SDH, a novel diarylheptane compound, alleviates dextran sulfate sodium (DSS)-induced colitis by reducing Th1/Th2/Th17 induction and regulating the gut microbiota in mice.

Ulcerative colitis, a chronic inflammatory condition affecting the rectum and colon to varying degrees, is linked to a dysregulated immune response and the microbiota. Sodium (aS,9R)-3-hydroxy-16,17-dimethoxy-15-oxidotricyclo[12.3.1.12,6]nonadeca-1(18),2,4,6(19),14,16-hexene-9-yl sulfate hydrate (SDH) emerges as a novel diarylheptane compound aimed at treating inflammatory bowel diseases. However, the mechanisms by which SDH modulates these conditions remain largely unknown. In this study, we assessed SDH's impact on the clinical progression of dextran sodium sulfate (DSS)-induced ulcerative colitis. Our results demonstrated that SDH significantly mitigated the symptoms of DSS-induced colitis, reflected in reduced disease activity index scores, alleviation of weight loss, shortening of the colorectum, and reduction in spleen swelling. Notably, SDH decreased the proportion of Th1/Th2/Th17 cells and normalized inflammatory cytokine levels in the colon. Furthermore, SDH treatment modified the gut microbial composition in mice with colitis, notably decreasing Bacteroidetes and Proteobacteria populations while substantially increasing Firmicutes, Actinobacteria, and Patescibacteria. In conclusion, our findings suggest that SDH may protect the colon from DSS-induced colitis through the regulation of Th1/Th2/Th17 cells and gut microbiota, offering novel insights into SDH's therapeutic potential.

The involvement of E3 ubiquitin ligases in the development and progression of colorectal cancer.

To date, colorectal cancer (CRC) still has limited therapeutic efficacy and poor prognosis and there is an urgent need for novel targets to improve the outcome of CRC patients. The highly conserved ubiquitination modification mediated by E3 ubiquitin ligases is an important mechanism to regulate the expression and function of tumor promoters or suppressors in CRC. In this review, we provide an overview of E3 ligases in modulating various biological processes in CRC, including proliferation, migration, stemness, metabolism, cell death, differentiation and immune response of CRC cells, emphasizing the pluripotency of E3 ubiquitin ligases. We further focus on the role of E3 ligases in regulating vital cellular signal pathways in CRC, such as Wnt/ß-catenin pathway and NF-κB pathway. Additionally, considering the potential of E3 ligases as novel targets in the treatment of CRC, we discuss what aspects of E3 ligases can be utilized and exploited for efficient therapeutic strategies.

DGT, a novel heterocyclic diterpenoid, effectively suppresses psoriasis via inhibition of STAT3 phosphorylation.

BACKGROUND AND PURPOSE: Psoriasis is a chronic immune-mediated inflammatory skin disease that easily recurs and is difficult to cure. DGT is a novel synthetic heterocyclic diterpenoid, whose structure has not been previously reported. We have investigated the action of DGT against psoriasis, specifically the hyperproliferation of epidermal keratinocytes, angiogenesis and pathogenic inflammatory responses. EXPERIMENTAL APPROACH: We investigated its pharmacokinetics in skin after topical administration. We characterized its pharmacological actions in vitro and in vivo using cell proliferation assay, cell apoptosis assay, diethylstilbestrol-induced mouse vaginal epithelial cell mitosis model, tube formation assay, cell migration assay, chick embryonic chorioallantoic membrane (CAM) assay, histological, flow cytometric analysis and imiquimod (IMQ)-induced psoriasis-like model. KEY RESULTS: DGT was found to be mainly distributed in the epidermis and dermis, which indicated that DGT was suitable as a topical treatment. DGT inhibited cell proliferation and induced apoptotic cell death of keratinocytes in vitro and in vivo. Moreover, DGT inhibited endothelial cell proliferation, tube formation and migration of in vitro angiogenesis, as well as in vivo CAM angiogenesis. In an IMQ-induced psoriasis-like skin inflammation murine model, topical application of DGT ameliorated keratinocyte proliferation and inflammatory response, especially in IL-17-related psoriasiform dermatitis. Furthermore, our results demonstrated that DGT prevented these pathological processes of psoriasis through suppression of STAT3 phosphorylation. CONCLUSION AND IMPLICATIONS: DGT has great potential as a novel therapeutic agent for the treatment of psoriatic skin disease.

N-(4-Fluorobenzoyl)-2-hydroxy-4-methyl-benzohydrazide.

In the title compound, C(15)H(13)FN(2)O(3), the aromatic rings are aligned at an angle of 10.15 (3)°. The mol-ecules are packed with π-π stacking inter-actions [mean inter-planar distances of 3.339 (2) and 3.357 (3) Å] and the crystal structure is stabilized by inter-molecular N-H⋯O and O-H⋯O hydrogen bonds. An intramolecular N-H⋯O interaction also occurs.

2-[(E)-Benzyl-imino-meth-yl]-4-methyl-phenol.

In the title Schiff base, C(15)H(15)NO, the benzene rings form a dihedral angle of 74.91 (1)°. There is a strong intra-molecular O-H⋯N hydrogen bond.

N'-Benzoyl-3-hydr-oxy-2-naphthohydrazide.

In the title compound, C(18)H(14)N(2)O(3), the dihedral angle between the planes of the naphthalene and phenyl ring systems is 2.64 (2)°. Mol-ecules are engaged in π-π stacking (mean interplanar distance = 3.339 between naphthalene rings and 3.357 Šbetween benzene rings )and hydrogen-bonding inter-actions.

The cocrystal 2-hydr-oxy-4-methyl-N-propanoylbenzohydrazide-2-hydr-oxy-N-(2-hydr-oxy-4-methyl-benzo-yl)-6-methyl-benzohydrazide (2/1).

The asymmetric unit of the title compound, 2C(11)H(14)N(2)O(3)·C(16)H(16)N(2)O(4), contains one mol-ecule of 2-hydr-oxy-4-methyl-N-propanoylbenzohydrazide and one-half of a mol-ecule of 2-hydr-oxy-N-(2-hydr-oxy-4-methyl-benzo-yl)-6-methyl-benzohydrazide. The latter is located on a centre of inversion. Intra-molecular N-H⋯O inter-actions stabilize the conformations of both mol-ecules. The crystal structure is stabilized by inter-molecular N-H⋯O and O-H⋯O hydrogen bonds.

4,4'-Dimethyl-2,2'-[1,2-phenyl-enebis(nitrilo-methyl-idyne)]diphenol.

In the title Schiff base, C(22)H(20)N(2)O(2), the benzene ring forms dihedral angles of 53.92 (1) and 3.62 (1)° with the two salicylaldimine groups. There are two strong O-H⋯N intra-molecular hydrogen bonds. The crystal packing is stabilized by weak inter-molecular C-H⋯O hydrogen bonds and π-π stacking inter-actions (average distance 3.39 Å).