Network pharmacology dissection of multiscale mechanisms of herbal medicines in stage IV gastric adenocarcinoma treatment

Abstract Background Adenosquamous carcinoma (ASC) of the ampulla of Vater (AmV) is exceedingly rare with more aggressive behavior and worse prognosis than adenocarcinoma. The finding of ASC at the AmV in combination to the gastric adenocarcinoma has never been reported in the literature before. Case presentation An old lady was diagnosed as gastric adenocarcinoma at stage IV with enlargement of supraclavicular lymph nodes by gastroscopy and histopathological evaluation 3 years ago. Afterwards, the patient achieved complete remission after regular chemotherapy. However, the patient manifested yellow sclera and skin, choluria and clay colored stool 3 months ago. Preoperative contrast-enhanced CT, ERCP, MRCP, and PET/CT revealed the presence of an ampullary tumor. The patient then underwent laparoscopic radical gastrectomy and pancreaticoduodenectomy with regional lymph node dissection. Postoperative cytological analyses confirmed the diagnosis of gastric ulcer with complete response to neoadjuvant therapy and ASC at the AmV. The patient’s postoperative outcome was uneventful. Conclusion Drawing firm conclusions about the diagnosis of ampullary ASC is difficult because of the difficulty in acquiring both adenocarcinoma and SCC components by fine needle biopsy. The rarity of ASC of the AmV coexistent with gastric carcinoma makes it difficult to elucidate their clinicopathological characteristics, therapeutic strategies and overall prognosis. Surgical resection still remains the main treatment method.

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Her2+ and b-HCG Producing Undifferentiated Gastric Adenocarcinoma

Case Reports in Medicine ◽

10.1155/2014/268919 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5

Author(s):

Sahar Eivaz-Mohammadi ◽

Fernando Gonzalez-Ibarra ◽

Waheed Abdul ◽

Omer Tarar ◽

Khurram Malik ◽

...

Keyword(s):

Gastric Adenocarcinoma ◽

Stage Iv ◽

Stomach Body ◽

Ct Angiogram ◽

Lytic Lesions ◽

Night Sweats ◽

History Of ◽

Stomach Fundus ◽

Poorly Differentiated ◽

Lesser Curvature

A 25-year-old Hispanic female with a history of anemia, schizoaffective disorder, and psychosis was admitted for anemia associated with fatigue, weakness, shortness of breath, night sweats, weight loss, and abdominal and lower back pain for the past two months. On routine management, she was found to have a positive serum b-HCG of 80.4 (0–5 mIU/mL) but the patient denied any sexual activity in her life. During her admission, U/S of the pelvis was noncontributory. CT angiogram of the chest was significant for prominent mediastinal and hilar lymph nodes, diffusely thickened stomach suggesting gastric malignancy with multiple hypoenhancing lesions in the liver and diffuse lytic lesions in the spine and sacrum suspicious for metastatic disease. The MRI of the abdomen confirmed the CT angiogram findings. After these findings, EGD was performed which showed lesions in the antrum, body of the stomach, fundus, and cardia on the lesser curvature of the stomach body correlating with carcinoma. The biopsy was positive for Her2, b-HCG producing poorly differentiated gastric adenocarcinoma. Patient underwent one successful round of chemotherapy with Taxotene, Cisplatin, and 5-FU for Stage IV gastric adenocarcinoma.

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Network Pharmacology-Based Approaches of Rheum undulatum Linne and Glycyrriza uralensis Fischer Imply Their Regulation of Liver Failure with Hepatic Encephalopathy in Mice

Biomolecules ◽

10.3390/biom10030437 ◽

2020 ◽

Vol 10 (3) ◽

pp. 437 ◽

Cited By ~ 1

Author(s):

Su Youn Baek ◽

Eun Hye Lee ◽

Tae Woo Oh ◽

Hyun Ju Do ◽

Kwang-Youn Kim ◽

...

Keyword(s):

Hepatic Encephalopathy ◽

Liver Failure ◽

Transforming Growth Factor ◽

Neurological Diseases ◽

Herbal Medicines ◽

Chronic Liver ◽

Network Pharmacology ◽

Treatment And Prevention ◽

Rheum Undulatum ◽

Target Disease

Rheum undulatum and Glycyrrhiza uralensis have been used as supplementary ingredients in various herbal medicines. They have been reported to have anti-inflammatory and antioxidant effects and, therefore, have potential in the treatment and prevention of various liver diseases. Considering that hepatic encephalopathy (HE) is often associated with chronic liver failure, we investigated whether an R. undulatum and G. uralensis extract mixture (RG) could reduce HE. We applied systems-based pharmacological tools to identify the active ingredients in RG and the pharmacological targets of RG by examining mechanism-of-action profiles. A CCl4-induced HE mouse model was used to investigate the therapeutic mechanisms of RG on HE. We successfully identified seven bioactive ingredients in RG with 40 potential targets. Based on an integrated target–disease network, RG was predicted to be effective in treating neurological diseases. In animal models, RG consistently relieved HE symptoms by protecting blood–brain barrier permeability via downregulation of matrix metalloproteinase-9 (MMP-9) and upregulation of claudin-5. In addition, RG inhibited mRNA expression levels of both interleukin (IL)-1β and transforming growth factor (TGF)-β1. Based on our results, RG is expected to function various biochemical processes involving neuroinflammation, suggesting that RG may be considered a therapeutic agent for treating not only chronic liver disease but also HE.

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Network Pharmacology of Yougui Pill Combined with Buzhong Yiqi Decoction for the Treatment of Sexual Dysfunction

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2019/1243743 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Yangyun Wang ◽

Wandong Yu ◽

Chaoliang Shi ◽

Wei Jiao ◽

Junhong Li ◽

...

Keyword(s):

Sexual Dysfunction ◽

Signaling Pathway ◽

Herbal Medicines ◽

Mapk Signaling ◽

Glycyrrhetinic Acid ◽

Network Pharmacology ◽

Receptor Interaction ◽

Chemical Components ◽

Target Proteins ◽

Yougui Pill

Purpose. We aimed to find the possible key targets of Yougui pill and Buzhong Yiqi decoction for the treatment of sexual dysfunction. Materials and Methods. The composition of Yougui pill combined with Buzhong Yiqi decoction was obtained, and its effective components of medicine were screened using ADME; the component target proteins were predicted and screened based on the TCMSP and BATMAN databases. Target proteins were cross-validated using the CTD database. We performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for target proteins using the Cytoscape plugin ClueGO + CluePedia and the R package clusterProfiler, respectively. Subsequently, protein-protein interaction (PPI) analyses were conducted using the STRING database. Finally, a pharmacological network was constructed. Results. The pharmacological network contained 89 nodes and 176 relation pairs. Among these nodes, there were 12 for herbal medicines (orange peel, licorice, Eucommia, Aconite, Astragalus, Chinese wolfberry, yam, dodder seed, ginseng, Cornus officinalis, Rehmannia, and Angelica), 9 for chemical components (18-beta-glycyrrhetinic acid, carvacrol, glycyrrhetinic acid, higenamine, nobilin, quercetin, stigmasterol, synephrine, and thymol), 62 for target proteins (e.g., NR3C1, ESR1, PTGS2, CAT, TNF, INS, and TP53), and 6 for pathways (MAPK signaling pathway, proteoglycans in cancer, dopaminergic synapse, thyroid hormone signaling pathway, cAMP signaling pathway, and neuroactive ligand-receptor interaction). Conclusion. NR3C1, ESR1, PTGS2, CAT, TNF, INS, and TP53 may be important targets for the key active elements in the decoction combining Yougui pill and Buzhong Yiqi. Furthermore, these target proteins are relevant to the treatment of sexual dysfunction, probably via pathways associated with cancer and signal transduction.

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Monocyte Chemiluminescence Traits in Gastric Cancer

Russian Journal of Gastroenterology Hepatology Coloproctology ◽

10.22416/1382-4376-2021-31-2-34-39 ◽

2021 ◽

Vol 31 (2) ◽

pp. 34-39

Author(s):

O. V. Smirnova ◽

A. A. Sinyakov ◽

V. V. Tsukanov

Keyword(s):

Gastric Cancer ◽

Cancer Patients ◽

Gastric Adenocarcinoma ◽

Stage Iv ◽

Stage I ◽

Control Cohort ◽

Chemiluminescence Intensity ◽

Stage Iv Gastric Cancer ◽

Spontaneous Chemiluminescence ◽

Gastric Cancer Patients

Aim. A study of monocyte chemiluminescent activity at variant stages of gastric cancer.Materials and methods. The study enrolled 90 gastric cancer patients and 70 healthy donors. Spontaneous and induced chemiluminescence in monocytes was assessed for 90 min with a “BLM 3607” 36-channel chemiluminescence analyser (Russia). Opsonized zymosan-induced chemiluminescence enhancement was measured as a ratio of the areas under the induced vs. spontaneous chemiluminescence curves, the activation index. Statistical significance was estimated with the Mann—Whitney criterion (p < 0.05).Results. The maximal spontaneous monocyte chemiluminescence intensity significantly decreased in stage IV gastric cancer patients compared to the control cohort (p = 0.035). Time to maximum in spontaneous chemiluminescence increased in all gastric cancer patients vs. control (p = 0.001), and in stage IV gastric cancer vs. stage I patients (p = 0.043). The areas under a curve in spontaneous and induced monocyte chemiluminescence increased in all gastric cancer patients vs. control (p = 0.001), and in stage IV gastric cancer vs. stage I patients (p = 0.037). The activation index was higher in all gastric cancer cases compared to control (p = 0.001).Conclusion. All patients with gastric adenocarcinoma, irrespective of the stage, revealed changes in the monocyte chemiluminescence activity, i.e. a longer time to maximum in spontaneous chemiluminescence and larger area under the curve of spontaneous and induced chemiluminescence, the activation index. Maximal monocyte spontaneous chemiluminescence intensity diminished in stage IV gastric cancer compared to the control cohort. Immune activity reflected in monocyte chemiluminescence correlates with the stage of gastric adenocarcinoma.

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Network Pharmacology/Metabolomics-Based Validation of AMPK and PI3K/AKT Signaling Pathway as a Central Role of Shengqi Fuzheng Injection Regulation of Mitochondrial Dysfunction in Cancer-Related Fatigue

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5556212 ◽

2021 ◽

Vol 2021 ◽

pp. 1-23

Author(s):

Wei Guo ◽

Shan Liu ◽

Xinting Zheng ◽

Zhiwei Xiao ◽

Hanrui Chen ◽

...

Keyword(s):

Signaling Pathways ◽

Muscle Cell ◽

Herbal Medicines ◽

Enrichment Analysis ◽

Akt Signaling ◽

Network Pharmacology ◽

Cancer Therapies ◽

Cancer Related Fatigue ◽

Associated Proteins

Chinese herbal medicines have multiple targets and properties, and their use in multidisciplinary cancer therapies has consequently received increasing attention. Here, we have investigated the possible active ingredients associated with cancer-related fatigue (CRF) in the Shengqi Fuzheng Injection (SFI). In vitro cell models were used to measure the regulation effects of SFI on CRF. Metabolomic analysis was used to identify the potential genes and pathways in C2C12 mouse myoblasts treated with SFI, and the interaction of compounds and CRF targets was predicted using network pharmacology and molecular docking analyses. The putative pathways were further verified using immuno-blotting assays. The results showed that SFI significantly inhibited muscle cell apoptosis and increased the mitochondrial membrane potential of muscle cells. The network pharmacology analysis results identified 36 candidate compounds, and 244 potential targets were yielded by SFI, and they shared 10 key targets associated with cancer-related fatigue. According to the enrichment analysis and experimental validation, SFI might ameliorate muscle cell mitochondrial function by activating AMPK and inhibiting the PI3K/Akt signaling pathways, and the expression changes of mitochondrial metabolic enzymes MnSOD and apoptosis-associated proteins Bax and Bcl-2 were also triggered. The functions and mechanisms of SFI in anticancer-related fatigue were found here to be at least partly due to the targeting of the AMPK and PI3K/Akt signaling pathways, and this has highlighted new potential applications for network pharmacology when researching Chinese Medicines.

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A Network Pharmacology Study on the Molecular Mechanisms of FDY003 for Breast Cancer Treatment

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/3919143 ◽

2021 ◽

Vol 2021 ◽

pp. 1-18

Author(s):

Ho-Sung Lee ◽

In-Hee Lee ◽

Kyungrae Kang ◽

Sang-In Park ◽

Seung-Joon Moon ◽

...

Keyword(s):

Breast Cancer ◽

Molecular Mechanisms ◽

Therapeutic Targets ◽

Herbal Medicines ◽

Enrichment Analysis ◽

Estrogen Signaling ◽

Network Pharmacology ◽

Pathway Enrichment Analysis ◽

Anticancer Efficacy ◽

Artemisia Capillaris

Herbal medicines have drawn considerable attention with regard to their potential applications in breast cancer (BC) treatment, a frequently diagnosed malignant disease, considering their anticancer efficacy with relatively less adverse effects. However, their mechanisms of systemic action have not been understood comprehensively. Based on network pharmacology approaches, we attempted to unveil the mechanisms of FDY003, an herbal drug comprised of Lonicera japonica Thunberg, Artemisia capillaris Thunberg, and Cordyceps militaris, against BC at a systemic level. We found that FDY003 exhibited pharmacological effects on human BC cells. Subsequently, detailed data regarding the biochemical components contained in FDY003 were obtained from comprehensive herbal medicine-related databases, including TCMSP and CancerHSP. By evaluating their pharmacokinetic properties, 18 chemical compounds in FDY003 were shown to be potentially active constituents interacting with 140 BC-associated therapeutic targets to produce the pharmacological activity. Gene ontology enrichment analysis using g:Profiler indicated that the FDY003 targets were involved in the modulation of cellular processes, involving the cell proliferation, cell cycle process, and cell apoptosis. Based on a KEGG pathway enrichment analysis, we further revealed that a variety of oncogenic pathways that play key roles in the pathology of BC were significantly enriched with the therapeutic targets of FDY003; these included PI3K-Akt, MAPK, focal adhesion, FoxO, TNF, and estrogen signaling pathways. Here, we present a network-perspective of the molecular mechanisms via which herbal drugs treat BC.

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Network pharmacology-based analysis of the role of traditional Chinese herbal medicines in the treatment of COVID-19

Annals of Palliative Medicine ◽

10.21037/apm.2020.03.27 ◽

2020 ◽

Vol 9 (2) ◽

pp. 437-446 ◽

Cited By ~ 7

Author(s):

Shengwei Yu ◽

Junwu Wang ◽

Haitao Shen

Keyword(s):

Herbal Medicines ◽

Network Pharmacology ◽

Chinese Herbal Medicines ◽

Chinese Herbal ◽

Traditional Chinese Herbal Medicines

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Discovery of Herbal Pairs Containing Gastrodia elata Based on Data Mining and the Delphi Expert Questionnaire and Their Potential Effects on Stroke through Network Pharmacology

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/4263591 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Rongrong Zhou ◽

Yan Zhu ◽

Wei Yang ◽

Fengrong Zhang ◽

Junwen Wang ◽

...

Keyword(s):

Data Mining ◽

Association Rules ◽

Clinical Investigation ◽

Herbal Medicines ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Gastrodia Elata ◽

Pathway Network ◽

Biological Targets ◽

Medicinal Value

Background. Traditional Chinese medicine (TCM) formulae can be regarded as a source of new antistroke drugs. The aim of this study was to discover herbal pairs containing Gastrodia elata (Tianma, TM) from formulae based on data mining and the Delphi expert questionnaire. The proposed approach for discovering new herbal combinations, which included data mining, a clinical investigation, and a network pharmacology analysis, was evaluated in this study. Methods. A database of formulae containing TM was established. All possible herbal pairs were acquired by data mining association rules, and herbal pairs containing TM were screened according to the Support and Confidence levels. Taking stroke as the research object, the relationships between herbal pairs containing TM and stroke were explored by the Delphi expert questionnaire and statistical methods. To explore the effects of herbal pairs containing TM on stroke, a network pharmacology analysis was performed to predict core targets, biological functions, pathways, and mechanisms of action. Results. A total of 1903 formulae containing TM, involving 896 Chinese herbal medicines (CHMs) and 126 herbal pairs containing RG, were analyzed by association rules. A total of 27 herbal pairs were further screened according to the Support and Confidence levels. Twelve herbal pairs containing RG were added according to the expert questionnaires. Weightiness analysis showed that 9 groups of core herbal pairs contained RG, including TM-QX, TM-JH, TM-CX, TM-GG, TM-SJM, TM-JC, TM-SCP, TM-MJZ, and TM-GT. Two core herbal pairs, TM-JH and TM-CX, were randomly screened to explore their network pharmacological mechanisms in stroke. The important biological targets for network pharmacological analysis of TM-CX and TM-JH related to stroke were PTGS2, ACE, APP, NOS1, and NOS2. An herbal pair-compound-core target-pathway network (H-C-T-P network) was established, and arginine biosynthesis, arginine and proline metabolism, and the relaxin signaling pathway were identified by enrichment analysis. Conclusion. The herbal pairs of TM-CX and TM-JH obtained from data mining and the expert investigation were found to have effects of preventing and treating stroke through network pharmacology. This could be a viable approach to uncover hidden knowledge about TCM formulae and to discover herbal combinations with clinical and medicinal value based on data mining and questionnaires.

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Analysis of Herbal Mechanisms and Prescriptions for Chronic Cerebral Circulatory Insufficiency Based on Data Mining and Network Pharmacology

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207324999210120194312 ◽

2021 ◽

Vol 24 ◽

Author(s):

Ying Yu ◽

Gong Zhang ◽

Tao Han ◽

Hai-liang Huang

Keyword(s):

Signaling Pathways ◽

Target Genes ◽

Herbal Medicines ◽

Circulatory System ◽

Enrichment Analysis ◽

Network Pharmacology ◽

Hormone Regulation ◽

Active Ingredients ◽

The Core ◽

Circulatory Insufficiency

Background: Traditional Chinese medicine has accumulated rich resources and experience through clinical research to explore the prevention and treatment of chronic cerebral circulatory insufficiency, but current medicine lacks in-depth research and confirmation on the established protocols and mechanism of prescribed TCMs at the macro and micro levels. Objective: To explore the prescription of Chinese medicines for the treatment of chronic cerebral circulation insufficiency (CCCI) and to explore the mechanism of core drugs. Methods: 229 Chinese prescriptions for CCCI were collected from CNKI, CBM, VIP and WANFANG databases. Analyze the frequency and association rules of drugs and to extract the core drugs by TCMISSV2.5 software. The active ingredients and targets were obtained by TCMSP, and genes of CCCI were collected from the DisGeNET, OMIM, DrugBank disease databases. The intersection targets of herbal medicine and disease was imported into the STRING database for PPI network. The key targets were screened by network topology algorithm. The Systems Dock website was used to verify the molecular docking. The GOEAST and DAVID tools were used to perform GO and KEGG pathway analysis with the key target genes. Results: 117 drugs involved in 229 prescriptions were identified, 2 core drugs were identified. We identified 8 active ingredients, which were mandenol, myricanone, perlolyrine, senkyunone, wallichilide, sitosterol, beta-sitosterol and stigmasterol. 371 herbal targets predicted and 335 disease targets. The enrichment analysis showed that the core herbal medicines could prevent CCCI by 15 key signaling pathways. Conclusion: There are direct or indirect connections in key signaling pathways, which not only participate in energy metabolism, hormone regulation, signal transduction, but also play a role in the comprehensive intervention of nervous system, immune system, circulatory system and other systems, which is consistent with the comprehensive pathogenesis of CCCI induced by multiple factors.

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