Iron-induced kidney cell damage: insights into molecular mechanisms and potential diagnostic significance of urinary FTL

Background: Iron overload can lead to organ and cell injuries. Although the mechanisms of iron-induced cell damage have been extensively studied using various cells, little is known about these processes in kidney cells.Methods: In this study, we first examined the correlation between serum iron levels and kidney function. Subsequently, we investigated the molecular impact of excess iron on kidney cell lines, HEK293T and HK-2. The presence of the upregulated protein was further validated in urine.Results: The results revealed that excess iron caused significant cell death accompanied by morphological changes. Transcriptomic analysis revealed an up-regulation of the ferroptosis pathway during iron treatment. This was confirmed by up-regulation of ferroptosis markers, ferritin light chain (FTL), and prostaglandin-endoperoxide synthase 2 (PTGS2), and down-regulation of acyl-CoA synthetase long-chain family member 4 (ACSL4) and glutathione peroxidase 4 (GPX4) using real-time PCR and Western blotting. In addition, excess iron treatment enhanced protein and lipid oxidation. Supportively, an inverse correlation between urinary FTL protein level and kidney function was observed.Conclusion: These findings suggest that excess iron disrupts cellular homeostasis and affects key proteins involved in kidney cell death. Our study demonstrated that high iron levels caused kidney cell damage. Additionally, urinary FTL might be a useful biomarker to detect kidney damage caused by iron toxicity. Our study also provided insights into the molecular mechanisms of iron-induced kidney injury, discussing several potential targets for future interventions

Development of a high-accuracy, low-cost, and portable fluorometer with smartphone application for the detection of urinary albumin towards the early screening of chronic kidney and renal diseases

This study presents the development of a portable fluorometer with a smartphone application designed to facilitate the early screening of chronic kidney and renal diseases by enabling the sensitive detection of urinary albumin. Utilizing a fluorescence-based aptasensor, the device achieved a linear calibration curve (0.001–1.5 mg/mL) with a linearity of up to 0.98022 and a detection limit of 0.203 µg/mL for human serum albumin (HSA). The analysis of 130 urine samples demonstrated comparable performance between this study’s fluorometer, a commercial fluorometer, and the standard automated method. These findings validate the feasibility of the portable fluorometer and aptasensor combination as a reliable instrument for the sensitive and specific measurement of HSA in urine samples. Moreover, the fluorometer’s portability offers potential applications in portable point-of-care testing, enhancing its utility in clinical settings for early disease screening

Effects of particulate matter (PM2.5) concentration and components on mortality in chronic kidney disease patients: a nationwide spatial–temporal analysis

Abstract Chronic kidney disease (CKD) is a major global public health issue and the leading cause of death in Thailand. This study investigated the spatial–temporal association between PM2.5 and its components (organic carbon, black carbon, dust, sulfate, and sea salt) and CKD mortality in Thailand from 2012 to 2021. The Modern-Era Retrospective analysis for Research and Application version 2 (MERRA-2), a NASA atmospheric satellite model, was assessed for the temporal data of PM2.5 concentration and aerosol components. Spatial resources of 77 provinces were integrated using the Geographical Information System (GIS). Multivariate Poisson regression and Bayesian inference analyses were conducted to explore the effects of PM2.5 on CKD mortality across the provinces. Our analysis included 718,686 CKD-related deaths, resulting in a mortality rate of 1107 cases per 100,000 population where was the highest rate in Northeast region. The average age of the deceased was 72.43 ± 13.10 years, with males comprising 50.46% of the cases. Adjusting for age, sex, underlying diseases, co-morbidities, CKD complications, replacement therapy, population density, and income, each 1 µg/m3 increase in PM2.5, black carbon, dust, sulfate, and organic carbon was significantly associated with increased CKD mortality across 77 provinces. Incidence rate ratios were 1.04 (95% CI 1.03–1.04) for PM2.5, 1.11 (95% CI 1.10–1.13) for black carbon, 1.24 (95% CI 1.22–1.25) for dust, 1.16 (95% CI 1.16–1.17) for sulfate, and 1.05 (95% CI 1.04–1.05) for organic carbon. These findings emphasize the significant impact of PM2.5 on CKD mortality and underscore the need for strategies to reduce PM emissions and manage CKD co-morbidities effectively

Response to Dr. Roger¿s letter: further studies are necessary in order to conclude a causal association between the consumption of monosodium L-glutamate (MSG) and the prevalence of metabolic syndrome in the rural Thai population

See related article: http://www.nutritionandmetabolism.com/content/10/1/1

Overexpression of lactate dehydrogenase A in cholangiocarcinoma is correlated with poor prognosis

Lactate dehydrogenase A (LDHA), a key metabolic enzyme, plays a crucial role in the final step of anaerobic glycolysis. Overexpression of LDHA is observed in many human malignancies in association with tumor progression. The purpose of this study was to investigate LDHA expression pattern during carcinogenesis, its clinico-pathological association, and evaluate the prognostic value of LDHA in CCA patients. LDHA expression was investigated using immunohistochemistry technique in both hamster- (n=60) and human-CCA tissues (n=82). Plasma LDH from healthy control (n=40) and CCA patients (n=29) were determined using an enzymatic based assay. The association of LDHA expression with clinicopathological findings and prognostic value were evaluated by statistical analysis. In the CCA hamster model, an increase of LDHA expression was associated with the progression of CCA-genesis. Higher LDHA overexpression was associated with shorter survival of CCA patients. Multivariate analysis indicated that LDHA expression including histological type were independent prognostic risk factor of patient’s survival. However, there was no difference in plasma LDH level between CCA patients and healthy controls. LDHA expression is involved in cholangio-carcinogenesis. Overexpression of LDHA can be a marker of poor prognosis in CCA patients and it might be a potential target for CCA treatment

Effects of Boric Acid and Storage Temperature on the Analysis of Microalbumin Using Aptasensor-Based Fluorescent Detection

The instability of human serum albumin (HSA) in urine samples makes fresh urine a requirement for microalbumin analyses using immunoturbidimetry. Here, we determined the ability of an aptasensor-based fluorescent platform to detect microalbumin in old, boric acid-preserved urine samples. Our results show that the cleavage site of protease enzymes on urine albumin protein differed from the binding position of the aptamer on HSA protein, suggesting the aptasensor may be effective for albumin detection in non-fresh urine. Furthermore, the addition of boric acid in urine samples over a short term (at ambient temperature (Ta) and 4 °C), long term (−20 and −80 °C), and following freeze–thawing (1–3 cycles) did not significantly affect albumin stability, as analyzed using the aptasensor. Therefore, boric acid stabilized has in urine stored over a short- and long-term. Thus, the aptasensor developed by us is applicable for HSA detection in boric acid-preserved urine that has been stored for 7-d at Ta and 4 °C, and in the long-term at −80 °C

Two-dimensional gel electrophoresis of rat kidney lysate; Coomassie blue-stained gels from control (a) and MSG-treated rats (b).

<p>Proteins were resolved on 7 cm pH 3–11 IEF strips (NL) followed by SDS-PAGE (12%). The differentially expressed spots detected by the image Master 2D Platinum 7.0 software are circled. The gels shown are representative of three independent experiments.</p

Proposed model of MSG-induced ROS production in rat kidney.

<p>The higher level of glutamate on chronic MSG intake accelerates TCA cycle. The increased level of α-KGDH may stimulate ROS production hence oxidative stress occurs in the kidney of the MSG-treated rats.</p

List of renal proteins with significantly altered expression after long term chronic MSG treatment.

<p>List of renal proteins with significantly altered expression after long term chronic MSG treatment.</p