A Microbial Community Cultured in Gradient Hydrogel for Investigating Gut Microbiome-Drug Interaction and Guiding Therapeutic Decisions.

Despite the recognition that the gut microbiota acts a clinically significant role in cancer chemotherapy, both mechanistic understanding and translational research are still limited. Maximizing drug efficacy requires an in-depth understanding of how the microbiota contributes to therapeutic responses, while microbiota modulation is hindered by the complexity of the human body. To address this issue, a 3D experimental model named engineered microbiota (EM) is reported for bridging microbiota-drug interaction research and therapeutic decision-making. EM can be manipulated in vitro and faithfully recapitulate the human gut microbiota at the genus/species level while allowing co-culture with cells, organoids, and isolated tissues for testing drug responses. Examination of various clinical and experimental drugs by EM reveales that the gut microbiota affects drug efficacy through three pathways: immunological effects, bioaccumulation, and drug metabolism. Guided by discovered mechanisms, custom-tailored strategies are adopted to maximize the therapeutic efficacy of drugs on orthotopic tumor models with patient-derived gut microbiota. These strategies include immune synergy, nanoparticle encapsulation, and host-guest complex formation, respectively. Given the important role of the gut microbiota in influencing drug efficacy, EM will likely become an indispensable tool to guide drug translation and clinical decision-making.

[Effect of surface pretreatment with chemical etchants on bond strength between a silicone-based resilient liner and denture base resin].

OBJECTIVE: To evaluate the effect of denture base resin surface pretreatment with chemical etchants on microleakage and bond strength between silicone-based resilient liner and denture base resin. The initial bending strength of denture base resin after surface pretreatment was also examined. METHODS: Thirty-six polymethyl methacrylate (PMMA) denture base resin blocks (30 mm × 30 mm × 2 mm) were prepared and divided into three groups: group acetone, group methyl methy acrylate (MMA) and group control. Subsequently, a 2 mm silicone-based resilient liner was applied between every two blocks. After 5000 cycles in the thermal cycler (5 and 55°C), they were immersed in the (131) I solution for 24 hours and γ-ray counts were measured. Another 36 PMMA resin blocks (30 mm × 10 mm × 7.5 mm) were prepared. The blocks were divided into three groups and treated as mentioned above. A 3 mm silicone-based resilient liner was applied between every two blocks. After 5000 thermal cycles, tensile bond strength of the sample was measured in a universal testing machine. Another 18 PMMA resin blocks (65 mm × 10 mm × 3.3 mm) were prepared. They were divided into 3 groups and treated in the same way. After an adhesive was applied, the bending strength was measured with three-piont bending test. RESULTS: Two experimental groups showed lower microleakage (520.0 ± 562.2 and 493.5 ± 447.9) and higher tensile bond strength [(1.5 ± 0.4) and (1.4 ± 0.5) MPa] than the group control [microleakage: (1369.5 ± 590.2); tensile bond strength: (0.9 ± 0.2) MPa, P < 0.05]. There was no statistically significant difference between group acetone and MMA in microleakage and tensile bond strength (P > 0.05). There was no statistically significant difference in bending strength among the three groups (P > 0.05). CONCLUSIONS: Treating the denture base resin surface with acetone and MMA decreased the microleakage, increased the tensile bond strength between the two materials and did not make the initial bending strength of denture base resin decline.