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Funding
There was no funding for this work.
PMC10523642
Availability of data and materials
The trial has been registered at ClinicalTrials.gov (identifier NCT03590509). Deidentified individual participant data will not be made available.
PMC10523642
Declarations
PMC10523642
Ethics approval and consent to participate
Ethics approval was obtained from all participants, as described in Mosquera et al.
PMC10523642
Consent for publication
All the authors have consented to the publication.
PMC10523642
Competing interests
The authors declare that they have no competing interests.
PMC10523642
References
PMC10523642
2. Materials and Methods
PMC10000597
2.2. Mouse Splenocyte Stimulation and Enzyme-Linked Immunosorbent Assay–Based Detection of Cytokines
LYSIS, FRANKLIN
The mouse spleen was excised, passed through a 45 µm cell strainer (BD Biosciences, Franklin Lakes, NJ, USA) for conversion into a single-cell suspension, then subjected to red blood cell lysis by using RBC lysis buffer (eBiosciences Inc., San Diego, CA, USA). Isolated splenocytes were seeded into a 96-well-plate at a ...
PMC10000597
2.3. Antimicrobial Susceptibility Profiling
SEPARATION, FRANKLIN, MRS
Antimicrobial susceptibility was determined by using the broth microdilution method and lymphocyte separation medium (LSM, including 90% IST medium [Cat. No. CM0473; Oxoid, Basingstoke, Hampshire, UK] and 10% MRS medium (Cat. No. 288130; Difco Laboratories Inc., Franklin Lakes, NJ, USA) in accordance with the guideline...
PMC10000597
2.4. DNA Extraction, Whole-Genome Sequencing, and Hybrid Genome Assembly
We established a whole-genome sequencing (WGS) assembly pipeline in accordance with a previously reported procedure [
PMC10000597
2.5. Annotation of Protein-Coding Genes, Virulence Factors, and Antibiotic Resistance
The protein-coding genes in the GM-080 genome were annotated by using Prokka [
PMC10000597
2.6. OVA-Induced AHR Mouse Model
Allergic airway inflammation
Seven-week-old female BALB/c mice were purchased from The Experimental Animal Facility of the College of Medicine, National Taiwan University (Taipei, Taiwan). Allergic airway inflammation was induced with an intraperitoneal injection of 50 µg of OVA (purchased from Sigma-Aldrich) mixed with the Th2-adjuvant aluminum h...
PMC10000597
2.7. ELISA Determination of OVA-Specific Immunoglobulins
A 96-well plate was coated with OVA at 1 µg/well and then incubated with blocking solution (1% bovine serum albumin in PBS buffer) at room temperature. The wells were added with mouse serum followed by antibodies diluted with the blocking solution (1:50, 1:1000, and 1:10,000 dilutions for IgE, IgG2a, and IgG1, respecti...
PMC10000597
2.8. AHR Determination
In mice, the development of AHR was determined on a Buxco system (Biosystem XA; Buxco Electronics, Sharon, CT, USA). The enhanced pause (Penh) values were calculated with the following formula: (
PMC10000597
2.9. BALF Collection and White Blood Cell Count
BALF was collected through lung flushing with HBSS buffer containing 2% bovine serum albumin three times by using a trachea cannula (Angiocath, BD Biosciences). BALF cells were then collected through centrifugation at 300×
PMC10000597
2.10. Patient Recruitment
PAR was diagnosed in accordance with the definition of Saleh and Durham, i.e., symptoms lasting more than 4 days per week and illness duration lasting more than 4 weeks [
PMC10000597
2.11. Randomized, Double-Blind, Placebo-Controlled Trial Design
ALLERGY
The randomized, double-blind, placebo-controlled trial on PAR was designed in accordance with the guidance for developing drug products for AR treatment published by the Division of Pulmonary, Allergy, and Rheumatology Products in the Center for Drug Evaluation and Research at the Food and Drug Administration (April 20...
PMC10000597
2.12. Skin Prick Tests and Serum Biomarkers
SKIN
Skin prick tests were performed with commercial allergen extracts of egg, milk, crab, mite, cockroach, and animal dander (ALK-Abell & Oacute, Round Rock, TX, USA). Skin reactivity to allergen sensitization was classified into four grades as previously described [
PMC10000597
2.13. Statistical Analysis
inflammation
INFLAMMATION
The data from in vitro and OVA-induced airway inflammation mouse model experiments were presented as means ± standard deviations and were analyzed for differences between groups by using one-way analysis of variance (ANOVA), followed by Tukey’s Honestly Significant Difference test. The chi-square test was conducted to ...
PMC10000597
3. Results
PMC10000597
3.1. GM-080 Induces Th1 Cytokine Production in Mouse Splenocytes
The Th1 cytokines of IFN-γ or IL-12 have been demonstrated to suppress AHR in response to allergens [
PMC10000597
3.2. WGS Analysis Revealed That GM-080 Is a Safe L. paracasei Strain
We performed WGS analysis on GM-080 by using next-generation sequencing. The genetic organization of GM-080 was illustrated in a genome atlas created by using Circos (
PMC10000597
3.3. GM-080 Genome Contains Immunosuppressive Motifs and CpG-Containing Oligonucleotides That Induce Th1 Cytokines in Mouse Splenocytes
We compared the genomes of GM-080 and BCRC 16100 to identify the potential functional genes in GM-080. As indicated by the phylogenetic tree (
PMC10000597
3.4. Orally Gavage GM-080 Alleviates OVA-Induced Allergic Airway Inflammation in Mice
We established an OVA-induced AHR mouse model by using the protocol shown in
PMC10000597
3.5. GM-080 Alleviates PAR in Children
Finally, we conducted a double-blind, randomized, placebo-controlled trial to investigate the beneficial effects of GM-080 in children with PAR. The study design was summarized in We next examined the effects of GM-080 on patients’ quality of life by using TNSSs. TNSSs are a convenient tool for symptom description and ...
PMC10000597
Supplementary Materials
The following supporting information can be downloaded at: Click here for additional data file.
PMC10000597
Author Contributions
W.-H.T. designed the in vitro and animal studies. C.-H.C. performed the in vitro and animal studies. J.-H.J. performed the WGS analysis. W.-H.T. and I.-J.W. analyzed the data. E.-K.L., W.-W.C., W.-H.T. and I.-J.W. wrote the article. All authors have read and agreed to the published version of the manuscript.
PMC10000597
Institutional Review Board Statement
The study was conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of Taipei Veterans General Hospital (Taipei City, Taiwan) with a reference number of 05-016-A at the date of 13 November 2006, and it was registered on ISRCTN registry (ISRCTN14829274,
PMC10000597
Informed Consent Statement
Informed consent was obtained from all subjects involved in the study. Written informed consent has been obtained from the patient(s) to publish this paper.
PMC10000597
Data Availability Statement
The whole genome sequencing data of BCRC 16100 were available in GenBank
PMC10000597
Conflicts of Interest
Taipei Hospital, Ministry of Health and Welfare Authority has a contract with GenMont Biotech, which provided funds for probiotics. W.H.T. and C.H.C. are the employee in GenMont Biotech.
PMC10000597
Abstract
Acute exercise suppresses appetite and alters food‐cue reactivity, but the extent exercise‐induced changes in cerebral blood flow (CBF) influences the blood‐oxygen‐level‐dependent (BOLD) signal during appetite‐related paradigms is not known. This study examined the impact of acute running on visual food‐cue reactivity ...
PMC10203797
INTRODUCTION
SECONDARY
The interaction of exercise with appetite control and food intake attracts widespread interest due to the ability of exercise to influence weight management (Blundell et al., Appetite‐related brain responses can be explored using blood‐oxygen‐level‐dependent (BOLD) functional magnetic resonance imaging (fMRI), which is...
PMC10203797
METHODS
PMC10203797
Ethical approval and participant eligibility
RECRUITMENT
The study received approval from Loughborough University's Research Ethics Sub‐Committee. Twenty‐three healthy men provided written informed consent to participate in the study. Recruitment was restricted to men as previous work has identified sex‐based differences in neural responses to visual food cues particularly u...
PMC10203797
Preliminary measures
Participants were screened to determine eligibility for the study and completed questionnaires assessing general health status, MRI safety, habitual physical activity levels (short form International Physical Activity Questionnaire; Craig et al., 
PMC10203797
Experimental design
SE, HED
Using a within‐measures, crossover design, participants completed two experimental trials in a random order separated by at least 1 week: (1) exercise and (2) control. The study design is presented in Figure Schematic of the study protocol. (a) Timeline of the trial procedures and functional magnetic resonance imaging ...
PMC10203797
Main trials
HEART, STAGGERED
Participants were instructed to consume 250 mL of plain water before arrival at the laboratory between 08:00 and 08:30 having fasted overnight for at least 12 h. Body mass and body fat percentage were measured at the start of each trial using bioelectrical impedance analysis (Seca Ltd, Hamburg Germany). After 20 min of...
PMC10203797
Ratings of perceived appetite
fullness
Subjective ratings of hunger, fullness, satisfaction and prospective food consumption were recorded using 100 mm visual analogue scales (Flint et al., 
PMC10203797
Food cue paradigm
HED
During the food cue reactivity task, four categories of colour images were presented in a single run using a block design: (1) very low‐ and low‐energy density foods (LED; Stimuli were presented in eight blocks each containing five images from the LED, HED and non‐food object categories, which were interspersed with 16...
PMC10203797
Structural and functional MRI was performed on a GE 3.0 T Discovery MR750w scanner (General Electric, Boston, USA) using a 32‐channel head coil. A timeline of the scan protocol is shown in Figure 
PMC10203797
Analysis of functional data (pCASL and task based) was conducted in the FMRIB Software Library (FSL) version 6.0.4 (Jenkinson et al., 
PMC10203797
Pre‐processing stages and regions of interest
Detailed information on pre‐processing of functional data is presented in the supplementary methods (Section 
PMC10203797
Main analysis
PMC10203797
Pseudo‐continuous arterial spin labelling
Using a non‐parametric permutation approach in FSL's Randomise (Winkler et al., a the Separate models were run for each grey matter and ROI mask using threshold‐free cluster enhancement (TFCE) and a family‐wise corrected
PMC10203797
Task‐based fMRI
HED
In whole‐brain analysis at the first level, explanatory variables were entered into a general linear model in FSL's fMRI Expert Analysis Tool (FEAT) for the three image categories (LED, HED and non‐food cues) with a separate model run for each scan session per participant. Three contrasts were defined to examine respon...
PMC10203797
Regions of interest analysis
For the primary analysis, pre‐to‐post difference images for the exercise and control trials were created from the first level contrasts of parameter estimates to generate the input images. Paired In all functional analysis (pCASL and task‐based fMRI), only clusters comprising ≥10 continuous voxels are reported. In sens...
PMC10203797
Statistical analyses
The model residuals of the appetite perceptions were shown to follow a Gaussian distribution after inspection using histograms and are presented as mean ± SD unless indicated otherwise. Time‐averaged (per hour) area under the curve (AUC) values for each rating of perceived appetite were computed using the trapezium rul...
PMC10203797
RESULTS
PMC10203797
Exercise responses
Treadmill running was performed at an average speed of 11.6 ± 1.4 km/h which elicited a mean heart rate of 169 ± 14 beats/min and a mean oxygen consumption of 3.08 ± 0.39 L/min equivalent to 68% ± 3% of peak oxygen uptake. The non‐protein respiratory exchange ratio was 0.93 ± 0.03, which corresponded to a proportional ...
PMC10203797
Ratings of perceived appetite
Time‐averaged intervention AUC for appetite perceptions (Figure Ratings of perceived (a) hunger, (b) fullness, (c) satisfaction and (d) prospective food consumption (PFC) in the control and exercise trials (
PMC10203797
Grey matter and regional
PMC10203797
Baseline analysis
Grey matter and regional CBF was not statistically different between the exercise and control trial at baseline (all
PMC10203797
Primary analysis
CORTEX
Main effects of trial identified voxel clusters with greater CBF in the exercise than control trial in grey matter, bilaterally in the region of the amygdala/hippocampus and in the right posterior insula (all Differences in regional cerebral blood flow (CBF) measured using pseudo‐continuous arterial spin labelling (pCA...
PMC10203797
PMC10203797
PMC10203797
Whole‐brain analysis
HED
CORTEX
Activation in the left frontal pole and right central opercular cortex was lower at baseline in the exercise than control trial in response to food (HED + LED) versus non‐food cues and LED versus non‐food cues (Table CBF‐adjusted whole‐brain analysis results of voxel clusters activated in the baseline difference betwee...
PMC10203797
PMC10203797
Whole‐brain analysis
HED
Whole‐brain group analysis revealed exercise increased the neural response to food (HED + LED) versus non‐food cues and LED versus non‐food cues in the left paracingulate gyrus compared to control (Figure Voxel clusters showing greater blood‐oxygen‐level‐dependent (BOLD) activity in the pre‐to‐post change between the e...
PMC10203797
Regions of interest analysis
HED
Greater pre‐to‐post reactivity to food (HED + LED) versus non‐food cues was identified in the left hippocampus in the exercise compared to control trial (
PMC10203797
Unadjusted
Analysis of food cue reactivity at baseline and in response to exercise without adjustment for CBF yielded broadly comparable findings to the CBF‐adjusted models and is presented in the supplementary results (Sections 
PMC10203797
Exploratory correlations
fullness
REGRESSION
The exercise‐induced change in time‐averaged total AUC for fullness was positively correlated with the between‐trial difference in hippocampus (Correlation between the exercise‐induced change in (a) hippocampus and (b) striatum cerebral blood flow (CBF) measured using pseudo‐continuous arterial spin labelling (pCASL) a...
PMC10203797
DISCUSSION
HED, adiposity, emotions and external stimulus‐orientated
RECRUITMENT, ADIPOSITY, CORTEX
The main findings from this study are that overall between‐trial differences in grey matter and regional CBF were apparent but the time‐course of CBF was not influenced directly by exercise in healthy young men. A single bout of running suppressed subjective appetite ratings and increased food cue reactivity in brain r...
PMC10203797
CONCLUSION
Despite identification of overall between‐trial differences in CBF, acute vigorous‐intensity running did not directly influence the time‐course of CBF suggesting food‐cue related BOLD acquisitions immediately after exercise may not be time sensitive at least in relation to any residual influence of CBF. Acute running t...
PMC10203797
AUTHOR CONTRIBUTIONS
PMC10203797
CONFLICT OF INTEREST STATEMENT
The authors declare no conflicts of interest.
PMC10203797
Supporting information
Click here for additional data file.
PMC10203797
ACKNOWLEDGEMENTS
This research was funded by King Saud bin Abdulaziz University for Health Sciences (Saudi Arabia), Jeddah University (Saudi Arabia), and the National Institute for Health and Care Research (NIHR) Leicester Biomedical Research Centre (United Kingdom). The views expressed are those of the authors and not necessarily thos...
PMC10203797
DATA AVAILABILITY STATEMENT
The de‐identified neuroimaging, physiological and behavioural data generated in this study are available from the corresponding author upon reasonable request.
PMC10203797
REFERENCES
PMC10203797
Background
inflammation, Periodontitis
INFLAMMATION, CHRONIC INFLAMMATORY DISEASE, CHRONIC PERIODONTITIS, PERIODONTITIS
Periodontitis is one of the most common chronic inflammatory diseases in the world, which affects oral health. Resveratrol is a polyphenol with therapeutic effects on the inflammation caused by periodontal pathogens. This study aimed to evaluate the impact of resveratrol supplementation on clinical parameters and infla...
PMC10045616
Methods
PD, bleeding
BLEEDING, CHRONIC PERIODONTITIS, PLAQUE
In this randomized, double-blind study, 40 chronic periodontitis patients underwent non-surgical therapy and were randomly assigned to two intervention and control groups, receiving either resveratrol supplements or a placebo for four weeks. Salivary levels of interleukin-8 (IL-8), interleukin-1β (IL-1β), and clinical ...
PMC10045616
Results
PD, bleeding
BLEEDING, PLAQUE
The results showed that in both the case and control groups, after four weeks of using resveratrol, only plaque index (PI) was significantly different compared to the control group (P = 0.0001). However, there were no significant differences in the mean pocket depth (PD), clinical attachment loss (CAL), bleeding index ...
PMC10045616
Conclusion
CHRONIC PERIODONTITIS
Resveratrol complement was helpful as an anti-inflammatory food supplement, along with other non-surgical periodontal treatments in chronic periodontitis patients.
PMC10045616
Supplementary Information
The online version contains supplementary material available at 10.1186/s12903-023-02877-4.
PMC10045616
Keywords
PMC10045616
Introduction
tooth loss, Periodontitis
PERIODONTITIS, PERIODONTAL DISEASES, INFLAMMATORY DISEASE, PERIODONTITIS
Periodontitis is an inflammatory disease that leads to the destruction of dental supporting tissues and tooth loss [Given the complex processes created by different pro-inflammatory and anti-inflammatory mediators, studies have investigated different strategies for regulating immune-inflammatory responses to periodonta...
PMC10045616
Methods
PMC10045616
Subjects and study design
renal and hepatic diseases, periodontitis, allergy
OVARIAN CANCER, PERIODONTITIS, DISEASE, ALLERGY, PEMPHIGUS, LEUKOPLAKIA
In this randomized, double-blind clinical trial, 40 periodontitis patients referring to the Periodontics Department of Dental School, Shahid Sadoughi University of Medical Sciences, Yazd, were selected. According to the principles of the Helsinki declaration, after examination and diagnosis of periodontal symptoms and ...
PMC10045616
Periodontal examination
periodontitis, teeth and disease, tooth loss, PD
PERIODONTITIS, PLAQUE, PERIODONTITIS
Periodontitis patient with stage II (moderate periodontitis) to stage IV (advanced periodontitis with extensive tooth loss) based on clinical attachment loss (CAL) of ≥ 3 mm around the teeth and disease severity according to 2017 international periodontology workshop were selected. As all patients in our study didn’t h...
PMC10045616
Biochemical measurement
STERILE, CAVITY
Salivary samples of all the patients were collected at baseline and four weeks after the intervention to assess IL-8 and IL-1β levels. All the salivary samples were collected between 9 a.m. and 12 p.m. The patients were asked to refrain from brushing 12 h before sampling and refrain from eating, drinking, and chewing g...
PMC10045616
Intervention
For all the patients (both case and control groups), scaling and root planning by an ultrasonic scaler (ultrasonic piezo scaler Uds-K, Woodpecker, China) was performed. Patients in the case group received 480 mg (2 capsules) of resveratrol (HERBAFIT Co.) daily for four weeks, while patients in the control group receive...
PMC10045616
Outcome (primary and secondary)
PD
SECONDARY, PLAQUE
The primary outcome of this study was to determine the CAL and PD before and after the intervention. The secondary outcome of this study was to evaluate the O’Leary plaque index, BI and the mean salivary levels of IL-8 and IL-1β before and after intervention between two groups.
PMC10045616
Sample size calculation
Considering a 5% significance level, 80% test power, and according to the results of a previous study [
PMC10045616
Statistical analysis
SPSS 23.0 was used to compare the results and determine the differences in different experiments. A Kolmogorov-Smirnov test was to assess distribution normality. Also, the chi-squared test, independent-samples t-test, and paired-samples statistics were used to compare the changes between the two groups. Statistical sig...
PMC10045616
Discussion
PD, bleeding, periodontitis, periodontium
SYSTEMIC DISEASE, BLEEDING, PERIODONTITIS, CHRONIC PERIODONTITIS, PLAQUE, TYPE 2 DIABETES
The present research is one of the first studies to investigate the effect of resveratrol supplementation on periodontitis. In this double-blind study with a placebo control, the effectiveness of resveratrol as a supplementary treatment for clinical indicators (PD, CAL, PI, and BI) and salivary inflammatory indicators ...
PMC10045616
Conclusion
periodontitis
PERIODONTITIS, PLAQUE
In view of the above findings and within the limits of present study the results indicated that supplementation with resveratrol in combination with non-surgical periodontal treatment has significant effect on reduction of plaque index (PI) during 4 weeks. Collectively, it seems that using resveratrol along with nonsur...
PMC10045616
Acknowledgements
We would like to thank the Vice-Chancellor for Technology Research of Shahid Sadoughi University of Medical Sciences in Yazd for approving and fnancially supporting the project with the code no: 5824.
PMC10045616
Authors’ contributions
Shabnam Nikniaz
All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Farzane Vaziri, Reza Mansouri and Shabnam Nikniaz. The first draft of the manuscript was written by Shabnam Nikniaz and all authors commented on previous versions of the manuscript. All autho...
PMC10045616
Funding
The Vice Chancellor for Research and Technology of Yazd Shahid Sadoughi University of Medical Sciences. (Grant no: 5824).
PMC10045616
Data availability
The data generated and analyzed during the current study are available from the corresponding author on reasonable request.
PMC10045616
Declarations
PMC10045616
Ethics approval and consent to participate
The study was approved in the Ethics Committee of Shahid Sadoughi University of Medical Sciences under the code IR.SSU.REC.1396.206, and the IRCT Registration code was IRCT20171015036782N6. After examination and diagnosis of periodontal symptoms, the necessary information was provided and written informed consent was o...
PMC10045616
Consent for publication
Not applicable.
PMC10045616
Competing interests
The author declare there is no competing interest.
PMC10045616
Abbreviations
Interleukin 8Interleukin 1 betaPocket depthClinical attachment lossPlaque index (oral hygiene)Bleeding index
PMC10045616
References
PMC10045616
Key Points
PMC10277935
Question
aneurysmal subarachnoid hemorrhage
Does prophylactic lumbar cerebrospinal fluid drainage improve clinical outcomes measured by the modified Rankin Scale score among patients with aneurysmal subarachnoid hemorrhage?
PMC10277935