AIM To explore whether plasma vasoactive substances and neutrophil infiltration make different contribution in cerebral ischemia-reperfusion injury and protective effect of triacetylshikimic acid(TSA). METHODSThe rat models of ischemia 90 min and reperfusion 3-48 h were prepared with middle cerebral artery occlusion. TSA 50-200 mg·kg-1 were given (ig) immediately and 60 min again after the onset of ische- mia. Serotonin and thromboxane B2 (TXB2) concentrations in plasma were detected by fluorescence spectrophotometry and radioimmunoassay respectively. Myeloperoxidase(MPO) activity in brain tissue was quantified by chemical analysis. RESULTS At 3-24 h after reperfusion, the concentrations of plasmic serotonin, TXB2, and brain MPO activity increased obviously in a time-dependent manner. At 48 h after reperfusion, the concentrations of serotonin and TXB2 decreased to the same level of sham. Nevertheless, brain MPO activity remained more elevated than the contralateral cortex. At 24 h after reperfusion, TSA (100 and 200 mg·kg-1) was shown to possess the ability to inhibit the increased plasmic serotonin, TXB2 concentrations, and brain MPO activity induced by focal cerebral ischemia-reperfusion. CONCLUSION Vasoactive substances in plasma and MPO activity in brain tissue show different time courses during focal cerebral ischemia-reperfusion and make different contribution to brain damage. TSA is effective to protect the ischemic brain tissue from ischemia-reperfusion injury.

AIM: To investigate the expression of the nephrin in podocyte of the diabetic nephropathy(DN) rats and the mechanism of irbesartan-induced renal protection.METHODS: The DN model was established by a single injection of streptozotocin(STZ),and DN rats were randomly divided into 2 groups: model group and irbesartan treatment group.In addition,the normal rats served as a normal control group. All the rats were received daily gavage respectively for 8 weeks. The urinary protein quality in 24 hours,body weight(BW),kidney weight (KW),KW/BW,glucemia,urea nitrogen,creatinine,total cholesterol, triacylglycerol were detected with correlative methods and the pathological changes of kidney were also detected with optic microscope and transmission electron microscope.The expression of nephrin in podocyte were detected by immunohistochemistry. RESULTS: In DN rats, irbesartan reduced the urinary protein quality in 24 hours (P

4-Hydroxybenzoate (4HBA) is an important chemical compound used for synthesis of liquid crystal. Production of 4HBA from renewable resources is an effective mean to solve problems such as environmental pollution and petroleum shortage. This review briefly introduces the chemical synthesis of 4HBA from oil compounds, and mainly describes the progress in 4HBA biosynthesis from renewable resources by plants and microorganisms. In most intriguing aspect of plant-based synthesis of 4HBA is the appeal of directly synthesizing a chemical from CO2. However, the glucosylation system in plant cells converting 4HBA to glucose conjugates, causing the post treatment a problem. The recombinant microorganisms produce pure 4HBA, but less efficient. A new strain of Microbulbifer has ability to naturally accumulate 4HBA from glucose. Elucidation of the metabolic pathways and regulation systems would improve 4HBA synthesis efficiency.
Alteromonadaceae ; metabolism ; Glucose ; chemistry ; Glycosylation ; Industrial Microbiology ; Metabolic Networks and Pathways ; Parabens ; metabolism ; Plants ; metabolism

OBJECTIVE:To explore the application of topic model in the study of type 2 diabetes treatment plan. METHODS:Clinical data of 650 inpatients with type 2 diabetes in our hospital during Jan. 2012-Jun. 2016 were analyzed retrospectively. The data of clinical diagnosis,lab indexes and clinical drug use were exchanged,summarized and merged by MATLAB R2014a software. Latent Dirichlet allocation and author topic model were adopted to extract the typical topics with topic probability value>0.1,and the topics was described by the complications with cumulative probability value>0.5. RESULTS:A total of 62 complications words,16 abnormal laboratory indexes groups and 20 treatment plans were obtained. A total of 4 typical topics were excavated(cumulative probability values for the first few complications were 0.8786,0.8247,0.8215,0.7536;topic probability value were 0.3364,0.2773,0.2035,0.1176,respectively) and were mainly characterized by peripheral neuropathy,peripheral vascular disease,abnormal lipid metabolism and microvascular lesions;abnormal lab indexes groups met the above characteristics. The complications with high distribution rate included diabetic peripheral neuropathy (0.5787), hypertension (0.3631),atherosclerosis (0.2789),hyperlipidemia (0.4578) and diabetic retinopathy (0.3143);main drugs included Insulin aspart injection,Insulin injection,Methylcobalamin dispersible tablets,etc. CONCLUSIONS:The complications of type 2 diabetes are characterized by peripheral neuropathy,peripheral vascular disease,abnormal lipid metabolism and microvascular lesions. The medication rules with clinical significance can be extracted from the clinical data by topic model.

OBJECTIVE:To excavate the drug use rules of type 2 diabetes,and to provide reference for clinical treatment. METHODS:Clinical data of 807 patients with type 2 diabetes were collected from our hospital during Jan. 2012-Jun. 2017. Complex network and subnetworks for drug compatibility and their visual chromatograms were established by Gephi 0.9.1 software. MATLAB R2014a software was used for topic model mining. The complex network,subnetworks and the overlapping structures of community were analyzed in respects of node distance and degree centrality. Core drugs for type 2 diabetes were screened. RESULTS & CONCLUSIONS:The drug complication complex network established in the study included 119 nodes and 24 412 edges with maximum edge weight of 378. Drugs with high frequency included Insulin aspart injection,Fluvastatin sodium extended release tablets,Metformin hydrochloride tablets,Acarbose tablets,etc. Average distance of network was 1.89,and maximum distance was 4. The distance of 89.90% drugs was 1 or 2,and the links between the various drugs were close. Insulin aspart injection(0.914),Metformin hydrochloride tablets(0.887)and Voglibose tablets(0.866)were core drugs of the network. Totally 4 typical topics were excavated, including peripheral neuropathy, peripheral vascular disease, abnormal lipid metabolism and microangiopathy. Results of subnetwork analysis showed that typical topics were based on hypoglycemic therapy and supplemented by neurotrophic drugs,antihypertensive drugs,lipid regulating drugs and drugs for improvement of retinopathy. Complex network analysis showed that drug use regularity was in line with related guideline of type 2 diabetes and clinical practice. The method has practical significance of data mining in clinic.

Objective To explore the effects of parthenolide (PTL) on high glucose-stimulated cell proliferation, NF-κB activation and monocyte chemoattractant protein-1 (MCP-1) expression in rat mesangial cells (MCs). Methods MCs were cultured in normal glucose (5.6 mmol/L), high glucose (30 mmol/L), or high glucose with PTL. MTT assay was used to detect the cell proliferation. MCP-1 content in the supernatant was measured by ELISA, and the level of IκBα was detected by Western blotting to reflect NF-κB activity. EMSA method was used to measure the activation of NF-κB. Results MC proliferation, MCP-1 expression and NF-κB activation were significantly enhanced and the expression of NF-κB-binding protein IκBα was obviously reduced in cells cultured in high glucose. Application of PTL obviously abolished the effects of high glucose. Conclusion PTL can suppress high glucose-stimulated NF-κB activation and MCP-1 expression in rat MC. These data provide a theoretical basis for the clinical application of PTL in prevention and control of diabetic nephropathy.

Objective To explore the effects of parthenolide (PTL) on high glucose-stimulated cell proliferation, NF-κB activation and monocyte chemoattractant protein-1 (MCP-1) expression in rat mesangial cells (MCs). Methods MCs were cultured in normal glucose (5.6 mmol/L), high glucose (30 mmol/L), or high glucose with PTL. MTT assay was used to detect the cell proliferation. MCP-1 content in the supernatant was measured by ELISA, and the level of IκBα was detected by Western blotting to reflect NF-κB activity. EMSA method was used to measure the activation of NF-κB. Results MC proliferation, MCP-1 expression and NF-κB activation were significantly enhanced and the expression of NF-κB-binding protein IκBα was obviously reduced in cells cultured in high glucose. Application of PTL obviously abolished the effects of high glucose. Conclusion PTL can suppress high glucose-stimulated NF-κB activation and MCP-1 expression in rat MC. These data provide a theoretical basis for the clinical application of PTL in prevention and control of diabetic nephropathy.

OBJECTIVETo explore the effects of parthenolide (PTL) on high glucose-stimulated cell proliferation, NF-κB activation and monocyte chemoattractant protein-1 (MCP-1) expression in rat mesangial cells (MCs).

METHODSMCs were cultured in normal glucose (5.6 mmol/L), high glucose (30 mmol/L), or high glucose with PTL. MTT assay was used to detect the cell proliferation. MCP-1 content in the supernatant was measured by ELISA, and the level of IκBα was detected by Western blotting to reflect NF-κB activity. EMSA method was used to measure the activation of NF-κB.

RESULTSMC proliferation, MCP-1 expression and NF-κB activation were significantly enhanced and the expression of NF-κB-binding protein IκBα was obviously reduced in cells cultured in high glucose. Application of PTL obviously abolished the effects of high glucose.

CONCLUSIONPTL can suppress high glucose-stimulated NF-κB activation and MCP-1 expression in rat MC. These data provide a theoretical basis for the clinical application of PTL in prevention and control of diabetic nephropathy.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; isolation & purification ; pharmacology ; Asteraceae ; chemistry ; Cell Proliferation ; drug effects ; Cells, Cultured ; Chemokine CCL2 ; metabolism ; Dose-Response Relationship, Drug ; Glucose ; administration & dosage ; pharmacology ; I-kappa B Proteins ; metabolism ; Mesangial Cells ; cytology ; metabolism ; NF-KappaB Inhibitor alpha ; NF-kappa B ; antagonists & inhibitors ; metabolism ; Plants, Medicinal ; chemistry ; Rats ; Sesquiterpenes ; isolation & purification ; pharmacology

OBJECTIVETo investigate the effect of the serum of rats fed with Shenkang pill in regulating monocyte chemoattractant protein 1 (MCP-1) expression induced by advanced oxidation protein products (AOPP) in mouse podocyte clone 5 (MPC5) and explore the underlying mechanism.

METHODSMPC5 cultured in vitro were incubated for different time lengths in the presence of different concentrations of serum of rats medicated with Shenkang pill, and the cell proliferation was assessed using MTT assay. In MPC5 treated with AOPP prior to exposure to the rat serum, the changes in the protein expressions of p38MAPK and IκBα were examined with Western blotting, NF-κB p65 nuclear translocation was analyzed with immunofluorescence assay, and MCP-1 expression in the supernatant was determined using ELISA kits.

RESULTSThe medicated rat serum time- and concentration-dependently promoted the proliferation of MPC5, with the optimal serum concentration of 5% and incubation time of 24 h. AOPP significantly increased MCP-1 expression in the cell supernatant in a time-and concentration-dependent manner; pretreatment with SB203580 (a p38 inhibitor) or parthenolide (a NF-κB inhibitor) significantly decreased MCP-1 expression, and treatment with the medicated serum significantly decreased AOPP-induced MCP-1 expression. AOPP concentration-dependently increased the protein expression of P-p38 but decreased that of IκBα. Both the medicated serum and SB203580 increased IκBα protein in AOPP-induced cells, but the effect was more obvious with the medicated serum. The medicated serum also decreased NF-κB p65 nuclear translocation in AOPP-induced MPC5.

CONCLUSIONShenkang pill-medicated serum can decrease AOPP-induced expression of MPC-1 in MPC5 by regulating p38MAPK/NF-κB to mediate its anti-inflammatory effect. This finding provides a new theoretical basis for the application of Shenkang pill to treat diabetic nephropathy.

Advanced Oxidation Protein Products ; pharmacology ; Animals ; Cell Line ; Cell Proliferation ; Chemokine CCL2 ; metabolism ; Down-Regulation ; Drugs, Chinese Herbal ; pharmacology ; I-kappa B Proteins ; metabolism ; Imidazoles ; Mice ; NF-KappaB Inhibitor alpha ; Pyridines ; Rats ; Serum ; chemistry ; Sesquiterpenes ; Transcription Factor RelA ; metabolism ; p38 Mitogen-Activated Protein Kinases ; metabolism

OBJECTIVE: To explore the effect of telmisartan on the expression of metadherin in the kidney of mice with unilateral ureter obstruction. METHODS: Eighteen male C57 mice were randomized into sham-operated group, model group and telmisartan treatment group. In the latter two groups, renal interstitial fibrosis as the result of unilateral ureter obstruction (UUO) was induced by unilateral ureteral ligation with or without telmisartan intervention. Renal pathological changes of the mice were assessed using Masson staining, and immunohistochemistry and Western blotting were used to detect the expression of extracellular matrix proteins and metadherin in the kidney of the mice. In the experiment, cultured mouse renal tubular epithelial cells (mTECs) were stimulated with transforming growth factor-β1 (TGF-β1) and transfected with a siRNA targeting metadherin, and the changes in the expressions of extracellular matrix proteins and metadherin were detected using Western blotting. RESULTS: The expressions of extracellular matrix proteins and metadherin increased significantly in the kidney of mice with UUO ( < 0.05). Intervention with telmisartan significantly lowered the expressions of extracellular matrix proteins and metadherin and alleviated the pathology of renal fibrosis in mice with UUO ( < 0.05). In cultured mTECs, siRNA-mediated knockdown of metadherin obviously reversed TGF-β1-induced increase in the expressions of extracellular matrix proteins and metadherin. CONCLUSIONS Telmisartan can suppress the production of extracellular matrix proteins and the expression of metadhein to attenuate UUO-induced renal fibrosis in mice.
Angiotensin II Type 1 Receptor Blockers ; Animals ; Antihypertensive Agents ; Extracellular Matrix Proteins ; metabolism ; Fibrosis ; Kidney ; drug effects ; metabolism ; pathology ; Male ; Membrane Proteins ; genetics ; metabolism ; Mice ; Mice, Inbred C57BL ; RNA, Small Interfering ; Random Allocation ; Telmisartan ; pharmacology ; Transforming Growth Factor beta1 ; pharmacology ; Ureteral Obstruction ; complications ; metabolism