Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma Mitigate Renal Fibrosis： A Review / 中国实验方剂学杂志

Renal fibrosis， the final pathological outcome of end-stage chronic kidney diseases， is associated with inflammation， oxidative stress， epithelial-mesenchymal transdifferentiation （EMT）， and extracellular matrix deposition. It belongs to the categories of edema， ischuria， anuria and vomiting， and consumptive disease in traditional Chinese medicine （TCM）， with the key pathogenesis of Qi deficiency and blood stasis and the primary treatment principle of replenishing Qi and activating blood. Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma mainly contains astragalosides， polysaccharides， calycosin， salvianolic acid， and tanshinone， with the effect of tonifying Qi and activating blood. Studies have shown that this herb pair and its active components can delay the progress of renal fibrosis by regulating multiple signaling pathways. With consideration to the pathogenesis of Qi deficiency and blood stasis， this article reviews the research progress in the mitigation of renal fibrosis by Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma from the aspects of protecting glomerular filtration barrier， inhibiting EMT and mesangial cell proliferation， improving renal hemodynamics， and protecting renal function. Furthermore， the mechanisms were summarized. Specifically， Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma and its effective components can improve mitochondrial function and fatty acid metabolism， alleviate endoplasmic reticulum stress and autophagy disorders， and inhibit immune inflammation and oxidative stress by regulating nuclear factor E2-related factor 2 （Nrf2）/PTEN-induced kinase 1 （Pink1）， Nrf2/antioxidant response element （ARE）， tumor necrosis factor-α （TNF-α）/nuclear transcription factor-κB （NF-κB）， miR-21/Smad7/transforming growth factor beta （TGF-β）， Wnt/β-catenin， long non-coding RNA-taurine up-regulated gene 1 （lncRNA-TUG1）/tumor necrosis factor receptor-associated factor 5 （TRAF5）， Ras-related C3 botulinum toxin substrate 1 （Rac1）/cell division cycle protein 42 （CDC42）， Ras homolog （Rho）/Rho-associated coiled-coil containing protein kinase （ROCK）， phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）， Janus kinase （JAK）/signal transducer and activator of transcription （STAT）， peroxisome proliferator-activated receptor α （PPARα）/peroxisome proliferator-activated receptor γ coactivator l alpha （PGC-1α）， and p38 mitogen-activated protein kinase （p38 MAPK）. This review aims to provide references for the relevant research， give play to the role of Astragali Radix-Salviae Miltiorrhizae Radix et Rhizoma， and provide guidance for the clinical treatment of renal fibrosis.

Analysis of Mechanism of Yishen Huashi Granules for Improving Diabetic Nephropathy Based on Metabonomics and Transcriptomics / 中国实验方剂学杂志

ObjectiveIn this study， based on ultra-high performance liquid chromatography-mass spectrometry（UHPLC-MS/MS） and high-throughput transcriptome sequencing technology（RNA-seq）， we investigated the mechanism of Yishen Huashi granules in regulating serum metabolites and renal messenger ribonucleic acid（mRNA） expression to improve diabetic kidney disease（DKD）. MethodSD rats were randomly divided into normal group ， model group and Yishen Huashi granules group， with 8 rats in each group. The rat model of DKD was established by intraperitoneal injection of streptozotocin. Yishen Huashi granules group was given 5.54 g·kg-1·d-1 of Yishen Huashi granules by gavage， and the normal group and the model group were given the same amount of normal saline for 6 weeks. During the experiment， the body weight and blood glucose of rats were monitored， and the rats were anesthetized 24 hours after the last administration， blood was collected from the inferior vena cava， serum was separated， and renal function， blood lipid， and inflammatory indicators were detected. Kidney tissue of rats was fixed in neutral paraformaldehyde， and stained with hematoxylin-eosin（HE）， Masson and periodic acid-Schiff（PAS） to observe the renal pathological changes. UHPLC-MS/MS and RNA-seq were used to identify the changes of serum metabolism and the differences of renal mRNA expression， and real time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to detect the differential mRNA and protein expression in renal tissue to explore the common expression mechanism. ResultCompared with the normal group， rats in the model group showed a decrease in body weight， a significant increase in blood glucose， urinary microalbumin to urinary creatinine ratio（UACR）， blood urea nitrogen（BUN）， cystatin-C（Cys-C）， β2-microglobulin（β2-MG）， interleukin-6（IL-6）， triglyceride（TG） and total cholesterol（TC）， and a significant decrease in total superoxide dismutase（T-SOD）（P<0.01）. After the intervention of Yishen Huashi granules， all the indexes were improved to different degrees in rats（P<0.05， P<0.01）. Compared with the normal group， the model group showed renal mesangial stromal hyperplasia， fibrous tissue hyperplasia and tubular vacuolar degeneration. Compared with the model group， the renal pathology of rats in Yishen Huashi granules group was improved to a certain extent. A total of 14 target metabolites and 96 target mRNAs were identified， the target metabolites were mainly enriched in 20 metabolic pathways， including sphingolipid metabolism， glycerophospholipid metabolism， and the biosynthesis of phenylalanine， tyrosine and tryptophan. The target mRNAs were enriched to obtain a total of 21 differential mRNAs involved in the TOP20 pathways closely related to glycolipid metabolism. A total of 6 pathways， glycerophospholipid metabolism， arachidonic acid metabolism， purine metabolism， primary bile acid biosynthesis， ascorbic acid and uronic acid metabolism， and galactose metabolism， were enriched by serum differential metabolites and renal differential mRNAs， among them， there were 7 differential metabolites such as phosphatidylethanolamine（PE） and 7 differential mRNAs such as recombinant adenylate cyclase 3（ADCY3）. Seven differential metabolites had high predictive accuracy as verified by receiver operating characteristic（ROC） curve， and the results of Real-time PCR and Western blot were highly consistent with the sequencing results. ConclusionYishen Huashi granules can reduce UACR， BUN and other biochemical indexes， correct the disorder of glucose and lipid metabolism， and improve renal function of DKD rats. And its mechanism may be related to the regulation of the level of PE and other blood metabolites， and expression of Phospho1 and other mRNAs in the kidney， of which six pathways， including glycerophospholipid metabolism， may play an important role.

Determination of Immunoglobulin Content in Humoral Immunity Evaluation of Biomedical Material Products by Cytometric Beads Array / 中国医疗器械杂志

In this study, cytometric beads array(CBA) was used to determine the immunoglobulin content in humoral immunity evaluation of biomedical materials. The bovine-derived acellular dermal matrix was selected as a test sample and implanted into Balb/C mice subcutaneously to 4 weeks according to the high, medium and low dose groups. Four weeks later, IgG1, IgG2a, IgG2b, IgG3, IgA, and IgM were measured by CBA. The data of the test group and the control group were analyzed statistically. The results showed that compared with the negative control group, there was no significant difference in the IgG3, IgA content in the positive control group, while the IgG1, IgG2a, IgG2b, and IgM contents were significantly higher than the negative control group; no significant differences were seen in the sample groups. The results show that the method is suitable for analysis of immunoglobulin content in humoral immunity evaluation of biomedical materials.

Comparative Genome Analysis of Scutellaria baicalensis and Scutellaria barbata Reveals the Evolution of Active Flavonoid Biosynthesis / 基因组蛋白质组与生物信息学报·英文版

Scutellaria baicalensis (S. baicalensis) and Scutellaria barbata (S. barbata) are common medicinal plants of the Lamiaceae family. Both produce specific flavonoid compounds, including baicalein, scutellarein, norwogonin, and wogonin, as well as their glycosides, which exhibit antioxidant and antitumor activities. Here, we report chromosome-level genome assemblies of S. baicalensis and S. barbata with quantitative chromosomal variation (2n = 18 and 2n = 26, respectively). The divergence of S. baicalensis and S. barbata occurred far earlier than previously reported, and a whole-genome duplication (WGD) event was identified. The insertion of long terminal repeat elements after speciation might be responsible for the observed chromosomal expansion and rearrangement. Comparative genome analysis of the congeneric species revealed the species-specific evolution of chrysin and apigenin biosynthetic genes, such as the S. baicalensis-specific tandem duplication of genes encoding phenylalanine ammonia lyase and chalcone synthase, and the S. barbata-specific duplication of genes encoding 4-CoA ligase. In addition, the paralogous duplication, colinearity, and expression diversity of CYP82D subfamily members revealed the functional divergence of genes encoding flavone hydroxylase between S. baicalensis and S. barbata. Analyzing these Scutellaria genomes reveals the common and species-specific evolution of flavone biosynthetic genes. Thus, these findings would facilitate the development of molecular breeding and studies of biosynthesis and regulation of bioactive compounds.

Microbial Transformation of Gracillin by Penicillium Lilacinum ACCC 31890 / 中国药师

Objective: To study the biotransformation of gracillin by Penicillium lilacinumACC 31890,to isolate and to identify the structures of metabolites and investigate the pharmacological activities.Methods: The conversion products were isolated and purified by silica gel column chromatography and semi-preparative reversed phase liquid chromatography.Their structures were identified by MS and NMR, and the anti-inflammatory activity of the conversion products was investigated as well.Results: Three metabolites were isolated and purified, and identified as 5R-spirost-5-ene-3-ol-O-β-D-Glucopyranoside-(1→3)-β-D-glucopyranosyl (1), trillin (2) and diosgenin (3) with the conversion rate of 1%, 1% and 45%, respectively.In vitro study showed that the three products showed certain degrees of activity to inhibit the production of NO, IL-6 and MCP-1 in LPS-primed RAW264.7 macrophages.Moreover, the anti-inflammatory activity of the bioconversion products increased along with the hydrolyzation of carbohydrate chain.Diosgenin, the final product, showed the strongest anti-inflammatory activity among the three products.Conclusion: The biotransformation of gracillin by Penicillium lilacinum has a high productivity of diosgenin.The amount of glycosyls has notable influence on the anti-inflammatory activity of steroid sapoinin.

Value of heart-type fatty acid-binding protein in predicting prognosis of patients with sepsis / 中华急诊医学杂志

Objective To study the predictive value of heart-type fatty acid-binding protein (H-FABP) in the improvement of survival rate in patients with severe sepsis.Methods There was a prospective case-control study in 50 patients with severe sepsis from October 2014 to October 2015.According to the international guidelines for severe sepsis and septic shock set in 2012,all patients were divided into sepsis group (n =16),severe sepsis group (n =14) and septic shock group (n =20),and these patients were further divided into to survival group (n =22) and non-survival group (n =28) as per patients surviving within 28 days.Gender,age,ethnic,and Acute Physiology and Chronic Health Evaluation score (APACHE Ⅱ) were recorded.H-FABP,B-type natriuretic peptide (BNP),creatine kinase (CK),creatine kinase isoenzyme (CK-MB),and troponin-T (cTn-T) were determined within 6 hours after admission.The statistical software SPSS21.0 was used to do t test,test,and the receiver operating characteristic curve for comparison between groups.Results H-FABP in septic shock group was higher than severe sepsis group and sepsis group (P ＜ 0.01).The 28-day mortality of septic group (80％) and severe sepsis group (71.4％) were higher than sepsis group (12.5％) (P ＜ 0.01).Non-survival' s H-FABP,BNP,cTn-T,CK,CKMB was higher than survivals (P ＜ 0.05).Through the ROC of H-FABP (AUC=0.748,P=0.003,95％ C I:0.605-0.890) and BNP (AUC =0.714,P=0.010,95％ CI:0.573-0.856),it shows that H-FABP is better than BNP.when H-FABP take 9.902 ng/mL,the sensitivity of 82.1％,specificity of 63.6％.H-FABP,BNP has a certain value in 28-day mortality prediction.Conclusions Sepsis shock has significantly higher 28-day mortality than sepsis and severe sepsis.Compared with BNP,H-FABP has greater predictive value in sepsis patients,it will increase along with the aggravation of the disease;it can also predict 28-day mortality.