Observations of TCRVβ Gene Expression in Rats with Dampness Syndrome

Cao, Yan; Sun, Baoguo; Zhang, Shijun; Chen, Zexiong; Hardi, Carlini Fan; Xiang, Ting

doi:10.1155/2014/373608

Cited by 7 publications

(5 citation statements)

References 17 publications

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“…Interestingly, the majority of patients with cancer cachexia have been diagnosed with SD in China ( Sun et al, 2016a ; Zhang et al, 2020 ). According to the literature, SD may lead to dysfunction in T cell recognition by disordering the expression of TCRVβ in rats ( Chen et al, 2014 ). In addition, another study reported that immunoregulatory traditional Chinese medicine is beneficial to liver cancer and induces cell apoptosis through the Caspase-3/PARP signaling pathway ( Yu et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Exosome CTLA-4 Regulates PTEN/CD44 Signal Pathway in Spleen Deficiency Internal Environment to Promote Invasion and Metastasis of Hepatocellular Carcinoma

Wang

Mao

et al. 2021

Front. Pharmacol.

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Hepatocellular carcinoma (HCC) is one of the most common primary cancers, and its pathogenesis is complicated and difficult to screen. Currently, there is no effective treatment. In traditional Chinese medicine, a large proportion of patients with HCC have been diagnosed with spleen deficiency (SD) syndrome and treated with tonifying traditional Chinese medicine, which has significant clinical efficacy. However, the role and molecular mechanism of SD in HCC remain unclear. In this study, 40 mice were randomly divided into four groups: control, SD, HCC, and SD-HCC groups. The liver cancer model of SD was established by reserpine induction and orthotopic transplantation. The effects of SD on the proliferation, apoptosis, invasion, and metastasis of HCC cells were studied by cell proliferation, cell apoptosis, cell scratch, and transwell assay. We found that compared with the HCC group, the protein expressions of cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), phosphatase and tensin homolog (PTEN), and AKT (also known as protein kinase B or PKB) in the exosomes of the SD-HCC group were upregulated. In addition, the metastases and self-renewal of exosomes in the SD-HCC group were more aggressive than those in the HCC group, which could be partially reversed with the addition of CTLA-4 inhibitors. Further studies showed that in the internal environment of SD, CTLA-4 promoted tumor invasion and metastasis by regulating the PTEN/CD44 pathway. In conclusion, our findings suggest that during SD in the internal environment, exosome CTLA-4 regulates the PTEN/CD44 signal pathway to promote the proliferation, self-renewal, and metastasis of liver cancer.

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Section: Introductionmentioning

confidence: 99%

Exosome CTLA-4 Regulates PTEN/CD44 Signal Pathway in Spleen Deficiency Internal Environment to Promote Invasion and Metastasis of Hepatocellular Carcinoma

Wang

Mao

et al. 2021

Front. Pharmacol.

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“…In the theory of TCM, HCC can be referred to as the disease “abdominal dropsy,” which is mainly caused by “external dampness” and “internal dampness.” Therefore, the therapeutic strategy for HCC in TCM is to resolve the “dampness.” At the same time, the “dampness” in TCM has been verified to be correlated with the obstruction of immunological recognition function [ 12 ]. As one of the representative herbal medicines in resolving dampness, Yinchen has been used in liver diseases in TCM for many years.…”

Section: Discussionmentioning

confidence: 99%

“…It is the key point to improve the “internal dampness” microenvironment of HCC patients. Based on the theory of TCM, Yinchen aims at the liver and can ameliorate the “internal dampness.” Meanwhile, it has been reported that the obstruction of immunological recognition function might be caused by “internal dampness” [ 12 ]. Consequently, we speculated that Yinchen may have an effect on HCC through the immunologic regulation.…”

Section: Introductionmentioning

confidence: 99%

An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma

Cao

et al. 2020

BioMed Research International

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Aims. Abundant evidences in traditional Chinese medicine (TCM) supported the therapeutic value of herbal medicine Yinchen in hepatocellular carcinoma (HCC), but the underlying mechanism remains to be investigated. Main Methods. The intersection of immune gene set, module genes, HCC-associated genes, and target genes of Yinchen was employed for further analyses. The module genes were identified by weighted gene coexpression network analysis, and the other three gene sets were obtained from public databases. Subsequently, we further explored the clinical value and immunoregulation of the hub gene of intersection. The relevant pathways related to hub gene expression were investigated by gene set enrichment analysis. Finally, the interaction of active compounds and target genes was validated by molecular docking. Key Findings. Thirteen active compounds and 90 target genes of Yinchen were included. After constructing the network among Yinchen, target genes, and HCC, BIRC5 was identified as the hub gene. Significant difference was found between the high-expressed group and the low-expressed group in survival and stage. Different immune subtypes also presented significant difference in BIRC5 expression. Moreover, NK cell and T cell (CD4+ effector memory and CD4+ memory resting) were negatively correlated with BIRC5 expression, while CTLA4 and LAG3 were positively correlated. The results of molecular docking further validated a good binding activity of quercetin-BIRC5 interaction. Significance. In summary, our research identified for the first time a novel underlying association among herbal medicine Yinchen, BIRC5, immunotherapy, and HCC. We speculated that Yinchen may target the immune checkpoints (CTLA4 and LAG3) and activate the immune cells by suppressing BIRC5.

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“…Due to its importance and complexity, researchers have focused on the properties of the spleen. It is well documented that the spleen is not only an anatomical concept, but is also associated with the digestive system (29,30) in particular, in addition to the immune (31), circulatory (32) and endocrine systems (33). Previously, Huang et al (14,15) suggested that the spleen was involved in the pharmacokinetics hypothesis, which assumes that the spleen is responsible for the absorption, distribution, metabolism and excretion of drugs.…”

Section: Discussionmentioning

confidence: 99%

Traditional Chinese medicine: Pivotal role of the spleen in the metabolism of aristolochic acid I in rats is dependent on oatp2a1

Xiang

Yang

Sun

et al. 2016

Molecular Medicine Reports

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The genotoxicity and cytotoxicity of aristolochic acids is well documented, and the Aristolochiaceae plant family has been widely used in China and India for medical purposes. However, the mechanisms of aristolochic acid I (AAI) in treatment and toxicity remain to be fully elucidated. According to the theory of traditional Chinese medicine (TCM), the spleen is responsible for transportation and transformation, in which a substance is transformed, absorbed and distributed in the body. In the present study, rats were randomized into a blank group without spleen deficiency and a spleen deficiency group to investigate the metabolism of AAI. The results showed that the concentration of AAI was higher in the spleen deficiency group, compared with that of the blank group. To further elucidate this process, the expression of organic anion transporting peptide (oatp)2a1 in the rats of the two groups were examined following oral administration of AAI. It was observed that the mRNA level of oatp2a1 in the small intestine of the blank+AAI 60 min group was downregulated, compared with that in the blank group. Compared with the mRNA level of oatp2a1 in the spleen deficiency group, the expression levels in the lung and liver were downregulated in the spleen deficiency+AAI 5 min group, whereas expression levels in the kidney in the spleen deficiency+AAI 60 min group were upregulated. Based on the above results, it was hypothesized that the expression of oatp2a1 may be one of the mechanisms of AAI metabolism in rats. In TCM, the spleen and certain functions of the small intestine, are important in AAI metabolism, and affect the toxicity of AAI. In addition, the lung, liver and kidney may also be involved in spleen deficiency syndrome in rats.

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Observations of TCRVβ Gene Expression in Rats with Dampness Syndrome

Cited by 7 publications

References 17 publications

Exosome CTLA-4 Regulates PTEN/CD44 Signal Pathway in Spleen Deficiency Internal Environment to Promote Invasion and Metastasis of Hepatocellular Carcinoma

Exosome CTLA-4 Regulates PTEN/CD44 Signal Pathway in Spleen Deficiency Internal Environment to Promote Invasion and Metastasis of Hepatocellular Carcinoma

An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma

Traditional Chinese medicine: Pivotal role of the spleen in the metabolism of aristolochic acid I in rats is dependent on oatp2a1

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