Sequential Serum-dependent Activation of CREB and NRF-1 Leads to Enhanced Mitochondrial Respiration through the Induction of Cytochrome c

Progression through the cell cycle requires ATP for protein synthesis, cytoskeletal rearrangement, chromatin remodeling, and protein degradation. The mechanisms by which mammalian cells increase respiratory capacity and ATP production in preparation for cell division are largely unexplored. Here, we demonstrate that serum induction of cytochrome c mRNA and processed protein in quiescent BALB/3T3 fibroblasts is associated with a marked increase in mitochondrial respiration. Cytochrome c was induced in the absence of any increase in citrate synthase activity or in subunit IV of the cytochrome c oxidase complex mRNA or protein, indicating that the enhanced respiratory rate did not require a general increase in mitochondrial biogenesis or respiratory chain expression. Transfections with a series of cytochrome c promoter mutants showed that both nuclear respiratory factor 1 (NRF-1) and cAMP-response element-binding protein (CREB) binding sites contributed equally to induced expression by serum. Moreover, CREB and NRF-1 were phosphorylated sequentially in response to serum, and the NRF-1 phosphorylation was accompanied by an increase in its ability to trans-activate target gene expression. The results demonstrate that the differential transcriptional expression of cytochrome c, through sequential transcription factor phosphorylations, leads to enhanced mitochondrial respiratory capacity upon serum-induced entry to the cell cycle

Mesenchymal Stem Cells as Promoters, Enhancers, and Playmakers of the Translational Regenerative Medicine.

Since their first isolation and characterization by Friedenstein et al. in 1974 [1], mesenchymal stem cells (MSCs) were proven essential for tissue regeneration and homeostasis

Microbiota and Obesity: Where Are We Now?

Simple Summary Emerging new data reported in the international scientific literature show that specific alterations in the human gut microbiota are characteristic in obesity and obesity-related metabolic diseases. Obesity is conditioned by a multitude of factors, and the microbiota is certainly an important player. The analysis of the data obtained from experimental studies allow us to hypothesize that changes in the composition of the microbiota may be the cause, and not simply the consequence, of alterations in human metabolism. Clinical trials on wide samples that investigate the role of diet-induced modulation of the gut microbiota on the host metabolism are needed to understand the interactions at the molecular level for the observed correlations between metabolism and microbiota changes. Abstract Genetic and environmental factors are underlying causes of obesity and other metabolic diseases, so it is therefore difficult to find suitable and effective medical treatments. However, without a doubt, the gut microbiota—and also the bacteria present in the oral cavity—act as key factors in the development of these pathologies, yet the mechanisms have not been fully described. Certainly, a more detailed knowledge of the structure of the microbiota—composition, intra- and inter-species relationships, metabolic functions—could be of great help in counteracting the onset of obesity. Identifying key bacterial species will allow us to create a database of “healthy” bacteria, making it possible to manipulate the bacterial community according to metabolic and clinical needs. Targeting gut microbiota in clinical care as treatment for obesity and health-related complications—even just for weight loss has become a real possibility. In this topical review we provide an overview of the role of the microbiota on host energy homeostasis and obesity-related metabolic diseases, therefore addressing the therapeutic potential of novel and existing strategies (impact of nutrition/dietary modulation, and fecal microbiota transplantation) in the treatment of metabolic disease

Bioimpedance detection of Oral Lichen Planus used as preneoplastic model

Introduction: Bioimpedance is a measure of the electrical properties of biological tissues. In the last two decades bioimpedance has been successfully introduced in clinical diagnosis of cancer. It has been demonstrated that tumoral tissues often show lower bioimpedance values than healthy tissues. The aim of this work is to assess the bioimpedentiometric differences between healthy and Oral Lichen Planus (OLP) affected oral mucosa, taking attention to the erosive form which may represent a potential pre-cancerous condition. Methods: 52 patients affected by OLP were recruited for bioimpedance examination of oral mucosa. Four electrical properties, resistance (R), reactance (Xc), phase angle (θ) and impedance (Z) of the tongue and of the intraoral mucosa, were measured. Results: We observed a significant increase of Z and a significant decrease of θ values in correspondence of OLP lesions compared to healthy oral mucosa, and a marked decrease of Z values in correspondence of erosive OLP lesions. Conclusions: These results provide evidence of the usefulness of bioimpedance assay for the characterization of healthy and clinically OLP affected mucosa. Bioimpedance is a valid aid in the early detection and clinical monitoring of the suspicious lesions which could lead to a potentially malignant evolution. The present research article is a valuable addition to the scientific literature of cancer prevention, and our findings can be considered extremely encouraging as they represent the initial step for a more wide clinical study for better define the different cut-off values in the different precancerous conditions occurring in the oral mucosa

The Intestinal Microbiota May Be a Potential Theranostic Tool for Personalized Medicine

he human intestine is colonized by a huge number of microorganisms from the moment of birth. This set of microorganisms found throughout the human body, is called the microbiota; the microbiome indicates the totality of genes that the microbiota can express, i.e., its genetic heritage. Thus, microbiota participates in and influences the proper functioning of the organism. The microbiota is unique for each person; it differs in the types of microorganisms it contains, the number of each microorganism, and the ratio between them, but mainly it changes over time and under the influence of many factors. Therefore, the correct functioning of the human body depends not only on the expression of its genes but also on the expression of the genes of the microorganisms it coexists with. This fact makes clear the enormous interest of community science in studying the relationship of the human microbiota with human health and the incidence of disease. The microbiota is like a unique personalized “mold” for each person; it differs quantitatively and qualitatively for the microorganisms it contains together with the relationship between them, and it changes over time and under the influence of many factors. We are attempting to modulate the microbial components in the human intestinal microbiota over time to provide positive feedback on the health of the host, from intestinal diseases to cancer. These interventions to modulate the intestinal microbiota as well as to identify the relative microbiome (genetic analysis) can range from dietary (with adjuvant prebiotics or probiotics) to fecal transplantation. This article researches the recent advances in these strategies by exploring their advantages and limitations. Furthermore, we aim to understand the relationship between intestinal dysbiosis and pathologies, through the research of resident microbiota, that would allow the personalization of the therapeutic antibiotic strategy

Mitochondrial Oxidative Stress due to Complex I Dysfunction Promotes Fibroblast Activation and Melanoma Cell Invasiveness

Increased ROS (cellular reactive oxygen species) are characteristic of both fibrosis and tumour development. ROS induce the trans-differentiation to myofibroblasts, the activated form of fibroblasts able to promote cancer progression. Here, we report the role of ROS produced in response to dysfunctions of mitochondrial complex I, in fibroblast activation and in tumour progression. We studied human fibroblasts with mitochondrial dysfunctions of complex I, leading to hyperproduction of ROS. We demonstrated that ROS level produced by the mutated fibroblasts correlates with their activation. The increase of ROS in these cells provides a greater ability to remodel the extracellular matrix leading to an increased motility and invasiveness. Furthermore, we evidentiated that in hypoxic conditions these fibroblasts cause HIF-1α stabilization and promote a proinvasive phenotype of human melanoma cells through secretion of cytokines. These data suggest a possible role of deregulated mitochondrial ROS production in fibrosis evolution as well as in cancer progression and invasion

Gingival crevicular blood as a potential screening tool: a cross sectional comparative study.

Background: Diabetes is known to be one of the major global epidemic diseases, significantly associated with mortality and morbidity worldwide, conferring a substantial burden to the health care system. The epidemiological transition of this chronic disease tends to worsen unless preventive health strategies are implemented. Appropriate screening devices and standardized methods are crucial to prevent this potentially inauspicious life condition. Currently, the glucometer is the conventional device employed for blood glucose level determination that outputs the blood glucose reading. Glucometer performed in the dental oce may be an important device in screening diabetes, so it can be addressed during a periodontal examination. Because gingival blood is a useful source to detect the glucose level, the focus is placed on the opportunity that might provide valuable diagnostic information. This study aimed to compare gingival crevicular blood with finger-stick blood glucose measurements using a self-monitoring glucometer, to evaluate whether gingival crevicular blood could be an alternative to allow accurate chairside glucose testing. Methods: A cross-sectional comparative study was performed among a 31–67-year-old population. Seventy participants with diagnosed type 2 diabetes and seventy healthy subjects, all with positive bleeding on probing, were enrolled. The gingival crevicular blood was collected using a glucometer to estimate the blood glucose level and compared with finger-stick blood glucose level. Results: The mean capillary blood glucose and gingival crevicular blood levels from all samples were, respectively, 160.42 31.31 mg/dL and 161.64 31.56 mg/dL for diabetic participants and 93.51 10.35 mg/dL and 94.47 9.91 mg/dL for healthy patients. In both groups, the dierence between gingival crevicular blood and capillary blood glucose levels was non-significant (P < 0.05). The highly significant correlation between capillary blood glucose and gingival crevicular blood (r = 0.9834 for diabetic patients and r = 0.8153 for healthy participants) in both the groups was found. Conclusions: Gingival crevicular blood test was demonstrated as a feasible and useful primary screening tool test for detecting diabetes and for glucose estimation in non-diabetic patients. Use of gingival crevicular blood for screening is an attractive way of identifying a reasonable option of finger-stick blood glucose measurement under the appropriate circumstances. Rapid assessment may precede diagnostic evaluation in diabetic as well as healthy patients with acute severe bleeding. In addition, gingival crevicular blood levels may be needed to monitor the diabetic output

Probiotics May Improve Serum Folate Availability in Pregnant Women: A Pilot Study

BACKGROUND: Probiotics are living microorganisms that confer a health benefit when administered in adequate amounts. There is evidence in the current literature about the importance of probiotic use in pregnancy. The early supplementation of probiotics in the perinatal and postnatal periods seems to have a positive impact on the overall mother’s health and future health of infants. AIM: Our pilot study aimed to test the ability of specific probiotics strains in combination with the kiwi-unique enzyme actinidin to improve the availability of folic acid in 20 pregnant women. METHODS: We investigate 20 pregnant women in early (4–10 weeks) (6 patients), intermedium (11–20 weeks) (6 patients), and late (21–30 weeks) (8 patients) pregnancy. RESULTS: Our findings show that the tested formula promotes increased concentration of serum folate in women’s blood and contributes to the control of blood sugar and body weight, regardless of the gestational period (early, intermediate or late). CONCLUSIONS: Our data support the main results reported in the scientific literature about the importance of probiotics intake in pregnancy

Update on COVID-19 and Effectiveness of a Vaccination Campaign in a Global Context

The COVID-19 pandemic caused by SARS-CoV-2 remains a significant issue for global health, the economy, and society. When SARS-CoV-2 began to spread, the most recent serious infectious disease of this century around the world, with its high morbidity and mortality rates, it is understandable why such infections have generally been spread in the past, mainly from international travel movements. This perspective review aimed to provide an update for clinicians on the recent developments related to the microbiological perspectives in pandemics, diagnostics, prevention (such as the spread of a virus), vaccination campaigns, treatment options, and health consequences for COVID-19 based on the current literature. In this way, the authors attempt to raise awareness on the transversal nature of these challenges by identifying the main risk/vulnerability factors that the scientific community must face including our current knowledge on the virus capacity of the mechanism of entry into the cells, the current classifications of viral variants, the knowledge of the mathematical model on the spread of viruses (the possible routes of transmission), and the effectiveness of vaccination campaigns in a global context of pandemic, particularly from COVID-19, with a look at new or future vaccines

Exploring the Role of Fusobacterium nucleatum in Preterm Birth: A Narrative Review

In recent years, substantive attention has been drawn to the relationship between oral microbiome homeostatic equilibrium disruption and systemic health, demonstrating the negative impacts of this reciprocal biological interplay. Increasingly, there is a concern over the potential noxious effect of oral microbiome dysbiosis on obstetric poor outcomes, focusing on preterm birth. This epidemiological observation remains unexplained, although biologically plausible mechanism has been proposed. Intrauterine infection has long been associated with adverse pregnancy, when the elicitation of an immune response is determinant. There is evidence that Fusobacterium nucleatum (FN), a Gram-negative anaerobe ubiquitous in the oral cavity, infects the mouse placenta originating in the decidua basalis. Based on the current data in literature, we performed a review to provide resources for the explanation of the potential impact of microbiome dysbiosis on poor obstetric outcomes, focusing on the role of FN