Bladder cancer (BC) is a common urological malignancy that lacks the non-invasive biomarkers that would make it suitable for early diagnosis. Human alpha-satellite DNA (hASAT) is a tandemly repeated centromeric/pericentromeric DNA family associated with chromosomal stability and cancer-related genomic instability. We quantified extracellular hASAT (ec-hASAT) in plasma circulating cell-free DNA by nanoplate-based digital PCR in a pilot cohort including 29 BC-negative samples, 10 patients with non-muscle-invasive BC (NMIBC), and 7 patients with muscle-invasive BC (MIBC). Plasma ec-hASAT copy number was higher in patients with BC than in the BC-negative group (Mann-Whitney U test, p = 6.61 × 10-7). BC-negative samples ranged from 225 to 11,864 copies/µL plasma, whereas BC samples ranged from 1138 to 16,097 copies/µL plasma. ROC analysis yielded an AUC of 0.944 for discriminating BC from BC-negative samples. At an exploratory threshold of 2000 copies/µL plasma, sensitivity was 94.1% (16/17; exact 95% CI, 71.3-99.9%) and specificity was 89.7% (26/29; exact 95% CI, 72.6-97.8%). These preliminary data support plasma ec-hASAT as a candidate minimally invasive biomarker for BC detection, including NMIBC, and justify validation in larger prospective cohorts.

The transcription of satellite DNA is highly sensitive to environmental factors and represents a source of genomic instability. Therefore, tight regulation of (peri)centromeric transcription is essential for genome maintenance. Antibiotics are routinely used for in vitro studies and for medical treatment, however, their effect on pericentromeric satellite DNA transcription was not investigated. Here we show that antibiotics geneticin and hygromycin B, conveniently used in cell culture, as well as rifampicin (along with five other antibiotics), used to treat bacterial infections, increase transcription of a major human pericentromeric alpha satellite DNA in cell lines at standard concentrations. However, response differs among cell lines - maximal increase in A-1235 cells is obtained by rifampicin while in HeLa cells and fibroblasts by geneticin. There is also a positive correlation between antibiotic concentration and the level of alpha satellite transcription. The increase of transcription is accompanied with either H3K9me3 decrease or H3K18ac increase at tandemly arranged alpha satellite arrays while H3K4me2 remains unchanged. Our results suggest that induced alpha satellite DNA transcription upon antibiotic stress could be linked to epigenetic changes - histone modifications H3K9me3 and H3K18ac, which are associated with transcription of heterochromatin.

Satellite DNAs are highly abundant sequences that build functional centromeres and pericentromeric heterochromatin in many eukaryotes. Apart from this structural role, their involvement in gene expression modulation has been demonstrated, although a detailed understanding of the molecular mechanisms is still lacking. Here, using the major human alpha satellite as a model system, we investigate the role of satellite transcripts in gene expression regulation. We generated cell lines with forced, exogenous overexpression of alpha satellite RNA and followed the expression levels of genes containing alpha satellite repeats within introns. Our results reveal a positive correlation between exogenous alpha satellite expression and the downregulation of alpha-associated genes, strongly suggesting that alpha satellite RNA affects their transcription. Notably, the elevated levels of exogenous alpha satellite RNA did not affect histone modifications characteristic of pericentromeric heterochromatin (e.g., H3K9me3 or H3K18Ac) or euchromatin (e.g., H3K4me2) at intronic alpha satellite loci. We propose that alpha satellite RNA directly interacts with homologous DNA at dispersed intronic satellite loci by forming RNA-DNA hybrid structures, which may affect chromatin structure and transcriptional activity. The results demonstrate that alpha satellite RNA is not only involved in centromere and heterochromatin assembly but, as shown here for the first time, also plays a role in modulating the expression of alpha-associated genes.

Nutrition has a significant effect and a crucial role in disease prevention. Low consumption of fruit and vegetables and a sedentary lifestyle are closely related with the onset and development of many types of cancer. Recently, nutraceuticals have gained much attention in cancer research due to their pleiotropic effects and relatively non-toxic behavior. In fact, although in the past there have been conflicting results on the role of some antioxidant compounds as allies against cancer, numerous recent clinical studies highlight the efficacy of dietary phytochemicals in the prevention and treatment of cancer. However, further investigation is necessary to gain a deeper understanding of the potential anticancer capacities of dietary phytochemicals as well as the mechanisms of their action. Therefore, this review examined the current literature on the key properties of the bioactive components present in the diet, such as carotenoids, polyphenols, and antioxidant compounds, as well as their use in cancer therapy. The review focused on potential chemopreventive properties, evaluating their synergistic effects with anticancer drugs and, consequently, the side effects associated with current cancer treatments.

The procedure illustrated in this paper represents a new method for transcriptome analysis by PCR (Polymerase Chain Reaction), which circumvents the need for elimination of potential DNA contamination. Compared to the existing methodologies, our method is more precise, simpler and more reproducible because it preserves the RNA's integrity, does not require materials and/or reagents that are used for elimination of DNA and it also reduces the number of samples that should be set up as negative controls. This novel procedure involves the use of a specifically modified primer during reverse transcription step, which contains mismatched bases, thus producing cDNA molecules that differ from genomic DNA. By using the same modified primer in PCR amplification, only cDNA template is amplified since genomic DNA template is partially heterologous to the primer. In this way, amplification by PCR is unaffected by any potential DNA contamination since it is specific only for the cDNA template. Furthermore, it accurately reflects the initial RNA concentration of the sample, which is prone to changes due to various physical or enzymatic treatments commonly used by the current methodologies for DNA elimination. The method is particularly suitable for quantification of highly repetitive DNA transcripts, such as satellite DNA.

Celiac disease (CD) is a permanent intolerance to gliadin contained in gluten proteins found in wheat, barley, rye, barley and other cereals. Celiac disease is not a disease to Mendelian genetic transmission, but there is a certain degree of genetic disposition in the patient's relatives. An intolerance to gluten determine severe damage to the intestinal mucosa, as villous atrophy. The intolerance to gluten is contrasted by the body with the production of antibodies that, in turn, damage the intestinal mucosa causing a decrease of intestinal absorption. Recently, 39 genomic regions were identified associated with CD and located on chromosome 2; the genes located in this area are physically in contiguity with the HOXD locus present on chromosome 2q31. The Class I homeobox genes (HOX in human), are 39 transcription factors able to control embryonic development and the cell memory program interacting with non coding RNA. I consider the HOX network “The Rosetta stone” of human biology; therefore, does HOX gene network able to control the change of the cell memory program in the CD?

Bacterial SSB proteins, as well as their eukaryotic RPA analogues, are essential and ubiquitous. They avidly bind single-stranded DNA and regulate/coordinate its metabolism, hence enabling essential DNA processes such as replication, transcription, and repair. The prototypic Escherichia coli SSB protein is encoded by an ssb gene. Although the ssb gene promoters harbor an SOS box, multiple studies over several decades failed to elucidate whether ssb gene expression is inducible and SOS dependent. The SOS regulon is comprised of about 50 genes, whose transcription is coordinately induced under stress conditions. Using quantitative real-time PCR, we determined the ssb gene expression kinetics in UV- and γ-irradiated E. coli and revealed that ssb gene expression is elevated in irradiated cells in an SOS-dependent manner. Additionally, the expression of the sulA gene was determined to indicate the extent of SOS induction. In a mutant with a constitutively induced SOS regulon, the ssb gene was overexpressed in the absence of DNA damage. Furthermore, we measured ssb gene expression by droplet digital PCR during unaffected bacterial growth and revealed that ssb gene expression was equal in wild-type and SOS− bacteria, whereas sulA expression was higher in the former. This study thus reveals a complex pattern of ssb gene expression, which under stress conditions depends on the SOS regulon, whereas during normal bacterial growth it is unlinked to SOS induction. The E. coli ssb gene is SOS regulated in such a way that its basal expression is relatively high and can be increased only through stronger SOS induction. The remarkable SOS induction observed in undisturbed wild-type cells may challenge our notion of the physiological role of the SOS response in bacteria.

Dear editor, The COVID-19 pandemic has stimulated the production of different therapeutic approaches for the resolution of coronavirus infections. On one hand, nanobiomolecules have been proposed as bait material for viruses, 1 on the other hand unconventional messenger RNA vaccines have been produced like SARS-CoV-2 mRNA vaccines (BioNTech / Pfizer BNT162b2 and Moderna mRNA-1273). [...]

Breast cancer in women is the second most commonly cancer, after skin cancer. The percentage of mortality risk for breast cancer is 1 in 37 women (2.7%), which makes breast cancer represent the second cause of cancer death in women. Recently, new research based on previously published work in systemic chemotherapy and endocrine therapy field, have improved the incidence rates. The quinonic nucleus is common to many natural and synthetic products associated with anticancer and antibacterial activities, these compounds are typically DNA-intercalating agents. The Class I Homeobox genes (HOX in human and hox in mouse) control embryonic development and specific determination of positional identity anteroposterior axis of the human body. The HOX genes, are 39 transcription factors related to morphological, physiological disease. It has been demonstrated that any deregulation into the network is able to induce neoplastic transformation. Particularly, HOXC locus collaborating with lncRNA HOTAIR play a key role in breast cancer. In this study, our group evaluated the chemical and metabolic stability of new anticancer molecule 5H-pyro[3,2-a] phenoxazin-5-one (PPH). In a recent paper, we have already demonstrated that a new and potent anticancer synthetic iminoquinone, the 5H-pyrido[3,2-a]phenoxazin-5-one (PPH), is able to inhibit a large number of lymphoblastoid and solid-tumor-derived cells at submicromolar concentrations. Based on our previous research, we decided to analyze the cytotoxic effect and capability of PPH to control the lncRNA HOTAIR and HOXC locus gene expression in human breast cancer cells MCF-7, in order to demonstrate its role like potential new breast cancer antitumor drug.

We are proposinga the use of pulmonary-proteoliposome as a new therapeutic approach for Coronaviruses. The designed strategy represents a potential treatment to reduce the overall viral load in the lungs and to help the immune system to successfully stave off the infection.

Purpose The aim of this study was to evaluate the effects of various prophylactic treatments of titanium implants on bacterial biofilm formation, correlating surface modifications with the biofilms produced by Pseudomonas aeruginosa PAO1, Staphylococcus aureus, and bacteria isolated from saliva. Methods Pure titanium disks were treated with various prophylactic procedures, and atomic force microscopy (AFM) was used to determine the degree to which surface roughness was modified. To evaluate antibiofilm activity, we used P. aeruginosa PAO1, S. aureus, and saliva-isolated Streptococcus spp., Bacteroides fragilis, and Staphylococcus epidermidis. Results AFM showed that the surface roughness increased after using the air-polishing device and ultrasonic scaler, while a significant reduction was observed after using a curette or polishing with Detartrine ZTM (DZ) abrasive paste. In addition, we only observed a significant (P<0.01) reduction in biofilm formation on the DZ-treated implant surfaces. Conclusion In this study, both AFM and antibiofilm analyses indicated that using DZ abrasive paste could be considered as the prophylactic procedure of choice for managing peri-implant lesions and for therapy-resistant cases of periodontitis.

The osteogenesis is a complex process that involves an accurate control of bone development and growth as well as remodeling during postnatal life. Although the understanding of the transcriptional control of osteogenesis is increased considerably, the molecular regulatory basis is still poorly understood [1]. In the near future, the knowledge about the role of transcriptional factors in the control of osteoblast differentiation consequent to post-genome will be expected. In order to identify the molecular mechanisms useful in the tissue regeneration and tissue engineering methodologies of clinical practice [2]. Bone development is regulated by 500 genes, particularly Fibroblast Growth Factor-4, Bone Morphogenetic Protein-4, lymphoid enhancer binding factor-1, cyclin dependent kinase inhibitor-1 and sonic hedgehog (FGF4, SHH, BMP4, LEF1 and p21) genes, constitute the first regulators of osteogenesis; also homeobox-containing genes as Msx sonic hedgehog, distal-less homeobox and paired box (Msx, Dlx, PAX), are the best candidates in the control of cranio-facial development and organization (Figures 1-3) [3].

Studies have failed to identify the molecular mechanisms that regulate the genotoxic and cytotoxic effects of methacrylate resins, which are important in the biocompatibility of dental materials. Interleukin (IL)-6 has a crucial role in the control of acute-phase protein response during inflammation. In humans, the synthesis and release of two major acute-phase proteins, C-reactive protein and serum amyloid A, are regulated by IL-6. This study focused on IL-6 and activation of its receptors gp80 and gp130 in human gingival fibroblasts in order to assess the effects of the commercial acid resins Jet Kit, Unifast, and Duralay on control of inflammation.

Class I homeobox genes (HOX), are 39 transcription factors involved in the regulation of different cell processes: i) cell identity; ii) cell growth and proliferation; iii) cell communication; iv) determining anteroposterior axis during embryonic development; these genes are characterized by 183 nucleotide sequence (homeobox) encoding for a 61 amino acid domain (hoemodomain). HOX network controls the cell memory program during cell differentiation and is related to neoplastic transformation. Three gene families regulate the cell memory program: the Polycomb genes, able to block DNA-chromatin interaction leading to HOX genes silencing; the Trithorax genes, able to induce an open configuration of DNA-chromatin interaction and leading to HOX genes activation. Finally the HOX genes involved in the orchestration of the cell phenotype through the fine regulation of specific gene program. The proposal of this review, considering the recent literature and my personal research, is clarify the involvement Class I homeobox genes in the control of neoplastic transformation.

Class I homeobox genes (Hox in mice and HOX in humans), encode for 39 transcription factors and display a unique genomic network organization mainly involved in the regulation of embryonic development and in the cell memory program. The HOX network controls the aberrant epigenetic modifications involving in the cell memory program. In details, the HOX cluster plays a crucial role in the generation and evolution of several diseases: congenic malformation, oncogenesis, metabolic processes and deregulation of cell cycle. In this review, I discussed about the role of HOX gene network in the control of cardiovascular development.

Celiac disease is one of the most frequent diseases genetically determined, with vast and heterogeneous series of clinical manifestations, interests all ages of life. A gliadin peptide, P31-43, is being able to induce an immune response in patients with CD, mainly by means of IL15 and IL15Ralpha activation has been identified. Recently, 30 genes were identified in the small bowel which are able to control the epithelial cell differentiation and celiac disease pathogenesis. Two regions on the chromosome 2, ITG4/UBE2E3 (2q31.3) and CTLA4/ICOS/CD28 (2q33.2) are in contiguity with HOXD genes, located on chromosome 2q31-32. HOX genes or Class I homeobox genes, consist of 39 transcription factors involved in the regulation of embryonic and body plan development, they are related to the cell memory program through the interaction with noncoding-RNAs. LncRNA HOTAIR is a non-coding RNA located at chromosome 12q13.13 and transcribed from HOXC locus; the overexpression of the HOTAIR has been linked to several diseases, originally, it was found in colorectal, gastric cancer and hepatoma. In general, HOTAIR is crucial in Epithelial- Mesenchymal Transition (EMT). HOTAIR is epigenetically able to promote EMT mainly by means of silencing miRNA34a and interacting with Polycomb-Responsive-Element-2 (PRC2). The purpose of this report is to evaluate the capability of P31-43 toxic peptide of the gliadin, and to regulate the transcriptional control of the lncRNA HOTAIR, HOXC11 and HOXC12 genes. Keywords: HOX genes, celiac disease, toxic peptide, lncRNA, HOTAIR.

OBJECTIVES:The aim was to test the properties of experimental calcium silicate/calcium phosphate biphasic cements with hydraulic properties designed for vital pulp therapy as direct pulp cap and pulpotomy.METHODS:CaSi-αTCP and CaSi-DCDP were tested for ion-releasing ability, solubility, water sorption, porosity, ability to nucleate calcium phosphates, and odontoblastic differentiation—alkaline phosphatase (ALP) and osteocalcin (OCN) upregulation—of primary human dental pulp cells (HDPCs).RESULTS:The materials showed high Ca and OH release, high open pore volume and apparent porosity, and a pronounced ability to nucleate calcium phosphates on their surface. HDPCs treated with CaSi-αTCP showed a strong upregulation of ALP and OCN genes, namely a tenfold increase for OCN and a threefold increase for ALP compared to the control cells. Conversely, CaSi-DCDP induced a pronounced OCN gene upregulation but had no effect on ALP gene regulation.CONCLUSIONS:Both cements showed high biointeractivity (release of Ca and OH ions) correlated with their marked ability to nucleate calcium phosphates. CaSi-αTCP cement proved to be a potent inducer of ALP and OCN genes as characteristic markers of mineralization processes normally poorly expressed by HDPCs.CLINICAL RELEVANCE:Calcium silicate/calcium phosphate cements appear to be attractive new materials for vital pulp therapy as they may provide odontogenic/dentinogenic chemical signals for pulp regeneration and healing, and dentin formation in regenerative endodontics.

Celiac disease (CD) is a permanent intolerance to gliadin contained in gluten proteins found in wheat, barley, rye, barley and other cereals. Celiac disease is not a disease to Mendelian genetic transmission, but there is a certain degree of genetic disposition in the patient's relatives. An intolerance to gluten determine severe damage to the intestinal mucosa, as villous atrophy. The intolerance to gluten is contrasted by the body with the production of antibodies that, in turn, damage the intestinal mucosa causing a decrease of intestinal absorption. Recently, 39 genomic regions were identified associated with CD and located on chromosome 2; the genes located in this area are physically in contiguity with the HOXD locus present on chromosome 2q31. The Class I homeobox genes (HOX in human), are 39 transcription factors able to control embryonic development and the cell memory program interacting with non coding RNA. I consider the HOX network “The Rosetta stone” of human biology; therefore, is HOX gene network able to control the change of the cell memory program in the CD?

Celiac disease (CD) is immune-mediated enteropathy that occurs in genetically predisposed subjects following ingestion of an alcohol-soluble component of gluten, gliadin, found in some cereals (wheat, barley, rye, spelled, etc.). HOX, are 39 transcription factors mostly involved in the regulation of embryonic development and regulates the cell memory program through the interaction with non coding RNA. I have already titled this network as “The Rosetta stone” of human biology; therefore, does HOX network able to control change in the cell memory program during CD?