Reconfigurable moiré nanolaser arrays with phase synchronization.

Miniaturized lasers play a central role in the infrastructure of modern information society. The breakthrough in laser miniaturization beyond the wavelength scale has opened up new opportunities for a wide range of applications1-4, as well as for investigating light-matter interactions in extreme-optical-field localization and lasing-mode engineering5-19. An ultimate objective of microscale laser research is to develop reconfigurable coherent nanolaser arrays that can simultaneously enhance information capacity and functionality. However, the absence of a suitable physical mechanism for reconfiguring nanolaser cavities hinders the demonstration of nanolasers in either a single cavity or a fixed array. Here we propose and demonstrate moiré nanolaser arrays based on optical flatbands in twisted photonic graphene lattices, in which coherent nanolasing is realized from a single nanocavity to reconfigurable arrays of nanocavities. We observe synchronized nanolaser arrays exhibiting high spatial and spectral coherence, across a range of distinct patterns, including P, K and U shapes and the Chinese characters '' and '' ('China' in Chinese). Moreover, we obtain nanolaser arrays that emit with spatially varying relative phases, allowing us to manipulate emission directions. Our work lays the foundation for the development of reconfigurable active devices that have potential applications in communication, LiDAR (light detection and ranging), optical computing and imaging.

Association between serum uric acid levels and clinical outcomes in patients with acute kidney injury.

BACKGROUND: The effects of serum uric acid (SUA) on clinical outcomes in patients with acute kidney injury (AKI) are unclear. The aim of this study was to investigate the association of SUA levels with clinical outcomes of AKI patients. METHODS: The data of AKI patients hospitalized in the Affiliated Hospital of Qingdao University were retrospectively reviewed. Multivariable logistic regression was utilized to assess the association between SUA levels and the clinical outcomes of AKI patients. Receiver operating characteristic (ROC) analysis was applied to assess the predictive ability of SUA levels for in-hospital mortality in patients with AKI. RESULTS: A total of 4,646 AKI patients were eligible for study inclusion. In multivariable analysis, after adjustment for various confounding factors in the fully adjusted model, a higher SUA level was found to be associated with increased in-hospital mortality of AKI patients with an odds ratio (OR) of 1.72 (95% CI, 1.21-2.33, p = 0.005) for the SUA level >5.1-6.9 mg/dl group and 2.75 (95% CI, 1.78-4.26, p < 0.001) for the SUA level >6.9 mg/dl group compared with the reference group (SUA ≤3.6 mg/dl). In the ROC analysis, the area under the curve (AUC) of SUA was 0.65 with a sensitivity of 51% and a specificity of 73%. CONCLUSIONS: An elevated SUA level is associated with an increased risk of in-hospital mortality in patients with AKI, and it appears to be an independent prognostic marker for these patients.

Mesenchymal stem cells protect against sepsis-associated acute kidney injury by inducing Gal-9/Tim-3 to remodel immune homeostasis.

OBJECTIVE: The present study investigated the specific mechanism by which mesenchymal stem cells (MSCs) protect against sepsis-associated acute kidney injury (SA-AKI). METHODS: Male C57BL/6 mice underwent cecal ligation and puncture surgery to induce sepsis and then received either normal IgG or MSCs (1 × 106 cells, intravenously) plus Gal-9 or soluble Tim-3 3 h after surgery. RESULTS: After cecal ligation and puncture surgery, the mice injected with Gal-9 or MSCs plus Gal-9 had a higher survival rate than the mice in the IgG treatment group. Treatment with MSCs plus Gal-9 decreased serum creatinine and blood urea nitrogen levels, improved tubular function recovery, reduced IL-17 and RORγt levels and induced IL-10 and FOXP3 expression. Additionally, the Th17/Treg cell balance was altered. However, when soluble Tim-3 was used to block the Gal-9/Tim-3 pathway, the septic mice developed kidney injury and exhibited increased mortality. Treatment with MSCs plus soluble Tim-3 blunted the therapeutic effect of MSCs, inhibited the induction of Tregs, and suppressed the inhibition of differentiation into Th17 cells. CONCLUSION: Treatment with MSCs significantly reversed the Th1/Th2 balance. Thus, the Gal-9/Tim-3 pathway may be an important mechanism of MSC-mediated protection against SA-AKI.

Land Use Influencing the Distribution of Pesticides in Surface Water: The Case of the Ma River and Its Tributaries in Thanh Hoa Province, Vietnam.

Pesticide residues are regularly found in surface water, which could be dangerous for freshwater ecosystems and biodiversity. Pesticides may enter waters through a variety of pathways, but runoff from irrigation or precipitation has the highest quantities. Previous studies analyzing the pesticides pollution or ecological risks of pesticides focused on few regions (e.g., European and United States), whereas analysis of pesticide pollution in Southeast Asia and especially in Vietnam is limited. This study presents an investigation of banned pesticides used across the range of land use in catchments of the Ma river and its tributaries in Thanh Hoa province, Vietnam. Applying principal component analysis (PCA), we investigated the relationship between specific pesticides and land use. Besides, cluster analysis (CA), the method of aggregating monitoring locations, was applied in this study to find spatial pattern of pesticides pollution. Due to their persistence and remobilization during floods and runoff, all ten banned pesticides-eight insecticides (aldrin/dieldrin, BHC, chlordane, endrin, heptachlor, lindane, malathion, and parathion) and two herbicides (paraquat, and 2,4D)-still remain in surface water and are not presumably influenced by the fraction of land use area in the catchments. Clustering results revealed that banned pesticides still occur in some areas. Site TH08 close to Le Mon industrial zone and TH18 in Thanh Hoa city have higher concentrations of banned pesticides than other sites due to their highly toxic and long-time existence in the environment. Overall, our study provides approach to investigate pesticides in surface water for a province in Vietnam that may be used for future ecotoxicological studies to enhance risk assessment for stream ecosystems.

The identification of liver metastasis- and prognosis-associated genes in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is an often fatal malignancy with an extremely low survival rate. Liver metastasis, which causes high mortality, is the most common recurring metastasis for PDAC. However, the mechanisms underlying this liver metastasis and associated candidate biomarkers are unknown. METHODS: We performed mRNA profiling comparisons in 8 primary tumors (T) and 12 liver metastases (M) samples using the Gene Expression Omnibus (GEO) database. After determining differentially expressed genes (DEG), gene ontology (GO), pathway enrichment and protein-protein interaction (PPI) network analyses were performed to determine DEG functions. Then, Cytoscape was used to screen out significant hub genes, after which their clinical relevance was investigated using The Cancer Genome Atlas (TCGA) resources. Furthermore, prognosis-associated gene expression was validated using Oncomine and TCGA database. Lastly, associations between prognosis-associated genes, immune cells and immunological checkpoint genes were evaluated using the Tumor Immune Estimation Resource (TIMER). RESULTS: In total, 102 genes were related to liver metastasis and predominantly involved in cell migration, motility, and adhesion. Using Cytoscape, this number was narrowed down to 16 hub genes. Elevated mRNA expression levels for two of these genes, SPARC (P = 0.019) and TPM1 (P = 0.037) were significantly correlated with poor disease prognosis. For the remaining 14, expression was not related to overall patient survival. SPARC had higher expression in patients with metastatic PDAC than those with non-metastatic PDAC in TCGA dataset. SPARC and TPM1 levels were also positively correlated with the immune infiltration of specific cell types. Additionally, both genes exhibited strong co-expression associations with immune checkpoint genes. CONCLUSIONS: Combined, we suggest SPARC has high potential as biomarker to predict liver metastasis during PDAC. Additionally, both SPARC and TPM1 appeared to recruit and regulate immune-infiltrating cells during these pathophysiological processes.

Associations between early thiamine administration and clinical outcomes in critically ill patients with acute kidney injury.

The effects of early thiamine use on clinical outcomes in critically ill patients with acute kidney injury (AKI) are unclear. The purpose of this study was to investigate the associations between early thiamine administration and clinical outcomes in critically ill patients with AKI. The data of critically ill patients with AKI within 48 h after ICU admission were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. PSM was used to match patients early receiving thiamine treatment to those not early receiving thiamine treatment. The association between early thiamine use and in-hospital mortality due to AKI was determined using a logistic regression model. A total of 15 066 AKI patients were eligible for study inclusion. After propensity score matching (PSM), 734 pairs of patients who did and did not receive thiamine treatment in the early stage were established. Early thiamine use was associated with lower in-hospital mortality (OR 0·65; 95 % CI 0·49, 0·87; P < 0·001) and 90-d mortality (OR 0·58; 95 % CI 0·45, 0·74; P < 0·001), and it was also associated with the recovery of renal function (OR 1·26; 95 % CI 1·17, 1·36; P < 0·001). In the subgroup analysis, early thiamine administration was associated with lower in-hospital mortality in patients with stages 1 to 2 AKI. Early thiamine use was associated with improved short-term survival in critically ill patients with AKI. It was possible beneficial role in patients with stages 1 to 2 AKI according to the Kidney Disease: Improving Global Outcomes criteria.

Dynamic multivariate analysis for pollution assessment and river habitat conservation in the Vietnamese La Buong watershed.

Analysis of temporal patterns of high-dimensional time-series water quality data is essential for pollution management worldwide. This study has applied dynamic factor analysis (DFA) and cluster analysis (CA) to analyze time-series water quality data monitored at the five stations installed along the La Buong river in Southern Vietnam. Application of the DFA identified two types of temporal patterns, one of the run-off driven parameters (total suspended solid (TSS), turbidity, and iron) and the other of diffuse source pollution. The association of the variables like BOD5 and COD at most stations to the run-off-driven parameters revealed their sharing of drivers. On the contrary, separating variables like phosphate (PO43) at the three upstream stations from the run-off patterns suggested their local point-source origin. The DFA-derived factors were later used in the time-point CA to explore the seasonality of water quality parameters and their pollution intensities compared to regulatory levels. The result suggested intensification in wet season of Fe, TSS, BOD5, and COD concentrations at most sites, which are unobservable in run-off detached parameters like reactive nitrogen, phosphate (PO43-), and E. coli. These findings generated robust insights to support water quality management for river habitat conservation.

Nicotiflorin attenuates cell apoptosis in renal ischemia-reperfusion injury through activating transcription factor 3.

INTRODUCTION: Nicotiflorin is the main characteristic component of Nymphaea candida, which is a natural product that reportedly ameliorates acute injury of the liver and cerebral cortex, but the effect of nicotiflorin on acute kidney injury (AKI) remains unknown. This study aimed to investigate the effects of nicotiflorin on ischaemia/reperfusion (I/R) AKI and the associated mechanisms. METHODS: We performed both (a) in vivo experiments with C57BL/6 mice with bilateral renal pedicles clamped for 45 minutes and (b) in vitro experiments with human kidney epithelial cells (HK-2) exposed to hypoxia/reoxygenation to mimic I/R injury to study the role of nicotiflorin in AKI. RESULTS: In vivo, nicotiflorin administration exerted protective effects on renal injury, as demonstrated by reductions in the levels of caspase3 and Bad (P < .05), the upregulation of Bcl-2 expression (P < .05) and improved renal histologic changes, which suggested that nicotiflorin can alleviate I/R injury and cell apoptosis. In vitro, nicotiflorin at a concentration of 75 µg/mL protected cells from hypoxia, which further confirmed that nicotiflorin exerts beneficial effects on hypoxia/reoxygenation. Through computational molecular docking, we found that activating transcription factor 3 (ATF3) exhibits a robust interaction with nicotiflorin with a simulated binding energy of -9.2°. We verified the interaction of nicotiflorin with ATF3 in HK-2 cells, and found that nicotiflorin reduced the apoptosis of HK-2 through ATF3. CONCLUSION: Based on the above-described results, nicotiflorin appears to have a beneficial impact on deteriorated renal function, as demonstrated using an experimental I/R model. The underlying mechanisms of nicotiflorin might inhibit HK-2 cell apoptosis through ATF3.

Malnutrition screening and acute kidney injury in hospitalised patients: a retrospective study over a 5-year period from China.

Malnutrition and acute kidney injury (AKI) are common complications in hospitalised patients, and both increase mortality; however, the relationship between them is unknown. This is a retrospective propensity score matching study enrolling 46 549 inpatients, aimed to investigate the association between Nutritional Risk Screening 2002 (NRS-2002) and AKI and to assess the ability of NRS-2002 and AKI in predicting prognosis. In total, 37 190 (80 %) and 9359 (20 %) patients had NRS-2002 scores <3 and ≥3, respectively. Patients with NRS-2002 scores ≥3 had longer lengths of stay (12·6 (sd 7·8) v. 10·4 (sd 6·2) d, P < 0·05), higher mortality rates (9·6 v. 2·5 %, P < 0·05) and higher incidence of AKI (28 v. 16 %, P < 0·05) than patients with normal nutritional status. The NRS-2002 showed a strong association with AKI, that is, the risk of AKI changed in parallel with the score of the NRS-2002. In short- and long-term survival, patients with a lower NRS-2002 score or who did not have AKI achieved a significantly lower risk of mortality than those with a high NRS-2002 score or AKI. Univariate Cox regression analyses indicated that both the NRS-2002 and AKI were strongly related to long-term survival (AUC 0·79 and 0·71) and that the combination of the two showed better accuracy (AUC 0·80) than the individual variables. In conclusion, malnutrition can increase the risk of AKI and both AKI and malnutrition can worsen the prognosis that the undernourished patients who develop AKI yield far worse prognosis than patients with normal nutritional status.

Long Noncoding RNA LINC00265 Promotes Glycolysis and Lactate Production of Colorectal Cancer through Regulating of miR-216b-5p/TRIM44 Axis.

AIM: To examine the expression status of long-noncoding RNA LINC00265 and mechanistically elucidate its involvements in colorectal cancer (CRC). METHODS: Relative abundances of LINC00265, miR-216b-5p, and tripartite-motif (TRIM)44 transcript were determined with real-time polymerase chain reaction. Cell viability was measured with cell counting kit-8 kit. Glucose uptake, pyruvate, and lactate production were quantified with commercially available kits. The potential regulatory effects of miR-216b-5p on both LINC00265 and TRIM44 were interrogated by luciferase reporter assay. The direct association between miR-216b-5p with both LINC00265 and TRIM44 was analyzed with pull-down assay. The TRIM44 protein was quantitated by western blotting. RESULTS: LINC00265 was upregulated in CRC both in vivo and in vitro, which intimately associated with poorer prognosis. LINC00265-deficiency resulted into decreases in cell viability, glucose uptake, pyruvate production, and lactate production. Mechanistically, LINC00265 directly bound to miR-216b-5p and negatively regulated miR-216b-5p. Consequently, the suppression on TRIM44 expression was released. Supplementation with ectopic miR-216b-5p significantly compromised the oncogenic activities of LINC00265 in CRC cells. CONCLUSION: Our study highlighted the contribution of LINC00265/miR-216b-5p/TRIM44 signaling axis in CRC.

Acute kidney injury after nephrectomy: a new nomogram to predict postoperative renal function.

BACKGROUND: We aimed to develop a nomogram based on preprocedural features for early prediction of acute kidney injury (AKI) and to assess the prognosis in patients after radical and partial nephrectomy. METHODS: The study included a development cohort of 1111 patients who were treated between June 2012 and June 2017 and an additional validation cohort of 356 patients who were treated between July 2017 and June 2018. Stepwise regression and logistic regression analyses were used to evaluate the association between predictors and AKI. Incorporating all independent predictors, a nomogram for postoperative AKI was developed and externally validated. Patients were followed up for 5 years to assess renal function, acute kidney disease (AKD), chronic kidney disease (CKD), hospital readmission and mortality were key prognosis we focused on. RESULTS: After multivariate logistic regression, radical nephrectomy (odds ratio (OR) = 3.57, p < 0.001), aspirin (OR = 1.79, p = 0.008), systolic blood pressure (OR = 1.41, p = 0.004), triglyceride (OR = 1.26, p = 0.024), and alkaline phosphatase (OR = 1.75, p = 0.034) were independent risk factors for postoperative AKI, while albumin (OR = 0.72, p = 0.031) was a protective factor for postoperative AKI. Patients with a higher estimated glomerular filtration rate (eGFR) (60-90 ml/min/1.73 m2, OR = 0.41, p = 0.004; ≥ 90 ml/min/1.73 m2, OR = 0.37, p < 0.001) were less prone to AKI than those with a lower eGFR (< 15 ml/min/1.73 m2). These predictors were all included in the final nomogram. The area under the receiver operating characteristics curve for the model were 0.77 (p < 0.001) in the development cohort and 0.72 (p < 0.001) in the validation cohort. The incidence of AKD and CKD were 27.12 and 18.64% in AKI group, which were much higher than those in no AKI group (p < 0.001). CONCLUSIONS: The nomogram had excellent predictive ability and might have significant clinical implications for the early detection of AKI in patients undergoing nephrectomy.

Serum response factor increases renal cell carcinoma migration and invasion through promoting epithelial-mesenchymal transition.

OBJECTIVE: To explore the regulation and function of serum response factor in epithelial-mesenchymal transition in renal cell carcinoma. METHODS: First, bioinformatics analysis of human renal cell carcinoma tissues was carried out. Then, the expression of serum response factor, mesenchymal markers (N-cadherin, vimentin and fibronectin) and epithelial markers (zonula occludens-1 and epithelial cadherin) was examined in 786-O cells (a human renal cell carcinoma cell line). Serum response factor was overexpressed with pcDNA-serum response factor plasmid, and suppressed by CCG-1423 (a small molecule inhibitor of serum response factor) to study how serum response factor affects epithelial-mesenchymal transition in renal cell carcinoma. A xenograft nude mouse model was established to explore whether serum response factor affected the tumorigenic ability of renal cell carcinoma cells. RESULTS: Serum response factor interacted with several important differentially expressed genes in renal cell carcinoma. In 786-O cells, serum response factor, N-cadherin, vimentin and fibronectin were upregulated, whereas zonula occludens-1 and epithelial cadherin were downregulated. Serum response factor upregulation in 786-O cells increased the Snail expression. Serum response factor suppression reduced Snail induction, and migration and invasion in renal cell carcinoma, which decreased the xenograft tumor volume. CONCLUSIONS: Serum response factor is a critical transcription factor in human renal cell carcinoma. Increased serum response factor activity induces epithelial-mesenchymal transition, migration and invasion in 786-O cells, and facilitates the progression of renal cell carcinoma. Targeting serum response factor with CCG-1423 might be an attractive therapeutic strategy for renal cell carcinoma.

A visual risk assessment tool for acute kidney injury after intracranial aneurysm clipping surgery.

OBJECTIVE: The aim of the study was to establish a predictive postoperative nomogram for acute kidney injury (AKI) after intracranial aneurysm clipping surgery, in order to early identify patients with high postoperative AKI risk. METHODS: This is a retrospective study, which included patients who underwent intracranial aneurysm clipping surgery. Multivariate logistic regression was employed to select confound factors that associated with AKI, then incorporated into the nomogram. The predictive accuracy of the model was assessed by concordance index (C-Index). RESULTS: A total of 365 patients after intracranial aneurysm clipping surgery were enrolled in the study eventually, of which 68 (18.63%) suffered postoperative AKI, and the incidence of stage 1, stage 2 and stage 3 were 92.65% (63/68), 5.88% (4/68), and 1.47% (1/68), respectively. Univariate logistic regression revealed that high density lipoprotein (HDL), prothrombin time (PT), estimated glomerular filtration rate (eGFR), size of aneurysm ≥10 mm, and aneurysm ruptured before surgery were associated with AKI after surgery, while multivariate logistic regression showed same results as the size of aneurysm ≥10 mm and aneurysm ruptured were independent AKI risk factors. In addition, the nomogram demonstrated a good accuracy in estimating intracranial aneurysm clipping associated AKI, as a C-Index and a bootstrap-corrected one of 0.772 and 0.737, respectively. Moreover, calibration plots showed consistency with the actual presence of AKI. CONCLUSION: The novel nomogram model can serve as a promising predictive tool to improve the identification of AKI among those who underwent intracranial aneurysm clipping surgery.

Cast nephropathy associated with monoclonal immunoglobulin M-secreting mucosa-associated lymphoid tissue B-cell lymphoma
.

The kidney is among the various anatomical sites involved in mucosa-associated lymphoid tissue (MALT) lymphoma. A variety of renal pathological types, including membranous glomerulopathy, membranoproliferative glomerulonephritis, crescentic IgA nephropathy, minimal change disease, and cryoglobulinemic glomerulopathy, have been reported in MALT lymphoma patients. However, cast nephropathy is extremely rare in MALT lymphoma. Herein, we describe the case of a patient with a history of MALT lymphoma of the stomach and small intestine 7 years before presenting with acute kidney failure 1 year after chemotherapy cessation. Monoclonal IgM-λ was detected in the serum, and kidney biopsy showed λ light chain deposition-based cast nephropathy. In addition, MALT recurrence was discovered in the stomach rather than intestinal tissue by gastrointestinal endoscope, and no lymphoplasmacytic infiltration was found in bone marrow. After 1 year of chemotherapy, renal function was partially restored, and the level of serum λ chain, serum IgM, and 24-hour urine protein all decreased. Our case illustrates that MALT lymphoma is prone to recurrence and grows slowly, moreover, with the characteristic of monoclonal immunoglobulin production and kidney infiltration.

Cysteine-rich protein 61, a specific ultra-early biomarker in kidney ischemia/reperfusion injury.

AIM: Studies have shown that cysteine-rich protein 61 (Cyr61) increased in the post-ischemic human kidney tissue. However, it is still unknown whether Cyr61 can be used as a biomarker in kidney ischemia/reperfusion (I/R) injury. METHODS: Microarray data were collected from GSE58438 and GSE52004. The rat I/R model was established to evaluate the messenger RNA and protein expression of Cyr61, localization of Cyr61 by immunohistochemical and immunofluorescence staining, and changes in serum creatinine (Scr) at the same time. RESULTS: Bioinformatics result showed that Cyr61 was significantly increased at 3 h after I/R in rat kidney, and involved in angiogene, positive regulation of locomotion and single organism cell adhesion. The rat I/R model results showed that Cyr61 was mainly expressed in renal tubular epithelial cells with I/R injury and the expression of Cyr61 was up-regulated at I/R 1 h, peaked at 4-8 h and began to decay at 12 h. The area under curve of receiver operating characteristics of kidney tissue Cyr61 messenger RNA and urine Cyr61 were 90.2% and 86.1%, which all better than Scr 67.1% (P < 0.05). CONCLUSION: We made a preliminary investigation of the relationship between Cyr61 and AKI, which identifies that Cyr61 may replace Scr as an ultra-early new biomarker in AKI.

Bioinformatics analysis in menopause transition promotes distinct modulation in calvaria and bone marrow osteoblastic cells.

We read with great interest the recent report by Semeghini et al. (2017), Cell Biol Int, "Menopause transition promotes distinct modulation of mRNAs and miRNAs expression in calvaria and bone marrow osteoblastic cells," which appeared on 24 May 2017 in Cell Biology International. The results of the report are very helpful for us; however, from our perspective, the author's method in bioinformatics analysis is inappropriate: Student's t-test is an inappropriate statistical method for detecting differentially expressed mRNA or miRNA in osteoblastic cells from calvaria of ovariectomized rats compared to control or in osteoblastic cells from bone marrow of ovariectomized rats compared to control.

Identification, expression pattern and potential role of variable lymphocyte receptor Aj-VLRA from Apostichopus japonicus in response to bacterial challenge.

The variable lymphocyte receptors (VLRs) are found in jawless vertebrates (agnathans), and specifically recognize bacteria and viruses via their leucine-rich repeats (LRRs). VLRs are believed to be adaptive immune response molecules. Echinoderms do not have adaptive immune systems; however, in the present study, a VLR cDNA named Aj-VLRA was cloned and characterized from sea cucumber, Apostichopus japonicus. The complete cDNA of Aj-VLRA was 3072 bp, including a 1995 bp open reading frame encoding 664 amino acids comprising LRR domains, a predicted transmembrane helix and an N-terminal signal peptide. As determined by quantitative real-time reverse transcription polymerase chain reaction, Aj-VLRA transcripts are ubiquitously expressed in the body wall, longitudinal muscles, intestine and respiratory tree of A. japonicus. The expression level of Aj-VLRA was upregulated after challenge with four common marine bacteria. In situ hybridization showed that the expression of Aj-VLRA was widely distributed in the four tissues, particularly in the cytoplasm of epidermal cells. Recombinantly expressed Aj-VLRA (including the LRR domains) could bind to bacteria including Micrococcus lysodeikticus (Gram+) and Vibrio anguillarum (Gram-). Collectively, the results suggested that Aj-VLRA is related to an innate immune response of A. japonicus.

Enzymatic hydrolysis of 7-xylosyltaxanes by an extracellular xylosidase from Cellulosimicrobium cellulans.

OBJECTIVES: To find extracellular biocatalysts that can specifically and efficiently remove the C-7 xylosyl group from 7-xylosyltaxanes. RESULTS: A Cellulosimicrobium cellulans strain F16 that can remove the C-7 xylosyl group from 7-xylosyltaxanes was isolated from the root soil of an old Taxus yunnanensis tree. Using corn cob as sole carbon source, the maximum 7-xylosyl-10-deacetylpaclitaxel ß-xylosidase activity of 9.6 U l(-1) was achieved. The ß-xylosidase could be trapped by a ceramic tubular membrane (pore size 50 nm), and exhibited an apparent molecular weight much greater than 500 kDa. Under optimized conditions, 3.75 l cell-free culture medium transformed 2 grams 7-xylosyltaxane mixtures to their corresponding aglycones within 3 h, with a conversion >98%. CONCLUSION: This is the first report that C. cellulans can produce extracellular ß-xylosidases capable of removing the C-7 xylosyl group from 7-xylosyltaxanes.

[Pandanus tectorius derived caffeoylquinic acids inhibit lipid accumulation in HepG2 hepatoma cells through regulation of gene expression involved in lipid metabolism].

The fruit of Pandanus tectorius (PTF) has a long history of use as a folk medicine to treat hyperlipidemia in Hainan province, South China. Our previous studies have shown that the n-butanol extract of PTF is rich in caffeoylquinic acids and has an adequate therapeutic effect on dyslipidemic animals induced by high-fat diet. In this work, seven caffeoylquinic acids isolated from PTF were screened for the lipid-lowering activity in HepG2 hepatoma cells. Oil-Red O staining, microscopy and intracellular triglyceride (TG) and total cholesterol (TC) quantification showed that 3-O-caffeoylquinic acid (3-CQA), 3, 5-di-O-caffeoylquinic acid (3,5-CQA), and 3,4,5-tri-O-caffeoylquinic acid (3,4,5-CQA) significantly inhibited lipid accumulation induced by oleic acid and decreased intracellular levels of TC and TG in a dose-dependent manner. These three caffeoylquinic acids showed no significant cytotoxicity at concentrations of 1 -50 µmol x L(-1) as determined by MTT assay. Realtime quantitative PCR revealed that 3-CQA and 3, 5-CQA significantly increased the expression of lipid oxidation-related genes PPARα, CPT-1 and ACOX1 while 3-CQA, 3, 5-CQA and 3,4,5-CQA decreased the expression of lipogenic genes SREBP-1c, SREBP-2, HMGR, ACC, FAS. Overall, 3-CQA, 3, 5-CQA and 3, 4, 5-CQA may be the principal hypolipidemic components in PTF which can decrease intracellular lipid accumulation through up-regulating the expression of lipid oxidative genes and down-regulating the expression of lipogenic genes.

Chrysin inhibits foam cell formation through promoting cholesterol efflux from RAW264.7 macrophages.

CONTEXT: Chrysin, a natural flavonoid, has been shown to possess multiple pharmacological activities including anti-atherosclerosis. OBJECTIVE: The effects of chrysin on foam cell formation and cholesterol flow in RAW264.7 macrophages were investigated in this work to explore the potential mechanism underlying its anti-atherogenic activity. MATERIALS AND METHODS: The inhibitive effect of chrysin on foam cell formation and cholesterol accumulation induced by oxidized low-density lipoprotein cholesterol (ox-LDL) was assessed by oil red O staining and intracellular total cholesterol and triglyceride quantification in RAW264.7 macrophages. The action of chrysin on cholesterol efflux and influx was tested by fluorescent assays. Real-time quantitative PCR was used to quantify the relative expression of cholesterol flow-associated genes and luciferase assay was applied to test the transcription activity of peroxisome proliferator-activated receptor gamma (PPARγ). RESULTS: Chrysin dose dependently inhibited the formation of foam cells and prevented the enhanced cholesterol accumulation by ox-LDL. Treatment with chrysin (10 µM) significantly enhanced cholesterol efflux and substantially inhibited cholesterol influx. Simultaneously, chrysin significantly increased the mRNA levels of PPARγ, liver X receptor alpha (LXRα), ATP-binding cassette, sub-family A1 (ABCA1), and sub-family G1 (ABCG1), decreased scavenger receptor A1 (SR-A1) and SR-A2, and increased the transcriptional activity of PPARγ. DISCUSSION AND CONCLUSION: Chrysin is a new inhibitor of foam cell formation that may stimulate cholesterol flow. Up-regulation of the classical PPARγ-LXRα-ABCA1/ABCG1 pathway and down-regulation of SR-A1 and SR-A2 may participate in its suppressive effect on intracellular cholesterol accumulation.