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Biology subjects

Pardini, B.

Publications and source records attributed to Pardini, B..

3 recordsLinked to original sources

Altered salivary miRNA profiles and microbiome composition correlate with psychosocial stress

BackgroundPsychosocial stress is a risk factor for mental and physical illness. Previous studies have shown the potential of microRNAs (miRNAs) and the microbiome as biomarkers and/or mediators for stress responses. Here, we aimed to identify changes in these molecular markers in saliva samples from a cohort of 113 male police officers in service, stratified by stress response (SR) level (low, intermediate, and high), as a reference model for psychosocial stress. MethodsSalivary miRNome profiles and microbiome composition were analyzed by small RNA sequencing and shotgun metagenomics, respectively. SR-related miRNAs were identified with Docker4Seq and DESeq2 and functionally characterized using RBiomirGS. Differences in microbial communities among study groups were analyzed using MetaPhlAn, and microbial pathway prediction was performed with HUMAnN. A multi-omics integration of miRNA and microbial profiles was performed with the mixOmics framework. ResultsEighteen miRNAs were dysregulated (adj. p<0.05) between high- and low-SR groups and showed a progressive alteration from low- to high-SR groups. Functional enrichment analysis indicated that dysregulated miRNA targets were involved in apoptosis, cellular stress responses, and metabolic regulation. Despite limited shifts in oral microbial composition and diversity among the SR groups, the high-SR group showed a significant (adj. p<0.1) increase in microbial species involved in inositol degradation pathways, as well as a decrease in bacteria involved in L-tryptophan and thiamine biosynthesis, whose altered levels distinguished the high-SR group. ConclusionsSalivary miRNAs and oral microbiota may serve as non-invasive indicators of SR, helping to understand chronic psychosocial stress and cellular and behavioral responses. Plain language summaryPsychosocial stress is a major risk factor for mental and physical illness, with emerging evidence pointing to oral miRNAs and the microbiome as potential biomarkers. This study investigated stress-associated molecular changes in saliva from 113 male police officers stratified by perceived stress response (SR) into low, intermediate, or high responders. Eighteen miRNAs were dysregulated between high- and low-SR groups, whose target genes were involved in apoptosis, cellular stress responses, and metabolic regulation. Despite limited shifts in microbial populations, a functional analysis indicated increased taxa involved in inositol degradation and reduced taxa involved in L-tryptophan and thiamine biosynthesis, distinguishing high-SR individuals. These findings suggest that salivary miRNAs and microbiota may serve as non-invasive indicators of psychosocial stress, whose altered levels could reflect different SR.

molecular biology↗

Fasting-mimicking diet counteracts gut microbial dysbiosis in experimental Lynch syndrome

The development of colorectal cancer (CRC) is largely influenced by hereditary factors, with up to one-third of cases linked to genetic predisposition. In parallel, environmental factors such as diet and intestinal microbiota play a significant role. Lynch syndrome (LS), the most common form of hereditary CRC, is due to mutations in DNA mismatch repair genes. Diet interventions such as calorie restriction (CR) can modify the course of the disease, altering nutrient supply and promoting beneficial microbial populations. Fasting-mimicking diets (FMD) are plant-based CR regimens that showed promise in modulating the gut microbiota and suppressing CRC progression in pre-clinical ectopic cancer models. In this study, Villin-Cre/Msh2-floxed (VCM) mice, modelling LS, were subjected to periodic FMD cycles for 10 months. Although not impacting on macroscopic tumor development, FMD influenced animal weight in a sexually dimorphic manner. Moreover, shotgun metagenomic sequencing revealed that FMD mitigated the dysbiotic longitudinal changes associated with cancer onset, preserving beneficial species, such as Lactobacillus johnsonii, and reducing adverse species, such as Escherichia coli. Metabolic pathway analysis also showed significant differences, with FMD preventing the upregulation of pathways involved in amino acid and nucleotide synthesis, potentially promoting tumor growth. Overall, the findings suggest that periodic FMD may be adopted as an adjuvant therapy in LS management, counteracting gut microbiota alterations.

pathology↗

TACSTD2 expression marks the early transition to colon adenomas

This study aimed to address new molecular events occurring in precancerous stages of colorectal cancer (CRC) by integrated analysis of gene expression data and DNA methylation profiles. Whole-transcriptome sequencing analysis was performed on 16 fresh frozen colorectal adenoma and matched mucosa specimens along with validation of candidates in an independent cohort of 20 fresh frozen paired adenoma and adjacent mucosa tissues as well as eight independent public datasets (335 cases). Genome-wide methylation profiles were determined for 5 adenoma pairs and confirmed by pyrosequencing on 20 tissue pairs used for validation. Functional analysis was performed in vitro and in vivo using the inflammation-associated azoxymethane/dextran sodium sulfate (AOM/DSS) and the sporadic colorectal carcinogenesis (six AOM injections) mouse models as well as ApcMin/+ mice. Candidates were investigated by immunohistochemical staining of human adenomas and early-stage (pT1) CRC tumors. A total of 1,917 differentially expressed genes and 148,191 differentially methylated CpG sites were detected in adenomas compared with adjacent mucosa samples. Based on the transcriptome data and relevance to CRC, TACSTD2, MMP7, MMP1, CLDN2, CLDN1, and ETV4, were selected for further validation. TACSTD2 promoter hypomethylation in adenoma tissues was validated in 20 additional tissue pairs and corresponded with increased TACSTD2 expression. TACSTD2 was also overexpressed in an in vitro transformation model of human colonic epithelial cells. The TACSTD2 protein TROP2 was elevated in human adenomas, pT1 tumors, and in murine adenomas, while it was absent in the unaffected adjacent mucosa. TROP2 overexpression might trigger the development of precancerous lesions and could help identify early transformation foci in colon biopsies. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/620817v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@1f23753org.highwire.dtl.DTLVardef@10e6abeorg.highwire.dtl.DTLVardef@181f500org.highwire.dtl.DTLVardef@fc0d38_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗