[Palisade Bio, Inc.] Palisade Bio, Inc. announced that the US FDA has cleared the Company’s Investigational New Drug (IND) application for PALI-2108, enabling initiation of the Phase 2 ASCENTRA-CD clinical trial in patients with moderate to severe Crohn’s disease.

[Nature Genetics] built a comprehensive atlas of cell-type-resolved chromatin accessibility, identifying cell-type-specific, anatomical location-specific and context-specific cis-regulatory elements and characterizing the regulatory programs underlying inflammatory responses in the intestinal mucosa of patients with Crohn’s disease

[Signal Transduction and Targeted Therapy] Investigators demonstrated that PiZ transgenic mice expressing the polymer-forming ATZ display increased susceptibility to dextran sodium sulfate-induced colitis, accompanied by marked Paneth cell abnormalities.

[Nature Microbiology] Scientists used mouse colonization models and found that enterotoxigenic Bacteroides fragilis-secreted B. fragilis toxin causes loss of colonic myenteric neurons, which are crucial regulators of intestinal motility.

[Blood] Researchers used lysozyme1-DTR mice to ablate paneth cells (PCs) and found stable WNT3 expression in vivo, and crypts from PC-ablated mice that retained organoid-forming capacity, further reflecting persistent WNT3 production.

[Nature Communications] Conditional deletion of epithelial Arhgef2-207 induces Arhgef2-201 expression, disrupts barrier integrity, activates autophagy, and causes small-intestinal inflammation. In human intestinal organoids, Listeria monocytogenes selectively depletes junction-associated ARHGEF2-219, triggering a switch to ARHGEF2-201 and RhoA- and STING-mediated autophagic signaling.

[Journal of Extracellular Vesicles] The authors examined the relationship between fat digestibility and gut microbial composition, and found that piglets with higher apparent crude fat digestibility exhibited enhanced lipid absorption and oxidation, accompanied by reduced abundance of Clostridium butyricum in the ileal mucosa.

[Science Advances] Researchers showed that RNF43 p.G659fs (RNF43659mut) mutation shapes an immunosuppressive natural killer cell landscape in microsatellite instability–high (MSI-H) colorectal cancer (CRC).

[Journal for Immunotherapy of Cancer] The authors revealed a “Bile acid-associated metabolites-Immune checkpoint” regulatory axis that drives immunosuppression in colorectal cancer, illuminating the role of gut microbial metabolites in modulating the PD-1/SHP-2 interaction.

[Pharmacological Research] Scientists attempted to elucidate how indoleamine 2,3-dioxygenase 1 (IDO1) functions as a convergent downstream effector of both microbiota-derived signals and host oncogenic pathways in order to mediate the chemopreventive effects of licorice flavonoids on colorectal cancer.

[Oncogene] The authors investigated the molecular mechanisms through which the histone methyltransferase SET domain bifurcated 1 (SETDB1) regulates colorectal cancer progression, prompted by SETDB1's exertion of oncogenic functions in multiple solid tumors.

[Journal of Lipid Research] Researchers utilized human colon epithelial cells to determine the role of ceramide synthases 5 and 6 on myristate-induced endoplasmic reticulum stress using pharmacologic inhibitors and small interfering RNA.