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Patients with end-stage kidney disease (ESKD) exhibit an elevated cardiovascular risk. Chronic inflammation is one of the main mechanisms of cardiovascular disease (CVD). Lipopolysaccharide has been proposed as a link between systemic inflammation and CVD. Herein, we evaluated whether lipopolysaccharide-binding protein (LBP), a surrogate marker of lipopolysaccharide and consequent inflammation, is associated with cardiovascular events in ESKD.We performed a prospective cohort study of maintenance haemodialysis patients. Baseline serum LBP levels were categorized into tertiles and also modelled continuously for analyses. Cox regression methods were used to evaluate the association of serum LBP levels with cardiovascular events.A total of 360 haemodialysis patients were included in this analysis. During a median follow-up of 3.1 years, 90 (25.0%) patients had cardiovascular events. Patients in the upper tertile of serum LBP levels had a significantly greater risk of cardiovascular events [hazard ratio (HR) 4.87; 95% confidence intervals (CI), 2.12-11.15] than those in the lower tertile, independent of age, sex, hypertension, diabetes, CVD, dialysis vintage, body mass index, non-high-density lipoprotein cholesterol, albumin, phosphorus, high-sensitivity C-reactive protein, and interleukin-6. The association was consistent regardless of whether competing risk of death was accounted for (subdistribution HR 4.87; 95% CI, 1.96-12.11 for upper versus lower tertiles) or serum LBP was analysed as a continuous variable (HR 1.30; 95% CI, 1.02-1.66 per 1 SD increment).Serum LBP levels were independently associated with cardiovascular events in heomodialysis patients. LBP might serve as a novel biomarker for CVD in ESKD.

Background/aim Cetyltrimethylammonium bromide (CTAB), a quaternary ammonium surfactant, was shown to have antitumor effects in a cellular mode of head and neck squamous cell carcinoma (HNSCC), modulating apoptotic and cytotoxic processes. However, the mechanisms by which CTAB exerts its effects against the epithelial- mesenchymal transition in HNSCC remain poorly understood. In the present study, we investigated whether CTAB inhibits cellular mobility and invasiveness of hypopharyngeal squamous cell carcinoma (HPSCC) cells. Materials and methods WST-1, cell-cycle phase distribution, and wound healing, as well as transwell assays were conducted. Changes in protein expression patterns and related signaling pathways involved in effects of CTAB on HPSCC cell lines were evaluated by western blotting. Results Treatment of human HPSCC cell lines with CTAB significantly altered their morphology from spindle-like to cobblestone-like by diminishing mesenchymal-like phenotypic characteristics. CTAB also hindered cell functional properties, including migration and invasion, independently of cell viability. In addition, western blot results demonstrated that treatment with CTAB reduced expression of mesenchymal markers. Further investigation showed that CTAB treatment suppressed the phosphorylation of extracellular-regulated kinase 1/2, mechanistic target of rapamycin kinase and AKT serine/threonine kinase 1. CTAB also repressed the expression and phosphorylation levels of epidermal growth factor receptor (EGFR) and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), and the partial restoration of mesenchymal phenotype by EGF addition confirmed that CTAB inhibited migration and invasion in HPSCC cells by blocking the EGFR signaling pathway. Conclusion Our results suggest that CTAB is involved in the suppression of EGFR-mediated mesenchymal phenotype and the molecular mechanism by which CTAB obstructs HPSCC cell metastasis may represent a promising strategy for use in HPSCC treatment.

Vitamin C and vitamin E are well‐known antioxidant vitamins, both of which are also applied as adjunct treatments for cancer therapy. Methotrexate (MTX) is a clinical drug that is used widely for rheumatoid arthritis and cancer treatment. Human glioblastoma multiforme (GBM) is an aggressive malignant brain tumor; the mean survival time for GBM patients is, This study showed that vitamins C and E can promote anticancer effects on low‐concentration methotrexate‐treated glioblastoma. Additionally, this study suggested that MTX alone or combined with vitamins C/E inhibits GBM cell growth via the caspase‐3 death pathway.

Objectives This study was performed to determine the effects of probiotic supplementation on cholesterol-triglyceride ratio, an indirect marker of insulin resistance, protein-bound uremic toxins, biomarkers of inflammation, and microbial translocation in end-stage renal disease patients on hemodialysis. Methods Fifty-six patients aged 39–75 years were assigned into two groups to receive either probiotic sachets (n = 28) or a placebo (n = 28) in a randomized double-blinded placebo-controlled clinical trial. The patients in the probiotic group received twice daily sachets that contained a mixture of three viable and freeze-dried strains: Lactococcus lactis subsp. Lactis LL358, Lactobaccillus salivarius LS159, and Lactobaccillus pentosus LPE588 at high dose (100 billion; 1 × 1011 cfu/day) for 6 months. Results A total of 50 patients were available for final analysis. Probiotic supplementation did not have a significant influence on cholesterol-triglyceride ratio. Probiotic supplementation for 6 months caused a significant decrease in serum levels of indoxyl sulfate. Compared with the placebo, probiotic supplementation did not result in significant changes in hemoglobin levels, blood urea nitrogen, blood glucose, serum p-cresyl sulfate, inflammatory, and microbial translocation markers. No clinically significant changes in body composition were observed between the two groups during the study period. The probiotic supplementation was well tolerated by all subjects with minimal adverse effects during the 6-month-long study. Conclusion Our results suggest that high-dose multistrain lactobaccillus probiotic supplementation over 6 months as a monotherapy did not significantly decrease markers of insulin resistance, cholesterol-triglyceride ratio, and most of the studied markers, with the exception of levels of indoxyl sulfate in patients on HD.

Lysosomal cell death is induced by lysosomal membrane permeabilization (LMP) and the subsequent release of lysosomal proteolytic enzymes, including cathepsins (CTSs), which results in mitochondrial dysfunction and apoptosis. Imiquimod (IMQ), a synthetic TLR7 ligand, has both antiviral and antitumor activity against various skin malignancies in clinical treatment. Previously, we demonstrated IMQ not only caused lysosomal dysfunction but also triggered lysosome biogenesis to achieve lysosomal adaptation in cancer cells.To determine whether lysosomes are involved in IMQ-induced apoptosis.The human skin cancer cell lines BCC, A375 and mouse melanoma cell line B16F10 were used in all experiments. Cell death was determined by the Cell Counting Kit-8 (CCK-8) assay and DNA content assay. Protein expression was determined by immunoblotting. Caspase-8 activity was assessed using a fluorescence caspase-8 kit and determined by flow cytometry and confocal microscopy.IMQ not only induced lysosome damage but also abrogated lysosome function in skin cancer cells. IMQ-induced caspase-8 activation contributed to the processes of lysosomal cell death. Moreover, the use of ROS scavengers significantly abolished caspase-8 activation and inhibited IMQ-induced LMP. Additionally, pharmacological inhibition of CTSD not only abrogated caspase-8 activation but also rescued IMQ-induced cell death. Finally, lysosome-alkalizing agents enhanced the cytotoxicity of IMQ in vitro and in vivo.IMQ-induced ROS accumulation promotes LMP, releases CTSs into the cytosol, stimulates caspase-8 activation and finally causes lysosomal cell death. Lysosomal cell death and the CTSD/caspase-8 axis may play a crucial role in IMQ-induced cell death.

Background/aim Liver cancer is the fourth leading cause of cancer-related mortality globally, of which hepatocellular carcinoma (HCC) accounts for 85-90% of total primary liver cancer. A drug shortage for HCC therapy triggered us to screen the small-molecule database with a high-throughput cellular screening system. Herein, we examined whether cetyltrimethylammonium bromide (CTAB) inhibits cellular mobility and invasiveness of Mahlavu HCC cells. Materials and methods The effects of CTAB on cell viability were assessed using WST-1 assay, cell-cycle distribution using flow cytometric analysis, migration/invasion using woundhealing and transwell assays, and associated protein levels using western blotting. Results Treatment of Mahlavu cells with CTAB transformed its mesenchymal spindle-like morphology. In addition, CTAB exerted inhibitory effects on the migration and invasion of Mahlavu cells dose-dependently. CTAB also reduced the protein levels of matrix metalloproteinase-2 (MMP2), MMP9, RAC family small GTPase 1, SNAIL family transcriptional repressor 1 (SNAI1), SNAI2, TWIST family basic helix-loop-helix transcription factor 1 (TWIST1), vimentin, N-cadherin, phospho-fibroblast growth factor (FGF) receptor, phospho-phosphoinositide 3-kinase, phospho-v-Akt murine thymoma viral oncogene and phospho-signal transducer and activator of transcription 3 but increased the protein levels of tissue inhibitor of metalloproteinases-1/2 and E-cadherin. Rescue experiments proved that CTAB induced mesenchymal-epithelial transition in Mahlavu cells and this was significantly dose-dependently mitigated by basic FGF. Conclusion CTAB suppressed the migration and invasion of Mahlavu cells through inhibition of the FGF signaling pathway. CTAB seems to be a potential agent for preventing metastasis of hepatic cancer.

Indoxyl sulfate (IS) and p-cresyl sulfate (PCS), protein-bound uremic toxins, can induce oxidative stress and cause renal disease progression. However, the different cytotoxic effects on renal cells between IS and PCS are not stated. Due to uremic toxins are generally found in CKD patients, the mechanisms of uremic toxins-induced renal injury are required to study. Curcumin has anti-oxidant, anti-inflammatory and anti-apoptotic effects which may be potential used to protect against renal damage. In contrast, curcumin also exert cytotoxic effects on various cells. In addition, curcumin may reduce or enhance cytotoxicity combined with different chemicals treatments. However, whether curcumin may influence uremic toxins-induced renal injury is unclear. The goal of this study is to compare the different cytotoxic effects on renal cells between IS and PCS treatment, as well as the synergistic or antagonistic effects by combination treatments with curcumin and PCS. Our experimental result shows the PCS exerts a stronger antiproliferative effect on renal tubular cells than IS treatment. In addition, our study firstly demonstrates that curcumin enhances PCS-induced cell cytotoxicity through caspase-dependent apoptotic pathway and cell cycle alteration.

Triple-negative breast cancer (TNBC) is the third most common female cancer in Taiwan. EZH2 plays an important role in cancer development through transcriptional repression by chromatin remodeling. However, the expression of EZH2 in breast cancer is highly correlated with tumorigenesis, and patient survival is not matched to TNBC. Furthermore, it has not been determined if specific EZH2 genetic variants are associated with breast cancer risk. In this paper, we evaluated the survival of different types of breast cancer. The results indicated that a lower expression of EZH2 led to poor survival of TNBC patients. Therefore, we aimed at studying the relationship between genetic polymorphisms of EZH2 and susceptibility to TNBC in Taiwan. Four single-nucleotide polymorphisms (SNPs) of EZH2 (rs6950683, rs2302427, rs3757441, and rs41277434) were analyzed by real-time PCR genotyping in 176 patients with TNBC and 1000 cancer-free controls. The results showed that TNBC patients under 60 years old who carried a TC or CC genotype at EZH2 rs6950683 and re3757441 had a tumor size of 20 mm or smaller (T1). Thus, this study is the first to examine the age and mutant genes associated with EZH2 SNPs in TNBC progression and development in Taiwan.

Tripartite motif 21 (TRIM21) plays an important role in hepatocellular carcinoma (HCC). However, the gene polymorphisms of TRIM21 in HCC is not as well known. In this study, two single nucleotide polymorphisms (SNPs) in the TRIM21 gene, rs4144331, and re915956, were selected to investigate correlations between these SNPs and susceptibility to HCC. Two SNPs of the TRIM21 gene from 1196 controls without cancer and 394 HCC patients were analyzed using real-time polymerase chain reaction. These results were further analyzed to expound the associations between these TRIM21 polymorphisms and the risk of HCC as well as the impact of these SNPs on clinicopathological characteristics of HCC. After adjustment for other covariants, we observed that that younger patients (&lt, 65 years) with the TRIM21 rs915956 A allele had a probability of HCC (AOR = 3.153, 95% CI: 1.315–7.516, p = 0.010). Moreover, patients with a smoking habit who carried the T allele of rs4144331 had more probability of HCC (AOR = 2.940, 95% CI: 1.331–6.491, p = 0.008). In addition, we observed that the polymorphic T allele of rs4144331 led to distant metastasis. Thus, our findings suggest that genetic variations in TRIM21 may correlate to HCC and evaluate distant metastasis in patients with HCC.

Aristolochic acid (AA) is a component identified in traditional Chinese remedies for the treatment of arthritic pain, coughs and gastrointestinal symptoms. However, previous studies have indicated that AA can induce oxidative stress in renal cells leading to nephropathy. α‑tocopherol exists in numerous types of food, such as nuts, and belongs to the vitamin E isoform family. It possesses antioxidant activities and has been used previously for clinical applications. Therefore, the aim of the present study was to determine whether α‑tocopherol could reduce AA‑induced oxidative stress and renal cell cytotoxicity, determined by cell survival rate, reactive oxygen species detection and apoptotic features. The results indicated that AA markedly induced H2O2 levels and caspase‑3 activity in renal tubular epithelial cells. Notably, the presence of α‑tocopherol inhibited AA‑induced H2O2 and caspase‑3 activity. The present study demonstrated that antioxidant mechanisms of α‑tocopherol may be involved in the increased survival rates from AA‑induced cell injury.

Despite the continuous progression in dialysis medicine, mortality and the burden of cardiovascular disease (CVD) among hemodialysis patients are still substantial. Substantial evidence suggests that proinflammatory (CD16+) monocytes contribute to the development of atherosclerosis. A cohort of 136 stable hemodialysis patients (follow-up: 6.25 year) was assessed to investigate the association between the proportion of CD16+ monocytes for all-cause and CVD mortalities. The CD16+ monocytes were associated with both mortalities after adjusting for a preexisting CVD history. Compared to the reference group (CD16+ monocytes within [15.6–18.6], the first and second quartile), patients with CD16+ monocytes above the highest quartile level (>21.5) had an adjusted hazard ratio (HR) of 30.85 (95% confidence interval [CI]: 7.12–133.8) for CVD mortality and 5.28 (2.07–13.49) for all-cause mortality, and those with CD16+ monocytes below the lowest quartile ≤15.6), had significantly elevated death risks after 3.5-year follow-up (HR [95% CI]: 10.9 [2.42–48.96] and 4.38 [1.45–13.24] for CV and all-cause mortalities, respectively). The hemodialysis patients with CD16+ monocyte level in a low but mostly covering normal range also portended a poor prognosis. The findings shed some light for nephrologists on future prospects of early recognizing immune dysfunction and improving early intervention outcomes.

Background/aim Cetrimonium bromide (CTAB), a quaternary ammonium surfactant, is an antiseptic agent against bacteria and fungi. However, the mechanisms by which its pharmacological actions affect epithelial-mesenchymal transition (EMT) in hepatocellular carcinoma (HCC) cells, such as adenocarcinoma in SK-HEP-1 cells, have not been investigated. We, thereby, investigated whether CTAB inhibits cellular mobility and invasiveness of human hepatic adenocarcinoma in SK-HEP-1 cells. Materials and methods SK-HEP-1 cells were treated with CTAB, and subsequent migration and invasion were measured by wound healing and transwell assays. Protein expression was detected by immunoblotting analysis. Results Our data revealed that treatment of SK-HEP-1 cells with CTAB altered their mesenchymal spindle-like morphology. CTAB exerted inhibitory effects on the migration and invasion of SK-HEP-1 cells dose-dependently, and reduced protein levels of matrix metalloproteinase-2 (MMP-2), MMP-9, snail, slug, twist, vimentin, fibronectin, N-cadherin, Smad2, Smad3, Smad4, phosphoinositide-3-kinase (PI3K), p-PI3K, Akt, p-Akt, β-catenin, mammalian target of rapamycin (mTOR), p-mTOR, p-p70S6K, p-extracellular signal-regulated kinases (ERK)1/2, p-p38 mitogen-activated protein kinase (MAPK) and p-c-Jun N-terminal kinase (JNK), but increased protein levels of tissue inhibitor matrix metalloproteinase-1 (TIMP-1), TIMP-2, claudin-1 and p-GSK3β. Based on these observations, we suggest that CTAB not only inhibits the canonical transforming growth factor-β (TGF-β) signaling pathway though reducing SMADs (an acronym from the fusion of Caenorhabditis elegans Sma genes and the Drosophila Mad, Mothers against decapentaplegic proteins), but also restrains the non-canonical TGF-β signaling including MAPK pathways like ERK1/2, p38 MAPK, JNK and PI3K. Conclusion CTAB is involved in the suppression of TGF-β-mediated mesenchymal phenotype and could be a potent medical agent for use in controlling the migration and invasion of hepatic adenocarcinoma.

p-Cresyl sulfate (pCS), a uremic toxin, can cause renal damage and dysfunction. Studies suggest that renal dysfunction increases the prevalence of renal cancer. However, the effect of pCS on the proliferation and migration of renal cancer is unclear. Clear cell renal cell carcinoma (ccRCC) expresses mutant von Hippel-Lindau gene and is difficult to treat. Hypoxia-inducible factor-1α and 2-α (HIF-1α and HIF-2α) as well as microRNA-21 (miR-21) can regulate the proliferation and migration of ccRCC cells. However, the association between HIF-α and miR-21 in ccRCC remains unclear. Therefore, the effects of pCS on ccRCC cells were investigated for HIF-α and miR-21 signals. Our results showed that pCS induced overexpression of HIF-1α and promoted the proliferation and regulated epithelial-mesenchymal transition-related proteins, including E-cadherin, fibronectin, twist and vimentin in ccRCC cells. pCS treatment increased miR-21 expression. Specifically, inhibition of miR-21 blocked pCS-induced proliferation and migration. Taken together, the present results demonstrate that pCS directly induced the proliferation and migration of ccRCC cells through mechanisms involving miR-21/HIF-1α signaling pathways.

Background: In hemodialysis (HD) patients, impaired gut barrier and alteration in microbiota in the gut is thought to increase the risk of bacterial translocation and chronic inflammation. Lipopolysaccharide-binding protein (LBP) is an acute-phase reactant that mediates immune responses triggered by microbial products. Our aim is to investigate the relationship between circulating levels of LBP, and various metabolic and inflammatory markers in HD patients. Besides, we also aim to determine its relationship among ­patients with different body mass index. Patients and Methods: A total of 123 HD patients were stratified into three ­tertiles, according to serum LBP level. The LBP and inflammatory markers were determined using immunoassay methods. A bioimpedance spectroscopy device was used for body composition measurement. Results: The serum levels of the two proinflammatory markers, high-sensitivity C-reactive protein (hsCRP) and interleukin (IL)-6, were significantly higher in patients in the upper tertile when compared with the rest of the tertiles. In HD patients, a significant positive correlation was found between serum LBP levels and CRP, IL-6, soluble CD14 (sCD14), and fasting blood glucose levels. Patients with metabolic syndrome and pre-existing cardiovascular disease had higher LBP levels than those without metabolic syndrome. Besides, obese patients were also associated with higher serum LBP levels. Multivariate regression analyses showed that IL-6 level was the strongest correlate of LBP level, followed by hsCRP level and sCD14. Conclusions: Our study suggested that elevated plasma LBP was associated with metabolic syndrome and obesity. In addition, increased LBP level was correlated positively to markers of inflammation, and sCD14 levels.

Aristolochic acid (AA) is a component of Chinese medicinal herbs, including asarum and aristolochia and has been used in Traditional Chinese Medicine for a long time. Recent studies found that AA has a cytotoxic effect resulting in nephropathy. These studies indicated that AA‑induced cytotoxicity is associated with increases in oxidative stress and caspase‑3 activation. The present study further demonstrated that AA mainly elevates the H2O2 ratio, leading to increases in oxidative stress. Furthermore, the results indicated that AA induces cell death can via caspase‑dependent and ‑independent pathways. It is desirable to identify means of inhibiting AA‑induced renal damage; therefore, the present study applied an anti‑oxidative nutrient, vitamin C, to test whether it can be employed to reduce AA‑induced cell cytotoxicity. The results showed that vitamin C decreased AA‑induced H2O2 levels, caspase‑3 activity and cytotoxicity in renal tubular cells. In conclusion, the present study was the first to demonstrate that AA‑induced increases of the H2O2 ratio resulted in renal tubular cell death via caspase‑dependent and ‑independent pathways, and that vitamin C can decrease AA‑induced increases in H2O2 levels and caspase‑3 activity to attenuate AA‑induced cell cytotoxicity.

Retinoic acid (RA), vitamin D and 12-O‑tetradecanoyl phorbol-13-acetate (TPA) can induce HL-60 cells to differentiate into granulocytes, monocytes and macrophages, respectively. Similar to RA and vitamin D, ascorbic acid also belongs to the vitamin family. High‑dose ascorbic acid (>100 µM) induces HL‑60 cell apoptosis and induces a small fraction of HL‑60 cells to express the granulocyte marker, CD66b. In addition, ascorbic acid exerts an anti‑oxidative stress function. Oxidative stress is required for HL‑60 cell differentiation following treatment with TPA, however, the effect of ascorbic acid on HL‑60 cell differentiation in combination with TPA treatment remains to be fully elucidated. The aim of the present study was to investigate the cellular effects of ascorbic acid treatment on TPA-differentiated HL-60 cells. TPA-differentiated HL-60 cells were used for this investigation, this study and the levels of cellular hydrogen peroxide (H2O2), caspase activity and ERK phosphorylation were determined following combined treatment with TPA and ascorbic acid. The results demonstrated that low‑dose ascorbic acid (5 µM) reduced the cellular levels of H2O2 and inhibited the differentiation of HL‑60 cells into macrophages following treatment with TPA. In addition, the results of the present study further demonstrated that low‑dose ascorbic acid inactivates the ERK phosphorylation pathway, which inhibited HL‑60 cell differentiation following treatment with TPA.

Acetaminophen (APAP) is an analgesic and antipyretic agent primarily used in the clinical setting. However, high doses of APAP can cause oxidative stress. Guavas have been reported to provide anti‑inflammatory, anti‑microbial, anti‑oxidative and anti‑diarrheal functions. In addition, guavas have been reported to prevent renal damage due to progression of diabetes mellitus. Therefore, the aim of the present study was to investigate whether guavas can reduce APAP‑induced renal cell damage. In the present study, extracts from guavas were obtained and added to APAP‑treated renal tubular endothelial cells. The present results demonstrated that APAP induces cytotoxicity in renal tubular endothelial cells, while guava extracts inhibited this cytotoxicity. In addition, the study demonstrated that the protective effects of guava extracts against APAP‑induced cytotoxicity may be associated with inhibition of oxidative stress and caspase‑3 activation.

Acetaminophen (APAP), is a safe analgesic and antipyretic drug at therapeutic dose, and is widely used in the clinic. However, high doses of APAP can induce hepatotoxicity and nephrotoxicity. Most studies have focused on high‑dose APAP‑induced acute liver and kidney injury. So far, few studies have investigated the effects of the therapeutic dose (1/10 of the high dose) or of the low dose (1/100 of the high dose) of APAP on the cells. The aim of this study was to investigate the cellular effects of therapeutic- or low‑dose APAP treatment on hepatoma cells and kidney fibroblasts. As expected, high‑dose APAP treatment inhibited while therapeutic and low‑dose treatment did not inhibit cell survival of kidney tubular epithelial cells. In addition, therapeutic-dose treatment induced an increase in the H2O2 level, activated the caspase‑9/‑3 cascade, and induced cell apoptosis of hepatoma cells. Notably, APAP promoted fibroblast proliferation, even at low doses. This study demonstrates that different cellular effects are exerted upon treatment with different APAP concentrations. Our results indicate that treatment with the therapeutic dose of APAP may exert an antitumor activity on hepatoma, while low‑dose treatment may be harmful for patients with fibrosis, since it may cause proliferation of fibroblasts.

Rapid screening and monitoring of nutritional status is mandatory in hemodialysis population because of the increasingly encountered nutritional problems. Considering the limitations of previous composite nutrition scores applied in this population, we tried to develop a standardized composite nutrition score (SCNS) using low lean tissue index as a marker of protein wasting to facilitate clinical screening and monitoring and to predict outcome.This retrospective cohort used 2 databases of dialysis populations from Taiwan between 2011 and 2014. First database consisting of data from 629 maintenance hemodialysis patients was used to develop the SCNS and the second database containing data from 297 maintenance hemodialysis patients was used to validate this developed score.SCNS containing albumin, creatinine, potassium, and body mass index was developed from the first database using low lean tissue index as a marker of protein wasting. When applying this score in the original database, significantly higher risk of developing protein wasting was found for patients with lower SCNS (odds ratio 1.38 [middle tertile vs highest tertile, P .0001] and 2.40 [lowest tertile vs middle tertile, P .0001]). The risk of death was also shown to be higher for patients with lower SCNS (hazard ratio 4.45 [below median level vs above median level, P .0001]). These results were validated in the second database.We developed an SCNS consisting of 4 easily available biochemical parameters. This kind of scoring system can be easily applied in different dialysis facilities for screening and monitoring of protein wasting. The wide application of body composition monitor in dialysis population will also facilitate the development of specific nutrition scoring model for individual facility.

Background. Peripheral arterial disease (PAD) and its relevant complications are more common in hemodialysis (HD) patients, while the evidence regarding antiplatelet therapy in CKD patients is scarce. We retrospectively analyzed the efficacy of cilostazol on outcomes in HD patients with asymptomatic PAD (aPAD).Methods. This cohort study enrolled 217 HD patients (median follow-up time: 5.75 years). Associations between cilostazol use and the outcomes were evaluated by time-dependent Cox regression analysis.Results. During follow-up, 39.5% (47/119) patients used cilostazol for aPAD and 31.8% (69/217) patients died. Cilostazol users had significantly lower CVD and all-cause mortalities (adjusted HR [95% CI]: 0.11 [0.03, 0.51] and 0.2 [0.08, 0.52]) than nonusers. Both death risks were nonsignificantly higher in cilostazol users than in HD patients without aPAD. The unadjusted and adjusted HR [95% CI] of CVD death risk were 0.4 [0.07, 2.12] and 0.14 [0.02, 0.8] for patients with aPAD during follow-up and were 0.74 [0.16, 3.36] and 0.19 [0.04, 0.93] for those with aPAD at initial.Conclusions. In HD patients with aPAD, lower CVD and all-cause mortality rates were observed in low-dose cilostazol user. Further evidences from large-scale prospective study and randomization trial are desired to confirm the effect of cilostazol.

SUMMARY: Aim: The CD40–CD40L system has been implicated in the pathogenesis of atherothrombotic complications in cardiovascular disease. The aim of this study was to determine the relationship between plasma soluble CD40 ligand (sCD40L) and symptomatic coronary heart disease (CHD) in end-stage renal disease (ESRD) patients on maintenance haemodialysis (HD). Methods: This cross-sectional study included 57 HD patients, 31 of whom had symptomatic CHD. Lipid profile, markers of endothelial activation such as sCD40L, and both inflammatory and oxidative stress markers were measured and analyzed. Results: The sCD40L concentration was significantly higher in HD patients than in controls (1.34 ± 0.53 vs 0.86 ± 0.12 ng/mL, P

Human glioblastoma multiforme is one of the most aggressive malignant brain tumor types, and the mean survival time of patients with a brain tumor is

Retinoic acid (RA), vitamin D and 12-O‑tetradecanoyl phorbol-13-acetate (TPA) can induce HL-60 cells to differentiate into granulocytes, monocytes and macrophages, respectively. Similar to RA and vitamin D, ascorbic acid also belongs to the vitamin family. High‑dose ascorbic acid (100 µM) induces HL‑60 cell apoptosis and induces a small fraction of HL‑60 cells to express the granulocyte marker, CD66b. In addition, ascorbic acid exerts an anti‑oxidative stress function. Oxidative stress is required for HL‑60 cell differentiation following treatment with TPA, however, the effect of ascorbic acid on HL‑60 cell differentiation in combination with TPA treatment remains to be fully elucidated. The aim of the present study was to investigate the cellular effects of ascorbic acid treatment on TPA-differentiated HL-60 cells. TPA-differentiated HL-60 cells were used for this investigation, this study and the levels of cellular hydrogen peroxide (H2O2), caspase activity and ERK phosphorylation were determined following combined treatment with TPA and ascorbic acid. The results demonstrated that low‑dose ascorbic acid (5 µM) reduced the cellular levels of H2O2 and inhibited the differentiation of HL‑60 cells into macrophages following treatment with TPA. In addition, the results of the present study further demonstrated that low‑dose ascorbic acid inactivates the ERK phosphorylation pathway, which inhibited HL‑60 cell differentiation following treatment with TPA.

Frog ribonucleases have been demonstrated to have anticancer activities. However, whether RC-6 ribonuclease exerts anticancer activity on human embryonal carcinoma cells remains unclear. In the present study, RC-6 induced cytotoxicity in NT2 cells (a human embryonal carcinoma cell line) and our studies showed that RC-6 can exert anticancer effects and induce caspase-9 and -3 activities. Moreover, to date, there is no evidence that frog ribonuclease-induced cytotoxicity effects are related to cellular senescence. Therefore, our studies showed that RC-6 can increase p16 and p21 protein levels and induce cellular senescence in NT2 cells. Notably, similar to retinoic acid-differentiated NT2 cells, neuron-like morphology was found on some remaining live cells after RC-6 treatment. In conclusion, our study is the first to demonstrate that RC-6 can induce cytotoxic effects, caspase-9/-3 activities, cellular senescence and neuron-like morphology in NT2 cells.

Background Substantial evidence suggests that increased oxidative stress in hemodialysis (HD) patients may contribute to cardiovascular complications. Oxidative modifications of human serum albumin (HSA), the largest thiol pool in plasma, alter its biological properties and may affect its antioxidant potential in HD patients. Methods We conducted a long-term follow-up study in a cohort of normoalbuminemic HD patients to examine the impact of redox state of serum albumin on patients’ survival by measuring the human nonmercaptoalbumin (HNA) fraction of HSA. Results After adjusting for potential demographic, anthropometric, and clinical confounders, a positive association of HNA level with the risk of death from cardiovascular disease (CVD) and all-cause mortality was observed in normoalbuminemic HD patients. Using stratified analysis, we found a stronger association between HNA level and the risk of death from CVD and all-cause mortality in patients with pre-existing CVD. Conclusions Serum HNA level is a positive predictor of mortality in normoalbuminemic HD patients, especially among those with pre-existing CVD. Increased oxidative stress resulting from biological changes in serum albumin levels could contribute to accelerated atherosclerosis and the development of cardiovascular disease in HD patients.

SUMMARY: Background: Peripheral arterial disease (PAD) is a leading cause of morbidity in haemodialysis (HD) patients. Recent evidence suggests that adiponectin, an adipose-derived cytokine, may play a role in atherosclerosis. However, the association between plasma levels of the adiponectin and the ankle-brachial index (ABI), an indicator of the presence and severity of PAD, has not been thoroughly studied in HD patients. Methods: The present cross-sectional study attempted to examine the relationship between plasma adiponectin and PAD in a cohort of 136 chronic HD patients. The ABI was used as an estimate of the presence of PAD. Plasma adiponectin, high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor-α and lipid profiles were measured. Logistic regression was used to estimate the association between presence of PAD and adiponectin as well as other potential risk factors. Results: Plasma levels of adiponectin were significantly lower among patients with evidence of PAD than among those without (8.51 ± 5.75 vs 17.15 ± 11.53; P

Background: Recent evidence suggests that oxidative stress may be an instigator of the metabolic syndrome, and adiponectin, an adipocyte-derived polypeptide, may modulate oxidative stress, ameliorating the atherosclerotic process. Aim: Oxidative stress is increased in hemodialysis (HD) patients. We hypothesize that a relationship between plasma levels of adiponectin and markers of inflammation and oxidative stress exists. Methods and Results: In 124 HD patients, plasma adiponectin levels and three separate oxidative stress markers, tumor necrosis factor-α as well as high-sensitivity C-reactive protein (hsCRP) were determined. Plasma adiponectin was significantly and negatively correlated with serum hsCRP (r = –0.247, p = 0.008) and plasma malondialdehyde (MDA) levels (r = –0.326; p < 0.001). Multiple regression analyses suggested that plasma MDA, serum HDL cholesterol levels and logarithmically transformed hsCRP were the variables independently associated with plasma adiponectin levels. Conclusion: Plasma adiponectin was significantly associated with plasma MDA, serum HDL cholesterol levels and serum hsCRP levels. Our results suggest the possibility that plasma adiponectin may play a role in alleviating oxidative stress in HD patients.