Adrenergic beta-Agonists ; therapeutic use ; Aged ; Androstadienes ; therapeutic use ; Cholinergic Antagonists ; therapeutic use ; Fluticasone ; Humans ; Male ; Middle Aged ; Scopolamine Derivatives ; therapeutic use ; Silicosis ; drug therapy ; Tiotropium Bromide

OBJECTIVESTo investigate whether antisense human telomerase reverse transcriptase (hTERT) could inhibit the activity of telomerase and the proliferation of K562 cells.

METHODSThe antisense plasmid was constructed by reverse insertion of hTERT PCR product into plasmid pLNCX-neo. Then the constructed plasmid was introduced into K562 cells by liposomes-mediated DNA transfection. The inhibition effects of telomerase on the proliferation of K562 cells were analyzed by MTT and colony formation assay, the telomerase activity of K562 cells by TRAP-PCR ELISA methods.

RESULTSThe growth rate of antisense hTERT transfected K562 cells was significantly lower than those of the controls, and the colony formation capacity of the transfected cells decreased significantly (P < 0.01), the colony number is (100.33 +/- 7.57)/10(3) cells, (92.67 +/- 5.86)/10(3) cells and (50.33 +/- 6.11)/10(3) cells for control K562 cells, K562 neo cells and antisense hTERT transfected HL60 cells, respectively. The telomerase activity of antisense hTERT transfected K562 cells was significantly inhibited.

CONCLUSIONThe expression of an antisense sequence to the mRNA sequence of telomerase protein subunit can inhibit the activity of telomerase, slow the cell growth and inhibit the capacity of colony formation of K562 cells.

Cell Division ; drug effects ; Humans ; K562 Cells ; Plasmids ; genetics ; RNA, Antisense ; genetics ; pharmacology ; RNA, Messenger ; genetics ; Telomerase ; drug effects ; genetics ; metabolism ; Transfection

OBJECTIVEThe structure-activity relationship between traditional Chinese medicine (TCM) compounds and antibacterial activity was studied by chemoinformatics approach.

METHODCytoscape and its plug-in ChemViz were applied to compute the 2D chemical structure similarity and topological parameter TPSA (topological molecular polar surface area), which measures cell permeability of chemicals, between TCM compounds and clinical antibacterials. The overall degree of structure similarity was then calculated and represented by E-value for the eight categories of TCM compounds and the known antibacterials.

RESULTOur results indicated that flavonoids showed good structural similarity with antibacterials and appropriate cell permeability, compared with those of the TCM compounds of the other categories. As flavonoids were featured by good drug safety, it suggested that they can be regarded as the preferred lead compounds skeleton structure source for further antibacterials synthesis.

CONCLUSIONThe application of chemoinformatics helps explore the structure-activity relationship between TCM compounds and the antibacterial activity and search for suitable antibacterial lead compounds skeleton structure source.

Anti-Bacterial Agents ; chemistry ; pharmacology ; Informatics ; methods ; Medicine, Chinese Traditional ; Software ; Statistics as Topic ; Structure-Activity Relationship

OBJECTIVEDesign a convenient and stable eye refractometer based on the theory of blur circle.

METHODSAnalyze the retinal blur circle in both Emsly reduced eye model and Liou & Brennan 1997 eye model by ZEMAX. Design the coefficients including PD (pupil diameter) and NO' (length between node point and fovea) with the purpose of improving the accuracy. At last, compare the clinical optometry data from this refractor with the data obtained from optometry hospital in Wenzhou.

RESULTSThe blur circle diameters are nearly the same in both reduced eye model and the Liou & Brennan 1997 eye model. With the PD = 4 mm and NO' = 20 mm, the refractor shows a fine accuracy in optometry. The paired t test shows that the myopia group and the astigmatism axial direction group have no statistical difference between the data from the blur circle refractor and the hospital (P > 0.05), while the astigmatism degree group has the result of P = 0.41 which may be caused by the poor cooperation of pediatric patients. 80% of the astigmatism degree data differ from the data from the hospital in less than 0.75D.

CONCLUSIONThe blur circle refractor, with the features of convenience and fine accuracy, is promised to be a new style of refractometer in the future.

Astigmatism ; Equipment Design ; Fovea Centralis ; Humans ; Models, Statistical ; Myopia ; Ophthalmoscopes ; Ophthalmoscopy ; Refraction, Ocular ; Visual Acuity

This study is to investigate the protective effect of quercetin against adriamycin-induced cardiotoxicity and its mechanism. The cardiotoxicity was induced by intraperitoneal injection of adriamycin (ADR) at a single dose of 20 mg x kg(-1). Mice were randomly divided into 5 groups (n=20): normal control group, ADR 20 mg x kg(-1) group, quercetin (50, 100, and 200 mg x kg(-1) groups, intragastric administration, once a day, for 7 days before ADR administration). The health conditions, electrocardiogram, activity of iNOS, SOD and LDH, levels of NO and MDA in serum or tissue homogenate, the ultrastructure and the expression of p53 protein in cardiac tissue of mice were observed. Compared with the normal control group, ADR decreased the amplitude of ECG's R wave (P < 0.001), increased the incidence of arrhythmia (to 60%), injured myocardial ultrastructure, increased the activity of LDH and iNOS, and levels of NO and MDA, decreased the activity of SOD, and increased the expression of p53 (P < 0.001). Compared with ADR 20 mg x kg(-1) group, the quercetin decreased the levels of LDH, iNOS, NO and MDA, increased the activity of SOD, restored the amplitude of R wave, decreased the incidence of arrhythmia and p53 expression (P < 0.001 , P < 0.01 or P < 0.05), and markedly reduced the myocardial ultrastructure injury. Quercetin had protective effect against adriamycin-induced cardiotoxicity. The mechanism may be related to its enhancing myocardial SOD activity, decreasing iNOS activity and inhibiting myocardial apoptosis.
Animals ; Apoptosis ; drug effects ; Arrhythmias, Cardiac ; blood ; chemically induced ; metabolism ; pathology ; Doxorubicin ; Female ; L-Lactate Dehydrogenase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Mice ; Myocardium ; metabolism ; ultrastructure ; Myocytes, Cardiac ; metabolism ; ultrastructure ; Nitric Oxide ; blood ; Nitric Oxide Synthase Type II ; blood ; Protective Agents ; pharmacology ; Quercetin ; pharmacology ; Random Allocation ; Superoxide Dismutase ; metabolism ; Tumor Suppressor Protein p53 ; metabolism

Objective To explore the molecular mechanism of pituitary growth hormone adenoma cell proliferation.Methods Functional growth hormone-secreting pituitary adenoma(fGH-PA)tissue samples were collected from 12 patients with acromegaly.The exchange protein 1 directly activated by cAMP(Epac1)mRNA expression levels in fGH-PA tissues and rat RGC-5,MMQ and GH3 cells were determined by qPCR.The expression levels of Epac1 in fGH-PA tissues were determined by immunohistochemistry.Western blot was used to determine the expression levels of Epac1 in MMQ and GH3 cells.Overexpression or knockdown of Epac1,or knockdown of cAMP response element-binding protein(CREB)in GH3 cells,cell cycle changes were determined by flow cytometry,cell proliferation ability was determined by CCK-8 assay,and the expression levels of p-CREB,CREB,Cyclin D1,CDK2 and p21 in cells were determined by Western blot.Results qPCR and immunohistochemistry results showed that the expression levels of Epac1 mRNA and protein in fGH-PA tissues were significantly higher than those in adjacent normal tissues(P<0.05).qPCR and Western blot results showed that compared with RGC-5 cells,the expression levels of Epac1 mRNA and protein in MMQ and GH3 cells were significantly increased(P<0.05).After overexpres-sion of Epac1 in GH3 cells,compared with the Control group,the proportion of cells in G0/G1 phase and S phase in the Epac1-OE group were significantly reduced(P<0.05),and the proportion of cells in G2/M phase were significantly increased(P<0.05);the cell prolifera-tion ability were significantly enhanced(P<0.05);the expression levels of p-CREB and Cyclin D1 in cells were significantly increased(P<0.05),the expression levels of CDK2 and p21 were significantly decreased(P<0.05),while there was no significant change in the expression level of CREB between the two groups(P>0.05).After knockdown of Epac1 or knockdown of CREB in GH3 cells,all of the above results were reversed(P<0.05).Conclusion The overexpression of Epac1 in pituitary growth hormone adenoma cells can up-regulate the levels of p-CREB in cells,and promote adenoma cells to pass through G1/S phase checkpoint,resulting in cell cycle checkpoint disorder and massive proliferation,but it does not affect the expression levels of CREB.

OBJECTIVES: To explore the characteristics of immune function of healthy full-term infants at the age of 3 months, and to analyze the relationship of immune function with feeding pattern and sex. METHODS: A total of 84 healthy full-term infants born in four hospitals in Beijing and Hohhot, China were prospectively recruited. Their feeding patterns remained unchanged within 4 months after birth. They were divided into a breast-feeding group and a milk powder feeding group according to their feeding patterns. At the age of 3 months after birth, peripheral venous blood samples of the two groups were collected to evaluate cellular immunity and humoral immunity and perform routine blood test. The laboratory indices were compared between infants with different feeding patterns and sexes. RESULTS: Compared with the milk powder feeding group, the breast-feeding group had significantly lower proportion of T cell second signal receptor CD28, immunoglobulin M, and proportion and absolute count of neutrophils ( CONCLUSIONS Sex has no significant effect on the proportion of lymphocyte subsets in 3-month-old full-term infants, but feeding patterns are associated with the proportion of CD28
Breast Feeding ; CD8-Positive T-Lymphocytes ; Female ; HLA-DR Antigens ; Humans ; Infant ; Lymphocyte Activation ; Male ; Prospective Studies

Metabolic syndrome has become a global epidemic that adversely affects human health. Both genetic and environmental factors contribute to the pathogenesis of metabolic disorders; however, the mechanisms that integrate these cues to regulate metabolic physiology and the development of metabolic disorders remain incompletely defined. Emerging evidence suggests that SWI/SNF chromatin-remodeling complexes are critical for directing metabolic reprogramming and adaptation in response to nutritional and other physiological signals. The ATP-dependent SWI/SNF chromatin-remodeling complexes comprise up to 11 subunits, among which the BAF60 subunit serves as a key link between the core complexes and specific transcriptional factors. The BAF60 subunit has three members, BAF60a, b, and c. The distinct tissue distribution patterns and regulatory mechanisms of BAF60 proteins confer each isoform with specialized functions in different metabolic cell types. In this review, we summarize the emerging roles and mechanisms of BAF60 proteins in the regulation of nutrient sensing and energy metabolism under physiological and disease conditions.
Chromatin Assembly and Disassembly ; DNA-Binding Proteins ; metabolism ; Disease ; Humans ; Metabolism ; Nutrients ; metabolism ; Signal Transduction

Aim To explore the mechanism of Fluspirilene inhibiting HCC through decreasing the expression of Akt.Methods The difference of mRNA was verified by the test of protein expression between Fluspirilenc treatment group and control group by HCC experiment in vivo and vitro, including Western blot, IHC after mRNA array.Results Akt expression was lower in Fluspirilene treatment group than that in control group by mRNA array.Protein expression of Akt, phosphorylate-CDK2 and phos- phorylate-Rb decreased massively in Fluspirilene treatment group in a concentration-dependent manner in HepG2 and Huh7 cells by Western blotting compared with those in control group.Declined expression of phosphorylate-Akt was proved in a concen- tration-dependent manner in xenograft tumor tissues in Fluspirilene treatment group compared with that in control group in IHC test.Conclusions Fluspirilene inhibits HCC by decreasing significantly the protein expression of Akt, phosphorylat-Akt, phos- phorylate-CDK2 and phosphorylate-Rb.

Objective: Present study investigated the mechanism of heart failure associated with coronavirus infection and predicted potential effective therapeutic drugs against heart failure associated with coronavirus infection. Methods: Coronavirus and heart failure were searched in the Gene Expression Omnibus (GEO) and omics data were selected to meet experimental requirements. Differentially expressed genes were analyzed using the Limma package in R language to screen for differentially expressed genes. The two sets of differential genes were introduced into the R language cluster Profiler package for gene ontology (GO) and Kyoto gene and genome encyclopedia (KEGG) pathway enrichment analysis. Two sets of intersections were taken. A protein interaction network was constructed for all differentially expressed genes using STRING database and core genes were screened. Finally, the apparently accurate treatment prediction platform (EpiMed) independently developed by the team was used to predict the therapeutic drug. Results: The GSE59185 coronavirus data set was searched and screened in the GEO database, and divided into wt group, ΔE group, Δ3 group, Δ5 group according to different subtypes, and compared with control group. After the difference analysis, 191 up-regulated genes and 18 down-regulated genes were defined. The GEO126062 heart failure data set was retrieved and screened from the GEO database. A total of 495 differentially expressed genes were screened, of which 165 were up-regulated and 330 were down-regulated. Correlation analysis of differentially expressed genes between coronavirus and heart failure was performed. After cross processing, there were 20 GO entries, which were mainly enriched in virus response, virus defense response, type Ⅰ interferon response, γ interferon regulation, innate immune response regulation, negative regulation of virus life cycle, replication regulation of viral genome, etc. There were 5 KEGG pathways, mainly interacting with tumor necrosis factor (TNF) signaling pathway, interleukin (IL)-17 signaling pathway, cytokine and receptor interaction, Toll-like receptor signaling pathway, human giant cells viral infection related. All differentially expressed genes were introduced into the STRING online analysis website for protein interaction network analysis, and core genes such as signal transducer and activator of transcription 3, IL-10, IL17, TNF, interferon regulatory factor 9, 2'-5'-oligoadenylate synthetase 1, mitogen-activated protein kinase 3, radical s-adenosyl methionine domain containing 2, c-x-c motif chemokine ligand 10, caspase 3 and other genes were screened. The drugs predicted by EpiMed's apparent precision treatment prediction platform for disease-drug association analysis were mainly TNF-α inhibitors, resveratrol, ritonavir, paeony, retinoic acid, forsythia, and houttuynia cordata. Conclusions: The abnormal activation of multiple inflammatory pathways may be the cause of heart failure in patients after coronavirus infection. Resveratrol, ritonavir, retinoic acid, amaranth, forsythia, houttuynia may have therapeutic effects. Future basic and clinical research is warranted to validate present results and hypothesis.
Betacoronavirus ; COVID-19 ; Computational Biology ; Coronavirus Infections/complications* ; Gene Expression Profiling ; Gene Ontology ; Heart Failure/virology* ; Humans ; Pandemics ; Pneumonia, Viral/complications* ; SARS-CoV-2