A comprehensive evaluation of circ_0065214/ miR-188-3p/GPNMB axis in breast cancer.

CircRNAs are involved in multiple aspects during carcinogenesis, including tumorigenesis, vascularization, apoptosis and others. Exploring the role of circRNAs in breast cancer (BC) enables us to understand the development mechanism of BC more comprehensively. Here, we screened out and verified an up-regulated circRNA in BC from GEO data. Quantitative Real-time PCR (qRT-PCR) showed that circ_0065214 had a high expression level in BC patients. Besides, circ_0065214 had good diagnostic value in BC serum, and the area under the diagnostic curve, sensitivity and specificity were 0.78, 0.63 and 0.85, respectively. The combined application of circ_0065214 with CEA and CA-153 can further improve the diagnostic efficiency. The knockdown of circ_0065214 in vivo and in vitro inhibited the proliferation, migration and invasion of BC, but promoted autophagy. At last, dual-luciferase reporter assay and rescue assays revealed that circ_0065214 acted as a decoy to adsorb miR-188-3p, and then relieved the repressive effect of miR-188-3p on its target GPNMB. Our results demonstrated that circ_0065214 regulated the expression of GPNMB by competitively binding to miR-188-3p, thus promoting the proliferation, migration and invasion of breast cancer cells and inhibiting autophagy. These findings provided an original therapeutic strategy for BC.

Enantioselective Alkynylation of 2-Aryl-3H-indol-3-ones via Cooperative Catalysis of Copper/Chiral Phosphoric Acid.

A facile enantioselective alkynylation of cyclic ketimines attached to a neutral functional group utilizing the dual Cu(I)-CPA catalysis is described. The strategy of the alkynylation of 2-aryl-3H-indol-3-one directly to chiral propargylic amines containing indolin-3-one moiety in good yields and enantioselectivities. Moreover, gram-scale synthesis of chiral propargylamines based C2-quaternary indolin-3-ones was performed. The synthetic applications were confirmed by transformations of the products with no decrease in the yield and enantioselectivity.

B(C6F5)3-catalyzed ß-C(sp3)-H alkylation of tertiary amines with 2-aryl-3H-indol-3-ones.

The ß-C-H functionalization of amines is one of the most powerful tools for the synthesis of saturated nitrogen-containing heterocycles in organic synthesis. However, the ß-C-H functionalization of amines via redox-neutral addition with cyclic-ketimines is still unprecedented. Herein, the ß-C-H functionalization of tertiary amines is described, providing the corresponding 1,3-diamines containing the indolin-3-one moiety in high yields via the B(C6F5)3-catalyzed borrowing hydrogen strategy. According to the experimental results, a possible catalytic cycle has been proposed to rationalize the process of this reaction. Notably, the ß-C-H alkylation of amines is external oxidant- and transition-metal-free, which makes a significant contribution to promoting economical chemical synthesis.

Organocatalyzed Enantioselective Aza-Morita-Baylis-Hillman Reaction of Cyclic Ketimine with α,ß-Unsaturated γ-Butyrolactam.

The enantioselective aza-MBH reaction is an efficient strategy for constructing novel carbon-carbon bonds, providing access to multitudinous chiral densely functionalized MBH products. However, the enantioselective aza-MBH reaction of cyclic-ketimines that would generate a versatile synthon is still missing and challenging. Herein, we developed a challenging direct organocatalytic asymmetric aza-MBH reaction involving cyclic ketimines attached to a neutral functional group. Moreover, the α,ß-unsaturated γ-butyrolactam was utilized as a rare nucleophile alkene in this work. The reactions provide enantiomerically enriched 2-alkenyl-2-phenyl-1,2-dihydro-3H-indol-3-ones, bearing with a tetra-substituted stereogenic center. Moreover, this reaction features high α-selectivities, high enantioselectivities (up to 99% ee), and good yields (up to 80%).

Asymmetric aza-Friedel-Crafts Reaction of Cyclic Ketimines with 5-Aminopyrazole Derivatives: Expedient Access to Pyrazole-Based C2-quaternary Indolin-3-Ones.

A chiral phosphoric acid-catalyzed enantioselective aza-Friedel-Crafts reaction of 5-aminopyrazole derivatives with cyclic ketimines attached to a neutral functional group is reported. This protocol allows the formation of pyrazole-based C2-quaternary indolin-3-ones with high enantioselectivities and regioselectivities. Moreover, gram-scale synthesis of the 5-aminopyrazole-based C2-quaternary indolin-3-ones was performed, with no decrease in the yield and enantioselectivity.

Chiral phosphoric acid-catalyzed enantioselective aza-Friedel-Crafts reaction of naphthols and electron-rich phenols with 2-aryl-3H-indol-3-ones.

The enantioselective aza-Friedel-Crafts reaction is one of the most straightforward and efficient strategies for constructing a new carbon-carbon bond bearing quaternary stereocenter in organic synthesis, but the catalytic asymmetric aza-Friedel-Crafts reaction of naphthols/phenols with cyclic-ketimines attached to a neutral functional group remains still relatively unexplored. Herein, a highly enantioselective aza-Friedel-Crafts reaction of cyclic-ketimines and naphthols/phenols has been realized using a chiral phosphoric acid catalyst. A variety of chiral aminonaphthols (chiral indolin-3-ones) containing a quaternary stereocenter at the C2 position were obtained with excellent outcomes (up to 97% yield, 98% ee). Moreover, the synthetic utility of the enantiomerically enriched chiral aminonaphthols was demonstrated in some efficient transformations. According to the experimental results, a possible transition state model has been proposed to rationalize the origin of asymmetric induction.

acNASH index to diagnose nonalcoholic steatohepatitis: a prospective derivation and global validation study.

BACKGROUND: There is an unmet need for non-invasive biomarkers for the diagnosis of nonalcoholic steatohepatitis (NASH) in non-specialized settings. We aimed to develop and validate a non-invasive test for diagnosing NASH in individuals with biopsy-proven nonalcoholic fatty liver disease (NAFLD). METHODS: We developed a non-invasive test named the acNASH index that combines serum creatinine and aspartate aminotransferase levels in a derivation cohort of 390 Chinese NAFLD patients admitted to the hepatology center of the First Affiliated Hospital of Wenzhou Medical University (China) between December 2016 and September 2019 and subsequently validated in five external cohorts of different ethnicities of patients with biopsy-confirmed NAFLD (pooled n=1,089). FINDINGS: The performance of the acNASH index for identifying NASH (defined as NAFLD activity score ≥5 with score of ≥1 for each steatosis, lobular inflammation and ballooning) was good in the derivation cohort with an area under receiver operating characteristics (AUROC) of 0·818 (95%CI 0·777-0·860). A cutoff of acNASH index <4·15 gave a sensitivity (Se) of 91%, a specificity (Sp) of 48% and a negative predictive value (NPV) of 83% for ruling-out NASH, conversely, a cutoff of acNASH >7·73 gave a Sp of 91%, Se of 53% and a positive predictive value (PPV) of 85% for ruling-in NASH. In the pooled validation cohort (n=1,089), the diagnostic performance of the index was also good with AUROC=0·805 (95%CI 0·780-0·830), NPV of 93% for ruling-out NASH and PPV of 73% for ruling-in NASH. Subgroup analyses showed similar performance in patients with diabetes or subjects with normal serum transaminase levels. INTERPRETATION: The acNASH index shows promising utility as a simple non-invasive biomarker for diagnosing NASH among adults with biopsy-proven NAFLD of different ethnicities from different countries. FUNDING: The National Natural Science Foundation of China (82070588), High Level Creative Talents from Department of Public Health in Zhejiang Province (S2032102600032) and Project of New Century 551 Talent Nurturing in Wenzhou.

Individualized Polygenic Risk Score Identifies NASH in the Eastern Asia Region: A Derivation and Validation Study.

INTRODUCTION: Strong evidence indicates that multiple genetic and environmental risk factors play a role in the pathogenesis of nonalcoholic steatohepatitis (NASH). We aimed to develop and validate a novel nomogram, incorporating both genetic and clinical factors, for predicting NASH. METHODS: A total of 1,070 Asian individuals with biopsy-confirmed nonalcoholic fatty liver disease (NAFLD) from 2 countries (China and South Korea) were recruited. The histological spectrum of NAFLD was classified according to the NASH clinical research network scoring system. The nomogram was developed in the Chinese training set (n = 402), and then, it was validated in both the Chinese internal validation set (n = 136) and the external Korean validation cohort (n = 532), respectively. RESULTS: Sex, metabolic syndrome, insulin resistance, serum aspartate aminotransferase levels, and PNPLA3 (rs738409) and HSD17B13 (rs72613567) genetic variants were strongly associated with NASH. Based on their regression coefficients, we developed a nomogram with good discriminatory ability (area under the receiver operating characteristic curve: 0.81, 95% confidence interval [CI] 0.77-0.85) and good calibration (Hosmer-Lemeshow test, P = 0.794) for identifying NASH. In the 2 validation cohorts, the nomogram showed high area under the receiver operating characteristic curves (internal validation set: 0.80, 95% CI 0.72-0.88; external validation cohort: 0.76, 95% CI 0.72-0.80) and good calibration. DISCUSSION: Our newly developed and externally validated nomogram, incorporating both genetic and clinical risk factors, may be conveniently used to predict NASH. Further validation studies in other ethnic groups are warranted to confirm its diagnostic utility to identify NASH, among patients with biopsy-proven NAFLD.

Combined and sequential non-invasive approach to diagnosing non-alcoholic steatohepatitis in patients with non-alcoholic fatty liver disease and persistently normal alanine aminotransferase levels.

BACKGROUND AND AIM: Imaging-confirmed non-alcoholic fatty liver disease (NAFLD) with normal alanine aminotransferase (nALT) levels is infrequently the subject for further evaluation. Early diagnosis of non-alcoholic steatohepatitis (NASH) is needed to prevent disease progression. Thus, we tested the clinical utility of serum Golgi protein 73 (GP73) levels and developed a new non-invasive score to diagnose NASH in patients with biopsy-confirmed NAFLD and persistent nALT levels. METHODS: Serum GP73 and cytokeratin-18 M30 fragments (CK18-M30) levels were measured in 345 patients with biopsy-proven NAFLD. We developed a new score, named G-NASH model (by incorporating serum GP73), and combined it with serum CK18-M30 measurement in a sequential non-invasive approach to accurately identify NASH among patients with NAFLD and persistent nALT levels. RESULTS: 105 (30.4%) patients had persistent nALT, 53 of whom had histologically confirmed NASH. Both serum GP73 and CK18-M30 levels alone had poor diagnostic accuracy in identifying NASH (55.2% and 51.6%, respectively) in these patients. Conversely, G-NASH model performed better than other established non-invasive scoring systems, and by using our proposed sequential non-invasive approach 82.9% of patients with NASH were correctly identified. CONCLUSIONS: NASH is highly prevalent in patients with NAFLD with persistent nALT levels. The G-NASH model accurately identifies NASH in this patient group.

Data Mining the Prognostic Biomarkers: miRNAs Targeting the Chemotherapeutic Agent 5-Fluorouracil in Colon Cancer.

BACKGROUND: Colon cancer is one of the most common and has the highest mortality rate in the world. MicroRNAs (miRNAs) as potential biomarkers play crucial roles in diagnosis, prognosis, and drug-response prediction of colon cancer. METHODS: In this study, we collected miRNA expression data from the Broad GDAC Firehose and screened specific miRNA-gene pairs after treatment with 5-fluorouracil treatment and used COAD analysis to study the association of miRNAs and inhibitor of the inhibitory genes. Potential drug-related miRNAs were further extracted via hypergeometric testing. RESULTS: The results showed that 13,651 miRNA-gene pairs were retrieved, including 242 miRNAs and 5,179 genes. The association between miRNAs and the inhibitor of inhibitory genes DPYD, TYMS, UNG was indicated. We further extracted 4 potential drug-related miRNAs, including hsa-mir-551a, hsa-mir-144, hsa-mir-519b, hsa-mir-506. The miRNA-gene pairs associated with 5-fluorouracil exhibit better prognosis in patients with CRC. CONCLUSIONS: We expected that up-regulation of hsa-mir-551a, hsa-mir-144, and hsa-mir-506 and down-regulation of hsa-mir-519b would exhibit better prognosis. The findings would underpin the fundamental hypothesis of mi-RNAs being prognostic signal biomarkers in therapy of 5-fluorouracil in CRC.

Effect of PNPLA3 polymorphism on diagnostic performance of various noninvasive markers for diagnosing and staging nonalcoholic fatty liver disease.

BACKGROUND AND AIM: Patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M (rs738409) genotype influences clinical/biochemical characteristics in patients with nonalcoholic fatty liver disease (NAFLD), but whether PNPLA3-I148M (rs738409) genotype also influences the diagnostic performance of noninvasive diagnostic tests for NAFLD is uncertain. Our aim was to investigate the differences in diagnostic performance of noninvasive diagnostic tests for NAFLD according to PNPLA3-I148M (rs738409) genotype. METHODS: Fifty-eight healthy controls and 349 patients with biopsy-proven NAFLD were included. Areas under the receiver operating characteristic curve (AUROCs) were calculated to predict hepatic steatosis (fatty liver index and hepatic steatosis index), nonalcoholic steatohepatitis (cytokeratin-18 M30 and M65), and significant fibrosis (≥F2 fibrosis) (fibrosis-4 and BARD), stratifying by rs738409 genotypes (CC and CG + GG groups). RESULTS: Fatty liver index and hepatic steatosis index showed good diagnostic performance for diagnosing steatosis only in the CG + GG group with AUROCs ranging from 0.819 to 0.832. Cytokeratin-18 M30 (AUROC = 0.688) and M65 (AUROC = 0.678) had suboptimal performance for diagnosing nonalcoholic steatohepatitis in the CG + GG group, whereas both had good performance (AUROC = 0.814 and 0.813, respectively) in the CC group. BARD score showed good performance in the CG + GG group compared with the CC group (AUROC = 0.805 and 0.532, respectively). Fibrosis-4 had suboptimal performance in the CG + GG group and good performance in the CC group (AUROC = 0.662 and 0.801, respectively). CONCLUSIONS: Diagnostic performance of noninvasive tests for NAFLD varied markedly according to PNPLA3 genotypes. Clinicians should be aware that PNPLA3 genotype limits the clinical utility of noninvasive diagnostic tests for diagnosing NAFLD.

FGL2 regulates IKK/NF-κB signaling in intestinal epithelial cells and lamina propria dendritic cells to attenuate dextran sulfate sodium-induced colitis.

Inflammatory bowel disease (IBD) is an autoimmune disease characterized by an abnormal immune response. Fibrinogen-like protein 2 (FGL2) is known to have immunoregulatory and anti-inflammatory activity. The level of FGL2 is elevated in patients with IBD; however, its comprehensive function in IBD is almost unknown. In our study, we explored the effect of FGL2 on dextran sulfate sodium (DSS)-induced colitis in mice and on NF-κB signaling in intestinal epithelial cells (IECs) and lamina propria dendritic cells (LPDCs). We founded that FGL2-/- mice in the colitis model showed more severe colitis manifestations than WT mice did, including weight loss, disease activity index (DAI), and colon histological scores. FGL2-/- mice treated with DSS produced more proinflammatory cytokines (IL-1ß, IL-6, TNF-α) in serum than WT mice did and demonstrated upregulated expression of TNF-α and inflammatory marker enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (Cox-2) in the colon tissue. Our data suggested that DSS-treated FGL2-/- mice showed stronger activation of NF-κB signaling, especially in IECs. Next, we demonstrated that recombinant FGL2 (rFGL2) inhibited the production of proinflammatory cytokines and the expression of inflammatory marker enzymes by downregulating the NF-κB signaling in HT-29 cells. Finally, we discovered that LPDCs from the colon of DSS-treated FGL2-/- mice showed significantly upregulated expression of surface maturation co-stimulatory molecules, including CD80, CD86, CD40, and MHC class II molecules compared with that in WT mice. In addition, LPDCs in FGL2-/- treated with DSS exhibited excessive NF-κB activity and the administration of rFGL2 to FGL2-/- mice could rescue the aggravated results of FGL2-/- mice. Taken together, our findings demonstrated that FGL2 might be a target for further therapy of IBD.

Individualized risk prediction of significant fibrosis in non-alcoholic fatty liver disease using a novel nomogram.

Background: Fibrosis is deemed to be a pivotal determinant of the long-term prognosis in non-alcoholic fatty liver disease (NAFLD). Objective: We aimed to develop a novel nomogram-based non-invasive model to accurately predict significant fibrosis in patients with NAFLD. Methods: We designed a prospective cohort study including 207 patients with biopsy-proven NAFLD. Detailed anthropometric and fibrosis-related laboratory parameters were collected. A nomogram was established based on variables that were independently associated with significant fibrosis identified by the logistic regression model. Then it was compared with aspartate aminotransferase-to-platelet ratio index (APRI), NAFLD fibrosis score (NFS), FIB-4 and BARD score. Diagnostic accuracy was assessed according to area under the receiver operator characteristic curve (AUROC), sensitivity, specificity, positive and negative predictive values, and decision curve analysis. Results: Variables included in the nomogram were: waist-to-height ratio, hyaluronic acid, procollagen-III-peptide, chitinase-3-like protein 1, and cytokeratine-18 neoepitope M65. The discrimination ability of the nomogram (AUROC = 0.829, 95%CI 0.755-0.904) was significantly superior to APRI (AUROC = 0.670, 95%CI 0.563-0.777), NFS (AUROC = 0.601, 95%CI 0.480-0.722), FIB-4 (AUROC = 0.624, 95%CI 0.511-0.736) and BARD (AUROC = 0.579, 95%CI 0.459-0.699) for significant fibrosis (all p < 0.05). The nomogram showed a larger net benefit to aid in decision-making as to whether biopsy is required. Conclusions: This novel nomogram was more accurate, and achieved higher net benefit than APRI, NFS, FIB-4 and BARD to detect significant fibrosis. It can be useful as a non-invasive method to screen ≥F2 fibrosis in the overall population with NAFLD.

Paeoniflorin Prevents Intestinal Barrier Disruption and Inhibits Lipopolysaccharide (LPS)-Induced Inflammation in Caco-2 Cell Monolayers.

Inflammatory bowel disease (IBD) in humans is closely related to bacterial infection and the disruption of the intestinal barrier. Paeoniflorin (PF), a bioactive compound from Paeonia lactiflora Pallas plants, exerts a potential effect of anti-inflammatory reported in various researches. However, the effect of PF on intestinal barrier function and its related mechanisms has not been identified. Here, we investigate the PF potential anti-inflammatory effect on lipopolysaccharide (LPS)-stimulated human Caco-2 cell monolayers and explore its underlying key molecular mechanism. In this context, PF significantly increased TEER value, decreased intestinal epithelium FITC-dextran flux permeability, and restored the expressions of occludin, ZO-1, and claudin5 in LPS-induced Caco-2 cell. In vitro, treatment of PF significantly inhibited LPS-induced expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9). In addition, we found that PF suppressed nuclear factor kappa B (NF-κB) signaling via activating the Nrf2/HO-1 signaling pathways in ILPS-stimulated Caco-2 cells. Our findings indicate that PF has an inhibitory effect on endothelial injury. Our findings suggested that PF has an anti-inflammatory effect in ILPS-stimulated Caco-2 cells, which might be a potential therapeutic agent against IBD and intestinal inflammation.

Nomogram predicting cancer-specific mortality in patients with esophageal adenocarcinoma: a competing risk analysis.

BACKGROUND: Many factors are reported to be related to the prognosis of patients with esophageal adenocarcinoma (EAC), but few reliable and straightforward tools for clinicians to estimate individual mortalities have been developed. This study aimed to evaluate the probability of cancer-specific death for patients with EAC and to build nomograms for predicting long-term cancer-specific mortality and overall mortality for EAC patients. METHODS: Between 2004 and 2013, a total of 20,623 patients were identified from the surveillance, epidemiology, and end results (SEER) database and randomly divided into training (N=14,436) and validation (N=6,187) cohorts. The cumulative incidence functions (CIFs) of EAC-specific death and other causes were evaluated at the 1st, 3rd, and 5th year after diagnosis. We integrated the significant prognostic factors to construct nomograms and subjected them to internal and external validation. RESULTS: The CIFs of EAC-specific survival at 1, 3, and 5 years after diagnosis were 60.9%, 37.1%, and 31.3%, respectively. Predictors for cancer-specific mortality for EAC comprised tumor grade, tumor extension, the involvement of lymph nodes, distant metastasis, surgery of primary site, insurance recode, and marital status. For overall mortality, it also included the predictor of age at diagnosis. The nomograms were well-calibrated and had good discriminative ability with concordance indexes (c-indexes) of 0.733, 0.728, and 0.728 for 1-, 3- and 5-year prognosis prediction of EAC-specific mortality respectively, and 0.726, 0.720, 0.719 for 1-, 3-, and 5-year prognosis prediction of overall mortality respectively. CONCLUSIONS: We proposed and validated the effective and convenient nomograms to predict cancer-specific mortality and the overall mortality for patients with EAC, which only require the basic information available in clinical practice.

Lifestyle interventions for patients with nonalcoholic fatty liver disease: a network meta-analysis.

Lifestyle interventions remain the first-line therapy for nonalcoholic fatty liver disease (NAFLD). This study aims to evaluate the individual impact of exercise and/or dietary interventions on the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), homeostasis model of assessment for insulin resistance index (HOMA-IR), and BMI. Randomized-controlled trials from patients diagnosed with NAFLD were included in the meta-analysis if they reported the associations between changes in ALT, AST, HOMA-IR, or BMI and types of lifestyle interventions. Nineteen eligible articles were included. Compared with observation, aerobic exercise training (AEx) plus diet [weighted mean difference (WMD)=-25.85; 95% confidence interval (CI): -43.90 to -7.80], AEx (WMD=-8.81; 95% CI: -20.22-2.60) and diet (WMD=-11.85; 95% CI: -47.65-24.95) showed significant efficacy in the improvement of ALT levels. Also AST, AEx plus diet showed a significant tendency to reduce AST levels. In addition, progressive resistance training (WMD=-1.70; 95% CI: -5.61-2.21) led to the most obvious reduction in HOMA-IR compared with observation, but appeared to show no significant effect in BMI (WMD=0.27; 95% CI: -0.48 to -0.07), whereas AEx plus diet (WMD=-0.96; 95% CI: -1.54 to -0.38 and WMD=-1.96; 95% CI: -2.79 to -1.12) showed great efficacy both in the improvement of HOMA-IR and BMI. AEx plus diet is the most effective intervention in the management of patients with NAFLD. Dietary intervention may be more effective in the improvements of aminotransferases, whereas exercise shows superiority in improving insulin sensitivity and reduction of BMI.

Tangshen formula improves inflammation in renal tissue of diabetic nephropathy through SIRT1/NF-κB pathway.

The present study investigated the mechanism underlying the anti-inflammatory effects of Tangshen formula (TS) in Sprague Dawley (SD) rats with diabetic nephropathy (DN). A rat model of DN was established by intraperitoneal injection of 1% (40 mg/kg) streptozotocin and administration of a high fat and glucose diet. Subsequently, SD rats were randomly divided into six groups (n=8): A DN group, a valsartan group, a high-dose TS group, a middle-dose TS group, a low-dose TS group and a control group with normal SD rats. Once rats received their allocated treatment for 12 weeks, body weight and kidney weight were recorded, and fasting blood glucose, ratio of urinary protein, ß2-MG and creatinine clearance rate were determined. Furthermore, hemodynamic indices, including plasma viscosity and whole blood reduction viscosity were detected. Immunohistochemistry was used to detect the infiltration of macrophages in the kidneys of rats. Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to investigate the activation; mRNA and protein expression levels of monocyte chemoattractant protein-1 (MCP-1), macrophage migration inhibitory factor (MIF), nuclear factor-κB (NF-κB) and sirtuin-1 (SIRT1) in each group. In comparison with the DN group, each biochemical indicator of rats in the high-dose TS group was significantly decreased (P<0.05). Blood viscosity in each treatment group was significantly decreased when compared with the DN group (P<0.01). Hematoxylin and eosin staining indicated that the infiltration of macrophages was significantly decreased in the high-dose TS group when compared with the DN group (P<0.01). mRNA and protein expression levels of MCP-1 and MIF in the high-dose TS group were significantly decreased when compared with the DN group (P<0.05). In the treatment groups, SITR1 mRNA expression levels were significantly increased, whereas the mRNA expression levels of NF-κB were significantly decreased (P<0.01). Western blotting results indicated a significant decrease in the protein expression levels of acetylated NF-κB in the treatment groups when compared with the DN group (P<0.01) and the propensity of protein expression of the other inflammatory factors were consistent with the mRNA findings. The results of the high-dose TS group were similar to those of the valsartan group. The present study indicates that TS was able to activate SITR1, which lead to NF-κB deacetylation, thus reducing the release of inflammatory factors and decreasing the severity of diabetic nephropathy.

[Study on combined effects of chemical components for different flowers blossoming degree of yellow medicinal Chrysanthemum morifolium from Zhejiang].

The ingredients of five kinds of Zhejiang's yellow Chrysanthemum morifolium with different flower blossoming stages were comparatively analyzed. Polysaccharides, total flavonoids, volatile oil, alcohol extract, water extract, chlorogenic acid, luteolin, 3,5-O-dicaffeoyl quinic acid and fingerprint of the ingredient were determined as indicators. During flower blossoming stages, the ingredients of Ch. morifolium showed a big difference with a certain variation. At the early opening stage, the contents of flavonoids and volatile oil were higher, the content of chlorogenic acid, luteolin, 3,5-O-dicaffeoyl quinic acid were higher in the middle of the flowers 50% -80% fowers blossoming degree is the optimal time for harvest.

Ethyl 7-methyl-2-((1-methyl-1H-pyrrol-2-yl)methyl-ene)-3-oxo-5-phenyl-3,5-dihydro-2H-thia-zolo[3,2-a]pyrimidine-6-carboxyl-ate.

In the structure of the title compound, C(22)H(21)N(3)O(3)S, the thia-zole ring forms dihedral angles of 88.83 (7) and 9.39 (9)°, respectively, with the benzene and pyrrole rings. The dihydro-pyrimidine ring adopts a flattened boat conformation. The olefinic double bond is in a Z conformation.