Kinetics of phase separation and coarsening in dilute surfactant pentaethylene glycol monododecyl ether solutions

We investigated the phase separation phenomena in dilute surfactant pentaethylene glycol monodedecyl ether (C12E5) solutions focusing on the growth law of separated domains. The solutions confined between two glass plates were found to exhibit the phase inversion, characteristic of the viscoelastic phase separation; the majority phase (water-rich phase) nucleated as droplets and the minority phase (micelle-rich phase) formed a network temporarily, then they collapsed into an usual sea-island pattern where minority phase formed islands. We found from the real-space microscopic imaging that the dynamic scaling hypothesis did not hold throughout the coarsening process. The power law growth of the domains with the exponent close to 1/3 was observed even though the coarsening was induced mainly by hydrodynamic flow, which was explained by Darcy's law of laminar flow

Extracellular vesicles shed from gastric cancer mediate protumor macrophage differentiation

Background Peritoneal dissemination often develops in gastric cancer. Tumor-associated macrophages (TAMs) are present in the peritoneal cavity of gastric cancer patients with peritoneal dissemination, facilitating tumor progression. However, the mechanism by which macrophages differentiate into tumor-associated macrophages in the peritoneal cavity is not well understood. In this study, the interplay between gastric cancer-derived extracellular vesicles (EVs) and macrophages was investigated. Methods The association between macrophages and EVs in peritoneal ascitic fluid of gastric cancer patients, or from gastric cancer cell lines was examined, and their roles in differentiation of macrophages and potentiation of the malignancy of gastric cancer were further explored. Results Immunofluorescent assays of the ascitic fluid showed that M2 macrophages were predominant along with the cancer cells in the peritoneal cavity. EVs purified from gastric cancer cells, as well as malignant ascitic fluid, differentiated peripheral blood mononuclear cell-derived macrophages into the M2-like phenotype, which was demonstrated by their morphology and expression of CD163/206. The macrophages differentiated by gastric cancer-derived EVs promoted the migration ability of gastric cancer cells, and the EVs carried STAT3 protein. Conclusion EVs derived from gastric cancer play a role by affecting macrophage phenotypes, suggesting that this may be a part of the underlying mechanism that forms the intraperitoneal cancer microenvironment

Targeting neutrophil extracellular traps with thrombomodulin prevents pancreatic cancer metastasis

Surgery is the only curative treatment option for pancreatic cancer, but patients often develop postoperative recurrence. Surgical invasiveness might be involved in the mechanism of recurrence. The associations among inflammation caused by surgery, neutrophils, and cancer metastasis were investigated. At first, neutrophil extracellular traps (NETs) were examined in clinical specimens, and NETs were observed around metastatic tumors. To explore how NETs were induced, neutrophils were cultured with pancreatic cancer or in cancer-conditioned medium. Neutrophils formed NETs when they were cultured with pancreatic cancer or even its conditioned medium. The effects of NETs on cancer cells were further investigated in vitro and in vivo. NETs induced the epithelial to mesenchymal transition in cancer cells and thereby promoted their migration and invasion. HMGB1 derived from NETs appeared to potentiate the malignancy of cancer cells. In a mouse model of liver metastasis with inflammation, NETs participated in the metastatic process by enhancing extravasation. Interestingly, thrombomodulin degraded HMGB1 and consequently inhibited the induction of NETs, thereby preventing pancreatic cancer metastasis to the liver. In conclusion, NETs interact reciprocally with pancreatic cancer cells, which play a pivotal role in inflammation-associated metastasis. Targeting NETs with thrombomodulin can be a novel strategy to improve the surgical outcome of pancreatic cancer patients

Intraperitoneal cancer-immune microenvironment promotes peritoneal dissemination of gastric cancer

A solid tumor consists of cancer and stromal cells, which comprise the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are usually abundant in the TME, contributing to tumor progression. In cases of peritoneal dissemination of gastric cancer (GC), the contribution of intraperitoneal TAMs remains unclear. Macrophages from peritoneal washings of GC patients were analyzed, and the link between intraperitoneal TAMs and GC cells was investigated to clarify the interaction between them in peritoneal dissemination. Macrophages were predominant among leukocytes constituting the microenvironment of the peritoneal cavity. The proportion of CD163-positive TAMs was significantly higher in stage IV than in stage I GC. Co-culture with TAMs potentiated migration and invasion of GC. IL-6 was the most increased in the medium of in vitro co-culture of macrophages and GC, and IL-6 elevation was also observed in the peritoneal washes with peritoneal dissemination. An elevated concentration of intraperitoneal IL-6 was correlated with a poor prognosis in clinical cases. In conclusion, intraperitoneal TAMs are involved in promoting peritoneal dissemination of GC via secreted IL-6. TAM-derived IL-6 could be a potential therapeutic target for peritoneal dissemination of GC

Protein crystallization induced by poly(ethylene) glycol : A small angle x-ray scattering study(Poster session 1, New Frontiers in Colloidal Physics : A Bridge between Micro- and Macroscopic Concepts in Soft Matter)

この論文は国立情報学研究所の電子図書館事業により電子化されました。水溶性高分子が球状タンパク質分子間にどのような相互作用をどのようなメカニズムで誘起するのかを知ることは、タンパク質溶液の制御(安定化や結晶化など)のために重要である。また、通常電荷を持ち、静電的に安定化しているタンパク質溶液の構造を、電荷を持たない水溶性の高分子が不安定化するメカニズムはソフトマターの液体構造という視点からも興味深い。本研究では、モデルタンパク質として直径約8nmのグルコースイソメラーゼを用い、水溶性高分子ポリエチレングリコールが誘起するタンパク質の溶液構造変化を、X線小角散乱法によって測定した。Proteins in aqueous solutions usually have surface charges which stabilize the solution. By adding salt or changing pH of the solution to decrease the electrostatic stabilization induces the molecular aggregation. On the other hand, it is well known that water-soluble polymers such as polyethylene glycol can destabilize protein solutions. Since these polymers often do not have any charges, it is believed that the primary mechanism of the destabilization is the depletion attraction at so-called protein limit, where the size of polymers is much larger than that of proteins. The real situation is, however, far more complicated than the model in theories. For example, the size of typical proteins (a few nanometers) is more or less similar to that of polymers frequently used for protein solutions. Moreover, as mentioned above, proteins have charges, which can a ect the depletion interaction. Croze and Cates suggested that there is a nonadditive property between the electrostatic interaction and the depletion interaction. Our aim of this study, therefore, is to give experimental information on the structure of protein solutions with polymers while controlling the electrostatic interactions with added salt

Progesterone Suppresses Uterine Contraction by Reducing Odontogenic Porphyromonas gingivalis Induced Chronic Inflammation in Mice

Preterm birth is one of the most significant obstetric complications. Inflammation reportedly promotes uterine contraction and weakening of the fetal membrane, which induces preterm birth. Previous studies using animal models of lipopolysaccharide-induced acute inflammation have shown that progesterone (P4) promotes uterine quiescence. However, this effect is not fully understood in chronic inflammation. This study aimed to investigate the effects of P4 on uterine contractility and inflammation of the fetal membrane in mice infected with Porphyromonas gingivalis (P.g.), a major periodontal pathogen as a model of preterm birth caused by chronic inflammation. Mice were injected with 1 mg of P4 from day 15.5 to 17.5. P4 prolonged the mean gestation period of P.g mice from 18.3 to 20.4 days, and no reduction in the gestation period was observed. P4 treatment suppressed spontaneous uterine contractility and decreased oxytocin sensitivity. In addition, the expression of inflammatory cytokines in the fetal membrane was significantly reduced. Thus, P4 prevented preterm birth by suppressing enhanced uterine contractility induced by chronic inflammation in this model. This result describes the effects of P4 in a chronic inflammation model, which may lead to a better understanding of the efficacy of P4 in preventing preterm birth in humans

Dual antiplatelet therapy inhibits neutrophil extracellular traps to reduce liver micrometastases of intrahepatic cholangiocarcinoma

The involvement of neutrophil extracellular traps (NETs) in cancer metastasis is being clarified, but the relationship between intrahepatic cholangiocarcinoma (iCCA) and NETs remains unclear. The presence of NETs was verified by multiple fluorescence staining in clinically resected specimens of iCCA. Human neutrophils were co-cultured with iCCA cells to observe NET induction and changes in cellular characteristics. Binding of platelets to iCCA cells and its mechanism were also examined, and their effects on NETs were analyzed in vitro and in in vivo mouse models. NETs were present in the tumor periphery of resected iCCAs. NETs promoted the motility and migration ability of iCCA cells in vitro. Although iCCA cells alone had a weak NET-inducing ability, the binding of platelets to iCCA cells via P-selectin promoted NET induction. Based on these results, antiplatelet drugs were applied to these cocultures in vitro and inhibited the binding of platelets to iCCA cells and the induction of NETs. Fluorescently labeled iCCA cells were injected into the spleen of mice, resulting in the formation of liver micrometastases coexisting with platelets and NETs. These mice were treated with dual antiplatelet therapy (DAPT) consisting of aspirin and ticagrelor, which dramatically reduced micrometastases. These results suggest that potent antiplatelet therapy prevents micrometastases of iCCA cells by inhibiting platelet activation and NET production, and it may contribute to a novel therapeutic strategy