scholarly journals Chlorogenic Acid Alleviates Thiram-Induced Tibial Dyschondroplasia by Modulating Caspases, BECN1 Expression and ECM Degradation

2019 ◽  
Vol 20 (13) ◽  
pp. 3160 ◽  
Author(s):  
Jialu Zhang ◽  
Shucheng Huang ◽  
Xiaole Tong ◽  
Lihong Zhang ◽  
Xiong Jiang ◽  
...  
Keyword(s):  
Chlorogenic Acid ◽  
Growth Plate ◽  
Therapeutic Effect ◽  
Performance Indicator ◽  
Parameter Analysis ◽  
Matrix Mineralization ◽  
Tibial Dyschondroplasia ◽  
Ecm Extracellular Matrix ◽  
Abnormal Cells ◽  
Underlying Mechanisms

Chlorogenic acid (CGA) is a widely applied traditional Chinese medicine ingredient which can be used for the treatment of osteoporosis. In this experiment, we investigated the potential therapeutic effect of chlorogenic acid on thiram-induced tibial dyschondroplasia (TD) and explored the underlying mechanisms that have been rarely mentioned by others yet. Performance indicator analysis and tibial parameter analysis showed that CGA exhibited a definite positive effect on thiram-induced TD chickens. In order to further explore the mechanisms underlying the positive actions of CGA, apoptotic, autophagic genes and MMPs involved in matrix mineralization of growth plate were evaluated in this study. The results showed that CGA decreased the expression of pro-apoptotic genes caspases-3 and caspases-9, leading to the reduction of apoptotic cells accumulated in growth plate. In addition, CGA also increased the level of BECN1, an important gene involved in autophagy, which benefits the survival of abnormal cells. Furthermore, CGA also increased the expression of MMP-9, MMP-10, and MMP-13, which can directly affect the ossification of bones. Altogether, these results demonstrate that CGA possesses a positive therapeutic effect on thiram-induced TD via modulating the expression of caspases and BECN1 and regulating the degradation of ECM (extracellular matrix).

scholarly journals A Combination of Geniposide and Chlorogenic Acid Combination Ameliorates Nonalcoholic Steatohepatitis in Mice by Inhibiting Kupffer Cell Activation

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Xin Xin ◽  
Yue Jin ◽  
Xin Wang ◽  
Beiyu Cai ◽  
Ziming An ◽  
...  
Keyword(s):  
Chlorogenic Acid ◽  
Nonalcoholic Steatohepatitis ◽  
Cell Activation ◽  
Raw264.7 Cells ◽  
Chemical Components ◽  
Gm Csf ◽  
Tnf Α ◽  
Macrophage Colony ◽  
Underlying Mechanisms ◽  
Factor Α

The incidence of nonalcoholic steatohepatitis (NASH) is increasing worldwide. Activation of Kupffer cells (KCs) is central to the development of diet-induced NASH. We investigated whether a combination of two active chemical components, geniposide and chlorogenic acid (GC), at a specific ratio (67 : 1), ameliorates diet-induced NASH and the underlying mechanisms involved. C57BL/6J mice exposed to a high-fat and high-cholesterol (HFHC) diet containing cholesterol, choline, and high-sugar drinking water, as well as RAW264.7 cells stimulated with lipopolysaccharide (LPS) were studied. The combination exerted a therapeutic effect on HFHC-induced NASH in mice. Simultaneously, GC was found to reduce the expression of cytokines secreted by hepatic macrophages, including tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α), IL-1β, IL-6, monocyte chemotactic protein 1 (MCP-1), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Moreover, GC reduced the number of KCs expressing F4/80. Furthermore, TNF-α, inducible nitric oxide synthase (INOS), IL-1β, and IL-6 mRNA and TNF-α protein expression levels were suppressed upon GC treatment in RAW264.7 cells. Our findings suggest that GC has a strong anti-inflammatory effect in NASH, and this effect can be attributed to the suppression of KC activity in the liver.

scholarly journals Restoration of antitumor immunity through anti-MICA antibodies elicited with a chimeric protein

2020 ◽  
Vol 8 (1) ◽  
pp. e000233 ◽  
Author(s):  
Nicolas Torres ◽  
María Victoria Regge ◽  
Florencia Secchiari ◽  
Adrián David Friedrich ◽  
Raúl Germán Spallanzani ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Antitumor Immunity ◽  
Immune Escape ◽  
Chimeric Protein ◽  
Antitumor Effects ◽  
Tumor Immune Escape ◽  
Mouse Tumors ◽  
Antitumor Vaccine ◽  
Dependent Cell ◽  
Underlying Mechanisms

BackgroundNatural killer and cytotoxic CD8+T cells are major players during antitumor immunity. They express NKG2D, an activating receptor that promotes tumor elimination through recognition of the MHC class I chain-related proteins A and B (MICA and MICB). Both molecules are overexpressed on a great variety of tumors from different tissues, making them attractive targets for immunotherapy. However, tumors shed MICA and MICB, and the soluble forms of both (sMICA and sMICB) mediate tumor-immune escape. Some reports indicate that anti-MICA antibodies (Ab) can promote the restoration of antitumor immunity through the induction of direct antitumor effects (antibody-dependent cell-mediated cytotoxicity, ADCC) and scavenging of sMICA. Therefore, we reasoned that an active induction of anti-MICA Ab with an immunogenic protein might represent a novel therapeutic and prophylactic alternative to restore antitumor immunity.MethodsWe generated a highly immunogenic chimeric protein (BLS-MICA) consisting of human MICA fused to the lumazine synthase fromBrucellaspp (BLS) and used it to generate anti-MICA polyclonal Ab (pAb) and to investigate if these anti-MICA Ab can reinstate antitumor immunity in mice using two different mouse tumors engineered to express MICA. We also explored the underlying mechanisms of this expected therapeutic effect.ResultsImmunization with BLS-MICA and administration of anti-MICA pAb elicited by BLS-MICA significantly delayed the growth of MICA-expressing mouse tumors but not of control tumors. The therapeutic effect of immunization with BLS-MICA included scavenging of sMICA and the anti-MICA Ab-mediated ADCC, promoting heightened intratumoral M1/proinflammatory macrophage and antigen-experienced CD8+T cell recruitment.ConclusionsImmunization with the chimeric protein BLS-MICA constitutes a useful way to actively induce therapeutic anti-MICA pAb that resulted in a reprogramming of the antitumor immune response towards an antitumoral/proinflammatory phenotype. Hence, the BLS-MICA chimeric protein constitutes a novel antitumor vaccine of potential application in patients with MICA-expressing tumors.

scholarly journals Enhanced Effect of IL-1β-Activated Adipose-Derived MSCs (ADMSCs) on Repair of Intestinal Ischemia-Reperfusion Injury via COX-2-PGE2 Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Liu Liu ◽  
Yi Ren He ◽  
Shao Jun Liu ◽  
Lei Hu ◽  
Li Chuang Liang ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Suppressive Effect ◽  
Signaling Axis ◽  
Cox 2 ◽  
Underlying Mechanisms ◽  
Intestinal Ischemia Reperfusion

Adipose-derived mesenchymal stem cells (ADMSCs) have been used for treating tissue injury, and preactivation enhances their therapeutic effect. This study is aimed at investigating the therapeutic effect of activated ADMSCs by IL-1β on the intestinal ischaemia-reperfusion (IR) injury and exploring potential mechanisms. ADMSCs were pretreated with IL-1β in vitro, and activation of ADMSCs was assessed by α-SMA and COX-2 expressions and secretary function. Activated ADMSCs was transplanted into IR-injured intestine in a mouse model, and therapeutic effect was evaluated. In addition, to explore underlying mechanisms, COX-2 expression was silenced to investigate its role in activated ADMSCs for treatment of intestinal IR injury. When ADMSCs were pretreated with 50 ng/ml IL-1β for 24 hr, expressions of α-SMA and COX-2 were significantly upregulated, and secretions of PGE2, SDF-1, and VEGF were increased. When COX-2 was silenced, the effect of IL-1β treatment was abolished. Activated ADMSCs with IL-1β significantly suppressed inflammation and apoptosis and enhanced healing of intestinal IR injury in mice, and these effects were impaired by COX-2 silencing. The results of RNA sequencing suggested that compared with the IR injury group activated ADMSCs induced alterations in mRNA expression and suppressed the activation of the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways induced by intestinal IR injury, whereas silencing COX-2 impaired the suppressive effect of activated ADMSCs on these pathway activations induced by IR injury. These data suggested that IL-1β pretreatment enhanced the therapeutic effect of ADMSCs on intestinal IR injury repairing via activating ADMSC COX-2-PGE2 signaling axis and via suppressing the NF-κB-P65, MAPK-ERK1/2, and PI3K-AKT pathways in the intestinal IR-injured tissue.

scholarly journals Effect of Anacardic Acid against Thiram Induced Tibial Dyschondroplasia in Chickens via Regulation of Wnt4 Expression

Animals ◽  
2019 ◽  
Vol 9 (3) ◽  
pp. 82 ◽  
Author(s):  
Xiong Jiang ◽  
Hui Zhang ◽  
Khalid Mehmood ◽  
Kun Li ◽  
Lihong Zhang ◽  
...  
Keyword(s):  
Growth Plate ◽  
Conversion Ratio ◽  
Anacardic Acid ◽  
Feed Conversion ◽  
Bone Parameters ◽  
Tibial Dyschondroplasia ◽  
Tibia Bone ◽  
Poultry Birds ◽  
Antioxidant Parameters ◽  
Tibial Growth Plate

Tibial dyschondroplasia (TD) is a tibia bone problem in broilers. Anacardic acid (AA) is a traditional Chinese medicine, which is commonly used to treat arthritis in human. The purpose of the present study is to investigate the effect of AA against TD. A total of 300 day-old poultry birds were equally divided and distributed into three different groups: Control, TD and AA groups. The results showed that the feed conversion ratio was significantly lower in the TD group than control chickens. The tibia bone parameters including weight, length and width were of low quality in TD chickens, while the width of the tibial growth plate was enlarged remarkably. Whereas, in the AA treatment group, the tibia bone parameters showed improvement and tend to return to normal. The antioxidant parameters level of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), total and antioxidant capacity (T-AOC) was significantly decreased, while malondialdehyde (MDA) level was increased significantly in TD affected chickens. AA administration restored the antioxidant parameters significantly. The gene expression revealed a decrease in Wnt4 expression in TD chickens as compared to control chickens, while AA treatment up-regulated the Wnt4 expression. The present study demonstrates that the AA plays an important role to prevent the lameness and restore the size of tibial growth plate of chickens by regulating the expression of Wnt4.

Rab27B enhances drug resistance in hepatocellular carcinoma by promoting exosome-mediated drug efflux

2020 ◽  
Vol 41 (11) ◽  
pp. 1583-1591 ◽  
Author(s):  
Rui Li ◽  
Chengyong Dong ◽  
Keqiu Jiang ◽  
Rui Sun ◽  
Yang Zhou ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Liver Cancer ◽  
Therapeutic Effect ◽  
Efflux Pump ◽  
Human Life ◽  
Therapeutic Effects ◽  
Drug Efflux ◽  
Glycoprotein P ◽  
Chemotherapy Drugs ◽  
Underlying Mechanisms

Abstract Liver cancer is a major threat to human life and health, and chemotherapy has been the standard non-surgical treatment for liver cancer. However, the emergence of drug resistance of liver cancer cells has hindered the therapeutic effect of chemical drugs. The discovery of exosomes has provided new insights into the mechanisms underlying tumour cell resistance. In this study, we aimed to determine the proteins associated with drug resistance in tumour cells and to elucidate the underlying mechanisms. We found that Rab27B expression in drug (5-fluorouracil, 5Fu)-resistant Bel7402 (Bel/5Fu) cells increased significantly compared with that in drug-sensitive Bel7402 cells. In addition, Bel/5Fu cells secreted more exosomes under 5Fu stimulation. The number of exosomes secreted by Bel/5Fu cells significantly reduced after knocking down Rab27B, and the cellular concentration of 5Fu increased, enhancing its therapeutic effect. We also found that the administration of classical drug efflux pump (P-glycoprotein, P-gp) inhibitors together with knockdown of Rab27B further improved the therapeutic effects of chemotherapy drugs. In conclusion, our findings suggest that Rab27B could be a new therapeutic target in liver cancer.

Recovery of Chicken Growth Plate by Heat-Shock Protein 90 Inhibitors Epigallocatechin-3-Gallate and Apigenin in Thiram-Induced Tibial Dyschondroplasia

2016 ◽  
Vol 60 (4) ◽  
pp. 773-778 ◽  
Author(s):  
Muhammad Kashif Iqbal ◽  
Jingying Liu ◽  
Fazul Nabi ◽  
Mujeeb Ur Rehman ◽  
Hui Zhang ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Growth Plate ◽  
Heat Shock Protein 90 ◽  
Tibial Dyschondroplasia

Growth plate vitamin D receptors in tibial dyschondroplasia

Bone ◽  
1995 ◽  
Vol 16 (6) ◽  
pp. 687-688 ◽  
Author(s):  
J.L. Berry ◽  
C. Farquharson ◽  
C.C. Whitehead ◽  
E.B. Mawer
Keyword(s):  
Vitamin D ◽  
Growth Plate ◽  
Vitamin D Receptors ◽  
Tibial Dyschondroplasia

scholarly journals Role and regulation of growth plate vascularization during coupling with osteogenesis in tibial dyschondroplasia of chickens

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Shu-cheng Huang ◽  
Li-hong Zhang ◽  
Jia-lu Zhang ◽  
Mujeeb Ur Rehman ◽  
Xiao-le Tong ◽  
...  
Keyword(s):  
Growth Plate ◽  
Tibial Dyschondroplasia ◽  
Regulation Of Growth
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