Dose-dependent progressive sunscreens. A new strategy for photoprotection?

2010 ◽  
Vol 9 (4) ◽  
pp. 530 ◽  
Author(s):  
Adaya Gallardo ◽  
Jordi Teixidó ◽  
Ricardo Miralles ◽  
Manuel Raga ◽  
Antonio Guglietta ◽  
...  
Keyword(s):  
New Strategy ◽  
Dose Dependent

Enhanced red luminescence and improved crystallinity in NaEu(WO4)2 phosphors: an electron beam irradiation study

2018 ◽  
Vol 42 (4) ◽  
pp. 2726-2732 ◽  
Author(s):  
Archana K. Munirathnappa ◽  
Vikash C. Petwal ◽  
Jishnu Dwivedi ◽  
Nalini G. Sundaram
Keyword(s):  
Electron Beam ◽  
Band Gap ◽  
Fluorescence Intensity ◽  
Electron Beam Irradiation ◽  
Beam Irradiation ◽  
Band Gap Engineering ◽  
New Strategy ◽  
Red Luminescence ◽  
Dose Dependent

Band gap engineering in NaEu(WO4)2 red phospors via dose-dependent EB irradiation: a new strategy for improving fluorescence intensity.

scholarly journals Antimicrobial Activity of Quinazolin Derivatives of 1,2-Di(quinazolin-4-yl)diselane against Mycobacteria

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Bikui Tang ◽  
Meili Wei ◽  
Qun Niu ◽  
Yinjiu Huang ◽  
Shuo Ru ◽  
...  
Keyword(s):  
New Drugs ◽  
Dependent Manner ◽  
Anticancer Activities ◽  
Quinazoline Derivative ◽  
Damage Level ◽  
New Strategy ◽  
Quinazoline Derivatives ◽  
Clinical Drugs ◽  
Dose Dependent ◽  
Derivatives Of

Mycobacterium tuberculosis (M. tuberculosis) is one of the leading causes of morbidity and mortality. Currently, the emergence of drug resistance has an urgent need for new drugs. In previous study, we found that 1,2-di(quinazolin-4-yl)diselane (DQYD), a quinazoline derivative, has anticancer activities against many cancers. However, whether DQYD has the activity of antimycobacterium is still little known. Here our results show that DQYD has a similar value of the minimum inhibitory concentration with clinical drugs against mycobacteria and also has the ability of bacteriostatic activity with dose-dependent and time-dependent manner. Furthermore, the activities of DQYD against M. tuberculosis are associated with intracellular ATP homeostasis. Meanwhile, mycobacterium DNA damage level was increased after DQYD treatment. But there was no correlation between survival of mycobacteria in the presence of DQYD and intercellular reactive oxygen species. This study enlightens the possible benefits of quinazoline derivatives as potential antimycobacterium compounds and furtherly suggests a new strategy to develop new methods for searching antituberculosis drugs.

The Role of 5-HT1A/BAutoreceptors in the Antinociceptive Effect of Systemic Administration of Acetaminophen

2003 ◽  
Vol 98 (3) ◽  
pp. 741-747 ◽  
Author(s):  
Aránzazu Roca-Vinardell ◽  
Antonio Ortega-Alvaro ◽  
Juan Gibert-Rahola ◽  
Juan A. Micó
Keyword(s):  
Antinociceptive Effect ◽  
Serotonin Release ◽  
Hot Plate ◽  
Hot Plate Test ◽  
Plate Test ◽  
Way 100635 ◽  
New Strategy ◽  
Dose Dependent ◽  
Different Doses

Background It has been proposed that serotonin participates in the central antinociceptive effect of acetaminophen. The serotonin activity in the brainstem is primarily under the control of 5-HT1A somatodendritic receptors, although some data also suggest the involvement of 5-HT1B receptors. In the presence of serotonin, the blockade of 5-HT(1A/B) receptors at the level of the raphe nuclei leads to an increase in serotonin release in terminal areas, thus improving serotonin functions. This study examines the involvement of 5-HT(1A/B) receptors in the antinociceptive effect of acetaminophen in mice. Methods The effects of acetaminophen (600 mg/kg intraperitoneal) followed by different doses of antagonists (WAY 100635 [0.2-0.8 mg/kg subcutaneous] and SB 216641 [0.2-0.8 mg/kg subcutaneous]) or agonists (8-OH-DPAT [0.25-1 mg/kg subcutaneous] and CP 93129 [0.125-0.5 mg/kg subcutaneous]) of 5-HT1A and 5-HT1B receptors, respectively, were determined in the hot-plate test in mice. Results Acetaminophen (300-800 mg/kg) showed a dose-dependent antinociceptive effect in the hot-plate test in mice. WAY 100635 (0.2-0.8 mg/kg; 5-HT1A antagonist) induced an increase in the antinociceptive effect of 600 mg/kg acetaminophen, but this increase was not dose related. Conversely, 8-OH-DPAT (0.25-1 mg/kg; 5-HT1A agonist) decreased the antinociceptive effect of acetaminophen. SB 216641 (0.2-0.8 mg/kg; 5-HT1B antagonist) induced a dose-related increase in the antinociceptive effect of acetaminophen, and CP 93129 (0.25 mg/kg; 5-HT1B agonist) significantly decreased the antinociceptive effect of acetaminophen. Conclusions These results suggest that the combination of acetaminophen with compounds having 5-HT1A and 5-HT1B antagonist properties could be a new strategy to improve the analgesia of acetaminophen, thanks to its mild serotonergic properties.

scholarly journals Effect of multiple emulsion on mortality of drosophila virils

2019 ◽  
Vol 10 (3) ◽  
pp. 2446-2451
Author(s):  
Areej Al-Khalaf
Keyword(s):  
Peritrophic Membrane ◽  
Dependent Manner ◽  
Multiple Emulsion ◽  
Frequent Use ◽  
New Strategy ◽  
Insect Populations ◽  
Hind Gut ◽  
Pass Through ◽  
Number Of Individuals ◽  
Dose Dependent

The frequent use of insecticides has led to the development of insecticide resistance by many insects. In some insect populations, resistance can be developed to multiple pesticides. Up to this, insecticides resistance became a key challenge, and the amounts of the used pesticides must be as lower as possible. In this study, we measured the potency of multiple emulsions on the mortality of Drosophila virils and the ability of the fly to ingest and excrete the emulsions as a new strategy to avoid the great use of pesticides.  The obtained data showed that the value of the lethal concentration of half the number of individuals decreases when the exposure duration increases, which demonstrates the sensitivity of the larvae to the toxic effect of the formulation. This can help to suggest that this type of material can be more effective and lasting effect for as long as possible. Moreover, the ingestion and excretion of the formulated product in the hind-gut can help to suggest the ability of the studied formulation to pass through the peritrophic membrane and the midgut acidic regions as two important barriers. In conclusion, the formulated microcapsule has a satisfactory insecticidal potency against D. virilis in a dose-dependent manner which might help to avoid the developed resistance to commonly used insecticides.

scholarly journals Dose-Dependent Antifibrotic Effect of Chrysin on Regression of Liver Fibrosis: The Role in Extracellular Matrix Remodeling

Dose-Response ◽  
2018 ◽  
Vol 16 (3) ◽  
pp. 155932581878983 ◽  
Author(s):  
Cornel Balta ◽  
Alina Ciceu ◽  
Hildegard Herman ◽  
Marcel Rosu ◽  
Oana Maria Boldura ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Liver Fibrosis ◽  
Mouse Liver ◽  
Ultrastructural Changes ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Tissue Inhibitors Of Metalloproteinase ◽  
Spontaneous Reversion ◽  
New Strategy ◽  
Dose Dependent

Liver fibrosis represents an overaccumulation of extracellular matrix (ECM). This study was designed to investigate the effect of chrysin on established ECM overproduction in carbon tetrachloride (CCl4) mouse liver fibrosis. Experimental fibrosis was induced by intraperitoneal injection of 2 mL/kg CCl4 twice a week, for 7 weeks. Mice were orally treated with 3 doses of chrysin (5,7-dihydroxyflavone). For the assessment of the spontaneous reversion of fibrosis, CCl4-treated mice were investigated after 2 weeks of recovery time. Silymarin was used as a standard of liver protection. In fibrotic livers, the results showed the upregulation of collagen I (Col I) and tissue inhibitors of metalloproteinase 1 (TIMP-1) and modulation of matrix metalloproteinases (MMPs), which led to an altered ECM enriched in Col, confirmed as well by electron microscopy investigations. Treatment with chrysin significantly reduced ultrastructural changes, downregulated Col I, and restored TIMP-1/MMP balance, whereas in the group observed for the spontaneous regression of fibrosis, they remained in the same pattern with fibrotic livers. In this study, we have shown chrysin efficacy to attenuate dose-dependent CCl4-stimulated liver ECM accumulation by regulation of MMP/TIMP imbalance and inhibition of Col production. We have shown the dose-dependent chrysin efficiency in attenuation of CCl4-induced liver ECM accumulation by regulation of MMP/TIMP imbalance and inhibition of Col production. Our findings suggest that chrysin oral administration may introduce a new strategy for treating liver fibrosis in humans.

ATP gradients inhibit the migratory capacity of specific human dendritic cell types: implications for P2Y11 receptor signaling

Blood ◽  
2003 ◽  
Vol 102 (2) ◽  
pp. 613-620 ◽  
Author(s):  
Max Schnurr ◽  
Tracey Toy ◽  
Patrizia Stoitzner ◽  
Paul Cameron ◽  
Amanda Shin ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Cell Types ◽  
Calcium Flux ◽  
Dependent Manner ◽  
Vaccination Site ◽  
Migratory Capacity ◽  
New Strategy ◽  
Antigen Presenting ◽  
Dying Cells ◽  
Dose Dependent

AbstractDendritic cells (DCs) are specialized antigen-presenting cells residing in tissues, from which they take up antigen. Activated DCs migrate through chemokine gradients from sites of inflammation to lymph nodes to stimulate T cells. At sites of inflammation, nucleotides, such as adenosine triphosphate (ATP), are released by activated or dying cells and can function as signaling molecules through P2 receptors (P2Rs). We investigated P2R expression in different DC populations and the effect of nucleotides on chemokine-directed migration. Exposure of monocyte-derived DCs (MoDCs) and CD1a+ dermal DCs to gradients of ATP inhibited their migratory capacity in a dose-dependent manner. Studies using P2R agonists and antagonists implicated signaling through the P2Y11R. On maturation, MoDCs down-regulated P2Y11R expression and were less sensitive to ATP-mediated inhibition of migration. In contrast, ATP did not inhibit the migration of CD1c+ peripheral blood (PB) DCs or interleukin-3 receptor-positive (IL-3R+) plasmacytoid DCs. Although all 4 DC populations expressed mRNA for P2Y11R, calcium-flux studies showed that blood DC types were unresponsive to P2Y11R agonists. In conclusion, DCs use distinct subtypes of P2R. The formation of ATP gradients at sites of inflammation may transiently inhibit the migration of local DCs, thus prolonging the time of antigen encounter. P2R inhibition may represent a new strategy to improve the migration of antigen-loaded DCs from the vaccination site to lymph nodes.

scholarly journals Targeting autophagy with hydroxychloroquine potentiates ponatinib- and axitinib-induced cell death in BCR-ABL T315I-containing CML

2021 ◽  
Author(s):  
biqing han ◽  
Dandan Yao ◽  
Yongfang Jiang ◽  
Liyan Chen ◽  
Shuqiu Zhou ◽  
...  
Keyword(s):  
Cardiovascular Events ◽  
Killing Effect ◽  
Cell Clones ◽  
Increased Risk ◽  
New Strategy ◽  
Apoptosis Assay ◽  
T315i Mutation ◽  
Dose Dependent ◽  
Autophagy Inhibition

Abstract Purpose Because of the dose-dependent increased risk of cardiovascular events we tried to lower the dose of ponatinib without reducing its efficacy in the treatment of BCR-ABL T315I-containing CML. Combination with hydroxychloroquine can enhance the efficiency of ponatinib and axitinib through autophagy inhibition in CML cell with T315I. Methods Cell viability, cell cycle, cellular senescence, formation of cell clones and apoptosis assay were taken to test the efficiency of medicine. Lentiviral vectors containing shRNA was used to block autophagy and to verify the mechanism of the medicine. Establish tumor models in nude mice, and verify the experimental results in vivo. Results ponatinib and axitinib killed 32Dp210-T315I cells as well as inducing autophagy, which promoted their survival under pressure from TKIs. By inhibiting autophagy, HCQ enhanced the killing effect of ponatinib and axitinib on 32Dp210-T315I cells. In vivo HCQ also enhanced the killing effect of axitinib on 32Dp210-T315I cells. Conclusion HCQ combined with ponatinib may be a new strategy for treating CML and ALL that harbor the T315I mutation. Thus, this combination may make it possible to reduce the dose of ponatinib and reduce its side effects without compromising efficacy.

scholarly journals Dual Silencing of Hsp27 and c-FLIP Enhances Doxazosin-Induced Apoptosis in PC-3 Prostate Cancer Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Sang Soo Kim ◽  
Hee-Ju Cho ◽  
Jeong-Man Cho ◽  
Jung Yoon Kang ◽  
Hyun-Won Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Gene Silencing ◽  
Single Gene ◽  
Tunel Staining ◽  
Dependent Manner ◽  
Apoptosis Inhibition ◽  
New Strategy ◽  
Induced Apoptosis ◽  
Dose Dependent

We evaluated effect of dual gene silencing of Hsp27 and c-FLIP in doxazosin-induced apoptosis of PC-3 cell. After transfection using Hsp27 and c-FLIP siRNA mixture (dual silencing), doxazosin treatment was done at the concentrations of 1, 10, and 25 μM. We checked apoptosis of PC-3 cells with and TUNEL staining. We also checked interaction between Hsp27 and C-FLIP in the process of apoptosis inhibition. Spontaneous apoptotic index was 5% under single gene silencing of Hsp27 and c-FLIP and 7% under dual silencing of Hsp27 and c-FLIP. When doxazosin treatment was added, apoptotic indices increased in a dose-dependent manner (1, 10, and 25 μM): nonsilencing 10, 27, and 52%; Hsp27-silencing: 14, 35, and 68%; c-FLIP silencing: 21, 46, and 78%; dual silencing: 38, 76, and 92%. While c-FLIP gene expression decreased in Hsp27- silenced cells, Hsp27 gene expression showed markedly decreased pattern in the cells of c-FLIP silencing. The knockout of c-FLIP and Hsp27 genes together enhances apoptosis even under 1 μM, rather than low concentration, of doxazosin in PC-3 cells. This finding suggests a new strategy of multiple knockout of antiapoptotic and survival factors in the treatment of late-stage prostate cancer refractory to conventional therapy.

scholarly journals Activating the Intrinsic Pathway of Apoptosis Using BIM BH3 Peptides Delivered by Peptide Amphiphiles with Endosomal Release

Materials ◽  
2019 ◽  
Vol 12 (16) ◽  
pp. 2567
Author(s):  
Mathew R. Schnorenberg ◽  
Joseph A. Bellairs ◽  
Ravand Samaeekia ◽  
Handan Acar ◽  
Matthew V. Tirrell ◽  
...  
Keyword(s):  
Immune Modulation ◽  
Death Domain ◽  
Intracellular Accumulation ◽  
Intrinsic Pathway ◽  
Peptide Amphiphile ◽  
New Strategy ◽  
Full Complement ◽  
Hydrophobic Tail ◽  
Endosomal Release ◽  
Dose Dependent

Therapeutic manipulation of the BCL-2 family using BH3 mimetics is an emerging paradigm in cancer treatment and immune modulation. For example, peptides mimicking the BIM BH3 helix can directly target the full complement of anti- and pro-apoptotic BCL-2 proteins to trigger apoptosis. This study has incorporated the potent BH3 α-helical death domain of BIM into peptide amphiphile (PA) nanostructures designed to facilitate cellular uptake and induce cell death. This study shows that these PA nanostructures are quickly incorporated into cells, are able to specifically bind BCL-2 proteins, are stable at physiologic temperatures and pH, and induce dose-dependent apoptosis in cells. The incorporation of a cathepsin B cleavable linker between the BIM BH3 peptide and the hydrophobic tail resulted in increased intracellular accumulation and mitochondrial co-localization of the BIM BH3 peptide while also improving BCL-2 family member binding and apoptotic reactivation. This PA platform represents a promising new strategy for intracellular therapeutic peptide delivery for the disruption of intracellular protein:protein interactions.

scholarly journals Novel Compound Induces Erythropoietin Secretion through Liver Effects in Chronic Kidney Disease Patients and Healthy Volunteers

2018 ◽  
Vol 48 (3) ◽  
pp. 157-164 ◽  
Author(s):  
Aya Shinfuku ◽  
Toshiharu Shimazaki ◽  
Masanori Fujiwara ◽  
Fumihiko Sato ◽  
Hirotaka Watase ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Healthy Volunteers ◽  
Hypoxia Inducible Factor ◽  
Correlation Coefficients ◽  
Two Phase ◽  
New Strategy ◽  
The Mean ◽  
Oral Doses ◽  
Dose Dependent

Background: TP0463518 is a novel hypoxia-inducible factor prolyl hydroxylase inhibitor developed to aid in the treatment of anemia associated with chronic kidney disease (CKD) and is expected to increase erythropoietin (EPO) derived from liver. Two phase I studies were conducted in healthy volunteers (HV) and CKD patients undergoing hemodialysis (i.e., HD patients) or those not undergoing dialysis (i.e., ND patients). Methods: Pharmacokinetics, pharmacodynamics, and safety profiles of TP0463518 were assessed. Forty HV received single oral doses of TP0463518 at 3, 6, 11, 20, and 36 mg or placebo. Twenty ND patients received single doses of TP0463518 at 1, 6, and 11 mg and 9 HD patients received TP0463518 at 1 and 11 mg doses. To identify the source organ of EPO, glycosylation patterns were determined using percentage migrated isoform (PMI) values. Results: Declining renal function slowed elimination of TP0463518 and increased the mean AUC0–∞. ∆Emax of serum EPO in 11-mg groups of HV, ND patients, and HD patients were 24.37 ± 11.37, 201.57 ± 130.34, and 1,324.76 ± 1,189.24 mIU/mL respectively. A strong correlation was ­observed between logarithm conversions of ∆Emax and AUC0–∞ with correlation coefficients of 0.945. PMI values of blood after TP0463518 administration were elevated to similar or higher levels in comparison with those of umbilical cord blood, which mainly contains liver-derived EPO. Conclusions: TP0463518 induced dose-dependent EPO production, mainly derived from the liver in HV and CKD patients. These results suggest that TP0463518 is a new strategy for treating anemia in CKD, which can be used regardless of renal functions.

Sign in / Sign up

Export Citation Format

Share Document