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Journal articles on the topic 'Inhibit'

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Published: 4 June 2021
Last updated: 20 February 2023

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1

Katiyar, Santosh K. "Hsp90 Inhibitor Can Inhibit UV Carcinogenesis." Journal of Investigative Dermatology 135, no. 4 (April 2015): 945–47. http://dx.doi.org/10.1038/jid.2014.504.

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2

Ferrarelli, L. K. "Inhibit PIM to inhibit PI3K." Science Signaling 9, no. 449 (October 11, 2016): ec237-ec237. http://dx.doi.org/10.1126/scisignal.aal1638.

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3

Balasubramanian, Sujata, Meiyun Fan, Angela F. Messmer-Blust, Chuan H. Yang, Jill A. Trendel, Jonathan A. Jeyaratnam, Lawrence M. Pfeffer, and Deborah J. Vestal. "The Interferon-γ-induced GTPase, mGBP-2, Inhibits Tumor Necrosis Factor α (TNF-α) Induction of Matrix Metalloproteinase-9 (MMP-9) by Inhibiting NF-κB and Rac Protein." Journal of Biological Chemistry 286, no. 22 (April 18, 2011): 20054–64. http://dx.doi.org/10.1074/jbc.m111.249326.

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Matrix metalloproteinase-9 (MMP-9) is important in numerous normal and pathological processes, including the angiogenic switch during tumor development and tumor metastasis. Whereas TNF-α and other cytokines up-regulate MMP-9 expression, interferons (IFNs) inhibit MMP-9 expression. We found that IFN-γ treatment or forced expression of the IFN-induced GTPase, mGBP-2, inhibit TNF-α-induced MMP-9 expression in NIH 3T3 fibroblasts, by inhibiting MMP-9 transcription. The NF-κB transcription factor is required for full induction of MMP-9 by TNF-α. Both IFN-γ and mGBP-2 inhibit the transcription of a NF-κB-dependent reporter construct, suggesting that mGBP-2 inhibits MMP-9 induction via inhibition of NF-κB-mediated transcription. Interestingly, mGBP-2 does not inhibit TNF-α-induced degradation of IκBα or p65/RelA translocation into the nucleus. However, mGBP-2 inhibits p65 binding to a κB oligonucleotide probe in gel shift assays and to the MMP-9 promoter in chromatin immunoprecipitation assays. In addition, TNF-α activation of NF-κB in NIH 3T3 cells is dependent on Rac activation, as evidenced by the inhibition of TNF-α induction of NF-κB-mediated transcription by a dominant inhibitory form of Rac1. A role for Rac in the inhibitory action of mGBP-2 on NF-κB is further shown by the findings that mGBP-2 inhibits TNF-α activation of endogenous Rac and constitutively activate Rac can restore NF-κB transcription in the presence of mGBP-2. This is a novel mechanism by which IFNs can inhibit the cytokine induction of MMP-9 expression.
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4

&NA;. "Inhibit pancreatic tumour growth with PKD inhibitor." Oncology Times UK 6, no. 5 (May 2009): 4. http://dx.doi.org/10.1097/01434893-200905000-00003.

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5

Xu, W., C. Gatto, and M. A. Milanick. "Positive charge modifications alter the ability of XIP to inhibit the plasma membrane calcium pump." American Journal of Physiology-Cell Physiology 271, no. 3 (September 1, 1996): C736—C741. http://dx.doi.org/10.1152/ajpcell.1996.271.3.c736.

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Exchange inhibitory peptide (XIP; RRLLFYKYVYKRYRAGKQRG) is the shortest peptide that inhibits the plasma membrane Ca pump at high Ca (A. Enyedi, T. Vorherr, P. James, D. J. McCormick, A. G. Filoteo, E. Carafoli, and J. T. Penniston, J. Biol. Chem. 264: 12313-12321, 1989). Sulfosuccinimidyl acetate (SNA)-modified XIP does not inhibit the Ca pump; SNA neutralizes the positive charge on Lys at positions 7, 11, and 17. Peptide 2CK-XIP (RRLLFYRYVYRCYCAGRQKG) inhibits the pump, but the iodoacetamido-modified peptide does not inhibit. Three peptide analogues, in which 7, 11, and 17 were Ala, Cys, or Lys, inhibited about as well as XIP. SNA modification of these analogues (each with 1 Lys) did not inhibit. SNA modification of 2CK-XIP results in a peptide that does not inhibit; thus position 19 is important. Our results suggest that it is critical that position 19 be positively charged, that positions 7, 11, and 17 are important contact points between XIP and the Ca pump (with at least one positively charged), and that, whereas it is not essential that residues 12 and 14 be positive, they cannot be negative.
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6

Yan, Huifang, Xiwei Peng, Hao Xu, Jiahuan Zhu, and Changqing Deng. "Inhibition of Aortic Intimal Hyperplasia and Vascular Smooth Muscle Proliferation and Extracellular Matrix Protein Expressions by Astragalus–Angelica Combination." Evidence-Based Complementary and Alternative Medicine 2018 (August 13, 2018): 1–15. http://dx.doi.org/10.1155/2018/1508637.

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VSMC proliferation and ECM deposition always resulted in intimal hyperplasia. Astragalus–Angelica combination has a protective effect on the cardiovascular system. The inhibition effect of different Astragalus–Angelica combination on the hyperplastic intima after vascular balloon injury in rats was investigated in this study. Astragalus–Angelica combination can inhibit the intima hyperplasia after balloon injury, in which a 1:1 ratio shows excellent results. Astragalus–Angelica combination can enhance the expression of smooth muscleα-actin (SMа-actin) and inhibit the expression of proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin E, collagen I (Col-I), fibronectin (FN), and matrix metallopeptidase-9 (MMP-9) in hyperplastic intima, suggesting that Astragalus–Angelica combination can inhibit the intimal hyperplasia of blood vessels in rats. The mechanism is related to the inhibition of PI3K/Akt signaling pathway activation and thereby inhibits the phenotypic transformation and cell proliferation of VSMCs and thus inhibits the extracellular matrix (ECM) deposition of vascular wall during intimal hyperplasia.
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7

BISWAS, Swati, Manju RAY, Sanjoy MISRA, D. P. DUTTA, and Subhankar RAY. "Selective inhibition of mitochondrial respiration and glycolysis in human leukaemic leucocytes by methylglyoxal." Biochemical Journal 323, no. 2 (April 15, 1997): 343–48. http://dx.doi.org/10.1042/bj3230343.

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The effect of methylglyoxal on the oxygen consumption of mitochondria of both normal and leukaemic leucocytes was tested by using different respiratory substrates and complex specific artificial electron donors and inhibitors. The results indicate that methylglyoxal strongly inhibits mitochondrial respiration in leukaemic leucocytes, whereas, at a much higher concentration, methylglyoxal fails to inhibit mitochondrial respiration in normal leucocytes. Methylglyoxal strongly inhibits ADP-stimulated α-oxoglutarate and malate plus NAD+-dependent respiration, whereas, at a higher concentration, methylglyoxal fails to inhibit succinate and α-glycerophosphate-dependent respiration. Methylglyoxal also fails to inhibit respiration which is initiated by duroquinone and cannot inhibit oxygen consumption when the N,N,N´,N´-tetramethyl-p-phenylenediamine by-pass is used. NADH oxidation by sub-mitochondrial particles of leukaemic leucocytes is also inhibited by methylglyoxal. Lactaldehyde, a catabolite of methylglyoxal, can exert a protective effect on the inhibition of leukaemic leucocyte mitochondrial respiration by methylglyoxal. Methylglyoxal also inhibits l-lactic acid formation by intact leukaemic leucocytes and critically reduces the ATP level of these cells, whereas methylglyoxal has no effect on normal leucocytes. We conclude that methylglyoxal inhibits glycolysis and the electron flow through mitochondrial complex I of leukaemic leucocytes. This is strikingly similar to our previous studies on mitochondrial respiration, glycolysis and ATP levels in Ehrlich ascites carcinoma cells [Ray, Dutta, Halder and Ray (1994) Biochem. J. 303, 69–72; Halder, Ray and Ray (1993) Int. J. Cancer 54, 443–449], which strongly suggests that the inhibition of electron flow through complex I of the mitochondrial respiratory chain and inhibition of glycolysis by methylglyoxal may be common characteristics of all malignant cells.
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8

King, Frank W., and Emma Shtivelman. "Inhibition of Nuclear Import by the Proapoptotic Protein CC3." Molecular and Cellular Biology 24, no. 16 (August 15, 2004): 7091–101. http://dx.doi.org/10.1128/mcb.24.16.7091-7101.2004.

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ABSTRACT We report here that the normal cellular protein CC3/TIP30, when in excess, inhibits nuclear import in vitro and in vivo. CC3 binds directly to the karyopherins of the importin β family in a RanGTP-insensitive manner and associates with nucleoporins in vivo. CC3 inhibits the nuclear import of proteins possessing either the classical nuclear localization signal or the M9 signal recognized by transportin. CC3 also inhibits nuclear translocation of transportin itself. Cells modified to express higher levels of CC3 have a slower rate of nuclear import and, as described earlier, show an increased sensitivity to death signals. A mutant CC3 protein lacking proapoptotic activity has a lower affinity for transportin, is displaced from it by RanGTP, and fails to inhibit nuclear import in vitro and in vivo. Together, our results support a correlation between the ability of CC3 to form a RanGTP-resistant complex with importins, inhibit nuclear import, and induce apoptosis. Significantly, a dominant-negative form of importin β1 shown previously to inhibit multiple transport pathways induces rapid cell death, strongly indicating that inhibition of nuclear transport serves as a potent apoptotic signal.
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9

Sicher, S. C., M. A. Vazquez, and C. Y. Lu. "Inhibition of macrophage Ia expression by nitric oxide." Journal of Immunology 153, no. 3 (August 1, 1994): 1293–300. http://dx.doi.org/10.4049/jimmunol.153.3.1293.

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Abstract Bacterial LPS inhibits the expression of Ia by macrophages stimulated by IFN-gamma. We now present the following observations that suggest a causal relationship between nitric oxide (NO) and this inhibition of Ia expression: 1) NO production precedes inhibition of Ia, 2) the ability of LPS to inhibit Ia expression by IFN-gamma stimulated macrophages is correlated in a dose-dependent fashion with NO production, 3) Ia expression is restored if NO production is inhibited by NG-monomethyl-L-arginine or culturing the macrophages in L-arginine-free medium, and 4) exogenous NO inhibits IFN-gamma-stimulated Ia expression. Taken together these experiments indicate that NO inhibits macrophage expression of Ia. Furthermore, the following studies showed that inhibition of Ia by NO was not due to macrophage death: trypan blue exclusion, macrophage adhesion, conversion of the tetrazolium dye (MTT) to its formazan by a functioning electron transport system, and phagocytosis of IgG opsonized SRBCs. By inhibiting Ia expression, NO may inhibit Ag-presentation to T cells, secretion of IFN-gamma by these T cells, and ultimately inhibit the IFN-gamma-dependent production of NO synthetase. This inhibitory mechanism may prevent excessive NO formation and tissue injury.
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10

Gilbert, R. L., C. J. Blunt, D. R. Harper, D. J. Jeffries, and R. A. J. Mcllhinney. "Effect of Inhibitors of Protein Myristoylation on Varicella-Zoster Virus Replication." Antiviral Chemistry and Chemotherapy 5, no. 3 (June 1994): 182–86. http://dx.doi.org/10.1177/095632029400500307.

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Inhibitors of N-myristoyltransferase (NMT) have been shown to inhibit retrovirus replication, notably that of the human immunodeficiency virus (HIV), where the absence of protein myristoylation inhibits viral replication. The authors have assayed 14 compounds derived from myristic acid for activity against varicella-zoster virus (human herpesvirus 3; VZV) by plaque reduction assay. Seven showed cytotoxicity and of the others, two failed to inhibit VZV replication. One of these was N-myristoylglycinaldiethylacetal (GoA), which has been reported to be active against HIV. 12-(methoxy) dodecanoic acid (13-oxamyristic acid), which has also been reported to inhibit HIV replication, was found to inhibit VZV replication but was cytotoxic at high concentrations. The greatest inhibitory effect without apparent toxicity was induced by 2-hydroxytetradecanoic acid and its enantiomers. The results of these assays provide further evidence that inhibitors of NMT have potential as antiviral agents against the many viruses with myristoylated proteins.
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11

Gershburg, Edward, Ke Hong, and Joseph S. Pagano. "Effects of Maribavir and Selected Indolocarbazoles on Epstein-Barr Virus Protein Kinase BGLF4 and on Viral Lytic Replication." Antimicrobial Agents and Chemotherapy 48, no. 5 (May 2004): 1900–1903. http://dx.doi.org/10.1128/aac.48.5.1900-1903.2004.

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ABSTRACT The human cytomegalovirus (HCMV) homolog of the Epstein-Barr virus (EBV) protein kinase (PK), UL97, is inhibited by maribavir (1263W94) and selected indolocarbazoles. Here we show that only one of these indolocarbazoles (K252a), but not maribavir, inhibits autophosphorylation of the EBV PK, BGLF4. However, maribavir and another indolocarbazole, NGIC-I, do inhibit EBV DNA synthesis, suggesting that although these last compounds inhibit both HCMV and EBV, they seem to operate through differ-ent pathways.
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12

Kopecky-Bromberg, Sarah A., Luis Martínez-Sobrido, Matthew Frieman, Ralph A. Baric, and Peter Palese. "Severe Acute Respiratory Syndrome Coronavirus Open Reading Frame (ORF) 3b, ORF 6, and Nucleocapsid Proteins Function as Interferon Antagonists." Journal of Virology 81, no. 2 (November 15, 2006): 548–57. http://dx.doi.org/10.1128/jvi.01782-06.

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ABSTRACT The severe acute respiratory syndrome coronavirus (SARS-CoV) is highly pathogenic in humans, with a death rate near 10%. This high pathogenicity suggests that SARS-CoV has developed mechanisms to overcome the host innate immune response. It has now been determined that SARS-CoV open reading frame (ORF) 3b, ORF 6, and N proteins antagonize interferon, a key component of the innate immune response. All three proteins inhibit the expression of beta interferon (IFN-β), and further examination revealed that these SARS-CoV proteins inhibit a key protein necessary for the expression of IFN-β, IRF-3. N protein dramatically inhibited expression from an NF-κB-responsive promoter. All three proteins were able to inhibit expression from an interferon-stimulated response element (ISRE) promoter after infection with Sendai virus, while only ORF 3b and ORF 6 proteins were able to inhibit expression from the ISRE promoter after treatment with interferon. This indicates that N protein inhibits only the synthesis of interferon, while ORF 3b and ORF 6 proteins inhibit both interferon synthesis and signaling. ORF 6 protein, but not ORF 3b or N protein, inhibited nuclear translocation but not phosphorylation of STAT1. Thus, it appears that these three interferon antagonists of SARS-CoV inhibit the interferon response by different mechanisms.
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13

Diwan, Prerna, Jonathan J. Lacasse, and Luis M. Schang. "Roscovitine Inhibits Activation of Promoters in Herpes Simplex Virus Type 1 Genomes Independently of Promoter-Specific Factors." Journal of Virology 78, no. 17 (September 1, 2004): 9352–65. http://dx.doi.org/10.1128/jvi.78.17.9352-9365.2004.

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ABSTRACT Flavopiridol, roscovitine, and other inhibitors of Cyclin-Dependent Kinases (CDK) inhibit the replication of a variety of viruses in vitro while proving nontoxic in human clinical trials of their effects against cancer. Consequently, these and other Pharmacological CDK inhibitors (PCIs) have been proposed as potential antivirals. Flavopiridol potently inhibits all tested CDKs and inhibits the transcription of most cellular and viral genes. In contrast, roscovitine and other purine PCIs inhibit with high potency only CDK1, CDK2, CDK5, and CDK7, and they specifically inhibit the expression of viral but not cellular genes. The levels at which purine PCIs inhibit gene expression are unknown, as are the factors which determine their specificity for expression of viral but not cellular genes. We show herein that roscovitine prevents the initiation of transcription of herpes simplex virus type 1 (HSV-1) genes but has no effect on transcription elongation. We further show that roscovitine does not inhibit the initiation or elongation of cellular transcription and that its inhibitory effects are specific for promoters in HSV-1 genomes. Therefore, we have identified a novel biological activity for PCIs, i.e., their ability to prevent the initiation of transcription. We have also identified genome location as one of the factors that determine whether the transcription of a given gene is inhibited by roscovitine. The activities of roscovitine on viral transcription resemble one of the antiherpesvirus activities of alpha interferon and could be used as a model for the development of novel antivirals. The genome-specific effects of roscovitine may also be important for its development against virus-induced cancers.
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14

Wu, Miaomiao, Samir El Qaidi, and Philip Hardwidge. "SseL Deubiquitinates RPS3 to Inhibit Its Nuclear Translocation." Pathogens 7, no. 4 (November 7, 2018): 86. http://dx.doi.org/10.3390/pathogens7040086.

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Many Gram-negative bacterial pathogens use type III secretion systems to deliver virulence proteins (effectors) into host cells to counteract innate immunity. The ribosomal protein S3 (RPS3) guides NF-κB subunits to specific κB sites and plays an important role in the innate response to bacterial infection. Two E. coli effectors inhibit RPS3 nuclear translocation. NleH1 inhibits RPS3 phosphorylation by IKK-β, an essential aspect of the RPS3 nuclear translocation process. NleC proteolysis of p65 generates an N-terminal p65 fragment that competes for full-length p65 binding to RPS3, thus also inhibiting RPS3 nuclear translocation. Thus, E. coli has multiple mechanisms by which to block RPS3-mediated transcriptional activation. With this in mind, we considered whether other enteric pathogens also encode T3SS effectors that impact this important host regulatory pathway. Here we report that the Salmonella Secreted Effector L (SseL), which was previously shown to function as a deubiquitinase and inhibit NF-κB signaling, also inhibits RPS3 nuclear translocation by deubiquitinating this important host transcriptional co-factor. RPS3 deubiquitination by SseL was restricted to K63-linkages and mutating the active-site cysteine of SseL abolished its ability to deubiquitinate and subsequently inhibit RPS3 nuclear translocation. Thus, Salmonella also encodes at least one T3SS effector that alters RPS3 activities in the host nucleus.
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15

Cao, Y., C. Chen, J. A. Weatherbee, M. Tsang, and J. Folkman. "gro-beta, a -C-X-C- chemokine, is an angiogenesis inhibitor that suppresses the growth of Lewis lung carcinoma in mice." Journal of Experimental Medicine 182, no. 6 (December 1, 1995): 2069–77. http://dx.doi.org/10.1084/jem.182.6.2069.

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We have found that two chemokines, recombinant gro-alpha and gro-beta, specifically inhibit growth factor-stimulated proliferation of capillary endothelial cells in a dose-dependent manner, whereas gro-gamma has no inhibitory effect. In vivo, gro-beta inhibits blood vessel formation in the chicken chorioallantoic membrane assay. It is sufficiently potent to effectively suppress basic fibroblast growth factor-induced corneal neovascularization after systemic administration in mice. Further, gro-beta significantly inhibits the growth of murine Lewis lung carcinoma in syngeneic C57B16/J and immunodeficient nude mice without toxicity. In vitro, Lewis lung carcinoma cells are completely insensitive to recombinant gro-beta at high concentrations that significantly inhibit endothelial cell proliferation. This finding supports the conclusion that gro-beta inhibits Lewis lung tumor growth by suppression of tumor-induced neovascularization.
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16

Han, ShouWei, Ying Zheng, and Jesse Roman. "Rosiglitazone, an Agonist of PPARγ, Inhibits Non-Small Cell Carcinoma Cell Proliferation In Part through Activation of Tumor Sclerosis Complex-2." PPAR Research 2007 (2007): 1–8. http://dx.doi.org/10.1155/2007/29632.

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PPARγligands inhibit the proliferation of non-small cell lung carcinoma (NSCLC) cells in vitro. The mechanisms responsible for this effect remain incompletely elucidated, but PPARγligands appear to inhibit the mammalian target of rapamycin (mTOR) pathway. We set out to test the hypothesis that PPARγligands activate tuberous sclerosis complex-2 (TSC2), a tumor suppressor gene that inhibits mTOR signaling. We found that the PPARγligand rosiglitazone stimulated the phosphorylation of TSC2 at serine-1254, but not threonine-1462. However, an antagonist of PPARγand PPARγsiRNA did not inhibit these effects. Rosiglitazone also increased the phosphorylation of p38 MAPK, but inhibitors of p38 MAPK and its downstream signal MK2 had no effect on rosiglitazone-induced activation of TSC2. Activation of TSC2 resulted in downregulation of phosphorylated p70S6K, a downstream target of mTOR. A TSC2 siRNA induced p70S6K phosphorylation at baseline and inhibited p70S6K downregulation by rosiglitazone. When compared to a control siRNA in a thymidine incorporation assay, the TSC2 siRNA reduced the growth inhibitory effect of rosiglitazone by fifty percent. These observations suggest that rosiglitazone inhibits NSCLC growth partially through phosphorylation of TSC2 via PPARγ-independent pathways.
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17

Ray, S., S. Dutta, J. Halder, and M. Ray. "Inhibition of electron flow through complex I of the mitochondrial respiratory chain of Ehrlich ascites carcinoma cells by methylglyoxal." Biochemical Journal 303, no. 1 (October 1, 1994): 69–72. http://dx.doi.org/10.1042/bj3030069.

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The effect of methylglyoxal on the oxygen consumption of Ehrlich-ascites-carcinoma (EAC)-cell mitochondria was tested by using different respiratory substrates, electron donors at different segments of the mitochondrial respiratory chain and site-specific inhibitors to identify the specific respiratory complex which might be involved in the inhibitory effect of methylglyoxal on the oxygen consumption by these cells. The results indicate that methylglyoxal strongly inhibits ADP-stimulated alpha-oxo-glutarate and malate plus pyruvate-dependent respiration, whereas, at a much higher concentration, methylglyoxal fails to inhibit succinate-dependent respiration. Methylglyoxal also fails to inhibit respiration which is initiated by duroquinol, an artificial electron donor. Moreover, methylglyoxal cannot inhibit oxygen consumption when the NNN'N′-tetramethyl-p-phenylenediamine by-pass is used. The inhibitory effect of methylglyoxal is identical on both ADP-stimulated and uncoupler-stimulated respiration. Lactaldehyde, a catabolite of methylglyoxal, can exert a protective effect on the inhibition of EAC-cell mitochondrial respiration by methylglyoxal. We suggest that methylglyoxal possibly inhibits the electron flow through complex I of the EAC-cell mitochondrial respiratory chain.
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18

Schlesinger, L. S., C. G. Bellinger-Kawahara, N. R. Payne, and M. A. Horwitz. "Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3." Journal of Immunology 144, no. 7 (April 1, 1990): 2771–80. http://dx.doi.org/10.4049/jimmunol.144.7.2771.

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Abstract We have examined the receptor-ligand interactions and the method of phagocytosis of virulent Mycobacterium tuberculosis by human monocytes. mAb against complement receptors (CR) inhibit adherence and phagocytosis of M. tuberculosis in fresh nonimmune serum. A mAb against the type 1 CR (CR1) inhibits adherence of M. tuberculosis by 40 +/- 5%, and three different mAb against the type 3 CR (CR3) each inhibit adherence by 39 +/- 5% to 47 +/- 4%. A mAb against CR1 used in combination with one of the three mAb against CR3 inhibits adherence by up to 64 +/- 7%. Most strikingly, two mAb used in combination against CR3 inhibit adherence by up to 81 +/- 2%. mAb against other monocyte surface Ag do not significantly influence adherence. In like fashion, mAb against CR but not other monocyte surface Ag inhibit adherence of preopsonized M. tuberculosis in the presence of heat-inactivated serum. By electron microscopy, monocytes ingest all M. tuberculosis that adhere in the presence of nonimmune serum; mAb against CR3 markedly inhibit ingestion. In contrast to CR, the FcR and the beta-glucan-inhibitable receptor for zymosan play little or no role in mediating M. tuberculosis adherence or ingestion. Adherence of M. tuberculosis is serum-dependent, requiring greater than or equal to 2.5% serum for optimal adherence. Heat inactivation of serum markedly reduces adherence of M. tuberculosis (75.5 +/- 7%) and preopsonization of bacteria enhances adherence by 2.9 +/- 0.4-fold. Adherence is also markedly reduced in C3- or factor B-depleted serum; repletion with C3 or factor B increases adherence by 2.1 +/- 0.4-fold and 1.86 +/- 0.05-fold, respectively. Fab anti-C3 IgG markedly inhibits monocyte adherence of preopsonized M. tuberculosis (71 +/- 1%). C component C3 is fixed to M. tuberculosis by the alternative C pathway as determined by a whole bacterial cell ELISA. Human monocytes ingest M. tuberculosis by conventional phagocytosis as viewed by electron microscopy. This study demonstrates that human monocyte CR1 and CR3 mediate phagocytosis of M. tuberculosis and C component C3 in serum is acting as the major bacterium-bound ligand.
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19

Mills, G. B., R. K. Cheung, E. J. Cragoe, S. Grinstein, and E. W. Gelfand. "Activation of the Na+/H+ antiport is not required for lectin-induced proliferation of human T lymphocytes." Journal of Immunology 136, no. 4 (February 15, 1986): 1150–54. http://dx.doi.org/10.4049/jimmunol.136.4.1150.

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Abstract Interaction of some mitogenic lectins and growth factors with the cell surface leads to activation of the Na+/H+ antiport and a resultant cytoplasmic alkalinization. Because amiloride inhibits both Na+/H+ exchange and cell proliferation, it has been hypothesized that activation of the antiport is an obligatory requirement and may, perhaps, be the "trigger" for proliferation. However, concentrations of amiloride which inhibit the antiport also inhibit several other intracellular processes, including protein synthesis and phosphorylation. To determine whether activation of the Na+/H+ antiport is necessary for lectin-induced proliferation, we examined the inhibitory activity of a series of potent amiloride analogs by measuring [3H]thymidine incorporation, cell cycle progression, and induction of the interleukin 2 (IL 2) receptor on human lymphocytes. In medium containing bicarbonate, and at concentrations at least 10 times higher than required to inhibit the antiport, these drugs did not inhibit the proliferative response of human peripheral blood T cells to the mitogen phytohemagglutinin. The amiloride analogs also failed to inhibit induction of the IL 2 receptor. Similarly, with human thymocytes, the amiloride analogs did not inhibit the co-mitogenic effects of the lectins phytohemagglutinin and concanavalin A together with IL 2 or the phorbol ester 12-O-tetradecanoylphorbol-13-acetate. This finding suggests that Na+/H+ exchange through the antiport is not an obligatory requirement for activation or proliferation of human lymphocytes or thymocytes.
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20

Fortenberry, Yolanda, Anne B. Cook, and Frank C. Church. "Inhibition of Factor VIIa-Tissue Factor by Protein C Inhibitor." Blood 110, no. 11 (November 16, 2007): 1743. http://dx.doi.org/10.1182/blood.v110.11.1743.1743.

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Abstract Protein C inhibitor (PCI) is a plasma serine protease inhibitor (serpin) that inhibits several proteases in blood coagulation including thrombin, thrombin-thromobomodulin and activated protein C. Although PCI has been shown to inhibit these key blood coagulation proteases, a clearly defined hemostatic role for PCI remains to be elucidated. Preliminary results from our laboratory show that exogenously added PCI prolongs venous thrombus formation upon blood vessel injury in a murine model of vascular injury. These results suggest that PCI may be responsible for inhibiting other proteases in blood coagulation, possibly including factor VIIa. Blood coagulation is initiated when factor VIIa binds to TF on cell surfaces. We investigated the ability of PCI to inhibit factor VIIa, both in the presence and absence of TF in vitro, and in a cellular environment. It has been shown previously and we have confirmed that the serpin antithrombin (AT) inhibits both factor VIIa and factor VIIa/TF; however, the ability of PCI to inhibit this protease has not been fully investigated. PCI and AT inhibit factor VIIa in the presence of TF and heparin (AT: k2=1.1 × 104 M−1 s−1; PCI: k2=7.2 × 103 M−1s−1). In the absence of heparin the inhibition of factor VIIa/TF by PCI is reduced 10-fold. Interestingly, PCI is unable to inhibit VIIa in the absence of TF with or without heparin. Furthermore, both PCI and AT form SDS-stable complexes with factor VIIa (in the presence of TF). We also investigated whether PCI is able to inhibit VIIa-mediated cell migration of the breast cancer cell line MDA-MB-231 that constitutively expresses TF. AT and PCI are able to inhibit cell surface derived factor VIIa/TF. Interestingly, the rate of factor VIIa inhibition on MDA-MB-231 cells is 1.2 and 0.4 × 103 M−1s−1 for PCI and AT, respectively. The factor VIIa-mediated cell migration of MD-MB-231 cells is attenuated in the presence of PCI, but not in the presence of the PCI inactive mutant (T341R). Given that both AT and PCI are able to inhibit factor VIIa/TF both in vitro and in a cellular environment, suggests that more potent derivatives (prepared by site-directed mutagenesis) of these serpins may be useful alternatives as novel therapeutics anticoagulants that target the initial step in the coagulation pathway.
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21

Ramsay, R., and M. Gravestock. "Monoamine Oxidases: to Inhibit or Not to Inhibit." Mini-Reviews in Medicinal Chemistry 3, no. 2 (March 1, 2003): 129–36. http://dx.doi.org/10.2174/1389557033405287.

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22

Yoon, Joobyoung, Hyunyong Lee, Hwan Bong Chang, Hyunsik Choi, Yong Sung Kim, Yang Kook Rho, Seungkyoo Seong, Dong Hwa Choi, Dongeun Park, and Bonchul Ku. "DW1029M, a novel botanical drug candidate, inhibits advanced glycation end-product formation, rat lens aldose reductase activity, and TGF-β1 signaling." American Journal of Physiology-Renal Physiology 306, no. 10 (May 15, 2014): F1161—F1170. http://dx.doi.org/10.1152/ajprenal.00651.2013.

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DW1029M is a botanical extract consisting of Morus bark and Puerariae radix, produced by Dong-Wha Pharmaceutical, for nephroprotective drug development; it has been in phase II clinical trials in Korea. In our mechanistic investigations, we found that DW1029M inhibits advanced glycation end products (AGEs), rat lens aldose reductase (RLAR), and transforming growth factor (TGF)-β1 signaling, all of which are implicated in diabetic complications such as diabetic nephropathy and diabetic retinopathy. DW1029M inhibits AGE formation via Fe2+ chelation. The extract contains 13 active constituents that inhibit AGE formation, 8 active constituents that inhibit RLAR activity, and 1 inhibitor of TGF-β1 signaling. Our results suggest DW1029M protects against diabetic nephropathy via blockade of AGE formation, RLAR activity, and TGF-β1 signaling.
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23

Gilmour, Raymond, J. Estelle Foster, Qin Sheng, Jonathan R. McClain, Anna Riley, Pei-Ming Sun, Wai-Leung Ng, et al. "New Class of Competitive Inhibitor of Bacterial Histidine Kinases." Journal of Bacteriology 187, no. 23 (December 1, 2005): 8196–200. http://dx.doi.org/10.1128/jb.187.23.8196-8200.2005.

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ABSTRACT Bacterial histidine kinases have been proposed as targets for the discovery of new antibiotics, yet few specific inhibitors of bacterial histidine kinases have been reported. We report here a novel thienopyridine (TEP) compound that inhibits bacterial histidine kinases competitively with respect to ATP but does not comparably inhibit mammalian serine/threonine kinases. Although it partitions into membranes and does not inhibit the growth of bacterial or mammalian cells, TEP could serve as a starting compound for a new class of histidine kinase inhibitors with antibacterial activity.
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24

Lannigan, D. A., J. B. Bennington, E. J. Cragoe, and P. A. Knauf. "Phenamil, an amiloride analogue, inhibits differentiation of Friend murine erythroleukemic cells." American Journal of Physiology-Cell Physiology 254, no. 1 (January 1, 1988): C122—C129. http://dx.doi.org/10.1152/ajpcell.1988.254.1.c122.

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Amiloride has been reported to inhibit Friend murine erythroleukemic (MEL) cell commitment to differentiate by inhibiting the MEL cell plasma membrane Na+-Ca2+ antiporter (R. L. Smith, I. G. Macara, R. Levenson, D. Housman, and L. Cantley. J. Biol. Chem. 257: 773-780, 1982). We therefore screened a series of amiloride analogues to determine whether a more potent and specific inhibitor of MEL cell differentiation could be found. In our experiments, as in those of Lubin (J. Cell. Physiol. 124: 539-544, 1985), amiloride itself did not inhibit MEL cell differentiation. However, we did find that the amiloride analogue phenamil reversibly inhibits dimethyl sulfoxide (DMSO)-induced MEL cell commitment to differentiate with a K1/2 of 2.5-5.0 microM (in plasma clot assay). At an extracellular concentration of 15 microM, phenamil inhibits commitment to differentiate by approximately 90% in the plasma clot assay while having a minimal effect on growth. Phenamil is not metabolized but is rapidly taken up by MEL cells. Phenamil was most effective as an inhibitor when present during the first 12 h of DMSO treatment, indicating that phenamil affects the early commitment process rather than later steps involved in hemoglobin synthesis. Phenamil does not, however, inhibit the early differentiation-induced decrease in [Na+]i and the concomitant drop in the Na+-K+ pump rate. A specific binding site for phenamil is suggested because some analogues in which the phenamil structure is slightly modified are unable to inhibit differentiation.
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25

Tonsgard, J. H., and S. C. Meredith. "Characterization of the binding sites for dicarboxylic acids on bovine serum albumin." Biochemical Journal 276, no. 3 (June 15, 1991): 569–75. http://dx.doi.org/10.1042/bj2760569.

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Dicarboxylic acids are prominent features of several diseases, including Reye's syndrome and inborn errors of mitochondrial and peroxisomal fatty acid oxidation. Moreover, dicarboxylic acids are potentially toxic to cellular processes. Previous studies [Tonsgard, Mendelson & Meredith (1988) J. Clin. Invest. 82, 1567-1573] demonstrated that long-chain dicarboxylic acids have a single high-affinity binding site and between one and three lower-affinity sites on albumin. Medium-chain-length dicarboxylic acids have a single low-affinity site. We further characterized dicarboxylic acid binding to albumin in order to understand the potential effects of drugs and other ligands on dicarboxylic acid binding and toxicity. Progesterone and oleate competitively inhibit octadecanedioic acid binding to the single high-affinity site. Octanoate inhibits binding to the low-affinity sites. Dansylated probes for subdomain 2AB inhibit dodecanedioic acid binding whereas probes for subdomain 3AB do not. In contrast, low concentrations of octadecanedioic acid inhibit the binding of dansylated probes to subdomain 3AB and 2AB. L-Tryptophan, which binds in subdomain 3AB, inhibits hexadecanedioic acid binding but has no effect on dodecanedioic acid. Bilirubin and acetylsalicylic acid, which bind in subdomain 2AB, inhibit the binding of medium-chain and long-chain dicarboxylic acids. Our results suggest that long-chain dicarboxylic acids bind in subdomains 2C, 3AB and 2AB. The single low-affinity binding site for medium-chain dicarboxylic acids is in subdomain 2AB. These studies suggest that dicarboxylic acids are likely to be unbound in disease states and may be potentially toxic.
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26

Burch, R. M., L. Noronha-Blob, J. M. Bator, V. C. Lowe, and J. P. Sullivan. "Mice treated with a leumedin or antibody to Mac-1 to inhibit leukocyte sequestration survive endotoxin challenge." Journal of Immunology 150, no. 8 (April 15, 1993): 3397–403. http://dx.doi.org/10.4049/jimmunol.150.8.3397.

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Abstract Endotoxin challenge causes metabolic dysfunction mediated by TNF, and sequestration of leukocytes. NPC 15669, N-carboxy-L-leucine, N-[2,7-dimethylfluoren-9-yl)methyl] ester, inhibits leukocyte recruitment into inflammatory lesions in animals, and inhibits endotoxin-induced neutropenia and lymphopenia in mice. This study was carried out to determine whether the ability of NPC 15669 to inhibit leukocyte sequestration is sufficient to promote survival after endotoxin challenge. To inhibit leukocyte sequestration directly, mice were treated with anti-CD11a (LFA-1) or anti-CD11b (Mac-1) before endotoxin challenge. Anti-CD11b partly inhibited neutropenia and lymphopenia in response to challenge with LPS, but anti--CD11a had little effect on leukopenia. At doses of 100 and 1000 micrograms/kg, anti-CD11b increased survival to endotoxin challenge from 0 to 20 and 40%, respectively, whereas anti-CD11a was without effect. These observations, coupled with the finding that NPC 15669 does not inhibit endotoxin-induced TNF release suggest that inhibition of leukocyte sequestration can increase survival after endotoxin challenge, and that NPC 15669 or antibodies to Mac-1 may represent effective therapies for gram-negative sepsis and shock.
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27

Harrison, David N., Elena V. Gazina, Damian F. Purcell, David A. Anderson, and Steven Petrou. "Amiloride Derivatives Inhibit Coxsackievirus B3 RNA Replication." Journal of Virology 82, no. 3 (November 21, 2007): 1465–73. http://dx.doi.org/10.1128/jvi.01374-07.

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ABSTRACT Amiloride derivatives are known blockers of the cellular Na+/H+ exchanger and the epithelial Na+ channel. More recent studies demonstrate that they also inhibit ion channels formed by a number of viral proteins. We previously reported that 5-(N-ethyl-N-isopropyl)amiloride (EIPA) modestly inhibits intracellular replication and, to a larger extent, release of human rhinovirus 2 (HRV2) (E. V. Gazina, D. N. Harrison, M. Jefferies, H. Tan, D. Williams, D. A. Anderson and S. Petrou, Antiviral Res. 67:98-106, 2005). Here, we demonstrate that amiloride and EIPA strongly inhibit coxsackievirus B3 (CVB3) RNA replication and do not inhibit CVB3 release, in contrast to our previous findings on HRV2. Passaging of plasmid-derived CVB3 in the presence of amiloride generated mutant viruses with amino acid substitutions in position 299 or 372 of the CVB3 polymerase. Introduction of either of these mutations into the CVB3 plasmid produced resistance to amiloride and EIPA, suggesting that they act as inhibitors of CVB3 polymerase, a novel mechanism of antiviral activity for these compounds.
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28

Sainz, Bruno, and William P. Halford. "Alpha/Beta Interferon and Gamma Interferon Synergize To Inhibit the Replication of Herpes Simplex Virus Type 1." Journal of Virology 76, no. 22 (November 15, 2002): 11541–50. http://dx.doi.org/10.1128/jvi.76.22.11541-11550.2002.

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ABSTRACT In vivo evidence suggests that T-cell-derived gamma interferon (IFN-γ) can directly inhibit the replication of herpes simplex virus type 1 (HSV-1). However, IFN-γ is a weak inhibitor of HSV-1 replication in vitro. We have found that IFN-γ synergizes with the innate IFNs (IFN-α and -β) to potently inhibit HSV-1 replication in vitro and in vivo. Treatment of Vero cells with either IFN-β or IFN-γ inhibits HSV-1 replication by <20-fold, whereas treatment with both IFN-β and IFN-γ inhibits HSV-1 replication by ∼1,000-fold. Treatment with IFN-β and IFN-γ does not prevent HSV-1 entry into Vero cells, and the inhibitory effect can be overcome by increasing the multiplicity of HSV-1 infection. The capacity of IFN-β and IFN-γ to synergistically inhibit HSV-1 replication is not virus strain specific and has been observed in three different cell types. For two of the three virus strains tested, IFN-β and IFN-γ inhibit HSV-1 replication with a potency that approaches that achieved by a high dose of acyclovir. Pretreatment of mouse eyes with IFN-β and IFN-γ reduces HSV-1 replication to nearly undetectable levels, prevents the development of disease, and reduces the latent HSV-1 genome load per trigeminal ganglion by ∼200-fold. Thus, simultaneous activation of IFN-α/β receptors and IFN-γ receptors appears to render cells highly resistant to the replication of HSV-1. Because IFN-α or IFN-β is produced by most cells as an innate response to virus infection, the results imply that IFN-γ secreted by T cells may provide a critical second signal that potently inhibits HSV-1 replication in vivo.
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29

Ponka, P., H. M. Schulman, and J. Martinez-Medellin. "Haem inhibits iron uptake subsequent to endocytosis of transferrin in reticulocytes." Biochemical Journal 251, no. 1 (April 1, 1988): 105–9. http://dx.doi.org/10.1042/bj2510105.

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Haem controls the rate of haem synthesis in erythroid cells by inhibiting iron incorporation from transferrin. The present results indicate that haem primarily inhibits the release of iron from transferrin subsequent to transferrin endocytosis and that the inhibition of transferrin endocytosis caused by relatively high concentrations of haem is a secondary effect. Low concentrations of haem (10-25 microM) significantly inhibit reticulocyte iron uptake and to a greater extent its incorporation into haem, but do not inhibit either the initial rate of transferrin uptake or its internalization by the cells.
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30

Todisco, A., C. Seva, Y. Takeuchi, C. J. Dickinson, and T. Yamada. "Somatostatin inhibits AP-1 function via multiple protein phosphatases." American Journal of Physiology-Gastrointestinal and Liver Physiology 269, no. 1 (July 1, 1995): G160—G166. http://dx.doi.org/10.1152/ajpgi.1995.269.1.g160.

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We have reported previously that the widespread inhibitory actions of somatostatin might be mediated by its ability to inhibit the expression of the immediate early genes c-fos and c-jun. The products of these genes form a heterodimeric transcription factor complex [activator protein 1 (AP-1)], which is known to be induced by treatment with phorbol esters. In the present study, we sought to investigate the mechanisms by which somatostatin inhibits immediate early gene expression. For our experiments, we used a rat pituitary adenoma cell line (GH3), which is known to express multiple subclasses of somatostatin receptors. The phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated both AP-1 binding and transcriptional activity in GH3 cells and the somatostatin analogue octreotide inhibited this response by 40-70%. In the presence of two different phosphatase inhibitors, sodium orthovanadate or okadaic acid, the ability of somatostatin to inhibit AP-1 binding and transcriptional activity was abolished. This effect of octreotide, which appears to be mediated by the SSTR2 and SSTR5 subtypes of somatostatin receptors, was paralleled by its ability to inhibit TPA-stimulated GH3 cell proliferation. Pretreatment of the GH3 cells with pertussis toxin (200 ng/ml) reversed the inhibitory effect of octreotide on both AP-1 function and cellular proliferation. Our observations lead us to conclude that somatostatin not only inhibits immediate early gene expression but also inhibits AP-1 binding and transcriptional activity via the action of several classes of protein phosphatases. This effect, which is pertussis toxin sensitive, might be one mechanism by which somatostatin inhibits cellular proliferation.
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31

Newburg, David S. "Human Milk Glycoconjugates That Inhibit Pathogens." Current Medicinal Chemistry 6, no. 2 (February 1999): 117–27. http://dx.doi.org/10.2174/0929867306666220207212739.

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Abstract: Breast-fed infants have lower incidence of diarrhea, respiratory disease, and otitis media. The protection by human milk has long been attributed to the presence of secretory lgA. However, human milk contains large numbers and amounts of complex carbohydrates, including glycopro­ teins, glycolipids, glycosaminoglycans, mucins, and especially oligosaccharides. The oligosaccharides comprise the third most abundant solid constituent of human milk, and contain a myriad of structures. Complex carbohydrate moieties of glycoconjugates and oligosaccharides are synthesized by the many glycosyltransferases in the mammary gland; those with homology to cell surface glycoconjugate pathogen receptors may inhibit pathogen binding, thereby protecting the nursing infant. Several examples are reviewed: A fucosyloligosaccharide inhibits the diarrheagenic effect of stable toxin of Escherichia coli. A different fucosyloligosaccharide inhibits infection by Campylobacter jejuni. Binding of Streptococcus pneumoniae arid of enteropathogenic E. coli to their respective receptors is inhibited by human milk oligosaccharides. The 46-kD glycoprotein, lactadherin, inhibits rotavirus binding and infectivity. Low levels of lactadherin in human milk are associated with a higher incidence of symptomatic rotavirus in breast-fed infants. A mannosylated glycopeptide inhibits binding by enterohemorrhagic E. coli. A glycosaminoglycan inhibits binding of gp120 to CD4, the first step in HIV infection. Human milk mucin inhibits binding by $-fimbriated E. coli. The ganglioside, GM 1, reduces diarrhea production by cholera toxin and labile toxin of E. coli. The neutral glycosphingolipid, Gb3, binds to Shigatoxin. Thus, many complex carbohydrates of human milk may be novel antipathogenic agents, and the milk glycoconjugates and oligosaccharides may be a major source of protection for breastfeeding infants.
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32

Kennedy, Scott G., Eugene S. Kandel, Torry K. Cross, and Nissim Hay. "Akt/Protein Kinase B Inhibits Cell Death by Preventing the Release of Cytochrome c from Mitochondria." Molecular and Cellular Biology 19, no. 8 (August 1, 1999): 5800–5810. http://dx.doi.org/10.1128/mcb.19.8.5800.

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ABSTRACT Growth factors signaling through the phosphoinositide 3-kinase/Akt pathway promote cell survival. The mechanism by which the serine/threonine kinase Akt prevents cell death remains unclear. We have previously shown that Akt inhibits the activity of DEVD-targeted caspases without changing the steady-state levels of Bcl-2 and Bcl-xL. Here we show that Akt inhibits apoptosis and the processing of procaspases to their active forms by delaying mitochondrial changes in a caspase-independent manner. Akt activation is sufficient to inhibit the release of cytochrome c from mitochondria and the alterations in the inner mitochondrial membrane potential. However, Akt cannot inhibit apoptosis induced by microinjection of cytochrome c. We also demonstrated that Akt inhibits apoptosis and cytochrome c release induced by several proapoptotic Bcl-2 family members. Taken together, our results show that Akt promotes cell survival by intervening in the apoptosis cascade before cytochrome c release and caspase activation via a mechanism that is distinct from Bad phosphorylation.
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33

Kalimuthu, Shanthini, Becky P. K. Cheung, Joyce Y. Y. Yau, Karthi Shanmugam, Adline Princy Solomon, and Prasanna Neelakantan. "A Novel Small Molecule, 1,3-di-m-tolyl-urea, Inhibits and Disrupts Multispecies Oral Biofilms." Microorganisms 8, no. 9 (August 20, 2020): 1261. http://dx.doi.org/10.3390/microorganisms8091261.

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An imbalance of homeostasis between the microbial communities and the host system leads to dysbiosis in oral micro flora. DMTU (1,3-di-m-tolyl-urea) is a biocompatible compound that was shown to inhibit Streptococcus mutans biofilm by inhibiting its communication system (quorum sensing). Here, we hypothesized that DMTU is able to inhibit multispecies biofilms. We developed a multispecies oral biofilm model, comprising an early colonizer Streptococcus gordonii, a bridge colonizer Fusobacterium nucleatum, and late colonizers Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans. We performed comprehensive investigations to demonstrate the effect of DMTU on planktonic cells and biofilms. Our findings showed that DMTU inhibits and disrupts multispecies biofilms without bactericidal effects. Mechanistic studies revealed a significant down regulation of biofilm and virulence-related genes in P. gingivalis. Taken together, our study highlights the potential of DMTU to inhibit polymicrobial biofilm communities and their virulence.
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34

McGarry, Niamh, Catherine M. Greene, Noel G. McElvaney, Sinéad Weldon, and Clifford C. Taggart. "The Ability of Secretory Leukocyte Protease Inhibitor to Inhibit Apoptosis in Monocytes Is Independent of Its Antiprotease Activity." Journal of Immunology Research 2015 (2015): 1–6. http://dx.doi.org/10.1155/2015/507315.

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Secretory Leukocyte Protease Inhibitor (SLPI) is a serine protease inhibitor produced by epithelial and myeloid cells with anti-inflammatory properties. Research has shown that SLPI exerts its anti-inflammatory activity by directly binding to NF-κB DNA binding sites and, in so doing, prevents binding and subsequent transcription of proinflammatory gene expression. In the current study, we demonstrate that SLPI can inhibit TNF-α-induced apoptosis in U937 cells and peripheral blood monocytes. Specifically, SLPI inhibits TNF-α-induced caspase-3 activation and DNA degradation associated with apoptosis. We go on to show that this ability of SLPI to inhibit apoptosis is not dependent on its antiprotease activity as antiprotease deficient variants of SLPI can also inhibit TNF-α-induced apoptosis. This reduction in monocyte apoptosis may preserve monocyte function during inflammation resolution and promote infection clearance at mucosal sites.
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35

Chen, Yabing, Burton E. Sobel, and David J. Schneider. "The effect of plasminogen activator inhibitor type 1 on apoptosis." Thrombosis and Haemostasis 100, no. 12 (2008): 1037–40. http://dx.doi.org/10.1160/th08-04-0234.

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SummaryPlasminogen activator inhibitor type-1 (PAI-1), an inhibitor of plasminogen activators, inhibits formation of plasmin and plasmin-mediated proteolysis. Apoptosis,or programmed cell death, is a potentially important phenomenon in mediating overall cell death. This review focuses on the influence of PAI-1 on apoptosis. Greater expression of PAI-1 has been associated with increased survival of cells and resistance to apoptosis. PAI-1 appears to influence apoptosis by decreasing cell adhesion (anoikis) as well as its effect on intracellular signaling. Mechanisms by which PAI-1 may render a cell resistant to apoptosis include its ability to inhibit generation of plasmin,its ability to inhibit caspase 3, and its ability to inhibit cell adhesion mediated by vitronectin. Inhibition of caspase 3 by PAI-1 may divert intracellular signalling from induction of apoptosis to induction of proliferation.
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36

Flatman, P. W., N. C. Adragna, and P. K. Lauf. "Role of protein kinases in regulating sheep erythrocyte K-Cl cotransport." American Journal of Physiology-Cell Physiology 271, no. 1 (July 1, 1996): C255—C263. http://dx.doi.org/10.1152/ajpcell.1996.271.1.c255.

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K-Cl cotransport in sheep erythrocytes can be activated by treatment either with A-23187 and EDTA to reduce concentration of internal ionized Mg [Mg]i) to submicromolar levels, with staurosporine, a potent kinase inhibitor, or with N-ethylmaleimide (NEM). Activation by these maneuvers is prevented and reversed by genistein [inhibition constant (Ki) of 15 microM], which inhibits tyrosine kinases (TK). The related glycosidated compound genistin, which does not inhibit TK, does not inhibit transport, whereas another TK inhibitor, tyrphostin B46, inhibits both basal and stimulated transport (Ki of 28 microM). Cotransport activation by NEM is prevented and reversed by the phosphatase inhibitor, calyculin A, and activation by staurosporine occurs only if cells contain ATP. Increasing [Mg]i inhibits cotransport in the presence of calyculin A whether or not staurosporine is present as well. Our work suggests that genistein inhibits cotransport through a TK and that staurosporine and NEM activate cotransport, probably through inhibition of other kinases, causing stimulation through dephosphorylation of a protein (possibly the transporter itself) be a serine/threonine phosphatase. [Mg]i inhibits cotransport by activating a kinase (concentration for half-maximal activation of 10 microM) that phosphorylates this protein.
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37

Ninomiya, Soranobu, Neeharika Narala, Leslie Huye, Shigeki Yagyu, Barbara Savoldo, Gianpietro Dotti, Helen E. Heslop, Malcolm K. Brenner, Cliona M. Rooney, and Carlos A. Ramos. "Tumor indoleamine 2,3-dioxygenase (IDO) inhibits CD19-CAR T cells and is downregulated by lymphodepleting drugs." Blood 125, no. 25 (June 18, 2015): 3905–16. http://dx.doi.org/10.1182/blood-2015-01-621474.

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Key Points Tumor IDO inhibits CD19-CART activity, likely via induction of the kynurenine pathway, whose metabolites directly inhibit T cells. Fludarabine and cyclophosphamide, frequently used before CART administration, downregulate IDO expression in lymphoma cells.
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38

Ishii, Hidemi, Masaaki Kuboki, Junichi Fujii, Sayuri Hiraishi, and Mutsuyoshi Kazama. "Thiolprotease inhibitor, EST, can inhibit thrombin-induced platelet activation." Thrombosis Research 57, no. 6 (March 1990): 847–61. http://dx.doi.org/10.1016/0049-3848(90)90152-3.

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39

Oka, Natsuo, Yuushi Okumura, Hiro-Omi Kanayama, Hirofumi Izaki, Masumi Okamoto, Hiroshi Kido, and Susumu Kagawa. "Amiloride and Urinary Trypsin Inhibitor Inhibit Urothelial Cancer Invasion." European Urology 44, no. 6 (December 2003): 737–41. http://dx.doi.org/10.1016/s0302-2838(03)00383-x.

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40

Ayad, Onsy, James M. Stark, Michael M. Fiedler, Ingrid Y. Menendez, Marnie A. Ryan, and Hector R. Wong. "The Heat Shock Response Inhibits RANTES Gene Expression in Cultured Human Lung Epithelium." Journal of Immunology 161, no. 5 (September 1, 1998): 2594–99. http://dx.doi.org/10.4049/jimmunol.161.5.2594.

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Abstract The chemokine RANTES is thought to be involved in the pathophysiology of inflammation-associated acute lung injury. Although much is known regarding signals that induce RANTES gene expression, relatively few data exist regarding signals that inhibit RANTES gene expression. The heat shock response, a highly conserved cellular defense mechanism, has been demonstrated to inhibit a variety of lung proinflammatory responses. We tested the hypothesis that induction of the heat shock response inhibits RANTES gene expression. Treatment of A549 cells with TNF-α induced RANTES gene expression in a concentration-dependent manner. Induction of the heat shock response inhibited subsequent TNF-α-mediated RANTES mRNA expression and secretion of immunoreactive RANTES. Transient transfection assays involving a RANTES promoter-luciferase reporter plasmid demonstrated that the heat shock response inhibited TNF-α-mediated activation of the RANTES promoter. Inhibition of NF-κB nuclear translocation with isohelenin inhibited TNF-α-mediated RANTES mRNA expression, indicating that RANTES gene expression is NF-κB dependent in A549 cells. Induction of the heat shock response inhibited degradation of the NF-κB inhibitory protein, I-κBα but did not significantly inhibit phosphorylation of I-κBα. We conclude that the heat shock response inhibits RANTES gene expression by a mechanism involving inhibition of NF-κB nuclear translocation and subsequent inhibition of RANTES promoter activation. The mechanism by which the heat shock response inhibits NF-κB nuclear translocation involves stabilization of I-κBα, without significantly affecting phosphorylation of I-κBα.
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41

Gray, Vanessa Seals. "Syncopal Episodes Associated with Cisapride and Concurrent Drugs." Annals of Pharmacotherapy 32, no. 6 (June 1998): 648–51. http://dx.doi.org/10.1345/aph.17288.

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OBJECTIVE: To report a case of QT prolongation and syncopal episodes resulting from concomitant use of cisapride and agents known to inhibit its metabolism. CASE SUMMARY: A 53-year-old white woman was involved in two motor vehicle accidents on the same day after experiencing syncopal episodes. Cardiac and neurologic evaluations were negative; the syncopal episodes were attributed to QT prolongation associated with the concomitant use of cisapride and agents known to inhibit its metabolism. DISCUSSION: This is the first case published in the English-language literature describing QT prolongation resulting from the concomitant use of cisapride and agents known to inhibit its metabolism. Clarithromycin inhibits CYP3A4, the isoenzyme responsible for the metabolism of cisapride. Concomitant administration of cisapride with agents known to inhibit CYP3A4 (i.e., azole antifungals, erythromycin, clarithromycin) may result in elevated cisapride concentrations. Elevated cisapride concentrations have been associated with QT prolongation, syncopal episodes, and cardiac dysrhythmias. CONCLUSIONS: Acquired QT prolongation is a well-recognized adverse effect of several drugs. Recognition of newer drugs and drug combinations that place patients at risk for this potentially fatal adverse event is imperative for appropriate monitoring and prevention.
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42

Chandrasekaran, Lakshmi, Chao-Zhen He, Hebah Al-Barazi, Henry C. Krutzsch, M. Luisa Iruela-Arispe, and David D. Roberts. "Cell Contact–dependent Activation of α3β1 Integrin Modulates Endothelial Cell Responses to Thrombospondin-1." Molecular Biology of the Cell 11, no. 9 (September 2000): 2885–900. http://dx.doi.org/10.1091/mbc.11.9.2885.

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Thrombospondin-1 (TSP1) can inhibit angiogenesis by interacting with endothelial cell CD36 or proteoglycan receptors. We have now identified α3β1 integrin as an additional receptor for TSP1 that modulates angiogenesis and the in vitro behavior of endothelial cells. Recognition of TSP1 and an α3β1 integrin–binding peptide from TSP1 by normal endothelial cells is induced after loss of cell–cell contact or ligation of CD98. Although confluent endothelial cells do not spread on a TSP1 substrate, α3β1 integrin mediates efficient spreading on TSP1 substrates of endothelial cells deprived of cell–cell contact or vascular endothelial cadherin signaling. Activation of this integrin is independent of proliferation, but ligation of the α3β1 integrin modulates endothelial cell proliferation. In solution, both intact TSP1 and the α3β1 integrin–binding peptide from TSP1 inhibit proliferation of sparse endothelial cell cultures independent of their CD36 expression. However, TSP1 or the same peptide immobilized on the substratum promotes their proliferation. The TSP1 peptide, when added in solution, specifically inhibits endothelial cell migration and inhibits angiogenesis in the chick chorioallantoic membrane, whereas a fragment of TSP1 containing this sequence stimulates angiogenesis. Therefore, recognition of immobilized TSP1 by α3β1 integrin may stimulate endothelial cell proliferation and angiogenesis. Peptides that inhibit this interaction are a novel class of angiogenesis inhibitors.
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43

Chen, Yuguang, Ge Yang, and Yining Zhao. "Application of Dienogest In the Treatment of Endometriosis." Highlights in Science, Engineering and Technology 8 (August 17, 2022): 69–73. http://dx.doi.org/10.54097/hset.v8i.1112.

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Endometriosis is a condition that exists endometrioid epithelium and/or endometrialmatrix muscular layer,usually accompanied by inflammatory processes.The new progesterone,Dienogest (DNG),has no estrogen,anti-estrogen and androgen activities,at the same time,DNGhas anti androgen activity.With a favorable safety and tolerability profile,DNG could relief pain and reduce ovarian endometriosis cysts,reduces the recurrence,meanwhile,DNG also has good effect on recurrent endometriosis.DNG mainly mediates the hypothalamus,pituitary and ovarian axis to inhibit the functions of ovarian.It can also inhibit the synthesis of estrogen metabolic enzymes,to reduce estrogen level.Through anti-inflammation and anti-angiogenesis,DNG could inhibit the development of pain,inhibite the occurrence and development of EMT lesions,which can be used as medicine for long-term management of endometriosis.Side effects such as uterine bleeding was observed,inform the patient in advance of compliance,careful long-term follow-up is required.
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44

Mishina, Yuliya V., Sanjeev Krishna, Richard K. Haynes, and John C. Meade. "Artemisinins Inhibit Trypanosoma cruzi and Trypanosoma brucei rhodesiense In Vitro Growth." Antimicrobial Agents and Chemotherapy 51, no. 5 (March 5, 2007): 1852–54. http://dx.doi.org/10.1128/aac.01544-06.

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ABSTRACT Artemisinin compounds inhibit in vitro growth of cultured Trypanosoma cruzi and Trypanosoma brucei rhodesiense at concentrations in the low micromolar range. Artemisinin also inhibits calcium-dependent ATPase activity in T. cruzi membranes, suggesting a mode of action via membrane pumps. Artemisinins merit further investigation as chemotherapeutic options for these pathogens.
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45

Arola, J., J. Liu, P. Heikkila, V. Ilvesmaki, K. Salmenkivi, R. Voutilainen, and AI Kahri. "Expression of inhibin alpha in adrenocortical tumours reflects the hormonal status of the neoplasm." Journal of Endocrinology 165, no. 2 (May 1, 2000): 223–29. http://dx.doi.org/10.1677/joe.0.1650223.

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Inhibins are gonadal glycoprotein hormones whose main endocrine function is to inhibit pituitary FSH secretion. In addition to testes and ovaries, other steroid-producing organs are sites of inhibin alpha subunit expression. To study the role of inhibins in human adrenal gland, we screened a panel of 150 adrenals (10 normal adrenals, 25 adrenocortical hyperplasias, 65 adrenocortical adenomas, 30 adrenocortical carcinomas and 20 phaeochromocytomas) for inhibin alpha expression. mRNA levels of inhibin alpha subunit were studied in 57 samples and all tissues were stained immunohistochemically with an inhibin alpha subunit-specific antibody. Inhibin alpha mRNA was detected in all adrenocortical tissues. Virilizing adenomas possessed a 10-fold higher median inhibin alpha mRNA expression than did normal adrenals. Bilaterally and nodularly hyperplastic adrenals and other than virilizing adrenocortical tumours had their median inhibin alpha mRNA levels close to those of normal adrenals. Immunohistochemically, inhibin alpha subunit was detectable in all normal and hyperplastic adrenals, as well as in 73% of the adrenocortical tumours. However, the percentage of inhibin alpha-positive cells varied greatly in different tumour types. The median percentage of positive cells was 10 in non-functional and Conn's adenomas, 30 in Cushing's adenomas and 75 in virilizing adenomas. In malignant adrenocortical tumours the median percentage of inhibin alpha-immunopositive cells was 20 in non-functional carcinomas, 30 in Conn's carcinomas, 65 in Cushing's carcinomas and 75 in virilizing carcinomas. All phaeochromocytomas were negative for inhibin alpha subunit both at the mRNA level and immunohistochemically. Our data show that inhibin alpha subunit is highly expressed in both normal and neoplastic androgen-producing adrenocortical cells, with less expression in cortisol-producing and hardly any in aldosterone-producing cells. This suggests a specific role for inhibins in the regulation of adrenal androgen production. We did not find any significant difference in inhibin alpha expression between benign and malignant adrenocortical tumours. Thus inhibin alpha gene does not seem to have a tumour suppressor role in human adrenal cortex.
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46

Seither, Katelyn M., Heather A. McMahon, Nikita Singh, Hejia Wang, Mimi Cushman-Nick, Geronda L. Montalvo, William F. DeGrado, and James Shorter. "Specific aromatic foldamers potently inhibit spontaneous and seeded Aβ42 and Aβ43 fibril assembly." Biochemical Journal 464, no. 1 (October 23, 2014): 85–98. http://dx.doi.org/10.1042/bj20131609.

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We report specific aromatic foldamers that inhibit fibrillization by amyloid-β (Aβ) peptides connected with Alzheimer's disease. One foldamer inhibits formation of toxic Aβ-species as well as the self-templating activity of Aβ fibrils, properties that could have therapeutic utility.
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47

Patel, Rajesh N., Mukundan G. Attur, Mandar N. Dave, Indravadan V. Patel, Steven A. Stuchin, Steven B. Abramson, and Ashok R. Amin. "A Novel Mechanism of Action of Chemically Modified Tetracyclines: Inhibition of COX-2-Mediated Prostaglandin E2 Production." Journal of Immunology 163, no. 6 (September 15, 1999): 3459–67. http://dx.doi.org/10.4049/jimmunol.163.6.3459.

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Abstract Tetracyclines (doxycycline and minocycline) inhibit inducible NO synthase expression and augment cyclooxygenase (COX)-2 expression and PGE2 production. In contrast, chemically modified tetracyclines (CMTs), such as CMT-3 and -8 (but not CMT-1, -2, and -5), that lack antimicrobial activity, inhibit both NO and PGE2 production in LPS-stimulated murine macrophages, bovine chondrocytes, and human osteoarthritis-affected cartilage, which spontaneously produces NO and PGE2 in ex vivo conditions. Furthermore, CMT-3 augments COX-2 protein expression but inhibits net PGE2 accumulation. This coincides with the ability of CMT-3 and -8 to inhibit COX-2 enzyme activity in vitro. The action of CMTs is distinct from that observed with tetracyclines because 1) CMT-3-mediated inhibition of PGE2 production coincides with modification of COX-2 protein, which is distinct from the nonglycosylated COX-2 protein generated in the presence of tunicamycin, as observed by Western blot analysis and 2) CMT-3 and -8 have no significant effect on COX-2 mRNA accumulation. In contrast, CMT-3 and -8 do not inhibit COX-1 expression in A549 human epithelial cells at the level of protein and mRNA accumulation or modification of COX-1 protein. CMT-3 and -8 inhibit the sp. act. of COX-2 (but not COX-1) in cell-free extracts. These results demonstrate differential action of CMT-3 (Metastat) on COX-1 and -2 expression, which is distinct from other tetracyclines.
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48

Lin, Mei-Hui, Fang-Rong Chang, Mu-Yi Hua, Yang-Chang Wu, and Shih-Tung Liu. "Inhibitory Effects of 1,2,3,4,6-Penta-O-Galloyl-β-d-Glucopyranose on Biofilm Formation byStaphylococcus aureus." Antimicrobial Agents and Chemotherapy 55, no. 3 (December 20, 2010): 1021–27. http://dx.doi.org/10.1128/aac.00843-10.

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ABSTRACT1,2,3,4,6-Penta-O-galloyl-β-d-glucopyranose (PGG) is an active ingredient in plants that are commonly used in Chinese medicine to treat inflammation. We demonstrate here that PGG, at 6.25 μM, does not inhibit the growth ofStaphylococcus aureus, and yet it prevents biofilm formation on polystyrene and polycarbonate surfaces. At the same concentration, PGG is not toxic to human epithelial and fibroblast cells. PGG has an IB50value, i.e., the PGG concentration that inhibits 50% biofilm formation, of 3.6 μM. The value is substantially lower than that ofN-acetylcysteine, iodoacetamide, andN-phenyl maleimide, which are known to inhibit biofilm formation byS. aureus. Biochemical and scanning electron microscopy results also reveal that PGG inhibits initial attachment of the bacteria to solid surface and the synthesis of polysaccharide intercellular adhesin, explaining how PGG inhibits biofilm formation. The results of this study demonstrate that coating PGG on polystyrene and silicon rubber surfaces with polyaniline prevents biofilm formation, indicating that PGG is highly promising for clinical use in preventing biofilm formation byS. aureus.
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49

Larrick, J. W., M. Hirata, H. Zheng, J. Zhong, D. Bolin, J. M. Cavaillon, H. S. Warren, and S. C. Wright. "A novel granulocyte-derived peptide with lipopolysaccharide-neutralizing activity." Journal of Immunology 152, no. 1 (January 1, 1994): 231–40. http://dx.doi.org/10.4049/jimmunol.152.1.231.

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Abstract Rabbit CAP18 (cationic antimicrobial protein, 18 kDa) is a leukocyte protein identified and purified using as an assay its capacity to bind and inhibit various activities of LPS. Oligonucleotide probes designed from the putative N-terminal protein sequence were used to obtain the corresponding cDNA from a rabbit bone marrow cDNA library. Examination of the cDNA sequence revealed that the protein fragment of the putative N-terminus was actually a 37-amino-acid C-terminal fragment. This fragment, designated CAP18(106-142), inhibits many activities of LPS. In the present studies, synthetic CAP18(106-142) is shown to: 1) bind to erythrocytes coated with diverse strains of LPS; 2) inhibit LPS-induced release of cytokines (TNF, IL-1, IL-6) and nitric oxide from macrophages; 3) inhibit LPS-induced LAL coagulation and 4) protect mice from LPS lethality. CAP18(106-142) may have therapeutic utility for conditions associated with elevated concentrations of LPS.
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50

Losman, J. A., X. P. Chen, D. Hilton, and P. Rothman. "Cutting Edge: SOCS-1 Is a Potent Inhibitor of IL-4 Signal Transduction." Journal of Immunology 162, no. 7 (April 1, 1999): 3770–74. http://dx.doi.org/10.4049/jimmunol.162.7.3770.

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Abstract IL-4 is an important regulator of the activation, proliferation, and differentiation of many hematopoetic cells. Many of these biological effects result from the activation of Janus kinases (JAK)1 and JAK3 and the transcription factor Stat6. Recent data suggest that members of the SOCS (suppressor of cytokine signaling) family of proteins can inhibit JAK-STAT signaling. We have examined the ability of SOCS family members to suppress IL-4 signaling, and we have found that SOCS-1 potently inhibits the activation of JAK1 kinase and Stat6 in response to IL-4. Furthermore, SOCS-1 can inhibit the induction of CD23 expression by IL-4. SOCS-2 does not inhibit induction of signaling by IL-4, while inhibition of IL-4 signaling by SOCS-3 can be detected in transient transfection systems, but not in stable cell lines. These studies implicate SOCS-1 in modulation of IL-4 signaling and suggest that SOCS-1 may play a role in regulating the immune response.
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