Mitochondrial fission enhances IL-6-induced metastatic potential in ovarian cancer via ERK1/2 activation.

Ovarian cancer is a lethal gynecologic cancer mostly diagnosed in an advanced stage with an accumulation of ascites. Interleukin-6 (IL-6), a pro-inflammatory cytokine is highly elevated in malignant ascites and plays a pleiotropic role in cancer progression. Mitochondria are dynamic organelles that undergo fission and fusion in response to external stimuli and dysregulation in their dynamics has been implicated in cancer progression and metastasis. Here, we investigate the effect of IL-6 on mitochondrial dynamics in ovarian cancer cells (OVCs) and its impact on metastatic potential. Treatment with IL-6 on ovarian cancer cell lines (SKOV3 and PA-1) led to an elevation in the metastatic potential of OVCs. Interestingly, a positive association was observed between dynamin-related protein 1 (Drp1), a regulator of mitochondrial fission, and IL-6R in metastatic ovarian cancer tissues. Additionally, IL-6 treatment on OVCs was linked to the activation of Drp1, with a notable increase in the ratio of the inhibitory form p-Drp1(S637) to the active form p-Drp1(S616), indicating enhanced mitochondrial fission. Moreover, IL-6 treatment triggered the activation of ERK1/2, and inhibiting ERK1/2 mitigated IL-6-induced mitochondrial fission. Suppressing mitochondrial fission through siRNA transfection and a pharmacological inhibitor reduced the IL-6-induced migration and invasion of OVCs. This was further supported by 3D invasion assays using patient-derived spheroids. Altogether, our study suggests the role of mitochondrial fission in the metastatic potential of OVCs induced by IL-6. The inhibition of mitochondrial fission could be a potential therapeutic approach to suppress the metastasis of ovarian cancer.

Elastic Network of Droplets for Underwater Adhesives.

Functionality in biological materials arises from complex hierarchical structures formed through self-assembly processes. Here, we report a kinetically trapped self-assembly of an elastic network of liquid droplets and its utility for tough and fast-acting underwater adhesives. This complex structure was made from a one-pot mixture of scalable small-molecule precursors. Liquid-liquid phase separation accompanied by silanol hydrolysis, condensation, and zwitterionic self-association yields a viscoelastic solid with interconnected liquid droplets. These hierarchical microstructures increase toughness and enable underwater adhesion for a range of substrates, offering a platform for robust adhesives for rapid underwater repair or emergency wound care.

Sugar-Fueled Dissipative Living Materials.

Dissipative behaviors in biology are fuel-driven processes controlled by living cells, and they shape the structural and functional complexities in biological materials. This concept has inspired the development of various forms of synthetic dissipative materials controlled by time-dependent consumption of chemical or physical fuels, such as reactive chemical species, light, and electricity. To date, synthetic living materials featuring dissipative behaviors directly controlled by the fuel consumption of their constituent cells is unprecedented. In this paper, we report a chemical fuel-driven dissipative behavior of living materials comprising Staphylococcus epidermidis and telechelic block copolymers. The macroscopic phase transition is controlled by d-glucose which serves a dual role of a competitive disassembling agent and a biological fuel source for living cells. Our work is a significant step toward constructing a synthetic dissipative living system and provides a new tool and knowledge to design emergent living materials.

Catalytic Materials Enabled by a Programmable Assembly of Synthetic Polymers and Engineered Bacterial Spores.

Natural biological materials are formed by self-assembly processes and catalyze a myriad of reactions. Here, we report a programmable molecular assembly of designed synthetic polymers with engineered bacterial spores. This self-assembly process is driven by dynamic covalent bond formation on spore surface glycan and yields macroscopic materials that are structurally stable, self-healing, and recyclable. Molecular programming of polymer species shapes the physical properties of these materials while metabolically dormant spores allow for prolonged ambient storage. Incorporation of spores with genetically encoded functionalities enables operationally simple and repeated enzymatic catalysis. Our work combines molecular and genetic engineering to offer scalable and programmable synthesis of robust materials for sustainable biocatalysis.

Computational modeling of malignant ascites reveals CCL5-SDC4 interaction in the immune microenvironment of ovarian cancer.

Fluid accumulation in the abdominal cavity is commonly found in advanced-stage ovarian cancer patients, which creates a specialized tumor microenvironment for cancer progression. Using single-cell RNA sequencing (scRNA-seq) of ascites cells from five patients with ovarian cancer, we identified seven cell types, including heterogeneous macrophages and ovarian cancer cells. We resolved a distinct polarization state of macrophages by MacSpectrum analysis and observed subtype-specific enrichment of pathways associated with their functions. The communication between immune and cancer cells was predicted through a putative ligand-receptor pair analysis using NicheNet. We found that CCL5, a chemotactic ligand, is enriched in immune cells (T cells and NK cells) and mediates ovarian cancer cell survival in the ascites, possibly through SDC4. Moreover, SDC4 expression correlated with poor overall survival in ovarian cancer patients. Our study highlights the potential role of T cells and NK cells in long-term survival patients with ovarian cancer, indicating SDC4 as a potential prognostic marker in ovarian cancer patients.

Increasing serum gamma-glutamyltransferase level accompanies a rapid increase in the incidence of endometrial cancer in Korea: A nationwide cohort study.

OBJECTIVE: This study aimed to determine the association of serum GGT levels with the risk of developing endometrial cancer. Women's obesity and menopausal status were also taken into account in our analysis. METHODS: We used a nationwide cohort to examine the association between serum GGT levels and endometrial cancer development in Korean women. Data were retrieved from the Korean National Health Insurance Service (NHIS) healthcare system. Women aged over 19 years who participated in the Korea National Health Screening Examination in 2009 and were not diagnosed with endometrial cancer 1-year post-examination were included in our study (n = 2,736,588). RESULTS: Obese (BMI, ≥25 kg/m2) women with increased GGT levels were at high risk of endometrial cancer (HR = 1.415, 95% CI: 1.236-1.621). Interestingly, in pre-menopausal women, high GGT level (Q4) was associated with the increased endometrial cancer risk only for obese women (HR = 1.482, 95% CI: 1.205-1.821). In post-menopausal women, only a high GGT level (Q4) was also associated with the increased cancer risk for obese women (HR = 1.313, 95% CI: 1.096-1.573). We observed a significant association between high GGT levels and increased risk of endometrial cancer in pre-menopausal women with abdominal obesity (WC, ≥85 cm) (HR = 1.647, 95% CI: 1.218-2.227). CONCLUSIONS: Increased GGT level is an independent risk factor of endometrial cancer, especially for post-menopausal women and obese pre-menopausal women. These results may suggest that serum GGT levels might be useful in the risk stratification of endometrial cancer. Adopting a healthy lifestyle for lowering serum GGT level is warranted, especially for women with a higher risk of developing endometrial cancer.

Bio-adhesive Nanoporous Module: Toward Autonomous Gating.

Here we report a bio-adhesive porous organic module (Glue COF) composed of hexagonally packed 1D nanopores based on a covalent organic framework. The nanopores are densely decorated with guanidinium ion (Gu+ ) pendants capable of forming salt bridges with oxyanionic species. Glue COF strongly adheres to biopolymers through multivalent salt-bridging interactions with their ubiquitous oxyanionic species. By taking advantage of its strong bio-adhesive nature, we succeeded in creating a gate that possibly opens the nanopores through a selective interaction with a reporter chemical and releases guest molecules. We chose calmodulin (CaM) as a gating component that can stably entrap a loaded guest, sulforhodamine B (SRB), within the nanopores (CaM COF⊃SRB). CaM is known to change its conformation on binding with Ca2+ ions. We confirmed that mixing CaM COF⊃SRB with Ca2+ resulted in the release of SRB from the nanopores, whereas the use of weakly binding Mg2+ ions resulted in a much slower release of SRB.

Resveratrol as a Tumor-Suppressive Nutraceutical Modulating Tumor Microenvironment and Malignant Behaviors of Cancer.

Tumor-suppressive effects of resveratrol have been shown in various types of cancer. However, regulation of tumor microenvironment by resveratrol is still unclear. Recent findings suggest resveratrol can potentiate its tumor-suppressive effect through modulation of the signaling pathways of cellular components (fibroblasts, macrophages and T cells). Also, studies have shown that resveratrol can suppress malignant phenotypes of cancer cells acquired in response to stresses of the tumor microenvironment, such as hypoxia, oxidative stress and inflammation. We discuss the effects of resveratrol on cancer cells in stress environment of tumors as well as interactions between cancer cells and non-cancer cells in this review.

Luminescent Metal-Organic Framework Sensor: Exceptional Cd2+ Turn-On Detection and First In Situ Visualization of Cd2+ Ion Diffusion into a Crystal.

With regard to fluorescence quenching commonly observed during metal-ion detection, "turn-on" chemical sensing has been rarely reported, but could be extremely important because it facilitates the selective recognition of target objects of interest against a dark background. A metal-organic framework (MOF) chemosensor has been prepared that serves as an efficient platform for the selective detection of Cu2+ and Cd2+ ions over other metal ions. In particular, this framework shows the highest fluorescence enhancement (≈60-fold relative to Cd-free MOF) for the hazardous metal ion Cd2+ among luminescent MOFs and displays excellent reusability in repeated cycles. The direct diffusion of Cd2+ into the crystal pores has also been visualized for the first time.

Adsorption of Carbon Dioxide on Unsaturated Metal Sites in M2 (dobpdc) Frameworks with Exceptional Structural Stability and Relation between Lewis Acidity and Adsorption Enthalpy.

A series of metal-organic frameworks (MOFs) M2 (dobpdc) (M=Mn, Co, Ni, Zn; H4 dobpdc=4,4'-dihydroxy-1,1'-biphenyl-3,3'-dicarboxylic acid), with a highly dense arrangement of open metal sites along hexagonal channels were prepared by microwave-assisted or simple solvothermal reactions. The activated materials were structurally expanded when guest molecules including CO2 were introduced into the pores. The Lewis acidity of the open metal sites varied in the order MnZn, as confirmed by C=O stretching bands in the IR spectra, which are related to the CO2 adsorption enthalpy. DFT calculations revealed that the high CO2 binding affinity of transition-metal-based M2 (dobpdc) is primarily attributable to the favorable charge transfer from CO2 (oxygen lone pair acting as a Lewis base) to the open metal sites (Lewis acid), while electrostatic effects, the underlying factor responsible for the particular order of binding strength observed across different transition metals, also play a role. The framework stability against water coincides with the order of Lewis acidity. In this series of MOFs, the structural stability of Ni2 (dobpdc) is exceptional; it endured in water vapor, liquid water, and in refluxing water for one month, and the solid remained intact on exposure to solutions of pH 2-13. The DFT calculations also support the experimental finding that Ni2 (dobpdc) has higher chemical stability than the other frameworks.