Accumulated LPS induced by colitis altered the activities of vitamin D-metabolizing hydroxylases and decreased the generation of 25-hydroxyvitamin D.

It is generally accepted that low vitamin D (VD) levels are associated with a high prevalence factor for Inflammatory bowel disease (IBD). IBD patients have observed higher levels of lipopolysaccharide (LPS), ALT, and AST than healthy people. Gut-derived LPS causes inflammatory injury in the liver and kidney. The VD-metabolizing mechanism is involved in the liver and kidney, which means IBD might impact VD metabolism. However, whether IBD affects VD metabolism has not been studied. In vitro LPS resulted in decreased CYP2R1 in liver cells as well as decreased CYP27B1 and increased CYP24A1 in kidney cells, revealing that LPS changed the activities of several hydroxylases. Mice with acute colitis had an increased LPS in serum and liver with mild hepatic injuries, while mice with chronic colitis had a significant elevation of LPS in serum, liver, and kidney with hepatorenal injuries. Thus, the liver hydroxylase for VD metabolism would be the first to be affected in IBD. Consequently, serum 25-hydroxyvitamin D declined dramatically with a significant elevation of 24,25-dihydroxyvitamin D and 1,24,25-trihydroxyvitamin D. Unchanged serum levels of 1,25-dihydroxyvitamin D might be the result of other factors in vivo. In acute colitis, a small dosage (4 IU/day) of cholecalciferol could protect the colon, decrease the serum level of LPS, and finally increase serum 25-hydroxyvitamin D. However, this improvement of cholecalciferol was fading in chronic colitis. These results suggested that VD supplementations for preventing and curing IBD in the clinic should consider hepatorenal hydroxylases and be employed as soon as possible for a better outcome.

LncRNADisease v3.0: an updated database of long non-coding RNA-associated diseases.

Systematic integration of lncRNA-disease associations is of great importance for further understanding their underlying molecular mechanisms and exploring lncRNA-based biomarkers and therapeutics. The database of long non-coding RNA-associated diseases (LncRNADisease) is designed for the above purpose. Here, an updated version (LncRNADisease v3.0) has curated comprehensive lncRNA (including circRNA) and disease associations from the burgeoning literatures. LncRNADisease v3.0 exhibits an over 2-fold increase in experimentally supported associations, with a total of 25440 entries, compared to the last version. Besides, each lncRNA-disease pair is assigned a confidence score based on experimental evidence. Moreover, all associations between lncRNAs/circRNAs and diseases are classified into general associations and causal associations, representing whether lncRNAs or circRNAs can directly lead to the development or progression of corresponding diseases, with 15721 and 9719 entries, respectively. In a case study, we used the data of LncRNADisease v3.0 to calculate the phenotypic similarity between human and mouse lncRNAs. This database will continue to serve as a valuable resource for potential clinical applications related to lncRNAs and circRNAs. LncRNADisease v3.0 is freely available at http://www.rnanut.net/lncrnadisease.

Monotropein inhibits colitis associated cancer through VDR/JAK1/STAT1 regulation of macrophage polarization.

Colorectal cancer (CRC) is a growing concern due to its high morbidity and mortality, and the search for effective and less toxic active substances against inflammatory bowel diseases has been a hot topic in the research and development of drugs against CRC. It is reported that monotropein isolated from the roots of Morinda officinalis, can improve Dextran Sodium Sulfate (DSS)-induced ulcerative colitis in mice, but its therapeutic effects and mechanisms for CRC treatment are still to be investigated. In the present study, we first used molecular docking, BLI, CESTA, and DARTS methods to detest whether monotropein targets VDR proteins. In addition, we used tumor cell conditioned co-culture and four models of macrophage polarisation to investigate the regulation of four macrophage polarisations by monotropein using RT-PCR, IF and western blot. Furthermore, we further validated the target of action of monotropein for the treatment of Azoxymethane (AOM)/DSS induced colitis associated cancer (CAC) using knockout animals. Meanwhile, we further explored the mechanism of action of monotropein in regulating polarisation by detecting JAK/STAT1-related genes and proteins. Molecular docking and biofilm interference techniques showed that monotropein bound to the VDR, and additional results from CESTA and DARTS suggested that VDR proteins are targets of monotropein. Furthermore, in tumor cell conditioned co-cultures or LPS + IFN-γ induced RAW264.7 cells, VDR translocation to the nucleus was reduced, JAK1/STAT1 signaling pathway proteins were up-regulated, and macrophages were polarised towards the M1-type after monotropein intervention. Animal models in which normal VDR or myeloid VDR was knocked out confirmed that JAK1 levels in intestinal tissues were increased after monotropein intervention, macrophages were polarised towards the M1 type, and CAC paracarcinomas were ameliorated. Taken together, the present study concluded that monotropein inhibited colitis-associated cancers through macrophage polarisation regulated by VDR/JAK1/STAT1.

G Protein-Coupled Receptor 40 Agonist LY2922470 Alleviates Ischemic-Stroke-Induced Acute Brain Injury and Functional Alterations in Mice.

Stroke is a major cause of fatalities and disabilities around the world, yet the available treatments for it are still limited. The quest for more efficacious drugs and therapies is still an arduous task. LY2922470 is currently used as a G protein-coupled receptor 40 (GPR40) agonist for the treatment of type 2 diabetes. Previous studies have reported protective effects of other GPR40 activators on the brain; however, it remains unclear whether LY2922470 could be a new stroke therapy and improve the stroke-induced brain damage. Here, we first reveal that the transcriptomic gene signature induced by LY2922470 is highly similar to those induced by some agents being involved in defending from cerebrovascular accidents and transient ischemic attacks, including acetylsalicylic acid, progesterone, estradiol, dipyridamole, and dihydroergotamine. This result thus suggests that LY2922470 could have protective effects against ischemic stroke. As a result, further experiments show that giving the small molecule LY2922470 via oral administration or intraperitoneal injection was seen to have a positive effect on neuroprotection with a reduction in infarct size and an improvement in motor skills in mice. Finally, it was demonstrated that LY2922470 could successfully mitigate the harm to the brain caused by ischemic stroke.

Scientometric and multidimensional contents analysis of PM2.5 concentration prediction.

The foundation for the environmental department to take suitable measures and make a significant contribution towards improving air quality is the precise and dependable prediction of PM2.5 concentration. It is essential to review the development process and hotspots of PM2.5 concentration prediction studies over the past 20 years (2000-2021) comprehensively and quantitatively. This study used detailed bibliometric methods and CiteSpace software to visually analyze the PM2.5 pollution level. The outcomes found that the prediction research phases of PM2.5 can be broadly divided into three phases and enter the rapid growth phase after 2017. Five categories of keywords are clustered, and the forecasting data and forecasting methods are typical cluster representatives. Then, the construction and processing of PM2.5 concentration prediction datasets, the prediction methods and technical processes, and the determination of the prediction spatial-temporal scales are the main content of the analysis. In the future, it is necessary to concentrate on multi-source data fusion for PM2.5 concentration prediction at multiple spatial-temporal scales and focus on technology integration and innovative applications in forecasting models, especially the optimal use of deep machine learning methods to improve prediction accuracy and practical application conversion.

A Novel M6A-Related Genes Signature Can Impact the Immune Status and Predict the Prognosis and Drug Sensitivity of Lung Adenocarcinoma.

Lung adenocarcinoma (LUAD) is a primary cause of cancer-related death around the world and has a poor outcome and high incidence. Treatment options are, however, restricted. One of the most critical factors in cancer and metastasis is the N6-methyladenine (m6A) alteration on RNA. This modification could alter gene expression and even function at numerous levels, such as the stability, translocation and translation of RNA splicing. This study aimed to construct an m6A-related genes signature to accurately predict the prognosis of LUAD patients. From TCGA datasets, the LUAD patient data and m6A-related genes were retrieved. LUAD patients' mutational features and differentially expressed genes (DEGs) were investigated. An univariate and LASSO model with m6A-related genes were constructed for the prediction of outcomes in LUAD. It was possible to develop a prognostic nomogram that could quantitatively predict LUAD patients' overall survival chances at 1, 3, and 5 years. Research into biological processes and cell pathways was carried out using GSEA. This study found six m6A-related DEGs in LUAD patients, and three of these DEGs(HNRNPC, IGFBP3 and IGF2BP1) were linked to the clinical outcomes of LUAD patients. We found that the overall survival rate for all LUAD patients with high-risk subgroup was considerably lower. According to ROC curves, the prognostic signature demonstrated a high degree of accuracy in predicting future outcomes. In addition, we created a novel nomogram achieved great accuracy with this one as well. The researchers also found that the novel signature might favorably modulate the immune response, and high-risk scores samples were more susceptible to numerous chemotherapeutic medicines. Overall, we developed a m6A-related gene prognostic signature that effectively predicted outcomes of LUAD patients and gave an immunological perspective for creating customized therapeutics.

Asperuloside inhibited epithelial-mesenchymal transition in colitis associated cancer via activation of vitamin D receptor.

BACKGROUND: Asperuloside is a natural compound extracted from various herbs with several bioactivities. Its effects on anti-inflammation and anti-tumor indicated that asperuloside might prevent colorectal cancer developing from inflammatory bowel diseases (IBD). But there were few reports about the efficacy and mechanism of asperuloside on improving colorectal cancer. It has been reported that vitamin D receptor (VDR) could regulate the expression of SMAD3. In previous study, asperuloside could significantly improve the expression of VDR and reduced Smad3 mRNA in IEC-6 cell. PURPOSE: The present study was aimed to investigate the potential mechanism of asperuloside on inhibiting epithelial-mesenchymal transition (EMT) in colitis associated cancer. STUDY DESIGN: First, in LPS-injured IEC-6 cell, asperuloside inhibited phosphorylated p65 (p-p65) level, improved VDR expression and reduced Smad3 mRNA. Second, we wonder the relationship between VDR signaling and nucleus factor-kappaB (NF-κB) signaling during asperuloside on reducing Smad3 mRNA. And then, the effect of asperuloside on inhibiting EMT development through VDR/Smad3 was investigated. Finally, we testified the effect of asperuloside on protecting against colitis associated cancer (CAC) by inhibiting EMT development through VDR/Smad3. METHODS: Pyrrolidinedithiocarbamate ammonium (PDTC) was used for established NF-κB-inhibited IEC-6 cell. This cell was applied for investigating the relationship between NF-κB and VDR of asperuloside on inhibiting Smad3. VDR-inhibited cell was established by small interfering RNA (siRNA) of VDR and was employed to investigate the role of VDR for asperuloside on decreasing Smad3. Transforming growth factor ß1 (TGFß1) was used for inducing EMT/fibrosis in IEC-6 cell. TGFß1-stimulated cell was used for testifying the effect of asperuloside on inhibiting EMT development. AOM/DSS-induced CAC was established to investigate the effect of asperuloside on suppressing cancer development. RESULTS: Asperuloside inhibited the level of p-p65 which was up-regulated by LPS. Asperuloside could up-regulate VDR signaling and reduce Smad3 mRNA in NF-κB-knockdown IEC-6 cells. Asperuloside failed to reduce Smad3 mRNA due to VDR knockdown, which implied that asperuloside might down-regulate Smad3 mRNA dependently on activation of VDR signaling and independently on inhibiting NF-κB signaling. Asperuloside exhibited significant prevention of EMT development in TGFß1-induced IEC-6 cell (EMT cell) and mice CAC. Asperuloside reduced the transform of epithelial phenotype into motile mesenchymal phenotype in EMT cell along with decreasing levels of EMT markers by inhibiting Smad3 mRNA via activation of VDR. In mice with CAC, expression of VDR in colon was improved by asperuloside. Symptoms of colitis, tumor number and tumor size were significantly inhibited by asperuloside. Suppressed EMT development was determined by reduced α-SMA expression and decreased mRNAs of several EMT markers. CONCLUSION: Asperuloside might prevent CAC through inhibiting EMT development via regulation of VDR/Smad3 pathway.

Combined Administration of Vitamin D3 and Geniposide Is Less Effective than Single Use of Vitamin D3 or Geniposide in the Treatment of Ulcerative Colitis.

With the increasing incidence of ulcerative colitis (UC) in China, Chinese medicinal herbs or relatively active compounds are widely applied in treating UC. These medicines may be combined with other therapeutic agents such as vitamin D3. Nevertheless, the efficacy of these combinations for UC is unclear. Geniposide is an active component in many Chinese herbal medicines. It could ameliorate dextran sulfate sodium (DSS)-induced colitis in mice. This study was designed to determine the efficacy and mechanism of the single use and combination of geniposide and vitamin D3 on a mouse model of acute colitis. Data showed that a single administration of geniposide (2 mg/kg) or vitamin D3 (4 IU/day) could significantly improve the symptoms of UC and relieve colon damage. Geniposide and vitamin D could significantly decrease the levels of TNF-α and IL-6 in serum and colon, and increase the level of IL-10 in the colon. However, the combined treatment of geniposide (2 mg/kg) and vitamin D3 (4 IU/day) exerted less beneficial effects on UC in mice, indicating by less improvement of UC symptoms, colon damage, and inflammatory infiltration. The combination only downregulated the level of TNF-α in serum and IL-6 in the colon. Our data further demonstrated that geniposide could inhibit the activation of p38 MAPK and then restrict the vitamin D receptor signaling stimulated by vitamin D3. These results implied that the combination of geniposide and vitamin D3 might not be an ideal combined treatment for acute colitis, and the combination of vitamin D supplementary and geniposide (or herbal medicines rich in geniposide) need more evaluation before being applied to treat UC in clinic.

Asperuloside suppressing oxidative stress and inflammation in DSS-induced chronic colitis and RAW 264.7 macrophages via Nrf2/HO-1 and NF-κB pathways.

BACKGROUND: Inflammatory bowel diseases (IBDs), which mainly include Crohn's disease (CD) and ulcerative colitis (UC), are chronic idiopathic inflammatory disease of the gastrointestinal tract for which effective pharmacological treatments are lacking or options are very limited. PURPOSE: Here, we aim to investigate the therapeutic effects of an iridoid glycoside, asperuloside (ASP) on mice experimental chronic colitis induced by dextran sulfate sodium (DSS) and further explore underlying mechanisms in vitro and in vivo. METHODS: LPS-treated RAW 264.7 cells showed inflammation and were assessed for various physiological, morphological and biochemical parameters in the absence or presence of ASP. Chronic colitis was induced by 2% DSS in mice, which were used as an animal model to explore the pharmacodynamics of ASP. We detected p65 and Nrf2 pathway proteins via Western blot and RT-PCR analysis, assessed the cytokines TNF-α and IL-6 via ELISA, tested p65 and Nrf2 nuclear translocation via fluorescence. In addition, the docking affinity of ASP and p65 or Nrf2 proteins in the MOE 2015 software. RESULTS: We found that ASP attenuated weight loss, disease activity index (DAI) and colonic pathological damage in colitis mice and restored the expressions of inflammatory cytokines in the colon. In addition, ASP restored antioxidant capacity in DSS-induced chronic colitis mice and lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Furthermore, ASP suppressed oxidative stress through increasing Nrf2, HO-1 and NQO-1 proteins expressions, and down-regulated nuclear levels of p65 to inhibit DSS-induced colonic oxidative stress and inflammation. Validation of the molecular docking results also indicated that ASP interacts with Nrf2 or p65 proteins. In summary, ASP improved DSS-induced chronic colitis by alleviating inflammation and oxidative stress, activating Nrf2/HO-1 signaling and limiting NF-κB signaling pathway, which may be an effective candidate for the treatment of IBD.

Vitexin prevents colitis-associated carcinogenesis in mice through regulating macrophage polarization.

BACKGROUND: Patients with inflammatory bowel disease are at increased risks of developing ulcerative colitis-associated colorectal cancer (CAC). Vitexin can suppress the proliferation of colorectal carcinoma cells in vitro orin vivo. However, different from colorectal carcinoma, CAC is more consistent with the transformation from inflammation to cancer in clinical chronic IBD patients. Therefore, we aim to investigated that vitexin whether possess benefic effects on CAC mice. PURPOSE: We aimed to determine the beneficial effects of vitexin on CAC mice and reveal its underlying mechanism. METHODS: The mouse CAC model was induced by Azoxymethane and dextran sodium sulfate (AOM/DSS) and CAC mice were treated with vitexin. At the end of this study, inflammatory cytokines of IL-1ß, IL-6, TNF-α, IL-10 as well as nitric oxide (NO) were detected by kits after long-term treatment of vitexin. Pathological changes and macrophage polarization were determined by H&E and immunofluorescence in adjacent noncancerous tissue and carcinomatous tissue respectively of CAC mice. RESULTS: Our results showed that oral administration of vitexin could significantly improve the clinical signs and symptoms of chronic colitis, relieve colon damage, regulate colonic inflammatory cytokines, as well as suppress tumor incidence and tumor burden. Interesting, vitexin caused a significant increase in serum level of NO and a higher content of NO in tumor tissue. In addition, vitexin significantly decreased M1 phenotype macrophages in the adjacent noncancerous tissue, while markedly up-regulated M1 macrophage polarization in the tumor tissue in the colon of CAC mice. CONCLUSION: Vitexin can attenuate chronic colitis-associated carcinogenesis induced by AOM/DSS in mice and its protective effects are partly associated with its alternations in macrophage polarization in the inflammatory and tumor microenvironment .

Monotropein alleviates secondary liver injury in chronic colitis by regulating TLR4/NF-κB signaling and NLRP3 inflammasome.

Recently, it has reported that many inflammatory bowel disease (IBD) patients were contracted secondary liver injury. Monotropein (MON), an iridoid glycoside, is demonstrated to possess protective effects on acute colitis mice due to its anti-inflammatory activities. However, it was remained unknown whether MON could inhibit secondary liver injury caused by IBD. The aim of the present study was to investigate the protective roles and mechanisms of MON on secondary liver injury in chronic colitis mice model. In this study, 2% Dextran sodium sulfate (DSS) was used to induce mice model of chronic colitis. The results showed that MON attenuated DSS-induced hepatic pathological damage, liver parameters, infiltration of macrophages and cytokines levels. Furthermore, we found that MON attenuated liver injury through suppressing the activation of the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway and down-regulating the activity of NLRP3 (NOD-, LRR- and pyrin domain-containing 3) inflammasome. All the data indicated that MON may be an effective therapeutic reagent to attenuate secondary liver injury induced by chronic colitis.

Characteristics of Blood Transfusion During Induction Remission in Children With Acute Lymphoblastic Leukemia: A Single-Center Retrospective Investigation.

OBJECTIVE: To investigate the allogeneic blood transfusion (ABT) characteristics of children with acute lymphoblastic leukemia (ALL) in different risk stratification during vincristine, daunorubicin, L-asparaginase and prednisone (VDLP) induction remission. SUBJECTS AND METHODS: By referring to electronic medical records, the demographic characteristics, diagnosis, test, and treatment information including ABT were collected. According to the risk stratification of the CCCG-ALL-2015 protocol, ABTs between groups were compared, and the differences were statistically analyzed. RESULTS: One hundred sixty-three newly treated children with ALL were enrolled in this study, who received 643.5 U of red blood cells and 377.6 U of platelets (PLTs) during the VDLP. The amount of ABT in the intermediate-risk (IR) group (n=102) was significantly higher than that in the low-risk group (n=61), which were reflected in the red blood cells in the first half of VDLP (P=0.033) and the PLTs in the second half of VDLP (P<0.001). Meanwhile, the PLT counts in the IR group were significantly lower in the same period. The time node was bounded by the minimal residual disease test on the 19th day. CONCLUSIONS: Children in the IR group or with unsatisfactory induction may need more ABTs during the VDLP, and the relatively low PLT counts seem to contribute to this. The results of this study can provide a basis for patient blood management, as well as a reference for studying the long-term effects of ABT on children with ALL.

Protective roles and mechanisms of polysaccharides from Dendrobium officinal on natural aging-induced premature ovarian failure.

This study was designed to investigate the pharmacological effects and mechanisms of polysaccharides from Dendrobium officinal (DOP) on premature ovarian failure (POF) in natural aging mice. Fifteen months old female mice (n  =  28) and young adult female mice (n  =  14, 6 weeks) were used. DOP (70 mg/kg) was administrated to mice by oral gavage for 10 weeks and the protection effects of DOP on ovaries were investigated in vivo. The results showed that DOP reduced body weight, ovary and uterus/body weight parameters to normal level and alleviated ovarian pathological damage. Moreover, DOP could reduce pro-inflammatory cytokines (TNF-α, IL-6) and MDA levels and improve estradiol, SOD, GSH-Px, T-AOC and IL-10 levels in serum. These results suggested that DOP may alleviate the damage caused by aging through the inhibition of the nuclear factor -κB (NF-κB) and p53/Bcl-2-mediate signaling pathways. Moreover, we found that DOP can increase the numbers of mitochondria and endoplasmic reticulum. Moreover, DOP increased the numbers of different stages of follicular cells and improved mitochondrial membrane potential in ovaries. These results indicated that DOP may relieve ovarian damage through the protection of mitochondria in the ovaries. These findings suggest that DOP may be a promising drug for treating POF caused by natural aging in females.

Observation of the influences of diosgenin on aging ovarian reserve and function in a mouse model.

BACKGROUND: The aim of this study was to investigate the impact of diosgenin, an important monomer of sapogenins in yams, on ovarian reserve in a natural aging mice model. STUDY DESIGN: This randomized controlled trial included 60 9-month-old C57 naturally aging female mice. Twenty-one mice were assigned to the dio group and were fed a single dose of diosgenin (200 mg/kg/day) suspended in 0.3% CMC. Twenty mice were assigned to the DHEA group and were fed a single dose of DHEA (1.25 mg/kg/day) suspended in 0.3% CMC. The remaining 20 mice were assigned to the old control group and were fed a single dose of 0.3% CMC. Three months later, the reproductive performance of these female mice was determined by evaluating ovarian follicles and oocyte number and quality in IVF and comparing age-matched and young controls. The impact of NOBOX, GDF9 and BMP15 mRNA expression was also evaluated. RESULTS: Diosgenin improves ovarian reserve in naturally aging mice in terms of increasing the number of primary follicles (P < 0.05) and serum levels of AMH (P < 0.05). CONCLUSIONS: Diosgenin could counteract age-associated ovarian dysfunction by improving the ovarian reserve in a natural aging mice model.

Reference values for kaolin-activated thromboelastography in volunteers of Anhui Province in China.

BACKGROUND: The assessment of the coagulation status using thromboelastography (TEG) in Chinese population has less been reported. This study aimed to establish reliable reference values for kaolin-activated TEG in Chinese volunteers. METHODS: A total of 1681 Chinese adult individuals were recruited for this study. The reference individuals were stratified by gender and age, and the TEG values were measured on the basis of strict quality control. The 95% reference values were determined using nonparametric statistical methods. RESULTS: The sex-related 95% reference values were reaction time (R):4.2-8.7 minutes; clotting time (K): 1.2-3.2 minutes; alpha angle (α): 47.0-72.3 degree; maximum amplitude (MA): 49.1-70.5 mm for males, and R: 3.7-9.0 minutes; K: 1.0-3.2 minutes; α: 48.4-74.4 degree; MA: 46.8-72.4 mm for females. Also, the TEG parameters indicated a relatively more hypercoagulable profile in both female and elder groups. CONCLUSIONS: This study established the reference values for kaolin-activated TEG in the target Chinese population, which might provide a reference for both clinical and laboratory studies.

Ursolic acid inhibits proliferation and reverses drug resistance of ovarian cancer stem cells by downregulating ABCG2 through suppressing the expression of hypoxia-inducible factor-1α in vitro.

Hypoxia in tumors is closely related to drug resistance. It has not been verified whether hypoxia-inducible factor-1α (HIF-1α) or ABCG2 is related to hypoxia-induced resistance. Ursolic acid (UA), when used in combination with cisplatin can significantly increase the sensitivity of ovarian cancer stem cells (CSCs) to cisplatin, but the exact mechanism is unknown. The cell growth inhibitory rate of cisplatin under different conditions was evaluated using Cell Counting Kit-8 (CCK-8) in adherence and sphere cells (SKOV3, A2780, and HEY). The expression of HIF-1α and ABCG2 was tested using quantitative PCR, western blotting, and immuno-fluorescence under different culture conditions and treated with UA. Knockdown of HIF-1α by shRNA and LY294002 was used to inhibit the activity of PI3K/Akt pathway. Ovarian CSCs express stemness-related genes and drug resistance significantly higher than normal adherent cells. Under hypoxic conditions, the ovarian CSCs grew faster and were more drug resistant than under normoxia. UA could inhibit proliferation and reverse the drug resistance of ovarian CSC by suppressing ABCG2 and HIF-1α under different culture conditions. HIF-1α inhibitor YC-1 combined with UA suppressed the stemness genes and ABCG2 under hypoxic condition. The PI3K/Akt signaling pathway activation plays an important functional role in UA-induced downregulation of HIF-1α and reduction of ABCG2. UA inhibits the proliferation and reversal of drug resistance in ovarian CSCs by suppressing the expression of downregulation of HIF-1α and ABCG2.

Sandwich-type electrochemiluminescence immunosensor based on N-(aminobutyl)-N-ethylisoluminol labeling and gold nanoparticle amplification.

A novel electrochemiluminescence (ECL) sandwich-type immunosensor for human immunoglobulin G (hIgG) on a gold nanoparticle modified electrode was developed by using N-(aminobutyl)-N-ethylisoluminol (ABEI) labeling. The primary antibody, goat-anti-human IgG was first immobilized on a gold nanoparticle modified electrode, then the antigen (human IgG) and the ABEI-labeled second antibody was conjugated successively to form a sandwich-type immunocomplex. ECL was carried out with a double-step potential in carbonate buffer solution (CBS) containing 1.5mM H(2)O(2). The ECL intensity increased linearly with the concentration of hIgG over the range 5.0-100 ng/mL. The limit of detection was 1.68 ng/mL (S/N=3). The relative standard deviation was 3.79% at 60 ng/mL (n=9). The present immunosensor is simple and sensitive. It has been successfully applied to the detection of hIgG in human serums.