Effect of experimental gingivitis induction and erythritol on the salivary metabolome and functional biochemistry of systemically healthy young adults

Introduction

Understanding the changes occurring in the oral ecosystem during development of gingivitis could help improve prevention and treatment strategies for oral health. Erythritol is a non-caloric polyol proposed to have beneficial effects on oral health.

Objectives

To examine the effect of experimental gingivitis and the effect of erythritol on the salivary metabolome and salivary functional biochemistry.

Methods

In a two-week experimental gingivitis challenge intervention study, non-targeted, mass spectrometry-based metabolomic profiling was performed on saliva samples from 61 healthy adults, collected at five time-points. The effect of erythritol was studied in a randomized, controlled trial setting. Fourteen salivary biochemistry variables were measured with antibody- or enzymatic activity-based assays.

Results

Bacterial amino acid catabolites (cadaverine, N-acetylcadaverine, and α-hydroxyisovalerate) and end-products of bacterial alkali-producing pathways (N-α-acetylornithine and γ-aminobutyrate) increased significantly during the experimental gingivitis. Significant changes were found in a set of 13 salivary metabolite ratios composed of host cell membrane lipids involved in cell signaling, host responses to bacteria, and defense against free radicals. An increase in mevalonate was also observed. There were no significant effects of erythritol. No significant changes were found in functional salivary biochemistry.

Conclusions

The findings underline a dynamic interaction between the host and the oral microbial biofilm during an experimental induction of gingivitis.

     

Metabolic profiling by <Superscript>1</Superscript>H NMR spectroscopy of saliva shows clear distinction between control and diseased case of periodontitis

Introduction

Periodontitis is a chronic, non-reversible inflammatory disease of the oral cavity leading to destruction of periodontal tissues. Thus, the estimation of bacterial metabolite, tissue damage and secretory metabolites of the triggered inflammatory cells likely to yield results. It may be of value for understanding the pathophysiology of the disease by metabolic profiling of saliva samples using high-resolution NMR spectroscopy.

Objective

The study will evaluate the difference in salivary metabolites in healthy and periodontal condition along with fetching of possible biomarkers in case of chronic periodontitis.

Methods

¹H- NMR spectroscopy has been employed in 114 saliva samples in search of distinctive differences and spectral data were further subjected to multivariate analysis.

Result

One-hundred metabolites were characterised and assigned in the ¹H NMR spectra of saliva. The statistical analysis of control (Healthy subjects) and diseased (Periodontal subjects) using PLS-DA model resulted in R² of 0.84 and Q² of 0.79. There was an elevation in the concentration of statistically discriminant metabolites. The twenty newly identified metabolites in saliva indicates bacterial population shift along with change in homeostasis. These disturbs the biofilm, a real protector against any possible bio-damage on tooth surface. These newly identified metabolites could define better geographically diversified periodontal condition.

Conclusion

Analysis clearly differentiates healthy subjects from the diseased ones. Few newly identified metabolites along with the pool of metabolites may serve as biomarkers for distinguishing the severity and complexity of periodontitis.

     

Steroid concentrations in antepartum and postpartum saliva: normative values in women and correlations with serum

Background

Saliva has been advocated as an alternative to serum or plasma for steroid monitoring. Little normative information is available concerning expected concentrations of the major reproductive steroids in saliva during pregnancy and the extended postpartum.

Methods

Matched serum and saliva specimens controlled for time of day and collected less than 30?minutes apart were obtained in 28 women with normal singleton pregnancies between 32 and 38?weeks of gestation and in 43 women during the first six months postpartum. Concentrations of six steroids (estriol, estradiol, progesterone, testosterone, cortisol, dehydroepiandrosterone) were quantified in saliva by enzyme immunoassay.

Results

For most of the steroids examined, concentrations in antepartum saliva showed linear increases near end of gestation, suggesting an increase in the bioavailable hormone component. Observed concentrations were in agreement with the limited data available from previous reports. Modal concentrations of the ovarian steroids were undetectable in postpartum saliva and, when detectable in individual women, approximated early follicular phase values. Only low to moderate correlations between the serum and salivary concentrations were found, suggesting that during the peripartum period saliva provides information that is not redundant to serum.

Conclusions

Low correlations in the late antepartum may be due to differential rates of change in the total and bioavailable fractions of the circulating steroid in the final weeks of the third trimester as a consequence of dynamic changes in carrier proteins such as corticosteroid binding globulin.

     

High correlation between salivary cortisol awakening response and the psychometric profiles of healthy children

Background

Cortisol awakening response (CAR) as an indicator of psychological stress and related physical and psychiatric diseases has attracted growing attention from researchers. Although CAR changes have been investigated extensively in children with behavioral and psychiatric disorders, the association between CAR and conventional psychometric scales for healthy children has not been reported. The aim of this study was to investigate the association between salivary CAR and subscales of Profiles of Mood States (POMS), a self-assessment questionnaire widely used to evaluate the temporal emotional states of healthy children.

Findings

This study included 18 healthy girls aged 13–16 years. Saliva was collected immediately on awakening, 30 min and 60 min after waking, and then at 2-hour intervals from 9 am to 5 pm. The current mood state, including depression, anxiety, fatigue, and other psychometric profiles were assessed using POMS. The magnitude of salivary CAR and the area under the concentration-time curve (AUC) for diurnal salivary cortisol were compared with the profiles. There were significant positive correlations between the magnitude of CAR and the POMS subscales for "Depression-Dejection", "Tension-Anxiety", "Fatigue", and "Confusion". No correlation was found between the AUC salivary cortisol level and the psychometric profiles.

Conclusions

Salivary CAR was associated with various mood states of healthy female children but diurnal salivary cortisol AUC was not. Salivary CAR may be a biomarker of the physical and mental condition of healthy female children.

     

Possible benefits of singing to the mental and physical condition of the elderly

Background

The evaluation and management of stress are important for the prevention of both depression and cardiovascular disease. In addition, the maintenance of the oral condition of the elderly is essential to enable them to stay healthy, especially to prevent aspiration pneumonia and improve mental health in an aging society. Therefore, we examined the efficacy of singing on the oral condition, mental health status, and immunity of the elderly to determine if singing could contribute to the improvement of their physical condition.

Methods

Forty-four subjects (10 men, 34 women), aged 60 years or older, participated in this study. The efficacy of singing on mental health status and immunocompetence was examined by swallowing function, oral condition, blood, and saliva tests, as well as through questionnaires taken before and after singing.

Results

The results showed that the amount of saliva increased and the level of cortisol, a salivary stress marker, decreased after singing. The Visual Analog Scale (VAS) scores for feeling refreshed, comfortable, pleasurable, light-hearted, relieved, and relaxed; the tension and confusion subscale score; and the total mood disturbance (TMD) score of the Profile of Mood States (POMS) all showed improvements. Furthermore, the same tendencies were shown regardless of whether or not the subjects liked singing.

Conclusions

Our results suggest that singing can be effective in improving the mental health and oral condition of the elderly.

     

Effect of food intake on myocardial performance index

Background

Myocardial performance index (MPI) has been investigated in a variety of populations, but the effect of food intake has not been evaluated. We assessed whether myocardial performance index is affected by food intake in healthy subjects.

Methods

Twenty-three healthy subjects aged 25.6?±?4.5 years were investigated. MPI was measured before, 30 min after, and 110 min after a standardized meal.

Results

MPI decreased significantly (P?<?0.05) from fasting values 30 min after the meal, and had almost returned to baseline after 110 min. MPI decreased from 0.28?±?0.06 (fasting) to 0.20?±?0.07 30 min after eating. At 110 min after eating the index value was almost back to the baseline value 0.26?±?0.06. (P?=?0.15).

Conclusions

This study shows that myocardial performance index is affected by food intake in healthy subjects.

     

MicroRNA-144-3p inhibits proliferation and induces apoptosis of human salivary adenoid carcinoma cells via targeting of mTOR

Objectives

To investigate the biological functions of microRNA-144-3p with respect to proliferation and apoptosis of human salivary adenoid carcinoma cell lines via mTOR.

Results

After transfection of microRNA-144-3p agomir, cell viability assays confirmed that the salivary adenoid carcinoma cell (SACC) proliferation was inhibited and apoptosis was induced. Dual luciferase reporter assay validated that the mammalian target of rapamycin (mTOR) was a direct target of miR-144-3p. Western blot, immunofluorescent analysis and a xenograft mouse model of adenoid cystic carcinoma indicated that miR-144-3p was a tumor suppressor and repressed mTOR expression and signaling in SACCs.

Conclusions

MicroRNA-144-3p inhibits proliferation and induces apoptosis of human salivary adenoid carcinoma cells by downregulating mTOR expression in vitro and in vivo.

     

Bile acid quantification of 20 plasma metabolites identifies lithocholic acid as a putative biomarker in Alzheimer’s disease

Introduction

There is still a clear need for a widely available, inexpensive and reliable method to diagnose Alzheimer’s disease (AD) and monitor disease progression. Liquid chromatography–mass spectrometry (LC-MS) is a powerful analytic technique with a very high sensitivity and specificity.

Objectives

The aim of the present study is to measure concentrations of 20 bile acids using the novel Kit from Biocrates Life Sciences based on LC-MS technique.

Methods

Twenty bile acid metabolites were quantitatively measured in plasma of 30 cognitively healthy subjects, 20 patients with mild cognitive impairment (MCI) and 30 patients suffering from AD.

Results

Levels of lithocholic acid were significantly enhanced in plasma of AD patients (50?±?6 nM, p?=?0.004) compared to healthy controls (32?±?3 nM). Lithocholic acid plasma levels of MCI patients (41?±?4 nM) were not significantly different from healthy subjects or AD patients. Levels of glycochenodeoxycholic acid, glycodeoxycholic acid and glycolithocholic acid were significantly higher in AD patients compared to MCI patients (p?<?0.05). All other cholic acid metabolites were not significantly different between healthy subjects, MCI patients and AD patients. ROC analysis shows an overall accuracy of about 66%. Discriminant analysis was used to classify patients and we found that 15/23 were correctly diagnosed. We further showed that LCA levels increased by about 3.2 fold when healthy subjects converted to AD patients within a 8–9 year follow up period. Pathway analysis linked these changes to a putative toxic cholesterol pathway.

Conclusion

In conclusion, 4 bile acids may be useful to diagnose AD in plasma samples despite limitations in diagnostic accuracy.

     

Characterization of ankylosing spondylitis and rheumatoid arthritis using <Superscript>1</Superscript>H NMR-based metabolomics of human fecal extracts

Introduction

The differences in fecal metabolome between ankylosing spondylitis (AS)/rheumatoid arthritis (RA) patients and healthy individuals could be the reason for an autoimmune disorder.

Objectives

The study explored the fecal metabolome difference between AS/RA patients and healthy controls to clarify human immune disturbance.

Methods

Fecal samples from 109 individuals (healthy controls 34, AS 40, and RA 35) were analyzed by ¹H NMR spectroscopy. Data were analyzed with principal component analysis (PCA) and orthogonal projection to latent structure discriminant (OPLS-DA) analysis.

Results

Significant differences in the fecal metabolic profiles could distinguish AS/RA patients from healthy controls but could not distinguish between AS and RA patients. The significantly decreased metabolites in AS/RA patients were butyrate, propionate, methionine, and hypoxanthine. Significantly increased metabolites in AS/RA patients were taurine, methanol, fumarate, and tryptophan.

Conclusion

The metabolome variations in feces indicated AS and RA were two homologous diseases that could not be distinguished by ¹H NMR metabolomics.

     

A randomized,double-masked,placebo-controlled crossover trial on the effects of L-ornithine on salivary cortisol and feelings of fatigue of flushers the morning after alcohol consumption

Background

Residual alcohol effects on physiological and psychological symptoms are commonly experienced the morning after alcohol consumption. The purpose of this study was to assess the effects of L-ornithine on subjective feelings and salivary stress markers the morning after alcohol consumption and to investigate whether L-ornithine acutely accelerates ethanol metabolism.

Methods

This study had a randomized, placebo-controlled, double-masked crossover design. Subjects were all healthy Japanese adults with the ‘flusher’ phenotype for alcohol tolerance. In experiment 1, 11 subjects drank 0.4 g/kg body weight alcohol 1.5 h before their usual bedtime. Half an hour after drinking, they ingested either a placebo or 400 mg ornithine. The next morning on awakening, subjects completed a questionnaire containing a visual analog scale (VAS), the Oguri-Shirakawa-Azumi sleep inventory MA version (OSA-MA), and a profile of mood states (POMS) and collected a saliva sample for measurement of salivary stress markers (cortisol, secretory immunoglobulin A, and α-amylase). In experiment 2, placebo or 400 mg ornithine were administrated to 16 subjects both before and after drinking, and the feeling of drunkenness, breath ethanol concentration and one-leg standing time were repeatedly investigated until 180 min after alcohol consumption.

Results

There were significant decreases in “awareness”, “feeling of fatigue” and “lassitude” VAS scores and in “anger-hostility” and “confusion” POMS scores and a significant increase in “sleep length” in the OSA-MA test. Salivary cortisol concentrations on awakening were reduced after ornithine supplementation. There were no differences between ornithine and placebo in any of the subjective or physiological parameters of acute alcohol metabolism.

Conclusions

Taking 400 mg ornithine after alcohol consumption improved various negative feelings and decreased the salivary stress marker cortisol the next morning. These effects were not caused by an increase in acute alcohol metabolism.

     

Psychosocial distress and functioning of Greek youth with cystic fibrosis: a cross-sectional study

Background

To assess psychosocial functioning and distress of children and adolescents with cystic fibrosis compared to healthy controls.

Methods

Thirty-six patients with cystic fibrosis aged 8–18 years (24 boys, mean age?±?SD: 11.5?±?2.6 years) and 31 sex- and age-matched healthy control subjects (18 boys, mean age?±?SD: 12?±?2.5 years) were enrolled in the study. In order to assess the self-esteem, social adjustment, and family functioning of these young people, the Culture-free Self-esteem Inventory, the Social Adjustment Scale–Self-Report, and the Family Assessment Device were administered. Emotional/ behavioral problems were assessed through the Youth Self Report and the Child Behavior Checklist given to both the subjects and their parents.

Results

No significant differences were found for self-esteem between the two study groups. Regarding social adjustment, children with cystic fibrosis reported significantly worse friendship and overall adjustment (P?<?0.05). Moreover, no difference was found in the levels of family functioning between the two groups. No significant differences between the groups were found in emotional/ behavioral problems from the self-reports. On the contrary, parents of children with cystic fibrosis reported significantly higher levels of withdrawal/ depression, thought problems, and delinquent behavior (P?≤?0.01) as compared to controls.

Conclusions

Children and adolescents with cystic fibrosis appear to be a psychosocially vulnerable group. A biopsychosocial approach should emphasize the assessment and treatment of the psychosocial distress of these patients alongside multiple somatic treatments.

     

Optimization of fecal sample preparation for untargeted LC-HRMS based metabolomics

Introduction

Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.

Objectives

In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.

Methods

The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.

Results

A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.

Conclusion

The workflow generated repeatable and informative fingerprints for robust metabolome characterization.

     

Minimal variation of the plasma lipidome after delayed processing of neonatal cord blood

Background

Cord blood lipids are potential disease biomarkers. We aimed to determine if their concentrations were affected by delayed blood processing.

Method

Refrigerated cord blood from six healthy newborns was centrifuged every 12 h for 4 days. Plasma lipids were analysed by liquid chromatography/mass spectroscopy.

Results

Of 262 lipids identified, only eight varied significantly over time. These comprised three dihexosylceramides, two phosphatidylserines and two phosphatidylethanolamines whose relative concentrations increased and one sphingomyelin that decreased.

Conclusion

Delay in separation of plasma from refrigerated cord blood has minimal effect overall on the plasma lipidome.

     

Factor XIII Val34Leu polymorphism and risk of recurrent pregnancy loss in Iranian population: a case control study

BACKGROUND

Recurrent pregnancy loss (RPL) is a heterogeneous condition and thrombophilias have been considered as a probable cause.

OBJECTIVE

The aim of this study was to investigate the prevalence of the coagulation factor XIII Val34Leu polymorphism among women with unexplained RPL.

METHODS

A total of 140 women with a history of unexplained RPL and 100 age-matched healthy fertile women were recruited. The presence of FXIII Val34Leu polymorphism among the cases and controls was investigated using PCR-RFLP method.

RESULTS

Genotype analyses of the subjects revealed that the patients had a significantly higher prevalence of V/L and L/L than the controls (P<0.05): 33.5% vs. 15%, and 9.2% vs. 2%, respectively.

CONCLUSION

These results indicate a significant association between FXIII Val34Leu polymorphism and unexplained RPL in the Iranian patient.

     

A lost opportunity for science: journals promote data sharing in metabolomics but do not enforce it

Introduction

Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.

Objectives

(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.

Methods

A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.

Results

Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.

Conclusion

Further efforts are required to improve data sharing in metabolomics.

     

FimAsartaN proTeinuriA SusTaIned reduCtion in comparison with losartan in diabetic chronic kidney disease (FANTASTIC): study protocol for randomized controlled trial

Background

Fimasartan is the ninth angiotensin receptor blocker to be developed. However, it has not yet been evaluated for reno-protective effects in hypertensive diabetic chronic kidney disease (CKD). The target blood pressure (BP) for hypertensive diabetic CKD is also a controversial topic. This trial was designed to assess the reno-protective effects of fimasartan compared to those of losartan as a primary outcome. This study also compares the two drugs with regard to cardiovascular and renal outcomes in accordance with target systolic BP (SBP) (as secondary outcomes).

Methods

This study is a prospective, phase III, randomized, double-blind, active-controlled, non-inferiority, four-parallel group, dose-titration, multicenter trial. We recruit patients with hypertensive diabetic CKD with overt proteinuria. Participants will be randomized into four groups (1:1:1:1): fimasartan standard SBP control (SBP?<?140 mmHg); fimasartan strict SBP control (SBP?<?130 mmHg); losartan standard SBP control; and losartan strict SBP control. After 24 weeks, all individuals are treated with fimasartan for an additional 120 weeks in an open-label design, maintaining their assigned SBP control groups as randomized. The primary endpoint is the rate of change in proteinuria, which is assessed using the spot urine albumin–creatinine ratio at 24 weeks. The secondary endpoints are the cardiovascular and renal outcomes at 144 weeks compared between the strict SBP and standard SBP control groups.

Discussion

The FANTASTIC is a clinical study to provide: (1) the reno-protective effect of fimasartan; and (2) the target BP to reduce adverse outcomes in hypertensive diabetic CKD with overt proteinuria.

Trial registration

Clinicaltrials.gov, NCT02620306. Registered on 1 December 2015.

     

Successful pregnancy after breast cancer therapy: dream or reality?

Background

Nowadays, more breast cancer patients want to have children after the diagnosis of cancer. The purpose of this study is to review the possibility and risks of giving birth among women with breast cancer previously treated by chemotherapy.

Case presentation

Two young women aged 28 and 34 respectively, were treated in our clinic for breast cancer, the first (negative hormonal receptors) by surgery, chemotherapy and radiotherapy and the second (positive hormonal receptors) by surgery, radiotherapy and tamoxifen. They both became pregnant, 1 and 8 years after completion of the therapy respectively.

Results

Laboratory testing during pregnancy was negative in both cases and after an uneventful course each woman gave birth to a perfectly healthy child. The first patient breastfed her baby for three months, while the second one did not breastfeed her baby at all.

Conclusion

Women undergoing chemotherapy for breast cancer can maintain their fertility and get pregnant. Previous chemotherapy for breast cancer does not present any supplementary risks for the child's mental or physical health.

     

Pseudo current density maps of electrophysiological heart,nerve or brain function and their physical basis

Background

In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.

Methods

The physical basis of these intuitive maps is clarified by means of analytically solvable problems.

Results

Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.

Conclusion

Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.

     

Untargeted metabolomics suffers from incomplete raw data processing

Introduction

Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.

Objectives

Assessment of the quality of raw data processing in untargeted metabolomics.

Methods

Five published untargeted metabolomics studies, were reanalyzed.

Results

Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.

Conclusion

Incomplete raw data processing shows unexplored potential of current and legacy data.

     

Factors associated with anxiety in family caregivers of children with chronic diseases

Background

Currently, information on factors associated with anxiety in family caregivers of children with chronic diseases is unavailable, indicating a significant gap in the literature. Therefore, this study aims to identify the psychosocial and sociodemographic variables associated with anxiety in family caregivers of children with chronic diseases.

Methods

In 2018, a nonprobability sample of 446 family caregivers was recruited at the National Institute of Health in Mexico City. The participants completed a sociodemographic variable questionnaire, clinical questions, and 18 psychosocial assessment scales, including a scale to assess family caregiver anxiety.

Results

Family caregiver anxiety was correlated with almost all psychosocial variables and one out of three clinical variables but with none of the sociodemographic variables. Furthermore, a multiple linear regression model with five psychosocial variables was established to predict family caregiver anxiety.

Conclusions

Some psychosocial variables have effects on caregiver anxiety that are relevant for interventions. Clinical interventions should be implemented based on the psychosocial variables associated with family caregiver anxiety.