The PI3 K/AKT/mTOR signalling pathway plays an important role in the regulation of signal transduction and biological processes such as cell proliferation, apoptosis, metabolism and angiogenesis. Compared with those of other signalling pathways, the components of the PI3K/AKT/mTOR signalling pathway are complicated. The regulatory mechanisms and biological functions of the PI3K/AKT/mTOR signalling pathway are important in many human diseases, including ischaemic brain injury, neurodegenerative diseases, and tumours. PI3K/AKT/mTOR signalling pathway inhibitors include single-component and dual inhibitors. Numerous PI3K inhibitors have exhibited good results in preclinical studies, and some have been clinically tested in haematologic malignancies and solid tumours. In this review, we briefly summarize the results of research on the PI3K/AKT/mTOR pathway and discuss the structural composition, activation, communication processes, regulatory mechanisms and biological functions of the PI3K/AKT/mTOR signalling pathway in the pathogenesis of neurodegenerative diseases and tumours.

https://link.springer.com/content/pdf/10.1186/s13578-020-00416-0.pdf

Roles of the PI3K/AKT/mTOR signalling pathways in neurodegenerative diseases and tumours.

Hypoxia signaling in human health and diseases: implications and prospects for therapeutics

Crosstalk between miRNA and PI3K/AKT/mTOR signaling pathway in cancer

Therapeutic effects and potential mechanism of dehydroevodiamine on N-methyl-N'-nitro-N-nitrosoguanidine-induced chronic atrophic gastritis.

Hypoxia-inducible factor (HIF) is a central regulator involved in detection and adaption to cellular oxygen stress through regulation of the hypoxic transcriptional program in angiogenesis, erythropoiesis, and metabolism. The HIF pathway is involved in many diseases. On one hand, overexpression of the HIF pathway is associated with solid tumors such as renal cell carcinoma (RCC). On the other hand, suppression of the HIF pathway is correlated with inflammatory, anemia, and other hypoxic–ischemic diseases. Therefore, modulation of the HIF pathway has been perceived as a promising strategy for treating HIF-related diseases. Recent advances in understanding of the biochemistry underlying the HIF pathway have stimulated small-molecule drugs development, and therapeutically, manipulation of the HIF-mediated response has been shown to have considerable medicinal potential. This review will summarize and provide insight into recent advances in research that have expanded our knowledge of the HIF pathway, includi...

Small-Molecule Modulators of the Hypoxia-Inducible Factor Pathway: Development and Therapeutic Applications

Objective
To evaluate the feasibility and efficacy of enhanced recovery after surgery (ERAS) combined with laparoscopy-assisted distal gastrectomy (LADG) for gastric cancer.


Methods
60 patients with distal gastric cancer from April 2016 to September 2016 in Shanxi Cancer Hospital were enrolled. According to the admission time, the patients were numbered randomly by odd and even. 30 odd patients received conventional treatment (traditional group), and were even 30 incorporated into ERAS group. Record and comparison of two groups were conducted, including age, sex, weight, body mass index (BMI), 1-day preoperative serum albumin (ALB) level, operation time, anastomosis type, total intraoperative blood loss, postoperative TNM staging, bowel movement recovery time, postoperative hospital stay, total cost of hospitalization, complications, and serum ALB level after operation.


Results
The level of ALB in ERAS group was (36.16 ± 2.46) g/L at 4th day after operation, and (39.61±2.03) g/L at 7th day after operation, which were higher than those in traditional group [(34.38±2.31) g/L and (37.98±1.96) g/L, respectively], with stable changes and statistical difference (P= 0.006, P= 0.003). The recovery time of intestinal peristalsis in ERAS group was shorter than that in traditional group [(51.23±9.05) h vs. (58.97±9.61) h, P= 0.003], and the total hospitalization cost in ERAS group was less than that in traditional group [(7.23±0.34) × 104 yuan vs. (7.58±0.37) × 104 yuan,P 0.05).


Conclusion
The combination of ERAS and laparoscopic-assisted distal gastrectomy is safe and effective compared with traditional ways, which can relieve the stress reaction, promote the recovery of gastrointestinal function, reduce the hospitalization cost, and accelerate the rehabilitation of patients.


Key words: 
Stomach neoplasms; Laparoscopic assisted; Enhanced recovery after surgery; Surgical procedures, minimally invasive

Application of enhanced recovery after surgery in laparoscopy-assisted distal gastrectomy

In view of the high incidence of gastric cancer and the functions of hypoxia-inducible factor 1α (HIF-1α), our study aimed to investigate the functionality of HIF-1α in gastric cancer, and to explore the diagnostic and prognostic values of HIF-1α for this disease. Expression of HIF-1α in tumor tissues and adjacent healthy tissues as well as serum collected from both gastric cancer patients and normal healthy controls was detected by qRT-PCR. Survival analysis was performed using Kaplan-Meier method. HIF-1α siRNA silencing cell lines were established. Effects of HIF-1α siRNA silencing as well as PI3K activator sc3036 on proliferation, migration, and invasion of gastric cancer cells were detected by Cell counting kit (CCK-8) assay, and Transwell migration and invasion assay. Effects of HIF-1α siRNA silencing on AKT and VEGF were detected by Western blot. Expression of HIF-1α was significantly down-regulated in tumor tissues than in adjacent healthy tissues in most gastric cancer patients. Serum levels of HIF-1α were also higher in gastric cancer patients than in normal healthy people. Serum HIF-1α showed promising diagnostic and prognostic values for gastric cancer. HIF-1α siRNA silencing inhibited the proliferation, migration, and invasion of gastric cancer cells, while PI3K activator sc3036 treatment reduced those inhibitory effects. Down-regulation of HIF-1α can inhibit the proliferation, migration, and invasion of gastric cancer possibly by inhibiting PI3K/AKT pathway and VEGF expression.

Down-regulation of HIF-1α inhibits the proliferation, migration, and invasion of gastric cancer by inhibiting PI3K/AKT pathway and VEGF expression

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Application of enhanced recovery after surgery in laparoscopy-assisted distal gastrectomy

Down-regulation of HIF-1α inhibits the proliferation, migration, and invasion of gastric cancer by inhibiting PI3K/AKT pathway and VEGF expression