Mechanistic insights into the ameliorative effects of Xianglianhuazhuo formula on chronic atrophic gastritis through ferroptosis mediated by YY1/miR-320a/TFRC signal pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xianglianhuazhuo formula (XLHZ) has a potential therapeutic effect on chronic atrophic gastritis (CAG). However, the specific molecular mechanism remains unclear. AIM OF THE STUDY: To evaluate the effect of XLHZ on CAG in vitro and in vivo and its potential mechanisms. METHODS: A rat model of CAG was established using a composite modeling method, and the pathological changes and ultrastructure of gastric mucosa were observed. YY1/miR-320a/TFRC and ferroptosis-related molecules were detected. An MNNG-induced gastric epithelial cell model was established in vitro to evaluate the inhibitory effect of XLHZ on cell ferroptosis by observing cell proliferation, migration, invasion, apoptosis, and molecules related to ferroptosis. The specific mechanism of action of XLHZ in treating CAG was elucidated by silencing or overexpression of targets. RESULTS: In vivo experiments showed that XLHZ could improve the pathological status and ultrastructure of gastric mucosa and inhibit ferroptosis by regulating the YY1/miR-320a/TFRC signaling pathway. The results in vitro demonstrated that transfection of miR-320a mimics inhibited cell proliferation, migration, and invasion while promoting cell apoptosis. MiR-320a targeted TFRC and inhibited ferroptosis. Overexpression of TFRC reversed the inhibitory effect of miR-320a overexpression on cell proliferation. The effect of XLHZ was consistent with that of miR-320a. YY1 targeted miR-320a, and its overexpression promoted ferroptosis. CONCLUSION: XLHZ inhibited ferroptosis by regulating the YY1/miR-320a/TFRC signaling pathway, ultimately impeding the progression of CAG.

Effects of folic acid supplementation on chronic atrophic gastritis based on MTHFR C677T polymorphism.

BACKGROUND: It has been shown the methylenetetrahydrofolate reductase (MTHFR) 677TT (rs 1801133) genotype predicts histopathological alterations in the incisura of patients with chronic atrophic gastritis (CAG). MTHFR is a crucial enzyme in fatty acid (FA) metabolism. This study aimed to evaluate the influence of FA supplementation in CAG patients without Helicobacter pylori infection and the MTHFR C677T (rs 1801133) genotype as a potential CAG predictor. METHODS: A total of 96 CAG patients, aged 21 to 72 years old, were enrolled in this study. After 6 months of treatment, histopathological outcomes were compared among patients treated with weifuchun (WFC) (1.44 g 3 times per os per day), those treated with WFC and FA (5 mg once daily), and those treated with WFC, FA, and vitamin B12 (VB12) (0.5 mg 3 times per day) based on the Operative Link on Gastritis/Intestinal Metaplasia assessment staging systems. RESULTS: Atrophic lesions in patients treated with WFC and FA improved more than in patients treated only with WFC therapy (78.1% vs 53.3%, P = .04). Atrophic or intestinal metaplasia (IM) lesions in the incisura of patients with the TT genotype were better than those in patients with the CC/CT genotype (P = .02). CONCLUSION: The treatment of CAG patients with 5 mg of FA supplements daily for 6 months improved their gastric atrophy status, especially for the Operative Link on Gastritis/Intestinal Metaplasia assessment stages I/II. Moreover, our study is the first to reveal that patients with the MTHFR 677TT genotype require more timely and effective FA treatment than those with the CC/CT genotype.

Study on tongue coating microbes of bitter taste, sticky and greasy taste in chronic atrophic gastritis.

OBJECTIVE: To objectively reveal the relationship between tongue coating microbes and bitter taste, sticky and greasy taste in chronic atrophic gastritis (CAG) patients. METHODS: 16S rRNA high-throughput sequencing was used to detect bacterial diversity and community composition of tongue coating microbes from samples of CAG patients. LEfSe algorithm was used for discovering the different tongue coating microbes in CAG patients with or without bitter taste, also that in CAG patients with or without sticky and greasy taste. RESULTS: We respectively compared the features of tongue coating microbes in bitter taste, sticky and greasy taste of CAG patients. At the genus level, 25 tongue coating microbes were significantly different in CAG patients with bitter taste or without bitter taste; 17 tongue coating microbes were significantly different in CAG patients with sticky and greasy taste or without sticky and greasy taste. and were closely related to CAG patients with bitter taste. , , and were closely related to CAG patients with stick and greasy taste. CONCLUSION: and possibly contribute to bitter taste of CAG patients, and and contribute to stick and greasy taste of CAG patients, which is potential for the diagnosis and treatment of CAG.

Medicine for chronic atrophic gastritis: a systematic review, meta- and network pharmacology analysis.

PURPOSE: The aim of this study is to determine the effectiveness and reliability of adding traditional Chinese medicine (TCM) in the clinical intervention and explore mechanisms of action for chronic atrophic gastritis (CAG) through meta- and network pharmacology analysis (NPAs). METHODS: A predefined search strategy was used to retrieve literature from PubMed, Embase database, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese BioMedical Literature Database (CBM), Wan Fang Data and China Science and Technology Journal Database (VIP). After applying inclusion and exclusion criteria, a total of 12 randomized controlled trials (RCTs) were included for meta-analysis to provide clinical evidence of the intervention effects. A network meta-analysis using Bayesian networks was conducted to observe the relative effects of different intervention measures and possible ranking of effects. The composition of the TCM formulation in the experimental group was analysed, and association rule mining was performed to identify hub herbal medicines. Target genes for CAG were searched in GeneCards, Online Mendelian Inheritance in Man, PharmGKB, Therapeutic Target Database and DrugBank. A regulatory network was constructed to connect the target genes with active ingredients of the hub herbal medicines. Enrichment analyses were performed using the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to examine the central targets from a comprehensive viewpoint. Protein-protein interaction networks (PPINs) were constructed to identify hub genes and conduct molecular docking with differentially expressed genes (DEGs) and corresponding active molecules. RESULTS: A total of 1140 participants from 12 RCTs were included in the statistical analysis, confirming that the experimental group receiving the addition of TCM intervention had better clinical efficacy. Seven hub TCMs (Paeonia lactiflora, Atractylodes macrocephala, Pinellia ternata, Citrus reticulata, Codonopsis pilosula, Salvia miltiorrhiza and Coptis chinensis) were identified through association rule analysis of all included TCMs. Thirteen hub genes (CDKN1A, CASP3, STAT1, TP53, JUN, MAPK1, STAT3, MAPK3, MYC, HIF1A, FOS, MAPK14 and AKT1) were obtained from 90 gene PPINs. Differential gene expression analysis between the disease and normal gastric tissue identified MAPK1 and MAPK3 as the significant genes. Molecular docking analysis revealed that naringenin, luteolin and quercetin were the main active compounds with good binding activities to the two hub targets. GO analysis demonstrated the function of the targets in protein binding, while KEGG analysis indicated their involvement in important pathways related to cancer. CONCLUSIONS: The results of a meta-analysis of 12 RCTs indicate that TCM intervention can improve the clinical treatment efficacy of CAG. NPAs identified seven hub TCM and 13 target genes associated with their actions, while bioinformatics analysis identified two DEGs between normal and CAG gastric tissues. Finally, molecular docking was employed to reveal the mechanism of action of the active molecules in TCM on the DEGs. These findings not only reveal the mechanisms of action of the active components of the TCMs, but also provide support for the development of new drugs, ultimately blocking the progression from chronic gastritis to gastric cancer.

[Effect of modified Danggui Shaoyao Powder on SOCS3/TLR4 signaling pathway in rats with chronic atrophic gastritis].

This study aims to investigate the effect of modified Danggui Shaoyao Powder on the suppressor of cytokine signaling 3(SOCS3)/Toll-like receptor 4(TLR4) signaling pathway in gastric tissue of rats with chronic atrophic gastritis(CAG).Sixty SPF-grade SD rats were randomly assigned into the normal group, model group, Moluo Pills group, and high-, medium-, and low-dose groups of modified Danggui Shaoyao Powder.The rats in other groups except the normal group were treated with N-methyl-N'-nitro-N-nitrosoguanidine(MNNG) to establish the CAG model.After 12 weeks of modeling, the rats in each group were administrated with corresponding drugs by gavage for 8 weeks.After the last administration, the histopathological changes of rat gastric mucosa were observed via hematoxylin-eosin(HE) staining.The serum levels of IL-6, TNF-α, and CRP were determined by enzyme-linked immunosorbent assay(ELISA).The mRNA levels of SOCS3 and TLR4 were determined by real-time PCR.The protein levels of SOCS3, TLR4, JAK2, p-JAK2, STAT3, and p-STAT3 in rat gastric tissue were measured by Western blot.Immunohistochemical method was employed to determine the protein levels of NF-κB, MyD88, NLRP3, Bcl-2, Bax, and Bad in rat gastric tissue.The results showed that modified Danggui Shaoyao Powder alleviated gastric mucosal atrophy of rats, significantly lowered the levels of IL-6, TNF-α, and CRP in rat serum, up-regulated the mRNA level of SOCS3, and down-regulated the mRNA level of TLR4 in rat gastric tissue.Furthermore, modified Danggui Shaoyao Powder up-regulated the protein level of SOCS3, down-regulated the protein levels of TLR4, p-JAK2, p-STAT3, NF-κB, MyD88, NLRP3, Bax, and Bad, and promoted the expression of Bcl-2 protein.Therefore, modified Danggui Shaoyao Powder may mitigate the gastric mucosal atrophy of rats by regulating the SOCS3/TLR4 signaling pathway.

Regulation of gut microbiota of Astragali Radix in treating for chronic atrophic gastritis rats based on metabolomics coupled with 16S rRNA gene sequencing.

Astragali Radix (HQ), a common traditional Chinese medicine (TCM), is widely used to treat chronic atrophic gastritis (CAG). However, its mechanism in treating CAG is still not clear. Accumulating evidence highlights the link between gut microbiota and CAG. We hypothesized that the gut microbiota might be involved in the effect of HQ. Ultra-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-Q-TOF/MS) based metabolomics and 16S rRNA gene sequencing techniques of the cecal contents were applied to study its mechanisms. As a result, nine metabolites and fifteen gut microbiotas changed significantly in cecal contents samples between control group and model group. Among them, two metabolites (7-keto-3A ·12-α-hydroxyalkanoic acid and deoxycholic acid) and two gut microbiota genera (Acetobacter and Escherichia), had the most obvious callback effect after the administration of HQ. Sixty-seven correlated pairs exhibited the significant link between the involved metabolites and gut microbiotas through the correlation analysis, where two strong correlation pairs: Tetrahydrohydroxone âˆ¼ Bacteroides (r = 0.895) and Deoxycholic acid âˆ¼ Acetobacter (r = -0.843) were regulated by HQ. The results showed that HQ had the potential protection from metabolic perturbation involved into gut microbiotas induced by CAG. Two gut microbiotas, Acetobacter and Escherichia, and two metabolites, 7-keto-3A ·12-α-hydroxyalkanoic acid and deoxycholic acid were the potential targets of HQ.

Therapeutic effect of Qinghuayin against chronic atrophic gastritis through the inhibition of toll or interleukin-1 receptor domain-containing adaptor inducing interferon-ß signaling pathway.

OBJECTIVE: To examine the efficacy of Qinghuayin (, QHY) in rat chronic atrophic gastritis (CAG) models and explored the molecular mechanism of QHY in treating CAG. METHODS: In total, 65 Wistar rats were randomly divided into the control (= 10) and CAG groups ( = 55). CAG model rats were further divided into five groups: model ( = 10), vitacoenzyme ( = 10), low-dose QHY ( = 10), medium-dose QHY ( = 10), and high-dose QHY groups ( = 10). We analyzed histopathological changes using hematoxylin and eosin staining and measured interleukin (IL)-6 and IL-8 levels in serum using enzyme-linked immunosorbent assay (ELISA) (Boster Bio, Pleasanton, USA). In addition, gastrin (GAS), pepsinogen I (PGI), and PGII expressions were evaluated using ELISA. The protein and mRNA expression of toll-like receptor 4 (TLR4) and toll or interleukin-1 receptor domain-containing adaptor inducing interferon-ß (TRIF) was detected by Western blotting and quantitative reverse transcription-polymerase chain reaction, respectively. RESULTS: Our results revealed that histopathological changes in CAG model rates could be restored by low-, medium-, and high-dose QHY. The changes in GAS and PGI/II expression demonstrated that QHY improved CAG. Serum IL-6 and IL-levels were decreased by QHY administration. TLR4 and TRIF were upregulated at the mRNA and protein levels in the model group but downregulated by QHY administration. CONCLUSION: We concluded that QHY could effectively improve the histopathological changes of the gastric mucosa induced by CAG in rats. The therapeutic mechanism of QHY may be related to inhibition of the inflammatory factors IL-6 and IL-8 and suppression of TLR4/TRIF mRNA and protein expression.

[Effect of moxibustion and acupuncture on gastric mucosal cell apoptosis and expression of NF-κB, Bcl-2 in chronic atrophic gastritis rats].

OBJECTIVE: To observe the effect of moxibustion and acupuncture on apoptosis in gastric mucosal cell and expression of NF-κB, Bcl-2 in chronic atrophic gastritis (CAG) rats, so as to explore its mechanisms underlying improvement of CAG. METHODS: Forty-eight male SD rats were randomly divided into normal, model, moxibustion and acupuncture groups, with 12 rats in each group. The CAG model was established by gavage of N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) solution and irregular diet for 12 weeks. Moxibustion or acupuncture was applied to "Zusanli" (ST36) and "Zhongwan" (CV12) for 15 min, once daily for two weeks in the moxibustion or acupuncture group. The histopathological changes of the gastric mucosa were observed by HE staining. The apoptosis index of gastric mucosa was measured by TUNEL method. The gene expression levels of NF-κB and Bcl-2 were detected by real-time PCR. RESULTS: After modeling, the color of gastric mucosa was pale and dark, with low folds and significant bleeding points. The glands in lamina propria were atrophied, arranged disorderly, and the numbers were significantly reduced, with inflammatory cells infiltrated. Those histopathological changes were evidently milder in the moxibustion and acupuncture groups. Compared with the normal group, the apoptosis index, NF-κB and Bcl-2 gene expression of the model group were significantly increased (P<0.01). After the treatment, the apoptosis index, NF-κB and Bcl-2 gene expression were significantly reduced in the moxibustion and acupuncture groups (P<0.05，P<0.01). The NF-κB expression was lower in the acupuncture group than that of moxibustion group (P<0.01). CONCLUSION: Moxibustion and acupuncture therapy can improve the injury of gastric mucosa in CAG rats, which may be associated with its function in down-regulating the expression of NF-κB and Bcl-2 genes in the gastric mucosa.

Effects of moxibustion and acupuncture at Zusanli (ST 36) and Zhongwan (CV 12) on chronic atrophic gastritis in rats.

OBJECTIVE: To evaluate the effects of moxibustion and acupuncture of Zusanli (ST 36) and Zhongwan (CV 12) acupoints on chronic atrophic gastritis (CAG) in rats, and to study the mechanisms behind their actions. METHODS: Forty-four male Sprague-Dawley rats were induced with CAG by intragastric administration of 40% ethanol combined with free drinking of N-methyl-N'nitro-N-nitrosoguanidine and irregular feeding for 12 weeks, followed by daily treatment with moxibustion or acupuncture for 2 weeks. Histopathologic examination, Western blotting of cytokines [epidermal growth factor (EGF), EGF receptor (EGFR), extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK)], and 1H NMR-based metabolic profiling of gastric tissues were used to measure changes related to CAG modeling and treatment. RESULTS: Moxibustion and acupuncture at Zusanli (ST 36) and Zhongwan (CV 12) each relieved CAG-induced abnormalities in histopathology and cytokine expression of ERK and p-ERK. Only moxibustion treatment regulated the expression of EGF and EGFR. Metabolites that were increased in gastric tissue by CAG induction (alanine, nicotinamide adenine dinucleotide phosphate, uracil DNA glycosylase, lactate, glycerol and adenosine) were restored to normal levels after moxibustion treatment; acupuncture treatment only normalized the levels of adenosine monophosphate and glycerol. CONCLUSION: Our findings suggest that moxibustion or acupuncture at Zusanli (ST 36) and Zhongwan (CV 12) can significantly improve the condition of CAG in rats. These treatments exert their effects on CAG through different mechanisms.

Palmatine ameliorates Helicobacter pylori-induced chronic atrophic gastritis by inhibiting MMP-10 through ADAM17/EGFR.

Palmatine (Pal), a plant-based isoquinoline alkaloid, was initially isolated from Coptidis Rhizoma (CR, Huanglian in Chinese) and considered to be a potential non-antibiotic therapeutic agent that can safely and effectively improve Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). However, underlying mechanisms are unclear. In this study, we explored the protective effect of Pal on H. pylori induced CAG in vivo and in vitro. As a result, Pal alleviated the histological damage of gastric mucosa and the morphological changes of gastric epithelial cell (GES-1) caused by H. pylori. Furthermore, Pal significantly inhibited the expression of EGFR-activated ligand genes, including a disintegrin and metalloproteinase 17 (ADAM17) and heparin-binding epidermal growth factor-like growth factor (HB-EGF), and the proinflammatory factors, such as chemokine 16 (CXCL-16) and interleukin 8 (IL-8), were suppressed. In addition, Pal attenuated inflammatory infiltration of CD8+ T cells while promoted Reg3a expression to enhance host defense. Taken together, we concluded that Pal attenuated the MMP-10 dependent inflammatory response in the gastric mucosa by blocking ADAM17/EGFR signaling, which contributed to its gastrointestinal protective effect.

Mechanism of berberine in treating Helicobacter pylori induced chronic atrophic gastritis through IRF8-IFN-γ signaling axis suppressing.

AIMS: In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated. MATERIALS AND METHODS: H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured. KEY FINDINGS: Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.

Dietary Intervention of Artemisia and Green Tea Extracts to Rejuvenate Helicobacter pylori-Associated Chronic Atrophic Gastritis and to Prevent Tumorigenesis.

OBJECT: As nonmicrobial dietary approach is capable of controlling Helicobacter pylori infection, we evaluated the efficacy of long-term dietary administration of Artemisia and/or green tea extracts on H. pylori-initiated, high-salt-promoted chronic atrophic gastritis and gastric tumorigenesis mouse model. METHODS: Helicobacter pylori-infected and high-salt-diet-administered C57BL/6 mice were administered with Artemisia extracts (MP group) and/or green tea extracts (GT group) for 36 weeks in addition to the control group (ES group, gastroprotective drug, ecabet sodium 30 mg/kg, diet pellet). Gross and pathological gastric lesions were evaluated after 24 and 36 weeks, respectively, and their underlying molecular changes were measured in gastric homogenates. Detailed mechanisms were further evaluated in in vitro cell models. RESULTS: The erythematous and nodular changes and mucosal ulcerative and erosive lesions were noted in the control group at 24 weeks. MP, GT, MPGT, and ES groups all showed significantly ameliorated pathologic lesion compared to the control group (p < .05). After the 36 weeks, scattered nodular masses with some central ulcers and thin gastric surface were noted in the control stomach, whereas no tumorous lesion and milder atrophic changes were observed in all MP, GT, and MPGT groups except ES group (p < .05). On molecular analysis, increased expressions of COX-2, TNF-α, IL-6, lipid peroxide, and activated STAT3 relevant to H. pylori infection were significantly decreased with MPGT administration (p < .01), whereas HSP70 was significantly increased. PGDH expressions, core tumor suppressor involved in carcinogenesis, were significantly decreased with H. pylori infection (p < .05), but significantly increased in MPGT group (p < .05). Increased mucosal apoptotic index noted in the control group was significantly decreased with MP and/or GT along with significantly preserved gastric gastroprotective mediators (p < .01) such as mucins, HSP27, and HSP70. H. pylori-induced serum TNF-α and NF-κB activations were significantly decreased with MPGT administration (p < .05). CONCLUSION: Long-term dietary intake of MP and/or GT can be an effective strategy either to rejuvenate H. pylori atrophic gastritis or to suppress tumorigenesis.

[Correlation Study on Chinese Medical Syndrome Types of Chronic Atrophic Gastritis Patients, Hp, and IL-1ß Polymorphism].

OBJECTIVE: To explore the correlation between Chinese medical (CM) syndrome types of chronic atrophic gastritis (CAG) patients and Helicobacter pylori (Hp) infection, polymorphisms of IL-1B, and IL-1ß. METHODS: Totally 192 CAG patients and 202 healthy subjects (as the healthy control group) were recruited in this case-control study. The Hp infection was tested by 13C-urea breath test and colloidal gold-labeled assay (GICA). The concentration of peripheral blood IL-1ß was measured by ELISA. The polymorphisms of IL-1B gene in the promoter region were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: Pi-Wei weakness syndrome (PWWS) was dominant in CAG patients (31.77%, 61/192 cases). The Hp infection ratio in CAG patients was 53.65% (103/192 cases), of which, Pi-Wei damp-heat syndrome(PWDHS, 64.86%, 24/37 cases) and Gan-Wei disharmony syndrome (GWDS, 66.67%, 24/36 cases) were dominant. Compared with the health control group, the plasma concentration of IL-1ß was obviously elevated in CAG patients with PWDHS, GWDS, and static blood obstructing collaterals syndrome (SBOCS) (all P < 0.05). Additionally, there was no difference in the distribution of polymorphisms in the promoter region of IL-1 B gene between the CAG patients and the healthy control group (P > 0.05). CONCLUSIONS: The incidence risk of CAG was not associated with IL-1B polymorphism. But CM syndrome types of CAG patients was associated with Hp infection and peripheral blood IL-1ß levels.

[Effects of moxibustion on cell proliferative factors in gastric mucosa in rats with precancerous lesions of chronic atrophic gastritis].

OBJECTIVE: To explore the molecular mechanism of moxibustion at stomach meridian acupoints for precancerous lesions of chronic atrophic gastritis (CAG). METHODS: Fifty male SD rats were randomly divided into a normal group, a model group, a stomach meridian group, a control point group and a vitacoenzyme group, 10 rats in each group. The CAG precancerous lesion model was made in all the groups except the normal group. The rats in the normal group and model group were bundled for 30 min per day; the rats in the stomach meridian group and control point group were bundled and treated with moxibustion at stomach meridian acupoints or control points for 30 min per day; the rats in the vitacoenzyme group were treated with intragastric administration of vitacoenzyme, once per day. All the treatment was given for 20 weeks. The pathological morphological change of gastric mucosa was observed under optical microscope; the expression of epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha), vascular endothelial growth factor (VEGF), gastric mucosal proliferatig cell nuclear antigen (PCNA), argyrophilic protein of nucleolar organizer regions (Ag-NORs) in gastric mucosal cells were detected by enzyme linked immuno sorbent assay (ELISA). RESULTS: Compared with the normal group, in the model group the gastric mucosal cells showed dysplasia and the expression of EGF, TGF-alpha, PCNA, VEGF, Ag-NORs in gastric mucosa cells in the model group was increased significantly (all P < 0.05). Compared with the model group, the gastric mucosa lesion gradually recovered and the expression of EGF, TGF-alpha, PCNA, VEGF, Ag-NORs in gastric mucosal cells was gradually decreased in the stomach meridian group, control point group and vitacoenzyme group, in which the stomach meridian group had the most significant effects (all P < 0.05). CONCLUSION: Moxibustion at stomach meridian acupoints can obviously decrease the expression of cell proliferative factors in gastric mucosa in rats with CAG precancerous lesions, inhibit the gastric mucosal cell dysplasia, and promote the recovery of gastric mucosa.

Imbalanced network biomarkers for traditional Chinese medicine Syndrome in gastritis patients.

Cold Syndrome and Hot Syndrome are thousand-year-old key therapeutic concepts in traditional Chinese medicine (TCM), which depict the loss of body homeostasis. However, the scientific basis of TCM Syndrome remains unclear due to limitations of current reductionist approaches. Here, we established a network balance model to evaluate the imbalanced network underlying TCM Syndrome and find potential biomarkers. By implementing this approach and investigating a group of chronic superficial gastritis (CSG) and chronic atrophic gastritis (CAG) patients, we found that with leptin as a biomarker, Cold Syndrome patients experience low levels of energy metabolism, while the CCL2/MCP1 biomarker indicated that immune regulation is intensified in Hot Syndrome patients. Such a metabolism-immune imbalanced network is consistent during the course from CSG to CAG. This work provides a new way to understand TCM Syndrome scientifically, which in turn benefits the personalized medicine in terms of the ancient medicine and complex biological systems.

KRAS mutations predict progression of preneoplastic gastric lesions.

Eight hundred sixty-three subjects with atrophic gastritis were recruited to participate in an ongoing chemoprevention trial in Nariño, Colombia. The participants were randomly assigned to intervention therapies, which included treatment to eradicate Helicobacter pylori infection followed by daily dietary supplementation with antioxidant micronutrients in a 2 x 2 x 2 factorial design. A series of biopsies of gastric mucosa were obtained according to a specified protocol from designated locations in the stomach for each participant at baseline (before intervention therapy) and at year three. A systematic sample of 160 participants was selected from each of the eight treatment combinations. DNA was isolated from each of these biopsies (n = 320), and the first exon of KRAS was amplified using PCR. Mutations in the KRAS gene were detected using denaturing gradient gel electrophoresis and confirmed by sequence analysis. Of all baseline biopsies, 14.4% (23 of 160) contained KRAS mutations. Among those participants with atrophic gastritis without metaplasia, 19.4% (6 of 25) contained KRAS mutations, indicating that mutation of this important gene is likely an early event in the etiology of gastric carcinoma. An important association was found between the presence of KRAS mutations in baseline biopsies and the progression of preneoplastic lesions. Only 14.6% (20 of 137) of participants without baseline KRAS mutations progressed from atrophic gastritis to intestinal metaplasia or from small intestinal metaplasia to colonic metaplasia; however, 39.1% (9 of 23) with baseline KRAS mutations progressed to a more advanced lesion after 3 years [univariate odds ratio (OR), 3.76 (P = 0.05); multivariate OR adjusted for treatment, 3.74 (P = 0.04)]. In addition, the specificity of the KRAS mutation predicted progression. For those participants with G-->T transversions at position 1 of codon 12 (GGT-->TGT), 19.4% (5 of 17) progressed (univariate OR, 2.4); however, 60.0% (3 of 5) of participants with G-->A transitions at position 1 of codon 12 (GGT-->AGT) progressed (univariate OR, 8.7; P = 0.004 using chi2 test).