Hang Ma

Breast cancer remains a significant clinical challenge, with treatment failure and patient mortality primarily attributable to tumor metastasis. Daucosterol linoleate (DL) was previously isolated from sweet potato (Ipomoea batatas). Using HPLC analysis of ten commercial dried sweet potato products from different regions of China, DL was detected in all samples, with concentrations ranging from 1.24 mg to 6.05 mg per 100 g, confirming its widespread presence in commercially processed sweet potato products. Pharmacokinetic analysis showed that DL exhibited a peak plasma concentration (C_max) of 1452.28 ng/mL, an elimination half-life (t_1/2) of 11.14 h, and a mean residence time (MRT) of 9.62 h, supporting its potential for oral administration. DL significantly suppressed proliferation and migration of MCF-7, 4T1, and MDA-MB-231 cells in vitro and reduced lung metastasis in vivo. Proteomic analysis identified SCD1 as a key molecule mediating the effects of DL. Mechanistically, DL downregulated SCD1 to inhibit epithelial-mesenchymal transition (EMT), as evidenced by decreased expression of N-Cadherin, MMP2, Vimentin, and Snail, alongside increased E-Cadherin expression. Collectively, DL inhibits breast cancer metastasis by downregulating SCD1 and suppressing EMT, supporting its dual potential as a functional food ingredient and adjuvant therapeutic.

Nearly half of the global population is infected with Helicobacter pylori. Antibiotic use has led to substantial antimicrobial resistance and unintended gut microbiota depletion, creating an urgent need for alternative therapeutic strategies. Here, we demonstrate that urease, a key enzyme that enables H. pylori survival by hydrolysing urea to neutralize stomach acid, is a conserved antibacterial target with low risk of resistance development. Using comprehensive deep mutational scanning coupled with phage-based functional screening, we systematically evaluated how mutations in core residues affect urease expression, enzymatic activity, bacterial colonization, and virulence, uncovering the catalytic nature of H. pylori urease. We found exceptional evolutionary conservation within the urease catalytic pocket, and potential mutation sites that affect urease activity are not close to the core of this pocket. Analysis of existing urease inhibitors revealed that their binding sites are not typically in these potential mutation sites, which indicates that the potential for resistance development is low. In addition, we show that targeting urease alone is effective in eradicating H. pylori and synergistically boosts the efficacy of antibiotics. Notably, the incorporation of urease inhibitors into antibiotic-based therapeutic regimens effectively preserves gut microbiota diversity and microbial genomic stability, thereby lowering the risk of antibiotic resistance. Collectively, our study elucidate the inherent resistance-resistant property of urease and establish the clinical value of combining urease inhibitors with antibiotics to reduce antibiotic resistance.

Periodontitis is a chronic oral inflammatory disease whose treatment is often hindered by poor drug retention, prolonged therapeutic regimens, and the rise of antibiotic resistance. In this study, we developed a Hydrogel@ZIF-8@metronidazole (Hydrogel@ZIF-8@MNZ) nanocomposite dressing for targeted, sustained, and in situ antimicrobial therapy. This system integrates ZIF-8, a pH-responsive metal–organic framework, with the antimicrobial agent metronidazole (MNZ), encapsulated within a crosslinked hydrogel matrix to enhance stability and retention in the oral environment. Drug release studies demonstrated that MNZ release was significantly accelerated under acidic conditions (pH 5.0), mimicking the periodontal microenvironment. The Hydrogel@ZIF-8 composite achieved a maximum MNZ adsorption capacity of 132.45 mg·g⁻¹, with a spontaneous and exothermic uptake process best described by a pseudo-second-order kinetic model, suggesting chemisorption as the dominant mechanism. The nanoplatform exhibited strong pH-responsive behavior, with enhanced drug release under acidic conditions and potent dose-dependent bactericidal activity against Fusobacterium nucleatum (Fn). At the highest tested concentration, bacterial survival was reduced to approximately 30%, with extensive membrane disruption observed through live/dead fluorescence microscopy. In summary, the stimuli-responsive Hydrogel@ZIF-8@MNZ nanocomposite offers an intelligent and effective therapeutic strategy for periodontitis. By tailoring its action to the disease microenvironment, this platform enables sustained and localized antibacterial therapy, addressing major challenges in the treatment of chronic oral infections.

Colorectal cancer, a prevalent digestive system malignancy, is characterized by a high incidence, low early detection rate, limited surgical resection opportunities, and high mortality. Palmatine (PAL), an active ingredient primarily found in Coptidis Rhizoma, exhibits diverse pharmacological effects, including antibacterial, anti-inflammatory, and anti-tumor properties. While PAL has been shown to effectively curb the progression of colorectal cancer, the underlying mechanisms have yet to be fully elucidated. In this study, we demonstrated the inhibitory effect of PAL on colorectal cancer growth via the miR-363-3p/AURKA axis, utilizing an AOM/DSS-induced colorectal cancer model in C57BL/J mice, a subcutaneous tumor xenograft model in nude mice, and in vitro assays using HCT-116 and SW620 cells. PAL upregulates miR-363-3p expression, promotes the interaction between AURKA 3'UTR mRNA and miR-363-3p, impedes AURKA mRNA translation into AURKA protein, thereby inhibiting colorectal cancer cell proliferation and migration, and suppressing the initiation and progression of colorectal cancer. These results expand the understanding of the regulatory mechanisms by which PAL influences colorectal cancer development, and may provide new potential targets for colorectal cancer diagnosis and therapy.