SIRT1 mediated gastric cancer progression under glucose deprivation through the FoxO1-Rab7-autophagy axis

PurposeSilent mating type information regulator 2 homolog 1 (SIRT1) and autophagy have a two-way action (promoting cell death or survival) on the progression and treatment of gastric cancer (GC) under different conditions or environments. This study aimed to investigate the effects and underlying mechanism of SIRT1 on autophagy and the malignant biological behavior of GC cells under conditions of glucose deprivation (GD).Materials and methodsHuman immortalized gastric mucosal cell GES-1 and GC cell lines SGC-7901, BGC-823, MKN-45 and MKN-28 were utilized. A sugar-free or low-sugar (glucose concentration, 2.5 mmol/L) DMEM medium was used to simulate GD. Additionally, CCK8, colony formation, scratches, transwell, siRNA interference, mRFP-GFP-LC3 adenovirus infection, flow cytometry and western blot assays were performed to investigate the role of SIRT1 in autophagy and malignant biological behaviors (proliferation, migration, invasion, apoptosis and cell cycle) of GC under GD and the underlying mechanism.ResultsSGC-7901 cells had the longest tolerance time to GD culture conditions, which had the highest expression of SIRT1 protein and the level of basal autophagy. With the extension of GD time, the autophagy activity in SGC-7901 cells also increased. Under GD conditions, we found a close relationship between SIRT1, FoxO1 and Rab7 in SGC-7901 cells. SIRT1 regulated the activity of FoxO1 and upregulated the expression of Rab7 through deacetylation, which ultimately affected autophagy in GC cells. In addition, changing the expression of FoxO1 provided feedback on the expression of SIRT1 in the cell. Reducing SIRT1, FoxO1 or Rab7 expression significantly inhibited the autophagy levels of GC cells under GD conditions, decreased the tolerance of GC cells to GD, enhanced the inhibition of GD in GC cell proliferation, migration and invasion and increased apoptosis induced by GD.ConclusionThe SIRT1-FoxO1-Rab7 pathway is crucial for the autophagy and malignant biological behaviors of GC cells under GD conditions, which could be a new target for the treatment of GC

The impact of insulin on chemotherapeutic sensitivity to 5-fluorouracil in gastric cancer cell lines SGC7901, MKN45 and MKN28

BACKGROUND: The role of insulin in the pathogenesis of cancer has been increasingly emphasized because of the high incidence of obesity and metabolic syndrome and their correlated complication including cancer. This study aimed to explore the impact of insulin on chemoresistance to 5-fluorouracil in gastric cancer and the possible mechanisms. METHODS: Tissue samples of gastric cancer and adjacent normal gastric mucosa from patients with or without obesity were performed immunohistochemical staining for P-glycoprotein. The follow-up was done after the surgical treatment. The effect of insulin on chemotherapeutic sensitivity of the three gastric cancer cell lines to 5-fluorouracil was evaluated by pre-incubation with insulin before administration of 5-fluorouracil. The expression of P-glycoprotein was determined by Western blotting. RESULTS: P-glycoprotein were overexpressed in tissues from patients who suffered gastric cancer and were higher in those simultaneously suffered gastric cancer and obesity. Addition of 1 μM insulin remarkably promoted the proliferation of SGC7901, MKN45 and MKN28 cells and decreased the cytotoxicity of 5-fluorouracil. In addition, the expression of P-glycoprotein was upregulated in SGC7901, MKN45 and MKN28 cells. CONCLUSION: Insulin improved the proliferation of gastric cancer cell lines and contributed to chemoresistance of gastric cancer cells to 5-fluorouracil which is likely to involve upregulation of P-glycoprotein

A response to commenter Ke Lan's comment on our paper published in Nature Communications (2023)14:5782 by J. Yan et al

A response to commenter Ke Lan's comment on our paper published in Nature Communications (2023)14:5782 by J. Yan et a

Application of Intelligent Detection of Neural Signal in Depth Evaluation of Obstetrics and Gynecology Anesthesia

In order to evaluate the application of EEG intelligent detection in gynecological anesthesia depth, the application of ANGEL-6000 EEG depth monitor in laparoscopic gynecological anesthesia was proposed. This method was applied to 60 patients who underwent elective laparoscopic gynecological surgery in our hospital from February to August 2016. Inclusion criteria were ASA i ∼ ii; the average age was (37.8 ± 6.6) years from 20 to 50 years old; the average body weight was (51.53 ± 3.87) kg; conscious and no communication barriers; and patients without instrument ventilation. The patients were divided into observation group and control group according to the random number table method, with 30 patients in each group. The two groups were anesthetized with the same anesthetic drugs, and their consciousness index was monitored. IoC values were recorded before induction of anesthesia (T0), 5 min after intubation (T1), 5 min after operation (T2), intraoperative exploration (T3), at the end of operation (T4), 1 min before extubation (T5), and 5 min after extubation (T6). The dosage of anesthetic drugs, operation time, extubation time, and operation time of the two groups were statistically analyzed. Compared with the operation time of patients in the two groups, the extubation time, awake time, and time out of the operating room of patients in the control group were longer than the observation group. The IoC values of patients in the control group at T0 and T6 time points were lower than those in the observation group at each time point from T1 to T5. Comparison of perioperative dose of remifentanil and atracurium between the two groups was performed. The control group used more propofol dose in perioperative period. The application of neuroelectric signal in laparoscopic gynecological surgery to detect changes in perioperative IoC value can well reflect the level of consciousness of patients and reflect the effect of perioperative stimulation at different time points on the EEG of patients in real time.</jats:p

Intraoperative cell salvage for obstetrics: a prospective randomized controlled clinical trial

Abstract Background The latest basic studies and clinical evidence have confirmed the safety and efficacy of intraoperative autologous blood cell transfusion in cardiac surgery and orthopaedics. However, in caesarean section, there are still concerns about the contamination of amniotic fluid and foetal components, and consequently the application of intraoperative autologous blood cell transfusion is not universal. Therefore, this study aimed to evaluate the clinical value of intraoperative autologous blood cell transfusion in obstetric surgery. Methods A prospective, randomized, controlled, feasibility study was performed in women undergoing caesarean section. One hundred sixteen participants were randomly assigned at a 1:1 ratio into either the intraoperative cell salvage group or the control group. Allogeneic blood cells were transfused into patients with haemoglobin concentrations &lt; 80 g/dL in both the intraoperative cell salvage group and the control group. Results No significant differences were found between the two groups in age, weight, maternal parity, history of previous caesarean section, gestational weeks of delivery, etc. However, compared with the control group, patients in the intraoperative cell salvage group had a significantly lower amount of allogeneic blood cell transfusion, lower incidence of postoperative incision infection, delayed wound healing, perioperative allergy, adverse cardiovascular events, hypoproteinaemia and shorter hospital stay. Conclusion The results of this study suggest that the use of autologous blood cell transfusion is safe and effective for patients with obstetric haemorrhage. Trial registration: All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional and/or National Research Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (2016-XJS-003-01) as well as the 1964 Helsinki Declaration and its later amendments or other comparable ethical standards. The clinical trials were registered (ChiCTR-ICC-15,007,096) on September 28, 2015. </jats:sec