Multiple sclerosis involves demyelination and axonal degeneration of the central nervous system. The molecular mechanisms of axonal degeneration are relatively unexplored in both multiple sclerosis and its mouse model, experimental autoimmune encephalomyelitis. We previously reported that targeting the axonal growth inhibitor, Nogo-A, may protect against neurodegeneration in experimental autoimmune encephalomyelitis; ...

The caudal nucleus tractus solitarii (cNTS), the predominant site of termination of cough-related afferents, has been shown to be a site of action of some centrally acting antitussive agents. A role of Extracellular Signal Regulated Kinases-1 and -2 (ERK1/2) has been suggested in acute central processing of nociceptive inputs. Since ...

Since the Gβγ subunit of Gi protein has been importantly implicated in regulating immune and inflammatory responses, this study investigated the potential role and mechanism of action of Gβγ signaling in regulating the induction of airway hyperresponsiveness (AHR) in a rabbit model of allergic asthma. Relative to non-sensitized animals, OVA-sensitized ...

Regulator of G-protein Signaling 4 (RGS4) plays an important role in regulating smooth muscle contraction, cardiac development, neural plasticity and psychiatric disorder. However, the underlying regulatory mechanisms remain elusive. Our recent studies have shown that upregulation of Rgs4 by interleukin (IL)-1β is mediated by the activation of NFκB signaling and ...

Introduction: Phosphatidylinositol 3-kinase (PI3K), a lipid kinase, is the first kinase involved in, and a key component of, the PI3K/Akt/mTOR signalling pathway, and is significantly upregulated in many cancers. However, four distinct isoforms of PI3K are known with different expression patterns and different pathophysiological roles. The PI3Kδ isoform is expressed ...

Psychogenic stress in rabbits caused by fixation of the animal to a frame was accompanied by an increase in duodenal contractile activity. In the jejunum, initial inhibition of motor activity gave way to activation more pronounced in the proximal part. In both parts of the ileum, inhibition of contractile activity ...

In some cellular systems, the information suggests that EGFR, somatostatin receptors, SHP-1, Akt and PI3K can regulate carcinogenesis implied process through regulated the activity of NF-κB. Current patents related to signaling pathway that includes somatostatin receptors, phosphotyrosine phosphatases, tyrosine kinases, AKT/PKB and PI3K are focusing in diagnosis, prognosis and treatment. ...

Introduction: Mitosis is a key step in the cell cycle and is controlled by several cell cycle regulators, including aurora kinases. Aurora family members A, B and C are essential for spindle assembly, centrosome maturation, chromosomal segregation and cytokinesis. Overexpression/amplification of aurora kinases has been implicated in oncogenic transformation, including ...

AIMS: The anti-human rhinovirus (HRV) activity of orobol 7-O-d-glucoside (O7G) from Lagerstroemia speciosa L. (Lythraceae) was evaluated in Hela cells. METHODS AND RESULTS: We tested anti-HRV activity of O7G using a cytopathic effect (CPE) reduction method, which exhibited broad-spectrum anti-HRVs activity with a 50% inhibitory concentration (IC(50)) ranging from 0.58 ...

Induction of type I interferons by the transcription factor IRF3 is essential in the initiation of antiviral innate immunity. Activation of IRF3 requires C-terminal phosphorylation by the upstream kinases TBK1-IKKi, where IRF3 phosphorylation promotes dimerization, and subsequent nuclear translocation to the IFNbeta promoter. Recent studies have described the ubiquitin-editing enzyme ...

Activation of the prophenoloxidase (proPO) system and synthesis of antimicrobial peptides (including lysozyme) are two key defense mechanisms in arthropods. Activation of proPO involves a cascade of serine proteinases that eventually converts proPO to active phenoloxidase (PO). However, a trade-off between lysozyme/antibacterial activity and PO activity has been observed in ...

Human cytomegalovirus infections are still associated with severe morbidity and mortality in immunocompromised individuals, despite the availability of five drugs that are currently licensed for antiviral therapy. Furthermore, human cytomegalovirus is the most frequent cause of congenital infections for which antiviral treatment options are very limited. Thus, the need for ...

Ribonucleases identified from zebrafish possess angiogenic and bactericidal activities. Zebrafish RNases have three intramolecular disulfide bonds, a characteristic structural feature of angiogenin, different from the typical four disulfide bonds of the other members of the RNase A superfamily. They also have a higher degree of sequence homology to angiogenin than ...

BACKGROUND: Human thioredoxin (TRX) is one of redox-active proteins that regulate reactive oxidative metabolisms. In recent study, we found that serum levels of TRX were elevated in asthmatic patients with exacerbation; however, few details are known about the physiological role of TRX in allergic inflammation, involving eosinophil infiltration. OBJECTIVE: In ...

BACKGROUND: Eosinophils play a pivotal role in the pathogenesis of asthma. Thus, it is of paramount importance to investigate the mechanism of eosinophil activation. Although a number of factors including cytokines/chemokines activate eosinophils, the potency of each stimulus to phosphorylate intracellular molecules and activate eosinophils remains to be elucidated. In ...

APOBEC3G (APO3G) is a cellular cytidine deaminase with potent antiviral activity. Initial studies of the function of APO3G demonstrated extensive mutation of the viral genome, suggesting a model in which APO3G's antiviral activity is due to hypermutation of the viral genome. Recent studies, however, found that deaminase-defective APO3G mutants transiently ...

Phosphonopropoxymethyl-guanine is the methylene phosphonate analogue of acyclovir. Although not highly active against HSV, 4-38 microM of phosphonopropoxymethyl-guanine has been reported to be active against human and murine cytomegalovirus. Recently we found that cidofovir, when esterified with alkoxyalkyl moieties, showed greatly increased antiviral activity against cytomegalovirus, herpes simplex virus and ...

Alkoxyalkyl esters of cidofovir (CDV) have substantially greater antiviral activity and selectivity than unmodified CDV against herpesviruses and orthopoxviruses in vitro. Enhancement of antiviral activity was also noted when cyclic CDV was esterified with alkoxyalkanols. In vitro antiviral activity of the most active analogs against human cytomegalovirus (HCMV) and orthopoxviruses ...

Pegylated interferon alpha-2, alone or in combination with ribavirin, has become the standard therapy for patients with chronic hepatitis C infection. Pegylation of interferon alpha-2 results in a substantially extended half-life that permits once-weekly dosing, because of reduced clearance and more sustained absorption. The size of PEG moiety appears to ...

We herein describe the development of aryloxy phosphoramidate triesters as an effective pro-tide motif for the intracellular delivery of charged bio-active antiviral nucleoside monophosphates. The review covers the discovery of such aryl phosphoramidates, their mechanism of action and structure-activity relationships. The application of this strategy to a range of antiviral ...

Fourteen catechol and bis-catechol derivatives have been synthesised and tested for their HIV-1 inhibitory activities. The six more active molecules have been tested for their antiviral activity and cytotoxicity. We have found that bis-catechols 1 and 2 are the most active HIV-1 integrase inhibitor whereas the best antiviral compound is ...

A series of antiviral compounds were examined for their activity against human herpesvirus type 6 (HHV-6), type 7 (HHV-7) and type 8 (HHV-8). They were selected either because they are already approved for clinical use in the treatment of herpesvirus infections (acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, brivudin, foscarnet and cidofovir) ...

Two protein bound polysaccharides, a neutral protein bound polysaccharide (NPBP) and an acidic protein bound polysaccharide (APBP), were isolated from water soluble substances of Ganoderma lucidum by EtOH precipitation and DEAE-cellulose column chromatography. Their antiviral activities against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) were then investigated ...

Monoalkyl ether lipid analogues of foscarnet (phosphonoformate, PFA) exhibit substantially greater in vitro antiviral activity than unmodified PFA against human immunodeficiency virus type 1 (HIV-1). Our previous studies indicate that the length of the alkyl chain must be 14-22 carbons for optimal antiviral activity. To further evaluate the structure-activity relationship, ...

Onconase, a homolog of ribonuclease A (RNase A) with low ribonucleolytic activity, is cytotoxic and has efficacy as a cancer chemotherapeutic. Here variants of RNase A were used to probe the interplay between ribonucleolytic activity and evasion of the cytosolic ribonuclease inhibitor protein (RI) in the cytotoxicity of ribonucleases. K41R/G88R ...

A range of polyether para-substituted phosphoramidates were synthesised and found to have substantially elevated aqueous solubilities compared to the underivatised parent prodrug. A 30-fold increase in aqueous solubility could be achieved without a substantial decrease of in vitro activity against HIV-1. Replacement of the aryl (i.e. phenolic) moiety by tyrosine ...

The antiviral activity of a substance (L4-1) purified from silkworm faeces was examined in an HVJ (Sendai virus)-LLC-MK2 cell system. Its antiviral effect depended on the period of light irradiation and was inhibited by sodium sulfite and anaerobic conditions. These results indicate that the antiviral activity of L4-1 is associated ...

Triciribine and triciribine monophosphate have antiviral and antiproliferative activity at low or submicromolar concentrations. In an effort to improve and better understand this activity, we have synthesized a series of acyclic analogs and evaluated them for activity against select viruses and cancer cell lines. We conclude that the rigid ribosyl ...

Aspirin-induced asthma (AIA) is frequently accompanied by nasal polyps. Eosinophil infiltration is a characteristic feature of nasal polyps associated with AIA. Even though steroids are well known to be effective on managing AIA and its nasal polyps, histochemical examinations after steroid therapy and at recurrence, involving eosinophil infiltration of nasal ...

The light-induced antiviral activity of hypericin and hypocrellin in the presence and absence of oxygen was examined under experimental conditions where the effect of oxygen depletion could be quantified. There was a significant reduction of light-induced antiviral activity of hypericin and hypocrellin under hypoxic conditions. Interestingly, antiviral activity of hypocrellin ...

A study of quantitative structure-activity relationships (QSAR) has been performed for some sulphonamidobenzophenone oximes to investigate the mechanism of their antiviral activity against polio and rhino viruses. It has been shown that viral macromolecule synthesis could be the target of their action and that the antiviral activity of the compounds ...

A case of hypereosinophilic syndrome with eosinophilic colitis, eosinophilic cholecystitis, and increased serum levels of interleukin-5 (IL-5) and soluble interleukin-2 receptor (sIL-2R) is reported. Immunohistochemical studies of cholecystectomy and colon biopsy specimens with monoclonal antibodies, which are specific for activated eosinophils, secreted eosinophil cationic protein (ECP) and for major basic ...

Recently, a new class of immunomodulating agents, represented by the molecules imiquimod and R-842, has demonstrated potent antiviral and antitumor activities in animal models. In this study, another representative of this class, S-28463 (4-amino-2-ethoxymethyl-alpha,alpha-dimethyl-1H-imidazo[4,5-c]quinoline- 1- ethanol) was evaluated for its immunomodulating and antiviral activities. S-28463 induced IFN and other cytokines ...

A series of halogenated propanes and propenes were studied for mutagenic effects in Salmonella typhimurium TA100 in the absence or presence of NADPH plus liver microsomes from phenobarbital-induced rats as an exogenous metabolism system. The cytotoxic and mutagenic effects of the halogenated propane 1,2-dibromo-3-chloropropane (DBCP) has previously been studied in ...

When ethidium bromide (EB) is combined with poly r(A-U) at an EB/ribonucleotide ratio of 1/4, the antiviral activity of the EB increases 22-fold. The increased antiviral activity is not due to increased interferon induction, direct viral inactivation or host cell cytotoxicity. Phase contrast, confocal and fluorescence microscopic observations reveal an ...

Several simple 8-substituted 9-alkyl- and 7,8-disubstituted 9-alkylguanine derivatives were synthesized as potential antiviral agents. These were tested for antiviral protection against a lethal Semliki Forest virus (SFV) infection in mice, and their antiviral properties were evaluated from a structure-activity standpoint. In this model system, 9-alkylguanines with the alkyl chain consisting ...

Immunoenhancing activity of synthetic muramyl dipeptide (MDP) was investigated in relation to the activation of rainbow trout (Oncorhynchus mykiss) phagocytes and to nonspecific protection against challenge with the fish pathogen Aeromonas salmonicida. Head kidney phagocytes collected from MDP-injected fish showed significant chemotactic activity against zymosan-activated normal rainbow trout serum, and ...

T. brucei cytoplasmic calcium-dependent alkaline ribonuclease activity from DEAE-cellulose fractionation was separated into endoribonuclease and exoribonuclease activities by hydroxyapatite chromatography. T. brucei cytoplasmic extract markedly decreased the endoribonuclease activity, but slightly potentiated the activities of the exoribonuclease and bovine ribonuclease A. While the endoribonuclease was activated by trypsin, the exoribonuclease ...

Experiments were conducted to study the major constituents of Zingiber officinale responsible for its molluscicidal activity and the effect of the active component on different stages of Schistosoma mansoni. Gingerol and shogaol exhibited potent molluscicidal activity on Biomphalaria glabrata. Gingerol (5.0 ppm) completely abolished the infectivity of Schistosoma mansoni miracidia ...

Seventeen nucleoside derivatives (derived from arabinosylcytosine, resp. cytidine, 5-fluorouracil and uracil) were tested by agar-diffusion plaque-inhibition test for their antiviral activity with herpes simplex, vaccinia, fowl plague, Newcastle disease and western equine encephalomyelitis viruses. The highest antiviral activity against DNA viruses exhibited arabinosylcytosine, N4-acylarabinosylcytosines, arabinosylthiouracil, cyclocytidine and its 5'-chloroderivative. RNA ...

The role of riboflavin (RFN), FAD or FMN in modulating the antiviral activity of poly r(A-U) was examined by the human foreskin fibroblast-vesicular stomatitis virus bioassay in which the concentrations of poly r(A-U) was fixed at 0.1 mM or 0.2 mM while the riboflavin, FAD or FMN concentration was varied ...

A series of clones has been derived from an interferon-resistant murine cell line, Ltk- aprt-, and their antiviral properties have been characterized. In the parental Ltk- aprt- line interferon is unable to establish antiviral properties or to increase the levels of 2,5-oligo(A) synthetase, the 2,5-oligo(A)-activated endonuclease F, 2',5'-phosphodiesterase, or eIF-2 ...

5-Methoxymethyl-1-(2'-deoxy-beta-D-lyxofuranosyl)uracil (MMdLU) was not active against the herpes simplex viruses. The relationship between molecular conformation and antiviral activity for the two epimers, 5-methoxymethyl-2'-deoxyuridine (MMdUrd) and MMdLU, is discussed. MMdUrd was phosphorylated by the virus-induced deoxythymidine kinase. In contrast, MMdLU did not serve as a substrate for the kinase. The geometry ...

There is good evidence that a variety of viruses encode functions that inhibit activation of either ribonuclease L or the Pl/eIF-2 alpha kinase. In general, this capability is evident among viruses that maintain long-term active or latent infections, and must therefore deal with interferon-induced antiviral responses of their hosts.

Human beta-interferon (HuIFN-beta) exhibits antiproliferative and antiviral properties. Successful clinical application of this drug depends on knowledge of the thermal stability of these activities under physiological conditions. In the present study, both the antiproliferative and antiviral activities were stabilized by the addition of very small quantities of serum proteins. This ...

Antiviral and cell-differentiating (CD) activities of immune interferon (IFN-gamma) preparation were investigated. Male STD-ddY mice were sensitized with BCG. Three weeks later, they were challenged with BCG or purified protein derivative (PPD), and exsanguinated at intervals. The sera were assayed for antiviral and CD activities. The CD activity appeared and ...

(XyloA2'p)2xyloA, the xyloadenosine core analog of the interferon mediator 2-5A [ppp(A2'p)2A], was found to exhibit potent antiviral activity against herpes simplex viruses 1 and 2 (D. A. Eppstein, J. W. Barnett, Y. V. Marsh, G. Gosselin, and J. -L. Imbach (1983a) Nature (London) 302: 723-724). This xylo 2-5A core analog ...

An extensive series of alkylated phenanthrenes was assayed for mutagenic activity in Salmonella typhimurium TA98 and TA100. Among the alkylated phenanthrenes assayed, 1-methylphenanthrene, 9-methylphenanthrene, 1,4-dimethylphenanthrene and 4,10-dimethylphenanthrene were active as mutagens. These studies suggest that the structural requirements favoring mutagenic activity among alkylated phenanthrenes are inhibition of 9,10-dihydrodiol formation and ...

Methylated fluorenes were assayed for mutagenic activity towards Salmonella typhimurium TA98 and TA100. None of these methylfluorenes were mutagenic in the absence of metabolic activation. In the presence of 9000 X g supernatant from Aroclor-induced rats, 9-methylfluorene and 1,9-dimethylfluorene were active towards TA98 and TA100. The structural requirement for mutagenic ...

L1210 cells resistant to the antiviral and anticellular effects of interferon are not inducible for the 2,5A synthetase and for the protein kinase activities. Cloning of one resistant L1210 strain has revealed heterogeneity of the cell population with respect to their antiviral and anticellular response as well as protein kinase ...