Matrix solid-phase dispersion combined with micro-fractionation bioactivity evaluation screening polymethoxylated flavones from Citrus peels.

Polymethoxyflavones were a unique class of natural and safe flavonoids containing two or more methoxy groups, which were also the most abundant edible part in Citrus peel. The optimum condition in the process of selective extraction of polymethoxylated flavones from Citrus peel by matrix solid-phase dispersion (MSPD) was as follows: SBA-15 as adsorbent, ethyl acetate as eluent, the mass ratio of adsorbent to sample 1:1, and the mixture of sample and adsorbent was ground for 3 min. Twelve antioxidants were successfully screened by micro-fractionation bioactivity evaluation assay, in which four of them were flavonoid glycosides, seven of them were polymethoxylated flavones, and one was phenylpropanoid. 1-sinapoly-ß-D-glucopyranoside (1) was reported for the first time in Citrus peel. And antioxidant capacity of 1-sinapoly-ß-D-glucopyranoside, 5, 7, 8, 3', 4', 5'-hexamethoxyflavone (6), hexamethoxyflavone (11), and 5, 6, 7, 4'-tetramethoxyflavone (7) were reported for the first time. Nobiletin (compound 8), 3, 5, 6, 7, 8, 3', 4'-heptamethoxyflavone (9) and tangeretin (10) were isolated and purified by countercurrent chromatography combined with preparative liquid chromatography. Antioxidant activity evaluation indicated that the three isolated polymethoxylated flavones owned similar antioxidant activity. This study indicated that MSPD combined with micro-fractionation bioactive evaluation was efficient in screening bioactive compounds for rapid extraction and effective pinpointing bioactive substances in natural products.

An enzyme-based system for extraction of small extracellular vesicles from plants.

Plant-derived nanovesicles (NVs) and extracellular vesicles (EVs) are the next generation of nanocarrier platforms for biotherapeutics and drug delivery. EVs exist not only in the extracellular space, but also within the cell wall. Due to the limitations of existing isolation methods, the EVs extraction efficiency is low, and a large amount of plant material is wasted, which is of concern for rare and expensive medicinal plants. We proposed and validated a novel method for isolation of plant EVs by enzyme degradation of the plant cell wall to release the EVs. The released EVs can easily be collected. The new method was used for extraction of EVs from the roots of Morinda officinalis (MOEVs). For comparison, nanoparticles from the roots (MONVs) were extracted using the grinding method. The new method yielded a greater amount of MOEVs, and the vesicles had a smaller diameter compared to MONVs. Both MOEVs and MONVs were readily absorbed by endothelial cells without cytotoxic effect and promoted the expression of miR-155. The promotion of miR-155 by MOEVs was dose-dependent. More importantly, we found that MOEVs and MONVs were enriched toward bone tissue. These results support our hypothesis that EVs in plants could be efficiently extracted by enzymatic cell wall digestion and confirm the potential of MOEVs as therapeutic agents and drug carriers.

Discovery of potential hypoglycemic metabolites in Cassiae Semen by coupling UHPLC-QTOF-MS/MS combined plant metabolomics and spectrum-effect relationship analyses.

Cassiae Semen (CS) is consumed as fried tea or medicinal food in Asian areas. Its two commercial forms, namely raw and fried CS, exert different clinical applications, in which fried CS is commonly applied as a functional tea for losing weight. To prevent confusion in the use of the two forms of CS, a comprehensive strategy by combining plant metabolomics and spectrum-effect relationship analyses was developed for the fast and efficient discrimination of raw and fried CS, and further for the discovery of the potential hypoglycemic metabolites of CS to control its quality. First, the plant metabolic profiling of raw and processed samples was performed by UHPLC-QTOF-MS/MS. A total of 1111 differential metabolites were found to well distinguish the raw and fried CS after analyzing by MPP software. Subsequently, α-glucosidase inhibition of raw and fried CS was investigated. As a result, fried CS demonstrated much stronger α-glucosidase inhibition activity than the raw sample. By analyzing the spectrum-effect relationship with GRA, BCA, and PLSR, 14 potential hypoglycemic-related compounds were discovered. As anticipated, they were also found as the differential metabolites of the raw and fried samples with a potential hypoglycemic effect, which might be beneficial for the quality control of CS tea. Additionally, molecular docking analysis was conducted to reveal the underlying inhibition mechanisms of the four most critical constituents, including physcion, chrysoobtusin, aurantio-obtusin, and obtusifolin. This study provides a powerful tool for the discrimination of processed samples and fast screening of the active constituents in complex natural products on a high-throughput basis.

Targeting CC chemokine ligand (CCL) 20 by miR-143-5p alleviate lead poisoning-induced renal fibrosis by regulating interstitial fibroblasts excessive proliferation and dysfunction.

Environmental lead contamination can cause chronic renal disease with a common clinical manifestation of renal fibrosis and constitutes a major global public health threat. Aberrant proliferation and extracellular matrix (ECM) accumulation in renal interstitial fibroblasts are key pathological causes of renal fibrosis. However, the mechanism underlying lead-induced kidney fibrosis remains unclear. The present study analyzed gene expression prolifes in lead acetate-treated primary mice renal interstitial fibroblasts and confirmed the aberrant expression of CC chemokine ligand (CCL) 20, one of the most obvious up-regulated genes. Analogously, lead acetate exposure dose-dependently increased CCL20 transcription, protein expression and release. Knockdown of CCL20 suppressed lead acetate-induced fibroblast proliferation, hydroxyproline contents, transforming growth factor-beta production and ECM-related protein (Collagen I and fibronectin) expression. Bioinformatics analysis predicted five top miRNAs targeting CCL20. Among them, miR-143-5p expression was dose-dependently decreased in lead acetate-treated fibroblasts. Mechanistically, miR-143-5p directly targeted CCL20. Elevation of miR-143-5p antagonized lead acetate-induced fibroblast proliferation, hydroxyproline and ECM-related protein expression, which were reversed by CCL20 overexpression. Additionally, CCL20 knockdown suppressed lead acetate-mediated Smad2/3 and AKT pathway activation. Notably, miR-143-5p overexpression attenuated the activation of the Smad2/3 and AKT pathway in lead acetate-exposed fibroblasts, which was counteracted by CCL20 elevation. miR-143-5p injection ameliorated renal fibrosis progression in mice in vivo. Thus, targeting CCL20 by miR-143-5p could alleviate renal fibrosis progression by regulating fibroblast proliferation and ECM deposition via the Smad2/3 and AKT signaling, providing a potential therapeutic target for environmental lead contamination-evoked fibrotic kidney disease.

External light-dark cycle shapes gut microbiota through intrinsically photosensitive retinal ganglion cells.

Gut microbiota are involved in many physiological functions such as metabolism, brain development, and neurodegenerative diseases. Many microbes in the digestive tract do not maintain a constant level of their relative abundance but show daily oscillations under normal conditions. Recent evidence indicates that chronic jetlag, constant darkness, or deletion of the circadian core gene can alter the composition of gut microbiota and dampen the daily oscillation of gut microbes. However, the neuronal circuit responsible for modulating gut microbiota remained unclear. Using genetic mouse models and 16s rRNA metagenomic analysis, we find that light-dark cycle information transmitted by the intrinsically photosensitive retinal ganglion cells (ipRGCs) is essential for daily oscillations of gut microbes under temporal restricted high-fat diet conditions. Furthermore, aberrant light exposure such as dim light at night (dLAN) can alter the composition, relative abundance, and daily oscillations of gut microbiota. Together, our results indicate that external light-dark cycle information can modulate gut microbiota in the direction from the brain to the gut via the sensory system.

A simple and sensitive preconcentration strategy by coupling salting-out assisted liquid-liquid extraction with online three-step stacking for the determination of potent anti-tumour compound vinblastine and its precursor in biological samples by capillary electrophoresis.

A sensitive capillary electrophoresis strategy was developed by combining salting-out assisted liquid-liquid extraction and online three-step stacking to detect trace quantities of antitumour indole alkaloids in complex biological samples. The proposed strategy fully exploits these two technologies such that extraction, online stacking and separation are combined in a fast and efficient manner. First, salting-out assisted liquid-liquid extraction was used to extract three indole alkaloids (vinblastine sulfate, catharanthine sulfate and vindoline) from complex biomasses. An appropriate volume of acetonitrile (ACN) was mixed with a faecal aqueous solution to precipitate proteins. The mixed solution was vortexed, followed by the addition of ammonium sulfate ((NH4)2SO4) to induce two-phase separation. Alkaloids were effectively extracted into the organic phase, which was then subjected to capillary electrophoresis (CE) analysis. The sensitivity of capillary electrophoresis was effectively improved by online three-step stacking. Good linearity of the calibration curve for each indole alkaloid was obtained in the concentration range of 0.1-1 µg/mL. Under optimal conditions, the sensitivity of ordinary injection was increased by up to 2366-fold, confirming the applicability of the proposed strategy for the sensitive determination of trace indole alkaloids in complex biological samples.

A review on the chemical constituents and pharmacological efficacies of Lindera aggregata (Sims) Kosterm.

Lindera aggregata (Sims) Kosterm. (L. aggregata), which belongs to the genus Lindera in the family Lauraceae, is widely distributed in Asia and the temperate, tropical regions of North America. Its roots and leaves have been used for thousands of years as traditional Chinese medicine and/or functional food. To further explore its underlying nutritional value, this review provided a comprehensive insight into chemical constituents and pharmacological effects on L. aggregata. The phytochemical investigation of different parts of L. aggregata led to the identification of up to 349 components belonging to sesquiterpenoids, alkaloids, flavonoids, essential oils, and other compounds. Among them, sesquiterpenoids, flavonoids, and alkaloids are assessed as representative active ingredients of L. aggregata. A wide variety of pharmacological effects of L. aggregata, such as anti-hyperlipidemic, anti-tumor, anti-inflammatory, analgesic, and anti-oxidant, have been proved in vitro and in vivo. In summary, this review aims to provide a scientific basis and reference for further research and utilization of L. aggregata and lay the foundation for developing functional foods with potential active ingredients for the prevention and management of related diseases.

Circular RNA Hsa_circ_0006766 targets microRNA miR-4739 to regulate osteogenic differentiation of human bone marrow mesenchymal stem cells.

Circular RNAs (circRNAs) are emerging as important regulators in bone metabolism, which is mediated by microRNA (miRNA) sponges. However, it is not clear how circRNA regulates osteogenic differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs).Therefore, based on the previous circRNA chip results, hsa_circ_0006766, which is differentially expressed in the osteogenic differentiation of hBM-MSCs, was screened out, and bioinformatics analysis was performed to predict potential target miRNAs. During osteogenic differentiation of hBM-MSCs, hsa_circ_0006766 and its target miRNAs (miR-4739, miR-619-5p, miR-5787, miR-7851-3p, and miR-3192-5p) were detected by quantitative Real Time-PCR (qRT-PCR). Target gene prediction for the differentially expressed target miRNAs was performed, and target genes were validated by dual-luciferase reporter gene assay and qRT-PCR. It is shown that hsa_circ_0006766 was up-regulated and miR-4739 was down-regulated during osteogenic differentiation of hBM-MSCs.Moreover, the target gene Notch2 was predicted to be highly expressed during osteogenic differentiation. And dual-luciferase assay proved that Notch2 was the gene targeting to miR-4739. Taken together, our finding confirmed that hsa_circ_0006766 may act as a major regulatory part in osteogenic differentiation of hBM-MSCs via an hsa_circ_0006766-miR-4739-Notch2 regulatory axis. Accordingly, hsa_circ_0006766 may affect the development of osteoporosis and may thus become a therapeutic target.

Asymmetric dimethylarginine compartmental behavior during high-flux hemodialysis.

AIM: The accumulation of uremic toxins, such as asymmetric dimethylarginine (ADMA), has emerged as one of the major cardiovascular disease-related risk factors in patients with end-stage renal disease (ESRD). Based on the low molecular weight of ADMA, hemodialysis (HD) should theoretically effectively remove ADMA. In this study, we investigated the clearance behavior of ADMA during high-flux HD. METHODS: Eight HD patients without residual renal function were included. Blood samples were collected at 0, 30, 60, 120 and 240 min after dialysis started, as well as 1 h and 48 h after dialysis. ADMA level was detected by HPLC-MS/MS. Herein, the ADMA level in blood cells and the ADMA protein binding rate were measured. Accordingly, the dialyzer extraction ratio was also determined. RESULTS: The reduction ratio (RR) of ADMA (corrected for hemoconcentration) was significantly lower, at only 37.21 ± 6.44%, than that of urea and creatinine (p < .05). Interestingly, its clearance from plasma was precipitous early in dialysis and became slowly from 60 to 240 min. Additionally, a greater inlet erythrocyte than plasma concentration was found for ADMA. The dialyzer extraction ratio was comparable between ADMA and creatinine or urea (83 ± 5% for ADMA vs. 84 ± 3% and 88 ± 2% for creatinine and urea, respectively; both p>.05). Urea and creatinine had a slight rebound ratio of less than 10% at 1 h after the completion of HD. In contrast, considerable rebound of approximately 30% was detected in ADMA. CONCLUSION: This study suggests that ADMA may present a multicompartmental distribution that cannot be representatively reflected by the urea kinetics model.

Serum pre-albumin is prognostic for all-cause mortality in patients with community-acquired and post-operative acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) is a critical clinical syndrome characterised by a rapid decrease in renal filtration, with the accumulation of products of metabolism such as creatinine and urea. In recent years, the incidence of AKI has increased not only in critically ill hospitalised patients but also in community patients. Also, the prognosis of AKI is poor and treatment is limited in these populations. The increasing incidence and poor prognosis may be the reasons why more investigators are involved in epidemiological and risk factor analysis of AKI. AIMS: To investigate the effects of these risk factors on outcomes in both community-acquired and hospitalised AKI populations to provide certain guidance for clinics and to explore the prognostic value of prealbumin on all-cause mortality in patients with community-acquired and post-operative AKI. METHODS: From 2000 to 2010, 477 patients diagnosed with AKI and treated in the Department of Nephrology, Ruijin Hospital, Shanghai Jiaotong University, were enrolled in the community-acquired AKI (CA-AKI) group and 138 patients diagnosed with AKI after an operation were enrolled in the post-operative AKI (PO-AKI) group. Data were collected at AKI onset and 1 year after discharge and analysed retrospectively. RESULTS: Compared with PO-AKI patients, more patients in CA-AKI group had chronic kidney disease, obesity and hyperlipidaemia, and fewer patients had cerebrovascular disease (CVD), anaemia, shock or arrhythmia. Risks for CA-AKI were atherosclerosis, CVD, arrhythmia, multiple organ dysfunction syndrome and usage of vasoactive agents, and risks for PO-AKI were elderly, arrhythmia and requirement of renal replacement therapy. A higher level of serum PA was associated with a better outcome in the CA-AKI group (hazard ratio 0.92, 95% confidence interval 0.85-0.996) and PO-AKI group (hazard ratio 0.91, 95% confidence interval 0.84-0.99). In the CA-AKI group, the cumulative survival rate of patients with a normal PA level (PA >20 mg/dL) was higher than that among patients with a lower PA (PA ≤20 mg/dL; 95.4% vs 88.3%, P = 0.031). Similarly, in the PO-AKI group, a normal PA level was associated with a higher survival rate (74.1% vs 47.6%, P = 0.019). CONCLUSION: Serum PA may serve as a prognostic marker for CA-AKI and PO-AKI, and further research is warranted to confirm this finding.

Analysis of experience-regulated transcriptome and imprintome during critical periods of mouse visual system development reveals spatiotemporal dynamics.

Visual system development is light-experience dependent, which strongly implicates epigenetic mechanisms in light-regulated maturation. Among many epigenetic processes, genomic imprinting is an epigenetic mechanism through which monoallelic gene expression occurs in a parent-of-origin-specific manner. It is unknown if genomic imprinting contributes to visual system development. We profiled the transcriptome and imprintome during critical periods of mouse visual system development under normal- and dark-rearing conditions using B6/CAST F1 hybrid mice. We identified experience-regulated, isoform-specific and brain-region-specific imprinted genes. We also found imprinted microRNAs were predominantly clustered into the Dlk1-Dio3 imprinted locus with light experience affecting some imprinted miRNA expression. Our findings provide the first comprehensive analysis of light-experience regulation of the transcriptome and imprintome during critical periods of visual system development. Our results may contribute to therapeutic strategies for visual impairments and circadian rhythm disorders resulting from a dysfunctional imprintome.

Role of microRNA in the detection, progression, and intervention of acute kidney injury.

Acute kidney injury, characterized by sharply decreased renal function, is a common and important complication in hospitalized patients. The pathological mechanism of acute kidney injury is mainly related to immune activation and inflammation. Given the high morbidity and mortality rates of hospitalized patients with acute kidney injury, the identification of biomarkers useful for assessing risk, making an early diagnosis, evaluating the prognosis, and classifying the injury severity is urgently needed. Furthermore, investigation into the development of acute kidney injury and potential therapeutic targets is required. While microRNA was first discovered in Caenorhabditis elegans, Gary Ruvkun's laboratory identified the first microRNA target gene. Together, these two important findings confirmed the existence of a novel post-transcriptional gene regulatory mechanism. Considering that serum creatinine tests often fail in the early detection of AKI, testing for microRNAs as early diagnostic biomarkers has shown great potential. Numerous studies have identified microRNAs that can serve as biomarkers for the detection of acute kidney injury. In addition, as microRNAs can control the expression of multiple proteins through hundreds or thousands of targets influencing multiple signaling pathways, the number of studies on the functions of microRNAs in AKI progression is increasing. Here, we mainly focus on research into microRNAs as biomarkers and explorations of their functions in acute kidney injury. Impact statement Firstly, we have discussed the potential advantages and limitations of miRNA as biomarkers. Secondly, we have summarized the role of miRNA in the progress of AKI. Finally, we have made a vision of miRNA's potential and advantages as therapeutic target intervention AKI.

MicroRNA-30c-5p ameliorates hypoxia-reoxygenation-induced tubular epithelial cell injury via HIF1α stabilization by targeting SOCS3.

The cellular hypoxia-reoxygenation (H/R) model is an ideal method to study ischemia-reperfusion injury, which is associated with high mortality. The role of microRNA-30c-5p (miR-30c-5p) in the H/R epithelial cell model remains unknown. In the current study, we observed a significant reduction in apoptosis when miR-30c-5p was up-regulated. We also found decreased levels of C-caspase-3 (C-CASP3) and Bcl-2-associated X (BAX) proteins and increased levels of B-cell lymphoma-2 (BCL2). Epidermal growth factor receptor (EGFR) showed similar results. Down-regulating miR-30c-5p increased the levels of apoptosis and C-CASP3 and BAX expression; additionally, cell proliferation was inhibited. Hypoxia-inducible factor 1α (HIF1α) protein expression levels were up-regulated in response to up-regulation of miR-30c-5p expression. The anti-apoptotic and proliferative effects of miR-30c-5p decreased significantly after the HIF1α protein levels were knocked down. Using a luciferase reporter assay, we confirmed that miR-30c-5p targets suppressor of cytokine signaling-3 (SOCS3). HIF1α levels increased when SOCS3 was blocked. Our data show that SOCS3 expression enhances apoptosis in the H/R model. In conclusion, up-regulating miR-30c-5p protects cells from H/R -induced apoptosis and induces cell proliferation; furthermore, HIF1α markedly contributes to this protective effect. MiR-30c-5p stabilizes HIF1α expression by targeting SOCS3 to achieve anti-apoptotic and proliferative effects.

MicroRNA-140-5p attenuated oxidative stress in Cisplatin induced acute kidney injury by activating Nrf2/ARE pathway through a Keap1-independent mechanism.

Oxidative stress was predominantly involved in the pathogenesis of acute kidney injury (AKI). Recent studies had reported the protective role of specific microRNAs (miRNAs) against oxidative stress. Hence, we investigated the levels of miR140-5p and its functional role in the pathogenesis of Cisplatin induced AKI. A mice Cisplatin induced-AKI model was established. We found that miR-140-5p expression was markedly increased in mice kidney. Bioinformatics analysis revealed nuclear factor erythroid 2-related factor (Nrf2) was a potential target of miR-140-5p, We demonstrated that miR-140-5p did not affect Kelch-like ECH-associated protein 1 (Keap1) level but directly targeted the 3'-UTR of Nrf2 mRNA and played a positive role in the regulation of Nrf2 expression which was confirmed by luciferase activity assay and western blot. What was more, consistent with miR140-5p expression, the mRNA and protein levels of Nrf2, as well as antioxidant response element (ARE)-driven genes Heme Oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase l (NQO1) were significantly increased in mice kidney tissues. In vitro study, Enforced expression of miR-140-5p in HK2 cells significantly attenuated oxidative stress by decreasing ROS level and increasing the expression of manganese superoxide dismutase (MnSOD). Simultaneously, miR-140-5p decreased lactate dehydrogenase (LDH) leakage and improved cell vitality in HK2 cells under Cisplatin-induced oxidative stress. However, HK2 cells transfected with a siRNA targeting Nrf2 abrogated the protective effects of miR-140-5p against oxidative stress. These results indicated that miR-140-5p might exert its anti-oxidative stress function via targeting Nrf2. Our findings showed the novel transcriptional role of miR140-5p in the expression of Nrf2 and miR-140-5p protected against Cisplatin induced oxidative stress by activating Nrf2-dependent antioxidant pathway, providing a potentially therapeutic target in acute kidney injury.

Urinary MicroRNA-30c-5p and MicroRNA-192-5p as potential biomarkers of ischemia-reperfusion-induced kidney injury.

Early detection of acute kidney injury is difficult due to lack of known biomarkers; previous studies have tried to identify new biomarkers for detecting acute kidney injury at an early stage. MicroRNA, a 21-23 nucleotide noncoding RNA molecule, has emerged as a desirable marker in the diagnosis and prognosis of various diseases. This study aims to identify the expression profile of microRNA in ischemia-reperfusion-induced kidney injury and determine the possibility of using the candidate microRNA as biomarker for the detection of I/R-induced kidney injury. Based on the established rat model of I/R-induced kidney injury, a microarray analysis of rat urine was performed at the beginning of operation (0 h) as well as 72 h post operation. To validate the results, urine samples from 71 patients who underwent cardiac surgery were collected, after which urinalysis was conducted to determine the microRNA concentration. An alternative expression profile of microRNAs was detected in rat urine. The quantitative validation of microRNA showed that the expression of miR-30c-5p, miR-192-5p, and miR-378a-3p was elevated significantly in urine post operation, which was consistent with those of the microarray analysis and earlier than kidney injury molecule-1 (KIM-1). In patients with acute kidney injury, increased levels of miR-30c-5p and miR-192-5p were also detected 2 h post operation, and miR-30c-5p showed preferable diagnostic value compared with protein-based biomarkers. In conclusion, an aberrant expression profile of microRNA was detected in rat urine based on the established ischemia-reperfusion animal model. Both miR-30c-5p and miR-192-5p served as important potential diagnostic markers for I/R-induced kidney injury. Impact statement Firstly, one differentiating factor in our study is that the candidate miRNAs were screened in a controlled animal model rather than in patients with acute kidney injury (AKI) to ensure the purity of the cause of disease and to avoid possible effects of comorbidities on the spectrum of urine miRNA. This ensured the presence of only the relevant candidate miRNA (that associated with I/R injury); and what's more, the alterative expression of miR-192-5p and miR-30c-5p in animal model, patients with AKI, and cell model was confirmed simultaneously, which is likely to be more convincing. Secondly, the candidate miRNAs were screened sequentially at regular time points, which covered the initiation, progression, and partial repair stages, thus ensuring that no significant miRNAs were omitted in the screening process, and miR-biomarkers in 2 h post operation showed preferable diagnostic performance.

Inhibitor of DNA Binding 1 Is Induced during Kidney Ischemia-Reperfusion and Is Critical for the Induction of Hypoxia-Inducible Factor-1α.

In this study, rat models of acute kidney injury (AKI) induced by renal ischemia-reperfusion (I/R) and HK-2 cell models of hypoxia-reoxygenation (H/R) were established to investigate the expression of inhibitor of DNA binding 1 (ID1) in AKI, and the regulation relationship between ID1 and hypoxia-inducible factor 1 alpha (HIF-1α). Through western blot, quantitative real-time PCR, immunohistochemistry, and other experiment methods, the induction of ID1 after renal I/R in vivo was observed, which was expressed mainly in renal tubular epithelial cells (TECs). ID1 expression was upregulated in in vitro H/R models at both the protein and mRNA levels. Via RNAi, it was found that ID1 induction was inhibited with silencing of HIF-1α. Moreover, the suppression of ID1 mRNA expression could lead to decreased expression and transcription of HIF-1α during hypoxia and reoxygenation. In addition, it was demonstrated that both ID1 and HIF-1α can regulate the transcription of twist. This study demonstrated that ID1 is induced in renal TECs during I/R and can regulate the transcription and expression of HIF-1α.

One-year survival and renal function recovery of acute kidney injury patients with chronic heart failure.

OBJECTIVE: To describe and analyze the clinical characteristics of acute kidney injury (AKI) patients with preexisting chronic heart failure (CHF) and to identify the prognostic factors of the 1-year outcome. METHODS: A total of 120 patients with preexisting CHF who developed AKI between January 2005 and December 2010 were enrolled. CHF was diagnosed according to the European Society of Cardiology guidelines, and AKI was diagnosed using the RIFLE criteria. Clinical characteristics were recorded, and nonrecovery from kidney dysfunction as well as mortality were analyzed. RESULTS: The median age of the patients was 70 years, and 58.33% were male. 60% of the patients had an advanced AKI stage ('failure') and 90% were classified as NYHA class III/IV. The 1-year mortality rate was 35%. 25.83% of the patients progressed to end-stage renal disease after 1 year. Hypertension, anemia, coronary atherosclerotic heart disease and chronic kidney disease were common comorbidities. Multiple organ dysfunction syndrome (MODS; OR, 35.950; 95% CI, 4.972-259.952), arrhythmia (OR, 13.461; 95% CI, 2.379-76.161), anemia (OR, 6.176; 95% CI, 1.172-32.544) and RIFLE category (OR, 5.353; 95% CI, 1.436-19.952) were identified as risk factors of 1-year mortality. For 1-year nonrecovery from kidney dysfunction, MODS (OR, 8.884; 95% CI, 2.535-31.135) and acute heart failure (OR, 3.281; 95% CI, 1.026-10.491) were independent risk factors. CONCLUSION: AKI patients with preexisting CHF were mainly elderly patients who had an advanced AKI stage and NYHA classification. Their 1-year mortality and nonrecovery from kidney dysfunction rates were high. Identifying risk factors may help to improve their outcome.

Identification of nestin as a urinary biomarker for acute kidney injury.

OBJECTIVES: Acute kidney injury (AKI) is a common complication in hospitalized patients and the incidence of AKI is rapidly increasing. Despite the advances in treatment of AKI, many patients still progress to end-stage renal disease and depend on dialysis. Therefore, early diagnosis and adequate treatment of AKI could improve prognosis. METHODS: We established rat models of AKI induced by cisplatin nephrotoxicity and renal ischemia-reperfusion (I/R). Urine samples were collected, labeled with isobaric tags for relative and absolute quantification agents, and then subjected to nano-LC-MS/MS-based proteomic analysis. Results of the proteomic study were confirmed by Western blot. We also performed RNAi to silence nestin and investigate its role in renal I/R injury. We then validated its clinical application by studying urine nestin levels in AKI patients with cardiovascular surgeries. RESULTS: Our proteomic analysis showed that fetuin-A, nestin, hamartin and T-kininogen were differentially expressed in the urine samples of rats after cisplatin or I/R treatment. Western blot confirmed the differential expression of these proteins in animal models and ELISA confirmed the differential expression of nestin in human urine samples. To explore the expression of nestin in the development of AKI, our results showed that nestin was primarily detected in the glomeruli and barely detected in tubular cells but increased in tubular cells during I/R- and cisplatin-induced AKI. The urine nestin-to-creatinine ratio increased earlier than serum creatinine in AKI patients with postcardiovascular surgeries. The role of nestin in AKI might be related to the p53 signaling pathway. CONCLUSIONS: Thus, our results demonstrated that urinary nestin could be a urinary biomarker for patients with AKI and its role in AKI might be related to the p53 signaling pathway.