Iron in renal diseases

Coraz powszechniej występujące choroby nerek mają wpływ na prawidłowe funkcjonowanie całego organizmu, w tym również na metabolizm żelaza. Przewlekła choroba nerek, jako jedna z przyczyn przewlekłego subklinicznego stanu zapalnego, prowadzi do zmniejszenia dostępności żelaza dla erytropoezy, czego następstwem jest rozwój niedokrwistości chorób przewlekłych. W procesie tym kluczową rolę odgrywa hepcydyna. Poznanie szczegółowego patomechanizmu rozwoju niedokrwistości spowodowanej funkcjonalnym niedoborem żelaza jest niezwykle istotne w kontekście wdrożenia skutecznego i bezpiecznego leczenia. Stosowanie preparatów żelaza z jednej strony prowadzi do wyrównania cech anemii, z drugiej zaś istnieje niebezpieczeństwo przeładowania ustroju żelazem, szczególnie przy dożylnej podaży tego pierwiastka.Increased prevalence of kidney diseases have an impact on the proper functioning of the entire body, including the iron metabolism. Chronic kidney disease, as one of the causes of chronic subclinical inflammation, leads to reduced availability of iron for erythropoiesis, which results in the development of anaemia of chronic disease.The key role in this process is played by hepcidin. Understanding the detailed pathomechanism of development of anaemia caused by functional iron deficiency is very important in regard to the implementation of an effective and safe treatment. Iron supplementation on the one hand leads to compensation of anaemia, on the other hand there is associated with the risk of iron overload, especially for the intravenous iron supplementation

Iron Status and Inflammation in Early Stages of Chronic Kidney Disease

Background/Aims: One of the most common causes of anemia of chronic disease (ACD) is chronic kidney disease. The main pathomechanism responsible for ACD is subclinical inflammation. The key element involved in iron metabolism is hepcidin, however, studies on new indices of iron status are in progress.The aim of the study was to assess the iron status in patients in early stages of chronic kidney disease, iron correlation with inflammation parameters and novel biomarkers of iron metabolism. Methods: The study included 69 patients. Standard laboratory measurements were used to measure the iron status, complete blood count, fibrinogen, prothrombin index, C-reactive protein concentration (CRP), creatinine, urea, uric acid. Commercially available kits were used to measure high-sensitivity CRP, interleukin 6 (IL-6), hepcidin-25, hemojuvelin, soluble transferrin receptor (sTfR), growth differentiation factor-15 (GDF-15) and zonulin. Results: Absolute iron deficiency was present in 17% of the patients, functional iron deficiency was present in 12% of the patients. Functional iron deficiency was associated with significantly higher serum levels of fibrinogen, ferritin, transferrin saturation, total iron binding capacity, hepcidin and older age relative to patients with absolute iron deficiency. In comparison with patients without iron deficiency, patients with functional iron deficiency were older, with lower prothrombin index, higher fibrinogen, CRP, hsCRP, sTfR, GDF-15, urea and lower eGFR. Hepcidin was predicted by markers of inflammation:ferritin, fibrinogen and IL-6. Conclusion: Inflammation is correlated with iron status. Novel biomarkers of iron metabolism might be useful to distinguish iron deficiency anemia connected with inflammation and absolute iron deficiency

Identification of Mortality Risks in the Advancement of Old Age: Application of Proportional Hazard Models Based on the Stepwise Variable Selection and the Bayesian Model Averaging Approach

Identifying factors that affect mortality requires a robust statistical approach. This study’s objective is to assess an optimal set of variables that are independently associated with the mortality risk of 433 older comorbid adults that have been discharged from the geriatric ward. We used both the stepwise backward variable selection and the iterative Bayesian model averaging (BMA) approaches to the Cox proportional hazards models. Potential predictors of the mortality rate were based on a broad range of clinical data; functional and laboratory tests, including geriatric nutritional risk index (GNRI); lymphocyte count; vitamin D, and the age-weighted Charlson comorbidity index. The results of the multivariable analysis identified seven explanatory variables that are independently associated with the length of survival. The mortality rate was higher in males than in females; it increased with the comorbidity level and C-reactive proteins plasma level but was negatively affected by a person’s mobility, GNRI and lymphocyte count, as well as the vitamin D plasma level

Cognitive Functioning of Geriatric Patients: Is Hypovitaminosis D the Next Marker of Cognitive Dysfunction and Dementia?

The study objective is to investigate whether vitamin D is associated with the cognitive function of geriatric patients. This cross-sectional study involved 357 patients hospitalized in the geriatric ward who complained of memory problems (mean age: 82.3 years). The level of cognitive function was measured with the Mini-Mental State Examination (MMSE) and the clinical diagnosis of dementia was established according to the International Classification of Diseases (ICD-10) criteria. The serum 25-hydroxy vitamin D was measured with liquid chromatography-tandem mass spectrometry. The iterative Bayesian model averaging (BMA) procedure was applied to linear and logistic regression models in order to identify the best set of factors describing cognitive dysfunction and dementia, respectively. According to BMA, there is strong evidence that higher vitamin D levels, higher body mass index (BMI), and higher mobility function measured with the Timed Up and Go (TUG) test are independently associated with better cognitive performance and lower risk of dementia. Additionally, there is strong evidence that fewer years of education and lower vitamin B12 plasma levels independently describe worse cognitive performance. However, vitamin B12 levels higher than 800 pg/mL is negatively associated with the MMSE performance. Hypovitaminosis D in geriatric patients is an underrated marker of cognitive dysfunction and dementia

Lichen Secondary Metabolites Inhibit the Wnt/β-Catenin Pathway in Glioblastoma Cells and Improve the Anticancer Effects of Temozolomide

Lichens are a source of secondary metabolites with significant pharmacological potential. Data regarding their possible application in glioblastoma (GBM) treatment are, however, scarce. The study aimed at analyzing the mechanism of action of six lichen secondary metabolites: atranorin, caperatic acid, physodic acid, squamatic acid, salazinic acid, and lecanoric acid using two- and three-dimensional GBM cell line models. The parallel artificial membrane permeation assay was used to predict the blood-brain barrier penetration ability of the tested compounds. Their cytotoxicity was analyzed using the MTT test on A-172, T98G, and U-138 MG cells. Flow cytometry was applied to the analysis of oxidative stress, cell cycle distribution, and apoptosis, whereas qPCR and microarrays detected the induced transcriptomic changes. Our data confirm the ability of lichen secondary metabolites to cross the blood-brain barrier and exert cytotoxicity against GBM cells. Moreover, the compounds generated oxidative stress, interfered with the cell cycle, and induced apoptosis in T98G cells. They also inhibited the Wnt/β-catenin pathway, and this effect was even stronger in case of a co-treatment with temozolomide. Transcriptomic changes in cancer related genes induced by caperatic acid and temozolomide were the most pronounced. Lichen secondary metabolites, caperatic acid in particular, should be further analyzed as potential anti-GBM agents

Lichen Secondary Metabolites Inhibit the Wnt/β-Catenin Pathway in Glioblastoma Cells and Improve the Anticancer Effects of Temozolomide

Lichens are a source of secondary metabolites with significant pharmacological potential. Data regarding their possible application in glioblastoma (GBM) treatment are, however, scarce. The study aimed at analyzing the mechanism of action of six lichen secondary metabolites: atranorin, caperatic acid, physodic acid, squamatic acid, salazinic acid, and lecanoric acid using two- and three-dimensional GBM cell line models. The parallel artificial membrane permeation assay was used to predict the blood-brain barrier penetration ability of the tested compounds. Their cytotoxicity was analyzed using the MTT test on A-172, T98G, and U-138 MG cells. Flow cytometry was applied to the analysis of oxidative stress, cell cycle distribution, and apoptosis, whereas qPCR and microarrays detected the induced transcriptomic changes. Our data confirm the ability of lichen secondary metabolites to cross the blood-brain barrier and exert cytotoxicity against GBM cells. Moreover, the compounds generated oxidative stress, interfered with the cell cycle, and induced apoptosis in T98G cells. They also inhibited the Wnt/β-catenin pathway, and this effect was even stronger in case of a co-treatment with temozolomide. Transcriptomic changes in cancer related genes induced by caperatic acid and temozolomide were the most pronounced. Lichen secondary metabolites, caperatic acid in particular, should be further analyzed as potential anti-GBM agents