Endoscopic Combined Drainage of One Giant and Multiple Small Pancreatic Pseudocysts: A Case Report.

A pancreatic pseudocyst (PPC) is a frequent complication of pancreatitis, often stemming from alcohol, gallstones, or hyperlipidemia. Endoscopic treatment of PPC has become the mainstream treatment. A case of one giant and multiple small PPCs was observed, manifesting as repeated abdominal bloating, abdominal pain, nausea, and vomiting after meals. Initial computed tomography scans revealed the presence of multiple PPCs. Despite ineffective medical treatment, the pseudocysts progressively increased. In response, we conducted a combined endoscopic intervention, involving Hot AXIOS (Boston Scientific, Marlborough, MA) stenting through endoscopic ultrasound-guided transmural drainage (EUS-TMD) and the placement of the endoscopic nasopancreatic drainage (ENPD) mimic stent through endoscopic retrograde pancreatography (ERP). Remarkably, after nine months of postoperative follow-up, the patient had no discomfort symptoms and the cyst disappeared. We conducted a literature review on endoscopic combined drainage for PPCs, which is still controversial. Our presented case serves as a demonstration that endoscopic combined drainage can effectively and successfully manage giant and multiple PPCs.

Sensitive, Low-Background-Signal miRNA Analysis via the Self-Priming-Initiated Color Reaction Loaded on a Rolling Circle Amplification Product.

MicroRNAs (miRNAs) have been regarded as potential biomarkers in evaluating various diseases, such as pregnancy-induced hypertension and cancers. However, sensitive and reliable miRNA detection is still a challenge due to the low amplification efficiency and high background signal. Herein, we developed a colorimetric method for miRNA detection utilizing the self-priming-initiated color reaction loaded on a rolling circle amplification (RCA) product. In this method, a biotin-labeled RCA product is fixed on the surface of the streptavidin-coated wells, and the interfering components in samples are removed to avoid false reactions, thus reducing the background signals. Two signal amplification processes, including RCA and self-priming-initiated chain extension, endow the method with high sensitivity and a low limit of detection at the 10 fM level. In conclusion, our approach offers a promising perspective on sensitive and reliable miRNA detection and has the potential to be further utilized in biomedical research and early cancer detection.

Cystatin C-based estimated glomerular filtration rate and risk of stroke in the general population: a prospective cohort study.

Background: Previous results on the association between the estimated glomerular filtration rate (eGFR) and stroke are mixed. Most studies derived the eGFR from serum creatinine, which is affected by non-kidney determinants and thus has possibly biased the association with stroke risk. Methods: In this cohort study, we included 429 566 UK Biobank participants (94.5% white, 54% women, age 56 ± 8 years) free of stroke at enrollment. The eGFRcys and eGFRcr were calculated with serum cystatin C and creatinine, respectively. Outcomes of interest were risk of total stroke and subtypes. We investigated the linear and nonlinear associations using Cox proportional hazards models and restricted cubic splines, corrected for regression dilution bias. Results: During an average follow-up of 10.11 years, 4427 incident strokes occurred, among which 3447 were ischemic and 1163 were hemorrhagic. After adjustment for confounders, the regression dilution-corrected hazard ratios (95% confidence intervals) for every 10 mL/min/1.73 m2 decrement in eGFRcys were 1.10 (1.05-1.14) for total stroke and 1.11 (1.08-1.15) for ischemic stroke. A similar pattern was observed with eGFRcr, although the association was weaker. When either type of eGFR was below 75 mL/min/1.73 m2, the risks of total and ischemic stroke increased exponentially as eGFR decreased. A U-shaped relationship was witnessed if eGFRcr was used instead. There was a null association between eGFR and hemorrhagic stroke. Conclusions: The risks of total stroke and ischemic stroke increased exponentially when the eGFRcys fell below 75 mL/min/1.73 m2.

Development and validation of a deep learning-based approach to predict the Mayo endoscopic score of ulcerative colitis.

Background: The ulcerative colitis (UC) Mayo endoscopy score is a useful tool for evaluating the severity of UC in patients in clinical practice. Objectives: We aimed to develop and validate a deep learning-based approach to automatically predict the Mayo endoscopic score using UC endoscopic images. Design: A multicenter, diagnostic retrospective study. Methods: We collected 15120 colonoscopy images of 768 UC patients from two hospitals in China and developed a deep model based on a vision transformer named the UC-former. The performance of the UC-former was compared with that of six endoscopists on the internal test set. Furthermore, multicenter validation from three hospitals was also carried out to evaluate UC-former's generalization performance. Results: On the internal test set, the areas under the curve of Mayo 0, Mayo 1, Mayo 2, and Mayo 3 achieved by the UC-former were 0.998, 0.984, 0.973, and 0.990, respectively. The accuracy (ACC) achieved by the UC-former was 90.8%, which is higher than that achieved by the best senior endoscopist. For three multicenter external validations, the ACC was 82.4%, 85.0%, and 83.6%, respectively. Conclusions: The developed UC-former could achieve high ACC, fidelity, and stability to evaluate the severity of UC, which may provide potential application in clinical practice. Registration: This clinical trial was registered at the ClinicalTrials.gov (trial registration number: NCT05336773).

Why was this study done? The development of an auxiliary diagnostic tool can reduce the workload of endoscopists and achieve rapid assessment of ulcerative colitis (UC) severity. What did the researchers do? We developed and validated a deep learning-based approach to automatically predict the Mayo endoscopic score using UC endoscopic images. What did the researchers find? The model that was developed in this study achieved high accuracy, fidelity, and stability, and demonstrated potential application in clinical practice. What do the findings mean? Deep learning could effectively assist endoscopists in evaluating the severity of UC in patients using endoscopic images.

Implantation underneath the abdominal anterior rectus sheath enables effective and functional engraftment of stem-cell-derived islets.

Human pluripotent stem cell-derived islets (hPSC islets) are a promising alternative to primary human islets for the treatment of insulin-deficient diabetes. We previously demonstrated the feasibility of this approach in nonhuman primates; however, the therapeutic effects of hPSC islets can be limited by the maladaptive processes at the transplantation site. Here, we demonstrate successful implantation of hPSC-derived islets in a new transplantation site in the abdomen, the subanterior rectus sheath, in eight nonhuman primates (five male and three female). In this proof-of-principle study, we find that hPSC islets survive and gradually mature after transplantation, leading to improved glycemic control in diabetic primates. Notably, C-peptide secretion responds to meal challenge from 6 weeks post-transplantation (wpt), with stimulation indices comparable to those of native islets. The average post-prandial C-peptide level reaches approximately 2.0 ng ml-1 from 8 wpt, which is five times higher than the peak value we previously obtained after portal vein infusion of hPSC islets and was associated with a decrease of glycated hemoglobin levels by 44% at 12 wpt. Although additional studies in larger cohorts involving long-term follow-up of transplants are needed, our results indicate that the subanterior rectus sheath supports functional maturation and maintenance of hPSC islets, suggesting that it warrants further exploration as a transplantation target site in the context of for hPSC-based cell-replacement therapies.

Trends in medication use and treatment patterns in Chinese patients with inflammatory bowel disease.

BACKGROUND: Medications for inflammatory bowel disease (IBD) have changed dramatically over time. However, no study on long-term medication profiles has been conducted in the Chinese population. AIM: To evaluate temporal changes in medication use and treatment patterns for Chinese patients with IBD. METHODS: A multicenter retrospective cohort study was conducted among Chinese patients newly diagnosed with Crohn's disease (CD) and ulcerative colitis (UC) between January 1999 and December 2019. Baseline characteristics and drug prescriptions were collected. Trends in medication use and therapeutic patterns were analyzed. RESULTS: In total, 3610 patients were analyzed. During follow-up, 5-aminosalicylates (5-ASA) and corticosteroids (CS) prescriptions gradually decreased, accompanied by a notable increase in immunosuppressants (IMS) and infliximab (IFX) prescriptions in patients with CD. Prescription rates of 5-ASA and CS were stable, whereas IMS and IFX slightly increased since 2007 in patients with UC. Subgroup (n = 957) analyses showed a switch from conventional medications to IFX in patients with CD, while 5-ASA and CS were still steadily prescribed in patients with UC. Logistic regression analyses revealed that surgical history, disease behavior, and disease location were associated with initial therapeutic strategies in patients with CD. However, medications before diagnosis, disease location, and diagnostic year might affect initial strategies in patients with UC. CONCLUSION: Long-term treatment strategies analyses has provided unique insight into the switch from conventional drugs to IFX in Chinese patients with CD.

Is metformin a possible treatment for diabetic neuropathy?

Metformin is a hypoglycemic drug widely used in the treatment of type 2 diabetes. It has been proven to have analgesic and neuroprotective effects. Metformin can reverse pain in rodents, such as diabetic neuropathic pain, neuropathic pain caused by chemotherapy drugs, inflammatory pain and pain caused by surgical incision. In clinical use, however, metformin is associated with reduced plasma vitamin B12 levels, which can further neuropathy. In rodent diabetes models, metformin plays a neuroprotective and analgesic role by activating adenosine monophosphate-activated protein kinase, clearing methylgloxal, reducing insulin resistance, and neuroinflammation. This paper also summarized the neurological adverse reactions of metformin in diabetic patients. In addition, whether metformin has sexual dimorphism needs further study.

Development and Validation of a Deep Neural Network for Accurate Identification of Endoscopic Images From Patients With Ulcerative Colitis and Crohn's Disease.

Background and Aim: The identification of ulcerative colitis (UC) and Crohn's disease (CD) is a key element interfering with therapeutic response, but it is often difficult for less experienced endoscopists to identify UC and CD. Therefore, we aimed to develop and validate a deep learning diagnostic system trained on a large number of colonoscopy images to distinguish UC and CD. Methods: This multicenter, diagnostic study was performed in 5 hospitals in China. Normal individuals and active patients with inflammatory bowel disease (IBD) were enrolled. A dataset of 1,772 participants with 49,154 colonoscopy images was obtained between January 2018 and November 2020. We developed a deep learning model based on a deep convolutional neural network (CNN) in the examination. To generalize the applicability of the deep learning model in clinical practice, we compared the deep model with 10 endoscopists and applied it in 3 hospitals across China. Results: The identification accuracy obtained by the deep model was superior to that of experienced endoscopists per patient (deep model vs. trainee endoscopist, 99.1% vs. 78.0%; deep model vs. competent endoscopist, 99.1% vs. 92.2%, P < 0.001) and per lesion (deep model vs. trainee endoscopist, 90.4% vs. 59.7%; deep model vs. competent endoscopist 90.4% vs. 69.9%, P < 0.001). In addition, the mean reading time was reduced by the deep model (deep model vs. endoscopists, 6.20 s vs. 2,425.00 s, P < 0.001). Conclusion: We developed a deep model to assist with the clinical diagnosis of IBD. This provides a diagnostic device for medical education and clinicians to improve the efficiency of diagnosis and treatment.

Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates.

Human pluripotent stem-cell-derived islets (hPSC-islets) are a promising cell resource for diabetes treatment1,2. However, this therapeutic strategy has not been systematically assessed in large animal models physiologically similar to humans, such as non-human primates3. In this study, we generated islets from human chemically induced pluripotent stem cells (hCiPSC-islets) and show that a one-dose intraportal infusion of hCiPSC-islets into diabetic non-human primates effectively restored endogenous insulin secretion and improved glycemic control. Fasting and average pre-prandial blood glucose levels significantly decreased in all recipients, accompanied by meal or glucose-responsive C-peptide release and overall increase in body weight. Notably, in the four long-term follow-up macaques, average hemoglobin A1c dropped by over 2% compared with peak values, whereas the average exogenous insulin requirement reduced by 49% 15 weeks after transplantation. Collectively, our findings show the feasibility of hPSC-islets for diabetic treatment in a preclinical context, marking a substantial step forward in clinical translation of hPSC-islets.

RFWD3 Participates in the Occurrence and Development of Colorectal Cancer via E2F1 Transcriptional Regulation of BIRC5.

Objectives: Colorectal cancer (CRC) is one of the most common human malignancies. It was reported that the alterations in the DNA damage response (DDR) pathways are emerging as novel targets for treatment across different cancer types including CRC. RFWD3 plays a critical role in replication protein A (RPA)-mediated DNA damage in cancer cells. More importantly, RFWD3 can response to DNA damage by positively regulating p53 stability when the G1 cell cycle checkpoint is activated. However, the functional significance of RFWD3 in CRC has not been reported in the existing documents. Materials and Methods: Here, we revealed high expression of RFWD3 in CRC tissues by IHC analysis and The Cancer Genome Atlas (TCGA) database. Besides, overexpression of RFWD3 in CRC cell lines was also confirmed by qRT-PCR and western blot assay. The Celigo cell counting method and wound-healing/transwell migration assay were applied to evaluate CRC cell proliferation and migration. The tumor growth indicators were quantified in nude mice xenografted with shRFWD3 and shCtrl RKO cells. Results: The results indicated that RFWD3 knockdown restricted CRC development in vitro and in vivo. In exploring the downstream mechanism of RFWD3's action, we found that RFWD3 could transcriptionally activate BIRC5 by interacting with E2F transcription factor 1 (E2F1). Accordingly, we identified BIRC5 as a downstream gene of RFWD3 regulating CRC. Subsequent loss- and gain- of function experiments demonstrated that upon overexpressing BIRC5 in RKO cells with down-regulated RFWD3, the inhibitory effects of cell proliferation, migration and colony formation could be reversed, while the capacity of cell apoptosis was ameliorated, suggesting that the effects of RFWD3 depletion was mainly due to BIRC5 suppression. Conclusion: Taken together, this study revealed that RFWD3 participates in the occurrence and development of colorectal cancer via E2F1 transcriptional regulation of BIRC5.

Erythromycin inhibits cigarette smoke-induced inflammation through regulating the PPARγ/NF-κB signaling pathway in macrophages.

Chronic obstructive pulmonary disease is characterized by chronic inflammation of the airway and lungs. Accumulating evidence has suggested that erythromycin (EM) plays a protective role against cigarette smoke-induced oxidative stress and the inflammatory response. However, the underlying mechanisms remain relatively unclear. The present study aimed to investigate the role of EM in inhibiting cigarette smoke-induced inflammation in human macrophages and its potential mechanism. A Cell Counting Kit-8 assay was used to determine the optimum concentration of EM and cigarette smoke extract (CSE) and it was found that 0.1 and 1% CSE and 0.1, 1.0 and 10 µg/ml EM exerted no significant effect on the cell proliferation activity, whereas 2 and 3% CSE exerted a significant inhibitory effect over the cell proliferation activity. We observed that 10 µmol/ml GW9662 (A PPARγ antagonist) and the presence of 1% CSE could promote the expression and activation of NF-κB p65. And this increased the expression of IL-6, IL-8 and reactive oxygen species (ROS). At the same time, 10 µmol/ml GW9662 and 1% CSE was found to inhibit the expression and activation of peroxisome proliferator activated receptors γ (PPARγ); However, 1 µg/ml EM was discovered to reverse these effects. Co-immunoprecipitation subsequently discovered an interaction between PPARγ and NF-κB p65. In conclusion, the present study suggested that EM may reduce the damage of PPARγ by inhibiting oxidative stress and reducing the expression of ROS and finally relieving cigarette smoke-induced inflammation through the PPARγ/NF-κB signaling pathway in macrophages.

Autophagy and Gastrointestinal Diseases.

Normal gastrointestinal physiology is fundamental for all the living beings. Gastrointestinal diseases mainly include gastrointestinal motility disorders, infectious inflammation (such as Helicobacter pylori infection, cholera, and intestinal parasites), non-infectious inflammation (such as chronic gastritis and Crohn's disease), and gastrointestinal cancers. In addition, intestinal microbial disorder is also an important cause of intestinal diseases, so intestinal microecological treatment (fecal microbiota transplantation) is an important mean of treating gastrointestinal diseases. In recent years, the role of autophagy in gastrointestinal diseases has been studied extensively. Autophagy is observed under various pathological processes of the gastrointestinal tract. For example, it has been demonstrated that autophagy plays an important role in maintaining the homeostasis and integrity of intestinal epithelium. Additionally, autophagy regulates host response to H. pylori infection and development of gastrointestinal cancers. Therefore, we will discuss pivotal roles of autophagy in various gastrointestinal diseases and analyze the underlying molecular mechanisms, which may provide new therapeutic targets applicable for the treatment of gastrointestinal diseases.

Pharmacological Targeting of Vacuolar H+-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer.

Multidrug resistance (MDR) in cancer remains a major challenge for the success of chemotherapy. Natural products have been a rich source for the discovery of drugs against MDR cancers. Here, we applied high-throughput cytotoxicity screening of an in-house natural product library against MDR SGC7901/VCR cells and identified that the cyclodepsipeptide verucopeptin demonstrated notable antitumor potency. Cytological profiling combined with click chemistry-based proteomics revealed that ATP6V1G directly interacted with verucopeptin. ATP6V1G, a subunit of the vacuolar H+-ATPase (v-ATPase) that has not been previously targeted, was essential for SGC7901/VCR cell growth. Verucopeptin exhibited strong inhibition of both v-ATPase activity and mTORC1 signaling, leading to substantial pharmacological efficacy against SGC7901/VCR cell proliferation and tumor growth in vivo. Our results demonstrate that targeting v-ATPase via its V1G subunit constitutes a unique approach for modulating v-ATPase and mTORC1 signaling with great potential for the development of therapeutics against MDR cancers.

Taenia solium insulin receptors: promising candidates for cysticercosis treatment and prevention.

Insulin signaling pathway is an ancient and highly conserved pathway known to play critical roles in cell growth, control and metabolic regulation. In this study, we identified and characterized two insulin receptor genes (TsIR-1316 and TsIR-4810) from Taenia solium. TsIR-1316 was grouped with E. multilocularis insulin receptor (EmIR-1) and TsIR-4810 was closer to Taenia pisiformis insulin-like growth factor receptor (TpIR) on the same branch with a very high bootstrap value. TsIR-1316 was located on the integument of larvae and adult worms, as well as the ovary of adults and eggs. Alternatively, TsIR-4810 was located in the parenchyma and reproductive organs of the adult worms. By using in vitro cultivation systems with Cysticercus pisiformis as a model, we demonstrated that anti-TsIRs-LBD antibodies could effectively block the insulin signaling pathway, resulting in reduced phosphorylation of the insulin receptor as well as lower levels of glucose uptake and glycogen synthesis. The rabbits immunized with TsIR-1316-LBD, TsIR-4810-LBD and TsIR-1316-LBD + TsIR-4810-LBD produced protection against infection of T. pisiformis as demonstrated by a 94.6%, 96% and 80% reduction of establishment of larvae, respectively. These data suggested that TsIR-1316-LBD and TsIR-4810-LBD are promising vaccine candidates or novel drug targets against swine cysticercosis.

BRD4 Promotes Gastric Cancer Progression and Metastasis through Acetylation-Dependent Stabilization of Snail.

Cancer metastasis, a leading cause of death in patients, is associated with aberrant expression of epigenetic modifiers, yet it remains poorly defined how epigenetic readers drive metastatic growth and whether epigenetic readers are targetable to control metastasis. Here, we report that bromodomain-containing protein 4 (BRD4), a histone acetylation reader and emerging anticancer therapeutic target, promotes progression and metastasis of gastric cancer. The abundance of BRD4 in human gastric cancer tissues correlated with shortened metastasis-free gastric cancer patient survival. Consistently, BRD4 maintained invasiveness of cancer cells in vitro and their dissemination at distal organs in vivo. Surprisingly, BRD4 function in this context was independent of its putative transcriptional targets such as MYC or BCL2, but rather through stabilization of Snail at posttranslational levels. In an acetylation-dependent manner, BRD4 recognized acetylated lysine 146 (K146) and K187 on Snail to prevent Snail recognition by its E3 ubiquitin ligases FBXL14 and ß-Trcp1, thereby inhibiting Snail polyubiquitination and proteasomal degradation. Accordingly, genome-wide transcriptome analyses identified that BRD4 and Snail regulate a partially shared metastatic gene signature in gastric cancer cells. These findings reveal a noncanonical posttranscriptional regulatory function of BRD4 in maintaining cancer growth and dissemination, with immediate translational implications for treating gastric metastatic malignancies with clinically available bromodomain inhibitors. SIGNIFICANCE: These findings reveal a novel posttranscriptional regulatory function of the epigenetic reader BRD4 in cancer metastasis via stabilizing Snail, with immediate translational implication for treating metastatic malignancies with clinically available bromodomain inhibitors. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/79/19/4869/F1.large.jpg.

Identification of Candidate Genes Associated with Chemotherapy Resistance in Ovarian Cancer.

Ovarian cancer is the leading cause of death due to malignant tumors in female reproductive organs. However, the lack of understanding regarding its pathogenesis brings difficulties to study it. In this study, we analyze the differently expressed genes in both GSE54388 (ovarian cancer vs. normal ovarian tissues) and GSE51373 (chemotherapy-resistant vs. chemotherapy-sensitive tissues). By intersecting the differently expressed genes, 79 genes were identified. Then, further function enrichment analysis, including GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis, was performed. Also, a protein-protein network analysis was conducted to reveal the potential relationship between genes. Finally, survival analysis was utilized to find out that FOXL2 (Forkhead Box L2), TIMP3 (TIMP Metallopeptidase Inhibitor 3), and ZEB1 (Zinc Finger E-Box Binding Homeobox 1) may serve as biomarkers for predicting the prognosis of ovarian cancer patients.

Epigenetic restriction of Hippo signaling by MORC2 underlies stemness of hepatocellular carcinoma cells.

The evolutionarily conserved Hippo signaling pathway is a key regulator of stem cell self-renewal, differentiation, and organ size. While alterations in Hippo signaling are causally linked to uncontrolled cell growth and a broad range of malignancies, genetic mutations in the Hippo pathway are uncommon and it is unclear how the tumor suppressor function of the Hippo pathway is disrupted in human cancers. Here, we report a novel epigenetic mechanism of Hippo inactivation in the context of hepatocellular carcinoma (HCC). We identify a member of the microrchidia (MORC) protein family, MORC2, as an inhibitor of the Hippo pathway by controlling upstream Hippo regulators, neurofibromatosis 2 (NF2) and kidney and brain protein (KIBRA). Mechanistically, MORC2 forms a complex with DNA methyltransferase 3A (DNMT3A) at the promoters of NF2 and KIBRA, leading to their DNA hyper-methylation and transcriptional repression. As a result, NF2 and KIBRA are crucial targets of MORC2 to regulate confluence-induced activation of Hippo signaling and contact inhibition of cell growth under both physiological and pathological conditions. The MORC2-NF2/KIBRA axis is critical for maintaining self-renewal, sorafenib resistance, and oncogenicity of HCC cells in vitro and in nude mice. Furthermore, MORC2 expression is elevated in HCC tissues, associated with stem-like properties of cancer cells, and disease progression in patients. Collectively, MORC2 promotes cancer stemness and tumorigenesis by facilitating DNA methylation-dependent silencing of Hippo signaling and could be a potential molecular target for cancer therapeutics.

Nonsense-mediated mRNA decay: a 'nonsense' pathway makes sense in stem cell biology.

Nonsense-mediated mRNA decay (NMD) is a highly conserved post-transcriptional regulatory mechanism of gene expression in eukaryotes. Originally, NMD was identified as an RNA surveillance machinery in degrading 'aberrant' mRNA species with premature termination codons. Recent studies indicate that NMD regulates the stability of natural gene transcripts that play significant roles in cell functions. Although components and action modes of the NMD machinery in degrading its RNA targets have been extensively studied with biochemical and structural approaches, the biological roles of NMD remain to be defined. Stem cells are rare cell populations, which play essential roles in tissue homeostasis and hold great promises in regenerative medicine. Stem cells self-renew to maintain the cellular identity and differentiate into somatic lineages with specialized functions to sustain tissue integrity. Transcriptional regulations and epigenetic modulations have been extensively implicated in stem cell biology. However, post-transcriptional regulatory mechanisms, such as NMD, in stem cell regulation are largely unknown. In this paper, we summarize the recent findings on biological roles of NMD factors in embryonic and tissue-specific stem cells. Furthermore, we discuss the possible mechanisms of NMD in regulating stem cell fates.

Prenatal Exposure to Lipopolysaccharide Alters Renal DNA Methyltransferase Expression in Rat Offspring.

Prenatal exposure to inflammation results in hypertension during adulthood but the mechanisms are not well understood. Maternal exposure to lipopolysaccharide (LPS) alters interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels in the fetal environment. As reported in many recent studies, IL-6 regulates DNA methyltransferases (DNMTs) through the transcription factor friend leukemia virus integration 1 (Fli-1). The present study explores the role of intrarenal DNMTs during development of hypertension induced by prenatal exposure to LPS. Pregnant rats were randomly divided into four treatment groups: control, LPS, pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor), and the combination of LPS and PDTC. Expression of IL-6, Fli-1, TNF-α, DNMT1 and DNMT3B was significantly increased in the offspring of LPS-treated rats. Global DNA methylation level of renal cortex also increased dramatically in rat offspring of the LPS group. Prenatal PDTC administration reversed the increases in gene expression and global DNA methylation level. These findings suggest that prenatal exposure to LPS may result in changes of intrarenal DNMTs through the IL-6/Fli-1 pathway and TNF-α, which probably involves hypertension in offspring due to maternal exposure to inflammation.