Is Alzheimer's disease a type 3 diabetes? A review Janoutová, Jana; Machaczka, Ondřej; Zatloukalová, Anna ...
Central European journal of public health,
09/2022, Letnik:
30, Številka:
3
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Objectives: This is a review article that deals with the question of whether type 2 diabetes is a risk factor for the development of Alzheimer's disease. Methods: We searched the PubMed database and ...relevant publications were selected for review. The introduction, which describes the possibilities of how type 2 diabetes can affect the development of Alzheimer's disease, is followed by other questions related to this issue: May on the contrary Alzheimer's disease induce type 2 diabetes? What is a relative risk for type 2 diabetes to induce dementia? How type 2 diabetes influence conversion of mild cognitive impairment to Alzheimer's disease? What is the role of antidiabetic medication? Proposition of term type 3 diabetes for Alzheimer's disease. Results: Type 2 diabetes mellitus has been shown to increase the risk for cognitive decline and dementia, such as Alzheimer's disease and vascular dementia. Despite extensive research and numerous publications, the mechanisms underlying these associations remain unclear. Conclusions: Because of similar molecular and cellular features among type 1 and type 2 diabetes and insulin resistance associated with memory deficit and cognitive decline, some researches proposed the term type 3 diabetes for Alzheimer's disease.
Out-of-hospital cardiac arrest Porzer, Martin; Mrazkova, Eva; Homza, Miroslav ...
Biomedical papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
161, Številka:
4
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Out-of-hospital cardiac arrest (OHCA) is a leading cause of death in developed industrial countries. The global worldwide average of OHCA incidence in adults is 95.9/100,000/year. European incidences ...vary according to source from 16 to 119/100,000/year. The aim of this study was to provide an overview of current information on OHCA. The incidences in various populations are discussed, along with the factors affecting the prognosis and outcome of these patients. The etiology and pathophysiological mechanisms are also described, especially in relation to the most common causes - acute and chronic forms of coronary artery disease and cardiomyopathies. Measures that could improve survival rates are discussed, with emphasis on the role of the general public and deployment of automatic external defibrillators.
We applied a training and testing approach to develop and validate a plasma metabolite panel for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC) alone and in combination with a ...previously validated protein panel for early-stage PDAC.
A comprehensive metabolomics platform was initially applied to plasmas collected from 20 PDAC cases and 80 controls. Candidate markers were filtered based on a second independent cohort that included nine invasive intraductal papillary mucinous neoplasm cases and 51 benign pancreatic cysts. Blinded validation of the resulting metabolite panel was performed in an independent test cohort consisting of 39 resectable PDAC cases and 82 matched healthy controls. The additive value of combining the metabolite panel with a previously validated protein panel was evaluated.
Five metabolites (acetylspermidine, diacetylspermine, an indole-derivative, and two lysophosphatidylcholines) were selected as a panel based on filtering criteria. A combination rule was developed for distinguishing between PDAC and healthy controls using the Training Set. In the blinded validation study with early-stage PDAC samples and controls, the five metabolites yielded areas under the curve (AUCs) ranging from 0.726 to 0.842, and the combined metabolite model yielded an AUC of 0.892 (95% confidence interval CI = 0.828 to 0.956). Performance was further statistically significantly improved by combining the metabolite panel with a previously validated protein marker panel consisting of CA 19-9, LRG1, and TIMP1 (AUC = 0.924, 95% CI = 0.864 to 0.983, comparison DeLong test one-sided P= .02).
A metabolite panel in combination with CA19-9, TIMP1, and LRG1 exhibited substantially improved performance in the detection of early-stage PDAC compared with a protein panel alone.
CA19-9, which is currently in clinical use as a pancreatic ductal adenocarcinoma (PDAC) biomarker, has limited performance in detecting early-stage disease. We and others have identified protein ...biomarker candidates that have the potential to complement CA19-9. We have carried out sequential validations starting with 17 protein biomarker candidates to determine which markers and marker combination would improve detection of early-stage disease compared with CA19-9 alone.
Candidate biomarkers were subjected to enzyme-linked immunosorbent assay based sequential validation using independent multiple sample cohorts consisting of PDAC cases (n = 187), benign pancreatic disease (n = 93), and healthy controls (n = 169). A biomarker panel for early-stage PDAC was developed based on a logistic regression model. All statistical tests for the results presented below were one-sided.
Six out of the 17 biomarker candidates and CA19-9 were validated in a sample set consisting of 75 PDAC patients, 27 healthy subjects, and 19 chronic pancreatitis patients. A second independent set of 73 early-stage PDAC patients, 60 healthy subjects, and 74 benign pancreatic disease patients (combined validation set) yielded a model that consisted of TIMP1, LRG1, and CA19-9. Additional blinded testing of the model was done using an independent set of plasma samples from 39 resectable PDAC patients and 82 matched healthy subjects (test set). The model yielded areas under the curve (AUCs) of 0.949 (95% confidence interval CI = 0.917 to 0.981) and 0.887 (95% CI = 0.817 to 0.957) with sensitivities of 0.849 and 0.667 at 95% specificity in discriminating early-stage PDAC vs healthy subjects in the combined validation and test sets, respectively. The performance of the biomarker panel was statistically significantly improved compared with CA19-9 alone (P < .001, combined validation set; P = .008, test set).
The addition of TIMP1 and LRG1 immunoassays to CA19-9 statistically significantly improves the detection of early-stage PDAC.
Purpose: To provide a comprehensive, thorough analysis of somatic mutation and promoter hypermethylation of the von Hippel-Lindau ( VHL ) gene in the cancer genome, unique to clear cell renal cancer ...(ccRCC). Identify relationships between the prevalence of VHL gene alterations and alteration subtypes with patient and tumor characteristics.
Experimental Design: As part of a large kidney cancer case-control study conducted in Central Europe, we analyzed VHL mutations and promoter methylation in 205 well-characterized, histologically confirmed patient tumor biopsies using a combination
of sensitive, high-throughput methods (endonuclease scanning and Sanger sequencing) and analysis of 11 CpG sites in the VHL promoter.
Results: We identified mutations in 82.4% of cases, the highest VHL gene mutation prevalence reported to date. Analysis of 11 VHL promoter CpG sites revealed that 8.3% of tumors were hypermethylated and all were mutation negative. In total, 91% of ccRCCs
exhibited alteration of the gene through genetic or epigenetic mechanisms. Analysis of patient and tumor characteristics revealed
that certain mutation subtypes were significantly associated with Fuhrman nuclear grade, metastasis, node positivity, and
self-reported family history of RCC.
Conclusion: Detection of VHL gene alterations using these accurate, sensitive, and practical methods provides evidence that the vast majority of histologically
confirmed ccRCC tumors possess genetic or epigenetic alteration of the VHL gene and support the hypothesis that VHL alteration is an early event in ccRCC carcinogenesis. These findings also indicate that VHL molecular subtypes can provide a sensitive marker of tumor heterogeneity among histologically similar ccRCC cases for etiologic,
prognostic, and translational studies.
Insulin-degrading enzyme (IDE) is an important gene in studies of the pathophysiology of type 2 diabetes mellitus (T2DM). Recent studies have suggested a possible link between type 2 diabetes ...mellitus (T2DM) and the pathophysiology of schizophrenia (SZ). At the same time, significant changes in insulin-degrading enzyme (IDE) gene expression have been found in the brains of people with schizophrenia. These findings highlight the need to further investigate the role of IDE in schizophrenia pathogenesis.
We enrolled 733 participants from the Czech Republic, including 383 patients with schizophrenia and 350 healthy controls. Our study focused on the single nucleotide polymorphism (SNP) rs2421943 in the IDE gene, which has previously been associated with the pathogenesis of Alzheimer's disease. The SNP was analyzed using the PCR-RFLP method.
The G allele of the rs2421943 polymorphism was found to significantly increase the risk of developing SZ (p < 0.01) when a gender-based analysis showed that both AG and GG genotypes were associated with a more than 1.55 times increased risk of SZ in females (p < 0.03) but not in males. Besides, we identified a potential binding site at the G allele locus for has-miR-7110-5p, providing a potential mechanism for the observed association.
Our results confirm the role of the IDE gene in schizophrenia pathogenesis and suggest that future research should investigate the relationship between miRNA and estrogen influence on IDE expression in schizophrenia pathogenesis.
Only a few researchers have addressed the issue of lifetime exposure related to air pollutant concentration. This study aims to develop a methodology to obtain the most reliable estimates of ...historical concentrations of air pollutants, which would be further applied to the long-term exposure evaluation. In particular, PM10, PM2.5, NO2, SO2, benzene, and B(a)P concentrations have been obtained. Data of monitored concentrations, model calculations, and subsequent implementation of several corrections based on previous work on temporal and spatial correlations of these substances in the air have been deployed. This work makes an original contribution to the field of meteorology and epidemiology because of this innovative technique to estimate the most reliable historical concentrations of air pollutants. The novelty of our work lies in the additional implications of this study because historical concentration data serve as input data for the construction of epidemiological associations. The approach is based primarily on the availability of monitoring results of air pollutants.
Renal tumor heterogeneity studies have utilized the von Hippel-Lindau VHL gene to classify disease into molecularly defined subtypes to examine associations with etiologic risk factors and prognosis. ...The aim of this study was to provide a comprehensive analysis of VHL inactivation in clear cell renal tumors (ccRCC) and to evaluate relationships between VHL inactivation subgroups with renal cancer risk factors and VHL germline single nucleotide polymorphisms (SNPs). VHL genetic and epigenetic inactivation was examined among 507 sporadic RCC/470 ccRCC cases using endonuclease scanning and using bisulfite treatment and Sanger sequencing across 11 CpG sites within the VHL promoter. Case-only multivariate analyses were conducted to identify associations between alteration subtypes and risk factors. VHL inactivation, either through sequence alterations or promoter methylation in tumor DNA, was observed among 86.6% of ccRCC cases. Germline VHL SNPs and a haplotype were associated with promoter hypermethylation in tumor tissue (OR = 6.10; 95% CI: 2.28-16.35, p = 3.76E-4, p-global = 8E-5). Risk of having genetic VHL inactivation was inversely associated with smoking due to a higher proportion of wild-type ccRCC tumors former: OR = 0.70 (0.20-1.31) and current: OR = 0.56 (0.32-0.99); P-trend = 0.04. Alteration prevalence did not differ by histopathologic characteristics or occupational exposure to trichloroethylene. ccRCC cases with particular VHL germline polymorphisms were more likely to have VHL inactivation through promoter hypermethylation than through sequence alterations in tumor DNA, suggesting that the presence of these SNPs may represent an example of facilitated epigenetic variation (an inherited propensity towards epigenetic variation) in renal tissue. A proportion of tumors from current smokers lacked VHL alterations and may represent a biologically distinct clinical entity from inactivated cases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Gene expression microarray and next generation sequencing efforts on conventional, clear cell renal cell carcinoma (ccRCC) have been mostly performed in North American and Western European ...populations, while the highest incidence rates are found in Central/Eastern Europe. We conducted whole-genome expression profiling on 101 pairs of ccRCC tumours and adjacent non-tumour renal tissue from Czech patients recruited within the "K2 Study", using the Illumina HumanHT-12 v4 Expression BeadChips to explore the molecular variations underlying the biological and clinical heterogeneity of this cancer. Differential expression analysis identified 1650 significant probes (fold change ≥2 and false discovery rate <0.05) mapping to 630 up- and 720 down-regulated unique genes. We performed similar statistical analysis on the RNA sequencing data of 65 ccRCC cases from the Cancer Genome Atlas (TCGA) project and identified 60% (402) of the downregulated and 74% (469) of the upregulated genes found in the K2 series. The biological characterization of the significantly deregulated genes demonstrated involvement of downregulated genes in metabolic and catabolic processes, excretion, oxidation reduction, ion transport and response to chemical stimulus, while simultaneously upregulated genes were associated with immune and inflammatory responses, response to hypoxia, stress, wounding, vasculature development and cell activation. Furthermore, genome-wide DNA methylation analysis of 317 TCGA ccRCC/adjacent non-tumour renal tissue pairs indicated that deregulation of approximately 7% of genes could be explained by epigenetic changes. Finally, survival analysis conducted on 89 K2 and 464 TCGA cases identified 8 genes associated with differential prognostic outcomes. In conclusion, a large proportion of ccRCC molecular characteristics were common to the two populations and several may have clinical implications when validated further through large clinical cohorts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mild Cognitive Impairment (MCI) may be a precursor of Alzheimer's disease (AD). There is a boundary area between normal aging and dementia. In practice, the term "age related cognitive decline" has ...been used interchangeably with "normal aging". Alternatively, the term "aging associated cognitive decline" was introduced and defined by a performance on a standardized cognitive scale focused on learning and memory, attention and cognitive speed, language, or visuoconstructional abilities. The term "mild cognitive impairment" was adopted by Petersen in 2004 to describe a period in the course of neurodegenerative disease where cognition is no longer normal relative to age expectations, however, daily functions are not sufficiently disrupted to correlate with the diagnosis of dementia. Most of the literature refers to the amnestic form of MCI, which is likely a precursor of AD. The rate of conversion from amnestic form of MCI to AD is estimated to reach 10-15% per year. That is why MCI generated a great deal of research. When considering MCI a precursor of AD, it seems reasonable to study AD genetic markers in the MCI patients. In AD, association studies focus on genetic polymorphisms assumed to have an effect on the expression and modulation function of genes associated with AD pathogenesis (ApoE, APP, presenilin 1, presenilin 2, tau protein), and on polymorphisms related to metabolism of the aforementioned proteins (splicing, degradation). Neuropsychological assesment plays a substantial role in the diagnosis of MCI, especially in the case of identification of different MCI subtypes or typical profiles of cognitive performance in prodromal phases of neurodegenerative diseases. The optimal composition of diet may increase an average age and prevent impairment of cognitive functions at the same time. Despite the progress in early diagnosis of MCI and dementia, further research is needed on differential diagnosis and treatment. In amnestic subtype of MCI some genetic markers may already be present, predicting possible future development of AD. Pointing to the need of secondary prevention, lifestyle modifications and possible early treatment could be implemented.
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