Meta-analysis and GRADE evaluation of Guanxinning Tablets in treatment of angina pectoris of coronary heart disease / 中国中药杂志

This study aims to evaluate the efficacy and safety of Guanxinning Tablets+conventional western medicine in the treatment of angina pectoris of coronary heart disease, and provide evidence-based references for clinical medication. Retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, randomized controlled trial(RCT) about Guanxinning Tablets for the treatment of angina pectoris of coronary heart disease from the inception to April 2022 were collected. After literature screening and data extraction, the bias risk assessment tool recommended by the Cochrane evaluation manual handbook 5.1.0 was used to evaluate the quality of the included literature, and RevMan 5.3 and Stata 14.0 were used for Meta-analysis. Eighteen RCTs were finally included, involving 2 281 patients. Meta-analysis showed that, compared with conventional western medicine treatment alone, Guanxinning Tablets+conventional western medicine significantly improved angina pectoris efficacy(RR=1.33, 95%CI[1.13, 1.57], P=0.000 8), electrocardiogram efficacy(RR=1.32, 95%CI[1.02, 1.71], P=0.03), and exercise duration(MD=59.53, 95%CI[39.16, 79.90], P<0.000 01) and reduced the incidence of cardiovascular events(MACE)(RR=0.43, 95%CI[0.30, 0.61], P<0.000 01), high sensitivity C-reactive protein(hs-CRP)(MD=-2.75, 95%CI[-3.71,-1.79], P<0.000 01), and endothelin-1(ET-1) levels(MD=-9.34, 95%CI[-11.36,-7.32], P<0.000 01). There was no statistically significant difference in the incidence of adverse reactions between two groups(RR=0.91, 95%CI[0.68, 1.22], P=0.52). Subgroup analysis showed that Guanxinning Tablets may have better short-term efficacy(less than 6 months) in the treatment of heart-blood stasis syndrome. GRADE grading showed that angina pectoris efficacy, electrocardiogram efficacy, MACE, and ET-1 were in the medium grade, hs-CRP and adverse reactions were in the low grade, and exercise duration was in the extremely low grade. In conclusion, the efficacy of Guanxinning Tablets+conventional western medicine is better than conventional western medicine treatment alone, with good safety. Therefore, it is recommended for the short-term treatment of patients with heart-blood stasis syndrome. However, the evidence quality of some results is low, and more rigo-rous RCT is still needed to enhance the reliability of evidence.

Trichostatin C attenuates TNFα-induced inflammation in endothelial cells by up-regulating Krüppel-like factor 2 / 药学学报

Krüppel-like transcription factor 2 (KLF2) plays a key regulatory role in endothelial inflammation, thrombosis, angiogenesis and macrophage inflammation and polarization, and up-regulation of KLF2 expression has the potential to prevent and treatment atherosclerosis. In this study, trichostatin C (TSC) was obtained from the secondary metabolites of rice fermentation of Streptomyces sp. CPCC 203909 as a KLF2 up-regulator by using a high throughput screening model based on a KLF2 promoter luciferase reporter assay. TSC significantly inhibited the adhesion of tumor necrosis factor-α (TNFα) induced monocytes (THP-1) to human umbilical vein endothelial cells (HUVECs). Western blot results showed that TSC decreased TNFα induced the protein expression increase of vascular cell adhesion molecule-1 (VCAM-1), and thereby inhibited endothelial inflammation. The results of histone deacetylase (HDAC) overexpression and molecular docking experiments showed that TSC upregulated the expression of KLF2 by inhibiting subtypes of HDAC 4/5/7. In conclusion, this study suggests that TSC up-regulates the expression of KLF2 through inhibiting HDAC 4/5/7 and thus inhibits TNFα induced endothelial inflammation, and it has the potential to prevent and treat atherosclerosis.

Terpine-4-ol on inhibiting vascular smooth muscle cell calcification by improving mitochondrial dynamics / 药学学报

The aim of this study was to investigate the role and mechanism of terpinen-4-ol (T4O) on high glucose (HG) -induced calcification in vascular smooth muscle cell (VSMC). To investigate the role of T4O on HG-induced calcium deposition, osteogenic phenotypic transformation and mitochondrial dynamics in VSMC, Mdivi-1, a mitochondrial dynamin-related protein 1 (Drp-1) inhibitor, was used to analyze the correlation between mitochondrial dynamics and VSMC calcification and the role of T4O. Alizarin red S staining was used to observe calcium salt deposition and flow cytometry to detect intracellular Ca2+ content; Western blot and immunofluorescence were used to detect the expression of phenotypic switching-related markers α-smooth muscle actin (α-SMA), bone morphogenetic protein 2 (BMP2) and Runt related transcription factor 2 (Runx2), and mitochondrial dynamics-related markers mitofusin 1 (MFN1), mitofusin 2 (MFN2) and Drp-1. The results showed that low and high doses of T4O could inhibit HG-induced down-regulation of α-SMA, MFN1 and MFN2 expression levels, and up-regulation of BMP2, Runx2 and Drp-1 expression levels, reduce intracellular Ca2+ content and calcium salt deposition, and effectively inhibit HG-induced VSMC calcification and mitochondrial dynamics disorders. The T4O group, Mdivi-1 group and T4O+Mdivi-1 group were able to up-regulate the expression levels of HG-induced α-SMA, MFN1 and MFN2, down-regulate the protein expression levels of BMP2, Runx2 and Drp-1, and inhibit calcium salt deposition, and there was no significant difference between the above indexes in the T4O and T4O+Mdivi-1 groups. The above findings suggest that T4O can inhibit the expression level of Drp-1, regulate the disturbance of mitochondrial dynamics, and suppress HG-induced VSMC calcification.

Etiological identification and phylogenetic analysis of a clustered epidemic caused by norovirus on a patrol boat / 上海预防医学

ObjectiveTo determine the pathogen and phylogenetic characteristics of an uncommon outbreak of recombinant norovirus infection in Daishan County in February 2022. MethodsFluorescence quantitative PCR was used to detect the norovirus in the eight anal swabs collected in the outbreak. In the positive samples， reverse transcription PCR were used to amplify the norovirus. Norovirus sequences were characterized by MEGA7 and Simplot. ResultsNorovirus GⅠ was identified in all eight anal samples. It was further determined to be recombinant norovirus GⅠ.6 ［P11］， with the recombination site at the ORF1-ORF2 junction. The sequence had the highest nucleotide identity （98.75%） to a GⅠ.6［P11］ strain collected in 2018 （GenBank accession number MT357995）. ConclusionAccording to the etiological identification and phylogenetic analysis， this outbreak is confirmed to be caused by the uncommon recombinant norovirus GⅠ.6 ［P11］ in China.

A metabolite of Danshen formulae (IDHP) induces angiogenesis and protects rat brains against focal ischemia via CaMKKβ/AMPK(Thr172)/eNOS(Ser1177) signaling / 中国药理学与毒理学杂志

OBJECTIVE Only limited number of drugs are currently available for treating ischemic stroke. Therapeu?tic angiogenesis has recently emerged as one of the most promising therapies for cerebral ischemic injury. Isopropyl-β-(3,4-dihydroxyphenyl)-α-hydroxypropanoate (IDHP) is a metabolite derived from the botanical formulation for Dantonic?. Here, we investigated the angiogenic efficacy of IDHP in cerebral ischemia. METHODS The in vivo effects of IDHP were evaluated in the C57BL/6 mouse Matrigel plug and rat transient middle cerebral artery occlusion (tMCAO) models. Primary human umbilical vein endothelial cells (HUVEC) and human brain microvascular endothelial cells (HBMEC) were used to explore the effects of IDHP on stimulating proliferation, migration and tube formation in vitro. ELISA and Western blotting were used to quantitate the release and expression of relevant target molecules and signaling path?ways. RESULTS IDHP reduced infarct volume and improved sensorimotor function in rats subjected to tMCAO by pro?moting angiogenesis, and promoted Matrigel neovascularization in mice. Moreover, IDHP produced a biphasic modula?tion on proliferation and migration both in HUVEC and HBMEC. It also induced tube formation in a 12-day HUVEC-HDF co-culture model and in Matrigel assays. IDHP-induced angiogenesis was accompanied by increased levels of p-AMPKα (Thr172) and p-eNOS (Ser1177) both in vitro and in vivo, and the decreased level of VEGF in rat brains on day 1 whereas enhanced level of VEGF on day 3 and 7 after tMCAO. Mechanistically, AMPK knockdown or pharmacologi?cally inhibiting AMPK and its upstream kinases (CaMKKβ) inhibited the eNOS phosphorylation induced by IDHP in HUVEC. Furthermore, selective eNOS inhibitor (L-NIO), selective CaMKKβ inhibitor (STO) and AMPKa inhibitor (Com?pound C) blocked the capillary-like tube formation in the co-culture model induced by IDHP (10 nmol · L-1). CONCLU?SION Collectively, these findings showed that IDHP protected rats from cerebral ischemia-reperfusion injury by promot?ing angiogenesis via activating CaMKKβ/AMPK(Thr172)/eNOS(Ser1177) signaling, and suggest it to be a promising new drug candidate for the prevention and/or treatment of cerebral ischemia and other vascular occlusive diseases.

Rutaecarpine exerted anti-osteroporosis / 药学学报

Osteoprotegerin (OPG), secreted by osteoblasts, is a marker of bone turnover. OPG can inhibit osteoclastic differentiation by binding receptor activator of nuclear factor-κB ligand (RANKL). In this study, we found that rutaecarpine (RUT) had the up-regulating OPG activity, and it could significantly increase OPG protein levels in both mouse embryonic osteogenic precursor MC3T3-E1 and human osteosarcoma U-2OS cells. Osteoblastogenic differentiation calcified nodules staining results showed that RUT significantly promoted the osteogenic differentiation of MC3T3-E1 cells. Osteoclastic differentiation tartrate resistant acid phosphatase (TRAP) staining results showed that RUT obviously inhibited the osteoclast differentiation of mouse macrophages RAW264.7 induced by RANKL. In vivo studies showed that low-dose RUT group (5 mg·kg-1·day-1) and high-dose RUT group (45 mg·kg-1·day-1) treatments for 3 months significantly increased bone density in ovariectomized (OVX) rats; calcein double labeling experiment and toluidine blue staining results indicated that low-dose RUT group promoted bone formation and decreased bone loss in vivo; immunohistochemistry results showed that low-dose RUT group increased the expression of OPG in rat femur. All animal procedures were performed in accordance with the regulations of the Institutional Animal Care and Use Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences. In summary, this study demonstrated that RUT could up-regulate OPG expression and had promoting osteoblastic differentiation and inhibiting osteoclastic differentiation effects in vitro and in vivo.

Effect of Ultrafine Powder of Gastrodiae Rhizoma in Improving Learning and Memory Ability of Vascular Dementia Rats by Regulating Cholinergic System / 中国实验方剂学杂志

Objective:To investigate whether ultrafine powder of Gastrodiae Rhizoma （UPG） can alleviate the learning and memory impairment of vascular dementia rats and delay the process of VD， and whether this effect is related to the release of acetylcholine （Ach） through the regulation with acetylcholinesterase （AChE） and choline acetyltransferase （ChAT） and control of cholinergic system. Method:SD rats were randomly divided into sham operation group， UPG low dose group （0.45 g·kg-1）， UPG high dose group （1.8 g·kg-1） and Huperzine A group （80 μg·kg-1）， with 12 rats in each group. The drug administration groups were given orally drugs once a day for 8 weeks， and sham group and model group were given orally the same amount of distilled water. The learning and memory ability of the rats with VD were evaluated by the Morris water maze. Htoxylin eosin（HE） staining was used for pathomorphological observation of hippocampus CA1 area of the rats. The content of Ach was determined by enzyme-linked immunosorbent assay（ELISA）， AChE and ChAT protein expressions were detected by Western blot， and expression of ChAT in hippocampus CA1 area was observed by immunohistochemistry. Result:Compared with the sham operation group， the escape latency of the model group was significantly increased （P<0.01）， and the frequency of crossings platform and the time of staying in the target quadrant were reduced significantly （P<0.01）. HE staining of hippocampal tissues from VD rat showed neuron disorders， loss and degeneration and necrosis， pyknosis of the nucleus and light coloration of the cytoplasm. The level of acetylcholine in the hippocampus was significantly decreased by ELISA （P<0.05）， the expression level of AChE protein was significantly up-regulated， and the expression level of ChAT protein was significantly down-regulated （P<0.01）. Compared with model group， each administration group could significantly reduce the escape latency of the model rats， and significantly increase the frequency of crossing platform and the time of staying in the target quadrant （P<0.01）， the content of Ach was significantly increased （P<0.05）， the expression of AChE protein was significantly down-regulated （P<0.01）， while the expression of ChAT protein was significantly up-regulated （P<0.01）. Conclusion:UPG improves the learning and memory ability of vascular dementia rats， and its mechanism may be related to the increase of Ach， ChAT level and the decrease of AChE level.

Effect of Oxymatrine in Inhibiting Proliferation and Migration of HT-29 Cells Induced by Insulin / 中国实验方剂学杂志

Objective:To investigate the effect of oxymatrine (OMT) on the proliferation and migration of human colon cancer cell line HT-29 under Type Ⅱ diabetes environment by co-culturing HT-29 with insulin to simulate hyperinsulinemia. Method:The effect of OMT (2, 4, 8 mmol·L-1) on insulin-induced proliferation of HT-29 was detected by methyl thiazolyl tetrazolium (MTT) assay and cloning assay. The morphology change and cell migration were evaluated under microscope and by wound healing assay. The Annexin V/propidium iodide(PI) assay was used to detect the change of insulin-induced HT-29 cell cycle and apoptosis. Western blot was performed to validate the expression of cell cycle-related protein and cell migration protein. Result:Insulin significantly increased growth of HT-29 (P-1 showed a significant inhibitory effect in this model (P0/G1 phase (P1, CDK4 and the up-regulation of p27 by OMT might involve the growth inhibition mechanism. Furthermore, OMT reduced the migration of insulin-induced HT-29 according to wound healing assay(PPPConclusion:OMT can inhibit the proliferation and migration of insulin-induced HT-29 cells. The changes of cell cycle and migration related proteins may be correlated with the mechanism.

Survey of the readiness for hospital discharge and its influencing factors among chronic renal failure patients undergoing arteriovenous fistula surgery / 中国实用护理杂志

0bjective To investigate the status of readiness for hospital discharge of chronic renal failure patients undergoing arteriovenous fistula surgery and analyze its influencing factors. Methods A total of 229 diabetic patients who were discharged from the department of endocrinology were surveyed by the general data questionnaire, Readiness for Hospital Discharge Scale (RHDS), Quality of Discharge Teaching Scale (QDTS) and Social Support Rating S1cale (SSRS). Results The total score of RHDS was (157.20±19.39) points, and the items were equally (7.15±0.88) points. Education level, inhabiting pattern, discharge guidance skills and subjective support entered the readiness for hospital discharge regression equation of chronic renal failure patients undergoing arteriovenous, accounting for a total of 33.1% of all the variation. Conclusions The readiness for hospital discharge of chronic renal failure patients undergoing arteriovenous fistula surgery is intermediate level. Education level, inhabiting pattern, discharge guidance skills and subjective support could exert important influence on readiness for hospital discharge of chronic renal failure patients undergoing arteriovenous fistula surgery.

The anti-atherosclerotic effect and mechanism study of berberine in hyperlipidemic ApoE-/- mice / 药学学报

The purpose of this research is to study the anti-atherosclerotic effects and mechanisms of berberine (BBR) in high fat diet (HFD) fed ApoE-/- mice, and then to lay a solid foundation of the clinical studies of BBR treatment. The hyperlipidemic ApoE-/- mice model was established by feeding HFD for 12 weeks. Mice were randomly divided into control group (chow diet), model group, BBR group (BBR-L: 50 mg·kg-1, BBR-H: 150 mg·kg-1) and atorvastatin (5 mg·kg-1) group. Mice were intragastric administration with BBR in 0.5% sodium salt of caboxy methyl cellulose. After 12 weeks, enface aortas were stained with oil red O, and the lesions area were analyzed by Image J software. The inflammatory factor levels were detected by suspension microarray kits. Liver total cholesterol (TC), triglyceride (TG) and free fatty acids (FFA) were determined by commercial kits. Western blot was performed to examine the inflammatory pathway related and cholesterol and lipid transport related proteins' expression. All animal experiments were performed in accordance with the Regulation on the Administration of Laboratory Animals of Institute of Medicinal Biotechnology. After 12 weeks treatment, compared with model group, BBR treatment significantly reduced the lesions area of en face aortas and obviously inhibited serum proinflammatory factors such as IL-1β and IL-6 compared with model group. In addition, BBR treatment obviously reduced liver TC, TG and FFA levels compared with model group. Furthermore, mechanic study showed that BBR significantly inhibited MAPKs and NF-κB pathways, and increased cholesterol and lipid regulated proteins expression such as p-AMPK, LDLR, ABCA1 and SR-BI. In conclusion, BBR can obviously reduce enface aortas lesions in ApoE-/- mice, which is related to inhibit inflammation and liver cholesterol and lipid accumulation.

A study on the stable inheritance of chromosome aberration karyotype in three families of two generations in Hainan province

Objective:To examine chromosomes of a total of 10 857 people who asked for prenatal genetic counseling in our hospital from February 1994 to July 2018. The important diagnostic reference index for the clinical diagnosis, screening for genetic abnormality and carrying out appropriate guidance have been done for them to adopt appropriate prenatal strategies and realize a first-degree prevention and control of birth defects.Methods:Routine G banding analysis was performed on genetic counselors. C banding, N banding analysis and whole genome sequencing were performed according to abnormal karyotypes.Results:The chromosome aberration karyotype 46, X, inv(Y)(p11.2q11.2) pat/45, X pat, number: 3 574 was found and reported for the first time across the globe; Besides, this aberrant chromosome karyotype experienced stable inheritance of two generations in 8 adult males of three families.Conclusions:The adult males in three families have normal phenotype and they can still have normal fertility. Among those people, no pathogenic gene has been detected and no genetic material has lost or increased. The same aberration karyotype has been found in all 8 adult males of two generations. The ratio of these two generations’ karyotype is one out of ten thousand. As a rare genetic polymorphism, the abnormal karyotype can be regarded as an evolutionary marker, and play a unique role in paternity testing. In addition, the inverted Y chromosome can also be used to study the route of population migration. As a marker of genetic relationship, it may provide a method to study population genetics and historical geography.

Circulating Serum MicroRNA as Diagnostic Biomarkers for Multiple Myeloma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the diagnostic value of circulating serum miRNA for multiple myeloma.</p><p><b>METHODS</b>Forty blood samples from patients with multiple myeloma were collected from July 2013 to June 2014 in Department of Hematology, Zhongshan Hospital Affiliated to Xiamen University. The real-time quantitative PCR was performed to detect the serum expression levels of miRNAs (miR-29a, miR-155, miR-16 and miR-92a) circulating in the different stages of patients with multiple myeloma and evaluate the diagnostic value for patients with multiple myeloma.</p><p><b>RESULTS</b>The serum level of miR-29a significantly increased in newly diagnosed patients as compared to healthy donor (P<0.01), serum miR-155 levels were significantly lower as compared with healthy donor(P<0.001); The ratio of miR-29a and miR-155 was an effective biomarker for distinguishing multiple myeloma from healthy donor, their sensitivity and specificity were 80.8% and 83.3% respectively for myeloma diagnosis. the change of miR-29a expression was consistent with the changes of bone marrow plasma cells and M protein levels.</p><p><b>CONCLUSION</b>These circulating serum microRNA, such as miR-29a, miR-155 and miR-16, may serve as potential diagnostic biomarkers for multiple myeloma, and the ratio of miR-29a/miR-155 may serve as a most useful biomarker for myeloma diagnosis.</p>

Relationship between vitamin D level and related indicators in breastfeeding infants in People's Hospital of Longhua New District in Shenzhen City / 中华临床营养杂志

Objective To investigate the changes of vitamin D level and its relationship with bone alkaline phosphatase(BAP)and parathyroid hormone(PTH)in infants fed with breast milk and vitamin D supplementation for 0-8 months in People`s Hospital of Longhua New District in Shenzhen city.MethodsTotally 67 newborns in the Department of Obstetrics and Gynecology of People`s Hospital of Longhua New District were selected.These newborns were breastfed and began to supplement vitamin D 400 U/d in the 15th day after birth.The serum 25-(OH)D3 and BAP and PTH levels were measured in newborns and 4-/8-month-old infants,and the correlations of serum 25-(OH)D3 with BAP and PTH were analyzed by Pearson correlation analysis.ResultsCompared with the newborns,the serum 25-(OH)D3 [(78.47±36.41)nmol/L,(75.26±34.73)nmol/L],BAP[(231.43±78.81)μg/L,(205.97±71.64)μg/L],PTH[(31.76±11.54)pg/ml,and(32.94±13.82)pg/ml] levels of 4-and 8-month-old infants were significantly higher,and the difference were statistically significant(t4 months=7.823,12.568,11.852,t8 months=7.364,9.473,11.947;all P=0.000).There was a negative correlation between serum 25-(OH)D3 and BAP in newborns and 4-/8-monthold infants(r=-0.372,-0.463,-0.309;P=0.008,0.016,0.021),the serum BAP was positively correlated with PTH in infants aged 4 months and 8 months(r=0.487,0.338;P=0.005,0.032),and the serum 25-(OH)D3 was negatively correlated with PTH in infants aged 4 months(r=-0.297,P=0.041).Conclusions Infants at birth are prone to vitamin D deficiency in Shenzhen City.After 4 months of breastfeeding and vitamin D400U/d supplementation,the vitamin D levels in most infants become normal.25-(OH)D3 is correlated with BAP and PTH in different months.

Induce and differentiation of pig Müller cells into photoreceptors in vitro / 中华实验眼科杂志

Background Recent studies indicated that rat and mouse Müller cells can be induced and differentiated into photoreceptor-like cells in vitro, but it is not known whether this also happens to adult pig Müller cells nowadays.Objective This study was to test whether adult pig Müller cells can be differentiated to the retinal photoreceptors (the primary transmission neurons of the retina) in vitro.Methods Müller cells were isolated from the neural retina of adult pig eyes and cultured and passaged.The 3rd and 4th generation of cells were themonolayerly cultured,and the cells forced to form spheres in suspension in altra-low adherent dishes for 2-3 days first and then reseeded in normal adherent plates,and both of them were cultured in a specifically formulated medium to induce the differentiation of retinal photoreceptor.The cells was verified by immunocytochemistry.Cell morphology and immunofluorescence staining were utilized to measure the efficacy of the differentiation.Results The 2nd,3rd and 4th generation of Müller cells expressed glutamate synthetase (GS) , a specific maker of Müller cells.Inaddition, the 3rd generation of cells also expressed glial fibrillary acidic protein (GFAP) and another specific maker of Müller cells.Three visual fields under fluorescence-microscope were randomly chosen to calculate the average positive ratio of rhodopsin,a specific marker of mature photoreceptors.The photoreceptor differentiation ratios of the 2nd generation of cells for monolayer culture only and with additional sphere suspension culture were (27.99±6.53 (％ and (16.54±3.40) ％ , respectively.With passages, the number of rhodopsin positive cells gradually decreased, and the intensity of rhodopsin expression gradually weakened.The directed rhodopsin positive ratios of the 2nd,3rd and 4th generation of cells from sphere formation were (56.23±7.32)％ , (36.26 ±8.55)％ and (12.68 ±3.18)％ , respectively.Although the rhodopsin expression was weakened over passages,the differentiated cells were more slender and elongated.There was no statistic ally significant difference between different groups (F =2.618, P =0.099).Conclusions Adult pig Müller cells can be differentiated into retinal photoreceptors in vitro.The morphology of the differentiated cells appears moreslender and elongates if the sphere-induced differentiation method is used and/or the directed differentiation time is further extended.

In vitro effect and mechanistic study of compound E23869 on lipid metabolism / 药学学报

This study was designed to identify inducers of ATP-binding cassette transporter A1(ABCA1) and CD36 and lysosomal integral membrane protein-II analogous-1(CLA-1) and to evaluate the in vitro effect of the active compound on lipid metabolism. Among 20000 compounds screened, E23869 was found as a positive hit using cell-based high throughput screening models. The up-regulating activities of E23869 in ABCA1p-LUC and CLA-1p-LUC HepG2 cells were 196% and 198%, respectively. The EC50 values of E23869 in ABCA1p-LUC and CLA-1p-LUC HepG2 cells were 0.25 μmol·L-1 and 0.66 μmol·L-1, respectively. E23869 significantly upregulated the protein levels of ABCA1, scavenger receptor class B type I (SR-BI)/CLA-1 and ATP-binding cassette transporter G1(ABCG1) in both macrophages RAW264.7 and L02 cells by Western blotting analysis. Foam cell assay showed that E23869 inhibited lipids accumulations in macrophages RAW264.7. Cholesterol efflux assay showed that E23869 induced HDL-mediated cholesterol efflux in macrophages RAW264.7. Moreover, E23869 up-regulated ABCA1, SR-BI/CLA-1 and ABCG1 expressions through activation of PPARα and PPARγ. In addition, E23869 weakly promoted in vitro differentiation of mouse preadipocytes 3T3-L1. In conclusion, E23869 up-regulated ABCA1, SR-BI/CLA-1 and ABCG1 expressions to promote cholesterol efflux, which is a good leading compound for regulation of lipid metabolism.

OMT inhibited TGF-β1-induced cardiac fibroblast proliferation via down-regulating p38MAPK phosphorylation in vitro / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the inhibitory effects of OMT on TGF-β1-induced CFBs proliferation, and then explore the mechanism.</p><p><b>METHOD</b>The experiment was randomly divided into 6 groups as following: control group (serum free DMEM), model group (20 μg x L(-1) TGF-β1), OMT low dose group (1.89 x 10(-4) mol x L(-1) + 20 μg x L(-1) TGF-β1), OMT medium dose group (3.78 x 10(-4) mol x L(-1) + 20 μg x L(-1) TGF-β1), OMT high dose group (7.56 x 10(-4) mol x L(-1) + 20 μg x L(-1) TGF-β1), SB203580 group (p38MAPK blocking agent, 1 x 10(-5) mol x L(-1) + 20 μg x L(-1) TGF-β1). Vimentin of CFBs was identified by immunocytochemical methods, α-SMA of myFBs as well. Inhibitory effects of OMT on CFBs proliferation was detected by the MTT assay. Picric acid Sirius red staining was analyzed collagen type I and collagen type III deposition. Western blot was determined the expression of p38MAPK, p-p38MAPK, collagen type I and collagen type III.</p><p><b>RESULT</b>MTT results showed that OMT significantly inhibited CFBs proliferation induced by TGF-β1 (P < 0.01) α-SMA immunocytochemical experiments suggested that OMT could protect against the CFBs proliferation. OMT could significantly decrease the deposition of collagen type I and collagen type III by Western bloting and picric acid Sirius red staining. Western blot results showed that TGF-β1 enhanced p38MAPK phosphorylation, however OMT attenuated the phosphorylation of p38MAPK induced by TGF-β1 (P < 0.01).</p><p><b>CONCLUSION</b>OMT can inhibit the CFBs proliferation induced by TGF-β1, and its mechanism may be involved in inhibiting p38MAPK phosphorylation.</p>

A novel trichostatin analogue culture of Streptomyces sp. CPCC 203909 / 中国中药杂志

By using a cell-based high throughput screening model for the CLA-1 up-regulator, Streptomyces 203909 was found to produce up-regulator of CLA-1. A novel trichostatin analogue was isolated from the rice fermentation of Streptomyces sp. CPCC 203909by a combination of various chromatographic techniques including column chromatography (CC) over silica gel, flash C18 CC, and reversed-phase HPLC. Its structure was identified as (-)-(R,2E,4Z)-7-[(4'-dimethylamino) phenyl]-4,6-dimethyl-7-oxohepta-2,4-dienoyl-L-glutamine (1) by the spectroscopic and chemical methods, and combination with the CD spectroscopy and Marfey's method. In the prelimi- nary assays, Compound 1 showed cytotoxicity against human embryonic kidney 293 cell line with IC50 value 35.3 [µmol · L(-1).

The in vitro anti-atherosclerotic activity of compound E0869 / 药学学报

ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI/CLA-1) are the key proteins in reverse cholesterol transport (RCT). The high expression of ABCA1 and SR-BI/CLA-1 can decrease the danger of atherosclerosis. The purpose of the study is to find ABCA1 and CLA-1up-regulators for treating atherosclerosis by using cell-based high throughput screening models. Among 20 000 compounds screened, E0869 [1-(3, 4-dimethylphenyl)-1-oxopropan-2-yll4-((methylsulfonyl)methyl)benzoate] was found as the positive hit. The up-regulated activities of E0869 in ABCAl1-LUC and bCA-l1-LUC HepG2 cell were 160% and 175%, respectively. The EC50 values of E0869 in ABCAl1-LUC and CLA-l1-LUC HepG2 cell were 3.79 and 1.42 pμol- x ,(-1) respectively. E0869 could upregulate the mRNA and protein levels of ABCA1, SR-BI/CLA-1 and ABCGJ1genes in HepG2 and RAW264.7 cells by Real-Time Quantitative PCR and Western blotting analysis, but could not influence the expression of FAS, SREBP-l1 and CD36. Foam cell assay showed that E0869 could inhibit lipids accumulation in mouse peritoneal macrophages RAW264.7. Cholesterol efflux assay showed that E0869 could induce HDL-mediated cholesterol efflux in mouse peritoneal macrophages RAW264.7. In conclusion, E0869 could up-regulate ABCA1 and CLA-1 activity, and had good anti-atherosclerotic activity in vitro.

Application of locomotor activity test to evaluate functional injury after global cerebral ischemia in C57BL/6 mice / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To evaluate the application of locomotor activity test in functional injury after global cerebral ischemia (GCI) in C57BL/6 mice.</p><p><b>METHODS</b>GCI was induced by bilateral carotid arteries occlusion for 30 min in C57BL/6 mice. Mice were divided into sham group, GCI group and minocycline group. Saline or minocycline (45 mg/kg) was i.p. injected once daily for 6 d after ischemia. At Day 6 after ischemia, locomotor activity was recorded for 1 h in open field test. Total distance, central distance, central distance ratio, periphery distance, periphery distance ratio, central time and periphery time were used to evaluate the behavior characteristics of locomotor activity in C57BL/6 mice after ischemia. The survival neuron density was detected by Nissl staining in hippocampus, cortex and striatum.</p><p><b>RESULTS</b>Compared with sham group, total distance, central distance and central time increased and periphery time decreased in C57BL/6 mice after GCI (Ps<0.05). However, minocycline significantly reduced the central distance and central time and increased the periphery time (Ps<0.05). Neurons were damaged in hippocampus, cortex and striatum after GCI, which manifested by decreased neurons and the most serious damage in hippocampal CA1 region. Minocycline significantly improved the neuron appearance and increased the neuron number in hippocampus and striatum (P<0.001 or P<0.05).</p><p><b>CONCLUSION</b>Locomotor activity in open field test can objectively evaluate the behavior injury after GCI in mice. Central distance and central time can be used as indexes of quantitative assessment.</p>

The in vitro anti-atherosclerotic activity of compound IMB-1680 / 药学学报

In the previous study, a high-throughput screening method was established to find the antagonists of CD36. In the present study, a new compound named IMB-1680 was found using this method. The anti-atherosclerotic activities of IMB-1680 were then evaluated. Dose-dependent activities of IMB-1680 were detected by using Sf9 [hCD36] and CHO [hCD36] models. Fluorescence microscopic photography and flow cytometry were used to analyze uptake of mLDL. Foam cell test with RAW264.7 macrophages was used to examine lipid accumulation. The results showed that IMB-1680 inhibited CD36 activity with IC50 of 2.80 and 8.79 micromol x L(-1) in Sf9[hCD36] and CHO [hCD36] cells, respectively. Fluorescence microscopic photography and flow cytometry revealed that IMB-1680 could significantly reduce DiI-AcLDL uptake. Meanwhile, IMB-1680 also could reduce lipids accumulation in RAW264.7 macrophages. In all, the data indicated that IMB-1680 might be a potent effective anti-atherosclerotic leading compound.