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.

Antagonizing Effects of Chromium Against Iron-Decreased Glucose Uptake by Regulating ROS-Mediated PI3K/Akt/GLUT4 Signaling Pathway in C2C12.

To investigate the effect of chromium and iron on glucose metabolism via the PI3K/Akt/GLUT4 signaling pathway. Skeletal muscle gene microarray data in T2DM (GSE7014) was selected using Gene Expression Omnibus database. Element-gene interaction datasets of chromium and iron were extracted from comparative toxicogenomics database (CTD). Gene ontology (GO)and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using DAVID online tool. Cell viability, insulin-stimulated glucose uptake, intracellular reactive oxygen species (ROS) level, and protein expression level were measured in C2C12 cells. The bioinformatics research indicated that PI3K/Akt signaling pathway participated in the effects of chromium and iron associated with T2DM. Insulin-stimulated glucose uptake level was significantly higher in chromium picolinate (Cr group) and lower in ammonium iron citrate (FA group) than that for the control group (P < 0.05); chromium picolinate + ammonium iron citrate (Cr + FA group) glucose uptake level was higher than that for the FA group (P < 0.05). Intracellular ROS level was significantly higher in the FAC group than that for the control group (P < 0.05), and that for the Cr + FA group was lower than that for the FA group (P < 0.05). p-PI3K/PI3K, p-Akt/Akt, and GLUT4 levels were significantly lower in the FA group than that for the control group (P < 0.05), and the Cr + FA group had higher levels than the FA group (P < 0.05). Chromium might have a protective effect on iron-induced glucose metabolism abnormalities through the ROS-mediated PI3K/Akt/GLUT4 signaling pathway.

Relationship between body composition and pulmonary function in the general population-a cross-sectional study in Ningxia.

Studies considering the relationship between non-obesity-related body composition and lung function are few; therefore, this study aimed to explore these correlations and effects. This cross-sectional study conducted in rural Qingtongxia City and Pingluo County, Ningxia, China, included 776 participants aged 30-75 years. Body composition and lung function were measured using direct segmental multifrequency bioelectrical impedance analysis and a digital spirometer, respectively. Their correlation was assessed using partial correlation analysis, controlling for age and smoking status, and the body composition effect on lung function was analyzed using binomial logistic regression analysis. The body components total body water content, protein content, mineral content, muscle mass, fat-free mass (FFM), skeletal muscle mass, basal metabolic volume, and chest circumference (CC) positively correlated with pulmonary function (forced vital capacity and forced expiratory volume in one second) in both sexes. Neck circumference and hip circumference positively correlated with pulmonary function in women. Additionally, lung function declines more slowly in women (odds ratio [OR] = 0.66, 95% confidence interval [CI] = 0.44-0.98, p = 0.04); CC (OR = 0.92, 95% CI = 0.86-0.98, p = 0.01) increased as a protective factor for decreased lung function. Increased waist circumference (OR = 1.04, 95% CI = 1.00-1.09, p = 0.04) was a risk factor for reduced lung function. FFM contains body composition indicators positively correlating with lung function, excluding fat-related body composition. Abdominal obesity increases the risk of decreased lung function.

2,4-dichlorophenoxyacetic acid induces ROS activation in NLRP3 inflammatory body-induced autophagy disorder in microglia and the protective effect of Lycium barbarum polysaccharide.

The pesticide 2,4-dichlorophenoxyacetic acid (2,4-D) exerts neurotoxic effects; however, its action mechanism remains unclear. Here, we used BV2 cells as a model and divided them into six groups: control group (serum-free medium), lipopolysaccharide (LPS) (1 µg/mL), 2,4-D (1.2 µmol/mL), Lycium barbarum polysaccharide (LBP; 300 µg/mL LBP), LPS (1 µg/mL) + LBP (300 µg/mL), and 2,4-D (1.2 µmol/mL) + LBP (300 µg/mL) with dimethyl sulfoxide as the solvent. Our results showed that 2,4-D treatment decreased superoxide dismutase and glutathione peroxidase activities and increased malondialdehyde content. The percentage of microglial activation (co-expression of ionized calcium-binding adaptor protein-1 + CD68) in the LPS and 2,4-D groups and the levels of tumor necrosis factor alpha, interleukin (IL) 1 beta, IL-6, and IL-18 in the cell supernatant were increased. The protein and mRNA levels of Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein, caspase-1, IL-1ß, IL-18, and p62 increased, whereas those of LC3II/I and Beclin-1 decreased in the 2,4-D group. The protein expression and mRNA levels of NLRP3, cleaved caspase-1, IL-1ß, IL-18, and p62 decreased significantly, whereas the protein expression and mRNA levels of LC3II/I and Beclin-1 increased in small interfering RNA of NLRP3-treated BV2 cells stimulated with 2,4-D and LPS. In conclusion, 2,4-D enhanced cell migration, promoted oxidative stress, induced excessive release of mitochondrial reactive oxygen species, promoted microglial cell activation, released inflammatory factors, activated NLRP3 inflammasomes, and inhibited autophagy. Meanwhile, LBP reduced inflammation and the release of mitochondrial reactive oxygen species, inhibited NLRP3 inflammasome activation, and regulated autophagy, thereby playing a neuroprotective role.

Family with sequence similarity 13 member A mediates TGF-ß1-induced EMT in small airway epithelium of patients with chronic obstructive pulmonary disease.

BACKGROUND: To explore the role of family with sequence similarity 13 member A (FAM13A) in TGF-ß1-induced EMT in the small airway epithelium of patients with chronic obstructive pulmonary disease (COPD). METHODS: Small airway wall thickness and protein levels of airway remodeling markers, EMT markers, TGF-ß1, and FAM13A were measured in lung tissue samples from COPD and non-COPD patients. The correlations of FAM13A expression with COPD severity and EMT marker expression were evaluated. Gain- and loss-of-function assays were performed to explore the functions of FAM13A in cell proliferation, motility, and TGF-ß1-induced EMT marker alterations in human bronchial epithelial cell line BEAS-2B. RESULTS: Independent of smoking status, lung tissue samples from COPD patients exhibited significantly increased small airway thickness and collagen fiber deposition, along with enhanced protein levels of remodeling markers (collagen I, fibronectin, and MMP-9), mesenchymal markers (α-SMA, vimentin, and N-cadherin), TGF-ß1, and FAM13A, compared with those from non-COPD patients. FAM13A expression negatively correlated with FEV1% and PO2 in COPD patients. In small airway epithelium, FAM13A expression negatively correlated with E-cadherin protein levels and positively correlated with vimentin protein levels. In BEAS-2B cells, TGF-ß1 dose-dependently upregulated FAM13A protein levels. FAM13A overexpression significantly promoted cell proliferation and motility in BEAS-2B cells, whereas FAM13A silencing showed contrasting results. Furthermore, FAM13A knockdown partially reversed TGF-ß1-induced EMT marker protein alterations in BEAS-2B cells. CONCLUSIONS: FAM13A upregulation is associated with TGF-ß1-induced EMT in the small airway epithelium of COPD patients independent of smoking status, serving as a potential therapeutic target for anti-EMT therapy in COPD.

Anti­fibrotic effects and the mechanism of action of miR­29c in silicosis.

Despite increasing evidence suggesting a role for the miR­29 family in the suppression of fibrosis, its role in silicosis remains unknown. The present study aimed to examine the anti­fibrotic effects and specific mechanism of action of microRNA (miR)­29c in pulmonary silicosis using animal and cell models. miR­29c expression levels were examined in the lungs of silicotic rats via reveres transcription­quantitative (RT­q)PCR. A Transwell system employing co­cultures of pulmonary fibroblasts and macrophages was used to establish an in vitro cell model of silicosis, and lentivirus was used to overexpress or knockdown miR­29c in cultured cells. Changes in collagen type I α I (COL1α1), COL3α1, α­smooth muscle actin (α­SMA) and TGF­ß1 expression levels were determined via RT­qPCR and western blotting. Data analysis was performed using R software. miR­29c expression was significantly downregulated in the lungs of silicotic rats and in the pulmonary fibroblasts of the in vitro model of silicosis. Furthermore, COL1α1, COL3α1, α­SMA and TGF­ß1 expression levels were significantly increased in cultured fibroblasts following 12 or 18 h exposure to SiO2. Lentiviral­mediated knockdown of miR­29c resulted in increased the expression levels of COL1α1, COL3α1, α­SMA and TGF­ß1, while lentiviral­mediated miR­29c overexpression significantly suppressed the expression levels of these fibrosis­related genes. Taken together, these results demonstrated that miR­29c was significantly associated with silica­induced pulmonary fibrosis and the expression levels of COL1α1, COL3α1, TGF­ß1 and α­SMA are under the regulation of miR­29c to different extents. This study therefore identified possible candidate molecular targets for preventing or delaying the occurrence and progression of silicosis.

Prospective, randomised, controlled study on the efficacy and safety of different strategies of tranexamic acid with total blood loss, blood transfusion rate and thrombogenic biomarkers in total knee arthroplasty: study protocol.

INTRODUCTION: Total knee arthroplasty (TKA) is a common and highly effective orthopaedic procedure for treating end-stage knee osteoarthritis. Tranexamic acid (TXA) has become a routine part of perioperative care in TKAs. The best practices regarding the delivery method of TXA in TKA remain controversial. Plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin (TAT) complexes and prothrombin fragment F1+2 (F1+2) have been demonstrated to be elevated in patients with venous thromboembolism (VTE). The aim of this trial was to investigate the most efficacious delivery method of TXA (comparison of intravenous and topical applications and comparison of three topical applications) and to evaluate the safety of TXA strategies by investigating the effect of TXA on the plasma D-dimer, PAI-1, TAT and F1+2 levels. METHODS AND DESIGN: This trial is a prospective, randomised, controlled study that will evaluate the efficacy and safety of strategies of TXA. A total of 250 patients undergoing primary TKA will be randomly allocated to five groups for different TXA applications. The primary outcome is total blood loss. The secondary outcomes are blood transfusion rate, drainage volume, plasma D-dimer, PAI-1, TAT and F1+2 levels, maximum haemoglobin drop, wound complications, VTE and length of hospital stay. ETHICS AND DISSEMINATION: This study's protocol is in accordance with the declaration of Helsinki. The ethics committee of the General Hospital of Ningxia Medical University approved this study (approval ID: 2020-505). The results of this study will be disseminated in international peer reviewed journals. TRIAL REGISTRATION NUMBER: ChiCTR2000030624.

Typical phthalic acid esters induce apoptosis by regulating the PI3K/Akt/Bcl-2 signaling pathway in rat insulinoma cells.

Di-(2-ethylhexyl) phthalate (DEHP) and dibutyl phthalate (DBP) are representative phthalic acid esters (PAEs), a class of environmental endocrine disruptors used as plasticizers. PAEs exposure is associated with glucose metabolism, insulin resistance, and glucose tolerance; however, the mechanism and various PAE effects on human glucose metabolism remain largely unknown. In this study, we investigated the effects of DEHP, DBP, and their mixture on rat insulinoma (INS-1) cell apoptosis and the mechanism involved in vitro. The INS-1 cells were cultured in RPMI-1640 + 10% fetal bovine serum for 24 h and pretreated with dimethyl sulfoxide (vehicle, <0.1%), DEHP (30 µM), DBP (30 µM), and their mixture (30 µM DEHP + 30 µM DBP). The methyl-thiazolyl tetrazolium bromide test was used to measure cell viability. Hoechst 33342/propidium iodide (PI) staining and Annexin V-FITC/PI staining, 2',7'-dichlorofluorescein diacetate assay, and glucose-induced insulin secretion assay were used to detect cell apoptosis rates, intracellular reactive oxygen species (ROS), and insulin secretion in INS-1, respectively. The mRNA expression levels of Bcl-2, Bax, Caspase 9, Caspase 8, Caspase 3, phosphoinositide 3-kinase (PI3K), and Akt were detected using real-time quantitative reverse transcription PCR; their protein expression levels were detected using western blotting. To the best of our knowledge, this study was the first to show that the combined effect of the two PAEs promotes a ROS-mediated PI3K/Akt/Bcl-2 pathway-induced pancreatic ß cell apoptosis that is significantly higher than the effects of each PAE. Thus, safety standards and studies do not consider this effect as a significant oversight when blending PAEs. We assert that this must be addressed and corrected for establishing more impactful and safer standards.

The circadian clock gene PER2 enhances chemotherapeutic efficacy in nasopharyngeal carcinoma when combined with a targeted nanosystem.

Treatment failure occurs in more than 40% of advanced nasopharyngeal carcinoma (NPC) patients including local recurrence and distant metastasis due to chemoradioresistance. Circadian clock genes were identified as regulating cancer progression and chemoradiosensitivity in a time-dependent manner. A novel nanosystem can ensure the accumulation and controllable release of chemotherapeutic agents at the tumour site at a set time. In this study, we investigated the expression of circadian clock genes and identified that period circadian regulator 2 (PER2) as a tumour suppressor plays a key role in NPC progression. A label-free proteomic approach showed that PER2 overexpression can inhibit the ERK/MAPK pathway. The chemotherapeutic effect of PER2 overexpression was assessed in NPC together with the nanosystem comprising folic acid (FA), upconverting nanoparticles covalently coupled with Rose Bengal (UCNPs-RB), 10-hydroxycamptothecin (HCPT) and lipid-perfluorohexane (PFH) (FURH-PFH-NPs). PER2 overexpression combined with the targeted and controlled release of nanoagents elevated chemotherapeutic efficacy in NPC, which has potential application value for the chronotherapy of tumours.

Comparison of sodium, potassium, calcium, magnesium, zinc, copper and iron concentrations of elements in 24-h urine and spot urine in hypertensive patients with healthy renal function.

Sodium, potassium, calcium, magnesium, zinc, copper and iron are associated with the sequela of hypertension. The most reliable method for testing those elements is by collecting 24-h urine samples. However, this is cumbersome and collection of spot urine is more convenient in some circumstance. The aim of this study was to compare the concentrations of different elements in 24-h urine and spot urine. METHODS: Data was collected from a sub-study of China Salt Substitute and Stroke Study. 240 participants were recruited randomly from 12 villages in two counties in Ningxia, China. Both spot and 24-h urine specimens were collected from each patient. Routine urine test was conducted, and concentration of elements was measured using microwave digestion and Inductively Coupled Plasma-Optical Emission Spectrometry. Partial correlation analysis and Spearman correlation analysis were used to investigate the concentration of different elements and the relationship between 24- h urine and spot urine. RESULTS: A partial correlation in sodium, potassium, calcium, magnesium and iron was found between paired 24-h urine and spot urine samples except copper and zinc: 0.430, 0.426, 0.550, 0.221 and 0.191 respectively. CONCLUSIONS: Spot urine can replace 24-h urine for estimating some of the elements in hypertensive patients with normal renal function.

[Multiplicity and prevention for patients with hydrocephalus secondary to severe traumatic brain injury after surgery].

OBJECTIVE: To investigate the factors for hydrocephalus secondary to severe traumatic brain injury after surgery, and to explore a new theory and guideline for clinical early prevention and treatment for hydrocephalus.
 METHODS: The clinical data regarding 107 patients with severe traumatic brain injury, who were admitted to our hospital from June 2010 to June 2013, were analyzed. Logistic multi-factor regression was used to analyze the different factors including ages, gender, the Glasgow coma scale (GCS) score before or after surgery, the situation of ventricular system bleeding secondary to surgery, the situation of midbrain aqueduct and ambient cistern before or after surgery, the relationship between early lumbar puncture and the hydrocephalus. The risk and protective factors for postoperative hydrocephalus were discussed.
 RESULTS: The results showed that patients with low GCS score in pre/postoperative (OR=0.099, 95%CI: 0.028-0.350)/(OR=0.088, 95%CI: 0.012-0.649), ventricular system bleeding in postoperative (OR=0.168, 95%CI: 0.029-0.979) and dim CT image for midbrain aqueduct and ambient cistern (OR=0.134, 95%CI: 0.038-0.473)/(OR=0.221, 95%CI: 0.055-0.882) are risk factors. Whereas lumbar puncture (OR=75.885, 95%CI: 9.612-599.122) is a protective factor for postoperative hydrocephalus in STBI patients. The secondary hydrocephalus was mainly occurred in 2 weeks and 2 weeks to 3 months after operation. The incidence of the control group that occurred secondary hydrocephalus is higher than that of the lumbar puncture group (P<0.05). The secondary hydrocephalus were mainly occurred in 2 weeks and 2 weeks to 3 months after operation, with no statistical significance between the 2 groups after 3 months of operation (P>0.05).
 CONCLUSION: For patients with stable vital signs, early lumbar puncture could significantly reduce the incidence of secondary hydrocephalus in acute and subacute stage after severe traumatic brain injury.

Roles of microRNA-146a and microRNA-181b in regulating the secretion of tumor necrosis factor-α and interleukin-1ß in silicon dioxide-induced NR8383 rat macrophages.

Despite increasing evidence to suggest that microRNA (miR)-146a and miR-181b are involved in the regulation of immune responses and tumor progression, their roles in silicosis remain to be fully elucidated. Therefore, the present study examined the roles of miR­146a and miR­181b in inflammatory responses, and their effect on the expression of the tumor necrosis factor­α (TNF­α) and interleukin­1ß (IL­1ß) inflammatory chemokines in silicon dioxide (SiO2)­induced NR8383 rat macrophages. Alterations in the expression levels of miR­146a and miR­181b in rats with silicosis have been previously investigated using miRNA arrays. In the present study, the expression levels of miR­146a and miR­181b were assessed using reverse transcription­quantitative polymerase chain reaction (RT­qPCR). The NR8383 cells were transfected with miRNA­146a and miR­181b mimics or inhibitors, and the cells and culture supernatants were collected following SiO2 treatment for 12 h. The expression levels of TNF­α and IL­1ß were detected using western blotting, RT­qPCR and ELISA. Analysis of variance and Student's two­tailed t­test were used to perform statistical analyses. The expression level of miR­146a was significantly increased, while the expression level of miR­181b was significantly decreased in the fibrotic lungs of the rats with silicosis, compared with the levels in the normal rats. It was observed that, following treatment of the NR8383 cells with SiO2 for 12 h, the levels of TNF­α were significantly increased following miR­181b knockdown and the levels of IL­1ß were significantly increased following miR­146a knockdown, compared with the inhibitor­treated controls (P<0.05). By contrast, miR­181b mimic transfection led to a significant reduction in the levels of TNF­α (P<0.05), and miR­146a mimics were responsible for the decrease in IL-1ß (P<0.05). The results of the present study provide evidence supporting the roles of miR­146a and miR­181b in the pathogenesis of silicosis, and suggest that they may be candidate therapeutic target in this disease.

Influence of vanadium on serum lipid and lipoprotein profiles: a population-based study among vanadium exposed workers.

BACKGROUND: Some experimental animal studies reported that vanadium had beneficial effects on blood total cholesterol (TC) and triglyceride (TG). However, the relationship between vanadium exposure and lipid, lipoprotein profiles in human subjects remains uncertain. This study aimed to compare the serum lipid and lipoprotein profiles of occupational vanadium exposed and non-exposed workers, and to provide human evidence on serum lipid, lipoprotein profiles and atherogenic indexes changes in relation to vanadium exposure. METHODS: This cross-sectional study recruited 533 vanadium exposed workers and 241 non-exposed workers from a Steel and Iron Group in Sichuan, China. Demographic characteristics and occupational information were collected through questionnaires. Serum lipid and lipoprotein levels were measured for all participants. The ratios of total cholesterol to high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) to HDL-C and apoB to apoA-I were used as atherogenic indexes. A general linear model was applied to compare outcomes of the two groups while controlling possible confounders and multivariate logistic regression was performed to evaluate the relationship between low HDL-C level, abnormal atherogenic index and vanadium exposure. RESULTS: Higher levels of HDL-C and apoA-I could be observed in the vanadium exposed group compared with the control group (P < 0.05). Furthermore, atherogenic indexes (TC/HDL-C, LDL-C/HDL-C, and apoB/apoA-I ratios) were found statistically lower in the vanadium exposed workers (P < 0.05). Changes in HDL-C, TC/HDL-C, and LDL-C/HDL-C were more pronounced in male workers than that in female workers. In male workers, after adjusting for potential confounding variables as age, habits of smoking and drinking, occupational vanadium exposure was still associated with lower HDL-C (OR 0.41; 95% CI, 0.27-0.62) and abnormal atherogenic index (OR 0.38; 95% CI, 0.20-0.70). CONCLUSION: Occupational vanadium exposure appears to be associated with increased HDL-C and apoA-I levels and decreased atherogenic indexes. Among male workers, a significantly negative association existed between low HDL-C level, abnormal atherogenic index and occupational vanadium exposure. This suggests vanadium has beneficial effects on blood levels of HDL-C and apoA-I.