The correlation between serum 25-hydroxyvitamin D level and ulcerative colitis: a systematic review and meta-analysis.

OBJECTIVE: The incidence of UC has increased yearly. Many studies have suggested that patients with ulcerative colitis have abnormal vitamin D levels. A systematic review and meta-analysis were conducted to investigate the association between vitamin D levels and ulcerative colitis. METHODS: We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang and China Science and Technology Journal Database (VIP) from inception to December 2022. We included case-control studies comparing the differences in vitamin D levels between patients with ulcerative colitis and healthy populations. Meta-analysis was performed using Review Manager5.4, Stata17.0 and other software. RESULTS: Sixteen eligible observational studies were selected from 473 articles involving 2234 subjects, and they included 987 patients with ulcerative colitis and 1247 controls. The results showed that the serum level of vitamin D in patients with ulcerative colitis was significantly lower than that in healthy controls (SMD = -0.83, 95% CI: -1.18, -0.48). Vitamin D deficiency was reported in five studies. The prevalence of vitamin D deficiency was significantly higher in the ulcerative colitis group than in the healthy control group (OR = 1.90, 95% CI: 1.38, 2.62). CONCLUSION: Serum vitamin D levels were significantly lower in patients with ulcerative colitis than in healthy controls.

Non-invasive model for predicting high-risk esophageal varices based on liver and spleen stiffness.

BACKGROUND: Acute bleeding due to esophageal varices (EVs) is a life-threatening complication in patients with cirrhosis. The diagnosis of EVs is mainly through upper gastrointestinal endoscopy, but the discomfort, contraindications and complications of gastrointestinal endoscopic screening reduce patient compliance. According to the bleeding risk of EVs, the Baveno VI consensus divides varices into high bleeding risk EVs (HEVs) and low bleeding risk EVs (LEVs). We sought to identify a non-invasive prediction model based on spleen stiffness measurement (SSM) and liver stiffness measurement (LSM) as an alternative to EVs screening. AIM: To develop a safe, simple and non-invasive model to predict HEVs in patients with viral cirrhosis and identify patients who can be exempted from upper gastrointestinal endoscopy. METHODS: Data from 200 patients with viral cirrhosis were included in this study, with 140 patients as the modelling group and 60 patients as the external validation group, and the EVs types of patients were determined by upper gastrointestinal endoscopy and the Baveno VI consensus. Those patients were divided into the HEVs group (66 patients) and the LEVs group (74 patients). The effect of each parameter on HEVs was analyzed by univariate and multivariate analyses, and a non-invasive prediction model was established. Finally, the discrimination ability, calibration ability and clinical efficacy of the new model were verified in the modelling group and the external validation group. RESULTS: Univariate and multivariate analyses showed that SSM and LSM were associated with the occurrence of HEVs in patients with viral cirrhosis. On this basis, logistic regression analysis was used to construct a prediction model: Ln [P/(1-P)] = -8.184 -0.228 × SSM + 0.642 × LSM. The area under the curve of the new model was 0.965. When the cut-off value was 0.27, the sensitivity, specificity, positive predictive value and negative predictive value of the model for predicting HEVs were 100.00%, 82.43%, 83.52%, and 100%, respectively. Compared with the four prediction models of liver stiffness-spleen diameter to platelet ratio score, variceal risk index, aspartate aminotransferase to alanine aminotransferase ratio, and Baveno VI, the established model can better predict HEVs in patients with viral cirrhosis. CONCLUSION: Based on the SSM and LSM measured by transient elastography, we established a non-invasive prediction model for HEVs. The new model is reliable in predicting HEVs and can be used as an alternative to routine upper gastrointestinal endoscopy screening, which is helpful for clinical decision making.

Effectiveness of Water-Assisted Colonoscopy without Sedation in Patients with Ulcerative Colitis.

BACKGROUND: Studies have found that water-assisted colonoscopy (WAC) including water immersion colonoscopy (WIC) and water exchange colonoscopy (WEC) is superior to air insufflation colonoscopy (AIC) in terms of the cecal intubation rate. However, the application of WAC in ulcerative colitis (UC) has rarely been reported. This study aimed to explore the effectiveness of WAC without sedation in patients with UC. METHODS: One hundred and seventy-two UC patients were randomly divided into the AIC group (n = 56), WIC group (n = 58), and WEC group (n = 58). The cecal intubation rate, abdominal pain score, operator difficulty, bowel cleanliness, insertion, and total time were compared. RESULTS: The cecal intubation rate was higher in the WIC (91.4% vs. 75.0%; mean difference = 16.4%; 95% CI: 3.0-29.8%) and WEC (93.1% vs. 75.0%; mean difference = 18.1%; 95% CI: 5.0-31.2%) compared to the AIC group, while there was no difference between the WIC and WEC groups. The abdominal pain score and operator difficulty were lower in the WIC and WEC groups than in the AIC group, while there was no difference between the WIC and WEC groups. The bowel cleanliness during withdrawal was higher in the WIC and WEC groups than in the AIC group, while the WEC was superior to WIC. Compared with the AIC and WIC groups, the insertion time and total time were longer in the WEC group, and there was no difference in the AIC group and WIC group. CONCLUSION: In comparison with AIC, WAC can increase the cecal intubation rate, reduce abdominal pain scores and improve bowel cleanliness in patients with UC.

Adherent-invasive Escherichia coli LF82 aggravated intestinal inflammation in colitis mice by affecting the gut microbiota and Th17/Treg cell differentiation balance.

The imbalance of Th17 and Treg cell differentiation, intestinal flora imbalance, and intestinal mucosal barrier damage may be important links in the occurrence and development of inflammatory bowel disease (IBD) since Th17 and Treg differentiation are affected by the intestinal flora. This study aimed to explore the effect of Escherichia coli (E. coli) LF82 on the differentiation of Th17 and Treg cells and the role of the intestinal flora in mouse colitis. The effects of E. coli LF82 infection on intestinal inflammation were evaluated by analyzing the disease activity index, histology, myeloperoxidase activity, FITC-D fluorescence value, and claudin-1 and ZO-1 expression. The effects of E. coli LF82 on the Th17/Treg balance and intestinal flora were analyzed by flow cytometry and 16S rDNA sequencing. Inflammatory markers, changes in the intestinal flora, and Th17/Treg cells were then detected after transplanting fecal bacteria from normal mice into colitis mice infected by E. coli LF82. We found that E. coli LF82 infection can aggravate the intestinal inflammation of mice colitis, destroy their intestinal mucosal barrier, increase intestinal mucosal permeability, and aggravate the imbalance of Th17/Treg differentiation and the disorder of intestinal flora. After improving the intestinal flora imbalance by fecal bacteria transplantation, intestinal inflammation and intestinal mucosal barrier damage were reduced, and the differentiation balance of Th17 and Treg cells was restored. This study showed that E. coli LF82 infection aggravates intestinal inflammation and intestinal mucosal barrier damage in colitis by affecting the intestinal flora composition and indirectly regulating the Th17 and Treg cell differentiation balance.

Disruption of Periaqueductal Gray-default Mode Network Functional Connectivity in Patients with Crohn's Disease with Abdominal Pain.

Abdominal pain in Crohn's disease (CD) has been known to be associated with changes in the central nervous system. The periaqueductal gray (PAG) plays a well-established role in pain processing. However, the role of PAG-related network and the effect of pain on the network in CD remain unclear.Resting-state functional magnetic imaging (fMRI) data were collected from 24 CD patients in remission with abdominal pain, 24 CD patients without abdominal pain and 28 healthy controls (HCs). Using the subregions of PAG (dorsomedial (dmPAG), dorsolateral (dlPAG), lateral (lPAG) and ventrolateral (vlPAG)) as seeds, the seed-based FC maps were calculated and one-way analysis of variance (ANOVA) was performed to investigate the differences among the three groups.Results showed that the group differences were mainly involved in the FC of the vlPAG with the precuneus, medial prefrontal cortex (mPFC) as well as orbitofrontal cortex (OFC), and the FC of the right lateral PAG (lPAG) with the precuneus, inferior parietal lobule (IPL), angular gyrus and premotor cortex. The FC values of all these regions decreased successively in the order of HCs, CD without abdominal pain and CD with abdominal pain. The pain score was negatively correlated with the FC of the l/vlPAG with the precuneus, angular gyrus and mPFC in CD patients with abdominal pain.This study implicated the disrupt communication between the PAG and the default mode network (DMN). These findings complemented neuroimaging evidence for the pathophysiology of visceral pain in CD patients.

Zinc finger protein 671 has a cancer-inhibiting function in colorectal carcinoma via the deactivation of Notch signaling.

Zinc finger protein 671 (ZNF671) has been described as a vital cancer inhibitor in multiple neoplasms, yet the functional roles of ZNF671 in colorectal carcinoma (CRC) remain unresolved. This project examined the possible link between ZNF671 and CRC. Lower levels of ZNF671 were observed in CRC tissue compared with noncancerous tissue, which were related to a worse survival rate in CRC patients. High methylation levels at the ZNF671 gene promoter region were shown in CRC tissue, which were inversely correlated with ZNF671 expression. Treatment with demethylation agents restored ZNF671 levels in CRC cell lines. Up-regulation of ZNF671 resulted in suppressive effects on the proliferative ability and metastatic potency of CRC cells. Moreover, the up-regulation of ZNF671 reinforced the chemosensitivity of CRC cells. A mechanism study determined ZNF671 to be a vital mediator of Notch signaling. The up-regulation of ZNF671 decreased the expression of Notch1 and lowered the levels of NICD, HES1, and HEY1. The overexpression of NICD1 diminished ZNF671-mediated antitumor effects. ZNF671 depletion reinforced Notch signaling, and Notch suppression reversed ZNF671-depletion-elicited protumor effects. Moreover, the overexpression of ZNF671 weakened the tumorigenicity of CRC cells in a xenograft model in vivo. In summary, ZNF671 exerts a cancer-inhibiting function in CRC via the deactivation of Notch signaling. Low ZNF671 levels caused by gene promoter hypermethylation contribute to the malignant transformation of CRC. This work underlines the interest of ZNF671 as a target candidate for exploiting novel anti-CRC therapies.

Activation of YAP1 by STK25 contributes to the progression of hepatocellular carcinoma.

A pathogenic role of serine/threonine protein kinase 25 (STK25) has been observed in several chronic liver diseases. However, whether STK25 participates in hepatocellular carcinoma (HCC) remains unexplored. The current work aimed to explore the role and mechanism of STK25 in HCC. A high STK25 level was found in HCC tissue, which was associated with reduced overall survival. HCC cells with STK25 silencing displayed a marked decrease in proliferative and invasive ability, but were highly sensitive to apoptosis induced by the chemotherapy drug sorafenib. Reciprocally, HCC cells with forced expression of STK25 displayed the opposite effects. Further data unveiled that STK25 silencing restrained the activation of Yes-associated protein 1 (YAP1) associated with regulation of mammalian STE20-like protein kinase 1/2 (MST1/2). Forced expression of constitutively active YAP1 abolished STK25 silencing-induced antitumor effects, while repression of YAP1 reversed STK25 upregulation-induced protumor effects. Additionally, HCC cells with STK25 silencing exhibited reduced tumorigenic potential in vivo. Collectively, the results show that STK25 exerts a protumor function in HCC by enhancing YAP1 activation via regulation of MST1/2. These findings propose STK25 as a viable target for the development of anti-HCC therapy.

Altered structural covariance and functional connectivity of the insula in patients with Crohn's disease.

BACKGROUND: Crohn's disease (CD) is a clinically chronic inflammatory bowel disease, which has been shown to be closely related to the brain-gut axis dysfunction. Although traditionally considered to be a limbic region, the insula has also been commonly identified as an abnormal brain region in previous CD-related studies. METHODS: Structural magnetic resonance imaging (MRI) and resting-state functional MRI images were acquired from 45 CD patients in remission and 40 healthy controls (HCs). Three neuroimaging analysis methods including voxel-based morphometry (VBM), structural covariance, and functional connectivity (FC) were applied to investigate structural and functional alterations of the insulae between the CD patients and HCs. Pearson correlation was then used to examine the relationships between neuroimaging findings and clinical symptoms. RESULTS: Compared with the HCs, CD patients exhibited decreased gray matter volume (GMV) in the left dorsal anterior insula (dAI) and bilateral posterior insula (PI). Taking these three areas including the left dAI, right PI, and left PI as regions of interest (ROIs), differences were observed in the structural covariance and FC of the ROI with several regions between the two groups. After controlling for psychological factors, the differences of several regions involved in emotional processing in GMV in the left dAI, the FC of the dAI, and the right PI were not significant. The FC of the parahippocampus/hippocampus with dAI and PI were negatively correlated with the CD activity index (CDAI). CONCLUSIONS: We suggest that the insula-centered structural and/or functional changes may be associated with abnormal visceral sensory processing and related emotional responses in CD patients.

Regional Gray Matter Volume Changes in Brains of Patients With Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are 2 subtypes of inflammatory bowel disease (IBD). Several studies have reported brain abnormalities in IBD patients. This study aims to identify differences of gray matter volume (GMV) between patients with UC and healthy controls (HCs). METHODS: Fifty-seven patients with UC and 40 HCs underwent structural magnetic resonance imaging. Voxel-based morphometry method was used to detect GMV differences. Receiver operating characteristic (ROC) curve was applied to investigate reliable biomarkers for identifying patients with UC from HCs. Regression analysis was used to examine relationships between the structure alternations and clinical symptoms. RESULTS: Compared with HCs, patients with UC showed decreased GMV in the insula, thalamus, pregenual anterior cingulate cortex, hippocampus/parahippocampus, amygdala, and temporal pole; they showed increased GMV in the putamen, supplementary motor area, periaqueductal gray, hypothalamus, and precentral gyrus. Receiver operating characteristic analysis showed the highest classification power of thalamus. The inclusion of anxiety and depression as covariates eliminated the differences in the right insula, pregenual anterior cingulate cortex, supplementary motor area, and precentral gyrus. Most of the GMV changes were found in active patients with UC, with few changes in patients with UC in remission. We also found significantly negative correlation between UC duration and GMV in several regions. CONCLUSION: The current neuroimaging findings were involved in visceral sensory pathways and were partially associated with the levels of anxiety and depression and clinical stage of patients with UC. This study might provide evidence for possible neuromechanisms of UC.

The AC006262.5-miR-7855-5p-BPY2C axis facilitates hepatocellular carcinoma proliferation and migration.

Hepatocellular carcinoma (HCC) is typically fatal, and patients with hepatocellular carcinoma are usually diagnosed at the late stages. Although the treatments for HCC have been rapidly advancing, novel targets for HCC are still desperately needed, especially for targeted therapies. Here, we identified an enriched long non-coding RNA, AC006262.5, associated with HCC, that promoted the proliferation, migration, and invasiveness of HCC cells, both in vitro and in vivo. In addition, our results revealed that AC006262.5 bound to and regulated miR-7855-5p, a tumor-suppressive miRNA, in HCC. Moreover, our data show that AC006262.5 regulates the expression of BPY2C via miR-7855-5p. Finally, we found that AC006262.5 and miR-7855-5p formed a regulatory loop. Upregulation of AC006262.5 resulted in decreased expression of miR-7855-5p, and downregulation of miR-7855-5p further facilitated the expression of AC006262.5. Our work provides novel targets for HCC diagnosis and treatment, and sheds light on the lncRNA-miRNA regulatory nexus that controls the pathology of HCC.

Spindle and kinetochore-associated protein 2 facilitates the proliferation and invasion of hepatocellular carcinoma via the regulation of Wnt/ß-catenin signaling.

Recent studies have shown that spindle and kinetochore-associated protein 2 (SKA2) is dysregulated in multiple tumors and acts as a key regulator of tumor progression. However, whether SKA2 plays a role in hepatocellular carcinoma (HCC) has not been fully elucidated. The purpose of this study was to explore the expression, function and underlying molecular mechanism of SKA2 in HCC. We found that SKA2 was highly expressed in HCC tissues and cell lines. Knockdown of SKA2 caused marked reductions in the proliferative, colony-forming and invasive capacities of HCC cells, while SKA2 overexpression had opposite effects. Further experiments revealed that overexpression of SKA2 enhanced expression levels of phosphorylated glycogen synthase kinase-3ß (GSK-3ß) and active ß-catenin in HCC cells. Moreover, SKA3 overexpression enhanced transcriptional activity mediated by Wnt/ß-catenin signaling. Knockdown of SKA3 downregulated the activation of Wnt/ß-catenin signaling, and the effect was significantly reversed by the inhibition of GSK-3ß. Notably, inhibition of Wnt/ß-catenin signaling markedly abrogated SKA2-mediated promotion effect on HCC proliferation and invasion. In addition, knockdown of SKA2 impeded tumor formation and growth in HCC cells in a nude mouse in vivo model. Overall, these findings indicate that SKA2 accelerates the progression of HCC through the upregulation of Wnt/ß-catenin signaling. Our study highlights a potential role of SKA2 in HCC progression and suggests it as a possible target for HCC treatment.

MicroRNA-383 inhibits proliferation, migration, and invasion in hepatocellular carcinoma cells by targeting PHF8.

BACKGROUND: To study the effect of microRNA-383 (miR-383) on cell proliferation, migration, and invasion of hepatocellular carcinoma (HCC) cells, and explore its mechanism. METHODS: The expressions of miR-383 and plant homology domain that refers to protein 8 (PHF8) were detected in tissues and cells by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot respectively. The miR-383 group (transfected miR-383 mimics), miR-con group (transfected miR-con), si-con group (transfected si-con), si-PHF8 group (transfected si-PHF8), miR-383 + ctrl group (cotransfected miR-383 mimics and pcDNA-3.1), miR-383 + PHF8 group (cotransfected miR-383 mimics and pcDNA-3.1-PHF8) were transfected into HepG2 cells by liposome method. Cell proliferation, migration and invasion were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) or trans-well assays respectively. The luciferase activity of each group was detected by dual luciferase reporter gene assay. RESULTS: Compared with normal adjacent tissues, the expression of miR-383 was significantly down-regulated and the expression of PHF8 was significantly up-regulated (p < .05). Compared with normal hepatocellular cell LO2, the expression of miR-383 was significantly reduced (p < .05) in HCC cells. Moreover, overexpression of miR-383 or silencing of PHF8 significantly inhibited the proliferation, migration, and invasion of HCC cells. In addition, PHF8 was targeted by miR-383 and its restoration rescued the inhibitory effect of miR-383 on cell proliferation, migration, and invasion of HCC cells. CONCLUSION: miR-383 could inhibit the proliferation, migration, and invasion of HCC cells by targeting PHF8, which will provide a basis for miR-383 targeted therapy for HCC.

RP11-81H3.2 promotes gastric cancer progression through miR-339-HNRNPA1 interaction network.

Recent studies have demonstrated that various long non-coding RNAs (lncRNAs) participate in the gastric cancer (GC) development and metastasis. Some lncRNAs exert their regulatory function by interacting with microRNAs. Here we identified a novel lncRNA RP11-81H3.2 that was highly expressed in the GC tissue and cell lines. RP11-81H3.2 knockdown significantly inhibited the proliferation, migration, and invasion of GC cells. Mechanistically, we demonstrated that RP11-81H3.2 directly interacted with miR-339 while miR-339 regulated the HNRNPA1 expression by targeting HRRNPA1 3'-UTR. RP11-81H3.2-miR-339-HNRNPA1 interaction network regulated the GC cell proliferation, migration, and invasion. Moreover, our results confirmed that RP11-81H3.2 knockdown suppressed the tumor growth of GC in a xenograft model in vivo. In summary, the results suggest that RP11-81H3.2 functions as an oncogene in GC and could be utilized as a promising diagnosis and therapeutic marker for GC treatment.

Extrinsic ghrelin in the paraventricular nucleus increases small intestinal motility in rats by activating central growth hormone secretagogue and enteric cholinergic receptors.

BACKGROUND/OBJECTIVES: Ghrelin is a brain-gut peptide that regulates gastrointestinal (GI) motility. We hypothesized that the excitatory effect of ghrelin on the paraventricular nucleus (PVN) increases GI motility by activating the central growth hormone secretagogue receptor (GHSR) and central neuropeptide Y (NPY) signaling pathways, leading to increased enteric cholinergic activity. METHODS: Thirty-six male Sprague Dawley rats were maintained on duodenal catheterization and PVN cannulation. Small intestinal transit (SIT) was observed and rats were divided as follows: experimental animals received ghrelin injections in the PVN (0.03, 0.08, or 0.24 nM); 1 nM GHSR antagonist D-Lys3-GHRP6 alone; 1nM D-Lys3-GHRP6 before ghrelin injection in the PVN, respectively. Electrophysiologic parameters of the interdigestive myoelectric complex (IMC) were examined by administration of 0.24 nM ghrelin in the PVN after small intestinal electrode implantation and PVN cannulation. GI cholinergic pathway activation was analyzed after intravenous atropine administration. The involvement of central NPY signaling was evaluated by injecting an anti-NPY immunoglobulin (IgG) in the PVN. Neuronal expression of c-Fos in the brain and GI tract was examined using immunohistochemistry. RESULTS: Injection of ghrelin in the PVN dose-dependently accelerated SIT, and this excitatory effect was competitively inhibited by a GHSR antagonist. The excitatory effect of ghrelin on IMC activity was diminished by GHSR antagonism and NPY neutralization, as well as by blockade of peripheral muscarinic acetylcholine receptors. Extrinsic ghrelin significantly upregulated c-Fos expression in the PVN and other central nuclei, as well as in the enteric nervous plexuses of the stomach, duodenum, and proximal colon. The ghrelin-induced upregulation of central and enteric c-Fos expression was also dependent on central GHSR activation. CONCLUSIONS: Ghrelin positively regulates GI motility by exciting both central and enteric neurons, including those of the PVN, by activating GHSR and NPY pathways, and peripheral muscarinic acetylcholine receptors.

Gastrointestinal symptoms and associated factors in Chinese patients with functional dyspepsia.

AIM: To study the evolution of gastrointestinal symptoms and associated factors in Chinese patients with functional dyspepsia (FD). METHODS: From June 2008 to November 2009, a total of 1049 patients with FD (65.3% female, mean age 42.80 ± 11.64 years) who visited the departments of gastroenterology in Wuhan, Beijing, Shanghai, Guangzhou, and Xi'an, China were referred for this study. All of the patients fulfilled the Rome III criteria for FD. Baseline demographic data, dyspepsia symptoms, anxiety, depression, sleep disorder, and drug treatment were assessed using self-report questionnaires. Patients completed questionnaires at baseline and after 1, 3, 6 and 12 mo follow-up. Comparison of dyspepsia symptoms between baseline and after follow-up was explored using multivariate analysis of variance of repeated measuring. Multiple linear regression was done to examine factors associated with outcome, both longitudinally and horizontally. RESULTS: Nine hundred and forty-three patients (89.9% of the original population) completed all four follow-ups. The average duration of follow-up was 12.24 ± 0.59 mo. During 1-year follow-up, the mean dyspeptic symptom score (DSS) in FD patients showed a significant gradually reduced trend (P < 0.001), and similar differences were found for all individual symptoms (P < 0.001). Multiple linear regression analysis showed that sex (P < 0.001), anxiety (P = 0.018), sleep disorder at 1-year follow-up (P = 0.019), weight loss (P < 0.001), consulting a physician (P < 0.001), and prokinetic use during 1-year follow-up (P = 0.035) were horizontally associated with DSS at 1-year follow-up. No relationship was found longitudinally between DSS at 1-year follow-up and patient characteristics at baseline. CONCLUSION: Female sex, anxiety, and sleep disorder, weight loss, consulting a physician and prokinetic use during 1-year follow-up were associated with outcome of FD.

Silencing Prx1 and/or Prx5 sensitizes human esophageal cancer cells to ionizing radiation and increases apoptosis via intracellular ROS accumulation.

AIM: To investigate whether down-regulation of peroxiredoxin 1 (Prx1) and/or peroxiredoxin 5 (Prx5) sensitizes human esophageal cancer cells to ionizing radiation (IR). METHODS: Human esophageal carcinoma cell lines Eca-109 and TE-1 were used. Prx mRNA expression profiles in Eca-109 and TE-1 cells were determined using RT-PCR. Two highly expressed isoforms of Prxs, Prx1 and Prx5, were silenced by RNA interference (RNAi). Following IR, intracellular reactive oxygen species (ROS) and apoptosis were measured using flow cytometry, the activities of catalase, superoxide dismutase and glutathione peroxidase were measured, and the radiosensitizing effect of RNAi was observed. Tumor xenograft model was also used to examine the radiosensitizing effect of RNAi in vivo. RESULTS: Down-regulation of Prx1 and/or Prx5 by RNAi does not alter the activities of catalase, superoxide dismutase and glutathione peroxidase, but made human tumor cells more sensitive to IR-induced apoptosis both in vitro and in vivo. When the two isoforms were decreased simultaneously, intracellular ROS and apoptosis significantly increased after IR. CONCLUSION: Silencing Prx1 and/or Prx5 by RNAi sensitizes human Eca-109 and TE-1 cells to IR, and the intracellular ROS accumulation may contribute to the radiosensitizing effect of the RNAi.