scholarly journals Traditional Chinese Medicine QPYF as Preventive Treatment forClostridium difficileAssociated Diarrhea in a Mouse Model

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Guo Ya-Nan ◽  
Wang Jun ◽  
Zhang Hao-Jun ◽  
Jia Hong-Bing ◽  
Li Ping ◽  
...  

Traditional Chinese medicine QPYF has a good effect for treating antibiotic-associated diarrhea in clinical practice. The aim of this study is to test its efficacy to preventClostridium difficileassociated diarrhea (CDAD) in a mouse model. C57BL/6 mice were infected withClostridium difficileVPI 10463 after exposure to antimicrobial mixture. QPYF was administered from 7 days prior toClostridium difficileinfection to 20 days after infection, and its effect was compared with no treatment and receiving placebo. The mice were monitored for 20 days and the percent survival, disease activity index, weight loss, colon histopathology, and the levels of toxins in the feces were measured. The expressions of TNFα, MCP-1, NF-κB p65, and phospho-NF-κB p65 in the colon were presented by immunohistochemistry. The survival rate of QPYF group (93.75%) was higher than that of model control group (65%). The mice treated with QPYF had a lower weight loss and disease activity index, compared to the mice with placebo. A significantly lower level of histopathology scores, toxins in the feces, and TNFα, MCP-1, NF-κB p65, and phospho-NF-κB p65 were detected for QPYF-treated mice. Traditional Chinese medicine QPYF showed a good preventive effect for CDAD in a mouse model.

Author(s):  
Suzanne Mashtoub ◽  
Bang V. Hoang ◽  
Megan Vu ◽  
Kerry A. Lymn ◽  
Christine Feinle-Bisset ◽  
...  

Plant-sourced formulations such as Iberogast and the traditional Chinese medicine formulation, Cmed, purportedly possess anti-inflammatory and radical scavenging properties. We investigated Iberogast and Cmed, independently, for their potential to decrease the severity of the large bowel inflammatory disorder, ulcerative colitis. Sprague Dawley rats (n = 8/group) received daily 1 mL gavages (days 0-13) of water, Iberogast (100 μL/200 μL), or Cmed (10 mg/20 mg). Rats ingested 2% dextran sulfate sodium or water ad libitum for 7 days commencing on day 5. Dextran sulfate sodium administration increased disease activity index scores from days 6 to 12, compared with water controls ( P < .05). On day 10, 200 μL Iberogast decreased disease activity index scores in colitic rats compared with colitic controls ( P < .05). Neither Iberogast nor Cmed achieved statistical significance for daily metabolic parameters or colonic crypt depth. The therapeutic effects of Iberogast and Cmed were minimal in the colitis setting. Further studies of plant extracts are required investigating greater concentrations and alternative delivery systems.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ji-Young Lim ◽  
Byung-Su Kim ◽  
Da-Bin Ryu ◽  
Tae Woo Kim ◽  
Gyeongsin Park ◽  
...  

Abstract Background Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSCs) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the IFN-γ and poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods To compare the therapeutic effects between the unstimulated MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were assessed daily until day 9. Results Mice receiving the IFN-γ and poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 upregulation in colon tissue and diminished the protective effects of the primed MSC. Conclusions The priming of MSCs with the IFN-γ and poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.


2020 ◽  
Author(s):  
Ji-Young Lim ◽  
Byung-Su Kim ◽  
Da-Bin Ryu ◽  
Tae Woo Kim ◽  
Gyeongsin Park ◽  
...  

Abstract Background:Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSC) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods:To compare the therapeutic effects between the naïve MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfatein drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were significantly improved after injection of the primed MSCs. Results:Mice receiving the poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 up-regulation in colon tissue and diminished the protective effects of the primed MSC. Conclusions: The priming of MSCs with poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.


2021 ◽  
Vol 12 ◽  
Author(s):  
Martin Killian ◽  
Fabien Colaone ◽  
Philippe Haumont ◽  
Carole Nicco ◽  
Olivier Cerles ◽  
...  

Sjögren’s syndrome (SjS) is a frequent systemic autoimmune disease responsible for a major decrease in patients’ quality of life, potentially leading to life-threatening conditions while facing an unmet therapeutic need. Hence, we assessed the immunogenicity, efficacy, and tolerance of IFN-Kinoid (IFN-K), an anti-IFNα vaccination strategy, in a well-known mouse model of systemic autoimmunity with SjS-like features: MRL/MpJ-Faslpr/lpr (MRL/lpr) mice. Two cohorts (with ISA51 or SWE01 as adjuvants) of 26 female MRL/lpr were divided in parallel groups, “controls” (not treated, PBS and Keyhole Limpet Hemocyanin [KLH] groups) or “IFN-K” and followed up for 122 days. Eight-week-old mice received intra-muscular injections (days 0, 7, 28, 56 and 84) of PBS, KLH or IFN-K, emulsified in the appropriate adjuvant, and blood samples were serially collected. At sacrifice, surviving mice were euthanized and their organs were harvested for histopathological analysis (focus score in salivary/lacrimal glands) and IFN signature evaluation. SjS-like features were monitored. IFN-K induced a disease-modifying polyclonal anti-IFNα antibody response in all treated mice with high IFNα neutralization capacities, type 1 IFN signature’s reduction and disease features’ (ocular and oral sicca syndrome, neuropathy, focus score, glandular production of BAFF) improvement, as reflected by the decrease in Murine Sjögren’s Syndrome Disease Activity Index (MuSSDAI) modelled on EULAR Sjögren’s Syndrome Disease Activity Index (ESSDAI). No adverse effects were observed. We herein report on the strong efficacy of an innovative anti-IFNα vaccination strategy in a mouse model of SjS, paving the way for further clinical development (a phase IIb trial has just been completed in systemic lupus erythematosus with promising results).


2020 ◽  
Author(s):  
Ji-Young Lim ◽  
Byung-Su Kim ◽  
Da-Bin Ryu ◽  
Tae Woo Kim ◽  
Gyeongsin Park ◽  
...  

Abstract Background: Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSC) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the IFN-γ and poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods: To compare the therapeutic effects between the unstimulated MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were assessed daily until day 9.Results: Mice receiving the IFN-γ and poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 up-regulation in colon tissue and diminished the protective effects of the primed MSC.Conclusions: The priming of MSCs with the IFN-γ and poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.


Trials ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Lianyu Zhao ◽  
Meilin Li ◽  
Yanping Xu ◽  
Lijuan Liu ◽  
Mingying Zhang ◽  
...  

Abstract Background Rheumatoid arthritis (RA) is a common chronic autoimmune disease that seriously affects the quality of life of patients because of damage to joints. Presently, RA is mainly treated with disease-modifying antirheumatic drugs (DMARDs) or biological agents; however, they offer limited efficacy in some patients. Therefore, additional therapeutic strategies need to be developed. Yishen Tongbi decoction is a traditional Chinese medicine formulation widely used to treat RA in China. However, currently, there is insufficient evidence to recommend its use for the treatment of RA. Therefore, we aim to verify the efficacy of Yishen Tongbi decoction to treat RA by a noninferiority trial, and to provide a basis for its use with a full-scale clinical trial. Methods/design One hundred eligible patients with RA will be randomized into two groups of 50 patients. One group will receive Yishen Tongbi decoction and placebo replacing methotrexate (MTX), while the other group will receive MTX and placebo replacing Yishen Tongbi decoction. Patient’s whose visual analogue scale score for pain is greater than 40 mm will be administered nonsteroidal anti-inflammatory drugs (such as enteric-coated diclofenac sodium, 25 mg three times a day); administration of all medications will be recorded. The clinical indicators of patients and their disease activity will be assessed at baseline and at 4, 12 and 24 weeks after treatment initiation. The primary outcome of efficacy will be the proportion of patients who demonstrate a favourable response based on their Clinical Disease Activity Index score at 24 weeks after treatment. All adverse events will be reported. Discussion Traditional Chinese medicine theory and modern western medicine research have identified the efficacy of Yishen Tongbi decoction to treat RA. Previous clinical observation and efficacy trials of Yishen Tongbi decoction in animal models for the treatment of RA has demonstrated significant effect. Because of the potential benefits of Yishen Tongbi decoction in the treatment of patients with RA, we designed this double-blind, prospective, randomized controlled trial; the results and conclusions of the trail will be published after the completion of the study. Trial registration Chinese Clinical Trials Registry, ChiCTR1900024902. Registered on 3 August 2019.


2020 ◽  
Author(s):  
Ji-Young Lim ◽  
Byung-Su Kim ◽  
Da-Bin Ryu ◽  
Tae Woo Kim ◽  
Gyeongsin Park ◽  
...  

Abstract Background: Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSC) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the IFN-γ and poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods: To compare the therapeutic effects between the naïve MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were assessed daily until day 9. Results: Mice receiving the IFN-γ and poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 up-regulation in colon tissue and diminished the protective effects of the primed MSC. Conclusions: The priming of MSCs with the IFN-γ and poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.


2020 ◽  
Author(s):  
Ji-Young Lim ◽  
Byung-Su Kim ◽  
Da-Bin Ryu ◽  
Tae Woo Kim ◽  
Gyeongsin Park ◽  
...  

Abstract Background: Inflammatory bowel disease is a chronic and excessive inflammation of the colon and small intestine. We previously reported that priming of mesenchymal stromal cells (MSC) with poly(I:C) induced them to express indoleamine 2,3-dioxygenase (IDO). We tried to find out whether the IFN-γ and poly(I:C)-primed MSCs have better therapeutic efficacy on the experimental colitis in the IDO1-dependent manner. Methods: To compare the therapeutic effects between the unstimulated MSCs and primed MSCs on murine colitis, mice (C57BL6) were administered with 2.5% dextran sodium sulfate (DSS) in drinking water for 5 days and injected with MSCs intraperitoneally on days 1 and 3 following DSS ingestion. The disease activity index score and body weight loss were assessed daily until day 9. Results: Mice receiving the IFN-γ and poly(I:C)-primed MSCs showed a reduced disease activity index and less weight loss. Colon tissue from the same mice presented attenuated pathological damage, increased Paneth cells, increased IDO1-expressing cells, and better proliferation of enterocytes. The primed MSC treatment upregulated the mRNA expression of intestinal stem cell markers (Lgr5, Olfm4, and Bmi1), enterocyte differentiation markers (Muc2, Alpi, Chga, and occludin), and regulatory T (Treg) cells (Foxp3). The same treatment decreased inflammatory cell infiltration to lymphoid organs and the level of pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, and MCP-1) in colon tissue. Notably, in vivo pharmacologic inhibition of the IDO1 activity blocked the Foxp3 up-regulation in colon tissue and diminished the protective effects of the primed MSC. Conclusions: The priming of MSCs with the IFN-γ and poly(I:C) is a promising new strategy to improve the therapeutic efficacy of MSC and is worth further research.


Lupus ◽  
2020 ◽  
Vol 29 (2) ◽  
pp. 182-190
Author(s):  
W Batista Cicarini ◽  
R C Figueiredo Duarte ◽  
K Silvestre Ferreira ◽  
C de Mello Gomes Loures ◽  
R Vargas Consoli ◽  
...  

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.


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