Rapid Endoscopic Diagnosis of Benign Ulcerative Colorectal Diseases With an Artificial Intelligence Contextual Framework.

BACKGROUND & AIMS: Benign ulcerative colorectal diseases (UCDs) such as ulcerative colitis, Crohn's disease, ischemic colitis, and intestinal tuberculosis share similar phenotypes with different etiologies and treatment strategies. To accurately diagnose closely related diseases like UCDs, we hypothesize that contextual learning is critical in enhancing the ability of the artificial intelligence models to differentiate the subtle differences in lesions amidst the vastly divergent spatial contexts. METHODS: White-light colonoscopy datasets of patients with confirmed UCDs and healthy controls were retrospectively collected. We developed a Multiclass Contextual Classification (MCC) model that can differentiate among the mentioned UCDs and healthy controls by incorporating the tissue object contexts surrounding the individual lesion region in a scene and spatial information from other endoscopic frames (video-level) into a unified framework. Internal and external datasets were used to validate the model's performance. RESULTS: Training datasets included 762 patients, and the internal and external testing cohorts included 257 patients and 293 patients, respectively. Our MCC model provided a rapid reference diagnosis on internal test sets with a high averaged area under the receiver operating characteristic curve (image-level: 0.950 and video-level: 0.973) and balanced accuracy (image-level: 76.1% and video-level: 80.8%), which was superior to junior endoscopists (accuracy: 71.8%, P < .0001) and similar to experts (accuracy: 79.7%, P = .732). The MCC model achieved an area under the receiver operating characteristic curve of 0.988 and balanced accuracy of 85.8% using external testing datasets. CONCLUSIONS: These results enable this model to fit in the routine endoscopic workflow, and the contextual framework to be adopted for diagnosing other closely related diseases.

Effect of Weight Loss on the Apnea Hypopnea Index is Related to Waist Circumference in Chinese Adults with Overweight and Obesity.

Purpose: The present study aimed to evaluate the efficiency of traditional anthropometric and body composition parameters in predicting apnea hypopnea index (AHI) change after weight loss. Patients and Methods: Chinese adults with overweight and obesity were included into this study containing two parts. A cross-sectional study was conducted in 137 individuals using the baseline data from two weight loss intervention trials. The second part was the weight-loss intervention study conducted in 60 overweight and obese patients with obstructive sleep apnea (OSA). All participants underwent physical examination, bioelectrical impedance analysis and overnight polysomnography. Multivariate linear regression models were used to identify the most accurate parameters to predict AHI and the mediation analysis to evaluate the mediators between weight loss and AHI reduction. Results: Waist circumference (WC), body mass index and fat mass were positively associated with AHI after adjusting multiple collinearities in the cross-sectional study. After weight-loss intervention, body weight decreased from 94.6 ± 15.3 to 88.0 ± 13.9 kg, and AHI decreased from 41.9 (13.0,66.9) to 20.7 (8.7,51.2) events/h. Among these parameters, only percentage changes in WC and AHI across the intervention were positively intercorrelated after controlling for covariates (adjusted r = 0.271, P = 0.041). The mediation analysis supported WC as a mediator between weight loss and AHI reduction (standardized indirect effect [95% CI] = 4.272[0.936,7.999]). Conclusion: Both general and abdominal obesity are of high prognostic value for OSA. WC as an easily accessible parameter mediates the effects of weight loss in decreasing OSA severity.

Weight Loss Promotion in Individuals with Obesity through Gut Microbiota Alterations with a Multiphase Modified Ketogenic Diet.

The occurrence of obesity and related metabolic disorders is rising, necessitating effective long-term weight management strategies. With growing interest in the potential role of gut microbes due to their association with responses to different weight loss diets, understanding the mechanisms underlying the interactions between diet, gut microbiota, and weight loss remains a challenge. This study aimed to investigate the potential impact of a multiphase dietary protocol, incorporating an improved ketogenic diet (MDP-i-KD), on weight loss and the gut microbiota. Using metagenomic sequencing, we comprehensively analyzed the taxonomic and functional composition of the gut microbiota in 13 participants before and after a 12-week MDP-i-KD intervention. The results revealed a significant reduction in BMI (9.2% weight loss) among obese participants following the MDP-i-KD intervention. Machine learning analysis identified seven key microbial species highly correlated with MDP-i-KD, with Parabacteroides distasonis exhibiting the highest response. Additionally, the co-occurrence network of the gut microbiota in post-weight-loss participants demonstrated a healthier state. Notably, metabolic pathways related to nucleotide biosynthesis, aromatic amino acid synthesis, and starch degradation were enriched in pre-intervention participants and positively correlated with BMI. Furthermore, species associated with obesity, such as Blautia obeum and Ruminococcus torques, played pivotal roles in regulating these metabolic activities. In conclusion, the MDP-i-KD intervention may assist in weight management by modulating the composition and metabolic functions of the gut microbiota. Parabacteroides distasonis, Blautia obeum, and Ruminococcus torques could be key targets for gut microbiota-based obesity interventions.

Modulating the Human Gut Microbiota through Hypocaloric Balanced Diets: An Effective Approach for Managing Obesity.

This study aimed to investigate the effects of a hypocaloric balanced diet (HBD) on anthropometric measures and gut microbiota of 43 people with obesity. Fecal samples were collected from the study subjects at weeks 0 and 12, and a detailed analysis of gut microbiota was performed using 16S rRNA gene sequencing. By comparing anthropometric measures and microbiota changes in subjects before and after the HBD intervention, we revealed the potential effects of HBD on weight loss and gut microbiota. Our results indicated that the HBD resulted in a significant decrease in body mass index (BMI), and most of the physiological indicators were decreased to a greater degree in the effective HBD group (EHBD, weight loss ≥ 5%) than in the ineffective HBD group (IHBD, weight loss < 5%). The HBD intervention also modified the gut microbiota of the subjects with obesity. Specifically, Blautia, Lachnoclostridium, Terrisporobacter, Ruminococcus (R. torques, R. gnavus), and Pseudomonas were significantly reduced. In addition, we employed machine learning models, such as XGBRF and GB models, to rank the importance of various features and identified the top 10 key bacterial genera involved. Gut microbiota co-occurrence networks showed the dominance of healthier microbiota following successful weight loss. These results suggested that the HBD intervention enhanced weight loss, which may be related to diet-induced changes in the gut microbiota.

A Novel Multiphase Modified Ketogenic Diet: An Effective and Safe Tool for Weight Loss in Chinese Obese Patients.

Purpose: The aim of the present study was to investigate the effect and safety of a multiphase modified ketogenic diet (MMKD) compared to beinaglutide treatment or lifestyle modification (LM) alone on weight loss in obese patients in China. Patients and Methods: The present study was conducted in adults with obesity who did not have diabetes with two phases as follows: a 4-week run-in phase to guide diet and exercise, followed by a 12-week intervention phase aiming to lose weight. All participants performed aerobic and resistance exercise, and they were free to select any one of three weight-loss strategies as follows: LM group, 12 weeks of hypocaloric balanced diet (HBD); MMKD group, two cycles of a multiphase diet with each cycle comprised of 2 weeks of ketogenic diet (KD), 2 weeks of transition diet and 2 weeks of HBD; and beinaglutide group, 12 weeks of HBD plus daily injection of beinaglutide (0.4 mg per day). Body weight, body composition and metabolic variables were measured before and after the 12 weeks of treatment. Results: All intervention strategies had significant weight loss, and the MMKD led to greater weight loss than LM (difference, -3.7 kg; 95% confidence interval [CI], -6.1 to -1.4; P = 0.001) but not beinaglutide (difference, -1.5 kg; 95% CI, -4.3 to 1.3; P = 0.587). Waist circumference (WC), fat mass, body fat percentage (BFP) and visceral fat area (VFA) were also significantly decreased, and the MMKD had a greater effect on these parameters than LM or beinaglutide. In addition, significant reductions in blood pressure and homoeostatic model assessment of insulin resistance (HOMA-IR) were observed in all three groups, but the MMKD resulted in the most significant improvement in insulin resistance. Almost no adverse events, except for two cases of dizziness, were observed in the MMKD group, which was significantly fewer events than the other two groups. Conclusion: These findings demonstrated that the MMKD is an effective and safe treatment for weight loss, thus providing an additional option for obese Chinese patients.

Dietary xylo-oligosaccharide ameliorates colonic mucus microbiota penetration with restored autophagy in interleukin-10 gene-deficient mice.

BACKGROUND: Inflammatory bowel disease (IBD) is, nowadays, highly prevalent and presents a global clinical challenge. The objective of this study is to assess the effects of xylo-oligosaccharide (XOS) on Il10-/- mice, a classic animal model of IBD. METHODS: Male wild-type (WT) mice were assigned to WT group, and Il10-/- mice were assigned to interleukin-10 gene-deficient (IL-10-KO) group and XOS group, respectively. There were 6-8 mice aged 8 weeks in each group. Mice in the XOS group received 1.0 g/kg/day XOS by gavage for 4 weeks. RESULTS: Compared with mice in IL-10-KO group, Il10-/- mice with XOS intervention presented significant mild spontaneous colitis with lower disease activity index, histological scores, and bowel inflammatory cytokine levels. Dietary XOS downregulated bowel mucus bacterial penetration, which occurred as early as the onset of bowel colitis. The effect of XOS was associated with restored expression of LC3II/I and decreased expression of p62 and beclin-1 in colon. CONCLUSIONS: Therefore, XOS decreases colonic mucus microbiota penetration with restored function of antophagy. Our findings suggest that XOS may be a potential dietary supplement or functional food for early management of IBD.

A multiphase dietetic protocol incorporating an improved ketogenic diet enhances weight loss and alters the gut microbiome of obese people.

The prevalence of obesity and its associated diseases is increasing. In the current study, 15 obese subjects took part in a 12-week multiphase dietetic protocol incorporating an improved ketogenic diet (MDP-i-KD) (KYLLKS 201806). We investigated the effects of the MDP-i-KD on the anthropometric parameters and the gut microbiota of obese subjects. Our results showed that the MDP-i-KD led to significant reductions in body mass index in obese subjects. The MDP-i-KD significantly decreased the relative abundance of the Lachnospiraceae_ND3007_group, the Eubacterium_hallii_group, and Pseudomonas and Blautia. In addition, gut microbiota co-occurrence networks in obese subjects were restructured to a more healthy condition after weight loss. These results show that the MDP-i-KD enhanced weight loss, which may be associated with dietary-induced changes in the gut microbiome. Our results emphasise the importance of determining the interaction between the host and microbial cells to comprehensively understand the mechanism by which diet affects host physiology and the microbiota.

Evidence summary of human milk fortifier in preterm infants.

BACKGROUND: To search for and collect evidence on human milk fortifier in preterm infants, and to summarize the latest and best evidence, so as to provide reference for clinical work. METHODS: We searched the databases of UpToDate, American Guide Network, Cochrane Library, Joanna Briggs Institute (JBI), PubMed, ResearchGate, China National Knowledge Infrastructure (CNKI), Wan Fang, Chinese Biology Medicine disc (CBM), and Yi Maitong, and collected relevant guidelines, systematic reviews, evidence summaries, expert consensuses, and randomized controlled trials (RCTs). The retrieval time limit was from the database establishment to July 2021. The quality of the literature was independently evaluated by 2 researchers, who then extracted and summarized the evidence from qualifying articles. RESULTS: A total of 16 articles were selected, including 3 guidelines, 3 systematic reviews, 5 expert consensuses, 3 RCTs, and 1 best practice guideline, including indications, time for usage, methods, monitoring and management, time of cessation, health education, and post-discharge feeding. CONCLUSIONS: This study summarized the best evidence for human milk fortifier in preterm infants. Medical staff should assess the specific clinical conditions and parental wishes when applying the best evidence to ensure the effectiveness and safety of human milk fortifier, thus improving the quality of clinical nursing.

Radiation-induced miR-208a increases the proliferation and radioresistance by targeting p21 in human lung cancer cells.

BACKGROUND: Lung cancer has long been the most dangerous malignant tumor among males in both well developed and poorly developed countries. Radiotherapy plays a critical role in the curative management of inoperable non-small cell lung cancer (NSCLC) and is also used as a post-surgical treatment in lung cancer patients. Radioresistance is an important factor that limits the efficacy of radiotherapy for NSCLC patients. Increasing evidence suggests that microRNAs (miRNAs) possess diverse cellular regulatory roles in radiation responses. METHODS: In this study, we used miRNA microarray technology to identify serum miRNAs that were differentially expressed before and after radiotherapy in lung cancer patients. We further examined the biological function of miR-208a on cell viability, apoptotic death and cell cycle distribution in human lung cancer cells and explored the probable mechanism. RESULTS: Nine miRNAs, including miR-29b-3p, miR-200a-3p, and miR-126-3p were significantly down-regulated, whereas miR-208a was the only miRNA that was up-regulated in the serum of the patients after radiation treatment (P < 0.05). The expression of miR-208a could be induced by X-ray irradiation in lung cancer cells. Forced expression of miR-208a promoted cell proliferation and induced radioresistance via targeting p21 with a corresponding activation of the AKT/mTOR pathway in lung cancer cells, whereas down-regulation of miR-208a resulted in the opposite effects. In addition, down-regulation of miR-208a increased the percentage of cells undergoing apoptosis and inhibited the G1 phase arrest in NSCLC cells. Moreover, miR-208a from the serum exosome fraction of lung cancer patients could shuttle to A549 cells in a time-dependent manner, which was likely to contribute to the subsequent biological effects. CONCLUSIONS: The present study provides evidence that miR-208a can affect the proliferation and radiosensitivity of human lung cancer cells by targeting p21 and can be transported by exosomes. Thus, miR-208a may serve as a potential therapeutic target for lung cancer patients.

[Regulatory role of serum miR-224 in invasiveness and metastasis of cholangiocarcinoma].

OBJECTIVE: To investigate the expression profile of serum micro (mi)RNAs in cholangiocarcinoma (CCA) and investigate the regulatory contribution of miRNAs to the invasive and metastasis. METHODS: Microarray analysis was carried out using serum samples collected from 30 patients with CCA, bile duct cancer tissues and the corresponding normal tissues collected from 10 patients, and serum samples from 50 healthy volunteers. The miRNAs identified as dysregulated in CCA were verified by RT-PCR. Focused analysis on miR-224 was carried out using the human CCA cell lines HCCC-9810 and RBE to investigate the role of this miRNA in IL-6 expression (using IL-6 induction), cell growth, invasiveness and metastasis (using miR-224 mimic transfection). The one-way ANOVA test was used for statistical analysis. RESULTS: Forty-three miRNAs were dysregulated in CCA (vs. non-CCA, P<0.01), of which 22 were upregulated and 21 were downregulated. RT-PCR data showed that the miR-224 was significantly upregulated in serum as well as in cancer tissue from CCA patients. Induction of HCCC-9810 and RBE cells with IL-6 showed a time-dependent upregulation of miR-224. Furthermore, the HCCC-9810 and RBE cells transfected with miR-224 mimic showed enhanced cell growth, invasiveness and migratory ability. CONCLUSION: IL-6 may promote the invasive and metastatic properties of CCA through upregulated miR-224. Studies of the differentially expressed serum miRNAs in CCA may help to further elucidate the pathogenic processes of this disease and aid in the development of a novel and effective therapeutic strategy.

Sodium Butyrate Reduces Organ Injuries in Mice with Severe Acute Pancreatitis Through Inhibiting HMGB1 Expression.

OBJECTIVE: The present study was designed to evaluate the effect of sodium butyrate on pancreas damage and to investigate the role of high-mobility group box-1 (HMGB1) and nuclear factor-κB (NF-κB) in the development of severe acute pancreatitis (SAP) in a mouse model. METHODS: The SAP model was established by intraperitoneal injection of two doses of 20 % L-2 arginine (200 mg/g). Female Sprague-Dawley mice were randomly allocated into three groups (n = 48/group): the control, untreated SAP, and sodium butyrate-treated SAP groups. The animals were euthanized at 0, 12, 24, and 48 h after the establishment of the SAP. Histopathology of the pancreas was performed, and the NF-κB levels were determined by immunohistochemistry. The serum levels of tumor necrosis factor (TNFα), interleukin-6 (IL-6), and HMGB1 were measured by ELISA. The HMGB1 mRNA levels were determined by qRT-PCR. RESULTS: The sodium butyrate-treated SAP animals showed significantly improved pancreas histopathology and lower serum amylase levels than the untreated SAP animals. In the SAP group, the mRNA levels of HMGB1 were remarkably increased at the 12 h, peaked at 24 h, and remained at a high level up to 48 h after L-2 arginine injection. The levels of TNFα and IL-6 were decreased at 48 h. Treatment with sodium butyrate reduced the pathological lesions, the serum levels of HMGB1, TNFα, and IL-6, the HMGB1 mRNA levels, and NF-κB activity. CONCLUSION: Sodium butyrate inhibits the NF-κB activation and reduces pancreas injury in SAP through the modulation of HMGB1 and other inflammatory cytokine responses.

Risk factors for depth of infiltration in the differentiated depressed early gastric carcinoma: a preliminary analysis.

BACKGROUND: To analyze the clinicopathologic factors associated with mucosal and submucosal infiltration in differentiated depressed early gastric cancer, and screening factors that can predict depth of infiltration before endoscopic treatment. METHODS: The study included 35 cases of mucosal carcinomas and 66 cases of submucosal carcinomas according to the pathological diagnosis. The relevant clinicopathologic factors were investigated by univariate and multivariate analysis. RESULTS: The average depth of the depressed lesions for the submucosal group was significantly more than that for the mucosal group. The proportion of the lesions with rough bottom surface and abnormal surrounding folds was significantly higher in the submucosal group compared to that in the mucosal group. Logistic regression analysis indicated that the above-mentioned three factors were independent risk factors that could be used to predict mucosal and submucosal infiltration. Area under the curve (AUC) of receiver operating characteristic (ROC) of the ordinal above-mentioned three factors for predicting submucosal infiltration was 0.716, 0.663, 0.704, respectively. Stratified analysis showed that the 100% cases with lesion depth ≥ 2.5 mm and rough bottom surface developed submucosal infiltration regardless of the morphological changes of the folds. CONCLUSION: The study identified independent risk factors for predicting mucosal and submucosal infiltration in depressed differentiated early gastric cancer, which may evaluate the degree of penetration before endoscopic treatment. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_206.

Decreased fetal pre-adipocyte factor-1 in pregnancies complicated by gestational diabetes mellitus.

BACKGROUND: Serum pre-adipocyte factor-1 (pref-1) is an inhibitor of adipocyte differentiation that increases in small for gestational age fetuses. It plays a role in adipose metabolism and is associated with an increased risk of metabolic diseases in adulthood. We hypothesized that preadipocyte factor-1 (pref-1) concentration is altered in fetuses born to women with gestational diabetes mellitus (GDM). METHODS: Umbilical cord blood pref-1 concentrations were determined by enzyme-linked immunosorbant assay in 37 fetuses from pregnancies complicated by GDM and 45 fetuses from normal pregnancies. RESULTS: Serum pref-1 concentrations were significantly lower in fetuses of women with GDM compared to normal pregnancies (16.12±6.48 vs. 22.09±7.22 µg/l, P=0.001). Birth weight was significantly higher in GDM fetuses compared to normal pregnancies (3567±544 vs. 3253±370 g, P=0.003). CONCLUSIONS: Pregnancies complicated by GDM have decreased fetal pref-1 concentrations compared to normal pregnancies. These differences may be significant in terms of their later development of metabolic conditions.

Potential role of mannose-binding lectin in intrauterine transmission of hepatitis B virus.

Intrauterine transmission of hepatitis B virus (HBV) is the main cause of the high prevalence of HBV in endemic areas; however, the mechanisms underlying intrauterine transmission of HBV remain unknown. To explore the role of mannose-binding lectin (MBL), a pattern recognition molecule of the innate immune system, in intrauterine transmission of HBV, we determined MBL levels using an enzyme-linked immunosorbent assay (ELISA) in cord serum of 7 intrauterine-infected neonates and 30 non-infected neonates born to HBV-positive mothers, and 30 control neonates born to HBV-negative mothers. We observed significant differences in cord serum MBL levels among the three groups (P < 0.001). Non-infected neonates had significantly higher MBL levels than controls (P < 0.001), and intrauterine-infected neonates had significantly lower serum MBL levels than non-infected neonates (P < 0.001). However, serum MBL levels were not significantly different between intrauterine-infected neonates and controls (P = 0.800). Our results indicate that maternal HBV infection induces an increase in fetal MBL levels and the absence of this increase is possibly associated with intrauterine transmission of HBV, suggesting that MBL plays a role in intrauterine transmission of HBV.

Serum preadipocyte factor-1 is increased in fetuses of pregnancy complicated with severe preeclampsia.

BACKGROUND: Preadipocyte factor-1 (Pref-1), an inhibitor of adipocyte differentiation, is increased in fetal blood of small for gestational age (SGA) and is considered a factor involved in determining adiposity and associated with high risk of metabolic diseases in adulthood. Preeclampsia is a condition closely associated with SGA, however, the alteration of Pref-1 of in fetuses of preeclampsia remains unknown. The aims of the current investigation were to clarify the alteration of serum Pref-1 in fetuses of preeclamptic pregnancy and to explore possible role of Pref-1 in metabolic diseases in late life. METHODS: Cord blood samples were taken at birth from 45 fetuses of normal pregnancy, 16 of gestational hypertension, 29 of mild preeclampsia and 29 of severe preeclampsia. Serum Pref-1 concentrations were measured with ELISA. RESULTS: There were significant differences in cord blood Pref-1 and neonatal birth weight among normal pregnancy, gestational hypertension, mild and severe preeclampsia (F=8.557, P<0.001 for Pref-1; F=38.405, P<0.001 for birth weight). Serum Pref-1 was significantly higher while birth weight were lower in severe preeclampsia than normal pregnancy, gestational hypertension and mild preeclampsia respectively (P<=0.001 for all). However, either serum Pref-1 or birth weight did not significantly differ among normal pregnancy, gestational hypertension and mild preeclampsia (P>0.05 for all). Fetal Pref-1 concentration was significantly negatively correlated with birth weight (R(2)=0.175, P=0.027 for severe preeclampsia; R(2)=0.209, P<0.001 for preeclampsia; R(2)=0.25, P<0.001 for all subjects). CONCLUSIONS: Increased serum Pref-1 was demonstrated in fetuses of preeclampsia-complicated pregnancy, and it may be proposed that Pref-1 is among the possible mediators leading to high risk of metabolic diseases in adulthood.

Evaluation of the BISAP score in predicting severity and prognoses of acute pancreatitis in Chinese patients.

The present study was to evaluate the accuracy of bedside index for severity in acute pancreatitis (BISAP) in predicting the severity and prognoses of acute pancreatitis (AP) in Chinese patients. Clinical data for 497 patients with AP were analyzed retrospectively to compare BISAP with acute physiology and chronic health evaluation II, Ranson, and computed tomography severity index scores in predicting the severity of AP and the occurrence of pancreatic necrosis, mortality, and organ failure in patients with severe AP (SAP) using the area under the receiver-operating characteristic curve. Of the 497 patients, 396 had mild AP and 101 had SAP. There were significant correlations between the scores of any two systems. BISAP performed similarly to other scoring systems in predicting SAP, as well as pancreatic necrosis, mortality, and organ failure in SAP patients, in terms of the area under the receiver-operating characteristic curve. BISAP score is valuable in predicting the severity of AP and prognoses of SAP in Chinese patients.

The regenerating gene iα is overexpressed in atrophic gastritis rats with hypergastrinemia.

The role of gastrin on the development of atrophic gastritis (AG) and its relationship with the expression of RegIα in vivo remain unclear. We established experimental AG in rats by combination administration with sodium salicylate, alcohol, and deoxycholate sodium. The mean score of inflammation in gastric antrum in AG rats was significantly elevated (P < 0.05), while the number of glands dramatically decreased (P < 0.05). In addition, the cell proliferation in gastric glands was increased in experimental AG rats, as determined by immunohistochemistry staining of PCNA and GS II. The level of serum gastrin in AG rats was significantly elevated relative to that of normal rats (P < 0.01). Moreover, the expression of RegIα protein and its receptor mRNA was increased in gastric tissues in AG rats (P < 0.05). Taken together, we demonstrated that the overexpression of Reglα is related with hypergastrinemia in AG rats.

[Construction of RegIα over-expression vector and its effect on proliferation and apoptosis of gastric cancer cells].

OBJECTIVE: To construct RegIα over-expression vector and to evaluate the effect of RegIα on the proliferation and apoptosis of gastric cancer MKN28 cells in vitro. METHODS: Full sequence of RegIα cDNA was amplified from normal gastric tissue samples by RT-PCR and cloned into pIRES2-EGFP vector. RT-PCR and Western blot were performed to detect expression levels of RegIα in MKN28 cells. The effects of over-expression RegIα on cell proliferation was measured by MTT assay and apoptosis was detected by flow cytometry. RESULT: RegIα cDNA over-expression vector of pIRES2-RegIα-EGFP was successfully constructed. The expressions of RegIα in MKN28 cells, including mRNA and protein levels, were significantly increased after stable transfection, which resulted in cell proliferation and anti-apoptotic effect induced by H(2)O(2). CONCLUSION: The over-expression of RegIα can promote cell proliferation and reduce cell apoptosis when induced by H(2)O(2) in gastric cancer cells.

Role of REG Iα in gastric carcinogenesis: Gastrin-associated proliferative and anti-apoptotic activities.

Gastric carcinogenesis is a multiple-stage process. It is believed that a premalignant lesion often precedes or accompanies gastric cancer, although the underlying mechanisms have not been fully elucidated. Here, we revealed that REG Iα was frequently overexpressed not only in gastric cancer tissues, but also in the intestinal metaplastic and atypical dysplasia gland, which are considered precancerous lesions, in 102 patients. To investigate the role of REG Iα in gastric cancer, we employed siRNA-mediated silencing techniques and found that the downregulation of REG Iα significantly inhibited gastric cancer cell proliferation, whereas overexpression of REG Iα promoted proliferation. In addition, REG Iα appeared to have an anti-apoptotic effect in gastric cancer cells, which was associated with the Bad/Bcl-xL/caspase-3 pathway. Furthermore, gastrin was found to activate REG Iα expression and nuclear translocation of ß-catenin in gastric cancer cells. Thus, these data suggest that REG Iα, a potential downstream of gastrin, may be involved in gastric carcinogenesis.