[4, 5-dimethylthiazol-2-yl] -2, 5-diphenyltetrazolium bromide) assay and Hochst33258 staining. Moreover, Western blot analysis was employed to examine the alterations of apoptosis protein: cellular Fas-associated death domain-like interleukin-1 ß converting enzyme inhibitory protein (cFLIP) and caspase-8 in A549 cells in response to the different exogenous stimuli. RESULTS: Compared with single-agent treatment, the co-treatment of A549 cells with TSA and cisplatin synergistically inhibited cell proliferation, induced apoptosis, and increased the inhibition rate. Treatment with TSA and cisplatin led to a significant decrease of cFLIP expression. Furthermore, the treatment of A549 cells with TSA and cisplatin resulted in a significant decrease of pro-caspase-8 and a significant increase of caspase-8. CONCLUSIONS: Synergistic anti-tumor effects are observed between cisplatin and TSA in lung cancer cells. The combination of TSA with cisplatin may be a more effective method in human lung cancer treatment.

[Clinical features of patients with primary biliary cirrhosis and anti-SP100 autoantibody positivity].

OBJECTIVE: To evaluate the clinical features of patients with primary biliary cirrhosis (PBC) and positive expression of sp100 autoantibody in order to generate a clinical screening profile that may help to increase early diagnosis and timely initiation of therapy. METHODS: The clinical data of 70 patients who were diagnosed with PBC by liver biopsy between January 2006 to December 2009 at the Second Affiliated Hospital of Kunming Medical University of Hepatobiliary and Pancreatic Medicine were retrospectively collected for analysis. The patients were divided according to expression of anti-sp100: positive patients, n = 12; negative patients, n = 58. The groups were comparatively analyzed for differences in clinical, biochemical, immunological, and histopathological parameters. Normally distributed data was compared by t-test, and non-normally data was compared by rank-sum test. RESULTS: There was no significant difference in age among the sp100-positive and sp100-negative patients (51.6 +/- 9.5 vs. 50.0 +/- 14.7 years, P more than 0.05). The sp100-positive group had significantly more women (80.0% vs. 61.9%, X2 = 0.32, P more than 0.05) and more patients with atypical symptoms (18.2% vs. 13.8%) but the difference of the latter did not reach statistical significance. The sp100-positive group had significantly higher levels of alkaline phosphatase (ALP; 466 vs. 163 U/L, Z = 3.71), gamma-glutamyl-transpeptidase (GGT; 728 vs. 154 U/L, Z = 3.38), and immunoglobulin M (IgM; 4.25 +/- 2.86 vs. 2.81 +/- 2.15, t = 2.06, P less than 0.05). Forty of the total patients tested negative for antimitochondrial (AMA)-M2 antibodies, and eight of those were sp100-positive (20.0%) while 18 were antinuclear (ANA) antibody-positive (45.0%). There were significantly more AMA-M2-negative/ANA-positive patients than sp100-positive patients (P = 0.021). Anti-sp100 expression was not associated with the pathological stage of PBC (R1 = 5.500, P more than 0.05). CONCLUSION: SP100-positive PBC may show a bias towards the female sex, and may be characterized by enhanced serum levels of ALP, GGT, and IgM. Further clinical differences may manifest as the disease progresses, and changes in autoantibodies' expression and liver function markers should be carefully monitored in follow-up.

Phosphorylation of the α-subunit of the eukaryotic initiation factor-2 (eIF2α) alleviates benzo[a]pyrene-7,8-diol-9,10-epoxide induced cell cycle arrest and apoptosis in human cells.

Benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE) is a carcinogen causing bulky-adduct DNA damage and inducing extensive cell responses regulating cell cycle, cell survival and apoptosis. However, the mechanism of cellular responses to BPDE exposure is not fully understood. In this study, we demonstrated the involvement of the phosphorylation of the α-subunit of the eukaryotic initiation factor-2 (eIF2α) in the cellular response to BPDE exposure and addressed the role of eIF2α phosphorylation in the regulation of the cellular stress. Phosphorylation of eIF2α was induced in a normal human FL amnion epithelial cell line, and the expression of ATF4, a conserved downstream transcriptional factor of eIF2α phosphorylation, was up-regulated after BPDE exposure; however, the four known primary kinases for eIF2α phosphorylation (GCN2, HRI, PKR, and PERK) were not found activated. While BPDE induced severe cell cycle arrest and apoptosis and decreased cell viability in FL cells, salubrinal, a selective inhibitor of eIF2α dephosphorylation, maintained the eIF2α phosphorylation and attenuated cell cycle arrest and apoptosis and promoted cell survival. The findings reveal that when BPDE causes cellular damages, it induces eIF2α phosphorylation as well, which produces a pro-survival and anti-apoptotic effect to alleviate the cellular damages. Thus, the present study proposes a new cellular defensive mechanism during the environmental mutagen and carcinogen attack.

Response of human DNA polymerase ι promoter to N-methyl-N'-nitro-N-nitrosoguanidine.

Human Pol ι is a highly distributed, low-fidelity DNA polymerase lacking intrinsic exonuclease proofreading activity, thus its effects are strictly regulated. We predicted and cloned the promoter region of the human POLI gene. Successively, by transfection of deletion constructs of the POLI promoter, we demonstrated that the regions -848/-408 and -30/+215 contained positive regulatory elements, and the region +215/+335 had proximal promoter activity. Overexpression of Sp1 significantly increased the transcriptional activity of the promoter, and mutation of the Sp1 site reversed Sp1-induced promoter transactivation. Quantitative RT-PCR showed that POLI mRNA expression was up-regulated in human amnion FL cells treated by the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Reporter gene assays demonstrated that MNNG also significantly increased the transcriptional activity of the predicted promoter (-848/+335) and the proximal promoter (+215/+335). However, the promoter with the Sp1 site mutation had no response to MNNG treatment, suggesting that Sp1 plays an important role in the transcriptional regulation of the POLI gene stimulated by MNNG. Our data suggest that abnormal regulation of Pol ι may be involved in the mutagenesis and carcinogenesis induced by environmental chemicals.

Inhibitory mechanisms of heterocyclic carboxaldehyde thiosemicabazones for two forms of human ribonucleotide reductase.

Two forms of ribonucleotide reductase (RR), consisting of M1 with M2 subunits and M1 with p53R2 subunits, are involved in DNA replication and damage repair, respectively. 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3AP), one of the heterocyclic carboxaldehyde thiosemicabazones (HCTs), is a potent RR inhibitor in clinical trial for cancer treatment. In this study, 3AP and its 7 derivatives showed 100-1000-fold higher inhibitory potency on KB nasopharyngeal carcinoma cells than hydroxyurea and were fully active against hydroxyurea- and gemcitabine-resistant KB cells. In vitro RR assays using two recombinant RRs showed that all 8 HCTs decreased the activity of both RRs in a dose-dependent manner and the efficiency was compatible with that on cell proliferation inhibition. Iron has different impact on the behavior of the compounds toward RRs. In the absence of iron, the HCTs showed more selective inhibition for p53R2-M1 than M2-M1, while addition of iron increased their activity but reduced their selectivity for two RRs. Radioligand binding assays showed that [(3)H]3AP directly bounded to the small subunits. Electron paramagnetic resonance measurements demonstrated that these HCTs generated reactive oxygen species with ferrous iron, which quenched the diiron-tyrosyl radical co-factor of the small subunits and hence the enzyme activity. While the ROS may be a common mediator responsible for the potent activity of the HCTs, the different characteristics of the small subunit proteins are probably associated with the subunit-selectivity of inhibition. Better understanding of the mechanism of action of RR inhibition may improve design of new potent and subunit-selective RR inhibitors for cancer therapy.