Dataset Information

Metabolomic Study on the Therapeutic Effect of the Jianpi Yangzheng Xiaozheng Decoction on Gastric Cancer Treated with Chemotherapy Based on GC-TOFMS Analysis.

ABSTRACT:

Objective

This study aimed to find new biomarkers of prognosis and metabolomic therapy for gastric carcinoma (GC) treated with chemotherapy and investigate the metabolic mechanism of the Jianpi Yangzheng Xiaozheng (JPYZXZ) decoction in the treatment of GC.

Methods

First, 36 patients with GC were randomly assigned to the treatment (chemotherapy plus JPYZXZ) and control (chemotherapy alone) groups. The clinical efficacy, side effects, and quality of life of patients in the two groups were evaluated after treatment. Then, the serum samples taken from 16 randomly selected patients (eight treatment cases and eight control cases with no evident pattern characters) and eight healthy volunteers were tested to identify the differential metabolite under the gas chromatography-time-of-fight mass spectrometry platform. The relevant metabolic pathways of differential substances were analyzed using multidimensional statistical analysis.

Results

JPYZXZ combined with chemotherapy resulted in a lower risk of leucopenia, thrombocytopenia, and gastrointestinal reaction (P < 0.05). Additionally, patients in the treatment group showed a higher Karnofsky (KPS) scale (P < 0.05). Compared with healthy persons, patients with GC were found to have 26 significant differential metabolites after chemotherapy; these metabolites are mainly involved in 12 metabolic pathways, such as valine, leucine, and isoleucine biosynthesis. JPYZXZ primarily influences the pentose phosphate pathway; glutathione metabolism; glyoxylate and dicarboxylate metabolism; porphyrin and chlorophyll metabolism; and glycine, serine, and threonine metabolism of patients with GC treated with chemotherapy.

Conclusions

The metabolic characteristics of patients with GC after chemotherapy are mainly various amino acid metabolic defects, especially L-glutamine, L-leucine, L-alloisoleucine, and L-valine. These defects lead to a series of problems, such as decreased tolerance and effectiveness of chemotherapy, increased side effects, decreased immunity, and shortened survival time. In addition, the remarkable upregulation of the gluconolactone level in patients with GC suggests the high proliferative activity of GC cells. Thus, gluconolactone may be used as a potential prognostic and diagnostic evaluation index. Moreover, JPYZXZ can reduce the incidence of ADRs and improve the life quality of patients by the correction of L-glutamine, L-leucine, L-alloisoleucine, and L-valine metabolism deficiency. In addition, gluconolactone metabolism is inhibited by JPYZXZ. Such inhibition may be one of the antitumor mechanisms of JPYZXZ.

SUBMITTER: Hou C

PROVIDER: S-EPMC7994103 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

Metabolomic Study on the Therapeutic Effect of the Jianpi Yangzheng Xiaozheng Decoction on Gastric Cancer Treated with Chemotherapy Based on GC-TOFMS Analysis.

Hou Chao C Chu Hua-Jian HJ Dai Xiao-Jun XJ Wu Yin-Qiu YQ He Zheng-Fei ZF Yu Yan-Wei YW Lu Qing-Yun QY Liu Yan-Qing YQ Zhang Xiao-Chun XC

Evidence-based complementary and alternative medicine : eCAM 20210317

<h4>Objective</h4>This study aimed to find new biomarkers of prognosis and metabolomic therapy for gastric carcinoma (GC) treated with chemotherapy and investigate the metabolic mechanism of the Jianpi Yangzheng Xiaozheng (JPYZXZ) decoction in the treatment of GC.<h4>Methods</h4>First, 36 patients with GC were randomly assigned to the treatment (chemotherapy plus JPYZXZ) and control (chemotherapy alone) groups. The clinical efficacy, side effects, and quality of life of patients in the two group ...[more]

PMID: 33790982

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Project description:Jianpi Yangzheng Xiaozheng decoction (JPYZXZ) is an empirical traditional Chinese medicine formula that has been reported to significantly prolong the survival of patients with advanced gastric cancer (GC). However, its underlying mechanism have not been fully elucidated. The present work aims to explore the possible mechanism of JPYZXZ on regulating GC progression. We firstly confirmed the inhibitory effect of JPYZXZ in GC MKN74 cells and 615-strain mice, which was possibly mediated with IL-6/JAK2/STAT3 pathway dependent PD-L1 expression. Moreover, we showed that JPYZXZ diminished the expression levels of GC-derived exosomal PD-L1 in MFC murine cells and xenograft GC model, as well as stage IIA-IIIB GC patients. We further found that in different types of tumor-infiltrating immune cells, PD-L1 expression was most positively correlated with myeloid-derived suppressor cells (MDSCs) in GC in the TISIDB database. We isolated exosomes derived from supernatants of MFC cells and co-cultured with bone marrow cells derived from C57BL/6 mice, and further revealed that the expansion of MDSCs was mediated by GC-derived exosomal PD-L1. Meanwhile, our results indicated that JPYZXZ inhibited the delivery of exosomal PD-L1 from GC cells to bone marrow cells, thereby alleviating exosomal PD-L1-induced differentiation and expansion of MDSCs in the tumor microenvironment. This led to a decrease in the levels of several immunosuppressive factors, including iNOS, Arg-1, TGF-β, IL-10, and IL-6, in 615-strain mice. Moreover, clinical data also revealed a significant positive relationship between exosomal PD-L1 and polymorphonuclear MDSCs under the JPYZXZ treatment in stage IIA-IIIB GC patients. In conclusion, our study confirmed that exosomal PD-L1 could be a key factor in controlling MDSCs differentiation in GC. JPYZXZ alleviated GC progression via suppressing exosomal PD-L1 mediated expansion of MDSCs, thereby remodeling the immunosuppressive tumor microenvironment, which provided the experimental evidence for the clinical application of JPYZXZ in the treatment of GC via PD-L1.

Project description:The incidence of Poorly cohesive carcinoma (PCC) has steadily risen in recent years, posing a significant clinical challenge. To reveal the anti-tumor effects of Jianpi Yangzheng Xiaozheng granule (JPYZXZ) in PCC, an initial investigation was performed using CCK-8, colony formation, scratch, and transwell assays. This was followed by network pharmacology studies to gain a deeper understanding of JPYZXZ's impact on gastric cancer (GC). Then reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA), glutathione (GSH), Oil Red O staining, BODIPY493/503, triglyceride (TG), and cholesterol (TC) assay kits and western blot (Wb) analysis were applied to exam the regulatory effects of JPYZXZ on ferroptosis and lipid metabolism. Additionally, molecular docking studies and Wb analysis were used to further investigate the mechanisms of JPYZXZ on PCC. Finally, in vivo animal studies were conducted. The results show that JPYZXZ can inhibit the proliferation and migration of PCC cell. It increases the levels of ROS, Fe2+, MDA, while declining the content of GSH, TC, TG, and lipid droplet accumulation within cellular compartments. Wb indicates that JPYZXZ can negatively regulate the expression of proteins, including glutathione peroxidase 4 (GPX4), cystine/glutamate antipoter SLC7A11 (xCT), fatty acid synthase (FASN), and acetyl coenzyme A carboxylase 1 (ACC1). Furthermore, ferrostatin-1 (fer-1) is able to reverse the effects of JPYZXZ on the aforementioned markers of ferroptosis and lipid metabolism. Molecular docking analyses reveal that JPYZXZ exhibits a favorable binding affinity towards Stearoyl-Coenzyme A desaturase 1 (SCD1). Mechanism studies demonstrate that JPYZXZ is capable of down-regulating the expressions of proteins like SCD1, β-catenin, GPX4, and xCT, which is analogous to the effects of SCD1 knockdown and the application of SCD1 inhibitor A939572. Nevertheless, when SCD1 is knocked down, JPYZXZ is unable to further downregulate the expressions of these proteins. Animal studies have corroborated the in vitro tumor-inhibiting effects of JPYZXZ. Therefore, this study offers the first evidence that JPYZXZ inhibits PCC progression by orchestrating ferroptosis and altering lipid metabolism, mediated by the SCD1/Wnt/β-catenin pathway.

Project description:Parkinson's disease (PD) is an age-related neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra (SN) pars compacta. Dopamine (DA) replacement therapy is one of the most effective drug treatments for PD; however, long-term levodopa treatment can lead to various side effects that negatively impact the quality of life of patients. Therefore, finding safe and effective alternative drugs to treat PD is of clinical importance. The Bushen-Jianpi decoction (BSJPD) was derived from classic traditional Chinese medicine and has been shown to be effective in the treatment of PD. This study explored the effects and mechanisms of action of BSJPD in PD. In our study, rats were randomly divided into six groups: the vehicle group, rotenone (ROT) + Saline group, ROT + low-dose BSJPD group, ROT + high-dose BSJPD group, ROT + Madopar group, and ROT + low-dose BSJPD + Madopar group. Treatment was administered to the rats once a day for 28 days, and behavioral tests were assessed. Tyrosine hydroxylase (TH), catechol-O-methyltransferase (COMT), monoamine oxidase B (MAO-B), dopa decarboxylase (DDC), alpha-synuclein (α-syn), and heme oxygenase-1 (HO-1) levels were detected. Our results show that BSJPD increases the body weight of rats, improves their motor coordination, reverses decreasing TH levels in the SN, and increases the expression level of DDC and HO-1 in the striatum (ST), but it fails to affect TH levels in the ST in the PD model. In addition, BSJPD reduced the expression of MAO-B in the ST in the PD model, but it did not have a significant effect on COMT. Rather, COMT in the plasma and liver increased in the low-dose BSJPD treatment group. Upregulation of α-syn in the PD model was also observed, but BSJPD has shown no obvious effect to clear it. Our results suggest that BSJPD exhibits a therapeutic effect on PD and may play a neuroprotective role by regulating HO-1 expression and participating in the metabolic process of DA.

Dataset Information

Metabolomic Study on the Therapeutic Effect of the Jianpi Yangzheng Xiaozheng Decoction on Gastric Cancer Treated with Chemotherapy Based on GC-TOFMS Analysis.

Objective

Methods

Results

Conclusions

Publications

Metabolomic Study on the Therapeutic Effect of the Jianpi Yangzheng Xiaozheng Decoction on Gastric Cancer Treated with Chemotherapy Based on GC-TOFMS Analysis.

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