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Hepatocellular carcinoma (HCC) is an aggressive human cancer with increasing incidence worldwide. Multiple efforts have been made to explore pharmaceutical therapies to treat HCC, such as targeted tyrosine kinase inhibitors, immune based therapies and combination of chemotherapy. However, limitations exist in current strategies including chemoresistance for instance. Tumor initiation and progression is driven by reprogramming of metabolism, in particular during HCC development. Recently, metabolic associated fatty liver disease (MAFLD), a reappraisal of new nomenclature for non-alcoholic fatty liver disease (NAFLD), indicates growing appreciation of metabolism in the pathogenesis of liver disease, including HCC, thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment. In this review, we introduce directions by highlighting the metabolic targets in glucose, fatty acid, amino acid and glutamine metabolism, which are suitable for HCC pharmaceutical intervention. We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment. Furthermore, opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.
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In recent years, the overexpression dopamine (DA) due to the use of addictive drugs has caused concern and urgently needs to be addressed. The method used in our study is known as biomimetic sol-gel synthesis. We undertook the experiment to develop molecularly imprinted xerogel polymers (MIXPs) through template molecules dopamine polymerized with polyethyleneimine (PEI), then self-assembled and crosslinked with tetramethoxysilane (TMOS) in the form of non-covalent hydrogen bonds by using biomimetic sol-gel process, and then eluted template DA will leave a blotting site. Monoamine oxidase immobilized MIXPs (MAO-MIXPs) was obtained by coating monoamine oxidase onto MIXPs. The synthesis optimization of MAO-MIXPs was finally set as the ratio of DA template, PEI and MAO coating (DA 40 mg, PEI 0.6 mL, MAO 2.5 mg·g-1) to achieve highly selective adsorption toward DA in artificial cerebrospinal fluid based on the adsorption performance and degradation performance. The micromorphologies and physical-chemical properties of MAO-MIXPs were characterized by scanning electron microscopy, differential scanning calorimeter and Fourier transform infrared spectroscopy, and then amount of adsorption was calculated with adsorption equation. Simultaneously, the Brunner-Emmet-Teller (BET) and Langmuir model were simulated. It was found that the adsorption behavior tended to be monolayer adsorption. This new molecularly imprinted polymer demonstrated potential dopamine expression regulation for highly selective recognition, adsorption and degradation of dopamine.
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BACKGROUND@#Pulmonary fibrosis is a respiratory disease caused by the proliferation of fibroblasts and accumulation of the extracellular matrix (ECM). It is known that the lung ECM is mainly composed of a three-dimensional fiber mesh filled with various high-molecular-weight proteins. However, the small-molecular-weight proteins in the lung ECM and their differences between normal and fibrotic lung ECM are largely unknown.@*METHODS@#Healthy adult male Sprague-Dawley rats (Rattus norvegicus) weighing about 150 to 200 g were randomly divided into three groups using random number table: A, B, and C and each group contained five rats. The rats in Group A were administered a single intragastric (i.g.) dose of 500 μL of saline as control, and those in Groups B and C were administered a single i.g. dose of paraquat (PQ) dissolved in 500 μL of saline (20 mg/kg). After 2 weeks, the lungs of rats in Group B were harvested for histological observation, preparation of de-cellularized lung scaffolds, and proteomic analysis for small-molecular-weight proteins, and similar procedures were performed on Group C and A after 4 weeks. The differentially expressed small-molecular-weight proteins (DESMPs) between different groups and the subcellular locations were analyzed.@*RESULTS@#Of the 1626 small-molecular-weight proteins identified, 1047 were quantifiable. There were 97 up-regulated and 45 down-regulated proteins in B vs. A, 274 up-regulated and 31 down-regulated proteins in C vs. A, and 237 up-regulated and 28 down-regulated proteins identified in C vs. B. Both the up-regulated and down-regulated proteins in the three comparisons were mainly distributed in single-organism processes and cellular processes within biological process, cell and organelle within cellular component, and binding within molecular function. Further, more up-regulated than down-regulated proteins were identified in most sub-cellular locations. The interactions of DESMPs identified in extracellular location in all comparisons showed that serum albumin (Alb) harbored the highest degree of node (25), followed by prolyl 4-hydroxylase beta polypeptide (12), integrin β1 (10), apolipoprotein A1 (9), and fibrinogen gamma chain (9).@*CONCLUSIONS@#Numerous PQ-induced DESMPs were identified in de-cellularized lungs of rats by high throughput proteomics analysis. The DESMPs between the control and treatment groups showed diversity in molecular functions, biological processes, and pathways. In addition, the interactions of extracellular DESMPs suggested that the extracellular proteins Alb, Itgb1, Apoa1, P4hb, and Fgg in ECM could be potentially used as biomarker candidates for pulmonary fibrosis. These results provided useful information and new insights regarding pulmonary fibrosis.
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To explore the mechanism of β-carboline alkaloids inhibiting the migration and invasion of SGC-7901 cells and its correlation with FAK gene expression,CCK-8 method was used to determine the inhibitory rate of β-carboline alkaloids on the proliferation of gastric cancer SGC-7901 cells under different concentrations.The effect of β-carboline alkaloids on the migration and invasion of SGC-7901 cells was used by Transwell compartment.Detection of mRNA and protein expression of FAK genes were used by qRT-PCR and Western blot.Then si-FAK-1051 recombinant plasmid was transfected into SGC-7901 cells.FAK gene silencing effect was identified by qRT-PCR and Western blot technique again.Finally,the effects of FAK gene silencing on proliferation and migration of gastric cancer SGC-7901 cells were detected by CCK-8 kit and Transwell chamber assay respectively.With the increase of the concentration ofβ-carboline alkaloids,the inhibitory rate of SGC-7901 cells in human gastric cancer cells increased gradually,with IC5013.364 mg·L-1.The number of SGC-7901 cells of Transwell compartment in the positive experimental group(5-FU,5 mg·L-1) and the β-carboline alkaloids group decreased significantly(P<0.01) and the number of SGC-7901 cells in the β-carboline alkaloids group was significantly lower than that in the positive experimental group(P<0.01).Compared with the blank control group,the mRNA and protein expression level of FAK genes in the positive experimental group was significantly lower than that in the experimental group of β-carboline alkaloids(P<0.05).After transfection of si-FAK-1051 into gastric cancer SGC-7901 cells,the expression of mRNA and protein of FAK gene was significantly down regulated(P<0.05).SGC-7901 cell proliferation and cell migration ability also decreased significantly(P<0.05).β-carboline alkaloids are more effective than 5-FU in inhibiting migration and invasion of gastric cancer SGC-7901 cells,and the mechanism may be related to the inhibition of mRNA and protein expression of FAK gene by β-carboline alkaloids.
Subject(s)
Humans , Alkaloids , Pharmacology , Carbolines , Pharmacology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Focal Adhesion Kinase 1 , Genetics , Gene Expression Regulation, Neoplastic , Gene Silencing , Neoplasm Invasiveness , Stomach Neoplasms , Drug Therapy , PathologyABSTRACT
Objective: To explore the relevant gene, signaling pathway for permanent atrial fibrillation (pAF) occurrence in order to provide the molecular basis of the pathogenesis of pAF. Methods: Our research included in 2 groups: pAF group, n=7 patients and Control group, n=4 healthy subjects with sinus rhythm. Agilent 4x44K microarray was used to analyze the mRNA in left atrium for differential gene expression profile. Based on Gene Ontology, KEGG and Biocarta databases, differentially expressed genes were studied for their relevant function and signaling pathway. Furthermore, the genes with significant differences were verified by quantitative real time PCR (qRT-PCR) in pathological specimen from 5 pAF patients and 5 normal heart donors. Results: The expression profile identified 987 abnormally expressed genes, 567 of them were down-regulated and 420 were up-regulated. 9 genes with significant differences were verified by qRT-PCR in pathological specimen and the changes were similar to microarray; those genes were closely related to pAF by involving left atrium fibrosis, electrical remodeling, inflammation, cellular stress response, metabolism and transcription regulation. GO and Pathway analysis indicated that down-regulated genes were mainly involved in metabolic processes; up-regulated genes had the effects on cellular stress response, immune response and platelet activation. Conclusion: Microarray technology identified some important genes related to pAF occurrence; such genes involved in left atrial structural and functional remodeling via affecting cellular metabolism, inflammation, immune response and thrombogenesis in relevant patients.
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@#This study aimed at investigating the effect of miR-21 on the apoptosis of hepatocellular carcinoma HepG2 cells induced by ursolic acid(UA). MTT assay was used to determine the inhibition effect of ursolic acid on proliferation of hepatocellular carcinoma cells. The expression level of miR-21 in hepatocellular carcinoma cells and the regulation effect of ursolic acid on the expression of miR-21 in HepG2 cells were determined by qPCR. To up-regulate the expression of miR-21, miR-21 mimics were transfected into HepG2 cells. Then MTT assay, flowcytometry(Annexin V-FITC staining), and RT-PCR were used to detect the regulation effects of ursolic acid on the proliferation, apoptosis, and the expression of apoptosis-related genes after miR-21 over-expression. The results showed that the proliferation inhibition effect of ursolic acid on HepG2 cells and the expression level of miR-21 in HepG2 cells were higher than in hepatic cell L-02 and hepatocellular carcinoma SMCC-7721, Bel-7402 cells. So further study was performed in the HepG2 cells. Ursolic acid inhibited the expression of miR-21 in HepG2 cells. And the greatest inhibition effect was at 24 h after treatment with UA. Over-expression of miR-21 partially offset the effects of ursolic acid on the proliferation, apoptosis, and the expression of apoptosis-related genes such as Bcl-2, survivin and Bax after 24 h. The results suggested that apoptosis of hepatocellular carcinoma HepG2 cells could be induced by ursolic acid by down-regulating the expression of miR-21.
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@#To investigate the effects of miRNA-10b(miR-10b)on breast cancer proliferation and apoptosis in MCF-7 and MDA-MB-231, the miR-10b mimics used to increase the endogenous expression of miR-10b, and miR-10b inhibitor used to decrease the endogenous expression of miR-10b, were stably transfected into MCF-7 and MDA-MB-231 breast cancer cells. The expression level of miR-10b was determined by real-time PCR. The effects of miR-10b on proliferation were evaluated by MTT assay, while cell cycle assay and the apoptosis rate were measured by flow cytometry. Bioinformatic software was used to predict the potential targets of miR-10b, and 3′UTR luciferase reporter and qRT-PCR assay were used to verify a direct target of miR-10b. The expression levels of caspase-3 and p21 protein were measured by Western blot. Results confirmed that over-expression of miR-10b could promote the proliferation of breast cancer cells and inhibit the apoptosis by up-regulating the endogenous miR-10b, while the miR-10b inhibitor could restrain the proliferation of breast cancer cells and increase the apoptosis by reducing the endogenous miR-10b. In conclusion, miR-10b could negatively regulate the expression of caspase-3 and p21 by targeting TP53INP1, hence highlighting its potential as an oncogene in breast cancer cells.
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DEC1 is a basic helix-loop-helix(bHLH)transcription factor involved in the regulation of cell prolif-eration;cell differentiation;lymphocytes maturation;circadian rhythms;immune response and response to hypoxia.Recent studies have revealed that the expression of DEC1 is abnormally high in various tumor tissues and cells.In addition;the expression of DEC1 in the tumor tissue is related to the malignancy of various cancer types.This paper;therefore;focuses on the relationship between DEC1 and proliferation;apoptosis;cellular senes-cence;invasion and metastasis of tumor cells;in order to elaborate the role of DEC1 in the pathogenesis and pro-gression of tumor.
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AIM@#Ursolic acid (UA), a pentacyclic triterpenoid, is used as an anti-inflammatory and anti-cancer agent. There were few studies on the effects of UA on differentiation, and this is the first time to elucidate the potential effect and molecular mechanism of UA on inducing differentiation in the human leukemia cell line U937.@*METHODS@#Wright-Giemsa staining, nitroblue tetrazolium reduction assay and flow cytometric analysis were utilized to demonstrate the differentiation of U937 cells induced by UA. Western blotting and immunofluorescence assay were used to investigate the possible mechanism.@*RESULTS@#It was found that UA could induce the differentiation of U937cells and Akt-activity was significantly increased during differentiation. Additionally, LY294002, a PI3K-Akt inhibitor, could block the differentiation of U937 cells induced by UA.@*CONCLUSION@#UA could induce the differentiation of U937 cells by activating the PI3K/Akt pathway, and it could be a potential candidate as a differentiation-inducing agent for the therapy of leukemia.
Subject(s)
Humans , Apoptosis , Cell Proliferation , Leukemia , Genetics , Phosphatidylinositol 3-Kinases , Genetics , Metabolism , Proto-Oncogene Proteins c-akt , Genetics , Metabolism , Signal Transduction , Triterpenes , Pharmacology , U937 CellsABSTRACT
<p><b>OBJECTIVE</b>To investigate a manipulating therapy for treatment of anterior shoulder dislocation in elderly.</p><p><b>METHODS</b>From October 2011 to June 2012,27 elderly patients with anterior shoulder dislocation were treated by extorsion traction and pushing manipulation with fingers, including 7 males and 20 females aged from 65 to 86 years old with an average of 77. The course of disease ranged from 1 h to 1 d. The shoulder manifested square deformity, Dugus signs showed positive, and X-ray displayed anterior shoulder dislocation. Dugus fixation was applied for and removed external fixation at 3 weeks after operation and carried out shoulder functional exercise. Functional evaluation standard on shoulder joint injuries was used for evaluate clinical outcomes.</p><p><b>RESULTS</b>All patients were gained reduction for the first time, and followed up at 3 months after operation, no dislocation occurred. According to functional evaluation standard on shoulder joint injuries, 22 cases got an excellent result,2 cases good,and 1 case moderate.</p><p><b>CONCLUSION</b>Extorsion traction and pushing manipulating therapy for treatment of anterior shoulder dislocation in elderly, which has advantages of simple, convenient, less painful, and can avoid iatrogenic injury, is feasible to widespread.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Manipulation, Orthopedic , Shoulder Dislocation , Therapeutics , Shoulder Joint , Traction , Treatment OutcomeABSTRACT
Marine actinomyces LYG-1 was isolated from marine mud flats in Lianyungang,China.Strain LYG-1 was identified using the methods of morphology,physiological and ehemotaxonomic characterization and 16S rRNA gene sequence analysis.The results showed that strain LYG-1 was a marine variable species of Streptomyces roseosporus.The fermentation broth of strain LYG-1 exhibited conspicuous antitumor activity against HepG2,MCF-7,HCT116 and MDA-MB-231 cell lines,and the IC50 values were defined by MTT method respectively.
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The antitumor effect and the mechanism of action of ursolic acid in A549 cells(human non-small-cell lung cancer cells) was investigated in this paper. Firstly, MTT assay was performed to test whether ursolic acid could inhibit the growth of A549 cells. Secondly, Western blot was utilized to measure the expression level of COX-2 and the activation of MAPKs. The MTI assay revealed that ursolic acid inhibited the growth of A549 cells. The result of Western blot suggested that ursolic acid inhibited the expression of COX-2 and activation of ERK and ERK specific inhibitor PD98059 suppressed the expression of COX-2 synergistically with ursolic acid. Taken together, our data suggest that ursolic acid can suppress LPS-induced COX-2 expression in A549 cells, which could be due to the inhibition of the activation of ERK.
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The generation and activity of serum neuralizing antibody in cynomolgus monkeys and SD rats undergoing long-term toxicity study with antitumor peptides HM-3 were investigated.The rats were administered intravenously with HM-3 at doses of 4.5 mg/kg,13.5 mg/kg,and 40.5 mg/kg for 6 months,and the cynomolgus monkeys were administrated intravenously with HM-3 at doses of 3 mg/kg,9 mg/kg and 27 mg/kg for 6 months,respectively.Anti-HM-3 antibodies and their neutralizing activities in serum samples taken every month after the administrations were determined by ELISA and cell migration assay,respectively.During the long-term administrations,anti-HM-3 antibodies were generated in some SD rats at high and moderate dose groups,and the antibody-neutralizing activities could be detected in a number of these samples (P ＜0.05).However,activity could be detected in very few monkeys (P ＜ 0.05),and the antibody titers were not correlated with the neutralizing activities.Therefore,we conclude that the antigenicity of HM-3 was low,but after long-term administration at high dose,low affinity neutralizing antibody could be generated in small number of samples.
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OBJECTIVE To study risk factors in senile diabetics complicated with urinary tract infections and find out measures to cut down the incidence rate with urinary tract infection.METHODS The age,sex,hospital day,course of diabetes,blood sugar level and catheterization in 181 hospital patients of senile diabetics complicated with urinary tract infections from 2004 to 2007 were analyzed retrospectively.RESULTS The incidence of senile diabetics complicated with urinary tract infections was closely related with age,sex,hospitalization days,course of diabetes,blood sugar level and catheterization.CONCLUSIONS Control measure for risk factors in senile diabetics can actively cut down the incidence rate of urinary tract infection.
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Aim: To construct a prokaryotic expression vector carrying NuBCP-9-tumstatin(74-98) (abbreviated as NT) gene and to obtain the fusion peptide with antitumor activity. Methods: Nucleotide sequences of antitumor peptides, NuBCP-9 and Tumstatin( 74-98), were connected via a linker(G_4S)_3 based on biased codons of E. coli the fused NT gene was reconstructed using SOE PCR, and inserted into pET32a(+) vector, and transformed in E. coli BL21(DE3). After expression, the novel fusion peptide was purified through nickel-affinity chromatogra-phy, Factor Xa digestion and ultrafiltration. Biological activity of the fusion peptide on ECV304 and A549 cells was evaluated by MTT assay. Results: A prokaryotic expression system with NT gene was successfully constructed. The soluble fusion peptide was accounted for approximately 25% when induced by 0. 5 mmol/L IPTG at 30 ℃ for 4 h. The purified fusion peptide could inhibit cell growth of ECV304 and A549 with inhibition rates of 60. 8% and 65. 2% at 20 μmol/L, respectively. Conclusion: A novel fusion peptide with antitumor activity was cloned, expressed and purified.
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Aim: To investigate the mechanism of anti-proliferation, anti-migration and anti-angiogenic effects of tanshinone ⅡA. Methods: In this study, MTT, 2-D/3-D migration, tube formation, PCR, chick embryo chorioallan-toic membrane (CAM) were used to evaluate the anti-proliferation, anti-migration and anti-angiogenic effects of tanshinone ⅡA. Results: Tanshinone ⅡA significantly inhibited the proliferation of human breast cancer line MDA-MB-435 with an IC_(50) of 21 nmol/mL And it is showed that breast cancer cells migration was effectively prevented by tanshinone ⅡA at 5 and 6 nmol/mL in a wound healing assay and a transwell migration assay. In ad-dition, tanshinone ⅡA inhibited the tube formation of newborn cattle aortic endothelial cells( NCAECs) after 2 h co-incubation with MDA-MB-435. These effects were not due to the inhibition of NCAECs proliferation; because tanshinone ⅡA non-selectively inhibited NCAECs growth with an IC_(50) of 124 nmol/mL Tanshinone ⅡA showed dose-dependent inhibitory effects on mRNA expression of VEGF and two transcription factors (HIF-1α/c-Myc) . Tashinone ⅡA was also found to inhibit angiogenic in vivo in the CAM assay. Conclusion: These results suggest that tanshinone ⅡA may exert its anti-proliferation, anti-migration and anti-angiogenic effects through down-regu-lating two transcription factors and VEGF. These novel anti-proliferations, anti-migrations, anti-angiogenic activi-ties of tanshinone ⅡA are likely to contribute to its cancer chemopreventive and therapeutic potential, especially in the treatment of breast cancer.
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<p><b>OBJECTIVE</b>To evaluate the efficacy of transcatheter arterial chemoembolization (TACE) on postoperative recurrence of hepatocellular carcinoma.</p><p><b>METHODS</b>A total of consecutive 823 patients with hepatocellular carcinoma from October 1996 to September 2001 were included in this study. All patients underwent curative liver resection and 126 patients (15.3%) received TACE post operation. The effects of postoperative TACE on the recurrence of hepatocellular carcinoma with different pathological characteristics such as tumor size, tumor capsule, number of nodules, vascular invasion and surgical margin was analyzed.</p><p><b>RESULTS</b>Postoperative TACE had not decreased the recurrence rate in patients with a tumor diameter less than 3 cm. Postoperative TACE increased the disease-free survival for patients with tumor diameter of 3 - 10 cm, positive in alpha fetoprotein (AFP), presented vascular invasion or patients with tumor diameter larger than 10 cm, positive in AFP, multi-nodular, presented vascular invasion, resection margin less than 1 cm.</p><p><b>CONCLUSIONS</b>Postoperative TACE can decrease recurrence rate and prolong the survival of hepatocellular carcinoma patients with high risk factors for recurrence.</p>
Subject(s)
Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Carcinoma, Hepatocellular , Pathology , General Surgery , Therapeutics , Chemoembolization, Therapeutic , Disease-Free Survival , Follow-Up Studies , Hepatectomy , Hepatic Artery , Liver Neoplasms , Pathology , General Surgery , Therapeutics , Neoplasm Recurrence, Local , Neoplasm Staging , Postoperative Care , PrognosisABSTRACT
<p><b>OBJECTIVE</b>To detect the expression of voltage-gated Na(+) channel (NaCh) isoforms in rat sinoatrial node and explore their functions.</p><p><b>METHODS</b>Expressions of NaCh isoforms Nav1.1, Nav1.2, Nav1.3, Nav1.5, Nav1.6 and Nav1.7 in the rat sinoatrial node were detected by immunohistochemistry. The functional roles of the NaChs were tested by observing the effect of tetrodotoxin, a specific blocker of NaChs, on the intrinsic heart rate of isolated rat working heart.</p><p><b>RESULTS</b>The tetrodotoxin- sensitive neuronal isoforms Nav1.1, Nav1.6 and Nav1.7 as well as the tetrodotoxin-resistant cardiac isoform Nav1.5 were present in the rat sinoatrial node, and the neuronal isoforms were more abundant than Nav1.5 (P<0.05). The selective blockade of tetrodotoxin-sensitive isoforms (presumably Nav1.1, Nav1.6 and Nav1.7) by 100 nmol/L tetrodotoxin scarcely affected the intrinsic heart rate (0.5-/+2.9%, P>0.05) while blockade of tetrodotoxin-resistant isoform (presumably Nav1.5) by 2 micromol/L tetrodotoxin resulted in an obvious decline in the intrinsic heart rate (22.1-/+2.1%, P<0.001).</p><p><b>CONCLUSIONS</b>Nav1.1, Nav1.5, Nav1.6 and Nav1.7 are all present in rat sinoatrial node. Although neuronal isoforms are more abundant, Nav1.5 seems to contribute more to activity of the sinoatrial node.</p>
Subject(s)
Animals , Male , Rats , Heart Rate , Physiology , Immunohistochemistry , Ion Channel Gating , Physiology , Nerve Tissue Proteins , Protein Isoforms , Sinoatrial Node , Metabolism , Physiology , Sodium Channels , Tetrodotoxin , PharmacologyABSTRACT
OBJECTIVE@#To investigate the expression of Kv1.3 and Kir2.1 during human monocyte-derived macrophages differentiation into foam cells and their function in foam cells formation.@*METHODS@#The human macrophage-derived foam cells were obtained by incubating macrophages with ox-LDL (30 mg/L) for 60 h. The expression of Kv1.3 and Kir2.1 channels were examined by immunocytochemistry, RT-PCR and Western blot. Effects of channel blockers (rMargatoxin and BaCl2) on the cellular cholesterol metabolism were studied by measuring the cellular contents of total cholesterol (TC), free cholesterol (FC), and cholesterol ester (CE) in the presence or absence of the channel blockers.@*RESULTS@#After incubating macrophages with 30 mg/L ox-LDL for 60 h, the cellular contents of TC, FC and CE were markedly increased and the ratio of CE/TC was raised from (14.4+/-6.8)% to (57.9+/-3.5)% (P0.05); After being blocked specifically (rMargatoxin: 0.1, 10 nmol/L; BaC(12): 75, 125 micromol/L), the cellular contents of TC and CE were markedly reduced without exception and the ratios of CE/TC were all less than 50% (P<0.05).@*CONCLUSION@#Both Kv1.3 and Kir2.1 channels play a critical role in differentiation of macrophages into foam cells and blockage of corresponding potassium channels would prevent the formation of the foam cells.
Subject(s)
Humans , Barium Compounds , Pharmacology , Cell Differentiation , Cells, Cultured , Chlorides , Pharmacology , Cholesterol Esters , Metabolism , Foam Cells , Cell Biology , Macrophages , Cell Biology , Monocytes , Cell Biology , Potassium Channels, Inwardly Rectifying , Scorpion Venoms , PharmacologyABSTRACT
A novel antimicrobial peptide, named as perinerin (GenBank accession No. P84117), was isolated and characterized from Asian marine clamworms, Perinereis aibuhitensis Grube. Perinerin showes powerful and broad activity against both grampositive and gramnegtive bacteria in vitro, especially on Pseudemonas aeruginosa. To obtain large amounts of active perinerin and characterize its main physiochemical features, The perinerin weve expressed in Pichia pastoris. Intact perinerin gene amplified by the modified gene SOEing method(Gene splicing by overlap extension)was cloned into expression vector pPICZ?A and obtained recombinant vector pPICZ?APEN, then pPICZ?APEN was expressed in the Pichia pastoris GS115. The expressed sample was analyzed by TricineSDSPAGE. The results showed that Pichia pastoris was a suitable system producing the secreted form of perinerin. Bioactivity assay showed that the recombinant perinerin had marked antimicrobial effects.