A Cytosolic Multiprotein Complex Containing p85\u3cem\u3eα\u3c/em\u3e is Required for \u3cem\u3eβ\u3c/em\u3e-Catenin Activation in Colitis and Colitis-Associated Cancer

Wnt/β-catenin signaling is required for crypt structure maintenance. We previously observed nuclear accumulation of Ser-552 phosphorylated β-catenin (pβ-CatSer-552) in intestinal epithelial cells (IEC) during colitis and colitis-associated cancer. Data here delineate a novel multiprotein cytosolic complex (MCC) involved in β-catenin signaling in the intestine. The MCC contains p85α, the class IA subunit of PI3K, along with β-catenin, 14-3-3ζ, Akt, and p110α. MCC levels in IEC increase in colitis and colitis-associated cancer patients. IEC-specific p85α-deficient (p85ΔIEC) mice develop more severe dextran sodium sulfate colitis due to delayed ulcer healing and reduced epithelial β-catenin activation. In colonic IEC, p85α deficiency did not alter PI3K signaling. In vitro shRNA depletion of individual complex members disrupts the MCC and reduces β-catenin signaling. Despite worse colitis, p85ΔIEC mice have reduced tumor burden after azoxymethane/dextran sodium sulfate treatment. Together the data indicate that the β-catenin MCC is needed for mucosal repair and carcinogenesis. This novel MCC may be an attractive therapeutic target in preventing cancer in colitis patients

Disruption of Microtubules Sensitizes the DNA Damage-induced Apoptosis Through Inhibiting Nuclear Factor κB (NF-κB) DNA-binding Activity

The massive reorganization of microtubule network involves in transcriptional regulation of several genes by controlling transcriptional factor, nuclear factor-kappa B (NF-κB) activity. The exact molecular mechanism by which microtubule rearrangement leads to NF-κB activation largely remains to be identified. However microtubule disrupting agents may possibly act in synergy or antagonism against apoptotic cell death in response to conventional chemotherapy targeting DNA damage such as adriamycin or comptothecin in cancer cells. Interestingly pretreatment of microtubule disrupting agents (colchicine, vinblastine and nocodazole) was observed to lead to paradoxical suppression of DNA damage-induced NF-κB binding activity, even though these could enhance NF-κB signaling in the absence of other stimuli. Moreover this suppressed NF-κB binding activity subsequently resulted in synergic apoptotic response, as evident by the combination with Adr and low doses of microtubule disrupting agents was able to potentiate the cytotoxic action through caspase-dependent pathway. Taken together, these results suggested that inhibition of microtubule network chemosensitizes the cancer cells to die by apoptosis through suppressing NF-κB DNA binding activity. Therefore, our study provided a possible anti-cancer mechanism of microtubule disrupting agent to overcome resistance against to chemotherapy such as DNA damaging agent

Vitrification of Liquid Metal‐in‐Oil Emulsions Using Nano‐Mineral Oxides

Abstract Ga and Ga‐based alloys have recently received significant attention as “liquid metals (LMs)” with the combined advantages of a low toxicity, low melting point, high fluidity, and high conductivity. An important method for modifying LMs for enhanced processabilities and new applications is to tailor them into colloidal microdroplets suspended in a liquid medium. In this study, the unique vitrification behavior of oil‐based colloidal systems is shown with suspended LM microdroplets induced by various mineral oxide (MO) nanoparticles that are added as solid rheology modifiers. MOs exhibit a high affinity for the surfaces of suspended LM droplets in an apolar oil medium due to the polar interaction between the MO surface and the oxide skin of the LM. Thus, even minute amounts of added MOs (ΦMO < 0.01) transform a free‐flowing LM suspension (ΦMO ≈ 0.55) into a highly viscoelastic fluid that enables advanced processing (e.g., 3D printing). At high MO loadings (ΦMO ≥ 0.1), an emulsion with unprecedentedly high rheological strength is obtained, characterized by a yield stress of ≈104 Pa. In highly vitrified emulsions, partial sintering effects are induced by high internal sample stress, which improves the thermophysical properties of emulsions that may be useful for several practical applications

Comparison of Microbial Gene Diversity in Grassland Topsoil Depending on Soil Quality

Soil has multiple functions, including the provision of habitat to organisms, and most biological activities occur in the surface soil. Due to the negative effects of soil erosion, efforts for soil conservation are being made, including the development of a reliable index that can help assess soil quality. In this study, the physical and chemical properties and biological genes from grassland topsoil were analyzed, in order to identify surface soil organism markers that could be used as a soil quality index. Six spots of grassland topsoil were analyzed, one high-quality and five low-quality, based on a web-based soil quality assessment module. Consequently, eukaryotes and prokaryotes with different soil quality ratios were compared and examined. The following bacteria and archaea have the potential to be used in soil quality assessment: circulation of materials including nitrogen, Nitrospira spp., Candidatus Nitrososphaera, and Candidatus Nitrosotalea; biological purification, Geobacter spp.; pathogens, Burkholderia spp., Paraburkholderia spp., Pseudomonas brassicacearum, and Rhizobacter spp.; antibiotic secretion, Candidatus Udaeobacter; and material degradation Steroidobacter spp. and Rhodanobacter spp. This study provides primary data for identifying biological markers for soil quality evaluation. In the future, a wider variety of data need to be accumulated to develop a highly reliable index related to soil quality

Impact of COPD Treatment on Survival in Patients with Advanced Non-Small Cell Lung Cancer

Chronic obstructive pulmonary disease (COPD) is associated with a poor prognosis in patients with non-small cell lung cancer (NSCLC). However, the impact of COPD treatment on the survival of patients with advanced NSCLC remains uncertain. We retrospectively investigated COPD patients among patients newly diagnosed with advanced NSCLC between September 2005 and August 2019 at a university hospital. The clinical characteristics, lung function, and survival outcomes were analyzed and compared between patients who did and did not receive COPD treatment. Among 221 patients with advanced NSCLC and COPD, 124 patients received treatment for COPD and 97 patients did not receive treatment for COPD. Forced expiratory volume in 1 s (FEV1) % predicted value was greater in the no-treatment group than in the COPD treatment group (p p = 0.007). In the multivariate analysis, COPD treatment was independently associated with improved OS (hazard ratio 0.71, 95% confidence interval 0.53–0.95, and p = 0.021). COPD treatment was associated with improved OS in patients with advanced NSCLC and COPD. Therefore, pretreatment spirometry and maximal treatment for COPD may offer a chance of optimal management for patients with advanced NSCLC