DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for intestinal impaction — screening already-approved drugs against its 24-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleIntestinal impaction maps to a 24-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for intestinal impaction is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
late endosomal/lysosomal adaptor, MAPK and MTOR activator 5 (LAMTOR5) — LAMTOR5 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet ipadrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3MSH · 1.51 Å · ligand ISOPROPYL ALCOHOL (IPA). Experimental structure, not a prediction.
What the evidence adds up to
The abstracts provided do not address intestinal impaction directly; they concern enteric infections, inflammatory bowel disease models, short bowel syndrome, radiation injury, and a surgical reconstruction case series. One 2013 study of twelve patients with short bowel syndrome (small-bowel remnant length 59±9 cm) treated with growth hormone (0.05 mg/kg/day), oral glutamine (30 g/day), and enteral nutrition for four weeks reported significantly improved intestinal absorptive capacity and plasma protein levels, with increased body weight, lean body mass, total body water, and body cell mass, and no deaths at three-month follow-up. The authors themselves note that benefit remains controversial and depends on patient selection. No data on impaction are given.
Two cell-culture studies (2020 and 2019) using Caco-2 cells show that Lycium barbarum polysaccharides and total polysaccharides of adlay bran each reduced TNF-α-induced increases in paracellular permeability, restored transepithelial electrical resistance, and suppressed pro-inflammatory cytokine secretion (IL-8, IL-6, ICAM-1, MCP-1) and NF-κB p65 activation. These are in vitro findings on barrier dysfunction, not evidence for treating impaction. A 2024 mouse study of the TLR5 agonist CBLB502 (0.2 mg/kg) before ionising radiation reported reduced intestinal injury and improved survival, with gene expression changes reversed after irradiation; again, no relevance to impaction is established.
A 2014 mouse study found that early-life exposure to airborne particulate matter increased colonic pro-inflammatory cytokines, bacterial translocation to mesenteric lymph nodes, and reduced IL-17A and Bifidobacterium, and worsened responses to dextran sodium sulfate-induced colitis. A 2020 piglet study of porcine circovirus type 2 infection showed ileal villus damage, epithelial cell exfoliation, decreased secretory IgA, and altered immune-related gene expression. A 1995 retrospective review of seven patients (six children, one adult) undergoing lower urinary tract reconstruction with stomach and ileum reported no renal deterioration, one episode of hyponatremia during gastrointestinal illness, and one case of hematuria-dysuria syndrome; no ulceration in six evaluable patients.
For intestinal impaction specifically, there is no clinical trial, no animal model of impaction, and no drug tested against that condition in these abstracts. What is missing is any study that defines impaction as an endpoint, any randomised controlled trial in humans, and any stratification by cause (e.g., obstruction, constipation, post-surgical adhesions) or by patient comorbidity. Without such data, no agent from these papers can be assessed for efficacy in impaction.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of Clinical Investigation · 2008 · 501 citations · open access
Enteric infections, diarrhea, and their impact on function and development
AbstractEnteric infections, with or without overt diarrhea, have profound effects on intestinal absorption, nutrition, and childhood development as well as on global mortality. Oral rehydration therapy has reduced the number of deaths from dehydration caused by infection with an enteric pathogen, but it has not changed the morbidity caused by such infections. This Review focuses on the interactions between enteric pathogens and human genetic determinants that alter intestinal function and inflammation and profoundly impair human health and development. We also discuss specific implications for novel approaches to interventions that are now opened by our rapidly growing molecular understanding.
<i>Lycium barbarum</i> polysaccharides ameliorate intestinal barrier dysfunction and inflammation through the MLCK-MLC signaling pathway in Caco-2 cells
AbstractImpairment of the intestinal barrier often occurs in inflammatory bowel diseases, and pro-inflammatory factors play a vital role in the pathogenesis of intestinal diseases. In our study, the potential protective effects of Lycium barbarum polysaccharides (LBP) against intestinal barrier dysfunction evoked by pro-inflammatory factors and its anti-inflammatory effects were investigated. Caco-2 cells were stimulated with or without tumor necrosis factor (TNF)-α in the presence or absence of LBP. Our findings showed that LBP assuaged the increase of paracellular permeability and the decrease of transepithelial electrical resistance (TER) in Caco-2 cells. In addition, LBP also prevented the secretion of pro-inflammatory markers (IL-8, IL-6, ICAM-1 and MCP-1) in TNF-α-challenged Caco-2 cells. Moreover, LBP inhibited the overexpression of tight junction (TJ) proteins (claudin-1, ZO-3, and occludin) and the increase of MLCK, pMLC, p-IκBα and NFκBp65 protein expression evoked by TNF-α was suppressed by LBP pre-incubation. This finding indicated that LBP improve TNF-α-evoked intestinal barrier dysfunction via suppressing the MLCK-MLC signaling pathway mediated by NFκB.
Exposure to Ingested Airborne Pollutant Particulate Matter Increases Mucosal Exposure to Bacteria and Induces Early Onset of Inflammation in Neonatal IL-10–Deficient Mice
AbstractBACKGROUND: Epidemiological associations between early-life air pollution exposure and increased risk of inflammatory bowel diseases have been shown. Our aim was to determine if exposure to airborne particulate matter (PM(10)) during the neonatal period would alter colitis in the interleukin (IL)-10(-/-) mouse model. METHODS: IL-10(-/-) pregnant dams and pups were fed chow ± PM(10) (9 μg/g) and pups were studied at 10, 14, and 20 weeks. Twenty-week-old mice were given 2% dextran sodium sulfate. Metagenomic analysis of stool was performed. Bacterial translocation was assessed by serum lipopolysaccharide and culturing bacteria from mesenteric lymph nodes and spleen. Cytokine expression was measured in gut homogenates using the MesoScale discovery platform. PM(10) was applied to CMT93 cells ± J744 macrophages, and resistance and cytokine secretion were assessed. THP-1 macrophages were incubated with Escherichia coli HB101 ± PM(10) for assessment of uptake and killing. RESULTS: PM(10) exposure increased colonic proinflammatory cytokines and bacterial translocation into mesenteric lymph nodes, whereas IL-17A levels were reduced in PM(10)-fed 10-week-old mice. Bifidobacterium was decreased in mice fed PM(10), whereas serum lipopolysaccharide was increased. PM(10) interfered with phagocytosis and killing in THP-1 cells. In coculture, PM(10) increased tumor necrosis factor α and fluorescein isothiocyanate-dextran flux. After dextran sodium sulfate treatment, PM10-fed mice responded with increased colonic tumor necrosis factor α and IL-1β and a larger percentage of PM(10)-fed mice had live bacteria in the mesenteric lymph nodes. CONCLUSIONS: Our data suggest that early exposure to pollution particulates can result in an earlier onset of intestinal disease in genetically susceptible hosts and can alter responses to gut injury in later life.
Total polysaccharides of adlay bran ( <i>Coix lachryma-jobi</i> L.) improve TNF-α induced epithelial barrier dysfunction in Caco-2 cells <i>via</i> inhibition of the inflammatory response
AbstractDysfunction of the intestinal epithelial barrier plays an important role in the pathogenesis of several intestinal diseases, including celiac disease, inflammatory bowel disease, and irritable bowel syndrome. The present research was carried out to investigate the protective effect of total polysaccharides of adlay bran (TPA) on TNF-α-evoked epithelial barrier dysfunction in Caco-2 cells. Caco-2 cells were treated with or without TPA in the absence or presence of TNF-α, and transepithelial electrical resistance (TEER) and Phenol Red flux were assayed to evaluate the intestinal epithelial barrier function. The results indicated that TPA suppressed the TNF-α-induced release of pro-inflammatory factors. Furthermore, TPA obviously assuaged both the increased paracellular permeability and the decrease of TEER in TNF-α-challenged Caco-2 cells. Furthermore, TPA obviously assuaged TNF-α-evoked up-regulation of IL-8 and IL-6 expression, down-regulation of occludin and ZO-3 expression, and markedly suppressed the activation and protein expression of NF-κB p65. Our results indicated that TPA assuages the TNF-α-evoked dysfunction of the intestinal epithelial barrier by inhibiting the NF-κB p65-mediated inflammatory response.
Stomach in Combination with Other Intestinal Segments in Pediatric Lower Urinary Tract Reconstruction
AbstractPURPOSE: We report the results of combining gastric and ileal segments in a small group of predominantly pediatric patients. MATERIALS AND METHODS: We retrospectively reviewed the records of 6 children and 1 adult who underwent lower urinary tract reconstruction using stomach and ileum, including 3 simultaneous and 4 staged procedures. Followup was 13 to 59 months. RESULTS: No patient had deterioration of renal function due to impaired upper tract drainage. One patient had an episode of hyponatremia during a gastrointestinal illness. The adult has the hematuria-dysuria syndrome and receives omeprazole. No ulceration developed in the 6 evaluable patients. CONCLUSIONS: The combined use of stomach and ileum has been effective in this small group of challenging patients. Long-term followup is mandatory.
The Turkish Journal of Gastroenterology · 2013 · 19 citations · open access
Effect of growth hormone, glutamine, and enteral nutrition on intestinal adaptation in patients with short bowel syndrome
AbstractBACKGROUND/AIMS: In the management of short bowel syndrome, the benefits of treatment with growth hormone, glutamine, and enteral nutrition for intestinal adaptation is still controversial. The aim of the current study was to determine whether growth hormone, glutamine, and enteral nutrition had positive effect on intestinal adaptation. MATERIALS AND METHOD: Twelve patients with short bowel syndrome (small-bowel remnant length, 59±9 cm; mean±SEM) received growth hormone (0.05 mg/kg/day), oral glutamine (30 g/day), plus enteral nutrition for 4 weeks. Intestinal absorptive capacity and biochemical parameters were investigated before treatment and after treatment. Body composition was determined by bioelectric impedance analysis. RESULT: All patients completed the treatment. Intestinal absorptive capacity and plasma levels of proteins were significantly improved after treatment. Body weight, lean body mass, total body water, and body cell mass also increased without any major adverse effects. At the 3-month follow-up, the nutritional status of patients was also well maintained, and there was no death during this period. CONCLUSION: Four weeks of intestinal rehabilitation therapy significantly improved intestinal absorption if appropriate patient with short bowel syndrome was selected.
Journal of Veterinary Science · 2020 · 8 citations · open access
The changes of immune-related molecules within the ileal mucosa of piglets infected with porcine circovirus type 2
AbstractBACKGROUND: Enteritis is one of the most frequently reported symptoms in piglets infected with porcine circovirus type 2 (PCV2), but the immunopathogenesis has not been reported. OBJECTIVES: This study examined the effect of a PCV2 infection on the intestinal mucosal immune function through morphological observations and immune-related molecular detection. METHODS: Morphological changes within the ileum of piglets during a PCV2 infection were observed. The expression of the related-molecules was analyzed using a gene chip. The immunocyte subsets were analyzed by flow cytometry. The secretory immunoglobulin A (SIgA) content was analyzed by enzyme-linked immunosorbent assay. RESULTS: The PCV2 infection caused ileal villus damage, intestinal epithelial cells exfoliation, and an increase in lymphocytes in the lamina propria at 21 days post-infection. Differentially expressed genes occurred in the defense response, inflammatory response, and the complement and coagulation cascade reactions. Most of them were downregulated significantly at the induction site and upregulated at the effector site. The genes associated with SIgA production were downregulated significantly at the induction site. In contrast, the expression of the Toll-like receptor-related genes was upregulated significantly at the effector site. The frequencies of dendritic cells, B cells, and CD8⁺T cells were upregulated at the 2 sites. The SIgA content decreased significantly in the ileal mucosa. CONCLUSIONS: PCV2 infections can cause damage to the ileum that is associated with changes in immune-related gene expression, immune-related cell subsets, and SIgA production. These findings elucidated the molecular changes in the ileum after a PCV2 infection from the perspective of intestinal mucosal immunity, which provides insights into a further study for PCV2-induced enteritis.
Toll-like Receptor Agonist CBLB502 Protects Against Radiation-induced Intestinal Injury in Mice
AbstractBACKGROUND/AIM: The small intestine is one of the organs most vulnerable to ionizing radiation (IR) damage. However, methods to protect against IR-induced intestinal injury are limited. CBLB502, a Toll-like receptor 5 (TLR5) agonist from Salmonella flagellin, exerts radioprotective effects on various tissues and organs. However, the molecular mechanisms by which CBLB502 protects against IR-induced intestinal injury remain unclear. Thus, this study aimed to elucidate the mechanisms underlying IR-induced intestinal injury and the protective effects of CBLB502 against this condition in mice. MATERIALS AND METHODS: Mice were administered 0.2 mg/kg CBLB502 before IR at different doses for different time points, and then the survival rate, body weight, hemogram, and histopathology of the mice were analyzed. RESULTS: CBLB502 reduced IR-induced intestinal injury. RNA-seq analysis revealed that different doses and durations of IR induced different regulatory patterns. CBLB502 protected against intestinal injury mainly after IR by reversing the expression of IR-induced genes and regulating immune processes and metabolic pathways. CONCLUSION: This study preliminarily describes the regulatory mechanism of IR-induced intestinal injury and the potential molecular protective mechanism of CBLB502, providing a basis for identifying the functional genes and molecular mechanisms that mediate protection against IR-induced injury.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works using Disease Ontology synonyms, resolved on OpenAlex.
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