S6K1 Phosphorylation of H2B Mediates EZH2 Trimethylation of H3: A Determinant of Early Adipogenesis.

S6K1 has been implicated in a number of key metabolic responses, which contribute to obesity. Critical among these is the control of a transcriptional program required for the commitment of mesenchymal stem cells to the adipocytic lineage. However, in contrast to its role in the cytosol, the functions and targets of nuclear S6K1 are unknown. Here, we show that adipogenic stimuli trigger nuclear translocation of S6K1, leading to H2BS36 phosphorylation and recruitment of EZH2 to H3, which mediates H3K27 trimethylation. This blocks Wnt gene expression, inducing the upregulation of PPARγ and Cebpa and driving increased adipogenesis. Consistent with this finding, white adipose tissue from S6K1-deficient mice exhibits no detectable H2BS36 phosphorylation or H3K27 trimethylation, whereas both responses are highly elevated in obese humans or in mice fed a high-fat diet. These findings define an S6K1-dependent mechanism in early adipogenesis, contributing to the promotion of obesity.

Microbial Community Changes in Silkworms Suspected of Septicemia and Identification of Serratia sp.

Diseases that occur in silkworms include soft rot, hardening disease, digestive diseases, and sepsis. However, research on the causes of bacterial diseases occurring in silkworms and the resulting changes in the microbial community is lacking. Therefore, we examined the morphological characteristics of sepsis and changes in the microbial community between silkworms that exhibit a unique odor and healthy silkworms; thus, we established a relationship between disease-causing microorganisms and sepsis. After producing a 16S rRNA amplicon library for samples showing sepsis, we obtained information on the microbial community present in silkworms using next-generation sequencing. Compared to that in healthy silkworms, in silkworms with sepsis, the abundance of the Firmicutes phylum was significantly reduced, while that of Proteobacteria was increased. Serratia sp. was dominant in silkworms with sepsis. After bacterial isolation, identification, and reinfection through the oral cavity, we confirmed this organism as the disease-causing agent; its mortality rate was 1.8 times higher than that caused by Serratia marcescens. In summary, we identified a new causative bacterium of silkworm sepsis through microbial community analysis and confirmed that the microbial community balance was disrupted by the aberrant proliferation of certain bacteria.

Molecular diagnosis of 5 silkworm strains endemic to South Korea using single-nucleotide polymorphisms selected from whole-genome sequences.

The domesticated silkworm, Bombyx mori Linnaeus (Lepidoptera: Bombycidae), often poses a challenge in strain identification due to similarities in morphology and genetic background. In South Korea, around 40 silkworm strains are classified as premium, including 5 endemic tri-molting strains: Goryeosammyeon, Sammyeonhonghoeback, Hansammyeon, Sun7ho, and Sandongsammyeon. These strains have potential for breeding programs in response to emerging industry demands, necessitating a reliable strain identification method. In this study, we established a molecular diagnosis approach for these 5 strains. We selected 2-4 single-nucleotide polymorphisms (SNPs) for each strain from whole-genome sequences of 39 strains, encompassing 37 previously studied and 2 newly added. These SNPs were utilized to construct decision trees for each endemic strain identification. The SNPs can be used to distinguish each target strain from the 38 nontarget strains by the tetra-primer amplification refractory mutation system-polymerase chain reaction, with the exception of HMS which needs the addition of PCR-restriction fragment length polymorphism method at the final step. This decision tree-based method using genomic SNPs, coupled with the 2 typing methods, produced consistent and accurate results, providing 100% accuracy. Additionally, the significant number of remaining SNPs identified in this study could be valuable for future diagnosis of the other strains.

Nuclear S6K1 Enhances Oncogenic Wnt Signaling by Inducing Wnt/ß-Catenin Transcriptional Complex Formation.

Ribosomal protein S6 kinase 1 (S6K1), a key downstream effector of the mammalian target of rapamycin (mTOR), regulates diverse functions, such as cell proliferation, cell growth, and protein synthesis. Because S6K1 was previously known to be localized in the cytoplasm, its function has been mainly studied in the cytoplasm. However, the nuclear localization and function of S6K1 have recently been elucidated and other nuclear functions are expected to exist but remain elusive. Here, we show a novel nuclear role of S6K1 in regulating the expression of the Wnt target genes. Upon activation of the Wnt signaling, S6K1 translocated from the cytosol into the nucleus and subsequently bound to ß-catenin and the cofactors of the Wnt/ß-catenin transcriptional complex, leading to the upregulation of the Wnt target genes. The depletion or repression of S6K1 downregulated the Wnt target gene expression by inhibiting the formation of the Wnt/ß-catenin transcriptional complex. The S6K1-depleted colon cancer cell lines showed lower transcription levels of the Wnt/ß-catenin target genes and a decrease in the cell proliferation and invasion compared to the control cell lines. Taken together, these results indicate that nuclear S6K1 positively regulates the expression of the Wnt target genes by inducing the reciprocal interaction of the subunits of the transcriptional complex.

Implantable Biosupercapacitor Inspired by the Cellular Redox System.

The carbon nanotube (CNT) yarn supercapacitor has high potential for in vivo energy storage because it can be used in aqueous environments and stitched to inner parts of the body, such as blood vessels. The biocompatibility issue for frequently used pseudocapacitive materials, such as metal oxides, is controversial in the human body. Here, we report an implantable CNT yarn supercapacitor inspired by the cellular redox system. In all living cells, nicotinamide adenine dinucleotide (NAD) is a key redox biomolecule responsible for cellular energy transduction to produce adenosine triphosphate (ATP). Based on this redox system, CNT yarn electrodes were fabricated by inserting a twist in CNT sheets with electrochemically deposited NAD and benzoquinone for redox shuttling. Consequently, the NAD/BQ/CNT yarn electrodes exhibited the maximum area capacitance (55.73 mF cm-2 ) under physiological conditions, such as phosphate-buffered saline and serum. In addition, the yarn electrodes showed a negligible loss of capacitance after 10 000 repeated charge/discharge cycles and deformation tests (bending/knotting). More importantly, NAD/BQ/CNT yarn electrodes implanted into the abdominal cavity of a rat's skin exhibited the stable in vivo electrical performance of a supercapacitor. Therefore, these findings demonstrate a redox biomolecule-applied platform for implantable energy storage devices.

Inhibition of mTOR by Rapamycin Aggravates Corneal Epithelial Stem Cell Deficiency by Upregulating Inflammatory Response.

The mammalian target of rapamycin (mTOR) signaling is critical to the regulation of stem cell maintenance and function in a cell-type and context-dependent manner. However, the effects of mTOR signaling on corneal epithelial stem cells (CESCs) under inflammatory conditions are not clear. Here, we demonstrate that mTOR inhibition with rapamycin promotes apoptosis of CESCs in a mouse model of sterile inflammation-induced CESC deficiency, and thereby aggravates the disease. Apoptosis induction in CESCs by rapamycin is not due to direct effect of rapamycin on the cells, but mediated by increase in neutrophilic inflammation. The interleukin (IL)-10/signal transducer and activator of transcription 3 anti-inflammatory pathway was downregulated in a Toll-like receptor 2-independent manner after rapamycin treatment and IL-10 replenishment abrogated the effects of rapamycin on inflammation and CESC apoptosis. Hence, our data reveal that the mTOR signaling is implicated in the control of the pro-inflammatory and anti-inflammatory balance in the cornea and that mTOR inhibition with rapamycin is detrimental to CESCs by accelerating inflammation-induced collateral damage to the cells. Stem Cells 2019;37:1212-1222.

Myeloid-Derived Suppressor Cells Mediate Inflammation Resolution in Humans and Mice with Autoimmune Uveoretinitis.

Resolution of inflammation is an active process that leads to tissue homeostasis and involves multiple cellular and molecular mechanisms. Myeloid-derived suppressor cells (MDSCs) have recently emerged as important cellular components in the resolution of inflammation because of their activities to suppress T cell activation. In this article, we show that HLA-DR-CD11b+CD33+CD14+ human MDSCs and CD11b+Ly6G-Ly6C+ mouse MDSCs markedly increased in patients and mice during and before the resolution phase of autoimmune uveoretinitis. CD11b+Ly6C+ monocytes isolated from autoimmune uveoretinitis mice were able to suppress T cell proliferation in culture, and adoptive transfer of the cells accelerated the remission of autoimmune uveoretinitis in mice. Alternatively, depletion of CD11b+Ly6C+ monocytes at the resolution phase, but not CD11b+Ly6G+ granulocytes, exacerbated the disease. These findings collectively indicate that monocytic MDSCs serve as regulatory cells mediating the resolution of autoimmune uveoretinitis.

Fermented Ginseng Extract, BST204, Suppresses Tumorigenesis and Migration of Embryonic Carcinoma through Inhibition of Cancer Stem Cell Properties.

The pharmacological effects of BST204-a fermented ginseng extract-on several types of cancers have been reported. However, the effects of ginseng products or single ginsenosides against cancer stem cells are still poorly understood. In this study, we identified the anti-tumorigenic and anti-invasive activities of BST204 through the suppression of the cancer stem cell marker, CD133. The treatment of embryonic carcinoma cells with BST204 induced the expression of the tumor suppressor protein, p53, which decreased the expression of cell cycle regulatory proteins and downregulated the expression of CD133 and several stemness transcription factors. These changes resulted in both the inhibition of tumor cell proliferation and tumorigenesis. The knockdown of CD133 suggests that it has a role in tumorigenesis, but not in cancer cell proliferation or cell cycle arrest. Treatment with BST204 resulted in the reduced expression of the mesenchymal marker, N-cadherin, and the increased expression of the epithelial marker, E-cadherin, leading to the suppression of tumor cell migration and invasion. The knockdown of CD133 also exhibited an anti-invasive effect, indicating the role of CD133 in tumor invasion. The single ginsenosides Rg3 and Rh2-major components of BST204-exhibited limited effects against cancer stem cells compared to BST204, suggesting possible synergism among several ginsenoside compounds.

Reversine promotes browning of white adipocytes by suppressing miR-133a.

Brown adipocytes are characterized by a high number of uncoupling protein 1 (UCP1)-positive mitochondrial content and increased thermogenic capacity. As UCP1-enriched cells can consume lipids by generating heat, browning of white adipocytes is now highlighted as a promising approach for the prevention of obesity and obesity-associated metabolic diseases. Upon cold exposure or ß-adrenergic stimuli, downregulation of microRNA-133 (miR-133) elevates the expression levels of PR domain containing 16 (Prdm16), which has been shown to be a brown adipose determination factor, in brown adipose tissue and subcutaneous white adipose tissues (WAT). Here, we show that treatment of reversine to white adipocytes induces browning via suppression of miR-133a. Reversine treatment promoted the expression of brown adipocyte marker genes, such as Prdm16 and UCP1, increasing the mitochondrial content, while decreasing the levels of miR-133a and white adipocyte marker genes. Ectopic expression of miR-133a mimic reversed the browning effects of the reversine treatment. Moreover, intraperitoneal administration of reversine in mice upregulated thermogenesis and resulted in resistance to high-fat diet-mediated weight gain as well as browning of subcutaneous and epididymal WAT. Taken together, we found a novel way to promote browning of white adipocytes through downregulation of miR-133a followed by activation of Prdm16, with a synthetic chemical, reversine.

Identification of a novel S6K1 inhibitor, rosmarinic acid methyl ester, for treating cisplatin-resistant cervical cancer.

BACKGROUND: The mTOR/S6K1 signaling pathway is often activated in cervical cancer, and thus considered a molecular target for cervical cancer therapies. Inhibiting mTOR is cytotoxic to cervical cancer cells and creates a synergistic anti-tumor effect with conventional chemotherapy agents. In this study, we identified a novel S6K1 inhibitor, rosmarinic acid methyl ester (RAME) for the use of therapeutic agent against cervical cancer. METHODS: Combined structure- and ligand-based virtual screening was employed to identify novel S6K1 inhibitors among the in house natural product library. In vitro kinase assay and immunoblot assay was used to examine the effects of RAME on S6K1 signaling pathway. Lipidation of LC3 and mRNA levels of ATG genes were observed to investigate RAME-mediated autophagy. PARP cleavage, mRNA levels of apoptotic genes, and cell survival was measured to examine RAME-mediated apoptosis. RESULTS: RAME was identified as a novel S6K1 inhibitor through the virtual screening. RAME, not rosmarinic acid, effectively reduced mTOR-mediated S6K1 activation and the kinase activity of S6K1 by blocking the interaction between S6K1 and mTOR. Treatment of cervical cancer cells with RAME promoted autophagy and apoptosis, decreasing cell survival rate. Furthermore, we observed that combination treatment with RAME and cisplatin greatly enhanced the anti-tumor effect in cisplatin-resistant cervical cancer cells, which was likely due to mTOR/S6K1 inhibition-mediated autophagy and apoptosis. CONCLUSIONS: Our findings suggest that inhibition of S6K1 by RAME can induce autophagy and apoptosis in cervical cancer cells, and provide a potential option for cervical cancer treatment, particularly when combined with cisplatin.

Mesenchymal Stromal Cells Inhibit Inflammatory Lymphangiogenesis in the Cornea by Suppressing Macrophage in a TSG-6-Dependent Manner.

The cornea is a transparent tissue devoid of blood and lymphatic vessels. However, various inflammatory conditions can cause hemangiogenesis and lymphangiogenesis in the cornea, compromising transparency and visual acuity. Mesenchymal stem/stromal cells (MSCs) have therapeutic potentials in a variety of diseases because of anti-inflammatory properties. Herein, we investigated the effects of MSCs on corneal angiogenesis using a model of suture-induced inflammatory corneal neovascularization. Data demonstrated that an intravenous administration of MSCs suppressed corneal inflammation and neovascularization, inhibiting both hemangiogenesis and lymphangiogenesis. MSCs reduced the levels of vascular endothelial growth factor (VEGF)-C, VEGF-D, Tek, MRC1, and MRC2 in the cornea, which are expressed by pro-angiogenic macrophages. Moreover, the number of CD11b+ monocytes/macrophages in the cornea, spleen, peripheral blood, and draining lymph nodes was decreased by MSCs. Depletion of circulating CD11b+ monocytes by blocking antibodies replicated the effects of MSCs. Importantly, knockdown of tumor necrosis factor alpha (TNF-α)-stimulated gene/protein 6 (TSG-6) in MSCs abrogated the effects of MSCs in inhibiting corneal hemangiogenesis and lymphangiogenesis and monocyte/macrophage infiltration. Together, the results suggest that MSCs inhibit inflammatory neovascularization in the cornea by suppressing pro-angiogenic monocyte/macrophage recruitment in a TSG-6-dependent manner.

S6K1 controls epigenetic plasticity for the expression of pancreatic α/ß cell marker genes.

The failure of insulin production by pancreatic ß cells is a common hallmark of type 1 diabetes mellitus (T1DM). Because administration of exogenous insulin is associated with diabetes-derived complications, endogenous α to ß cell transition can be an attractive alternative. Although decreased ß cell size and hypoinsulinaemia have been observed in S6K1-deficient mice, the molecular mechanism underlying the involvement of S6K1 in the transcriptional regulation of insulin remains elusive. Here, we show that the hypoinsulinaemic phenotype of S6K1-deficient mice stems from the dysregulated transcription of a set of genes required for insulin and glucagon production. First, we observed that increased expression of α cell marker genes and decreased expression of ß cell marker genes in pancreas tissues from S6K1-deficient mice. Furthermore, S6K1 was highly activated in murine ß cell line, ßTC6, compared to murine α cell line αTC1. In both α and ß cells, active S6K1 promoted the transcription of ß cell marker genes, including insulin, whereas S6K1 inhibition increased the transcription of α cell marker genes. Moreover, S6K1 mediated pancreatic gene regulation by modifying two histone marks (activating H3K4me3 and repressing H3K27me3) on gene promoters. These results suggest that S6K1 drives the α to ß transition through the epigenetic regulation of cell-specific genes, including insulin and glucagon. This novel role of S6K1 in islet cells provides basic clues to establish therapeutic strategies against T1DM.

Eudesmin impairs adipogenic differentiation via inhibition of S6K1 signaling pathway.

Eudesmin has been reported to possess diverse therapeutic effects, including anti-tumor, anti-inflammatory, and anti-bacterial activities. However, its molecular action has not been implicated in metabolic disease. In this study, we show that treatment of mesenchymal stem cells (MSCs) with eudesmin disturbs adipogenesis via suppression of S6K1 signaling pathway. Eudesmin treatment inhibited activation and nuclear translocation of S6K1. Consequently, S6K1-mediated phosphorylation of H2B at serine 36 (H2BS36p) was reduced upon eudesmin treatment, further inducing the expression of Wnt6, Wnt10a, and Wnt10b, which disturbed adipogenic differentiation. Moreover, eudesmin promoted myogenic and osteogenic gene expression in MSCs. Taken together, we found a novel small molecule, eudesmin, to block adipogenesis through down-regulation of S6K1-H2BS36p axis, followed by regulation of cell fate determination genes. This study suggests a promising therapeutic approach with eudesmin to cure obesity and metabolic diseases.

Flexible resistive random access memory devices by using NiO x /GaN microdisk arrays fabricated on graphene films.

We report flexible resistive random access memory (ReRAM) arrays fabricated by using NiO x /GaN microdisk arrays on graphene films. The ReRAM device was created from discrete GaN microdisk arrays grown on graphene films produced by chemical vapor deposition, followed by deposition of NiO x thin layers and Au metal contacts. The microdisk ReRAM arrays were transferred to flexible plastic substrates by a simple lift-off technique. The electrical and memory characteristics of the ReRAM devices were investigated under bending conditions. Resistive switching characteristics, including cumulative probability, endurance, and retention, were measured. After 1000 bending repetitions, no significant change in the device characteristics was observed. The flexible ReRAM devices, constructed by using only inorganic materials, operated reliably at temperatures as high as 180 °C.

Newly designed delta neutrophil index-to-serum albumin ratio prognosis of early mortality in severe sepsis.

PURPOSE: We evaluated the ratio of delta neutrophil index (DNI) to albumin (A) in patients receiving early goal-directed therapy (EGDT) to determine the prognostic significance of the DNI/A ratio as a marker of early mortality in critically ill patients with suspected sepsis. METHODS: We retrospectively analyzed records from a prospective EGDT registry in an emergency department (ED) and screened eligible adult patients who were admitted to the ED with severe sepsis and/or septic shock. The new DNI/A ratio was calculated as the DNI value on each hospital day divided by the initial albumin level on ED admission. The clinical outcome was mortality after 28 days. RESULTS: A total of 120 patients receiving EGDT were included in this study. Multivariate Cox proportional-hazard models revealed that higher DNI/A ratios on day 1 (hazard ratio [HR], 1.068; 95% confidence interval [CI], 1.01-1.13; P = .0209) and the peak day (HR, 1.057; 95% CI, 1.001-1.116; P = .0456) were independent risk factors for mortality at 28 days. Our study demonstrated that the increased trend toward 28-day mortality was associated with a DNI/A ratio greater than 8.4 on day 1 (HR, 2.513; 95% CI, 0.950-6.64; P = .0528) and a higher DNI/A ratio (>6.4) on the peak day (average, 4.2 days; HR, 2.953; 95% CI, 1.033-8.441; P < .001) in patients with severe sepsis receiving EGDT. CONCLUSION: The ratio of DNI to serum albumin on ED admission is a promising prognostic marker of 28-day mortality in patients with severe sepsis receiving EGDT.

Pleiotropic effects of a vibrio extracellular protease on the activation of contact system.

Many proteases secreted by pathogenic bacteria can affect seriously on hemostatic system. We have reported that an extracellular zinc metalloprotease (named vEP-45) from Vibrio vulnificus ATCC29307 activates prothrombin to active thrombin, leading the formation of fibrin clot. In this study, the effects of vEP-45 on the intrinsic pathway of coagulation and the kallikrein/kinin system were examined. The protease could activate proteolytically clotting factor zymogens, including FXII, FXI, FX, and prothrombin, to their functional enzymes in vitro and plasma milieu. In addition, it could cleave plasma prekallikrein (PPK) to form an active kallikrein as well as actively digest high-molecular weight kininogen (HK), probably producing bradykinin. In fact, vEP-45 could induce a vascular permeability in a dose-dependent manner in vivo. Taken together, the results demonstrate that vEP-45 can activate plasma contact system by cleaving key zymogen molecules, participating in the intrinsic pathway of coagulation and the kallikrein/kinin system.

Modulatory Effects of the Kuwanon-Rich Fraction from Mulberry Root Bark on the Renin-Angiotensin System.

In this study, we investigated the anti-hypertensive properties of mulberry products by modulating the renin-angiotensin system (RAS). Comparative analysis showed that the ethyl acetate fractions, particularly from the Cheongil and Daeshim cultivars, contained the highest levels of polyphenols and flavonoids, with concentrations reaching 110 mg gallic acid equivalent (GE)/g and 471 mg catechin equivalent (CE)/g of extract, respectively. The ethyl acetate fraction showed superior angiotensin-converting enzyme (ACE) inhibitory activity, mainly because of the presence of the prenylated flavonoids kuwanon G and H. UPLC/Q-TOF-MS analysis identified kuwanon G and H as the primary active components, which significantly contributed to the pharmacological efficacy of the extract. In vivo testing of mice fed a high-salt diet showed that the ethyl acetate fraction substantially reduced the heart weight and lowered the serum renin and angiotensinogen levels by 34% and 25%, respectively, highlighting its potential to modulate the RAS. These results suggested that the ethyl acetate fraction of mulberry root bark is a promising candidate for the development of natural ACE inhibitors. This finding has significant implications for the management of hypertension through RAS regulation and the promotion of cardiovascular health in the functional food industry.

CK2 inhibitor CX4945 induces sequential inactivation of proteins in the signaling pathways related with cell migration and suppresses metastasis of A549 human lung cancer cells.

Casein kinase 2 (CK2) is known to be involved in various cellular processes such as cell cycle, apoptosis and proliferation. It has been reported that the inhibition of CK2 induced by recently developed small molecule CX4945 shows anti-cancer effects including anti-proliferation and anti-angiogenesis in several different cancers including prostate cancer. Here we report that migration and invasion of A549 human lung cancer cells are suppressed by the inhibition of CK2 induced by CX4945. We found that CX4945 sequentially attenuates the proteins in PI3K/Akt and MAPK pathways, two signaling pathways related with cell migration. This sequential control of signal pathways inhibits the expression of membrane type 1-matrix metalloproteinase and this leads to the selective attenuation of one of the gelatinases, MMP-2, which can degrade components of extracellular matrix, and metastasis of A549 human lung cancer cell.

Predictive value of the Cincinnati Prehospital Stroke Scale for identifying thrombolytic candidates in acute ischemic stroke.

BACKGROUND: Despite the usefulness of the Cincinnati Prehospital Stroke Scale (CPSS) for rapid recognition of acute stroke, its ability to assess stroke severity is unclear. We investigated the usefulness of CPSS for assessment of stroke severity by comparing CPSS and National Institutes of Health Stroke Scale (NIHSS) scores in patients who were candidates for thrombolytic therapy at hospital admission within 6 hours of symptom onset. METHODS: We conducted a retrospective analysis of a prospective registry database of consecutive patients included in the brain salvage through emergency stroke therapy program. In the emergency department, CPSS score was determined by emergency medical technicians. A CPSS cut-off score was estimated for candidates of thrombolytic therapy by comparing CPSS and NIHSS scores of patients who actually received thrombolytic therapy. Clinical outcomes were compared among patients with scores near the cut-off. Independent predictors of outcome were evaluated by multivariate logistic regression analysis. RESULTS: Strong correlations were observed between CPSS and NIHSS scores within 3 hours (R = 0.778) and 6 hours (R = 0.769) of symptom onset. The optimal cut-off score was 2 for CPSS was associated with actual usage of intravenous tissue plasminogen activator (odds ratio [OR] 34.455; 95% confidence interval [CI] 7.924-149.817, P < .0001) and actual usage of thrombolytic therapy overall (intravenous tissue plasminogen activator or intra-arterial urokinase) (OR 36.310; 95% CI 10.826-121.782, P < .0001). CONCLUSION: The CPSS is an effective prehospital stroke scale for the determination of stroke severity and identification of candidates for thrombolytic therapy.

The usefulness of rapid point-of-care creatinine testing for the prevention of contrast-induced nephropathy in the emergency department.

BACKGROUND: Renal dysfunction is the most important factor to consider when predicting a patient's risk of developing contrast-induced nephropathy (CIN). Measurement of creatinine (Cr) via rapid point-of-care blood urea nitrogen/creatinine testing (POCT-BUN/Cr) to determine CIN risk could potentially reduce the time required to achieve an accurate diagnosis and to initiate and complete treatment in the emergency department (ED). The aim of our study was to compare the results of POCT-BUN/Cr and reference laboratory tests for BUN and serum Cr. MATERIALS AND METHODS: A retrospective analysis of suspected stroke patients who presented between November 2009 and November 2010, and had BUN and Cr levels measured by POCT-BUN/Cr, and the reference laboratory tests performed with the blood sample which was transferred to the central laboratory by an air-shoot system. Two assays were conducted on the whole blood (POCT) and serum (reference) by trained technicians. The time interval from arrival at the ED to reporting of the results was assessed for both assays via a computerised physician order entry system. RESULTS: The mean standard deviation (SD) interval from arrival at the ED to reporting of the results was 11.4 (4.9) min for POCT-BUN/Cr and 46.8 (38.5) min for the serum reference laboratory tests (p<0.001). Intra-class correlation coefficient (ICC) analysis demonstrated a high level of agreement (the consistency agreement) between POCT and the serum reference tests for both BUN (ICC=0.914) and Cr (ICC=0.980). CONCLUSIONS: This study suggests that POCT-BUN/Cr results correlate well with those of serum reference tests in terms of BUN and Cr levels and, in turn, predicting CIN. POCT-BUN/Cr is easily performed with a rapid turnaround time, suggesting its use in the ED may have substantial clinical benefit.