This review offers a synthesis of the current understanding of the impact of low-dose thallium (Tl) on public health, specifically emphasizing its diverse effects on various populations and organs. ...The article integrates insights into the cytotoxic effects, genotoxic potential, and molecular mechanisms of thallium in mammalian cells. Thallium, a non-essential heavy metal present in up to 89 different minerals, has garnered attention due to its adverse effects on human health. As technology and metallurgical industries advance, various forms of thallium, including dust, vapor, and wastewater, can contaminate the environment, extending to the surrounding air, water sources, and soil. Moreover, the metal has been identified in beverages, tobacco, and vegetables, highlighting its pervasive presence in a wide array of food sources. Epidemiological findings underscore associations between thallium exposure and critical health aspects such as kidney function, pregnancy outcomes, smoking-related implications, and potential links to autism spectrum disorder. Thallium primarily exerts cellular toxicity on various tissues through mitochondria-mediated oxidative stress and endoplasmic reticulum stress. This synthesis aims to shed light on the intricate web of thallium exposure and its potential implications for public health, emphasizing the need for vigilant consideration of its risks.
Ochratoxin A (OTA) is a mycotoxin widely found in various foods and feeds that have a deleterious effect on humans and animals. It has been shown that OTA causes multiorgan toxicity, and the kidney ...is the main target of OTA among them. This present article aims to review recent and latest intracellular molecular interactions and signaling pathways of OTA-induced nephrotoxicity. Pyroptosis, lipotoxicity, organic anionic membrane transporter, autophagy, the ubiquitin-proteasome system, and histone acetyltransferase have been involved in the renal toxicity caused by OTA. Meanwhile, the literature reviewed the alternative or method against OTA toxicity by reducing ROS production, oxidative stress, activating the Nrf2 pathway, through using nanoparticles, a natural flavonoid, and metal supplement. The present review discloses the molecular mechanism of OTA-induced nephrotoxicity, providing opinions and strategies against OTA toxicity.
Pathological insults usually disturb the folding capacity of cellular proteins and lead to the accumulation of misfolded proteins in the endoplasmic reticulum (ER), which leads to so-called “ER ...stress”. Increasing evidence indicates that ER stress acts as a trigger factor for the development and progression of many kidney diseases. The unfolded protein responses (UPRs), a set of molecular signals that resume proteostasis under ER stress, are thought to restore the adaptive process in chronic kidney disease (CKD) and renal fibrosis. Furthermore, the idea of targeting UPRs for CKD treatment has been well discussed in the past decade. This review summarizes the up-to-date literature regarding studies on the relationship between the UPRs, systemic fibrosis, and renal diseases. We also address the potential therapeutic possibilities of renal diseases based on the modulation of UPRs and ER proteostasis. Finally, we list some of the current UPR modulators and their therapeutic potentials.
Epigenetic changes, particularly non‐coding RNAs, have been implicated extensively in the pathogenesis of vascular diseases. Specific miRNAs are involved in the differentiation, phenotypic switch, ...proliferation, apoptosis, cytokine production and matrix deposition of endothelial cells and/or vascular smooth muscle cells. MicroRNA‐125b has been studied in depth for its role in carcinogenesis with a double‐edged role; that is, it can act as an oncogene in some cancer types and as a tumour suppressor gene in others. However, cumulative evidence from the use of advanced miRNA profiling techniques and bioinformatics analysis suggests that miR‐125b can be a potential mediator and useful marker of vascular diseases. Currently, the exact role of miR‐125b in vascular diseases is not known. In this systematic review, we intend to provide an updated compilation of all the recent findings of miR‐125b in vascular diseases, using a systematic approach of retrieving data from all available reports followed by data summarization. MiR‐125b serves as a pathogenic player in multiple vascular pathologies involving endothelia and vascular smooth muscle cells and also serves as a diagnostic marker for vascular diseases. We further provide a computational biologic presentation of the complex network of miR‐125b and its target genes within the scope of vascular diseases.
Vascular calcification (VC) describes the pathophysiological phenotype of calcium apatite deposition within the vascular wall, leading to vascular stiffening and the loss of compliance. VC is never ...benign; the presence and severity of VC correlate closely with the risk of myocardial events and cardiovascular mortality in multiple at-risk populations such as patients with diabetes and chronic kidney disease. Mitochondrial dysfunction involving each of vascular wall constituents (endothelia and vascular smooth muscle cells (VSMCs)) aggravates various vascular pathologies, including atherosclerosis and VC. However, few studies address the pathogenic role of mitochondrial dysfunction during the course of VC, and mitochondrial reactive oxygen species (ROS) seem to lie in the pathophysiologic epicenter. Superoxide dismutase 2 (SOD2), through its preferential localization to the mitochondria, stands at the forefront against mitochondrial ROS in VSMCs and thus potentially modifies the probability of VC initiation or progression. In this review, we will provide a literature-based summary regarding the relationship between SOD2 and VC in the context of VSMCs. Apart from the conventional wisdom of attenuating mitochondrial ROS, SOD2 has been found to affect mitophagy and the formation of the autophagosome, suppress JAK/STAT as well as PI3K/Akt signaling, and retard vascular senescence, all of which underlie the beneficial influences on VC exerted by SOD2. More importantly, we outline the therapeutic potential of a novel SOD2-targeted strategy for the treatment of VC, including an ever-expanding list of pharmaceuticals and natural compounds. It is expected that VSMC SOD2 will become an important druggable target for treating VC in the future.
The association between incident chronic kidney disease (CKD) or end-stage renal disease (ESRD) and exposure to outdoor air pollution is under debate. We aimed to examine this relationship based on a ...systematic review with random-effects meta-analysis.
We screened the literature on long-term air pollution exposure assessment in the general population using an electronic search of PubMed, Medline, Embase, and Cochrane Library from inception to 20 October 2019. Observational studies investigating the association between long-term exposure to gaseous (CO, SO2, NO2, O3) or particulate (PM2.5 or PM10) outdoor air pollutants and CKD, ESRD, or renal dysfunction were included, and summary risks were estimated.
Of 4419 identified articles, 23 met our inclusion criteria after screening and 14 were included in the meta-analysis. Pooled effect estimates had the following summary risk ratios (RRs) for CKD: 1.10 (95% confidence intervals CI 1.00, 1.21; derived from four studies) per 10 μg/m3 increase in PM2.5 and 1.16 (95% CI 1.05, 1.29; derived from four studies) for PM10; 1.31 (95% CI 0.86, 2.00; derived from two studies) per 10 ppm increase in CO; and 1.11 (95% CI 1.09, 1.14; derived from three studies) per 10 ppb increase in NO2. For the pooled effect on eGFR, increases in PM10 and PM2.5 (of 10 μg/m3) were associated with eGFR decline by −0.83 (95% CI –1.54, −0.12; derived from two studies) and −4.11 (95% CI –12.64, 4.42; derived from two studies) mL/min/1.73 m2, respectively.
Air pollution was observed to be associated with CKD and renal function decline. Although more longitudinal studies are required, we argue that air pollution is pernicious to kidney health.
Forest plot and pooled estimates of the effect of air pollutants on the risk of chronic kidney disease.
(The size of the gray boxes for each point estimate represents the size of the included study.) Display omitted
•Long-term exposure to air pollutants, especially ambient PM and NO2, is associated with an increased risk of CKD.•PM2.5 substantially contributed to the global burden of CKD in 2016.•Considerable statistical heterogeneities were revealed in this meta-analysis.•An inverse relationship between the concentration of ambient air particulate matter and eGFR were identified.
Uremic toxins are defined as harmful metabolites that accumulate in the human body of patients whose renal function declines, especially chronic kidney disease (CKD) patients. Growing evidence ...demonstrates the deteriorating effect of uremic toxins on CKD progression and CKD-related complications, and removing uremic toxins in CKD has become the conventional treatment in the clinic. However, studies rarely pay attention to uremic toxin clearance in the early stage of acute kidney injury (AKI) to prevent progression to CKD despite increasing reports demonstrating that uremic toxins are correlated with the severity of injury or mortality. This review highlights the current evidence of uremic toxin accumulation in AKI and the therapeutic value to prevent CKD progression specific to protein-bound uremic toxins (PBUTs).
Continuous renal replacement therapy (CRRT) is one of the dialysis modalities for critically ill patients. Despite intensive dialysis care, a high mortality rate is found in these patients. Our ...objective was to investigate the factors associated with poor outcomes in these patients. We conducted a retrospective cohort study using the National Health Insurance Research Database. Records of critically ill patients who received CRRT between 2007 and 2011 were retrieved, and the patients were categorized into two groups: those with acute kidney injury (AKI) and those with history of end-stage renal disease (ESRD). Our primary and secondary outcomes were in-hospital mortality and long-term survival and non-renal recovery (long-term dialysis dependence), respectively, in the AKI group. We enrolled 15,453 patients, with 13,204 and 2249 in the AKI and ESRD groups, respectively. Overall, 66.5% patients died during hospitalization. In-hospital mortality did not differ significantly between groups (adjusted odds ratio, 0.93; 95% CI, 0.84-1.02). Age, chronic liver disease, and cancer history were identified as independent risk factors for in-hospital mortality in both groups. Hypertension was associated with higher risk of in-hospital mortality in patients with AKI. Age, coronary artery disease, and admission to the medical intensive care unit (MICU) were risk factors for long-term dialysis dependence in patients with AKI. Patients with AKI and ESRD have similarly poor outcomes after CRRT. Older age and presence of chronic liver disease and cancer were associated with higher mortality. Older age, presence of coronary artery disease, and admission to MICU were associated with lower renal recovery rate in patients with AKI.
Low-intensity pulsed ultrasound (LIPUS), a therapeutic type of ultrasound, is known to enhance bone fracture repair processes and help some tissues to heal. Here, we investigated the therapeutic ...potential of LIPUS for the treatment of chronic kidney disease (CKD) in two CKD mouse models. CKD mice were induced using both unilateral renal ischemia/reperfusion injury (IRI) with nephrectomy and adenine administration. The left kidneys of the CKD mice were treated using LIPUS with the parameters of 3 MHz, 100 mW/cm2, and 20 min/day, based on the preliminary experiments. The mice were euthanized 14 days after IRI or 28 days after the end of adenine administration. LIPUS treatment effectively alleviated the decreases in the body weight and albumin/globulin ratio and the increases in the serum renal functional markers, fibroblast growth factor-23, renal pathological changes, and renal fibrosis in the CKD mice. The parameters for epithelial–mesenchymal transition (EMT), senescence-related signal induction, and the inhibition of α-Klotho and endogenous antioxidant enzyme protein expression in the kidneys of the CKD mice were also significantly alleviated by LIPUS. These results suggest that LIPUS treatment reduces CKD progression through the inhibition of EMT and senescence-related signals. The application of LIPUS may be an alternative non-invasive therapeutic intervention for CKD therapy.
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