Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated. Meanwhile, LGR4, but not LGR5, was responsible for the activation of WNT signaling pathway. Importantly, FABP5 and NME1 were identified and validated as crucial for both normal gastric stem/progenitor cells and gastric cancer cells. Finally, we explored the epigenetic regulation of critical genes for gastric corpus epithelium at chromatin state level, and identified several important cell-type-specific transcription factors. In summary, our work provides novel insights to systematically understand the cellular diversity and homeostasis of human gastric corpus epithelium in vivo.
Humans ; Epigenesis, Genetic ; Gastric Mucosa/metabolism* ; Chromatin/metabolism* ; Stem Cells ; Epithelium/metabolism* ; Fatty Acid-Binding Proteins/metabolism*

In the present study, a gastric retention floating system for Brucea javanica oil, composed of alginate and carrageenan, was prepared using ionotropic gelation. Parameters for floatability, drug load, encapsulation efficiency, bead morphology, in vitro release, and in vivo gastric retention were evaluated. The optimized formulation via Box-Behnken design consisted of 1.7% alginate (W/V), 1.02% carrageenan (W/V), 1.4% CaCO (W/V), and a gelling bath of pH 0.8. The alginate-carrageenan-Brucea javanica oil beads had a porous structure and exhibited up to 24 h of in vitro floatability with a load capacity of 45%-55% and an encapsulation efficiency of 70%-80%. A 6-h sustained release was observed in vitro. The beads had a prolonged gastric retention (> 60% at 6 h) in fasted rats, compared to non-floating beads (15% at 6 h), as measured by gamma scintigraphy with single-photon emission tomography/computed tomography (SPET/CT). In conclusion, the alginate-carrageenan-Brucea javanica oil system showed enhanced oil encapsulation efficiency, excellent floating and gastric retention abilities, and a favorable release behavior.
Alginates ; chemistry ; Animals ; Biological Availability ; Brucea ; chemistry ; Carrageenan ; chemistry ; Delayed-Action Preparations ; administration & dosage ; chemistry ; pharmacokinetics ; Drug Carriers ; chemistry ; Drug Delivery Systems ; methods ; Drug Evaluation, Preclinical ; Gastric Mucosa ; metabolism ; Glucuronic Acid ; chemistry ; Hexuronic Acids ; chemistry ; Microspheres ; Plant Oils ; administration & dosage ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

The epithelial cytokine response, associated with reactive oxygen species (ROS), is important in Helicobacter pylori (H. pylori)-induced inflammation. H. pylori induces the production of ROS, which may be involved in the activation of mitogen-activated protein kinases (MAPK), janus kinase/signal transducers and activators of transcription (Jak/Stat), and oxidant-sensitive transcription factor, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB), and thus, expression of interleukin-8 (IL-8) in gastric epithelial cells. alpha-lipoic acid, a naturally occurring thiol compound, is a potential antioxidant. It shows beneficial effects in treatment of oxidant-associated diseases including diabetes. The present study is purposed to investigate whether alpha-lipoic acid inhibits expression of inflammatory cytokine IL-8 by suppressing activation of MAPK, Jak/Stat, and NF-kappaB in H. pylori-infected gastric epithelial cells. Gastric epithelial AGS cells were pretreated with or without alpha-lipoic acid for 2 h and infected with H. pylori in a Korean isolate (HP99) at a ratio of 300:1. IL-8 mRNA expression was analyzed by RT-PCR analysis. IL-8 levels in the medium were determined by enzyme-linked immunosorbent assay. NF-kappaB-DNA binding activity was determined by electrophoretic mobility shift assay. Phospho-specific and total forms of MAPK and Jak/Stat were assessed by Western blot analysis. ROS levels were determined using dichlorofluorescein fluorescence. As a result, H. pylori induced increases in ROS levels, mRNA, and protein levels of IL-8, as well as the activation of MAPK [extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun NH2-terminal kinase 1/2 (JNK1/2), p38], Jak/Stat (Jak1/2, Stat3), and NF-kappaB in AGS cells, which was inhibited by alpha-lipoic acid. In conclusion, alpha-lipoic acid may be beneficial for prevention and/or treatment of H. pylori infection-associated gastric inflammation.
Enzyme-Linked Immunosorbent Assay ; Epithelial Cells/metabolism ; Gastric Mucosa/*drug effects/metabolism/microbiology ; Gene Expression Regulation, Bacterial ; Helicobacter Infections/immunology/*metabolism ; Helicobacter pylori/drug effects/*pathogenicity ; Humans ; Interleukin-8/genetics/*metabolism ; JNK Mitogen-Activated Protein Kinases ; Janus Kinase 1 ; Mitogen-Activated Protein Kinases/*biosynthesis ; NF-kappa B/*metabolism ; RNA, Messenger/isolation & purification/metabolism ; Reactive Oxygen Species/metabolism ; STAT3 Transcription Factor ; Stomach/metabolism/*microbiology ; Thioctic Acid/*pharmacology

OBJECTIVETo study the efficacy and mechanism of Weiyangning pills against experimental gastric ulcer.

METHODThe gastric ulcer model were established by acetic acid, water-immersion stress, aspirin induction, pyloric ligation in rats, in order to observe the effect of Weiyangning pills against experimental gastric ulcer and study its effect on the content of nitric oxide (NO) and epidermal growth factor (EGF), gastric mucosal blood flow, the content of PGE2, gastric secretion, gastric acid content and the activity of pepsin.

RESULTWeiyangning pills markedly reduced index of gastric ulcers of various types, increased the content of NO, EGF, PGE2 and gastric mucosal blood flow, inhibited gastric secretion and gastric acid content, and decreased the activity of pepsin.

CONCLUSIONWeiyangning pills has a significant effect against experimental gastric ulcer, which is related to the reduction of gastric mucosa damage factors (gastric acid and pepsin) and the increase in gastric mucosa's function as a barrier and its recovery effects, such as NO, EGF, PGE2 and gastric mucosal blood flow.

Acetic Acid ; adverse effects ; Animals ; Aspirin ; adverse effects ; Dinoprostone ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Epidermal Growth Factor ; metabolism ; Female ; Gastric Acid ; metabolism ; secretion ; Ligation ; adverse effects ; Male ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley ; Regional Blood Flow ; drug effects ; Stomach Ulcer ; drug therapy ; etiology ; metabolism ; physiopathology

OBJECTIVETo observe the effects and mechanisms of Pongamia pinnata root flavonoids (PRF) on the experimental gastric ulcer induced by acetic acid and to study the mechanism of PRF on the quality of ulcer healing.

METHODSThe models were established by acetic acid erosion, the quality of ulcer healing of PRF on the model of gastric ulcer were observed. The contents of epidermal growth factor (EGF) in serum were determined by radioimmunoassay. The expression of EGF and transforming growth factor-alpha (TGF-alpha) were detected by immunohistochemistry (SP).

RESULTSPRF significantly inhibited ulcerative formation induced by acetic acid (P < 0.05, P < 0.01). PRF could significantly increase the EGF and TGF-alpha (P < 0.05, P < 0.01) expression of para-ulcer mucosa tissue and improve the EGF contents in blood serum (P < 0.05, P < 0.01).

CONCLUSIONPRF increases the contents of EGF in serum and the expression of EGF and TGF-alpha in the tissue around gastric ulcer which might be one of possible mechanisms that PRF improves quality of ulcer healing.

Acetic Acid ; Animals ; Epidermal Growth Factor ; blood ; Female ; Flavonoids ; pharmacology ; Gastric Mucosa ; metabolism ; Male ; Millettia ; chemistry ; Plant Roots ; chemistry ; Rats ; Rats, Sprague-Dawley ; Stomach Ulcer ; chemically induced ; drug therapy ; metabolism ; Transforming Growth Factor alpha ; metabolism

This study was performed to determine the ability of eliminating sodium nitrite and blocking nitrosamine synthesis by anthocyanin from the skin of Alpinia galanga. purified by macroporous resin. The test was conducted under the condition of the simulated human gastric juice (pH 3.0, 37 degrees C) with VitC as positive control. The results showed that the max capability of eliminating sodium nitrite was 87.14%, which is 1.6 times sronger than that of VitC, and the max capability of blocking nitrosamine synthesis was 97.82%, which is 8 times sronger than that of VitC.
Alpinia ; chemistry ; Anthocyanins ; isolation & purification ; pharmacology ; Antioxidants ; pharmacology ; Ascorbic Acid ; pharmacology ; Gastric Juice ; chemistry ; Humans ; Hydrogen-Ion Concentration ; Hydrolysis ; drug effects ; Nitrosamines ; antagonists & inhibitors ; metabolism ; Plant Epidermis ; chemistry ; Sodium Nitrite ; metabolism

OBJECTIVETo study the changes of mucosa irritation of crude and processed Radix Phytolaccae.

METHODGastrointestinal experiments on rats and mice and the rabbits' eyes irritation experiments were applied to investigate the changes of mucosa irritation of crude and processed Radix Phytolaccae.

RESULTThe mucosa irritation of processed Radix Phytolaccae decreased obviously compared to crude one.

CONCLUSIONAfter being processed with vinegar, the mucosa irritation on Radix Phytolaccae decreased obviously.

Acetic Acid ; chemistry ; Animals ; Dinoprostone ; metabolism ; Drug Compounding ; Drugs, Chinese Herbal ; adverse effects ; chemistry ; Eye ; drug effects ; Gastric Mucosa ; drug effects ; metabolism ; Male ; Mice ; Phytolacca ; chemistry ; Plant Roots ; chemistry ; Rats

To prepare and evaluate in vitro the 20 (S) -Protopanaxadiol (Ppd) pharmacosome. The Ppd pharmacosome was successfully prepared by thin film-dispersion and its stability in vitro was studied. The particle size of pharmacosome was evaluated by dynamic scattering (DLS) and the encapsulation efficiency was determined by using centrifugal ultra-filtration. The encapsulation efficiency of Ppd pharmacosome was (80.84 +/- 0.53)% with the diameter of 100. 1 nm; While the encapsulation efficiency of Ppd pharmacosome that added Brij 78 added was (72.76 +/- 0.63)% with the diameter of 117. 3 nm. In addition, the effect of some factors on the encapsulation efficiency and the particles size, such as temperature, alcohol, pH and artificial gastrointestinal fluids, were investigated respectively. The selected formulation and technology are simple and practical to prepare Ppd pharmacosome and preparation properties are more stable.
Chemistry, Pharmaceutical ; Drug Stability ; Ethanol ; chemistry ; Gastric Acid ; metabolism ; Hydrogen-Ion Concentration ; Light ; Particle Size ; Sapogenins ; chemistry ; metabolism ; Scattering, Radiation ; Temperature

OBJECTIVETo investigate the therapeutic mechanism of Weiweifang (WWF, a Chinese herbal preparation) on gastric ulcer in rats viewing from metabonomics.

METHODSWistar rats were made to gastric model by acetic acid cauterization and randomized into the model group, the spontaneously healing group and the three WWF treatment groups, and a group of normal rats was set for control. Metabolic spectra of gastric mucosa extraction of rats were acquired with gas chromatography-mass spectrometry (GC-MS) technique. After being pre-processing, data were subjected to partial least squares discriminant analysis (PLS-DA) to discover the biomarkers in rats of the normal group and the model group. The therapeutic effect of WWF on experimental gastric ulcer was assessed by principal component analyses (PCA), and its action of mechanism was explained viewing from the changes of biomarkers.

RESULTSSpectra of biomarkers, including organic acids, fatty acids, amino acids, etc. in model rats were statistically different to those in normal rats, which demonstrated that the energy and substance metabolisms were disordered in rats with gastric ulcer. WWF could cure gastric ulcer effectively by way of regulating the metabolism of gastric mucosa.

CONCLUSIONThe therapeutic mechanism of WWF on experimental gastric ulcer in rats is revealed integrally by metabonomics in this study, displaying prominently the characteristics of Chinese medicine multiple targets comprehensive therapy.

Acetic Acid ; Amino Acids ; metabolism ; Animals ; Drugs, Chinese Herbal ; therapeutic use ; Fatty Acids ; metabolism ; Gas Chromatography-Mass Spectrometry ; Gastric Mucosa ; metabolism ; Male ; Metabolomics ; methods ; Phytotherapy ; Rats ; Rats, Wistar ; Stomach Ulcer ; chemically induced ; drug therapy ; metabolism

This study is to investigate therapeutic effect of astaxanthin on acetic acid-induced gastric ulcer in rats. Rats were divided into control group, ulcer control group, and astaxanthin (5, 10, and 25 mg x kg(-1)) groups at random, 8 rats in each group. After administered for 10 days consecutively, all the rats were sacrificed. The area of ulcer and the levels of MDA, SOD, CAT and GSH-Px in gastric mucosa were measured. Compared with ulcer control group, in astaxanthin (5, 10, and 25 mg x kg(-1)) groups, the area of ulcer was decreased significantly. Level of MDA decreased while activities of SOD, CAT and GSH-Px increased (P < 0.05). Astaxanthin has good therapeutic effect on acetic acid-induced gastric ulcer in rats. Eliminating free radical and improving local blood circulation of the ulcer may be the mechanism of action.
Acetic Acid ; Animals ; Anti-Ulcer Agents ; therapeutic use ; Antioxidants ; therapeutic use ; Catalase ; metabolism ; Gastric Mucosa ; metabolism ; pathology ; Glutathione Peroxidase ; metabolism ; Male ; Malondialdehyde ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Stomach Ulcer ; chemically induced ; drug therapy ; metabolism ; pathology ; Superoxide Dismutase ; metabolism ; Xanthophylls ; therapeutic use