scholarly journals Bee venom stimulation of a lung meridian acupoint reduces inflammation in a mouse model of carrageenan-induced pleurisy

2020 ◽  
Vol 13 (2) ◽  
pp. 73
Author(s):  
Hoon-Seong Choi
Keyword(s):  
Mouse Model ◽  
Bee Venom ◽  
Lung Meridian ◽  
Stimulation Of

scholarly journals 15 A novel CD28 humanized mouse model for efficacy assessment of CD28-targeting therapies

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A15-A15
Author(s):  
Fabiane Sônego ◽  
Gaelle Martin ◽  
Chloé Beuraud ◽  
Audrey Beringer ◽  
Yacine Cherifi ◽  
...  
Keyword(s):  
T Cells ◽  
Amino Acid ◽  
Mouse Model ◽  
Cytokine Production ◽  
List Type ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Efficacy Assessment ◽  
Human And Mouse ◽  
Stimulation Of

BackgroundImmuno-intervention through targeting of activating and inhibitory immune checkpoints (ICP), has shown promising results in the clinic over the last years. To facilitate these researches, mouse models expressing humanized ICP instead of their mouse counterparts were developed. Herein, we describe a novel CD28 humanized mouse model (hCD28 model), designed to test compounds targeting human CD28 (hCD28).MethodsHuman and mouse CD28 (mCD28) have different signalling responses, with hCD28 being known for inducing higher levels of pro-inflammatory cytokines upon stimulation with ligands/superagonists. This can be explained by the expression of CD28i, a hCD28 amplifier isoform which is not found in mouse. Additionally, evidences suggested that the different signalling between human and mCD28 relies on one amino acid change in the intracellular domain (ICD).1 Because the hCD28 model was developed to assess hCD28-targeting therapeutics, we decided to keep the expression of both canonical and CD28i isoforms to avoid undermining the biological effects of the testing antibodies. Although keeping the human ICD could favour the evaluation of cytokine production and therefore the safety of the test therapeutics, we decided to keep the mouse ICD to enable a proper interaction of CD28 with its signalling partners, allowing a physiological stimulation of CD28 in efficacy studies.Results hCD28 mice express hCD28 on T cells and the frequency of CD3 T cells is comparable in both WT and hCD28 mice. Stimulation of hCD28 mice-isolated T cells with hCD28 ligands and agonist antibodies resulted in T cell proliferation and cytokine production, suggesting that hCD28 is functional in mouse cells. MC38 uptake rate and kinetic of growth were comparable in WT and hCD28 mice, suggesting no major defect in the immune response in the hCD28 mice. Importantly, splenocytes and tumor draining lymph nodes cells isolated from tumor-bearing hCD28 mice showed higher production of IL-2 and IFN-gamma upon in vitro re-challenged with MC38 when compared to WT cells. Since the frequency of CD3 cells (Treg, CD4+ and CD8+) is comparable to WT mice, this could be explained by the expression of the amplifier CD28i isoform, which is absent in WT mice.ConclusionsThe hCD28 model described here supports the efficacy assessment of hCD28-targeting biologics, enabling PK/PD studies as hCD28 expression levels and pattern are physiological. However, after careful consideration of the CD28 biology, we decided to keep the mouse ICD, although it triggers lower pro-inflammatory cytokine production than CD28 human ICD. As such, this model is not suitable for toxicology/safety studies.ReferencePorciello N, Grazioli P, Campese AF, et al. A non-conserved amino acid variant regulates differential signalling between human and mouse CD28. Nat Commun 2018; 9:1–16.

scholarly journals Effect of Bee Venom Pharmacopuncture on Inflammation in Mouse Model of Induced Atopic Dermatitis

2020 ◽  
Vol 37 (2) ◽  
pp. 123-127
Author(s):  
Kyeong Ju Park ◽  
Ho-Sueb Song
Keyword(s):  
Atopic Dermatitis ◽  
Mouse Model ◽  
Treated Group ◽  
Bee Venom ◽  
Related Protein ◽  
Griess Reaction ◽  
Cox 2 ◽  
Dose Dependent Decrease ◽  
Dose Dependent ◽  
Inflammatory Effect

Background: This study was designed using a mouse model of atopic dermatitis [phthalic anhydride (PA)-treated mice], to investigate the anti-inflammatory effect of bee venom pharmacopuncture (BVP) in keratinocytes.Methods: Western blot analysis was performed to investigate inflammation related protein expression of iNOS, COX-2, phospho-ERK (p-ERK), and ERK, in LPS (1 μg/mL)-activated keratinocytes, following BVP treatment, and in PA-treated mice, after BVP treatment. Griess reaction was performed to investigate NO concentration. Enzyme-linked immunosorbent assays were used to determine the concentrations of interleukin (IL)-4+, IL-17A+, IL-13 and IL-4 in PA-treated mice after BVP treatment. In addition, monocyte, macrophage, neutrophil, and eosinophil counts were measured to observe the changes in white blood cell infiltration.Results: The keratinocytes of the BVP-treated group showed a decreased expression of iNOS, COX-2, ERK at 5 OX-2, ERK E, and p-ERK at 1, 2 and 5 RKRK ERK ERK, and a dose-dependent decrease in NO concentration at 2 and 5 ntrationof s. In the BVP-treated groups (0.1 μ.1-trea μ.1-treated gr), PA-treated mice showed recovery after 4 weeks which was dose-dependent, showing a significant decrease in clinical scores for AD, and a decreased concentration of IL-13 and IL-4 with BV treatment. There was a dose-dependent decrease in the infiltration of eosinophils, neutrophils, monocytes, macrophages, and a decreased thickness of the epidermis due to inflammation, and decreased expressions of iNOS, COX-2, p-ERK, ERK, especially in the 0.1 μ0/mL BVP-treated group,<br>Conclusion: These results suggest that BVP may be an effective alternative treatment for atopic dermatitis.

scholarly journals Optogenetic gamma stimulation rescues memory impairments in an Alzheimer’s disease mouse model

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Guillaume Etter ◽  
Suzanne van der Veldt ◽  
Frédéric Manseau ◽  
Iman Zarrinkoub ◽  
Emilie Trillaud-Doppia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Mouse Model ◽  
Spatial Memory ◽  
Gamma Oscillations ◽  
Optogenetic Stimulation ◽  
Phase Amplitude ◽  
Ad Mouse Model ◽  
Parvalbumin Neurons ◽  
Stimulation Of ◽  
40 Hz

AbstractSlow gamma oscillations (30–60 Hz) correlate with retrieval of spatial memory. Altered slow gamma oscillations have been observed in Alzheimer’s disease. Here, we use the J20-APP AD mouse model that displays spatial memory loss as well as reduced slow gamma amplitude and phase-amplitude coupling to theta oscillations phase. To restore gamma oscillations in the hippocampus, we used optogenetics to activate medial septal parvalbumin neurons at different frequencies. We show that optogenetic stimulation of parvalbumin neurons at 40 Hz (but not 80 Hz) restores hippocampal slow gamma oscillations amplitude, and phase-amplitude coupling of the J20 AD mouse model. Restoration of slow gamma oscillations during retrieval rescued spatial memory in mice despite significant plaque deposition. These results support the role of slow gamma oscillations in memory and suggest that optogenetic stimulation of medial septal parvalbumin neurons at 40 Hz could provide a novel strategy for treating memory deficits in AD.

I16 Stimulation of SPHK1 with selective activator K6PC-5 is beneficial in the transgenic R6/2 mouse model of huntington disease

2018 ◽  
Author(s):  
Alba Di Pardo ◽  
Salvatore Castaldo ◽  
Luca Capocci ◽  
Alfredo Giovannelli ◽  
Enrico Amico ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington Disease ◽  
Stimulation Of

scholarly journals Comparison of the Protective Effects of Bee Venom Extracts with Varying PLA2 Compositions in a Mouse Model of Parkinson’s Disease

Toxins ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 358 ◽  
Author(s):  
Kyung Hwa Kim ◽  
Minhwan Kim ◽  
Jaehwan Lee ◽  
Hat Nim Jeon ◽  
Se Hyun Kim ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mouse Model ◽  
Therapeutic Potential ◽  
Bee Venom ◽  
Neuroprotective Activity ◽  
Protective Effects ◽  
Active Components ◽  
Therapeutic Benefits ◽  
Pharmacologically Active

Bee venom contains a number of pharmacologically active components, including enzymes and polypeptides such as phospholipase A2 (PLA2) and melittin, which have been shown to exhibit therapeutic benefits, mainly via attenuation of inflammation, neurotoxicity, and nociception. The individual components of bee venom may manifest distinct biological actions and therapeutic potential. In this study, the potential mechanisms of action of PLA2 and melittin, among different compounds purified from honey bee venom, were evaluated against Parkinson’s disease (PD). Notably, bee venom PLA2 (bvPLA2), but not melittin, exhibited neuroprotective activity against PD in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. MPTP-induced behavioral deficits were also abolished after bvPLA2 treatment, depending on the PLA2 content. Further, bvPLA2 administration activated regulatory T cells (Tregs) while inhibiting inflammatory T helper (Th) 1 and Th17 cells in the MPTP mouse model of PD. These results indicate that bvPLA2, but not melittin, protected against MPTP and alleviated inflammation in PD. Thus, bvPLA2 is a promising and effective therapeutic agent in Parkinson’s disease.

Erythropoietin Stimulates Thrombopoiesis in the Absence of C-Mpl Signaling

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2451-2451
Author(s):  
Norma E Fox ◽  
Rose Chen ◽  
Ian Hitchcock ◽  
Kenneth Kaushansky ◽  
Amy Geddis
Keyword(s):  
Mouse Model ◽  
Stem Cell Factor ◽  
Statistical Significance ◽  
Null Mouse ◽  
Platelet Response ◽  
Platelet Production ◽  
Platelet Counts ◽  
Severe Reduction ◽  
Stimulation Of

Abstract Thrombopoietin (TPO) is essential for normal megakaryopoiesis, and mice and humans lacking the TPO receptor c-Mpl have significantly impaired platelet production. However, in the c-Mpl-null mouse model platelet counts, while reduced to ~10% of normal, are not zero, suggesting that another cytokine is able to support some degree of residual thrombopoiesis. We and others have reported that elimination or severe reduction of stem cell factor, G-CSF, IL-3, IL-6 or IL-11 does not eliminate residual thrombopoiesis. Because megakaryocytes (MKs) and erythrocytes are derived from a common progenitor, we asked if erythropoietin (EPO) can stimulate thrombopoiesis in c-Mpl-null mice. We administered 90 u recombinant EPO or vehicle by subcutaneous injection every 3 days to c-Mpl-null or WT control mice and measured baseline and weekly platelet counts. In three independent experiments, at 2 weeks platelet counts in c-Mpl-null mice receiving EPO were significantly higher that at baseline (5–7 mice per group, average of mean platelet counts 425,000/mm3 vs. 285,000/mm3, p=0.0015). There was a trend towards higher platelet counts in WT mice receiving EPO but this did not reach statistical significance. No difference in platelet counts was observed in mice injected with vehicle. In one experiment c-Mpl-null or WT mice were injected with EPO for 4 weeks and the platelet response in the c-Mpl-null animals was sustained for the duration of the experiment. Western blotting showed that murine MKs express the EPO receptor. To determine if EPO stimulates MK production directly we stimulated WT murine MKs in vitro with either 6 u/ml EPO, 100 ng/ml rhTPO or both and monitored activation of ERK and STAT5 signaling by immunoblotting. Stimulation of MKs with EPO resulted in phosphorylation of ERK and STAT5 (15- and 14-fold above baseline, respectively), compared to TPO (97- and 75-fold above baseline). Stimulation with EPO and TPO together had an additive effect (phospho-ERK increased 121-fold and phospho-STAT5 increased 100-fold). To determine if EPO acts primarily on early or late MKs, we harvested bone marrow from c-Mpl-null mice after 2 weeks of treatment with EPO or vehicle and measured CFU-MK frequency and MK ploidy. Although there was a small increase in the frequency of CFU-MK in mice treated with EPO compared to vehicle, these differences were not significant (n=3, p=0.7), possibly due to the difficulty in assaying CFU-MK in vitro without TPO. In addition, EPO did not significantly enhance MK ploidy in c-Mpl-null mice, although MKs in the 32N and greater peaks were slightly more numerous. Therefore, we conclude that EPO can augment platelet production in the absence of c-Mpl signaling, although it is not yet clear if EPO primarily acts on early or late cells. Additional experiments are underway to determine if ablating EPO receptors in a TPO-null mouse model will eliminate residual thrombopoiesis. These findings may have clinical relevance for treating patients with congenital amegakaryocytic thrombocytopenia and other causes of thrombocytopenia in which c-Mpl signaling is impaired.

Duloxetine improves cancer-associated pain in a mouse model of pancreatic cancer through stimulation of noradrenaline pathway and its antitumor effects

Pain ◽  
2020 ◽  
Vol 161 (12) ◽  
pp. 2909-2919 ◽  
Author(s):  
Ichie Kajiwara ◽  
Makoto Sano ◽  
Yoshimi Ichimaru ◽  
Yukino Oshima ◽  
Osamu Kitajima ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Mouse Model ◽  
Antitumor Effects ◽  
Stimulation Of
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