Non-IgE-mediated hypersensitivity induced by multivitamins containing Tween-80.

Multivitamins have been widely used for years. Adverse reactions, especially hypersensitivity, to multivitamins are becoming noteworthy. However, the classification of hypersensitivity is confusing, and the trigger is unknown. Multivitamins consist of two vials labelled vial 1 containing Tween-80 and vial 2. Multivitamins without Tween-80 were used as a contrast. Behaviouristics, histamine, IgE, and blood pressure of beagle dogs and guinea-pigs were investigated by observation, ELISA and sphygmomanometer, and degranulation and apoptotic of RBL-2H3 cells were assayed by spectrophotometry and flow cytometry. The results showed that dogs suffered from multiorgan anaphylactoid symptoms, and dramatically decreased blood pressure, and high plasma concentrations of histamine after the first administration of multivitamins and multivitamins vial 1, which contains Tween-80, compared to the control, multivitamins vial 2 or multivitamins without Tween-80. In anaphylaxis assay, guinea-pigs did not display any anaphylaxis symptoms and there were no changes in plasma histamine and IgE concentrations in the multivitamins and multivitamins vial 1 groups or in the multivitamins vial 2 and multivitamins without Tween-80 groups except ovalbumin. Compared to the control, the release of ß-hexosaminidase and histamine, and the apoptosis of non-antigen-sensitized RBL-2H3 cells significantly increased in the Tween-80 and multivitamins and multivitamins vial 1 groups in a concentration-dependent manner. However, there was no alteration in multivitamins vial 2 and multivitamins without Tween-80 groups. The results indicate that the hypersensitivity induced by multivitamins may be anaphylactoid reaction, but not anaphylaxis. Multivitamin-induced release of inflammatory factors is triggered by Tween-80 through a non-IgE-mediated pathway.

Craniocervical posture in patients with skeletal malocclusion and its correlation with craniofacial morphology during different growth periods.

The association between craniocervical posture and craniofacial structures in the various sagittal skeletal malocclusion during different growth stages has been the focus of intense interest in fields of orthodontics, but it has not been conclusively demonstrated. Thus, this study aimed to investigate the association between craniofacial morphology and craniocervical posture in patients with sagittal skeletal malocclusion during different growth periods. A total of 150 from a large pool of cephalograms qualified for the inclusion and exclusion were evaluated and classified into three groups according to the Cervical Vertebral Maturation (CVM) by examining the morphological modifications of the second through fourth cervical vertebrae, each group consisted of 50 cephalograms. In each growth period, for the comparison of head and cervical posture differences among various skeletal classes, the radiographs were further subdivided into skeletal Class I (0° < ANB < 5°, n = 16), skeletal Class II (ANB ≥ 5°, n = 18), and skeletal Class III (0° ≤ ANB, n = 16) on the basis of their ANB angle. There was no significant difference in gender (P > 0.05). Some variables were found to be significant during pubertal growth and later in patients with sagittal skeletal malocclusion (P < 0.05). Most indicators describing craniocervical posture were largest in skeletal Class II and smallest in skeletal Class III during the peak growth periods and later. Cervical inclination variables were greater in skeletal Class III than in skeletal Class II. Variables of craniofacial morphology and craniocervical posture are more correlated during the pubertal growth period and later in patients with sagittal skeletal malocclusion. A tendency is an indication of the close interrelationship that a more extended head was in skeletal Class II while a flexed head was in skeletal Class III. Nevertheless, with the considerations of some limitations involved in this study, further longitudinal studies with large samples are required to elucidate the relationship clearly.

Integrated analyses revealed the potential role and immune link of mitochondrial dysfunction between periodontitis and type 2 diabetes mellitus.

There is a reciprocal comorbid relationship between periodontitis and type 2 diabetes mellitus (T2DM). Recent studies have suggested that mitochondrial dysfunction (MD) could be the key driver underlying this comorbidity. The aim of this study is to provide novel understandings into the potential molecular mechanisms between MD and the comorbidity, and identify potential therapeutic targets for personalized clinical management. MD-related differentially expressed genes (MDDEGs) were identified. Enrichment analyses and PPI network analysis were then conducted. Six algorithms were used to explore the hub MDDEGs, and these were validated by ROC analysis and qRT-PCR. Co-expression and potential drug targeting analyses were then performed. Potential biomarkers were identified using LASSO regression. The immunocyte infiltration levels in periodontitis and T2DM were evaluated via CIBERSORTx and validated in mouse models. Subsequently, MD-related immune-related genes (MDIRGs) were screened by WGCNA. The in vitro experiment verified that MD was closely associated with this comorbidity. GO and KEGG analyses demonstrated that the connection between periodontitis and T2DM was mainly enriched in immuno-inflammatory pathways. In total, 116 MDDEGs, eight hub MDDEGs, and two biomarkers were identified. qRT-PCR revealed a distinct hub MDDEG expression pattern in the comorbidity group. Altered immunocytes in disease samples were identified, and their correlations were explored. The in vivo examination revealed higher infiltration levels of inflammatory immunocytes. The findings of this study provide insight into the mechanism underlying the gene-mitochondria-immunocyte network and provide a novel reference for future research into the function of mitochondria in periodontitis and T2DM.

Can salivary lactate be used as an anaerobic biomarker?

Background: Salivary lactate has been suggested as a non-invasive anaerobic biomarker in sports medicine for decades, yet has not been widely applied until now. This study aimed to explore possible issues related to its application and suggest directions for future method improvement. Methods: A liquid chromatography-mass spectrometry (LC-MS) method for the determination of salivary lactate was developed, validated and applied on saliva samples collected from a group of professional sprinters (n = 20). The samples were collected via chewing a cotton ball for one minute and centrifuging it afterwards. The evaluation included variation with mouth rinse times, consistency at different sampling times, change after treadmill or cycle ergometer trainings, and association with blood lactate. Sample sizes were calculated prior to the study. One-way analysis of variance (ANOVA), intra-class correlation coefficients (ICC) and relative standard deviation (RSD) were used to evaluate data variances. Pearson correlation was applied to show correlation between salivary and blood lactate. Effect sizes and power were calculated following ANOVA and correlation analyses. Results: The RSD of the LC-MS method was 19.70%. Salivary lactate concentration was affected by mouth rinse times before sampling (ANOVA p = 0.025, η 2 = 0.40, 1 - ß = 0.99, ICC = 0.23, mean RSD of four sampling = 55.30%), and stabilized after mouth rinsing for three times. The concentrations at resting state across three weeks were consistent at group level (ANOVA p = 0.57, η 2 = 0.03, 1 - ß = 0.20), but varied greatly individually (ICC = 0.22, mean RSD = 56.16%). Salivary lactate level significantly increased after treadmill and cycle ergometer trainings (ANOVA p = 0.0002, η 2 = 0.46, 1 - ß = 0.9999 and ANOVA p = 0.0019, η 2 = 0.40, 1 - ß = 0.9993, respectively), and displayed positive correlation with blood lactate concentration (r = 0.61, p = 0.0004, 1 - ß = 0.9596). Significant difference between male and female participants was observed in none of the tests conducted in this study. Discussion: Salivary lactate was found to be a potential anaerobic biomarker. However, reproducible methods for sample collection and analysis, as well as more knowledge on the secretion mechanism and pattern of salivary lactate are required to make it a practical anaerobic biomarker.

Label-Free Quantitative Proteomic Profiling of LAD2 Mast Cell Releasates Reveals the Mechanism of Tween-80-Induced Anaphylactoid Reaction.

PURPOSE: Tween-80 is one of the most important causes resulting in anaphylactoid reaction. However, its mechanism remains unclear. Proteomic characterizations of mast cells' excreta in response to Tween-80 are assayed to investigate the mechanism of anaphylactoid reaction. EXPERIMENTAL DESIGN: A label-free LCMS/MS-based proteomics is used to analyze Tween-80-stimulated Laboratory of Allergic Diseases 2 (LAD2) mast cells releasates. The results of proteomic are analyzed by bioinformatics analysis. Western blotting is used to verify the expression of proteins. RESULTS: Overall, endocytosis, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and calcium signaling pathways play important roles in Tween-80-induced LAD2 cells activation by bioinformatics analysis. The expressions of relative proteins including actin-related protein 2/3 complexes, vacuolar protein sorting-associated protein, phosphorylation of transcription factor of P105 and P65, phosphorylation of inositol 1,4,5-trisphosphate receptor (IP3 R), phosphoinositide phospholipase Cγ (PLCγ), and protein kinase C (PKC), are significantly increased in Tween-80 group compared to control. Tween-80 might be internalized via endocytosis, which induces degranulation by PLCγ/PKC pathways mediated calcium influx, and promotes the generation of inflammatory mediators via NF-κB pathway resulting in anaphylactoid reaction.

COL1A2 gene polymorphisms (Pvu II and Rsa I), serum calciotropic hormone levels, and dental fluorosis.

OBJECTIVES: To investigate the relationship between dental fluorosis, polymorphisms in the COL1A2 gene, and serum calciotropic hormone levels. METHODS: We conducted a case-control study among children between 8 and 12 years of age with (n = 75) and without (n = 165) dental fluorosis in two counties in Henan Province, China. The PvuII and RsaI polymorphisms in the COL1A2 gene were genotyped using the PCR-RFLP procedure. Calcitonin and osteocalcin levels in the serum were measured using radioimmunassays. RESULTS: Children carrying the homozygous genotype PP of COL1A2 PvuII had a significantly increased risk of dental fluorosis (OR =4.85, 95% CI: 1.22-19.32) compared to children carrying the homozygous genotype pp in an endemic fluorosis village (EFV). However, the risk (OR = 1.07, 95% CI: 0.45-2.52) was not elevated when the control population was recruited from a non-endemic fluorosis village. Additionally, fluoride levels in urine and osteocalcin levels in serum were found to be significantly lower in controls from non-endemic villages compared to cases. However, the differences in fluoride and osteocalcin levels were not observed when cases were compared to a control population from endemic fluorosis villages. CONCLUSIONS: This study provides the first evidence of an association between polymorphisms in the COL1A2 gene with dental fluorosis in high fluoride exposed populations. Future studies are needed to confirm the association.