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- Gkoliou, G, et al.
(author)
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Differences in the immunoglobulin gene repertoires of IgG versus IgA multiple myeloma allude to distinct immunopathogenetic trajectories
- 2023
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In: Frontiers in oncology. - : Frontiers Media SA. - 2234-943X. ; 13, s. 1123029-
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Journal article (peer-reviewed)abstract
- The analysis of the immunogenetic background of multiple myeloma (MM) has proven key to understanding disease ontogeny. However, limited information is available regarding the immunoglobulin (IG) gene repertoire in MM cases carrying different heavy chain isotypes. Here, we studied the IG gene repertoire in a series of 523 MM patients, of whom 165 and 358 belonged to the IgA and IgG MM groups, respectively. IGHV3 subgroup genes predominated in both groups. However, at the individual gene level, significant (p<0.05) differences were identified regarding IGHV3-21 (frequent in IgG MM) and IGHV5-51 (frequent in IgA MM). Moreover, biased pairings were identified between certain IGHV genes and IGHD genes in IgA versus IgG MM. Turning to the imprints of somatic hypermutation (SHM), the bulk of rearrangements (IgA: 90.9%, IgG: 87.4%) were heavily mutated [exhibiting an IGHV germline identity (GI) <95%]. SHM topology analysis disclosed distinct patterns in IgA MM versus IgG MM cases expressing B cell receptor IG encoded by the same IGHV gene: the most pronounced examples concerned the IGHV3-23, IGHV3-30 and IGHV3-9 genes. Furthermore, differential SHM targeting was also identified between IgA MM versus IgG MM, particularly in cases utilizing certain IGHV genes, alluding to functional selection. Altogether, our detailed immunogenetic evaluation in the largest to-date series of IgA and IgG MM patients reveals certain distinct features in the IGH gene repertoires and SHM. These findings suggest distinct immune trajectories for IgA versus IgG MM, further underlining the role of external drive in the natural history of MM.
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- Grigoriadis, A, et al.
(author)
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Prediabetes/Diabetes Can Be Screened at the Dental Office by a Low-Cost and Fast Chair-Side/Point-of-Care aMMP-8 Immunotest
- 2019
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In: Diagnostics (Basel, Switzerland). - : MDPI AG. - 2075-4418. ; 9:4
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Journal article (peer-reviewed)abstract
- Pre-diabetes and diabetes are strongly associated with periodontal disease (gingivitis and periodontitis), and these conditions are known to upregulate aMMP-8 in inflamed gingiva and oral fluids. Thus, it would be feasible to screen for prediabetes and diabetes at the dental office by chairside tests. Chair-side assessment of HbA1c and a quantitative point-of-care (PoC) active matrix metalloproteinase (aMMP)-8 oral rinse immunotest developed for periodontal diseases, were performed on patients (n = 69) attending a Periodontology University Clinic who fulfilled the criteria for testing according to the screening questionnaire of the Centers for Disease Control and Prevention, USA. Clinical parameters of periodontal disease were also recorded with an automated probe. Twenty seven-point-five percent of the subjects were found with previously unknown hyperglycemia (HbA1c ≥ 5.7%). There was a statistically-significant positive association between the aMMP-8test and prediabetes (p < 0.05, unadjusted and adjusted for BMI and age ≥ 45 years logistic regression models). The dental setting is suitable for opportunistic screening for undiagnosed diabetes and pre-diabetes and point-of-care HbA1c, especially when combined with aMMP-8 assessment by dental professionals, being convenient and effective.
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- Papaevgeniou, Nikoletta, et al.
(author)
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18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression in Caenorhabditis elegans and Neuronal Cultures
- 2016
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In: Antioxidants and Redox Signaling. - New Rochelle, USA : Mary Ann Liebert. - 1523-0864 .- 1557-7716. ; 25:16, s. 855-869
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Journal article (peer-reviewed)abstract
- Aims: Proteasomes are constituents of the cellular proteolytic networks that maintain protein homeostasis through regulated proteolysis of normal and abnormal (in any way) proteins. Genetically mediated proteasome activation in multicellular organisms has been shown to promote longevity and to exert protein antiaggregation activity. In this study, we investigate whether compound-mediated proteasome activation is feasible in a multicellular organism and we dissect the effects of such approach in aging and Alzheimer's disease (AD) progression.Results: Feeding of wild-type Caenorhabditis elegans with 18α-glycyrrhetinic acid (18α-GA; a previously shown proteasome activator in cell culture) results in enhanced levels of proteasome activities that lead to a skinhead-1- and proteasome activation-dependent life span extension. The elevated proteasome function confers lower paralysis rates in various AD nematode models accompanied by decreased Aβ deposits, thus ultimately decelerating the progression of AD phenotype. More importantly, similar positive results are also delivered when human and murine cells of nervous origin are subjected to 18α-GA treatment.Innovation: This is the first report of the use of 18α-GA, a diet-derived compound as prolongevity and antiaggregation factor in the context of a multicellular organism.Conclusion: Our results suggest that proteasome activation with downstream positive outcomes on aging and AD, an aggregation-related disease, is feasible in a nongenetic manipulation manner in a multicellular organism. Moreover, they unveil the need for identification of antiaging and antiamyloidogenic compounds among the nutrients found in our normal diet.
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