Genetic bistable systems are a large class of important biological systems. Bistability, the capacity to achieve two distinct stable steady states in response to a set of external stimuli, arises within biological systems ranging from the ? phage switch in bacteria to cellular signal transduction pathways in mammalian cells. On the other hand, the increasing experimental evidence in the form of bimodal population distribution has indicated that noise plays a very key role in the switching of bistable systems. However, the physiological mechanism underling noise-induced switching behaviors has not been well explored yet. In the previous work, it has been showed that noise can induce coherent switch for a single genetic Toggle switch system. Here the influence of several kinds of noises (including intracellular and extracellular noises) on synchronized switch was investigated for a multicell gene toggle switch network system. It has been found that multiplicative noises resulting from fluctuations of either synthesis or degradation rates and the additive noise within each cell (they altogether are called as intracellular noises) all can induce the synchronized switch, and that there exists an optimal noise intensity such that the synchronized switch is optimally achieved and the amplification factor has the maximal value. On the other hand, the extracellular noises arising from the stochastic fluctuation of the cellular environment, not only brings about the synchronized switch, but also enhances it by suppressing intracellular fluctuations when the intracellular noises are not enough to induce the synchronized switch. Finally, the influence of the diffusive rate of signal molecules affected by noise on the dynamics of the multicellular system was also investigated, showing that the larger the diffusive rate, the better the synchronized switch and the larger the amplification factor.

AIMTo study the effect of proanthocyanidins on the COX-2 enzyme activity and COX-2 protein expression in LPS-induced RAW264.7 cells.

METHODSAfter being pretreated with different concentrations of proanthocyanidins for 30 min, and then 1 mg x L(-1) LPS for 9 h, the effect of proanthocyanidins on the activity of COX-2 enzyme in RAW264.7 cells was analysed by radioimmunoassay (RIA). After being pretreated with different concentrations of proanthocyanidins for 30 min, and then 1 mg x L(-1) LPS for 9 h, the effects of proanthocyanidins on the expressions of COX-2 mRNA and protein in RAW264.7 cells were analysed by RT-PCR and Western blotting.

RESULTSThe activity of COX-2 enzyme was not inhibited by proanthocyanidins (0. 8, 4 and 20 mg x L(-1), P > 0.05 vs LPS group), but the activity of COX-2 enzyme was significantly inhibited by 10 micromol x L(-01) NS-398 (P < 0.01 vs LPS group). The expression of COX-2 mRNA was inhibited by proanthocyanidins (0. 8, 4 and 20 mg x L(-1)). The expression of COX-2 protein was inhibited by proanthocyanidins (4 and 20 mg x L(-1)).

CONCLUSIONProanthocyanidins had no effect on the activity of COX-2 enzyme in LPS-induced RAW264. 7 cells. Proanthocyanidins inhibited significantly the expression of COX-2 mRNA and protein in LPS-induced RAW264.7 cells.

Animals ; Anti-Inflammatory Agents ; pharmacology ; Cell Line ; Cyclooxygenase 2 ; biosynthesis ; genetics ; Lipopolysaccharides ; Macrophages, Peritoneal ; cytology ; enzymology ; Mice ; Proanthocyanidins ; pharmacology ; RNA, Messenger ; biosynthesis ; genetics

OBJECTIVETo investigate the inhibitory effects of bcl-xl antisense oligodeoxynucleotides (ASODN) on growth and gene expression of human nasopharyngeal carcinoma (NPC) in nude mice.

METHODSCNE-2Z cell line was implanted subcutaneously into nude mice. Twenty four h after implantation, bcl-xl ASODN and mismatch control oligonucleotides (SCODN) were injected subcutaneously into nude mice, respectively. The tumor volume and weight were measured twice weekly. The histopathological changes of the tumors were observed by HE staining. RT-PCR and Western-blot were performed for bcl-xl gene expression.

RESULTSGrowth of NPC was significantly inhibited in the ASODN therapy group as compared with that in the control group (P < 0.01). The growth inhibitory rate was 41.7% in the ASODN group and 19.0% in the SCODN group. The expression level of bcl-xl mRNA and protein was decreased in the ASODN group, whereas in the SCODN group there was no significant difference in contrast with saline-treated control group.

CONCLUSIONOur findings suggest that bcl-xl antisense oligodeoxynucleotides results in marked inhibition of NPC growth in nude mice. It may be a novel treatment approach for human nasopharyngeal carcinoma.

Animals ; Female ; Humans ; Male ; Mice ; Mice, Inbred BALB C ; Nasopharyngeal Neoplasms ; drug therapy ; pathology ; Neoplasm Transplantation ; Oligonucleotides, Antisense ; therapeutic use ; Proto-Oncogene Proteins c-bcl-2 ; antagonists & inhibitors ; genetics ; RNA, Messenger ; analysis ; Transplantation, Heterologous ; bcl-X Protein

OBJECTIVETo find out the vector ability and function of Nosopsyllus wualis leizhouensis in the transmitting plague.

METHODSIn T: 19 degrees C +/- 1 degrees C, RH: 85% +/- 5%, data regarding the vector ability as cluster spreading, single flea spreading, single flea transmitting plague to single animal, formative bacterial embolus and infection fleas life-span through experiments was gathered.

RESULTSThe rate of infection on fleas was 94.64%, with 100% transmission rate of colony to spread, and 30% from single flea spreading to single animal. In the experiment of single flea transmission, all of the 388 rattus loseas were bitten by the fleas with bacterial, but only 9 animals were characteristically infected with the transmission potential, vector efficiency, survival potential of embolus, vector index as 0.360, 0.257, 0.868 and 0.223 respectively. The mean survive days of infected flea feed with blood were 17.58 (1 - 58), and the mean survive days of hunger infected flea were 7.25 (1 - 16). Formative bacterial embolus days were 8.80 (2 - 16) and the rate of embolus flea was 78.12%.

CONCLUSIONNosopsyllus wualis leizhouensis could serve as vector and important in the mode of plague transmittion.

Animals ; Female ; Insect Vectors ; microbiology ; Male ; Plague ; transmission ; Rats ; Siphonaptera ; microbiology

OBJECTIVE: To analyze the effects of alterations in the expressions of methyltransferase on protein expression profiles in human nasopharyngeal carcinoma (NPC) cells and enrich the differential signaling pathways. METHODS: The total protein was extracted from -knockout cell line CNE1 and the wild-type cell line CNE1, and the differentially expressed proteins were screened by tandem mass tag (TMT) labeled protein quantification technique and tandem mass spectrometry. GO analysis was used to annotate and enrich the differentially expressed proteins, and the KEGG database was used to enrich and analyze the pathways of the differential proteins. RESULTS: With a fold change (FC)≥1.2 and < 0.05 as the screening standard, 2049 differentially expressed proteins were identified in CNE1 cells, among which 904 were up-regulated and 1145 were down-regulated. GO functional annotation results indicated that knockout caused characteristic changes in multiple biological processes (cell processes and regulation, cell movement, metabolic processes, and biosynthesis of cellular components), molecular functions (catalytic activity and molecular binding, transcription factor activity), and cellular components (cell membrane, organelle, macromolecular complex). KEGG analysis showed that the differentially expressed proteins were involved in an array of signaling pathways closely related to tumors, including MAPK, PI3K-Akt, Ras, Rap1, mTOR, Hippo, HIF-1, Wnt, AMPK, FoxO, ErbB, P53 and JAK-STAT. CONCLUSIONS knockout significantly changes the protein expression characteristics of NPC cells and affects a number of signal pathways closely related to tumors. The results provide evidence for investigation of the pathogenesis and therapeutic target screening of NPC.

OBJECTIVETo investigate the appropriate therapy for treating recurrent vulvovaginal candidiasis (RVVC).

METHODSIndividual consolidated and maintenance therapy were chosen according to fungal culture of vaginal secretion and antifungal drug sensitivity per month as one therapy duration. Drugs were used orally and vaginally together to consolidate the therapy. Oral drugs were fluconazole (0.15 qw after 0.15 q3d for 2 times) or ketoconazole (0.2, bid for 3 days ) or itraconazole (0.2 bid for 3 days ). After Nystain (400 000 unit qn for 7 days ) or clotrimazole(0.1 qn for 7 days) or amphotericin B (0.01 qn for 6 days ) being vaginally used, Living preparation of lactobacillus (0.25 qn for 5 days) was vaginally used. The therapy was continued for 2 to 5 therapy durations after the symptoms disappeared with negative fungal culture.

RESULTSAmong 80 cases of RVVC, C. albicans was mostly detected (74%), C. glabrata was 20%. The susceptivity to candidas of oral agents revealed that the sensitive rare of ketoconazole, fluconazole and itraconazole were (91.3%), (81.3%) and (62.5%), respectively. As for vaginal agents, nystain and amphotericin B were 100% sensitive, clotrimazole was 92.5%sensitive, miconazole was 55.0% sensitive. The remote cure of 3 and 6 therapy durations after discontinuing for 12 months was 78.9% and 90.4%

CONCLUSIONThe predominant pathogen in RVVC is C. albicans. The effective measures to cure RVVC are to choose sensitive drugs for individual consolidated, maintenance therapy and restore vaginal acidic environment.

Adult ; Antifungal Agents ; therapeutic use ; Candida albicans ; drug effects ; Candidiasis, Vulvovaginal ; diagnosis ; drug therapy ; microbiology ; Drug Resistance, Fungal ; Female ; Humans ; Microbial Sensitivity Tests ; Middle Aged ; Recurrence ; Young Adult

Marine fungi are important members of the marine microbiome, which have been paid growing attention by scientists in recent years. The secondary metabolites of marine fungi have been reported to contain rich and diverse compounds with novel structures (Chen et al., 2019). Aspergillus terreus, the higher level marine fungus of the Aspergillus genus (family of Trichocomaceae, order of Eurotiales, class of Eurotiomycetes, phylum of Ascomycota), is widely distributed in both sea and land. In our previous study, the coral-derived A. terreus strain C23-3 exhibited potential in producing other biologically active (with antioxidant, acetylcholinesterase inhibition, and anti-inflammatory activity) compounds like arylbutyrolactones, territrems, and isoflavones, and high sensitivity to the chemical regulation of secondary metabolism (Yang et al., 2019, 2020; Nie et al., 2020; Ma et al., 2021). Moreover, we have isolated two different benzaldehydes, including a benzaldehyde with a novel structure, from A. terreus C23-3 which was derived from Pectinia paeonia of Xuwen, Zhanjiang City, Guangdong Province, China.
Acetylcholinesterase/metabolism* ; Animals ; Anthozoa/microbiology* ; Anti-Inflammatory Agents/pharmacology* ; Aspergillus/chemistry* ; Benzaldehydes/pharmacology* ; Mice ; RAW 264.7 Cells ; Signal Transduction

OBJECTIVETo investigate the effect of tanshinone IIA (TanIIA) on the expression of tissue factor (TF) and matrix metalloproteinase-12 (MMP-12) in RAW264.7 cells and explore the possible mechanism.

METHODSRAW 264.7 cells were incubated with ox-LDL in the presence or absence of different concentrations of tanshinone IIA. At the end of the incubation, the cell proliferation was assessed by MTT assay, and superoxide dismutase (SOD) activity and malondialdehyde (MDA) and TF concentrations in the supernatant were detected by xanthine oxidase method, thiobarbituric acid method and ELISA, respectively. Western blotting was employed to determine MMP-12 expression in the cells.

RESULTSThe cell proliferation was dose-dependently inhibited by TanIIA. SOD activity in the supernatant was increased significantly, while the MDA and TF concentration and MMP-12 expression in cells decreased after treatment of the cells with different concentrations of TanIIA.

CONCLUSIONTanIIA inhibits the cell proliferation and TF and MMP-12 expressions in RAW264.7 cells stimulated by ox-LDL, and these effects may be related with the anti-oxidation property of TanIIA.

Animals ; Cell Line ; Diterpenes, Abietane ; pharmacology ; Lipoproteins, LDL ; adverse effects ; Macrophages ; drug effects ; secretion ; Malondialdehyde ; metabolism ; Matrix Metalloproteinase 12 ; metabolism ; Mice ; Thromboplastin ; metabolism

OBJECTIVETo isolate, culture and identify a dog periodontal ligament stem cells (PDLSC) line in vitro.

METHODSThe adult dog periodontal ligament cells were isolated by limited dilution of culture cell for single cell clone. Cells originated from one of these clones were assessed through colony-forming efficiency and immunocytochemistry assay and alkaline phosphatase stain was used to identify the source of adult dog periodontal stem cells, at the same time, PDLSC were induced with mineralizatin solution and was found to have long protrude like an osteoblast. Differentiation of PDLSC were assessed. Mineralized potential was studied by Von-Kossa staining.

RESULTSThe dog PDLSC expressed STRO-1, which was the marker of mesenchymal stem cells. Also Vimentin, osteoblast-like marker alkaline phosphatase and Collagen-I expressed weakly. Cells were clonegenic, highly proliferative cells and capable of differentiating into osteoblasts/cementoblasts.

CONCLUSIONThe evidence suggests that the cultured cells were stem cells from adult dog periodontal ligament.

Adult ; Adult Stem Cells ; Alkaline Phosphatase ; Animals ; Cell Culture Techniques ; Cell Differentiation ; Cells, Cultured ; Dental Cementum ; Dogs ; Humans ; Mesenchymal Stromal Cells ; Osteoblasts ; Periodontal Ligament ; Stem Cells

OBJECTIVETo screen out related microRNAs in keloid tissue, and identify their effect on the proliferation of keloid fibroblasts.

METHODS8 cases of keloid tissue and 8 cases of normal skin tissue were collected as specimens. The differently expressed miRNA in keloid tissue from normal skin tissue were screened out with gene chip( Exiqon company), which was validated with quantitative real-time PCR. Then miRNA mimics was transfected into keloid fibroblasts line to stimulate high expression of mature miRNA in cells. The effect on the proliferation of fibroblasts in keloid was tested by Edu.

RESULTS(1) A total of 17 differently expressed microRNAs were found, including miR-199a-5p. (2) The expression of miR-199a-5p had been verified by qRT-PCR to be down-regulated in keloid, which was consistent with the result of array. (3) The positive rate of EdU in miR-199a-5p mimics transfected group and negative control group was (20.72 +/- 2.50)% and (27.68 +/- 4.92)%, respectively. The proliferative rate of keloid fibroblasts turned down in miR-199a-5p-transfected group (t = 2.183, P = 0.047). Besides that, the cell cycle changed after transfection. The percentage of S and G2/M phase in miR-199a-5p mimics transfected group was 33.93 +/- 1.30 and 10.87 +/- 0.80, respectively, while it was 31.39 +/- 0.79 and 9.27 +/- 0.46 in negative control group, and the difference was statistically significant.

CONCLUSIONS(1) The miRNA expression profile is different between keloid and normal skin; (2) The expression of miR-199a-5p is down-regulated in keloid and miR-199a-5p can affect the cell cycle and suppress proliferation of keloid fibroblasts. It indicateds that miR-199a-5p may be involved in regulating fibroblastic proliferation.

Cell Proliferation ; Cells, Cultured ; Down-Regulation ; Female ; Fibroblasts ; metabolism ; Gene Expression Profiling ; Humans ; Keloid ; genetics ; metabolism ; pathology ; Male ; MicroRNAs ; genetics ; metabolism