Validation of hyperthermia as an enhancer of chemotherapeutic efficacy: insights from a bladder cancer organoid model.

OBJECTIVE: This study aimed to evaluate the combined efficacy of hyperthermia and chemotherapy using a bladder cancer organoid model and to explore hyperthermia-related molecular pathways. METHOD: Tumor organoids were generated by embedding RT4 bladder cancer cells into Matrigel. The resulting organoids were treated with pirarubicin or gemcitabine at 37 °C or 42 °C. Proliferation was determined by Ki67 immunofluorescence staining, and apoptosis was assessed using a TdT-mediated dUTP nick end labeling (TUNEL) assay. RNA sequencing was used to identify the differentially expressed genes. RESULTS: Bladder cancer organoids were successfully established and exhibited robust proliferative abilities. Treatment with gemcitabine or pirarubicin under hyperthermic conditions caused pronounced structural damage to the organoids and increased cell death compared to that in the normothermically treated group. Furthermore, Ki67 labeling and TUNEL assays showed that the hyperthermia chemotherapy group showed a significantly reduced proliferation rate and high level of apoptosis. Finally, RNA sequencing revealed the IFN-γ signaling pathway to be associated with hyperthermia. CONCLUSION: Overall, hyperthermia combined with chemotherapy exerted better therapeutic effects than those of normothermic chemotherapy in grade 1-2 non-muscle-invasive bladder cancer, potentially through activation of the IFN-γ-JAK-STAT pathway.

In Situ Fabrication of Silver Peroxide Hybrid Ultrathin Co-Based Metal-Organic Frameworks for Enhanced Chemodynamic Antibacterial Therapy.

Bacterial-induced infectious diseases have always caused an unavoidable problem and lead to an increasing threat to human health. Hence, there is an urgent need for effective antibacterial strategies to treat infectious diseases. Current methods are often ineffective and require large amounts of hydrogen peroxide (H2O2), with harmful effects on normal healthy tissue. Chemodynamic therapy (CDT) provides an ideal infection microenvironment (IME)-activated paradigm to tackle bacterial-related diseases. To take full advantage of the specificity of IME and enhanced CDT for wounds with bacterial infection, we have designed an intelligent antibacterial system that exploits nanocatalytic ZIF-67@Ag2O2 nanosheets. In this system, silver peroxide nanoparticles (Ag2O2 NPs) were grown on ultrathin zeolitic imidazolate framework-67 (ZIF-67) nanosheets by in situ oxidation, and then, ZIF-67@Ag2O2 nanosheets with the ability to self-generate H2O2 were triggered by the mildly acidic environment of IME. Lamellar ZIF-67 nanosheets were shown to rapidly degrade and release Co2+, allowing the conversion of less reactive H2O2 into the highly toxic reactive oxygen species hydroxyl radicals (•OH) for enhanced CDT antibacterial properties. In vivo results revealed that the ZIF-67@Ag2O2 nanosheet system exhibits excellent antibacterial performance against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria. The proposed hybrid strategy demonstrates a promising therapeutic strategy to enable antibacterial agents with IME-responsive nanocatalytic activity to circumvent antibiotic resistance against bacterial infections.

Unveiling the retrogradation mechanism of a novel high amylose content starch-Pouteria campechiana seed.

The research of starch retrogradation have been attracting interest. Thereby, the long-term retrogradation mechanism (0-21 days) of Pouteria campechiana seed starch (PCSS) was investigated. The results showed that crystal type was changed from A- to B + V-type during retrogradation. The retrogradation PCSS (RPCSS) exhibited faster retrogradation rate and more compact internal ultra-structure compared to rice, wheat and maize starch. Pearson correlation indicated that, as retrogradation days increased, values of α-1,4-glycosidic bond, A chains, double helix, V-type polymorphism, Mw, relative crystallinity (Rc) and short-range order gradually significantly increased, and B1 chains, B3 + chains values gradually significantly dropped (p < 0.05). These inferred an increasing peak temperature and compactness of morphology with increasing retrogradation days. Compared to native starch, RPCSS α-1.4-glycosidic bond was increased, which indicated that its quick molecules degradation including decreased Mw, B3 + chains, Rc, semicrystalline order, and ΔH. These might provide a theoretical direction for preparation of starch-basis food.

A multifunctional nanocatalytic system based on Chemodynamic-Starvation therapies with enhanced efficacy of cancer treatment.

A multi-functional nanocatalytic system based on combined therapies has attracted considerable research attention in recent years due to its potential in the treatment of cancer. Herein, ZnO2@Au@ZIF-67 nanoparticles (NPs) based on hydroxyl radical (•OH) mediated chemodynamic therapy (CDT) and glucose-exhausting starvation therapy (ST) were constructed. Specifically, in the acidic tumor microenvironment (TME), the pH responsive decomposition of the shell ZIF-67 triggered the release of the Fenton-like catalyst Co2+, after which the exposed zinc peroxide (ZnO2) reacted with H2O (H+) to generate O2 and hydrogen peroxide (H2O2). The generated O2 could alleviate hypoxia in the TEM and interact with ultra-small Au NPs originally coated on ZnO2 to catalyze intracellular glucose and to produce another source of H2O2. While the glucose consumption caused the starvation of tumor cells, the generated H2O2 from dual sources reacted with the catalyst Co2+ to generate highly toxic •OH for CDT. Systematic in vitro and in vivo experiments were carried out to evaluate this nanocatalytic system, and the results showed an enhanced efficacy of this cancer therapy.

Effect of new type extrusion modification technology on supramolecular structure and in vitro glycemic release characteristics of starches with various estimated glycemic indices.

Nowadays, the highly effective modified technology to starch with various digestibility is gaining interest in food science. Here, the interactions between glycemic release characteristics and fine supramolecular structure of cassava (ECS), potato (EPS), jackfruit seed (EJFSS), maize (EMS), wheat (EWS), and rice starches (ERS) prepared with improved extrusion modification technology (IEMS) were investigated. The crystalline structures of all extruded cooking starches changed from the A-type to V-type. IEMS-treated cassava, potato, and rice starches had broken α-1.6-glycosidic amylopectin (long chains). The others sheared α-1.4-glycosidic amylopectin. The molecular weight, medium and long chain counts, and relative crystallinity decreased, whereas the number of amylopectin short chains increased. The glycemic index (GI) and digestive speed rate constant (k) of ECS, EPS, EJFSS, and EWS were improved compared to those of raw starch. Although EMS and ERS had degraded molecular structures, their particle morphology changed from looser polyhedral to more compact with less enzymolysis channels due to the rearrangement of side chain clusters of amylopectin, leading to enzyme resistance. The starch characteristics of IEMS-treated samples significantly differed. EPS had the highest amylose content, medium chains, long chains, and molecular weight but lowest GI, relative crystallinity, and k. ERS showed the opposite results. Thus, IEMS may affect starches with different GIs to varying degrees. In this investigation, we provide a basis for wider applications of conventional crop starch in the food industry corresponding to different nutrition audience.