Fourty-three cases of globoid dysplasia and signet ring cell carcinoma were stained by mucin and CEA (ABC method). It was found that there were three kinds of mucins (neutral, sialo and sulphomucin in both globoid dys...Fourty-three cases of globoid dysplasia and signet ring cell carcinoma were stained by mucin and CEA (ABC method). It was found that there were three kinds of mucins (neutral, sialo and sulphomucin in both globoid dysplastic cells and signet ring cells. The percentages of the three kinds of mucins seen in the two kinds of cells were not much different. It was indicated that the altered mucins in the gastric epithelial cells must be a sign of dedifferentiation of the cells and the results of malfunction. The globoid dysplasia type I mainly contained neutral mucin, whereas type II, the acid mucin was predominant, especially the sulphomucin. The CEA positive reaction became stronger as the atypia being remarkable, and the characteristics of distribution of CEA positive particles were similar in the two kinds of cells namely, randomly or disorderly in the cells. Based on the analysis of the results, a conclusion can be made that the variety of mucins in globoid dysplastic cells can be used as a reference point in classification and is not much significant in grading, but the amount of CEA positive matter can be a reference point in grading. The globoid dysplasia is such a lesion with special features in morphology and function manifested in the process of de-differentiation towards signet ring cell carcinoma following the successive action of carcinogens upon the cells of gastric epithelium.展开更多
The fact that the acidsecreting parietal cells undergo continuous renewal has been ignored by many gastroenterologists and cell biologists. In the past, it was thought that these cells were static. However, by using 3...The fact that the acidsecreting parietal cells undergo continuous renewal has been ignored by many gastroenterologists and cell biologists. In the past, it was thought that these cells were static. However, by using 3Hthymidine radioautography in combination with electron microscopy, it was possible to demonstrate that parietal cells belong to a continuously renewing epithelial cell lineage. In the gastric glands, stem cells anchored in the isthmus region are responsible for the production of parietal cells. The stem cells give rise to three main progenitors: prepit, preneck and preparietal cells. Parietal cells develop either directly from the noncycling preparietal cells or less commonly via differentiation of the cycling prepit and preneck cell progenitors. The formation of a parietal cell is a sequential process which involves diminishment of glycocalyx, production of cytoplasmic tubulovesicles, an increase in number and length of microvilli, an increase in number and size of mitochondria, and fi nally, expansion and invagination of the apical membrane with the formation of an intracellular canalicular system. Little is known about the genetic counterparts of these morphological events. However, the time dimension of parietal cell production and the consequences of its alteration on the biological features of the gastric gland are well documented. The production of a new parietal cell takes about 2 d. However, mature parietal cells have a long lifespan during which they migrate bidirectionally while their functional activity for acid secretion gradually diminishes. Following an average lifespan of about 54 d, in mice, old parietal cells undergo degeneration and elimination. Various approaches for genetic alteration of the development of parietal cells have provided evidence in support of their role as governors of the stem/progenitor cell proliferation and differentiation programs. Revealing the dynamic features and the various roles of parietal cells would help in a better understanding of the biological features of the gastric glands and would hopefully help in providing a basis for the development of new strategies for prevention, early detection and/or therapy of various gastric disorders in which parietal cells are involved, such as atrophic gastritis, peptic ulcer disease and gastric cancer.展开更多
AIM To identify the type localization andmorphology of APUD endocrine cells in thegastroenteropancreatic(GEP)system ofstomach-containing teleosts,and study APUDendocrine system in the stomach,intestine andpancreas of ...AIM To identify the type localization andmorphology of APUD endocrine cells in thegastroenteropancreatic(GEP)system ofstomach-containing teleosts,and study APUDendocrine system in the stomach,intestine andpancreas of fish species.METHODS Two kinds of immunocytochemical(ICC)techniques of the streptavidin biotin-peroxidase complex(SABC)and streptavidin-peroxidase(S-P)method were used.Theidentification,localization and morphology ofAPUD endocrine cells scattered in the mucosa ofdigestive tract,intermuscular nerve plexus andglandular body of northern snakehead(Channaargus),ricefield eel(Monopterus albus),yellow catfish(Pelteobagrus fulvidraco),mandarinfish(Siniperca chuatsi),largemouthbass(Micropterus salmoides),orientalsheatfish(Silurus asotus),freshwater pomfret(Colossoma brachypomum)and nile tilapia(Tilapia nilotica)were investigated with 8 kindsof antisera.RESULTS The positive reaction of 5-hydroxytryptamine(5-HT)immunoreactiveendocrine(IRE)cells was found in the digestive tract and glandular body of 8 fish species indifferent degree.Only a few gastrin(GAS)-IREcells were seen in C.argus,M.albus and P.fulvidraco.Glucagon(GLU)-IRE cells were notfound in the digestive tract and glandular bodybut existed in pancreatic island of most fishspecies.The positive reaction of growthhormone(GH)-IRE cells was found only inpancreatic island of S.Chuatsi and S.Asotus,no positive reaction in the other 6 fish species.Somatostatin(SOM)-,calcitonin(CAL)-,neurofilament(NF)-and insulin(INS)-IRE cellsin the stomach,intestine and pancreas of 8 kindsof fish were different in distribution and types.The distribution of all 8 APUD cells was the mostin gastrointestinal epithelium mucosa and then indigestive glands.The positive reaction of SOM-and 5-HT-IRE cells was found in intermuscularnerve plexus of intestine of P.fulvidraco andS.chuatsi.Only GH-IRE cells were denselyscattered in the pancreatic islands of S.chuatsiand S.asotus,and odd distribution in thepancreas of S.asotus,SOM-IRE cells weredistributed in the pancreatic islands of S.asotus,C.Brachypomum and T.nilotica.There were INS-IRE cells in the pancreaticislands of S.chuatsi and S.asolus.Eightkinds of APUD cells had longer cell body andcytoplasmic process when they were located inthe gastrointestinal epithelium,and had shortercell body and cytoplasmic process in the gastricgland,and irregular shape in the esophagus andpancreatic island.CONCLUSION Eight kinds of IRE cells were identified in the GEP system of stomach-containing teleosts. These endocrine cells were scattered in gastrointestinal mucosa, intermuscular nerve plexus, gland body, pancreatic gland and islands under APUD system. CAL- and GH-IRE cells in the pancreatic islands of fishes showed functional diversity for these two hormones. Their morphological feature provides evidence of endocrine-paracrine and endocrine-exocrine acting mode. This research can morphologically prove that the GEP endocrine system of fish ( the lowest vertebrate) is almost the same as of mammal and human.展开更多
AIM:To determine the cytological and molecular effects of peroxisome proliferation-activated receptor(PPAR)-γ and PPAR-γ agonists on stomach cancer cells.METHODS:To determine the proliferation-suppressive effects of...AIM:To determine the cytological and molecular effects of peroxisome proliferation-activated receptor(PPAR)-γ and PPAR-γ agonists on stomach cancer cells.METHODS:To determine the proliferation-suppressive effects of troglitazone and ciglitazone,SNU-216 and SNU-668 stomach cancer cells were plated in media containing 40 μmol/L troglitazone and ciglitazone at a density of 1 × 104 cells/well.After 3,5 and 7 d,the cells were counted with a hemocytometer.To assess the appearance of PPAR-γ,a reverse-transcription polymerase chain reaction analysis was performed.On day 7,Western blotting was used to determine the effects of troglitazone and ciglitazone on the expression of p21 and phosphorylated-ERK(pERK) genes.Flow cytometry analysis was used to determine which portion of the cell cycle was delayed when troglitazone was used to suppress cell proliferation.In order to clarify the mechanism underlying the activity of troglitazone,microarray analysis was conducted.RESULTS:PPAR-γ was manifested in both SNU-216 and SNU-668 cells.Ciglitazone and troglitazone suppressed cell growth,and troglitazone was a stronger suppressor of stomach cancer cells than ciglitazone,an inducer of cell cycle arrest in the G1 phase.SNU-668 cells were also determined to be more sensitive to ciglitazone and troglitazone than SNU-216 cells.When troglitazone and ciglitazone were administered to stomach cancer cells,levels of p21 expression were increased,but ERK phosphorylation levels were reduced.When GW9662,an antagonist of PPAR-γ,was applied in conjunction with ciglitazone and troglitazone,the cell growth suppression effect was unaffected.The gene transcription program revealed a variety of alterations as the consequence of troglitazone treatment,and multiple troglitazone-associated pathways were detected.The genes whose expression was increased by troglitazone treatment were associated with cell development,differentiation,signal transmission between cells,and cell adhesion,and were also associated with reductions in cell proliferation,the cell cycle,nuclear metabolism,and phosphorylation.CONCLUSION:Troglitazone and ciglitazone suppress the proliferation of stomach cancer cells via a PPAR-γ-independent pathway.展开更多
AIM: To investigate the effect of serum derived from rats treated with electroacupuncture at stomach meridian acupoints on the expression of epidermal growth factor receptor (EGFR) gene in gastric mucosal cells. METHO...AIM: To investigate the effect of serum derived from rats treated with electroacupuncture at stomach meridian acupoints on the expression of epidermal growth factor receptor (EGFR) gene in gastric mucosal cells. METHODS: The stress-induced gastric mucosal injury in rat model was established by water-immersion and restrained stress methods. 52 rats were randomly divided into: normal group (n = 8), model group (n = 8), model serum group (n = 12), stomach serum group (n = 12), and gallbladder serum group (n = 12). The gastric mucosal cells were separated by pronase-EDTA digestion method and incubated with serum. The EGFR gene expression in gastric mucosal cells was detected by reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: Compared with normal group (0.6860 ± 0.0594), the serum derived from rats of the stomach group (1.2272 ± 0.0813, P = 0.00 < 0.01) and gallbladder group (0.9640 ± 0.0387, P = 0.00 < 0.01) had a tendency to enhance the EGFR gene expression in gastric mucosal cells. Such tendency existed in the model group (0.7104 ± 0.0457) but with no signifi cant difference (P = 0.495 > 0.05) and in model serum group (0.8516 ± 0.0409) with an extremely obvious difference (P = 0.001 < 0.01). Furthermore, the EGFR gene expression in stomach serum group was significantly higher than that in gallbladder serum group (P = 0.00 < 0.01). CONCLUSION: The present study shows that serumderived from rats treated with electroacupuncture at stomach meridian acupoints can distinctly increase the EGFR gene expression of gastric mucosal cells. Therefore, there is certain meridian specificity in the serum, which could provide a proof for the TCM theory “particular relation between meridian and internal organ”.展开更多
The research of degree of incidence of genomic changes (of micronuclei) in mucous cells of gastric superficial-foveolar epithelium in contaminated and not contaminated mucous of stomach was made. Histopathological res...The research of degree of incidence of genomic changes (of micronuclei) in mucous cells of gastric superficial-foveolar epithelium in contaminated and not contaminated mucous of stomach was made. Histopathological research of micronuclei and helicobacter was made in gastric biopsy specimen of patients with diagnosis-chronical gastritis (ICD-10K29.3) in group of patients who lived in radiation contaminated areas and in groups of people, who had no factors of radiation influence in anamnesis. People, who lived in the radiation contaminated areas, whose mucous was infected by Helicobacter pylori, had the highest frequency of mucous cells with micronuclei. In the group of patients from radiation contaminated areas with HP-associated gastritis frequency of appearance of mucous cells with micronucleus in the mucous of stomach have five time more, than patients, whose mucous of stomach was not infected (p Helicobacter pylori can success in mutagenic effect of radiation factor.展开更多
Gastric parietal cells are important in acid secretion, but it is unclear which cells throughout the gastric gland have the highest secretion potency. Here, we used immunohistochemical methods with anti-H+, K+-ATPase,...Gastric parietal cells are important in acid secretion, but it is unclear which cells throughout the gastric gland have the highest secretion potency. Here, we used immunohistochemical methods with anti-H+, K+-ATPase, phosphoryl ezrin and CD44 antibodies to study the distribution of gastric acid secretion activity. Stomach tissues from freely fed and starved rats were cryofixed for light microscopy or fixed by high-pressure freezing for electron microscopy. Parietal cells from freely fed animals corresponded to the active secretion phase and to the inactive resting phase from starved rats. Anti-H+, K+-ATPase and anti-phosphoryl ezrin labeling were observed on the membrane of the intracellular canaliculi and the tubulovesicle from freely fed rats, while cells from starved animals showed weak labeling with anti-phosphoryl ezrin antibody staining. Morphometrical analysis at the electron microscopic level was performed on active and inactive acid secretory phases between the upper and base regions of the gland. H+, K+-ATPase and CD44 were distributed on both sites of the microvillous and tubulovesicle membrane in the same cells, but phosphoryl ezrin localized predominantly on the microvillous membrane in active cells of the glandular neck and upper base. Therefore, the highest secreting potency appeared to be in cells of the glandular neck and upper base.展开更多
Objective: To find out the relationship of the expressions of proliferating cell nuclear antigen (proliferating cell nuclear antigen, PCNA), alkaline phosphotase (alkaline phosphotase, AKP) and acid phosphotase ...Objective: To find out the relationship of the expressions of proliferating cell nuclear antigen (proliferating cell nuclear antigen, PCNA), alkaline phosphotase (alkaline phosphotase, AKP) and acid phosphotase (acid phosphotase, ACP) with the development of mouse fore stomach cancerization. Methods: The animal models, including the various stages during the development of NIH mouse fore stomach carcinoma, were made by N-Nitrososarcosineethylester (N-Nitrososarcosineethylester, NSEE). The mice were sacrificed on the 14th, 28th, 42nd, 56th, 70th and 84th days respectively after mice were irrigated with NSEE. The fore stomach was taken out and dissected. The methods of histopathology, immunohistochemistry and isoenzyme electrophoresis were adopted to study the dynamic changes of cell shape and expression of PCNA, AKP and ACP. Results: On the 42nd and 56th days after NSEE treatment, the expression of PCNA increased gradually along with the cancerization. Comparing with the control, there were significant differences (P〈0.05). On the 70th and 84th days, the expression of PCNA increased further (compared with the control P〈0.01). The activity of AKP increased gradually along with the cancerization. On the 14th, 28th, 42nd and 56th days, there were significant differences (P〈0.05); on the 70th and 84th days, the activity of AKP increased further (P〈0.01). The activity of ACP also increased on the 14th, 28th, 42nd and 56th days, and there were significant differences on the 70th days (P〈0.05) and on the 84th days (P〈0.01) compared with the control. Conclusion: During the carcinogenesis of NIH mouse fore stomach, the expressions of PCNA, AKP and ACP increased gradually and were consisted with the changes of cell shapes.展开更多
Perivascular epithelioid cell tumor(PEComa) is a rare mesenchymal neoplasia and currently well recognized as a distinct entity with characteristic morphological,immunohistochemical and molecular findings.We report a c...Perivascular epithelioid cell tumor(PEComa) is a rare mesenchymal neoplasia and currently well recognized as a distinct entity with characteristic morphological,immunohistochemical and molecular findings.We report a case of PEComa arising in the antrum of a 71-year-old female with melena.The tumor,located predominantly in the submucosa as a well delimited nodule,measured 3.0 cm in diameter and was completely resected,with no evidence of the disease elsewhere.Histologically,it was composed predominantly of eosinophilic epithelioid cells arranged in small nests commonly related to variably sized vessels,with abundant extracellular material,moderate nuclear variation and discrete mitotic activity.No necrosis,angiolymphatic invasion or perineural infil-tration was seen.Tumor cells were uniformly positive for vimentin,smooth muscle actin,desmin and melan A.Although unusual,PEComa should be considered in the differential diagnosis of gastric neoplasia with characteristic epithelioid and oncocytic features and prominent vasculature.展开更多
AIM: To measure biochemical parameters in stomach biopsies and test their suitability as diagnostic biomarkers for gastritis and precancerous lesions.METHODS: Biopsies were obtained from the stomachs of two groups of ...AIM: To measure biochemical parameters in stomach biopsies and test their suitability as diagnostic biomarkers for gastritis and precancerous lesions.METHODS: Biopsies were obtained from the stomachs of two groups of patients(n = 40) undergoing fiberoptic endoscopy due to upper gastrointestinal symptoms. In the first group(n = 17), only the corpus region was examined. Biopsies were processed for microscopic examination and measurement of mitochondrial O2 consumption(cellular respiration), cellular adenosine triphosphate(ATP), glutathione(GSH), and caspase activity. In the second group of patients(n = 23), both corpus and antral regions were studied. Some biopsies were processed for microscopic examination, while the others were used for measurements of cellular respiration and GSH level.RESULTS: Microscopic examinations of gastric corpus biopsies from 17 patients revealed normal mucosae in 8 patients, superficial gastritis in 7 patients, and chronic atrophic gastritis in 1 patient. In patients with normal histology, the rate(mean ± SD) of cellular respiration was 0.17 ± 0.02 μmol/L O2 min-1 mg-1, ATP content was 487 ± 493 pmol/mg, and GSH was 469 ± 98 pmol/mg. Caspase activity was detected in 3 out of 8 specimens. The values of ATP and caspase activity were highly variable. The presence of superficial gastritis had insignificant effects on the measured biomarkers. In the patient with atrophic gastritis, cellular respiration was high andATP was relatively low, suggesting uncoupling oxidative phosphorylation. In the second cohort of patients, the examined biopsies showed either normal or superficial gastritis. The rate of cellular respiration(O2. μmol/L min-1 mg-1) was slightly higher in the corpus than the antrum(0.18 ± 0.05 vs 0.15 ± 0.04, P = 0.019). The value of GSH was about the same in both tissues(310 ± 135 vs 322 ± 155, P = 0.692).CONCLUSION: The corpus mucosa was metabolically more active than the antrum tissue. The data in this study will help in understanding the pathophysiology of gastric mucosa.展开更多
AIM: Mechanisms underlying the chemopreventive effects of cyclooxygenase (COX) inhibitors remain elusive. We have previously shown that celecoxib but not indomethacin could prevent carcinogen-induced gastric cancer de...AIM: Mechanisms underlying the chemopreventive effects of cyclooxygenase (COX) inhibitors remain elusive. We have previously shown that celecoxib but not indomethacin could prevent carcinogen-induced gastric cancer development in Wistar rats. This chemopreventive effect appeared to be independent of COX-2 and prostaglandin (PG) E2 suppression since the lowest PGE2 was obtained in indomethacin group.This study compared the cell kinetic changes in stomachs of rats after treatment with celecoxib (5, 10, 20 mg/(kg·d)) or indomethacin (3 mg/(kg·d)) to gain more insights into the chemopreventive mechanism.METHODS: The apoptosis and proliferation indexes in gastric tumor, adjacent non-cancer tissues and normal gastric tissues were determined. Apoptosis was quantified by apoptotic nuclei counting and TUNEL, whereas proliferation was determined by Ki67 immunostaining.RESULTS: Treatment with either celecoxib or indomethacin inhibited gastric tumor proliferation by more than 65% (P<0.02). However, celecoxib caused a dose-dependent increase in apoptosis (P<0.05) which was not seen in indomethacin-treated tumors (P = 0.54). The highest apoptosis to proliferation ratio was seen in tumors treated with celecoxib at 10 mg/(kg·d). Treatment with this dose of celecoxib was associated with the lowest incidence of gastric cancer development.CONCLUSION: Our findings suggest that the difference in chemopreventive effects of indomethacin and celecoxib in this animal model of gastric carcinogenesis is largely due to the differential cell kinetic changes, which does not correlate with the degree of COX-2 and PG suppression.展开更多
Inflammatory myofibroblastic tumor (IMT) of the stomach in adults is extremely rare, with unpredictable prognosis. We present a 55-year-old woman with a gastric IMT. She experienced sudden abdominal pain 4 d previousl...Inflammatory myofibroblastic tumor (IMT) of the stomach in adults is extremely rare, with unpredictable prognosis. We present a 55-year-old woman with a gastric IMT. She experienced sudden abdominal pain 4 d previously. Physical examination showed mild abdominal tenderness in the hypogastrium, but no palpable abnormal abdominal mass. Abdominal CT showed a mass of approximately 8 cm in the gastrocolic ligament. On laparoscopic exploration, unexpected hemoperitoneum of approximately 1.5 L of blood was found, and an exophytic gastric mass of approximately 10 cm, appeared from the anterior wall of the gastric body along the greater curvature. Laparoscopy further showed that non-clotting blood in the abdominal cavity seemed to be from the gastric tumor. After conversion to open surgery for more precise evaluation of the cause of hemoperitoneum and the large friable tumor, gastric wedge resection, including the tumor, was conducted. The final diagnosis was consistent with IMT that originated from the gastric wall.展开更多
The combination of classical Hodgkin’s lymphoma(cHL)and non-Hodgkin lymphoma coexisting in the same patient is not common,especially in one extranodal location.Here we present a rare case of composite diffuse large B...The combination of classical Hodgkin’s lymphoma(cHL)and non-Hodgkin lymphoma coexisting in the same patient is not common,especially in one extranodal location.Here we present a rare case of composite diffuse large B-cell lymphoma(DLBCL)and cHL occurring simultaneously in the stomach of a 53-year-old female who presented with upper abdominal discomfort and gas pain.Surgery was performed and the disease was diagnosed pathologically as composite lymphoma of DLBCL and cHL using hematoxylin-eosin and immunohistochemical staining.Epstein-Barr virus(EBV)infection was not detected by in situ hybridization for EBV-encoded RNA or immunohistochemistry for EBV latent membrane protein-1.Polymerase chain reaction analysis from the two distinct components of the tumor demonstrated clonal immunoglobulinκlight chain gene rearrangements.The patient died approximately 11 mo after diagnosis in spite of receiving eight courses of the CHOP and two courses of the rituximab-CHOP(RCHOP) chemotherapy regimen.This case report showed that the two distinct components,DLBCL and cHL,appeared to originate from the same clonal progenitor cell,and that EBV infection was not essential for transformation during the course of tumorigenesis.展开更多
BACKGROUND Squamous cell carcinoma(SCC)in pancreas and stomach is a rare histologic subtype with aggressive behavior,poor prognosis,and no standardized therapy.Pancreatic SCC or gastric SCC has been previously reporte...BACKGROUND Squamous cell carcinoma(SCC)in pancreas and stomach is a rare histologic subtype with aggressive behavior,poor prognosis,and no standardized therapy.Pancreatic SCC or gastric SCC has been previously reported.However,case of SCC occurring in both the pancreas and the stomach has not been reported yet.CASE SUMMARY A 75-year-old female with prior history of hypertension and diabetes mellitus visited our hospital with complaint of abdominal pain that started three months ago.Computed tomography(CT)scan of the abdomen showed 3.3 cm mass at the distal pancreas.She received surgical resection which was histologically found to be SCC of the pancreas with clear resection margins.After she was discharged,she no longer visited the hospital.Three years later,she was referred to our hospital after showing abnormal findings on a gastroscopy performed at another hospital.Gastroscopy revealed a single,2cm sized,ill-defined irregular flat and hyperemic mass at high body.Histologic finding of the mass was SCC.CT scan and positive emission tomography CT showed metastatic lesions to the liver and the peritoneum.She received combination chemotherapy with capecitabine and oxaliplatin.However,she passed away 6 mo after diagnosis of gastric SCC.CONCLUSION To the best of our knowledge,this is the first case of metachronous SCC of stomach occurring after diagnosis of pancreatic SCC.展开更多
Primary stomach lymphoblastic B-cell lymphoma (B-LBL) is a rare tumor. We describe a primary stomach B-LBL in a 38 years old female who presented with nonspecific complaints of fatigue and vomiting for 2 mo. Gastrofib...Primary stomach lymphoblastic B-cell lymphoma (B-LBL) is a rare tumor. We describe a primary stomach B-LBL in a 38 years old female who presented with nonspecific complaints of fatigue and vomiting for 2 mo. Gastrofiberscopy revealed a large gastric ulcer, which was successfully resected. Pathology showed a lymphoblastic cell lymphoma arising from the stomach, and there was no evidence of disease at any extrastomach site. Immunohistochemical staining and gene rearrangement studies supported that the stomach tumor was a clonal B-cell lymphoma. Therefore, the diagnosis of B-LBL was made based on the stomach specimen.展开更多
Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered ...Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.展开更多
Parietal cells are one of the largest epithelium cells of the mucous membrane of the stomach that secrete hydrochloric acid. To study the function of gastric parietal cells during gastric epithelium homeostasis, we ge...Parietal cells are one of the largest epithelium cells of the mucous membrane of the stomach that secrete hydrochloric acid. To study the function of gastric parietal cells during gastric epithelium homeostasis, we generated a transgenic mouse line, namely, Atp4b-Cre, in which the expression of Cre recombinase was controlled by a 1.0 kb promoter of mouse β-subunit of H^+-, K^+-ATPase gene (Atp4b). In order to test the tissue distribution and excision activity of Cre recombinase in vivo, the Atp4b-Cre transgenic mice were bred with the reporter strain ROSA26 and a mouse strain that carries Smad4 conditional alleles (Smad4Ca/Co). Multiple-tissue PCR of Atp4b-Cre;Smad4Co/+ mice revealed that the recombination only happened in the stomach. As indicated by LacZ staining, ROSA26;Atp4b-Cre double transgenic mice showed efficient expression of Cre recombinase within the gastric parietal cells. These results showed that this Atp4b-Cre mouse line could be used as a powerful tool to achieve conditional gene knockout in gastric parietal cells.展开更多
文摘Fourty-three cases of globoid dysplasia and signet ring cell carcinoma were stained by mucin and CEA (ABC method). It was found that there were three kinds of mucins (neutral, sialo and sulphomucin in both globoid dysplastic cells and signet ring cells. The percentages of the three kinds of mucins seen in the two kinds of cells were not much different. It was indicated that the altered mucins in the gastric epithelial cells must be a sign of dedifferentiation of the cells and the results of malfunction. The globoid dysplasia type I mainly contained neutral mucin, whereas type II, the acid mucin was predominant, especially the sulphomucin. The CEA positive reaction became stronger as the atypia being remarkable, and the characteristics of distribution of CEA positive particles were similar in the two kinds of cells namely, randomly or disorderly in the cells. Based on the analysis of the results, a conclusion can be made that the variety of mucins in globoid dysplastic cells can be used as a reference point in classification and is not much significant in grading, but the amount of CEA positive matter can be a reference point in grading. The globoid dysplasia is such a lesion with special features in morphology and function manifested in the process of de-differentiation towards signet ring cell carcinoma following the successive action of carcinogens upon the cells of gastric epithelium.
基金Supported by Terry Fox Fund for Cancer Research and UAE University
文摘The fact that the acidsecreting parietal cells undergo continuous renewal has been ignored by many gastroenterologists and cell biologists. In the past, it was thought that these cells were static. However, by using 3Hthymidine radioautography in combination with electron microscopy, it was possible to demonstrate that parietal cells belong to a continuously renewing epithelial cell lineage. In the gastric glands, stem cells anchored in the isthmus region are responsible for the production of parietal cells. The stem cells give rise to three main progenitors: prepit, preneck and preparietal cells. Parietal cells develop either directly from the noncycling preparietal cells or less commonly via differentiation of the cycling prepit and preneck cell progenitors. The formation of a parietal cell is a sequential process which involves diminishment of glycocalyx, production of cytoplasmic tubulovesicles, an increase in number and length of microvilli, an increase in number and size of mitochondria, and fi nally, expansion and invagination of the apical membrane with the formation of an intracellular canalicular system. Little is known about the genetic counterparts of these morphological events. However, the time dimension of parietal cell production and the consequences of its alteration on the biological features of the gastric gland are well documented. The production of a new parietal cell takes about 2 d. However, mature parietal cells have a long lifespan during which they migrate bidirectionally while their functional activity for acid secretion gradually diminishes. Following an average lifespan of about 54 d, in mice, old parietal cells undergo degeneration and elimination. Various approaches for genetic alteration of the development of parietal cells have provided evidence in support of their role as governors of the stem/progenitor cell proliferation and differentiation programs. Revealing the dynamic features and the various roles of parietal cells would help in a better understanding of the biological features of the gastric glands and would hopefully help in providing a basis for the development of new strategies for prevention, early detection and/or therapy of various gastric disorders in which parietal cells are involved, such as atrophic gastritis, peptic ulcer disease and gastric cancer.
基金the National Natural Science Foundation of China,No.39470554
文摘AIM To identify the type localization andmorphology of APUD endocrine cells in thegastroenteropancreatic(GEP)system ofstomach-containing teleosts,and study APUDendocrine system in the stomach,intestine andpancreas of fish species.METHODS Two kinds of immunocytochemical(ICC)techniques of the streptavidin biotin-peroxidase complex(SABC)and streptavidin-peroxidase(S-P)method were used.Theidentification,localization and morphology ofAPUD endocrine cells scattered in the mucosa ofdigestive tract,intermuscular nerve plexus andglandular body of northern snakehead(Channaargus),ricefield eel(Monopterus albus),yellow catfish(Pelteobagrus fulvidraco),mandarinfish(Siniperca chuatsi),largemouthbass(Micropterus salmoides),orientalsheatfish(Silurus asotus),freshwater pomfret(Colossoma brachypomum)and nile tilapia(Tilapia nilotica)were investigated with 8 kindsof antisera.RESULTS The positive reaction of 5-hydroxytryptamine(5-HT)immunoreactiveendocrine(IRE)cells was found in the digestive tract and glandular body of 8 fish species indifferent degree.Only a few gastrin(GAS)-IREcells were seen in C.argus,M.albus and P.fulvidraco.Glucagon(GLU)-IRE cells were notfound in the digestive tract and glandular bodybut existed in pancreatic island of most fishspecies.The positive reaction of growthhormone(GH)-IRE cells was found only inpancreatic island of S.Chuatsi and S.Asotus,no positive reaction in the other 6 fish species.Somatostatin(SOM)-,calcitonin(CAL)-,neurofilament(NF)-and insulin(INS)-IRE cellsin the stomach,intestine and pancreas of 8 kindsof fish were different in distribution and types.The distribution of all 8 APUD cells was the mostin gastrointestinal epithelium mucosa and then indigestive glands.The positive reaction of SOM-and 5-HT-IRE cells was found in intermuscularnerve plexus of intestine of P.fulvidraco andS.chuatsi.Only GH-IRE cells were denselyscattered in the pancreatic islands of S.chuatsiand S.asotus,and odd distribution in thepancreas of S.asotus,SOM-IRE cells weredistributed in the pancreatic islands of S.asotus,C.Brachypomum and T.nilotica.There were INS-IRE cells in the pancreaticislands of S.chuatsi and S.asolus.Eightkinds of APUD cells had longer cell body andcytoplasmic process when they were located inthe gastrointestinal epithelium,and had shortercell body and cytoplasmic process in the gastricgland,and irregular shape in the esophagus andpancreatic island.CONCLUSION Eight kinds of IRE cells were identified in the GEP system of stomach-containing teleosts. These endocrine cells were scattered in gastrointestinal mucosa, intermuscular nerve plexus, gland body, pancreatic gland and islands under APUD system. CAL- and GH-IRE cells in the pancreatic islands of fishes showed functional diversity for these two hormones. Their morphological feature provides evidence of endocrine-paracrine and endocrine-exocrine acting mode. This research can morphologically prove that the GEP endocrine system of fish ( the lowest vertebrate) is almost the same as of mammal and human.
文摘AIM:To determine the cytological and molecular effects of peroxisome proliferation-activated receptor(PPAR)-γ and PPAR-γ agonists on stomach cancer cells.METHODS:To determine the proliferation-suppressive effects of troglitazone and ciglitazone,SNU-216 and SNU-668 stomach cancer cells were plated in media containing 40 μmol/L troglitazone and ciglitazone at a density of 1 × 104 cells/well.After 3,5 and 7 d,the cells were counted with a hemocytometer.To assess the appearance of PPAR-γ,a reverse-transcription polymerase chain reaction analysis was performed.On day 7,Western blotting was used to determine the effects of troglitazone and ciglitazone on the expression of p21 and phosphorylated-ERK(pERK) genes.Flow cytometry analysis was used to determine which portion of the cell cycle was delayed when troglitazone was used to suppress cell proliferation.In order to clarify the mechanism underlying the activity of troglitazone,microarray analysis was conducted.RESULTS:PPAR-γ was manifested in both SNU-216 and SNU-668 cells.Ciglitazone and troglitazone suppressed cell growth,and troglitazone was a stronger suppressor of stomach cancer cells than ciglitazone,an inducer of cell cycle arrest in the G1 phase.SNU-668 cells were also determined to be more sensitive to ciglitazone and troglitazone than SNU-216 cells.When troglitazone and ciglitazone were administered to stomach cancer cells,levels of p21 expression were increased,but ERK phosphorylation levels were reduced.When GW9662,an antagonist of PPAR-γ,was applied in conjunction with ciglitazone and troglitazone,the cell growth suppression effect was unaffected.The gene transcription program revealed a variety of alterations as the consequence of troglitazone treatment,and multiple troglitazone-associated pathways were detected.The genes whose expression was increased by troglitazone treatment were associated with cell development,differentiation,signal transmission between cells,and cell adhesion,and were also associated with reductions in cell proliferation,the cell cycle,nuclear metabolism,and phosphorylation.CONCLUSION:Troglitazone and ciglitazone suppress the proliferation of stomach cancer cells via a PPAR-γ-independent pathway.
基金Supported by the National Natural Science Foundation of China, No. 90209023 the State 973 Project, No. 2005CB523308
文摘AIM: To investigate the effect of serum derived from rats treated with electroacupuncture at stomach meridian acupoints on the expression of epidermal growth factor receptor (EGFR) gene in gastric mucosal cells. METHODS: The stress-induced gastric mucosal injury in rat model was established by water-immersion and restrained stress methods. 52 rats were randomly divided into: normal group (n = 8), model group (n = 8), model serum group (n = 12), stomach serum group (n = 12), and gallbladder serum group (n = 12). The gastric mucosal cells were separated by pronase-EDTA digestion method and incubated with serum. The EGFR gene expression in gastric mucosal cells was detected by reverse transcription-polymerase chain reaction (RT-PCR) method. RESULTS: Compared with normal group (0.6860 ± 0.0594), the serum derived from rats of the stomach group (1.2272 ± 0.0813, P = 0.00 < 0.01) and gallbladder group (0.9640 ± 0.0387, P = 0.00 < 0.01) had a tendency to enhance the EGFR gene expression in gastric mucosal cells. Such tendency existed in the model group (0.7104 ± 0.0457) but with no signifi cant difference (P = 0.495 > 0.05) and in model serum group (0.8516 ± 0.0409) with an extremely obvious difference (P = 0.001 < 0.01). Furthermore, the EGFR gene expression in stomach serum group was significantly higher than that in gallbladder serum group (P = 0.00 < 0.01). CONCLUSION: The present study shows that serumderived from rats treated with electroacupuncture at stomach meridian acupoints can distinctly increase the EGFR gene expression of gastric mucosal cells. Therefore, there is certain meridian specificity in the serum, which could provide a proof for the TCM theory “particular relation between meridian and internal organ”.
文摘The research of degree of incidence of genomic changes (of micronuclei) in mucous cells of gastric superficial-foveolar epithelium in contaminated and not contaminated mucous of stomach was made. Histopathological research of micronuclei and helicobacter was made in gastric biopsy specimen of patients with diagnosis-chronical gastritis (ICD-10K29.3) in group of patients who lived in radiation contaminated areas and in groups of people, who had no factors of radiation influence in anamnesis. People, who lived in the radiation contaminated areas, whose mucous was infected by Helicobacter pylori, had the highest frequency of mucous cells with micronuclei. In the group of patients from radiation contaminated areas with HP-associated gastritis frequency of appearance of mucous cells with micronucleus in the mucous of stomach have five time more, than patients, whose mucous of stomach was not infected (p Helicobacter pylori can success in mutagenic effect of radiation factor.
文摘Gastric parietal cells are important in acid secretion, but it is unclear which cells throughout the gastric gland have the highest secretion potency. Here, we used immunohistochemical methods with anti-H+, K+-ATPase, phosphoryl ezrin and CD44 antibodies to study the distribution of gastric acid secretion activity. Stomach tissues from freely fed and starved rats were cryofixed for light microscopy or fixed by high-pressure freezing for electron microscopy. Parietal cells from freely fed animals corresponded to the active secretion phase and to the inactive resting phase from starved rats. Anti-H+, K+-ATPase and anti-phosphoryl ezrin labeling were observed on the membrane of the intracellular canaliculi and the tubulovesicle from freely fed rats, while cells from starved animals showed weak labeling with anti-phosphoryl ezrin antibody staining. Morphometrical analysis at the electron microscopic level was performed on active and inactive acid secretory phases between the upper and base regions of the gland. H+, K+-ATPase and CD44 were distributed on both sites of the microvillous and tubulovesicle membrane in the same cells, but phosphoryl ezrin localized predominantly on the microvillous membrane in active cells of the glandular neck and upper base. Therefore, the highest secreting potency appeared to be in cells of the glandular neck and upper base.
基金This work was supported by Henan Technologies R & D Project (No. 0424420043) and Henan Zoology Key Subject.
文摘Objective: To find out the relationship of the expressions of proliferating cell nuclear antigen (proliferating cell nuclear antigen, PCNA), alkaline phosphotase (alkaline phosphotase, AKP) and acid phosphotase (acid phosphotase, ACP) with the development of mouse fore stomach cancerization. Methods: The animal models, including the various stages during the development of NIH mouse fore stomach carcinoma, were made by N-Nitrososarcosineethylester (N-Nitrososarcosineethylester, NSEE). The mice were sacrificed on the 14th, 28th, 42nd, 56th, 70th and 84th days respectively after mice were irrigated with NSEE. The fore stomach was taken out and dissected. The methods of histopathology, immunohistochemistry and isoenzyme electrophoresis were adopted to study the dynamic changes of cell shape and expression of PCNA, AKP and ACP. Results: On the 42nd and 56th days after NSEE treatment, the expression of PCNA increased gradually along with the cancerization. Comparing with the control, there were significant differences (P〈0.05). On the 70th and 84th days, the expression of PCNA increased further (compared with the control P〈0.01). The activity of AKP increased gradually along with the cancerization. On the 14th, 28th, 42nd and 56th days, there were significant differences (P〈0.05); on the 70th and 84th days, the activity of AKP increased further (P〈0.01). The activity of ACP also increased on the 14th, 28th, 42nd and 56th days, and there were significant differences on the 70th days (P〈0.05) and on the 84th days (P〈0.01) compared with the control. Conclusion: During the carcinogenesis of NIH mouse fore stomach, the expressions of PCNA, AKP and ACP increased gradually and were consisted with the changes of cell shapes.
文摘Perivascular epithelioid cell tumor(PEComa) is a rare mesenchymal neoplasia and currently well recognized as a distinct entity with characteristic morphological,immunohistochemical and molecular findings.We report a case of PEComa arising in the antrum of a 71-year-old female with melena.The tumor,located predominantly in the submucosa as a well delimited nodule,measured 3.0 cm in diameter and was completely resected,with no evidence of the disease elsewhere.Histologically,it was composed predominantly of eosinophilic epithelioid cells arranged in small nests commonly related to variably sized vessels,with abundant extracellular material,moderate nuclear variation and discrete mitotic activity.No necrosis,angiolymphatic invasion or perineural infil-tration was seen.Tumor cells were uniformly positive for vimentin,smooth muscle actin,desmin and melan A.Although unusual,PEComa should be considered in the differential diagnosis of gastric neoplasia with characteristic epithelioid and oncocytic features and prominent vasculature.
基金Supported by Grants from United Arab Emirates UniversityNational Research Foundation,No.UAEU-NRF 31M096
文摘AIM: To measure biochemical parameters in stomach biopsies and test their suitability as diagnostic biomarkers for gastritis and precancerous lesions.METHODS: Biopsies were obtained from the stomachs of two groups of patients(n = 40) undergoing fiberoptic endoscopy due to upper gastrointestinal symptoms. In the first group(n = 17), only the corpus region was examined. Biopsies were processed for microscopic examination and measurement of mitochondrial O2 consumption(cellular respiration), cellular adenosine triphosphate(ATP), glutathione(GSH), and caspase activity. In the second group of patients(n = 23), both corpus and antral regions were studied. Some biopsies were processed for microscopic examination, while the others were used for measurements of cellular respiration and GSH level.RESULTS: Microscopic examinations of gastric corpus biopsies from 17 patients revealed normal mucosae in 8 patients, superficial gastritis in 7 patients, and chronic atrophic gastritis in 1 patient. In patients with normal histology, the rate(mean ± SD) of cellular respiration was 0.17 ± 0.02 μmol/L O2 min-1 mg-1, ATP content was 487 ± 493 pmol/mg, and GSH was 469 ± 98 pmol/mg. Caspase activity was detected in 3 out of 8 specimens. The values of ATP and caspase activity were highly variable. The presence of superficial gastritis had insignificant effects on the measured biomarkers. In the patient with atrophic gastritis, cellular respiration was high andATP was relatively low, suggesting uncoupling oxidative phosphorylation. In the second cohort of patients, the examined biopsies showed either normal or superficial gastritis. The rate of cellular respiration(O2. μmol/L min-1 mg-1) was slightly higher in the corpus than the antrum(0.18 ± 0.05 vs 0.15 ± 0.04, P = 0.019). The value of GSH was about the same in both tissues(310 ± 135 vs 322 ± 155, P = 0.692).CONCLUSION: The corpus mucosa was metabolically more active than the antrum tissue. The data in this study will help in understanding the pathophysiology of gastric mucosa.
基金Supported by an unrestricted grant From the Hong Kong Society of Digestive Endoscopy and the Natural Science Foundation of Guangdong Province of China(No.010713)
文摘AIM: Mechanisms underlying the chemopreventive effects of cyclooxygenase (COX) inhibitors remain elusive. We have previously shown that celecoxib but not indomethacin could prevent carcinogen-induced gastric cancer development in Wistar rats. This chemopreventive effect appeared to be independent of COX-2 and prostaglandin (PG) E2 suppression since the lowest PGE2 was obtained in indomethacin group.This study compared the cell kinetic changes in stomachs of rats after treatment with celecoxib (5, 10, 20 mg/(kg·d)) or indomethacin (3 mg/(kg·d)) to gain more insights into the chemopreventive mechanism.METHODS: The apoptosis and proliferation indexes in gastric tumor, adjacent non-cancer tissues and normal gastric tissues were determined. Apoptosis was quantified by apoptotic nuclei counting and TUNEL, whereas proliferation was determined by Ki67 immunostaining.RESULTS: Treatment with either celecoxib or indomethacin inhibited gastric tumor proliferation by more than 65% (P<0.02). However, celecoxib caused a dose-dependent increase in apoptosis (P<0.05) which was not seen in indomethacin-treated tumors (P = 0.54). The highest apoptosis to proliferation ratio was seen in tumors treated with celecoxib at 10 mg/(kg·d). Treatment with this dose of celecoxib was associated with the lowest incidence of gastric cancer development.CONCLUSION: Our findings suggest that the difference in chemopreventive effects of indomethacin and celecoxib in this animal model of gastric carcinogenesis is largely due to the differential cell kinetic changes, which does not correlate with the degree of COX-2 and PG suppression.
文摘Inflammatory myofibroblastic tumor (IMT) of the stomach in adults is extremely rare, with unpredictable prognosis. We present a 55-year-old woman with a gastric IMT. She experienced sudden abdominal pain 4 d previously. Physical examination showed mild abdominal tenderness in the hypogastrium, but no palpable abnormal abdominal mass. Abdominal CT showed a mass of approximately 8 cm in the gastrocolic ligament. On laparoscopic exploration, unexpected hemoperitoneum of approximately 1.5 L of blood was found, and an exophytic gastric mass of approximately 10 cm, appeared from the anterior wall of the gastric body along the greater curvature. Laparoscopy further showed that non-clotting blood in the abdominal cavity seemed to be from the gastric tumor. After conversion to open surgery for more precise evaluation of the cause of hemoperitoneum and the large friable tumor, gastric wedge resection, including the tumor, was conducted. The final diagnosis was consistent with IMT that originated from the gastric wall.
文摘The combination of classical Hodgkin’s lymphoma(cHL)and non-Hodgkin lymphoma coexisting in the same patient is not common,especially in one extranodal location.Here we present a rare case of composite diffuse large B-cell lymphoma(DLBCL)and cHL occurring simultaneously in the stomach of a 53-year-old female who presented with upper abdominal discomfort and gas pain.Surgery was performed and the disease was diagnosed pathologically as composite lymphoma of DLBCL and cHL using hematoxylin-eosin and immunohistochemical staining.Epstein-Barr virus(EBV)infection was not detected by in situ hybridization for EBV-encoded RNA or immunohistochemistry for EBV latent membrane protein-1.Polymerase chain reaction analysis from the two distinct components of the tumor demonstrated clonal immunoglobulinκlight chain gene rearrangements.The patient died approximately 11 mo after diagnosis in spite of receiving eight courses of the CHOP and two courses of the rituximab-CHOP(RCHOP) chemotherapy regimen.This case report showed that the two distinct components,DLBCL and cHL,appeared to originate from the same clonal progenitor cell,and that EBV infection was not essential for transformation during the course of tumorigenesis.
文摘BACKGROUND Squamous cell carcinoma(SCC)in pancreas and stomach is a rare histologic subtype with aggressive behavior,poor prognosis,and no standardized therapy.Pancreatic SCC or gastric SCC has been previously reported.However,case of SCC occurring in both the pancreas and the stomach has not been reported yet.CASE SUMMARY A 75-year-old female with prior history of hypertension and diabetes mellitus visited our hospital with complaint of abdominal pain that started three months ago.Computed tomography(CT)scan of the abdomen showed 3.3 cm mass at the distal pancreas.She received surgical resection which was histologically found to be SCC of the pancreas with clear resection margins.After she was discharged,she no longer visited the hospital.Three years later,she was referred to our hospital after showing abnormal findings on a gastroscopy performed at another hospital.Gastroscopy revealed a single,2cm sized,ill-defined irregular flat and hyperemic mass at high body.Histologic finding of the mass was SCC.CT scan and positive emission tomography CT showed metastatic lesions to the liver and the peritoneum.She received combination chemotherapy with capecitabine and oxaliplatin.However,she passed away 6 mo after diagnosis of gastric SCC.CONCLUSION To the best of our knowledge,this is the first case of metachronous SCC of stomach occurring after diagnosis of pancreatic SCC.
文摘Primary stomach lymphoblastic B-cell lymphoma (B-LBL) is a rare tumor. We describe a primary stomach B-LBL in a 38 years old female who presented with nonspecific complaints of fatigue and vomiting for 2 mo. Gastrofiberscopy revealed a large gastric ulcer, which was successfully resected. Pathology showed a lymphoblastic cell lymphoma arising from the stomach, and there was no evidence of disease at any extrastomach site. Immunohistochemical staining and gene rearrangement studies supported that the stomach tumor was a clonal B-cell lymphoma. Therefore, the diagnosis of B-LBL was made based on the stomach specimen.
基金partially supported by the Natural Science Foundation of Zhejiang Province(Award number:D21C170001)the National Natural Science Foundation of China(Award number:31973000)。
文摘Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.
基金supported by Chinese National Key Program on Basic Research (Nos. 2006CB943501 and 2006BAI23B01-3)Key Project for Drug Discovery and Development in China (No. 2009ZX09501-027)+1 种基金Key Project for Infectious Diseases in China (No. 2008ZX10002-016)E-Institutes of Shanghai Municipal Education Commission (E03003)
文摘Parietal cells are one of the largest epithelium cells of the mucous membrane of the stomach that secrete hydrochloric acid. To study the function of gastric parietal cells during gastric epithelium homeostasis, we generated a transgenic mouse line, namely, Atp4b-Cre, in which the expression of Cre recombinase was controlled by a 1.0 kb promoter of mouse β-subunit of H^+-, K^+-ATPase gene (Atp4b). In order to test the tissue distribution and excision activity of Cre recombinase in vivo, the Atp4b-Cre transgenic mice were bred with the reporter strain ROSA26 and a mouse strain that carries Smad4 conditional alleles (Smad4Ca/Co). Multiple-tissue PCR of Atp4b-Cre;Smad4Co/+ mice revealed that the recombination only happened in the stomach. As indicated by LacZ staining, ROSA26;Atp4b-Cre double transgenic mice showed efficient expression of Cre recombinase within the gastric parietal cells. These results showed that this Atp4b-Cre mouse line could be used as a powerful tool to achieve conditional gene knockout in gastric parietal cells.