scholarly journals Inhibitory effect of gamma irradiation against Cucumber green mottle mosaic virus

2017 ◽  
Vol 53 (No. 4) ◽  
pp. 201-207 ◽  
Author(s):  
Hong Jin-Sung ◽  
Jeong Mi-Ae ◽  
Jeong Rae-Dong
Keyword(s):  
Gamma Irradiation ◽  
Mosaic Virus ◽  
Fungal Pathogens ◽  
Inhibitory Effect ◽  
Plant Viruses ◽  
Dependent Manner ◽  
Genomic Rna ◽  
Transmission Electron ◽  
Virion Structure ◽  
Dose Dependent

Gamma irradiation has been shown to be an effective method of controlling plant bacterial and fungal pathogens, but data on its effect against plant viruses is limited. A mechanism for the inactivation of plant viruses by gamma irradiation has not been proposed. Gamma irradiation was evaluated for the inactivation of Cucumber green mottle mosaic virus (CGMMV) in Nicotiana tabacum plants. CGMMV infectivity decreased gradually in a dose-dependent manner, and the virus was completely inactivated at over 40 kGy. Transmission electron microscopy revealed that gamma irradiation disrupts the virion structure and degrades viral protein and genomic RNA, suggesting that damage to viral constituents is the mechanism by which gamma irradiation inactivates the virus.

scholarly journals MicroRNA-106a Inhibits Autophagy Process and Antimicrobial Responses by Targeting ULK1, ATG7, and ATG16L1 During Mycobacterial Infection

2021 ◽  
Vol 11 ◽  
Author(s):  
Kunmei Liu ◽  
Dantong Hong ◽  
Fan Zhang ◽  
Xin Li ◽  
Meng He ◽  
...  
Keyword(s):  
Immune Response ◽  
Electron Microscope ◽  
Mycobacterial Infection ◽  
Inhibitory Effect ◽  
Innate Immune ◽  
Negative Regulator ◽  
Dependent Manner ◽  
Transmission Electron ◽  
Dose Dependent

Autophagy is a key element of innate immune response against invading pathogens including Mycobacterium tuberculosis (M. tuberculosis). The emerging roles of microRNAs in regulating host antimicrobial responses against M. tuberculosis have gained widespread attention. However, the process by which miRNAs specifically influence antibacterial autophagy during mycobacterial infection is largely uncharacterized. In this study, we demonstrate a novel role of miR-106a in regulating macrophage autophagy against M. tuberculosis. H37Ra infection leads to downregulation of miR-106a in a time- and dose-dependent manner and concomitant upregulation of its three targets (ULK1, ATG7, and ATG16L1) in THP-1 macrophages. MiR-106a could inhibit autophagy activation and antimicrobial responses to M. tuberculosis by targeting ULK1, ATG7, and ATG16L1. Overexpression of miR-106a dramatically inhibited H37Ra-induced activation of autophagy in human THP-1 macrophages, whereas inhibitors of miR-106a remarkably promoted H37Ra-induced autophagy. The inhibitory effect of miR-106a on autophagy process during mycobacterial infection was also confirmed by Transmission Electron Microscope (TEM) observation. More importantly, forced expression of miR-106a increased mycobacterial survival, while transfection with miR-106a inhibitors attenuated the survival of intracellular mycobacteria. Taken together, these data demonstrated that miR-106a functioned as a negative regulator in autophagy and antimicrobial effects by targeting ULK1, ATG7, and ATG16L1 during M. tuberculosis infection, which may provide a potential target for developing diagnostic reagents or antibacterials against tuberculosis.

Synthesis and Assessment of Novel Anti-chlamydial Benzylidene Acylhydrazides Derivatives

2018 ◽  
Vol 15 (1) ◽  
pp. 31-36 ◽  
Author(s):  
Xiaofeng Bao ◽  
Ying Xue ◽  
Chao Xia ◽  
Yin Lu ◽  
Ningjing Yang ◽  
...  
Keyword(s):  
Inhibitory Effect ◽  
Dependent Manner ◽  
Iron Starvation ◽  
Hydrochloride Salt ◽  
Obligate Intracellular ◽  
Biphasic Life Cycle ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Dose Dependent ◽  
Better Than

Background: Chlamydiae, characterized by a unique biphasic life cycle, are a group of Gram-negative obligate intracellular bacterial pathogens responsible for diseases in a range of hosts including humans. Benzylidene acylhydrazide CF0001 could inhibit chlamydiae independent of iron starvation and T3SS inhibition. This finding promoted us to design and synthesize more benzylidene acylhydrazides to find novel anti-chlamydial agents. Methods: The carboxylic acids 1a-1d were coupled with Boc-hydrazide inpresence of EDCI and DMAP to obtain the intermediate 2a-2d in 60-62% yields. N-Boc deprotections were performed to obtain hydrazide hydrochloride salt 3a-3d. Nextly, the hydrazides were subjected to condensation with aldehydes to obtain benzylidene acylhydrazides 4a-4g in 30-52% yields in two steps. Results: Compound 4d exhibited best inhibitory effect on the formation and growth of chlamydial inclusions. The IC50 value of compound 4d for infectious progenies was 3.55 µM, better than 7.30 µM of CF0001. Conclusion: To find novel anti-chlamydial agents, we have designed and synthesized benzylidene acylhydrazides 4a-4g. Compounds 4a, 4d, 4g showed inhibitory activity on C. muridarum with the IC50 values from 3.55-12 µM. The 3,5-dibromo-4-hydroxyl substitutes on ring B are critical to keep their anti-chlamydial activity. Compound 4d inhibited C. muridarum in a dose-dependent manner without apparent cytotoxicity.

scholarly journals In vitro study on the effect of cornin on the activity of cytochrome P450 enzymes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qun Zhang ◽  
Zengqiang Qu ◽  
Yanqing Zhou ◽  
Jin Zhou ◽  
Junwei Yang ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Drug Interaction ◽  
Liver Microsomes ◽  
In Vitro Study ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Drug Drug Interaction ◽  
Dose Dependent

Abstract Background Cornin is a commonly used herb in cardiology for its cardioprotective effect. The effect of herbs on the activity of cytochrome P450 enzymes (CYP450s) can induce adverse drug-drug interaction even treatment failure. Therefore, it is necessary to investigate the effect of cornin on the activity of CYP450s, which can provide more guidance for the clinical application of cornin. Methods Cornin (100 μM) was incubated with eight isoforms of CYP450s, including CYP1A2, 2A6, 3A4, 2C8, 2C9, 2C19, 2D6, and 2E1, in pooled human liver microsomes. The inhibition model and corresponding parameters were also investigated. Results Cornin exerted significant inhibitory effect on the activity of CYP3A4, 2C9, and 2E1 in a dose-dependent manner with the IC50 values of 9.20, 22.91, and 14.28 μM, respectively (p < 0.05). Cornin inhibited the activity of CYP3A4 non-competitively with the Ki value of 4.69 μM, while the inhibition of CYP2C9 and 2E1 by cornin was competitive with the Ki value of 11.31 and 6.54 μM, respectively. Additionally, the inhibition of CYP3A4 by cornin was found to be time-dependent with the KI/Kinact value of 6.40/0.055 min− 1·μM− 1. Conclusions The inhibitory effect of cornin on the activity of CYP3A4, 2C9, and 2E1 indicated the potential drug-drug interaction between cornin and drugs metabolized by these CYP450s, which needs further investigation and validation.

Immunomodulatory activities of whey fractions in efferent prefemoral lymph of sheep

1996 ◽  
Vol 63 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Chun W. Wong ◽  
Geoffrey O. Regester ◽  
Geoffrey L. Francis ◽  
Dennis L. Watson
Keyword(s):  
Immune Responses ◽  
Bovine Milk ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Milk Whey ◽  
Significant Difference ◽  
Lymphocyte Phenotypes ◽  
Dose Dependent

SummaryStudies on the immunomodulatory activities of ruminant milk and colostral whey fractions were undertaken. By comparing with boiled colostral whey in a preliminary experiment, a putative heat-labile immunostimulatory factor for antibody responses was found to be present in ovine colostral whey. Studies were then undertaken in sheep in which the efferent prefemoral lymphatic ducts were cannulated bilaterally, and immune responses in the node were measured following subcutaneous injection in the flank fold of whey protein preparations of various purities. A significant sustained decline of efferent lymphocyte output was observed following injection with autologous crude milk whey or colostral whey preparations, but no changes were observed in interferon-gamma levels in lymph plasma. Two bovine milk whey fractions (lactoperoxidase and lactoferrin) of high purity were compared in bilaterally cannulated sheep. A transient decline over the first 6 h was seen in the efferent lymphocyte output and lymph flow rate after injection of both fractions. A significant difference was seen between the two fractions in interferongamma levels in lymph at 6 h after injection. However, no significant changes in the proportion of the various efferent lymphocyte phenotypes were seen following either treatment. Whereas both fractions showed a significant inhibitory effect in a dose-dependent manner on the proliferative response of T lymphocytes, but not B lymphocytes, to mitogenic stimulation in vitro, no similar changes were seen following in vivo stimulation with these two fractions.

Reversible arrest of Artemia development by cadmium

1986 ◽  
Vol 64 (8) ◽  
pp. 1633-1641 ◽  
Author(s):  
Parvaneh Rafiee ◽  
Christopher O. Matthews ◽  
Joseph C. Bagshaw ◽  
Thomas H. MacRae
Keyword(s):  
Normal Development ◽  
Developmental Process ◽  
Inhibitory Effect ◽  
Microtubule Assembly ◽  
Abnormal Development ◽  
Dependent Manner ◽  
Physiological Changes ◽  
Molecular Aspects ◽  
Reduced Rate ◽  
Dose Dependent

Under normal conditions, an encysted Artemia embryo undergoes a developmental process that culminates in the gradual, uninterrupted emergence of the prenauplius from the cyst. The hatching membrane surrounding the emerged organism is then ruptured, usually beginning at the posterior end, and a motile nauplius is released. We have observed this process microscopically in the presence and absence of cadmium and report that cadmium disrupts Artemia development in a dose–dependent manner. At 0.1 μM, cadmium slows emergence but nauplii eventually resume rellatively normal development. Emergence and hatching are either delayed considerably or almost entirely prevented at 1 μM cadmium. Cadmium at 10 μM, completely arrests emergence but development continues at a reduced rate, eventually resulting in hatching of some organisms without need for complete emergence. If organisms exposed to 10 μM cadmium are washed, abnormally shaped emerged forms are released and many of these eventually hatch, although in an unusual manner. Cadmium at 10 μM causes complete, rapid precipitation of purified Artemia tubulin at 0 °C but cadmium at the lower concentrations tested has no apparent inhibitory effect on microtubule assembly. Although we do not know the actual cadmium–induced physiological changes that result in abnormal development of Artemia, our results indicate that we can now examine the interdependence of morphological and molecular aspects of Artemia development in a way not previously possible.

Role Of Cyclic Amp In The Inhibition Of Human Platelet Functions By Quercetin, A Flav0N0Id That Potentiates PGI2 Effect

1981 ◽  
Author(s):  
J P Cazenave ◽  
A Beretz ◽  
A Stierlé ◽  
R Anton
Keyword(s):  
Maximum Level ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Pde Inhibitors ◽  
Pde Inhibition ◽  
Induced Aggregation ◽  
Camp Levels ◽  
Dose Dependent

Injury to the endothelium (END) and subsequent platelet (PLAT)interactions with the subEND are important steps in thrombosis and atherosclerosis. Thus,drugs that protect the END from injury and also inhibit PLAT function are of interest. It has been shown that some flavonoids(FLA), a group of compounds found in plants, prevent END desquamation in vivo, inhibit cyclic nucleotide phosphodiesterases(PDE)and inhibit PLAT function. We have studied the structure-activity relationships of 13 purified FLA on aggregation and secretion of 14c-5HT of prelabeled washed human PLAT induced by ADP, collagen(COLL) and thrombin(THR). All the FLA were inhibitors of the 3 agents tested. Quercetin(Q), was the second best after fisetin. It inhibited secretion and aggregation with I50 of 330µM against 0.1 U/ML.THR, 102µM against 5µM ADP and 40 µM against COLL. This inhibitory effect is in the range of that of other PDE inhibitors like dipyridamole or 3-isobutyl-l- methylxanthine. The aggregation induced by ADP, COLL and THR is at least mediated by 3 mechanisms that can be inhibited by increasing cAMP levels. We next investigated if Q, which is a PDE inhibitor of bovine aortic microsomes,raises PLAT cAMP levels. cAMP was measured by a protein-binding method. ADP- induced aggregation(5µM) was inhibited by PGI2 (0.1 and 0.5 nM) . Inhibition was further potentiated(l.7 and 3.3 times) by lOµM Q, which alone has no effect on aggregation. The basal level of cAMP(2.2 pmol/108PLAT) was not modified by Q (50 to 500µM). Using these concentrations of Q,the rise in cAMP caused by PGI2(0.1 and 0.5nM) was potentiated in a dose dependent manner. Q potentiated the effect of PGI2 on the maximum level of cAMP and retarded its breakdown. Thus Q and possibly other FLA could inhibit the interaction of PLAT with the components of the vessel wall by preventing END damage and by inhibiting PLAT function through a rise in cAMP secondary to PDE inhibition and potentiation of the effect of vascular PGI2 on PLAT adenylate cyclase.

scholarly journals Synthesis, Characterization, and Optimization of Green Silver Nanoparticles Using Neopestalotiopsis clavispora and Evaluation of Its Antibacterial, Antibiofilm, and Genotoxic Effects

2021 ◽  
Vol 5 (3) ◽  
pp. 109-122
Author(s):  
Tuğba Kahraman ◽  
Safiye Elif Korcan ◽  
Recep Liman ◽  
İbrahim Hakkı Ciğerci ◽  
Yaser Acikbas ◽  
...  
Keyword(s):  
Silver Nanoparticles ◽  
Nuclear Ribosomal Dna ◽  
Diffusion Method ◽  
Dependent Manner ◽  
Transmission Electron ◽  
Infrared Spectrophotometer ◽  
Average Size ◽  
Novel Applications ◽  
Dose Dependent

Abstract Silver nanoparticles (AgNPs) have been used in a variety of biomedical applications in the last two decades, including antimicrobial, anti-inflammatory, and anticancer treatments. The present study highlights the extracellular synthesis of silver nanoparticles AgNPs using Neopestalotiopsis clavispora MH244410.1 and its antibacterial, antibiofilm, and genotoxic properties. Locally isolated N. clavispora MH244410.1 was identified by Internal transcribed spacer (ITS) sequences of nuclear ribosomal DNA. Optimization of synthesized AgNPs was performed by using various parameters (pH (2, 4, 7, 9 and 12), temperature (25, 35 and 45 °C), and substrate concentration (0.05, 0.1, 0.15, 0.2 and 0.25 mM)). After 72 hours of incubation in dark conditions, the best condition for the biosynthesis of AgNPs was determined as 0.25 mM metal concentration at pH 12 and 35 °C. Fungal synthesized AgNPs were characterized via spectroscopic and microscopic techniques such as Fouirer Transform Infrared Spectrophotometer (FTIR), UV-Visible Spectroscopy, and Transmission Electron Microscopy (TEM). The average size of the AgNPs was determined less than 60 nm using the TEM and Zetasizer measurement system (measured in purity water suspension). The characteristic peak of AgNPs was observed at ~414 nm from UV-Vis results. Antibacterial and genotoxic activity of synthesized AgNPs (0.1, 1, and 10 ppm) were also determined by using the agar well diffusion method and in vivo Somatic Mutation and Recombination Test (SMART) in Drosophila melanogaster. AgNPs exhibited potential antimicrobial activity against all the tested bacteria (Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa) except Escherichia coli in a dose-dependent manner. AgNPs did not induce genotoxicity in the Drosophila SMART assay. 79.33, 65.47, and 41.95% inhibition of biofilms formed by P. aeruginosa were observed at 10, 1, and 0.1 ppm of AgNPs, respectively. The overall results indicate that N. clavispora MH244410.1 is a good candidate for novel applications in biomedical research.

scholarly journals In vitro inhibitory effect of obtusofolin on the activity of CYP3A4, 2C9, and 2E1

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Na Liu ◽  
Ping Chen ◽  
Xiaojun Du ◽  
Junxia Sun ◽  
Shasha Han
Keyword(s):  
Human Liver ◽  
Competitive Inhibition ◽  
Liver Microsomes ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cytochrome P450 Enzymes ◽  
Inhibition Model ◽  
Dose Dependent

Abstract Background Obtusofolin is the major active ingredient of Catsia tora L., which possesses the activity of improving eyesight and protecting the optic nerve. Investigation on the interaction of obtusofolin with cytochrome P450 enzymes (CYP450s) could provide a reference for the clinical application of obtusofolin. Methods The effect of obtusofolin on the activity of CYP450s was investigated in the presence of 100 μM obtusofolin in pooled human liver microsomes (HLMs) and fitted with the Lineweaver–Burk plots to characterize the specific inhibition model and kinetic parameters. Results Obtusofolin was found to significantly inhibited the activity of CYP3A4, 2C9, and 2E1. In the presence of 0, 2.5, 5, 10, 25, 50, and 100 μM obtusofolin, the inhibition of these CYP450s showed a dose-dependent manner with the IC50 values of 17.1 ± 0.25, 10.8 ± 0.13, and 15.5 ± 0.16 μM, respectively. The inhibition of CYP3A4 was best fitted with the non-competitive inhibition model with the Ki value of 8.82 μM. While the inhibition of CYP2C9 and 2E1 was competitive with the Ki values of 5.54 and 7.79 μM, respectively. After incubating for 0, 5, 10, 15, and 30 min, the inhibition of CYP3A4 was revealed to be time-dependent with the KI value of 4.87 μM− 1 and the Kinact value of 0.0515 min− 1. Conclusions The in vitro inhibitory effect of obtusofolin implying the potential drug-drug interaction between obtusofolin and corresponding substrates, which needs further in vivo validations.

Microinjection of exogenous somatostatin in the dorsal vagal complex inhibits pancreatic secretion via somatostatin receptor-2 in rats

2007 ◽  
Vol 292 (3) ◽  
pp. G746-G752 ◽  
Author(s):  
Zhuan Liao ◽  
Zhao-Shen Li ◽  
Yan Lu ◽  
Wei-Zhong Wang
Keyword(s):  
Pancreatic Secretion ◽  
Exocrine Pancreas ◽  
Feedback Inhibition ◽  
Somatostatin Receptor ◽  
Inhibitory Effect ◽  
Receptor Subtype ◽  
Dependent Manner ◽  
Dorsal Vagal Complex ◽  
Somatostatin Receptor Antagonist ◽  
Dose Dependent

Previous studies have suggested that somatostatin inhibits pancreatic secretion at a central vagal site, and the dorsal vagal complex (DVC) is involved in central feedback inhibition of the exocrine pancreas. The aim of this study was to investigate the effect of exogenous somatostatin in the DVC on pancreatic secretion and the somatostatin receptor subtype(s) responsible for the effect. The effects of somatostatin microinjected into the DVC on pancreatic secretion stimulated by cholecystokinin octapeptide (CCK-8) or 2-deoxy-d-glucose (2-DG) were examined in anesthetized rats. To investigate the somatostatin inhibitory action site, a somatostatin receptor antagonist [SRA; cyclo(7-aminoheptanoyl-Phe-d-Trp-Lys-Thr)] was microinjected into the DVC before intravenous infusion of somatostatin and CCK-8/2-DG. The effects of injection of a somatostatin receptor-2 agonist (seglitide) and combined injection of somatostatin and a somatostatin receptor-2 antagonist (CYN 154806) in the DVC on the pancreatic secretion were also investigated. Somatostatin injected into the DVC significantly inhibited pancreatic secretion evoked by CCK-8 or 2-DG in a dose-dependent manner. SRA injected into the DVC completely reversed the inhibitory effect of intravenous administration of somatostatin. Seglitide injected into the DVC also inhibited CCK-8/2-DG-induced pancreatic protein secretion. However, combined injection of somatostatin and CYN 154806 did not affect the CCK-8/2-DG-induced pancreatic secretion. Somatostatin in the DVC inhibits pancreatic secretion via somatostatin receptor-2, and the DVC is the action site of somatostatin for its inhibitory effect.

Discovery of a Novel Small-Molecule Interleukin-6 Inhibitor through Virtual Screening Using Artificial Intelligence

2021 ◽  
Vol 18 ◽  
Author(s):  
Yoshiaki Sato ◽  
Ikuo Kashiwakura ◽  
Masaru Yamaguchi ◽  
Hironori Yoshino ◽  
Takeshi Tanaka ◽  
...  
Keyword(s):  
Artificial Intelligence ◽  
Small Molecule ◽  
Interleukin 6 ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cell Functions ◽  
Dependent Cell ◽  
Dose Dependent

Background: Interleukin-6 (IL-6) is a multifunctional cytokine involved in various cell functions and diseases. Thus far, several IL-6 inhibitors, such as, humanized monoclonal antibody have been used to block excessive IL-6 signaling causing autoimmune and inflammatory diseases. However, anti-IL-6 and anti-IL-6 receptor monoclonal antibodies have some clinical disadvantages, such as a high cost, unfavorable injection route, and tendency to mask infectious diseases. While a small-molecule IL-6 inhibitor would help mitigate these issues, none are currently available. Objective: The present study evaluated the biological activities of identified compounds on IL-6 stimulus. Methods: We virtually screened potential IL-6 binders from a compound library using INTerprotein’s Engine for New Drug Design (INTENDD®) followed by the identification of more potent IL-6 binders with artificial intelligence (AI)-guided INTENDD®. The biological activities of the identified compounds were assessed with the IL-6-dependent cell line 7TD1. Results: The compounds showed the suppression of IL-6-dependent cell growth in a dose-dependent manner. Furthermore, the identified compound inhibited expression of IL-6-induced phosphorylation of signal transducer and activator of transcription 3 in a dose-dependent manner. Conclusion: Our screening compound demonstrated an inhibitory effect on IL-6 stimulus. These findings may serve as a basis for the further development of small-molecule IL-6 inhibitors.

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