Gastric cancer, one of the most common types of cancers, develops over a series of consecutive histopathological stages. As such, the analysis and research of the gastric precancerous lesions (GPLs) play an important role in preventing the occurrence of gastric cancer. Ginsenoside Rg3 (Rg3), an herbal medicine, plays an important role in the prevention and treatment of various cancers. Studies have demonstrated a correlation between glycolysis and gastric cancer progression. Herein, the aim of the present study was to clarify the potential role for glycolysis pathogenesis in Rg3‐treated GPL in Atp4a^−/− mice. The GPL mice model showed chronic gastritis, intestinal metaplasia, and more atypical hyperplasia in gastric mucosa. According to the results of HE and AB‐PAS staining, it could be confirmed that GPL mice were obviously reversed by Rg3. Additionally, the increased protein levels of PI3K, AKT, mTOR, HIF‐1α, LDHA, and HK‐II, which are crucial factors for evaluating GPL in the aspect of glycolysis pathogenesis in the model group, were downregulated by Rg3. Meanwhile, the miRNA‐21 expression was decreased and upregulated by Rg3. Furthermore, the increased gene levels of Bcl‐2 and caspase‐3 were attenuated in Rg3‐treated GPL mice. In conclusion, the findings of this study imply that abnormal glycolysis in GPL mice was relieved by Rg3 via regulation of the expressions of PI3K, AKT, mTOR, HIF‐1α, LDHA, HK‐II, and miRNA‐21. Rg3 is an effective supplement for GPL treatment and can be harnessed to inhibit proliferation and induce apoptosis of GPL cells.

The Wei Pi Xiao (WPX) decoction, based on the theory of traditional Chinese medicine, has been widely used for the treatment of gastric precancerous lesions (GPL). Although WPX is known to be effective for the treatment of GPL, its active ingredients, cellular targets, and the precise molecular mechanism of action are not known. This study aimed to identify the multiple mechanisms of action of the WPX decoction in the treatment of GPL. The active compounds, drug targets, and the key pathways involved in the therapeutic effect of WPX in the treatment of GPL were analyzed by an integrative analysis pipeline. The information pertaining to the compounds present in WPX and their disease targets was obtained from TCMSP and GeneCards, respectively. The mechanisms underlying the therapeutic effect of WPX were investigated with gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A total of 82 bioactive compounds and 146 related targets were identified in this study. Following target analyses, the targets were further mapped to 26 key biological processes and 21 related pathways to construct a target-pathway network and an integrated GPL pathway. The study demonstrated that the WPX formula primarily treats the dysfunctions of GPL arising from cell proliferation, apoptosis, and mucosal inflammation, which offered a novel insight into the pathogenesis of GPL and revealed the molecular mechanism underlying the therapeutic effects of the WPX formula in GPL. This study offers a novel approach for the systematic investigation of the mechanisms of action of herbal medicines, which will provide an impetus to the GPL drug development pipeline.

This study was aimed at elucidating the potential mechanisms of quercetin in the treatment of gastric cancer (GC). A network pharmacology approach was used to analyze the targets and pathways of quercetin in treating GC. The predicted targets of quercetin against GC were obtained through database mining, and the correlation of these targets with GC was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Next, the protein‐protein interaction (PPI) network was constructed, and overall survival (OS) analysis of hub targets was performed using the Kaplan–Meier Plotter online tool. Finally, the mechanism was further analyzed via molecular docking of quercetin with the hub targets. Thirty‐six quercetin‐related genes were identified, 15 of which overlapped with GC‐related targets. These targets were further mapped to 319 GO biological process terms and 10 remarkable pathways. In the PPI network analysis, six hub targets were identified, including AKT1, EGFR, SRC, IGF1R, PTK2, and KDR. The high expression of these targets was related to poor OS in GC patients. Molecular docking analysis confirmed that quercetin can bind to these hub targets. In conclusion, this study provided a novel approach to reveal the therapeutic mechanisms of quercetin on GC, which will ease the future clinical application of quercetin in the treatment of GC.

Parietal cells of the gastric mucosa contain a complex and extensive secretory membrane system that harbors gastric H⁺, K⁺-adenosine triphosphatase, the enzyme primarily responsible for gastric lumen acidification. Here, we describe the characterization of mice deficient in the H⁺, K⁺-ATPase α subunit (Atp4a^-/-) to determine the role of this protein in the biosynthesis of this membrane system and the biology of the gastric mucosa. Wild-type and Atp4a^-/- mice, paired for age, were examined at 10, 12, 14 and 16 weeks for histopathology, and the expression of MUC2, AMACR, Ki-67, and p53 proteins was analyzed by immunohistochemistry. For further information, PI3K, AKT, mTOR, HIF-1α, LDHA, and SIRT6 were detected by western blotting. Compared to the WT mice, Atp4a^-/- mice developed parietal cell atrophy and significant antral inflammation and intestinal metaplasia with elevated MUC2 expression. Areas of dysplasia in the Atp4a^-/- mouse stomach showed increased AMACR and Ki-67 expression. Consistent with elevated antral proliferation, tissue isolated from Atp4a^-/- mice showed elevated p53 expression. The expression of P-PI3K, P-AKT, P-mTOR, HIF-1α, LDHA, and SIRT6 was significantly higher in tissue from the Atp4a^-/- mice compared with the WT mice. The H⁺, K⁺-ATPase α subunit is required for acid-secretory activity of parietal cells in vivo, the normal development and cellular homeostasis of the gastric mucosa, and attainment of the normal structure of the secretory membranes. Chronic achlorhydria and hypergastrinemia in aged Atp4a^-/- mice produced progressive hyperplasia and mucolytic and intestinal metaplasia and activated the Warburg effect via PI3K/AKT/mTOR signaling.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Haobin Cai2, 1, Yijie Wang1, Jiayang He1, Tiantian Cai1, Jun Wu1, Jiansong Fang1, Rong Zhang1, Zhouke Guo2, Li Guan1, Qinkai Zhan1, Li Lin3, Yao Xiao4, Huafeng Pan1 and Qi Wang1 1Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510405, China 2Department of Neurology & Psychology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen 518033, China 3Guangzhou University of Chinese Medicine, Guangzhou 510405, China 4Guangzhou Medical University, Guangzhou 510182, China Correspondence to: Qi Wang, email: wangqi@gzucm.edu.cn Huafeng Pan, email: gzphf@126.com Keywords: dementia, bajijiasu, amyloid-β, cognitive impairment, APP/PS1 mice Received: July 13, 2017 Accepted: September 03, 2017 Published: October 04, 2017 ABSTRACT Alzheimer's disease (AD) is a progressive neurological degenerative disease. The main clinical manifestations of AD include progressive cognitive impairment and alteration of personality. Senile plaques, neuroinflammation, and destruction of synapse structure stability are the main pathological features of AD. Bajijiasu(BJJS) is extracted from Morinda Officinalis, a Chinese herb. In this study, we explored the effect of BJJS on AD from many aspects in APPswe/PSEN1ΔE9 (APP/PS1) double transgenic mice. The Morris water maze and novel object recognition tests results showed that BJJS could significantly improve the learning and memory abilities in APP/PS1 mice. BJJS treatment increased the level of insulin degradation enzyme (IDE) and neprilysin (NEP) and decreased the level of β-site app cleaving enzyme 1(BACE1) in the brain of APP/PS1 mice. BJJS-treated APP/PS1 mice appeared to have reductions of Aβ deposition and senile plaques, and showed higher levels of neurotrophic factors in the brain. We also found that BJJS had an inhibitory function on neuroinflammation in APP/PS1 mice. In addition, the synapse structure relevant proteins were elevated in the brain of BJJS-treated APP/PS1 mice. The present results indicated that BJJS could attenuate cognitive impairment via ameliorating the AD-related pathological alterations in APP/PS1 mice. These findings suggest that BJJS may be a potential therapeutic strategy in Alzheimer's disease.