Immune cells and commensal microbes in the human intestine constantly communicate with and react to each other in a stable environment in order to maintain healthy immune activities. Immune ...system-microbiota cross-talk relies on a complex network of pathways that sustain the balance between immune tolerance and immunogenicity. Probiotic bacteria can interact and stimulate intestinal immune cells and commensal microflora to modulate specific immune functions and immune homeostasis. Growing evidence shows that probiotic bacteria present important health-promoting and immunomodulatory properties. Thus, the use of probiotics might represent a promising approach for improving immune system activities. So far, few studies have been reported on the beneficial immune modulatory effect of probiotics. However, many others, which are mainly focused on their metabolic/nutritional properties, have been published. Therefore, the mechanisms behind the interaction between host immune cells and probiotics have only been partially described. The present review aims to collect and summarize the most recent scientific results and the resulting implications of how probiotic bacteria and immune cells interact to improve immune functions. Hence, a description of the currently known immunomodulatory mechanisms of probiotic bacteria in improving the host immune system is provided.
Merkel cell polyomavirus (MCPyV) is a small DNA virus with oncogenic potential. MCPyV is the causative agent of Merkel Cell Carcinoma (MCC), a rare but aggressive tumor of the skin. The role of ...epigenetic mechanisms, such as histone posttranslational modifications (HPTMs), DNA methylation, and microRNA (miRNA) regulation on MCPyV-driven MCC has recently been highlighted. In this review, we aim to describe and discuss the latest insights into HPTMs, DNA methylation, and miRNA regulation, as well as their regulative factors in the context of MCPyV-driven MCC, to provide an overview of current findings on how MCPyV is involved in the dysregulation of these epigenetic processes. The current state of the art is also described as far as potentially using epigenetic dysregulations and related factors as diagnostic and prognostic tools is concerned, in addition to targets for MCPyV-driven MCC therapy. Growing evidence suggests that the dysregulation of HPTMs, DNA methylation, and miRNA pathways plays a role in MCPyV-driven MCC etiopathogenesis, which, therefore, may potentially be clinically significant for this deadly tumor. A deeper understanding of these mechanisms and related factors may improve diagnosis, prognosis, and therapy for MCPyV-driven MCC.
In recent years, a number of studies focused on the role of epigenetics, including DNA methylation, in spermatogenesis and male infertility. We aimed to provide an overview of the knowledge ...concerning the gene and genome methylation and its regulation during spermatogenesis, specifically in the context of male infertility etiopathogenesis. Overall, the findings support the hypothesis that sperm DNA methylation is associated with sperm alterations and infertility. Several genes have been found to be differentially methylated in relation to impaired spermatogenesis and/or reproductive dysfunction. Particularly, DNA methylation defects of MEST and H19 within imprinted genes and MTHFR within non-imprinted genes have been repeatedly linked with male infertility. A deep knowledge of sperm DNA methylation status in association with reduced reproductive potential could improve the development of novel diagnostic tools for this disease. Further studies are needed to better elucidate the mechanisms affecting methylation in sperm and their impact on male infertility.
Merkel cell polyomavirus (MCPyV) is a small DNA tumor virus ubiquitous in humans. MCPyV establishes a clinically asymptomatic lifelong infection in healthy immunocompetent individuals. Viral ...infections are considered to be risk factors for spontaneous abortion (SA), which is the most common adverse complication of pregnancy. The role of MCPyV in SA remains undetermined. Herein, the impact of MCPyV infection in females affected by SA was investigated. Specifically, an indirect enzyme-linked immunosorbent assay (ELISA) method with two linear synthetic peptides/mimotopes mimicking MCPyV antigens was used to investigate immunoglobulin G (IgG) antibodies against MCPyV in sera from 94 females affected by SA mean ± standard deviation (SD) age 35 ± (6) years and from 96 healthy females undergoing voluntary pregnancy interruption VI, mean (±SD) age 32 ± (7) years. MCPyV seroprevalence and serological profiles were analyzed. The overall prevalence of serum IgG antibodies against MCPyV was 35.1% (33/94) and 37.5% (36/96) in SA and VI females, respectively (
> 0.05). Notably, serological profile analyses indicated lower optical densities (ODs) in females with SA compared to those undergoing VI (
< 0.05), thus indicating a reduced IgG antibody response in SA females. Circulating IgGs were identified in sera from SA and VI females. Our immunological findings indicate that a relatively reduced fraction of pregnant females carry serum anti-MCPyV IgG antibodies, while SA females presented a more pronounced decrease in IgG antibody response to MCPyV. Although yet to be determined, this immunological decrease might prompt an increase in MCPyV multiplication events in females experiencing abortive events. The role of MCPyV in SA, if present, remains to be determined.
Innovative Biomaterials for Bone Regrowth Iaquinta, Maria Rosa; Mazzoni, Elisa; Manfrini, Marco ...
International journal of molecular sciences,
01/2019, Letnik:
20, Številka:
3
Journal Article
Recenzirano
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The regenerative medicine, a new discipline that merges biological sciences and the fundamental of engineering to develop biological substitutes, has greatly benefited from recent advances in the ...material engineering and the role of stem cells in tissue regeneration. Regenerative medicine strategies, involving the combination of biomaterials/scaffolds, cells, and bioactive agents, have been of great interest especially for the repair of damaged bone and bone regrowth. In the last few years, the life expectancy of our population has progressively increased. Aging has highlighted the need for intervention on human bone with biocompatible materials that show high performance for the regeneration of the bone, efficiently and in a short time. In this review, the different aspects of tissue engineering applied to bone engineering were taken into consideration. The first part of this review introduces the bone cellular biology/molecular genetics. Data on biomaterials, stem cells, and specific growth factors for the bone regrowth are reported in this review.
Human papillomaviruses (HPVs) are small DNA tumor viruses that mainly infect mucosal epithelia of anogenital and upper respiratory tracts. There has been progressive demand for more analytical assays ...for HPV DNA quantification. A novel droplet digital PCR (ddPCR) method was developed to simultaneously detect and quantify HPV DNA from different HPV types. DdPCR was initially tested for assay sensitivity, accuracy, specificity as well as intra- and inter-run assay variation employing four recombinant plasmids containing HPV16, HPV18, HPV11, and HPV45 DNAs. The assay was extended to investigate/quantify HPV DNA in Cervical Intraepithelial Neoplasia (CIN,
= 45) specimens and human cell lines (
= 4). DdPCR and qPCR data from clinical samples were compared. The assay showed high accuracy, sensitivity and specificity, with low intra-/inter- run variations, in detecting/quantifying HPV16/18/11/45 DNAs. HPV DNA was detected in 51.1% (23/45) CIN DNA samples by ddPCR, whereas 40% (18/45) CIN tested HPV-positive by qPCR. Five CIN, tested positive by ddPCR, were found to be negative by qPCR. In CIN specimens, the mean HPV DNA loads determined by ddPCR were 3.81 copy/cell (range 0.002-51.02 copy/cell), whereas 8.04 copy/cell (range 0.003-78.73 copy/cell) by qPCR. DdPCR and qPCR concordantly detected HPV DNA in SiHa, CaSki and Hela cells, whereas HaCaT tested HPV-negative. The correlation between HPV DNA loads simultaneously detected by ddPCR/qPCR in CINs/cell lines was good (
= 0.9706,
< 0.0001). Our data indicate that ddPCR is a valuable technique in quantifying HPV DNA load in CIN specimens and human cell lines, thereby improving clinical applications, such as patient management after primary diagnosis of HPV-related lesions with HPV-type specific assays.
Mesenchymal stem cells (MSCs) have been identified in many adult tissues. MSCs can regenerate through cell division or differentiate into adipocytes, osteoblasts and chondrocytes. As a result, MSCs ...have become an important source of cells in tissue engineering and regenerative medicine for bone tissue and cartilage. Several epigenetic factors are believed to play a role in MSCs differentiation. Among these, microRNA (miRNA) regulation is involved in the fine modulation of gene expression during osteogenic/chondrogenic differentiation. It has been reported that miRNAs are involved in bone homeostasis by modulating osteoblast gene expression. In addition, countless evidence has demonstrated that miRNAs dysregulation is involved in the development of osteoporosis and bone fractures. The deregulation of miRNAs expression has also been associated with several malignancies including bone cancer. In this context, bone-associated circulating miRNAs may be useful biomarkers for determining the predisposition, onset and development of osteoporosis, as well as in clinical applications to improve the diagnosis, follow-up and treatment of cancer and metastases. Overall, this review will provide an overview of how miRNAs activities participate in osteogenic/chondrogenic differentiation, while addressing the role of miRNA regulatory effects on target genes. Finally, the role of miRNAs in pathologies and therapies will be presented.
Simian virus 40 (SV40) is a small DNA tumor virus of monkey origin. This polyomavirus was administered to human populations mainly through contaminated polio vaccines, which were produced in ...naturally infected SV40 monkey cells. Previous molecular biology and recent immunological assays have indicated that SV40 is spreading in human populations, independently from earlier SV40-contaminated vaccines. SV40 DNA sequences have been detected at a higher prevalence in specific human cancer specimens, such as the brain and bone tumors, malignant pleural mesotheliomas, and lymphoproliferative disorders, compared to the corresponding normal tissues/specimens. However, other investigations, which reported negative data, did not confirm an association between SV40 and human tumors. To circumvent the controversies, which have arisen because of these molecular biology studies, immunological researches with newly developed indirect ELISA tests were carried out in serum samples from patients affected by the same kind of tumors as mentioned above. These innovative indirect ELISAs employ synthetic peptides as mimotopes/specific SV40 antigens. SV40 mimotopes do not cross-react with the homologous human polyomaviruses, BKPyV, and JCPyV. Immunological data obtained from indirect ELISAs, using SV40 mimotopes, employed to analyze serum samples from oncological patients, have indicated that these sera had a higher prevalence of antibodies against SV40 compared to healthy subjects. The main data on (i) the biology and genetics of SV40; (ii) the epidemiology of SV40 in the general population, (iii) the mechanisms of SV40 transformation; (iv) the putative role of SV40 in the onset/progression of specific human tumors, and (v) its association with other human diseases are reported in this review.
microRNAs in the Regulation of Melanogenesis Hushcha, Yekatsiaryna; Blo, Irene; Oton-Gonzalez, Lucia ...
International journal of molecular sciences,
06/2021, Letnik:
22, Številka:
11
Journal Article
Recenzirano
Odprti dostop
Melanogenesis is the process leading to the synthesis of melanin, the main substance that influences skin color and plays a pivotal role against UV damage. Altered melanogenesis is observed in ...several pigmentation disorders. Melanogenesis occurs in specialized cells called melanocytes, physically and functionally related by means of autocrine and paracrine interplay to other skin cell types. Several external and internal factors control melanin biosynthesis and operate through different intracellular signaling pathways, which finally leads to the regulation of microphthalmia-associated transcription factor (MITF), the key transcription factor involved in melanogenesis and the expression of the main melanogenic enzymes, including TYR, TYRP-1, and TYRP-2. Epigenetic factors, including microRNAs (miRNAs), are involved in melanogenesis regulation. miRNAs are small, single-stranded, non-coding RNAs, of approximately 22 nucleotides in length, which control cell behavior by regulating gene expression, mainly by binding the 3′ untranslated region (3′-UTR) of target mRNAs. This review collects data on the miRNAs involved in melanogenesis and how these miRNAs can modulate target gene expression. Bringing to light the biological function of miRNAs could lead to a wider understanding of epigenetic melanogenesis regulation and its dysregulation. This knowledge may constitute the basis for developing innovative treatment approaches for pigmentation dysregulation.
The purinergic P2X7 receptor (P2X7R) is a transmembrane protein whose expression has been related to a variety of cellular processes, while its dysregulation has been linked to inflammation and ...cancer. P2X7R is expressed in cancer and immune system cell surfaces. ATP plays a key role in numerous metabolic processes due to its abundance in the tumour microenvironment. P2X7R plays an important role in cancer by interacting with ATP. The unusual property of P2X7R is that stimulation with low doses of ATP causes the opening of a permeable channel for sodium, potassium, and calcium ions, whereas sustained stimulation with high doses of ATP favours the formation of a non-selective pore. The latter effect induces a change in intracellular homeostasis that leads to cell death. This evidence suggests that P2X7R has both pro- and anti-tumour proprieties. P2X7R is increasingly recognised as a regulator of inflammation. In this review, we aimed to describe the most relevant characteristics of P2X7R function, activation, and its ligands, while also summarising the role of P2X7R activation in the context of inflammation and cancer. The currently used therapeutic approaches and clinical trials of P2X7R modulators are also described.
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