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The rate/quality of human aging and the development/progression of diseases depend on a complex interplay among genetics, epigenetics and environment. In this scenario, mitochondrial function (or dysfunction) and mitochondrial DNA have emerged as major players. This is mainly due to their crucial role in energetic balance, in modulating epigenetic programs and in influencing cell stress response. Moreover, it is also emerging the existence of epigenetic changes in mitochondrial DNA and of non coding mitochondrial RNAs which, together with the nuclear ones, play regulatory roles in numerous human phenotypes. In this review we will provide an overview on “mitochondrial epigenetics” state of the art, by summarizing the involvement of mitochondrial function and of mitochondria–nucleus communication in regulating nuclear epigenome, as well as the key aspects of the epigenetic marks related to mitochondrial DNA. Despite the limited data available in the literature to date, mainly due to the novelty of the topic, the intriguing interplay of the mitochondrial epigenetic changes in both physiological and pathological conditions will also be presented.

The human gut microbiota is a complex ecosystem consisting of trillions of microorganisms that inhabit symbiotically on and in the human intestine. They carry out, through the production of a series of metabolites, many important metabolic functions that complement the activity of mammalian enzymes and play an essential role in host digestion. Interindividual variability of microbiota structure, and consequently of the expression of its genes (microbiome), was largely ascribed to the nutritional regime. Diet influences microbiota composition and function with short- and long-term effects. In spite of the vast literature, molecular mechanisms underlying these effects still remain elusive. In this review, we summarized the current evidence on the role exerted by gut microbiota and, more specifically, by its metabolites in the establishment of the host epigenome. The interest in this topic stems from the fact that, by modulating DNA methylation and histone modifications, the gut microbiota does affect the cell activities of the hosting organism.

Antimicrobial resistance is emerging as a significant threat to public health, prompting the search for novel natural molecules, such as Essential Oils (EOs), that can affect, alone or in combination with conventional antibiotics, growth and various biological activities in microorganisms. First, the effects of ten essential oils extracted from aromatic plants grown in Calabria (Southern Italy) and seven conventional antibiotics against cells were studied individually, determining the Minimum Inhibitory Concentrations (MICs) through broth microdilutions. Subsequently, limited to EO (OEO) only, the compounds were evaluated in combination through checkerboard and time kill assays. ZIP synergy scores and Fractional Inhibitory Concentrations Indexes (FIC ) were calculated to determine the interactive effects of the combinations. At 0.5 x MIC concentration values of OEO-antibiotic combinations, the biofilm and the expression of genes involved in the Quorum Sensing (QS) process were determined by the crystal violet method and quantitative real-time PCR reactions, respectively. At the same concentrations, adenine and cytosine methylation levels were quantified through ELISA. The results showed that was highly sensitive only to OEO, in which a small MIC value was noticed (0.312 mg/mL). Synergistic effects were observed when combining OEO and ampicillin, gentamicin, tetracycline, and tobramycin, resulting in reductions of antibiotic MICs. An inhibition of biofilm formation and a general down-regulation of the expression of , , , and genes were observed. Similarly, up- and down-methylation of cytosines and adenines, respectively, compared to antibiotics alone was noticed. Taken together, our observations provide evidence on the role of the OEO-antibiotic combinations in enhancing the action of antibiotics on the growth and suggest that these combinations could influence biological processes such as biofilm formation, QS, and epigenetic changes.

With the widespread phenomenon of antibiotic resistance and the diffusion of multiple drug-resistant bacterial strains, enormous efforts are being conducted to identify suitable alternative agents against pathogenic microorganisms. Since an association between biofilm formation and antibiotic resistance phenotype has been observed, a promising strategy pursued in recent years focuses on controlling and preventing this formation by targeting and inhibiting the Quorum Sensing (QS) system, whose central role in biofilm has been extensively demonstrated. Therefore, the research and development of Quorum Quenching (QQ) compounds, which inhibit QS, has gradually attracted the attention of researchers and has become a new strategy for controlling harmful microorganisms. Among these, a number of both natural and synthetic compounds have been progressively identified as able to interrupt the intercellular communication within a microbial community and the adhesion to a surface, thus disintegrating mature/preformed biofilms. This review describes the role played by QS in the formation of bacterial biofilms and then focuses on the mechanisms of different natural and synthetic QS inhibitors (QSIs) exhibiting promising antibiofilm ability against Gram-positive and Gram-negative bacterial pathogens and on their applications as biocontrol strategies in various fields.

The biological role played by essential oils extracted from aromatic plants is progressively being recognized. This study evaluated the potential antibacterial activity of ten essential oils against Chromobacterium violaceum, Pseudomonas aeruginosa, and Enterococcus faecalis by measuring their minimum inhibitory concentration. We found that essential oils exert different antimicrobial effects, with Origanum vulgare and Foeniculum vulgare demonstrating the most significant inhibitory effect on bacterial growth for C. violaceum and E. faecalis. The growth of P. aeruginosa was not affected by any essential oil concentration we used. Sub-inhibitory concentrations of essential oils reduced in C. violaceum and E. faecalis biofilm formation, violacein amount, and gelatinase activity, all of which are biomarkers of the Quorum Sensing process. These concentrations significantly affect the global methylation profiles of cytosines and adenines, thus leading to the hypothesis that the oils also exert their effects through epigenetic changes. Considering the results obtained, it is possible that essential oils can find a broad spectrum of applications in counteracting microbial contamination and preserving sterility of surfaces and foods, as well as inhibiting microbial growth of pathogens, alone or in combination with traditional antibiotics.

Blood bacterial DNA (BB-DNA) has been identified as a novel biomarker for metabolic dysfunction, yet its relationship with epigenetic features in type 2 diabetes mellitus (DM2) patients remains largely unexplored. This study investigated the relationship between BB-DNA and epigenetic, inflammatory, and aging-related markers in 285 elderly both with and without DM2. BB-DNA levels were higher in DM2 patients than in non-diabetic subjects, with the highest levels in those with severe renal impairment. BB-DNA showed a positive association with plasma IL-1β, linking bacterial DNA to systemic inflammation. Epigenetic analysis revealed a negative correlation between BB-DNA and DNA methylation-based leukocyte telomere length, suggesting accelerated aging in DM2. Additionally, BB-DNA was positively associated with DNAm-based biological age estimators, particularly DNAmPhenoAge and DNAmAge Skin Blood Clock. BB-DNA also correlated with DNAmVEGFA and DNAmCystatin C, key markers of diabetic nephropathy and vascular dysfunction. Furthermore, BB-DNA levels were associated with hypomethylation of genes involved in inflammation (e.g., IL1β, TNFα, IFNγ), cellular senescence (p16, p21, TP53), and metabolic regulation (e.g., IGF1, SREBF1, ABCG1, PDK4). These associations suggest that increased BB-DNA may reflect and potentially promote a pro-inflammatory and pro-senescent epigenetic profile in DM2. Importantly, many of these associations remained significant after adjusting for diabetes status, supporting BB-DNA as a robust biomarker across clinical subgroups. These findings provide new insights into the relationship between BB-DNA, inflammation, and epigenetic aging in DM2, highlighting BB-DNA as a potential biomarker for disease progression and complications, particularly in relation to renal dysfunction and systemic inflammation.

Nutrition plastically modulates the epigenetic landscape in various tissues of an organism during life via epigenetic changes. In the present study, to clarify whether this modulation involves RNA methylation, we evaluated global RNA methylation profiles and the expression of writer, reader, and eraser genes, encoding for enzymes involved in the RNA methylation. The study was carried out in the heart, liver, and kidney samples from rats of different ages in response to a low-calorie diet. We found that, although each tissue showed peculiar RNA methylation levels, a general increase in these levels was observed throughout the lifespan as well as in response to the six-month diet. Similarly, a prominent remodeling of the expression of writer, reader, and eraser genes emerged. Our data provide a comprehensive overview of the role exerted by diet on the tissue-specific epigenetic plasticity of RNA according to aging in rats, providing the first evidence that methylation of RNA, similarly to DNA methylation, can represent an effective biomarker of aging. What is more, the fact that it is regulated by nutrition provides the basis for the development of targeted approaches capable of guaranteeing the maintenance of a state of good health.

The spread of antibiotic-resistant pathogens has prompted the development of novel approaches to identify molecules that synergize with antibiotics to enhance their efficacy. This study aimed to investigate the effects of ten Essential Oils (EOs) on the activity of nine antibiotics in influencing growth and biofilm formation in Escherichia coli, Pseudomonas aeruginosa, and Enterococcus faecalis. The effects of the EOs alone and in combination with antibiotics on both bacterial growth and biofilm formation were analyzed by measuring the MIC values through the broth microdilution method and the crystal violet assay, respectively. All EOs inhibited the growth of E. coli (1.25 ≤ MIC ≤ 5 mg/mL) while the growth of P. aeruginosa and E. faecalis was only affected by EOs from Origanum vulgare, (MIC = 5 mg/mL) and O. vulgare (MIC = 1.25 mg/mL) and Salvia rosmarinus (MIC = 5 mg/mL), respectively. In E. coli, most EOs induced a four- to sixteen-fold reduction in the MIC values of ampicillin, ciprofloxacin, ceftriaxone, gentamicin, and streptomycin, while in E. faecalis such a reduction is observed in combinations of ciprofloxacin with C. nepeta, C. bergamia, C. limon, C. reticulata, and F. vulgare, of gentamicin with O. vulgare, and of tetracycline with C. limon and O. vulgare. A smaller effect was observed in P. aeruginosa, in which only C. bergamia reduced the concentration of tetracycline four-fold. EO-antibiotic combinations also inhibit the biofilm formation. More precisely, all EOs with ciprofloxacin in E. coli, tetracycline in P. aeruginosa, and gentamicin in E. faecalis showed the highest percentage of inhibition. Combinations induce up- and down-methylation of cytosines and adenines compared to EO or antibiotics alone. The study provides evidence about the role of EOs in enhancing the action of antibiotics by influencing key processes involved in resistance mechanisms such as biofilm formation and epigenetic changes. Synergistic interactions should be effectively considered in dealing with pathogenic microorganisms.

G protein-coupled estrogen receptor 1 (GPER1) activation is emerging as a promising therapeutic strategy against several cancer types. While GPER targeting has been widely studied in the context of solid tumors, its effect on hematological malignancies remains to be fully understood. Here, we show that GPER1 mRNA is down-regulated in plasma cells from overt multiple myeloma (MM) and plasma cell leukemia patients as compared to normal donors or pre-malignant conditions (monoclonal gammopathy of undetermined significance and smoldering MM); moreover, lower GPER1 expression associates with worse overall survival of MM patients. Using the clinically applicable GPER1-selective agonist G-1, we demonstrate that the pharmacological activation of GPER1 triggered in vitro anti-MM activity through apoptosis induction, also overcoming the protective effects exerted by bone marrow stromal cells. Noteworthy, G-1 treatment reduced in vivo MM growth in two distinct xenograft models, even bearing bortezomib-resistant MM cells. Mechanistically, G-1 upregulated the miR-29b oncosuppressive network, blunting an established miR-29b-Sp1 feedback loop operative in MM cells. Overall, this study highlights the druggability of GPER1 in MM, providing the first preclinical framework for further development of GPER1 agonists to treat this malignancy.

Background Coronavirus disease COVID-19 is a heterogeneous condition caused by SARS-CoV-2 infection. Generally, it is characterized by interstitial pneumonia that can lead to impaired gas-exchange, acute respiratory failure, and death, although a complex disorder of multi-organ dysfunction has also been described. The pathogenesis is complex, and a variable combination of factors has been described in critically ill patients. COVID-19 is a particular risk for older persons, particularly those with frailty and comorbidities. Blood bacterial DNA has been reported in both physiological and pathological conditions and has been associated with some haematological and laboratory parameters but, to date, no study has characterized it in hospitalized old COVID-19 patients The present study aimed to establish an association between blood bacterial DNA (BB-DNA) and clinical severity in old COVID-19 patients. Results BB-DNA levels were determined, by quantitative real-time PCRs targeting the 16S rRNA gene, in 149 hospitalized older patients (age range 65–99 years) with COVID-19. Clinical data, including symptoms and signs of infection, frailty status, and comorbidities, were assessed. BB-DNA was increased in deceased patients compared to discharged ones, and Cox regression analysis confirmed an association between BB-DNA and in-hospital mortality. Furthermore, BB-DNA was positively associated with the neutrophil count and negatively associated with plasma IFN-alpha. Additionally, BB-DNA was associated with diabetes. Conclusions The association of BB-DNA with mortality, immune-inflammatory parameters and diabetes in hospitalized COVID-19 patients suggests its potential role as a biomarker of unfavourable outcomes of the disease, thus it could be proposed as a novel prognostic marker in the assessment of acute COVID-19 disease.