Dysideanones F-G and dysiherbols D-E, unusual sesquiterpene quinones with rearranged skeletons from the marine sponge Dysidea avara / 中国天然药物

Four new sesquiterpene quinone meroterpenoids, dysideanones F-G (1-2) and dysiherbols D-E (3-4), were isolated from the marine sponge Dysidea avara collected from the South China Sea. The new structures were elucidated by extensive analysis of spectroscopic data including HR-MS and 1D and 2D NMR spectra, and their absolute configurations were assigned by single-crystal X-ray diffraction and ECD calculations. Anti-inflammatory evaluation showed that dysiherbols D-E (3-4) exhibited moderate inhibitory activity on TNF-α-induced NF-κB activation in human HEK-293T cells with IC50 values of 10.2 and 8.6 μmol·L-1, respectively.

New bisabolane-type phenolic sesquiterpenoids from the marine sponge Plakortis simplex / 中国天然药物

Six new bisabolane-type phenolic sesquiterpenoids, including plakordiols A-D (1-4), (7R, 10R)-hydroxycurcudiol (5) and (7R, 10S)-hydroxycurcudiol (6) were isolated from the marine sponge Plakortis simplex collected from the South China Sea. Their structures were determined based on extensive analysis of spectroscopic data. Their configurations were assigned by coupling constant analysis, NOESY correlations, and the modified Mosher's method. Furthermore, their cytotoxic and antibacterial activities were evaluated.

Study on the secondary metabolites of grasshopper-derived fungi Arthrinium sp. NF2410 / 中国天然药物

Two new 2-carboxymethyl-3-hexyl-maleic anhydride derivatives, arthrianhydride A (1) and B (2), along with three known compounds 3-5, were isolated from the fermentation broth of a grasshopper-associated fungus Arthrinium sp. NF2410. The structures of new compounds 1 and 2 were determined based on the analysis of the HR-ESI-MS and NMR spectroscopic data. Furthermore, compounds 1 and 2 were evaluated on inhibitory activity against the enzyme SHP2 and both of them showed moderate inhibitory activity against SHP2.

Effect of Crude Epimedii Folium and Processed Epimedii Folium on Kidney Yang Deficiency Edema Model Rats / 中国实验方剂学杂志

Objective: To compare the effects between crude and processed Epimedii Folium on the rats of kidney-Yang deficiency and edema, in order to discuss the mechanism. Method: The rat model of kidney-Yang edema was duplicated with hydrocortisone and doxorubicin hydrochloride. At day 1 and day 8 of modeling, the rats were injected with doxorubicin hydrochloride (3.5 mg·kg-1) via tail vein, while being intraperitoneally injected with hydrocortisone (3.75 mg·kg-1·d-1) for 15 days.After modeling,the rats were divided into model group,crude Epimedii Folium group(204.86 mg·kg-1)and processed Epimedii Folium group(204.86 mg·kg-1), and a normal control group was set up additionally.Rats in each treatment group were given the corresponding drugs,and those in normal and model groups were given the same volume of normal saline by gavage for continuous 14 days.At the end of the administration,24 h urine was measured by rat metabolic cage method; 24 h urinary protein was detected by ultraviolet spectrophotometry; the content of plasma albumin (ALB) and total serum protein (TP) were measured by an automatic biochemical analyzer; and the content of adenosine monophosphate was measured by enzyme-linked immunosorbent assay(ELISA). Cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), triiodothyronine (T3), thyroxine (T4), serum creatinine (SCr), serum urea(BUN), estradiol (E2), testosterone (T) indicator content were determined by enzyme-linked immunosorbent assay(ELISA). Kidney tissues were collected to make pathological section by htoxylin eosin(HE) staining. Result: Compared with the normal group, all the indicators of appearance, biochemistry and pathological section in the model group indicated kidney Yang deficiency edema in the rats (PP2, T indicators to varying degrees(PPP2, T (PPP3, T4 and anal temperature (PPConclusion: Both crude Epimedii Folium group and processed Epimedii Folium group have certain effect in treating kidney Yang deficiency edema, and the possible mechanism is to alleviate glomerular podocyte injury induced by doxorubicin. Their emphasis in the treatment of kidney Yang deficiency edema is different. Crude Epimedii Folium has a cold property, and can treat kidney Yang deficiency edema by strengthening renal excretion function of rats with kidney Yang deficiency edema. Processed Epimedii Folium is processed with sheep oil to produce icariin and other substances, and its property changed from cold to warm, with a focus on alleviating the kidney Yang deficiency status of rats with kidney Yang deficiency edema.

The determination of diflucortolone in rabbit plasma by liquid chromatography-tandem mass spectrometry (LC-MS/MS) / 药学学报

A sensitive and efficient liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantitative determination of diflucortolone in rabbit plasma after dermal administration of diflucortolone valerate cream to rabbits. After extraction with ethyl acetate, the chromatographic separation was performed on Zorbax Eclipse XDB-C18 (50 mm×4.6 mm, 5 μm) with a gradient mobile phase consisting of 50% acetonitrile-50% methanol and 0.1% formic acid-5% methanol-5 mmol·L-1 ammonium formate at a flow rate of 0.35 mL·min-1. The quantitative analysis was carried out using multiple reaction monitoring (MRM) at specific ion transitions of m/z [M+H]+ 395.2→m/z 355.2 for diflucortolone and m/z [M+H]+ 258.1→m/z 120.9 for ethoxyphenylethylamine (internal standard) in positive ion mode with electrospray ionization (ESI) source. This validated LC-MS/MS method had a linearity over the concentration range of 0.01-10 ng·mL-1 with the lower limit of quantification (LLOQ) at 0.01 ng·mL-1. At level of LLOQ, the inter and intra-assay precision (RSD) were no greater than 9.82% and 11.0%, respectively. The main pharmacokinetic parameters of the diflucortolone including tmax, Cmax, AUC0-72 h, and t1/2 were as follows: (6.33±1.21) h, (0.168±0.080 0) ng·mL-1, (3.15±0.834) h·ng·mL-1, (32.0±17.4) h. The method was validated in the pharmacokinetic study of diflucortolone in rabbit following dermal administration of diflucortolone valerate cream at dose of 0.01 g·cm-2. In this study, the program of animal testing had been approved by Committee on the management and usage of experimental animal in the Evaluation Company of Innovative Drug, Tianjin Institute of Pharmaceutical Research.

Dalestones A and B, two anti-inflammatory cyclopentenones from Daldinia eschscholzii with an edited strong promoter for the global regulator LaeA-like gene / 中国天然药物

Replacement of the native promoter of theglobal regulator LaeA-like gene of Daldinia eschscholzii by a strong gpdA promoter led to the generation of two novel cyclopentenone metabolites, named dalestones A and B, whose structures were assigned by a combination of spectroscopic analysis, modified Mosher's reaction, and electronic circular dichroism (ECD). Dalestones A and B inhibit the gene expression of TNF-α and IL-6 in LPS-induced RAW264.7 macrophages.

Bioactive phenazines from an earwig-associated Streptomyces sp / 中国天然药物

Three new phenazine-type compounds, named phenazines SA-SC (1-3), together with four new natural products (4-7), were isolated from the fermentation broth of an earwig-associated Streptomyces sp. NA04227. The structures of these compounds were determined by extensive analyses of NMR, high resolution mass spectroscopic data, as well as single-crystal X-ray diffraction measurement. Sequencing and analysis of the genome data allowed us to identify the gene cluster (spz) and propose a biosynthetic pathway for these phenazine-type compounds. Additionally, compounds 1-5 exhibited moderate inhibitory activity against acetylcholinesterase (AChE), and compound 3 showed antimicrobial activities against Micrococcus luteus.

Effect of chronic intermittent hypoxia on glycometabolism in rat' liver and the mechanism thereof / 解放军医学杂志

Objective To investigate the effects of chronic intermittent hypoxia on the adipose factor and the expressions of insulin receptor substrate 2 (IRS-2),glucose transporter 2 (GLUT-2) and leptin in rat liver.Methods Twenty-four mature SD rats were randomly divided into 3 groups:control group (UC),chronic intermittent hypoxia group (CIH) and reoxygenation group (RH).The arterial blood gas analysis was performed after the establishment of rat model.The serum fasting blood glucose (FBG) and fasting insulin (FINS) in each group were detected by peroxidase method;the concentrations of free fatty acids (FFA) and leptin were detected by ELISA.The expressions ofmRNA and protein of GLUT-2,IRS-2 and leptin were detected by qRT-PCR and Western blotting.Results The serous concentrations of FBG,FINS,FFA and leptin were significantly higher in CIH group than in UC group (P＜0.05),and were dramatically higher in RH group than in both CIH group (P=0.003) and UC group (P=0.000).Western blotting and qRT-PCR detection showed that the protein and mRNA expressions of GLUT-2 and IRS-2 were significantly lower in CIH group than in RH group of rat liver (P＜0.05),while were markedly lower in RH group than in UC group (P＜0.05);the expressions of leptin protein and mRNA were significantly higher in CIH group than in RH group (P＜0.05),while were obviously higher in RH group than in UC group of rat liver (P＜0.05).Conclusion Insulin resistance induced by chronic intermittent hypoxia may be associated with the elevation of serum FFA and leptin,and be related to the decreased expression of GLUT-2 and IRS-2 and increased expression of leptin in liver.

Evidence-based nursing practice of enteral nutrition support among ICU patients with diarrhea / 中华护理杂志

Objective To explore the best intervention based on evidences of enteral nutrition support complicated with diarrhea in critically ill patients and evaluate its clinical effects.Methods Evidence was obtained using Evidence-based Nursing,and was implemented in clinical practice after localization,we formulated numing recommendations for regulating nurses' clinical practice regarding enteral nutrition support complicated with diarrhea in ICU patients;we conducted multiple online and offline training for nurses.The rate of diarrhea in ICU patients undergoing enteral nutrition support before and after using best evidence was compared,and awareness and implementation of best evidence among nurses before and after training were also compared.Results After adapting the best evidence,the rate of enteral nutrition associated diarrhea decreased from 25.58％ to 13.89％;ICU nurses' diarrhea identification and evaluation,analysis of influencing factors of enteral nutrition associated diarrhea,selection of enteral nutrition formula,nasal feeding,etc.,were significantly improved (P＜0.05);there was no significant difference in enteral nutrition infusion,and nutrition preparation and preservation (P＞0.05);rare of implementation of best evidence in ICU nurses was greater than 80％.Conclusion Evidence-based practice can effectively prevent enteral nutrition associated diarrhea in ICU patients.Nurses can solve enteral nutrition associated diarrhea using scientific nursing methods through implementation of best evidence,in order to nursing quality.

Antibody-drug conjugates:design and clinical progress / 药学学报

Antibody-drug conjugates, constructed with monoclonal antibodies, linker and cytotoxins, have distinctive advantages over chemotherapy drugs and antibody drugs in cancer therapy. In this review, the strategy of developing ADCs, and the important progress in past decade are well summarized. The representative ADCs in the pipeline are introduced and characterized with their new features. While, perspective for future directions of ADCs is proposed.

The prognostic value of plasma brain natriuretic peptide in patients with acute pulmonary embolism / 中华全科医师杂志

The aim of the study is to investigate the prognostic value of plasma brain natriuretic peptide (BNP) in patients with acute pulmonary embolism. Plasma BNP concentrations were measured in 47 cases with acute pulmonary embolism. Plasma BNP levels in massive or sub-massive pulmonary embolism were higher than those in no-massive pulmonary embolism (P = 0. 001,0. 048) ; BNP levels in survival cases were higher than those in fatal cases ( P = 0. 027 ). The incidence of massive or sub-massive pulmonary embolism in patients with BNP >400 pg/ml was higher than that with BNP≤400 pg/ml ( 100% vs. 75%,P = 0. 023 ). Results indicate that plasma BNP concentration might be associated with risk stratification and prognosis of the disease.

The correlation of asymmetrical dimethylarginine level and oxidative stress to the onset of Alzheimer's disease / 药学学报

This study is to investigate the influence and mechanism of action of asymmetrical dimethylarginine (ADMA) and the induced oxidative stress level on Alzheimer's disease (AD) incidence. ADMA concentration, nitric oxide, Abeta(40)/Abeta(42) ratio, inducible NO synthase (iNOS) activity and the concentrations of the induced free radicals including malondialdehyde (MDA), 3-nitrotyrosine (3-NT) and peroxynitrite (ONOO-) in the cerebrospinal fluid (CSF) from 34 neurologically normal controls and 37 AD patients were quantitatively determined and statistically compared. The results showed that the ADMA concentration significantly decreased in AD patients, and it showed negative correlation with the NO, iNOS activity, and showed positive correlation with MMSE score. ADMA concentration was negatively correlated with Abeta(40)/Abeta(42) ratio (P<0.01) with the observation that Abeta(40)/Abeta(42) ratio increased while ADMA level decreased in CSF in AD patients. The concentration levels of MDA, 3-NT and ROS significantly increased compared with the control with all the P values less than 0.05. These findings suggested that the ADMA disorder and the oxidative damage effect of the induced free radicals in CSF of AD patients are an important mechanism of AD incidence, and their joint regulation may provide new idea for the prevention and clinical treatment of AD.

The inhibition of tamoxifen on sodium channel in SHG-44 glioma cell-line / 中国应用生理学杂志

<p><b>AIM</b>To explore the effect of tamoxifen on voltage-dependent sodium channels in SHG-44 glioma cell line.</p><p><b>METHODS</b>Whole-cell patch clamp technique was used to record the Na currents in SHG-44 cell line and to investigate the effect of tamoxifen of different concentration on this channel currents.</p><p><b>RESULTS</b>This channel activated and inactivated quickly. Tamoxifen could significantly decrease the amplitude of Na currents of SHG-44 cell line. This block effect was dose dependent and voltage dependent. When the holding potential was 0 mV, 8 micromol/L tamoxifen could block this currents 69%. The half inhibition concentration (IC50) was 5.54 micromol/L.</p><p><b>CONCLUSION</b>Tamoxifen could significantly block the voltage dependent sodium channel in malignant glioma cell line SHG-44. It might be one of the mechanisms that tamoxifen inhibit glioma proliferation. clamp technique was used to record the Na currents in SHG-44 cell line and to investigate the effect of tamoxifen of different concentration on this channel currents.</p><p><b>RESULTS</b>This channel activated and inactivated quickly. Tamoxifen could significantly decrease the amplitude of Na currents of SHG-44 cell line. This block effect was dose dependent and voltage dependent. When the holding potential was 0 mV, 8 micromol/L tamoxifen could block this currents 69%. The half inhibition concentration (IC50) was 5.54 micromol/L.</p><p><b>CONCLUSION</b>Tamoxifen could signifi-cantly block the voltage dependent sodium channel in malignant glioma cell line SHG-44. It might be one of the mechanisms that tamoxifen inhibit glioma proliferation.</p>

Screening, Identifying and Function Analysis of Polyketide Synthase I Cluster from the Environmental Strain X-2 Which Produce Macrolactins / 微生物学通报

Macrolactins are 24-membered macrolides produced by unidentified marine bacterium, Actinomadura sp. and Bacillus sp., which exhibit both antibacterial and antitumor activities in vitro. The environmental strain X-2 which was isolated from the sediment of the East China Sea produce Macrolatin A, B and O. In this study, a set of degenerate oligonucleotide primers, designed for amplification ketosynthase(KS) domains, had been employed to identify KS gene fragments of the X-2 DNA samples. One 645 bp KS fragment(GenBank accession no. EF486351)had been cloned and used as a probe to screen the genome DNA fosmid library of X-2. Three positive clones were selected and sequenced, Homologous analysis and the function prediction of the obtained PKS gene fragments suggested that macrolactin is the Polyketide Biosynthesis Product of the gene cluster obtained in the environmental strain X-2.

Tropism of bone marrow stromal cells to glioma and their neural differentiation potential / 肿瘤

Objective: To observe the tropism of bone marrow stromal cells (BMSCs) to intracranial glioma and their differentiation in the brain of rats bearing glioma, and to investigate the corresponding mechanism. Methods: The in vitro tropism of cultured BMSCs to glioma cells, vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), basic fibroblast growth factor(FGF), platelet derived growth factor (PDGF) were observed under microscope and detected by performing Transwell experiment. The in vivo tropism of BMSCs to intracranial glioma was observed by immunofluorescence method. The differentiation of BMSCs was induced in vitro and observed. After BMSCs were transplanted in the brain of glioma-bearing rats for 15 days, their in vivo differentiation was observed by immunofluorescence staining. Results: BMSCs displayed obvious in vitro tropism to glioma, PDGF, and EGF and in vivo tropism to intracranial glioma. They could migrate to satellite lesions of glioma in vivo. BMSCs were induced to differentiate into neural progenitor cells (8.4% ± 3.5%), neurons (53.7% ± 7.4%), and astrocytes (22.3% ± 5.2%) in vitro. After being transplanted into the brain of glioma-bearing rats, they also differentiated into neural progenitor cells (8.3% ± 3.6%), neurons (15.7% ± 4.3%) and astrocytes (32.5% ± 7.2%). There was significant difference in the differentiation ratio to neurons between in vitro and in vivo experiments (P0.05). Conclusion: BMSCs display extensive tropism to glioma. The direction of the differentiation of BMSCs may be related with local microenvironment.

Anti-glioma activity of treatment by bone marrow stromal cells transfected with HSV-tk in the rat / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the anti-glioma activity of treatment by bone marrow stromal cells (BMSCs) transfected with AdCMV-tk containing HSV-tk gene in rats.</p><p><b>METHODS</b>Primary cultured BMSCs were obtained and transfected with HSV-tk (BMSCs/tk) and were injected into contralateral brain of glioma-bearing rats to observe their tropism for glioma cells. RT-PCR was performed to examine the transduct of tk gene after it was transduced into BMSCs. C6 glioma cells were co-cultured with BMSCs transfected with HSV-tk. MTT test was performed to examine its antitumor activity. BMSCs, after being transfected with HSV-tk, were injected into contralateral brain tissue of glioma-bearing rats to show their in vivo antitumor activity. Dynamic MRI was performed to monitor the development of intracranial glioma.</p><p><b>RESULTS</b>Purified BMSCs were obtained by primary cultured bone marrow cells. After being transfected with HSV-TK, the cells still stably displayed extensive tropism for intracranial glioma and transcripted tk gene. RT-PCR showed that BMSCs/tk were transduced tk gene obviously at 21 days after AdCMV-tk transfection. BMSCs/tk showed a clear bystander effect after being co-cultured with C6 glioma cells in vitro. TUNEL assay showed that BMSCs/tk could obviously show bystander effect and induce apoptosis of glioma cells in vivo with an apoptosis positive ratio of 20.38% +/- 2.57%, showing a statistically significant difference in comparison with BMSCs group (2.56% +/- 0.52%, P = 0.023) and control group (2.74% +/- 0.38%, P = 0.025). Compared with the control group (21.40 +/- 1.63 days), BMSCs/tk transplantation significantly prolonged the survival time of glioma-bearing rats (52.60 +/- 13.11 days, P = 0.000). MRI detection showed that the least volume of intracranial glioma in BMSCs/tk group (8.28 +/- 2.64 mm3), significantly smaller than that in BMSCs group (134.51 +/- 16.37 mm3, P = 0.001) and control group (147.22 +/- 31.05 mm3, P = 0.001). Some of the intracranial gliomaa disappeared after transplantation of BMSCs/tk.</p><p><b>CONCLUSION</b>BMSCs transfected with AdCMV-tk may become an effective therapy method in the treatment for glioma.</p>

Research and development of marine bio-active substances and drugs / 第二军医大学学报

The ocean is a huge resource of organisms and about 80% of the world species live in it. Marine organisms synthesize various structurally-unique and pharmacologically-active metabolites which differ from those derived from the land organisms and serve as lead compounds for drug development. More than 15 000 new compounds have been isolated and identified from marine animals, plants and microorganisms since decades ago, and drugs like cephalosporins, ziconotide (Prialt), cytarabine (AraC) and vidarabine (AraA) were developed using these compounds as precursors.

Molecular cloning and expression of extremely thermostable and acid-stable amylase gene in Pichia pastoris / 生物工程学报

The gene encoding a extremely thermostable and acid-stable alpha-Amylase was amplified by PCR using hyperthermophilic archaebacterium pyrococcus furiosus genomic DNA as template. Then the gene was cloned into the vector of pPIC9K. The recombinant vector pPIC9K-amy was then transformed into E. coli DH5alpha strain. Sequencing test showed that the a-amylase gene cloned consisted of 1305 base pairs and the mature protein encoded by the gene consisted of 435 amino acids. The recombinant vector was transformed into chromosome of methylotrophic yeast Pichia pastoris GS115 strain. Regulated by the alpha-Factor, promoter of AOX1 gene and termination signal of yeast genomic, the recombinant a-Amylase was expressed and excreted out of the cells. The expression of the recombinant alpha-amylase was strictly induced by methanol. As induction time increased, the activity of amylase per milliliter medium went up accordingly. After 7 days induction, the activity of the amylase reached the max. The recombinant alpha-amylase exhibited maximal activity at 90 to approximately 100 degrees C and at pHranging from 4.5 to 5.0. The enzyme is so thermostable that after disposed at 100 degrees C for 5 hours over 60% of activity was retained.

Effect of Weikangfu granule on the physiopathologic figure of precancerosis of gastric mucosa in patients of chronic gastritis with Pi-deficiency syndrome / 中国结合医学杂志

<p><b>OBJECTIVE</b>To study the physiopathologic basis of Weikangfu Granule (WKFG) in treating precancerosis of gastric mucosa in patients of chronic gastritis with Pi-deficiency syndrome (CG-PDS).</p><p><b>METHODS</b>One hundred and fifteen patients of CG-PDS who suffered from intestinal metaplasia (IM) and atypical hyperplasia (ATHP) of gastric mucosa, were divided into two groups. The treated group (n = 61) was treated by WKFG with its ingredients modified according to the syndrome type of patients. The control group (n = 54) was treated with Weishu granule. The histopathological and subcellular ultrastructural changes were detected by optical microscope, screening electronic microscope, transmission electronic microscope and histochemical staining; the nuclear and mitochondrial ultrastructure of gastric mucosa were analyzed with energy dispersion X-ray analyser and image analysis system. And the changes of cAMP, lipid peroxide (LPO), superoxide dismutase (SOD) before and after treatment in the treated group were measured and compared with those of the health control group consisting of 15 volunteers.</p><p><b>RESULTS</b>The symptomatic and pathological therapeutic effect in the treated group were significantly superior to those in the control group (P < 0.05). The contents of Zn, Cu, cAMP, SOD and (3)H-TdR LCT in gastric mucosa of the treated group before treatment were all lower than those of the healthy control group, yet all these indexes markedly increased after treatment, while serum LPO level, which increased before treatment was lowered after treatment. All the changes showed statistical significance (P < 0.05 or P < 0.01).</p><p><b>CONCLUSION</b>WKFG can reverse IM and ATHP in patients of CG-PDS, and the effect may be realized by way of increasing the level of Zn, Cu, cAMP and SOD in gastric mucosa, promoting cell differentiation, enhancing cellular immunity and reducing oxygen free radicals and lipid peroxidation.</p>

Preliminary analysis on the gene expression profiles of medulloblastomas by use of cDNA array / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the molecular genesis of medulloblastomas with cDNA array.</p><p><b>METHODS</b>Four samples of medulloblastomas and 1 sample of normal brain tissue were collected freshly. After total RNA extraction, the (32)P targeted cDNA probes were converted and then hybridized with Atlas Human Cancer Array 1.2. The gene expression profiles were acquired through autoradiography. The discrepancy between the tumor and the normal brain tissue was analyzed with Atlas Image 1.01a.</p><p><b>RESULTS</b>In comparison with the genes in the normal brain tissue, 6 down-regulated and 35 up-regulated genes in the medulloblastomas were revealed by means of the microarrays and autoradiography, and were verified by reverse transcriptase-PCR. The regulatory trends of most differential expression genes were in compliance with the biological features of this tumor.</p><p><b>CONCLUSION</b>Medulloblastomas are diseases involving multiple genes with some molecular pathological mechanisms different from the astrocytic gliomas. There are complex interrelationships between these genes, which need to be further researched.</p>