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According to the theory of 'Xingben Dazao' of Psoralea corylifolia Linn. (BL), the susceptible syndromes and biomarkers of liver injury caused by BL were searched. Rat models of kidney-yin deficiency syndrome (M_yin) and kidney-yang deficiency syndrome (M_yang) were established, and all animal experimental operations and welfare following the provisions of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Traditional Chinese Medicine (No. YFYDW2020017). The results showed that BL significantly decreased the body weight, water intake, and urine weight of M_yin rats and increase the organ indexes of the liver, testis, adrenal gland, and spleen and the expression of alanine aminotransferase (ALT). Meantime, BL significantly increased the urine weight of M_yang rats and decreased the expression of ALT and aspartate aminotransferase (AST). Hematoxylin and eosin (HE) staining showed that BL could aggravate inflammatory infiltration of hepatocytes in rats with M_yin and alleviate liver injury in rats with M_yang. Metabolomics identified 17 BL co-regulated significant differential metabolic markers in M_yin and M_yang rats. Among them, 8 metabolites such as glutamine, quinolinate, biliverdin, and lactosylceramide showed opposite trends, mainly involving cysteine and methionine metabolism, tyrosine metabolism, tryptophan metabolism, purine metabolism, sphingolipid metabolism, glycerol phospholipid metabolism, glutamine metabolism, and other pathways. M_yin/M_yang may be the susceptible constitution of BL for liver damage or protection, which may be related to the regulation of amino acid metabolism and sphingolipid metabolism. The study can provide some experimental data support for the safe and accurate use of BL in the clinical practice of traditional Chinese medicine.
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OBJECTIVE@#To investigate the antileukemia activity of phosphatidylinositol-3 kinase (PI3K) inhibitor ZSTK474 on human leukemia cell line U937.@*METHODS@#MTT, soft agar assay, flow cytometric analysis and western blot were used to detect the effect of ZSTK474 on U937 cell proliferation, tumorigenicity, cell cycle, cell apoptosis and phosphorylation levels of the key factor of PI3K/AKT pathway. Chou-Talalay method was used to evaluate the combination of ZSTK474 with Cytarabine or Homoharringtonine.@*RESULTS@#PI3K inhibitor ZSTK474 could inhibit the proliferation and tumorigenicity of U937 cell, induce G@*CONCLUSION@#ZSTK474 can inhibit the pathway of PI3K/AKT, ZSTK474 alone or in combination with Homoharringtonine shows potential antileukemia activity on U937 cells.
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Humans , Apoptosis , Cell Line, Tumor , Cell Proliferation , Glycogen Synthase Kinase 3 beta , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Triazines , U937 CellsABSTRACT
Objective:To explore the effectiveness and feasibility of the machine learning models based on radiomics in the diagnosis of pituitary prolactin macroadenoma.Methods:Totally 122 histologically proven pituitary macroadenoma patients, including 70 cases of pituitary prolactin macroadenoma (PPM) and 52 cases of non-pituitary prolactin macroadenoma (NPPM), were retrospectively recruited. The differences of age, sex, serum prolactin value, bleeding, cystic degeneration and Knosp classification were compared between PPM and NPPM. The pre-processing, delineation of the region of interest and feature extraction of the preoperative axial contrast-enhanced T 1WI image were performed in the 3Dslicer software. The optimal feature set were selected by least absolute shrinkage and selection operator. All patients were randomly divided into the training group ( n=85) and the test group ( n=37) at a ratio of 7∶3. The models were established in the training group by logistic regression and support vector machine (SVM), and then verified by the test group. ROC curves were drawn respectively, and specificity, sensitivity, accuracy and area under the ROC curve (AUC) were calculated. Results:The age [(38±12) years vs . (43±11) years], gender ratio (male/female 50 cases/20 cases vs . 14 cases/38 cases) and prolactin value [366.00 (117.75, 1 156.25)μg/L vs . 47.25 (32.68, 62.40) μg/L] of patients with PPM and NPPM were statistically different ( P<0.05). The AUC values of logistic regression and SVM in the training group were 0.936 and 0.946, and the AUC values of the test group were 0.768 and 0.774, respectively. The diagnostic accuracy of logistic regression and SVM in the training group were 88.2% and 91.8%, and the accuracy of the test group were 73.0% and 77.8%. Conclusion:The machine learning models based on the radiomics can predict the pituitary prolactin macroadenoma well with a high accuracy.
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Applying poly(ADP-ribose) polymerase inhibitors (PARPi) to the treatment of cancers with homologous recombination deficiency (HRDness) has been a great advance in the field of molecular therapeutics. However, in the clinic patients lacking the specific mutations or developing reverse mutations in the process of PARPi treatment may not benefit from PARPi monotherapy. Therefore, targeting homologous recombination (HR) repair with molecularly targeted agents is becoming an attractive research focus and is raising the concept of "chemical HRDness". HR repair is an evolutionarily conserved and extensively regulated process that employs sister chromatids as the template to repair DNA double-strand breaks with high fidelity. In addition to directly targeting HR components, modulation of regulatory pathways controlling HR repair is effective in achieving the "HRDness" phenotype; this includes modulation of the cell cycle checkpoint regulatory pathway, the phosphatidylinositol 3-kinase (PI3K) signaling pathway, the chromatin remodeling pathway, etc. Targeting HR repair can not only result in "synthetic lethality" when combined with PARPi, but also sensitizes cancers to traditional radio/chemotherapy and novel immunotherapy. In this review we describe the HR repair pathway and its regulatory pathways, summarize the preclinical and clinical outcomes of targeting HR repair, discuss the remaining problems in this field and provide a prospective on its application in tumor therapy.
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Objective@#To investigate the differential expression of serum-and-glucocorticoid-inducible-kinase-2 (SGK2) in hepatocellular carcinoma (HCC) and normal liver tissues and the related mechanism mediating signal transduction of GSK-3 β / β catenin in HCC cells.@*Methods@#Twenty pairs of matched HCC and normal tissues were collected and the situation of expression of SGK2 mRNA was detected by real-time fluorescence quantitative PCR. Western blot was used to detect the levels of SGK2 protein in human HCC cell lines (Huh-7, SMMC-7721) and normal human liver cell line (L02). SGK2 siRNA was used to transfect human HCC cell lines (SMMC-7721 and Huh-7), and then the protein expression levels of GSK-3 β/ β - catenin was successfully detected with the above-mentioned transfected cell line by western blot. Measurement data were expressed as mean ± standard deviation (±s), and the Student t -test was used as the statistical method.@*Results@#SGK2 mRNA expression was up-regulated in all 20 HCC samples than that of the expression of matched normal liver tissues. SGK2 protein levels were significantly higher in Huh-7 and SMMC-7721 than normal human liver cell lines (P < 0.01). The downregulation of SGK2 expression in human HCC cell lines (SMMC-7721 and Huh-7) had inhibited the expression of unphosphorylated GSK-3 β. In addition, the downregulation of SGK2 expression in HCC cell lines had decreased the dephosphorylation of β - catenin to prevent degradation of the β - catenin proteasome.@*Conclusion@#SGK2 is overexpressed in HCC and mediates GSK-3β/β- catenin signaling in HCC cells.
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Lateral flow immunochromatography is a real-time detection technology based on chromatographic membranes and nano-markers. Because of its simplicity, fastness and low cost, it is widely used in many fields, such as biomedicine, pathogen detection and food safety. Traditional lateral-flow immunochromatography relies on the naked eye, that has lower sensitivity, and can only provide qualitative or semi-quantitative results. With the application of different types of markers and sensitive detection equipment, lateral flow immunochromatography has enabled the quantitative and multi-component detection of analytes. The purpose of this paper is to describe the latest research progress of lateral flow immunochromatographic detection systems in combination with nano-labels, chromatographic membranes and band detectors, with a view to providing a basis for the selection of markers, improvement of chromatography membrane materials and detection instruments.
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OBJECTIVE To explore the anti-atherosclerotic effect of the extract of traditional Chinese medicine formula Dan-yi-lian(DYL)and the related mechanism.METHODS Atherosclerosis(AS)mod-el was established in ApoE(-/-)mice with a western diet. The mice were orally administered with differ-ent doses of DYL or vehicle daily for 28 d.The anti-atherosclerotic effect was evaluated by measuring the aortic atherosclerotic lesion area and media thickness with ultrasound imaging and histological sec-tions staining method. The effect on blood lipid was investigated by determining TC, TG, LDL, HDL, Apo-A1, Apo-B, etc. The anti-oxidative activity as assessed by determining the level of SOD, CAT, GSH,GSH-Px and MDA.Western blot analysis was used to determine the effect on ICAM-1,VCAM-1, MMP-2 and TNF-α. RESULTS In Dan-yi-lian administered ApoE(-/-)mice,the plaque area and media thickness were significantly reduced. Meanwhile, serum TC, TG, LDL and Apo-B were decreased, in contrast to the increased level of HDL and Apo-A1.On the other hand,SOD,CAT,GSH and GSH-Px were increased, while MDA was reduced in liver homogenate. In addition, the expression of ICAM-1, VCAM-1,MMP-2 and TNF-α was obviously inhibited by Dan-yi-lian.CONCLUSION Dan-yi-lian exhibit-ed potent anti-athero-sclerotic efficacy,in which the lipid-regulating,anti-oxidative and anti-inflammato-ry mechanism might be involved.
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Objective To investigate the effect and molecular mechanisms of phosphatidylinositol-3 kinase(PI3K)inhibitor ZSTK474 on human melanoma A375 cells in vitro. Methods The effect of ZSTK474 on the proliferation of A375 cells was deter?mined by MTT assay.Flow cytometric analysis was carried out to examine effect of ZSTK474 on the cell cycle of A375 cells.Western-blot was conducted to evaluate the effect of ZSTK474 on the expression of the cell cycle related proteins,cyclin B1 and cdc2.Chou-Talalay method was used to evaluate the combination of ZSTK474 with PD0332991.Results In the MTT assay,ZSTK474 inhibited the proliferation of A375 cells in a dose-dependent manner with the IC50value of 1.535 μmol/L.Furthermore,ZSTK474 arrested the cell cycle progression of the A375 cells at the G2/M phase via downregulating the expression of cyclin B1 and cdc2 at 1 and 5 μmol/L. In the synergistic assay,the combination of ZSTK474 with PD0332991 in the ratio 8×IC50 ZSTK474:1×IC50 PD0332991showed a synergistic ef?fect,with the combination index(CI)values of 0.463 ± 0.113,0.658 ± 0.009 and 0.941 ± 0.034 for ED50、ED75and ED90,respectively. Conclusion ZSTK474 could inhibit the proliferation of A375 cells and arrest the cell cycle at the G2/M phase.The combination of ZSTK474 with PD0332991 could exert a synergistic effect.The precent result has revealed that the PI3K inhibitor ZSTK474 is likely to be applied alone or in combination with the CDK4/6 inhibitor PD0332991 for the human melanoma therapy.
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Objective: To study the effect of different concentration of plumbum (Pb) stress on antioxidase activity in different organs of Rabdosia Rubescentis Folium (RRF, the aerial parts of Rabdosia rubescens) and their growth, and provide the basis for the growth regulation of R. rubescens under Pb pollution. Methods: Ramets hydroponic test was performed with the concentration of Pb (0, 135, 270, and 540 mg/L) and the stress time (50 d), taking superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), relative growth rate (RGR), biomass, and Pb mass fraction as indexes, the determination of antioxidant enzyme activity was performed with spectrophotometer, and plant's Pb mass fraction of plant with plasma emission spectrometer was carried out. Results: Under Pb stress at different concentration (135-540 mg/L), SOD activity in the leaves and the roots of R. rubescens was increased first and then decreased, but no significant difference on SOD activity in the leaves at each level; POD activity in the leaves under Pb concentration (135-270 mg/L) was no significant difference compared with the control group, but was significantly increased at the concentration of 540 mg/L, while the POD activity in the roots under Pb stress at various concentration was significantly lower than that of the control group which gradually went up after declined; CAT activity in the leaves increased significantly with Pb concentration rising, and the activity in the root decreased gradually with Pb concentration rising. No significant effect on the growth of R. rubescens at low and mid levels of Pb concentration (135 and 270 mg/L), but under high concentration (540 mg/L) of Pb treatment compared with the control group, the biomass and RGR decreased by 33.33% and 46.59%, respectively. Conclusion: The stimulus response is different obviously for antioxidase activities between the leaves and roots of R. rubescens; Through fitting model predictive analysis, the critical Pb concentration is 301.99 mg/L, which decreases RGR by 10% compared with control group (P < 0.01). RRF shows a strong resistance to Pb stress.
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Anti-platelet specific antibody is one of the most important reasons leading to thrombocytopenia and megakaryocyte dysmaturity. The detection of platelet autoantibodies is an important step in the diagnosis of ITP because of the absence of specific clinic feature. The monoclonal antibody-specific immobilization of platelet antigens (MAIPA) has become a "gold standard" for determination of PLT specific antibody, which has high specificity and low sensitivity. However, this assay is time-consuming and tedious work. Routine use of this assay in hospital is difficult. Recently, some researches reporded the cytometric bead assay that has higher sensitivity than MAIPA, and so probably solves the problem of time-consuming partly, that also can use different beads for simultaneous detection. This review focuses on recent progress of the cytometric bead assay.
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Humans , Antibodies , Antibodies, Monoclonal , Antigens, Human Platelet , Blood Platelets , Megakaryocytes , ThrombocytopeniaABSTRACT
The seeds of Rabdosia rubescens were as the materials to research the impacts of different lead (Pb2+) concentrations(0, 135, 270, 540, 1 080 mg x L(-1)) on seed germination and seedling growth. The results show that: Low concentration of lead had no obvious effect on early germination of the seed, the germination vigor and germination speed were lightly higher but not significantly differed at the level of Pb concentration 135 mg x L(-1) with control group; Mid-high concentration of Pb solution (270-1 080 mg x L(-1)) significantly inhibited the seed germination and seedling growth, which reduced the seed germination rate, germination vigor, germination index, embryo root length and shoot length, growth index with increasing of Pb concentrations. There was a inhibitory effect on embryo shoot length and root length at mid-high lead concentrations stress, and stronger inhibitory effect on root , which was more sensitive than shoot to Pb stress(P < 0.05). Pb bioaccumulation coefficient (BC) was 0.76-2.59, increased with concentration of Pb; Pb enrichment in seedling mainly caused the growth inhibition. The fitting model predictive analyses show, the critical concentration of Pb, which causes the germination rate and biomass fresh weight reducing 10%, is 195.18, 101.65 mg x L(-1).
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Germination , Isodon , Lead , Toxicity , Seedlings , Seeds , Stress, PhysiologicalABSTRACT
Objective To explore clinical treatment of postoperative hyponatremia of pituitary tumor. Meth-ods 32 cases of patients with postoperative hyponatremia of pituitary tumor were randomly divided into control group and treatment group. The control group(n = 15) was treated with routine western medicine, and the treatment group(n = 17) was treated with water limited and sodium supplemented based on the control group. The clinical effect was observed between control group and treatment group. Results The clinical effect in the treatment group was signifi-cantly higher than that of the control group(P <0.05). Conclusion The treatment of water limited and sodium sup-plemented on postoperative hyponatremia of pituitary tumor is better.
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Objective To collect the basic information on publications in Chinese Journal of Perinatal Medicine,and understand the current situation and set the goals for the future. Methods Information on all publications in this journal from 1998 to 2007 was collected.The distribution of all publications,Price Index and relative data were analyzed. Results There were 1368 publications altogether during the past 10 years.The first six kinds of papers were original articles(508,31.7%),short articles(258,18.9%),case reports(194,14.2%),reviews(122,8.9%),experimental studies(90,6.6%)and brief communications(83,14.2%).47.9% of all publications were from Beijing,Guangdong and Shanghai.The first three areas who had the most submissions were Beijing,Shandong and Guangdong in 2007.The citation frequency analysis showed that 708 publications were cited at 1east once and only two were cited over 80 times.53.4% of all cited publications were original articles and experimental studies. Conclusions Original articles and short articles are the two main types of publications in this journal,however original articles and experimental studies contributed to half of the publications being cited.Publications in this journal are focused in few areas and this might be related to the number of submissions.
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<p><b>OBJECTIVE</b>To investigate the effectiveness of phosphorothioate multidrug resistance gene 1 (MDR1) antisense oligodeoxynucleotides (MDR1-AS) suppressing MDR1 expression in multidrug-resistant glioma cell line C6/adr.</p><p><b>METHODS</b>The glioma cell line C6/adr served as the tested model in vitro, MDR1-AS (5'-CTCCATCACCACCTC-3'), complementary to the -9- +6 sequence of first exon, was synthesized and phosphorothioate-modified. As control of sequence specificity, MDR1-S (5'-GAGGTGGTGA TGGAG-3') was used. Both antisense and sense oligodeoxynucleotides were transduced to C6/adr cells by lipofectin. The cytotoxity of MDR1-AS was tested using morphological observation and 3- (4,5-dimethylthiazol-2-yl) -2, 5-diphenyl tetrazolium bromide assay. Semi-quantitative reverse transcription polymerase chain reaction was used to monitor the expression levels of the MDR1 mRNA in the different groups. The positive rate of the MDR1 gene product P glycoprotein (P-gp) was determined by flow cytometry assessment.</p><p><b>RESULTS</b>No cytotoxicity of MDR1-AS was observed. The MDR1 mRNA expression level was decreased from 106% to about 30.44% 48 h after MDR1-AS treatment. The P-gp positive rate of MDR1-AS treated C6/adr cells decreased from 100% to 32.77%, with that of C6/adr cells considered as 100%.</p><p><b>CONCLUSIONS</b>MDR1-AS can effectively inhibit MDR1 expression in the C6/adr cell line at both the mRNA and protein level, and may be an alternative treatment of drug-resistant gliomas.</p>
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Humans , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Genetics , Cell Line, Tumor , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Glioma , Genetics , Metabolism , Oligodeoxyribonucleotides, Antisense , Pharmacology , RNA, Messenger , GeneticsABSTRACT
<p><b>OBJECTIVE</b>To investigate the efficiency of a peptide nucleic acid (PNA) delivery system by using liposome via PNA-DNA hybrids and to test the inhibitive action of antisense PNA on expression of multidrug resistance (MDR) related P-glycoprotein (P-gp) in human neuroblastoma cell line SK-N-SH.</p><p><b>METHODS</b>Two antisense PNAs were designed targeting at MDR-1 mRNA and then combined with partially complement DNAs respectively. The hybrids were delivered into cells using cationic liposome. The transfection efficiency, expression of P-gp and MDR-1 mRNA, intracellular adarimycin (ADM) were measured by flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR), and high performance liquid chromatography (HPLC).</p><p><b>RESULTS</b>Transfection of PNA increased the cell average fluorescence intensity significantly and the extent of increase was dependent on the concentration of PNA. After being transfected by both PNAs, P-gp expression of SK-N-SH cells decreased significantly and the intracellular ADM level was increased by about 3 times. The level of MDR-1 mRNA expression slightly decreased after transfection, but no statistical significance was observed.</p><p><b>CONCLUSIONS</b>PNA can be delivered into tumor cells in form of PNA-DNA hybrids by cationic liposome. Properly designed antisense PNA can inhibit MDR related P-gp expression of SK-N-SH cells efficiently and specifically.</p>
Subject(s)
Animals , Humans , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Genetics , Drug Resistance, Multiple , Genetics , Nervous System Neoplasms , Metabolism , Neuroblastoma , Metabolism , Oligonucleotides, Antisense , Pharmacology , Peptide Nucleic Acids , Pharmacology , RNA, Messenger , Genetics , Transfection , Tumor Cells, CulturedABSTRACT
<p><b>OBJECTIVE</b>To evaluate the animal model of the multidrug resistant glioma cell line C6/adr for further in vivo studies.</p><p><b>METHODS</b>The rat glioma cells C6 and multidrug resistance cells C6/adr were cultured in vitro and implanted into the brain of S-D rats. After implantation, all these animals were examined continually with magnetic resonance imaging (MRI) and histological examination. The growth procedure of intracranial implanted glioma and the survival span of the animal model were evaluated. The statistical analysis was made between the survival data of the two cell lines.</p><p><b>RESULTS</b>The symptoms of intracranial hypertension did not occur until 4 weeks after inoculation. The MRI findings of the implanted glioma in the rat brain were much earlier than the abnormal behavior observed. Pathological results after inoculation demonstrated the MRI findings. The two cell lines had similar growth characteristics and no significant differences in survival times.</p><p><b>CONCLUSION</b>These results suggest that by means of MRI and histology the growth procedure of the implanted glioma in vivo be successfully observed. All these data will proved to be a useful basis for study of glioma in vivo.</p>
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Animals , Male , Rats , Antibiotics, Antineoplastic , Pharmacology , Brain Neoplasms , Pathology , Disease Models, Animal , Doxorubicin , Pharmacology , Drug Resistance, Multiple , Genetics , Drug Resistance, Neoplasm , Genetics , Glioma , Pathology , Magnetic Resonance Imaging , Random Allocation , Rats, Sprague-Dawley , Tumor Cells, CulturedABSTRACT
<p><b>OBJECTIVE</b>In order to explore the existence of SARS coronavirus (Co-V) and/or its RNA in sewage of hospitals administered SARS patients.</p><p><b>METHODS</b>A novel electropositive filter was used to concentrate the SARS-CoV from the sewage of two hospitals administered SARS patients in Beijing, including twelve 2,500 ml sewage samples from the hospitals before disinfection, and ten 25,000 ml samples after disinfection; as well as cell culture, RT-PCR and sequencing of gene to detect and identify the viruses from sewage.</p><p><b>RESULTS</b>There was no live SARS-CoV detected in the sewage in this study. The nucleic acid of SARS-CoV had been found in the 12 sewage samples before disinfection from both hospitals by semi-nested PCR. After disinfection, SARS-CoV RNA could only be detected from the samples from the 309th Hospital, and the others were negative.</p><p><b>CONCLUSION</b>It provides evidence that there is no live SARS-Cov in the sewage from hospitals with SARS patients though SARS-CoV RNA can be detected.</p>
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Humans , Hospitals , Nucleocapsid , RNA, Viral , Reverse Transcriptase Polymerase Chain Reaction , Severe acute respiratory syndrome-related coronavirus , Genetics , Severe Acute Respiratory Syndrome , Virology , Sewage , VirologyABSTRACT
<p><b>OBJECTIVE</b>To establish a drug-resistance cell line of human glioma mediated by MGMT.</p><p><b>METHODS</b>Simulated the clinical usage of BCNU to establish a BCNU-resistant human glioma subline by cyclic exposing the U251 parent cells to a constant concentration of BCNU. The resistance index and the expression of MGMT mRNA of U251/BCNU were detected and compared the difference of in vitro proliferation between U251 and U251/BCNU.</p><p><b>RESULTS</b>A subline--U251/BCNU was successfully established in about 4-month culture, which had a stable resistance to BCNU. U251/BCNU cells showed 17-fold higher resistance to BCNU than did U251 cells by MTT assay, while U251/BCNU cells expressed MGMT mRNA. The doubling time of U251 and U251/BCNU had no statistical difference.</p><p><b>CONCLUSION</b>A drug-resistance cell line of human glioma mediated by MGMT is established, which could provide experimental basis for further studies on the resistance mechanism and reversal methods of glioma chemotherapy.</p>