RESUMO
Background: Gastric cancer (GC) is a common fatal malignancy. The aim of this study was to explore and validate the tumor-suppressive role and mechanism of Radix Bupleuri in GC. Methods: The active constituents of Radix Bupleuri were screened using TCMSP database. SwissTargetPrediction database was used to predict potential target genes of the compounds. GeneCards, TTD, DisGeNET, OMIM, and PharmGKB databases were used to search for GC-related targets. STRING database and Cytoscape 3.10 software were used for protein-protein interaction network construction and screening of core targets. DAVID database was used for GO and KEGG analyses. Core targets were validated using molecular docking. Cell proliferation and apoptosis were detected using CCK-8 and flow cytometry after GC cells were treated with isorhamnetin. The mRNA and protein expression levels of genes were detected using qRT PCR and Western blot. The metastasis potential of GC cells was evaluated in a nude mouse model. Results: A total of 371 potential targets were retrieved by searching the intersection of Radix Bupleuri and GC targets. Petunidin, 3',4',5',3,5,6,7-Heptamethoxyflavone, quercetin, kaempferol, and isorhamnetin were identified as the main bioactive compounds in Radix Bupleuri. SRC, HSP90AA1, AKT1, and EGFR, were core targets through which Radix Bupleuri suppressed GC. The tumor-suppressive effect of Radix Bupleuri on GC was mediated by multiple pathways, including PI3K-AKT, cAMP, and TNF signaling. The key compounds of Radix Bupleuri had good binding affinity with the core target. Isorhamnetin, a key component of Radix Bupleuri, could inhibit proliferation and metastasis, and induces apoptosis of GC cells. In addition, isorhamnetin could also reduce the mRNA expression of core targets, and the activation of PI3K/AKT pathway. Conclusion: This study identified potential targets and pathways of Radix Bupleuri against GC through network pharmacology and molecular docking, providing new insights into the pharmacological mechanisms of Radix Bupleuri in GC treatment.
Assuntos
Bupleurum , Medicamentos de Ervas Chinesas , Extratos Vegetais , Neoplasias Gástricas , Animais , Camundongos , Neoplasias Gástricas/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , RNA Mensageiro , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
BACKGROUND: This study aimed to evaluate the effect of perioperative transcutaneous electrical acupoint stimulation (TEAS) on postoperative cognitive dysfunction (POCD) in older patients who were diagnosed with gastrointestinal tumor and received radical resection of gastrointestinal tumors under general anesthesia. METHODS: A total of 68 patients who received radical resection of gastrointestinal tumors under general anesthesia were randomly divided into two groups. TEAS group patients received TEAS treatment. The treatment time was 30 min before the induction of anesthesia until the end of the surgery, 1 day before operation and from the first day to the third day after the operation. Except on the day of surgery, we treated the patients for 30 min once a day. In the sham TEAS group, the electronic stimulation was not applied and the treatment was the same as the TEAS group. The primary outcome was perioperative cognition evaluated by the Mini-Mental State Examination (MMSE) and secondary outcomes were the perioperative level of interleukin-6 (IL-6), S100 calcium-binding protein ß (S100ß), and C-reactive protein (CRP). RESULTS: The postoperative score of MMSE, orientation, memory, and short-term recall in the sham TEAS group was significantly lower than the preoperative and TEAS group (P < 0.05). The incidence of POCD in the TEAS group (21.88%) was lower than those in the sham TEAS group (40.63%). S100ß, IL-6, and CRP in the TEAS group were significantly lower than those in the sham TEAS group on the third day after the operation (P< 0.05). Postoperative S100ß, IL-6, and CRP in two groups were significantly higher than those before operation except for S100ß on the third day after the operation in the TEAS group (P < 0.05). CONCLUSIONS: Perioperative TEAS treatment reduced the postoperative inflammatory response and increased the postoperative cognitive function score and decrease the incidence of POCD in geriatric patients with gastrointestinal tumor. TRIAL REGISTRATION: ClinicalTrials.gov NCT04606888 . Registered on 27 October 2020. https://register.clinicaltrials.gov .
Assuntos
Neoplasias Gastrointestinais , Complicações Cognitivas Pós-Operatórias , Estimulação Elétrica Nervosa Transcutânea , Pontos de Acupuntura , Idoso , Anestesia Geral , Neoplasias Gastrointestinais/cirurgia , HumanosRESUMO
Background: The Zusanli (ST36) acupoint has been associated with treatment of various gastrointestinal conditions. There have been no studies of acupuncture therapy for paralytic postoperative ileus (PPOI). Materials and methods: Patients with PPOI following gastrectomy for gastric cancer were randomized to receive ST36 acupoint injection with neostigmine, gluteal intramuscular injection with 1.0 mg neostigmine, ST36 acupuncture alone, or standard therapy. The main outcome was the effectiveness rate for recovery of peristalsis. Secondary outcomes were time to bowel sound recovery, time to first flatus, and time to first defecation. Tertiary outcomes were drug-related adverse events, including abdominal pain, diarrhea, nausea, vomiting, tearing, delirium, seizure, and anxiety. Results: ST36 acupoint injection with neostigmine and gluteal intramuscular injection of neostigmine gave a higher rate of peristalsis recovery, and the ST36 acupoint injection group showed significantly higher total effectiveness rate than that of the intramuscular injection group. These interventions gave significantly shorter times to bowel sound recovery, shorter times to first flatus and first defecation compared with ST36 acupuncture and standard post-operative therapy (P < 0.01). ST36 acupoint injection group gave shorter time to bowel sound recovery, shorter time to first flatus and first defecation than those of the intramuscular injection group (P < 0.01). Drug-related adverse events in the intramuscular injection group were more serious than in the ST36 acupoint injection group (P < 0.05). Conclusion: ST36 acupoint injection with neostigmine is safe and effective for treatment of PPOI.
RESUMO
OBJECTIVES: We investigated the lethal effect of a hyperthermic CO2 pneumoperitoneum on gastric cancer cells. This could form the theoretical basis for further studies of the feasibility and safety of inflating hyperthermic CO2 in the abdominal cavity of gastric cancer patients during laparoscopy. METHODS: An in vitro hyperthermic CO2 pneumoperitoneum experimental model was built, where gastric cancer cell line SGC-7901 cells were grouped according to temperature. Cytotoxicity was detected using a cell counting kit; apoptosis was detected by Annexin V-FITC/PI flow cytometry and Hoechst 33342/PI fluorescent microscopy. Morphological alterations were observed by transmission electron microscopy. Invasion and migration were detected by a scratch test and by transwell migration, respectively. RESULTS: Cytotoxicity assays showed that a hyperthermic CO2 pneumoperitoneum significantly inhibited the proliferation of SGC-7901 cells (P<0.05); it also significantly induced apoptosis of SGC-7901 cells (P<0.05). Morphological observations showed that the cell membrane and nucleus had an apoptotic phenotype. The invasiveness and migration ability of the gastric cancer cells subjected to hyperthermic CO2 were significantly reduced. CONCLUSIONS: A hyperthermic CO2 pneumoperitoneum had a lethal effect on gastric cancer SGC-7901 cells by inhibiting their invasion and migration, and by inducing apoptosis.