Glycolytic stress deteriorates 229E virulence to improve host defense response.

Viral infection treatment is a difficult task due to its complex structure and metabolism. Additionally, viruses can alter the metabolism of host cells, mutate, and readily adjust to harsh environments. Coronavirus stimulates glycolysis, weakens mitochondrial activity, and impairs infected cells. In this study, we investigated the efficacy of 2-DG in inhibiting coronavirus-induced metabolic processes and antiviral host defense systems, which have not been explored so far. 2-Deoxy-d-glucose (2-DG), a molecule restricting substrate availability, has recently gained attention as a potential antiviral drug. The results revealed that 229E human coronavirus promoted glycolysis, producing a significant increase in the concentration of fluorescent 2-NBDG, a glucose analog, particularly in the infected host cells. The addition of 2-DG decreased its viral replication and suppressed infection-induced cell death and cytopathic effects, thereby improving the antiviral host defense response. It was also observed that administration of low doses of 2-DG inhibited glucose uptake, indicating that 2-DG consumption in virus-infected host cells was mediated by high-affinity glucose transporters, whose levels were amplified upon coronavirus infection. Our findings indicated that 2-DG could be a potential drug to improve the host defense system in coronavirus-infected cells.

Enhanced removal of cesium from hydrobiotite using polyacrylonitrile (PAN)-based nickel ferrocyanide beads.

The desorption of cesium (Cs) from contaminated clay minerals remains challenging because of the restricted efficiency of the removal process. Therefore, in the present study, a bead-type adsorbent was added during the conventional acid washing process to improve the removal of Cs+ from a clay mineral. As the Cs+ adsorbent, polyacrylonitrile-based nickel potassium hexacyanoferrate (NiFC-PAN) was used to selectively adsorb Cs+ in a strongly acidic solution containing competing ions. To prevent erosion of the adsorbent under harsh environmental conditions and to facilitate the separation of clay particles, PAN was deliberately constructed as large beads. The synthesized adsorbent (NiFC/PAN in a 2:1 ratio) showed high selectivity for Cs+, with a maximum capacity for Cs+ adsorption of 162.78 mg/g in 0.5 M HNO3 solution. Because the NiFC-PAN demonstrated greater Cs+ selectivity than the clay mineral (hydrobiotite, HBT), the addition of NiFC-PAN during the acid washing significantly increased Cs+ desorption (73.3%) by inhibiting the re-adsorption of Cs+ on the HBT. The radioactivity of 137Cs-HBT was substantially decreased from 209 to 27 Bq/g by the acid treatment in the presence of NiFC-PAN, corresponding to a desorption efficiency of 87.1%. Therefore, these results suggest that the proposed technique is a potentially useful and effective method for decontamination of radioactive clay.

The inactivation and destruction of viruses by reactive oxygen species generated through physical and cold atmospheric plasma techniques: Current status and perspectives.

BACKGROUND: Outbreaks of airborne viral infections, such as COVID-19, can cause panic regarding other severe respiratory syndrome diseases that may develop and affect public health. It is therefore necessary to develop control methods that offer protection against such viruses. AIM OF REVIEW: To identify a feasible solution for virus deactivation, we critically reviewed methods of generating reactive oxygen species (ROS), which can attack a wide range of molecular targets to induce antiviral activity, accounting for their flexibility in facilitating host defense mechanisms against a comprehensive range of pathogens. Recently, the role of ROS in microbial decontamination has been critically investigated as a major topic in infectious diseases. ROS can eradicate pathogens directly by inducing oxidative stress or indirectly by promoting pathogen removal through numerous non-oxidative mechanisms, including autophagy, T-cell responses, and pattern recognition receptor signaling. KEY SCIENTIFIC CONCEPTS OF REVIEW: In this article, we reviewed possible methods for the in vitro generation of ROS with antiviral activity. Furthermore, we discuss, in detail, the novel and environmentally friendly cold plasma delivery system in the destruction of viruses. This review highlights the potential of ROS as therapeutic mediators to modernize current techniques and improvement on the efficiency of inactivating SARS-CoV2 and other viruses.

Characterization of Bioactive Compounds Having Antioxidant and Anti-Inflammatory Effects of Liliaceae Family Flower Petal Extracts.

Beneficial natural products utilized in cosmetics formulation and pharmaceutical applications are of enormous interest. Lily (Lilium) serves as an essential edible and medicinal plant species with wide classification. Here, we have performed the screening of various extracts that were prepared from flower petals grown from the bulbs of eight Lilium varieties, with a viewpoint to their applicability as a viable source of natural anti-inflammatory and antioxidants agent. Interestingly, our findings indicated that all ethanol and water extracts exhibited a substantially differential spectrum of antioxidant as well as anti-inflammatory properties. Specifically, Serrano showed a close similarity among ethanol and water extracts among all tested lily petal extracts. Therefore, to obtain a detailed analysis of chemical compounds, liquid chromatography-mass spectroscopy was performed in ethanolic and water extracts of Serrano petals. Together, our preliminary results indicated that lily petals extracts used in this study could serve as a basis to develop a potential new whitening agent with powerful antioxidant and anti-inflammatory properties for medicinal, functional food, and cosmetic applications.

Current Nanomedicine for Targeted Vascular Disease Treatment: Trends and Perspectives.

Nanotechnology has been developed to deliver cargos effectively to the vascular system. Nanomedicine is a novel and effective approach for targeted vascular disease treatment including atherosclerosis, coronary artery disease, strokes, peripheral arterial disease, and cancer. It has been well known for some time that vascular disease patients have a higher cancer risk than the general population. During atherogenesis, the endothelial cells are activated to increase the expression of adhesion molecules such as Intercellular Adhesion Molecule 1 (ICAM-1), Vascular cell adhesion protein 1 (VCAM-1), E-selectin, and P-selectin. This biological activation of endothelial cells gives a targetability clue for nanoparticle strategies. Nanoparticle formation has a passive targeting pathway due to the increased adhesion molecule expression on the cell surface as well as increased cell activation. In addition, the VCAM-1-targeting peptide has been widely used to target the inflamed endothelial cells. Biomimetic nanoparticles using platelet and leukocyte membrane fragment strategies have been promising techniques for targeted vascular disease treatment. Cyclodextrin, a natural oligosaccharide with a hydrophobic cavity, increase the solubility of cholesterol crystals at the atherosclerotic plaque site and has been used to deliver the hydrophobic drug statin as a therapeutic in a targeted manner. In summary, nanoparticles decorated with various targeting molecules will be an effective and promising strategy for targeted vascular disease treatment.

Screening of Hibiscus and Cinnamomum Plants and Identification of Major Phytometabolites in Potential Plant Extracts Responsible for Apoptosis Induction in Skin Melanoma and Lung Adenocarcinoma Cells.

Carcinogenesis is a major concern that severely affects the human population. Owing to persistent demand for novel therapies to treat and prohibit this lethal disease, research interest among scientists is drawing its huge focus toward natural products, as they have minimum toxicity comparable with existing treatment methods. The plants produce secondary metabolites, which are known to have the anticancer potential for clinical drug development. Furthermore, the use of nanocarriers could boost the solubility and stability of phytocompounds to obtain site-targeting delivery. The identification of potential phytochemicals in natural compounds would be beneficial for the synthesis of biocompatible nanoemulsions. The present study aimed to investigate the potential cytotoxicity of ethanol extracts of Hibiscus syriacus and Cinnamomum loureirii Nees plant parts on human skin melanoma (G361) and lung adenocarcinoma (A549) cells. Importantly, biochemical analysis results showed the presence of high phenol (50-55 µgGAE/mg) and flavonoids [42-45 µg quercetin equivalents (QE)/mg] contents with good antioxidant activity (40-58%) in C. loureirii Nees plants extracts. This plant possesses potent antiproliferative activity (60-90%) on the malignant G361 and A549 and cell lines correlated with the production of nitric oxide. Especially, C. loureirii plant extracts have major metabolites that exhibit cancer cell death associated with cell cycle arrest. These findings support the potential application of Cinnamomum for the development of therapeutic nanoemulsion in future cancer therapy.

Blockade of Cellular Energy Metabolism through 6-Aminonicotinamide Reduces Proliferation of Non-Small Lung Cancer Cells by Inducing Endoplasmic Reticulum Stress.

The pentose phosphate pathway (PPP) is the most common pathway in most cancer cells and stimulates antioxidant defense mechanisms and synthesis of biomolecule precursors. It is believed that cancer cells persistently ameliorate glucose flux into the PPP to maintain their anabolic requirements and adjust oxidative stress. TCGA analyses have indicated the upregulation of enzymes involved in PPP in lung cancer. Hence, the present study aimed to determine whether the pharmacological blockade of glucose 6-phosphate dehydrogenase (G6PD), the primary and rate-limiting enzyme involved in PPP, using 6-aminonicotinamide (6-AN), could induce antiproliferative activity in two lung cancer cell lines. Exposure to 6-AN suppressed lactate production and glucose consumption, modified the mitochondrial potential and redox balance, and thereby induced the endoplasmic reticulum (ER) stress to reduce lung cancer cell proliferation and govern cellular apoptosis. Collectively, this is the first study in which PPP blockade by 6-AN causes reactive oxygen species (ROS)-mediated apoptosis by ER stress in lung cancer cells. Further preclinical studies will be conducted to validate the biological applicability of these findings.

Characteristic and remediation of radioactive soil in nuclear facility sites: a critical review.

A huge amount of radioactive soil has been generated through decommissioning of nuclear facilities around the world. This review focuses on the difficulties and complexities associated with the remediation of radioactive soils at the site level; therefore, laboratory studies were excluded from this review. The problems faced while remediating radioactive soils using techniques based on strategies such as dry separation, soil washing, flotation separation, thermal desorption, electrokinetic remediation, and phytoremediation are discussed, along with appropriate examples. Various factors such as soil type, particle size, the fraction of fine particles, and radionuclide characteristics that strongly influence radioactive soil decontamination processes are highlighted. In this review, we also survey and compare the pool of available technologies currently being used for the remediation of radionuclide-contaminated soils, as well as the economic aspects of soil remediation using different techniques. This review demonstrates the importance of the integrated role of various factors in determining the effectiveness of the radioactive soil decontamination process.

Eleutherococcus sessiliflorus Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-Induced Osteoclast Differentiation and Prevents Ovariectomy (OVX)-Induced Bone Loss.

The aim of this study was to evaluate the effects of root bark of Eleutherococcus sessiliflorus (ES) on osteoclast differentiation and function in vitro and in vivo. In vitro, we found that ES significantly inhibited the RANKL-induced formation of TRAP-positive multinucleated osteoclasts and osteoclastic bone resorption without cytotoxic effects. ES markedly downregulated the expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1); c-Fos; and osteoclast-related marker genes, such as TRAP, osteoclast-associated receptor (OSCAR), matrix metalloproteinase-9 (MMP-9), calcitonin receptor, cathepsin K, the 38 kDa d2 subunit of the vacuolar H+-transporting lysosomal ATPase (Atp6v0d2), dendritic cell-specific transmembrane protein (DC-STAMP), and osteoclast-stimulatory transmembrane protein (OC-STAMP). These effects were achieved by inhibiting the RANKL-mediated activation of MAPK signaling pathway proteins, including p38, ERK, and JNK. In vivo, ES attenuated OVX-induced decrease in bone volume to tissue volume ratio (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and bone mineral density, but increased trabecular separation (Tb.Sp) in the femur. Collectively, our findings showed that ES inhibited RANKL-activated osteoclast differentiation in bone marrow macrophages and prevented OVX-mediated bone loss in rats. These findings suggest that ES has the potential to be used as a therapeutic agent for bone-related diseases, such as osteoporosis.

Sorption behavior of cesium on silt and clay soil fractions.

The effect of clay mineral composition on Cs adsorption behavior of silt and clay fractions (SC-fractions) of soil was investigated. Surface soil samples were collected within 2 km of Kori and Wolsong nuclear power plants in South Korea, and SC-fractions (<20 µm) were separated. The physicochemical properties of SC-fractions and types of clay minerals contained in the SC-fractions were analyzed. The cesium adsorption capacity of the SC-fractions, and affinity between the SC-fractions and Cs, were investigated by isothermal adsorption analysis using the dual-site Langmuir adsorption model. To understand selective adsorption of Cs, the radiocesium interception potential and distribution coefficient of the SC-fractions were analyzed in the presence or absence of competing ions. The radiocesium distribution coefficient of the SC-fractions showed a trend similar to that of the Langmuir sorption coefficient of high-affinity binding sites for Cs in the SC-fractions. The SC-fractions of Kori soils that contain only non-expandable clay minerals including highly weathered mica had low Cs adsorption capacity. However, the SC-fractions of Kori soils showed higher Cs adsorption selectivity compared to the SC-fractions of Wolsong soils containing expandable clay minerals and micaceous mineral with a low degree of weathering. It is predicted that the highly weathered micas have high affinity to Cs, and such clay minerals contribute the most to the adsorption process in dilute solutions.

Median nerve swelling is an independent risk factor of carpal tunnel syndrome in chronic hemodialysis patients.

Carpal tunnel syndrome (CTS) has a wide variety of underlying causes and occurs in association with dialysis. Early diagnosis is essential to prevent permanent nerve damage and functional sequelae. We evaluated the association between CTS and cross-sectional area (CSA) of the median nerve in chronic hemodialysis (HD) patients. Patients with end-stage renal disease on maintenance HD via arteriovenous fistula were enrolled. We divided 43 patients into two groups; patients diagnosed with CTS (n = 19) and patients without CTS (n = 24). The median nerve CSA was measured at the wrist (CSA-W) and forearm (CSA-F) by ultrasonography. Median nerve swelling was assessed by the wrist-to-forearm ratio (WFR). There were no significant differences in the underlying causes of chronic kidney disease and adequacy of dialysis between the two groups (p = NS). The patients with CTS showed significantly higher WFR than the patients without CTS (p = 0.001). Univariate Cox regression analysis revealed that WFR >1.25 (odds ratio, 6.30; 95% confidence interval, 1.44-27.45; p = 0.014) was associated with CTS in HD patients. The factors traditionally associated with CTS such as age, sex, diabetes, vintage of HD, ß2-MG, intact PTH, and Kt/V were not associated with CTS. After adjustment for age and sex, we found a strong correlation between CTS and the WFR >1.25 (odds ratio, 10.8; 95% confidence interval, 1.85-62.4; p = 0.008). High WFR was associated with the development of CTS, and median nerve swelling was an independent risk factor of CTS in chronic HD patients.

Strategies for Using Polydopamine to Induce Biomineralization of Hydroxyapatite on Implant Materials for Bone Tissue Engineering.

In the field of tissue engineering, there are several issues to consider when designing biomaterials for implants, including cellular interaction, good biocompatibility, and biochemical activity. Biomimetic mineralization has gained considerable attention as an emerging approach for the synthesis of biocompatible materials with complex shapes, categorized organization, controlled shape, and size in aqueous environments. Understanding biomineralization strategies could enhance opportunities for novel biomimetic mineralization approaches. In this regard, mussel-inspired biomaterials have recently attracted many researchers due to appealing features, such as strong adhesive properties on moist surfaces, improved cell adhesion, and immobilization of bioactive molecules via catechol chemistry. This molecular designed approach has been a key point in combining new functionalities into accessible biomaterials for biomedical applications. Polydopamine (PDA) has emerged as a promising material for biomaterial functionalization, considering its simple molecular structure, independence of target materials, cell interactions for adhesion, and robust reactivity for resulting functionalization. In this review, we highlight the strategies for using PDA to induce the biomineralization of hydroxyapatite (HA) on the surface of various implant materials with good mechanical strength and corrosion resistance. We also discuss the interactions between the PDA-HA coating, and several cell types that are intricate in many biomedical applications, involving bone defect repair, bone regeneration, cell attachment, and antibacterial activity.

Percutaneous peritoneal dialysis catheter implantation with no break-in period: A viable option for patients requiring unplanned urgent-start peritoneal dialysis.

BACKGROUND: Urgent-start peritoneal dialysis (PD) is applied to patients who need PD within two weeks but are able to wait for more than 48 hours before starting PD. To evaluate the usefulness of percutaneous PD catheter insertion in urgent-start PD, we reviewed the clinical outcomes of percutaneous catheter insertion with immediate start PD and surgical insertion with longer break-in time in Pusan National University Hospital. METHODS: This study included 177 patients who underwent urgent-start PD. Based on the PD catheter insertion techniques, the patients with urgent-start PD were divided into percutaneous (n = 103) and surgical (n = 74) groups. For the percutaneous group, a modified Seldinger percutaneous catheter insertion with immediate initiation of continuous ambulatory PD was performed by nephrologists. RESULTS: The percutaneous group showed higher serum urea nitrogen, creatinine, and lower serum albumin compared with the surgical group (P < 0.05). Ninety-day infectious and mechanical complications showed no significant differences between the two groups. Ninety-day peritonitis in the percutaneous group was 9.7% compared to 5.4% in the surgical group (P = not significant [NS]). Major leakage was 3.9% in the percutaneous group compared to 1.4% in the surgical group (P = NS). Overall infectious and mechanical complication-free survival was not significantly different between the two groups. The percutaneous group and surgical group showed no statistical difference with respect to catheter survival over the entire observation period (P = NS). CONCLUSION: This study suggests that urgent-start PD can be applied safely with percutaneous catheter insertion by nephrologists with no break-in period.

Cs desorption behavior during hydrothermal treatment of illite with oxalic acid.

The desorption of radioactive cesium (Cs) in soil is influenced by the clay mineral type, adsorption site, and concentration of Cs. In this study, experiments to detect desorption of non-radioactive and radioactive Cs from illite using oxalic acid were performed for 2 days at 70 °C in hydrothermal conditions. The results showed that the 133Cs removal efficiency by oxalic acid and inorganic acid treatment was similar at high concentration (22.86 mmol/kg) of non-radioactive 133Cs. In the radioactive 137Cs experiment, the removal efficiency by oxalic acid was higher than that by inorganic acid at low concentration (0.79 × 10-6 mmol/kg) of radioactive 137Cs. Based on the illite hypothetical frayed edge site (FES) concentration of 0.612 mmol/kg, the results suggested that 137Cs was preferentially adsorbed to FES on illite. The 137Cs at low concentration was difficult to remove because it was irreversible adsorption to FES, while the non-radioactive Cs at high concentration was mainly adsorbed to planar sites, and so was easy to desorb by ion exchange. Based on the results of NMR, FTIR, and XPS analyses, we concluded that the higher efficiency of 137Cs removal at low concentration by oxalic acid treatment than by treatment with inorganic acid was because of chelation effects associated with the complexation of oxalic acid (ligands) and metal ions in irreversible site (FES).

Application of polyethylenimine-coated magnetic nanocomposites for the selective separation of Cs-enriched clay particles from radioactive soil.

The separation of Cs-enriched fine particles is a highly effective way to reduce the volume and radioactivity of contaminated soil. This work demonstrated the application of polyethylenimine (PEI)-coated Fe3O4 nanocomposites and a mesh filter for the selective separation of clay particles from Cs-contaminated soil. The PEI coating on the Fe3O4 nanoparticles enhanced the binding force between the magnetic nanoparticles and clay minerals via electrostatic attraction; thus, approximately 100% of the clay particles were magnetically separated from solution by Fe3O4-PEI nanocomposites at a low dose (0.04 g-nanocomposite per g-clay). In separation experiments with soil mixtures, clay- and silt-sized fine particles that had been magnetized by Fe3O4-PEI nanocomposites were selectively separated, and the separation efficiency improved when a mesh filter was added to exclude physically large particles. The combination of magnetic and sieving separation thoroughly separated fine particles from soil by reducing the volume of the magnetic fraction. We also evaluated the magnetic-sieving separation method for the selective removal of clay particles from 137Cs-contaminated soil. The decrease in radioactivity in the treated nonmagnetic fraction, which accounted for 87.5% of the total soil, corresponded to a high decontamination efficiency of approximately 90%. The developed separation technology offers great potential for the efficient remediation of radioactive soil.

Desorption of cesium from hydrobiotite by hydrogen peroxide with divalent cations.

In this study, hydrogen peroxide (H2O2) was used to enhance the cation-exchange treatment for Cs+ desorption from clay minerals. Among various investigated clay minerals, hydrobiotite (HBT), which has interstratified layers of vermiculite and biotite, exhibited the highest Cs+ sorption capacity and the most favorable H2O2 activation because of its high Fe content. In X-ray diffraction analysis, HBT treated with H2O2 and 0.1 M Mg2+ showed substantial changes in its basal spacing, indicating expansion of the interlayer region induced by treatment of H2O2 and strongly hydrated divalent cations. In addition, more than 80% of the Cs+ was readily desorbed from HBT with 35% H2O2 solution and 0.1 M Mg2+ at room temperature. After three cycles under the same treatment conditions (35% H2O2 solution and 0.1 M Mg2+), approximately 99% removal of radioactive Cs+ was achieved. These results suggested that H2O2 treatment with solvated Mg2+ enhanced Cs+ desorption from HBT by altering the interlayer region through intercalation of hydrated divalent cations in conjunction with the H2O2 decomposition reaction.

Selective separation of Cs-contaminated clay from soil using polyethylenimine-coated magnetic nanoparticles.

We evaluated the feasibility of using magnetic nanoparticles (MNPs) coated with polyethylenimine (PEI), a cationic polymer, to remediate radioactive contaminated soil by separating Cs-contaminated clay from the soil. The influences of the solution pH, PEI-to-MNPs mass ratio, and the PEI-MNPs dose on the magnetic separation performance were systematically examined. The highest SE% of illite from solution through electrostatic attraction was approximately 100% at a mass ratio of 0.04 g-PEI-MNPs/g-clay. The PEI coating clearly enhanced the adhesion between MNPs and clay minerals by increasing the quantity of functional amine groups available for adsorbing negatively charged clay minerals. In separation experiments using a soil mixture, the PEI-coated MNPs selectively separated clay- and silt-sized fine particles smaller than 0.038 mm even in the presence of a large amount of sand when used at a low dose (mass ratio of 0.05 g-PEI-MNPs/g-clay) and without pH control. We also used the PEI-MNPs to separate 137Cs-contaminated illite from soil under an external magnetic field. After magnetic separation, the highest removal efficiency achieved for 137Cs removal from the treated soil was 81.7% at a low nanoparticle dosage, which resulted in satisfying the reduction of radioactivity and waste volume. The results clearly demonstrate that the selective separation of Cs-contaminated clay using PEI-coated MNPs is a promising technique for remediating radioactive soil.

Prognostic significance of malnutrition for long-term mortality in community-acquired pneumonia: a propensity score matched analysis.

BACKGROUND/AIMS: The impact of malnutrition on the outcome of hospitalized adults with community-acquired pneumonia (CAP) has not been fully investigated. This study evaluated the prevalence and prognostic significance of malnutrition in a Korean population with CAP. METHODS: In total, 198 patients with CAP from November 2014 to September 2015 were analyzed retrospectively. We assessed the prevalence of malnutrition and the risk factors for 2-year mortality. Furthermore, we divided the patients into two groups: elderly (age ≥ 65 years, n = 131) and non-elderly (age < 65 years, n = 67). Subgroup analyses were performed in the elderly group through propensity score matching. RESULTS: The prevalence of malnutrition was 39.4%, and the proportion of patients with malnutrition was significantly higher (53.4% vs. 11.9%, p < 0.001) in the elderly group than in the non-elderly group. In-hospital mortality, 1-year mortality, and 2-year mortality rates were 4.5%, 19.2%, and 26.8%, respectively. Multivariate Cox regression analyses revealed that malnutrition (odds ratio [OR], 2.52; 95% confidence interval [CI], 1.39 to 4.60; p = 0.002) and the Charlson comorbidity index score (OR, 1.30; 95% CI, 1.17 to 1.45; p < 0.001) were associated with 2-year mortality. CONCLUSION: Malnutrition was common and associated with a poor long-term outcome in patients with CAP, particularly the elderly. A routine nutritional assessment at admission is mandatory as a first step for appropriate nutritional therapy.

Plasma neutrophil gelatinase-associated lipocalin is independently associated with left ventricular hypertrophy and diastolic dysfunction in patients with chronic kidney disease.

BACKGROUND: Cardiovascular disease (CVD) is a leading cause of death in patients with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD) are known as predictors of CVD in these patients. Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of acute kidney injury. Recently, elevated NGAL levels have been reported in patients with CVD. This study aimed to evaluate the association between plasma NGAL levels and LVH/LVDD in patients with CKD. METHODS: This study included 332 patients with pre-dialysis CKD (estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2). Two-dimensional echocardiography was performed to measure the left ventricular mass index (LVMI). Tissue Doppler imaging was used to measure early mitral inflow velocity (E) and the peak early mitral annular velocity (E'). Diastolic function was estimated using E' and the ratio of E to E' (E/E'). The associations of echocardiographic index with clinical and laboratory variables (age, sex, diabetes, hypertension, eGFR, albumin, uric acid, calcium, phosphate, total cholesterol, hemoglobin, C-reactive protein, intact parathyroid hormone (PTH), the inferior vena cava collapse index (IVCCI) < 50%, and plasma NGAL) were investigated using univariate and multivariate analyses. RESULTS: In multivariate logistic regression analysis, plasma NGAL was an independent predictor of LVH (OR: 1.02, 95% CI: 1.01-1.02), P < 0.001). In addition, hypertension, intact PTH, and IVCCI < 50% were independent predictors of LVH. Plasma NGAL (OR: 1.02, 95% CI: 1.01-1.02, P < 0.001) was also an independent factor of LVDD. Furthermore, hypertension, intact PTH, and IVCCI < 50% were independent predictors of LVDD. Receiver operating characteristic curve analysis (area under the curve: 0.835, 95% CI: 0.792-0.879) showed the best cutoff value of plasma NGAL for identifying LVDD was ≥ 258 ng/ml with an associated sensitivity of 77.6% and a specificity of 87.6%. CONCLUSION: Plasma NGAL levels were independent predictors of LVH and LVDD in patients with pre-dialysis CKD, suggesting that plasma NGAL could be a biomarker for LVH and LVDD in these patients.

Low 1,25-dihydroxyvitamin D level is associated with erythropoietin deficiency and endogenous erythropoietin resistance in patients with chronic kidney disease.

PURPOSE: Erythropoietin (EPO) deficiency and resistance to endogenous EPO is an important pathophysiological feature in anemia of chronic kidney disease (CKD). Low 1,25 dihydroxyvitamin D [1,25(OH)2D] level is known to contribute to anemia of CKD. We aimed to investigate the associations between serum 1,25(OH)2D and anemia, EPO deficiency, and endogenous EPO resistance in patients with CKD. METHODS: This study included 409 patients with CKD [glomerular filtration rate (GFR) < 60 ml/min/1.73 m2] who were not on dialysis therapy. Patients on exogenous EPO therapy and patients with iron deficiencies were excluded. Endogenous EPO resistance was assessed by calculating the ratio of endogenous EPO to hemoglobin (Hb) (endogenous EPO/Hb ratio). The associations of Hb level, endogenous EPO level, and the endogenous EPO/Hb ratio with clinical and laboratory variables were investigated by univariate and multivariate analyses. RESULTS: In univariate analysis, serum 1,25(OH)2D level was correlated with the Hb level, endogenous EPO level, and the endogenous EPO/Hb ratio. Multiple regression analysis revealed that the serum 1,25(OH)2D level remained significantly associated with the Hb level (ß = 0.532, P < 0.001), endogenous EPO level (ß = 0.149, P = 0.010), and the endogenous EPO/Hb ratio (ß = - 0.187, P = 0.002), even after adjusting for other confounding factors, including the levels of parathyroid hormone and the inflammatory marker C-reactive protein. CONCLUSION: The serum 1,25(OH)2D level exhibited significant associations with anemia, EPO deficiency, and endogenous EPO resistance in CKD patients. These associations were independent of secondary hyperparathyroidism and inflammation status.